On the relative roles of dynamics and chemistry governing the abundance and diurnal variation of low latitude thermospheric nitric oxide

We use data from two NASA satellites, the Thermosphere Ionosphere Energetics and Dynamics (TIMED) and the Aeronomy of Ice in the Mesosphere (AIM) satellites in conjunction with model simulations from the Thermosphere-Ionosphere-Mesosphere-Electrodynamics General Circulation Model (TIME-GCM) to elucidate the key dynamical and chemical factors governing the abundance and diurnal variation of nitric oxide (NO) at near solar minimum conditions and low latitudes. This analysis was enabled by the recent orbital precession of the AIM satellite which caused the solar occultation pattern measured by the Solar Occultation for Ice Experiment (SOFIE) to migrate down to low and mid latitudes for specific periods of time. We use a month of NO data collected in January 2017 to compare with two versions of the TIME-GCM, one driven solely by climatological tides and analysis-derived planetary waves at the lower boundary and free running at all other altitudes, while the other is constrained by a high-altitude analysis from the Navy Global Environmental Model (NAVGEM)up to the mesopause. We also compare SOFIE data with a NO climatology from the Nitric Oxide Empirical Model (NOEM). Both SOFIE and NOEM yield peak NO abundances of around 4×107cm−3; however, the SOFIE profile peaks about 6-8 km lower than NOEM. We show that this difference is likely a local time effect; SOFIE being a dawn measurement and NOEM representing late morning/near noon. The constrained version of TIME-GCM exhibits a low altitude dawn peak while the model that is forced solely at the lower boundary and free running above does not. We attribute this difference due to a phase change in the semi-diurnal tide in the NAVGEM-constrained model causing descent of high NO mixing ratio air near dawn. This phase difference between the two models arises due to differences in the mesospheric zonal mean zonal winds. Regarding the absolute NO abundance, all versions of the TIME-GCM overestimate this. Tuning the model to yield calculated atomic oxygen in agreement with TIMED data helps, but is insufficient. Further, the TIME-GCM underestimates the electron density [e-] as compared with the International Reference Ionosphere empirical model. This suggests a potential conflict with the requirements of NO modeling and [e-] modeling since one solution typically used to increase model [e-] is to increase the solar soft X ray flux which would, in this case, worsen the NO model/data discrepancy

FIRE (facilitating implementation of research evidence) : a study protocol

Research evidence underpins best practice, but is not always used in healthcare. The Promoting Action on Research Implementation in Health Services (PARIHS) framework suggests that the nature of evidence, the context in which it is used, and whether those trying to use evidence are helped (or facilitated) affect the use of evidence. Urinary incontinence has a major effect on quality of life of older people, has a high prevalence, and is a key priority within European health and social care policy. Improving continence care has the potential to improve the quality of life for older people and reduce the costs associated with providing incontinence aids

Coalescent-based genome analyses resolve the early branches of the euarchontoglires

Despite numerous large-scale phylogenomic studies, certain parts of the mammalian tree are extraordinarily difficult to resolve. We used the coding regions from 19 completely sequenced genomes to study the relationships within the super-clade Euarchontoglires (Primates, Rodentia, Lagomorpha, Dermoptera and Scandentia) because the placement of Scandentia within this clade is controversial. The difficulty in resolving this issue is due to the short time spans between the early divergences of Euarchontoglires, which may cause incongruent gene trees. The conflict in the data can be depicted by network analyses and the contentious relationships are best reconstructed by coalescent-based analyses. This method is expected to be superior to analyses of concatenated data in reconstructing a species tree from numerous gene trees. The total concatenated dataset used to study the relationships in this group comprises 5,875 protein-coding genes (9,799,170 nucleotides) from all orders except Dermoptera (flying lemurs). Reconstruction of the species tree from 1,006 gene trees using coalescent models placed Scandentia as sister group to the primates, which is in agreement with maximum likelihood analyses of concatenated nucleotide sequence data. Additionally, both analytical approaches favoured the Tarsier to be sister taxon to Anthropoidea, thus belonging to the Haplorrhine clade. When divergence times are short such as in radiations over periods of a few million years, even genome scale analyses struggle to resolve phylogenetic relationships. On these short branches processes such as incomplete lineage sorting and possibly hybridization occur and make it preferable to base phylogenomic analyses on coalescent methods

Comparison of two independent systematic reviews of trials of recombinant human bone morphogenetic protein-2 (rhBMP-2) : The Yale Open Data Access Medtronic Project

Background: It is uncertain whether the replication of systematic reviews, particularly those with the same objectives and resources, would employ similar methods and/or arrive at identical findings. We compared the results and conclusions of two concurrent systematic reviews undertaken by two independent research teams provided with the same objectives, resources, and individual participant-level data. Methods: Two centers in the USA and UK were each provided with participant-level data on 17 multi-site clinical trials of recombinant human bone morphogenetic protein-2 (rhBMP-2). The teams were blinded to each other's methods and findings until after publication. We conducted a retrospective structured comparison of the results of the two systematic reviews. The main outcome measures included (1) trial inclusion criteria; (2) statistical methods; (3) summary efficacy and risk estimates; and (4) conclusions. Results: The two research teams' meta-analyses inclusion criteria were broadly similar but differed slightly in trial inclusion and research methodology. They obtained similar results in summary estimates of most clinical outcomes and adverse events. Center A incorporated all trials into summary estimates of efficacy and harms, while Center B concentrated on analyses stratified by surgical approach. Center A found a statistically significant, but small, benefit whereas Center B reported no advantage. In the analysis of harms, neither showed an increased cancer risk at 48 months, although Center B reported a significant increase at 24 months. Conclusions reflected these differences in summary estimates of benefit balanced with small but potentially important risk of harm. Conclusions: Two independent groups given the same research objectives, data, resources, funding, and time produced broad general agreement but differed in several areas. These differences, the importance of which is debatable, indicate the value of the availability of data to allow for more than a single approach and a single interpretation of the data. Systematic review registration: PROSPERO CRD42012002040and CRD42012001907

A systematic review of the data, methods and environmental covariates used to map Aedes-borne arbovirus transmission risk

BACKGROUND: Aedes (Stegomyia)-borne diseases are an expanding global threat, but gaps in surveillance make comprehensive and comparable risk assessments challenging. Geostatistical models combine data from multiple locations and use links with environmental and socioeconomic factors to make predictive risk maps. Here we systematically review past approaches to map risk for different Aedes-borne arboviruses from local to global scales, identifying differences and similarities in the data types, covariates, and modelling approaches used. METHODS: We searched on-line databases for predictive risk mapping studies for dengue, Zika, chikungunya, and yellow fever with no geographical or date restrictions. We included studies that needed to parameterise or fit their model to real-world epidemiological data and make predictions to new spatial locations of some measure of population-level risk of viral transmission (e.g. incidence, occurrence, suitability, etc.). RESULTS: We found a growing number of arbovirus risk mapping studies across all endemic regions and arboviral diseases, with a total of 176 papers published 2002-2022 with the largest increases shortly following major epidemics. Three dominant use cases emerged: (i) global maps to identify limits of transmission, estimate burden and assess impacts of future global change, (ii) regional models used to predict the spread of major epidemics between countries and (iii) national and sub-national models that use local datasets to better understand transmission dynamics to improve outbreak detection and response. Temperature and rainfall were the most popular choice of covariates (included in 50% and 40% of studies respectively) but variables such as human mobility are increasingly being included. Surprisingly, few studies (22%, 31/144) robustly tested combinations of covariates from different domains (e.g. climatic, sociodemographic, ecological, etc.) and only 49% of studies assessed predictive performance via out-of-sample validation procedures. CONCLUSIONS: Here we show that approaches to map risk for different arboviruses have diversified in response to changing use cases, epidemiology and data availability. We identify key differences in mapping approaches between different arboviral diseases, discuss future research needs and outline specific recommendations for future arbovirus mapping

How heel oxygenation changes under pressure

The mechanism of heel pressure ulcers after hip surgery is not entirely understood. The purpose of this one-group, prospective, repeated-measures design study was to examine how the external pressure of the bed surface affects heel skin oxygen tension in adults on the first 3 days after hip surgery. Transcutaneous oxygen sensors were placed on the plantar surface of each foot, close to the heels. Measures were taken on room air and with an oxygen challenge with the heels (1) suspended above the bed surface (preload), (2) on the bed surface for 15 minutes (loading), and (3) again suspended above the bed surface for 15 minutes (unloading). Eighteen hip surgery patients (mean age 58.3±16.1 years) from two hospitals participated. When compared with preload on room air, both loading and unloading on all 3 days resulted in a reduction in heel oxygen tension bilaterally (p\u3c0.001). Heel oxygenation decreased without the anticipated hyperemic response, raising the question of whether this is a sign of increased pressure ulcer risk. Further work is needed to understand why this short period of external pressure results in decreased oxygenation and why oxygen tension does not return to baseline when pressure is removed

Measuring hsCRP—An Important Part of a Comprehensive Risk Profile or a Clinically Redundant Practice?

James McCormack and Michael Allan discuss issues and questions surrounding hsCRP measurements in patients

Implementing health research through academic and clinical partnerships : a realistic evaluation of the Collaborations for Leadership in Applied Health Research and Care (CLAHRC)

Background: The English National Health Service has made a major investment in nine partnerships between higher education institutions and local health services called Collaborations for Leadership in Applied Health Research and Care (CLAHRC). They have been funded to increase capacity and capability to produce and implement research through sustained interactions between academics and health services. CLAHRCs provide a natural ‘test bed’ for exploring questions about research implementation within a partnership model of delivery. This protocol describes an externally funded evaluation that focuses on implementation mechanisms and processes within three CLAHRCs. It seeks to uncover what works, for whom, how, and in what circumstances. Design and methods: This study is a longitudinal three-phase, multi-method realistic evaluation, which deliberately aims to explore the boundaries around knowledge use in context. The evaluation funder wishes to see it conducted for the process of learning, not for judging performance. The study is underpinned by a conceptual framework that combines the Promoting Action on Research Implementation in Health Services and Knowledge to Action frameworks to reflect the complexities of implementation. Three participating CLARHCS will provide indepth comparative case studies of research implementation using multiple data collection methods including interviews, observation, documents, and publicly available data to test and refine hypotheses over four rounds of data collection. We will test the wider applicability of emerging findings with a wider community using an interpretative forum. Discussion: The idea that collaboration between academics and services might lead to more applicable health research that is actually used in practice is theoretically and intuitively appealing; however the evidence for it is limited. Our evaluation is designed to capture the processes and impacts of collaborative approaches for implementing research, and therefore should contribute to the evidence base about an increasingly popular (e.g., Mode two, integrated knowledge transfer, interactive research), but poorly understood approach to knowledge translation. Additionally we hope to develop approaches for evaluating implementation processes and impacts particularly with respect to integrated stakeholder involvement