Reservoir host immunology and life history shape virulence evolution in zoonotic viruses

This is the final version. Available on open access from Public Library of Science via the DOI in this recordData Availability: All relevant data are available within the manuscript and Supporting information files or are deposited in our open access GitHub repository, 'brooklabteam/spillover-virulence: spillover-virulence-v1.0.0' (https://zenodo.org/record/8136864).The management of future pandemic risk requires a better understanding of the mechanisms that determine the virulence of emerging zoonotic viruses. Meta-analyses suggest that the virulence of emerging zoonoses is correlated with but not completely predictable from reservoir host phylogeny, indicating that specific characteristics of reservoir host immunology and life history may drive the evolution of viral traits responsible for cross-species virulence. In particular, bats host viruses that cause higher case fatality rates upon spillover to humans than those derived from any other mammal, a phenomenon that cannot be explained by phylogenetic distance alone. In order to disentangle the fundamental drivers of these patterns, we develop a nested modeling framework that highlights mechanisms that underpin the evolution of viral traits in reservoir hosts that cause virulence following cross-species emergence. We apply this framework to generate virulence predictions for viral zoonoses derived from diverse mammalian reservoirs, recapturing trends in virus-induced human mortality rates reported in the literature. Notably, our work offers a mechanistic hypothesis to explain the extreme virulence of bat-borne zoonoses and, more generally, demonstrates how key differences in reservoir host longevity, viral tolerance, and constitutive immunity impact the evolution of viral traits that cause virulence following spillover to humans. Our theoretical framework offers a series of testable questions and predictions designed to stimulate future work comparing cross-species virulence evolution in zoonotic viruses derived from diverse mammalian hosts

Antenatal atazanavir: a retrospective analysis of pregnancies exposed to atazanavir.

INTRODUCTION: There are few data regarding the tolerability, safety, or efficacy of antenatal atazanavir. We report our clinical experience of atazanavir use in pregnancy. METHODS: A retrospective medical records review of atazanavir-exposed pregnancies in 12 London centres between 2004 and 2010. RESULTS: There were 145 pregnancies in 135 women: 89 conceived whilst taking atazanavir-based combination antiretroviral therapy (cART), "preconception" atazanavir exposure; 27 started atazanavir-based cART as "first-line" during the pregnancy; and 29 "switched" to an atazanavir-based regimen from another cART regimen during pregnancy. Gastrointestinal intolerance requiring atazanavir cessation occurred in five pregnancies. Self-limiting, new-onset transaminitis was most common in first-line use, occurring in 11.0%. Atazanavir was commenced in five switch pregnancies in the presence of transaminitis, two of which discontinued atazanavir with persistent transaminitis. HIV-VL < 50 copies/mL was achieved in 89.3% preconception, 56.5% first-line, and 72.0% switch exposures. Singleton preterm delivery (<37 weeks) occurred in 11.7% preconception, 9.1% first-line, and 7.7% switch exposures. Four infants required phototherapy. There was one mother-to-child transmission in a poorly adherent woman. CONCLUSIONS: These data suggest that atazanavir is well tolerated and can be safely prescribed as a component of combination antiretroviral therapy in pregnancy

Acceptability and Preliminary Efficacy of a Web- and Telephone-Based Personalised Exercise Intervention for Individuals with Metastatic Prostate Cancer: The ExerciseGuide Pilot Randomised Controlled Trial.

Preliminary research has shown the effectiveness of supervised exercise-based interventions in alleviating sequela resulting from metastatic prostate cancer. However, many individuals encounter barriers that limit the uptake of face-to-face exercise. Technology-enabled interventions offer a distance-based alternative. This pilot study aimed to explore the acceptability, safety and preliminary efficacy of a web-based exercise intervention (ExerciseGuide) in individuals with metastatic prostate cancer. Forty participants (70.2 ± 8.5 years) with metastatic prostate cancer were randomised into the 8-week intervention (N = 20) or a wait-list control (N = 20). The intervention arm had access to a computer-tailored website, personalised exercise prescription and remote supervision. ExerciseGuide was deemed acceptable with a score ≥20 on the client satisfaction questionnaire; however, the usability score was just below the pre-specified score of ≥68 on the software usability scale. There were no serious adverse events reported. Moderate-to-vigorous physical activity levels between baseline and follow-ups were significantly higher (10.0 min per day; 95% CI = (1.3-18.6); p = 0.01) in the intervention group compared to wait-list control. There were also greater improvements in step count (1332; 95% CI = (159-2505); p = 0.02) and identified motivation (0.4, 95% CI = (0.0, 0.7); p = 0.04). Our findings provide preliminary evidence that ExerciseGuide is acceptable, safe and efficacious among individuals with metastatic prostate cancer

Promoting Physical Activity with Hard-to-Reach Women: An Iterative and Participatory Research Study

Approximately half of all UK women are insufficiently physically active, with the lowest activity rates among ‘Hard-to-Reach’ or unreached women. In this article, Kathryn Brook, Dr Andy Pringle FRSPH, Dr Jackie Hargreaves and Dr Nicky Kime of Leeds Beckett University outline their research into developing methods to assess and meet the needs of ‘Hard-to-Reach’ women in needs-led and person-centred interventions

Accelerated viral dynamics in bat cell lines, with implications for zoonotic emergence

This is the final version. Available on open access from eLife Sciences Publications via the DOI in this recordData availability: All data generated or analysed during this study are included in the manuscript and supporting files. All images and code used in this study have been made available for download at the following Figshare repository: https://doi.org/10.6084/m9.figshare.8312807Bats host virulent zoonotic viruses without experiencing disease. A mechanistic understanding of the impact of bats’ virus hosting capacities, including uniquely constitutive immune pathways, on cellular-scale viral dynamics is needed to elucidate zoonotic emergence. We carried out virus infectivity assays on bat cell lines expressing induced and constitutive immune phenotypes, then developed a theoretical model of our in vitro system, which we fit to empirical data. Best fit models recapitulated expected immune phenotypes for representative cell lines, supporting robust antiviral defenses in bat cells that correlated with higher estimates for within-host viral propagation rates. In general, heightened immune responses limit pathogen-induced cellular morbidity, which can facilitate the establishment of rapidly-propagating persistent infections within-host. Rapidly-transmitting viruses that have evolved with bat immune systems will likely cause enhanced virulence following emergence into secondary hosts with immune systems that diverge from those unique to bats.Natural Environment Research Council (NERC)Biotechnology & Biological Sciences Research Council (BBSRC)National Science FoundationPrinceton UniversityUC BerkeleyDARPA PREEMPT programNIHSingapore National Research FoundationGerman Research Council (DFG)Federal Ministry of Education and Research (BMBF)European Union Horizon 202

Bat conservation and zoonotic disease risk: a research agenda to prevent misguided persecution in the aftermath of COVID-19

Letter to the EditorCOVID-19 has spread around the globe, with massive impacts on global human health, national economies and conservation activities. In the timely editorial about conservation in the maelstrom of COVID-19, Evans et al. (2020) urged the conservation community to collaborate with other relevant sectors of society in the search for solutions to the challenges posed by the current pandemic, as well as future zoonotic outbreaks. Considering the association of COVID 19 with bats (Zhou et al., 2020), bat conservationists will undoubtedly be key actors in this dialogue, and thus an action plan on how best to adjust bat conservation to this new reality, alongside a transdisciplinary research agenda, are clear prioritiesinfo:eu-repo/semantics/publishedVersio

Methods for the guideline-based development of quality indicators--a systematic review

<p>Abstract</p> <p>Background</p> <p>Quality indicators (QIs) are used in many healthcare settings to measure, compare, and improve quality of care. For the efficient development of high-quality QIs, rigorous, approved, and evidence-based development methods are needed. Clinical practice guidelines are a suitable source to derive QIs from, but no gold standard for guideline-based QI development exists. This review aims to identify, describe, and compare methodological approaches to guideline-based QI development.</p> <p>Methods</p> <p>We systematically searched medical literature databases (Medline, EMBASE, and CINAHL) and grey literature. Two researchers selected publications reporting methodological approaches to guideline-based QI development. In order to describe and compare methodological approaches used in these publications, we extracted detailed information on common steps of guideline-based QI development (topic selection, guideline selection, extraction of recommendations, QI selection, practice test, and implementation) to predesigned extraction tables.</p> <p>Results</p> <p>From 8,697 hits in the database search and several grey literature documents, we selected 48 relevant references. The studies were of heterogeneous type and quality. We found no randomized controlled trial or other studies comparing the ability of different methodological approaches to guideline-based development to generate high-quality QIs. The relevant publications featured a wide variety of methodological approaches to guideline-based QI development, especially regarding guideline selection and extraction of recommendations. Only a few studies reported patient involvement.</p> <p>Conclusions</p> <p>Further research is needed to determine which elements of the methodological approaches identified, described, and compared in this review are best suited to constitute a gold standard for guideline-based QI development. For this research, we provide a comprehensive groundwork.</p

Emotional, behavioural problems and cigarette smoking in adolescence: findings of a Greek cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Although several studies have reported findings concerning the association between smoking and emotional/behavioural problems, little research has investigated this association after controlling for confounding factors which have been found to be significantly correlated with both cigarette smoking and emotional/behavioural problems and may have a strong effect on the relationship between adolescents' mental health and smoking. The present study attempted to assess the association between adolescents' smoking status and their emotional/behavioural problems after controlling for a number of possible confounders (i.e. age, gender, parental smoking status, exposure to family smoking, family socioeconomic status, adolescents' leisure time) in a Greek nation-wide school-based sample.</p> <p>Methods</p> <p>Participants completed a questionnaire which retrieved information about age, gender, family socioeconomic status, smoking status, parental smoking, adolescents' leisure time and emotional/behavioural problems. Data were modelled using multiple logistic regression analysis with adolescents' smoking status as the dependent variable.</p> <p>Results</p> <p>A total of 1194 (i.e. 63% response rate) of self-reported questionnaires (40.1% boys, 59.9% girls; 12-18 years old) were returned. Data from 1030 participants with full data were analyzed. Cigarette smoking was strongly associated with higher levels of emotional/behavioural problems (p < 0.001) and the association was not moderated (OR = 1.13, 95% CI: 1.08-1.18) after controlling for the effects of other covariates. Emotional symptoms, conduct problems and hyperactivity/inattention were all significantly associated with adolescents' current smoking.</p> <p>Conclusions</p> <p>This study supports the association between smoking and emotional/behavioural problems among adolescents. Addressing adolescents' needs regarding their emotional/behavioural health could be helpful in the development of effective anti-smoking strategies in school environment and elsewhere.</p

Teaching energy conservation as a unifying principle in physics

In this work we present the design and assessment of a teaching sequence aimed at introducing the principle of energy conservation at post-compulsory secondary school level (16-18 year olds). The proposal is based on the result of research into teaching-learning difficulties and on the analysis of the physics framework. Evidence is shown that this teaching sequence, together with the methodology used in the classroom, may result in students having a better grasp of the principle of energy conservation. Keywords Physics education · Energy conceptions · Teaching activitie