Unearthing late medieval children : health, status and burial practice in southern England

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Exploring the perspectives of selectors and collecters of trial outcome data : An international qualitative study

Acknowledgements The authors would like to thank all interviewees that took part in this study, as well as our colleagues and fellow members of the Trial Forge, HRB-TMRN, and MRC Trial Methodology Hubs networks that supported in identifying potential participants. Funding This project was funded by the Chief Scientist Office, grant number HIPS/18/04Peer reviewedPublisher PD

A good use of time? : Providing evidence for how effort is invested in primary and secondary outcome data collection in trials

BACKGROUND: Data collection is a substantial part of trial workload for participants and staff alike. How these hours of work are spent is important because stakeholders are more interested in some outcomes than others. The ORINOCO study compared the time spent collecting primary outcome data to the time spent collecting secondary outcome data in a cohort of trials. METHODS: We searched PubMed for phase III trials indexed between 2015 and 2019. From these, we randomly selected 120 trials evaluating a therapeutic intervention plus an additional random selection of 20 trials evaluating a public health intervention. We also added eligible trials from a cohort of 189 trials in rheumatology that had used the same core outcome set. We then obtained the time taken to collect primary and secondary outcomes in each trial. We used a hierarchy of methods that included data in trial reports, contacting the trial team and approaching individuals with experience of using the identified outcome measures. We calculated the primary to secondary data collection time ratio and notional data collection cost for each included trial. RESULTS: We included 161 trials (120 phase III; 21 core outcome set; 20 public health), which together collected 230 primary and 688 secondary outcomes. Full primary and secondary timing data were obtained for 134 trials (100 phase III; 17 core outcome set; 17 public health). The median time spent on primaries was 56.1 h (range: 0.0-10,746.7, IQR: 226.89) and the median time spent on secondaries was 190.7 hours (range: 0.0-1,356,832.9, IQR: 617.6). The median primary to secondary data collection time ratio was 1.0:3.0 (i.e. for every minute spent on primary outcomes, 3.0 were spent on secondaries). The ratio varied by trial type: phase III trials were 1.0:3.1, core outcome set 1.0:3.4 and public health trials 1.0:2.2. The median notional overall data collection cost was £8015.73 (range: £52.90-£31,899,140.70, IQR: £20,096.64). CONCLUSIONS: Depending on trial type, between two and three times as much time is spent collecting secondary outcome data than collecting primary outcome data. Trial teams should explicitly consider how long it will take to collect the data for an outcome and decide whether that time is worth it given importance of the outcome to the trial.Peer reviewe

An analysis of healthcare providers' online ratings

Background Many websites allow consumers to evaluate their healthcare experience yet scant data exist that explore the type and content of reviews. Objective To evaluate and describe online healthcare provider reviews. Methods We analysed 16 703 ratings on 6101 providers from four US cities. Ratings spanned five categories and an overall provider score. We also performed text analyses of narrative commentary (n = 15 952). Results Providers had a high mean score for each category (3.7_4.0 out of 5). Higher overall scores were associated with higher staff (adjusted odds ratio (aOR) 3.0, 95% CI 2.9_3.0, P< 0.01) and punctuality scores (aOR 2.1, 95% CI 2.05_2.15, P< 0.01). Review frequency was inversely associated with scores, (aOR 0.94, 95% CI 0.92_0.96, P<0.01). Analyses of narrative commentaries revealed more positive than negative terms (P< 0.01). Conclusions Online ratings were largely positive. Future research must discern how online surveys affect patient referrals, provider reputations and patients' perceptions of quality of care

Asymmetric Switching in a Homodimeric ABC Transporter: A Simulation Study

ABC transporters are a large family of membrane proteins involved in a variety of cellular processes, including multidrug and tumor resistance and ion channel regulation. Advances in the structural and functional understanding of ABC transporters have revealed that hydrolysis at the two canonical nucleotide-binding sites (NBSs) is co-operative and non-simultaneous. A conserved core architecture of bacterial and eukaryotic ABC exporters has been established, as exemplified by the crystal structure of the homodimeric multidrug exporter Sav1866. Currently, it is unclear how sequential ATP hydrolysis arises in a symmetric homodimeric transporter, since it implies at least transient asymmetry at the NBSs. We show by molecular dynamics simulation that the initially symmetric structure of Sav1866 readily undergoes asymmetric transitions at its NBSs in a pre-hydrolytic nucleotide configuration. MgATP-binding residues and a network of charged residues at the dimer interface are shown to form a sequence of putative molecular switches that allow ATP hydrolysis only at one NBS. We extend our findings to eukaryotic ABC exporters which often consist of two non-identical half-transporters, frequently with degeneracy substitutions at one of their two NBSs. Interestingly, many residues involved in asymmetric conformational switching in Sav1866 are substituted in degenerate eukaryotic NBS. This finding strengthens recent suggestions that the interplay of a consensus and a degenerate NBS in eukaroytic ABC proteins pre-determines the sequence of hydrolysis at the two NBSs

Mismatches in scale between highly mobile marine megafauna and marine protected areas

Marine protected areas (MPAs), particularly large MPAs, are increasing in number and size around the globe in part to facilitate the conservation of marine megafauna under the assumption that large-scale MPAs better align with vagile life histories; however, this alignment is not well established. Using a global tracking dataset from 36 species across five taxa, chosen to reflect the span of home range size in highly mobile marine megafauna, we show most MPAs are too small to encompass complete home ranges of most species. Based on size alone, 40% of existing MPAs could encompass the home ranges of the smallest ranged species, while only < 1% of existing MPAs could encompass those of the largest ranged species. Further, where home ranges and MPAs overlapped in real geographic space, MPAs encompassed < 5% of core areas used by all species. Despite most home ranges of mobile marine megafauna being much larger than existing MPAs, we demonstrate how benefits from MPAs are still likely to accrue by targeting seasonal aggregations and critical life history stages and through other management techniques.Fil: Conners, Melinda G.. University of Washington; Estados Unidos. State University of New York. Stony Brook University; Estados UnidosFil: Sisson, Nicholas B.. Old Dominion University; Estados UnidosFil: Agamboue, Pierre D.. Wildlife Conservation Society; GabónFil: Atkinson, Philip W.. British Trust For Ornithology; Reino UnidoFil: Baylis, Alastair M. M.. Macquarie University; Australia. South Atlantic Environmental Research Institute; Reino UnidoFil: Benson, Scott R.. Noaa National Marine Fisheries Service Southwest Regional Office; Estados Unidos. Moss Landing Marine Laboratories; Estados UnidosFil: Block, Barbara A.. University of Stanford; Estados UnidosFil: Bograd, Steven J.. Noaa National Marine Fisheries Service Southwest Regional Office; Estados UnidosFil: Bordino, Pablo. Mote Marine Laboratory; Estados UnidosFil: Bowen, W.D.. Bedford Institute Of Oceanography, Fisheries And Oceans Canada; Canadá. Dalhousie University Halifax; CanadáFil: Brickle, Paul. South Atlantic Environmental Research Institute; Reino Unido. University of Aberdeen; Reino Unido. University Of Aberdeeen; Reino UnidoFil: Bruno, Ignacio Matias. Instituto Nacional de Investigaciones y Desarrollo Pesquero; ArgentinaFil: González Carman, Victoria. Instituto Nacional de Investigaciones y Desarrollo Pesquero; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; ArgentinaFil: Champagne, Cory D.. University of Washington; Estados UnidosFil: Crocker, Daniel E.. Sonoma State University; Estados UnidosFil: Costa, Daniel P.. University of California; Estados UnidosFil: Dawson, Tiffany M.. University Of Central Florida; Estados Unidos. Old Dominion University; Estados UnidosFil: Deguchi, Tomohiro. Yamashina Institute For Ornithology; JapónFil: Dewar, Heidi. Noaa National Marine Fisheries Service Southwest Regional Office; Estados UnidosFil: Doherty, Philip D.. University of Exeter; Reino UnidoFil: Eguchi, Tomo. Noaa National Marine Fisheries Service Southwest Regional Office; Estados UnidosFil: Formia, Angela. Wildlife Conservation Society; Gabón. African Aquatic Conservation Fund; Estados UnidosFil: Godley, Brendan J.. University of Exeter; Reino UnidoFil: Graham, Rachel T.. Maralliance; PanamáFil: Gredzens, Christian. Padre Island National Seashore; Estados UnidosFil: Hart, Kristen M.. United States Geological Survey; Estados UnidosFil: Hawkes, Lucy A.. University of Exeter; Reino UnidoFil: Henderson, Suzanne. Scottish Natural Heritage; Reino UnidoFil: Henry, Robert William. Groundswell Coastal Ecology; Estados UnidosFil: Hückstädt, Luis A.. University of Exeter; Reino Unido. University of California; Estados Unido

Recycling Attitudes and Behavior among a Clinic-Based Sample of Low-Income Hispanic Women in Southeast Texas

We examined attitudes and behavior surrounding voluntary recycling in a population of low-income Hispanic women. Participants (N = 1,512) 18–55 years of age completed a self-report survey and responded to questions regarding household recycling behavior, recycling knowledge, recycling beliefs, potential barriers to recycling (transportation mode, time), acculturation, demographic characteristics (age, income, employment, marital status, education, number of children, birth country), and social desirability. Forty-six percent of participants (n = 810) indicated that they or someone else in their household recycled. In a logistic regression model controlling for social desirability, recycling behavior was related to increased age (P<0.05), lower acculturation (P<0.01), knowing what to recycle (P<0.01), knowing that recycling saves landfill space (P<0.05), and disagreeing that recycling takes too much time (P<0.001). A Sobel test revealed that acculturation mediated the relationship between recycling knowledge and recycling behavior (P<0.05). We offer new information on recycling behavior among Hispanic women and highlight the need for educational outreach and intervention strategies to increase recycling behavior within this understudied population

Meta-Analysis of the Alzheimer\u27s Disease Human Brain Transcriptome and Functional Dissection in Mouse Models.

We present a consensus atlas of the human brain transcriptome in Alzheimer\u27s disease (AD), based on meta-analysis of differential gene expression in 2,114 postmortem samples. We discover 30 brain coexpression modules from seven regions as the major source of AD transcriptional perturbations. We next examine overlap with 251 brain differentially expressed gene sets from mouse models of AD and other neurodegenerative disorders. Human-mouse overlaps highlight responses to amyloid versus tau pathology and reveal age- and sex-dependent expression signatures for disease progression. Human coexpression modules enriched for neuronal and/or microglial genes broadly overlap with mouse models of AD, Huntington\u27s disease, amyotrophic lateral sclerosis, and aging. Other human coexpression modules, including those implicated in proteostasis, are not activated in AD models but rather following other, unexpected genetic manipulations. Our results comprise a cross-species resource, highlighting transcriptional networks altered by human brain pathophysiology and identifying correspondences with mouse models for AD preclinical studies

Trial Forge Guidance 3: randomised trials and how to recruit and retain individuals from ethnic minority groups- practical guidance to support better practice

Randomised trials, especially those intended to directly inform clinical practice and policy, should be designed to reflect all those who could benefit from the intervention under test should it prove effective. This does not always happen. The UK National Institute for Health and Care Research (NIHR) INCLUDE project identified many groups in the UK that are under-served by trials, including ethnic minorities. This guidance document presents four key recommendations for designing and running trials that include the ethnic groups needed by the trial. These are (1) ensure eligibility criteria and recruitment pathway do not limit participation in ways you do not intend, (2) ensure your trial materials are developed with inclusion in mind, (3) ensure staff are culturally competent and (4) build trusting partnerships with community organisations that work with ethnic minority groups. Each recommendation comes with best practice advice, public contributor testimonials, examples of the inclusion problem tackled by the recommendation, or strategies to mitigate the problem, as well as a collection of resources to support implementation of the recommendations. We encourage trial teams to follow the recommendations and, where possible, evaluate the strategies they use to implement them. Finally, while our primary audience is those designing, running and reporting trials, we hope funders, grant reviewers and approvals agencies may also find our guidance useful

Mismatches in Scale Between Highly Mobile Marine Megafauna and Marine Protected Areas

Marine protected areas (MPAs), particularly large MPAs, are increasing in number and size around the globe in part to facilitate the conservation of marine megafauna under the assumption that large-scale MPAs better align with vagile life histories; however, this alignment is not well established. Using a global tracking dataset from 36 species across five taxa, chosen to reflect the span of home range size in highly mobile marine megafauna, we show most MPAs are too small to encompass complete home ranges of most species. Based on size alone, 40% of existing MPAs could encompass the home ranges of the smallest ranged species, while only \u3c 1% of existing MPAs could encompass those of the largest ranged species. Further, where home ranges and MPAs overlapped in real geographic space, MPAs encompassed \u3c 5% of core areas used by all species. Despite most home ranges of mobile marine megafauna being much larger than existing MPAs, we demonstrate how benefits from MPAs are still likely to accrue by targeting seasonal aggregations and critical life history stages and through other management techniques