Contribution of intrapulmonary shunt to the pathogenesis of profound hypoxaemia in viral infection: a mechanistic discussion with an illustrative case

Background: The formation of anastomoses between the pulmonary arteries and pulmonary veins, or the pulmonary and the bronchial circulation, is part of normal foetal lung development. They persist in approximately 30% of adults at rest, and open in almost all adults during exertion. Blood flowing through these anastomoses bypasses the alveolar surface and increases in such shunting can thus cause hypoxaemia. This is now known to contribute to the pathogenesis of hypoxaemia in COVID-19 disease. We here provide evidence to support a similar role in influenza A infection. Illustrative case presentation: We describe a case of influenza A infection associated with severe hypoxaemia, poorly responsive to supplemental oxygen and which worsened following the application of continuous positive airway pressure (CPAP), despite the presence of a normal physical examination, chest radiograph and echocardiogram. This combination suggests a significant intrapulmonary (extra-alveolar) shunt as a cause of the severe hypoxaemia. The shunt fraction was estimated to be approximately 57%. Discussion and conclusion: Intrapulmonary vascular shunts can contribute substantially to hypoxaemia in viral infection. Seeking to understand the pathogenesis of observed hypoxaemia can help guide respiratory therapy. Mechanistic research may suggest novel therapeutic targets which could assist in avoiding intubation and mechanical ventilatory support

Projects for regeneration: Making them work

YesThe study analyses approaches to the management of two projects within the regeneration portfolio of a large UK metropolitan council. Developing a theoretical framework drawing both from mainstream project methodologies and international development, the study highlights a number of key issues which need to be addressed, including entrepreneurship, participation, stakeholder buy-in, project lifecycles and benefit management. Key lessons emerging from the study include the need to foster entrepreneurship within the controlled environment of the project and the importance of setting programme targets which are appropriately orientated to harness the interdependent nature of benefits of regeneration projects in the public sector.Non

Is routine urine dip stick testing justified in asymptomatic women in early pregnancy?

Background: Routine urinalysis is commonly performed in early pregnancy units (EPUs) based on historic evidence that bacteriuria is linked to pyelonephritis, pre-term birth, mid trimester loss and low birth weight. Aim was to assess the cost and diagnostic yield of routine urinalysis in asymptomatic women in early pregnancy. A secondary outcome was the birth outcomes for women with proven bacteriuria.Methods: Retrospective review of all urinalysis performed over 12 month period in a tertiary EPU and analysis of pregnancy outcomes in the proven bacteriuria group.Results: 10,490 urinalyses performed at a cost of £40,385.50. 1162 (11%) positive urine dips; 68 (0.6%) nitrite positive. 179 microscopy, culture and sensitivity performed at a cost of £2593.71. Of the 179, 65 were culture positive giving a proven bacteriuria rate of 0.6%. The most common pathogen was E-Coli. There were no recorded episodes of pyelonephritis and no statistical significance in the pre-term birth, mid trimester loss or low birth weight rate in the culture positive versus culture negative group.Conclusions: The cost associated with routine urinalysis is significant and the diagnostic yield is extremely low. We did not identify an association between bacteriuria and adverse pregnancy outcomes. As such, urinalysis should only be performed in symptomatic/ high risk patients presenting to the EPU

FlyMine: an integrated database for Drosophila and Anopheles genomics.

FlyMine is a data warehouse that addresses one of the important challenges of modern biology: how to integrate and make use of the diversity and volume of current biological data. Its main focus is genomic and proteomics data for Drosophila and other insects. It provides web access to integrated data at a number of different levels, from simple browsing to construction of complex queries, which can be executed on either single items or lists

LabKey Server: An open source platform for scientific data integration, analysis and collaboration

<p>Abstract</p> <p>Background</p> <p>Broad-based collaborations are becoming increasingly common among disease researchers. For example, the Global HIV Enterprise has united cross-disciplinary consortia to speed progress towards HIV vaccines through coordinated research across the boundaries of institutions, continents and specialties. New, end-to-end software tools for data and specimen management are necessary to achieve the ambitious goals of such alliances. These tools must enable researchers to organize and integrate heterogeneous data early in the discovery process, standardize processes, gain new insights into pooled data and collaborate securely.</p> <p>Results</p> <p>To meet these needs, we enhanced the LabKey Server platform, formerly known as CPAS. This freely available, open source software is maintained by professional engineers who use commercially proven practices for software development and maintenance. Recent enhancements support: (i) Submitting specimens requests across collaborating organizations (ii) Graphically defining new experimental data types, metadata and wizards for data collection (iii) Transitioning experimental results from a multiplicity of spreadsheets to custom tables in a shared database (iv) Securely organizing, integrating, analyzing, visualizing and sharing diverse data types, from clinical records to specimens to complex assays (v) Interacting dynamically with external data sources (vi) Tracking study participants and cohorts over time (vii) Developing custom interfaces using client libraries (viii) Authoring custom visualizations in a built-in R scripting environment.</p> <p>Diverse research organizations have adopted and adapted LabKey Server, including consortia within the Global HIV Enterprise. Atlas is an installation of LabKey Server that has been tailored to serve these consortia. It is in production use and demonstrates the core capabilities of LabKey Server. Atlas now has over 2,800 active user accounts originating from approximately 36 countries and 350 organizations. It tracks roughly 27,000 assay runs, 860,000 specimen vials and 1,300,000 vial transfers.</p> <p>Conclusions</p> <p>Sharing data, analysis tools and infrastructure can speed the efforts of large research consortia by enhancing efficiency and enabling new insights. The Atlas installation of LabKey Server demonstrates the utility of the LabKey platform for collaborative research. Stable, supported builds of LabKey Server are freely available for download at <url>http://www.labkey.org</url>. Documentation and source code are available under the Apache License 2.0.</p

Effective health care for older people living and dying in care homes: A realist review

Background: Care home residents in England have variable access to health care services. There is currently no coherent policy or consensus about the best arrangements to meet these needs. The purpose of this review was to explore the evidence for how different service delivery models for care home residents support and/or improve wellbeing and health-related outcomes in older people living and dying in care homes. Methods: We conceptualised models of health care provision to care homes as complex interventions. We used a realist review approach to develop a preliminary understanding of what supported good health care provision to care homes. We completed a scoping of the literature and interviewed National Health Service and Local Authority commissioners, providers of services to care homes, representatives from the Regulator, care home managers, residents and their families. We used these data to develop theoretical propositions to be tested in the literature to explain why an intervention may be effective in some situations and not others. We searched electronic databases and related grey literature. Finally the findings were reviewed with an external advisory group. Results: Strategies that support and sustain relational working between care home staff and visiting health care professionals explained the observed differences in how health care interventions were accepted and embedded into care home practice. Actions that encouraged visiting health care professionals and care home staff jointly to identify, plan and implement care home appropriate protocols for care, when supported by ongoing facilitation from visiting clinicians, were important. Contextual factors such as financial incentives or sanctions, agreed protocols, clinical expertise and structured approaches to assessment and care planning could support relational working to occur, but of themselves appeared insufficient to achieve change. Conclusion: How relational working is structured between health and care home staff is key to whether health service interventions achieve health related outcomes for residents and their respective organisations. The belief that either paying clinicians to do more in care homes and/or investing in training of care home staff is sufficient for better outcomes was not supported.This research was funded by National Institute of Health Research Health Service Delivery and Research programme (HSDR 11/021/02)

The Third Fermi Large Area Telescope Catalog of Gamma-ray Pulsars

We present 294 pulsars found in GeV data from the Large Area Telescope (LAT) on the Fermi Gamma-ray Space Telescope. Another 33 millisecond pulsars (MSPs) discovered in deep radio searches of LAT sources will likely reveal pulsations once phase-connected rotation ephemerides are achieved. A further dozen optical and/or X-ray binary systems co-located with LAT sources also likely harbor gamma-ray MSPs. This catalog thus reports roughly 340 gamma-ray pulsars and candidates, 10% of all known pulsars, compared to $\leq 11$ known before Fermi. Half of the gamma-ray pulsars are young. Of these, the half that are undetected in radio have a broader Galactic latitude distribution than the young radio-loud pulsars. The others are MSPs, with 6 undetected in radio. Overall, >235 are bright enough above 50 MeV to fit the pulse profile, the energy spectrum, or both. For the common two-peaked profiles, the gamma-ray peak closest to the magnetic pole crossing generally has a softer spectrum. The spectral energy distributions tend to narrow as the spindown power $\dot E$ decreases to its observed minimum near $10^{33}$ erg s$^{-1}$, approaching the shape for synchrotron radiation from monoenergetic electrons. We calculate gamma-ray luminosities when distances are available. Our all-sky gamma-ray sensitivity map is useful for population syntheses. The electronic catalog version provides gamma-ray pulsar ephemerides, properties and fit results to guide and be compared with modeling results.Comment: 142 pages. Accepted by the Astrophysical Journal Supplemen

Gamma-ray and radio properties of six pulsars detected by the fermi large area telescope

We report the detection of pulsed γ-rays for PSRs J0631+1036, J0659+1414, J0742-2822, J1420-6048, J1509-5850, and J1718-3825 using the Large Area Telescope on board the Fermi Gamma-ray Space Telescope (formerly known as GLAST). Although these six pulsars are diverse in terms of their spin parameters, they share an important feature: their γ-ray light curves are (at least given the current count statistics) single peaked. For two pulsars, there are hints for a double-peaked structure in the light curves. The shapes of the observed light curves of this group of pulsars are discussed in the light of models for which the emission originates from high up in the magnetosphere. The observed phases of the γ-ray light curves are, in general, consistent with those predicted by high-altitude models, although we speculate that the γ-ray emission of PSR J0659+1414, possibly featuring the softest spectrum of all Fermi pulsars coupled with a very low efficiency, arises from relatively low down in the magnetosphere. High-quality radio polarization data are available showing that all but one have a high degree of linear polarization. This allows us to place some constraints on the viewing geometry and aids the comparison of the γ-ray light curves with high-energy beam models