High-Energy X-ray Imaging of the Pulsar Wind Nebula MSH~15-52: Constraints on Particle Acceleration and Transport

We present the first images of the pulsar wind nebula (PWN) MSH 15-52 in the hard X-ray band (>8 keV), as measured with the Nuclear Spectroscopic Telescope Array (NuSTAR). Overall, the morphology of the PWN as measured by NuSTAR in the 3-7 keV band is similar to that seen in Chandra high-resolution imaging. However, the spatial extent decreases with energy, which we attribute to synchrotron energy losses as the particles move away from the shock. The hard-band maps show a relative deficit of counts in the northern region towards the RCW 89 thermal remnant, with significant asymmetry. We find that the integrated PWN spectra measured with NuSTAR and Chandra suggest that there is a spectral break at 6 keV which may be explained by a break in the synchrotron-emitting electron distribution at ~200 TeV and/or imperfect cross calibration. We also measure spatially resolved spectra, showing that the spectrum of the PWN softens away from the central pulsar B1509-58, and that there exists a roughly sinusoidal variation of spectral hardness in the azimuthal direction. We discuss the results using particle flow models. We find non-monotonic structure in the variation with distance of spectral hardness within 50" of the pulsar moving in the jet direction, which may imply particle and magnetic-field compression by magnetic hoop stress as previously suggested for this source. We also present 2-D maps of spectral parameters and find an interesting shell-like structure in the NH map. We discuss possible origins of the shell-like structure and their implications.Comment: 15 pages, 9 figures, accepted for publication in Ap

Behaviour and Climate Change: Consumer Perceptions of Responsibility

This paper explores the under-researched notion of consumer responsibility, a potentially significant influence on consumer behaviour that marketers and policymakers may be able to harness as they attempt to respond to environmental challenges such as climate change. The paper uses data derived from a commercially motivated survey (n = 1513) to explore domestic consumption behaviours most closely associated with the issue of disruptive climate change. A measure of 'General Environmental Responsiveness' (GER) is used to test: (1) the effects of consumers both taking responsibility for their actions and placing responsibility on others for the consequences of their consumption behaviour; and (2) whether sociodemographic variables can aid the targeting of consumers by the level and type of responsibility and pro-environmental behavioural intentions expressed. The study's findings demonstrate clear, if not strong, relationships between consumer conceptions of responsibilities for causing and tackling climate change and environment-related consumer behaviour. The study's implications both challenge accepted wisdom about environment-related consumer behaviour and suggest avenues for future research

A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.

We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis

The Hubble Higher-Z Supernova Search: Supernovae to z=1.6 and Constraints on Type Ia Progenitor Models

We present results from the Hubble Higher-z Supernova Search, the first space-based open field survey for supernovae (SNe). In cooperation with the Great Observatories Origins Deep Survey, we have used the Hubble Space Telescope with the Advanced Camera for Surveys to cover 300 square arcmin in the area of the Chandra Deep Field South and the Hubble Deep Field North on five separate search epochs (separated by 45 day intervals) to a limiting magnitude of z'=26. These deep observations have allowed us to discover 42 SNe in the redshift range 0.2 < z < 1.6. As these data span a large range in redshift, they are ideal for testing the validity of Type Ia supernova progenitor models with the distribution of expected ``delay times,'' from progenitor star formation to SN Ia explosion, and the SN rates these models predict. Through a Bayesian maximum likelihood test, we determine which delay-time models best reproduce the redshift distribution of SNe Ia discovered in this survey. We find that models that require a large fraction of ``prompt'' (less than 2 Gyr) SNe Ia poorly reproduce the observed redshift distribution and are rejected at 95% confidence. We find that Gaussian models best fit the observed data for mean delay times in the range of 3 to 4 Gyr.Comment: 32 pages, 15 figures, accepted for publication in the Astrophysical Journa

The heart in sporadic inclusion body myositis: a study in 51 patients

The purpose of this study was to explore the prevalence and nature of cardiac abnormalities in sporadic inclusion body myositis (sIBM). Fifty-one sIBM patients were cross-sectionally studied using history-taking, physical examination, measurements of serum creatine kinase activity, the MB fraction (CK-MB), cardiac troponin T (cTnT) and I (cTnI), a 12-lead electrocardiogram (ECG) and 2-dimensional echocardiography. Present cardiac history was abnormal in 12 (24%) out of 51 patients, 12 (24%) patients had abnormalities on ECG, mostly aspecific, and in 12 (24%) patients the echocardiograph showed abnormalities. Elevated CK-MB was present in 42 (82%) patients and 40 (78%) had an elevated cTnT in the absence of acute cardiac pathology. In contrast, in one patient (2%) cTnI was elevated. There was no apparent association between elevated biomarkers, ECG or echocardiographic abnormalities. The prevalence of cardiac abnormalities in sIBM does not seem to be higher than would be expected in these elderly patients. Elevated CK-MB and cTnT levels are common, in contrast to cTnI, but do not reflect cardiac pathology

Identifying metabolite markers for preterm birth in cervicovaginal fluid by magnetic resonance spectroscopy

Introduction Preterm birth (PTB) may be preceded by changes in the vaginal microflora and metabolite profiles. Objectives We sought to characterise the metabolite profile of cervicovaginal fluid (CVF) of pregnant women by 1H NMR spectroscopy, and assess their predictive value for PTB. Methods A pair of high-vaginal swabs was obtained from pregnant women with no evidence of clinical infection and grouped as follows: asymptomatic low risk (ALR) women with no previous history of PTB, assessed at 20–22 gestational weeks, g.w., n = 83; asymptomatic high risk (AHR) women with a previous history of PTB, assessed at both 20–22 g.w., n = 71, and 26–28 g.w., n = 58; and women presenting with symptoms of preterm labor (PTL) (SYM), assessed at 24–36 g.w., n = 65. Vaginal secretions were dissolved in phosphate buffered saline and scanned with a 9.4 T NMR spectrometer. Results Six metabolites (lactate, alanine, acetate, glutamine/glutamate, succinate and glucose) were analysed. In all study cohorts vaginal pH correlated with lactate integral (r = -0.62, p\0.0001). Lactate integrals were higher in the term ALR compared to the AHR (20–22 g.w.) women (p = 0.003). Acetate integrals were higher in the preterm versus term women for the AHR (20–22 g.w.) (p = 0.048) and SYM (p = 0.003) groups; and was predictive of PTB\37 g.w. (AUC 0.78; 95 % CI 0.61–0.95), and delivery within 2 weeks of the index assessment (AUC 0.84; 95 % CI 0.64–1) in the SYM women, whilst other metabolites were not. Conclusion High CVF acetate integral of women with symptoms of PTL appears predictive of preterm delivery, as well as delivery within 2 weeks of presentation

Ultraviolet Irradiation Induces the Accumulation of Chondroitin Sulfate, but Not Other Glycosaminoglycans, in Human Skin

Ultraviolet (UV) light alters cutaneous structure and function. Prior work has shown loss of dermal hyaluronan after UV-irradiation of human skin, yet UV exposure increases total glycosaminoglycan (GAG) content in mouse models. To more fully describe UV-induced alterations to cutaneous GAG content, we subjected human volunteers to intermediate-term (5 doses/week for 4 weeks) or single-dose UV exposure. Total dermal uronyl-containing GAGs increased substantially with each of these regimens. We found that UV exposure substantially increased dermal content of chondroitin sulfate (CS), but not hyaluronan, heparan sulfate, or dermatan sulfate. UV induced the accumulation of both the 4-sulfated (C4S) and 6-sulfated (C6S) isoforms of CS, but in distinct distributions. Next, we examined several CS proteoglycan core proteins and found a significant accumulation of dermal and endothelial serglycin, but not of decorin or versican, after UV exposure. To examine regulation in vitro, we found that UVB in combination with IL-1α, a cytokine upregulated by UV radiation, induced serglycin mRNA in cultured dermal fibroblasts, but did not induce the chondroitin sulfate synthases. Overall, our data indicate that intermediate-term and single-dose UVB exposure induces specific GAGs and proteoglycan core proteins in human skin in vivo. These molecules have important biologic functions and contribute to the cutaneous response to UV

Neonatal Fc Receptor: From Immunity to Therapeutics

The neonatal Fc receptor (FcRn), also known as the Brambell receptor and encoded by Fcgrt, is a MHC class I like molecule that functions to protect IgG and albumin from catabolism, mediates transport of IgG across epithelial cells, and is involved in antigen presentation by professional antigen presenting cells. Its function is evident in early life in the transport of IgG from mother to fetus and neonate for passive immunity and later in the development of adaptive immunity and other functions throughout life. The unique ability of this receptor to prolong the half-life of IgG and albumin has guided engineering of novel therapeutics. Here, we aim to summarize the basic understanding of FcRn biology, its functions in various organs, and the therapeutic design of antibody- and albumin-based therapeutics in light of their interactions with FcRn