X-Ray Spectroscopy of Stars

(abridged) Non-degenerate stars of essentially all spectral classes are soft X-ray sources. Low-mass stars on the cooler part of the main sequence and their pre-main sequence predecessors define the dominant stellar population in the galaxy by number. Their X-ray spectra are reminiscent, in the broadest sense, of X-ray spectra from the solar corona. X-ray emission from cool stars is indeed ascribed to magnetically trapped hot gas analogous to the solar coronal plasma. Coronal structure, its thermal stratification and geometric extent can be interpreted based on various spectral diagnostics. New features have been identified in pre-main sequence stars; some of these may be related to accretion shocks on the stellar surface, fluorescence on circumstellar disks due to X-ray irradiation, or shock heating in stellar outflows. Massive, hot stars clearly dominate the interaction with the galactic interstellar medium: they are the main sources of ionizing radiation, mechanical energy and chemical enrichment in galaxies. High-energy emission permits to probe some of the most important processes at work in these stars, and put constraints on their most peculiar feature: the stellar wind. Here, we review recent advances in our understanding of cool and hot stars through the study of X-ray spectra, in particular high-resolution spectra now available from XMM-Newton and Chandra. We address issues related to coronal structure, flares, the composition of coronal plasma, X-ray production in accretion streams and outflows, X-rays from single OB-type stars, massive binaries, magnetic hot objects and evolved WR stars.Comment: accepted for Astron. Astrophys. Rev., 98 journal pages, 30 figures (partly multiple); some corrections made after proof stag

Psychometric properties of a generic, patient-centred palliative care outcome measure of symptom burden for people with progressive long term neurological conditions

Background There is no standard palliative care outcome measure for people with progressive long term neurological conditions (LTNC). This study aims to determine the psychometric properties of a new 8-item palliative care outcome scale of symptom burden (IPOS Neuro-S8) in this population. Data and Methods Data were merged from a Phase II palliative care intervention study in multiple sclerosis (MS) and a longitudinal observational study in idiopathic Parkinson's disease (IPD), multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). The IPOS Neuro-S8 was assessed for its data quality, score distribution, ceiling and floor effects, reliability, factor structure, convergent and discriminant validity, concurrent validity with generic (Palliative care Outcome Scale) and condition specific measures (Multiple Sclerosis Impact Scale; Non-motor Symptoms Questionnaire; Parkinson's Disease Questionnaire), responsiveness and minimally clinically important difference. Results Of the 134 participants, MS patients had a mean Extended Disability Status Scale score 7.8 (SD = 1.0), patients with an IPD, MSA or PSP were in Hoehn & Yahr stage 3±5. The IPOS Neuro-S8 had high data quality (2% missing), mean score 8 (SD = 5; range 0±32), no ceiling effects, borderline floor effects, good internal consistency (Cronbach's α = 0.7) and moderate test-retest reliability (intraclass coefficient = 0.6). The results supported a moderately correlated two-factor structure (Pearson's r = 0.5). It was moderately correlated with generic and condition specific measures (Pearson's r: 0.5±0.6). There was some evidence for discriminant validity in IPD, MSA and PSP (p = 0.020), and for good responsiveness and longitudinal construct validity. Conclusions IPOS Neuro-S8 shows acceptable to promising psychometric properties in common forms of progressive LTNCs. Future work needs to confirm these findings with larger samples and its usefulness in wider disease groups

Scaphoid Waist Internal Fixation for Fractures Trial (SWIFFT) protocol : a pragmatic multi-centre randomised controlled trial of cast treatment versus surgical fixation for the treatment of bi-cortical, minimally displaced fractures of the scaphoid waist in adults

BACKGROUND: A scaphoid fracture is the most common type of carpal fracture affecting young active people. The optimal management of this fracture is uncertain. When treated with a cast, 88 to 90 % of these fractures unite; however, for the remaining 10-12 % the non-union almost invariably leads to arthritis. The alternative is surgery to fix the scaphoid with a screw at the outset. METHODS/DESIGN: We will conduct a randomised controlled trial (RCT) of 438 adult patients with a "clear" and "bicortical" scaphoid waist fracture on plain radiographs to evaluate the clinical effectiveness and cost-effectiveness of plaster cast treatment (with fixation of those that fail to unite) versus early surgical fixation. The plaster cast treatment will be immobilisation in a below elbow cast for 6 to 10 weeks followed by mobilisation. If non-union is confirmed on plain radiographs and/or Computerised Tomogram at 6 to 12 weeks, then urgent surgical fixation will be performed. This is being compared with immediate surgical fixation with surgeons using their preferred technique and implant. These treatments will be undertaken in trauma units across the United Kingdom. The primary outcome and end-point will be the Patient Rated Wrist Evaluation (a patient self-reported assessment of wrist pain and function) at 52 weeks and also measured at 6, 12, 26 weeks and 5 years. Secondary outcomes include an assessment of radiological union of the fracture; quality of life; recovery of wrist range and strength; and complications. We will also qualitatively investigate patient experiences of their treatment. DISCUSSION: Scaphoid fractures are an important public health problem as they predominantly affect young active individuals in the more productive working years of their lives. Non-union, if untreated, can lead to arthritis which can disable patients at a very young age. There is a rapidly increasing trend for immediate surgical fixation of these fractures but there is insufficient evidence from existing RCTs to support this. The SWIFFT Trial is a rigorously designed and adequately powered study which aims to contribute to the evidence-base to inform clinical decisions for the treatment of this common fracture in adults. TRIAL REGISTRATION: The trial is registered with the International Standard Randomised Controlled Trial Register ( ISRCTN67901257 ). Date registration assigned was 13/02/2013

Prior immunity helps to explain wave-like behaviour of pandemic influenza in 1918-9

<p>Abstract</p> <p>Background</p> <p>The ecology of influenza may be more complex than is usually assumed. For example, despite multiple waves in the influenza pandemic of 1918-19, many people in urban locations were apparently unaffected. Were they unexposed, or protected by pre-existing cross-immunity in the first wave, by acquired immunity in later waves, or were their infections asymptomatic?</p> <p>Methods</p> <p>We modelled all these possibilities to estimate parameters to best explain patterns of repeat attacks in 24,706 individuals potentially exposed to summer, autumn and winter waves in 12 English populations during the 1918-9 pandemic.</p> <p>Results</p> <p>Before the summer wave, we estimated that only 52% of persons (95% credibility estimates 41-66%) were susceptible, with the remainder protected by prior immunity. Most people were exposed, as virus transmissibility was high with R₀credibility estimates of 3.10-6.74. Because of prior immunity, estimates of effective R at the start of the summer wave were lower at 1.57-3.96. Only 25-66% of exposed and susceptible persons reported symptoms. After each wave, 33-65% of protected persons became susceptible again before the next wave through waning immunity or antigenic drift. Estimated rates of prior immunity were less in younger populations (19-59%) than in adult populations (38-66%), and tended to lapse more frequently in the young (49-92%) than in adults (34-76%).</p> <p>Conclusions</p> <p>Our model for pandemic influenza in 1918-9 suggests that pre-existing immune protection, presumably induced by prior exposure to seasonal influenza, may have limited the pandemic attack-rate in urban populations, while the waning of that protection likely contributed to recurrence of pandemic waves in exposed cities. In contrast, in isolated populations, pandemic attack rates in 1918-9 were much higher than in cities, presumably because prior immunity was less in populations with infrequent prior exposure to seasonal influenza. Although these conclusions cannot be verified by direct measurements of historical immune mechanisms, our modelling inferences from 1918-9 suggest that the spread of the influenza A (H1N1) 2009 pandemic has also been limited by immunity from prior exposure to seasonal influenza. Components of that immunity, which are measurable, may be short-lived, and not necessarily correlated with levels of HI antibody.</p

EcoTILLING in Capsicum species: searching for new virus resistances

<p>Abstract</p> <p>Background</p> <p>The EcoTILLING technique allows polymorphisms in target genes of natural populations to be quickly analysed or identified and facilitates the screening of genebank collections for desired traits. We have developed an EcoTILLING platform to exploit <it>Capsicum </it>genetic resources. A perfect example of the utility of this EcoTILLING platform is its application in searching for new virus-resistant alleles in <it>Capsicum </it>genus. Mutations in translation initiation factors (eIF4E, eIF(iso)4E, eIF4G and eIF(iso)4G) break the cycle of several RNA viruses without affecting the plant life cycle, which makes these genes potential targets to screen for resistant germplasm.</p> <p>Results</p> <p>We developed and assayed a cDNA-based EcoTILLING platform with 233 cultivated accessions of the genus <it>Capsicum</it>. High variability in the coding sequences of the <it>eIF4E </it>and <it>eIF(iso)4E </it>genes was detected using the cDNA platform. After sequencing, 36 nucleotide changes were detected in the CDS of <it>eIF4E </it>and 26 in <it>eIF(iso)4E</it>. A total of 21 <it>eIF4E </it>haplotypes and 15 <it>eIF(iso)4E </it>haplotypes were identified. To evaluate the functional relevance of this variability, 31 possible eIF4E/eIF(iso)4E combinations were tested against <it>Potato virus Y</it>. The results showed that five new <it>eIF4E </it>variants (<it>pvr2¹⁰</it>, <it>pvr2¹¹</it>, <it>pvr2¹²</it>, <it>pvr2¹³</it>and <it>pvr2¹⁴</it>) were related to PVY-resistance responses.</p> <p>Conclusions</p> <p>EcoTILLING was optimised in different <it>Capsicum </it>species to detect allelic variants of target genes. This work is the first to use cDNA instead of genomic DNA in EcoTILLING. This approach avoids intronic sequence problems and reduces the number of reactions. A high level of polymorphism has been identified for initiation factors, showing the high genetic variability present in our collection and its potential use for other traits, such as genes related to biotic or abiotic stresses, quality or production. Moreover, the new <it>eIF4E </it>and <it>eIF(iso)4E </it>alleles are an excellent collection for searching for new resistance against other RNA viruses.</p

A Database of Wing Diversity in the Hawaiian Drosophila

Background. Within genus Drosophila, the endemic Hawaiian species offer some of the most dramatic examples of morphological and behavioral evolution. The advent of the Drosophila grimshawi genome sequence permits genes of interest to be readily cloned from any of the hundreds of species of Hawaiian Drosophila, offering a powerful comparative approach to defining molecular mechanisms of species evolution. A key step in this process is to survey the Hawaiian flies for characters whose variation can be associated with specific candidate genes. The wings provide an attractive target for such studies: Wings are essentially two dimensional, and genes controlling wing shape, vein specification, pigment production, and pigment pattern evolution have all been identified in Drosophila. Methodology/Principal Findings. We present a photographic database of over 180 mounted, adult wings from 73 species of Hawaiian Drosophila. The image collection, available at FlyBase.org, includes 53 of the 112 known species of picture wing\u27\u27 Drosophila, and several species from each of the other major Hawaiian groups, including the modified mouthparts, modified tarsus, antopocerus, and haleakalae (fungus feeder) groups. Direct image comparisons show that major wing shape changes can occur even between closely related species, and that pigment pattern elements can vary independently of each other. Among the 30 species closest to grimshawi, diverse visual effects are achieved by altering a basic pattern of seven wing spots. Finally, we document major pattern variations within species, which appear to result from reduced diffusion of pigment precursors through the wing blade. Conclusions/Significance. The database highlights the striking variation in size, shape, venation, and pigmentation in Hawaiian Drosophila, despite their generally low levels of DNA sequence divergence. In several independent lineages, highly complex patterns are derived from simple ones. These lineages offer a promising model system to study the evolution of complexity

Biomarkers of acute lung injury: worth their salt?

The validation of biomarkers has become a key goal of translational biomedical research. The purpose of this article is to discuss the role of biomarkers in the management of acute lung injury (ALI) and related research. Biomarkers should be sensitive and specific indicators of clinically important processes and should change in a relevant timeframe to affect recruitment to trials or clinical management. We do not believe that they necessarily need to reflect pathogenic processes. We critically examined current strategies used to identify biomarkers and which, owing to expedience, have been dominated by reanalysis of blood derived markers from large multicenter Phase 3 studies. Combining new and existing validated biomarkers with physiological and other data may add predictive power and facilitate the development of important aids to research and therapy

Small molecule neuropilin-1 antagonists combine anti-angiogenic and anti-tumour activity with immune modulation through reduction of transforming growth factor beta (TGFβ) production in regulatory T-cells

We report the design, synthesis and comprehensive studybiological evaluation of a range ofsome potent small-molecule neuropilin-1 (NRP1) antagonists. NRP1 is implicated in the immune response to tumours, particularly in Treg cell fragility, required for PD1 checkpoint blockade. The design of these compounds was based on a previously identified compound EG00229, EG00229 which was used a starting point for optimisation. Through targeting of specific amino-acid residues additional H-bonding interactions were introduced, which led to increases in binding affinity and potency. The design of these molecules was informed and supported by X-ray crystal structures. Pharmacokinetic data was obtained for some of the most potent compounds, and cCompound 1 (EG01377) was identified as having properties suitable for further investigation. Compound 1 was then tested in several in vitro assays, and was shown to have anti-angiogenic, anti-migratory and anti-tumour effects. Remarkably, 1 was shown to be selective for NRP1 over the closely related protein NRP2. In purified Nrp1+, FoxP3+, CD25+ populations of Tregs from mice 1 was able to block a glioma conditioned medium induced increase in TGFβ production. This study therefore represents a comprehensive characterisation of a small-molecule NRP1 antagonist, and provides the basis for future in vivo studies

E-commerce ethics and its impact on buyer repurchase intentions and loyalty: an empirical study of small and medium Egyptian businesses

The theoretical understanding of e-commerce has received much attention over the years; however, relatively little focus has been directed towards e-commerce ethics, especially the SMEs B2B e-commerce aspect. Therefore, the purpose of this paper is to develop and empirically test a framework that explains the impact of SMEs B2B e-commerce ethics on buyer repurchase intentions and loyalty. Using SEM to analyse the data collected from a sample of SME e-commerce firms in Egypt, the results indicate that buyers’ perceptions of supplier ethics construct is composed of six dimensions (security, non-deception, fulfilment/reliability, service recovery, shared value, and communication) and strongly predictive of online buyer repurchase intentions and loyalty. Furthermore, our results also show that reliability/fulfilment and non-deception are the most effective relationship-building dimensions. In addition, relationship quality has a positive effect on buyer repurchase intentions and loyalty. The results offer important implications for B2B e-commerce and are likely to stimulate further research in the area of relationship marketing