DOI: 10.1002/adfm.78515

Resource: RRID:AB_2938220

Curator: @scibot

SciCrunch record: RRID:AB_2938220

What is this?

DOI: 10.1002/adfm.78515

Resource: RRID:AB_1077187

Curator: @scibot

SciCrunch record: RRID:AB_1077187

What is this?

DOI: 10.1002/adfm.78515

Resource: (Thermo Fisher Scientific Cat# MA5-16402, RRID:AB_2537921)

Curator: @scibot

SciCrunch record: RRID:AB_2537921

What is this?

DOI: 10.1002/adfm.78515

Resource: (Millipore Cat# SCC008, RRID:CVCL_E921)

Curator: @scibot

SciCrunch record: RRID:CVCL_E921

What is this?

DOI: 10.1002/adfm.78515

Resource: (Thermo Fisher Scientific Cat# MA5-32876, RRID:AB_2802511)

Curator: @scibot

SciCrunch record: RRID:AB_2802511

What is this?

DOI: 10.70401/Geromedicine.2026.0035

Resource: RRID:SCR_002953

Curator: @AleksanderDrozdz

SciCrunch record: RRID:SCR_002953

What is this?

DOI: 10.6084/m9.figshare.31975344

Resource: RRID:IMSR_JAX:000664

Curator: @dhovakimyan1

SciCrunch record: RRID:IMSR_JAX:000664

What is this?

DOI: 10.1096/fj.202602231R

Resource: RRID:IMSR_RJ:BALB-C-NUDE

Curator: @dhovakimyan1

SciCrunch record: RRID:IMSR_RJ:BALB-C-NUDE

What is this?

DOI: 10.1016/j.neurot.2026.e01065

Resource: RRID:SCR_018510

Curator: @nmaralla

SciCrunch record: RRID:SCR_018510

What is this?

DOI: 10.1016/j.neuron.2026.08.019

Resource: RRID:IMSR_JAX:016962

Curator: @nmaralla

SciCrunch record: RRID:IMSR_JAX:016962

What is this?

DOI: 10.1016/j.immuni.2026.08.012

Resource: RRID:IMSR_JAX:000664

Curator: @nmaralla

SciCrunch record: RRID:IMSR_JAX:000664

What is this?

DOI: 10.1016/j.immuni.2026.08.012

Resource: RRID:IMSR_CRL:027

Curator: @nmaralla

SciCrunch record: RRID:IMSR_CRL:027

What is this?

DOI: 10.1016/j.cell.2026.08.034

Resource: RRID:SCR_008637

Curator: @nmaralla

SciCrunch record: RRID:SCR_008637

What is this?

DOI: 10.1002/glia.70218

Resource: RRID:Addgene_173154

Curator: @AleksanderDrozdz

SciCrunch record: RRID:Addgene_173154

What is this?

Note de Synthèse : La Répétition et la Régulation comme Gestes Professionnels

Résumé Exécutif

Ce document analyse les interventions d'Émilie Lefattan, coach professionnelle et ancienne enseignante, concernant deux aspects fondamentaux mais souvent mal vécus du métier d'enseignant : la répétition et la régulation.

La thèse centrale soutient que répéter des consignes ou réguler le climat sonore n'est pas un signe d'échec ou de manque d'autorité, mais un geste professionnel essentiel et inhérent à la dynamique de groupe.

Le document explore le décalage entre la compréhension intellectuelle de cette nécessité et le ressenti émotionnel de culpabilité des enseignants.

En identifiant les freins à une régulation efficace (manque de vigilance ou manque d'outils) et en redéfinissant la régulation comme le socle de l'autonomie des élèves, cette analyse vise à restaurer l'estime professionnelle des enseignants et à préserver leur énergie mentale.

1. Le Paradoxe de la Répétition

L'enseignement repose sur une contradiction vécue entre la théorie et la pratique émotionnelle.

Le décalage intellectuel vs émotionnel

• Connaissance théorique : Les enseignants savent, par leur formation et leur expérience, que la répétition est nécessaire aux apprentissages et à la gestion des comportements.

• Réalité intérieure : Malgré cette certitude, le fait de devoir répéter déclenche souvent une "petite voix intérieure" qui remet en cause l'efficacité du professeur.

La croyance limitante du "Premier Coup"

Une croyance profondément ancrée suggère qu'un "bon" professeur, doté de charisme et d'autorité, ne devrait pas avoir à répéter.

Selon cette logique erronée :

• Si l'enseignant doit répéter, il manque de compétence ou de charisme.

• Si les élèves n'obéissent pas immédiatement, ils manquent de respect ou de volonté.

2. La Régulation : Une Nécessité Biologique et Sociale

Pour déculpabiliser l'enseignant, la source propose une analogie avec des contextes sociaux d'adultes (mariages ou restaurants).

L'analogie du cadre social

Dans une salle de mariage ou un restaurant, le bruit monte naturellement.

L'hôte ou le serveur qui intervient pour faire baisser le volume n'est jamais perçu comme incompétent ; il fait simplement son travail de gestion de l'ambiance.

La "biologie sociale" du groupe

• L'effet de groupe : Un groupe humain, qu'il soit composé d'enfants ou d'adultes, ne s'autorégule pas indéfiniment de manière autonome.

• Le rôle du régulateur extérieur : L'intervention de l'enseignant est une réponse normale au "déroulement naturel" d'un groupe.

Ce n'est pas le signe d'une mauvaise explication, mais une nécessité pour ramener l'attention des individus pris dans le "flow" de l'action.

3. Définition et Enjeux du Geste Professionnel

La régulation doit être nommée et assumée comme une compétence technique à part entière.

| Aspect | Description | | --- | --- | | Définition | Toutes les interventions (répétitions, ajustements, rappels) visant à maintenir un climat d'apprentissage propice. | | Objectif | Garantir le niveau sonore souhaité et l'ambiance de travail définie en amont. | | Posture | Une attitude proactive et sereine, loin de l'utilisation de la peur, de l'intimidation ou de l'humiliation. |

4. Les Freins à une Régulation Efficace

Même lorsque l'enseignant accepte l'idée de réguler, deux obstacles principaux peuvent entraver son action :

A. Le déficit de vigilance (Attention partagée)

L'enseignant est parfois trop absorbé par une tâche précise (explication à un petit groupe, correction) pour percevoir la montée lente du bruit.

• Conséquence : L'intervention arrive trop tard, quand la situation a déjà débordé.

• Solution : Adopter une posture de "chef d'orchestre", capable de maintenir une attention globale tout en traitant un point spécifique (micropuses de régulation).

B. Le manque d'outils ou de posture

L'enseignant perçoit les signaux de dérive mais ne sait pas comment intervenir sans casser le rythme de la séance ou paraître s'acharner.

• Conséquence : Une stratégie d'évitement ("fermer les yeux") qui mène à une explosion émotionnelle ultérieure (frustration, sentiment de nullité).

• Solution : Développer des éléments de langage et des techniques d'intervention précoces.

5. Régulation et Autonomie : Une Relation de Complémentarité

Une idée reçue oppose souvent régulation et autonomie. La source affirme au contraire que :

• La régulation favorise l'autonomie : C'est en maintenant un cadre constant et sécurisant que l'enseignant permet aux élèves d'apprendre à s'autoréguler.

• L'exemplarité du cadre : Les élèves intègrent les limites en observant la régularité et la constance avec lesquelles le cadre est tenu, sans effondrement émotionnel de l'adulte.

6. Conclusion : Vers une Économie de l'Énergie Mentale

Le changement de regard sur la répétition et la régulation a des conséquences directes sur la santé professionnelle de l'enseignant :

• Préservation de l'énergie : En cessant de se juger ou de blâmer les élèves pour des comportements normaux de groupe, l'enseignant économise sa force émotionnelle.

• Discernement accru : En acceptant la "régulation normale", l'enseignant peut identifier plus clairement les situations réellement problématiques (comportements déviants ou récalcitrants) qui nécessitent, elles, une réponse différente et ciblée.

• Sentiment de compétence : Intégrer ces gestes comme faisant partie intégrante du métier permet de retrouver une sérénité quotidienne et une posture professionnelle solide.

Citation clé : _"Réguler, ça fait partie de votre métier.

Répéter, ça fait aussi partie de votre métier. [...] Ce n'est pas parce que vous répétez que vous avez échoué quelque part.

Vous êtes justement exactement dans votre posture professionnelle."_

This scene doesn't add much to the overall plot; it's enough for this episode to end with both characters feeling their feelings for each other grow stronger.

The scene changes seem a bit too frequent here. I think it would be fine to stay on this shot, but we could add some background sound—footsteps that get louder as the person approaches.

Similarly, don't let Julian say that line; instead, use the sounds of a closet door opening and clothes rustling coming from the dressing room.

I don't think this line is necessary; adding it to Julian's character would make him seem less sharp.

That's a bit unrealistic—fountain pens aren't that fragile. I think this could be changed to "snapped a pencil on the table."

same as the above

The phrase "rumpled covers" sounds a bit odd—the blanket should be smooth, but the area between Adrian's legs would be raised high, and the bulge in the blanket would create wrinkles.

It doesn't specify what kind of rhythm this is; it actually refers to the twitching of Adrian's hand, which causes the blanket to rise and fall—first high, then low—with the rate of change accelerating.

Can the dots start out all green?

The way I would run it: at the beginning the whole grid shows green, every dot alive. Then as the year passes they slowly turn grey. The greying itself still needs to be random, scattered across the grid, not going grey in a block.

I understand the line being spoken, but I cannot see how this picture relates to it.

Everything in the frame is the same envelope. When I look at it I think, what does an envelope have to do with changing jobs? The word "new job" is doing all the work and the drawing is doing none.

Each reason needs its own icon, something that actually shows the reason, instead of the same envelope repeated with a different label under it.

If the point is that phone numbers die, can we use an actual phone screen with the contact list on it. Show a thousand numbers in there. Tick the ones that are still reachable, cross the ones that are dying, then animate the dying numbers disappearing.

if this frame is meant to link back to the 100,000 from Frame 5, then the animation has to show that. The 100,000 itself should turn into the fragments that fly out. Right now there is no number anywhere in the sketch, so nothing on screen connects this beat to the one before it.

can we make the animation like the odometer stop at 10,000 and then go up 50,000 and then 100,000

I don't know about the art, was that the eyes

``` from scipy.optimize import linprog

Maximize x1 + x2 <=> minimize -(x1 + x2)

c = [-350, -300] A = [[18, 12], [1, 1], [6, 8], [-1, 0], [0, -1]] <br /> b = [3132, 200, 1440, 0, 0]

res = linprog(c, A_ub=A, b_ub=b, bounds=(0, None))

print("Optimal Value:", -res.fun) print("occurs in") for i, v in enumerate(res.x, start=1): print("x_%d = %f" % (i, v)) ```

R0:

Reviewer #1: In this work, Phu et al. present a comparison of CAD PRS distributions between populations, with an emphasis on Southeast Asian populations. While the population-wide findings are not novel, as Khera et al. Circulation. 2019 showed similar observed differences in raw CAD PRS distributions between populations, the emphasis here on Southeast Asian populations is relevant, as these individuals are largely underrepresented in genetic studies. However, I found the main analyses to be incorrectly performed, resulting in over-interpretation of the main findings of the papers, as detailed below.

1. Incorrect application of PRS The authors here download published PRS weights from the PGSCatalog, apply them into the full 1000G dataset using PLINK2, then standardize them in the entire population to mean 0 and variance 1. However, this process is incomplete for applying scores into multi-ancestry populations like 1000G. Allele frequency differences of the variants included in the PRS between populations induce differences in PRS distributions. Standard application of PRS into heterogeneous populations thus requires ancestry-related adjustment, as described by the PGSCatalog (https://pgsc-calc.readthedocs.io/en/latest/explanation/geneticancestry.html) and by Khera et al. 2019, which largely homogenizes the observed cross-population distribution differences of the PRS. Without this step, the authors are simply comparing PGS thresholds in a scenario where they would never be compared practically. After performing this step, the authors will also likely observe that PRS risk thresholds are largely calibrated.

2. Improper suggested calibration of PRS The authors propose that PRS thresholds should be selected per ancestry group to ensure calibrated risk estimation. However, this assumes that the populations the PRS are being applied in are homogeneous or have a completely matched reference population. In the manuscript, the authors propose calibrated thresholds based on KHV and CDX reference populations. However, these thresholds would only be calibrated in KHV or CDX populations respectively. This means applying them into the proposed GenomeAsia 100K would still yield uncalibrated risk estimates as GenomeAsia does not only contain KHV or CDX populations. Instead, standardized ancestry adjustment as described above is necessary to ensure risk thresholds are properly calibrated between population groups.

Reviewer #2: I have reviewed this manuscript as someone who works on cross-ancestry calibration of polygenic scores. I have declared a competing interest to the editor, and I have written this review in a way that makes each objection checkable from the manuscript itself or from the deposited code.

I want to begin with what is genuinely good here, because this is a substantial body of work. (a) The inputs are entirely public, the complete analysis pipeline is archived on Zenodo, and the authors state it reproduces every result and figure end to end on a laptop. This is commendable and I hope it survives into whatever form this work eventually takes. (b) The question of how European-derived CAD scores behave in Vietnamese and mainland Southeast Asian populations is important and in my opinion under-addressed, and the limitations section is candid about the distinction between calibration and predictive accuracy.

Nevertheless, my assessment is that the manuscript does not meet the key criterion that conclusions be appropriately drawn on the basis of the data presented, for two reasons. Whilst neither is a matter of the authors having chosen a suboptimal method; both concern what these data can and cannot establish.

1. The causal attribution underlying the central claim is not identifiable from the analysis performed.

The empirical content of the paper is a mean shift in a raw score standardised across the pooled 2,504-individual sample, and the fraction of each group exceeding a European percentile cut. That shift is a composite of at least three contributions: allele-frequency and linkage-disequilibrium differences between discovery and target populations; any real difference in the distribution of genetic liability; and residual population structure.

Section 4 attributes it mainly to the first: "this excess reflects allele-frequency and linkage-disequilibrium differences rather than demonstrated higher true risk." However, there is nothing in the analysis that separates these components, so this attribution is not based on evidence. The title and abstract then build on it. In particular, "over-flag genetic risk" suggests that the flagged excess is spurious, but this is never conclusively established.

The methods that address this separation are individual-level calibration on genetic principal components: regression of the raw score on leading PCs with subsequent work on the residual (Hao et al., Nat Med 2022;28:1006), and its continuous extension, which models both the PC-conditional mean and the PC-conditional variance to yield a per-individual calibrated score requiring no discrete population label (Ding et al., Nature 2023). Neither approach is applied here. The reported +0.47 SD shift is exactly the quantity these procedures are designed to remove, and it is being presented as a characterisation of clinical deployment.

I would therefore like to see the analysis repeated with a PC-calibrated arm alongside the raw arm. I do not regard this as a robustness check that the manuscript would be expected to pass: it is entirely possible that most of the reported shift is removed by PC calibration, in which case the stated finding does not hold. A result that may not survive the standard adjustment for the confounder in question is not, in my view, ready for publication.

The framing also rests on a premise that I could not find any support for. This is that a raw PGS Catalog scoring file would be deployed clinically against a fixed European percentile. I am not aware of a published clinical CAD PRS workflow that does this; the reporting pipelines I know of incorporate ancestry adjustment and within-ancestry normalisation as standard. If the authors can cite a deployed workflow that transfers a raw European cut-point directly, the framing is justified and should carry that citation. If not, the manuscript is characterising an artefact of an unused procedure rather than a risk in current practice, and the title and abstract should say so.

1. Section 3.3 presents an arithmetic identity as an empirical result.

By construction, defining the high-risk threshold as the 80th percentile of the target population's own score distribution flags 20% of that population. The post-recalibration column of Table 4 (KHV 20.2%, CDX 20.4%) is therefore not a finding but the rounding imposed by n=99 and n=93. It contains no information about the scores, the populations, or CAD.

Yet the abstract states that recalibration "restored the intended 20% high-risk proportion"; the conclusion states that it "corrects this over-flagging"; and Section 4 describes the miscalibration as demonstrated to be "correctable." These attribute empirical content to a definition. Section 4 does contain the correct caveat, that recalibration "does not by itself create predictive accuracy", but the abstract, title and conclusion do not carry it, and no revision can convert an identity into evidence.

Relatedly, within-population percentile thresholding carries a substantive cost the manuscript does not discuss: it renders the score structurally incapable of expressing any between-population difference in the distribution of genetic liability, whether or not one exists. That may be the correct conservative default, but it should be argued as a trade-off against continuous PC-based calibration, which requires no discrete label and therefore has defined behaviour for admixed and internally structured populations. This is concrete rather than abstract for the stated application: a reference keyed to "Vietnamese" has no defined application to highland minority populations or to individuals with southern-Chinese admixture, and a 99-person Kinh sample cannot represent either.

Additionally, I have identified the following issues with the manuscript as written:

1. Appendix Table A1 should be withdrawn.

The table supplies raw-score cut-points to seven significant figures, derived from 99 individuals, with a "Use" note instructing that a patient scored through the same pipeline be classified against them. The top-5% cut-point is determined by the fifth and sixth highest-scoring individuals in the sample (0.05 × 99 = 4.95). A manuscript arguing that unvalidated thresholds should not be used clinically should not distribute an unvalidated threshold table with patient-classification instructions. I would ask for removal rather than caveating.

1. Statistical reporting.

The abstract attributes Welch t = 7.77, p = 2.0×10⁻¹⁴ to the Vietnamese Kinh versus European comparison. Section 3.1 reports the identical statistic with df = 955, for the East Asian super-population against European. A KHV (n=99) versus EUR (n=503) Welch test on the standard deviations given in Table 2 yields df of roughly 130–160. The abstract therefore reports a super-population result as a Vietnamese result. This requires correction, and the KHV-specific test should be reported with its own df and confidence interval. No confidence intervals are given for any flagged fraction. At n=99 the binomial 95% intervals are wide enough to alter the conclusions: PGS004198 in KHV (22.2%) has an interval spanning the intended 20%, and PGS002809 (25.3%) is marginal against it. The claim that "three of the four scores over-flagged Vietnamese" is more accurately rendered as one score departing markedly, one moderately, and two indistinguishable from calibration at this sample size. Intervals should appear in Tables 3 and 4 and in Figure 3. Both directions of mis-stratification are present in the authors' own results. PGS000058 flags 9.1% of AFR against an intended 20%, and recalibration moves 10.9% of Africans into the high-risk group. The title selects one direction. "Mis-stratify" or "shift" is supported by these data; "over-flag" is not.

1. Score independence and score selection.

The four scores are described as independent. PGS000058 (204 variants) and PGS002809 (205 variants) are both genome-wide-significant-locus panels from broadly the same discovery era, and the 70 variants of PGS000349 may nest within them. I would ask for pairwise variant overlap, overlap of underlying discovery GWAS, and pairwise correlations of per-individual scores. If those correlations are high, the claim that the phenomenon "is not an artefact of a single score" does not follow.

No score above 5,723 variants is examined. The CAD scores actually proposed for clinical stratification are genome-wide or near it (Khera et al. 2018; Inouye et al. 2018) or explicitly multi-ancestry (Patel et al., Nat Med 2023;29:1793). The authors' own results indicate why this matters: the largest score tested is the one closest to calibrated in East and Southeast Asians. Sparse scores are expected on theoretical grounds to lose cross-ancestry LD tagging most readily, so a general conclusion about "European-derived CAD polygenic scores" is not supported by this panel. At minimum one genome-wide score and one PRS-CSx-derived multi-ancestry score should be included. Limitation 3 concedes the point; the abstract generalises regardless.

Please also justify the choice of PGS000058 as the primary score, given that it was derived in the ACCORD type 2 diabetes trial population.

1. Data and technical points.

PLINK2 --score mean-imputes missing dosages using the allele frequency of the file being scored. Applied to a pooled multi-ancestry file, this introduces an ancestry-dependent bias into precisely the quantity under measurement. Please state whether no-mean-imputation was used and, if not, re-run with it. On a 70-variant score, two missing variants constitute 3% of the score. Please state explicitly how strand and allele ambiguity were handled at A/T and C/G sites. 1000 Genomes phase 3 on GRCh37 is low-coverage-imputed. The 30× high-coverage resequencing of the same samples is available and permits exclusion of related individuals. Please state whether relatedness was addressed. CDX comprises Chinese Dai from Xishuangbanna, Yunnan, China. Treating this as a Southeast Asian replication sample for the Kinh should be stated as an explicit assumption rather than implied by pairing. The manuscript uses 1000 Genomes reference-panel labels interchangeably with "genetic ancestry." No ancestry inference was performed on any individual. This should be stated plainly, consistent with current guidance on the use of population descriptors in genomics research.

1. Literature.

The manuscript proposes ancestry-specific thresholding as a remedy without engaging the literature in which it is established, validated, and subsequently extended to continuous methods: Hao et al. 2022 (Nat Med); Ding et al. 2023 (Nature); Privé et al. 2022 (Am J Hum Genet 109:12); Patel et al. 2023 (Nat Med). Engagement is necessary both to position the contribution and because that literature defines the analysis this manuscript would need to perform.

1. Language.

The language is broadly clear, however several character-rendering errors should be checked in the source file, as they may be PDF artefacts: the exponent in "2.0×10 ¹⁴" (should read 2.0×10⁻¹⁴) in both abstract and Section 3.1; "European Genomephenome Archive" (Genome-Phenome); and the elided compounds "SoutheastAsia," "crossancestry," "overflagged" and "highrisk" at several line breaks.

What I would encourage.

The result I find most valuable is one the manuscript underplays. The direction and magnitude of cross-ancestry threshold mis-transfer are score-specific and are not predictable from a score's performance in Europeans: PGS004198 is close to calibrated in East and Southeast Asians while flagging 69.3% of Africans, and PGS000058 does approximately the reverse. That observation requires no phenotype, is not an identity, and makes a clean case for per-score, per-population validation before any threshold-based deployment. Built around that finding - with confidence intervals throughout, a PC-calibrated comparison arm, a wider range of score densities including at least one genome-wide and one multi-ancestry score, and Appendix Table A1 removed - this would be a useful contribution, but would also require substantial re-working.

R0:

Reviewer #1: The Title and the abstract are fully focused to the theme of the study. The introduction section written well with sufficient background to raise the research question. But the research question is only based on three parameters, which is not a comprehensive approach in Biomedical equipment management. The methodology section provided the process in detailed. But how the data were collected, who collected and how to reduce the bias should be included. How the 31-point criteria of adherence framed, validated not mentioned. The result section described with relevant figures and tables. However no statistical analysis was mentioned. The discussion enumerated in detailed with three objectives in thematic forms, but the numbering is wrong, 2 is missing. Limitation of the study may be a part of discussion not as separate numbering. The section of recommendations and regional relevance and Conclusion appeared same. Preferably, Policy recommendation may be provided after conclusion as separate paragraph. References are relevant, but more than 10 years old references need to be replaced with recent one. The Table and figures made properly as per guideline. Overall, the study needs to have a minor revision.

Reviewer #2: 1. Authors should explain the need and motivation for this research as well as the novelty of your work. 2. Authors should review all significant similar works that have been done. Also, review some good recent works that have been done in this area and are similar to your paper. For each work, first, describe the problem that has been addressed in the work. Then describe the tools used to address the problem. After that, compare the work with your work and summarize the differences and benefits of your work with the work. It is better to provide a contribution table to compare the contributions. 3. Authors should mention the methodology for ensuring reliability and validity of biological equipments. 4. Data collection period is too small. 5. Authors mentioned that World Health Organization document entitled "Needs Assessment for medical devices (reference 16)" can help guide policymakers and other decision makers. Now the question is that what is the contribution of authors for guiding policymakers and othes. 6. No maintenance strategy is not explored by the authors. 7. Authors should highlight the new contributions in the field.

Reviewer #3: The manuscript addresses a topic of relevance to public health and clinical engineering, namely the availability, functionality and management of medical equipment used in operating theatres and post-anesthesia care units in Rwanda. The study has practical value, especially in the context of resource-limited health systems. The use of direct inspection of equipment, together with the assessment of management practices, is a strength. A few clarifications are needed: 1. Only five purposively selected level 2 hospitals were included, one from each province. Therefore, wording such as “across Rwanda” and national conclusions should be rephrased. The authors acknowledge this limitation, but it should be consistently reflected in the title, abstract, discussion and conclusions. 2. Functionality was established through direct inspection and relatively simple operational checks, together with biomedical staff and users. These checks are not equivalent to standardized technical testing, electrical safety testing, calibration or performance evaluation according to manufacturer specifications. Consequently, the value of 96% “functional equipment” should be interpreted with caution. 3. The authors mainly use percentages for availability, functionality and adherence. It would be useful to present more clearly the denominators used and, where justified, confidence intervals. Also, interpretations that could suggest statistically significant differences between hospitals in the absence of inferential testing should be avoided. 4. The authors should explain whether the list of 19 types of equipment represents only the presence/absence of each type or also includes the quantity required relative to the number of operating rooms/PACUs. This clarification is important for interpreting the overall value of 45%. 5. The 31 criteria are apparently treated with the same weight, although their importance for safety and management may differ. In addition, some results are particularly important: none of the five hospitals had, among other things, calibration records, spare parts availability, or maintenance labels for all equipment. These shortcomings would merit further discussion than simply reporting an average adherence of approximately 66%. 6. . For 42% of the equipment, the source of purchase could not be identified. It would be useful for the authors to discuss in more depth the implications of this situation for inventory, maintenance, traceability, institutional accountability, and equipment life cycle planning. 7. The authors appropriately mention the small number of hospitals, the lack of PACUs in two facilities, and the absence of standardized performance testing. Explicit mention should be made of the purposive selection of hospitals, the possible bias associated with the participation of local staff in the assessment, and the limitations of predominantly face-validated instruments. 8. The manuscript is understandable, but contains grammatically incorrect or unnatural formulations and some terminological inconsistencies. A linguistic revision is recommended before publication.

This variant was found on one allele of a Stargardt patient, but no additional details are provided about the patient or the other allele. A combination of single-strand conformation polymorphism (SSCP) and automated DNA sequencing was used to evaluate the entire exonic and flanking intron sequence of the ABCA4 gene

Case#: Eisenberger Patient 92, female, 31yo, German

DiseaseAssertion: Autosomal dominant RP

FamilyInfo: non-consanguineous

CasePresentingHPOs:

CaseHPOFreeText: "The diagnoses of all patients were established by medical history, family history and detailed clinical evaluation of vision. Ophthalmological examination included stereoscopic funduscopy, standard ERG, perimetry, measurement of dark adaptation, and determination of best-corrected visual acuity in most patients."

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: NGS for the exons of 55 RP and LCA genes, Sanger for confirmation

PreviouslyPublished: n/a

Variant: Allele 1: RHO c.180C>A p.Tyr60; Allele 2*: ROM1: c.178C>A p.Pro60Thr; c.323C>T p.Thr108Met;

ABCA4: c.1654G>A p.Val552Ile; c.5714+5G>A; <br /> RP2: c.844C>T p.Arg282Trp; <br /> RPGRIP1: c.2510C>G p.Ala837Gly

ClinVar:

CAID: CA239745

SupplementalData: n/a

Annotating here since unable on the PDF.

Case 3 is a 6yo male. VA: OD: 20/150, OS: 20/200. Proband had macular atrophy and flecks at the posterior pole. In the autofluorescence exam, there was peripapillary sparing of the hyper-autofluorescent flecks. On OCT images the atrophic areas at the macula correlated to disruption of the elipsoid layer and decrease in the foveal thickness. OCT showed loss of the photoreceptor layer and EPR layer. Proband has only 1 ABCA4 variant, so not eligible for PP4. Also has a variant in PROM1 (p.Ala643Gly). ABCA4, PROM1, and ELOVL4 genes sequenced by next-generation sequencing (NGS) test.

Case#: German/British, 76

DiseaseAssertion: EOSRD

FamilyInfo: Grandparents from Germany and the United Kingdom

CasePresentingHPOs: HP:0007401, HP:0007913

CaseHPOFreeText: Macular atrophy and pigmentation, peripheral pigmentation, early-onset severe retinal dystrophy

CaseNotHPOs: N/a

CaseNotHPOFreeText: N/a

Genotyping Method: BGISeq-500 2 x 100-bp paired-end module, Burrows-Wheeler Aligner and Genome Analysis Tooklit HaploptypeCaller

PreviouslyPublished: n/a

Variant: c.1622T>C, c.4326C>A, and c.3113C>T

ClinVar: 99067, 417991, 7894

CAID: CA226911, CA957653, CA119135

SupplementalData: The c.1622T>C variants and c.3133C>T are thought to be same gene copy

PMID: 39421326 (PMCID: PMC11675205)

Gene: ABCA4

HGNC ID: 34

Case#: Patient 24 (male)

DiseaseAssertion: STGD (Stargardt disease)

FamilyInfo: Caucasian family from Germany. Patient has two siblings carrying the variant but they are not clinically affected according to pedigree information.

CasePresentingHPOs: Decreased central visual acuity (HP:0000545) Macular atrophy (HP:0007754) Retinal flecks (HP:0030638) Abnormal fundus autofluorescence (HP:0030647) Macular degeneration (HP:0007754) Abnormal electroretinogram (HP:0000763)

CaseHPOFreeText: Male patient diagnosed before age 50 with Stargardt disease. Best corrected visual acuity (BCVA) approximately 0.05–0.2. Fundus imaging shows paracentral scotoma, macular atrophy, and hyperfluorescent flecks with sparing of the fovea. Autofluorescence demonstrates hyperreflective spots and patchy lesions with parafoveal involvement.

CaseNotHPOs: None explicitly reported.

CaseNotHPOFreeText: Pattern-like distribution of lesions noted on clinical examination.

Genotyping Method: Whole-exome sequencing (WES) with an in-house RD-associated gene panel including 619 candidate and disease-associated genes.

PreviouslyPublished: No (novel complex deep-intronic allele described in this study).

Variant: c.[1555-5882C>A;1555-5784C>G]

ClinVar: Not reported in ClinVar in the provided information.

CAID: CA272741; CA227172

SupplementalData: Segregation data and functional splicing analysis available in the supplemental data (Table S1, Figure S1) of the article.

In HEK293T cells, p.Val552Ile expresses at close to WT levels, exhibits normal N-Ret-PE binding properties, and has only a modest reduction in ATPase activity. Consistent with mild disease phenotype

Case#: Bertelsen Patient D023, female, 9yo at onset

DiseaseAssertion: generalized choriocapillaris dystrophy

FamilyInfo:

CasePresentingHPOs:

CaseHPOFreeText: end-stage generalized choriocapillaris dystrophy characterized by semiconfluent multifocal areolar outer retinal atrophy, the severity of which decreases with increasing eccentricity. Central patches of visible sclera are surrounded by coarse confluent hyperpigmentation. The periphery shows isolated or clustered hyperpigmentation. In and around the fovea there is pronounced atrophy of the retinal pigment epithelium, the photoreceptor layer, and the outer nuclear layer and intraretinal hyperreflective material corresponding to the hyperpigmentation

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: microarray

PreviouslyPublished: n/a

Variant: c.203C>T p.P68L; c.3329-2A>G

ClinVar: 99113

CAID: CA226972

SupplementalData: n/a

Case#: Patient #43, male, 9yo at onset, 16yo at report, German

DiseaseAssertion: macular dystrophy or cone-rod dystrophy

FamilyInfo: inheritance= sporadic. phase not confirmed, but no other affected family members and no parental consanguinity

CasePresentingHPOs:

CaseHPOFreeText: reduced visual acuity, erg scotopic= reduced, erg-photopic=reduced

CaseNotHPOs:

CaseNotHPOFreeText: syndromic retinal disease, age-related macular degeneration, central serous retinopathy, autoimmune retinopathy, retinal vascular disease, achromatopsia, X-linked retinoschisis, North Carolina macular dystrophy

CasePreviousTesting: n/a

GenotypingMethod: Sanger sequencing of ABCA4

PreviouslyPublished: n/a

Variant: c.3098del (p.Lys1033Serfs*51); c.3243G>T (p.Lys1081Asn)

ClinVar: 236516

CAID: CA10581650

SupplementalData: Supplementary table 1

Case#: Patient 231, Female, age of onset at 7 y.o, Poland

DiseaseAssertion: STGD1

FamilyInfo: Mother was a carrier, unaffected father.

CasePresentingHPOs: HP:0007722, HP:0000608, HP:0025158

CaseHPOFreeText: RPE atrophy, macular degeneration, central hyper-autofluorescence in fundus autofluorescence

CaseNotHPOs: n/a

CaseNotHPOFreeText: n/a, non-proband identified HPO's mentioned, but not assignable to individual proband.

Genotyping Method: DNA isolated from peripheral blood from patients and relatives via MagNA Pure 24, samples screened with MIPs targeting 108 genes involved in pathogensis of IRD's. PCR completed on library, analysed with NGS fragment analysis kit.

PreviouslyPublished: yes

Variant: c.5882G>A

ClinVar:7888

gnomeAD: 0.00310 allelic freq.

CAID: n/a

SupplementalData: Fig1: List of families displaying pseudo-dominant inheritance. Fig2: Number of alleles for most common variants.

This paper is evaluating potential hotspots of ABC genes. The variant is mentioned as being in the C-loop2 motif, but no further information is provided on the variant.

This variant is found in compound heterozygosity with c.3386G>T p.(Arg1129Leu) in family MD-0560 in a previous publication (PMID: 23755871)

MonDO: MOND:08000406

Case: Female, onset 6 years VA 20/200 OU identify 1 ouf 15 Ishiara cards and overlooking symptom. Presumably diagnosed with Batten disease but found to harbor genetic variant for Stargardt disease.

DiseaseAssertion: Stargardt disease

FamilyInfo: No family history of visual loss in childhood.

"CasePresentingHPOs: HP:0007663, HP:0007988, HP:0030584, HP:0008043, HP:0008001, HP:0030609 (Reduced visual acuity, Macular hypopigmentation, Color vision test abnormality, Retinal arteriolar constriction, Foveal hyperpigmentation, Photoreceptor layer loss on macular OCT"

CaseHPOFreeText: bull's eye lesions, prominent overlooking, hyperreflective granular deposits

CaseNOTHPOFreeText: HP:0001336, HP:0001250, HP:0000648, HP:0000707

CasePreviousTesting: (Myoclonus, Seizure, Optic atrophy, Abnormality of the nervous system

GenotypingMethod: Genetic testing was negative for all mutations known to cause neuronal ceroid lipofuscinosis, but whole exome sequencing showed compound heterozygosity for 2 pathogenic variants in the ABCA4 gene

MultipleGeneVariants:

(1) GeneName: ABCA4

(1) Variant: c.3007C>T, p.Q1003X

(1) ClinVarID or CAID: CA119132

(1) gnomAD: 0.003406 total AF in gnomAD v4.1 (https://gnomad.broadinstitute.org/variant/1-94008251-C-T?dataset=gnomad_r4)

(2) GeneName: ABCA4

(2) Variant: c.768G>T

(2) ClinVarID or CAID: CA227458

(2) gnomAD: 0.00007930 total AF in gnomAD v4.1 (https://gnomad.broadinstitute.org/variant/1-94098794-C-A?dataset=gnomad_r4)

This variant is reported in Table S6, but only location, predictions, frequencies, etc are reported for it, not cases.

This variant is found in Table S5. "Five probands with one ABCA4 disease-associated allele" Proband #89. Since this proband has only one variant they are not eligible for PP4

Case#: Patient STG-16, 13yo at onset, Argentina

DiseaseAssertion: STGD1

FamilyInfo: n/a

CasePresentingHPOs:

CaseHPOFreeText: BCVA=0.7/0.7, FA=3B, AF pattern=2, OCT showed decreased retinal thickness with disruption of external layers

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: NGS of ABCA4 (NM_000350.2), ELOVL4 (NM_022726.3), PROM1 (NM_006017.2), and CNGB3 (NM_019098.4)

PreviouslyPublished: n/a

Variant: c.4457C>T (p.Pro1486Leu); c.1804C>T (p.Arg602Trp)

ClinVar: 99283

CAID: CA227192

SupplementalData: supplementary table 2 has genotype/phenotype info

Case#: Proband 95-0103, Spanish, onset at 8yo

DiseaseAssertion: cone-rod dystrophy

FamilyInfo: Family RP-0298. Affected sister, 95-0101, with same genotype

CasePresentingHPOs: HP:0001133, HP:0000529, HP:0000662, HP:0000512, HP:0000543, HP:0007737, HP:0007641, HP:0007787

CaseHPOFreeText: BCVA=0.1/0.1; ERG: scotopic-Low amplitude, normal latency, photopic-abolished, mixed-diminished a and b waves; dense pigment accumulation at macular region;, bilateral posterior subcapsular cataract.

CaseNotHPOs:

CaseNotHPOFreeText:

PreviouslyPublished: 19365591

Variant: c.4720G>T p.E1574; c.950delG p.G317Afs57. WES, All patients were previously tested and all resulted to be negative for known autosomal recessive retinitis pigmentosa (ARRP) or Leber Congenital Amaurosis (LCA) mutations by microarray screening

ClinVar: 1460063

CAID: 341283936

SupplementalData: Table S2 has phenotype details

Case#:patient, 25, male

DiseaseAssertion:Retinitis Pigmentosa

FamilyInfo:Unaffected brother with no variants, parents each heterozygous for one pathogenic variant in ABCA4

CasePresentingHPOs: HP:0000007, HP:0011462, HP:0007703, HP:0000662, HP:0007641

CaseHPOFreeText: Onset 20 year old. Gradual onset of blurred vision OD, dyschromatopsia. BCVA 1/20 OD 20/20 OS. Optic disc pale, retinal arteries and foveal reflex attenuated. Yellow deposits in perofoveal area and mid-peripheral retina, which showed mottled appearance OU. OCT - thinning of outer nuclear layer and disruption of ellipsoid zone with hyper-reflective flecks. Severe bilateral constriction in visual field. Hypofluorescence of optic disc OU

CaseNotHPOs: n/a

CaseNotHPOFreeText: n/a

Genotyping Method: whole exome (Sanger segregation test)

PreviouslyPublished: n/a

Variant: NM_000350.3:c.4793C>A; NM_000350.3:c.1769A>G

ClinVar: 99321

CAID: CA341279788

SupplementalData: n/a

PMID: 41458191 Gene: ABCA4 HGNC: 34

PMID: 28050124 Gene: ABCA4 HGNC: HGCN:34

PMID: 18334942

Gene: ABCA4

HGNCID: 34

Case#: patient 26, female, Spanish

DiseaseAssertion: early onset RP

FamilyInfo: Figure 1. One brother homozygous for ABCA4 c.5413A.G allele, parents and one brother heterozygous for ABCA4 c.5413A>G allele. All three brothers and father carriers of p.Cys948Tyr allele on the CRB1 gene. Mother heterozygous for p. Trp822ter (c.2465G>A)

CasePresentingHPOs: HP:0000662, HP:0001133, HP:0007663,

CaseHPOFreeText: hyperopia, astigmatism, nystagmus, roundish pigments distributed across entire retina including peripheral retina, posterior pole, and macular region, filiform constriction on retinal vessels.

CasePreviousTesting: N/A

GenotypingMethod: Microarray

PreviouslyPublished: 11385708, 12442277

Variant: ABCA4 p.Asn1805Asp (c.5413A>G)

ClinVar: 99373 https://www.ncbi.nlm.nih.gov/clinvar/variation/99373/?term=%22ABCA4%22%5BGENE%5D+AND+%22p.Asn1805Asp%22%5BVARNAME%5D+AND+%22(c.5413A%3EG)%22%5BVARNAME%5D

gnomAD: 0.000009292 https://gnomad.broadinstitute.org/variant/1-94014590-T-C?dataset=gnomad_r4

Bonus question: can you generalize this to a criterion for \(A\) being positive semidefinite? Why is it not enough to simply require

$$ a\geq 0\qquad\text{and}\qquad a b - c^2 \geq 0? $$

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The study concludes that many islands previously considered secure are actually within stoat swimming range which ultimately means that conservation strategies must be updated, as outdated assumptions could leave endangered species vulnerable to reinvasion.

This reinforces that the experimental results represent minimum capability, not maximum. Wild stoats, especially in ocean conditions, could travel significantly farther, expanding the realistic threat radius around offshore islands.

This fore-legged stroke largely explains the stoats' ability to sustain long-distance swimming, which contradicts the belief that small size limits their swimming potential.

This result shows that stoats have far greater endurance than conservation authorities originally assumed, especially since these were captive animals under stress. If a stoat can swim nearly 2 km in controlled conditions, wild stoats aided by tides or debris could easily surpass distances once believed impossible, meaning many offshore islands are more vulnerable to reinvasion than previously thought.

This shows how researchers had to build a controlled method to estimate real swimming ability because no reliable data existed before. The fact that such basic measurements were missing explains why earlier claims underestimated how far stoats could actually swim.

Even after major conservation successes, reinvasion remains a constant threat, especially if stoats can reach islands previously considered safe. This highlights how predator mobility directly affects long‑term conservation outcomes.

Stoats' abilities to disperse on land were already pretty great, but their willingness to swim across strong rivers shows that water is not a barrier for them. This challenges the assumption that offshore islands are protected simply because they are separated by water

One part of the reading that stood out to me was the idea that good hospital governance is not just about who is on the board, but how the board members work together. There's more attention placed on relationships, communication, and behaviour within the board, rather than just its structure and composition. I found this interesting because having people with different backgrounds and skills on a board does not necessarily mean they will make good decisions. Board members also need to feel comfortable sharing their opinions and speaking up when they disagree. The reading talks about the risk of “group thinking,” where people may just go along with the majority instead of questioning a decision. I think this is especially important in healthcare because board decisions can have a direct impact on patients and the quality of care.

I also found the discussion about the relationship between the board and management interesting. The board needs to make sure management is doing its job and is being held accountable, but it should not get too involved in the day-to-day operations of the hospital. If the board focuses too much on smaller operational issues, it can lose sight of larger strategic goals.

This line shows a metaphor. He pulls the homeland out of his bloodstream with a need , like drawing blood. So the homeland is literally part of his body. Calling it the needle of time suggests that each year away takes a little more out of him.

This shows Irony , he says he's in exile but he's "inside my house." I read this as a paradox : he has a house but not a home. Exile isn't only about location. It's a feeling that follows him indoors.

The title and the first line say the same thing, which makes it feel like the speaker is counting days. " Five years " is specific. This isn't a short displacement. It has become his life . The dash at the end of line I feels like a long breath before he explains what those years were like.

ここ修正

I think this is a really useful reminder that a single biodiversity metric can sometimes be misleading. Even though overall invertebrate diversity appears to increase, that pattern is heavily influenced by the abundance of certain taxa, while many others are negatively affected. This suggests that scientists need to look at community composition as well as summary diversity indices before concluding that an ecological effect is positive.

I think this result is important because it shows that the effects observed in individual pools may scale up to the entire watershed. A local reduction in fish diversity could seem relatively limited on its own, but a 41% decline in fish abundance at the watershed scale suggests a much broader ecological impact. It also makes me think about how local field measurements can be used to model consequences at much larger spatial scales.

I think this design is useful as the researchers compare both hippo density and hydrological conditions. High- versus low-density pools help identify effects associated with hippos, while wet- versus dry-season sampling tests whether river flow changes the strength of those effects. This allows them to ask not only whether hippos matter, but under what environmental conditions their effects become strongest.

I think this is an important limitation because the study clearly shows short-term dry-season effects, but it cannot tell us whether those losses translate into long-term biodiversity decline across the watershed. The authors note that high-density pools are recolonized once flow returns, which suggests some resilience. It would be interesting to know whether repeated drying over many years eventually overwhelms that ability to recover, especially as water abstraction and climate change intensify.

This seems like one of the most important biological results because the same seasonal pattern seen in water chemistry also appears in biodiversity. High hippo density is associated with lower fish and invertebrate diversity during the dry season, but that difference disappears when flow returns. This strengthens the argument that hydrology is regulating the effect of hippos rather than high hippo density always producing lower diversity.

I think this figure gives some of the clearest support for the authors’ hypothesis because the difference between high- and low-hippo-density pools becomes larger as river discharge decreases. Dissolved oxygen is similar when the river is flowing, but drops much more sharply in high-density pools as flow approaches zero. This suggests that hippo density alone is not enough to explain the effect, the impact becomes much stronger when reduced flow prevents organic matter from being diluted or carried downstream.

I like how the questions move from the local scale to the whole watershed. The authors first ask what hippos do to chemistry and biodiversity, then whether hydrology changes those effects, and finally whether those local effects matter at a larger scale. That last step seems especially important because finding a strong effect in one pool does not necessarily mean it has a major ecosystem-level consequence.

I think this is one of the most interesting ideas in the paper because the same ecological process can have opposite effects depending on environmental conditions. Hippo-derived nutrients may support aquatic life when water is flowing, but become harmful once those inputs build up during no-flow periods. This makes the effect of hippos much more context-dependent than simply labeling them as beneficial or harmful.

This seems to explain the mechanism behind the authors’ hypothesis. When river flow decreases, hippo-derived organic matter is less able to move downstream and instead builds up locally. I would therefore expect the biggest differences between high- and low-hippo-density pools during the dry season, when these inputs are less diluted or transported.

What I find interesting here is that the ecological effect of hippos is being changed indirectly by humans. Hippos already move nutrients from land into rivers, but reducing river flow changes what happens to those nutrients once they enter the water. This suggests that understanding a species’ ecological role requires looking at the environmental conditions humans are changing around it, rather than studying the species in isolation.

blood clotting is an example of a process that relies on the extracellular matrix as a vehicle for cellular communication

R0:

Reviewer #1:

This prospective cohort study compared simplified and standard protocols for treating acute malnutrition in 299 children (165 standard, 134 simplified) using appropriate descriptive, nonparametric, and survival analyses. Baseline characteristics were generally similar, supporting comparability, though the non-randomized design limits causal interpretation. Both protocols showed similar weight gain and time-to-recovery, while the simplified protocol achieved a higher recovery rate. The simplified approach also required fewer resources, suggesting improved efficiency without loss of effectiveness. However, the lack of a sample size justification, limited adjustment for confounding, and high default rates reduce the strength of the conclusions.

Suggested revisions: 1- The manuscript does not include a sample size or power calculation, and no justification is provided that the study was adequately powered to detect differences between protocols. 2- Although statistical methods are described, the manuscript lacks a clearly defined primary analysis framework (e.g., superiority vs. non-inferiority), which is important given the comparative objective. 3- The analyses comparing outcomes between the two protocols are largely unadjusted despite the observational (non-randomized) design, and potential confounding is not adequately addressed in regression modeling. 4- The Cox proportional hazards model does not clearly include a variable for the protocol (simplified vs. standard) as a primary exposure in the adjusted analysis, limiting interpretation of comparative effectiveness. 5- The manuscript does not describe whether model assumptions were assessed, including the proportional hazards assumption for Cox regression. 6- The methods do not specify how missing data were handled, if at all. 7- There is no discussion of multiple comparisons or control of type I error, despite numerous statistical tests being conducted. 8- The manuscript does not explicitly state the alpha level (significance threshold) used for statistical testing. 9- The description of continuous variable analyses should be clarified to explicitly state that nonparametric tests (e.g., Mann–Whitney U test) were used to compare continuous variables between the two protocols and why this choice was appropriate (e.g., non-normal distributions). 10- In Table 6, the variable “percentage of visit on time” requires clarification, particularly how it is defined and interpreted when values exceed 1 (or whether it is expressed as a percentage vs. proportion). 11- The interpretation of regression results should be reviewed, as some findings (e.g., large hazard ratios and counterintuitive effects of number of visits) suggest possible model misspecification or misinterpretation. 12- Although the statistical methods section lists the tests used, it would benefit from greater detail on model-building strategy, including justification for variable selection based on p-values (≤0.25). 13- In Tables 5 and 6, include the sample sizes for each category to improve clarity and interpretability of the results.

Reviewer #2:

This prospective observational cohort study compares a simplified protocol (single product RUTF; fixed dosing of 2 sachets/day for SAM and 1 sachet/day for MAM regardless of body weight; expanded admission criteria) with a WHO 2023-based standard protocol (weight-based dosing; separate SAM/MAM criteria) for children aged 6–59 months with acute malnutrition, across four Venezuelan states (February–August 2024). Allocation was by site rather than randomised: public clinics delivered the simplified protocol and Fe y Alegría centres the standard protocol. Of 299 admitted children (~87% MAM), both arms showed similar weight-gain velocity and time-to-recovery, but the simplified arm had a higher crude recovery rate (70.1% vs 59.4%), lower default, fewer inpatient referrals, and ~15% lower cost per recovered child. The authors conclude the simplified protocol is as effective as, and cheaper than, the standard protocol.

My main recommendation is to carefully examine alignment with WHO 2023 and clearly define that alignment. Also, consider revising the analysis to include both adjusted and unadjusted models when comparing outcomes, especially since this is an observational study without any randomisation.

Abstract

The abstract needs to clearly define what acute malnutrition is and what SAM is. Ideally, use consistent terminology throughout the abstract: either "acute malnutrition" or "severe acute malnutrition" (note that I did not jump to using the abbreviation SAM without first stating it in full). The abstract then suddenly mentions MAM, assuming the reader already knows what acute malnutrition, SAM, and MAM are, both on their own and in relation to one another.

In line 57, do you mean body weight or RUTF sachet weight? I think you mean body weight, but please be clear. You will have readers who are just starting out in acute malnutrition research, and this may be the first paper on acute malnutrition they read this year.

Indicate the anthropometric criteria used to define MAM, SAM, and acute malnutrition in this study, as these can vary.

Indicate the frequency of monitoring during the monitoring period, whether weekly, biweekly, or monthly.

Introduction

The anthropometric criteria for all forms of acute malnutrition used are missing.

Please expand on the criteria for high-risk MAM cases by referring to the WHO 2023 guidelines. You may also consider these papers: - https://pubmed.ncbi.nlm.nih.gov/41353631/ - https://pmc.ncbi.nlm.nih.gov/articles/PMC12352212/ - https://gh.bmj.com/content/11/7/e023264

In lines 121–135, I am not clear about which COVID-19-related problems were solved by implementing the simplified protocol.

Throughout the manuscript, I recommend writing "body weight" wherever body weight is meant, instead of just "weight".

Lines 136–139 can be strengthened by stating whether and why any differences in effectiveness are expected, and the implications of this potential difference or lack of difference.

Methods

In line 155, state the number of acute malnutrition cases in the study area relative to other areas. Simply stating that it has "the largest number" is not specific enough — please give figures.

Table 1: Please be specific about the grade of bilateral pitting oedema used for inclusion. For example, did the simplified protocol also treat children with +++ oedema?

The WHO 2023 protocol for MAM includes risk-stratification criteria. Can you add how this study applied these criteria? If it did not, I would refrain from calling it the WHO 2023 protocol and instead refer to it as a country adaptation of the WHO protocol, and address this as a limitation.

Please double-check that the WHO protocol allows children diagnosed with SAM to be treated as MAM once they reach the MAM threshold. This was not the case in 2013.

The study relied mainly on unadjusted between-group tests (Mann–Whitney U and chi-square/Fisher) rather than adjusted regression for the main protocol comparisons. I recommend reporting unadjusted and adjusted regression models for all comparisons between the simplified and standard treatments.

Results

I recommend presenting standardised mean differences instead of p-values in the baseline characteristics table.

The extremely wide confidence intervals for SES in Table 6 suggest to me that the adjusted model was highly unstable and did not have enough observations in each stratum; as a rule of thumb, you need at least ten events per variable (and per stratum of a categorical variable). As it stands, these findings may not be valid. Please also review the oedema result in Table 6, which likewise has a wide confidence interval. Please also indicate p-values in Table 6.

For all tables where the outcome is binary, it is best practice to add a column for the total n and another for the number that had the event.

Perhaps refer to the "side events" as "morbidity" for consistency.

Deaths appear to be reported as zero in Figure 1 and in the Discussion (lines 486–488), but mortality is not included as an outcome in Table 3, although it is listed as a secondary outcome. Please include mortality (even if zero) as an explicit row, and I would generally also include the other standard acute-malnutrition outcomes, such as deterioration to SAM. (Default and non-response are already reported.)

Discussion

Where you mention that higher RUTF doses do not automatically translate into higher caloric intake, it is worth exploring this further. You can read this non-peer-reviewed article, which summarises the argument well using peer-reviewed literature: https://www.ennonline.net/fex/74/en/treatment-dosage-surprising-controversy-arising-new-who-wasting-guidelines

In the paragraph beginning at line 435, the standard treatment arm actually had a much lower recovery rate, whereas Bailey et al. reported similar recovery rates between arms. This is therefore not the best study to demonstrate alignment with the existing literature.

In the paragraph beginning at line 475, I do not believe "efficacy" is the correct term in this research context. Perhaps use another word, or expand on what you mean by efficacy.

Conclusion

No comments

Reviewer #3:

The manuscript is well-written, the methodology is ethically rigorous, and the conclusions are appropriately drawn based on the data presented. The topic is okay although I wish it was more specific, that's "...four states of Venezuela"

Explanation

by a route outside the vascular system, requiring dissolution and absorption across biologic barriers before reaching systemic circulation; oral drugs must cross the GI tract wall, transdermal patches must penetrate the skin, and effect is delayed because absorption and subsequent distribution take time.

Check My Knowledge

1: Which term describes a substance being located outside blood vessels?

Options:
    A: Intravenously
    B: Extravascularly
    C: Subcutaneously
    D: Intravascularly

Answer: B. Extravascularly
2: A clinician documents that a medication has spread outside the vascular space. Which descriptor matches that location?

Options:
    A: Intravascularly
    B: Intravenously
    C: Subcutaneously
    D: Extravascularly

Answer: D. Extravascularly
3: Which option is the best match for the adverb meaning outside the vessels?

Options:
    A: Intravenously
    B: Intravascularly
    C: Subcutaneously
    D: Extravascularly

Answer: D. Extravascularly

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Is this too much info?

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Another idea is the interactive html below

My suggestion is to make this into an interactive html embed with their final avatar personas (AI generated)

For the video, I am thinking if theres a possibility if we can make it more visual and animated, to set-up the VET learners in their journey.

Additionally, for all the personas to be consistent across the courses.

Hi Jo, is this the image you imagine here [image peg]

I think in relation to Pound's poem, Eliot does some interesting work with representing how the characters in his poem are much like the "King down in the vortex,". Like Sienna said above, Lil is very much trapped by her marriage, and the expectations her husband has of a "good time" upon his return from the war. Not only is there an implicit expectation for her to obey this want of his, but there's also the speaker who enforces the rules when saying "Now Albert's coming back, make yourself a bit smart,". It's unclear who this is, but it reminds me of the Black Bishop's Pawn in Middleton's play whose goal is to coerce the virgin white pawn into sexual acts to satisfy the "violently [raging]" lust of the Black Bishop. This speaker not only embodies the deceitful Black Bishop's Pawn, but also the "straight stripe[s] of hard color" in Pound's poem. For Lil, her real life stripes are those of society's expectations of a woman, and her role as subservient and a body to be bent to a man's will. She is trapped in by not only the expectations of a wife, but also the threat of Albert's infidelity, in the line "if you don't give it him, there's other's will,". Unfortunately unlike the chess pieces in Pound's poem, Lil is unable to complete her "Escapes. Renewing of contest," because her world is decidedly dark. Filled with not only outside criticism, but more synthetics and superficial assessments to keep her trapped within the sad monotony of her life.

In Hamlet, Laertes hears Ophelia’s confused speech and says, “This nothing’s more than matter.” He understands that even words that seem to mean nothing can reveal something important about how she feels. Eliot’s couple seems to argue over that possibility. After the man’s thought, “Nothing again nothing,” the woman presses him: “Do you know nothing? Do you see nothing? Do you remember / Nothing?” She treats his silence as an absence of thought or feeling, while the echo of Laertes suggests that his “nothing” might contain more than he can say. The repeated word becomes the thing they cannot agree on: whether silence can communicate anything at all.

Pound, in The Game of Chess, imagines the traditional socialite class; read as a comment and construction of social patriarchy, the poem directly puts the male and female in competition. Lines 3-4 establish violence and tension between objects (the personified chess pieces): "Striking the board, falling in strong "1"s of color,/ Reaching and striking in angles,/ holding lines in one color./ This board is alive with light;/ these pieces are living in form, Their moves break and reform the pattern: ." 9-11, the final two lines, and the concluding stanza gender the poems subjects: "Clashing with "x"s of queens,/ looped with the knight-leaps./ [Stanza Break] "Y pawns, cleaving, embanking!" The nominal use of "x" and "y," one, can refer to the spatial position of the pieces within "The Game of Chess," but might also represent sex (xx & xy) . As the poem progresses, Chess pieces are increasingly humanized. In the final lines, with tone and manner of description growing abstract, the game becomes an allegory for human behavior (the male-female dynamic): "Whirl! Centripetal! Mate! Kind down in the vortex./ Clash, leaping of bands, straight stripe of hard color,/ Blocked light working in. Escapes. Renewing of contest." In this excerpt, the disjunct and illusory tone is apparent. The dramatic use of exclamation points and asyndeton (lack of conjunctions) make meaning tenuous—almost esoteric to the author. This said, the last two lines seem to contrast: while the first line illustrates humans behavior as cyclic, "centripetal," those following argue for its linear nature, a "straight stripe of hard color,/ Blocked light working in. Escapes." Then, again, the last word conflicts with its proceeding: "Renewing of contest," again, suggests a continuity in humanity and its patterns.

Within TWL, Lil and her friends depend upon subservience; within the luncheon (or dinner) party, all discuss Lil as a product of her marriage and husband. Judged to look "antique," Lil attempts to defend her physical appearance, stating "I can't help it." With Lil's reaction having such little consequence (not to say value), a power and monopoly is given to the action of 'judgment' and vocation of 'service.' As shown by the following lines, Lil is wholly defined by her offerings as a woman (wife): "You are a proper fool, I said. Well, if Albert won't leave you alone, there it is, I said,/ What you get married for if you don't want children? HURRY UP PLEASE ITS TIME." Ultimately, Lil is without a personal identity.

In all, works discuss gender, engendered normative law, and its illogical (or more so...) unintuitive perpetuation by subjugated sects of society ("the female").

Do you think we need to present this alphabetically

Even with claims we can spot out patterns/faults and limit one's argument with those. It is a powerful tool to use and could make one's claim seem not as sttong.

Pointing out any flaw in an argument always shows the reader that it is not as strong as they thought the argument to be, which in short makes it feel like it is invalid.

This is where the slow reading/thinking is good because during every first read we may not grasp everything as it is said. So, slowing down when reading the arguments it's best to get the full idea.

or transform this image and content to a hotspot?

Please check the image idea peg

o: I notice Kreon says "never" three times. He is very angry and scared of losing his power because of a woman. He does not care about family or the gods. He only cares about being the leader of this country. This becomes a big conflict with Antigone. Antigone fights for love and family, but Kreon fights for power and pride. This makes Kreon looks like a bad leader. I think this pattern of "power vs. family" is very important for my essay.

Q: Before Ismene told Antigone not to break the law, but now Ismene says that she wants to die with her sister. I don't really understand Ismene. If she wants to die, or just feel upset and lonely? Also, Antigone is very mean to her sister at here. Why does Antigone push her sister away when Ismene is trying to help her? I want to ask the class if Antigone is cruel or just want to safe Ismene's life.

E: I looked up the name "Oidipous" in my background knowledge (Source: Greek mythology). Oedipus is a famous tragic hero in Greek mythology, he is Antigone's father. He did terrible things without knowing it such as killing his own father, and this cause his own family have a bad luck. The Chorus calls the Antigone is a "poor awful child." This helps me understand why Antigone is so sad and why her family is cursed. this explains why she is not afraid to die.

This makes me think of how close-up can make an ordinary object suddenly feel strange or significant. The camera can transform everydayn reality by controlling what the viewer pays attention to.

ffofkrojgr

font too small , make it bigger

one inbox placement test, next steps and one call.

vs the full audit which is the deliverbaility audit, deep dive of what to correct or do, and prepare your list and semgentation and cleanup for black friday or high sending period.

we prep strategy but they execute it.

hard to rea, use the italics with the light green like in hero or titles, ad use regular font for most of it. italicsbold forimportant stuff

weird way to say this. how about we put flags of our nationalities vietnam, brazil canada greece wher we live greece brazil vietnam netherlands and languages we speak french english greek spanish protuguese vietnamese

lets creat our own icon in our brand for his. these dot' fit here . also i think of using these as stickers only or like backgroudn patterns for posts or shit or maybe not at all

remove the icon and just make the email 2-3 fonts bigger so iit fills te pill box better, just not too big

also animate the scroll things shoul daimate on scroll. but clever

1-2 and 2+ is the same math. we can make it a bit worst and just say 32% + int her atio so people unerstand it can be more than 32%

this can like so be an infographic.

like the square are base on how much of their list is crap. bu we might need to be or granualr pbased on contatsna dhow bad, caue ow it feels all options say same % lol

then the how much you spend a month on garbage+ how much on your esp when it could be a tier lower so moer money, hn inboxing how bad it is based on average from validiy, and then how much better it woul dbe if better inboxing. so like in my eye i can see stuff and then number might be in the infographic or unde or as labels, so i can see the impact of how many emails a month or a yea i send to the abys ,how much money i spend i could have kept money i lost from not conencting the money i lost from paing esp. id on'T know but its a lot to read for an inforgaphic ight now. but the nu mebrs are good though they are big numbers

this will be removed right? also the cta buttno at the bottom of page is good but once we sroll after hero it should float slowly up the page and maybe back down as if it was bobbing in the sea? so maybe change it to a bottle with message for you& and then we havr cool game that adds another % off maximum extra 5-10-maybe 15%% on list validation? or no? with upsell or somethign that mkes people lick to learn somethign that will make they buy or pop up that will make them buy or meeting or somethignt....let sbe clever with the floating idea different parts of the page can have different debris floating that is clickable ? id onT'know...

The world would be a better place in every aspect if everyone used critical thinking.

It's very important to look at every argument to see different perspectives.

are external or internal factors shaping my approach to this situation?

There are a lot of different concepts, so that's why it's important to create a mind map or some alternative way to make your information more digestable.

When you read, you naturally gather more information. This makes your ability to critical think stronger.

Asking questions is the most important form of critical thinking.

Every decision you make there has to be a little bit of scrutiny and skepticism.

Critical thinking develops more and more as you read. It's important to keep developing your ability to think critically.

Each decision you make is important and shows who you are as a person.

Open item for us where to store the files that they will download

Do we need a graphics that will represent the process?

Add image here

an issue they all still have is the top of the se i se wavy line and then rectangle laso light blue. it looks weirf

b the motion c the light beam also the icon next to labels are wrong, this keeps happenning. and remembe ew decided how much biggr the icons woul dbe(or did i stil lnot confirmm?)

This is a good way to get people to engage in literary analysis.

It's so much easier to understand what you're reading and feel less threatened by it when you can visually see all the information laid out.

It feels fufilling when you can go back and write an answer to your question. Like when I wondered what KWL was and then it told me in the next paragraph.

I wonder if this will help me organize my thoughts better when i'm reading.

Different genres require different thinking and annotation styles. Do they ever overlap?

I love when I buy a book second-hand and there are annotations in it! It's very special to me to be able to read what someone's thinking.

This is why if you read multiple genres, you will develop skills and gain information that you will keep for the rest of your life.

people are more inclined to do this when they actually care about what they're reading.

Asking questions in the margins and then going back to answer them is a great way to learn. Even connecting the author's different literary works to each other to compare and contrast them.

For me, reading is a vital part of life. A lot of lessons in life (at least for me) come from the books I read. I don't think i've ever really thought about my specific reading process. When I read it's for fun, but it also teaches me lessons that helped me become the person I am today.

There are so many different ways to read things and perceive them.

REMEMBER THIS, IDIOT (to me, don't worry)

How is the authot trying to change or affect your perspective?

It's almost as if each genre is a whole different culture.

Warming up is important if you want to be at your best at something.

Having the goal to win for one's country can be uniting.

Having wrestling in third world country is good for growing the sport.

How will this vary depending on the author?

What is heuristic of KWL?

Should be "wield" and not "yield"?

I like this quote because it describes selective thinking and having a preference for things which can be complicated.

This stands out because the founder is a young person which is less common.

This stands out because many niche food places have to find ways to keep there customers happy.

Seeing all these habits of mind for success makes me realize just how much we can learn from reading and writing.

Professors can make or break the way you think about school and learning.

Individual experience is important because by learning about everyone's personal experiences, it leads to more open mindedness and nuanced understandings of each other. More people are inclined to learn when what they're learning about connects to them in some way.