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Animal Models, Therapeutics, and Vaccine Approaches to Emerging and Re-Emerging Flaviviruses
Get PDFFlaviviruses are arthropod-borne viruses primarily transmitted through the mosquito Aedes aegypti or Culex genus of mosquitos. These viruses are predominantly found in tropical and subtropical regions of the world with their geographical spread predicted to increase as global temperatures continue to rise. These viruses cause a variety of diseases in humans with the most prevalent being caused by dengue, resulting in hemorrhagic fever and associated sequala. Current approaches for therapeutic control of flavivirus infections are limited, and despite recent advances, there are no approved drugs. Vaccines, available for a few circulating flaviviruses, still have limited potential for controlling contemporary and future outbreaks. Mouse models provide us with a valuable tool to test the effectiveness of drugs and vaccines, yet for many flaviviruses, well-established mouse models are lacking. In this review, we highlight the current state of flavivirus vaccines and therapeutics, as well as our current understanding of mouse models for various flaviviruses
Assessing self-determined motivation for drinking alcohol via the Comprehensive Relative Autonomy Index for Drinking
Get PDFSelf-Determination Theory (SDT) examines human motivation in multiple domains; however, the only existing measure assessing SDT-informed behavioral regulations for drinking focuses on responsible drinker behaviors, rather than drinking per se, which is important given the alignment between SDT and harm reduction approaches to alcohol use. The aim of this study was to test the structural validity of the SDT-informed Comprehensive Relative Autonomy Index for Drinking (CRAI-Drinking) among college students. Participants included two convenience samples with a total of 630 adult drinkers (Mage = 21.5, 55% female, 88% undergraduates). Participants rated drinking behavioral regulations on the 24 original CRAI-Drinking items on a 5-point Likert Scale. Multi-dimensional scaling analyses and factor analyses were used to investigate the underlying autonomy continuum and factor structure of the CRAI-Drinking. In Sample 1 (n = 274), multi-dimensional scaling analyses confirmed that CRAI-Drinking item and subscale order aligned with SDT's autonomy continuum. Confirmatory factor analyses supported a five factor, 19-item model of the CRAI-Drinking with factors for intrinsic, identified, positive introjected, external, and amotivation regulations (Cronbach's α: 0.68–0.85). In Sample 2 (n = 356), a confirmatory factor analysis confirmed that the 19-item model fit was comparable to Sample 1. This study provides evidence for the structural validity of CRAI-Drinking scores for assessing SDT-based behavioral regulations for drinking in adults
Effect of nirmatrelvir/ritonavir (Paxlovid) on hospitalization among adults with COVID-19: An electronic health record-based target trial emulation from N3C.
Get PDFBACKGROUND: Nirmatrelvir with ritonavir (Paxlovid) is indicated for patients with Coronavirus Disease 2019 (COVID-19) who are at risk for progression to severe disease due to the presence of one or more risk factors. Millions of treatment courses have been prescribed in the United States alone. Paxlovid was highly effective at preventing hospitalization and death in clinical trials. Several studies have found a protective association in real-world data, but they variously used less recent study periods, correlational methods, and small, local cohorts. Their estimates also varied widely. The real-world effectiveness of Paxlovid remains uncertain, and it is unknown whether its effect is homogeneous across demographic strata. This study leverages electronic health record data in the National COVID Cohort Collaborative's (N3C) repository to investigate disparities in Paxlovid treatment and to emulate a target trial assessing its effectiveness in reducing severe COVID-19 outcomes. METHODS AND FINDINGS: This target trial emulation used a cohort of 703,647 patients with COVID-19 seen at 34 clinical sites across the United States between April 1, 2022 and August 28, 2023. Treatment was defined as receipt of a Paxlovid prescription within 5 days of the patient's COVID-19 index date (positive test or diagnosis). To emulate randomization, we used the clone-censor-weight technique with inverse probability of censoring weights to balance a set of covariates including sex, age, race and ethnicity, comorbidities, community well-being index (CWBI), prior healthcare utilization, month of COVID-19 index, and site of care provision. The primary outcome was hospitalization; death was a secondary outcome. We estimated that Paxlovid reduced the risk of hospitalization by 39% (95% confidence interval (CI) [36%, 41%]; p < 0.001), with an absolute risk reduction of 0.9 percentage points (95% CI [0.9, 1.0]; p < 0.001), and reduced the risk of death by 61% (95% CI [55%, 67%]; p < 0.001), with an absolute risk reduction of 0.2 percentage points (95% CI [0.1, 0.2]; p < 0.001). We also conducted stratified analyses by vaccination status and age group. Absolute risk reduction for hospitalization was similar among patients that were vaccinated and unvaccinate, but was much greater among patients aged 65+ years than among younger patients. We observed disparities in Paxlovid treatment, with lower rates among black and Hispanic or Latino patients, and within socially vulnerable communities. This study's main limitation is that it estimates causal effects using observational data and could be biased by unmeasured confounding. CONCLUSIONS: In this study of Paxlovid's real-world effectiveness, we observed that Paxlovid is effective at preventing hospitalization and death, including among vaccinated patients, and particularly among older patients. This remains true in the era of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Omicron subvariants. However, disparities in Paxlovid treatment rates imply that the benefit of Paxlovid's effectiveness is not equitably distributed
University of North Carolina at Chapel Hill University Libraries' annual data submitted to Association of College and Research Libraries' Academic Library Trends and Statistics Survey
No full textThe University of North Carolina at Chapel Hill University Libraries submits data annually to the Association of College and Research Libraries' Academic Library Trends and Statistics Survey.
ACRL restricts access to their collected data. ACRL Benchmark subscribers have access to their reporting tools: https://librarybenchmark.org/
This spreadsheet contains the same data that UNC Chapel Hill University Libraries submitted to ACRL, back to the 2014-15 fiscal year.
The file is updated annually, usually in the Spring semester
Psychometric assessment of scales used to evaluate sexual assault prevention programming in the United States Air Force
Get PDFBackground Preventing sexual assault in the United States (U.S.) military is essential to safeguard the overall well-being of military personnel and support the military to function in alignment with its intended mission and objectives. Valid instruments are needed to accurately and reliably evaluate programming effectiveness. The goal of this research was to psychometrically assess measures used to evaluate the Sexual Communication and Consent (SCC) program within the Air Force Basic Military Training (BMT) context.
Methods We evaluated four measures used to assess the SCC program implemented at Air Force BMT in 2019–2020: Date Rape Attitudes, Self-Efficacy to Resist Unwanted Advances, Risky and Protective Dating Behaviors, and Bystander Intentions. The analytic sample included 7,126 BMT trainees (74% male). We assessed structural validity with exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). We used full information maximum likelihood estimation with robust standard errors in Mplus. We refined each scale based on factor analysis results and assessed internal consistency reliability by computing Cronbach’s coefficient alpha for each scale in the overall sample, by sex, and by tailored SCC intervention group.
Results We identified a two-factor structure for the Date Rape Attitudes scale; subscale reliability was moderate within the overall sample and among males, though low among females. We found single-factor structures and excellent reliability for both the Self-Efficacy to Resist Unwanted Advances scale and the Bystander Intentions scale. The Dating Behaviors scale CFA did not confirm the two-factor solution suggested by the EFA, but subscale reliability was acceptable.
Conclusion This research fills a critical gap in the psychometric literature in military settings. Based on our findings, we recommend approaches for using the finalized scales in future evaluations of sexual assault prevention programming in the U.S. Air Force BMT setting
Associations of nonoccupational sedentary behaviors with cardiometabolic outcomes: coronary artery risk development in young adults (CARDIA)
Get PDFBackground: The association between sedentary behavior (SB) and cardiometabolic risk may differ by SB domain and context. Nonoccupational SB is particularly important because it is discretionary and more amenable to change. This study estimated associations of nonoccupational SB contexts with hypertension (HTN) and diabetes mellitus (DM). Methods: A total of 3370 middle-aged adults (50.1 ± 3.6 years; 56% F) from the Coronary Artery Risk Development in Young Adults (CARDIA) study were included. Cross-sectional and 5-year prospective associations between self-report total SB and 6 context-specific SBs (television—TV, computer, transportation, phone, music, and paperwork) with HTN and DM were tested using logistic regression. Fully adjusted models controlled for sociodemographic variables, body mass index, and self-report moderate-vigorous intensity physical activity. Results: Prevalences of HTN and DM at baseline were 48% (1618 cases) and 10% (320 cases), respectively. Each hour per day of total-SB was cross-sectionally associated with HTN (OR: 1.03, 95% CI, 1.01-1.05) but not DM, with nonsignificant prospective associations for HTN and DM. Of the context-specific SBs, only TV-SB was significantly associated with HTN or DM. Each hour of TV-SB was cross-sectionally associated with HTN (OR: 1.09, 95% CI, 1.03-1.15) and DM (OR: 1.18, 95% CI, 1.09-1.29), and prospectively with HTN (OR: 1.14, 95% CI, 1.04-1.26) but not DM. Conclusion: When comparing total-SB and the 6 context-specific SBs, TV-SB was most robustly associated with HTN. The findings were less clear for DM. Behavior change strategies that target TV-SB reduction may be effective at reducing HTN risk in middle-aged adults
Dysregulation of lung epithelial cell homeostasis and immunity contributes to Middle East respiratory syndrome coronavirus disease severity
Get PDFCoronaviruses (CoV) emerge suddenly from animal reservoirs to cause novel diseases in new hosts. Discovered in 2012, the Middle East respiratory syndrome coronavirus (MERS-CoV) is endemic in camels in the Middle East and is continually causing local outbreaks and epidemics. While all three newly emerging human CoVs from the past 20 years (SARS-CoV, SARS-CoV-2, and MERS-CoV) cause respiratory disease, each CoV has unique host interactions that drive differential pathogeneses. To better understand the virus and host interactions driving lethal MERS-CoV infection, we performed a longitudinal multi-omics analysis of sublethal and lethal MERS-CoV infection in mice. Significant differences were observed in body weight loss, virus titers, and acute lung injury among lethal and sub-lethal virus doses. Virus-induced apoptosis of type I and II alveolar epithelial cells suggests that loss or dysregulation of these key cell populations was a major driver of severe disease. Omics analysis suggested differential pathogenesis was multi-factorial with clear differences among innate and adaptive immune pathways as well as those that regulate lung epithelial homeostasis. Infection of mice lacking functional T and B cells showed that adaptive immunity was important in controlling viral replication but also increased pathogenesis. In summary, we provide a high-resolution host response atlas for MERS-CoV infection and disease severity. Multi-omics studies of viral pathogenesis offer a unique opportunity to not only better understand the molecular mechanisms of disease but also to identify genes and pathways that can be exploited for therapeutic intervention all of which is important for our future pandemic preparedness.IMPORTANCEEmerging coronaviruses like SARS-CoV, SARS-CoV-2, and MERS-CoV cause a range of disease outcomes in humans from an asymptomatic, moderate, and severe respiratory disease that can progress to death but the factors causing these disparate outcomes remain unclear. Understanding host responses to mild and life-threatening infections provides insight into virus-host networks within and across organ systems that contribute to disease outcomes. We used multi-omics approaches to comprehensively define the host response to moderate and severe MERS-CoV infection. Severe respiratory disease was associated with dysregulation of the immune response. Key lung epithelial cell populations that are essential for lung function get infected and die. Mice lacking key immune cell populations experienced greater virus replication but decreased disease severity implicating the immune system in both protective and pathogenic roles in response to MERS-CoV. These data could be utilized to design new therapeutic strategies targeting specific pathways that contribute to severe disease
Evaluating Response to a Cognitive Behavioural Therapy for Psychosis‐Informed Family Intervention at Variable Duration of a Psychotic Illness
Get PDFObjective Early intervention in psychosis is associated with favourable outcomes. We investigated whether loved ones' illness duration moderated caregiver outcomes following a Cognitive Behavioural Therapy‐informed Family Intervention for psychosis (FIp). Methods We conducted a secondary analysis of measures of FIp participants' depression and anxiety symptoms, caregiver appraisals, expressed emotion and foundational psychotherapeutic competencies at pre‐, post‐ and 4‐month follow‐up. Our primary aim was to evaluate whether duration of illness moderated participant outcomes. Results Relative to pre‐intervention, all caregivers reported lower depression, anxiety and expressed emotion, as well as higher positive attitudes and mastery of cognitive behavioural skills, at post‐intervention and 4‐month follow‐up. Outcomes were not moderated by their loved one's illness duration. Conclusion Families may benefit equally from FIp regardless of illness duration. Although we recommend that FIp are offered as early as possible, modifications for families with lengthier illness courses are not implicated by our findings
Facilitators and Barriers to Hiv Pre-Exposure Prophylaxis Adherence and Retention Among Young Men Who have Sex With Men: A Meta-Ethnographic Scoping Review
Get PDFRetention and adherence to daily oral pre-exposure prophylaxis (PrEP) are critical for effective HIV prevention; however, YMSM exhibit lower rates of both compared to other populations. This is important because young men who have sex with men (YMSM) are at higher risk for HIV, and understanding their challenges can help create better support and interventions. This scoping review synthesizes evidence on the facilitators and barriers to HIV PrEP retention and adherence among YMSM, focusing on individuals aged 10 to 29 years. The review adheres to PRISMA-ScR and eMERGe guidelines, examining 14 studies involving 3,178 participants. It emphasizes the complex interactions of individual, interpersonal, community, and societal factors influencing PrEP adherence and retention. Key facilitators include psychological strategies, supportive health systems, and supportive social networks. Conversely, significant barriers encompass financial burdens, interpersonal stigma, and behavioral factors. The review highlights the critical role of tailored, multi-level interventions and the need for healthcare provider training in youth-specific approaches to care. This work contributes to a nuanced understanding of PrEP retention among YMSM, offering insights crucial for designing effective public health strategies to enhance prevention-effective PrEP utilization in this high-risk population