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Abstract Background To date, no study has examined influenza vaccine effectiveness (IVE) against laboratory-confirmed influenza-associated hospitalizations during pregnancy. Methods The Pregnancy Influenza Vaccine Effectiveness Network (PREVENT) consisted of public health or healthcare systems with integrated laboratory, medical, and vaccination records in Australia, Canada (Alberta and Ontario), Israel, and the United States (California, Oregon, and Washington). Sites identified pregnant women aged 18 through 50 years whose pregnancies overlapped with local influenza seasons from 2010 through 2016. Administrative data were used to identify hospitalizations with acute respiratory or febrile illness (ARFI) and clinician-ordered real-time reverse transcription polymerase chain reaction (rRT-PCR) testing for influenza viruses. Overall IVE was estimated using the test-negative design and adjusting for site, season, season timing, and high-risk medical conditions. Results Among 19450 hospitalizations with an ARFI discharge diagnosis (across 25 site-specific study seasons), only 1030 (6%) of the pregnant women were tested for influenza viruses by rRT-PCR. Approximately half of these women had pneumonia or influenza discharge diagnoses (54%). Influenza A or B virus infections were detected in 598/1030 (58%) of the ARFI hospitalizations with influenza testing. Across sites and seasons, 13% of rRT-PCR-confirmed influenza-positive pregnant women were vaccinated compared with 22% of influenza-negative pregnant women; the adjusted overall IVE was 40% (95% confidence interval = 12%–59%) against influenza-associated hospitalization during pregnancy. Conclusion Between 2010 and 2016, influenza vaccines offered moderate protection against laboratory-confirmed influenza-associated hospitalizations during pregnancy, which may further inform the benefits of maternal influenza vaccination programs. In this retrospective study of hospitals in Australia, Canada, Israel, and the United States from 2010 to 2016, influenza vaccines were 40% effective in preventing laboratory-confirmed influenza-associated hospitalizations during pregnancy.

•The World Health Organization prioritizes influenza vaccination for pregnant individuals.•Multi-country, multi-season influenza vaccine coverage assessments are sparce.•We examined influenza vaccine coverage among pregnant individuals in four countries over ten influenza seasons. Many countries recommend influenza vaccination during pregnancy. Despite this recommendation, influenza vaccine among pregnant individuals remains under-utilized and uptake varies by country. Factors associated with influenza vaccine uptake during pregnancy may also vary across countries. As members of the Pregnancy Influenza Vaccine Effectiveness Network (PREVENT), five sites from four countries (Australia, Canada, Israel, and the United States) retrospectively identified cohorts of individuals aged 18–50 years who were pregnant during pre-defined influenza seasons. Influenza vaccine coverage estimates were calculated for the 2010–11 through 2015–16 northern hemisphere and the 2012 through 2015 southern hemisphere influenza seasons, by site. Sites used electronic health records, administrative data, and immunization registries to collect information on pregnancy, health history, demographics, and vaccination status. Each season, vaccination coverage was calculated as the percentage of individuals who received influenza vaccine among the individuals in the cohort that season. Characteristics were compared between those vaccinated and unvaccinated, by site. More than two million pregnancies were identified over the study period. Influenza vaccination coverage ranged from 5% to 58% across sites and seasons. Coverage increased consistently over the study period at three of the five sites (Western Australia, Alberta, and Israel), and was highest in all seasons at the United States study site (39–58%). Associations with vaccination varied by country and across seasons; where available, parity >0, presence of a high-risk medical condition, and urban residence were consistently associated with increased likelihood of vaccination. Though increasing, uptake of influenza vaccine among pregnant individuals remains lower than recommended. Coverage varied substantially by country, suggesting an ongoing need for targeted strategies to improve influenza vaccine uptake in this population.

Extracellular matrix (ECM) is a dynamic tissue that contributes to organ integrity and function, and its regulation of cell phenotype is a major aspect of cell biology. However, standard in vitro culture approaches are of unclear physiologic relevance because they do not mimic the compositional, architectural, or distensible nature of a living organ. In the lung, fibroblasts exist in ECM-rich interstitial spaces and are key effectors of lung fibrogenesis. To better address how ECM influences fibroblast phenotype in a disease-specific manner, we developed a culture system using acellular human normal and fibrotic lungs. Decellularization was achieved using treatment with detergents, salts, and DNase. The resultant matrices can be sectioned as uniform slices within which cells were cultured. We report that the decellularization process effectively removes cellular and nuclear material while retaining native dimensionality and stiffness of lung tissue. We demonstrate that lung fibroblasts reseeded into acellular lung matrices can be subsequently assayed using conventional protocols; in this manner we show that fibrotic matrices clearly promote transforming growth factor-β-independent myofibroblast differentiation compared with normal matrices. Furthermore, comprehensive analysis of acellular matrix ECM details significant compositional differences between normal and fibrotic lungs, paving the way for further study of novel hypotheses. This methodology is expected to allow investigation of important ECM-based hypotheses in human tissues and permits future scientific exploration in an organ- and disease-specific manner.

Background The effectiveness of complex interventions, as well as their success in reaching relevant populations, is critically influenced by their implementation in a given context. Current conceptual frameworks often fail to address context and implementation in an integrated way and, where addressed, they tend to focus on organisational context and are mostly concerned with specific health fields. Our objective was to develop a framework to facilitate the structured and comprehensive conceptualisation and assessment of context and implementation of complex interventions. Methods The Context and Implementation of Complex Interventions (CICI) framework was developed in an iterative manner and underwent extensive application. An initial framework based on a scoping review was tested in rapid assessments, revealing inconsistencies with respect to the underlying concepts. Thus, pragmatic utility concept analysis was undertaken to advance the concepts of context and implementation. Based on these findings, the framework was revised and applied in several systematic reviews, one health technology assessment (HTA) and one applicability assessment of very different complex interventions. Lessons learnt from these applications and from peer review were incorporated, resulting in the CICI framework. Results The CICI framework comprises three dimensions—context, implementation and setting—which interact with one another and with the intervention dimension. Context comprises seven domains (i.e., geographical, epidemiological, socio-cultural, socio-economic, ethical, legal, political); implementation consists of five domains (i.e., implementation theory, process, strategies, agents and outcomes); setting refers to the specific physical location, in which the intervention is put into practise. The intervention and the way it is implemented in a given setting and context can occur on a micro, meso and macro level. Tools to operationalise the framework comprise a checklist, data extraction tools for qualitative and quantitative reviews and a consultation guide for applicability assessments. Conclusions The CICI framework addresses and graphically presents context, implementation and setting in an integrated way. It aims at simplifying and structuring complexity in order to advance our understanding of whether and how interventions work. The framework can be applied in systematic reviews and HTA as well as primary research and facilitate communication among teams of researchers and with various stakeholders.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the aetiological agent of coronavirus disease 2019 (COVID-19) that has caused a pandemic with millions of human infections. There continues to be a pressing need to develop potential therapies and vaccines to inhibit SARS-CoV-2 infection to mitigate the ongoing pandemic. Epidemiological data from the current pandemic indicates that there may be sex-dependent differences in disease outcomes. To investigate these differences, we proposed to use common small animal species that are frequently used to model disease with viruses. However, common laboratory strains of mice are not readily infected by SARS-CoV-2 because of differences in the angiotensin-converting enzyme 2 (ACE2), the cellular receptor for the virus. To overcome this limitation, we transduced common laboratory accessible strains of mice of different sexes and age groups with a novel a triple AAV6 mutant, termed AAV6.2FF, encoding either human ACE2 or luciferase via intranasal administration to promote expression in the lung and nasal turbinates. Infection of AAV-hACE2-transduced mice with SARS-CoV-2 resulted in high viral titers in the lungs and nasal turbinates, establishment of an IgM and IgG antibody response, and modulation of lung and nasal turbinate cytokine profiles. There were insignificant differences in infection characteristics between age groups and sex-related differences; however, there were significant strain-related differences between BALB/c vs. C57BL/6 mice. We show that AAV-hACE2-transduced mice are a useful for determining immune responses and for potential evaluation of SARS-CoV-2 vaccines and antiviral therapies, and this study serves as a model for the utility of this approach to rapidly develop small-animal models for emerging viruses.

Data from over 2,500 reefs worldwide is used to identify 15 bright spots—sites where reef biomass is significantly higher than expected—and surveys of local experts in these areas suggest that strong sociocultural institutions and high levels of local engagement are among the factors supporting higher fish biomass. Bright spots among the world's coral reefs The health of the world's coral reefs, which provide goods and services for millions of people, is declining. Effective management of these ecosystems requires an understanding of the underlying drivers of reef decline. In a study that spans the gap between ecology and the social sciences, Joshua Cinner and colleagues develop a Bayesian hierarchical model, using data from more than 2,500 reefs worldwide, to predict reef fish biomass based on various socioeconomic drivers and environmental conditions. They identify 15 bright spots — sites where reef biomass is significantly higher than expected. The bright spots are found not only among iconic remote and pristine areas, but also where there are strong sociocultural institutions and high levels of local engagement. On the basis of this analysis, the authors argue for a refocus of coral reef conservation efforts away from locating and protecting remote, pristine sites, towards unlocking potential solutions from sites that have successfully confronted the coral reef crisis. Ongoing declines in the structure and function of the world’s coral reefs 1 , 2 require novel approaches to sustain these ecosystems and the millions of people who depend on them 3 . A presently unexplored approach that draws on theory and practice in human health and rural development 4 , 5 is to systematically identify and learn from the ‘outliers’—places where ecosystems are substantially better (‘bright spots’) or worse (‘dark spots’) than expected, given the environmental conditions and socioeconomic drivers they are exposed to. Here we compile data from more than 2,500 reefs worldwide and develop a Bayesian hierarchical model to generate expectations of how standing stocks of reef fish biomass are related to 18 socioeconomic drivers and environmental conditions. We identify 15 bright spots and 35 dark spots among our global survey of coral reefs, defined as sites that have biomass levels more than two standard deviations from expectations. Importantly, bright spots are not simply comprised of remote areas with low fishing pressure; they include localities where human populations and use of ecosystem resources is high, potentially providing insights into how communities have successfully confronted strong drivers of change. Conversely, dark spots are not necessarily the sites with the lowest absolute biomass and even include some remote, uninhabited locations often considered near pristine 6 . We surveyed local experts about social, institutional, and environmental conditions at these sites to reveal that bright spots are characterized by strong sociocultural institutions such as customary taboos and marine tenure, high levels of local engagement in management, high dependence on marine resources, and beneficial environmental conditions such as deep-water refuges. Alternatively, dark spots are characterized by intensive capture and storage technology and a recent history of environmental shocks. Our results suggest that investments in strengthening fisheries governance, particularly aspects such as participation and property rights, could facilitate innovative conservation actions that help communities defy expectations of global reef degradation.

Zika virus (ZIKV) is an emerging pathogen causally associated with serious sequelae in fetuses, inducing fetal microcephaly and other neurodevelopment defects. ZIKV is primarily transmitted by mosquitoes, but can persist in human semen and sperm, and sexual transmission has been documented. Moreover, exposure of type-I interferon knockout mice to ZIKV results in severe damage to the testes, epididymis and sperm. Candidate ZIKV vaccines have shown protective efficacy in preclinical studies carried out in animal models, and several vaccines have entered clinical trials. Here, we report that administration of a synthetic DNA vaccine encoding ZIKV pre-membrane and envelope (prME) completely protects mice against ZIKV-associated damage to the testes and sperm and prevents viral persistence in the testes following challenge with a contemporary strain of ZIKV. These data suggest that DNA vaccination merits further investigation as a potential means to reduce ZIKV persistence in the male reproductive tract. Zika virus (ZIKV) can persist in human semen and sperm, which can result in sexual transmission. Here, Griffin et al . show that a DNA vaccine, expressing ZIKV pre-membrane and envelope proteins, protects mice from infection-associated damage to testes and sperm, and prevents viral persistence in testes.

Protocols of systematic reviews and meta-analyses allow for planning and documentation of review methods, act as a guard against arbitrary decision making during review conduct, enable readers to assess for the presence of selective reporting against completed reviews, and, when made publicly available, reduce duplication of efforts and potentially prompt collaboration. Evidence documenting the existence of selective reporting and excessive duplication of reviews on the same or similar topics is accumulating and many calls have been made in support of the documentation and public availability of review protocols. Several efforts have emerged in recent years to rectify these problems, including development of an international register for prospective reviews (PROSPERO) and launch of the first open access journal dedicated to the exclusive publication of systematic review products, including protocols (BioMed Central’s Systematic Reviews). Furthering these efforts and building on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines, an international group of experts has created a guideline to improve the transparency, accuracy, completeness, and frequency of documented systematic review and meta-analysis protocols—PRISMA-P (for protocols) 2015. The PRISMA-P checklist contains 17 items considered to be essential and minimum components of a systematic review or meta-analysis protocol.This PRISMA-P 2015 Explanation and Elaboration paper provides readers with a full understanding of and evidence about the necessity of each item as well as a model example from an existing published protocol. This paper should be read together with the PRISMA-P 2015 statement. Systematic review authors and assessors are strongly encouraged to make use of PRISMA-P when drafting and appraising review protocols.

The rapid growth in microplastic pollution research is influencing funding priorities, environmental policy, and public perceptions of risks to water quality and environmental and human health. Ensuring that environmental microplastics research data are findable, accessible, interoperable, and reusable (FAIR) is essential to inform policy and mitigation strategies. We present a bibliographic analysis of data sharing practices in the environmental microplastics research community, highlighting the state of openness of microplastics data. A stratified (by year) random subset of 785 of 6,608 microplastics articles indexed in Web of Science indicates that, since 2006, less than a third (28.5%) contained a data sharing statement. These statements further show that most often, the data were provided in the articles’ supplementary material (38.8%) and only 13.8% via a data repository. Of the 279 microplastics datasets found in online data repositories, 20.4% presented only metadata with access to the data requiring additional approval. Although increasing, the rate of microplastic data sharing still lags behind that of publication of peer-reviewed articles on environmental microplastics. About a quarter of the repository data originated from North America (12.8%) and Europe (13.4%). Marine and estuarine environments are the most frequently sampled systems (26.2%); sediments (18.8%) and water (15.3%) are the predominant media. Of the available datasets accessible, 15.4% and 18.2% do not have adequate metadata to determine the sampling location and media type, respectively. We discuss five recommendations to strengthen data sharing practices in the environmental microplastic research community.

Cultured brain slices rapidly replicate murine prions, exhibit prion pathology, and are amenable towards drug discovery, but have not been infected with human prions. As deer mice ( Peromyscus maniculatus ) are susceptible to human prions in vivo, here we investigated deer mouse organotypic brain slice cultures as a potential model of human prion disease. Deer mouse brain slices supported replication of rodent-adapted strains of scrapie and Creutzfeldt-Jakob disease (CJD), but they resisted infection with primary human prion inoculum. To better understand this discrepancy, we quantified prion replication rates, characterized cellular and molecular changes, and estimated inoculum clearance within wildtype CD1 and deer mouse brain slice cultures. Prion replication rates varied by species, strain, and brain region, independently of PrP sequence homology. Scrapie-infected CD1 cerebellar slice cultures exhibited the fastest prion replication rate, closely matching in vivo bioassay kinetics and showing neuronal and synaptic degeneration at similar timepoints. However, deer mouse slice cultures replicated deer mouse-adapted sCJD MM1 prions less efficiently than in vivo inoculation. These findings clarify both the utility and constraints of brain slice cultures in modeling prion disease and imply that the slice culture molecular environment may be suboptimal for human prion replication.