- Apr 2019
-
www.foxnews.com www.foxnews.com
-
Safety advocates urged college students to match the vehicle color and model, the license tag number, and the photo of their ride-share drivers before getting in a vehicle and make the driver say their names to them before they introduce themselves.
Students should follow this to be safe.
-
Safety advocates urged college students to match the vehicle color and model, the license tag number, and the photo of their ride-share drivers before getting in a vehicle and make the driver say their names to them before they introduce themselves.
Always make sure to do this
-
-
onlinelearningconsortium.org onlinelearningconsortium.org
-
Online Learning Consortium (OLC)
Hello OLC!
-
-
www.insidehighered.com www.insidehighered.com
-
But the offer came with a hefty price tag, the negotiators said, which the system was not willing to pay.
Doesn't it seem like everything comes with a hefty price these days...
-
-
digitalempathyvet.com digitalempathyvet.com
-
Dr. Sanha Kim should be moved over to Columbia. We need to add a space holder for Cynthia Loveland under Columbia doctors. For all doctors except Tanya Tag, list them as 'Emergency Veterinarian' instead of emergency and critical care. Under 'doctors' Dr. Tag looks great, could you add Towson & Columbia next to Medical Director? For Dr. Tag under administration, remove her middle initial and change DVM to match DACVECC as displayed for her under doctors. Leave medical director Towson & Columbia. Please display leadership in this order: Angelina Morgan, Tanya Tag, Tamara Santesse, Elizabeth Moyers, Beth Faux, Ashley Carlson, Victoria Syczurowski, Jeff Hawkins, Christine Wolff, Paul Heggie, Joey Sumby (I spelled his name wrong last time)
Beth Faux should display as "Beth Faux, RVT, VTS (ECC). Her title should be listed as Technician Manager Columbia. Tamara Santesse's title should be Office Manager, Towson. Elizabeth Moyers' title should be Office Manager, Columbia Victoria and Ashley's title are: Technician Co-Manager Towson Jeff Hawkins' title should be Financial Manager Towson & Columbia Paul Heggie's title should be Facilities Manager Towson & Columbia Joey Sumby's title should be Facilities Supervisor Columbia
Love the super heroes-are there gender specific?
-
- Mar 2019
-
alexan25.myhostpoint.ch alexan25.myhostpoint.ch
-
Twitter Facebook Instagram Impressum Haftungsausschluss
Alignierung kann angepasst werden
-
- gutes Teaserbild. Allerdings nimmt zuviel Platz. Für den Hauptinhalt (Wanderungen) muss man sofot scrollen. Eine Alternativ wäre mit einem "Karrussell" von den letzten 3 Wanderungsbilder oder so.
-
-
www.learning-theories.com www.learning-theories.com
-
Behaviorism
Learning-Theories.com published a very handy few pages that describe various learning theories. This is a quick, straightforward, simple way to access information on the different theories. This article, Behaviorism, explains that the theory assumes learners learn by responding to external stimuli in their environment. Learning under behaviorism is characterized by a change in the learner's behavior. I use this in my horse training as I use both positive reinforcement (clicker training) and negative reinforcement (pressure-release) to structure my horse's behaviors. Behaviorism can be translated to human work, too. I've used TAG teaching (clicker training for humans) to teach people to get on and off horses with ease and also to trim horses' hooves. I also use it to clicker train my cats! 6/10
-
-
-
Republicans immediately painted the plan as “disastrous,” pointing to studies that suggest the price tag could be as high as $32 trillion.
Source?<br> Which Republicans?
-
-
digitalempathyvet.com digitalempathyvet.comPricing1
-
health exam and vaccinations - $167.53 includes Doctor exam, rabies, Dhlpp, bordetella, send out to lab fecal, and heart worm occult and parish tag. puppy care 1st shots= $137.40 2nd- 9 weeks is $143.29 3rd - 12 weeks $147.01 4th - 15 weeks $187.08 Micro chips- $63.13 feline neuter- $100.89 feline front declaw- $232.87
-
-
web.hypothes.is web.hypothes.is
-
disallows it in our Public channel and in groups
You can, however, add a tag to a highlight in order to share it to the Public channel or a group.
-
-
elearninginfographics.com elearninginfographics.com
-
personalize learning infographic
This is not quite what it sounds like. It is a Pinterest style page with links to assorted articles that relate to personalized learning, most of which are presented in an infographic. It is sufficiently useful if one has the patience to click through to the infographics. Usability is satisfactory although the top half of the page is taken up with graphics that are not directly related to the content. rating 3/5
-
-
www.allisonrossett.com www.allisonrossett.com
-
This plain page incorporates an overview of job aids by Allison Rossett, who is the foremost authority on the topic. Not all information is given away for free as she wants to sell her books, which are also promoted on the page. This page can be a good way of tracking her current work. Rating 3/5
-
-
internal-developer.veevavault.com internal-developer.veevavault.com
-
LATESTVERSION
code tag here
-
-
typito.com typito.com
-
Create Stunning Videos Online
Templates by TYPITO
-
-
theladyalliance.com theladyalliance.com
-
CourseFolk
I've taken the focus off CourseFolk being educators who craft the lessons and made that something The Lady Alliance does and CourseFolk just does the techy website/members stuff. I think influencers will balk at a random company doing the lesson writing part for them. I'm still happy to do the interviews and workshop the lessons, but maybe I can do that with a Lady Alliance tag somehow. We can chat more about how this will work
-
- Feb 2019
-
arxiv.org arxiv.org
-
the agent model swaps the in-put and output sequences, and it also takes the tag of filledinformation slots as an input which is extracted from dia-logue in previous turns by pattern matching with the orderinformation in ground truth
agent model 构建前先预训练。网络结构和user model一样,但是输入和输出反转,同时也把之前对话中已经填充的槽位信息作为输入。但是这俩部分信息并不是简单的直接拼接在一起,而是来学习适合的attention 权重来更好的利用注意力机制。此外任何其他额外的语义意图标签都不必用。
Tags
Annotators
URL
-
-
www.wired.com www.wired.com
-
And who will write the software that makes this contraption useful and productive? We will. In fact, we’re already doing it, each of us, every day. When we post and then tag pictures on the community photo album Flickr, we are teaching the Machine to give names to images. The thickening links between caption and picture form a neural net that can learn. Think of the 100 billion times per day humans click on a Web page as a way of teaching the Machine what we think is important. Each time we forge a link between words, we teach it an idea. Wikipedia encourages its citizen authors to link each fact in an article to a reference citation. Over time, a Wikipedia article becomes totally underlined in blue as ideas are cross-referenced. That massive cross-referencing is how brains think and remember.
This was the main goal of the 'docuverse' where information will be cross referenced and everything will be related in someway to everything else.
-
-
-
tag those and only those who will really derive benefit
Implies you know who those people are and you may not know but for some of us that is the whole point of an ESN
-
Developing employees
An HBR tag for the article
-
-
www.anxietycanada.com www.anxietycanada.com
-
We're working on an improved
Do we just post to public or do we add a LDRS 626 tag?
-
-
law.yale.edu law.yale.edu
-
A study published in October of last year sought to determine how to make best use of digital out-of-home (DOOH) advertisements in the London Underground.7 An example of a DOOH ad would be a digital billboard programed to change the advertisement on display after a specific period of time. To achieve their goal, the researchers used the same Twitter Streaming API described in the previous study; however, this time they utilized Twitter’s geotagging function (a capability that allows Twitter users to “tag” their location when they post a tweet). Each London Underground station was carefully outlined on a map of London. Then, the researchers randomly sampled geotagged tweets falling within those zones (meaning the tweeter was at a station). The specific Underground station, the time of the tweet, and the content of the tweet were all extracted. The researchers continued this practice for one year, seemingly unbeknownst to the Twitter-using patrons of the London Underground, collecting over 10.5 million tweets. This data was then compiled and processed to determine what sort of things people were tweeting about in each London Underground station at certain times of the day on weekdays and on weekends. For example, nearly 35% of tweets from the Holloway Road station were about sports, and almost 40% of tweets posted between 6 PM and midnight on weekends at the North Greenwich station were about music.8 The authors of the study recommended using this data to create targeted DOOH advertising. For instance, a music-related ad on a rotating digital billboard at night on the weekends in North Greenwich station would probably be more successful than an ad for a sports team.
This entire passage gives a perfect example of how the data can be broken down and used to make money by advertisers. I intend to allude to the fact that it doesn't stop here.
-
-
www.w3schools.com www.w3schools.com
-
<p>This is a paragraph.</p> <p>This is another paragraph.</p>
Paragraph Tag
Tags
Annotators
URL
-
-
www.w3schools.com www.w3schools.com
-
<a href="default.asp"> <img src="smiley.gif" alt="HTML tutorial" style="width:42px;height:42px;border:0;"></a>
Image as a link - Ignore the style="…." part of the tag. Inline styles are bad!
-
<img src="https://www.w3schools.com/images/w3schools_green.jpg" alt="W3Schools.com">
Image Tag
Tags
Annotators
URL
-
-
www.w3schools.com www.w3schools.com
-
<a href="https://www.w3schools.com/html/">Visit our HTML tutorial</a>
Link Tag
-
-
worrydream.com worrydream.com
-
few
Is there a common tag that we are using for annotations here?
-
-
www.insidehighered.com www.insidehighered.com
-
it allows you to tag records
Since DH is such a collaborative subject, you have to make sure references are accurate so that everyone gets credit for their contributions
-
- Jan 2019
-
-
. The nofollow tag came about as a method to help stop automated blog comment, guest book, and link injection spam
Appreciated
-
-
static1.squarespace.com static1.squarespace.com
-
summary,
super helpful summary. Commenting just to tag it.
Tags
Annotators
URL
-
-
static1.squarespace.com static1.squarespace.com
-
posthumanitie
commenting just to tag this
-
-
dhdebates.gc.cuny.edu dhdebates.gc.cuny.edu
-
SGML, HTML, XML
SGML = Standard Generalized Markup Language, "a standard for how to specify a document markup language or tag set... SGML is not in itself a document language, but a description of how to specify one." So a set of guidelines, like TEI?
-
-
www.nytimes.com www.nytimes.com
-
$10 billion is a hefty price tag.
however Dr. Hossenfelder does not agree the cost outweighs the benefits
-
With a $5 billion price tag and a $1 billion annual operation cost, the L.H.C. is the most expensive instrument ever built
That is intense. 5 billion $ to build, yet it cost 1 billion to upkeep.
-
-
ucdenver.instructure.com ucdenver.instructure.com
-
. Social Media is where we will connect with the broader digital storytelling community, which are very active on Twitter and Instagram. You may participate anonymously if you prefer. Tag all class related communications with #inte5340 (Links to an external site.)Links to an external site. and #digstory (Links to an external site.)Links to an external site. .
Would using our personal social media be acceptable for public communication or would you suggest in creating a new account?
-
Articles and videos will be assigned each week.
Just wondering what the weekly deadline for discussion will be. Also, do I need to tag these comments...I just saw the option below?
-
Tag all related posts
So, we will not be sharing the blog directly on canvas, only tagging our posts correct?
-
-
-
Astros outfielder Josh Reddick is a big wrestling fan, so after he tied the knot this weekend, him and his bride came out to their friends and family using the same entrace as current WWE tag team champions Bobby Roode and Chad Gable.
"him and his bride came out to their friends"
-
-
www.ontotext.com www.ontotext.com
-
Tag Archives: linked open data
-
-
hypothes.is hypothes.is
-
Machines with interchangeable parts can now be constructed with great economy of effort. In spite of much complexity, they perform reliably. Witness the humble typewriter, or the movie camera, or the automobile. We have reached a point in technology now where all of these inventions can perform their jobs without human involvement.
His description of the "humble typewriter" seems like such an understatement in comparison to the computers and recording devices we now have
-
-
openedx.atlassian.net openedx.atlassian.net
-
the-tag/you-want-to-install
open-release/hawthorn.2
-
-
www.theatlantic.com www.theatlantic.com
-
burying their old professional competition in the demand of a common cause, have shared greatly and learned much. It has been exhilarating to work in effective partnership. Now, for many, this appears to be approaching an end.
What is interesting is how individuals still share their knowledge to create new things, artists and scientists collaborating together, but how there is still that tight restriction that controls what can be done. New inventions, artworks, music, and tools are still copyrighted and individuals must apply to work with them. You also have inventors that place an outrageous price tag on some of their products, limiting the number of people who can buy them and find out what things they can do that are beyond even the mind of the tool's creator.
-
-
crmintler.com crmintler.com
-
Hypothesis Annotation instructions:
1) Make 2-3 annotations. 2) If another student has already annotated a passage you wished to annotate, you have two options: reply to that annotation or choose another passage to annotate. 3) Reply to at least 2 annotations made by your peers 4) If someone replies to your annotation, reply to keep the conversation going. 5) TAG all annotations CITA2019
-
-
www.si.com www.si.com
-
New York City Fire Department
Sample, notice how I made it public and used a tag. You can also add links to other material.
Images are good too, but only if you think they add something to our understanding of the text. Here's the first female firefighter in the NYFD.
-
-
www.le24heures.fr www.le24heures.fr
-
Proche de la basilique Saint Sernin, haut lieu touristique de la ville rose, le quartier Arnaud Bernard ne profite pas de ce rayonnement. Beaucoup de rues sont sales et le quartier n’attire pas les visiteurs. Des tags et des graffs décorent les murs de certains immeubles. Le quartier fait partie des tout premiers de la ville à accueillir de nombreux artistes graffeurs, mais sans organisation. En 1997 l’association « carrefour culturel » décide de lancer un projet avec les habitants du quartier: réaliser une fresque géante dans la rue Gramat pour couvrir les tags. Après trois ans de discussions avec la municipalité, les propriétaires et les artistes, la fresque peut enfin voir le jour. Les riverains participent eux-mêmes au nettoyage de la rue pour accueillir les dessins. Elle est au cœur d’un projet citoyen. David Brunel explique : » le but c’est de créer à l’époque des actions culturelles où les citoyens sont à l’initiative, mais aussi acteur du projet du début à la fin » Il poursuit : » le quartier est vu comme une base d’expérience, avec une réflexion sur le civique ». Parmi les artistes, on retrouve un SDF du quartier, un peintre mais aussi des gens venu d’Espagne. Ils sont tous là pour donner une vision de la ville et de son histoire. Plus qu’une fresque ce sont des échanges, un projet construit par les habitants, pour les habitants. Annick Lodereau, l’une des meneuses, résume le projet à l’époque : » C’est une fresque anti-tag, une création qui démontre que l’on peut faire des choses ensemble et leur donner un sens ». Malgré l’ampleur du projet, au fil des ans la rue est de nouveau utilisée par les tagueurs qui repassent sur les fresques de l’époque dont il ne reste aujourd’hui plus rien.
Fais des retours ligne pour marque les paragraphes, sinon c'est trop difficile à lire.
-
-
unify.id unify.id
Tags
Annotators
URL
-
-
wendynorris.com wendynorris.com
-
In this section of the paper we broach two aspects of this articulation issue, onefocusing on the management of workflow, the other on the construction and manage-ment of what we term a ‘common information space’. The former concept has beenthe subject of discussion for some time, in the guise of such terms as office automa-tion and more recently, workflow automation. The latter concept has, in our view,been somewhat neglected, despite its critical importance for the accomplishmentof many distributed work activities
A quick scan of ACM library papers that tag "articulation work" seems to indicate the "common information space" problem still has not attracted a lot of study. This could be a good entry point for my work with CSCW because time cuts across both workflow and information space.
Nicely bundles boundary infrastructure, sense-making and distributed work
-
- Dec 2018
-
vitalirosati.net vitalirosati.net
-
inscription
Tags
Annotators
URL
-
-
spilledreality.tumblr.com spilledreality.tumblr.comOtessa1
-
But the real sex politics are more ingrained and foundational, relating to how ‘Tag perceives herself in the world and how that self-image as object lends itself to a specific and perhaps primarily female mode of suffering.
A. Saramandi: "She’s victim of a culture that bombards her with the message that she is in control, as long as she buys the necessary products, looks a certain way. In one of the most poignant moments of the novel, she doesn’t realise that this agency is a false god: when the narrator is molested by one of her father’s colleagues, she believes she was “letting [him] kiss me” and is confused as to why, since after all, as the epitome of desire, she must be responsible."
-
-
surfacescholar.com surfacescholar.com
-
The real question, I realized, was: how can I remember anything if I can only keep it in one place?
The biggest issue I have with iThoughts right now is the lack of ability to dynamically filter maps based on tags or other properties of nodes. I'd love to be able to view only the nodes I need for a specific query and have everything else dynamically vanish— particularly on large maps, where the existing method of filtering renders the nodes illegible...
That said, I've come to depend on text searches to return a filtered list of nodes. iThoughts allows for searching within a map and across all maps in the filesystem. It's not a fuzzy search, so search strings have to be constructed in a fixed way which necessitates a robust system of memorable tags, categories or conventions (for example, use of the tag "@due(2019-10-02)" allows me to filter for nodes with due dates, and nodes due within a specific year, month or on a specific date, by parsing incremental fragments of the tag. Simple, but effective.
-
-
adullact.net adullact.net
-
Tag Cloud
Le nuage de mots surcharge la page
Un nuage de mots n'apporte pas beaucoup d'informations aux utilisateur·rice·s qui arrivent sur cette page.
En revanche, cela surcharge la page à la place d'autres informations qui pourraient être plus utiles.
Suggestion : placer ce nuage de mots sur une page spécifique que les utilisateurs que ce nuage de mots intéresse pourront consulter.
-
-
web5.lib.pacificu.edu web5.lib.pacificu.edu
-
seine Grundschulen
nachdem sie am Tag von der Grundschule fertig sind
-
-
science.sciencemag.org science.sciencemag.org
-
We therefore developed protocols for fluorescent in situ hybridization (FISH) targeting specific ascomycete and cystobasidiomycete rRNA sequences.
A molecular probe is created against a specific DNA sequence, in this case rRNA from either ascomycetes or basidiomycetes. The probe is designed with a recognizable tag on the end. Then a second probe is used to match the first probe, and finally a third probe to match the second one with a fluorescent tag on it. By using multiple probes we can amplify even the smallest signals to our first probe. These probes are then mixed with a biological sample that is fixed in place. If fluorescence is observed the probe has found a target.
In some experiments, as in this example, researchers use multiple probes in a single experiment. This provides information about how close two organisms of interest are in a given sample.
-
-
www.huffpost.com www.huffpost.com
-
Pong in 1972 and Space Invaders in 1978, which kick started a cultural revolution. Notably in 1981, with Nintendo’s masterpiece, Donkey Kong
These were the first games to really kickstart video games' jump into popular culture. More than that, they left their mark on society as the first games to be accessible in your homes, which is an important note. That was the start of gaming being right in people's faces, as they have become everywhere now.
-
-
gutenberg.net.au gutenberg.net.auSanditon4
-
equipage
An equipage is an archaic term for a horse drawn carriage and its attendants. https://www.merriam-webster.com/dictionary/equipage
Here is an article about regency transportation (including video links): https://janeaustensworld.wordpress.com/tag/regency-transportation/
-
seen romantically situated among wood on a high eminence at some little distance
This description of a cottage reminds me of the contrast in Austen's Sense and Sensibility between how the upper classes and the landed gentry view cottages. The upper classes view cottages in a romantic way as cute, comfy homes, however the landed gentry know that cottages result out of a neccesity brough on by an oppresive and restrictive economic system.
https://janeaustensworld.wordpress.com/tag/19th-century-cottages/
-
leeches
"Bloodletting procedures, including leeching, became the most common medical procedure throughout the early modern period. By the early 19th century, many patients regularly submitted to various bloodletting practices as a means of preventing or treating infection and disease"
https://www.britannica.com/science/leeching
Leeching more specifically in Jane Austen's world: "One can imagine that during her final illness, Jane Austen was no stranger to leeches."
-
machine
"Wagons, called Bathing Machines, were invented especially for the purpose, and would be drawn out into the water by sturdy women, who might then assist you down into the water where you could paddle about or swim in relative privacy, shielded from view of the shore."
-
-
jrnl.global jrnl.global
-
KnowFlow in a visual knowledge management enviroment for collaborative groups. Collaborative SAAS, purely web-based multi-user application.
Although it is been created as a part of Neuroweb platform, it seems, that roots behind Douglas Engelbart conceptual framework and Neuroweb conceptual framework are the same. As one can see when reading D.Engelbart's group documents, cognitive science concepts were used in a context very similar to what is considered to be a conceptual framework of Cultural-historical psychology approach, based on undestanding of concept developement and role of symbolic representations in development of psyche and culture. One can see citations of authors connected to cultural-historical psychology throughout the works of Engelbart's group, i.e. of Alan's Keys and other members. KnowFlow system as it is and in scope of it's developement is a system that can easily be understood via DKR conceptual approach. It does not mean that it was build on D.Engelbarts framework alone, but still all the basic concepts of DRK are there. We build KnowFlow to be a living knowledge network, providing means to import, create, modify and view and export knowledge in a process of any complex product or project developement by a group of knowledge workers. That is basically a tool to boost group's IQ, its collective exocortex. KnowFlow can import different kinds of documents, including texts, maindmaps, presentations, media materials. We can do it via direct import, import from connected sources via public API, or via WebClipper that works as a Chrome Browser extention similar to one of Evernote, that can grab a page, fragment of text or a screenshot to save it as a knowledge element, rich format note. If the initial imported document is too large or consists of many subdocuments, special import algorythm can parce it up to a set of knowledge elements, saving each of them separately. Semantic engine is used to help user to parce the documents, finding the key statements in text, separating them and even instantly creating a concept-map our of the text.
User can work individually or with a group of other users on this knowledge material in different ways: He can work with element as a text, using simple text editor, adding additional materials to a body of the knowledge element, making a group of elements form one element or combining several elements into a group that can be presented as a group or as a complex element at the same time. One can also use element (card) templates to make his work easier. User can also work with his collection of knowledge as with a database, searching through elements, filtering them, group or combine them in a "collection view". One can use domain system to tag or classify elements of knowledge he is working with. Domain is a set of classes that can also me named ontology. So, user can place elements in context of different ontologies. User can work with elements or groups of elements (that can be seen as fractal elements) in a concept-map view. It means that one can connect elements with cinnection, set relations between them and work with them as one works with knowledge maps. One card (knowledge element) can be used in different maps, still being the same element, changing in all the maps it is being used it. Or elements can be copied or modified, That way the system will know who and how used elements to build a new knowledge upon them. Version control is also there. One can use his collection view not for his whole collection but for one knowledge space (map). This view disregards connections, still providing means to work with groups of cards and stacks or sets, similar to Kanban decs used in Trello (and yes we have an integration with trello. too) Knowledge spaces (maps) can be connected to each other through "portals" - these are cards (elements) or groups of cards that are present in several maps (knowlege spaces) at the same time. This way knowledge workers can create a multi-space flow of knowledge between different maps, belonging to one or many groups, working with different aspects of knowledge and different stages of its life-cycle. A special instrument - "Сass" can be used to import knowledge elements or portals from other maps during group work. Users can instantly view the map (knowledge space) in presentation view, when each element is one slide. navigating through complex knowledge structure, choosing different trajectories depending on what they want to focus on. Additional collaboration tools include, but not limited to voting, commentaries end collective editing of knowledge in any view, as well as using shared knowledge space templates for different kinds of collaboration (brainstorms, SWOT analisys etc), collaborators can share elements of knowledge, collections, maps or it branches between individual users, groups or make them publicly available.<br> All that work is augmented with voice recognition that lets users speak their knowledge in - and that is particularly useful in capruring debates or meetings. All functions of the KnowFlow system are augmented with machine learning semantic recommendation engine. That recommends fragments of knowledge already in the system, recommends templates and connections in knowledge map mode. We also have a Virtual Relity interface that can give one an opportunity to view multiple knowledge spaces at the same time, walk between knowledge networks and see them being created in real time.
All the results can be exported in any moment to a number of formats (including PDF, Mindmanager, Table, Text, etc) or streamed through API to other elements for additional ways of use. One of uses of KnowFlow is creation a templates or publically available knowledge spaces, knowledge elements, maps or chains that contain best practices and knowledge that can be used in other contexts, when needed.
Next version will also include timeline views usefull for sorting all the knowledge elements on a timeline. filtered by meta-data, VR interface will get edit capabilities and voice commands will be available for a group work in shared spaces. Additional libraries of semanic analisis will be added, text edit mode will be upgraged, and number of other software integrations will provide easy use of KnowFlow as a collaborative knowledge processing tool in any workflows.
That is, basically, DKR, as it seems to me.
“A dynamic knowledge repository is a living, breathing, rapidly evolving repository of all the stuff accumulating moment to moment throughout the life of a project or pursuit. This would include successive drafts and commentary leading up to more polished versions of a given document, brainstorming and conceptual design notes, design rationale, work lists, contact info, all the email and meeting notes, research intelligence collected and commented on, emerging issues, timelines, etc.” That are the forms of data that can be inmorted, used, transformed and contextually accessed, History tool provides ability to move back in time to a point in knowledge space developement, to access relevant data and fork new line of work from there, still being able to use all the knowledge being created later or in lateral lines of work, even by other groups, proven that access mode for them makes it available.
One can say that knowflow is created as a version of CoDIAK process, as it supports and speeds up ways to develop, integrate, and apply all this iterating knowledge from the swirl of disparate concurrent contributions. So, if KnowFlow is an “emerging collective record of all this activity captured on the fly -- the emerging collective vision, know-how, the group brain, memory, where the dots are connected and the right hand knows what the left hand is doing” it means that KnowFlow is really a version of DKR .
KnowFlow emerged as a result of best practices of work with project groups in business schools, methods and approaches to collective work (i.e. Rapid Foresight methodology, co-developed by KnowFlow team members, etc) and is already used to facilitiate the collective work “in a way that optimizes the capture, organization, and enhanced utility of the DKR”. Best practices would include special roles such as collaboration facilitators, as well as high performance knowledge specialists, who are continuously moderating the connectivity, capture, tagging, tracking, and portals into the emerging repository -- tools, practices, and people connecting in a way that renders the DKR optimally navigable, searchable, and useful.
-
- Nov 2018
-
imackinson.com imackinson.com
-
It’
The apostrophe isn't rendering correctly because you're missing the meta charset tag in your HTML head.
-
-
evanmillican.com evanmillican.com
-
â€
The apostrophe didn't render correctly because you forgot the meta charset tag in the HTML.
-
-
www.scienceintheclassroom.org www.scienceintheclassroom.org
-
only a small fraction of the neurons that receive odor information respond to each odor
Lin et al. discovered the neurological process that controls why so few olfactory neurons make up each odor "tag."
The reason is because when the cells that receive odor information, called Kenyon cells (KCs), become active, the anterior paired lateral neuron responds by slowing the activity of the KCs. The more active the KCs become, the harder the anterior paired lateral neuron works to block their activity. The few KCs that are left active after this process form the odor tag.
-
-
rachaellhead.com rachaellhead.com
-
it’s
This isn't rendering as an apostrophe because you forgot the meta charset tag in your HTML
-
-
robinderosa.net robinderosa.net
-
We have lost any sense of what we mean when we call a university “public.
It really loses the tag of public when it's hundred of dollars to take a single class almost anywhere.
-
-
www.aclweb.org www.aclweb.org
-
probabilistic model to tag English text
*
-
-
www.makeuseof.com www.makeuseof.com
-
Partial charges and discharges that combine to 100% are counted as a single full cycle
Really? I don't think anyone has tested partial charges and discharges. I would like to see a reference for this point!
-
research says
That is pretty weak evidence for such a strong statement
-
-
edegbor.digstonehill.org edegbor.digstonehill.org
-
Blog Posts
This is kind of a catch all tag, like uncategorized. Try to keep your tags specific.
-
-
www.technologyreview.com www.technologyreview.com
-
Gates calls the new approach a “breakthrough,” but some environmental groups say gene drives are too dangerous to ever use.
trying to add a tag
-
-
mpi4py.readthedocs.io mpi4py.readthedocs.io
-
comm.Send([data, MPI.INT], dest=1, tag=77)
Capital functions are lcosest to their C equivalent
-
-
Local file Local file
-
lgjuraj.digstonehill.org lgjuraj.digstonehill.org
-
Categories Uncategorized
You should have no uncategorized posts at this point. Start using tags and categories and back tag your earlier posts.
-
-
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
-
A-11122
Curator: @evieth
Curator note: Thermo Fisher Scientific Cat# A-11122, GFP Tag Polyclonal Antibody
Resource used:
(Thermo Fisher Scientific Cat# A-11122, RRID:AB_221569)
SciCrunch record: RRID:AB_221569
Alternate resolvers: SciCrunch xml N2T identifiers.org
-
-
www.sciencedirect.com www.sciencedirect.com
-
2278
Curator: @evieth
Curator note: Cell Signaling Technology Cat# 2278, Rabbit Anti-Myc-Tag Monoclonal Antibody, Unconjugated, Clone 71D10
Resource used:
(Cell Signaling Technology Cat# 2278, RRID:AB_490778)
SciCrunch record: RRID:AB_490778
Alternate resolvers: SciCrunch xml N2T identifiers.org
-
-
academic.oup.com academic.oup.com
-
IMSR_JAX:012 569
Curator: @bandrow @evieth
Curator note: IMSR Cat# JAX:012569
Curator note: The missing tag here is not correct. This RRID is there.
Resource used:
RRID:IMSR_JAX:012569
SciCrunch record: RRID:IMSR_JAX:012569
Alternate resolvers: SciCrunch xml N2T identifiers.org
-
-
elifesciences.org elifesciences.org
-
ab137839
Curator: @evieth
Curator note: Anti-6X His tag antibody, Abcam
Resource used:
(Abcam Cat# ab137839, RRID:AB_2732046)
SciCrunch record: RRID:AB_2732046
Alternate resolvers: SciCrunch xml N2T identifiers.org
Tags
Annotators
URL
-
-
bmcbiol.biomedcentral.com bmcbiol.biomedcentral.com
-
mouse monoclonal anti-His tag (ABclonal Technology Cat#AE003
Curator: @evieth
Resource used:
(ABclonal Cat# AE003, RRID:AB_2728734)
SciCrunch record: RRID:AB_2728734
Alternate resolvers: SciCrunch xml N2T identifiers.org
-
-
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
-
G10362
Curator: @evieth
Curator note: GFP Tag Antibody, ABfinity(TM) Rabbit Monoclonal
Resource used:
(Thermo Fisher Scientific Cat# G10362, RRID:AB_2536526)
SciCrunch record: RRID:AB_2536526
Alternate resolvers: SciCrunch xml N2T identifiers.org
-
-
www.sciencedirect.com www.sciencedirect.com
-
RRID:AB_2099233
Curator: @evieth
Resource used:
(Cell Signaling Technology Cat# 7074, RRID:AB_2099233)
SciCrunch record: RRID:AB_2099233
Alternate resolvers: SciCrunch xml N2T identifiers.org
-
- Oct 2018
-
wikimediafoundation.org wikimediafoundation.org
-
Oates soon realized navigating Wikimedia Commons and finding interesting materials is challenging. She noted how the category system used to organize and tag media files on Commons is confusing and hides—not shows—the richness of content there.
Problems with the category system making it difficult to search relevant information
-
-
www.inter-logic.gr www.inter-logic.gr
-
historiography
public test by marg with tag historians
-
-
tud.sg.dev.code.one tud.sg.dev.code.one
-
port From Doc
Tú coi a Phong tag nè
-
-
www.lenr-forum.com www.lenr-forum.com
-
agree, but "you can't prove a negative".
It's easy to mess up the quotation formatting. Also easy to fix with a close-quote tag. That errors like this commonly persist shows that people don't go back and read their own writing.
-
-
editions.lib.umn.edu editions.lib.umn.edu
-
Margaretta M. Lovell #pt-cv-view-29709a7js0.pt-cv-post-border { margin: 0; border-top-width: 1px; border-left-width: 1px } #pt-cv-view-29709a7js0.pt-cv-post-border { margin: 0; border-top-style: solid; border-left-style: solid } #pt-cv-view-29709a7js0.pt-cv-post-border .pt-cv-content-item { border-right-width: 1px; border-bottom-width: 1px; border-right-style: solid; border-bottom-style: solid; } #pt-cv-view-29709a7js0 .pt-cv-title a, #pt-cv-view-29709a7js0 .panel-title { font-weight: 600 !important; } #pt-cv-view-29709a7js0 .pt-cv-hover-wrapper::before { background-color: rgba(0,0,0,.3) !important; } #pt-cv-view-29709a7js0 .pt-cv-content-item:hover .pt-cv-hover-wrapper::before { background-color: rgba(51,51,51,.6) !important; } #pt-cv-view-29709a7js0:not(.pt-cv-nohover) .pt-cv-mask * { color: #fff; } #pt-cv-view-29709a7js0 .pt-cv-carousel-caption { background-color: rgba(51,51,51,.6) !important; } #pt-cv-view-29709a7js0 .pt-cv-specialp * { color: #fff !important; background-color: #CC3333 !important; } #pt-cv-view-29709a7js0 .pt-cv-pficon { color: #bbb !important; } #pt-cv-view-29709a7js0 .add_to_cart_button, #pt-cv-view-29709a7js0 .add_to_cart_button * { color: #ffffff !important; background-color: #00aeef !important; } #pt-cv-view-29709a7js0 .woocommerce-onsale { color: #ffffff !important; background-color: #ff5a5f !important; } #pt-cv-view-29709a7js0 .pt-cv-readmore { color: #ffffff !important; background-color: #00aeef !important; } #pt-cv-view-29709a7js0 .pt-cv-readmore:hover { color: #ffffff !important; background-color: #00aeef !important; } #pt-cv-view-29709a7js0 + .pt-cv-pagination-wrapper .pt-cv-more , #pt-cv-view-29709a7js0 + .pt-cv-pagination-wrapper .pagination .active a { color: #ffffff !important; background-color: #00aeef !important; } [id^='pt-cv-filter-bar-29709a7js0'] .active.pt-cv-filter-option, [id^='pt-cv-filter-bar-29709a7js0'] .active .pt-cv-filter-option, [id^='pt-cv-filter-bar-29709a7js0'] .selected.pt-cv-filter-option, [id^='pt-cv-filter-bar-29709a7js0'] .dropdown-toggle { color: #fff !important; background-color: #00aeef !important; } [id^='pt-cv-filter-bar-29709a7js0'] .pt-cv-filter-title { color: #fff !important; background-color: #00aeef !important; } #pt-cv-gls-29709a7js0 li a.pt-active { color: #fff !important; background-color: #ff5a5f !important; } #pt-cv-view-29709a7js0 .pt-cv-gls-header { color: #fff !important; background-color: #00aeef !important; } #pt-cv-view-29709a7js0 .cvp-responsive-image[style*="background-image"] { width: 200px; height: 200px; } #pt-cv-view-29709a7js0 .pt-cv-ocol:nth-child(2n+2) .cvp-responsive-image[style*="background-image"] { width: 150px; height: 150px; } Bully PulpitWhat Is the Role of Patriotism in the Study of American Art?M. Elizabeth Boone, Lauren LessingM. Elizabeth (Betsy) Boone and Lauren Lessing, Executive Editors Do we have a responsibility to the nation in our teaching and writing on American art? How would this responsibility be enacted and can it be done without seeming to be jingoistic? Does a new understanding of our nation impact our teaching and study of American art? How do you feel about the idea of a national narrative? Have you been challenged to rethink the relationship between American art, the nation, and its citizenry at any time in the last year?ResponsesDavid M. Lubin, Charlotte C. Weber Professor of Art, Wake Forest UniversityAngela Miller, Professor, Department of Art History and Archaeology, Washington University, Saint LouisPatricia Junker, Ann M. Barwick Curator of American Art, Seattle Art MuseumLauren Lessing, Mirken Director of Academic and Public ProgramsAlan Wallach, Professor Emeritus, Department of Art and Art History, The College of William and MarySally Webster, Professor Emerita, City University of New YorkResearch Notes “Kicked About”: Native Culture at Thomas Jefferson’s MonticelloKristine K. RonanKristine K. Ronan, Independent Scholar Two of the most prominent Native-made objects in Jefferson’s original hall were a pair of male and female figures that Jefferson had received several years prior to Lewis and Clark’s shipments. Curiously, the figures had disappeared from the historical record with Jefferson’s death in 1826. It came as quite a surprise, then, that during my #pt-cv-view-6f0799d3kr.pt-cv-post-border { margin: 0; border-top-width: 1px; border-left-width: 1px } #pt-cv-view-6f0799d3kr.pt-cv-post-border { margin: 0; border-top-style: solid; border-left-style: solid } #pt-cv-view-6f0799d3kr.pt-cv-post-border { margin: 0; border-top-color: #343434; border-left-color: #343434 } #pt-cv-view-6f0799d3kr.pt-cv-post-border .pt-cv-content-item { border-right-width: 1px; border-bottom-width: 1px; border-right-style: solid; border-bottom-style: solid; border-right-color: #343434; border-bottom-color: #343434; } #pt-cv-view-6f0799d3kr .pt-cv-title a, #pt-cv-view-6f0799d3kr .panel-title { font-weight: 600 !important; } #pt-cv-view-6f0799d3kr .pt-cv-title a:hover, #pt-cv-view-6f0799d3kr .panel-title:hover { color: #b53328 !important; } #pt-cv-view-6f0799d3kr .pt-cv-hover-wrapper::before { background-color: rgba(0,0,0,.3) !important; } #pt-cv-view-6f0799d3kr .pt-cv-content-item:hover .pt-cv-hover-wrapper::before { background-color: rgba(51,51,51,.6) !important; } #pt-cv-view-6f0799d3kr:not(.pt-cv-nohover) .pt-cv-mask * { color: #fff; } #pt-cv-view-6f0799d3kr .pt-cv-carousel-caption { background-color: rgba(51,51,51,.6) !important; } #pt-cv-view-6f0799d3kr .pt-cv-specialp * { color: #fff !important; background-color: #CC3333 !important; } #pt-cv-view-6f0799d3kr .pt-cv-pficon { color: #bbb !important; } #pt-cv-view-6f0799d3kr .add_to_cart_button, #pt-cv-view-6f0799d3kr .add_to_cart_button * { color: #ffffff !important; background-color: #00aeef !important; } #pt-cv-view-6f0799d3kr .woocommerce-onsale { color: #ffffff !important; background-color: #ff5a5f !important; } #pt-cv-view-6f0799d3kr .pt-cv-readmore { color: #ffffff !important; background-color: #2a6ca0 !important; } #pt-cv-view-6f0799d3kr .pt-cv-readmore:hover { color: #ffffff !important; background-color: #000000 !important; } #pt-cv-view-6f0799d3kr + .pt-cv-pagination-wrapper .pt-cv-more , #pt-cv-view-6f0799d3kr + .pt-cv-pagination-wrapper .pagination .active a { color: #ffffff !important; background-color: #00aeef !important; } [id^='pt-cv-filter-bar-6f0799d3kr'] .active.pt-cv-filter-option, [id^='pt-cv-filter-bar-6f0799d3kr'] .active .pt-cv-filter-option, [id^='pt-cv-filter-bar-6f0799d3kr'] .selected.pt-cv-filter-option, [id^='pt-cv-filter-bar-6f0799d3kr'] .dropdown-toggle { color: #fff !important; background-color: #00aeef !important; } [id^='pt-cv-filter-bar-6f0799d3kr'] .pt-cv-filter-title { color: #fff !important; background-color: #00aeef !important; } #pt-cv-gls-6f0799d3kr li a.pt-active { color: #fff !important; background-color: #ff5a5f !important; } #pt-cv-view-6f0799d3kr .pt-cv-gls-header { color: #fff !important; background-color: #00aeef !important; } #pt-cv-view-6f0799d3kr .cvp-responsive-image[style*="background-image"] { width: 150px; height: 150px; } Book ReviewsConsuming Stories: Kara Walker and the Imagining of American Race Enduring Truths: Sojourner’s Shadows and Substance The American School: Artists and Status in the Late Colonial and Early National Era Building the British Atlantic World: Spaces, Places, and Material Culture, 1600–1850 The Early American Daguerreotype: Cross-Currents in Art and Technology #pt-cv-view-4b4916esnz.pt-cv-post-border { margin: 0; border-top-width: 1px; border-left-width: 1px } #pt-cv-view-4b4916esnz.pt-cv-post-border { margin: 0; border-top-style: solid; border-left-style: solid } #pt-cv-view-4b4916esnz.pt-cv-post-border { margin: 0; border-top-color: #343434; border-left-color: #343434 } #pt-cv-view-4b4916esnz.pt-cv-post-border .pt-cv-content-item { border-right-width: 1px; border-bottom-width: 1px; border-right-style: solid; border-bottom-style: solid; border-right-color: #343434; border-bottom-color: #343434; } #pt-cv-view-4b4916esnz .pt-cv-title a, #pt-cv-view-4b4916esnz .panel-title { font-weight: 600 !important; } #pt-cv-view-4b4916esnz .pt-cv-title a:hover, #pt-cv-view-4b4916esnz .panel-title:hover { color: #b53328 !important; } #pt-cv-view-4b4916esnz .pt-cv-hover-wrapper::before { background-color: rgba(0,0,0,.3) !important; } #pt-cv-view-4b4916esnz .pt-cv-content-item:hover .pt-cv-hover-wrapper::before { background-color: rgba(51,51,51,.6) !important; } #pt-cv-view-4b4916esnz:not(.pt-cv-nohover) .pt-cv-mask * { color: #fff; } #pt-cv-view-4b4916esnz .pt-cv-carousel-caption { background-color: rgba(51,51,51,.6) !important; } #pt-cv-view-4b4916esnz .pt-cv-specialp * { color: #fff !important; background-color: #CC3333 !important; } #pt-cv-view-4b4916esnz .pt-cv-pficon { color: #bbb !important; } #pt-cv-view-4b4916esnz .add_to_cart_button, #pt-cv-view-4b4916esnz .add_to_cart_button * { color: #ffffff !important; background-color: #00aeef !important; } #pt-cv-view-4b4916esnz .woocommerce-onsale { color: #ffffff !important; background-color: #ff5a5f !important; } #pt-cv-view-4b4916esnz .pt-cv-readmore { color: #ffffff !important; background-color: #2a6ca0 !important; } #pt-cv-view-4b4916esnz .pt-cv-readmore:hover { color: #ffffff !important; background-color: #000000 !important; } #pt-cv-view-4b4916esnz + .pt-cv-pagination-wrapper .pt-cv-more , #pt-cv-view-4b4916esnz + .pt-cv-pagination-wrapper .pagination .active a { color: #ffffff !important; background-color: #00aeef !important; } [id^='pt-cv-filter-bar-4b4916esnz'] .active.pt-cv-filter-option, [id^='pt-cv-filter-bar-4b4916esnz'] .active .pt-cv-filter-option, [id^='pt-cv-filter-bar-4b4916esnz'] .selected.pt-cv-filter-option, [id^='pt-cv-filter-bar-4b4916esnz'] .dropdown-toggle { color: #fff !important; background-color: #00aeef !important; } [id^='pt-cv-filter-bar-4b4916esnz'] .pt-cv-filter-title { color: #fff !important; background-color: #00aeef !important; } #pt-cv-gls-4b4916esnz li a.pt-active { color: #fff !important; background-color: #ff5a5f !important; } #pt-cv-view-4b4916esnz .pt-cv-gls-header { color: #fff !important; background-color: #00aeef !important; } #pt-cv-view-4b4916esnz .cvp-responsive-image[style*="background-image"] { width: 150px; height: 150px; } Exhibition ReviewsSoul of a Nation: Art in the Age of Black Power The Wall of Respect: Vestiges, Shards and the Legacy of Black Power / Eugene Eda’s Doors for Malcolm X College We Wanted a Revolution: Black Radical Women, 1965–85 Marsden Hartley’s Maine #pt-cv-view-66aa710wr8.pt-cv-post-border { margin: 0; border-top-width: 1px; border-left-width: 1px } #pt-cv-view-66aa710wr8.pt-cv-post-border { margin: 0; border-top-style: solid; border-left-style: solid } #pt-cv-view-66aa710wr8.pt-cv-post-border { margin: 0; border-top-color: #343434; border-left-color: #343434 } #pt-cv-view-66aa710wr8.pt-cv-post-border .pt-cv-content-item { border-right-width: 1px; border-bottom-width: 1px; border-right-style: solid; border-bottom-style: solid; border-right-color: #343434; border-bottom-color: #343434; } #pt-cv-view-66aa710wr8 .pt-cv-title a, #pt-cv-view-66aa710wr8 .panel-title { font-weight: 600 !important; } #pt-cv-view-66aa710wr8 .pt-cv-hover-wrapper::before { background-color: rgba(0,0,0,.3) !important; } #pt-cv-view-66aa710wr8 .pt-cv-content-item:hover .pt-cv-hover-wrapper::before { background-color: rgba(51,51,51,.6) !important; } #pt-cv-view-66aa710wr8:not(.pt-cv-nohover) .pt-cv-mask * { color: #fff; } #pt-cv-view-66aa710wr8 .pt-cv-carousel-caption { background-color: rgba(51,51,51,.6) !important; } #pt-cv-view-66aa710wr8 .pt-cv-specialp * { color: #fff !important; background-color: #CC3333 !important; } #pt-cv-view-66aa710wr8 .pt-cv-pficon { color: #bbb !important; } #pt-cv-view-66aa710wr8 .add_to_cart_button, #pt-cv-view-66aa710wr8 .add_to_cart_button * { color: #ffffff !important; background-color: #00aeef !important; } #pt-cv-view-66aa710wr8 .woocommerce-onsale { color: #ffffff !important; background-color: #ff5a5f !important; } #pt-cv-view-66aa710wr8 .pt-cv-readmore { color: #ffffff !important; background-color: #2a6ca0 !important; } #pt-cv-view-66aa710wr8 .pt-cv-readmore:hover { color: #ffffff !important; background-color: #000000 !important; } #pt-cv-view-66aa710wr8 + .pt-cv-pagination-wrapper .pt-cv-more , #pt-cv-view-66aa710wr8 + .pt-cv-pagination-wrapper .pagination .active a { color: #ffffff !important; background-color: #00aeef !important; } [id^='pt-cv-filter-bar-66aa710wr8'] .active.pt-cv-filter-option, [id^='pt-cv-filter-bar-66aa710wr8'] .active .pt-cv-filter-option, [id^='pt-cv-filter-bar-66aa710wr8'] .selected.pt-cv-filter-option, [id^='pt-cv-filter-bar-66aa710wr8'] .dropdown-toggle { color: #fff !important; background-color: #00aeef !important; } [id^='pt-cv-filter-bar-66aa710wr8'] .pt-cv-filter-title { color: #fff !important; background-color: #00aeef !important; } #pt-cv-gls-66aa710wr8 li a.pt-active { color: #fff !important; background-color: #ff5a5f !important; } #pt-cv-view-66aa710wr8 .pt-cv-gls-header { color: #fff !important; background-color: #00aeef !important; } #pt-cv-view-66aa710wr8 .cvp-responsive-image[style*="background-image"] { width: 150px; height: 150px; } Home | Contact Publishing Services | My Account Privacy | Acceptable Use of IT Resources The copyright of these individual works published by the University of Minnesota Libraries Publishing remains with the original creator or editorial team. For uses beyond those covered by law or the Creative Commons license, permission to reuse should be sought directly from the copyright owner listed in the About pages.
This tag should take the reader to The Gustatory Turn as well as the two essays that are being referenced.
-
-
allred720fa18.commons.gc.cuny.edu allred720fa18.commons.gc.cuny.edu
-
the consequent prolonged beating about, the past sufferings from obstinate calms, and still continued suffering from thirst; in all these points, as well as others, Don Benito’s story had corroborated not only the wailing ejaculations of the indiscriminate multitude, white and black, but likewise–what seemed impossible to be counterfeit–by the very expression and play of every human feature, which Captain Delano saw.
These "obstinate calms" probably refer to the Intertropical Convergence Zone, or ITCZ. Also know as "the doldrums," in this zone around the equator wind currents of the northern and southern hemisphereshttps://en.wikipedia.org/wiki/Doldrums converge. The doldrums are known for both storms and minimal wind. "Colloquially, the "doldrums" are a state of inactivity, mild depression, listlessness, or stagnation" - which also seems to be the prevailing mood of Benito Cereno, as Capt. Delano perceives him. See also: Page note 1, Tag: "doldrums"
-
-
scholarlykitchen.sspnet.org scholarlykitchen.sspnet.org
-
The role of touch in the multi-sensory experience of reading turns out to be as important as we intuit it to be when we hold a volume or turn a page — or better yet, when we mark it up.
I've found that the way I read and my reading retention have changed since I started to regularly use digital annotation. The act of selecting what sentence to highlight, how to tag passages and articles, and what to make public has changed how I feel about reading online. I still prefer paper for pleasure reading, but for news, research, and collaborative reading, digital now works just fine for me.
-
-
editions.lib.umn.edu editions.lib.umn.edu
-
Roberta K. Tarbell
The tags for Tarbell and for Ciregna are blank. The tag for Wingate takes us to her essay on Sculpture and Lived Space.
-
-
editions.lib.umn.edu editions.lib.umn.edu
-
Dianne Harris
I may not be understanding how tags work, but here again, when I click on Dianne Harris's name, it takes me to a blank tag.
-
-
www.scienceintheclassroom.org www.scienceintheclassroom.org
-
We then found the top 2% of predicted nearest neighbors in m-dimensional hash space
For the fly, the data is organized into a higher dimensional space. For LSH, it is organized in a lower dimensional space. But if the algorithms work effectively, the data should still be arranged so that similar features are near one another.
Instead of feature vectors, the algorithms arrange items in hashes or "tags" (just like the fly brain uses a tag to represent an odor, the algorithms use a tag to represent a specific image or word). Finding the hashes that are closest to each other in this new m-dimensional space should reveal the images/words that are most similar to each other (again, if the algorithm works correctly).
These nearby hashes are called "predicted nearest neighbors" because they predict which items in the data set are the most similar.
-
sparse
Thinly populated. Here, it means that each tag consists of only a small percentage of the neurons present in the olfactory circuit. That is, only a small percentage of neurons fire action potentials in response to the odor.
-
The fly olfactory circuit generates a “tag” for each odor, which is a set of neurons that fire when that odor is presented
In 2015, Stevens identified a three-step code that the fly olfactory circuit uses to identify and respond to specific odors.
- Receptor neurons send odor information to specialized structures called glomeruli, which contain projection neurons.
- Projection neurons send the information to Kenyon cells in the mushroom body.
- These Kenyon cells form the odor label, or tag, and then pass the information along to another stage of neurons that then direct the fly's behavior.
-
-
soundstudiesblog.com soundstudiesblog.com
-
I’m sure that after a century of being “the noisiest city on Earth,” folks have gotten creative about it.
Response
-
Moreover, if we accounted for the history of zoning in the neighborhoods that have the most or the least complaints it would add another layer of analysis to the data. Are some of these neighborhoods used as entertainment zones, for example? Is it easier to open up bars there than elsewhere in the city?
Condition of Rebuttal/Evidence, depending on POV
-
Although it may not be possible to gather who the 311 callers are, including factors such as race and class may lead to very different noise maps. For example, what would a noise map of Manhattan look like if researchers brought income into the equation?
Condition of Rebuttal
-
This is where the data falls short. Can it be assumed that those who are calling about the noise are mostly people who live in the neighborhood?
Condition of Rebuttal
-
At a glance, loud parties, loud people, and loud car stereos seem to be the major complaints in those areas, according to Sluis’s visualizations
Evidence
-
This is key information because it reminds viewers that this neighborhood is a lot more ethnically diverse than other neighborhoods with a smaller number of complaints. It brings to mind: what role does race play in these complaints, in terms of those who complain and those who are the focus of the complaints?
Condition of Rebuttal/New Claim?
-
The city may be noisy, but “noisy” is relative. Sluis’s map shows some predictably noisy areas for those of us familiar with Manhattan’s soundscape (Union Square, Times Square) but it also draws attention to other areas not as predictable in the mainstream imagination (East Harlem South, Hamilton Heights).
Condition of Rebuttal
-
what stands out is that the major circles of noise complaints are also places where there are different racial and ethnic groups mingling (for example, Times Square) or places that are populated by mostly minorities (Hamilton Heights). Whereas Sluis flattens out the noise complaints, demographic stats point to the racial/ethnic contours of each neighborhood.
Evidence
-
Drawn from 2010 census data, the CUNY map clearly delineates neighborhoods and color-codes the groups in each neighborhood per block: blue for whites, green for Latino, orange for black, purple for Asian, and grey for “Other.” Although the Center for Urban Research, CUNY Graduate Center’s maps cannot be superimposed on Sluis’s maps, they help give a general idea as to where neighborhoods are located in addition to racial demographics.
Evidence
-
We must remember that annoyance oftentimes stems not just from physical reactions to noise but rather one’s perceptions about noise
Condition of Rebuttal
-
40, 412 complaints, to be exact
Evidence
-
but neither takes into account the fact that some of the areas with a higher concentration of noise complaints are not just densely populated but densely populated with racial and ethnic minorities
Backing or Qualifier?
-
New York City isn’t the only loud city out there
Qualifier
-
Although New York City isn’t the only loud city out there, there are many reasons it’s called “The City That Never Sleeps”—and sound has a lot to do with it, depending on which neighborhood you call home.
Claim
-
-
www.nxp.com www.nxp.com
-
Grammar [OK] Trademarks [OK] Components [OK] Helper Classes [OK] Analytics [OK] 404s [OK] Code Updates I [OK]
-
-
maildesigner-gangway.s3.amazonaws.com maildesigner-gangway.s3.amazonaws.com
-
jave ist endlich da! Und Mail Designer 365 ist natürlich seit dem ersten Tag voll kompatibel zum neuen Betriebssystem.Mit neuen Features, die perfekt auf macOS Mojave abgestimmt sind, gestaltest du jetzt noch effektivere Newsletter, die dein
Bisschen lang oder?
-
-
-
Share this
Related articles ? Add "coltrane" tag
-
-
www.npr.org www.npr.org
-
Hurricane
another test
-
-
en.wikipedia.org en.wikipedia.org
-
MLS constitutes one of the major professional sports leagues of the United States and Canada
test
Tags
Annotators
URL
-
-
wikimediafoundation.org wikimediafoundation.org
-
of Wikibase for historical research early on.
Wikibase for historical documents
-
Rhizome, an arts organization
Wikibase for GLAM
-
-
www.jofreeman.com www.jofreeman.com
-
political subcultures
Daniel Elizar asserted that the American political subcultures are traditionalistic, individualistic, and moralistic. Traditionalists support a government that maintains the status quo, individualists see government as a method to further their personal causes, and moralists believe government exists to further the greather good. Source: https://theamericanpartnership.com/tag/elazars-political-culture/
In this context we see that women in the 19th century split to a moralistic subculture.
-
-
ieeexplore.ieee.org ieeexplore.ieee.org
-
Memes were provided a categorical tag based on visual content. This tag provided a textual representation of the image even if the image had no embedded textual phrases
Holland's tags~
Tags
Annotators
URL
-
-
github.com github.com
-
-
tools.ietf.org tools.ietf.org
-
-
eskript.ethz.ch eskript.ethz.ch
-
Querschnitt
eine Querschnittsstudie ist zB eine Befragung oder ein Experiment das an einem Tag stattfindet.
-
-
claremontdh.net claremontdh.net
-
test page note
Tags
Annotators
URL
-
-
www.powazek.com www.powazek.com
-
Except that the aggregate selfish behavior of millions of people tagging billions of photos means that the public tag pages make entertaining surfing for everyone.
Reading this reminds me of some of Brad Enslen and Kicks Condor's conversations about discovery on the net.
How can one leverage selfish behaviour to the benefit of all?
Tags
Annotators
URL
-
- Sep 2018
-
www.thequint.com www.thequint.com
-
Import duty on air conditioners, refrigerators and washing machines under 10-kilogram capacity has been doubled to 20 percent each from 10 percent earlier. The basic customs duty on radial tyres is now 15 percent compared with 10 percent earlier,
dch hgchgcvh hkhk
-
-
www.deseretnews.com www.deseretnews.com
-
In all, Cassini collected more than 453,000 images and traveled 4.9 billion miles. It was an international endeavor, with 27 nations taking part. The final price tag was $3.9 billion.
The amount of data we have from Cassini is crazy to think about. Quite a few nations were involved in Her mission, and the price tag is relatively low in terms of exploration craft in the past and present.
-
-
www.adamhyde.net www.adamhyde.net
-
preparing them for the idea of designing a new system that is native to the web
native to the web
-
-
www.makeuseof.com www.makeuseof.com
-
Facebook does not allow third-party apps to display your newsfeed. This applies to Hootsuite. For this reason, you’ll always have to use Facebook natively. The same pretty much goes for Instagram.
Facebook does not allow third-party apps to display your newsfeed. This applies to Hootsuite. For this reason, you’ll always have to use Facebook natively. The same pretty much goes for Instagram.
Tags
Annotators
URL
-
-
www.chromium.org www.chromium.org
-
Cross-Origin Read Blocking (CORB) is a new web platform security feature that helps mitigate the threat of side-channel attacks (including Spectre). It is designed to prevent the browser from delivering certain cross-origin network responses to a web page, when they might contain sensitive information and are not needed for existing web features. For example, it will block a cross-origin text/html response requested from a <script> or <img> tag, replacing it with an empty response instead. This is an important part of the protections included with Site Isolation.
-
-
courses.cs.vt.edu courses.cs.vt.edu
-
static void f(void) {
defines local symbol f. local to file. without static, g is strong. 3rd line declares but doesnt defifne. right way to do things in c : 1. when you write func implemn/defn, you have 2 choices, you want func glbal enuf. if not global, local then declare fucn declare and declare it as static.
- funcs should be static in filewhenever possible.
you can get away without using header files but you should not do that. every func declaration should be included in header file for a global. implicit func declar. if global func, pople sized, it should have declration in header file but trouble is that lang doesnt require it. cpp requries it therefore its not an extension of c but a diff language. make fucnkign header files. if header files, how does compiler look at functions calls. it looks for dunc declares. you cant overload func names, there is one or none. paramenter list in defn and declare. checks #para and types are compatible. what if compiler doesnt find declaration for func, it makes one up. and assumes return type int always. jeez. cimpiler leaves note for linker, relocation tag, this has to be mapped toa call. that can break down at link time if implicit declareation that compiler made up doesnt match the linker's?. never ignore implicit func declaration warning. PAY ATTENTION TO THESE. main is entry point. lol recursive main?! system calls main. have main call main.
-
-
www.publiconsulting.com www.publiconsulting.com
-
famosísima
Ejemplo de anotación: recomiendo visitar esta página web https://disfrutamiruta.com/tag/smorfia-napolitana/
-
-
www.scienceintheclassroom.org www.scienceintheclassroom.org
-
we used 20k random projections for the fly to equate the number of mathematical operations used by the fly and LSH
As stated earlier in the article, the authors could only fairly compare the LSH and fly algorithms if each used the same number of mathematical operations.
They determined that if they used 20k random projections in the fly algorithm (where k is the length of the output tag, or hash) then the total number of operations for the fly and LSH algorithms would be equal.
For more detail, see the second paragraph under "Materials and Methods" in the Supplementary Materials document.
-
for image search, the tag of an elephant image will be more similar to the tag of another elephant image than to the tag of a skyscraper image.
Common Core State Standards English Language Arts-Literacy, RST 11-12.6: Students should be able to explain why the authors provided this example in the paper, specifically addressing how it adds to the reader's understanding of the research.
-
The tag for an odor is computed by a three-step procedure
AP Science Practices, Practice 1: The student can use representations and models to communicate scientific phenomena and solve scientific problems.
Looking at the model in Figure 1A, students should be able to provide a verbal explanation of what the diagram is showing and what each shape and symbol represents.
https://apcentral.collegeboard.org/courses/resources/science-practices
-
sparsifying the tag using WTA resulted in better performance than using random tag selection
The authors looked at how the LSH algorithm performed when using two different methods to create the tag:
- The tag is created from a random selection of Kenyon cells
- The tag is created from the Kenyon cells with the highest firing rates (this is the "winner takes all" or WTA approach)
The result was that the LSH performed better with the WTA approach. Note that the authors measured performance using the mean average precision (see Fig. 2B)
-
1. C. F. Stevens, Proc. Natl. Acad. Sci. U.S.A. 112, 9460–9465 (2015).
Stevens outlines the three-layer architecture that makes up the fly's olfactory circuit.
He also presents the idea of a unique odor label, or "tag" that is comprised of a small set of neurons and helps the fly identify distinct odors.
-
-
134.76.18.16:8084 134.76.18.16:8084
-
First Testtext to pdf embedded via object tag.
-
-
w3c.github.io w3c.github.io
-
The toc nav element
This makes it sound like there is an HTML element with a tag name of
<toc nav>
rather than<nav epub:type="toc">
(which seems to be what's intended).The
landmarks
example farther down is clearer--though the wording there of "the landmark nav element" is equally confusing.There remains only a
nav
element, but of varying types.
-
- Aug 2018
-
www.ed.gov www.ed.gov
-
Today, college remains the greatest driver of socioeconomic mobility in America, but if we don't do more to keep it within reach for middle-class families and those striving to get into the middle class, it could have the opposite effect—serving as a barrier, instead of as a ticket to the American Dream.
The American dream has a price tag to rich for all citizens and ergo represents inequality amongst Americans
-
-
www.scienceintheclassroom.org www.scienceintheclassroom.org
-
This tag is critical for learning behavioral responses to different odors
Owald and Waddell discovered that the fly olfactory circuit is able to recall previously-learned odors through the help of specialized dopamine neurons. After a fly smells an odor, these dopamine neurons trigger changes in parts of the olfactory circuit that cause the specific neurons associated with the odor (aka the "tag") to fire.
Reactivating the tag causes the fly to remember the odor, as well as the values/meanings/context associated with it. The fly can then exhibit the appropriate behavior based on its prior learning (e.g. avoidance if the odor is associated with danger or approach if the odor is associated with a reward).
-
-
lms.uconn.edu lms.uconn.edu
-
Hypothes.is lets you tag
How do you tag the lessons ?
-
-
smadzenuskalosana.wordpress.com smadzenuskalosana.wordpress.com
-
tāds kā “grēkāzis” (“ļaunie un maznesaprotošie abortu aizliedzēji”)
Šis cilvēks nesaprot, kā darbojas aktīvisms (un pasaule :D), right? Ak nē, Papardes zieds uzskata, ka aborti nav jāaizliedz un ka abortu aizliegt gribētāji nav jauki cilvēki. Nokrāsojiet mani šokētu! :D
-
neviens valstī par abortu aizliegšanu ar likumu nemaz nerunā kā reālu iespēju
Pag, kurā dienā un konkrētā minūtē valstī bija šis maģiskais brīdis? Zinu! Tas notika tad, kad visas planētas sastājās rindā. :D ("Nerunā" neuztvēru 100% burtiski, sorry.)
Un arī nav mūsu valsts vienīgā un pa visu planētu, kā tajā senajā TV reklāmā. :D Polija, Krievija, konservatīvie politiskie spēki, kas atrodami it visur utt? Mm? Tāda sajūta, ka autors dzīvus cilvēkus sen nav saticis un īsti nesaprot, kā tie uztver pasauli.
-
Tas arī izsaka šo informatīvo materiālu galveno domu un mērķi. Un, ja pēc tā, kāds uzdrošinātos teikt, ka ir par abortu aizliegšanu, viņš izpelnītos pārmetošus skatienus (kā, tu atbalsti tādas šausmas!).
No way! :D Cepums autoram, ka ir spējis pamanīt šo "slepeno" domu - ka nejaukās sekas no abortu aizliegšanas eksperte uzskata par sliktām (kur pilnībā viņai piekrītu) un negrib pieredzēt tādu nejaucību atkārtošanos.
-
Pirmkārt, atlasīti tie eksperti, kas pauž idejai atbalstošu viedokli; svarīgi tas, ka pieredzējuši.
No šit... A ko citu tad Papardes ziedam bija jādara, ņemot vērā šīs organizācijas mērķus? Tajos brīžos, kad tai rodas vēlme apspriest abortus, meklēt nepieredzējušus "ekspertus", kas uzskata, ka aborti ir grēks? :D
-
-
www.digitalethics.org www.digitalethics.org
-
This approach, I believe, works well for digital ethics, where we try to articulate rules that govern how we interact with each other through digital technologies. For example, when social media emerged, there was no fixed rule about when it is appropriate to tag someone in a picture and when it isn’t. So we figured out a netiquette and ethical norms as we were going along, based on experience, existing norms, insights from experts etc. There still might be areas of disagreement, but I would argue that overall we have come to an understanding of what is acceptable and what isn’t on this issue, and these norms are passed on to new users of social media.
-
-
www.spiegel.de www.spiegel.de
-
if (typeof ADI != 'undefined') ADI.writeAdScript('integrationteaser_1'); Der US-Präsident ist auf Twitter schon wieder zum Gegenangriff übergegangen. Über die "Hexenjagd" gegen ihn selbst und seine früheren Vertrauten empörte sich Donald Trump an diesem Mittwoch einmal mehr. Der Tag zuvor hat ihm zugesetzt, der Schuldspruch gegen seinen Ex-Berate
blabla
-
-
github.com github.com
-
There are times when the Hypothes.is browser extension (or the Hypothes.is Via proxy can't "reach" the PDF in a page because it's served in an <iframe> or <embed> tag. This code can be hosted alongside your PDF's to provide the necessary viewer environment and directly embed Hypothes.is, so that it can be used within the <iframe> to annotate the PDF. Simply serve the viewer.html?file= URL's mentioned below via the <iframe src=""> in your CMS, site, or code.
When to use this code
-
-
satsuma.dreamwidth.org satsuma.dreamwidth.org
-
dwmeta, future reference, social media
is there a feature hidden somewhere that lets you see all the posts on dreamwidth that use a particular tag? if so, i haven't found it, which definitely makes content discovery difficult
-
blogs can be subscribed to through RSS, which will help make the transition off the site easier
I was referencing dreamwidth's syndication feature, which allows you to add anything with an RSS or Atom feed to your reading page. This turned out not to really work - reblogs mean that 95 percent of tumblrs are just way too high volume to work, though certain techniques can mitigate this (a feed for a specific tag on a tumblr blog can be uncovered by adding /rss to the end of the tag URL though automatic feed discovery redirects back to the home feed for some reason)
-
-
developers.google.com developers.google.com
-
Split the code into routes and pages
Instead of having a single large bundle file for your whole website, you can have multiple bundles for each page. This improves the load time of your website as you can tag bundle files to the various webpage of your site instead of one initial big download of script file.
-
-
developers.google.com developers.google.com
-
providing a fallback to other browsers
For non module supporting browsers we can add another script tag with the nomodule attribute
-
mjs
modules have .mjs extension Not really important We can use .js as well The type attribute in our script tag is enough RECOMMENDED : We should use .mjs extension because during development it makes it easier to diffrentiate
-
Browsers that understand type="module" ignore scripts with a nomodule attribute.
Only the latest browsers are module-supporting. For these browsers you can use a script tag with a type attribute set to module.
-
-
jats.nlm.nih.gov jats.nlm.nih.gov
-
such as DOIs, which might be assigned by, for example, “crossref” or “figshare”
I have to say publicly that this sentence makes absolutely no sense as crossref and figshare are not comparable assigning authorities. CrossRef is a registration agency of the International DOI Foundation; FigShare is not. Based upon the example given, the assigning-authority for a DOI would only ever be the set of agencies that assign DOIs. FigShare is not one of those agencies. See it is not on the list: https://www.doi.org/registration_agencies.html
-
-
www.scienceintheclassroom.org www.scienceintheclassroom.org
-
open reading frames (ORFs)
A stretch of DNA sequence that has the ability to be translated into protein (exons only). An ORF usually begins with a start codon (ATG) and ends with a stop codon (TAA, TAG or TGA).
-
-
-
Yet, under the circumstances, David and his men were not condemned for eating them
Männer mussten rituell rein sein, um das reine Brot zu essen (daher die Frage nach sexuellen Beziehungen => rituell unrein für 1 Tag (3. Mose 15:16))
-
- Jul 2018
-
speakingjs.com speakingjs.com
-
This chapter is about “Basic JavaScript,”
The highlighted annotations with the airbnb tag were made to illustrate where Basic Javascript differs from the Airbnb Javascript Style Guide and typescript tag for differences from Typescript Deep Dive TIPs.
Tags
Annotators
URL
-
-
www.nytimes.com www.nytimes.com
-
“I let him know we can’t have this,” Mr. Trump said in an interview with “CBS Evening News.” “We’re not going to have it, and that’s the way it’s going to be.”
asdasd
-
-
astroterf.wordpress.com astroterf.wordpress.com
-
If we are now pretending that gay men can and should be induced or somehow ‘educated’ to pursue sexual relationships with people who have vaginas, how is that different from the appalling conversion therapy that used to be forced upon them? If we are now pretending that lesbians can and should be induced or somehow ‘educated’ to pursue sexual relationships with people who have a penis, how is that different from the ‘corrective rape’ forced upon them? It isn’t. Pretending that lesbians and gay men can ‘choose’ to have partners of the opposite sex is coercive heterosexuality and it’s regressive, reactionary nonsense.
-
-
www.kickscondor.com www.kickscondor.com
-
Likes, upvotes, replies, friending. What if it’s all just linking? In fact, what if linking is actually more meaningful!
This is sort of the fun, I think, in maintaining things like listen and read posts on my site. While they're a useful archive for me, in some part I hope they might speed some discovery for folks who find them or search them by category/tag as well.
I could post somewhere, "Hey I listen to this podcast," or retweet a headline, but invariably in the morass of content out there, there isn't actually an indication that I invested my finite amount of time actually listening to or reading that thing. Perhaps I was just doing some social signaling to make myself seem more interesting or worldly? To me this is a lot of the value of these types of posts.
-
-
localhost:8000 localhost:8000
-
In conceptual terms, the new LINSIGHT method is closely related to our previous fitCons method
- annotation test 1;
- annotation 2;
Tags
Annotators
URL
-
-
www.postgresql.org www.postgresql.org
-
A document is the unit of searching in a full text search system; for example, a magazine article or email message.
Test.
-
-
course-computational-literary-analysis.netlify.com course-computational-literary-analysis.netlify.com
-
She says what I have done so far isn’t in the least what I was wanted to do. I am asked to tell the story of the Diamond and, instead of that, I have been telling the story of my own self
Because the narrative jumps around, it would be interesting to map out each event chronologically and to tag it as to how it relates to the moonstone. Perhaps some kind of network / chronology?
-
-
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
-
On 2017 Jun 14, Youhe Gao commented:
I found two "overexpression"s in the paper. "Although the extent of bait overexpression is difficult to judge and varies across IP's, previous experimentation has shown that over-expression has little effect on identification of true interacting partners (Sowa et al., 2009)" "VAPBWT overexpression strongly increased the association of EGFP-LSG1 and OSBP with the ER (Figure 7E,G)" Personally, I am not sure if those are enough. In a system, increasing [A] or [B] will lead to more [AB]. As we know more about protein interaction now, this kind of systematic false positive should not be ignored any more. In cells, overexpression with tag may even change the location of the protein. That is why I think the next generation of massive protein interaction studies should start from in vivo crosslinking. I do not want to overemphasize the problem. Most of the protein interactions identified are probably true in cells. The amount of work done is very impressive and respected. I hope users who is using a particular interaction data as the only clue for their future experiment design, maybe they should start with an in vivo crosslinking as a conformation of that interaction. It may make them more confident to proceed.
This comment, imported by Hypothesis from PubMed Commons, is licensed under CC BY.
-
-
europepmc.org europepmc.org
-
On 2017 Jan 22, Eric Fauman commented:
I know nothing about cow genetics, but I have done some work on the genetics of metabolites in humans, so I was interested to see how the authors derived biological insights from this genetic study. In particular, I was intrigued by the suggestion in the abstract that they found evidence that genes involved in the synthesis of “milk components” are important for lactation persistence.
Unfortunately, the more I studied the paper the more problems I found that call this claim into question.
First off, the Q-Q plot is currently unavailable, but the text mentions there’s only a “slight deviation in the upper right tail”, which could mean there are no true significant signals.
To account for multiple testing, the authors decided to use a genome-wide association p-value cutoff of 0.95/44100 = 2.15e-5 instead of a more defensible 0.05/44100 = 1.1e-6.
Since their initial p-value cutoff yielded a relatively small number of significant SNPs, the authors used a much more lenient p-value cutoff of 5e-4 which presumably is well within the linear portion of the Q-Q plot.
The biggest problem with the enrichment analysis, however, is that they’ve neglected to account for genes drawn from a common locus. Often, paralogs of similar function are proximal in the genome. But typically we assume that a single SNP is affecting the function of only a single gene at a locus. So, for example, a SNP near the APOA4/APOA1/APOC3/APOA5 locus can tag all 4 genes, but it’s unfair to consider that 4 independent indications that “phospholipid efflux”, “reverse cholesterol transport”, “triglyceride homeostasis” and other pathways are “enriched” in this GWAS.
This issue, of overcounting pathways due to gene duplication, affects all their top findings, presumably rendering them non-significant. Besides lipid pathways, this issue also pertains to the “lactation” GO term, which was selected based on the genes GC, HK2, CSN2 and CSN3. GC, CSN2 and CSN3 are all co-located on Chromosome 6.
A perplexing claim in the paper is for the enrichment of the term “lipid metabolic process” (GO:0006629). According to the Ensembl Biomart, 912 Bos taurus genes fall into this category, or about 4% of the bovine protein coding genes (24616 according to Ensembl). So out of their set of 536 genes (flanking SNPs with P < 5e-4) we’d expect about 20 “lipid metabolic process” genes. And yet, this paper reports only 7. This might be significant, but for depletion, not enrichment.
Sample size is of course a huge issue in GWAS. While 3,800 cows is a large number, it appears this trait may require a substantially larger number of animals before it can yield biologically meaningful results.
This comment, imported by Hypothesis from PubMed Commons, is licensed under CC BY.
-
-
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
-
On 2016 Sep 16, Hilda Bastian commented:
There are many important issues raised in this paper on which I strongly agree with John Ioannidis. There is a lot of research waste in meta-analyses and systematic reviews, and a flood of very low quality, and he points out the contributing factors clearly. However, there are some issues to be aware of in considering the analyses in this paper on the growth of these papers, and their growth in comparison with randomized and other clinical trials.
Although the author refers to PubMed's "tag" for systematic reviews, there is no tagging process for systematic reviews, as there is for meta-analyses and trials. Although "systematic review" is available as a choice under "article types", that option is a filtered search using Clinical Queries (PubMed Help), not a tagging of publication type. Comparing filtered results to tagged results is not comparing like with like in 2 critical ways.
Firstly, the proportion of non-systematic reviews in the filter is far higher than the proportion of non-meta-analyses and non-trials in the tagged results. And secondly, full tagging of publication types for MEDLINE/PubMed takes considerable time. When considering a recent year, the gulf between filtered and tagged results widens. For example, as of December 2015 when Ioannidis' searches were done, the tag identified 9,135 meta-analyses. Today (15 September 2016), the same search identifies 11,263. For the type randomized controlled trial, the number tagged increased from 23,133 in December to 29,118 today.
In the absence of tagging for systematic reviews, the more appropriate comparisons are using filters for both systematic reviews and trials as the base for trends, especially for a year as recent as 2014. Using the Clinical Queries filter for both systematic reviews and therapy trials (broad), for example, shows 34,126 for systematic reviews and 250,195 trials. Page and colleagues estimate there were perhaps 8,000 actual systematic reviews according to a fairly stringent definition (Page MJ, 2016) and the Centre for Reviews and Dissemination added just short of 9,000 systematic reviews to its database in 2014 (PubMed Health). So far, the Cochrane Collaboration has around 38,000 trials in its trials register for 2014 (searching on the word trial in CENTRAL externally).
The number of systematic reviews/meta-analyses has increased greatly, but not as dramatically as this paper's comparisons suggest, and the data do not tend to support the conclusion in the abstract here that "Currently, probably more systematic reviews of trials than new randomized trials are published annually".
Ioannidis suggests some bases for some reasonable duplication of systematic reviews - these are descriptive studies, with many subjective choices along the way. However, there is another critical reason that is not raised: the need for updates. This can be by the same group publishing a new version of a systematic review or by others. In areas with substantial questions and considerable ongoing research, multiple reviews are needed.
I strongly agree with the concerns raised about conflicted systematic reviews. In addition to the issues of manufacturer conflicts, it is important not to underestimate the extent of other kinds of bias (see for example my comment here). Realistically, though, conflicted reviews will continue, building in a need for additional reviewers to tackle the same ground.
Systematic reviews have found important homes in clinical practice guidelines, health technology assessment, and reimbursement decision-making for both public and private health insurance. But underuse of high quality systematic reviews remains a more significant problem than is addressed here. Even when a systematic review does not identify a strong basis in favor of one option or another, that can still be valuable for decision making - especially in the face of conflicted claims of superiority (and wishful thinking). However, systematic reviews are still not being used enough - especially in shaping subsequent research (see for example Habre C, 2014).
I agree with Ioannidis that collaborations working prospectively to keep a body of evidence up-to-date is an important direction to go - and it is encouraging that the living cumulative network meta-analysis has arrived (Créquit P, 2016). That direction was also highlighted in Page and Moher's accompanying editorial (Page MJ, 2016). However, I'm not so sure how much of a solution this is going to be. The experience of the Cochrane Collaboration suggests this is even harder than it seems. And consider how excited people were back in 1995 at the groundbreaking publication of the protocol for prospective, collaborative meta-analysis of statin trials (Anonymous, 1995) - and the continuing controversy that swirls, tornado-like, around it today (Godlee, 2016).
We need higher standards, and skills in critiquing the claims of systematic reviews and meta-analyses need to spread. Meta-analysis factories are a serious problem. But I still think the most critical issues we face are making systematic reviews quicker and more efficient to do, and to use good ones more effectively and thoroughly than we do now (Chalmers I, 2009, Tsafnat G, 2014).
Disclosure: I work on projects related to systematic reviews at the NCBI (National Center for Biotechnology Information, U.S. National Library of Medicine), including some aspects that relate to the inclusion of systematic reviews in PubMed. I co-authored a paper related to issues raised here several years ago (Bastian H, 2010), and was one of the founding members of the Cochrane Collaboration.
This comment, imported by Hypothesis from PubMed Commons, is licensed under CC BY.
-
-
europepmc.org europepmc.org
-
On 2016 Jun 02, Michael Tatham commented:
Is SUMO5 a pseudogene?
There are known to be many SUMO pseudogenes in humans (http://www.ncbi.nlm.nih.gov/pubmed/12383504). A fair position when confronted with a claim that a new SUMO paralog has been discovered is to assume it is a non-expressed pseudogene until otherwise convincing evidence is provided. This paper lacks one piece of critical evidence supporting the idea that SUMO5 really exists as a protein, and that is the presence of endogenous protein.
When BLAST searched, the nucleotide sequence of SUMO5 (originally termed SUMO13 according to the authors’ GenBank entry: FJ042790.1), returns a top hit of “Homo sapiens SUMO1 pseudogene 1 (SUMO1P1), non-coding RNA Sequence ID: ref|NR_002189.3|”. The only difference is a single nucleotide T23 (in SUMO13/SUMO5), which is C in SUMO1P1. This may be a primer synthesis error or a DNA sequencing error.
To put beyond reasonable doubt that SUMO5 is not a pseudogene at least two pieces of new experimental evidence showing SUMO5 is expressed in cells is required. I can think of three good ways to do this:
(1) Mass-spectrometric evidence of a peptide unique to SUMO5.
(2) Cross-reaction of a SUMO5-specific antibody with an endogenous protein.
(3) Editing of the genome to insert an epitope tag into the endogenous SUMO5 gene, with the intention of detecting the protein using an antibody specific to the tag.
All three of these pieces of evidence will be strengthened by parallel studies comparing cells with and without SUMO5-specific knock-down.
RTPCR experiments intending to detect mRNA are particularly uninformative given that DNA contamination often leads to false-positives. This is especially true for SUMO5 given the fact the gene is intronless, a notable characteristic of pseudogenes.
This comment, imported by Hypothesis from PubMed Commons, is licensed under CC BY.
-
-
europepmc.org europepmc.org
-
On 2016 Jul 27, Duke RNA Biology Journal Club commented:
This is a summary of a journal club discussion:
This is one of four articles using similar imaging techniques to study translation in living cells published at the same time. These publications add to the growing number of techniques used to image translation such as mature fluorescent proteins Yu J, 2006, TRICK Halstead JM, 2015, and RNA-binding protein/mRNA co-fluorescence Wu B, 2015. The technique presented in this article is similar to the last except that it uses Suntag to image the nascent chain and PP7 aptamers on the mRNA. The colocalization of the two represents active translation in polysomes.
The technique is novel because co-localization is detected as the protein is translated. This brings fluorescent V4-peptide antibodies into concentrated foci at a single point, and can thus be used to follow multiple rounds of translation. Because of this, only detection of the translated protein is needed and indeed, past the first figure, the mRNA fluorescence is not shown. Fast changes in translation can be detected as shown using the ATF4 ORF construct translational response to stress shown in Figure 4 with the possibility of extending the time of tracking to hours by anchoring the mRNA Yan X, 2016 or using fast 3D imaging techniques. One unusual observation the authors made was the vast heterogeneity of transcript translation within a single cell; at any given time only a subset of the transcripts undergo translation and translation rates may vary depending on as yet unknown factors. A related observation is the diffusion of polysomes within the cell: polysomes translating cytosolic transcripts have slower diffusion rates in the perinuclear region of the cell compared to the cytoplasm. This could be due to the restrictive architecture of a membranous area but the exact mechanism remains unknown. A second surprising observation indicates mRNAs that have begun translation and are associated with polysomes can be transported in dendrites, contrary to earlier reports Besse F, 2008. However, the authors cannot detect if translation is temporarily stalled during transport.
While this technique makes substantial findings in the area of single transcript translation behavior, there are limitations. All in all, these images are dots that respond to translation inhibitors, meaning the resolution is not good enough to detect codon resolution and should be coupled with other techniques to verify observations and determine their mechanism. Additionally, since detection of the nascent chain wouldn’t be detected until the majority of the V4 peptides were translated, initiation would be overlooked; however, TRICK is an existing technique for studying the first round of translation.Our main criticism with this technique is the extensive construct engineering that must be performed which raises concerns over disturbing the mRNA and protein functions from both the PP7 aptamers, the Suntag peptides and an ornithine decarboxylase tag to facilitate rapid degradation of the protein. These engineering steps add over 2 kb to the original gene. Additionally, an antibody against the Suntag and a fluorescent PP7 coat protein must be expressed in the cytosol. While the constructs studied did not cause harm to the cell, each construct of interest must be tested individually. Along this line, while there is the possibility to multiplex by changing the aptamer loop or peptide-antibody combination, it would be difficult to multiplex above two individual transcripts. Thus large-scale studies involving individual translation dynamics of mRNA subsets would remain time consuming and technically challenging.
A quick comparison with the three other papers show agreements among all of them Iwasaki S, 2016 however, there is a great opportunity to learn by reading the papers to compare experimental approaches of three groups. We look forward to see what novel findings this technique uncovers as it becomes adopted in different laboratories.
This comment, imported by Hypothesis from PubMed Commons, is licensed under CC BY.
-
-
europepmc.org europepmc.org
-
On 2016 Jun 21, Evelina Tutucci commented:
We have also recently discussed Nelles et al. Nelles DA, 2016. Since we are interested in developing new techniques for studying gene expression and mRNA localization at the single molecule level, a potential tag-less system to detect mRNAs in fixed and live cells would be a further advance. As pointed out by the Duke RNA Biology journal club we think that Nelles et al. represents an attempt to apply the Cas9 System to detect endogenous mRNA molecules. Unfortunately, no evidence is presented to demonstrate that this system is ready to be used to study gene expression at the single molecule level, as the MS2-MCP system allows. The RNA letter by Garcia and Parker Garcia JF, 2015 showed that in S. cerevisiae the binding of the MS2 coat protein to the MS2-loops diminished tagged mRNA degradation by the cytoplasmic exonuclease Xrn1. However, these observations were not extended to higher eukaryotes. Previous work from our lab described the generation of the beta-actin-MS2 mouse, whereby all the endogenous beta-actin mRNAs were tagged with 24 MS2 loops in the 3’UTR (Lionnet T, 2011, Park HY, 2014). This mouse is viable and no phenotypic defects are observed. In addition, control experiments were performed to show that the co-expression of the MS2 coat protein in the beta-actin-MS2 mouse allowed correct mRNA degradation and expression (Supplementary figure 1b, Lionnet T. et al 2011). Furthermore, multi-color FISH (Supplementary figure 6, Lionnet T. et al 2011) showed substantial co-localization between the ORF FISH probes and MS2 FISH probes, demonstrating the validity of this model. We think that the observations by Garcia and Parker are restricted to yeast because of the short half-life of their mRNAs, wherein the degradation of the MS2 becomes rate-limiting. Based on our extensive use of the MS2-MCP system, we think that higher eukaryotes may have more time to degrade the high affinity complexes formed between MS2-MCP, providing validation for this system to study multiple aspects of gene expression. In conclusion, we think that the MS2-MCP system remains to date the best method to follow mRNAs at the single molecule level in living cells. For the use of the MS2-MCP system in S. cerevisiae we have taken the necessary steps to improve it for the study of rapidly degrading mRNAs and are preparing this work for publication.<br> Evelina Tutucci and Maria Vera, Singerlab
This comment, imported by Hypothesis from PubMed Commons, is licensed under CC BY.
-
-
europepmc.org europepmc.org
-
On 2016 Apr 18, Gwangseong Kim commented:
In two recent articles [1, 2] two techniques for removing or inactivating blood borne pathogens were introduced. The initial experiments were performed in vitro under simplified conditions. First, the primary achievement of the PDT work deserves clarification [1]. PDT is a powerful therapeutic modality, but its clinical application has been hampered by the inability of light to penetrate deep layers of the tissue, which is mainly due to hemoglobins in the blood readily absorbing photons. Utilizing a millimeter- diameter transparent tube for extracorporeal blood circulation allows PDT to function well despite the presence of hemoglobins in blood. Another point that deserves clarification is that the tube capturing device is not a microfluidic device [2]. This technique can be adapted using existing medical tubing without the need for complicated microfluidics and micro-fabrication. The device is a medical tube that has been chemically modified using simple steps to adapt the internal surface for cell capturing. We would like to take this opportunity to respond to concerns brought up in [3]. We start off by addressing concern (1), which speculates about the possibility of overheating during the use of near IR light. Our control data (Fig.3 and Fig.4 of [1]), confirmed that controls illuminated without photosensitizer-antibody conjugates did not undergo cell death, whereas those with photosensitizer-antibody conjugates underwent significant cell death under identical conditions. Thus it is clear from our data that temperature did not affect the outcome. It has been shown that 660 nm irradiation is safe and effective [4-6]. Moving on to concern (2) part (a) that brings up the problem of using the CD-44 antigen as a target. Limitations of antibody specificity are common knowledge and not unique to CD-44, but to all antibodies. To our knowledge, a targeting method that exclusively binds only to cancer cells does not yet exist, making the use of such a compound an unreasonable standard for publication. We used CD-44 antibody to demonstrate feasibility. As targeting methodologies advance and better selectivity to target cells becomes available, this technique will have improved selectivity. Our experiments were designed to avoid non-specific damage to other cells by pre-staining pure cancer cells with the photosensitizer-antibody conjugates and subsequently removing extra free conjugates before spiking into blood (described in detail in [1]). This elimination of the possibility of side effects due to undesired binding to other blood cells and excess free photosensitizer-antibody conjugates precluded the need for a toxicity study, particularly because we were at the proof-of-principle stage. Part (b) of concern (2) suggests that we may have caused non-specific damage to non-cancerous cells by ROS' convection in the blood stream. We believe that this is highly unlikely. One of the authors has been conducting research focusing on ROS and PDT for years, in collaboration with other researchers [7-15]. This research demonstrated that PDT is extremely selective to targeted cells [13]. Part (c) of concern (2) states that we should have used additional cytotoxicity assays, such as Annexin V, TUNEL, and MTT. However, because none of these techniques are cell-type specific, they would be useless for the particular objective they were suggested. Once our line of investigation reaches a more mature stage, we plan to undertake more useful studies, such as applying separate fluorescent tags, or radio labels, in addition to a cell viability assay and analyzing cell death with a cell sorting technology, such as FACS, MACS, density gradient centrifugation, etc. Concern (3) is that the capturing work [2] lacked purity confirmation concerning non-specific capturing of blood cells. Though purity confirmation is critical in diagnostic testing, our work was strictly limited to in vitro conditions, using spiked pure PC-3 cells as a model. To visualize and quantify PC-3 cells in the presence of whole blood, PC-3 cells were pre-labeled using a fluorescence tag (Calcein AM) and the extra free dye was subsequently removed before spiking PC-3 cells into blood. Because only PC-3 cells can have fluorescence in the blood mixture, and because quantification was based on fluorescing cells, false-positive results from other blood cells can be reasonably excluded. Furthermore, if other blood cells were captured but not identified by our detection method our data would then indicate that the simple tube captured cancer cells despite being blocked by other blood cells. If our technique were applied to CTC diagnosis, independent isolation procedures could be used to ensure the purity of captured cells. In contrast, if used for removal or killing, the purity of captured cells would not be as critical, provided that CTCs are effectively removed. If, by chance, capturing is hampered by accumulation of non-specific binding in filtering the entire blood volume, this issue can be addressed with strategies such as scaling up the tube and carefully determining the tube dimensions, flow rate, frequency of tube replacements, etc. Finally, concern (4), points out that the experimental conditions were not translatable to clinical applications. Part (a) regards scaling up the system to show high throughput. The concept of extracorporeal blood processing of the entire blood volume has been used for years in cases such as hemodialysis. We already are working on optimizing the technique for larger blood volume processing. Part (b) of concern (4) discusses the static no-flow condition as being unrealistic. This issue was brought up during the review process, and we provided with our results showing data under constant flow conditions by peristaltic pump (to be published in future publication). The reviewers agreed that the use of a no-flow condition as a conservative approach during a proof-of-concept stage was appropriate. Despite its preliminary nature, we believe that our work communicates novel ideas, an important objective of research and publication. Given the number of research articles dealing with diagnostics and microfluidics, perhaps a further point of confusion came about by thinking of our work in those terms. We want to clarify that diagnostics were not the primary objective in our work. Furthermore, as it becomes evident by this response our experimental design was carefully devised to minimized unnecessary interferences. We hope that this response mitigates any confusion and addresses the concerns raised. The entire response appears in the PLOS1 comment section under response: http://www.plosone.org/article/comments/info:doi/10.1371/journal.pone.0127219. Feel free to contact us for further clarifications.
- Kim G, Gaitas A. PloS One. 2014;10(5):e0127219-e.
- Gaitas A, Kim G. PLoS One. 2015;10(7):e0133194. doi: 0.1371/journal.pone.0133194.
- Marshall JR, King MR. DOI: 101007/s12195-015-0418-3. 2015;First online.
- Ferraresi C, et al. Photonics and Lasers in Medicine. 2012;1(4):267-86.
- Avci P, et al. Seminars in cutaneous medicine and surgery; 2013.
- Jalian HR, Sakamoto FH. Lasers and Light Source Treatment for the Skin. 2014:43.
- Ross B, et al. Biomedical Optics, 2004
- Kim G, et al. Journal of biomedical optics. 2007;12(4):044020--8.
- Kim G, et al Analytical chemistry. 2010;82(6):2165-9.
- Hah HJ, et al. Macromolecular bioscience. 2011;11(1):90-9.
- Qin M, et al. Photochemical & Photobiological Sciences. 2011;10(5):832-41.
- Wang S, et al. et al. Lasers in surgery and medicine. 2011;43(7):686-95.
- Avula UMR, et al.Heart Rhythm. 2012;9(9):1504-9.
- Kim G, et al. R. Oxidative Stress and Nanotechnology, 2013. p. 101-14.
- Lou X, et al. E. Lab on a Chip. 2014;14(5):892-901.
This comment, imported by Hypothesis from PubMed Commons, is licensed under CC BY.
-
-
europepmc.org europepmc.org
-
On 2016 Nov 29, James C Coyne commented:
This study makes some dubious claims that should be subject to independent scrutiny and re- evaluation. It was published in APA journal, which requires sharing of data upon request. However, as I detail and document below, the author responded to a request for just a few variables with an invoice for $450 and a demand that an independent researcher sign a contract not to depart from some arbitrary limits on reanalysis. This sort of behavior threatens routine data sharing. It is deplorable that the American Psychological Association does not support their members to exercise their right to data. See the blog post below for documentation.
This comment, imported by Hypothesis from PubMed Commons, is licensed under CC BY.
-
-
europepmc.org europepmc.org
-
On 2015 Sep 26, Eric Fauman commented:
I applaud the authors for identifying novel genetic associations with metabolites but I disagree with their interpretations and conclusions in several regards.
As tempting as it is to use eQTL data to assign causal genes to SNPs it is frequently seen that SNPs tag expression of unrelated genes as often as they tag the true causal gene for the given trait.
In this study the most obvious example is at rs2066938 where the authors report eQTL associations with 5 egenes (RNF10, MLEC, UNC1198B, CAMKK and COQ5), but not ACADS which is almost certainly the true causal gene, as the authors acknowledge in the text.
At the ARG1 and CRAT loci, other genes have stronger eQTL signals so here too the eQTL data is incomplete.
The ALMS1/NAT8 locus is less clear, but previous authors have assigned this locus to NAT8 given the association with N-acetylornithine and NAT8's presumed acetylation function. The biochemical linkage of N-acetylornithine and arginine in the urea cycle suggests that NAT8 is also the causal gene for this paper. If NAT8 is truly the causal gene, the eQTL data missed it at this locus.
A striking example of the over-reliance on eQTL data in this paper is at the "PPP1R16A" locus which associates with the ratio of aspartic acid to alanine. This SNP is in fact just upstream of GPT which encodes glutamic-pyruvic transaminase, also known as alanine transaminase. GPT is a far more plausible causal gene even though it is not one of the 10 egenes listed for this SNP. Interestingly, there is a coding variant in GPT in reasonable LD with the lead SNP (rs1063739, r2=0.77).
In fact 6 of the loci are linked to coding variants in the most probable causal gene (NAT8, GPT, ACADS, SLC22A16, MCCC1 and CPS1).
Again, it's great to see new SNP-metabolite associations still emerging. However any GWAS interpretation must make use of all biological lines of evidence and not rely only on one or two types of data or analysis.
This comment, imported by Hypothesis from PubMed Commons, is licensed under CC BY.
-
-
europepmc.org europepmc.org
-
On 2015 Sep 23, Angelo Gaitas commented:
The entire response appears in the PLOS1 comment section under response: http://www.plosone.org/article/comments/info:doi/10.1371/journal.pone.0127219
In two recent articles [1, 2] two techniques for removing or inactivating blood borne pathogens were introduced. The initial experiments were performed in vitro under simplified conditions. First, the primary achievement of the PDT work deserves clarification [1]. PDT is a powerful therapeutic modality, but its clinical application has been hampered by the inability of light to penetrate deep layers of the tissue, which is mainly due to hemoglobins in the blood readily absorbing photons. Utilizing a millimeter- diameter transparent tube for extracorporeal blood circulation allows PDT to function well despite the presence of hemoglobins in blood. Another point that deserves clarification is that the tube capturing device is not a microfluidic device [2]. This technique can be adapted using existing medical tubing without the need for complicated microfluidics and micro-fabrication. The device is a medical tube that has been chemically modified using simple steps to adapt the internal surface for cell capturing. We would like to take this opportunity to respond to concerns brought up in [3]. We start off by addressing concern (1), which speculates about the possibility of overheating during the use of near IR light. Our control data (Fig.3 and Fig.4 of [3]), confirmed that controls illuminated without photosensitizer-antibody conjugates did not undergo cell death, whereas those with photosensitizer-antibody conjugates underwent significant cell death under identical conditions. Thus it is clear from our data that temperature did not affect the outcome. It has been shown that 660 nm irradiation is safe and effective [4-6]. Moving on to concern (2) part (a) that brings up the problem of using the CD-44 antigen as a target. Limitations of antibody specificity are common knowledge and not unique to CD-44, but to all antibodies. To our knowledge, a targeting method that exclusively binds only to cancer cells does not yet exist, making the use of such a compound an unreasonable standard for publication. We used CD-44 antibody to demonstrate feasibility. As targeting methodologies advance and better selectivity to target cells becomes available, this technique will have improved selectivity. Our experiments were designed to avoid non-specific damage to other cells by pre-staining pure cancer cells with the photosensitizer-antibody conjugates and subsequently removing extra free conjugates before spiking into blood (described in detail in [1]). This elimination of the possibility of side effects due to undesired binding to other blood cells and excess free photosensitizer-antibody conjugates precluded the need for a toxicity study, particularly because we were at the proof-of-principle stage. Part (b) of concern (2) suggests that we may have caused non-specific damage to non-cancerous cells by ROS' convection in the blood stream. We believe that this is highly unlikely. One of the authors has been conducting research focusing on ROS and PDT for years, in collaboration with other researchers [7-15]. This research demonstrated that PDT is extremely selective to targeted cells [13]. Part (c) of concern (2) states that we should have used additional cytotoxicity assays, such as Annexin V, TUNEL, and MTT. However, because none of these techniques are cell-type specific, they would be useless for the particular objective they were suggested. Once our line of investigation reaches a more mature stage, we plan to undertake more useful studies, such as applying separate fluorescent tags, or radio labels, in addition to a cell viability assay and analyzing cell death with a cell sorting technology, such as FACS, MACS, density gradient centrifugation, etc. Concern (3) is that the capturing work [2] lacked purity confirmation concerning non-specific capturing of blood cells. Though purity confirmation is critical in diagnostic testing, our work was strictly limited to in vitro conditions, using spiked pure PC-3 cells as a model. To visualize and quantify PC-3 cells in the presence of whole blood, PC-3 cells were pre-labeled using a fluorescence tag (Calcein AM) and the extra free dye was subsequently removed before spiking PC-3 cells into blood. Because only PC-3 cells can have fluorescence in the blood mixture, and because quantification was based on fluorescing cells, false-positive results from other blood cells can be reasonably excluded. Furthermore, if other blood cells were captured but not identified by our detection method our data would then indicate that the simple tube captured cancer cells despite being blocked by other blood cells. If our technique were applied to CTC diagnosis, independent isolation procedures could be used to ensure the purity of captured cells. In contrast, if used for therapy, the purity of captured cells would not be as critical, provided that CTCs are effectively removed. If, by chance, capturing is hampered by accumulation of non-specific binding in filtering the entire blood volume, this issue can be addressed with strategies such as scaling up the tube and carefully determining the tube dimensions, flow rate, frequency of tube replacements, etc. Finally, concern (4), points out that the experimental conditions were not translatable to clinical applications. Part (a) regards scaling up the system to show high throughput. The concept of extracorporeal cleansing of the entire blood volume has been used for years in cases such as hemodialysis. We already are working on optimizing the technique for larger blood volume processing. Part (b) of concern (4) discusses the static no-flow condition as being unrealistic. This issue was brought up during the review process, and we provided with our results showing data under constant flow conditions by peristaltic pump (to be published in future publication). The reviewers agreed that the use of a no-flow condition as a conservative approach during a proof-of-concept stage was appropriate. Despite its preliminary nature, we believe that our work communicates novel ideas, an important objective of research and publication. Given the number of research articles dealing with diagnostics and microfluidics, perhaps a further point of confusion came about by thinking of our work in those terms. We want to clarify that diagnostics were not the primary objective in our work. Furthermore, as it becomes evident by this response our experimental design was carefully devised to minimized unnecessary interferences. We hope that this response mitigates any confusion and addresses the concerns raised.
- Kim G, Gaitas A. PloS One. 2014;10(5):e0127219-e.
- Gaitas A, Kim G. PLoS One. 2015;10(7):e0133194. doi: 10.1371/journal.pone.0133194.
- Marshall JR, King MR. DOI: 101007/s12195-015-0418-3. 2015;First online.
- Ferraresi C, et al. Photonics and Lasers in Medicine. 2012;1(4):267-86.
- Avci P, et al. Seminars in cutaneous medicine and surgery; 2013.
- Jalian HR, Sakamoto FH. Lasers and Light Source Treatment for the Skin. 2014:43.
- Ross B, et al. Biomedical Optics, 2004
- Kim G, et al. Journal of biomedical optics. 2007;12(4):044020--8.
- Kim G, et al Analytical chemistry. 2010;82(6):2165-9.
- Hah HJ, et al. Macromolecular bioscience. 2011;11(1):90-9.
- Qin M, et al. Photochemical & Photobiological Sciences. 2011;10(5):832-41.
- Wang S, et al. et al. Lasers in surgery and medicine. 2011;43(7):686-95.
- Avula UMR, et al.Heart Rhythm. 2012;9(9):1504-9.
- Kim G, et al. R. Oxidative Stress and Nanotechnology, 2013. p. 101-14.
- Lou X, et al. E. Lab on a Chip. 2014;14(5):892-901.
- https://www.roswellpark.org/patients/treatment-services/innovative-treatments/photodynamic-therapy.
- Yin H, et al. Artificial organs. 2014;38(6):510-5.
- Yin H, et al. Journal of Photochemistry and Photobiology B: Biology. 2015.
This comment, imported by Hypothesis from PubMed Commons, is licensed under CC BY.
-
-
europepmc.org europepmc.org
-
On 2017 Jul 09, Sunil Verma commented:
Comment on - Evaluation of Bar, Barnase, and Barstar recombinant proteins expressed in genetically engineered Brassica juncea (Indian mustard) for potential risks of food allergy using bioinformatics and literature searches
Sunil Kumar Verma, Principal Scientist CSIR-Centre for Cellular and Molecular Biology, Hyderabad 500 007, India.
In this study, the authors have tested the allergenic potential of the transgene Bar, Barnase, and Barstar expressed in Genetically Modified Indian Mustard for heterosis breeding. To this end, the authors have done the primary amino acid sequence comparisons of these proteins with the primary amino acid sequences of the known allergens listed in Allergenonline.org and NCBI Entrez protein database until January 2015 and 9 March 2015, respectively. Based on these bioinformatics comparisons authors concluded that the Bar, Barnase and Barstar proteins are unlikely to present any significant risk of food allergy to consumers. The authors also recommended not to perform any human serum IgE testing to further evaluate possible binding to the Bar, Barnase or Barstar proteins.
I hereby propose that the above conclusions drawn by the authors in this study are incorrect and require a major revision.
The main criteria used by the authors in these bioinformatics comparisons was the primary amino acid sequence homology searches of the proteins in question with that of the primary amino acid sequences of the potential allergen listed in above databases. All the hits with less than 50% primary amino acid sequence identities for full length proteins and less than 35% identity in the sliding window 80 amino acid segments of each proteins were ignored; the argument was that these matches could not have led to significant structural similarities among the proteins in question, therefore can be ignored.
Several independent studies have shown that in many cases, even though the primary amino acid sequence similarity between two proteins / domains are very less (<20%), but the tertiary structures of the proteins may be highly similar. One classical example of this is high structural similarity between N terminal half of the Krit-B41 domain with that of the RA domain of RalGDS (1RAX:A) with an r.m.s. deviation of 2.9A for 80 aligned positions; despite a very low homology in their primary amino acid sequences (sequence identity =8.7%). [1, S1] It is notable that both RalGDS and Krit-1 interact with Rap1A through the RA and B41 domains, respectively [2, 3], and so the talin [4]. Thus, the high primary amino acid sequence similarity between two proteins may though infer greater chances of structural homology between these proteins; however, low primary amino acid sequence similarity does not necessarily infer that proteins in question will necessarily have higher structural dissimilarities.
Since it is the conformationally determined structure of the proteins/epitopes which finally decide immunogenicity and allergenicity - and not just the primary amino acid sequences; the conclusion drawn in this study based on merely the primary amino acid sequence comparisons are scientifically inappropriate.
Secondly, in real scenario, both the Barnase and Barstar proteins are expressed simultaneously and these two proteins remain in a complex and not as individual proteins in plant [5, 6]. It is not unlikely that structure of a specific protein in complex may be different than that of the structure of the same individual protein in free form. Also, there may be the possibilities of formation/exposure of new epitope(s) surfaces, particularly as we know now that there are several antibodies known that recognize just the native proteins and some may indeed require complex assembly.
Thus, these conformationally determined epitopes that are recognized in the complex but not the free protein of interest may be reveled in differential screening between a protein and a complex form of the same protein. The conformationally determined epitopes could then be compared for structural homology with the epitopes in known allergens to determine the allergenic potential of two proteins in complex; such studies however, were not conducted in this paper; and the fact that Barnase and Barstar remain in complex and not in free form, was completely ignored throughout the study.
Finally, I found that the overall implication of the Allergenonline.org database itself on correctly predicting the allergenic potential of a new antigen was also questionable.<br> To test this, I assumed that 'Ani s 9' (which is a very well known allergen from SXP/RAL-2 protein family) [7] is a new putative allergen and that this group of proteins are not yet listed in the database; and asked whether or not one can predict if 'Ani s 9' is a potential food allergen using the strategy as was used in this study for Barnase, Barstar and Bar transgenic proteins. The full length primary amino acid sequence comparison of 'Ani s 9' (GenBank: ABV55106.1) using default parameter i.e 'E' value cut off = 1 identified 7 hits (excluding the hits with its own sequences) with 'tropomyosin' allergen from various organisms and 'AAEL002761-PC ' allergen from Aedes aegypti, respectively; however, none of the hits was with significant similarity cut off (>50%). Thus, this bioinformatics search criteria wrongly predicted that the 'Ani s 9' is not a potential food allergen. [S2]
The another criteria i.e. greater than 35% identity in the sliding window of 80 amino acid segment also did not produce any hit at all (other than self hits, which were excluded as explained above), indicating that this criteria also failed to identify 'Ani s 9' as potential food allergen. [S3] The third criteria i.e. 8 continuous amino acid segment search also did not identify any hit with any of the allergen in the database.[S4]
Thus, the bioinformatics search as used in this study following any of the criteria defined could not identify 'Ani s 9' as a potential food allergen. This confirms that the criteria used in this study by authors could easily give false negative results.
The only strategy that could have identified 'Ani s 9' as possible food allergen was a '6 continuous amino acid segment search, which could have identified its match with Allergen 'Lol p 5' for the 6-aa segment 'ANAPPA'. [S5]
This criteria however, was not used in current study to predict the allergenic potential of Bar, Barnase and Barstar. If this specific criteria was used, Barnase transgenic protein also could have given a potential hit with Allergen Ber e 2 and Ani s 9 for the 6 continuous amino acid patch LFSTAA, and WVASKG, respectively [S6]; hence, the conclusion of this paper could have been different.
In view of the above, I conclude that the criteria implemented in this study were not sufficient to exclude the possibility of the transgenic protein Bar, Barnase and Barstar being a possible allergen; therefore the conclusion drawn by authors that "the above transgenic proteins are unlikely to present any significant risk of food allergy to consumers" is not beyond a reasonable doubt, and hence need an appropriate correction by the way of erratum.
Further, as discussed above, the Barnase and Barstar proteins are expressed simultaneously in final plant and they remain in a tight complex (i.e. barnase-barstar complex) and not as free form. The current study has not even touched upon the barnase-barstar complex; therefore, until the systematic studies on this complex is conducted and concluded, it is not appropriate to give a 'safe' tag to these transgenic proteins. This is particularly important since the conclusion drawn from this study was one of the major evidence which was used by the Indian regulatory authorities to recently give a safety clearance to the genetically engineered Brassica juncea (Indian Mustard) for commercial cultivation in India. [8, 9]
This comment, imported by Hypothesis from PubMed Commons, is licensed under CC BY.
-
-
europepmc.org europepmc.org
-
On 2015 Sep 09, Bill Cayley commented:
A good example of when less is more in cardiac care - a collection of related examples is at: https://lessismoreebm.wordpress.com/tag/cardiovascular/
This comment, imported by Hypothesis from PubMed Commons, is licensed under CC BY.
-
-
europepmc.org europepmc.org
-
On 2015 Sep 23, Angelo Gaitas commented:
The entire response appears in the PLOS1 comment section under response: http://www.plosone.org/article/comments/info:doi/10.1371/journal.pone.0127219
In two recent articles [1, 2] two techniques for removing or inactivating blood borne pathogens were introduced. The initial experiments were performed in vitro under simplified conditions. First, the primary achievement of the PDT work deserves clarification [1]. PDT is a powerful therapeutic modality, but its clinical application has been hampered by the inability of light to penetrate deep layers of the tissue, which is mainly due to hemoglobins in the blood readily absorbing photons. Utilizing a millimeter- diameter transparent tube for extracorporeal blood circulation allows PDT to function well despite the presence of hemoglobins in blood. Another point that deserves clarification is that the tube capturing device is not a microfluidic device [2]. This technique can be adapted using existing medical tubing without the need for complicated microfluidics and micro-fabrication. The device is a medical tube that has been chemically modified using simple steps to adapt the internal surface for cell capturing. We would like to take this opportunity to respond to concerns brought up in [3]. We start off by addressing concern (1), which speculates about the possibility of overheating during the use of near IR light. Our control data (Fig.3 and Fig.4 of [3]), confirmed that controls illuminated without photosensitizer-antibody conjugates did not undergo cell death, whereas those with photosensitizer-antibody conjugates underwent significant cell death under identical conditions. Thus it is clear from our data that temperature did not affect the outcome. It has been shown that 660 nm irradiation is safe and effective [4-6]. Moving on to concern (2) part (a) that brings up the problem of using the CD-44 antigen as a target. Limitations of antibody specificity are common knowledge and not unique to CD-44, but to all antibodies. To our knowledge, a targeting method that exclusively binds only to cancer cells does not yet exist, making the use of such a compound an unreasonable standard for publication. We used CD-44 antibody to demonstrate feasibility. As targeting methodologies advance and better selectivity to target cells becomes available, this technique will have improved selectivity. Our experiments were designed to avoid non-specific damage to other cells by pre-staining pure cancer cells with the photosensitizer-antibody conjugates and subsequently removing extra free conjugates before spiking into blood (described in detail in [1]). This elimination of the possibility of side effects due to undesired binding to other blood cells and excess free photosensitizer-antibody conjugates precluded the need for a toxicity study, particularly because we were at the proof-of-principle stage. Part (b) of concern (2) suggests that we may have caused non-specific damage to non-cancerous cells by ROS' convection in the blood stream. We believe that this is highly unlikely. One of the authors has been conducting research focusing on ROS and PDT for years, in collaboration with other researchers [7-15]. This research demonstrated that PDT is extremely selective to targeted cells [13]. Part (c) of concern (2) states that we should have used additional cytotoxicity assays, such as Annexin V, TUNEL, and MTT. However, because none of these techniques are cell-type specific, they would be useless for the particular objective they were suggested. Once our line of investigation reaches a more mature stage, we plan to undertake more useful studies, such as applying separate fluorescent tags, or radio labels, in addition to a cell viability assay and analyzing cell death with a cell sorting technology, such as FACS, MACS, density gradient centrifugation, etc. Concern (3) is that the capturing work [2] lacked purity confirmation concerning non-specific capturing of blood cells. Though purity confirmation is critical in diagnostic testing, our work was strictly limited to in vitro conditions, using spiked pure PC-3 cells as a model. To visualize and quantify PC-3 cells in the presence of whole blood, PC-3 cells were pre-labeled using a fluorescence tag (Calcein AM) and the extra free dye was subsequently removed before spiking PC-3 cells into blood. Because only PC-3 cells can have fluorescence in the blood mixture, and because quantification was based on fluorescing cells, false-positive results from other blood cells can be reasonably excluded. Furthermore, if other blood cells were captured but not identified by our detection method our data would then indicate that the simple tube captured cancer cells despite being blocked by other blood cells. If our technique were applied to CTC diagnosis, independent isolation procedures could be used to ensure the purity of captured cells. In contrast, if used for therapy, the purity of captured cells would not be as critical, provided that CTCs are effectively removed. If, by chance, capturing is hampered by accumulation of non-specific binding in filtering the entire blood volume, this issue can be addressed with strategies such as scaling up the tube and carefully determining the tube dimensions, flow rate, frequency of tube replacements, etc. Finally, concern (4), points out that the experimental conditions were not translatable to clinical applications. Part (a) regards scaling up the system to show high throughput. The concept of extracorporeal cleansing of the entire blood volume has been used for years in cases such as hemodialysis. We already are working on optimizing the technique for larger blood volume processing. Part (b) of concern (4) discusses the static no-flow condition as being unrealistic. This issue was brought up during the review process, and we provided with our results showing data under constant flow conditions by peristaltic pump (to be published in future publication). The reviewers agreed that the use of a no-flow condition as a conservative approach during a proof-of-concept stage was appropriate. Despite its preliminary nature, we believe that our work communicates novel ideas, an important objective of research and publication. Given the number of research articles dealing with diagnostics and microfluidics, perhaps a further point of confusion came about by thinking of our work in those terms. We want to clarify that diagnostics were not the primary objective in our work. Furthermore, as it becomes evident by this response our experimental design was carefully devised to minimized unnecessary interferences. We hope that this response mitigates any confusion and addresses the concerns raised.
- Kim G, Gaitas A. PloS One. 2014;10(5):e0127219-e.
- Gaitas A, Kim G. PLoS One. 2015;10(7):e0133194. doi: 10.1371/journal.pone.0133194.
- Marshall JR, King MR. DOI: 101007/s12195-015-0418-3. 2015;First online.
- Ferraresi C, et al. Photonics and Lasers in Medicine. 2012;1(4):267-86.
- Avci P, et al. Seminars in cutaneous medicine and surgery; 2013.
- Jalian HR, Sakamoto FH. Lasers and Light Source Treatment for the Skin. 2014:43.
- Ross B, et al. Biomedical Optics, 2004
- Kim G, et al. Journal of biomedical optics. 2007;12(4):044020--8.
- Kim G, et al Analytical chemistry. 2010;82(6):2165-9.
- Hah HJ, et al. Macromolecular bioscience. 2011;11(1):90-9.
- Qin M, et al. Photochemical & Photobiological Sciences. 2011;10(5):832-41.
- Wang S, et al. et al. Lasers in surgery and medicine. 2011;43(7):686-95.
- Avula UMR, et al.Heart Rhythm. 2012;9(9):1504-9.
- Kim G, et al. R. Oxidative Stress and Nanotechnology, 2013. p. 101-14.
- Lou X, et al. E. Lab on a Chip. 2014;14(5):892-901.
- https://www.roswellpark.org/patients/treatment-services/innovative-treatments/photodynamic-therapy.
- Yin H, et al. Artificial organs. 2014;38(6):510-5.
- Yin H, et al. Journal of Photochemistry and Photobiology B: Biology. 2015.
This comment, imported by Hypothesis from PubMed Commons, is licensed under CC BY.
-
-
europepmc.org europepmc.org
-
On 2017 Jul 09, Jeffrey Ross-Ibarra commented:
In our manuscript exploring the population genetics of local adaptation (Tiffin and Ross-Ibarra 2014) we included a discussion about the potential uses of reduced representation data (e.g. RAD-seq, GBS). To provide a sense of the probability of using reduced representation data to identify targets of selection, we included a figure showing the probability of having a SNP included in a region of the genome in which diversity had been severely reduced due to a recent selective sweep. Unfortunately this figure is not correct; an error in the code inadvertently used centimorgans as morgans, causing the recombination rate to be off by a factor of 100.
To correct this we have generated a new figure (see http://rpubs.com/rossibarra/257207; raw code is available at https://gist.github.com/rossibarra/be44cc3b3796f45840d942ad11c01ba1) that corrects this error and presents a more realistic model. Our previous model assumed SNPs were distributed evenly across the genome and the presence of a single SNP near a sweep was sufficient for detection. Instead, here we explicitly model sequence “tags” coming from RAD-seq or GBS, and incorporate information about the variation in diversity expected among tags in neutral regions of the genome. The figure clearly shows that with dense marker coverage and strong selection, the probability of detecting reductions in diversity due to recent selective sweeps from new beneficial mutations can be relatively high. We emphasize, however, that the purpose of the figure is solely to develop an intuition of the likelihood of detecting a recent selective sweep. The many simplifying assumptions made in generating the figure (no recent demographic change, both sequence tags and recombination occur uniformly along the genome, selection is on a novel beneficial mutation with additive effect that has recently swept to fixation), as well as the specific mutation rates, sample size, sequence length, and recombination rates assumed will all affect the actual probability of a tag being included in a selective sweep. Moreover, this figure does not touch on many other relevant issue such as multiple testing, complex demography, background selection, or other modes of positive selection (e.g. from standing variation, balancing selection, or selection on polygenic traits).
We have submitted a correction to the journal.
We thank Eric Johnson for drawing our attention to the error, and Eric Johnson, Kathleen Lotterhos, and Graham Coop for kindly reviewing previous versions of the code and assumptions we have used in generating this new figure.
This comment, imported by Hypothesis from PubMed Commons, is licensed under CC BY.
-
-
europepmc.org europepmc.org
-
On 2014 Oct 27, David Colquhoun commented:
For all the reasons given by Hilda Bastian (and a few more, like P = 0.04 provides lousy evidence) it astonishes me that this study should have been trumpeted as though it represented a great advance. That's the responsibility of Nature Neuroscience (and, ultimately, of the authors).
I wonder whether what happens is as follows. Authors do big fMRI study. Glamour journal refuses to publish without functional information. Authors tag on a small human study. Paper gets published. Hyped up press releases issued that refer mostly to the add on. Journal and authors are happy. But science is not advanced.
I certainly got this impression in another recent fMRI paper in Science. Brain stimulation was claimed to improve memory (P = 0.043)
I guess these examples are quite encouraging for those who think that expensive glamour journals have had their day. Open access and open comments are the way forward.
This comment, imported by Hypothesis from PubMed Commons, is licensed under CC BY.
-
-
www.sciencedirect.com www.sciencedirect.com
-
On 2014 Oct 21, George McNamara commented:
This is a nice paper. The abstract refers to using 24 epitope tags (24mer), much of the paper uses a 10mer. Just doing GFP is boring. When I came up with the "Tattletales" (TALE-FPn ... I came up with the idea before sgRNA:Cas9 became popular), I immediately realized that multimerizing FP biosensors. The current paper is the same as my what I refer to as "Binary Tattletales", as in: 1. TALE-(linker-epitope tag)n 2. "binder"-(linker-FP)m with Tattletales being T-cells -- TALE FPs/Biosensors. Since I moved to MD Anderson Cancer Center, the first T now refers to "T-cells and Tumor cells". Likewise T-bow refers to rainbow T-cells and Tumor cells for promoter bashing and otherwise multicolor dots labeling cells (rainbow in homage of course to Brainbow mice etc, and especially to real rainbows). For more on Tattletales, Binary Tattletales, and T-Bow, see http://works.bepress.com/gmcnamara/63 http://works.bepress.com/gmcnamara/42
Giving credit where credit is due: The authors really should have cited the first mammalian cell paper localizing a lot of FPs in one spot (they came 'close' with a Gordon 1997 Cell paper on GFP:LacO in E.coli, but the Tanenbaum paper is all mammalian cells): Robinett et al 1996 JCB http://www.ncbi.nlm.nih.gov/pubmed/8991083 http://jcb.rupress.org/content/135/6/1685.long See their figure 4A. Straight, Robinett et al also published a yeast paper in 1996, http://www.ncbi.nlm.nih.gov/pubmed/8994824 and it would have been useful to cite that.
The PDF download at http://works.bepress.com/gmcnamara/63 has a table of 130 FP biosensors (if you are Laconic about ATeam and Fire, too bad) and an extensive reference list with ZF-FP, TALE-FP, Cas9-FP (the latter from the Weissman group), and more (PUF's and PPR's are RNA binding protein families with structural similarities to TALEs). My favorite name -- besides Tattletales and T-Bow, of course -- is "TALE-Lights" from Yuan, Shermoen, O'Farrell 2014, http://www.ncbi.nlm.nih.gov/pubmed/24556431
This comment, imported by Hypothesis from PubMed Commons, is licensed under CC BY.
-
-
europepmc.org europepmc.org
-
On 2014 Oct 06, Leonid Teytelman commented:
Dear Authors,
We have published an analysis in S. cerevisiae, showing expression-dependent artifactual ChIP enrichment at highly expressed loci (Teytelman L, 2013 "Highly expressed loci are vulnerable to misleading ChIP localization of multiple unrelated proteins"). As you know, our finding raises the question of whether HOT regions may also be influenced by the same artifact.
It is great that you have considered our work and have thoughtfully responded to our analysis. Below, I would like to continue this discussion in an effort to better understand the artifact, its causes, and whether it may be contributing to the enrichment at the HOT loci.
1. “we have demonstrated that there is no correlation between our non-specific binding controls (IgG) and our measured transcription factor occupancy;”
Considering our results with no-tag control experiments, an IgG may fail to control for the artifact. It would be great if you could instead perform a GFP ChIP-Seq, similarly to what we have done in yeast.
2. The regions determined in ref. 41 have very low enrichment (twofold or less) of non-specific immunoprecipation in anti-GFP antibody controls over input DNA evaluated using a non-standard sliding-window approach. Importantly, immunoprecipitation/input ratios at this level are typically not considered enriched for binding in modern peak-calling procedures. For example, the median immunoprecipitation/input ratio for our human RNA Pol II experiments is 20-fold, and only 0.033% of human RNA Pol II peaks contain an immunoprecipitation/input ratio ≤ twofold.
The mean is low, but in both anti-GFP experiments, there are loci with 3-5x enrichment (figure 4D). Most importantly, while the anti-GFP enrichment at the hyper-ChIPable loci is low, please note that the level of enrichment is variable from protein to protein (2-5X for Sir proteins, but often >10X for Cse4).
3. Thus, it is essential to note that the term ‘hyper-ChIPable’, coined by ref. 41, is quite misleading, as a correctly performed ChIP experiment will evaluate statistically enriched regions, with higher immunoprecipitation/input ratios. The so-called hyper-ChIPable regions in ref. 41 are not binding regions as determined under ChIP-seq best practices. Hence, when statistical peak-calling was performed in ref. 41 (using the established MACS peak-caller) to evaluate signals only at significantly enriched regions (Supplementary Table 1) only 17 (<7.5%) of the 238 claimed ‘hyper-ChIPable’ regions were called significant by all three Sir proteins. In fact, 68% of their 238 regions do not contain a binding site for any Sir protein as determined by MACS, despite even very liberal settings used (P < 10−5, no fold enrichment cut-off). Thus, the data of ref. 41 contradict its own major claim that all three Sir proteins showed enrichment at the 238 sites.
By reporting the 238 sites with >2fold enrichment of Sir2, Sir3, and Sir4, we are in fact being extra-demanding in terms of the threshold. We are stringently requiring all three proteins to be enriched above a threshold at the locus. So a target with 5x enrichment of Sir2 and 1.8X enrichment of Sir3 would not pass this cutoff. A typical ChIP study will focus on a single factor at a time. Had we done that, we would have many more artifactual targets for each silencing protein, with many at 5x or higher enrichment. Furthermore, the level of the artifactual signal varies from protein to protein or experiment to experiment. For example, the Cse4 signal at highly-expressed loci can give 10x or higher enrichment.
4. Furthermore, as indicated in Supplementary Table 3 of ref. 41, the Sir2, Sir3 and Sir4 ChIP-seq experiments were performed only once each, which raises the question as to whether enrichment of Sir proteins at the 238 sites is reproducible. More rigorously, even for the remaining 17 genomic loci, their status as hyper-ChIPable is questionable as each region would first have to be established as a reproducible binding site in replicate experiments for each individual Sir protein. If you consider that Sir2, Sir3 and Sir4 ChIP-seq constitutes three replicates of Sir proteins, their data show that most of their claimed sites were not reproducibly enriched.
Most of our artifact-cause analysis focuses on genome-wide data, not on the 238 sites. The 238 Sir-enriched euchromatic loci were a launching point for the analysis, but most of the paper looks comprehensively at the link between expression and ChIP levels. Figures 3, 4, and 5 are all on genome-wide correlations between Pol II/III and ChIP.
As for reproducibility, we see the same peaks, with often 10x enrichment, in Ste12, Cse4, two distinct GFP experiments, and each of the three Sir ChIP-Seq datasets. The same exact loci come up in the Sir3 paper from Oliver Rando’s group (Radman-Livaja M, 2011).
5. In addition to the analytical differences outlined above, other potential sources for the marked differences between our data and the Sir-enriched regions of ref. 41 are deviations from a typical ChIP protocol. In particular, ref. 41 employed a significantly longer cross-link time (1 h as opposed to the typical 10–20 min). This might contribute to formation of large non-specific protein–DNA complexes, which can in turn increase non-specific immunoprecipitation.
Though not discussed in the manuscript, we have in fact performed experiments to investigate if the crosslinking concentration contributed to the misleading signal. We performed ChIP with the 1 hour crosslinking at room temperature at the following formaldehyde concentrations: 0.0625%, .125%, .25%, .5% and 1%, but did not find a proportionate decrease in the hyper ChIPpable signal with the decreasing formaldehyde concentrations. Moreover, the presence of hyper-ChIPability in the Snyder datasets (Cse4, Ste12), ours (Sir2, 3, 4, GFP), and Rando (Sir3) make it clear that the problem is not in some unusual protocol steps in our hands.
We also note that we initially performed the Sir ChIP-Seq experiments because of our interest in the Sir protein biology. Because the Sir proteins do not directly interact with the DNA, we used longer crosslinking times. This is not unique to our work.
In summary, much more work is needed to pinpoint the cause of the artifact and to evaluate whether some or all of the signal at highly expressed genes in many other reported ChIP studies could be artifactual. Much more work is necessary to develop the best controls and corrections for the artifact. However, the artifact we report is not minor and is not a consequence of the methodological details of our manuscript.
Also, please note the following papers, published almost in parallel with ours, on this topic:
Park D, 2013 "Widespread Misinterpretable ChIP-seq Bias in Yeast" (Different analysis methods but the same conclusions in S. cerevisiae, analyzing an entirely different set of factors with ChIP-Seq experiments.)
Kasinathan S, 2014 "High-resolution mapping of transcription factor binding sites on native chromatin" (Questions specificity of standard ChIP in S. cerevisiae and at HOT regions of Drosophila. This work possibly provides a solution to the artifact with a modification of the ChIP technique.)
Also, the following discussion of our work on PubPeer may be useful.
This comment, imported by Hypothesis from PubMed Commons, is licensed under CC BY.
-
-
europepmc.org europepmc.org
-
On 2014 May 03, Stefanie Butland commented:
All interaction data from this paper are freely available at IntAct http://www.ebi.ac.uk/intact/query/24705354 and are featured as Dataset of the Month for May 2014. These include 312 binary interactions from yeast two-hybrid, anti tag coimmunoprecipitation, fluorescence microscopy and luminescence based mammalian interactome mapping (LUMIER) experiments.
We submitted our data directly to IntAct through the IMEx Consortium as part of the publication process. I encourage others to consider this route to making your data available for re-use and re-mixing as the expert biocuration service provided by IntAct was smooth, accurate, and required very little of our time. A very positive experience.
This comment, imported by Hypothesis from PubMed Commons, is licensed under CC BY.
-
-
europepmc.org europepmc.org
-
On 2014 May 14, David Keller commented:
Still waiting for anyone to answer my criticisms of this USPSTF report
When I first read the 2014 USPSTF update on vitamins for disease prevention, I expected, based on the headlines, to find evidence that there is no reason to take a multivitamin. Instead, I became convinced by the data presented by the USPSTF that the evidence of benefits versus harms favors men over 50 taking a multivitamin to prevent cancer and possibly reduce overall mortality. At the very least, the USPSTF would be fully justified in recommending that men over 50 who do not consume a diet rich in vegetables and fruits should consider adding a multivitamin. For some reason, most editorials and comments have completely ignored the significant reductions in cancer for men randomized to multivitamins in the 2 studies cited by USPSTF, and the significant reduction in overall mortality for men randomized to the high dose multivitamin tested in the French study. Instead, we saw headlines and editorials stating or implying that we now have proof that multivitamins are useless. I request that an expert in this area reply to my comments, giving good reasons why you are not convinced by the data we have, and what it would take to convince you. If you are knowledgeable in this area, and especially if you are a member of the USPSTF, I would greatly appreciate your pointing out where my thinking on this issue is wrong or even debatable. For details, data and references, please see my Open Letter to the USPSTF on the following PubMed Commons web page:
http://www.ncbi.nlm.nih.gov/pubmed/24566474#cm24566474_4093
Lastly, it is not helpful to tag a comment as "not helpful" without specifying why. PubMed Commons should foster meaningful debate, not merely anonymous unexplained contradiction of each other.
This comment, imported by Hypothesis from PubMed Commons, is licensed under CC BY.
-
-
europepmc.org europepmc.org
-
On 2014 Jan 04, Dorothy V M Bishop commented:
I was pleased to see that Professor Farthing took the opportunity to tackle the subject of research misconduct in his lecture. He cogently notes the nature of the problem and makes suggestions to deal with it. I thought his analysis was generally on-target, but I was concerned about his second suggested solution: enhanced monitoring and audit, and his failure to consider an additional approach, which is to change the incentive structure for researchers. The following points are taken from a blogpost I wrote on these topics (http://deevybee.blogspot.co.uk/2013/06/research-fraud-more-scrutiny-by.html).
I agree we need to think about how to fix science, and that many of our current practices lead to non-replicable findings. I just don't think more scrutiny by administrators is the solution.
So what would I do? The answers fall into three main categories: incentives, publication practices, and research methods.
Incentives: Currently, we have a situation where research stardom, assessed by REF criteria, is all-important. Farthing notes that RAE/REF criteria have been devised to stress quality rather than quantity of research, which is a good thing, but it is still the case that too much emphasis goes on the prestige of journals (see http://deevybee.blogspot.co.uk/2013/01/journal-impact-factors-and-ref-2014.html).
Instead of valuing papers in top journals, we should be valuing research replicability. This would entail a massive change in our culture, but a start has already been made in my discipline of psychology :see http://www.nature.com/news/psychologists-strike-a-blow-for-reproducibility-1.14232.
Publication practices: the top journals prioritize exciting results over methodological rigour. There is therefore a strong temptation to do post hoc analyses of data until an exciting result emerges. I agree with Farthing that pre-registration of research projects is a good way of dealing with this. I'm pleased to say that here too, psychology is leading the way in extending research registration beyond the domain of clinical trials: http://blogs.lse.ac.uk/impactofsocialsciences/tag/registered-reports/
Research methods: we need better training of scientists to become more aware of the limitations of the methods that they use. Too often statistical training is a dry and inaccessible discipline. All scientists should be taught how to generate random datasets: nothing is quite as good at instilling a proper understanding of p-values as seeing the apparent patterns in data that will inevitably arise if you look hard enough at some random numbers. In addition, not enough researchers receive training in best practices for ensuring quality of data entry, or in exploratory data analysis to check the numbers are coherent and meet assumptions of the analytic approach.
Finally, before any new regulation is introduced, there should be a cold-blooded cost-benefit analysis that considers, among other things, the cost of the regulation both in terms of the salaries of people who implement it, and the time and other costs to those affected by it. My concern is that among the 'other costs' is something rather nebulous that could easily get missed. Quite simply, doing good research takes time and mental space of the researchers. Most researchers are geeks who like nothing better than staring at data and thinking about complicated problems. If you require them to spend time satisfying bureaucratic requirements, this saps the spirit and reduces creativity.
I think we can learn much from the way ethics regulations have panned out. When a new system was first introduced in response to the Alder Hey scandal, I'm sure many thought it was a good idea. It has taken several years for the full impact to be appreciated. The problems are documented in a report by the Academy of Medical Sciences, which noted "Urgent changes are required to the regulation and governance of health research in the UK because unnecessary delays, bureaucracy and complexity are stifling medical advances, without additional benefits to patient safety"
This comment, imported by Hypothesis from PubMed Commons, is licensed under CC BY.
-
-
journals.plos.org journals.plos.org
-
On 2013 Jul 04, John Overington commented:
A standard for database tag structures would be really useful in general - 1ABC is a PDB code, but it's also many other things, so PDB1ABC would be more general and useful. However, as a database provider this paper highlighted several features that I didn't know and will now explore - e.g. the NLM JATS DTD.
This comment, imported by Hypothesis from PubMed Commons, is licensed under CC BY.
-
-
europepmc.org europepmc.org
-
On 2015 Sep 24, Bill Cayley commented:
A good example of when "less" is "more" in Obstetric care: https://lessismoreebm.wordpress.com/tag/obstetric-gynegologic/
This comment, imported by Hypothesis from PubMed Commons, is licensed under CC BY.
-
-
europepmc.org europepmc.org
-
On 2016 Jan 21, Sebastian Lourido commented:
The conditional dimerizable Cre recombinase (DiCre) has been a powerful technique for conditional genome engineering in Toxoplasma, as first established in this article, and elaborated later (see Pieperhoff, et al. 2015. PLoS One). It has worked well in our hands for a variety of applications. Recently, we discovered that the reporter construct used in this study was cloned down stream and in frame of a Ty-tag (EVHTNQDPLD), such that the KillerRed expressed prior to recombination contains and N-terminal Ty-tag. This observation does not affect any of the experiments presented in the article. However, it might be important to note for future investigators planning further manipulations of the existing DiCre strains or reporter constructs.
This comment, imported by Hypothesis from PubMed Commons, is licensed under CC BY.
-
-
europepmc.org europepmc.org
-
On 2014 Jan 08, Tom Kindlon commented:
Early diagnosis of CFS/ME has been shown to lead to a better prognosis
It was interesting to see the various views expressed by GPs in this paper[1]. However I think a couple of useful points could have been added. There is much discussion in the paper about whether a label of CFS/ME is useful or not. The authors refer to NICE guidelines which "emphasise the importance of a definitive diagnosis"[2]. However, I think it would have been useful to add some direct evidence on this issue.
For example, research published by the Centres for Disease Control and Prevention (CDC) which found that an earlier diagnosis led to a better prognosis[3]. This prompted the CDC to launch a two-pronged awareness drive aimed at both health professionals and the general public - the tag line for the latter was, "Get informed. Get diagnosed. Get help."[4].
A UK study found that the longer the interval between a patient falling ill and getting a diagnosis, the greater the likelihood that they would become severely affected. [5]
The authors mention the issue of CFS/ME being managed in primary care. It is important for GPs to know that GPs encouraging patients to do a graded exercise programme is associated with a higher rate of adverse reactions. For example, a survey which asked patients about their experiences of treatments over the previous three years found that 45% reported being made worse by a graded exercise therapy (GET) programme overseen by their GP, compared to 31% who reported being made worse by a GET under a NHS specialist and 29% of those who did a GET in other circumstances[6]. The NICE guidelines do not recommend that a GP oversee such an approach[2].
References:
[1] Chew-Graham C, Dowrick C, Wearden A, Richardson V, Peters S. Making the diagnosis of Chronic Fatigue Syndrome/Myalgic Encephalitis in primary care: a qualitative study. BMC Fam Pract. 2010 Feb 23;11:16.
[2] NICE CG 53 Chronic fatigue syndrome/Myalgic encephalomyelitis (or encephalopathy) guideline.
[3] Nisenbaum R, Jones JF, Unger ER, Reyes M and Reeves WC. A population-based study of the clinical course of chronic fatigue syndrome. Health and Quality of Life Outcomes 2003;1:49-58.
[4] CDC Chronic Fatigue Syndrome Awareness Campaign. http://cdc.gov/cfs/awareness.htm [Last accessed: 31 March, 2010]
[5] Pheby D and Saffron L. Risk factors for severe ME/CFS. Biology and Medicine (2009); 1 (4):50-74. http://biolmedonline.com/Articles/vol1_4_50-74.pdf [Last accessed: 31 March, 2010]
[6] Action for M.E. and AYME Survey 2008 Results http://afme.wordpress.com/5-treatments-and-symptoms/ [Last accessed: 31 March, 2010]
This comment, imported by Hypothesis from PubMed Commons, is licensed under CC BY.
-
-
europepmc.org europepmc.org
-
On 2015 Apr 18, Dorothy V M Bishop commented:
As a psychologist interested in the genetics of lateralization, I frequently come across this paper, which is cited as evidence for early genetic influences on brain asymmetry. As of today, 160 citations are shown in Web of Science.
When I read the paper a couple of years ago, I found some details that did not seem to support the conclusions of the authors. These are described in a blogpost: http://deevybee.blogspot.co.uk/2012/12/genes-brains-and-lateralisation-how.html
I will summarise the main issue below, but I was interested to note that, since that time, other papers have appeared, using larger datasets, which have stressed the remarkable symmetry of early gene expression, notably:
Johnson, M. B., et al (2009). Functional and evolutionary insights into human brain development through global transcriptome analysis. Neuron, 62(4), 494-509. doi: 10.1016/j.neuron.2009.03.027
and
Pletikos, M., Sousa, A. M. M., Sedmak, G., Meyer, K. A., Zhu, Y., Cheng, F., . . . Sestan, N. (2014). Temporal specification and bilaterality of human neocortical topographic gene expression. Neuron, 81(2), 321-332. doi: 10.1016/j.neuron.2013.11.018
Here is a brief account of the main issue I raised about the study. Please see the blogpost for more details.
Sun et al used a method called Serial Analysis of Gene Expression (SAGE) which compares gene expression in different tissues or – as in this case – in corresponding left and right regions of the embryonic brain. The analysis looks for specific sequences of 10 DNA base-pairs, or tags, which index particular genes. SAGE output consists of simple tables, giving the identity of each tag, its count (a measure of cellular gene expression) and an identifier and more detailed description of the corresponding gene. These tables are available for left and right sides for three brain regions (frontal, perisylvian and occipital) for 12- and 14-week old brains, and for perisylvian only for a 19-week-old brain. The perisylvian region is of particular interest because it is the brain region that will develop into the planum temporale, which has been linked with language development. One brain at each age was used to create the set of SAGE tags.
To verify asymmetrically expressed genes the authors performed chi square tests. The chi square involves testing whether the distribution of expression on left and right is significantly different from the distribution of left vs. right expression across all tags in this brain region – which is close to 50%. In the left-right perisylvian region of a 12-week-old embryonic human brain, there were 49 genes with chi square greater than 6.63 (p < .01): 21 were more highly expressed on the left and 28 more highly expressed on the right. But for each region the authors considered several thousand tags. My analysis indicated that the number of asymmetrically expressed genes appeared to be lower than you would expect by chance – entirely consistent with the conclusions of Pletikos et al.
Unless my analysis is mistaken, it would seem this paper should not be cited as evidence for asymmetric fetal gene expression, as it actually shows the opposite.
This comment, imported by Hypothesis from PubMed Commons, is licensed under CC BY.
-
-
europepmc.org europepmc.org
-
On 2015 Oct 07, Bill Cayley commented:
One of several examples showing that sometimes in obstetric care "less" is "more": https://lessismoreebm.wordpress.com/tag/obstetric-gynegologic/
This comment, imported by Hypothesis from PubMed Commons, is licensed under CC BY.
-
-
europepmc.org europepmc.org
-
On 2014 Feb 12, Diana Frame commented:
A note for researchers, MESH indexing terms on this article erroneously tag it as non-small cell lung cancer (NSCLC). It should be under Small Cell Lung Carcinoma[MeSH].
This comment, imported by Hypothesis from PubMed Commons, is licensed under CC BY.
-
-
scripting.com scripting.com
-
<link rel="alternate" type="application/rss+xml" href="http://scripting.com/rss.xml">#
A meta tag to put into the header to support RSS discovery.
-
- Jun 2018
-
inst-fs-iad-prod.inscloudgate.net inst-fs-iad-prod.inscloudgate.netzine.pdf1
-
There are many ways to make technology more just and equitable, and consent is one important consideration. Non-consentful features and interactions can be minor nuisances for some people, but can be very harmful to others. When Facebook introduced photo tagging, anyone could tag you in a photo, whether or not you were okay with it. For some users, that could lead to embarrassment if the photo wasn’t particularly flattering. But for other people, the harm could be much more serious. For trans users, tagging photos from their pre-transition lives without their consent could lead to them being outed, which can have consequences for employment, housing, safety, and more.In response to user outcry, Facebook eventually implemented a process by which users can approve tagged photos. However, it required a critical mass of complaints to make this happen. And, Facebook still stores photos that are tagged with your face in its database, which informs its facial recognition algorithms. Whether you consented to being tagged or not, Facebook has a 98% accurate idea of what your face looks like.
-
-
ktakahata.github.io ktakahata.github.iopage 691
-
Libra
If we choose to add an astrology/astronomy tag
-
-
ktakahata.github.io ktakahata.github.iopage 651
-
wood-nymphs
Not sure what to tag
-
-
ktakahata.github.io ktakahata.github.iopage 601
-
singing brown Setae
Not sure what to tag this
-
-
test.parthenos-project.eu test.parthenos-project.eu
-
This representation is
as we have seen this works pretty well...
Tags
Annotators
URL
-
-
cy.finndorby.com cy.finndorby.com
-
Display Advertising ist immer nur so erfolgreich wie es die Zielgruppen-Definition zulässt. catchyou® sorgt dafür, dass die richtigen Werbebotschaften die richtigen Leute zur richtigen Zeit erreichen. Deshalb erreichen wir auch Click-Through-Rates, die bis um den Faktor 10 höher sind als der Durchschnitt. Wobei wir Display-Werbung auch und gerade im Retargeting einsetzen. Unsere kontinuierliche Optimierung der Kampagnen nach individuellen Leistungskennzahlen sorgt dafür, dass die Kampagne von Tag zu Tag besser werden.
Display Advertising ist immer nur so erfolgreich wie es die Zielgruppen-Definition zulässt. catchyou® sorgt dafür, dass die richtigen Werbebotschaften die richtigen Leute zur richtigen Zeit erreichen. Deshalb erreichen wir auch Click-Through-Rates, die bis um den Faktor 10 höher sind als der Durchschnitt. Wobei wir Display-Werbung auch und gerade im Retargeting einsetzen. Unsere kontinuierliche Optimierung der Kampagnen nach individuellen Leistungskennzahlen sorgt dafür, dass die Kampagnen von Tag zu Tag besser werden.
-
-
demo.codetri.net demo.codetri.net
-
}
When writing PHP, if you have a file that is solely PHP, it is recommended that you do not add a closing PHP tag (
?>
). Doing so then having a bunch of whitespace after it can create some pretty weird errors. I lost a day of working time to this issue. Take it from an experienced PHP developer, save yourself lots of trouble and don't put the closing PHP tag.
-
-
en.wikipedia.org en.wikipedia.org
-
Tagging systems open to the public are also open to tag spam, in which people apply an excessive number of tags or unrelated tags to an item (such as a YouTube video) in order to attract viewers. This abuse can be mitigated using human or statistical identification of spam items.[48] The number of tags allowed may also be limited to reduce spam.
Tags
Annotators
URL
-
-
ucdenver.instructure.com ucdenver.instructure.com
-
http://inte5340.cu.studio (Links to an external site.)Links to an external site.
This is my blog URL: https://fcpayan.wixsite.com/portfolio/blog
So all I do is tag it with #inte5340 and that will be it? Does it work with the Wix website?
-
-
en.wikipedia.org en.wikipedia.org
-
[edit] The choice tag is used to represent sections of text which might be encoded or tagged in more than one possible way. In the following example, based on one in the standard, choice is used twice, once to indicate an original and a corrected year and once to indicate an original and regularised spelling.[10]
I love that this exists!
-
-
web.hypothes.is web.hypothes.is
-
example tag:
<link rel="canonical" href="http://where/your/old/page/is.html" />
-
-
thewirecutter.com thewirecutter.com
-
After more than 40 hours of research and over a month of testing 13 devices, we think the GreatCall Lively Mobile is the best medical alert system for most people. Unlike most devices, it can reach either 911 or a call center from anywhere in your home or out in the world. That means the GreatCall Lively Mobile can help in all manner of situations, from getting EMTs and loved ones on the scene after a fall to contacting a friend for you if you can’t find your phone (yes, really; we tried it). Share this review on Facebook Share this review on Twitter Save this review on Pocket Share this review on Pinterest Share this review with E-mail It’s less expensive per month than any similar device, and relatively stylish, too. But choosing a medical alert is a personal decision, so there are different factors to consider: If you won’t wear a medical alert that looks vaguely like a medical device, won’t remember to charge a medical alert, or will have trouble pushing a button during an emergency, we have picks for you, too. Our pick GreatCall Lively Mobile The best medical alert system Our favorite medical alert system is comfortable to wear around your neck or on a belt clip. We found that the call center picks up faster than the competition, typically 15 seconds after you push the button. $40 from GreatCall $34 from Walmart The water-resistant GreatCall Lively Mobile can dial a call center or 911 directly (the ability to do both is a rare feature) from anywhere, and it’s easier to wear than the competition: It can go on a lanyard (with a magnetic clasp) that’s long enough to slide over your head, or on a belt clip. The silver box and plain white indicator light are more understated than the competition, and GreatCall offers the lowest-cost month-to-month plan of anything we looked at. The battery lasts 24 hours, according to GreatCall, though we found it could go up to 50 hours with minimal use. The advertised battery life is on the low end of the models we tested, but our experts recommended getting in the habit of charging your medical alert every day anyway. The GreatCall Lively Mobile works anywhere there’s Verizon cell service, which we’ve found to be the most reliable network. Advertisement googletag.cmd.push(function() { googletag.display('div-gpt-ad-1524661673579-0'); }); Also great Lifestation At Home An at-home medical alert system Call for help from a room or two in your house with this less-expensive and easier-to-wear system, available in versions that connect to a landline or cell service. $26 from LifeStation If you are with someone whenever you leave your house and have a small living space, or just want protection in one place (like the shower), you might not need a mobile medical alert like our pick. An at-home medical alert is less expensive with a less bulky button to carry, but the range is very limited. Most at-home systems are similar, but we found the Lifestation At Home to be a little easier to use and less expensive than the competition (month-to-month plans are $30 per month for a device that connects to a landline, and $37 per month for one with cellular service). The major downside of the Lifestation At Home is that you cannot speak directly into the device. If you fall, you can push the button from a few hundred feet away from the base station to dial the call center, but you’ll need to be within shouting distance of the base station to communicate whether you’re in need of 911 help or just want an emergency contact to come help you get up. (If you are unable to speak, or the call center cannot hear you, they will follow a course of action that you specify when you sign up: call a family member, call EMTs, or some combination thereof.) The battery in the wearable button lasts three years, and the base unit plugs into the wall. The button connects to the base via radio signal. Also great Apple Watch Series 3 (aluminum) No call center and no contract Bare-bones emergency features, but the most stylish. $330 from Apple If looks matter to you and you have an iPhone, or if you may have trouble pushing a button in an emergency, consider the Apple Watch Series 3. Though it’s bare-bones in emergency functions, it’s much more discreet to wear than other devices we tested. Because compliance matters more than anything when it comes to these devices, wearability is important. At a one-time cost of a few hundred dollars, the Apple Watch works out to be less expensive than buying a separate medical alert with a monthly bill after about a year of use (not including the cost of iPhone service, which is required for the Apple Watch to place phone calls). A button on the side of the watch allows you to place a call to 911 and can alert your emergency contacts that you placed a call when you are in range of your phone or connected to the same Wi-Fi network, and you can speak directly into the watch. You can also place an ordinary nonemergency call through the watch, either by scrolling through your contacts list or saying, “Hey, Siri, call [contact].” The Apple Watch battery lasts 18 hours with some use (less if you’re using it to make frequent phone calls). In September 2017, Apple announced a version of the watch with LTE, but we recommend the one without cellular connectivity for now. Budget pick Ask My Buddy A bare-bones option for home A voice-controlled app that can give you added peace of mind, but can’t call 911. Buy from Ask My Buddy Amazon Echo Our favorite voice-controlled device It’s relatively easy to set up Ask My Buddy on the Amazon Echo, which can also play music, tell you the weather, and control smart devices. $180 from Amazon Buy from Amazon Buy from Amazon Buy from Amazon If you want an extra layer of security at home and are considering getting a voice-controlled smart-home device anyway, Ask My Buddy is a free service available on the Amazon Echo (here’s our full guide on Amazon’s Alexa devices). If you need help and are in the same room, you can say “Alexa, ask my buddy to send help” and your emergency contacts will get a notification via email, text, or robocall. You can also place a call through the Echo to anyone with an Alexa device, or the app. Of all the medical-alert-capable devices, the Echo plus Ask My Buddy is one of the least expensive and least intrusive options. However, it offers very minimal protection: It can’t travel with you, and it can’t actually call 911 or reach anyone who is constantly available to dial 911 for you if you ask. We wouldn’t rely on any medical alert alone to save us in an emergency where every second counts, anyway, but this one ranks the lowest in terms of how much it can help in a variety of situations. Keep up with everything Wirecutter from your inbox Wirecutter Weekly: New reviews and picks, sent weekly Deals We Love: The best deals we can find, sent daily Please choose a newsletter to subscribe to. Sign up for Wirecutter's Newsletter Subscribe That wasn't a valid email address. Please try again. Feel free to opt out or contact us at any time. Opt out or contact us at any time. Thanks for subscribing! You'll be hearing from us soon. The research Expand all Why you should trust us Who should get this Can I just use a cell phone, a smart watch, or Alexa/Google Voice? How we picked How we tested What medical alerts are like to use and wear Our pick: GreatCall Lively Mobile Flaws but not dealbreakers Also great: Lifestation At Home Also great: Apple Watch Also great: Amazon Echo with Ask My Buddy What to ask in a test call Why we don’t recommend Life Alert The competition Sources Why you should trust us Medical alert systems (sometimes referred to as personal emergency response systems) have been around for decades. Perhaps the most recognizable name brand, Life Alert, with its ear-worm of a slogan “I’ve fallen and I can’t get up,” was founded in the 1980s. To understand how people use medical alerts, I spoke to George Demiris, PhD, a professor in the department of biomedical informatics and medical education at the University of Washington; Marita Kloseck, PhD, director of the Sam Katz Community Health and Aging Research Unit at Western University in Ontario, Canada; and Majd Alwan, senior vice president of technology and executive director of the LeadingAge Center for Aging Services Technologies. I also spoke to experts who help people select medical alerts: Mindy Renfro, who has worked as a physical therapist and is currently a research assistant professor at the Rural Institute On Disabilities, part of the University of Montana; Richard Caro, who writes about medical alerts at Tech-enhanced Life; Tony Rovere, chair of the Long Island chapter of the National Aging in Place Council and blogger at StuffSeniorsNeed.com; and Melissa Kantor, the executive director of Long Island at Home, which sells medical alerts and aging-in-place services to local seniors. I fall well below the typical age at which people purchase a medical alert, so I approached the research as though I were selecting one for a loved one to use. According to experts, I’m not far off from a typical customer: Many medical alerts are purchased by adult children looking for ways to better support a parent who is aging in place. I spent weeks trying out the devices for myself. I also consulted a family member who already uses one, my great-aunt Kay. Who should get this Pull QuoteOut of the 30 medical alert users in Ontario, Canada, that Kloseck and her colleagues spoke to, 90 percent agreed that the devices helped them maintain their independence. My great-aunt Kay lives alone in Erie, Pennsylvania, near the farm where she and my grandma grew up. She’s had a couple nasty falls in the past five years, but she doesn’t want to live in a nursing home. She prefers her own house and her daily routines. But she wants to know that if she needs to, she’ll be able to call for help quickly. Her medical alert device helps her maintain an independent lifestyle, as it does for many. “I dread just being an ill person who can’t cope with daily looking after yourself,” said one participant in the focus groups researcher Marita Kloseck conducted on what it’s like to live with a medical alert. “The last thing I want to do is lose my independence and be an invalid, it’s my biggest fear.” If you’re living independently and at risk for falling or another medical emergency, a medical alert is one safety measure to consider. Out of the 30 medical alert users in Ontario, Canada, that Kloseck and her colleagues spoke to, 90 percent agreed that the devices helped them maintain their independence. Though many people, like Aunt Kay, turn to medical alert systems after they’ve had a scary incident, the best time to get one is before you need it. If you are having trouble standing up to get out of a chair, said Renfro, it’s a good time to consider one—especially if you live somewhere where neighbors are few and far between, as is the case in Montana, where Renfro works. It’s not just for falls. One interviewee in Kloseck’s focus group reported successfully contacting EMTs via a medical alert after indigestion-like pain for over a day. “I think they must have flew here!” Another said she liked having a medical alert in case someone suspicious showed up at the door. A medical alert might simply relieve anxiety about emergencies. “You hear about people who fall and then can’t get help and they lay there for sometimes hours, but it just scares you when you think that could happen,” noted one participant in Kloseck’s survey on what motivated her to get a medical alert. “Subscribers reported feeling a sense of security or peace of mind,” Kloseck writes. As Aunt Kay puts it: “I feel protected.” Pull QuoteYou should get a medical alert only if you’re committed to wearing and using it. A medical alert should be just one line of defense against any medical emergency, along with working with a physician or physical therapist to monitor or improve your health and eliminating any hazards around the house, said Alwan. No devices we tested worked perfectly, and no medical alert will undo the damage of a fall (or anything else). Though all experts I spoke to agreed that medical alert systems made you safer, it’s hard to tell by how much. Studies suggest that these systems can reduce the amount of time spent on the floor after a fall, but there’s nothing conclusive in the way of peer-reviewed work showing how many lives they save per year. (In fact, experts I spoke to mostly said that their own parents didn’t have medical alerts, preferring to rely instead on check-ins with a friend or neighbor). You should get a medical alert only if you’re committed to wearing and using it. “I don’t even move without it,” Aunt Kay said. It doesn’t do any good sitting atop your dresser, or if you don’t feel comfortable pushing the button in an emergency. They make poor surprise gifts, says Renfro. If you’d like to foot the bill for a device for a loved one, make sure it’s something they want, and involve them in the process of picking it out. Can I just use a cell phone, a smart watch, or Alexa/Google Voice? Today, many of us already carry around a emergency help button: our cell phones. In fact, for some, the ability to dial 911 is the main appeal of having a wireless device at all, according to the Federal Communications Commission. If you’re in the habit of carrying around a phone constantly, it might be a good alternative to a medical alert. There are a few downsides: Most important, your phone might not be water-resistant, or at least might be awkward to take in the shower and hard to reach if you slip. It doesn’t have an option for automatic fall detection, which some medical alerts do. In a nonemergency it can’t reach a call center, so you’ll have to dial family until someone picks up. And it’s not set up by default to automatically share your location, as many medical alerts will with the call center agent. A phone’s battery also doesn’t last as long as a medical alert system’s, if you’re using it to do other things. However, if you know you’ll have trouble remembering to wear a medical alert, or can’t afford $20+ per month, committing to keeping your phone on you at all times is better than nothing. Some companies have apps that provide access to a call center just like medical alerts do, at about a third of the price of a monthly medical alert subscription. However, some can be confusing to use, slow to load, and even sometimes freeze, according to Caro, who tested out three of the apps. They’re also stuck behind a lock screen. There are a few devices that offer medical-alert-like features that are not technically medical alerts, including the Apple Watch and other smart watches, Amazon Alexa devices, and Google Home. Though these devices can offer emergency features, none will be as reliable as a device that has the sole purpose of reaching help. If you know you won’t wear a traditional medical alert, these are better than nothing. How we picked There’s a medical alert for every lifestyle. The most important feature of a medical alert system is that it’s something you are willing to use. Not even the most reliable device will be of use if it’s stashed in a drawer. Comfort and stylishness tended to decrease with range, I found. (A notable exception to this was the Apple Watch, which was the most comfortable and stylish of the bunch, and can go anywhere as long as your iPhone goes too.) We ended up testing a wide range of devices that covered all the possible configurations, but here’s how to figure out which kind works best for you. (Finding a device that you like might involve some trial and error: it took Aunt Kay two tries to find a medical alert that works well for her needs, and some time after that to figure out how to wear the device in a way that’s comfortable.) If you have a living space that’s bigger than a couple rooms, or if you leave your house alone, a mobile medical alert, which can go anywhere there’s a cell signal, will work best to keep you safe. They consist of a unit a little smaller than a deck of cards that you wear around your neck or on a belt clip that houses a GPS system, a speaker, and a microphone. The button calls someone directly from the device, and you speak to them through the unit. The button on most mobile medical alerts dials a call center (though our favorite can also reach 911). Agents are available 24/7, and pick up anywhere between 15 seconds and two minutes after you press the button. They can send 911 to your house, call a friend or family member on your behalf, or simply keep you company while you troubleshoot the situation yourself. They typically have a $20 to $70 monthly fee that includes the cost of the service and the device. (There’s often an activation or equipment fee, too.) Mobile medical alerts work off mobile carriers (e.g., AT&T, Verizon), so you’ll need to check the coverage in your area before making a purchase. They also need to be charged daily, or every few days, depending on the model. If you don’t want to call 911 directly in a minor emergency or if you slip in the shower while you’re naked, mobile medical alerts offer a way to get a variety of help, via a call center. The call center employees are there 24/7, unlike family members who will inevitably be sleeping, in work meetings, or on vacation sometimes. Further, mobile systems that connect to a call center almost always come with an option for automatic fall detection for about $10 extra per month (if you don’t like it, you can turn it off). When the device senses a change in vertical acceleration, it calls for help. If you are totally knocked out, the operator will attempt to figure out your location via the GPS signal from the device. Fall detection is a great idea, in theory, said experts. In practice, it’s prone to registering false positives, or failing to detect actual falls. “It can be embarrassing, it can [disrupt] activities, it can be costly,” said Demiris. (Part of the problem: Stunt actors falling accidentally on purpose are often used to calibrate fall detection.) Even if the device does successfully make a call after you’ve slipped, if you’ve been knocked unconscious, the operator at the call center could still have trouble figuring out where to send help. Most mobile systems have built-in GPS, but the little dot that shows operators where you are is subject to drift around. (Have you ever opened Google Maps on your phone and had the blue dot appear somewhere you aren’t? That’s it.) There are technical improvements that can be made on bare-bones GPS—like a device that checks in with Wi-Fi signals, when possible—but no device will always pinpoint your location accurately. At-home medical alerts are devices that are for use just at home, with a base station that can be connected to cell service or a landline. With just a few exceptions, these consist of a small, light button that can be worn on your wrist or around your neck. Push the button within about 600 feet of the base station (they’re connected via a radio signal), and you can speak to an operator through the base, which looks kind of like an answering machine. These medical alert systems tend to have lower monthly costs, and a device that’s far less bulky and annoying to wear (it’s about the weight and diameter of a quarter). There’s nothing to remember to charge, either. But the limited range can be frustrating, according to participants in a survey conducted by researchers at Jönköping University in Sweden, not just because it limits movement. “In particular, they felt that the lack of new technical innovations in the alarm system, such as the inclusion of a global positioning system (GPS), was a clear indication that their needs were not considered priorities in society,” the researchers write. A homebound system can make you feel homebound, which isn’t useful for people who want to be active outside of the house. Some companies offer affordable devices that can be used to call a loved one or even 911 directly. They do not reach call centers or have their own cell service (the two features are typically paired). These are less expensive because they lack a monthly service fee; rather, they rely on Wi-Fi, a smartphone, or a landline. They range from specialized medical alerts to the Apple Watch. No matter what style of medical alert you want—mobile or traditional, with a call center or not—you have a few options for how you’ll wear the device. Medical alerts can hang around your neck or wrist, or clip to your belt; for any particular device, there are often at least two options. What works best is largely personal preference, though Demiris notes that a device worn around your neck can be easier to make a habit of wearing if you’re used to putting on jewelry in the morning (it’s also necessary if you are using automatic fall detection). Battery life varies broadly for medical alerts, anywhere from just a day to a week. Experts advised getting in the habit of charging the device every night, so we didn’t prioritize long battery life. There’s typically no volume control on medical alert systems, which are about as loud as a cell phone at top volume and on speaker. The advantage is that there’s no way to accidentally turn the volume down. However, if you’re hard of hearing, volume could potentially be an issue. We looked only at devices that came with the option to make monthly payments or required no payments at all, and we discarded any that require you to have an annual contract for the service on the advice of Tony Revere, who blogs at StuffSeniorsNeed.com. You should be able to send the device back without breaking a contract if you try a particular one and realize it—or the whole concept—just isn’t for you. There are various certifications that medical alert equipment and call center equipment can have to make sure they’re up to certain safety standards. For example, companies can pay Underwriter Laboratories to verify their device has certain features. Experts we spoke to disagreed on the level of importance of these certifications, but no one thought that it was a dealbreaker to not have one. And because we did our own testing, we were able to learn firsthand if a system was reliable. Some companies will advertise that their call center is based in the US. Caro, who writes about how to pick a medical alert on Tech-enhanced Life and logged many hours himself testing medical alerts, pointed out to me that all the call centers he’s encountered sounded like they were based in the States. How we tested It’s hard to tell a lot about how easy, effective, and comfortable a medical alert is from descriptions online or from people who may have only used one on their own with no point of comparison, so we decided to try the devices ourselves. I spent several weeks integrating the devices into my life, and then pushing their limits as much as possible. I went through the setup process for each device, which ranged from placing the device in a charging cradle (which all mobile medical alerts use) and following a few verbal instructions, to leafing through a fine-print manual. One device required a traditional landline; I trekked to a coworker’s parents’ apartment on the Upper West Side to use one after it wasn’t compatible with our VoIP system at work. I used each medical alert for at least a day, wearing the mobile medical alerts to work and out with friends, making test calls in all manner of locations. For a while in February, my outfit was consistently punctuated by a low-hanging, blinking device, my kitchen counter and bedside table littered with in-home devices and charging cradles. I made several test calls with each device and compared both response time and the quality of customer service. We prioritized devices that could be worn a variety of ways and made accommodations for people without fine motor skills, like a lanyard with a magnetic clasp that doesn’t need to be looped over a head. Some devices require dexterity not everyone has, like pushing a lanyard through a small hole, or attaching them to a belt clip. What medical alerts are like to use and wear When I wore the Medical Guardian Premium Guardian, a former runner-up pick, out one night with my coworkers, the diamond indicator light blinked red as I ate my food. In the course of chatting about work, I mentioned that I was trying out medical alerts. “Oh that’s what that thing is,” one coworker said. “I thought maybe you had an allergy.” While I was getting used to having a medical alert on me, they still read as a medical device and a little bit strange to the outside world. I was surprised and delighted to learn during this process that, despite the fact that advertising for these devices seems to prey on our fear of mortality and disaster, I didn’t have to be in a life-or-death situation in order to buzz the call centers. The operators are just as happy to help talk through a situation and provide support from afar, and never seemed to be itching to push me into declaring an emergency. The buttons for in-home medical alerts are all tiny and barely noticeable. Mobile medical alerts were the biggest nuisance to wear, in part because of their size, and in part because they tag along for all manner of social situations. They are heavier and can draw considerable attention. I got in the habit of tucking the medical alerts into my shirt, per Aunt Kay’s advice. Some made their presence known even when they were out of sight, chiming to indicate their charge status when I was in a crowded elevator at work, or even speaking up at inopportune times. One day at work, the Premium Guardian verbally announced to me and everyone in a two-cubicle range that its battery was low. I spent a lot of time doing the dreaded thing—pushing the button to ask for help—just to see what would happen. Some devices made chiming sounds, some vibrated, and some noted that they were dialing the call center. The best medical alerts continuously did something as I waited for someone to pick up, as long spaces of silence would leave me wondering if I had accidentally hung up or lost signal. For medical alerts with call centers, someone typically picked up within 30 seconds. Longer than that felt like an eternity, even from the safety of my desk or bed; I wouldn’t want a loved one waiting that long during an emergency. All call centers say more or less the same line when they pick up: “Hello, do you need help?” I usually said no, I was just placing a test call. In one instance, curious if the call center would be willing to help out in a truly minor situation, I asked the operator to call my boyfriend to tell him I was running late to meet him. The operator was happy to oblige. Voice-controlled units like the Amazon Echo don’t require you to wear anything, but work reliably only when you’re in the same room. I set up the Echo in my kitchen, and when the dishwasher was running, even when I was screaming “Hey, Alexa!”—the signal that you’re about to give the device a command—over and over from a room away, it could not hear me. (This is also a pitfall of relying on a device to play music and be able to hear you in an emergency.) I had similar experiences with traditional in-home medical alerts. The range on these devices is technically several hundred feet from the base station, and though the call center operators could hear me yelling from a room away, they had trouble understanding me. (I just moved closer to the base station, but in the event that you fall and they can’t hear you, they’ll follow a preplanned course of action that you decide when you sign up, like calling a family member and then EMTs.) Services that try to use both the button and a base station to communicate were suboptimal. In the case of one hybrid mobile and home device, an operator first tries to talk to you via a stationary home box, and then switches to the wearable if you don’t respond there. After pushing the button at work, I sat in an empty conference room for a full two minutes while, presumably, someone first tried asking my empty apartment if anyone needed help before switching over to the speaker around my neck. During test calls, I asked operators to identify my location. No GPS was consistently accurate, though they were often correct within a couple blocks. This makes backup measures attractive, like the GreatCall Lively Mobile’s Web interface where you can log your typical schedule. Sometimes the GPS was way off. Once, while testing the Bay Alarm Medical GPS Alert System, an operator said that I was at the New York Times building in midtown where the device had lost power, when in fact I’d gone home to Brooklyn. The device lost power downtown, and had only just been recharged when I placed the test call; I suspect that it hadn’t been on long enough to update its location. On another occasion, the GPS on a device wasn’t working at all, and took two phone calls to customer service to fix. I found that operators were rarely able to troubleshoot problems with the device or answer questions about service. Though call center employees were willing and able to help with even minor incidents, they weren’t inclined to make small talk. Once, after noting my location an operator did exclaim that she used to live on my street, and we had a short conversation about the rising rents in Brooklyn. But with few exceptions, the call center people hung up quickly after addressing my requests. Despite being vaguely worried when I started this project about accidentally having EMTs show up at my house, I never once pushed the button on a medical alert unintentionally during testing, including a few occasions when I just threw them in my purse. If you do accidentally hit the button, chances are you will be connected to a call center, and you can just clarify what happened with an operator. (Medical alerts make noise when they are placing a call, so a butt-dial will not go unnoticed.) Most medical alerts do not call 911 directly, and those that do require a more deliberate, prolonged push to reach emergency services. At first I skipped providing my emergency contacts, in part because I didn’t expect to be in immediate danger, but also because it was such an easy step to overlook. In all but one case, it was possible to get through the activation process without providing them, which you typically have to do over email, fax, or via snail mail to ensure that the contact information is entered correctly. Only one model, the GreatCall Lively Mobile, allowed you to enter them in an online interface. Our pick: GreatCall Lively Mobile The GreatCall Lively Mobile is intuitive to use, and has a plain design that won’t draw too much attention. Our pick GreatCall Lively Mobile The best medical alert system Our favorite medical alert system is comfortable to wear around your neck or on a belt clip. We found that the call center picks up faster than the competition, typically 15 seconds after you push the button. $40 from GreatCall $34 from Walmart The GreatCall Lively Mobile was one of the easiest mobile medical alerts to wear and use, and costs less than any other medical alert of its kind that we considered, with service starting at $20 per month, with one-time fees totaling $80. The rectangular silver and black (or gold and black) design draws minimal attention, and the call center consistently picks up quickly—up to eight times as fast as others. The battery life is 24 hours, according to the company, among the the shortest we considered, though I found it lasted nearly twice that long with minimal use. The device is a little smaller and lighter than a deck of cards. One big button in the middle dials the call center or—if you hold it down—911. A small button on the back turns it on and off. A small battery-indicator light changes colors when the Lively is low on charge, but it doesn’t draw a ton of attention to itself. When the Lively shuts off from low battery, it announces that it’s doing so. (It was loud enough to wake me up at 4 a.m. one day, a good feature if you’ve forgotten to charge it and have missed the battery light.) The Lively Mobile can go anywhere there’s Verizon cell service, including your shower, as it’s waterproof. In separate tests, we’ve found Verizon to be the most reliable network, though it doesn’t cover every part of the country. Check here to see if your area is covered. The Lively Mobile is one of the only medical alerts we looked at that has the option to call either a call center, or—by holding down the button—911 directly. The speaker and microphone in the device provide sound quality that’s better than that of many other devices we considered. If you dial an agent from the Lively, they’ll typically pick up about 15 seconds after you push the button; other devices left us hanging for what felt like forever. If you are lost, or unable to speak, the agent can look at a GPS signal and a list of places you frequent to help identify your location. The Lively Mobile is the only device that has an easy-to-use online interface where you can store emergency contact information. With all other devices, you have to email or snail mail your emergency contact information (this ensures accuracy compared with speaking the information over the phone). GreatCall offers the most affordable basic service packages of all the mobile medical alerts we tested, at $20. Fall detection costs an extra $15. GreatCall also has a middle tier, for $25, with access to doctors via the device (though they emphasize that this feature should not be used in an emergency), and allows family and friends to tell when you leave home or return via the GreatCall Link app. The first tier of service should work well for most people, though if the idea of being able to loosely track a loved one’s movements appeals to you, or if you want the extra security of (somewhat unreliable) fall detection, consider upgrading. The Lively Mobile has a separate on-off button, which means it’s impossible to accidentally turn it off when you’re calling for help. The lanyard is soft and black, shorter than those of much of the competition, and has a magnetic clasp so you don’t need to be able to lift your arms above your head to put it on or mess with a complicated closure. (There’s also an option to wear the device on a belt clip). The instruction booklet for the Lively Mobile is easy to read. This is a small point, but it was much better than the thick, tiny-print instruction books that some of the competition had. GreatCall has been around since 2006—the company is best known for making Jitterbug flip phones—and debuted the Lively Mobile in mid-2016. The device is an upgraded version of GreatCall’s previous mobile medical alert, the Splash, which garnered positive reviews. Medical alert reviewer Caro praised the Splash for the call center’s fast response time, ability to call 911 directly, and easy online interface, all qualities that the Lively shares. Flaws but not dealbreakers No medical alert is actively enjoyable to wear, and the Lively Mobile is no exception. It will likely take some time to get used to having the device around your neck. On the Lively, a white light flashes consistently to indicate that it’s in an area with service. Though this was less intrusive than the more colorful lights on some other devices, it could still be annoying; there were no mobile medical alerts without lights. The length of the Lively Mobile’s lanyard is not adjustable. Though I found the relatively short lanyard to be easier to wear than the competition’s, this might not be the case for everyone. Even though the lanyard can be easily swapped out, most traditional lanyards (which have a clasp that attaches to a badge) will be a little awkward. If you want a different lanyard with a specific length, you’ll need a little DIY savvy. If your area is not covered by Verizon, the Lively Mobile won’t work for you. Check your coverage here. Another flaw that all medical alerts share: the GPS signal can be unreliable. However, the Lively helps skirt this by prompting you to enter information into an online database (from a computer or a smartphone app) about your schedule and where you go during your days so the call center staff have something to fall back on. It’s the only medical alert that has this feature. Of all the medical alerts we tested, the Lively Mobile has one of the shortest advertised battery lives: 24 hours, as opposed to 36 hours or even several days. I found the battery lasted over 50 hours with minimal use, though I wouldn’t want a loved one counting on it working for that long on a single charge. Experts recommend getting in the habit of charging your medical alert nightly, so that you don’t have to think about it. If this will be hard for you, consider an in-home medical alert, which doesn’t need to be charged. Also great: Lifestation At Home The LifeStation At Home system has a small button and a base station. Also great Lifestation At Home An at-home medical alert system Call for help from a room or two in your house with this less-expensive and easier-to-wear system, available in versions that connect to a landline or cell service. $26 from LifeStation If you just need a medical alert to cover you in a couple rooms of your house, consider the Life Station At Home system, which is about $30 per month (there’s no activation fee). Like all in-home medical alert systems, it consists of a small button that you can wear around your neck or on your wrist that wirelessly connects to an answering-machine-like base station that lets you speak to a call center agent (there’s no option to dial 911 directly). Though it can’t leave your house, and you can’t speak through the button, it’s easier to wear than our top picks. There’s no charging required; the button’s battery lasts about three years. Home medical alert systems are all very similar, but Life Station’s is a little less expensive than other options we looked at, and didn’t give us any trouble during testing. The main perk of an at-home system is that the device is much easier to wear than those in mobile systems: The Life Station button is about the weight and diameter of a quarter, and just a little thicker. In comparison, our main pick and runner-up are just a little smaller and lighter than a deck of cards. If you don’t need a medical alert that you can leave the house with, are mostly concerned about slipping in one room—the bathroom, for example—or know that you just won’t wear anything but the least-intrusive device, the Life Station At Home might be a good option. The major downside of this or any at-home system is that its range is incredibly limited, even if you’re just using it in your home. The range of this device is several hundred feet—that is, the button can still communicate with the base station if you are on the other side of a small house. Though it’s difficult to communicate through the base station if you’re even one room away, you can choose at the time of setup what course of action the call center should take if you push the button and they don’t hear anything. Also great: Apple Watch A medical ID screen has a few details for paramedics. Apple Watch can dial 911 at the push of a button. The Emergency SOS feature dials 911 and texts your emergency contacts. Press the button on the right once to get this screen, or hold down to activate the SOS feature immediately. A medical ID screen has a few details for paramedics. Apple Watch can dial 911 at the push of a button. 1 of 3 Also great Apple Watch Series 3 (aluminum) No call center and no contract Bare-bones emergency features, but the most stylish. $330 from Apple Apple Watch Series 3 has basic emergency functions compared with most medical alerts we looked at, and requires a little tech savvy to use. Out of everything we tested, it’s the only wearable device that’s stylish and doesn’t look at all like a medical device. (We tested the Series 2 but it is no longer available). You will need to have an iPhone for the watch to work, but if you’re already paying for that service and you are comfortable with navigating Apple services, the watch may be relatively affordable—it currently costs $330, which will buy you less than 10 months of service with a typical mobile medical alert. (We recommend the version without cellular service; more on that in a minute.) The SOS feature (which was introduced on the Series 2 model) allows users to dial 911 by pushing and holding down the button on the side of the watch, and can automatically text up to three emergency contacts and give them your location when you do so. Apple Watch hasn’t had emergency features long enough for our experts to evaluate its usefulness as a medical alert, though they agreed it could be useful. Apple Watch’s battery lasts 18 hours with some use. You can speak to a 911 responder directly through the watch, or if it’s a nonemergency, you can dial a friend or family member through the watch verbally, by saying (for example), “Siri, call [name].” The sound quality of Apple Watch is better than any medical alert we considered. There are a variety of bands to choose from (some costing hundreds of dollars themselves, like a Hermes band), making Apple Watch Series 2 the most customizable of all the devices we looked at. Aside from the limited functionality, the major downside of Apple Watch is that you have to be within Bluetooth range or connected to the same Wi-Fi network as your phone for it to place a call. This means that you can’t necessarily just set your phone down in your house, wander away from it, and know that your Apple Watch is going to keep you safe in the event of an emergency (one of the key advantages of a true mobile medical alert system). There is an LTE version of the Series 3 that allows you to place calls without being in range of your phone, but we can’t recommend it. Preliminary reviews have noted connectivity and battery issues with the LTE version, plus you’ll need to pay about $10 a month for the Watch to have its own service. We plan to test the service for ourselves, and we’ll keep an eye out for improvements. I found that navigating the tiny screen on the watch could be challenging, though this was mostly an issue for using functions other than the SOS feature. (However, if you buy Apple Watch, you’ll likely want it to work for other things, too.) If you find yourself fairly comfortable with most Apple devices, and okay with the size of newspaper print (the font can be enlarged on some apps, like text messaging, but not all), scrolling through apps on your wrist shouldn’t be too much of an adjustment. Also great: Amazon Echo with Ask My Buddy At your verbal request, the Amazon Echo can send an alert to loved ones. Budget pick Ask My Buddy A bare-bones option for home A voice-controlled app that can give you added peace of mind, but can’t call 911. Buy from Ask My Buddy Amazon Echo Our favorite voice-controlled device It’s relatively easy to set up Ask My Buddy on the Amazon Echo, which can also play music, tell you the weather, and control smart devices. $180 from Amazon Buy from Amazon Buy from Amazon Buy from Amazon If you don’t carry your phone around in your home, won’t remember or want to wear even a small button, would have trouble using a button in an emergency but can vocalize and enunciate pretty clearly, or just want another layer of security, consider using Ask My Buddy paired with the Amazon Echo (you’ll need to have a smartphone or tablet to use it). When you say, “Alexa, ask my buddy for help” the service will send a text, email, and phone call to a list of contacts to let them know they should check in. You can also place a phone call through the Echo to anyone who has the free Amazon Alexa app on their phone. Though the Echo may be the easiest and least expensive device to fit into your lifestyle, this setup would not be helpful at all in emergencies, and only marginally helpful in nonemergencies. Still, it would be better than nothing. Pull Quote I wouldn’t want a loved one of mine counting on any medical alert alone to keep them safe, but especially not the Echo. There’s nothing to remember to wear or charge, and the device doesn’t look anything like a medical device because it’s not. You’ll get all the other capabilities of the Echo (here’s our full guide), and at $180, it costs less than four months’ worth of service with a traditional medical alert company. Unlike other services, this one can’t connect you to 911 directly or via a call center or confirm that someone received your request. The range is small; the feature works reliably only if you’re in the same room as the Echo (that said, multiple Echos or Echo Dots can all be linked together to cover many rooms or a larger home). As such, Ask My Buddy should be treated only as an additional tool for a little added peace of mind in addition to thoughtful design of a home around the person using it. I wouldn’t want a loved one of mine counting on any medical alert alone to keep them safe, but especially not the Echo. We think that the Echo will be the best device to pair with Ask My Buddy for most people, though it also works with other Amazon Alexa devices and Google Home (our full guide). The Echo indicates that it heard you with a ring of light at the top of the device, and it’s taller than Google Home (which has a slanted face with indicator lights) and other Alexa options, making it easier to see from across the room. Ask My Buddy was a little easier to set up and use on the Echo than on Google Home (you’ll still need a little app savvy, or have someone around who does, as you’ll need to connect the device to a smartphone and Wi-Fi). The range on any voice-controlled device is smaller than that of a home medical alert system with a base station. When I tried screaming “Hey, Alexa” over and over from a room away while the dishwasher was running, it didn’t pick up my voice. The sound quality on either end of the phone call placed through the Alexa wasn’t as good as it is on a traditional medical alert device. Though you may run into range problems with a home medical alert with a base station, it’s easier to get someone on the line (you just push a button), at which point, they’d at least know that you needed help even if you were unable to communicate; the same can’t be said of a call that’s not picked up or a text that goes unseen. Another concern we have about Ask My Buddy: It’s a free app run by volunteers. There’s no guarantee that it’s sticking around, and you can’t contact people otherwise through an Echo. There’s an email to send issues and questions to, but you can’t get in touch with a representative right away if you run into a problem with its service. Amazon does have a customer service line to help with Echo setup. Amazon’s Echo Connect, launched in September 2017, is the first Echo device with phone calling capabilities (rather than just Echo-to-Echo intercom communication). You can use it to call any landline, including 911 calls. It also has built-in speakerphone and caller ID features. We are looking into the possibility of using the Echo Connect as a medical alert system, and if we think it’s a better option than an Echo paired with Ask My Buddy we’ll update this section with our thoughts. What to ask in a test call For medical alerts that come with a monitoring service, experts recommend pushing the button on your medical alert at least once a month to confirm that it’s working well. This step is especially important when you first start using your medical alert. Pushing the button should feel like second nature during a true emergency. One participant in the University of Western Ontario focus group recalled forgetting about the device during a heart attack: “The button didn’t even come into my mind. All I knew I was in trouble.” Plus, you need to make sure that the device works the way you think it does. Aunt Kay fell outside her house, and, thinking she had a mobile system, pushed the button to call for help to no avail. Though she was able to crawl to her car to retrieve her cell phone, the incident left her and our family shaken. It’s scary to find out you don’t have help at the ready when you think you do. Through expert advice, and some trial and error, I learned that there are a few things that I’d want my loved ones doing during a test call to ensure that their device is working properly. Confirm that the company has your correct home address on file. In particular, if the device was shipped to another location, this could be wrong—and cause problems if you fall and say you’re at home. Ask the operator if they can tell you where you are right now. If they are off by more than a block, call customer service. In one case during my tests, the GPS wasn’t working at all, a problem that might not have come to light if I hadn’t asked about it. Again, in another case, when I called from my home in Brooklyn, the operator informed me that I was at the New York Times Building, in midtown Manhattan. If you think you have automatic fall detection, confirm that this is the case with the operator. Many devices will announce that they are activating automatic fall detection when you first plug them in, even if this feature isn’t something you are paying for and therefore won’t be able to use. If you do have automatic fall detection, do a test fall by dropping the device on the ground. I also learned that the agents at the call center are typically not able to help you troubleshoot any issues that the device itself is having. If you learn during a test call that anything is amiss, you’ll need to hang up and call customer service. Why we don’t recommend Life Alert We quickly eliminated Life Alert—the brand so ubiquitous it’s name is often used to describe medical alerts in general—from the running. The company requires users to sign a 36-month contract that can be broken only if you go into 24/7 care or die. That’s a dealbreaker because it’s hard to know if a particular medical alert (or any medical alert at all) is something you’ll use until you try it out. The ability to cancel your service with minimal penalties is key to a good medical alert. Beyond that, Life Alert’s marketing is aggressive, making perusing its products annoying at best. There are outsized claims about its products’ lifesaving abilities on the website, but minimal information on the devices themselves. When I called the customer service line for more information, a representative immediately asked for my address. As I asked questions about the service, a rep encouraged me to give my mom “the gift of life”—meaning its product—for Mother’s Day. The competition Our former runner-up pick, the Medical Guardian Premium Guardian, is no longer available. Medical Guardian now offers a different device, the Active Guardian instead. We tried this device, and don’t like it enough to recommend it as a pick, though if you don’t care about looks and are better covered in your area by AT&T service (as opposed to Verizon) it’s a fine choice.
.
-