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Nearly all pancreatic adenocarcinomas (PDAC) are genomically characterized by KRASexon 2 mutations. Most patients with PDAC present with advanced disease and are treated with cytotoxic therapy. Genomic biomarkers prognostic of disease outcomes have been challenging to identify. Herein leveraging a cohort of 2,336 patients spanning all disease stages, we characterize the genomic and clinical correlates of outcomes in PDAC. We show that a genomic subtype of KRASwild-type tumors is associated with early disease onset, distinct somatic and germline features, and significantly better overall survival. Allelic imbalances at the KRASlocus are widespread. KRASmutant allele dosage gains, observed in one in five (20%) KRAS-mutated diploid tumors, are correlated with advanced disease and demonstrate prognostic potential across disease stages. With the rapidly expanding landscape of KRAStargeting, our findings have potential implications for clinical practice and for understanding de novo and acquired resistance to RAS therapeutics.

Objectives: In 2014, New York City initiated a childcare influenza vaccine requirement to increase influenza vaccination rates among children aged 6-59 months attending city-regulated childcare, including prekindergarten. We evaluated the requirement’s effect on vaccination rates in childcare-aged children in New York City.Methods: We examined influenza vaccination rates in children aged 6-59 months and by age groups of 1, 2, 3, and 4 years for 8 influenza seasons (2012-2013 through 2019-2020), representing 2 seasons before the requirement, 2 seasons during the requirement, 2 seasons after its suspension, and 2 seasons after its reinstatement. We also assessed rates in a comparison group of children aged 5-8 years. We performed a difference-in-differences analysis to compare rate differences in age groups when the requirement was and was not in effect. We considered P< .05 as significant based on the Wald χ2test.Results: Influenza vaccination rates among children aged 6-59 months increased 3.7 percentage points (from 47.7% to 51.4%) by the requirement’s second year and declined 6.7 percentage points to 44.7% after suspension. After reinstatement, rates increased 10.7 percentage points to 55.4%. Rate changes were most pronounced among 4-year-olds, increasing 12.7 percentage points (from 45.3% to 58.0%) by the requirement’s second year, declining 14.1 percentage points to 43.9% after suspension, and increasing 22.2 percentage points to 66.1% after reinstatement. In the comparison group, rates increased 4.9 percentage points (from 36.5% to 41.4%) after reinstatement. Rates increased significantly among 4-year-olds before versus at the initial requirement and decreased significantly after suspension. After reinstatement, rates increased significantly among all groups except 1-year-olds.Conclusion: The New York City influenza vaccine requirement improved influenza vaccination rates among preschool-aged children, adding to the evidence base showing that vaccine requirements raise vaccination rates.

MacKenzie Scott, one of the richest women in the world with a $36 billion fortune, has gained attention for her philanthropic efforts. Scott has given away over $17 billion to charitable organizations, surprising them with unrestricted gifts. Her approach to philanthropy, which emphasizes trust and allowing organizations to define their work, has been transformative in the world of high-profile donors. Through initiatives like the Yield Giving Open Call, Scott has distributed millions to community-focused organizations, making a significant impact on various causes. [Extracted from the article]

abstract:Populists’ ideological opposition to global governance is well recognized, yet whether and how these actors systematically undermine international organizations remain unclear. The authors argue that a key means by which populists warp global governance is by distorting scientific information, which is necessary for global responses to many public health and environmental issues. Populists are motivated to withhold or misreport scientific information due to their anti-elite, prostate sovereignty views. Using new data on the source and quality of information provided to international organizations (ios), the authors find that populist leaders are significantly less likely to provide scientific information to ios than are other types of leaders. When they do offer such data, they are less accurate than the information that other sources supply. The authors’ findings suggest that populism may stymie international institutions’ ability to govern in areas of pressing international concern.

In epidemiological studies, the measurements of disease outcomes are carried out by different evaluators. In this paper, we propose a two-stage procedure for detecting outlier evaluators. In the first stage, a regression model is fitted to obtain the evaluators’ effects. Outlier evaluators have different effects than normal evaluators. In the second stage, stepwise hypothesis tests are performed to detect outlier evaluators. The true positive rate and true negative rate of the proposed procedure are assessed in a simulation study. We apply the proposed method to detect potential outlier audiologists among the audiologists who measured hearing threshold levels of the participants in the Audiology Assessment Arm of the Conservation of Hearing Study, which is an epidemiological study for examining risk factors of hearing loss.

AbstractThe Fact-or-Faux column addresses issues of misinformation and science media literacy. Here, we focus on the important role of key institutions in fostering critical discourse, developing scientific consensus, and providing reliable sources of scientific information.

Our Sun lies within 300 parsecs of the 2.7-kiloparsecs-long sinusoidal chain of dense gas clouds known as the Radcliffe Wave1. The structure’s wave-like shape was discovered using three-dimensional dust mapping, but initial kinematic searches for oscillatory motion were inconclusive2–7. Here we present evidence that the Radcliffe Wave is oscillating through the Galactic plane while also drifting radially away from the Galactic Centre. We use measurements of line-of-sight velocity8for 12CO and three-dimensional velocities of young stellar clusters to show that the most massive star-forming regions spatially associated with the Radcliffe Wave (including Orion, Cepheus, North America and Cygnus X) move as though they are part of an oscillating wave driven by the gravitational acceleration of the Galactic potential. By treating the Radcliffe Wave as a coherently oscillating structure, we can derive its motion independently of the local Galactic mass distribution, and directly measure local properties of the Galactic potential as well as the Sun’s vertical oscillation period. In addition, the measured drift of the Radcliffe Wave radially outwards from the Galactic Centre suggests that the cluster whose supernovae ultimately created today’s expanding Local Bubble9may have been born in the Radcliffe Wave.

AbstractMenstrual suppression, the reduction or elimination of occurrences of monthly bleeding, has become increasingly commonplace. As with many choices that women make about their bodies, however, the decision to suppress menstruation may be influenced at least in part by the socially constructed meanings associated with their bodies and its stigmatized functions. In this study, we investigated whether self-objectification may be associated with menstrual suppression using quantitative measures of objectified body consciousness. We found that one aspect of self-objectification in particular, body surveillance, was significantly correlated with menstrual suppression. We also explored menstruators’ self-reported motivations for pursuing suppression using open-ended responses and found that different groups of suppressors endorsed different motivations. That is, menstruators who sought short-term suppression were more likely to be motivated by specific activities for which periods are judged to be incompatible (i.e., sexual relations and important events), whereas menstruators who sought long-term suppression were more likely to be motivated by persistent unpleasant circumstances associated with menstruation (i.e., inconvenience and pain). Finally, we discuss the implications of these findings in context of health, stigma, objectification, and choice.

precis:This essay discusses how the Potiphar’s wife/Joseph interactions described in Genesis 39 are dealt with by sources both within Jewish tradition and from a Christian viewpoint. The Jewish sources begin with examples from the Late Second Temple period and beyond, followed by illustrations from midrashim from the ancient world and commentaries through the present. The events in Genesis 39 are then explored by way of Christian sources from the Patristics (church Fathers) through examples from the sixteenth to the twenty-first centuries.

Mpox is a viral infection, which primarily caused sporadic outbreaks in West and Central Africa until causing a global epidemic in 2022. The disease has disproportionately affected people with human immunodeficiency virus and men who have sex with men. Transmission is through close physical contact, including sexual contact. Infection presents with a characteristic rash, with frequent anogenital involvement—polymerase chain reaction of skin lesions is diagnostic. Vaccination is available for primary prevention and postexposure prophylaxis. Treatment consists of supportive care, with antiviral medications available via clinical trials and/or for patients with severe disease.

AbstractNGSSscientific and engineering practices include “asking questions” and “obtaining, evaluating and communicating information.” These are skills that students need to learn and practice to become lifelong science learners and they are skills that these instructional resources help teachers to teach.