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A mixed-methods study was used to determine if an online, mastery-based learning resource was successful in improving content knowledge and retention of critical elements and developmental stages of 16 fundamental movement skills (FMS); a secondary purpose was to determine participant perceptions of their experience with the online resource. Participants (N = 323; motor development (MD) = 94; movement education (ME) = 124; elementary physical education (EPE) = 105) were Teacher Candidates (TCs) in a Physical Education Teacher Education (PETE) Program. Pre- and post-survey data, and pre-, post-, and retention test scores were used to evaluate the program's effectiveness. Paired samples t-tests indicated higher post-test scores for MD ([delta]37.23, p < 0.001, d = 2.32) and ME ([delta]32.12, p < 0.001, d = 1.72). Results from a one-way ANOVA indicated significant improvement and retention of test scores over time, F(3, 331) = 27.761, p < 0.001, [eta-squared] = 0.963. Perceptions of PETE TCs reported positive reactions to the use of the online modules to improve their ability to analyze FMS. Based on these findings, the authors propose that implementing an online, mastery-based resource to analyze FMS may be a positive learning experience for TCs and could lead to long-term content knowledge acquisition of critical elements of FMS.

Distinguishing indolent from clinically significant localized prostate cancer is a major clinical challenge and influences clinical decision-making between treatment and active surveillance. The development of novel predictive biomarkers will help with risk stratification, and clinical decision-making, leading to a decrease in over or under-treatment of patients with prostate cancer. Here, we report that Trop2 is a prognostic tissue biomarker for clinically significant prostate cancer by utilizing the Canary Prostate Cancer Tissue Microarray (CPCTA) cohort composed of over 1100 patients from a multi-institutional study. We demonstrate that elevated Trop2 expression is correlated with worse clinical features including Gleason score, age, and pre-operative PSA levels. More importantly, we demonstrate that elevated Trop2 expression at radical prostatectomy predicts worse overall survival in men undergoing radical prostatectomy. Additionally, we detect shed Trop2 in urine from men with clinically significant prostate cancer. Our study identifies Trop2 as a novel tissue prognostic biomarker and a candidate non-invasive marker for prostate cancer.

Abstract Background Firearm suicide is a leading cause of death in the United States. Suicide prevention experts have advocated for upstream interventions that can be implemented prior to the development of suicidal thoughts, particularly those that focus on lethal means safety (LMS; e.g., increasing secure firearm storage). To reach firearm owners with LMS messaging, researchers have developed suicide prevention training content which can be incorporated into firearm training courses. However, no study to date has evaluated impact of such training on firearm course students’ subsequent knowledge, attitudes, and openness related to secure firearm storage. Thus, the current study sought to examine both the feasibility and acceptability of a LMS-focused suicide prevention training module among firearm course students, as well as the impact of this module on students’ secure firearm storage-related knowledge, attitudes, and openness. Methods Firearm instructors (N = 6) and students in firearm classes (N = 83) were recruited to participate. Students were invited to complete voluntary, anonymous pre- and post-surveys during courses they attended that were led by these instructors. Instructors and students were also invited to complete a brief qualitative interview. Results Results indicated that firearm instructors and students in firearm courses found the module feasible and acceptable. Additionally, students’ knowledge about the relationship between firearms and suicide, openness to changing firearm storage practices, and endorsement of the importance of discussing firearms and suicide with fellow firearm owners, as well as willingness and confidence to do so, all significantly increased after viewing the module. Conclusions These findings provide strong support for the use of such culturally competent LMS messaging as upstream suicide prevention in settings such as concealed carry courses.

Abstract Histotripsy is a noninvasive focused ultrasound therapy that mechanically fractionates tissue to create well-defined lesions. In a previous clinical pilot trial to treat benign prostatic hyperplasia (BPH), histotripsy did not result in consistent objective improvements in symptoms, potentially because of the fibrotic and mechanically tough nature of this tissue. In this study, we aimed to identify the dosage required to homogenize BPH tissue by different histotripsy modalities, including boiling histotripsy (BH) and cavitation histotripsy (CH). A method for histotripsy lesion quantification via entropy (HLQE) analysis was developed and utilized to quantify lesion area of the respective treatments. These data were correlated to changes in mechanical stiffness measured by ultrasound shear-wave elastography before and after treatment with each parameter set and dose. Time points corresponding to histologically observed complete lesions were qualitatively evaluated and quantitatively measured. For the BH treatment, complete lesions occurred with > = 30 s treatment time, with a corresponding maximum reduction in stiffness of −90.9 ± 7.2(s.d.)%. High pulse repetition frequency (PRF) CH achieved a similar reduction to that of BH at 288 s (−91.6 ± 6.0(s.d.)%), and low-PRF CH achieved a (−82.1 ± 5.1(s.d.)%) reduction in stiffness at dose > = 144 s. Receiver operating characteristic curve analysis showed that a > ~ 75% reduction in stiffness positively correlated with complete lesions observed histologically, and can provide an alternative metric to track treatment progression.

Abstract Introduction Cardiovascular (CV) risk factors can limit treatment options for migraine. Rimegepant is an orally administered small-molecule calcitonin gene-related peptide receptor antagonist that does not induce vasoconstriction. The aim of these post hoc subgroup analyses was to assess the safety of rimegepant according to CV risk. Methods In a multicenter, long-term, open-label, phase II/III safety study, participants with a history of 2–14 migraine attacks per month of moderate or severe pain intensity self-administered rimegepant 75 mg, orally, to treat migraine up to once daily for up to 52 weeks. Uncontrolled, unstable, or recently diagnosed CV disease was part of the exclusion criteria. Safety was assessed across subgroups according to number of CV risk factors (0, 1, or ≥ 2) and Framingham Risk Score (

Abstract Background In the US, over 50% of suicide deaths are by firearm injury. Studies have found that limiting access to firearms, including storing them temporarily outside of the home or locking and unloading them securely at home, helps prevent suicide. Family members and other loved ones are in a unique position to encourage secure firearm storage. This paper describes the development of a workshop to empower loved ones of individuals at risk for suicide to discuss secure firearm storage in New York State. Methods Using a multistakeholder engagement framework, we partnered with New York State county-level suicide prevention coalitions, local firearms experts, and other stakeholders to develop a 90-min workshop addressing secure firearm storage for suicide prevention. Pilot workshops were co-facilitated by a suicide prevention coalition member and a local firearms expert. Feedback gathered via surveys from workshop attendees and interviews with workshop co-facilitators were used to revise workshop content and inform dissemination. Following pilot workshops, a 1-day training event was held for potential future facilitators, and survey data were collected to assess trainee experiences and interest in facilitating future workshops. Data analysis included rapid qualitative analysis of interviews and statistical analysis of survey responses about acceptability of workshop. Results Four pilot workshops included a total of 23 attendees. Pilot workshop attendees endorsed willingness and confidence to discuss secure firearm storage with a family member or loved one. The training event included 42 attendees, of which 26 indicated interest in facilitating a workshop within the next year. Co-facilitators agreed on several key themes, including the importance of having a “trusted messenger” deliver the firearms portion of the workshop, keeping the conversation focused on firearm safety for suicide prevention, and developing interventions that reflect firearm owning community’s culture. Conclusions Consistent with a public health approach to suicide prevention, this study leveraged a multistakeholder engagement framework to develop a community-based workshop empowering loved ones of individuals at risk for suicide to discuss secure firearm storage. The workshop will be disseminated across New York State. We noted positive and collaborative relationships across stakeholder groups, and willingness to facilitate the workshop among both suicide prevention and firearm stakeholders.

Abstract Therapeutic approaches targeting proteins on the surface of cancer cells have emerged as an important strategy for precision oncology. To capitalize on the potential impact of drugs targeting surface proteins, detailed knowledge about the expression patterns of the target proteins in tumor tissues is required. In castration-resistant prostate cancer (CRPC), agents targeting prostate-specific membrane antigen (PSMA) have demonstrated clinical activity. However, PSMA expression is lost in a significant number of CRPC tumors. The identification of additional cell surface targets is necessary to develop new therapeutic approaches. Here, we performed a comprehensive analysis of the expression heterogeneity and co-expression patterns of trophoblast cell-surface antigen 2 (TROP2), delta-like ligand 3 (DLL3), and carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) in CRPC samples from a rapid autopsy cohort. We show that DLL3 and CEACAM5 exhibit the highest expression in neuroendocrine prostate cancer (NEPC), while TROP2 is expressed across different CRPC molecular subtypes, except for NEPC. We further demonstrated that AR alterations were associated with higher expression of PSMA and TROP2. Conversely, PSMA and TROP2 expression was lower in RB1-altered tumors. In addition to genomic alterations, we show a tight correlation between epigenetic states, particularly histone H3 lysine 27 methylation (H3K27me3) at the transcriptional start site and gene body of TACSTD2 (encoding TROP2), DLL3, and CEACAM5, and their respective protein expression in CRPC patient-derived xenografts. Collectively, these findings provide insights into patterns and determinants of expression of TROP2, DLL3, and CEACAM5 with implications for the clinical development of cell surface targeting agents in CRPC.

There has been a sea of change in our understanding of the contribution of food to both our well-being and disease states. When one addresses “food as medicine,” the concept of oxidative stress needs to be included. This review interconnects the basic science findings of oxidative stress and redox balance with the medicinal use of food, emphasizing optimization of the redox balance. To better illustrate the impacts of oxidative stress, the concept of the “triple oxidant sink” is introduced as a theoretical gauge of redox balance. Utilizing the concept, the true importance of dietary and lifestyle factors can be emphasized, including the limitations of supplements or a handful of “superfoods,” if the remainder of the factors are pro-oxidant. The effects of a whole plant food diet compared with those of dietary supplements, processed foods, animal based nutrients, or additional lifestyle factors can be visually demonstrated with this concept. This paper provides an overview of the process, acknowledging that food is not the only mechanism for balancing the redox status, but one that can be strategically used to dramatically improve the oxidative state, and thus should be used as medicine.

Recreation has become an increasingly important pursuit for urban people who maintain a fast and intense life cycle today. Daily recreational activities provide opportunities for citizens to regain their physical and psychological health through short-term e‘periences. The starting point of this research is to determine the daily recreational activity places of the inhabitants of Izmir and to reveal development strategies for these choices.Questionnaire and observation methods were used in the research. Prominent places were determined through the questionnaire. The percentage of participants in the questionnaire was taken as a basis and a total of 15 locations, 12 of which were within the metropolitan area, were evaluated by observation studies, one by one. As a general result it is found that the prominence of these spaces was effectively influenced by factors like geographic location, natural and cultural characteristics, and distance from the city center. At the end of the study, feasible and sustainable suggestions were made for the development of these recreational spaces.

BackgroundThe COVID-19 pandemic has exacerbated health and social disparities among US Pacific Islanders (PI). Historically, PIs have experienced a high burden of mental illness yet have underutilized mental health services. These already large treatment gaps in mental health care among PIs may worsen during the COVID-19 pandemic. In the face of pre-existing challenges, little is known about the impacts of the COVID-19 pandemic on mental health outcomes among PIs.MethodsA community-based, cross-sectional survey was administered to members of 13 PI churches across the San Francisco Bay Area. We assessed the burden of psychological distress among PIs and its associations with demographic, sociocultural, and health factors.Key resultsAmong 439 PI respondents, nearly half reported moderate or severe psychological distress. Only about one-tenth took prescription medication for mental health and less than half utilized a mental health provider in the past year. Most trusted PI churches to provide health and social services. Respondents reporting moderate or severe psychological distress were less likely to utilize a mental health provider in the past year and more likely to feel marginalized, excluded, isolated, or alienated from society "most of the time" or "always." Psychological distress was also associated with "fair" or "poor" health status, female gender, older adults, low trust in PI churches to provide health and social services, and concern over household finances.ConclusionPartnerships with faith-based and community-based organizations are essential to address unmet mental health needs and promote support-seeking behaviors among PIs during this ongoing pandemic and beyond.

Abstract Amidst the backdrop of the COVID-19 pandemic, vaccine innovation has garnered significant attention, but this field was already on the cusp of a groundbreaking renaissance. Propelling these advancements are scientific and technological breakthroughs, alongside a growing understanding of the societal and economic boons vaccines offer, particularly for non-pediatric populations like adults and the immunocompromised. In a departure from previous decades where vaccine launches could be seamlessly integrated into existing processes, we anticipate potentially than 100 novel, risk-adjusted product launches over the next 10 years in the adult vaccine market, primarily addressing new indications. However, this segment is infamous for its challenges: low uptake, funding shortfalls, and operational hurdles linked to delivery and administration. To unlock the societal benefits of this burgeoning expansion, we need to adopt a fresh perspective to steer through the dynamics sparked by the rapid growth of the global adult vaccine market. This article aims to provide that fresh perspective, offering a detailed analysis of the anticipated number of adult vaccine approvals by category and exploring how our understanding of barriers to adult vaccine uptake might evolve. We incorporated pertinent insights from external stakeholder interviews, spotlighting shifting preferences, perceptions, priorities, and decision-making criteria. Consequently, this article aspires to serve as a pivotal starting point for industry participants, equipping them with the knowledge to skillfully navigate the anticipated surge in both volume and complexity.

Abstract Background Random genetic drift is a difficult concept for biology undergraduates to understand. Active learning activities in a collaborative setting have the potential to improve student learning outcomes compared to traditional lectures alone and have been shown to help foster success for underrepresented students. However, few activities in this content area have been evaluated for effectiveness in improving student outcomes using peer-reviewed instruments backed by evidence of their validity and reliability. Our aim in this study was to use the Genetic Drift Instrument (GeDI) to evaluate and compare student learning gains in an upper division genetics course in which two different genetic drift activities, a faculty-developed collaborative exercise and a commercially published lab tutorial, were administered in an active-learning classroom with students working in small groups. Methods The GeDI was administered in both pre- and post-testing in two semesters (n = 95 and 98 students), with the semesters differing in which activity was assigned. Instrument dimensionality, person and item fit, and reliability were evaluated using Rasch analysis. Hierarchical Linear Models (HLMs) with two-way interactions were fitted to assess whether being in a certain Intervention Type, Race/ethnicity, Gender, or First Generation Status affected learning gains. HLMs with three-way interactions were used to assess whether the activities benefited students of all backgrounds equivalently. Results We found that the GeDI demonstrated unidimensionality, with high item reliability and relatively low person reliability, consistent with previous studies. Both the faculty-developed activity and the commercially available lab tutorial were associated with significant learning gains on genetic drift concepts. Students in the SimBio group had higher learning gains but the difference in effect size was small. No significant differences in learning gains were found between students from different demographic groups, and both activities appeared to benefit students of different backgrounds equivalently. Conclusions The GeDI instrument could be improved by adding items that more consistently differentiate students of different ability levels, especially at high ability levels. The greater impact on learning gains in the SimBio group while statistically significant does not translate into actual meaningful differences in student understanding. While students of different background variables in the sample have equivalent learning gains and are benefitted equivalently by the different interventions, our interventions did not ameliorate inequities in genetic drift understanding as measured by the GeDI that were uncovered in pre-testing.

Background: Civil engineers design systems that have the potential to impact existing oppressive societal conditions. Critical action--the ability to recognize and act against oppressive conditions--is an obligation for civil engineers committed to building a more just world. Purpose/Hypothesis: History reveals that civil engineers often do not take critical action and accrediting bodies (e.g., ABET) have responded by creating requirements to consider social factors and contexts. Considering these endeavors, we ask: To what extent do civil engineering students demonstrate critical action attitudes when prompted by engineering problem-solving? In what ways does culturally relevant problem-solving influence critical action attitudes? Design/Method: Employing transformative action as a theoretical framework, we assessed students' responses to a design question on three levels that perpetuate or disrupt oppression (avoidant, destructive, and critical action). The empirical study used qualitative and quantitative analysis to examine survey responses of 375 civil engineering undergraduate students across 12 US universities. Results: The results showed that engineering students largely avoided discussing taking critical action, remaining focused on technical and nontechnical factors that evaded acknowledgement of sociopolitical factors. Nevertheless, when exposed to culturally relevant problem-solving, students showed a statistically significant increase in both critical and destructive action responses. Conclusions: We posit that students' exposure to culturally relevant problem-solving can enhance students' critical action attitudes. The results call on the need for civil engineering educators to cultivate culturally relevant problem-solving in civil engineering curriculum.

The 'Articulate' programme is a high-intensity five-day widening participation programme designed to help students develop their communication skills and confidence through a range of activities led by an Articulacy tutor and culminates in students taking an examination for the English Speaking Board (ESB) Level 1 Award in speech on the final day. Additionally, students also develop their understanding of and aspirations towards higher education (HE) through sustained interaction with student ambassadors, who support all sessions throughout the week. Based on the conceptual framework of the theory of change, the intervention primarily addresses the barrier of soft skills, including increasing students' self-belief, while also addressing some of the barriers of socio-economic factors to HE participation namely knowledge, understanding and likelihood of applying to HE in future, through increased exposure to HE role models. In this paper we report our findings from the evaluation where we are studying the effectiveness of the programme. Through survey questionnaires data was collected from over 698 students in year 9 and year 10, studying at 42 schools across Cornwall, Devon, and Somerset who took part in the 'Articulate' programme, which was run in collaboration with Next Steps South West (NSSW). Results show the majority of participating students went on to perform well in the ESB exam; furthermore, participants were more likely to have positive attitudes towards HE and considered applying to HE in future. The findings will be of particular interest to practitioners and activity providers.

Summary: The COVID-19 pandemic has exposed and exacerbated the persistent racial and ethnic health disparities in the United States. The pandemic has also had profound spillover effects on other aspects of health and wellbeing, such as mental health, chronic diseases, education, and income, for marginalized groups. In this article, we provide a thorough analysis of the pandemic’s impact on racial and ethnic health disproportionalities, highlighting the multifaceted and interrelated factors that contribute to these inequities. We also argue for a renewed focus on health equity in healthcare policy and practice, emphasizing the need for systemic changes that address both the immediate and long-term consequences of these imbalances. We propose a framework for achieving health equity that involves creating equitable systems, care, and outcomes for all individuals, regardless of their race or ethnicity.

Cribriform growth pattern is well-established as an adverse pathologic feature in prostate cancer. The literature suggests "large" cribriform glands associate with aggressive behavior; however, published studies use varying definitions for "large". We aimed to identify an outcome-based quantitative cut-off for "large" vs "small" cribriform glands. We conducted an initial training phase using the tissue microarray based Canary retrospective radical prostatectomy cohort. Of 1287 patients analyzed, cribriform growth was observed in 307 (24%). Using Kaplan-Meier estimates of recurrence-free survival curves (RFS) that were stratified by cribriform gland size, we identified 0.25 mm as the optimal cutoff to identify more aggressive disease. In univariable and multivariable Cox proportional hazard analyses, size >0.25 mm was a significant predictor of worse RFS compared to patients with cribriform glands ≤0.25 mm, independent of pre-operative PSA, grade, stage and margin status (p 0.25 mm had a significantly lower RFS relative to patients with cribriform glands ≤0.25 mm (each subset p = 0.004). Furthermore, there was no significant difference in outcomes between patients with cribriform glands ≤ 0.25 mm and patients without cribriform glands. The >0.25 mm cut-off was validated as statistically significant in a separate 419 patient, completely embedded whole-section radical prostatectomy cohort by biochemical recurrence, metastasis-free survival, and disease specific death, even when cases with admixed Gleason pattern 5 carcinoma were excluded. In summary, our findings support reporting cribriform gland size and identify 0.25 mm as an optimal outcome-based quantitative measure for defining "large" cribriform glands. Moreover, cribriform glands >0.25 mm are associated with potential for metastatic disease independent of Gleason pattern 5 adenocarcinoma.