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The complexity of modern biology poses challenges in fostering interdisciplinary understanding, particularly between practicing scientists and the public. Furthermore, scientists often lack formal training in science communication, despite various motivations to engage the public. The science literacy of the public in the biological sciences can also vary across socio-economic and cultural backgrounds. Leveraging popular culture and informal learning practices to promote active learning offers promising avenues to enhance public understanding of biological systems. Organized sports hold collective recognition across various communities and cultures, serving as a means to bring people together. Notably, the NCAA March Madness event holds widespread national and international popularity, presenting an opportunity to laterally apply this concept to promote science communication within STEM and biology education. An educational social media and web-based contest tool was developed integrating NCAA-inspired brackets with animal biological systems concepts. The tool featured tournament-style matchups based on animal biological systems, interesting animal facts, and a voting system, all housed within a user-friendly interface. To encourage regular user access to the tool, graphic designs were developed for all social media posts to aid in visual recruitment to the voting website. Based on online metrics, the use of social media garnered repeat users across both the public and educators. The latter noted the tool's simplicity and informative content. Application of this social media and web-based bracket contest tool, which leverages informal settings for active learning for use in biology education, can foster science communication to engage audiences, improve comprehension, and promote interdisciplinary biology education.

As educational justice scholarship addressing racial oppression continues to name the role of the spirit, there is a need for Black and Brown Christian educators and researchers to locate ourselves as grounded in the epistemologies and pedagogies of Christ as our spiritual home. This paper brings together eight Black and Brown Christian educators and researchers to grapple with what it means to be Christians committed to racial justice in education against the backdrop of centuries of religious corruption. Through collaborative autoethnography, we turn to our spiritual and religious lives situated within our racialized identities to challenge the disciplinary and material boundaries of what critical qualitative research counts as "knowing." In doing this, we give ourselves, and all educators and researchers, permission to make evident the unseen forces that shape our ways of being in research and teaching.

College-in-prison programs are positioned to expand substantially under the reinstatement of Pell Grant eligibility for people in prison. While this change will enable more students who have been systemically excluded from higher education to attend college, degree completion is rare during incarceration and post-release. Student perspectives can shed light on both the value of college-in-prison and the financial barriers to realizing its value. This study analyzes data from 12 focus groups with 105 total college-in-prison student participants, 114 student survey responses, and 45 stakeholder interviews. The data were collected between 2018-2022 during a process evaluation of the College-in-Prison Reentry Initiative, which provided funding to college-in-prison programs in New York State as part of the Manhattan District Attorney's Office Criminal Justice Investment Initiative. The findings demonstrate that students value college-in-prison, describing how it fostered self-reflection and personal growth and provided them with a skillset that may help them gain employment upon release. However, students also raised concerns about reenrolling and completing their degrees following release. Intentional, holistic reentry support could address the largely financial barriers to reenrollment. In so doing, students will be more likely to earn their college degrees after incarceration and experience the full value of a college education.

BACKGROUND: Hypotension is associated with organ injury and death in surgical and critically ill patients. In clinical practice, treating hypotension remains challenging because it can be caused by various underlying haemodynamic alterations. We aimed to identify and independently validate endotypes of hypotension in big datasets of surgical and critically ill patients using unsupervised deep learning. METHODS: We developed an unsupervised deep learning algorithm, specifically a deep learning autoencoder model combined with a Gaussian mixture model, to identify endotypes of hypotension based on stroke volume index, heart rate, systemic vascular resistance index, and stroke volume variation observed during episodes of hypotension. The algorithm was developed with data from 871 surgical patients who had 6962 hypotensive events and validated in two independent datasets, one including 1000 surgical patients who had 7904 hypotensive events and another including 1000 critically ill patients who had 53 821 hypotensive events. We defined hypotension as a mean arterial pressure

Background/Objectives: Health care workers are at greater risk for death by suicide compared to the general population and are less likely to seek assistance. More information about correlates of suicidality and treatment-seeking behavior are needed to reduce risk. Methods: The American Foundation for Suicide Prevention developed an Interactive Screening Program to identify and engage at-risk staff and trainees in health care settings. The study reports on the prevalence and demographic and clinical predictors of current suicidal thoughts, behaviors and mental health treatment at a single site (n = 5898) from 2009 to 2024. Results: The study found that 18.2% of respondents reported current suicidal thoughts and behaviors. These were more common among respondents who were younger, male, and who identified as a race/ethnicity other than non-Hispanic White. Suicidal thoughts and behaviors were more likely among those with higher PHQ-8 scores (OR = 1.23, p < 0.01) and those who endorsed maladaptive coping behaviors, hopelessness, loneliness, stress and nervousness (ORs 1.36-3.04, ps < 0.01). Current mental health treatment was more likely among women, non-Hispanic White respondents compared with Asian or Pacific Islander respondents, and nurses relative to physicians. Mental health treatment was also associated with higher PHQ-8 scores, lifetime suicide attempts, difficulty controlling eating and alcohol consumption, and recent feelings of anxiety, stress and nervousness. Conclusions: Findings suggest a continued need to identify and engage health care trainees and staff who are at risk for suicide and to establish new approaches to linking these individuals to resources or interventions aimed at reducing risk. The study identified male and/or Asian/Pacific Islander-identifying health care workers who reported intense loneliness and/or hopelessness, use of non-prescription drugs and recent suicidal thoughts and/or behaviors as high-risk individuals who may require enhanced methods of outreach, identification, acceptance and accessibility of treatment.

Background: Circulating glycine levels have been associated with reduced risk of coronary artery disease (CAD) in humans but these associations have not been observed in all studies. We evaluated whether the relationship between glycine levels and atherosclerosis was causal using genetic analyses in humans and feeding studies in mice. Methods: Serum glycine levels were evaluated for association with risk of CAD in the UK Biobank. Genetic determinants of glycine levels were identified through a genome-wide association study (GWAS) and used to evaluate the causal relationship between glycine and risk of CAD by Mendelian randomization (MR). A dietary supplementation study was carried out with atherosclerosis-prone apolipoprotein E deficient (ApoE-/-) mice to determine the effects of increased circulating glycine levels on cardiometabolic traits and aortic lesion formation. Results: Among 105,718 UK Biobank subjects, elevated serum glycine levels were associated with significantly reduced risk of prevalent CAD (Quintile 5 vs. Quintile 1 OR = 0.76, 95% CI 0.67-0.87; p < 0.0001) and incident CAD (Quintile 5 vs. Quintile 1 HR = 0.70, 95% CI 0.65-0.77; p < 0.0001) after adjustment for age, sex, ethnicity, anti-hypertensive and lipid-lowering medications, blood pressure, kidney function, and diabetes. A GWAS meta-analysis with 230,947 subjects identified 61 loci for glycine levels, of which 26 were novel. MR analyses provided modest evidence that genetically elevated glycine levels were causally associated with reduced systolic blood pressure and risk of type 2 diabetes, but did not provide significant evidence for an association with decreased risk of CAD. Glycine supplementation in mice had no effects on cardiometabolic traits or atherosclerotic lesion development. Conclusions: While expanding the genetic architecture of glycine metabolism, MR analyses and in vivo feeding studies did not provide evidence that the clinical association of this amino acid with atherosclerosis represents a causal relationship.

BACKGROUND: 2022 survey data showed 29% of Veterans utilized Veterans Affairs (VA) paid health care at a non-VA facility, 6% higher than in 2021. Despite an increase in the number of Veterans accessing care in the community via the MISSION Act Community Care Program (CCP), there is limited information on the quality of mental health care delivered to Veterans in these settings. Further, Veterans report barriers to quality care, including poor communication between CCP and VA providers, which can result in negative patient outcomes. We aimed to evaluate the feasibility and acceptability of using electronic screening, eScreening, as part of a process involving remote symptom screening, symptom monitoring, and clinically driven communication from VA to CCP providers, for Veterans accessing mental health treatment in CCP settings. METHODS: Veterans (n = 150) diagnosed with major depressive disorder, an anxiety disorder, post-traumatic stress disorder, and/or an adjustment disorder referred to mental health care in CCP between August-November 2021 were eligible to participate. Veterans received an eScreening link to complete an initial web-based assessment and three follow-up assessments spaced 4-6 weeks apart over the course of their treatment. Quantitative assessment data was largely characterized using descriptive statistics and included patient-reported outcome (PRO) measures (PTSD and depression), health-related quality of life/functioning, community care information (e.g., number of sessions attended), and satisfaction with the eScreening technology. Qualitative interview data was also collected from participating Veterans and CCP providers to better understand experiences with eScreening. RESULTS: Findings support the feasibility and acceptability of using eScreening to administer and monitor PROs for Veterans accessing mental health treatment in CCP. Of the Veterans who provided eScreening satisfaction ratings (Ns = 45-55), 89% had no technical difficulties; 78% felt comfortable entering personal information; and 83% were neutral or positive about ease of use. Focus group interviews revealed strong support from Veterans, who stated the software was easy to use; they felt comfortable completing PRO measures; and they appreciated having their symptoms monitored. Similarly, providers indicated eScreening had a positive impact on communication, collaboration of care, and transparency. CONCLUSIONS: Technologies like eScreening represent a promising tool to support the mental health care Veterans receive when they access CCP.

INTRODUCTION: Addressing physician burnout is critical for healthcare systems. As electronic health record (EHR) workload and teamwork have been identified as major contributing factors to physician well-being, we aimed to mitigate burnout through EHR-based interventions and a compassion team practice (CTP), targeting EHR workload and team cohesion. METHODS: A modified stepped wedge-clustered randomized trial was conducted, involving specialties with heavy InBasket workloads. EHR interventions included quick-action shortcuts and recommended practice for secure chats. The CTP comprised 30-s practice between physicians and their dyad partners. Survey and EHR data were collected over four assessment periods. Linear and generalized mixed-effects models assessed intervention effects, accounting for covariates. RESULTS: Forty-four physicians participated (20% participation rate). While burnout prevalence decreased from 58.5% at baseline to 50.0% at the end of the study, burnout reduction was not statistically significant after EHR (OR 0.43, 95% CI 0.12 to 1.61, p = 0.21) or EHR + CTP (OR 0.60, 95% CI 0.17 to 2.10, p = 0.42) interventions. Statistically significant greater perceived ease of EHR work resulted from both the EHR intervention (coefficient 0.76, 95% CI 0.22 to 1.29, p = 0.01) and EHR + CTP intervention (coefficient 0.80, 95% CI 0.26 to 1.35, p

Current US clinical practice guidelines for advanced prostate cancer management contain recommendations based on high-level evidence from randomized controlled trials; however, these guidelines do not address the nuanced clinical questions that are unanswered by prospective trials but nonetheless encountered in day-to-day practice. To address these practical questions, the 2024 US Prostate Cancer Conference (USPCC 2024) was created to generate US-focused expert clinical decision-making guidance for circumstances in which level 1 evidence is lacking. At the second annual USPCC meeting (USPCC 2024), a multidisciplinary panel of experts convened to discuss ongoing clinical challenges related to 5 topic areas: biochemical recurrence; metastatic, castration-sensitive prostate cancer; poly [ADP-ribose] polymerase inhibitors; prostate-specific membrane antigen radioligand therapy; and metastatic, castration-resistant prostate cancer. Through a modified Delphi process, 34 consensus recommendations were developed and are intended to provide clinicians who manage prostate cancer with guidance related to the implementation of novel treatments and technologies. In this report, the authors review the areas of consensus identified by the USPCC 2024 experts and evaluate ongoing unmet needs regarding translational application of the current clinical evidence.

BACKGROUND: Californias relatively low smoking rate (10.1% in 2019-2020) (About CHIS, UCLA Center for Health Policy Research, 2024) masks deep disparities among low-income populations, where smoking rates are nearly double that of their middle- to upper-income peers. Low-income smokers report a similar desire to quit and similar rates of recent quit attempts as smokers from other groups; yet, they often face barriers in accessing effective resources to facilitate successful cessation. METHODS: Our team will conduct a pragmatic stepped-wedge cluster, randomized controlled trial of Enhanced Multicomponent Proactive Navigator-Assisted Cessation of Tobacco Use (EMPACT-Us), a suite of tobacco cessation services supported by patient navigators, designed in close partnership with patients, providers, and community stakeholders. The study will take place at Family Health Centers of San Diego (FHCSD), the largest federally qualified health center (FQHC) in San Diego. Eight primary care clinics are included, where 70% (n = 13,496) of smokers at FHCSD receive care. DISCUSSION: We hypothesize that multiple points of engagement and integration of navigation services into the workflow of existing staff will improve utilization and cessation success. This study will examine if the enhanced suite of services offers insights on how to best integrate evidence-based tobacco treatment services into usual care. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05750537, Registered on March 1, 2023. https://clinicaltrials.gov/study/NCT05750537 .

BACKGROUND: The American College of Cardiology, American Heart Association, and Centers for Medicare and Medicaid Services recommend shared decision-making (SDM) for patients with severe aortic stenosis choosing between transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR). Although tools such as patient decision aids (DAs) and training in SDM have been shown to improve SDM, implementation of SDM and DAs is limited. The IMproving treatment decisions for Patients with AortiC stenosis Through Shared Decision Making (IMPACT SDM) study aims to (1) determine the effectiveness of the interventions (a DA and clinician SDM training) in achieving SDM (primary outcome) and improving the quality of decisions about aortic valve replacement, (2) determine the reach of the DAs and adoption of training, and (3) explore potential mechanisms of effectiveness and implementation at the patient-, clinician-, and clinic-level. METHODS: The study is a hybrid type II effectiveness-implementation study using a cluster randomized batched stepped wedge trial with 8 sites across the USA. Eligible patients will be surveyed before and after visits with the heart valve team; clinicians will be surveyed after visits. Reach of DAs and adoption of training will be tracked. Clinicians will be interviewed regarding barriers and facilitators to implementation. DISCUSSION: The IMPACT SDM Study seeks to provide evidence of the ability of the interventions to improve SDM and decision quality, and also to shed light on barriers and facilitators to SDM implementation to promote future implementation efforts. TRIAL REGISTRATION: ClinicalTrials.gov NCT06171737. Registered on December 15, 2023.

OBJECTIVES: Targeted therapies have been shown to improve outcomes in metastatic non-small cell lung cancer (mNSCLC) with driver mutations. We evaluated the real-world prevalence of human epidermal growth factor receptor 2 (HER2; ERBB2) tumor gene mutations among patients with mNSCLC and described historical treatments and outcomes in patients with HER2-mutant mNSCLC, during a period when there was no approved targeted therapy for HER2-mutant mNSCLC. MATERIALS AND METHODS: This retrospective observational study used a US nationwide de-identified NSCLC clinico-genomic database. Eligible patients were adults diagnosed with HER2-mutant mNSCLC from January 2014 to July 2021 without co-occuring epidermal growth factor receptor (EGFR) tumor mutations. Descriptive statistics were used to summarize prevalence, baseline characteristics and treatment patterns. Clinical outcomes were estimated with Kaplan-Meier analyses. RESULTS: Among 9206 patients with mNSCLC, 164 (1.78%) met the eligibility criteria (mean age: 67.3 years, 63.4% White, 56.7% female, and 53.0% with a smoking history). 132/164 (80.5%) had at least one line of treatment. Platinum-based chemotherapy (45.5%) and immune checkpoint inhibitor (ICI) with chemotherapy (28.0%) were the most frequently used first-line treatments. The median (95% confidence interval [CI]) real-world (rw) progression-free survival in first-line was 5.5 (4.8, 6.2) months and 3.0 (2.3, 4.2) months in second-line. The median rw overall survival in first-line was 13.2 (10.6, 18.4) months and 8.2 (6.6, 13.2) months in second-line. CONCLUSION: During this study period, the most common regimens were platinum-based chemotherapy with or without ICI in first and second line, and median rwOS was 13.2 and 8.2 months, respectively. These results indicate the need for more effective targeted therapies in this patient population.

BACKGROUND: Clinical trials are increasingly using Bayesian methods for their design and analysis. Inference in Bayesian trials typically uses simulation-based approaches such as Markov Chain Monte Carlo methods. Markov Chain Monte Carlo has high computational cost and can be complex to implement. The Integrated Nested Laplace Approximations algorithm provides approximate Bayesian inference without the need for computationally complex simulations, making it more efficient than Markov Chain Monte Carlo. The practical properties of Integrated Nested Laplace Approximations compared to Markov Chain Monte Carlo have not been considered for clinical trials. Using data from a published clinical trial, we aim to investigate whether Integrated Nested Laplace Approximations is a feasible and accurate alternative to Markov Chain Monte Carlo and provide practical guidance for trialists interested in Bayesian trial design. METHODS: Data from an international Bayesian multi-platform adaptive trial that compared therapeutic-dose anticoagulation with heparin to usual care in non-critically ill patients hospitalized for COVID-19 were used to fit Bayesian hierarchical generalized mixed models. Integrated Nested Laplace Approximations was compared to two Markov Chain Monte Carlo algorithms, implemented in the software JAGS and stan, using packages available in the statistical software R. Seven outcomes were analysed: organ-support free days (an ordinal outcome), five binary outcomes related to survival and length of hospital stay, and a time-to-event outcome. The posterior distributions for the treatment and sex effects and the variances for the hierarchical effects of age, site and time period were obtained. We summarized these posteriors by calculating the mean, standard deviations and the 95% equitailed credible intervals and presenting the results graphically. The computation time for each algorithm was recorded. RESULTS: The average overlap of the 95% credible interval for the treatment and sex effects estimated using Integrated Nested Laplace Approximations was 96% and 97.6% compared with stan, respectively. The graphical posterior densities for these effects overlapped for all three algorithms. The posterior mean for the variance of the hierarchical effects of age, site and time estimated using Integrated Nested Laplace Approximations are within the 95% credible interval estimated using Markov Chain Monte Carlo but the average overlap of the credible interval is lower, 77%, 85.6% and 91.3%, respectively, for Integrated Nested Laplace Approximations compared to stan. Integrated Nested Laplace Approximations and stan were easily implemented in clear, well-established packages in R, while JAGS required the direct specification of the model. Integrated Nested Laplace Approximations was between 85 and 269 times faster than stan and 26 and 1852 times faster than JAGS. CONCLUSION: Integrated Nested Laplace Approximations could reduce the computational complexity of Bayesian analysis in clinical trials as it is easy to implement in R, substantially faster than Markov Chain Monte Carlo methods implemented in JAGS and stan, and provides near identical approximations to the posterior distributions for the treatment effect. Integrated Nested Laplace Approximations was less accurate when estimating the posterior distribution for the variance of hierarchical effects, particularly for the proportional odds model, and future work should determine if the Integrated Nested Laplace Approximations algorithm can be adjusted to improve this estimation.

This paper describes the iterative development, evaluation, and improvement of DAV 715: Human Factors in Aviation, an online doctoral course in the Ph.D. in Aviation program at Embry-Riddle Aeronautical University. From 2013 through 2017, data were collected from students enrolled in the course using a learning experience survey and an end-of-course evaluation survey. Participation was completely voluntary and responses were anonymous to encourage students to provide honest and accurate feedback on the course design, workload, and relevance. Data generated from the surveys informed each course update, guided by the 3-Phase Design (3PD) model.

The COVID-19 pandemic dramatically changed the practice of community-engaged scholarship and challenged internal and external boundary spanners to maintain and grow authentic and meaningful relationships. Female-identifying scholars and practitioners faced, and continue to face, extra personal and professional demands in the postpandemic era (Purcell et al., 2022). In this reflective essay, four female community-engaged scholar-practitioners reflect on the importance and value of cocreating a weekly, virtual coworking space to support professional and personal resilience. Over 4 years, this coworking space shifted in focus from solely a cowriting accountability time during the COVID-19 virtual work era to more of a "relational pause" (Barton et al., 2022) focused on encouraging, caring for, and uplifting one another. We offer readers practical ideas to organize and lead their own virtual coworking spaces or, for institutional leadership roles, strategies to support others in developing communities of care that sustain boundary spanners.

White backlash is the immediate, violent response of some white people to the actual and perceived racial and educational progress of oppressed groups. In this paper, we take a historical detour to map this phenomenon, specifically in the history of K-12 Black education. We demonstrate that the current state of education is not an exceptional moment, but part of a long genealogy of anti-Black educational violence and white backlash. Yet, we suggest that operating from an understanding of the inevitability and imminence of white backlash offers necessary tools in the continued fight for liberatory Black educational futures. [Note: The publication year (2026) shown in the header on the PDF is incorrect. The correct publication year is 2024.]

The purpose of the study was to better understand the extent to which middle school principals' transformational leadership styles affect teachers' data-informed instruction, the influence of teachers' data-informed instruction on middle school student achievement, and the extent to which transformational leaders affect student achievement through data-informed instruction. Therefore, for this study, survey data were collected using Kenneth Leithwood's Transformational School Leadership Survey, as well as Jingping Sun's Data-Informed Instruction Survey. Additionally, this study used Scantron performance data for sixth-grade math to determine the effects of transformational school leaders on student achievement through data-informed instruction. The results showed that transformational school leadership has no effect on middle school teachers' data-informed instruction, and middle school teachers' data-informed instruction has no significant effect on student achievement, with socioeconomic status controlled. The study also showed that transformational school leadership has no statistically significant effect on student achievement through teachers' data-informed instruction. The results of this study help us understand the extent to which transformational school leadership affects student achievement through teachers' data-informed instruction. It also provides knowledge that will help us better educate aspiring leaders, making them effective transformational leaders in schools.

This article examines study abroad personnel's rationale that Black and Latinx students participate in study abroad at a lower rate than their white peers. This article argues that this over-30-year-old rationale should be discontinued to achieve equitable study abroad participation for Black and Latinx students. The author introduces critical race theory as a theoretical lens for study abroad personnel to examine how the internal discourse of racial cultural differences among study abroad personnel is historically linked to pervasive racialized deficit mindsets about Black and Latinx students' achievement. The author reviews existing study abroad scholarship on Black and Latinx student participation to establish a foundation for how the rationale originated and uses critical race theory storytelling as a methodological framework to critique the lower participation rationale. Through this approach, the author advances emergent insights for study abroad personnel to be more equitable, conscious, and intentional in their advocacy for greater Black and Latinx student participation in study abroad programs.

Previous research has underscored the negative effects on students of the abrupt shift to online delivery of education due to the COVID-19 pandemic. Positive education applies the principles of positive psychology to education, which highlights the importance of students' well-being and fosters holistic development. This study investigated whether students' well-being at the start of the semester can predict their academic engagement mid-way through the semester. We collected data on students' well-being and academic engagement in two waves; first, at the beginning of the semester (Time 1) and then 3 months in the semester (Time 2). We tested the students' general well-being and the positive emotion, engagement, relationships, meaning, accomplishment (PERMA) elements at Time 1 with their academic engagement in terms of behavioral, emotional, and cognitive facets at Time 2. Our results show that general well-being at Time positively predicts their total academic engagement and all engagement facets. However, among the PERMA elements, the Meaning element is not correlated with students' engagement or any of its facets. We also tested whether there was a significant change in student well-being and engagement from the start of the semester and midway through. We found that there is a significant small increase in well-being and engagement. Our findings suggest the importance of well-being as a potentially positive resource for students where students with better well-being tend to be more academically engaged. Educational institutions may consider fostering student well-being in their goals to improve the academic success of students.

BACKGROUND: Time and money are limited resources to pursue quality improvement (QI) goals. Computer simulation using Monte Carlo methods may help focus resources towards the most efficacious interventions to pursue. METHODS: This observational, cross-sectional study analysed the length of stay (LOS) for adult American Society of Anesthesiologists (ASA) 1-3 patients in the postanaesthesia care unit (PACU) at a major academic medical centre. Data were collected retrospectively from 1 April 2023 to 31 March 2024. Statistical analysis with Monte Carlo methods simulated the per cent reduction in PACU LOS following the elimination of postoperative nausea and vomiting (PONV), hypothermia (initial temperature

ABSTRACT: Background: As healthcare moves from a one-size-fits-all approach towards precision care, individual risk prediction is an important step in disease prevention and early detection. Biobank-linked healthcare systems can generate knowledge about genomic risk and test the impact of implementing that knowledge in care. Risk-stratified prostate cancer screening is one clinical application that might benefit from such an approach. Methods: We developed a clinical translation pipeline for genomics-informed prostate cancer screening in a national healthcare system. We used data from 585,418 male participants of the Veterans Affairs (VA) Million Veteran Program (MVP), among whom 101,920 self-identify as Black/African-American, to develop and validate the Prostate CAncer integrated Risk Evaluation (P-CARE) model, a prostate cancer risk prediction model based on a polygenic score, family history, and genetic principal components. The model was externally validated in data from 18,457 PRACTICAL Consortium participants. A novel blended genome-exome (BGE) platform was used to develop a clinical laboratory assay for both the P-CARE model and rare variants in prostate cancer-associated genes, including additional validation in 74,331 samples from the All of Us Research Program. Results: In overall and ancestry-stratified analyses, the polygenic score of 601 variants was associated with any, metastatic, and fatal prostate cancer in MVP and PRACTICAL. Values of the P-CARE model at ≥80th percentile in the multiancestry cohort overall were associated with hazard ratios (HR) of 2.75 (95% CI 2.66-2.84), 2.78 (95% CI 2.54-2.99), and 2.59 (95% CI 2.22-2.97) for any, metastatic, and fatal prostate cancer in MVP, respectively, compared to the median. When high– and low-risk groups were defined as P-CARE HR>1.5 and HR

For patients with advanced non-small-cell lung cancer (NSCLC), dual immune checkpoint blockade (ICB) with CTLA4 inhibitors and PD-1 or PD-L1 inhibitors (hereafter, PD-(L)1 inhibitors) is associated with higher rates of anti-tumour activity and immune-related toxicities, when compared with treatment with PD-(L)1 inhibitors alone. However, there are currently no validated biomarkers to identify which patients will benefit from dual ICB1,2. Here we show that patients with NSCLC who have mutations in the STK11 and/or KEAP1 tumour suppressor genes derived clinical benefit from dual ICB with the PD-L1 inhibitor durvalumab and the CTLA4 inhibitor tremelimumab, but not from durvalumab alone, when added to chemotherapy in the randomized phase III POSEIDON trial3. Unbiased genetic screens identified loss of both of these tumour suppressor genes as independent drivers of resistance to PD-(L)1 inhibition, and showed that loss of Keap1 was the strongest genomic predictor of dual ICB efficacy-a finding that was confirmed in several mouse models of Kras-driven NSCLC. In both mouse models and patients, KEAP1 and STK11 alterations were associated with an adverse tumour microenvironment, which was characterized by a preponderance of suppressive myeloid cells and the depletion of CD8+ cytotoxic T cells, but relative sparing of CD4+ effector subsets. Dual ICB potently engaged CD4+ effector cells and reprogrammed the tumour myeloid cell compartment towards inducible nitric oxide synthase (iNOS)-expressing tumoricidal phenotypes that-together with CD4+ and CD8+ T cells-contributed to anti-tumour efficacy. These data support the use of chemo-immunotherapy with dual ICB to mitigate resistance to PD-(L)1 inhibition in patients with NSCLC who have STK11 and/or KEAP1 alterations.

Starting in the 1970s, individuals, businesses and the public have increasingly benefited from policies prohibiting smoking indoors, saving thousands of lives and billions of dollars in healthcare expenditures. Smokefree policies to protect against secondhand smoke exposure, however, do not fully protect the public from the persistent and toxic chemical residues from tobacco smoke (also known as thirdhand smoke) that linger in indoor environments for years after smoking stops. Nor do these policies address the economic costs that individuals, businesses and the public bear in their attempts to remediate this toxic residue. We discuss policy-relevant differences between secondhand smoke and thirdhand smoke exposure: persistent pollutant reservoirs, pollutant transport, routes of exposure, the time gap between initial cause and effect, and remediation and disposal. We examine four policy considerations to better protect the public from involuntary exposure to tobacco smoke pollutants from all sources. We call for (a) redefining smokefree as free of tobacco smoke pollutants from secondhand and thirdhand smoke; (b) eliminating exemptions to comprehensive smoking bans; (c) identifying indoor environments with significant thirdhand smoke reservoirs; and (d) remediating thirdhand smoke. We use the case of California as an example of how secondhand smoke-protective laws may be strengthened to encompass thirdhand smoke protections. The health risks and economic costs of thirdhand smoke require that smokefree policies, environmental protections, real estate and rental disclosure policies, tenant protections, and consumer protection laws be strengthened to ensure that the public is fully protected from and informed about the risks of thirdhand smoke exposure.