Myocardial fibrosis in Eisenmenger syndrome: a descriptive cohort study exploring associations of late gadolinium enhancement with clinical status and survival

BACKGROUND: A relationship between myocardial fibrosis and ventricular dysfunction has been demonstrated using late gadolinium enhancement (LGE) in the pressure-loaded right ventricle from congenital heart defects. In patients with Eisenmenger syndrome (ES), the presence of LGE has not been investigated. The aims of this study were to detect any myocardial fibrosis in ES and describe major clinical variables associated with the finding. METHODS: From 45 subjects screened, 30 subjects (age 43 ± 13 years, 20 female) underwent prospective cardiovascular magnetic resonance with LGE to quantify biventricular volume and function as well as maximal and submaximal exercise during a single visit. Standard cine acquisitions were obtained for ventricular volume and function. Further imaging was performed after administration of 0.1 mmol/kg gadolinium contrast. Regions of LGE were evaluated qualitatively and quantitatively by manual contouring of identified areas, with total area expressed as a percentage of mass. Patients were followed prospectively (mean follow up 7.4 ± 0.4 years) and any deaths recorded. Patients with LGE findings were compared to those without. RESULTS: LGE was present in 22/30 (73%) patients, specifically in RV myocardium (70%), RV trabeculae (60%), LV myocardium (33%) or LV papillary muscles (30%), though in small amounts (mean 1.4% of total ventricular mass, range 0.16 – 6.0%). Those with any LGE were not different in age, history of arrhythmia, desaturation, nor hemoglobin, nor ventricular size, mass, or function. Exercise capacity was low, but also not different between those with and without LGE. Similarly no significant associations were found with amount of fibrosis. There were five deaths among patients with LGE, versus two in patients without, but no difference in survival (log rank =0.03, P = 0.85). CONCLUSIONS: Myocardial fibrosis by LGE is common in ES, though not extensive. The presence and quantity of LGE did not correlate with ventricular size, function, degree of cyanosis, exercise capacity, or survival in this pilot study. More data are clearly required before recommendations for routine use of LGE in these patients can be made

Efficient assembly of very short oligonucleotides using T4 DNA Ligase

<p>Abstract</p> <p>Background</p> <p>In principle, a pre-constructed library of all possible short oligonucleotides could be used to construct many distinct gene sequences. In order to assess the feasibility of such an approach, we characterized T4 DNA Ligase activity on short oligonucleotide substrates and defined conditions suitable for assembly of a plurality of oligonucleotides.</p> <p>Findings</p> <p>Ligation by T4 DNA Ligase was found to be dependent on the formation of a double stranded DNA duplex of at least five base pairs surrounding the site of ligation. However, ligations could be performed effectively with overhangs smaller than five base pairs and oligonucleotides as small as octamers, in the presence of a second, complementary oligonucleotide. We demonstrate the feasibility of simultaneous oligonucleotide phosphorylation and ligation and, as a proof of principle for DNA synthesis through the assembly of short oligonucleotides, we performed a hierarchical ligation procedure whereby octamers were combined to construct a target 128-bp segment of the beta-actin gene.</p> <p>Conclusions</p> <p>Oligonucleotides as short as 8 nucleotides can be efficiently assembled using T4 DNA Ligase. Thus, the construction of synthetic genes, without the need for custom oligonucleotide synthesis, appears feasible.</p

Diffuse small bowel thickening in aids patient - a case report

<p>Abstract</p> <p>Background</p> <p>Diarrhea is common in HIV/AIDS patients, caused by both classic enteric pathogens and different opportunistic agents. <it>Infection with these different pathogens may lead to similar radiological findings, thus causing diagnostic confusion</it>.</p> <p>Case presentation</p> <p>A 30-yr-old female with AIDS presented with chronic diarrhea of 4 months duration. She had diffuse small bowel thickening present on CT scan of her abdomen, with stool examination showing no parasites. She was erroneously diagnosed as abdominal tuberculosis and given antituberculosis drugs with which she showed no improvement. Repeat stool examination later at a specialized laboratory revealed <it>Cryptosporidium parvum </it>infection.</p> <p>The patient was given an extended course of nitazoxanide treatment, as her stool examination was positive for <it>Cryptosporidium parvum </it>even after 2 weeks of drug consumption. Parasite clearance was documented after 10 weeks of treatment. Interestingly, the bowel thickening reversed with parasitological clearance.</p> <p>Conclusions</p> <p><it>Cryptosporidium parvum </it>may lead to small bowel thickening in AIDS patients. This small bowel thickening may reverse following parasitological clearance.</p

Aharonov-Bohm interferences from local deformations in graphene

One of the most interesting aspects of graphene is the tied relation between structural and electronic properties. The observation of ripples in the graphene samples both free standing and on a substrate has given rise to a very active investigation around the membrane-like properties of graphene and the origin of the ripples remains as one of the most interesting open problems in the system. The interplay of structural and electronic properties is successfully described by the modelling of curvature and elastic deformations by fictitious gauge fields that have become an ex- perimental reality after the suggestion that Landau levels can form associated to strain in graphene and the subsequent experimental confirmation. Here we propose a device to detect microstresses in graphene based on a scanning-tunneling-microscopy setup able to measure Aharonov-Bohm inter- ferences at the nanometer scale. The interferences to be observed in the local density of states are created by the fictitious magnetic field associated to elastic deformations of the sample.Comment: Some bugs fixe

Paying Refugees to Leave

States are increasingly paying refugees to repatriate, hoping to decrease the number of refugees residing within their borders. Drawing on in-depth interviews from East Africa and data from Israeli Labour Statistics, I provide a description of such payment schemes and consider whether they are morally permissible. In doing so, I address two types of cases. In the first type of case, governments pay refugees to repatriate to high-risk countries, never coercing them into returning. I argue that such payments are permissible if refugees’ choices are voluntary and if states allow refugees to return to the host country in the event of an emergency. I then describe cases where states detain refugees, and non-governmental organisations provide their own payments to refugees wishing to repatriate. In such cases, non-governmental organisations are only permitted to provide payments if the funds are sufficient to ensure post-return safety and if providing payments does not reinforce the government’s detention policy

Conceptualizing pathways linking women's empowerment and prematurity in developing countries.

BackgroundGlobally, prematurity is the leading cause of death in children under the age of 5. Many efforts have focused on clinical approaches to improve the survival of premature babies. There is a need, however, to explore psychosocial, sociocultural, economic, and other factors as potential mechanisms to reduce the burden of prematurity. Women's empowerment may be a catalyst for moving the needle in this direction. The goal of this paper is to examine links between women's empowerment and prematurity in developing settings. We propose a conceptual model that shows pathways by which women's empowerment can affect prematurity and review and summarize the literature supporting the relationships we posit. We also suggest future directions for research on women's empowerment and prematurity.MethodsThe key words we used for empowerment in the search were "empowerment," "women's status," "autonomy," and "decision-making," and for prematurity we used "preterm," "premature," and "prematurity." We did not use date, language, and regional restrictions. The search was done in PubMed, Population Information Online (POPLINE), and Web of Science. We selected intervening factors-factors that could potentially mediate the relationship between empowerment and prematurity-based on reviews of the risk factors and interventions to address prematurity and the determinants of those factors.ResultsThere is limited evidence supporting a direct link between women's empowerment and prematurity. However, there is evidence linking several dimensions of empowerment to factors known to be associated with prematurity and outcomes for premature babies. Our review of the literature shows that women's empowerment may reduce prematurity by (1) preventing early marriage and promoting family planning, which will delay age at first pregnancy and increase interpregnancy intervals; (2) improving women's nutritional status; (3) reducing domestic violence and other stressors to improve psychological health; and (4) improving access to and receipt of recommended health services during pregnancy and delivery to help prevent prematurity and improve survival of premature babies.ConclusionsWomen's empowerment is an important distal factor that affects prematurity through several intervening factors. Improving women's empowerment will help prevent prematurity and improve survival of preterm babies. Research to empirically show the links between women's empowerment and prematurity is however needed

Ten years of lesbian health survey research in the UK West Midlands

Abstract Background Very little is known about the physical health needs of lesbian and bisexual women in the UK; most research has looked at mental or sexual health only. This article reports the results of four surveys carried out in the West Midlands between 1995 and 2005. Methods The first two surveys were conducted in 1995–6 by a volunteer group, with participants from a lesbian health conference (n = 69) and in a convenience sample from a wide range of relevant groups and venues (n = 354). The second two surveys were commissioned by the West Midlands South Strategic Health Authority in partnership with the Gay Men's Health Network and were conducted in 2002 (n = 449) and 2005 (n = 166) and again used convenience sampling methods including the internet. Results The mean age of respondents varied between 29–33 years and 5–7% were from a non-white ethnic background. The smoking rates varied from 42% o 55%, being twice the West Midlands regional average of 21% for women aged 16 or more. Similarly, problems with alcohol were reported in 25–37% of respondents, higher than the West Midlands regional average of 7% for women aged 16+. The prevalence of any mental health problem varied between 31–35% and any suicide attempt between 20–31%. Only 29–45% had revealed their sexual orientation to their GP and of these, approximately 50% had experienced a positive reaction. Conclusion The results suggest health needs that current UK health services may not be meeting. There is a need to identify and target specific health measures for lesbians and bisexual women in order to ensure improved physical and mental health in the longer term.</p

Variation, variability, and the origin of the avian endocranium:Insights from the anatomy of alioramus altai (theropoda: Tyrannosauroidea)

The internal braincase anatomy of the holotype of Alioramus altai, a relatively small-bodied tyrannosauroid from the Late Cretaceous of Mongolia, was studied using high-resolution computed tomography. A number of derived characters strengthen the diagnosis of this taxon as both a tyrannosauroid and a unique, new species (e.g., endocranial position of the gasserian ganglion, internal ramification of the facial nerve). Also present are features intermediate between the basal theropod and avialan conditions that optimize as the ancestral condition for Coelurosauria--a diverse group of derived theropods that includes modern birds. The expression of several primitive theropod features as derived character states within Tyrannosauroidea establishes previously unrecognized evolutionary complexity and morphological plasticity at the base of Coelurosauria. It also demonstrates the critical role heterochrony may have played in driving patterns of endocranial variability within the group and potentially reveals stages in the evolution of neuroanatomical development that could not be inferred based solely on developmental observations of the major archosaurian crown clades. We discuss the integration of paleontology with variability studies, especially as applied to the nature of morphological transformations along the phylogenetically long branches that tend to separate the crown clades of major vertebrate groups

Maternal gestational vitamin D supplementation and offspring bone health (MAVIDOS): a multicentre, double-blind, randomised placebo-controlled trial.

BACKGROUND: Maternal vitamin D status has been associated with bone mass of offspring in many, but not all, observational studies. However, maternal vitamin D repletion during pregnancy has not yet been proven to improve offspring bone mass in a randomised controlled trial. We aimed to assess whether neonates born to mothers supplemented with vitamin D during pregnancy have greater whole-body bone mineral content (BMC) at birth than those of mothers who had not received supplementation. METHODS: The Maternal Vitamin D Osteoporosis Study (MAVIDOS) was a multicentre, double-blind, randomised, placebo-controlled trial that recruited pregnant women from three study sites in the UK (Southampton, Oxford, and Sheffield). Eligible participants were older than 18 years, with a singleton pregnancy, gestation of less than 17 weeks, and a serum 25-hydroxyvitamin D (25[OH]D) concentration of 25-100 nmol/L at 10-17 weeks' gestation. P'articipants were randomly assigned (1:1), in randomly permuted blocks of ten, to either cholecalciferol 1000 IU/day or matched placebo, taken orally, from 14 weeks' gestation (or as soon as possible before 17 weeks' gestation if recruited later) until delivery. Participants and the research team were masked to treatment allocation. The primary outcome was neonatal whole-body BMC, assessed within 2 weeks of birth by dual-energy x-ray absorptiometry (DXA), analysed in all randomly assigned neonates who had a usable DXA scan. Safety outcomes were assessed in all randomly assigned participants. This trial is registered with the International Standard Randomised Controlled Trial registry, ISRCTN 82927713, and the European Clinical Trials Database, EudraCT 2007-001716-23. FINDINGS: Between Oct 10, 2008, and Feb 11, 2014, we randomly assigned 569 pregnant women to placebo and 565 to cholecalciferol 1000 IU/day. 370 (65%) neonates in the placebo group and 367 (65%) neonates in the cholecalciferol group had a usable DXA scan and were analysed for the primary endpoint. Neonatal whole-body BMC of infants born to mothers assigned to cholecalciferol 1000 IU/day did not significantly differ from that of infants born to mothers assigned to placebo (61·6 g [95% CI 60·3-62·8] vs 60·5 g [59·3-61·7], respectively; p=0·21). We noted no significant differences in safety outcomes, apart from a greater proportion of women in the placebo group with severe post-partum haemorrhage than those in the cholecalciferol group (96 [17%] of 569 mothers in the placebo group vs 65 [12%] of 565 mothers in the cholecalciferol group; p=0·01). No adverse events were deemed to be treatment related. INTERPRETATION: Supplementation of women with cholecalciferol 1000 IU/day during pregnancy did not lead to increased offspring whole-body BMC compared with placebo, but did show that 1000 IU of cholecalciferol daily is sufficient to ensure that most pregnant women are vitamin D replete, and it is safe. These findings support current approaches to vitamin D supplementation in pregnancy. Results of the ongoing MAVIDOS childhood follow-up study are awaited. FUNDING: Arthritis Research UK, Medical Research Council, Bupa Foundation, and National Institute for Health Research