The Anti-Apoptotic Effect of Respiratory Syncytial Virus on Human Peripheral Blood Neutrophils is Mediated by a Monocyte Derived Soluble Factor

Respiratory Syncytial Virus (RSV) causes annual epidemics of respiratory disease particularly affecting infants. The associated airway inflammation is characterized by an intense neutrophilia. This neutrophilic inflammation appears to be responsible for much of the pathology and symptoms. Previous work from our group had shown that there are factors within the airways of infants with RSV bronchiolitis that inhibit neutrophil apoptosis. This study was undertaken to determine if RSV can directly affect neutrophil survival

Rotational Cooling of Polar Molecules by Stark-tuned Cavity Resonance

A general scheme for rotational cooling of diatomic heteronuclear molecules is proposed. It uses a superconducting microwave cavity to enhance the spontaneous decay via Purcell effect. Rotational cooling can be induced by sequentially tuning each rotational transition to cavity resonance, starting from the highest transition level to the lowest using an electric field. Electrostatic multipoles can be used to provide large confinement volume with essentially homogeneous background electric field.Comment: 10 pages, 6 figure

Statistical Determination of Bulk Flow Motions

We present here a new parameterization for the bulk motions of galaxies and clusters (in the linear regime) that can be measured statistically from the shape and amplitude of the two-dimensional two-point correlation function. We further propose the one-dimensional velocity dispersion (v_p) of the bulk flow as a complementary measure of redshift-space distortions, which is model-independent and not dependent on the normalisation method. As a demonstration, we have applied our new methodology to the C4 cluster catalogue constructed from Data Release Three (DR3) of the Sloan Digital Sky Survey. We find v_p=270^{+433}km/s (also consistent with v_p=0) for this cluster sample (at z=0.1), which is in agreement with that predicted for a WMAP5-normalised LCDM model (i.e., v_p(LCDM=203km/s). This measurement does not lend support to recent claims of excessive bulk motions (\simeq1000 km/s) which appear in conflict with LCDM, although our large statistical error cannot rule them out. From the measured coherent evolution of v_p, we develop a technique to re-construct the perturbed potential, as well as estimating the unbiased matter density fluctuations and scale--independent bias.Comment: 8 pages, 5 figure

Geometric Second Order Field Equations for General Tensor Gauge Fields

Higher spin tensor gauge fields have natural gauge-invariant field equations written in terms of generalised curvatures, but these are typically of higher than second order in derivatives. We construct geometric second order field equations and actions for general higher spin boson fields, and first order ones for fermions, which are non-local but which become local on gauge-fixing, or on introducing auxiliary fields. This generalises the results of Francia and Sagnotti to all representations of the Lorentz group.Comment: 34 pages, LaTeX. Reference adde

A randomised comparison evaluating changes in bone mineral density in advanced prostate cancer: luteinising hormone-releasing hormone agonists versus transdermal oestradiol

Background Luteinising hormone-releasing hormone agonists (LHRHa), used as androgen deprivation therapy (ADT) in prostate cancer (PCa) management, reduce serum oestradiol as well as testosterone, causing bone mineral density (BMD) loss. Transdermal oestradiol is a potential alternative to LHRHa. Objective To compare BMD change in men receiving either LHRHa or oestradiol patches (OP). Design, setting, and participants Men with locally advanced or metastatic PCa participating in the randomised UK Prostate Adenocarcinoma TransCutaneous Hormones (PATCH) trial (allocation ratio of 1:2 for LHRHa:OP, 2006–2011; 1:1, thereafter) were recruited into a BMD study (2006–2012). Dual-energy x-ray absorptiometry scans were performed at baseline, 1 yr, and 2 yr. Interventions LHRHa as per local practice, OP (FemSeven 100 μg/24 h patches). Outcome measurements and statistical analysis The primary outcome was 1-yr change in lumbar spine (LS) BMD from baseline compared between randomised arms using analysis of covariance. Results and limitations A total of 74 eligible men (LHRHa 28, OP 46) participated from seven centres. Baseline clinical characteristics and 3-mo castration rates (testosterone ≤1.7 nmol/l, LHRHa 96% [26 of 27], OP 96% [43 of 45]) were similar between arms. Mean 1-yr change in LS BMD was −0.021 g/cm3 for patients randomised to the LHRHa arm (mean percentage change −1.4%) and +0.069 g/cm3 for the OP arm (+6.0%; p < 0.001). Similar patterns were seen in hip and total body measurements. The largest difference between arms was at 2 yr for those remaining on allocated treatment only: LS BMD mean percentage change LHRHa −3.0% and OP +7.9% (p < 0.001). Conclusions Transdermal oestradiol as a single agent produces castration levels of testosterone while mitigating BMD loss. These early data provide further supporting evidence for the ongoing phase 3 trial

Hypoxia shapes the immune landscape in lung injury and promotes the persistence of inflammation

Hypoxemia is a defining feature of acute respiratory distress syndrome (ARDS), an often-fatal complication of pulmonary or systemic inflammation, yet the resulting tissue hypoxia, and its impact on immune responses, is often neglected. In the present study, we have shown that ARDS patients were hypoxemic and monocytopenic within the first 48 h of ventilation. Monocytopenia was also observed in mouse models of hypoxic acute lung injury, in which hypoxemia drove the suppression of type I interferon signaling in the bone marrow. This impaired monopoiesis resulted in reduced accumulation of monocyte-derived macrophages and enhanced neutrophil-mediated inflammation in the lung. Administration of colony-stimulating factor 1 in mice with hypoxic lung injury rescued the monocytopenia, altered the phenotype of circulating monocytes, increased monocyte-derived macrophages in the lung and limited injury. Thus, tissue hypoxia altered the dynamics of the immune response to the detriment of the host and interventions to address the aberrant response offer new therapeutic strategies for ARDS

Discovery of Genetic Variation on Chromosome 5q22 Associated with Mortality in Heart Failure

Failure of the human heart to maintain sufficient output of blood for the demands of the body, heart failure, is a common condition with high mortality even with modern therapeutic alternatives. To identify molecular determinant