Transcriptomic effects of adenosine 2A receptor deletion in healthy and endotoxemic murine myocardium

Influences of adenosine 2A receptor (A2AR) activity on the cardiac transcriptome and genesis of endotoxemic myocarditis are unclear. We applied transcriptomic profiling (39 K Affymetrix arrays) to identify A2AR-sensitive molecules, revealed by receptor knockout (KO), in healthy and endotoxemic hearts. Baseline cardiac function was unaltered and only 37 A2AR-sensitive genes modified by A2AR KO (≥1.2-fold change, \u3c5 \u3e% FDR); the five most induced are Mtr, Ppbp, Chac1, Ctsk and Cnpy2 and the five most repressed are Hp, Yipf4, Acta1, Cidec and Map3k2. Few canonical paths were impacted, with altered Gnb1, Prkar2b, Pde3b and Map3k2 (among others) implicating modified G protein/cAMP/PKA and cGMP/NOS signalling. Lipopolysaccharide (LPS; 20 mg/kg) challenge for 24 h modified \u3e4100 transcripts in wild-type (WT) myocardium (≥1.5-fold change, FDR \u3c 1 %); the most induced are Lcn2 (+590); Saa3 (+516); Serpina3n (+122); Cxcl9 (+101) and Cxcl1 (+89) and the most repressed are Car3 (−38); Adipoq (−17); Atgrl1/Aplnr (−14); H19 (−11) and Itga8 (−8). Canonical responses centred on inflammation, immunity, cell death and remodelling, with pronounced amplification of toll-like receptor (TLR) and underlying JAK-STAT, NFκB and MAPK pathways, and a ‘cardio-depressant’ profile encompassing suppressed ß-adrenergic, PKA and Ca2+ signalling, electromechanical and mitochondrial function (and major shifts in transcripts impacting function/injury including Lcn2, S100a8/S100a9, Icam1/Vcam and Nox2 induction, and Adipoq, Igf1 and Aplnr repression). Endotoxemic responses were selectively modified by A2AR KO, supporting inflammatory suppression via A2AR sensitive shifts in regulators of NFκB and JAK-STAT signalling (IκBζ, IκBα, STAT1, CDKN1a and RRAS2) without impacting the cardio-depressant gene profile. Data indicate A2ARs exert minor effects in un-stressed myocardium and selectively suppress NFκB and JAK-STAT signalling and cardiac injury without influencing cardiac depression in endotoxemia

Community-associated Methicillin-resistant Staphylococcus aureus and Healthcare Risk Factors

To determine frequency of methicillin-resistant Staphylococcus aureus infections caused by strains typically associated with community-acquired infections (USA300) among persons with healthcare-related risk factors (HRFs), we evaluated surveillance data. Of patients with HRFs, 18%–28% had a "community-associated" strain, primarily USA300; of patients without HRFs, 26% had a "healthcare-associated" strain, typically USA100

Early versus Later Rhythm Analysis in Patients with Out-of-Hospital Cardiac Arrest

Background In a departure from the previous strategy of immediate defibrillation, the 2005 resuscitation guidelines from the American Heart Association–International Liaison Committee on Resuscitation suggested that emergency medical service (EMS) personnel could provide 2 minutes of cardiopulmonary resuscitation (CPR) before the first analysis of cardiac rhythm. We compared the strategy of a brief period of CPR with early analysis of rhythm with the strategy of a longer period of CPR with delayed analysis of rhythm. Methods We conducted a cluster-randomized trial involving adults with out-of-hospital cardiac arrest at 10 Resuscitation Outcomes Consortium sites in the United States and Canada. Patients in the early-analysis group were assigned to receive 30 to 60 seconds of EMS-administered CPR and those in the later-analysis group were assigned to receive 180 seconds of CPR, before the initial electrocardiographic analysis. The primary outcome was survival to hospital discharge with satisfactory functional status (a modified Rankin scale score of ≤3, on a scale of 0 to 6, with higher scores indicating greater disability). Results We included 9933 patients, of whom 5290 were assigned to early analysis of cardiac rhythm and 4643 to later analysis. A total of 273 patients (5.9%) in the later-analysis group and 310 patients (5.9%) in the early-analysis group met the criteria for the primary outcome, with a cluster-adjusted difference of −0.2 percentage points (95% confidence interval, −1.1 to 0.7; P=0.59). Analyses of the data with adjustment for confounding factors, as well as subgroup analyses, also showed no survival benefit for either study group. Conclusions Among patients who had an out-of-hospital cardiac arrest, we found no difference in the outcomes with a brief period, as compared with a longer period, of EMS-administered CPR before the first analysis of cardiac rhythm. (Funded by the National Heart, Lung, and Blood Institute and others; ROC PRIMED ClinicalTrials.gov number, NCT00394706.

Binary and Millisecond Pulsars at the New Millennium

We review the properties and applications of binary and millisecond pulsars. Our knowledge of these exciting objects has greatly increased in recent years, mainly due to successful surveys which have brought the known pulsar population to over 1300. There are now 56 binary and millisecond pulsars in the Galactic disk and a further 47 in globular clusters. This review is concerned primarily with the results and spin-offs from these surveys which are of particular interest to the relativity community.Comment: 59 pages, 26 figures, 5 tables. Accepted for publication in Living Reviews in Relativity (http://www.livingreviews.org

The utility of B-type natriuretic peptide in the diagnosis of heart failure in the emergency department: a systematic review

<p>Abstract</p> <p>Background</p> <p>Dyspnea is a common chief complaint in the emergency department (ED); differentiating heart failure (HF) from other causes can be challenging. Brain Natriuretic Peptide (BNP) is a new diagnostic test for HF for use in dyspneic patients in the ED. The purpose of this study is to systematically review the accuracy of BNP in the emergency diagnosis of HF.</p> <p>Methods</p> <p>We searched MEDLINE (1975–2005) supplemented by reference tracking. We included studies that reported the sensitivity and specificity of BNP for diagnosing HF in ED patients with acute dyspnea. Two reviewers independently assessed study quality. We pooled sensitivities and specificities within five ranges of BNP cutoffs.</p> <p>Results</p> <p>Ten studies including 3,344 participants met inclusion criteria. Quality was variable; possible verification or selection bias was common. No studies eliminated patients with obvious medical causes of dyspnea. Most studies used the Triage BNP assay; all utilized a clinical reference standard. Pooled sensitivity and specificity at a BNP cutoff of 100–105 pg/ml were 90% and 74% with negative likelihood ratio (LR) of 0.14; pooled sensitivity was 81% with specificity of 90% at cutoffs between 300 and 400 pg/ml with positive LR of 7.6.</p> <p>Conclusion</p> <p>Our analysis suggests that BNP has moderate accuracy in detecting HF in the ED. Our results suggest utilizing a BNP of less than 100 pg/ml to rule out HF and a BNP of greater than 400 pg/ml to diagnose HF. Many studies were of marginal quality, and all included patients with varying degrees of diagnostic uncertainty. Further studies focusing on patients with diagnostic uncertainty will clarify the real-world utility of BNP in the emergency management of dyspnea.</p

Views and Experiences of Sex, Sexuality and Relationships Following Spinal Cord Injury: A Systematic Review and Narrative Synthesis of the Qualitative Literature

Research examining the effects of spinal cord injury on sexuality has largely focused on physiological functioning and quantification of dysfunction following injury. This paper reports a systematic review of qualitative research that focused on the views and experiences of people with spinal cord injury on sex and relationships. The review addressed the following research question: What are the views and experiences of people with spinal cord injury of sex, sexuality and relationships following injury? Five databases were relevant and employed in the review: CINAHL (1989-2016 only), PsychInfo, PubMed, Scopus and Web of Science, for research published between 1 January 1980 and 30 November 2019. After removing duplicates, 257 records remained and were screened using a two-stage approach to inclusion and quality appraisal. Following screening, 27 met the criteria for inclusion and are reported in the paper. The review includes studies from fifteen countries across five continents. Two main approaches to data analysis summary and thematic synthesis were undertaken to analyze the qualitative data reported in the papers. The analysis revealed four main themes: sexual identity; significant and generalized others, sexual embodiment; and; sexual rehabilitation and education

TRY plant trait database - enhanced coverage and open access

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Agent Orange and long-term outcomes after radical prostatectomy

PurposeTo investigate the association between Agent Orange (AO) exposure and long-term prostate cancer (PC) outcomes.Material and methodsData from 1,882 men undergoing radical prostatectomy for PC between 1988 and 2011 at Veterans Affairs Health Care Facilities were analyzed from the Shared Equal Access Regional Cancer Hospital database. Men were stratified by AO exposure (binary). Associations between AO exposure and biopsy and pathologic Gleason sum (GS) and pathologic stage were determined by logistic regression models adjusted for preoperative characteristics. Hazard ratios for biochemical recurrence (BCR), secondary treatment, metastases, and PC-specific mortality were determined by Cox models adjusted for preoperative characteristics.ResultsThere were 333 (17.7%) men with AO exposure. AO-exposed men were younger (median 59 vs. 62 y), had lower preoperative prostate-specific antigen levels (5.8 vs. 6.7 ng/ml), lower clinical category (25% vs. 38% palpable), and higher body mass index (28.2 vs. 27.6 kg/m(2)), all P&lt;0.01. Biopsy GS, pathologic GS, positive surgical margins, lymph node positivity, and extracapsular extension did not differ with AO exposure. At a median follow-up of 85 months, 702 (37.4%) patients had BCR, 603 (32.2%) patients received secondary treatment, 78 (4.1%) had metastases, and 39 (2.1%) died of PC. On multivariable analysis, AO exposure was not associated with BCR, secondary treatment, metastases, or PC mortality.ConclusionsAO exposure was not associated with worse preoperative characteristics such as elevated prostate-specific antigen levels or biopsy GS nor with BCR, secondary treatment, metastases, or PC death. Thus, as data on AO-exposed men mature, possible differences in PC outcomes observed previously are no longer apparent

The breakthrough listen search for intelligent life: a wideband data recorder system for the Robert C. Byrd green bank telescope

The Breakthrough Listen Initiative is undertaking a comprehensive search for radio and optical signatures from extraterrestrial civilizations. An integral component of the project is the design and implementation of wide-bandwidth data recorder and signal processing systems. The capabilities of these systems, particularly at radio frequencies, directly determine survey speed; further, given a fixed observing time and spectral coverage, they determine sensitivity as well. Here, we detail the Breakthrough Listen wide-bandwidth data recording system deployed at the 100-m aperture Robert C. Byrd Green Bank Telescope. The system digitizes up to 6 GHz of bandwidth at 8 bits for both polarizations, storing the resultant 24 GB/s of data to disk. This system is among the highest data rate baseband recording systems in use in radio astronomy. A future system expansion will double recording capacity, to achieve a total Nyquist bandwidth of 12 GHz in two polarizations. In this paper, we present details of the system architecture, along with salient configuration and disk-write optimizations used to achieve high-throughput data capture on commodity compute servers and consumer-class hard disk drives

"We're not short of people telling us what the problems are. We're short of people telling us what to do": An appraisal of public policy and mental health

Background: There is sustained interest in public health circles in assessing the effects of policies on health and health inequalities. We report on the theory, methods and findings of a project which involved an appraisal of current Scottish policy with respect to its potential impacts on mental health and wellbeing. Methods: We developed a method of assessing the degree of alignment between Government policies and the 'evidence base', involving: reviewing theoretical frameworks; analysis of policy documents, and nineteen in-depth interviews with policymakers which explored influences on, and barriers to cross-cutting policymaking and the use of research evidence in decisionmaking. Results: Most policy documents did not refer to mental health; however most referred indirectly to the determinants of mental health and well-being. Unsurprisingly research evidence was rarely cited; this was more common in health policy documents. The interviews highlighted the barriers to intersectoral policy making, and pointed to the relative value of qualitative and quantitative research, as well as to the imbalance of evidence between "what is known" and "what is to be done". Conclusion: Healthy public policy depends on effective intersectoral working between government departments, along with better use of research evidence to identify policy impacts. This study identified barriers to both these. We also demonstrated an approach to rapidly appraising the mental health effects of mainly non-health sector policies, drawing on theoretical understandings of mental health and its determinants, research evidence and policy documents. In the case of the social determinants of health, we conclude that an evidence-based approach to policymaking and to policy appraisal requires drawing strongly upon existing theoretical frameworks, as well as upon research evidence, but that there are significant practical barriers and disincentives