T'challa comes to the conclusion of rumors being spread by people claiming to be apart of his kingdom.
- Last 7 days
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Local file Local file
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This makes me visualize the green of their eyes being the effect of their hatred blinding them.
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The Wakandans believe T'challa is a tyrant which is the rumor being spread around his kingdom.
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www.biorxiv.org www.biorxiv.org
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Transparent Peer Review
Download the complete Review Process [PDF] including:
- reviews
- authors' reply
- editorial decisions
</br>
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www.opensourceshakespeare.org www.opensourceshakespeare.org
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Tybalt. Follow me close, for I will speak to them. 1535Gentlemen, good den: a word with one of you. Mercutio. And but one word with one of us? couple it with something; make it a word and a blow. Tybalt. You shall find me apt enough to that, sir, an you will give me occasion. 1540 Mercutio. Could you not take some occasion without giving? Tybalt. Mercutio, thou consort'st with Romeo,— Mercutio. Consort! what, dost thou make us minstrels? an thou make minstrels of us, look to hear nothing but discords: here's my fiddlestick; here's that shall 1545make you dance. 'Zounds, consort! Benvolio. We talk here in the public haunt of men: Either withdraw unto some private place, And reason coldly of your grievances, Or else depart; here all eyes gaze on us. 1550 Mercutio. Men's eyes were made to look, and let them gaze; I will not budge for no man's pleasure, I.
tybalts approches looking to confront romeo but mercutio challenges him to a fight
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Benvolio. I pray thee, good Mercutio, let's retire: The day is hot, the Capulets abroad, 1500And, if we meet, we shall not scape a brawl; For now, these hot days, is the mad blood stirring. Mercutio. Thou art like one of those fellows that when he enters the confines of a tavern claps me his sword upon the table and says 'God send me no need of 1505thee!' and by the operation of the second cup draws it on the drawer, when indeed there is no need. Benvolio. Am I like such a fellow? Mercutio. Come, come, thou art as hot a Jack in thy mood as any in Italy, and as soon moved to be moody, and as 1510soon moody to be moved. Benvolio. And what to? Mercutio. Nay, an there were two such, we should have none shortly, for one would kill the other. Thou! why, thou wilt quarrel with a man that hath a hair more, 1515or a hair less, in his beard, than thou hast: thou wilt quarrel with a man for cracking nuts, having no other reason but because thou hast hazel eyes: what eye but such an eye would spy out such a quarrel? Thy head is as fun of quarrels as an egg is full of 1520meat, and yet thy head hath been beaten as addle as an egg for quarrelling: thou hast quarrelled with a man for coughing in the street, because he hath wakened thy dog that hath lain asleep in the sun: didst thou not fall out with a tailor for wearing 1525his new doublet before Easter? with another, for tying his new shoes with old riband? and yet thou wilt tutor me from quarrelling! Benvolio. An I were so apt to quarrel as thou art, any man should buy the fee-simple of my life for an hour and a quarter. 1530 Mercutio. The fee-simple! O simple! Benvolio. By my head, here come the Capulets. Mercutio. By my heel, I care not. [Enter TYBALT and others] Tybalt. Follow me close, for I will speak to them. 1535Gentlemen, good den: a word with one of you. Mercutio. And but one word with one of us? couple it with something; make it a word and a blow. Tybalt. You shall find me apt enough to that, sir, an you will give me occasion. 1540 Mercutio. Could you not take some occasion without giving? Tybalt. Mercutio, thou consort'st with Romeo,— Mercutio. Consort! what, dost thou make us minstrels? an thou make minstrels of us, look to hear nothing but discords: here's my fiddlestick; here's that shall 1545make you dance. 'Zounds, consort! Benvolio. We talk here in the public haunt of men: Either withdraw unto some private place, And reason coldly of your grievances, Or else depart; here all eyes gaze on us. 1550 Mercutio. Men's eyes were made to look, and let them gaze; I will not budge for no man's pleasure, I.
benvolio is trying to get mercutio to leave because it is hot outside and their rivals the capulets are here mercutio jokes that benvolio is actually the one that likes to start fights and is easily angered
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academic.oup.com academic.oup.comHeat1
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you can add heat to an object, you cannot say that "an object contains a certain quantity of heat." This is very different from the case of the fuel in your car: you can add fuel to your car, and you are quite entitled to say that your car "contains a certain quantity of fuel". You even have a gauge for measuring it! But heat is quite different. Objects do not and cannot have gauges which read out how much heat they contain, because heat only makes sense when it is "in transit".1To see this, consider your co
hyfmhgmjg,mjh,kj
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calmatters.org calmatters.org
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“It’s great to say no phones, but I don’t think people realize the addiction of the phones and what students will go to to tell you ‘No, you’re not taking my phone.’”
Reading this article I understand why schools want fewer distractions, especially during class time, but I also think completely banning phones may not address the real issue.
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Instead of putting their devices in magnetically locked pouches, like they’re supposed to, some kids will stick something else in there instead, like a disused old phone, a calculator, a glue bottle or just the phone case.
When students do not follow the proper instructions of placing their phones in the pouches they make it difficult for staff to enforce the ban of cellphones. Especially since there are a lot of students who continue to have their phones out despite given instructions.
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nmoer.pressbooks.pub nmoer.pressbooks.pub
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. Your main research question should be substantial enough to form the guiding principle of your paper—but focused enough to guide your research. A strong research question requires you not only to find information but also to put together different pieces of information, interpret and analyze them, and figure out what you think. As you consider potential research questions, ask yourself whether they would be too hard or too easy to answer.
main research question should be focused enough to guide your research.
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A successful research process should go through these steps: Decide on the topic. Narrow the topic in order to narrow search parameters. Consider a question that your research will address. Generate sub-questions from your main question. Determine what kind of sources are best for your argument. Create a bibliography as you gather and reference sources.
The steps a research process should go through.
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After narrowing your focus, think about key search terms that will apply only to your subtopic. Develop specific questions that can be answered through your research process, but be careful not to choose a focus that is overly narrow. You should aim for a question that will limit search results to sources that relate to your topic, but will still result in a varied pool of sources to explore.
Try not to write something that is overly narrow. You need to keep the questions you want to ask broad enough to have enough resources to support your research.
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But the research process does not end when you have solved your mystery. Imagine what would happen if a detective collected enough evidence to solve a criminal case, but she never shared her solution with the authorities. Presenting what you have learned from research can be just as important as performing the research. Research results can be presented in a variety of ways, but one of the most popular—and effective—presentation forms is the research paper. A research paper presents an original thesis, or purpose statement, about a topic and develops that thesis with information gathered from a variety of sources.
A better way to describe the effort you have to put into researching all sides of the argument or thesis
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nmoer.pressbooks.pub nmoer.pressbooks.pub
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While it is true that some young women in today’s society are more sexualized than in the past, that is not true for all girls. The writer of this thesis should ask the following questions: Which teenage girls? What constitutes “too” sexualized? Why are they behaving that way? Where does this behavior show up? What are the repercussions?
An example of how to properly narrow down thesis.The questions to ask yourself to be more specific.
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Examples of Appropriate Thesis Statements The societal and personal struggles of Troy Maxon in the play “Fences” symbolize the challenge of black males who lived through segregation and integration in the United States. Shakespeare’s use of dramatic irony in Romeo and Juliet spoils the outcome for the audience and weakens the plot. J. D. Salinger’s character in Catcher in the Rye, Holden Caulfield, is a confused rebel who voices his disgust with phonies, yet in an effort to protect himself, he acts like a phony on many occasions. Compared to an absolute divorce, no-fault divorce is less expensive, promotes fairer settlements, and reflects a more realistic view of the causes for marital breakdown. Exposing children from an early age to the dangers of drug abuse is a sure method of preventing future drug addicts. In a crumbling job market, a high school diploma is not significant enough education to land a stable, lucrative job.
confident thesis statements
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Specificity A thesis statement must concentrate on a specific area of a general topic. As you may recall, the creation of a thesis statement begins when you choose a broad subject and then narrow down its parts until you pinpoint a specific aspect of that topic. For example, health care is a broad topic, but a proper thesis statement would focus on a specific area of that topic, such as options for individuals without health-care coverage. Precision A strong thesis statement must be precise enough to allow for a coherent argument and to remain focused on the topic.
Specificity: narrowing down thesis. Precision: Hitting the nail on the head so to speak, with the thesis statement.
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A thesis is generally one to two sentences long and appears toward the end of your introduction. It is specific and focuses on one to three points of a single idea—points that will be demonstrated in the body. The thesis forecasts the content of the essay and suggests how you will organize your information. Remember that a thesis statement does not summarize an issue but rather dissects it.
A description of how to utilize a thesis.
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hotelsierra.blogspot.com hotelsierra.blogspot.com
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www.reddit.com www.reddit.com
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nmoer.pressbooks.pub nmoer.pressbooks.pub
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When writing a personal narrative for class, first consider the prompt your teacher assigned you. Then, freewrite about topics that are of general interest to you.
Very good to do as it will open up your brain to good ideas and it will allow you to write a lot easier.
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The intention or purpose may be to expound on the grieving process (catharsis), or to encourage an emotional response from the reader, for example, making a person laugh or cry.
It is a good sign if the reader is very engaged and feeling all of the emotions, it means you have got through to the reader.
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a personal narrative is a form of creative writing that tells a story about personal experiences.
Personal Narratives are very important to have very good, strong, and organized writing as it will keep the audience engaged.
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nmoer.pressbooks.pub nmoer.pressbooks.pub
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Not all online search engines’ results will be useful or reliable.
Very accurate sometimes it confuses you even more.
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When selecting a topic, you may also want to consider something that interests you or something based on your own life and personal experiences.
Very important so you have a good writing flow without getting writers block.
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Effective writing can be simply described as good ideas that are expressed well and arranged in the proper order.
Being organized can lead to a great piece pf writing.
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Just as you need a recipe, ingredients, and proper tools to cook a delicious meal, you also need a plan, resources, and adequate time to create a good written composition
Everything has its steps and it is important to follow them if we want successful results.
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docdrop.org docdrop.org
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Yet large “leaks” in the metaphorical STEM pipeline likely occur by early child-hood in the U.S.
This is well worded and has strong imagery
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A practical implication of these findings is that factors present before kindergarten may largely explain racial and ethnic underrepresentation in STEM.
Implied, but not studied, indicating further study is required
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This unexplained
... but well documented...
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However, the study’s antecedent, opportunity, and pro-pensity factors do not fully explain the observed racial dis-parities.
Limitations, what wasn't conferred.
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largely consistent
Confirming
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We hypothesized
Restate the hypothesis
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followed from the fall of kindergarten to the spring of fifth grade
Longitudinal
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Asian students were initially less likely than White students to display advanced science achieve-ment in kindergarten (i.e., 7% versus 16%, respectively). Asian students then were more likely than White students to display advanced science achievement by fifth grade (i.e., 16% versus 13%, respectively).
I wonder how much familial + social pressures played into this? i.e. "The Model Minority"
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operationalized consistently
Good way to say "we defined this as..."
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We used White, non-Hispanic students as the reference group
Are they saying this was the baseline they used to compare? As in, they just assumed it was the standard, or this was the standard simply because of circumstances?
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Internalizing Problem Behaviors subscale consisted of four items (i.e., is the child lonely, sad, anxious, or displays low self-esteem). Problem behavior frequency was rated using a four-point response scale ranging from “never” to “very often.” Higher scores indicated that the behavior occurred more frequently. The internal consistency reliability coefficients for the externalizing and internalizing problem behaviors scales were .89 and .78, respectively (Tourangeau et al., 2019)
Very cool, as this aligns with the research I am interested in. Mirrors it in a way.
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he science achievement measure was designed to assess a student’s understanding about the physical, life, and Earth and space sciences as well as scientific inquiry. The mathe-matics achievement measure was designed to assess a stu-dent’s conceptual knowledge, procedural knowledge, and problem solving. The mathematics achievement measure included items on number sense, properties, and operations; measurement; geometry and spatial sense; data analysis, sta-tistics, and probability; and patterns, algebra, and functions. The reading achievement measure was designed to assess basic reading skills (e.g., print familiarity), vocabulary, and reading comprehension
It would have been nice to see data supporting these subgroupings.
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item response theory (IRT)
Also, it's cool that I will be using IRT. Used to determine if the distances from 1-2, 2-3, 3-4, & 4-5 are mathematically the same on a Likert-type scale.
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Emergent literacy (α = .57) was a standardized composite score of five items related to literacy activities. The first three items assessed the frequency of parents engaging in book reading and picture book reading with the child as well as the child reading outside school. The last two items reported the number of books that their child owned and how long the parent spent on reading to their child. We added standardized scores of the first three items and the last two items to obtain the standardized composite score
Cool to see this in practice. My research turns self-efficacy into several different subgroups in a similar fashion.
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dichotomous
Specifically noting only two potential outcomes for descriptive data. Coded as: Male = 0 & Female = 1 for example
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attrition
Can you measure, for example, all 1st graders in a district, then the following year, all 2nd graders, 3rd, 4th, etc... and just assume that with a large sample size, the data is apples to apples?
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We analyzed the public-use version of the nationally repre-sentative Early Childhood Longitudinal Study
Longitudinal and extant
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Hypothesis 1: Based on prior work examining the early onset and relative stability of racial or ethnic achievement disparities (e.g., Morgan et al., 2016; Von Hippel et al., 2018), we hypothesized that Black, Hispanic, or AINAPI students would be less likely than White students to dis-play advanced science or mathematics achievement during elementary school in unadjusted analyses. We expected the observed differences to be large (Morgan et al., 2016; Plucker & Peters, 2016; Rambo-Hernandez et al., 2019). We hypothesized that Black, Hispanic, or AINAPI stu-dents would be less likely than White students to display advanced levels of science or mathematics achievement by the end of kindergarten and throughout elementary school (Freyer & Levitt, 2004; Rambo-Hernandez et al., 2019; Von Hippel et al., 2018).
This feels like a strong hypothesis that was well written.
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Use of universal screen-ing using standardized measures
But also, we know students are already overtested, and even so, these tests are often heavily biased to favor the dominant group.
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Research Question 1: Are Black, Hispanic, or AINAPI students less likely than White students to display advanced science or mathematics achievement during elementary school? If so, how large are the observed gaps
This feels off. A big difference between research and evaluation is that research asks few, specific, and concise questions while evaluations go for as much bang for your buck. This first research question looks like it is stretched to thin by having two questions attached to it.
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Among antecedent, opportunity, and propensity factors, propensity factors most strongly predict student achievement
The cliche nature vs nurture argument comes to mind here...
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lead poisoning, environmental pollutants,
It will be microplastics for future generations.
Lead, asbestos, microplastics, it's all the same thing regirgitated for future generations.
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Black, Hispanic, and AINAPI students are more likely to experience concentrated poverty that results in fewer learn-ing opportunities and corresponding racial and ethnic achievement disparities during school because of histori-cally racialized policies and practices as well as ongoing residential and community segregation
Viscious cycle..
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(Fryer & Levitt, 2004; Henry et al., 2020; Morgan et al., 2016; National Assessment of Educational Progress [NAEP], 2015, 2020; Navarro et al., 2012; Reardon & Galindo, 2009; Von Hippel et al., 2018).
Clearly evident and well researched in the literature.
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2.6 percentage point increase in publica-tions, a 4.3 percentage point increase in citations, and a .03
2.6 and 4.3 feel signficant but 0.03 feels like a reach unless I am misunderstanding this.
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3% to 4%
Similarly as before with this I am wondering why this wouldn't be displayed as ~3.5%
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13% to 16%
I am wondering why they did not say 14% +/- 1.5%
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writingcommons.org writingcommons.org
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Researchers follow an iterative process to solve problems.
You repeat steps over and over again to improve the solutions each time like how we wrote our narrative essay.
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Part of becoming a skilled researcher is learning the epistemology of one’s discipline. Say
Its about how you think, question, and evaluate information for your own discipline.
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When scholarship is working right, publication of research results produces inquiry by other scholars, which in turn produces more research.
What does this mean exactly?
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Each discipline has its own methods for making or vetting knowledge claims
What disciplines has its own methods besides Psychology?
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On the other hand, doing research for other reasons than to answer a question can be half-hearted or sloppy.
I agree to this, sometimes when I read my research notes on something I don't have desire for it sounds not appealing.
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If students, for example, research a topic only because they are required to by an assignment, and not from a desire to learn anything in particular, the results will often be subpar.
I can agree on this because if I research something just cause I have to I won't be interested in learning and gather information about it.
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ict-user.demo.d-book.mobi ict-user.demo.d-book.mobi
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本の並び順を選ぶ
★/ゴミ箱等、ワンクリックのものは、確認画面を必ず表示する
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本の並び順を選ぶ
顔のアイコンはもう少し大きく
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本の並び順を選ぶ
読み終わった日＝追加した日？
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ict-user.demo.d-book.mobi ict-user.demo.d-book.mobi
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読書記録
読書記録は、オフライン時はできない。
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読書記録
読書記録は自動で入れるか？ 読書記録の削除を可能とすること
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ふうちゃんの本棚
削除したら、キャッシュからもクリアする。
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ふうちゃんの本棚
ダウンロードできる量は団体ごとに決定できるようにする。行政によってモデルが異なるため。キャッシュクリア方法はどうするか検討する。1冊100MB*20冊を想定。団体で1G程度を想定。冊数ではなくサイズで判断する。途中の変更はあり。少なくされる可能性もあり。次ダウンロードするときに、サイズチェックを行う。
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ふうちゃんの本棚
オンライン：ダウンロードした本＋お気に入り／オフライン：ダウンロードした本だけ
-
ふうちゃんの本棚
- オフラインのときは、ダウンロードした本だけが表示されます。読めるほんだけが表示されます。
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表示する本を変える
お願い本を追加する
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www.planalto.gov.br www.planalto.gov.br
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lei
- Depende de <u>lei</u> do ente que instituiu o tributo dispor sobre compensação de créditos tributários vencidos e vincendos
- Logo, é possível constatar que a compensação não é um direito subjetivo pleno, tendo em vista que depende de previsão e regulamentação legal para que possa ser efetivo.
- Com isso, a lei pode optar por 2 sistemáticas: a) prevê no texto legal as condições e garantias para a compensação; b) atribuir à autoridade administrativa a competência para estipular garantias e condições para compensação.
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churchofjesuschrist.sharepoint.com churchofjesuschrist.sharepoint.com
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Help missionaries plan the invitation based on the needs and progress of the person.
What needs does this person have that the Savior can fill through the baptismal covenant? How can you emphasize the Savior's power during your teaching?
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Invite missionaries to practice extending the invitation.
What promptings did you have from the Spirit as you were practicing this principle? How did you, or how can you, apply that into your practice?
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Demonstrate what this invitation might look like.
When did you feel the Spirit most strongly during that demonstration? What is the Spirit prompting you to do to apply that into your practice?
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Discuss the needs of the person missionaries will be inviting
What needs does this person have that the Savior can fill? How can they experience this through attending church?
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www.planalto.gov.br www.planalto.gov.br
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Fundo Nacional de Desenvolvimento Regional
1) Criado, através da EC 132/2023, o FNDR (Fundo Nacional de Desenvolvimento Regional).
2) Criado com o objetivo de reduzir as desigualdades <u>regionais</u> e <u>sociais</u>.
3) Os recursos do fundo são constituídos pela União e Estados/DF.
4) Servem-se para:
- Infraestrutura: obras, projetos e estudos;
- Potencial geração de emprego e renda (inclui-se subvenções);
- Ações de desenvolvimento tecnológico e científico.
5) Não previsão para que Municípios entreguem ou recebam recursos do FNDR
6) Não pode haver nenhuma restrição ao recebimento de recursos do FNDR.
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churchofjesuschrist.sharepoint.com churchofjesuschrist.sharepoint.com
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help missionaries encourage members to invite friends to sacrament meeting and help them get there.
What do you feel inspired to teach members to help them recognize the blessings they've received from coming to church?
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Help missionaries understand that these principles of love, share, and invite are for all members.
What are blessings you've seen from applying love, share, and invite before or on your mission? How do you think that this could apply to the members you teach?
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ict-user.demo.d-book.mobi ict-user.demo.d-book.mobiわいわい文庫2
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お願い本
残す
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算数
お願い本を一番上に置く
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ict-user.demo.d-book.mobi ict-user.demo.d-book.mobiわいわい文庫2
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読書記録 お願い本
読書記録ON／OFFは個人が設定する？団体で設定する？
-
お願い本
メニューに入れるか？本棚に入れるか？
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yieldcode.blog yieldcode.blog
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HTML, which is not a programming language
Sure it is:
It's not really a debate, HTML is a markup language [1], not a programming language
This is a false dichotomy, and untrue on two points (a) that HTML is "not a programming language", and (b) that the stance you have taken is not up for debate.
You're using the term "programming language" as shorthand to refer to the subset of languages more rigorously referred to as Turing-complete general-purpose programming languages.* There are programming languages outside this subset that no less have set membership with the larger "programming language" superset.
A programming language is a programming language in the sense that they have come to exist with the advent of the stored program computer. Though HTML and other markup languages are not** Turing-complete general-purpose programming languages, they are used every bit as much to describe a stored program as a language you might encounter when opening a file containing G-code "instructions" for controlling a CNC machine.
* We had a similar (but not the same) silly recurring argument in the 90s where people, at a loss for words to accurately capture their thoughts and grasping at whatever came to mind, argued that there were two distinct classes: "programming languages" and "scripting languages"—a category error arising from the same phenomenon of mistaking loose, off-the-cuff shorthand for The Real Idea Behind the Thing That's Involved Here
** No overlooking the fact that HTML is a proper superset of CSS, a provably Turing-complete (though not general-purpose) programming language—and JS, which is, of course, a true general-purpose programming language
(Originally drafted in response to https://news.ycombinator.com/item?id=46747778)
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accessmedicine.mhmedical.com accessmedicine.mhmedical.com
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Healing responses may include turning to music, art, religion, literature, nature, humor, or psychotherapy for solace and understanding. Spiritual questions of purpose and meaning in life become more immediate in the face of impending death.
.
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Under the Medicare Hospice Benefit, hospices provide bereavement support for at least a year to families of patients they have served. They also provide bereavement services to partners and close friends. Often, hospices provide this support to people in their community even if the death did not occur with hospice care.
.
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Physicians and nurses may want to call in clergy and social workers; each may have something to offer a family that is trying to integrate the shock and loss.
.
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If patients have lost the capacity to express their wishes and family members are in conflict about a certain plan, it is best to focus on what the patient would have wanted, applying the ethical principle of substituted judgment.
.
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The clinician needs to communicate clearly with the family members regarding plans for care, prognosis, complications, and who will make decisions should the patient be unable.
.
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The search for love, a connection to others, and a sense of meaning are essential in helping patients through the dying process.
.
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CASE ILLUSTRATION 9 A 64-year-old veterinarian, Richard, develops headaches so severe that he can no longer carry on his surgical practice.
.
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Guidelines for assisted suicide have been published, and clinicians confronted with a reasonable request to end life should refer to these, as well as to colleagues experienced in palliative care, for help. In almost all cases, legally permissible and clinically preferable alternatives can be found.
.
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A patient’s request to hasten death should be explored in detail. At first, it should be considered a cry for help. It may represent the wish to escape from depression, anxiety, uncontrolled physical pain, shame of dependency, and other psychosocial issues.
.
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CASE ILLUSTRATION 8 Sara, a bedridden 84-year-old woman with end-stage congestive heart failure, is seen on rounds.
.
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In assisted suicide, the physician provides the means (such as a prescription for barbiturates) at the request of the patient, but the patient must eventually take (or not take) the potentially lethal medication by his or her own hand.
.
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Voluntary active euthanasia is the act of intentionally intervening to cause the patient’s death, at the explicit request of, and with the full informed consent of, the competent patient.
.
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Table 42-2.Last resort interventions: definitions.
.
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Withdrawing life-sustaining but burdensome treatments, even though the withdrawal leads to death, is also an accepted part of practice based on the patient’s right to bodily integrity.
.
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CASE ILLUSTRATION 7 Marvin is a 63-year-old man with amyotrophic lateral sclerosis who has been on a respirator at home for one year.
.
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Patients who recover from delirium and coma sometimes report experiences that range from nightmarish, terrifying visions, on the one hand, to very pleasant out-of-body travel or visions of light and angelic beings on the other. Some may not be able to remember anything about the experience. Occasionally, the disorientation becomes profound and the sense of the world is lost. ++
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CASE ILLUSTRATION 6 Caleb, a 101-year-old rugged dairy farmer, has become partly deaf and then blind in the last 5 years of his life but remains alert and communicative.
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Patients have the right to forgo therapies such as intravenous fluids, nasogastric feeding, and supplemental oxygen, among others. Documentation of these choices is vital if the patient does not wish to undergo treatments and can be done on the MOLST form.
.
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The notion that being resuscitated from cardiopulmonary arrest will not add appreciably to the quality and/or quantity of life is an open acknowledgment that death might be near—and that reversing the dying process is not within the power of medicine.
.
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The “do-not-resuscitate” (DNR) order refers to the withholding of CPR, specifically closed-chest cardiac massage, defibrillation, and artificially supplied respiratory support. For most patients with a terminal disease, CPR is ineffective, and its harshness makes it a cruel, expensive, technological death ritual. Many studies have shown that CPR provides no increase in out-of-hospital survival for patients with progressive multisystem disease, particularly patients with advanced cancers and renal failure.
.
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Advance directives are formal documents that direct health care decisions should patients lose the capacity to speak for themselves in the future.
.
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There are two types of advance directives: living wills and health care proxies (also called durable powers of attorney). ++
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Invasive interventions that exceed the usual boundaries of hospice care but that extend meaningful life and improve quality of life are sometimes appropriate even within a hospice approach, as long as the patient consents. Remaining flexible in the face of changing, difficult situations and allowing the patient’s goals to guide the treatment as much as possible permit the clinician to hope along with the patient for a death with as little meaningless suffering as possible.
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CASE ILLUSTRATION 5 Rhea, a 64-year-old woman with metastatic breast cancer, is on high-dose long-acting morphine because of bone pain.
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CASE ILLUSTRATION 4 Max, a 63-year-old, recently retired, and previously healthy man, develops abdominal pain and is found to have widely metastasized colon cancer.
He is told to have 6-12 months to live. Max and his wife go to a different clinic for holistic treatment, but they ghost them after the visit. He goes back to the original clinic and recieved paalliative care before he passes.
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Providing ranges of survival times and allowing for outliers on either end is better than predicting an exact amount of time. (“The average person with your illness will live two to six months. It could be longer, and we will try to make that happen, but it could also be shorter, so you may want to make sure everything is prepared just in case things don’t go as we hope.”)
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CASE ILLUSTRATION 3 At 68 years old, Albert has severe end-stage emphysema from years of smoking, severe mitral regurgitation, congestive heart failure, cardiac arrhythmias, and alcoholism.
He bullied his wife for 40 years, does not want CPR or respirator care. He yells at healthcare professionals and family for him being sick, blames medication. Eventually reveals he's afraid to die, particularly being buried alive. He receives medication that helps him calm down but dies of rising CO2 later on
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For some, dying may be a time for personal growth, reflection, and meaning, but for others, personal factors and emotional reactions block an acceptance of death.
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CASE ILLUSTRATION 2 Carlos, a 70-year-old man, has been diagnosed with advanced hepatocellular carcinoma.
He's referred to hospice, responds very little to questions about death. He becomes bed bound, has routine visits to his home where he passes with his family.
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Progressive declines initially may be treated as another form of bad news, but they also potentially provide the opportunity for enhanced meaning and control in the dying process.
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Table 42-1.End-of-life issues to be discussed with patients.
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This sadness, which may be a way of preparing for death, has been called preparatory or anticipatory grief.
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Hospice programs provide comprehensive care to dying patients, with a multidisciplinary team of nurses, physicians, social workers, clergy, and volunteers. These programs, which accept only patients who are more likely than not to die in the next 6 months and are willing to forgo disease-directed therapies and hospitalizations, help patients and their families live as fully as possible by providing quality palliative care.
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The advantage of hospice programs is the expertise brought to techniques of palliative care by the multidisciplinary staff, as well as the added support for patient and family at home, including payment for palliative medications and medical equipment.
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Unlike Medicare-sponsored hospice programs, palliative care does not require patients to give up on aggressive treatment of their underlying disease, to accept a prognosis of less than 6 months, or to accept palliation as the central goal of therapy. Thus, it allows “hospice-like” treatments to be made available to those seriously ill patients who want to continue some or all disease-directed treatments.
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This “both/and” approach has been one of the most important conceptual breakthroughs for palliative care, for it allows quality-of-life issues to be addressed for all seriously ill patients, not just those who are referred to hospice.
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CASE ILLUSTRATION 1 Ella, a 71-year-old woman
Ella has a chest film and expects lung cancer. She has lung tumor and states that if she becomes too ill, she wants to stop treatment. She receives DNR and is referred to hospice where the main goal is to relieve her suffering.
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Figure 42-1. The place of palliative care in the course of illness.
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Enhancing the quality of life for those afflicted with serious chronic illness is the cornerstone of the rapidly developing specialty of palliative care.
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sourcebooks.fordham.edu sourcebooks.fordham.edu
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The consequent continuous impoverishment and exhaustion of the country,
Challenges the "progress" narrative by pointing out widespread poverty.
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Equal justice between man and man (sometimes vitiated by partiality to Europeans).
Acknowledges inequality within the imperial system despite claims of fairness.
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ict-user.demo.d-book.mobi ict-user.demo.d-book.mobiわいわい文庫7
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クリックすると
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クリックすると本が変わるよ
OPEN一覧に遷移するリンクが欲しい
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みんなが読める本
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海の生き物が出てくる絵本特集（財団のおすすめ本）
★再検討する
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重要なお知らせ システムメンテナンスのため、1月20日(月) 22:00〜23:00の間、サービスをご利用いただけません。 詳しくはこちら ↗︎
財団からの例外的なお知らせを想定している。→下の方でもいいのではないか？→上の方でOK。
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本を探す
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sourcebooks.fordham.edu sourcebooks.fordham.edu
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dmission of natives to high office must be effected by slow degrees
Macaulay supports limited inclusion, but still assumes Indians are not yet equal
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human.libretexts.org human.libretexts.org
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Bias Blind Spot: The tendency to see oneself as less biased than other people, or to be able to identify more cognitive biases in others than in oneself.
citation
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accessmedicine.mhmedical.com accessmedicine.mhmedical.com
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Patients with undetected trauma histories are often seen as “difficult” or “hostile,” frequently are late or miss appointments, are often in crisis, have poor self-care, and chronic pain. Such patients also may be labeled as “noncompliant,” with seemingly intractable health behavior problems.
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When trauma-focused psychotherapy is not available, national guidelines recommend pharmacotherapy, in particular sertraline, paroxetine, fluoxetine, or venlafaxine as first-line monotherapies.
Pharmacology
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In addition to the misuse of substances, another common comorbidity of PTSD is insomnia.
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Chronic pain, smoking, and obesity are also common comorbidities with PTSD.
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Other primary prevention strategies for primary care practices include support for new parents, support for home visiting programs, and universal preschool options, and firearm access reduction.
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In addition to risk reduction strategies, characteristics that promote resilience in survivors such as self-esteem, trust, humor, internal locus of control, secure attachments, and social relationships, as well as a personal sense of safety, religious affiliation, strong adult role models, and use of existing resources can be reinforced by primary care clinicians.
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Table 41-3.First steps to trauma-informed primary care.
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Unlike recent trauma, disclosures of past trauma do not require an immediate intervention. Rather, clinicians can express empathy (“I’m so sorry that happened to you. You didn’t deserve that”) and provide information about the availability of services to help cope with and heal from past trauma (“I am available to talk more with you about that.
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An appropriate response to recent IPV affirms that the patient does not deserve to be treated in this way and expresses concern for his/her safety. It also typically also includes a “warm handoff” to a domestic violence agency by telephone and/or to an onsite psychosocial team member who can construct a safety plan; lethality assessment, referrals for safe housing, legal, police, and other community resources; individual and/or group therapy; and peer support.
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Figure 41-1. Trauma-informed health care.
pic
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PTSD symptoms are grouped into four distinct clusters: re-experiencing the trauma (memories, nightmares, flashbacks), avoidance (emotional/cognitive vs. situational), negative changes in thinking/mood (not remembering aspects of the trauma, changes in beliefs about self/others/the world, self/other-oriented blame, persistent negative emotions, anhedonia, isolation, difficulty experiencing positive emotions), and arousal (sleep disturbances, irritability/anger outbursts, exaggerated startle, hypervigilance, attentional disruption, self-destructive behavior).
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When referrals are not available for your patients, primary care clinicians can be reasonably confident in their diagnosis of posttraumatic symptomatology and need for trauma-focused treatment referral when a patient:
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A score of 3 or more on the PC-PTSD-5 confers a high likelihood of trauma-related psychological distress and/or PTSD.
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Table 41-2.The Primary Care PTSD Screen for DSM-5.
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The most common forms of posttraumatic psychopathology include acute stress disorder (ASD) and posttraumatic stress disorder (PTSD).
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Patients with trauma exposure commonly present to primary care and other settings with seemingly unrelated acute or chronic physical and mental health conditions at much higher rates than patients without trauma exposure.
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Table 41-1.Four steps to inquire about trauma.
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Techniques described by Dr. Leigh Kimberg as the “Four C’s” can help prepare you to inquire about, and respond to, recent or past trauma:
Four C's
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Examples of patient education include: posters and flyers in the waiting area, brief informational pamphlets given to patients when taking their vital signs, and invite conversations as part of routine practice and/or when trauma-related conditions are discussed.
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Demographic factors such as female gender, age, socioeconomic status, and African American race often are thought of as nonmodifiable risk factors, but it is increasingly clear that societal response to race, gender, or age, and the resultant chronic stress, may create the actual risk in these populations.
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More than one-third of U.S. women experience stalking, physical violence, and/or rape from an intimate partner during their lifetimes. One in five men experiences sexual violence in their lifetimes.
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Individuals who reported four or more ACE categories had 2 times the rates of lung and liver disease, 3 times the rate of depression, 3 times the rate of alcoholism, 11 times the rate of intravenous drug use, and 14 times the rate of attempting suicide than those who reported ACE scores of 0.
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The study revealed a strong dose–response relationship between childhood trauma and adult heart, lung, and liver disease; depression; substance abuse; obesity; diabetes; sexually transmitted infection risk; and intimate partner violence (IPV).
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Notably, 25% of women and 16% of men reported having experienced childhood sexual abuse
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The Substance Abuse and Mental Health Services Administration (SAMHSA) defines trauma as “an event, series of events, or set of circumstances that is experienced by an individual as physically or emotionally harmful or threatening and that has lasting adverse effects.”
Trauma definition
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moodle.smith.edu moodle.smith.edu
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consumer studies continue to find that working-class, middle-class, andsub-working-class populations of color purchase conspicuous luxury goods,such as jewelry, cars, and clothing, at a higher rate than white populationsof the same socioeconomic groups
aspirational :(
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“bi directional” orientation of the “quare studies
lmao what
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unjournal-workshop.netlify.app unjournal-workshop.netlify.app
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uld the resulting adjustments change the cost-effectiven
Adjust this to 'meaningfully change' (as defined in the 'resolution criteria')
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WELLBY is a reasonably useful measure in this context
Clarify: the WELLBY with linear aggregation as in the definition above
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Given the available collected data [...], how should [funders] measure the impact on wellbeing? [...] What measures of well-being should charities, NGOs, and RCTs collect for impact analysis?
Let's split up the answer boxes within this question to ask separately about the best use of currently collected data for these cases, and also ask what data should be collected in the future.
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How reliable is the WELLBY measure [...] relative to other available measures in the 'wellbeing space'? How much insight is lost by using WELLBY and when will it steer us wrong?
signpost more that we are talking about the very simple use of the WELLBY measure
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More detailed questions on WELLBY reliability
Should be 'on WELLBY reliability and wellbeing measures' ... but also the folding box is still not ideal here -- better for this to link out to another page/subpage (open in new window)
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drive.google.com drive.google.com
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The ability to producenovice teachers who are resilient and persistent in the face of the complex problemsencountered in todayís schools is a goal to which every teacher education programaspires.
More than just educationally, but also in society. If educators are unable to model resiliency and persistence, the question arises: how will the next generation learn those qualities? It is our responsibility as educators to push the next generation to be greater than we are today.
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Both teachers spoke of their new positions as being an excellent fit for them
In my opinion, an educator's fit for the given role or school is not discussed nearly enough. If a person is not comfortable in some part of their occupational arena, the year can become a treacherous experience. A belief exists that one should be comfortable being uncomfortable. While that is aspirational, at some point one has to embrace something as comfortable if nothing else to have confidence that tomorrow is a new day.
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All three left theirpositions because of the perceived lack of administrative support and the failure ofthese schools to attend to the needs of their students.
Leadership in education is the secret sauce. In my time in the classroom, I’ve seen good teachers leave the classroom altogether because of questionable leadership. With that said, I’ve seen people who may not have been at the top of their class in education be brought under the umbrella of great leaders and have their entire perspective changed.
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Chandraís desire to continue teaching at this school despite the overwhelmingchallenges she faced might have to do with a strong sense of personal mission, whichwas linked to her twin sisterís work as a volunteer with homeless women as well asher family ethos
Chandra’s experiences are heartbreaking. She is the type of fighter that needs to be in education. Chandra’s lack of behavioral management is tough because she wants to give back so badly that she closes her eyes to problematic behaviors and the methods needed to fix them. She is the type of person who could potentially figure it out with time or when paired with a disciplinarian co-teacher. She also sounds like the type of person who could burn out very quickly. She could really go either way. In my opinion she has to find her niche’ and exhaust all options to accentuate those to her advantage. It may turn into a situatuation where she has to fake it till she makes it.
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Sally noted that one day of her teacher induction program was very goodbecause she got to share a bad situation she had with a student with her mentor group
Everyone loves success stories, but humbling dialogues with your mentor or other educators about reflecting on negative endeavors are where true growth arises.
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s3.amazonaws.com s3.amazonaws.com
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Building an Archives 139Then exactly what are we docubuildings?); the architect (likewisinstitutional context in which mworks departments; the many othence the architect's activities; theultimately, the ideal of architectfunction of architecture is, in shnumerous and varied, and the recgenerated b
While reading this article, I was impressed by the choice of an architect as a professional stand-in for appraisal theory and archival appraisal. Terry Cook could’ve picked any profession really but an architect is such a great choice in relation to macro-appraisal because of how broad an architects social and physical dynamics and interactions can be and also how varied the purpose of a architect’s design can be. It really seems like the perfect choice for this subject and I kind of got hung up in the second part of this article trying to think of a comparable or better example that wouldn’t necessarily overlap with an architect directly. A novelist? Some sort of mass transit (commercial plane, train, bus, etc.) designer? It’s tough to come up with a topic that suits this subject as well as an architect.
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Local file Local file
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landrecognition
land recognition or acknowledgement: - sdsu's attempt at land acknowledgement - (sdsu could do more) - going beyond post-colonial to decolonization
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pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
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NF1 Loss Promotes EGFR Activation and Confers Sensitivity to EGFR Inhibition in NF1-Mutant Melanoma
[Paper-level Aggregated] PMCID: PMC12221223
Evidence Type(s): Oncogenic, Predictive
Justification: Oncogenic: The text describes C>T transitions as characteristic of UV-induced mutations in melanoma, which are well-established features of cutaneous melanoma, indicating a role in tumorigenesis. Predictive: The identification of specific mutations, such as C>T transitions, suggests potential pharmacological targets for treatment in NF1Mut melanomas, indicating a predictive aspect for therapeutic response.
Gene→Variant (gene-first): NF1(4763):C>T
Genes: NF1(4763)
Variants: C>T
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pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
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Biochemical analysis of EGFR exon20 insertion variants insASV and insSVD and their inhibitor sensitivity
[Paper-level Aggregated] PMCID: PMC11551396
Evidence Type(s): Oncogenic, Predictive, Functional
Justification: Oncogenic: The text indicates that the exon 20 insertion variants (insASV and insSVD) exhibit enhanced catalytic rates and lower Km values compared to WT EGFR, suggesting their role in promoting cancer through increased activity. Predictive: The study evaluates the sensitivity of various EGFR mutations, including L858R and exon 20 insertions, to different inhibitors, indicating that the presence of specific mutations can predict the effectiveness of targeted therapies. Functional: The biochemical analysis of the variants, including kinetic studies and enzyme assays, demonstrates their functional characteristics, such as catalytic efficiency and inhibitor sensitivity, which are critical for understanding their role in cancer biology.
Gene→Variant (gene-first): EGFR(1956):C797 EGFR(1956):T790 EGFR(1956):T790M EGFR(1956):V948R TXK(7294):Glu4 EGFR(1956):L858R EGFR(1956):N771insSVD
Genes: EGFR(1956) TXK(7294)
Variants: C797 T790 T790M V948R Glu4 L858R N771insSVD
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pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
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Efficacy and Safety of Taletrectinib in Chinese Patients With ROS1+ Non–Small Cell Lung Cancer: The Phase II TRUST-I Study
[Paper-level Aggregated] PMCID: PMC11272140
Evidence Type(s): Oncogenic, Prognostic, Functional
Justification: Oncogenic: The G2032R mutation is associated with acquired resistance to crizotinib and is shown to respond to taletrectinib, indicating its role in cancer progression. Prognostic: The response rates and progression-free survival data for patients with G2032R mutations suggest that this variant can provide prognostic information regarding treatment outcomes with taletrectinib. Functional: The text indicates that taletrectinib has activity against the G2032R mutation, suggesting that this variant has functional implications in the context of treatment response.
Gene→Variant (gene-first): ROS1(6098):G2032R NTRK1(4914):G2101A TXK(7294):L2026M TXK(7294):S1986F
Genes: ROS1(6098) NTRK1(4914) TXK(7294)
Variants: G2032R G2101A L2026M S1986F
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pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
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CHK1 inhibitor SRA737 is active in PARP inhibitor resistant and CCNE1 amplified ovarian cancer
[Paper-level Aggregated] PMCID: PMC11253285
Evidence Type(s): Oncogenic, Functional
Justification: Oncogenic: The text discusses the resistance mechanisms in tumor cells and the effects of specific treatments, indicating that the variants S3C and S4D may be involved in oncogenic processes related to PARPi resistance and tumor growth. Functional: The study assesses the functional impact of SRA737 and PARPi on cell growth and signaling pathways, demonstrating how these variants influence the response to treatment and cellular behavior.
Gene→Variant (gene-first): CHEK1(1111):S3C PARP1(142):S4D
Genes: CHEK1(1111) PARP1(142)
Variants: S3C S4D
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pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
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A deregulated HOX gene axis confers an epigenetic vulnerability in KRAS-mutant lung cancers
[Paper-level Aggregated] PMCID: PMC10805385
Evidence Type(s): Oncogenic, Predictive
Justification: Oncogenic: The text indicates that HOXC10 is overexpressed in KRAS-mutant tumors, specifically mentioning the KRAS G12C variant, which is known to be associated with oncogenic activity in cancer. Predictive: The mention of robust HOXC10 expression in a patient-derived xenograft model with the KRAS G12C variant suggests that HOXC10 expression may predict response to treatment with MEK/BET inhibitors, indicating its potential as a predictive biomarker.
Gene→Variant (gene-first): KRAS(3845):G12C TP53(7157):G245V
Genes: KRAS(3845) TP53(7157)
Variants: G12C G245V
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pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
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Anticancer Efficacy of KRASG12C Inhibitors Is Potentiated by PAK4 Inhibitor KPT9274 in Preclinical Models of KRASG12C-Mutant Pancreatic and Lung Cancers
[Paper-level Aggregated] PMCID: PMC10690049
Evidence Type(s): Oncogenic, Predictive, Functional
Justification: Oncogenic: The text discusses the KRAS G12C and G12D mutations in the context of cancer cell lines, indicating that these variants are associated with tumorigenic properties, particularly highlighting the specific response of KRASG12C to treatment. Predictive: The evidence suggests that the presence of the KRAS G12C mutation predicts a positive response to the drug combination of MRTX849 and KPT9274, as indicated by the synergistic growth inhibition observed in KRASG12C-mutant cell lines. Functional: The study demonstrates the functional impact of KRAS G12C and G12D mutations on cell growth and drug response, showing that KRASG12C-mutant cells are sensitive to specific inhibitors while KRASG12D-mutant cells are not.
Gene→Variant (gene-first): KRAS(3845):G12C KRAS(3845):G12D
Genes: KRAS(3845)
Variants: G12C G12D
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pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
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Adavosertib Enhances Antitumor Activity of Trastuzumab Deruxtecan in HER2-Expressing Cancers
[Paper-level Aggregated] PMCID: PMC10618648
Evidence Type(s): Oncogenic, Functional
Justification: Oncogenic: The ERBB2 mutations V777L and G778A were identified in the tyrosine kinase domain, indicating their potential role in tumorigenesis. Functional: The T733I mutation was noted to be weakly transforming and associated with resistance to lapatinib, suggesting a functional impact on the behavior of the cancer cells.
Gene→Variant (gene-first): ERBB2(2064):G778A ERBB2(2064):V777L ERBB2(2064):T733I
Genes: ERBB2(2064)
Variants: G778A V777L T733I
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pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
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Breast cancer mutations HER2V777L and PIK3CAH1047R activate the p21-CDK4/6 –Cyclin D1 axis driving tumorigenesis and drug resistance
[Paper-level Aggregated] PMCID: PMC10527017
Evidence Type(s): Oncogenic, Functional, Predictive, Prognostic
Justification: Oncogenic: The HER2V777L and PIK3CAH1047R mutations are described as activating mutations that promote tumor formation and aggressive cancer characteristics, indicating their role in oncogenesis. Functional: The study demonstrates that the combination of HER2V777L and PIK3CAH1047R mutations enhances cellular migration and invasion, which are functional properties associated with metastatic cancer. Predictive: The findings suggest that the presence of HER2V777L and PIK3CAH1047R mutations can predict the effectiveness of specific drug combinations, such as neratinib plus trastuzumab deruxtecan, in treating breast cancer. Prognostic: The study indicates that the co-occurrence of HER2 and PIK3CA mutations is associated with accelerated tumor growth and metastasis, which can serve as a prognostic indicator for disease progression in breast cancer patients.
Gene→Variant (gene-first): ERBB2(2064):G776insYVMA ERBB2(2064):V777L PIK3CA(5290):H1047R
Genes: ERBB2(2064) PIK3CA(5290)
Variants: G776insYVMA V777L H1047R
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pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
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Osimertinib and selpercatinib efficacy, safety, and resistance in a multicenter, prospectively treated cohort of EGFR-mutant and RET fusion-positive lung cancers
[Paper-level Aggregated] PMCID: PMC10524391
Evidence Type(s): Oncogenic, Predictive, Functional, Prognostic
Justification: Oncogenic: The presence of mutations such as EGFR T790M, L858R, and RET G810S is associated with resistance to targeted therapies, indicating their role in tumor progression and oncogenic potential. Predictive: The identification of specific mutations like EGFR T790M and RET G810S can predict resistance to therapies such as osimertinib, guiding treatment decisions. Functional: The text discusses resistance mutations that affect the function of EGFR and RET kinases, indicating their functional impact on therapeutic engagement and resistance mechanisms. Prognostic: The presence of mutations such as BRAF V600E and KRAS G12S, along with the response rates to treatment, suggests that these mutations may have prognostic implications for patient outcomes.
Gene→Variant (gene-first): EGFR(1956):C797S KRAS(3845):G12S RET(5979):G810S EGFR(1956):T790M BRAF(673):V600E RET(5979):V804E RET(5979):V804M RET(5979):V804M/E EGFR(1956):L747S EGFR(1956):L858R
Genes: EGFR(1956) KRAS(3845) RET(5979) BRAF(673)
Variants: C797S G12S G810S T790M V600E V804E V804M V804M/E L747S L858R
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pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
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Functional and Clinical Characterization of Variants of Uncertain Significance Identifies a Hotspot for Inactivating Missense Variants in RAD51C
[Paper-level Aggregated] PMCID: PMC10390864
Evidence Type(s): Functional, Oncogenic, Predictive, Prognostic
Justification: Functional: The study assessed the influence of various RAD51C missense mutations on HDR DNA repair activity, categorizing them as deleterious, hypomorphic, or neutral based on their effects on HDR scores, indicating their functional impact on DNA repair mechanisms. Oncogenic: The loss of RAD51C function promotes HR deficiency and sensitizes cells to cisplatin and olaparib, suggesting that variants affecting RAD51C function may contribute to oncogenic processes by impairing DNA repair and influencing drug sensitivity in cancer cells. Predictive: The study evaluated the sensitivity of cells with different RAD51C variants to cisplatin and olaparib, indicating that specific variants can predict responses to these drugs, which is crucial for therapeutic decision-making in cancer treatment. Prognostic: The correlation between RAD51C variant status and drug response (IC50 values) suggests that these variants may serve as prognostic markers for treatment outcomes in patients receiving cisplatin or olaparib.
Gene→Variant (gene-first): RAD51C(5889):16 A RAD51C(5889):C135Y RAD51C(5889):E94K RAD51C(5889):G130R RAD51C(5889):G302V RAD51C(5889):K131 RAD51C(5889):L138F RAD51C(5889):P21S RAD51C(5889):Q133E RAD51C(5889):R168 RAD51C(5889):R168G RAD51C(5889):R312 RAD51C(5889):R312W RAD51C(5889):T132I RAD51C(5889):T132R RAD51D(5892):T86I RAD51C(5889):V140E RAD51C(5889):p.Cys135Tyr RAD51C(5889):p.Thr132Ile RAD51C(5889):p.Val140Glu RAD51C(5889):A126T RAD51C(5889):D159N RAD51C(5889):G125V RAD51C(5889):G153D RAD51C(5889):G264S RAD51C(5889):G264V RAD51C(5889):G3R RAD51C(5889):L219S RAD51C(5889):Q143R RAD51C(5889):R214C RAD51C(5889):R258H RAD51C(5889):R366Q RAD51C(5889):T287A RAD51C(5889):V169A RAD51C(5889):p.Arg214Cys RAD51C(5889):p.Arg258His RAD51C(5889):p.Arg312Trp RAD51C(5889):p.Arg366Gln RAD51C(5889):p.Asp159Asn RAD51C(5889):p.Gln143Arg RAD51C(5889):p.Gly125Val RAD51C(5889):p.Gly153Asp RAD51C(5889):p.Gly264Ser RAD51C(5889):p.Gly264Val RAD51C(5889):p.Gly3Arg RAD51C(5889):p.Leu219Ser RAD51C(5889):p.Thr287Ala RAD51C(5889):p.Val169Ala RAD51C(5889):D109Y RAD51C(5889):G162E RAD51C(5889):L27P RAD51C(5889):S163R RAD51C(5889):T336P RAD51C(5889):p.Gly162Glu RAD51C(5889):p.Ser163Arg RAD51C(5889):p.Thr336Pro RAD51D(5892):p.Thr86Ile RAD51C(5889):A155E RAD51C(5889):C147Y RAD51(5888):D108G RAD51C(5889):D159Y RAD51C(5889):G306R RAD51C(5889):p.Ala155Glu RAD51(5888):p.Asp108Gly RAD51C(5889):p.Asp109Tyr RAD51C(5889):p.Asp159Tyr RAD51C(5889):p.Cys147Tyr RAD51C(5889):p.Gly306Arg RAD51C(5889):p.Pro21Ser RAD51C(5889):p.Glu94Lys RAD51C(5889):K131I
Genes: RAD51C(5889) RAD51D(5892) RAD51(5888)
Variants: 16 A C135Y E94K G130R G302V K131 L138F P21S Q133E R168 R168G R312 R312W T132I T132R T86I V140E p.Cys135Tyr p.Thr132Ile p.Val140Glu A126T D159N G125V G153D G264S G264V G3R L219S Q143R R214C R258H R366Q T287A V169A p.Arg214Cys p.Arg258His p.Arg312Trp p.Arg366Gln p.Asp159Asn p.Gln143Arg p.Gly125Val p.Gly153Asp p.Gly264Ser p.Gly264Val p.Gly3Arg p.Leu219Ser p.Thr287Ala p.Val169Ala D109Y G162E L27P S163R T336P p.Gly162Glu p.Ser163Arg p.Thr336Pro p.Thr86Ile A155E C147Y D108G D159Y G306R p.Ala155Glu p.Asp108Gly p.Asp109Tyr p.Asp159Tyr p.Cys147Tyr p.Gly306Arg p.Pro21Ser p.Glu94Lys K131I
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pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
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Repotrectinib exhibits potent anti-tumor activity in treatment-naive and solvent-front-mutant ROS1-rearranged non-small cell lung cancer
[Paper-level Aggregated] PMCID: PMC10283448
Evidence Type(s): Oncogenic, Functional
Justification: Oncogenic: The presence of the ROS1-G2032R mutation is associated with crizotinib resistance in lung cancer, indicating its role in tumor progression and treatment failure. Functional: The study investigates the functional impact of various mutations, including E253Q, H178Q, H179Y, H555R, R143Q, and E171G, in the context of acquired resistance to repotrectinib, suggesting their potential roles in tumor biology and treatment response.
Gene→Variant (gene-first): CEBPA(1050):196_197insHP TP53(7157):E171G CCND3(896):E253Q ERBB2(2064):H178Q TP53(7157):H179Y RB1(5925):H555R ERBB2(2064):R143Q ROS1(6098):G2032R
Genes: CEBPA(1050) TP53(7157) CCND3(896) ERBB2(2064) RB1(5925) ROS1(6098)
Variants: 196_197insHP E171G E253Q H178Q H179Y H555R R143Q G2032R
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pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
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Activity of osimertinib in a patient with stage IV non-small cell lung cancer harboring HER2 exon 19, p.L755P mutation: case report
[Paper-level Aggregated] PMCID: PMC10183391
Evidence Type(s): Oncogenic, Predictive, Functional
Justification: Oncogenic: The text describes a patient with stage IV NSCLC harboring the HER2 exon 19 p.L755P mutation, which is associated with the disease and indicates a potential role in tumorigenesis. Predictive: The evidence suggests that the presence of the HER2 exon 19 p.L755P mutation may predict the efficacy of osimertinib treatment, as the patient achieved a partial response after treatment. Functional: The text indicates that osimertinib has demonstrated activity against the HER2 exon 19 p.L755P mutation in both pre-clinical studies and in the reported case, suggesting a functional impact of the mutation on treatment response.
Gene→Variant (gene-first): ERBB2(2064):c.2262_2264delinsTCC ERBB2(2064):p.(L755P) ERBB2(2064):p.L755P
Genes: ERBB2(2064)
Variants: c.2262_2264delinsTCC p.(L755P) p.L755P
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pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
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Targeting SWI/SNF ATPases in H3.3K27M diffuse intrinsic pontine gliomas
[Paper-level Aggregated] PMCID: PMC10161095
Evidence Type(s): Oncogenic, Functional
Justification: Oncogenic: The text describes how lysine-to-methionine mutations in histone H3 at lysine 27 (H3K27M) are associated with lethal childhood brain cancers, indicating that this variant contributes to tumorigenesis. Functional: The evidence shows that H3K27M mutations alter chromatin remodeling and affect protein levels of the SWI/SNF complex, demonstrating a functional impact on cellular processes related to cancer.
Gene→Variant (gene-first): H3-3B(3021):lysine 27 PBRM1(55193):lysine-to-methionine
Genes: H3-3B(3021) PBRM1(55193)
Variants: lysine 27 lysine-to-methionine
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pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
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Adjuvant Osimertinib for Resected EGFR-Mutated Stage IB-IIIA Non–Small-Cell Lung Cancer: Updated Results From the Phase III Randomized ADAURA Trial
[Paper-level Aggregated] PMCID: PMC10082285
Evidence Type(s): Predictive, Prognostic, Oncogenic
Justification: Predictive: The study involves patients with EGFR-mutated NSCLC, specifically mentioning the L858R variant, and evaluates the efficacy of osimertinib, indicating that the presence of this mutation can predict response to treatment. Prognostic: The study assesses disease-free survival (DFS) and overall survival in patients with the L858R variant, suggesting that this mutation may have implications for patient outcomes. Oncogenic: The mention of the L858R mutation in the context of EGFR-mutated NSCLC indicates its role in driving cancer development, classifying it as an oncogenic variant.
Gene→Variant (gene-first): EGFR(1956):L858R
Genes: EGFR(1956)
Variants: L858R
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pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
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Only SF3B1 Mutation involving K700E Independently Predicts Overall Survival in Myelodysplastic Syndromes
[Paper-level Aggregated] PMCID: PMC10015977
Evidence Type(s): Prognostic, Oncogenic, Functional
Justification: Prognostic: The text indicates that SF3B1 mutations, particularly K700E, are associated with a favorable prognosis in myelodysplastic syndromes (MDS), as evidenced by superior overall survival (OS) rates compared to SF3B1 wild-type patients. Oncogenic: The presence of SF3B1 mutations, including K700E and R625C, is implicated in the pathogenesis of myelodysplastic syndromes, suggesting their role as oncogenic drivers in this context. Functional: The analysis of splicing events and gene expression profiles between K700E and non-K700E SF3B1 mutations indicates functional differences that may impact disease characteristics and outcomes in MDS.
Gene→Variant (gene-first): SETBP1(26040):E862K SF3B1(23451):K700E SF3B1(23451):R625C SF3B1(23451):K666 SF3B1(23451):K700 SF3B1(23451):R625
Genes: SETBP1(26040) SF3B1(23451)
Variants: E862K K700E R625C K666 K700 R625
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pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
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A Phase Ib/II Trial of Combined BRAF and EGFR Inhibition in BRAF V600E Positive Metastatic Colorectal Cancer and Other Cancers: The EVICT (Erlotinib and Vemurafenib In Combination Trial) Study
[Paper-level Aggregated] PMCID: PMC10011885
Evidence Type(s): Oncogenic, Predictive, Functional
Justification: Oncogenic: The BRAF V600E mutation is identified as a significant alteration in metastatic colorectal cancer (mCRC) and is associated with the disease's progression and treatment resistance, indicating its role in oncogenesis. Predictive: Early ctDNA dynamics, including changes in BRAF V600E levels, were shown to predict treatment efficacy, with significant correlations between ctDNA levels and clinical outcomes such as progression-free survival (PFS) and overall survival (OS). Functional: The emergence of KRAS and NRAS mutations, including specific variants like KRAS Q61H and G13D, was linked to treatment resistance, suggesting that these mutations have functional implications in the context of therapy response.
Gene→Variant (gene-first): KDR(3791):A163G KRAS(3845):G12D KRAS(3845):G12N KRAS(3845):G13D KRAS(3845):Q61H NRAS(4893):Q61L SLTM(79811):R106H BRAF(673):V600E NRAS(4893):G13C
Genes: KDR(3791) KRAS(3845) NRAS(4893) SLTM(79811) BRAF(673)
Variants: A163G G12D G12N G13D Q61H Q61L R106H V600E G13C
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pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
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Efficacy of a Small-Molecule Inhibitor of KrasG12D in Immunocompetent Models of Pancreatic Cancer
[Paper-level Aggregated] PMCID: PMC9900321
Evidence Type(s): Oncogenic, Predictive
Justification: Oncogenic: The passage indicates that Gly-to-Asp mutations (KRASG12D) are commonly found in pancreatic ductal adenocarcinoma (PDAC), suggesting that this variant is associated with the development of cancer. Predictive: The text discusses the efficacy of a small-molecule KRASG12D inhibitor, MRTX1133, in models with KRASG12D mutations, indicating that the presence of this variant can predict the response to targeted therapy.
Gene→Variant (gene-first): KRAS(3845):Gly-to-Asp
Genes: KRAS(3845)
Variants: Gly-to-Asp
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pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
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Investigation of the prevalence and clinical implications of ERBB2 exon 16 skipping mutations in Chinese pan-cancer patients
[Paper-level Aggregated] PMCID: PMC9859631
Evidence Type(s): Oncogenic, Predictive, Functional
Justification: Oncogenic: The text describes various ERBB2 alterations, including ERBB2DeltaEx16 variants, which are suggested to play a role in resistance to targeted therapies, indicating their potential oncogenic nature. Predictive: The presence of specific mutations such as L858R, L755S, D769Y, and others in the context of treatment resistance suggests that these variants may predict response to therapies and disease progression. Functional: The identification of multiple ERBB2 alterations and their association with resistance mechanisms implies that these variants may have functional consequences on the gene's activity and its role in cancer progression.
Gene→Variant (gene-first): SLTM(79811):D1288N L1195I SLTM(79811):L1195V SLTM(79811):Y1230H ERBB2(2064):c.1899-936_1946+520del ERBB2(2064):D769Y ERBB2(2064):L755S EGFR(1956):L858R ERBB2(2064):c.1899-32_1909del ERBB2(2064):c.1899-2A>G ERBB2(2064):c.1899-880_1946+761del
Genes: SLTM(79811) ERBB2(2064) EGFR(1956)
Variants: D1288N L1195I L1195V Y1230H c.1899-936_1946+520del D769Y L755S L858R c.1899-32_1909del c.1899-2A>G c.1899-880_1946+761del
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pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
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Oncogenic mutations of PIK3CA lead to increased membrane recruitment driven by reorientation of the ABD, p85 and C-terminus
[Paper-level Aggregated] PMCID: PMC9837058
Evidence Type(s): Oncogenic, Functional, Predictive
Justification: Oncogenic: The text discusses multiple mutations (e.g., H1047R, G1049R, M1043L, N1068fs) that are frequently observed in cancer and describes their role in activating the PI3K pathway, indicating their oncogenic potential. Functional: The evidence describes how specific mutations (H1047R, G1049R, M1043L) lead to increased ATPase activity and enhanced membrane binding, demonstrating their functional impact on the PI3K enzyme activity. Predictive: The identification of specific mutations associated with increased membrane binding and PI3K activity suggests that these mutations could be used to predict the behavior of tumors and their response to therapies targeting the PI3K pathway.
Gene→Variant (gene-first): PIK3CA(5290):D915N PIK3CA(5290):E726K PIK3CA(5290):G1049R PIK3CA(5290):H1047R PIK3CA(5290):H1047R/L PIK3CA(5290):M1043L PIK3CA(5290):M1043L/I PIK3CA(5290):N1044K PIK3CA(5290):N1068fs PIK3CA(5290):M1043I/L PIK3CA(5290):G106V PIK3CA(5290):G118D PIK3CA(5290):N345K PIK3CA(5290):His1047 PIK3CA(5290):Met1043
Genes: PIK3CA(5290)
Variants: D915N E726K G1049R H1047R H1047R/L M1043L M1043L/I N1044K N1068fs M1043I/L G106V G118D N345K His1047 Met1043
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pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
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Multiplatform molecular analyses refine classification of gliomas arising in patients with neurofibromatosis type 1
[Paper-level Aggregated] PMCID: PMC9468105
Evidence Type(s): Predisposing, Oncogenic, Prognostic
Justification: Predisposing: The text describes gliomas arising in patients with a heterozygous germline mutation in NF1, indicating a genetic predisposition to tumor development. Oncogenic: The presence of somatic mutations and inactivation of the wild-type NF1 allele, along with the mention of specific mutations like p.R1276* and c.4110 + 2 T > G, supports the role of these variants in tumorigenesis. Prognostic: Kaplan-Meier survival analysis indicates that patients with NF1-associated gliomas have inferior outcomes, suggesting that the genetic alterations may have prognostic implications for patient survival.
Gene→Variant (gene-first): NF1(4763):c.4110 + 2 T > G NF1(4763):p.R1276* BRAF(673):p.V600E
Genes: NF1(4763) BRAF(673)
Variants: c.4110 + 2 T > G p.R1276* p.V600E
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pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
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RET fusions as primary oncogenic drivers and secondary acquired resistance to EGFR tyrosine kinase inhibitors in patients with non-small-cell lung cancer
[Paper-level Aggregated] PMCID: PMC9441062
Evidence Type(s): Oncogenic, Predictive, Prognostic
Justification: Oncogenic: The presence of EGFR mutations, including L858R and G719C/S768I, is associated with oncogenic activity in NSCLC, as they are known to drive tumorigenesis. Predictive: The identified second-site EGFR mutations, such as T790M and C797S/G, are recognized as predictive markers for resistance to EGFR-TKIs, indicating their role in treatment response. Prognostic: The study reports that certain genetic alterations, including bypass pathway mutations and co-mutations of TP53 and RB1, are associated with significantly shorter progression-free survival (PFS) in patients treated with EGFR-TKIs, highlighting their prognostic significance.
Gene→Variant (gene-first): EGFR(1956):C797S/G EGFR(1956):L718V/Q EGFR(1956):T790M EGFR(1956):G719C EGFR(1956):L858R EGFR(1956):S768I
Genes: EGFR(1956)
Variants: C797S/G L718V/Q T790M G719C L858R S768I
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pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
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Elongin C (ELOC/TCEB1)-associated von Hippel–Lindau disease
[Paper-level Aggregated] PMCID: PMC9402235
Evidence Type(s): Oncogenic, Diagnostic, Predictive
Justification: Oncogenic: The de novo pathogenic variant NM_005648.4(ELOC):c.236A>G (p.Tyr79Cys) is associated with VHL-independent renal tumorigenesis and has been previously described as a somatic variant in renal cell carcinomas (RCCs) without VHL inactivation, indicating its role in cancer development. Diagnostic: The identification of the NM_005648.4(ELOC):c.236A>G (p.Tyr79Cys) variant in a proband with VHL disease suggests that genetic testing for ELOC variants should be performed in individuals with suspected VHL disease, thereby aiding in diagnosis. Predictive: The presence of the NM_005648.4(ELOC):c.236A>G (p.Tyr79Cys) variant has implications for predicting the development of VHL disease and associated renal tumors, as it mimics the effects of pVHL deficiency on hypoxic signaling.
Gene→Variant (gene-first): HIF1A(3091):Tyr79 HIF1A(3091):Y79 HIF1A(3091):c.236A>G HIF1A(3091):p.Tyr79Cys ELOC(6921):c.261_272del RET(5979):c.274G>A ELOC(6921):c.311T>A KRT7(3855):c.74A>T KRT7(3855):p.Asp25Val VAV1(7409):p.Glu92Lys ELOC(6921):p.Leu104Gln ELOC(6921):p.Thr88_Pro91del
Genes: HIF1A(3091) ELOC(6921) RET(5979) KRT7(3855) VAV1(7409)
Variants: Tyr79 Y79 c.236A>G p.Tyr79Cys c.261_272del c.274G>A c.311T>A c.74A>T p.Asp25Val p.Glu92Lys p.Leu104Gln p.Thr88_Pro91del
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pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
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TPX-0131, a Potent CNS-penetrant, Next-generation Inhibitor of Wild-type ALK and ALK-resistant Mutations
[Paper-level Aggregated] PMCID: PMC9398166
Evidence Type(s): Oncogenic, Functional, Predictive, Prognostic
Justification: Oncogenic: The text discusses various ALK mutations, including G1202R and L1196M, which are described as major resistance mechanisms to ALK inhibitors, indicating their role in oncogenesis. Functional: The evidence describes the biochemical characterization of TPX-0131's potency against various ALK mutations, demonstrating its functional ability to inhibit both wild-type and mutant ALK, including resistance mutations. Predictive: The text indicates that TPX-0131 was designed to avoid resistance mutations and shows significant potency against them, suggesting its potential predictive value for treatment outcomes in patients with these mutations. Prognostic: The discussion of TPX-0131's efficacy against a range of ALK mutations, including those associated with resistance, implies that the presence of these mutations could influence treatment response and patient prognosis.
Gene→Variant (gene-first): ALK(238):C1156Y ALK(238):D1203N ALK(238):E1210K ALK(238):F1174C ALK(238):F1174L ALK(238):F1174S ALK(238):F1245C ALK(238):G1202 ALK(238):G1202R ALK(238):G1269A ALK(238):G1269S ALK(238):I1171N ALK(238):L1152P ALK(238):L1152R ALK(238):L1196M ALK(238):L1198F ALK(238):R1275Q ALK(238):S1206C ALK(238):S1206R ALK(238):T1151-L1152 insT ALK(238):T1151M ALK(238):V1180L ALK(238):I1171N/S ALK(238):L1204V ALK(238):S/T ALK(238):L1198
Genes: ALK(238)
Variants: C1156Y D1203N E1210K F1174C F1174L F1174S F1245C G1202 G1202R G1269A G1269S I1171N L1152P L1152R L1196M L1198F R1275Q S1206C S1206R T1151-L1152 insT T1151M V1180L I1171N/S L1204V S/T L1198
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pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
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A Novel Third-generation EGFR Tyrosine Kinase Inhibitor Abivertinib for EGFR T790M-mutant Non–Small Cell Lung Cancer: a Multicenter Phase I/II Study
[Paper-level Aggregated] PMCID: PMC9365372
Evidence Type(s): Predictive, Oncogenic
Justification: Predictive: The text indicates that patients with the EGFR T790M mutation showed responses to treatment with abivertinib, suggesting that the presence of this variant can predict treatment efficacy. Oncogenic: The T790M variant is associated with resistance to EGFR inhibitors and is implicated in the progression of non-small cell lung cancer (NSCLC), indicating its role in oncogenesis.
Gene→Variant (gene-first): EGFR(1956):T790M EGFR(1956):Thr790Met
Genes: EGFR(1956)
Variants: T790M Thr790Met
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pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
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Dabrafenib plus trametinib in patients with BRAF V600E-mutant anaplastic thyroid cancer: updated analysis from the phase II ROAR basket study
[Paper-level Aggregated] PMCID: PMC9338780
Evidence Type(s): Predictive, Oncogenic, Prognostic
Justification: Predictive: The text discusses the approval of dabrafenib plus trametinib for treatment of BRAF V600E-mutant anaplastic thyroid cancer, indicating that the presence of the V600E mutation predicts a positive response to this therapy. Oncogenic: The BRAF V600E mutation is implicated in the pathogenesis of anaplastic thyroid cancer, suggesting its role as an oncogenic driver in this disease. Prognostic: The updated results indicate that patients with BRAF V600E-mutant ATC experienced improved long-term survival with the treatment, suggesting that the mutation may serve as a prognostic marker for treatment outcomes.
Gene→Variant (gene-first): BRAF(673):V600E
Genes: BRAF(673)
Variants: V600E
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pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
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Poziotinib in Non–Small-Cell Lung Cancer Harboring HER2 Exon 20 Insertion Mutations After Prior Therapies: ZENITH20-2 Trial
[Paper-level Aggregated] PMCID: PMC8887939
Evidence Type(s): Prognostic, Oncogenic
Justification: Prognostic: The text provides data on overall response rates (ORR), median duration of response (DoR), and median progression-free survival (PFS) associated with specific mutations, indicating their potential to predict clinical outcomes. Oncogenic: The mention of specific mutations (A775dupYVMA and G776delinsVC) in the context of their frequency and associated clinical outcomes suggests a role in tumorigenesis.
Gene→Variant (gene-first): ERBB2(2064):A775dupYVMA ERBB2(2064):G776delinsVC
Genes: ERBB2(2064)
Variants: A775dupYVMA G776delinsVC
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pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov
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Integrated approach to functional analysis of an ERBB2 variant of unknown significance detected by a cancer gene panel test
[Paper-level Aggregated] PMCID: PMC8881279
Evidence Type(s): Oncogenic, Functional, Predictive
Justification: Oncogenic: The evidence indicates that the ERBB2 E401G variant enhances C-terminal phosphorylation and increases invasive capacity in cancer cells, suggesting its role in promoting oncogenic properties. Functional: The study demonstrates that ERBB2 E401G has functional properties similar to known activating mutations, affecting dimerization and phosphorylation mechanisms, which are critical for its role in signaling pathways. Predictive: The identification of the ERBB2 E401G variant as a variant of unknown significance (VUS) and its evaluation through computational tools predicting pathogenicity suggest its potential as a predictive marker for therapeutic targeting.
Gene→Variant (gene-first): MYC(4609):1157A > G FANCC(2176):E401G ERBB2(2064):D845A TP53(7157):E321G ERBB2(2064):S310F FANCC(2176):p.(E401G)
Genes: MYC(4609) FANCC(2176) ERBB2(2064) TP53(7157)
Variants: 1157A > G E401G D845A E321G S310F p.(E401G)
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