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Objectives: Cervical cancer screening rates have stagnated, but self-sampling modalities have the potential to increase uptake. This study compares the test characteristics of self-sampled high-risk human papillomavirus (hrHPV) tests with clinician-collected hrHPV tests in average-risk (i.e., undergoing routine screening) and high-risk patients (i.e., receiving follow-up after abnormal screening results). Methods: In this cross-sectional study, a relatively small cohort of average-risk (n?=?35) and high-risk (n?=?12) participants completed both clinician-collected and self-sampled hrHPV testing, along with a brief phone survey. We assessed hrHPV positivity, concordance, positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity across both methods (for types 16, 18, or other hrHPV). We also explored the relationship between test concordance and sociodemographic/behavioral factors. Results: Among average-risk participants, hrHPV positivity was 6% for both test methods (i.e., hrHPV-positive cases: n?=?2), resulting in reported concordance, PPV, NPV, sensitivity, and specificity of 100%. Among high-risk participants, hrHPV positivity was 100% for clinician-collected tests but only 67% for self-sampled tests, showing varied concordance and sensitivity. Concordance was not associated with sociodemographic or behavioral factors. Conclusions: Self-sampled hrHPV testing demonstrated high accuracy for average-risk patients in this exploratory study. However, its performance was less consistent in high-risk patients who had already received an abnormal screening result, which could be attributed to spontaneous viral clearance over time. The limited number of participants, particularly HPV-positive cases, suggests caution in interpreting these results. Further research with larger cohorts is necessary to validate these findings and to explore the integration of self-sampled hrHPV testing into routine clinical care, particularly for patients with a history of cervical abnormalities. Clinical Trial Registration: NCT04591977, NCT04585243.

Abstract Background Food insecurity is common in the United States, especially in Rhode Island, where it affects up to 33% of residents. Food insecurity is associated with adverse health outcomes and disproportionally affects people from minoritized backgrounds. Produce prescription programs, in which healthcare providers write “prescriptions” for free or reduced cost vegetables, have been used to address food insecurity and diet-related chronic disease. Although there is growing evidence for the effectiveness of produce prescription programs in improving food security and diet quality, there have been few efforts to use implementation science methods to improve the adoption of these programs. Methods This two-phase pilot study will examine determinants and preliminary implementation and effectiveness outcomes for an existing produce prescription program. The existing program is funded by an Accountable Care Organization in Rhode Island and delivered in primary care practices. For the first phase, we conducted a formative evaluation, guided by the Consolidated Framework for Implementation Research 2.0, to assess barriers, facilitators, and existing implementation strategies for the produce prescription program. Responses from the formative evaluation were analyzed using a rapid qualitative analytic approach to yield a summary of existing barriers and facilitators. In the second phase, we presented our formative evaluation findings to a community advisory board consisting of primary care staff, Accountable Care Organization staff, and staff who source and deliver the vegetables. The community advisory board used this information to identify and refine a set of implementation strategies to support the adoption of the program via an implementation blueprint. Guided by the implementation blueprint, we will conduct a single-arm pilot study to assess implementation antecedents (i.e., feasibility, acceptability, appropriateness, implementation climate, implementation readiness), implementation outcomes (i.e., adoption), and preliminary program effectiveness (i.e., food and nutrition security). The first phase is complete, and the second phase is ongoing. Discussion This study will advance the existing literature on produce prescription programs by formally assessing implementation determinants and developing a tailored set of implementation strategies to address identified barriers. Results from this study will inform a future fully powered hybrid type 3 study that will use the tailored implementation strategies and assess implementation and effectiveness outcomes for a produce prescription program. Trial registration Clinical trials: NCT05941403 , Registered June 9, 2023.

Abstract While hypoxic signaling has been shown to play a role in many cellular processes, its role in metabolism-linked extracellular matrix (ECM) organization and downstream processes of cell fate after musculoskeletal injury remains to be determined. Heterotopic ossification (HO) is a debilitating condition where abnormal bone formation occurs within extra-skeletal tissues. Hypoxia and hypoxia-inducible factor 1α (HIF-1α) activation have been shown to promote HO. However, the underlying molecular mechanisms by which the HIF-1α pathway in mesenchymal progenitor cells (MPCs) contributes to pathologic bone formation remain to be elucidated. Here, we used a proven mouse injury-induced HO model to investigate the role of HIF-1α on aberrant cell fate. Using single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics analyses of the HO site, we found that collagen ECM organization is the most highly up-regulated biological process in MPCs. Zeugopod mesenchymal cell-specific deletion of Hif1α (Hoxa11-CreER T2 ; Hif1a fl/fl ) significantly mitigated HO in vivo. ScRNA-seq analysis of these Hoxa11-CreER T2 ; Hif1a fl/fl mice identified the PLOD2/LOX pathway for collagen cross-linking as downstream of the HIF-1α regulation of HO. Importantly, our scRNA-seq data and mechanistic studies further uncovered that glucose metabolism in MPCs is most highly impacted by HIF-1α deletion. From a translational aspect, a pan-LOX inhibitor significantly decreased HO. A newly screened compound revealed that the inhibition of PLOD2 activity in MPCs significantly decreased osteogenic differentiation and glycolytic metabolism. This suggests that the HIF-1α/PLOD2/LOX axis linked to metabolism regulates HO-forming MPC fate. These results suggest that the HIF-1α/PLOD2/LOX pathway represents a promising strategy to mitigate HO formation.

Abstract Background Disease-modifying anti-rheumatic drugs (DMARDs), since their introduction in 1990, have revolutionized the management of rheumatoid arthritis. Newer DMARDs have recently been approved, influencing treatment patterns and clinical guidelines. Objective To update the current prescribing patterns of DMARDs in the pharmacotherapy of rheumatoid arthritis (RA) to include the pandemic era. Methods This was a retrospective cross-sectional multi-year study. Using Optum’s Clinformatics® Data Mart Database, we summarized trends in the prevalence of DMARD use in the USA from 2016 to 2021 by year for adult patients ≥ 18 years old with at least one medical RA claim and one pharmacy/medical claim of a DMARD medication. Trends included type of DMARD, class of DMARD (conventional (csDMARDs), biologics [tumor necrosis factor (TNFi) and Non-TNFi), and Janus kinase inhibitors (JAKs)], and triple therapy [methotrexate (MTX), hydroxychloroquine (HCQ), sulfasalazine (SUL)] used. Results The total sample from 2016 to 2021 was 670,679 commercially insured patients. The average age was 63.7 years (SD 13.6), and 76.7% were female and 70% were White. csDMARDs remain the most prescribed (ranging from 77.2 to 79.2%). Although JAKs were the least prescribed DMARD class, their proportion more than doubled from 2016 (1.5%) to 2021 (4%). MTX utilization declined from 40% in 2016 to 34% in 2021. In contrast, HCQ use increased during the pandemic era from

Abstract Background Low bone mineral density affects 53% of women over age 65 in the US, yet many are unaware and remain untreated. Underdiagnosis of forearm osteoporosis and related fragility fractures represent missed warning signs of more deadly, future fractures. This study aimed to determine if hand radiographs could serve as early, simple screening tools for predicting low forearm bone mineral density (BMD). Methods We evaluated posterior-anterior (PA) hand radiographs (x-rays) and Dual-energy X-ray absorptiometry (DXA) scans of 43 participants. The ratio of the intramedullary cavity to total cortical diameter of the second metacarpal (second metacarpal cortical percentage (2MCP)) was used as a potential diagnostic marker. Mixed-effects linear regression was performed to determine correlation of 2MCP with BMD from various anatomic regions. Repeated measures ANOVAs were used to compare BMD across sites. An optimal 2MCP cutoff for predicting forearm osteopenia and osteoporosis was found using Receiver Operating Curves. Results 2MCP is directly correlated with BMD in the forearm. The optimal 2MCP of 48.3% had 80% sensitivity for detecting osteoporosis of the 1/3 distal forearm. An 2MCP cutoff of 50.8% had 84% sensitivity to detect osteoporosis of the most distal forearm. Both 2MCP cutoffs were more sensitive at predicting forearm osteoporosis than femoral neck T-scores. Conclusions These findings support the expansion of osteoporosis screening to include low-cost hand x-rays, aiming to increase diagnosis and treatment of low forearm BMD and fractures. Proposed next steps include confirming the optimal 2MCP cutoff at scale and integrating automatic 2MCP measurements into PAC systems.

Abstract The purpose of the research was to examine whether policewomen have carved out their place and developed a sense of belonging in the profession, or whether they are faced with disrespect, self-doubt, and pressure to adopt constructed gender roles. The study employed in-depth, qualitative interviews with sixteen women police officers in the U.S. Emergent themes suggested that overt discrimination and harassment is uncommon, but women do report the continued need to prove themselves. While all have carved out a place for themselves in the profession and most reported acceptance and belonging, several expressed concerns that they are relegated to roles based on their gender. With nationwide challenges to recruit more women into policing, this study provides insights into ways women have integrated and the barriers they may still face.

Abstract Eating disorders (EDs) are serious, deadly disorders that emerge in adolescence and early adulthood. Further, reported incidences of EDs are increasing worldwide. As such, accessible, affordable, and effective early intervention and prevention efforts are critical. The Body Project is a well-established ED prevention program with demonstrated success at reducing ED symptom severity and the risk of onset of EDs in young females. However, it has not yet been formally evaluated in an Australian population, nor have the benefits of the treatment for young people of all genders been thoroughly investigated. This protocol paper outlines the design for a study which aims to investigate the outcomes and feasibility of the Body Project as a brief ED prevention program within an Australian youth mental health service: headspace Camperdown. This pragmatic trial will compare outcomes between a Body Project treatment group and a Treatment-as-usual control group. Primary outcomes include body image concerns, ED symptomatology and general psychological distress, measured pre- and post-treatment, and at one-month follow-up. All young people attending headspace Camperdown for care are eligible for participation in the trial. The Body Project program is comprised of four group-based 1.5 h sessions run over 4 consecutive weeks. Overall, a trial of the Body Project as an ED prevention program is warranted to investigate the outcomes of the intervention in this sample and will provide valuable information about the feasibility for widespread implementation of the treatment as part of a stepped-care approach to intervention for EDs at youth mental health service locations across Australia. ANZCTR Trial Registration Number: ACTRN12623000695606 (registered 29 June 2023).

Abstract Discovery of new small molecules that can activate distinct programmed cell death pathway is of significant interest as a research tool and for the development of novel therapeutics for pathological conditions such as cancer and infectious diseases. The small molecule raptinal was discovered as a pro-apoptotic compound that can rapidly trigger apoptosis by promoting the release of cytochrome c from the mitochondria and subsequently activating the intrinsic apoptotic pathway. As raptinal is very effective at inducing apoptosis in a variety of different cell types in vitro and in vivo, it has been used in many studies investigating cell death as well as the clearance of dying cells. While examining raptinal as an apoptosis inducer, we unexpectedly identified that in addition to its pro-apoptotic activities, raptinal can also inhibit the activity of caspase-activated Pannexin 1 (PANX1), a ubiquitously expressed transmembrane channel that regulates many cell death-associated processes. By implementing numerous biochemical, cell biological and electrophysiological approaches, we discovered that raptinal can simultaneously induce apoptosis and inhibit PANX1 activity. Surprisingly, raptinal was found to inhibit cleavage-activated PANX1 via a mechanism distinct to other well-described PANX1 inhibitors such as carbenoxolone and trovafloxacin. Furthermore, raptinal also interfered with PANX1-regulated apoptotic processes including the release of the ‘find-me’ signal ATP, the formation of apoptotic cell-derived extracellular vesicles, as well as NLRP3 inflammasome activation. Taken together, these data identify raptinal as the first compound that can simultaneously induce apoptosis and inhibit PANX1 channels. This has broad implications for the use of raptinal in cell death studies as well as in the development new PANX1 inhibitors.

Introduction: Pennsylvania opened its first medical marijuana (MMJ) dispensary in 2018. Qualifying conditions include six conditions determined to have no or insufficient evidence to support or refute MMJ effectiveness. We conducted a study to describe MMJ dispensary access in Pennsylvania and to determine whether dispensary proximity was associated with MMJ certifications and community demographics. Methods: Using data from the Pennsylvania Department of Health, we geocoded MMJ dispensary locations and linked them to US Census Bureau data. We created dispensary access measures from the population-weighted centroid of Zip Code Tabulation Areas (ZCTAs): distance to nearest dispensary and density of dispensaries within a 15-min drive. We evaluated associations between dispensary access and the proportion of adults who received MMJ certification and the proportion of certifications for low evidence conditions (amyotrophic lateral sclerosis, epilepsy, glaucoma, Huntington’s disease, opioid use disorder, and Parkinson’s disease) using negative binomial modeling, adjusting for community features. To evaluate associations racial and ethnic composition of communities and distance to nearest dispensary, we used logistic regression to estimate the odds ratios (OR) and 95% confidence intervals (CI), adjusting for median income. Results: Distance and density of MMJ dispensaries were associated with the proportion of the ZCTA population certified and the proportion of certifications for insufficient evidence conditions. Compared to ZCTAs with no dispensary within 15 min, the proportion of adults certified increased by up to 31% and the proportion of certifications for insufficient evidence decreased by up to 22% for ZCTAs with two dispensaries. From 2018 to 2021, the odds of being within five miles of a dispensary was up to 20 times higher in ZCTAs with the highest proportions of individuals who were not White (2019: OR: 20.14, CI: 10.7–37.8) and more than double in ZCTAs with the highest proportion of Hispanic individuals (2018: OR: 2.81, CI: 1.51–5.24), compared to ZCTAs with the lowest proportions. Conclusions: Greater dispensary access was associated with the proportions of certified residents and certifications for low evidence conditions. Whether these patterns are due to differences in accessibility or demand is unknown. Associations between community demographics and dispensary proximity may indicate MMJ access differences.

Abstract A core pathophysiologic feature underlying many respiratory diseases is multiciliated cell dysfunction, leading to inadequate mucociliary clearance. Due to the prevalence and highly variable etiology of mucociliary dysfunction in respiratory diseases, it is critical to understand the mechanisms controlling multiciliogenesis that may be targeted to restore functional mucociliary clearance. Multicilin, in a complex with E2F4, is necessary and sufficient to drive multiciliogenesis in airway epithelia, however this does not apply to all cell types, nor does it occur evenly across all cells in the same cell population. In this study we further investigated how co-factors regulate the ability of Multicilin to drive multiciliogenesis. Combining data in mouse embryonic fibroblasts and human bronchial epithelial cells, we identify RBL2 as a repressor of the transcriptional activity of Multicilin. Knockdown of RBL2 in submerged cultures or phosphorylation of RBL2 in response to apical air exposure, in the presence of Multicilin, allows multiciliogenesis to progress. These data demonstrate a dynamic interaction between RBL2 and Multicilin that regulates the capacity of cells to differentiate and multiciliate. Identification of this mechanism has important implications for facilitating MCC differentiation in diseases with impaired mucociliary clearance.

Abstract Introduction Perianal disease occurs in up to 34% of inflammatory bowel disease (IBD) patients. An estimated 25% of women will become pregnant after the initial diagnosis, thus introducing the dilemma of whether mode of delivery affects perianal disease. The aim of our study was to analyze whether a cesarean section (C-section) or vaginal delivery influence perianal involvement. We hypothesized the delivery route would not alter post-partum perianal manifestations in the setting of previously healed perianal disease. Methods All consecutive eligible IBD female patients between 1997 and 2022 who delivered were included. Prior perianal involvement, perianal flare after delivery and delivery method were noted. Results We identified 190 patients with IBD who had a total of 322 deliveries; 169 (52%) were vaginal and 153 (48%) were by C-section. Nineteen women (10%) experienced 21/322 (6%) post-partum perianal flares. Independent predictors were previous abdominal surgery for IBD (OR, 2.7; 95% CI, 1–7.2; p = 0.042), ileocolonic involvement (OR, 3.3; 95% CI, 1.1–9.4; p = 0.030), previous perianal disease (OR, 22; 95% CI, 7–69; p

Abstract Background Adult horses with proprioceptive ataxia and behavior changes that have histologic lesions consistent with neurodegenerative disease have been increasingly recognized. Hypothesis/Objectives Describe the history, clinical findings and histopathologic features of horses presented to a referral institution with neuroaxonal degeneration. Animals One hundred horses with a necropsy diagnosis of neuroaxonal degeneration compatible with neuroaxonal dystrophy/degenerative myeloencephalopathy (eNAD/EDM). Methods Retrospective study of horses presented to the University of Pennsylvania, New Bolton Center, between 2017 and 2021 with a necropsy diagnosis of eNAD/EDM. Results Affected horses had a median age of 8 years (range, 1‐22), and the majority were Warmbloods (72). Sixty‐eight horses had behavioral changes, and all 100 had proprioceptive ataxia (median grade, 2/5). Fifty‐seven horses had abnormal findings on cervical vertebral radiographs, and 14 had myelographic findings consistent with compressive myelopathy. No antemortem diagnostic test results were consistently associated with necropsy diagnosis of neurodegenerative disease. All 100 horses had degenerative lesions characteristic of eNAD in the brainstem gray matter, and 24 had concurrent degenerative features of EDM in the spinal cord white matter. Conclusions and Clinical Importance Clinical and histopathologic findings in this large group of horses with neurodegenerative disease were most consistent with eNAD/EDM, but with a different signalment and clinical presentation from earlier descriptions. The increasing occurrence of neurodegenerative disease in horses and the safety risk posed emphasize the importance of focused research in affected horses.

Abstract Objectives When referring patients to radiology, it is important that the most appropriate test is chosen to avoid inappropriate imaging that may lead to delayed diagnosis, unnecessary radiation dose, worse patient outcome, and poor patient experience. The current radiology appropriateness guidance standard at our institution is via access to a standalone web-based clinical decision support tool (CDST). A point-of-care (POC) CDST that incorporates guidance directly into the physician workflow was implemented within a subset of head and neck cancer specialist referrers. The purpose of this audit was to evaluate the imaging pathway, pre- and post-implementation to assess changes in referral behavior. Methods CT and MRI neck data were collected retrospectively to examine the relationship between imaging referrals pre- and post-POC CDST implementation. Effective radiation dose and estimated carbon emissions were also compared. Results There was an overall reduction in absolute advanced imaging volume by 8.2%, and a reduction in duplicate CT and MRI imaging by 61%, p

Primary central nervous system (CNS) ALK-negative anaplastic large cell lymphoma (ALCL) is a rare and enigmatic disease, with limited data available in the literature. This case report adds to the existing body of knowledge by describing a unique case of a 68-year-old, immunocompetent male who presented with a single ring-enhancing lesion, which upon further analysis proved to be an ALK-negative ALCL that was primary to the CNS. A comprehensive review of the existing literature is provided, highlighting the genetic characteristics and diverse neuroimaging findings of this disease entity. This report adds valuable information to the understanding of this rare disorder, and highlights the need for further research in the field of primary CNS ALK-negative ALCL.

The degradation of ice-rich permafrost ecosystems due to climate change and infrastructure development strongly impacts carbon exchange dynamics in tundra landscapes. This study investigates the effects of surficial geology and infrastructure disturbances from road dust and flooding on vegetation and trace gas fluxes in polygonal ice-wedge tundra in arctic Alaska. We compared CO2 and CH4 fluxes from closed-chamber measurements at common landform elements (polygon centers, troughs, and rims) at a natural site and a disturbed site within the Prudhoe Bay Oil Field. Relationships among environmental parameters, plant species composition, and trace gas fluxes were assessed through nonmetric multidimensional scaling. Map extrapolations showed spatial variations in midsummer landscape-level ecosystem productivity and CH4 efflux at the various geologic landforms. Highest carbon uptake occurred in ice-rich drained thaw lake basins with aquatic, graminoid-dominated polygon troughs. In contrast, wet, featureless areas associated with more recently drained, ice-poor thaw lake basins showed a net carbon loss even during summer. The damming effect of road infrastructure led to deeply flooded, minimally vegetated troughs with low ecosystem respiration and high CH4 fluxes close to the road. This work highlights the importance of the complex interactions among surficial geology, landform elements, vegetation type, and disturbance factors in understanding carbon exchange dynamics in ice-rich permafrost environments.

Autism spectrum disorders (ASD) are complex human neurodiversities increasing in prevalence within the human population. In search of therapeutics to improve quality-of-life for ASD patients, the gut microbiome (GM) has become a promising target as a growing body of work supports roles for the complex community of microorganisms in influencing host behavior via the gut-brain-axis. However, whether naturally-occurring microbial diversity within the host GM affects these behaviors is often overlooked. Here, we applied a model of population-level differences in the GM to a classic ASD model – the BTBR T+ Itpr3tf/J mouse – to assess how complex GMs affect host behavior. Leveraging the naturally occurring differences between supplier-origin GMs, our data demonstrate that differing, complex GMs selectively effect host ASD-related behavior – especially neonatal ultrasonic communication – and reveal a male-specific effect on behavior not typically observed in this strain. We then identified that the body weight of BTBR mice is influenced by the postnatal GM which was potentially mediated by microbiome-dependent effects on energy harvest in the gut. These data provide insight into how variability within the GM affects host behavior and growth, thereby emphasizing the need to incorporate microbial diversity within the host GM as an experimental factor in biomedical research.

ABSTRACTBackground Chronic pain and higher body weight frequently co-occur. This common comorbidity is thought to be mediated by the use of comfort eating as a strategy for managing both the physical and psychological pain and discomfort associated with flare-ups of chronic pain. Valid and reliable assessment tools are needed to inform the development of effective treatments.Aims This study aimed to assess the psychometric properties of a new brief measure of pain-induced comfort eating in chronic pain, the Pain-Induced Comfort Eating Scale (PICES).Methods A sample of 166 patients with chronic pain completed an online test battery including the PICES along with measures of chronic pain and pain-related symptoms, disordered eating, and related psychological factors.Results Results of exploratory factor analysis revealed a single-factor model for the four-item PICES. Further, the PICES demonstrated evidence of good internal consistency as well as convergent validity with demonstrated correlations with related measures. The results of this study also revealed that comfort eating in chronic pain appears to be related to psychological distress; the PICES correlated more strongly with measures assessing mood and psychological distress compared to interference/intensity of physical pain itself. Scores on the PICES also correlated strongly with measures of uncontrolled and emotional eating.Conclusions Overall, our results indicate that the PICES provides a valid and useful brief measure of comfort eating in chronic pain that might be useful to inform treatments targeting the comorbid disordered eating practices that can lead to higher body weights in patients with chronic pain.

IntroductionThere is a paucity of data on immune checkpoint inhibitors (ICIs) plus doublet chemotherapy (C) in patients with advanced lung cancer whose tumor harbors an actionable mutation. We sought to provide insight into the role of this combination in relation to chemotherapy alone in this patient population.MethodsWe conducted a retrospective study at the five University of California National Cancer Institute-designated Comprehensive Cancer Centers. The primary end point was progression-free survival (PFS). Secondary end points included overall survival (OS) and significant adverse events. Adverse events in patients who received a tyrosine kinase inhibitor (TKI) post-ICI were also captured.ResultsA total of 246 patients were identified, 170 treated with C plus ICI and 76 treated with C alone. Driver alterations included EGFR (54.9%), KRAS (32.9%), ALK (5.3%), HER2/ERBB2 (2.9%), ROS1 (1.2%), MET (1.2%), RET (0.8%), and BRAF non-V600 (0.8%). The overall PFS and OS hazard ratios were not significant at 1.12 (95% confidence interval 0.83-1.51; p = 0.472) and 0.86 (95% confidence interval: 0.60-1.24, p = 0.429), respectively. No significant differences in PFS or OS were observed in the mutational subgroups. Grade 3 or greater adverse events were lower in the C plus ICI group. The multivariate analysis for PFS and OS revealed a performance status (Eastern Cooperative Oncology Group) score of 2, and previous TKI treatment was associated with poorer outcomes with C plus ICI.ConclusionsOur study suggests that patients with oncogenic-driven NSCLC, primarily those with EGFR-driven tumors, treated with a TKI should not subsequently receive C plus ICI. Analysis from prospective clinical trials will provide additional information on the role of ICIs in this group of patients.

IntroductionChildren who are HIV-exposed uninfected (HEU), that is, children who do not acquire HIV infection despite being born to mothers with HIV, have a higher risk of mortality, infectious morbidity and growth deficits than children who are HIV-unexposed uninfected (HUU). Prior research has focused on breast feeding and has pointed to changes in human milk oligosaccharides (HMOs) associated with maternal HIV that may influence the infant microbiome and thereby lead to these adverse outcomes. However, to our knowledge, no study has attempted to intervene along this pathway to reduce the occurrence of the adverse outcomes in children HEU. We will conduct a double-blind, randomised trial of a synbiotic intervention, which combines an HMO and probiotic, in breastfed infants HEU in South Africa to evaluate whether this intervention has promise to reduce excess infectious morbidity and growth faltering compared with controls.Methods and analysisOne hundred and forty-four breastfed infants HEU, aged 4 weeks, will be 1:1 randomised to receive either a daily synbiotic or an identical-looking placebo through age 24 weeks. Infants will be followed until age 48 weeks and outcomes of infectious morbidity, growth and biological measurements (eg, microbiota, inflammation and metabolome) will be assessed. Analyses will follow intention-to-treat principles comparing the cohorts as randomised. Infants HEU will be compared across arms with respect to the occurrence of infectious morbidity and growth outcomes through 4-24 weeks and 4-48 weeks using appropriate parametric and non-parametric statistical tests. Additionally, an observational cohort of 40 breastfed infants HUU will be recruited as a comparator group with no intervention.Ethics and disseminationEthical approval for this study has been obtained from the ethics committees at Columbia University and Stellenbosch University. The findings will be disseminated in publications.Trial registration numberClinicalTrials.gov Identifier: NCT05282485. SANCTR ID number: DOH-27-122021-6543.

The coronavirus disease 2019 (COVID-19) pandemic has created a global health crisis, with disproportionate effects on vulnerable sociodemographic groups. Although the pandemic is showing potential to increase suicide ideation (SI), we know little about which sociodemographic characteristics or COVID-19 experiences are associated with SI. Our United States-based sample (n = 837 adults [mean age = 37.1 years]) completed an online survey during August-September 2020. The study utilized an online convenience sample from a prior study, which was enriched for exposure to trauma and experiences of posttraumatic stress symptoms. We assessed SI using the Beck Depression Inventory-II. Traditional (i.e., logistic regression) and machine learning (i.e., LASSO, random forest) methods evaluated associations of 148 self-reported COVID-19 factors and sociodemographic characteristics with current SI. 234 participants (28.0%) reported SI. Twenty items were significantly associated with SI from logistic regression. Of these 20 items, LASSO identified seven sociodemographic characteristics (younger age, lower income, single relationship status, sexual orientation other than heterosexual as well as specifically identifying as bisexual, non-full-time employment, and living in a town) and six COVID-19 factors (not engaging in protective COVID-19 behaviors, receiving mental health treatment (medication and/or psychotherapy) due to the COVID-19 pandemic, socializing during the pandemic, losing one's job due to COVID-19, having a friend with COVID-19, and having an acquaintance with COVID-19) associated with SI. Random forest findings were largely consistent with LASSO. These findings may inform multidisciplinary research and intervention work focused on understanding and preventing adverse mental health outcomes such as SI during and in the aftermath of the pandemic.

BackgroundDuring the COVID-19 pandemic within the United States, much of the responsibility for diagnostic testing and epidemiologic response has relied on the action of county-level departments of public health. Here we describe the integration of genomic surveillance into epidemiologic response within Humboldt County, a rural county in northwest California.MethodsThrough a collaborative effort, 853 whole SARS-CoV-2 genomes were generated, representing ~58% of the 1,449 SARS-CoV-2-positive cases detected in Humboldt County as of March 12, 2021. Phylogenetic analysis of these data was used to develop a comprehensive understanding of SARS-CoV-2 introductions to the county and to support contact tracing and epidemiologic investigations of all large outbreaks in the county.ResultsIn the case of an outbreak on a commercial farm, viral genomic data were used to validate reported epidemiologic links and link additional cases within the community who did not report a farm exposure to the outbreak. During a separate outbreak within a skilled nursing facility, genomic surveillance data were used to rule out the putative index case, detect the emergence of an independent Spike:N501Y substitution, and verify that the outbreak had been brought under control.ConclusionsThese use cases demonstrate how developing genomic surveillance capacity within local public health departments can support timely and responsive deployment of genomic epidemiology for surveillance and outbreak response based on local needs and priorities.

BackgroundRecent studies have reignited the tinderbox of debate surrounding the use of race and ancestry in medicine. These controversial studies have argued for a strong correlation between genetic ancestry and race, justifying continued use of genetic ancestry measures in studies of disease. These studies contend that increased use of continental ancestry estimates can inform clinical risk assessments and management. Further, recent studies of racial corrections used in clinical algorithms, such as those used to estimate 'normal' lung function, also advocate for use of genetic ancestry in place of race for refining risk algorithms.Main bodyThese positions are misleading, harmful, and reflect superficial interpretations of population genetics. In this Perspective, we argue that continental genetic ancestry, often proxied by race, serves as a poor indicator of disease risk, and reinforces racialized inequities.ConclusionInstead, we endorse that racial disparities in disease should be investigated by rigorous measures of structural racism alongside careful measures of genetic factors in relevant disease pathways, rather than relying on genetic ancestry or race as a crude proxy for disease-causing alleles.

Over the course of human life, health care decision-making is often interdependent. In this article, we use "interdependence" to refer to patients' engagement of nonclinicians-for example, family members or trusted friends-to reach health care decisions. Interdependence, we suggest, is common for patients in all stages of life, from early childhood to late adulthood. This view contrasts with the common bioethical assumption that medical decisions are either wholly independent or dependent and that independence or dependence is tightly coupled with a person's decision-making capacity. In this article, we array various approaches to decision-making along a continuum of interdependence. An appreciation of this continuum can empower patients and elucidate ethical challenges that arise when people transition between different kinds of interdependence across the life span.

Sleep disturbance has emerged as an independent, mechanistic, and modifiable risk factor for suicide. Sexual and gender minority (SGM) people disproportionately experience sleep disturbance and are at higher risk of death by suicide relative to cisgender and/or heterosexual individuals. The present narrative review evaluates nascent research related to sleep disturbance and suicide-related thoughts and behaviors (STBs) among SGM populations, and discusses how experiences of minority stress may explain heightened risk among SGM people. Although there is a growing understanding of the link between sleep disturbance and STBs, most research has not been conducted in SGM populations or has not examined suicide as an outcome. Research is needed to examine whether and how aspects of sleep disturbances relate to STBs among SGM people in order to better tailor sleep treatments for SGM populations.

AbstractOxygen bioavailability is declining in aquatic systems worldwide as a result of climate change and other anthropogenic stressors. For aquatic organisms, the consequences are poorly known but are likely to reflect both direct effects of declining oxygen bioavailability and interactions between oxygen and other stressors, including two-warming and acidification-that have received substantial attention in recent decades and that typically accompany oxygen changes. Drawing on the collected papers in this symposium volume ("An Oxygen Perspective on Climate Change"), we outline the causes and consequences of declining oxygen bioavailability. First, we discuss the scope of natural and predicted anthropogenic changes in aquatic oxygen levels. Although modern organisms are the result of long evolutionary histories during which they were exposed to natural oxygen regimes, anthropogenic change is now exposing them to more extreme conditions and novel combinations of low oxygen with other stressors. Second, we identify behavioral and physiological mechanisms that underlie the interactive effects of oxygen with other stressors, and we assess the range of potential organismal responses to oxygen limitation that occur across levels of biological organization and over multiple timescales. We argue that metabolism and energetics provide a powerful and unifying framework for understanding organism-oxygen interactions. Third, we conclude by outlining a set of approaches for maximizing the effectiveness of future work, including focusing on long-term experiments using biologically realistic variation in experimental factors and taking truly cross-disciplinary and integrative approaches to understanding and predicting future effects.

Inclusive sports have emerged as a potential tool for building social inclusion within diverse populations. The Special Olympics Unified Sports programs are an example of inclusion initiatives specific to students with intellectual disability and sports that can be reevaluated with new understandings of inclusion. This systematic mixed studies review aimed to capture athlete Unified Sports experiences and identify what athletes reported about their participation. The systematic review identified nine original studies conducted by six unrelated research groups. Results across the studies are synthesized and suggestions for future research are presented. Athletes in all nine studies reviewed reported positive experiences with Unified Sports leading to increased social inclusion and/or self-concepts.

Educational leaders, including directors of special education (DSE), often lack the depth and breadth of knowledge, skills, and dispositions needed to effectively manage the nuanced needs of special education. It is critically important, both legally and morally, for DSEs to have skills and mindsets to be effective in their roles. It is imperative that the field identify effective methods of training, developing, and supporting DSEs in the competencies they need to successfully serve all learners. This piece shares one Institute of Higher Education's (IHE's Council for Exceptional Children) process for revising an existing preparation program through an innovative partnership with statewide, practicing DSEs. Results of statewide program reviews and DSE surveys and focus groups highlight the critical capacities needed for DSEs to be effective on the job as well as ways to rethink what effective DSE licensure programs could and should look like.

Upholding critical race theory (CRT)'s transdisciplinary approach to unveil the educational violence against Students of Color, we apply W.E.B. Du Bois's story of John from the chapter "Of the Coming of John" in "The Souls of Black Folk." In doing so, we expose the problematic ideological and practical structures used for the identification and retention of Students of Color within gifted and talented programming. Examining the concepts of the Veil and double consciousness through the analogous relationship of Du Bois's John to a contemporary John, we parallel the insidious educational experiences of Students of Color that has remained relatively constant over time.

First-generation immigrants (FGIs) are eager to achieve the American dream and acquire the advantages a bachelor's degree affords. FGIs compared to their second-generation, third-generation and native peers fare better educationally. But, this comparison obscures across racial variation within a single-nativity status. As such, it is important to understand what mechanisms might produce inequality in college access among FGIs. One mechanism may be differences in how schools support students for college-going. The content of support may vary if racial stereotypes affect how support is given. Such variations could be decisive for FGIs' educational trajectories. We find that Latinx and black FGIs are less likely than other FGIs to enroll in bachelor-degree programs. The content of school support is a mechanism that can help partially explain this differential for black FGIs. Our findings indicate that how schools support black FGIs for college-going is different and is likely at least implicitly racially biased.

Objective: Human papillomavirus vaccination coverage is suboptimal, especially among males. Social networks influence young adults' health behaviors and could be leveraged to promote vaccination. We sought to describe how young sexual minority men communicate about human papillomavirus (HPV) vaccination with their sexual partners. Participants: National (U.S.) sample of sexual minority men ages 18-26 (n = 42) from January 2019. Methods: We conducted four online focus groups and identified salient themes using inductive content analysis. Results: Across groups, participants described that HPV vaccination is not a focus of their conversations with sexual partners. Other key themes related to HPV vaccine communication included: varying discussions based on relationship type, and valuing conversations with partners about safer sex. Conclusions: Findings provide novel insight into how young sexual minority men communicate with their sexual partners about HPV vaccination and identify potential areas for interventions to promote communication. Future research is needed to investigate associations between partner communication and HPV vaccine uptake.

This study examines how parents' mental health symptoms, emotion regulation and mindfulness relate to parent-child reminiscing conversations about past emotional events. Fifty-four children aged 8-12 years and their parents were recruited from a child psychology clinic (n = 28) and local schools (n = 26). Dyad's reminiscing conversations were recorded, transcribed, and coded for elaboration style, emotion content and emotion closure. Child language ability and mental health symptoms were measured, as was parent mindfulness, emotion regulation and mental health symptoms. Mindfulness acting with awareness was a unique predictor of dyad emotion closure. Depression, anxiety, and stress symptoms were not directly related to elaborative reminiscing, however, moderation by clinical status revealed a negative relationship for the community children only. These findings suggest a more complex relationship at play between parent and child mental health in reminiscing within clinical populations. Implications of these findings for a growing body of reminiscing interventions are discussed.

Purpose: Families and professionals often consider augmentative and alternative communication (AAC) a "last resort" for persons with communication challenges; however, speaking autistic adults have reported that they would have benefited from access to AAC as children. This tutorial discusses the history of this "last resort" practice and its perpetuation within the medical model of disability. The tutorial focuses on communication access, choice, and agency for autistic students. Method: We provide a brief overview of the AAC community and their preferred terminology, review the history of traditional approaches to research on AAC and autism, and then examine the relationship between disability models and ableism to views of spoken language as a priority of intervention. Studies on this topic are rare, and resisting ableism requires acknowledging and honoring disabled people's experiences and expertise. Therefore, we promote autistic expertise within the framework of evidence-based practice and discuss the experiences of autistic people and spoken language. Finally, we consider the role of the speech-language pathologist (SLP) in assessment and offer autistic-based strategies and recommendations for communication support. Conclusions: Speaking autistic students who could benefit from AAC may not have access to AAC due to the prioritization of spoken language and lack of awareness of the benefit of AAC. We recommend that SLPs and school-based professionals support and facilitate access, communicative choice, and agency by implementing multimodal communication strategies to include AAC use for autistic students regardless of their spoken language status. Promoting all types of communication and ensuring opportunities for communication across multiple modalities are paramount to a child's agency and self-determination, as is normalization of AAC.

The United States has a higher rate of teen pregnancy than any other developed country with 30% of American girls becoming pregnant before the age of 20. Laws regarding the inclusion and content of sexuality education vary across the country, which are associated with differences in pregnancy and sexually transmitted infection (STI) rates between states. This systematic review aims to determine whether comprehensive sexuality education (CSE) is more effective than abstinence-only or no sexuality education at reducing teenage pregnancy. Secondary objectives include analyzing the effect of CSE on STI incidence, sexual activity, safe-sex behaviors, and social discomfort. We searched multiple databases for studies published from 1990 to 2021. Twenty-nine studies met our inclusion criteria. Seven included pregnancy as an outcome, with three fitting our meta-analysis criteria. There was a decrease in pregnancy rates for participants in the CSE intervention compared to the control (n = 3, risk ratio = 0.89, 95%CI 0.79-1.00, I[superscript 2] = 0%). We found that CSE is likely to reduce pregnancy rates; however, there was limited data available on this outcome. CSE increased safe-sex behaviors but did not have a notable impact on sexual activity or STIs. This review can serve as evidence for the implementation of CSE in the US.