DOI: 10.1002/2211-5463.70186

Resource: (RRID:CVCL_0063)

Curator: @scibot

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DOI: 10.1002/2211-5463.70186

Resource: (RRID:CVCL_0013)

Curator: @scibot

SciCrunch record: RRID:CVCL_0013

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DOI: 10.1002/2211-5463.70186

Resource: (NIH-ARP Cat# 177-450, RRID:CVCL_0367)

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SciCrunch record: RRID:CVCL_0367

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DOI: 10.1002/2211-5463.70182

Resource: (RCB Cat# HPS0002, RRID:CVCL_B518)

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DOI: 10.1002/1878-0261.70199

Resource: (CCLV Cat# CCLV-RIE 1035, RRID:CVCL_0023)

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SciCrunch record: RRID:CVCL_0023

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DOI: 10.1002/1878-0261.70199

Resource: (RCB Cat# RCB0988, RRID:CVCL_0025)

Curator: @scibot

SciCrunch record: RRID:CVCL_0025

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DOI: 10.1002/1878-0261.70199

Resource: (TKG Cat# TKG 0205, RRID:CVCL_0027)

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DOI: 10.1002/1878-0261.70199

Resource: (RRID:CVCL_0090)

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SciCrunch record: RRID:CVCL_0090

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DOI: 10.1002/1878-0261.70199

Resource: (KCB Cat# KCB 200970YJ, RRID:CVCL_0336)

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DOI: 10.1002/1878-0261.70183

Resource: (ECACC Cat# 05092802, RRID:CVCL_1045)

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DOI: 10.1002/1878-0261.70183

Resource: (RRID:CVCL_4782)

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DOI: 10.1002/1873-3468.70270

Resource: (JCRB Cat# IFO50038, RRID:CVCL_0007)

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Resource: RRID:IMSR_RBRC06343

Curator: @AleksanderDrozdz

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DOI: 10.64898/2026.05.01.722324

Resource: RRID:IMSR_JAX:034711

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Resource: RRID:SCR_017858

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Resource: RRID:SCR_017799

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DOI: 10.1021/acsami.6c06870

Resource: RRID:SCR_025124

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Resource: RRID:AB_449517

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What is this?

Le Grand Défi de la Parentalité au XXIè Siècle : Analyse et Prévention du Burn-out Parental

Résumé Analytique

La parentalité contemporaine fait face à un défi inédit : la montée du burn-out parental. Si élever un enfant a toujours été associé au bonheur et à l'épanouissement, le contexte socioculturel du XXIe siècle exerce une pression sans précédent sur les parents. Le burn-out parental n'est pas un simple phénomène de mode, mais une réalité physiologique et psychologique caractérisée par un épuisement profond, une distanciation émotionnelle et une perte de plaisir dans le rôle parental.

Les recherches menées, notamment par Isabelle Roskam, démontrent que ce syndrome résulte d'un déséquilibre chronique entre les facteurs de stress et les ressources disponibles. Contrairement au burn-out professionnel, le burn-out parental ne permet aucune « démission », ce qui accroît la détresse des parents et peut mener à des conséquences graves : idées suicidaires, négligence ou violences envers l'enfant. La solution réside dans un rétablissement de l'équilibre de la « balance » parentale et une révision collective des injonctions à la perfection.

I. Le Contexte de la Parentalité Moderne : Pourquoi le XXIe Siècle ?

La parentalité est aujourd'hui investie d'une mission d'optimisation du développement de l'enfant qui n'existait pas pour les générations précédentes. Cinq facteurs majeurs expliquent cette pression accrue :

• L'évolution des rôles de genre : La fin de la séparation traditionnelle des tâches (mère aux soins, père aux ressources) impose aux deux parents d'exceller sur tous les fronts. Cela introduit également la nécessité de la « coparentalité », obligeant les parents à s'accorder sur des valeurs et des méthodes éducatives, ce qui peut être source de conflits.- La montée de l'individualisme : Les parents sont soumis à des injonctions contradictoires. Ils doivent s'épanouir personnellement tout en se consacrant entièrement aux besoins de l'enfant. Cette dualité génère une culpabilité constante.- Le concept de l'enfant « choisi » : Grâce à la contraception et à la procréation médicalement assistée, l'enfant est le fruit d'un projet de vie délibéré. Socialement, cela rend la plainte inacceptable : « Tu l'as tellement voulu, comment peux-tu ne pas être heureux ? ».- La révolution du statut de l'enfant : En un siècle, l'enfant est passé d'une force de travail à un sujet de droits (Convention de 1989). Le parent n'est plus celui qui impose son autorité, mais celui qui doit garantir l'épanouissement et les droits de l'enfant, sous la surveillance constante de l'État et de la société.- L'avènement des sciences psychologiques : La vulgarisation des théories de l'attachement et de la parentalité positive a créé des standards de « bonnes pratiques » extrêmement élevés. Les réseaux sociaux amplifient ces injonctions, laissant croire que la parentalité peut et doit être parfaite 24h/24.

II. Définition et Symptomatologie du Burn-out Parental

Le burn-out parental est un trouble du stress chronique qui se distingue de la dépression par son caractère strictement contextuel (lié au rôle de parent).

Les trois piliers du syndrome :

• L'épuisement émotionnel et physique : Le parent se sent vidé, incapable de faire face aux demandes quotidiennes des enfants. Cet épuisement est souvent flagrant le matin, avec une difficulté réelle à sortir du lit.- La distanciation émotionnelle : Pour se protéger, le parent met une barrière entre lui et ses enfants. Il assure le strict minimum (nourriture, hygiène, école) mais ne parvient plus à se connecter aux émotions de l'enfant. La parentalité devient « froide ».- La saturation et la perte de plaisir : Le parent ne trouve plus aucun épanouissement dans son rôle. Le mot « maman » ou « papa » peut même être perçu comme un signal de torture.

Un élément clé du diagnostic est le phénomène de contraste : le parent ne se reconnaît plus et son entourage constate un changement radical entre la personne investie qu'il était et le parent épuisé qu'il est devenu.

III. Le Modèle de la Balance : Stresseurs vs Ressources

Le burn-out survient lorsque les facteurs qui alourdissent la balance (stresseurs) l'emportent durablement sur les facteurs qui l'allègent (ressources).

| Type de facteur | Exemples de Stresseurs | Exemples de Ressources | | --- | --- | --- | | Sociodémographique | Famille nombreuse, monoparentalité, manque de revenus, logement exigu. | Aide financière, logement adapté, soutien logistique. | | Situationnel | Enfant malade ou à besoins spécifiques (autisme, troubles de l'apprentissage). | Relais de soins, aide spécialisée. | | Personnel | Perfectionnisme, manque d'empathie, antécédents de dépression. | Capacité à lâcher prise, auto-compassion, santé mentale stable. | | Relationnel / Familial | Conflits de coparentalité, manque de soutien du conjoint, inconsistance éducative. | Soutien du conjoint, partage équitable des tâches, routines familiales. |

Observation cruciale : Les recherches montrent que les stresseurs personnels (perfectionnisme) et relationnels (coparentalité) pèsent bien plus lourd dans le burn-out que les facteurs sociodémographiques (nombre d'enfants).

IV. Données Scientifiques et Prévalence

Preuves biologiques

L'étude du cortisol capillaire (prélevé dans les cheveux) confirme la réalité physique du burn-out. Les parents en burn-out présentent des taux de cortisol deux fois supérieurs à ceux des parents épanouis. Ces doses sont jugées « toxiques » et sont comparables, voire supérieures, à celles observées chez des victimes de violences conjugales ou des patients souffrant de douleurs chroniques.

Prévalence mondiale

Une étude menée dans 42 pays révèle que :

• Le burn-out parental touche 5 % à 8 % des parents dans les pays occidentaux (environ 200 000 en Belgique et 900 000 en France).- L'individualisme est le principal facteur expliquant la variation entre les pays. Les cultures collectivistes, où la solidarité est plus forte, sont moins touchées.- Le syndrome touche environ deux mères pour un père, partout dans le monde.

V. Conséquences du Burn-out

Le burn-out parental est particulièrement dangereux car il enferme le parent dans une situation sans issue apparente.

• Pour le parent : Problèmes psychosomatiques (migraines, mal de dos, troubles digestifs) et risques suicidaires élevés. Contrairement au travail, on ne peut pas démissionner de ses enfants, ce qui conduit certains parents à envisager la disparition ou le suicide comme seule porte de sortie.- Pour l'enfant : Le manque d'empathie lié à la distanciation émotionnelle lève les barrières inhibitrices. Cela mène à une flambée de la négligence (abandon des soins, des devoirs) et de la violence (verbale ou physique), même chez des parents qui n'avaient pas de profil maltraitant initialement.- Pour le couple : Augmentation des conflits, perte de cohésion et pensées adultères.

VI. Pistes de Solution et Prévention

Approche individuelle : Rétablir l'équilibre

Le traitement consiste à agir sur les quatre leviers de la balance :

• Éliminer les stresseurs non vitaux : S'autoriser à abandonner certaines activités extrascolaires ou à simplifier les repas (ex: raviolis plutôt que bio-maison).- Alléger le poids des stresseurs inévitables : Déléguer les devoirs d'un enfant en difficulté ou renégocier les exigences avec les enseignants.- Identifier et activer les ressources existantes : Oser demander de l'aide au conjoint ou à l'entourage.- Ajouter de nouvelles ressources : Favoriser la solidarité entre parents (ex: groupes d'échange de garde).

Approche collective et professionnelle

• La dyade parent-enfant : Les professionnels doivent cesser de se focaliser uniquement sur l'intérêt de l'enfant et prendre en compte le bien-être du parent. Si le parent s'étouffe, il ne peut plus aider l'enfant (métaphore du masque à oxygène).- La métaphore du phare : La parentalité positive doit être vue comme un phare qui donne une direction, et non comme une cible à atteindre absolument. S'en approcher trop près (vouloir être parfait) risque de briser le parent.- Lutter contre l'isolement : Recréer le « village » nécessaire pour élever un enfant. La parentalité est devenue une activité trop solitaire au XXIe siècle.

En conclusion, sortir du burn-out parental nécessite de briser le tabou de la « honte » et de la « culpabilité » pour permettre aux parents de dire leur souffrance et de retrouver, pas à pas, le plaisir d'être avec leurs enfants.

Some example of annotations

Case#: 13, M, Age of Onset: 2 y.o., Ethnicity: Indian.

CasePresentingHPOs: HP:0001954 (Recurrent fever), HP:0001876 (Pancytopenia)

CaseHPOFreeText: Proband has ALPS. Proband was reported to have borderline value for double negative TCRαβ+ T cells. Proband has normal range of B cells (484). Proband has normal IgG, IgA, IgM levels. Proband has normal range of NK cells.

CaseNotHPOs: N/A.

CaseNotHPOFreeText: N/A.

CasePreviousTesting: N/A.

CaseMethod1: N/A.

CaseMethod2: N/A.

CaseGenotypingMethod: Sanger sequencing and NGS targeting a customized panel of genes.

Variant: Variant 1: NM_005026.5:c.1726G>A. Variant 2: NM_005026.5:c.1394C>T.

ClinVar: Variant 1: 764550. Variant 2: 709503.

CAID: Variant 1: CA577314. Variant 2: CA577186.

gnomAD: Variant 1: Frequency: 0.00006758. Link: https://gnomad.broadinstitute.org/variant/1-9721163-G-A?dataset=gnomad_r4. Variant 2: Frequency: 0.0004085. Link: https://gnomad.broadinstitute.org/variant/1-9720166-C-T?dataset=gnomad_r4.

VariantEvidence: N/A.

CaseAddInfo: N/A.

CasePMIDs: N/A.

Case#:

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CaseNotHPOs:

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gnomAD:

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Case#: P01, Female, clinical diagnosis at the age of 45, genetic diagnosis at the age of 56, German, alive at the time of article's publication

DiseaseAssertion: Patient is classified as "Mildly affected" based on a CHAI score of 10.42%.

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs:N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: The percentage of transendocytosis using either CD80-GFP or CD80-mScarlet CHO cells was determined in eight LRBA-deficient patients. No difference in the percentage of transendocytosis was observed between CTLA4-variant carriers (GFP median=5.4%; mScarlet median= 49.8%) and LRBA-deficient patients (GFP median=9.9%; mScarlet median, 48.6%). However, significantly lower percentages of transendocytosis were observed in LRBA-deficient patients compared to healthy donors (HD) when using CD80-mScarlet CHO cells (median, 48.6% vs. 65.5% in HD) (Fig. ​(Fig.4e),4e). This difference was not observed with CD80-GFP CHO cells (patients median of 9.9% in patients vs. 13.9% in HD). In conclusion, the CTLA4 transendocytosis method using CD80-mScarlet CHO cells enables the functional verification of LRBA deficiency, but it cannot differentiate between LRBA deficiency and CTLA4 insufficiency.

GenotypingMethod: NGS and Sanger sequencing

PreviouslyPublished: N/A

Variant: NM_005214.5(CTLA4):c.109+1G>T

ClinVar ID: 161113

gnomAD: This variant was not found in any gnomAD version.

SupplementalData: Yes, all data regarding the patient was found in Table1.

Case#: P23, Female, German, 46 years old at the time of clinical diagnosis, 46.2 years old at the time of genetic diagnosis, alive at the time of publication

DiseaseAssertion: Severely affected based on a CHAI score of 15.56%

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs:N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: The percentage of transendocytosis using either CD80-GFP or CD80-mScarlet CHO cells was determined in eight LRBA-deficient patients. No difference in the percentage of transendocytosis was observed between CTLA4-variant carriers (GFP median=5.4%; mScarlet median= 49.8%) and LRBA-deficient patients (GFP median=9.9%; mScarlet median, 48.6%). However, significantly lower percentages of transendocytosis were observed in LRBA-deficient patients compared to healthy donors (HD) when using CD80-mScarlet CHO cells (median, 48.6% vs. 65.5% in HD) (Fig. ​(Fig.4e),4e). This difference was not observed with CD80-GFP CHO cells (patients median of 9.9% in patients vs. 13.9% in HD). In conclusion, the CTLA4 transendocytosis method using CD80-mScarlet CHO cells enables the functional verification of LRBA deficiency, but it cannot differentiate between LRBA deficiency and CTLA4 insufficiency.

GenotypingMethod: NGS and Sanger sequencing

PreviouslyPublished: N/A

Variant: ENST00000302823.7:c.511A>C

ClinVar ID:

CAID: CA350138977

gnomAD: not found

SupplementalData: Yes, all data regarding the patient was found in Table1.

Case#: P24, Female, 20 years old at the time of genetic diagnosis, alive at the time of publication

DiseaseAssertion: Unaffected based on a CHAI score of 6.67%

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs:N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: The percentage of transendocytosis using either CD80-GFP or CD80-mScarlet CHO cells was determined in eight LRBA-deficient patients. No difference in the percentage of transendocytosis was observed between CTLA4-variant carriers (GFP median=5.4%; mScarlet median= 49.8%) and LRBA-deficient patients (GFP median=9.9%; mScarlet median, 48.6%). However, significantly lower percentages of transendocytosis were observed in LRBA-deficient patients compared to healthy donors (HD) when using CD80-mScarlet CHO cells (median, 48.6% vs. 65.5% in HD) (Fig. ​(Fig.4e),4e). This difference was not observed with CD80-GFP CHO cells (patients median of 9.9% in patients vs. 13.9% in HD). In conclusion, the CTLA4 transendocytosis method using CD80-mScarlet CHO cells enables the functional verification of LRBA deficiency, but it cannot differentiate between LRBA deficiency and CTLA4 insufficiency.

GenotypingMethod: NGS and Sanger sequencing

PreviouslyPublished: N/A

Variant: NM_005214.5(CTLA4):c.515C>T (p.Ser172Leu)

ClinVar ID: 546887

gnomAD: 0.00001549 https://gnomad.broadinstitute.org/variant/2-203871435-C-T?dataset=gnomad_r4

SupplementalData: Yes, all data regarding the patient was found in Table1.

Case#: P25, male, German, 16 years old at the time of clinical diagnosis, 40.8 years old at the time of genetic diagnosis, alive at the time of publication

DiseaseAssertion: Severely affected based on a CHAI score of 43.75%

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs:N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: The percentage of transendocytosis using either CD80-GFP or CD80-mScarlet CHO cells was determined in eight LRBA-deficient patients. No difference in the percentage of transendocytosis was observed between CTLA4-variant carriers (GFP median=5.4%; mScarlet median= 49.8%) and LRBA-deficient patients (GFP median=9.9%; mScarlet median, 48.6%). However, significantly lower percentages of transendocytosis were observed in LRBA-deficient patients compared to healthy donors (HD) when using CD80-mScarlet CHO cells (median, 48.6% vs. 65.5% in HD) (Fig. ​(Fig.4e),4e). This difference was not observed with CD80-GFP CHO cells (patients median of 9.9% in patients vs. 13.9% in HD). In conclusion, the CTLA4 transendocytosis method using CD80-mScarlet CHO cells enables the functional verification of LRBA deficiency, but it cannot differentiate between LRBA deficiency and CTLA4 insufficiency.

GenotypingMethod: NGS and Sanger sequencing

PreviouslyPublished: N/A

Variant: ENST00000302823.7:c.536T>G

ClinVar ID:

CAID: CA350139037

gnomAD: not found

SupplementalData: Yes, all data regarding the patient was found in Table1.

Case#: P26, male, German, 9 years old at the time of clinical diagnosis, alive at the time of publication

DiseaseAssertion: Mildly affected based on a CHAI score of 10.42%

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs:N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: The percentage of transendocytosis using either CD80-GFP or CD80-mScarlet CHO cells was determined in eight LRBA-deficient patients. No difference in the percentage of transendocytosis was observed between CTLA4-variant carriers (GFP median=5.4%; mScarlet median= 49.8%) and LRBA-deficient patients (GFP median=9.9%; mScarlet median, 48.6%). However, significantly lower percentages of transendocytosis were observed in LRBA-deficient patients compared to healthy donors (HD) when using CD80-mScarlet CHO cells (median, 48.6% vs. 65.5% in HD) (Fig. ​(Fig.4e),4e). This difference was not observed with CD80-GFP CHO cells (patients median of 9.9% in patients vs. 13.9% in HD). In conclusion, the CTLA4 transendocytosis method using CD80-mScarlet CHO cells enables the functional verification of LRBA deficiency, but it cannot differentiate between LRBA deficiency and CTLA4 insufficiency.

GenotypingMethod: NGS and Sanger sequencing

PreviouslyPublished: N/A

Variant: NM_005214.5(CTLA4):c.619A>G (p.Thr207Ala)

ClinVar ID: 1307969

gnomAD: 0.00001177 https://gnomad.broadinstitute.org/variant/2-203872759-A-G?dataset=gnomad_r4

SupplementalData: Yes, all data regarding the patient was found in Table1.

Case#: P02, Female, the age of clinical and genetic diagnosis: Unknown, Finnish, alive at the time of article's publication

DiseaseAssertion: N/A

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs:N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: The percentage of transendocytosis using either CD80-GFP or CD80-mScarlet CHO cells was determined in eight LRBA-deficient patients. No difference in the percentage of transendocytosis was observed between CTLA4-variant carriers (GFP median=5.4%; mScarlet median= 49.8%) and LRBA-deficient patients (GFP median=9.9%; mScarlet median, 48.6%). However, significantly lower percentages of transendocytosis were observed in LRBA-deficient patients compared to healthy donors (HD) when using CD80-mScarlet CHO cells (median, 48.6% vs. 65.5% in HD) (Fig. ​(Fig.4e),4e). This difference was not observed with CD80-GFP CHO cells (patients median of 9.9% in patients vs. 13.9% in HD). In conclusion, the CTLA4 transendocytosis method using CD80-mScarlet CHO cells enables the functional verification of LRBA deficiency, but it cannot differentiate between LRBA deficiency and CTLA4 insufficiency.

GenotypingMethod: NGS and Sanger sequencing

PreviouslyPublished: N/A

Variant: NC_000002.12:g.203868053T>A

ClinVar ID:

CAID: CA350138070

gnomAD: not found in any gnomAD version.

SupplementalData: Yes, all data regarding the patient was found in Table1.

Case#: P03, Male, Age: N/A, ethnicity: N/A, Alive at the time of article's publication

DiseaseAssertion: N/A

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs:N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: The percentage of transendocytosis using either CD80-GFP or CD80-mScarlet CHO cells was determined in eight LRBA-deficient patients. No difference in the percentage of transendocytosis was observed between CTLA4-variant carriers (GFP median=5.4%; mScarlet median= 49.8%) and LRBA-deficient patients (GFP median=9.9%; mScarlet median, 48.6%). However, significantly lower percentages of transendocytosis were observed in LRBA-deficient patients compared to healthy donors (HD) when using CD80-mScarlet CHO cells (median, 48.6% vs. 65.5% in HD) (Fig. ​(Fig.4e),4e). This difference was not observed with CD80-GFP CHO cells (patients median of 9.9% in patients vs. 13.9% in HD). In conclusion, the CTLA4 transendocytosis method using CD80-mScarlet CHO cells enables the functional verification of LRBA deficiency, but it cannot differentiate between LRBA deficiency and CTLA4 insufficiency.

GenotypingMethod: NGS and Sanger sequencing

PreviouslyPublished: N/A

Variant: NM_005214.5(CTLA4):c.155G>A (p.Gly52Asp)

ClinVar ID: 871301

gnomAD: not found in any gnomAD version.

SupplementalData: Yes, all data regarding the patient was found in Table1.

Case#: P04, male, genetic diagnosis at the age of 71.4, ethnicity: N/A, Dead at the time of article's publication

DiseaseAssertion: N/A

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs:N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: The percentage of transendocytosis using either CD80-GFP or CD80-mScarlet CHO cells was determined in eight LRBA-deficient patients. No difference in the percentage of transendocytosis was observed between CTLA4-variant carriers (GFP median=5.4%; mScarlet median= 49.8%) and LRBA-deficient patients (GFP median=9.9%; mScarlet median, 48.6%). However, significantly lower percentages of transendocytosis were observed in LRBA-deficient patients compared to healthy donors (HD) when using CD80-mScarlet CHO cells (median, 48.6% vs. 65.5% in HD) (Fig. ​(Fig.4e),4e). This difference was not observed with CD80-GFP CHO cells (patients median of 9.9% in patients vs. 13.9% in HD). In conclusion, the CTLA4 transendocytosis method using CD80-mScarlet CHO cells enables the functional verification of LRBA deficiency, but it cannot differentiate between LRBA deficiency and CTLA4 insufficiency.

GenotypingMethod: NGS and Sanger sequencing

PreviouslyPublished: N/A

Variant: NM_005214.5(CTLA4):c.160G>A (p.Ala54Thr)

ClinVar ID: 430905

gnomAD: not found

SupplementalData: Yes, all data regarding the patient was found in Table1.

Case#: P05, Male, age: n/a, ethnicity:n/a, alive at the time of publication

DiseaseAssertion: N/A

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs:N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: The percentage of transendocytosis using either CD80-GFP or CD80-mScarlet CHO cells was determined in eight LRBA-deficient patients. No difference in the percentage of transendocytosis was observed between CTLA4-variant carriers (GFP median=5.4%; mScarlet median= 49.8%) and LRBA-deficient patients (GFP median=9.9%; mScarlet median, 48.6%). However, significantly lower percentages of transendocytosis were observed in LRBA-deficient patients compared to healthy donors (HD) when using CD80-mScarlet CHO cells (median, 48.6% vs. 65.5% in HD) (Fig. ​(Fig.4e),4e). This difference was not observed with CD80-GFP CHO cells (patients median of 9.9% in patients vs. 13.9% in HD). In conclusion, the CTLA4 transendocytosis method using CD80-mScarlet CHO cells enables the functional verification of LRBA deficiency, but it cannot differentiate between LRBA deficiency and CTLA4 insufficiency.

GenotypingMethod: NGS and Sanger sequencing

PreviouslyPublished: N/A

Variant: <br /> NM_005214.5(CTLA4):c.208C>T (p.Arg70Trp)

ClinVar ID: 161114

gnomAD: 6.195e-7 https://gnomad.broadinstitute.org/variant/2-203870684-C-T?dataset=gnomad_r4

SupplementalData: Yes, all data regarding the patient was found in Table1.

Case#: P06. Female, German, 52 years old at the time of clinical diagnosis, Alive at the time of publication

DiseaseAssertion: classified as "Severely affected" based on a CHAI score of 47.37%

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs:N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: The percentage of transendocytosis using either CD80-GFP or CD80-mScarlet CHO cells was determined in eight LRBA-deficient patients. No difference in the percentage of transendocytosis was observed between CTLA4-variant carriers (GFP median=5.4%; mScarlet median= 49.8%) and LRBA-deficient patients (GFP median=9.9%; mScarlet median, 48.6%). However, significantly lower percentages of transendocytosis were observed in LRBA-deficient patients compared to healthy donors (HD) when using CD80-mScarlet CHO cells (median, 48.6% vs. 65.5% in HD) (Fig. ​(Fig.4e),4e). This difference was not observed with CD80-GFP CHO cells (patients median of 9.9% in patients vs. 13.9% in HD). In conclusion, the CTLA4 transendocytosis method using CD80-mScarlet CHO cells enables the functional verification of LRBA deficiency, but it cannot differentiate between LRBA deficiency and CTLA4 insufficiency.

GenotypingMethod: NGS and Sanger sequencing

PreviouslyPublished: N/A

Variant: NM_005214.5(CTLA4):c.214A>C (p.Thr72Pro)

ClinVar ID: 546886

gnomAD: not found

SupplementalData: Yes, all data regarding the patient was found in Table1.

Case#: P07, Male, German, 18 years old at the time of clinical diagnosis and 24.2 years old at the time of genetic diagnosis, alive at the time of publication

DiseaseAssertion: Mildly affected based on a CHAI score of 17.65%

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs:N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: The percentage of transendocytosis using either CD80-GFP or CD80-mScarlet CHO cells was determined in eight LRBA-deficient patients. No difference in the percentage of transendocytosis was observed between CTLA4-variant carriers (GFP median=5.4%; mScarlet median= 49.8%) and LRBA-deficient patients (GFP median=9.9%; mScarlet median, 48.6%). However, significantly lower percentages of transendocytosis were observed in LRBA-deficient patients compared to healthy donors (HD) when using CD80-mScarlet CHO cells (median, 48.6% vs. 65.5% in HD) (Fig. ​(Fig.4e),4e). This difference was not observed with CD80-GFP CHO cells (patients median of 9.9% in patients vs. 13.9% in HD). In conclusion, the CTLA4 transendocytosis method using CD80-mScarlet CHO cells enables the functional verification of LRBA deficiency, but it cannot differentiate between LRBA deficiency and CTLA4 insufficiency.

GenotypingMethod: NGS and Sanger sequencing

PreviouslyPublished: N/A

Variant: <br /> NM_005214.5(CTLA4):c.224G>A (p.Arg75Gln)

ClinVar ID: 943305

gnomAD: 0.000008673

https://gnomad.broadinstitute.org/variant/2-203870700-G-A?dataset=gnomad_r4

SupplementalData: Yes, all data regarding the patient was found in Table1.

Case#: P08, Female, Canadian, age: n/a, alive at the time of publication

DiseaseAssertion: N/A

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs:N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: The percentage of transendocytosis using either CD80-GFP or CD80-mScarlet CHO cells was determined in eight LRBA-deficient patients. No difference in the percentage of transendocytosis was observed between CTLA4-variant carriers (GFP median=5.4%; mScarlet median= 49.8%) and LRBA-deficient patients (GFP median=9.9%; mScarlet median, 48.6%). However, significantly lower percentages of transendocytosis were observed in LRBA-deficient patients compared to healthy donors (HD) when using CD80-mScarlet CHO cells (median, 48.6% vs. 65.5% in HD) (Fig. ​(Fig.4e),4e). This difference was not observed with CD80-GFP CHO cells (patients median of 9.9% in patients vs. 13.9% in HD). In conclusion, the CTLA4 transendocytosis method using CD80-mScarlet CHO cells enables the functional verification of LRBA deficiency, but it cannot differentiate between LRBA deficiency and CTLA4 insufficiency.

GenotypingMethod: NGS and Sanger sequencing

PreviouslyPublished: N/A

Variant: NM_005214.5(CTLA4):c.257C>T (p.Ala86Val)

ClinVar ID: 661941

gnomAD: 0.00001859

https://gnomad.broadinstitute.org/variant/2-203870733-C-T?dataset=gnomad_r4

SupplementalData: Yes, all data regarding the patient was found in Table1.

Case#: P09, Male, age: n/a, ethnicity: n/a, alive at the time of publication

DiseaseAssertion: n/a

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs:N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: The percentage of transendocytosis using either CD80-GFP or CD80-mScarlet CHO cells was determined in eight LRBA-deficient patients. No difference in the percentage of transendocytosis was observed between CTLA4-variant carriers (GFP median=5.4%; mScarlet median= 49.8%) and LRBA-deficient patients (GFP median=9.9%; mScarlet median, 48.6%). However, significantly lower percentages of transendocytosis were observed in LRBA-deficient patients compared to healthy donors (HD) when using CD80-mScarlet CHO cells (median, 48.6% vs. 65.5% in HD) (Fig. ​(Fig.4e),4e). This difference was not observed with CD80-GFP CHO cells (patients median of 9.9% in patients vs. 13.9% in HD). In conclusion, the CTLA4 transendocytosis method using CD80-mScarlet CHO cells enables the functional verification of LRBA deficiency, but it cannot differentiate between LRBA deficiency and CTLA4 insufficiency.

GenotypingMethod: NGS and Sanger sequencing

PreviouslyPublished: N/A

Variant: NM_005214.5(CTLA4):c.265T>C (p.Tyr89His)

ClinVar ID: 1391402

gnomAD: 0.000003717 https://gnomad.broadinstitute.org/variant/2-203870741-T-C?dataset=gnomad_r4

SupplementalData: Yes, all data regarding the patient was found in Table1.

Case#: P10, Female, German, 24 years old at the time of clinical diagnosis, 25 years old at the time of genetic diagnosis, alive at the time of publication

DiseaseAssertion: Severely affected based on a CHAI score of 33.33%

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs:N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: The percentage of transendocytosis using either CD80-GFP or CD80-mScarlet CHO cells was determined in eight LRBA-deficient patients. No difference in the percentage of transendocytosis was observed between CTLA4-variant carriers (GFP median=5.4%; mScarlet median= 49.8%) and LRBA-deficient patients (GFP median=9.9%; mScarlet median, 48.6%). However, significantly lower percentages of transendocytosis were observed in LRBA-deficient patients compared to healthy donors (HD) when using CD80-mScarlet CHO cells (median, 48.6% vs. 65.5% in HD) (Fig. ​(Fig.4e),4e). This difference was not observed with CD80-GFP CHO cells (patients median of 9.9% in patients vs. 13.9% in HD). In conclusion, the CTLA4 transendocytosis method using CD80-mScarlet CHO cells enables the functional verification of LRBA deficiency, but it cannot differentiate between LRBA deficiency and CTLA4 insufficiency.

GenotypingMethod: NGS and Sanger sequencing

PreviouslyPublished: N/A

Variant: NM_005214.5(CTLA4):c.326G>A (p.Gly109Glu)

ClinVar ID: 542071

gnomAD: 0.0002354 https://gnomad.broadinstitute.org/variant/2-203870802-G-A?dataset=gnomad_r4

SupplementalData: Yes, all data regarding the patient was found in Table1.

Case#: P11, Female, German, age: n/a, alive at the time of publication

DiseaseAssertion: Severely affected based on a CHAI score of 18.75%

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs:N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: The percentage of transendocytosis using either CD80-GFP or CD80-mScarlet CHO cells was determined in eight LRBA-deficient patients. No difference in the percentage of transendocytosis was observed between CTLA4-variant carriers (GFP median=5.4%; mScarlet median= 49.8%) and LRBA-deficient patients (GFP median=9.9%; mScarlet median, 48.6%). However, significantly lower percentages of transendocytosis were observed in LRBA-deficient patients compared to healthy donors (HD) when using CD80-mScarlet CHO cells (median, 48.6% vs. 65.5% in HD) (Fig. ​(Fig.4e),4e). This difference was not observed with CD80-GFP CHO cells (patients median of 9.9% in patients vs. 13.9% in HD). In conclusion, the CTLA4 transendocytosis method using CD80-mScarlet CHO cells enables the functional verification of LRBA deficiency, but it cannot differentiate between LRBA deficiency and CTLA4 insufficiency.

GenotypingMethod: NGS and Sanger sequencing

PreviouslyPublished: N/A

Variant: NM_005214.5(CTLA4):c.326G>A (p.Gly109Glu)

ClinVar ID: 542071

gnomAD: 0.0002354 https://gnomad.broadinstitute.org/variant/2-203870802-G-A?dataset=gnomad_r4

SupplementalData: Yes, all data regarding the patient was found in Table1.

D=S-M Despair = Suffering without Meaning

21

Spend more time with friends and family, especially your kids and parents

1. Talk to kids every day
2. Play games with them
3. Help with school
4. Call parents/go over

That I have great-great grandchildren who still come visit. That I have students who remember me. That my husband is 110 next to me.

Everyday saints - everyday kindnesses

That they work together, so just one typel

Alfred's value.

I feel bad for Gen Alpha and kids going through grade school with no need to actually think, so much so that many of them can't even read.

This is my page note, fill:

To go through all the emotion and feeling like she did so much for you , this comment was very powerful.

I know its a cancer but what exactly is Ewing Sarcoma?

I think the effects of eating UPFs excessively makes you not want to eat them as much because they give you irritable systems that make you not enjoy eating.

-i 输入，-o 输出。

The GPU use in SSL.

it seems as if her brother began thinking he was to good for the family , or at least to educated to be around his family at this point.

I completely agree as there are more problems that other women face not just because they are women, but because they are not white..

I feel as though this sentence is empowering in a way that they do not understand their advantage, especially in todays society, even though they are women, in America I feel like they are put to a higher standard than other women, just because of their ethnicity and that leading to those white women to not understand anyone else's limitations due to not just their gender but their ethnicity.

Beautiful way of putting it.

I get what they mean, since its like I kind of don't know what exactly to write about or how to articulate what I wanna express in my writing, but also scared that if I don't do it, I have missed a great opportunity to show what kind of person I really am.

Period, this part made me feel like this is giving taking a bit of accountability and is very mature of them.

This highlighted both sides but I really like both of these quotes. For me the being loud and letting everyone one hear is something I wish I could do. I love seeing support for women's speech. And for the other with not faking it and being genuine is important and making sure your authentic voice is heard.

Any individual sentence that describes information designed to set the stage for the contribution of the paper.

Any individual sentence that describes information designed to set the stage for the contribution of the paper.

Any individual sentence that describes information designed to set the stage for the contribution of the paper.

Any individual sentence that describes information designed to set the stage for the contribution of the paper.

Any individual sentence that describes information designed to set the stage for the contribution of the paper.

An individual sentence describing the setting in which this work was done.

An individual sentence describing the setting in which this work was done.

An individual sentence describing the setting in which this work was done.

An individual sentence describing the setting in which this work was done.

An individual sentence describing the setting in which this work was done.

Assault requires (both): Defendant intends to cause the plaintiff to anticipate imminent, harmful contact to their person AND (2) Defendant's conduct caused them to anticipate such contact. (Defendant's ACTIONS caused them to think so.)

**What's intent?

Intent REQUIRES either: * Purpose (Desire) i.e. they wanted to make the defendant think that they were at risk of imminent harm to their physical person OR * Knowledge **(Substantial Certainty) i.e. they knew with substantial certainty that the defendant was going to think that.

So...

• Delaney says she is going to [redacted] and physically moves close to A's person with her arm raised while screaming.
• A ran from her, believing that D intended to harm her & that she was at imminent risk of D physically attacking her.
• A starts crying and tells D not to touch her. D says that she is not going to touch her, then chases her down the hallway with her arm raised.
• D did not touch her. D claims that she was not going to touch her and therefore is not responsible for harm to A.

Is D liable for assault?

Test: * D intended to cause A to believe that she was going to attack her. * D raising her fist, making oral threats, and chasing after A caused A to anticipate this contact.

Is the intent requirement met? * Did D have purpose (desire) to cause A to anticipate imminent harm to her physical person as a result of D's actions? OR * * Did D have knowledge (substantial certainty) that A would genuinely believe such harmful or offensive contact with her person was imminent (Did D knew A would think that D is going to hurt her)?

Application D DID have knowledge (substantial certainty). (A said this aloud.) * D DID intend to cause A to believe she was going to get physically attacked (whether or not D desired to attack her is irrelevant; D desired [intended] A to believe that she would be).

---> Did D's affirmative conduct cause A to anticipate... contact? * D's affirmative conduct DID cause A to anticipate such contact.

SO: (1) Is met. (2) is met. --> D had knowledge. Intent requirement is met. Therefore: Yes, D is liable for assault.*

Note

"The intent to make contact is a requirement for battery, not assault."

(Ref: Third Restatemnt of Torts. Intentional Torts to Person [Squiggley 105].)

I watched code-switching a lot growing up in a bilingual household. Specifically, from my mother who not only code-switched at home but also at work. It was always kind of impressive to me how seamless a conversation could be even with a mix of two different languages involved. It wasn't until I was older and we spoke less Spanish in the house that she shared it isn't always easy. She explained to me that there are many different dialects of Spanish, some similar and some very different. Even though speaking with family is easy at work, it can start to get more complicated. Often making conversations longer as more descriptors are needed to make sure everyone is on the same page.

I've never thought through the step-by-step process of a conversation with a stranger or new acquaintance. A lot of people joke that all people talk about the weather or the day of the week, but I find its often true. At least for the first moments of brief interactions. It's how I always start my conversations with customers. It helps having a neutral ground to then share some little details like how our day is going, what kind of weather we enjoy, or if we have plans. This usually creates a good segway to start a deeper conversation. Until reading this paragraph, I never realized how scripted and even ritualized the process was. Having a basic but successful conversation following these rules usually leads to a good first impression on the customers and a more comfortable checkout process.

goal of binding theory model

more on VWM

!

Very interesting

劳登县在过去20年建造了5300万平方英尺的数据中心，平均每年约265万平方英尺。这一规模相当于约244个标准足球场的大小，表明该地区已成为重要的数据中心集群。然而，缺乏与全国其他地区的比较数据，无法确定这一规模是否异常突出。

反对组织数量从约416个增加到833个，增长超过100%，覆盖49个州。这一增长速度表明数据中心反对运动在组织化和规模化方面取得了显著进展，可能反映了公众对AI基础设施环境和社会影响的担忧加剧。但缺乏2023年初始数据的绝对值，无法计算确切的增长率。

这一数据点表明，2026年前三个月因抗议而被阻止或延迟的数据中心项目价值高达1300亿美元，占2025年全年记录的1560亿美元的约83%。这一数字反映了数据中心反对运动的显著增长趋势，可能对AI基础设施建设产生重大影响，但需要确认这些数据的统计方法和来源可靠性。

大多数人认为马斯克的融资成功主要归因于他公司的创新技术和市场地位，但作者将其归结为'个人资本成本'这一概念。这挑战了传统商业融资理论，暗示创始人的个人品牌和声誉可能比公司基本面更重要，是一个反直觉的因果关系主张。

大多数人认为融资成本主要受市场环境和公司规模影响，但作者认为早期成功才是降低后续融资成本的关键因素。这挑战了传统融资观念，暗示创始人应该优先考虑小规模但可展示的成功，而非大规模扩张，这是一个非主流的融资策略观点。

大多数人认为初创公司的融资成本主要取决于商业计划、市场分析和财务预测等客观因素，但作者提出早期阶段的资本成本纯粹是个人化的。这挑战了传统融资理论，暗示创始人个人特质在融资初期可能比商业计划更重要，这是一个反直觉的观点。

大多数人认为筹集更多资本必然导致创始人股权被大幅稀释，但作者认为马斯克是个例外，他筹集的资金远超普通创始人，却仍能保留前10%的股权。这挑战了传统认知中'融资越多，股权越少'的常识，展示了个人品牌和成功轨迹如何创造独特的资本优势。

Norway = Good basis for research because * Youths recieving mental health benefits at increasing rate * High non-completion rate for upper secondary education * Lots of prior data about youths and mental health

Internalising = distress within (depression and anxiety) Externalising = Behaviors directed to environment (ADHD, ASPD)

I have had friends in high school that have struggled in school due to mental health. A large part of it is the lack of motivation to do homework or study.

I always think that style is something that has to be learned through rereading the work a few times through and truly understanding the piece as a whole. The style is also something that feels easier to understand when you have something to compare it to.

I really appreciate this! I have had classes where the level that is expected to earn an a is wild. Thank you!

This poem shows us Christ's return to heaven as a joyful event, highlighting divine triumph, salvation, and the restoration of order in God's kingdom.

The speaker ends with a prayer, recognizing Christ's suffering and sacrifice as the source of redemption and the promise of eternal life

The speaker is expressing hope for salvation believing the Cross will lead them from temporary life to eternal heaven and joy.

Honoring the Cross has become the purpose of life showing how faith transforms from a symbol of suffering into hope, salvation, and victory.

The speaker is praying to the cross as a symbol of salvation and showing that the vision transformed into devotion, hope and peace.

Those who follow Christ may endure suffering like he did, but everyone will stand before him in judgment, showing sacrifice, faith and accountability.

God will one day judge every person according to their actions in this life, highlighting faith, accountability, and living righteously.

Christ's suffering was a sacrifice made to save humanity from sin, which includes the original sin of Adam, showing the theme of redemption and salvation.

Important

https://youtu.be/ZXlYNEej9t0?si=gDN_6cDPn2N7fVB6&t=211

Ben Kingsley used a Continental typewriter in Schindler's List. It's housed at the Amblin Film Archive.

Yes - and what's going on behind the scenes here is that we assume that fertilizer contributes to the DP fraction only in the season of application, but with manure we account for DP contributions in the first season of application AND the second and third seasons after application (this is all based on work that Peter Vadas did). In the second season following application, 20% of the manure total P remaining on the soil surface is expected to become water soluble. In the third season following application, 5% of the total P remaining on the soil surface is expected to become water soluble.

Vadas, P.A., L.B. Owens, and A.N. Sharpley. 2008. An empirical model for dissolved phosphorus in runoff from surface-applied fertilizers. Agric. Ecosys. Environ. 127-59-65. Vadas, P.A., L.W. Good, P. A. Moore Jr., and N. Widman. 2009. Estimating phosphorus loss in runoff from manure and fertilizer for a phosphorus loss quantification tool. J. Environ. Qual. 38:1645-1653. Vadas, P. A. and P. J. A. Kleinman. 2006. Effect of methodology in estimating and interpreting water-extractable phosphorus in animal manures. J. Environ. Qual. 35: 1151-1159. Vadas, P.A., W.J. Gburek, A.N. Sharpley, P. J. Kleinamn, P. A. Morre, Jr., M. L. Cabrera, and R. D. Harmel. 2007. A model for phosphorus transformations and runoff loss for surface-applied manures. J. Environ. Qual. 36:324-332

Vadas, P.A., Gburek, W.J., Sharpley, A.N., Kleinman, P.J.A., Moore, P.A., and Cabrera, M.L. et al. 2007a. A model for phosphorus transformation and runoff loss for surface-applied manures. J. Environ. Qual. 36: 324–332. doi: https://doi.org/10.2134/jeq2006.0213

Unjournal data

There's some text overlap in the diagram.

what 'costs of negative findings'? This is a bit of a vague sentence.

also state and interpret the equation in terms of 'benefits vs cost' -- easier to interpret I think

don't use "+" and "-" as variables ... we can do better

links don't need to be bolded

overlapping text in diagram below

remove 'or policy relevance' perhaps -- The Unjournal prioritizes research with global impact potential (although that's not what we mainly rate the research on)

not sure I understand the logic behind the latter part

how would someone know this?

This is a possible set of considerations -- I don't want to state it as definitive

where do the defaults come from? Explain, reference, link (maybe as tooltips)

this needs fleshing out -- not sure what this is about

I don't see how this would 'alienate future donors'?

Faire un glossaire - vitrine linguistique du Québec. EPBE,

Revue de littérature globale (bref) > locale

Document à part?

switch 2 and 3

Remplacer par adresse CSBQ

Contactez nous so vous voulez contribuer si vous avez des compétences à une large échelle ou large group taxonomique.

Le comité va prendre un décision.

Ouverture à la science citoyenne.

Mettre de l'avant les cométences scientifiques et non techniques

this is meta -- I don't want meta, or at least put that into an 'opt-in' list

Grupo de Tareas 2

Important

I notice that the AI I use currently actually broadcasts little joke "progress" messages, designed to further obscure the actual information-generating process. How different it would be if it even broadcast random facts about the training data set,,,

cita

eLife Assessment

This important study examines the benefits of spatial cognition in a wild population of mountain chickadees. Using robust genetic analyses and experimental design, the authors show with compelling evidence that females seeking out extra-pair copulations prefer males with strong spatial cognition, and that these males have a reproductive advantage over other males. This work is of broad interest to evolutionary and behavioural biologists.

Reviewer #1 (Public review):

This manuscript presents compelling evidence from a wild chickadee population linking heritable spatial cognition to extra-pair paternity success, supporting sexual selection via good genes in a food-caching species. The integration of RFID cognition tests with ddRAD paternity assignment is methodologically strong and timely for behavioral ecology, though causal mechanisms and confounds warrant clarification.

Overall, a major revision of the manuscript is recommended, addressing the points below.

(1) Confirmation of manipulation and treatment effects. The central claim hinges on spatial cognition driving EP siring, but direct evidence that cognition predicts observed copulations (vs. post-copulatory mechanisms) is absent. While territories do not cluster by performance (Figure S4), quantify male aggression/movement data during fertile periods to rule out intrusion-based EPP. The authors should provide metrics like nearest-neighbor distances for EP sires or playback responses linking cognition to dominance, as in prior chickadee work. Without this, causal female preference remains correlational.

(2) Female cognition-EPY link inconsistency. Poor female cognition predicts more EPY (first-20-trials: offspring-level χ²=6.21, P=0.013; nests: χ²=6.79, P=0.009), but not for full-task (P>0.5). The authors should discuss why (e.g., learning speed vs. memory stability) and add exploratory correlations (female errors vs. EPY proportion). They should soften claims in the Discussion section of "female-driven" without consistent support and should frame this as a hypothesis.

(3) Cognitive task sensitivity and validity. Mean errors aggregate learning curves effectively, but single feeder-assignment (non-preferred) confounds neophobia/motivation with spatial ability. The authors should report trial-by-trial improvements (Figure S7 subset) or criterion-to-learn metrics. Justify excluding high-error birds (<3 mean); sensitivity analysis needed to check bias toward high performers.

(4) Paternity assignment robustness. ddRAD-CERVUS with bimodal LODs (Figure S8) is solid, but unassigned EPY (social-genotyped but no sire) implies missing sires (~?% of EPY?). Include all alive males as candidates yearly? Test power simulations for LOD thresholds. 2019 exclusion justified, but multi-year SNP alignment could boost resolution.

(5) Mechanistic speculation vs. data. Discussion invokes hippocampus genes (GWAS priors) and good genes, but no offspring cognition/survival data. Label as hypotheses; suggest tracking EPY recruitment. No brood size costs for EP sires is key, but monitor long-term nest investment (e.g., feeding rates).

Reviewer #2 (Public review):

Summary:

In this study, the authors ask whether spatial cognition is under sexual selection in mountain chickadees. To do so, the authors examined a large dataset that includes a) spatial cognition data for both males and females (obtained via use of a clever RFID-based feeder system) and b) social and extra-pair paternity nesting data. As predicted, males with higher spatial cognition sired more extra-pair offspring, and extra-pair sires had, on average, higher spatial cognition scores than the males they cuckolded. Interestingly, females with lower spatial cognition scores were more likely to seek extra-pair copulations, potentially to compensate for their own low spatial cognition. Surprisingly, there was no difference in spatial cognition scores between males that sired their own offspring and those that lost paternity at the nest. Also surprising was the fact that there were no differences in patterns of extra-pair paternity and spatial cognition between high- and low-elevation sites. The latter is particularly surprising in that spatial cognition should be under stronger selection at the high elevation site. Overall, this is a fascinating study that demonstrates that spatial cognition - a trait under natural selection as it directly impacts winter foraging and survival behaviour -is also under sexual selection.

Strengths:

The authors have a robust dataset (n = 732 offspring sampled over 3 years), high-quality spatial cognition data collected with a procedure that has been well-honed over the years, and couple the data with solid statistical procedures that address many potential covariates and potentially confounding factors. In addition, the authors are careful in the discussion to elaborate on the many potential alternative explanations from the results and questions that are likely to arise in the minds of readers (e.g., how are females assessing male spatial ability?)

Weaknesses:

Overall, no major weaknesses were identified in this study. As always, there are editorial issues that I would encourage the authors to consider, including presentation of data/results and clarification on some statistical issues. Overall, however, this is an excellent study that will make an important contribution to our understanding of the evolution of cognition and targets of sexual selection.

Reviewer #3 (Public review):

Summary:

The authors presented evidence that spatial cognition in this population is under sexual selection, with extra-pair males, primarily chosen by the females, having better spatial cognition than males they cuckolded and males with better spatial cognition having more extra-pair young.

Strengths:

This cognitive ecology study was conducted on a well-known long-term study population of free-ranging mountain chickadees. This strong base, alongside a thorough study design and extensive statistical analyses, enabled the authors to address research questions that few other labs can address, making this a potentially powerful study of broad general interest.

Weaknesses:

Throughout the manuscript, there is a focus on the "mean number of location errors per trial over the first 20 trials". Performance changes across trials, so why weren't learning vs peak performance analyzed separately? Similarly, authors also describe results in the context of the entire task, but sometimes in the context of the first 20 trials - why is one prioritised over the other, and why is the emphasis not always consistent? Are the results across the two generally the same? A more thorough explanation addressing all these points is necessary.

Lines 429-432: Why was a categorical (i.e., chi-square test) and not a numerical comparison implemented? A numerical statistical test would capture more of the variation (i.e., the number of years separating the social and EPY males).

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No olvidar al enlace

coma

para más detalles sobre esta reducción , sus ventajas y desventajas, consultar

cuando los conjuntos de estados y acciones son finitos

va para los prelinares

finalmente

hidrológica

Dichos valores serán tomados de los datos históricos con loque se cuenta. Tambien poner que k_i \in K_i

explicar porqué van hasta 7

hidrológica

explicar la escala de los u_m millones de mtros de cúbicos

colocar porqué con 600

centrar

Message clé!!

“经济上的显著生产力将提高生活水平，今天双职工家庭将变成单职工家庭。”

Prometheus融资120亿美元，估值达410亿美元，成为物理AI领域最大单笔投资之一。

贝索斯认为AI生产力提升将导致劳动力稀缺，与主流AI领袖预测的大规模失业观点相左。

“未来比我们预想的来得更快”，过去几年还只是假设的风险，现在已成为现实问题。

DeepMind联合多家机构设立1000万美元基金，专门研究多智能体系统的安全风险，但相比其内部研究预算仍显不足。

DeepMind认为学术界能比企业实验室看得更远，不受短期商业目标限制，这是推动多智能体安全研究的关键动力。

the 'suggest entry' is now going to a dead GH page -- find a better approach and solution

can these be restated as questions?

Better stated as a question ... something like "Do neuron counts reliably correlate with the welfare-relevant capacities organisms actually possess?" (of course 'reliably' probably would need operationalization, and this elides the possibility that it may "reliably correlate" but the correlation may be low)

these are good, but can they be separated out and flexhed out and made more explicit?

Not sure this one is an actual crux, rather an attempt to draw out Open Phil (now CG) on their moral weighting

'prioritizes' is not clear here. Do they better operationalize this ... how would it be decided/measured?

meta -- not an actual crix

clarify -- hard to read this

this is a fairly well-defined operationalized crux. It's old, but I guess 'we still are not confident'!

'is load-bearing on' ... that's too jargony; state it more clearly

this latter bit is closer to being a specific 'crux'. remember we want these stated as operationalizable questions,if possible. And try to find the single question crux that seems most important or most correlated to the others. You can have another column listing other cruxes raised.

you don't need "the authors ... " ... just state their crux question ... obviously it's the author

This one is getting good. It seems pretty relevant, but I want you to state it as an explicit opertionalizable question here.

too meta

State the actual crux. Your description here is more about the implications of the crux.

You can state somewhat general grounds, but then give a specific instantiation if possible. E.g., something about whether one form of slaughter is more painful to shrimp than another, or whether analgesia is good evidence, etc.

citar

dar cit de esa regla

citar de donde salió

revisar todos los asterisos

poner foto del refrigerador

quitar

revisar

revisar

espacio

citlar con link

A getter is a method whose job is to give you information about an object.