Infrared Emission from Supernova Remnants: Formation and Destruction of Dust

We review the observations of dust emission in supernova rem- nants (SNRs) and supernovae (SNe). Theoretical calculations suggest that SNe, particularly core-collapse, should make significant quantities of dust, perhaps as much as a solar mass. Observations of extragalactic SNe have yet to find anywhere near this amount, but this may be the result of observa- tional limitations. SN 1987A, in the process of transitioning from a SN to an SNR, does show signs of a significant amount of dust forming in its ejecta, but whether this dust will survive the passage of the reverse shock to be injected into the ISM is unknown. IR observations of SNRs have not turned up significant quantities of dust, and the dust that is observed is generally swept-up by the forward shock, rather than created in the ejecta. Because the shock waves also destroy dust in the ISM, we explore the question of whether SNe might be net destroyers, rather than net creators of dust in the universe.Comment: Published in the Springer Handbook of Supernova

Interleukin 18 and coronary heart disease: Prospective study and systematic review

Aim Previous studies suggest that circulating levels of interleukin-18 (IL-18) may be prospectively related to risk of coronary heart disease (CHD) in the general population. We report new data from the largest prospective study to date, which are combined with data from all published prospective studies in a meta-analysis. Methods We measured baseline IL-18 levels in stored serum samples of subjects from a case–control study nested within a prospective study of 5661 men aged 40–59 years recruited from general practices in 18 British towns in 1978–1980 and followed-up for up to 16 years (median time to event 8.4 years) for fatal CHD and non-fatal myocardial infarction (595 cases, 1238 controls). Results IL-18 concentrations were strongly related to cigarette smoking, triglyceride, HDL-cholesterol (inversely) and to circulating levels of several inflammatory and haemostatic markers. Men in the top third of baseline IL-18 levels had an age-adjusted odds ratio (OR) for CHD of 1.55 (95% CI 1.21, 1.98) compared with those in the lowest third; this was reduced to 1.30 (95% CI 0.99, 1.69) after additional adjustment for vascular risk factors and 1.12 (95% CI 0.84, 1.49) after further adjustment for CRP and IL-6. In meta-analyses of CVD, associations (or effect sizes) were consistent between studies; RRs were 1.63 (95% CI 1.46, 1.82) after age adjustment, 1.39 (95% CI 1.24, 1.55) after additional risk factor adjustment and 1.34 (95% CI 1.17, 1.54) after additional adjustment for inflammatory markers. Conclusions Circulating IL-18 is prospectively and independently associated with CVD risk

Searches for Gravitational Waves from Binary Neutron Stars: A Review

A new generation of observatories is looking for gravitational waves. These waves, emitted by highly relativistic systems, will open a new window for ob- servation of the cosmos when they are detected. Among the most promising sources of gravitational waves for these observatories are compact binaries in the final min- utes before coalescence. In this article, we review in brief interferometric searches for gravitational waves emitted by neutron star binaries, including the theory, instru- mentation and methods. No detections have been made to date. However, the best direct observational limits on coalescence rates have been set, and instrumentation and analysis methods continue to be refined toward the ultimate goal of defining the new field of gravitational wave astronomy.Comment: 30 pages, 5 Figures, to appear in "Short-Period Binary Stars: Observations, Analyses, and Results", Ed.s Eugene F. Milone, Denis A. Leahy, David W. Hobil

Birthweight and risk markers for type 2 diabetes and cardiovascular disease in childhood: the Child Heart and Health Study in England (CHASE).

AIMS/HYPOTHESIS: Lower birthweight (a marker of fetal undernutrition) is associated with higher risks of type 2 diabetes and cardiovascular disease (CVD) and could explain ethnic differences in these diseases. We examined associations between birthweight and risk markers for diabetes and CVD in UK-resident white European, South Asian and black African-Caribbean children. METHODS: In a cross-sectional study of risk markers for diabetes and CVD in 9- to 10-year-old children of different ethnic origins, birthweight was obtained from health records and/or parental recall. Associations between birthweight and risk markers were estimated using multilevel linear regression to account for clustering in children from the same school. RESULTS: Key data were available for 3,744 (66%) singleton study participants. In analyses adjusted for age, sex and ethnicity, birthweight was inversely associated with serum urate and positively associated with systolic BP. After additional height adjustment, lower birthweight (per 100 g) was associated with higher serum urate (0.52%; 95% CI 0.38, 0.66), fasting serum insulin (0.41%; 95% CI 0.08, 0.74), HbA1c (0.04%; 95% CI 0.00, 0.08), plasma glucose (0.06%; 95% CI 0.02, 0.10) and serum triacylglycerol (0.30%; 95% CI 0.09, 0.51) but not with BP or blood cholesterol. Birthweight was lower among children of South Asian (231 g lower; 95% CI 183, 280) and black African-Caribbean origin (81 g lower; 95% CI 30, 132). However, adjustment for birthweight had no effect on ethnic differences in risk markers. CONCLUSIONS/INTERPRETATION: Birthweight was inversely associated with urate and with insulin and glycaemia after adjustment for current height. Lower birthweight does not appear to explain emerging ethnic difference in risk markers for diabetes

GREENER pharmaceuticals for more sustainable healthcare

This is the final version. Available on open access from the American Chemical Society via the DOI in this record. Medicines are essential to human health but can also impact the aquatic and terrestrial environment after use by patients and release via excreta into wastewater. We highlight the need for a GREENER approach to identify and meet important environmental criteria, which will help reduce the impact of medicinal residues on the environment. These criteria include effect reduction by avoiding nontarget effects or undesirable moieties, exposure reduction via lower emissions or environmental (bio)degradability, no PBT (persistent, bioaccumulative, and toxic) substances, and risk mitigation. With all of these criteria, however, patient health is of primary importance as medicines are required to be safe and efficacious for treating diseases. We discuss the feasibility of including these criteria for green by design active pharmaceutical ingredients in the process of drug discovery and development and which tools or assays are needed to accomplish this. The integrated GREENER approach can be used to accelerate discussions about future innovations in drug discovery and development.Innovative Medicines Initiative 2 Joint Undertakin

Discovery of nucleotide polymorphisms in the Musa gene pool by Ecotilling

Musa (banana and plantain) is an important genus for the global export market and in local markets where it provides staple food for approximately 400 million people. Hybridization and polyploidization of several (sub)species, combined with vegetative propagation and human selection have produced a complex genetic history. We describe the application of the Ecotilling method for the discovery and characterization of nucleotide polymorphisms in diploid and polyploid accessions of Musa. We discovered over 800 novel alleles in 80 accessions. Sequencing and band evaluation shows Ecotilling to be a robust and accurate platform for the discovery of polymorphisms in homologous and homeologous gene targets. In the process of validating the method, we identified two single nucleotide polymorphisms that may be deleterious for the function of a gene putatively important for phototropism. Evaluation of heterozygous polymorphism and haplotype blocks revealed a high level of nucleotide diversity in Musa accessions. We further applied a strategy for the simultaneous discovery of heterozygous and homozygous polymorphisms in diploid accessions to rapidly evaluate nucleotide diversity in accessions of the same genome type. This strategy can be used to develop hypotheses for inheritance patterns of nucleotide polymorphisms within and between genome types. We conclude that Ecotilling is suitable for diversity studies in Musa, that it can be considered for functional genomics studies and as tool in selecting germplasm for traditional and mutation breeding approaches

A preliminary study of the effect of closed incision management with negative pressure wound therapy over high-risk incisions

Background Certain postoperative wounds are recognised to be associated with more complications than others and may be termed high-risk. Wound healing can be particularly challenging following high-energy trauma where wound necrosis and infection rates are high. Surgical incision for joint arthrodesis can also be considered high-risk as it requires extensive and invasive surgery and postoperative distal limb swelling and wound dehiscence are common. Recent human literature has investigated the use of negative pressure wound therapy (NPWT) over high-risk closed surgical incisions and beneficial effects have been noted including decreased drainage, decreased dehiscence and decreased infection rates. In a randomised, controlled study twenty cases undergoing distal limb high-energy fracture stabilisation or arthrodesis were randomised to NPWT or control groups. All cases had a modified Robert-Jones dressing applied for 72 h postoperatively and NPWT was applied for 24 h in the NPWT group. Morphometric assessment of limb circumference was performed at six sites preoperatively, 24 and 72 h postoperatively. Wound discharge was assessed at 24 and 72 h. Postoperative analgesia protocol was standardised and a Glasgow Composite Measure Pain Score (GCPS) carried out at 24, 48 and 72 h. Complications were noted and differences between groups were assessed. Results Percentage change in limb circumference between preoperative and 24 and 72 h postoperative measurements was significantly less at all sites for the NPWT group with exception of the joint proximal to the surgical site and the centre of the operated bone at 72 h. Median discharge score was lower in the NPWT group than the control group at 24 h. No significant differences in GCPS or complication rates were noted. Conclusions Digital swelling and wound discharge were reduced when NPWT was employed for closed incision management. Larger studies are required to evaluate whether this will result in reduced discomfort and complication rates postoperatively

G2i Knowledge Brief: A Knowledge Brief of the MacArthur Foundation Research Network on Law and Neuroscience

Courts are daily confronted with admissibility issues – such as in cases involving neuroscientific testimony – that sometimes involve both the existence of a general phenomenon (i.e., “G”) and the question of whether a particular case represents a specific instance of that general phenomenon (i.e., “i”). Unfortunately, courts have yet to carefully consider the implications of “G2i” for their admissibility decisions. In some areas, courts limit an expert’s testimony to the general phenomenon. They insist that whether the case at hand is an instance of that phenomenon is exclusively a jury question, and thus not an appropriate subject of expert opinion. In other cases, in contrast, courts hold that expert evidence must be provided on both the group-data issue (i.e., that the phenomenon exists) and what is called the “diagnostic” issue (i.e., that this case is an instance of that phenomenon). Consequently, the MacArthur Foundation Research Network on Law and Neuroscience has prepared this knowledge brief to help courts manage the G2i divide. Specifically, we recommend that courts first determine whether proffered expert testimony concerns only the existence of the general phenomenon or instead concerns both that and the diagnosis that a particular case represents an instance of that phenomenon. Only after making that determination should the court make its admissibility decision (guided, for instance, by the Daubert factors for admitting scientific evidence)

Altered splicing of the BIN1 muscle-specific exon in humans and dogs with highly progressive centronuclear myopathy

Amphiphysin 2, encoded by BIN1, is a key factor for membrane sensing and remodelling in different cell types. Homozygous BIN1 mutations in ubiquitously expressed exons are associated with autosomal recessive centronuclear myopathy (CNM), a mildly progressive muscle disorder typically showing abnormal nuclear centralization on biopsies. In addition, misregulation of BIN1 splicing partially accounts for the muscle defects in myotonic dystrophy (DM). However, the muscle-specific function of amphiphysin 2 and its pathogenicity in both muscle disorders are not well understood. In this study we identified and characterized the first mutation affecting the splicing of the muscle-specific BIN1 exon 11 in a consanguineous family with rapidly progressive and ultimately fatal centronuclear myopathy. In parallel, we discovered a mutation in the same BIN1 exon 11 acceptor splice site as the genetic cause of the canine Inherited Myopathy of Great Danes (IMGD). Analysis of RNA from patient muscle demonstrated complete skipping of exon 11 and BIN1 constructs without exon 11 were unable to promote membrane tubulation in differentiated myotubes. Comparative immunofluorescence and ultrastructural analyses of patient and canine biopsies revealed common structural defects, emphasizing the importance of amphiphysin 2 in membrane remodelling and maintenance of the skeletal muscle triad. Our data demonstrate that the alteration of the muscle-specific function of amphiphysin 2 is a common pathomechanism for centronuclear myopathy, myotonic dystrophy, and IMGD. The IMGD dog is the first faithful model for human BIN1-related CNM and represents a mammalian model available for preclinical trials of potential therapies

Diabetes Susceptibility in the Canadian Oji-Cree Population Is Moderated by Abnormal mRNA Processing of HNF1A G319S Transcripts

OBJECTIVE—The G319S HNF1A variant is associated with an increased risk of type 2 diabetes in the Canadian Oji-Cree population. We hypothesized that the variant site at the 3′ end of exon 4 might influence splicing and characterized mRNA transcripts to investigate the mutational mechanism underlying this susceptibility to diabetes