Correlated emission and spin-down variability in radio pulsars

The recent revelation that there are correlated period derivative and pulse shape changes in pulsars has dramatically changed our understanding of timing noise as well as the relationship between the radio emission and the properties of the magnetosphere as a whole. Using Gaussian processes we are able to model timing and emission variability using a regression technique that imposes no functional form on the data. We revisit the pulsars first studied by Lyne et al. (2010). We not only confirm the emission and rotational transitions revealed therein, but reveal further transitions and periodicities in 8 years of extended monitoring. We also show that in many of these objects the pulse profile transitions between two well-defined shapes, coincident with changes to the period derivative. With a view to the SKA and other telescopes capable of higher cadence we also study the detection limitations of period derivative changes.Comment: 4 pages, 2 Figures, Proceedings of IAU Symposium 337 "Pulsar Astrophysics - The Next 50 Years" held at Jodrell Bank Observatory, UK Sept. 4-8 201

Approximate Bayesian Computation Reveals the Crucial Role of Oceanic Islands for the Assembly of Continental Biodiversity

The perceived low levels of genetic diversity, poor interspecific competitive and defensive ability, and loss of dispersal capacities of insular lineages have driven the view that oceanic islands are evolutionary dead ends. Focusing on the Atlantic bryophyte flora distributed across the archipelagos of the Azores, Madeira, the Canary Islands, Western Europe, and northwestern Africa, we used an integrative approach with species distribution modeling and population genetic analyses based on approximate Bayesian computation to determine whether this view applies to organisms with inherent high dispersal capacities. Genetic diversity was found to be higher in island than in continental populations, contributing to mounting evidence that, contrary to theoretical expectations, island populations are not necessarily genetically depauperate. Patterns of genetic variation among island and continental populations consistently fitted those simulated under a scenario of de novo foundation of continental populations from insular ancestors better than those expected if islands would represent a sink or a refugium of continental biodiversity. We, suggest that the northeastern Atlantic archipelagos have played a key role as a stepping stone for transoceanic migrants. Our results challenge the traditional notion that oceanic islands are the end of the colonization road and illustrate the significant role of oceanic islands as reservoirs of novel biodiversity for the assembly of continental flora

Diesel exhaust particulate induces pulmonary and systemic inflammation in rats without impairing endothelial function ex vivo or in vivo

<p>Abstract</p> <p>Background</p> <p>Inhalation of diesel exhaust impairs vascular function in man, by a mechanism that has yet to be fully established. We hypothesised that pulmonary exposure to diesel exhaust particles (DEP) would cause endothelial dysfunction in rats as a consequence of pulmonary and systemic inflammation.</p> <p>Methods</p> <p>Wistar rats were exposed to DEP (0.5 mg) or saline vehicle by intratracheal instillation and hind-limb blood flow, blood pressure and heart rate were monitored <it>in situ </it>6 or 24 h after exposure. Vascular function was tested by administration of the endothelium-dependent vasodilator acetylcholine (ACh) and the endothelium-independent vasodilator sodium nitroprusside (SNP) <it>in vivo </it>and <it>ex vivo </it>in isolated rings of thoracic aorta, femoral and mesenteric artery from DEP exposed rats. Bronchoalveolar lavage fluid (BALF) and blood plasma were collected to assess pulmonary (cell differentials, protein levels & interleukin-6 (IL-6)) and systemic (IL-6), tumour necrosis factor alpha (TNFα) and C-reactive protein (CRP)) inflammation, respectively.</p> <p>Results</p> <p>DEP instillation increased cell counts, total protein and IL-6 in BALF 6 h after exposure, while levels of IL-6 and TNFα were only raised in blood 24 h after DEP exposure. DEP had no effect on the increased hind-limb blood flow induced by ACh <it>in vivo </it>at 6 or 24 h. However, responses to SNP were impaired at both time points. In contrast, <it>ex vivo </it>responses to ACh and SNP were unaltered in arteries isolated from rats exposed to DEP.</p> <p>Conclusions</p> <p>Exposure of rats to DEP induces both pulmonary and systemic inflammation, but does not modify endothelium-dependent vasodilatation. Other mechanisms <it>in vivo </it>limit dilator responses to SNP and these require further investigation.</p

A Novel Fluorescent Clinical Method to Rapidly Quantify Plasma Volume

Objectives To determine the performance of a rapid fluorescent indicator technique for measuring plasma volume (PV). Methods This was an open-label, observational evaluation of a two-component intravenous visible fluorescent dye technique to rapidly measure PV in 16 healthy subjects and 16 subjects with chronic kidney disease (8 stage 3 and 8 stage 4 CKD), at 2 clinical research sites. The method consisted of a single intravenous injection of 12 mg of a large 150-kDa carboxy-methyl dextran conjugated to a fluorescent rhodamine-derived dye as the PV marker (PVM), and 35 mg of a small 5-kDa carboxy-methyl dextran conjugated to fluorescein, the renal clearance marker. Dye concentrations were quantified 15 min after the injections for initial PV measurements using the indicator-dilution principle. Additional samples were taken over 8 h to evaluate the stability of the PVM as a determinant of PV. Blood volumes (BV) were calculated based on PV and the subject’s hematocrit. Pharmacokinetic parameters were calculated from the plasma concentration data taken over several days using noncompartmental methods (Phoenix WinNonlin®). Linear correlation and Bland-Altman plots were used to compare visible fluorescent injectate-measured PV compared to Nadler’s formula for estimating PV. Finally, 8 healthy subjects received 350 mL infusion of a 5% albumin solution in normal saline over 30 min and a repeat PV determination was then carried out. Results PV and BV varied according to weight and body surface area, with PV ranging from 2,115 to 6,234 mL and 28.6 to 41.9 mL/kg when weight adjusted. Both parameters were stable for > 6 h with repeated plasma measurements of the PVM. There was no difference between healthy subjects and CKD subjects. Overall, there was general agreement with Nadler’s estimation formula for the mean PV in subjects. A 24-h repeat dose measurement in 8 healthy subjects showed PV variability of 98 ± 121 mL (mean = 3.8%). Additionally, following an intravenous bolus of 350 mL of a 5% albumin solution in normal saline in 8 healthy subjects, the mean (SD) measured increase in PV was 356 (±50.0) mL post-infusion. There were no serious adverse events reported during the study. Conclusions This minimally invasive fluorescent dye approach safely allowed for rapid, accurate, and reproducible determination of PV, BV, and dynamic monitoring of changes following fluid administration

Innate and adaptive humoral responses coat distinct commensal bacteria with immunoglobulin A

Immunoglobulin A (IgA) is prominently secreted at mucosal surfaces and coats a fraction of the intestinal microbiota. However, the commensal bacteria bound by IgA are poorly characterized and the type of humoral immunity they elicit remains elusive. We used bacterial flow cytometry coupled with 16S rRNA gene sequencing (IgA-Seq) in murine models of immunodeficiency to identify IgA-bound bacteria and elucidate mechanisms of commensal IgA targeting. We found that residence in the small intestine, rather than bacterial identity, dictated induction of specific IgA. Most commensals elicited strong T-independent (TI) responses that originated from the orphan B1b lineage and from B2 cells, but excluded natural antibacterial B1a specificities. Atypical commensals including segmented filamentous bacteria and Mucispirillum evaded TI responses but elicited T-dependent IgA. These data demonstrate exquisite targeting of distinct commensal bacteria by multiple layers of humoral immunity and reveal a specialized function of the B1b lineage in TI mucosal IgA responses

Evaluating the feasibility of a web-based weight loss programme for naval service personnel with excess body weight.

Overweight and obesity are a major concern that may influence the operational capacity of the UK Naval Service (NS). This study was conducted to evaluate the feasibility of trialling and implementing a modified web-based weight loss programme for overweight and obese NS personnel.Royal Navy; University of Southampto

Evaluating the feasibility of a web-based weight loss programme for naval service personnel with excess body weight.

Overweight and obesity are a major concern that may influence the operational capacity of the UK Naval Service (NS). This study was conducted to evaluate the feasibility of trialling and implementing a modified web-based weight loss programme for overweight and obese NS personnel.Royal Navy; University of Southampto

Phase II Study of a Non-Platinum–Containing Doublet of Paclitaxel and Pemetrexed with Bevacizumab as Initial Therapy for Patients with Advanced Lung Adenocarcinomas

Many patients with lung cancers cannot receive platinum-containing regimens due to co-morbid medical conditions. We designed the PPB regimen of paclitaxel, pemetrexed, and bevacizumab to maintain or improve outcomes while averting the unique toxicities of platinum-based chemotherapies

Barriers and facilitators to the uptake of tuberculosis diagnostic and treatment services by hard-to-reach populations in countries of low and medium tuberculosis incidence: a systematic review of qualitative literature

Summary Tuberculosis disproportionately affects hard-to-reach populations, such as homeless people, migrants, refugees, prisoners, or drug users. These people often face challenges in accessing quality health care. We did a systematic review of the qualitative literature to identify barriers and facilitators to the uptake of tuberculosis diagnostic and treatment services by people from hard-to-reach populations in all European Union (EU), European Economic Area, EU candidate, and Organisation for Economic Co-operation and Development countries. The 12 studies included in this review mainly focused on migrants. Views on perceived susceptibility to and severity of tuberculosis varied widely and included many misconceptions. Stigma and challenges regarding access to health care were identified as barriers to tuberculosis diagnosis and treatment uptake, whereas support from nurses, family, and friends was a facilitator for treatment adherence. Further studies are required to identify barriers and facilitators to the improved identification and management of tuberculosis in hard-to-reach populations to inform recommendations for more effective tuberculosis control programmes