Sexual violence and general functioning among formerly abducted girls in Northern Uganda: the mediating roles of stigma and community relations--the WAYS study.

BACKGROUND: Although sexual violence in war is associated with long-term mental health problems, little is known about its association with general functioning and the factors that explain this association. This study aims to illuminate the path from sexual violence to poor functioning. The prevalence of sexual violence among formerly abducted girls in Northern Uganda was assessed as well as the extent to which stigma and community relations explain the association between sexual violence and general functioning. METHOD: In a cross-sectional analysis using data from the WAYS study (N = 210, baseline age 22.06, SD = 2.06, minimum-maximum 18-25), the extent of mediation of the association between sexual violence and general functioning was assessed in multiple regression models. RESULTS: Sexual violence was found to be associated with increased stigma, poor community relations, and poor general functioning. The association between sexual violence and general functioning was mediated by stigma and community relations. The bootstrap results indicated significant mediation by stigma of 47 % (95 % confidence interval [CI] 35 to 78 % and by community relations of 67 % (95 % CI: 52 to 78 %) in the association between sexual violence and general functioning. CONCLUSION: Thus, poor functioning among formerly abducted girls is largely mediated by stigma and poor community relations. However, due to the relatively small effect sizes of the associations, targeted interventions to prevent impaired functioning may have only modest benefits to the formerly abducted girls. Interventions to alleviate the toxic effects of sexual violence in formerly abducted girls would benefit from a holistic approach that targets stigma and poor relationships within communities

Sofosbuvir and Velpatasvir for HCV Genotype 2 and 3 Infection

BACKGROUND: In phase 2 trials, treatment with the combination of the nucleotide polymerase inhibitor sofosbuvir and the NS5A inhibitor velpatasvir resulted in high rates of sustained virologic response in patients chronically infected with hepatitis C virus (HCV) genotype 2 or 3. METHODS: We conducted two randomized, phase 3, open-label studies involving patients who had received previous treatment for HCV genotype 2 or 3 and those who had not received such treatment, including patients with compensated cirrhosis. In one trial, patients with HCV genotype 2 were randomly assigned in a 1:1 ratio to receive sofosbuvir-velpatasvir, in a once-daily, fixed-dose combination tablet (134 patients), or sofosbuvir plus weight-based ribavirin (132 patients) for 12 weeks. In a second trial, patients with HCV genotype 3 were randomly assigned in a 1:1 ratio to receive sofosbuvir-velpatasvir for 12 weeks (277 patients) or sofosbuvir-ribavirin for 24 weeks (275 patients). The primary end point for the two trials was a sustained virologic response at 12 weeks after the end of therapy. RESULTS: Among patients with HCV genotype 2, the rate of sustained virologic response in the sofosbuvir-velpatasvir group was 99% (95% confidence interval [CI], 96 to 100), which was superior to the rate of 94% (95% CI, 88 to 97) in the sofosbuvir-ribavirin group (P=0.02). Among patients with HCV genotype 3, the rate of sustained virologic response in the sofosbuvir-velpatasvir group was 95% (95% CI, 92 to 98), which was superior to the rate of 80% (95% CI, 75 to 85) in the sofosbuvir-ribavirin group (P CONCLUSIONS: Among patients with HCV genotype 2 or 3 with or without previous treatment, including those with compensated cirrhosis, 12 weeks of treatment with sofosbuvir-velpatasvir resulted in rates of sustained virologic response that were superior to those with standard treatment with sofosbuvir-ribavirin. (Funded by Gilead Sciences; ASTRAL-2 ClinicalTrials.gov number, NCT02220998; and ASTRAL-3, NCT02201953.)

Diverse University Students Across the United States Reveal Promising Pathways to Hunter Recruitment and Retention

Declining participation in hunting, especially among young adult hunters, affects the ability of state and federal agencies to achieve goals for wildlife management and decreases revenue for conservation. For wildlife agencies hoping to engage diverse audiences in hunter recruitment, retention, and reactivation (R3) efforts, university settings provide unique advantages: they contain millions of young adults who are developmentally primed to explore new activities, and they cultivate a social atmosphere where new identities can flourish. From 2018 to 2020, we surveyed 17,203 undergraduate students at public universities across 22 states in the United States to explore R3 potential on college campuses and assess key demographic, social, and cognitive correlates of past and intended future hunting behavior. After weighting to account for demographic differences between our sample and the larger student population, 29% of students across all states had hunted in the past. Students with previous hunting experience were likely to be white, male, from rural areas or hunting families, and pursuing degrees related to natural resources. When we grouped students into 1 of 4 categories with respect to hunting (i.e., non-hunters [50%], potential hunters [22%], active hunters [26%], and lapsed hunters [3%]), comparisons revealed differences based on demographic attributes, beliefs, attitudes, and behaviors. Compared to active hunters, potential hunters were more likely to be females or racial and ethnic minorities, and less likely to experience social support for hunting. Potential hunters valued game meat and altruistic reasons for hunting, but they faced unique constraints due to lack of hunting knowledge and skills. Findings provide insights for marketing and programming designed to achieve R3 objectives with a focus on university students. © 2021 The Wildlife Society

RAD21 Cooperates with Pluripotency Transcription Factors in the Maintenance of Embryonic Stem Cell Identity

For self-renewal, embryonic stem cells (ESCs) require the expression of specific transcription factors accompanied by a particular chromosome organization to maintain a balance between pluripotency and the capacity for rapid differentiation. However, how transcriptional regulation is linked to chromosome organization in ESCs is not well understood. Here we show that the cohesin component RAD21 exhibits a functional role in maintaining ESC identity through association with the pluripotency transcriptional network. ChIP-seq analyses of RAD21 reveal an ESC specific cohesin binding pattern that is characterized by CTCF independent co-localization of cohesin with pluripotency related transcription factors Oct4, Nanog, Sox2, Esrrb and Klf4. Upon ESC differentiation, most of these binding sites disappear and instead new CTCF independent RAD21 binding sites emerge, which are enriched for binding sites of transcription factors implicated in early differentiation. Furthermore, knock-down of RAD21 causes expression changes that are similar to expression changes after Nanog depletion, demonstrating the functional relevance of the RAD21 - pluripotency transcriptional network association. Finally, we show that Nanog physically interacts with the cohesin or cohesin interacting proteins STAG1 and WAPL further substantiating this association. Based on these findings we propose that a dynamic placement of cohesin by pluripotency transcription factors contributes to a chromosome organization supporting the ESC expression program

Introduction to special issue:New Times Revisited: Britain in the 1980s

The authors in this volume are collectively engaged with a historical puzzle: What happens if we examine the decade once we step out of the shadows cast by Thatcher? That is, does the decade of the 1980s as a significant and meaningful periodisation (equivalent to that of the 1960s) still work if Thatcher becomes but one part of the story rather than the story itself? The essays in this collection suggest that the 1980s only makes sense as a political period. They situate the 1980s within various longer term trajectories that show the events of the decade to be as much the consequence as the cause of bigger, long-term historical processes. This introduction contextualises the collection within the wider literature, before explaining the collective and individual contributions made

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570