Diagnosis and aetiology of congenital muscular dystrophy: we are halfway there

OBJECTIVES: To evaluate the diagnostic outcomes in a large cohort of congenital muscular dystrophy (CMD) patients using traditional and Next Generation Sequencing (NGS) technologies. METHODS: 123 CMD patients were investigated using the traditional approaches of histology, immunohistochemical analysis of muscle biopsy and candidate gene sequencing. Undiagnosed patients available for further testing were investigated using NGS. RESULTS: Muscle biopsy and immunohistochemical analysis found deficiencies of laminin α2, α-dystroglycan or collagen VI in 50% of patients. Candidate gene sequencing and chromosomal microarray established a genetic diagnosis in 32% (39/123). Of 85 patients presenting in the last 20 years, 28 of 51 who lacked a confirmed genetic diagnosis (55%) consented to NGS studies, leading to confirmed diagnoses in a further 11 patients. Using the combination of approaches, a confirmed genetic diagnosis was achieved in 51% (43/85). The diagnoses within the cohort were heterogeneous. 45/59 probands with confirmed or probable diagnoses had variants in genes known to cause CMD (76%), and 11/59 (19%) had variants in genes associated with congenital myopathies, reflecting overlapping features of these conditions. One patient had a congenital myasthenic syndrome and two had microdeletions. Within the cohort, five patients had variants in novel (PIGY and GMPPB) or recently published genes (GFPT1 and MICU1) and seven had variants in TTN or RYR1; large genes that are technically difficult to Sanger sequence. INTERPRETATION: These data support NGS as a first-line tool for genetic evaluation of patients with a clinical phenotype suggestive of CMD, with muscle biopsy reserved as a second-tier investigation. This article is protected by copyright. All rights reserved

The effects of glare and inhomogeneous visual fields on contrast detection in the context of driving

An experiment was carried out to investigate how contrast threshold for target detection is affected by the presence of glare and by extraneous light sources using the method of ascending limits. The target was located at either a foveal or a peripheral (10° right) location, glare was adjacent to the foveal location, simulating the headlamps of an oncoming vehicle, and extraneous light sources were at either foveal or peripheral (10° right or left) locations. Contrast threshold for a foveal target without glare was affected mainly by the surrounding local luminance distribution. However, in the presence of glare and also for the peripheral target (both with and without glare) the global luminance distribution matters. Glare increased the contrast needed for detection of the foveal target, but this effect was reduced by the presence of extraneous light sources that were peripheral to the target. For peripheral targets, contrast threshold was also reduced by the presence of extraneous light at a non-target location and this effect was increased in the presence of glare. Glare equations tend to be based on tests using uniform, homogenous fields: these data indicate that, in the presence of extraneous light sources, the influence of glare is over-estimated

P2X receptor-mediated purinergic sensory pathways to the spinal cord dorsal horn

P2X receptors are expressed on different functional groups of primary afferent fibers. P2X receptor-mediated sensory inputs can be either innocuous or nociceptive, depending on which dorsal horn regions receive these inputs. We provide a brief review of P2X receptor-mediated purinergic sensory pathways to different regions in the dorsal horn. These P2X purinergic pathways are identified in normal animals, which provides insights into their physiological functions. Future studies on P2X purinergic pathways in animal models of pathological conditions may provide insights on how P2X receptors play a role in pathological pain states

Foreign Aid Transaction Costs: What are they and when are they minimised?

'Transaction costs' are commonly referred to in the recent literature on aid effectiveness. Aid transaction costs, however, have been neither consistently defined nor measured. This article defines aid transaction costs as all the economic costs associated with aid management that add no value to aid delivery. This enables the 'net' transaction costs that should be minimised to be identified. An analytical framework is then developed for assessing these costs. This allows the effectiveness of different aid modalities to be compared, according to the characteristics of the aid transaction. The article shows that the choice of aid modality should depend on these characteristics and, therefore, that the minimisation of transaction costs should not be an end in itself.Peer reviewe

Governing and accelerating transformative entrepreneurship: exploring the potential for small business innovation on urban sustainability transitions

The alluring yet nebulous concept of transformative change is increasingly gaining traction in conversations about pathways to more sustainable futures. As such, new conceptual tools are needed to illuminate variety of actors, interests, and capacities at play in potentially radical experiments. This paper draws upon multi-level governance theory, sustainability transitions scholarship, and sustainability entrepreneurship literature, to interrogate the transformative potential of small and medium-sized enterprises (SMEs). We (1) identify characteristics of SMEs that might make them relatively more able to produce radical innovations, (2) explore dimensions of the broader socio-political context that influence the likelihood of this potential to be translated into action in urban spaces, and (3) discuss implications of these dynamics for transformative sustainability governance

Governing and accelerating transformative entrepreneurship: exploring the potential for small business innovation on urban sustainability transitions

The alluring yet nebulous concept of transformative change is increasingly gaining traction in conversations about pathways to more sustainable futures. As such, new conceptual tools are needed to illuminate variety of actors, interests, and capacities at play in potentially radical experiments. This paper draws upon multi-level governance theory, sustainability transitions scholarship, and sustainability entrepreneurship literature, to interrogate the transformative potential of small and medium-sized enterprises (SMEs). We (1) identify characteristics of SMEs that might make them relatively more able to produce radical innovations, (2) explore dimensions of the broader socio-political context that influence the likelihood of this potential to be translated into action in urban spaces, and (3) discuss implications of these dynamics for transformative sustainability governance

Postpartum mental health after Hurricane Katrina: A cohort study

<p>Abstract</p> <p>Background</p> <p>Natural disaster is often a cause of psychopathology, and women are vulnerable to post-traumatic stress disorder (PTSD) and depression. Depression is also common after a woman gives birth. However, no research has addressed postpartum women's mental health after natural disaster.</p> <p>Methods</p> <p>Interviews were conducted in 2006–2007 with women who had been pregnant during or shortly after Hurricane Katrina. 292 New Orleans and Baton Rouge women were interviewed at delivery and 2 months postpartum. Depression was assessed using the Edinburgh Depression Scale and PTSD using the Post-Traumatic Stress Checklist. Women were asked about their experience of the hurricane with questions addressing threat, illness, loss, and damage. Chi-square tests and log-binomial/Poisson models were used to calculate associations and relative risks (RR).</p> <p>Results</p> <p>Black women and women with less education were more likely to have had a serious experience of the hurricane. 18% of the sample met the criteria for depression and 13% for PTSD at two months postpartum. Feeling that one's life was in danger was associated with depression and PTSD, as were injury to a family member and severe impact on property. Overall, two or more severe experiences of the storm was associated with an increased risk for both depression (relative risk (RR) 1.77, 95% confidence interval (CI) 1.08–2.89) and PTSD (RR 3.68, 95% CI 1.80–7.52).</p> <p>Conclusion</p> <p>Postpartum women who experience natural disaster severely are at increased risk for mental health problems, but overall rates of depression and PTSD do not seem to be higher than in studies of the general population.</p

Millennial changes in North American wildfire and soil activity over the last glacial cycle

Climate changes in the North Atlantic region during the last glacial cycle were dominated by the slow waxing and waning of the North American ice sheet as well as by intermittent Dansgaard-­‐Oeschger (DO) events. However prior to the last deglaciation, little is known about the response of North American vegetation to such rapid climate changes and especially about the response of biomass burning, an important factor for regional changes in radiative forcing. Here we use continuous, high-­‐resolution ammonium (NH4+) records derived from the NGRIP and GRIP ice cores to document both North American NH4+ background emissions from soils and wildfire frequency over the last 110,000 yr. Soil emissions increased on orbital timescales with warmer climate, related to the northward expansion of vegetation due to reduced ice-­‐covered areas. During Marine Isotope Stage (MIS) 3 DO warm events, a higher fire recurrence rate is recorded, while NH4+ soil emissions rose only slowly during longer interstadial warm periods, in line with slow ice sheet shrinkage and delayed ecosystem changes. Our results indicate that sudden warming events had little impact on NH4+ soil emissions and NH4+ aerosol transport to Greenland during the glacial but triggered a significant increase in the frequency of fire occurrence.This paper has greatly benefitted from the Sir Nicholas Shackleton fellowship, Clare Hall, University of Cambridge, U.K., awarded to HF in 2014. The Division for Climate and Environmental Physics, Physics Institute, University of Bern acknowledges the long-­‐term financial support of ice core research by the Swiss National Science Foundation (SNSF) and the Oeschger Centre for Climate Change Research. EW is supported by a Royal Society professorship. NGRIP is directed and organized by the Department of Geophysics at the Niels Bohr Institute for Astronomy, Physics and Geophysics, University of Copenhagen. It is supported by funding agencies in Denmark (SNF), Belgium (FNRS-­‐CFB), France (IPEV and INSU/CNRS), Germany (AWI), Iceland (RannIs), Japan (MEXT), Sweden (SPRS), Switzerland (SNSF) and the USA (NSF, Office of Polar Programs).This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ngeo249

Use of mental health services among disaster survivors: predisposing factors

<p>Abstract</p> <p>Background</p> <p>Given the high prevalence of mental health problems after disasters it is important to study health services utilization. This study examines predictors for mental health services (MHS) utilization among survivors of a man-made disaster in the Netherlands (May 2000).</p> <p>Methods</p> <p>Electronic records of survivors (n = 339; over 18 years and older) registered in a mental health service (MHS) were linked with general practice based electronic medical records (EMRs) of survivors and data obtained in surveys. EMR data were available from 16 months pre-disaster until 3 years post-disaster. Symptoms and diagnoses in the EMRs were coded according to the International Classification of Primary Care (ICPC). Surveys were carried out 2–3 weeks and 18 months post-disaster, and included validated questionnaires on psychological distress, post-traumatic stress reactions and social functioning. Demographic and disaster-related variables were available. Predisposing factors for MHS utilization 0–18 months and 18–36 months post-disaster were examined using multiple logistic regression models.</p> <p>Results</p> <p>In multiple logistic models, adjusting for demographic and disaster related variables, MHS utilization was predicted by demographic variables (young age, immigrant, public health insurance, unemployment), disaster-related exposure (relocation and injuries), self-reported psychological problems and pre- and post-disaster physician diagnosed health problems (chronic diseases, musculoskeletal problems). After controlling for all health variables, disaster intrusions and avoidance reactions (OR:2.86; CI:1.48–5.53), hostility (OR:2.04; CI:1.28–3.25), pre-disaster chronic diseases (OR:1.82; CI:1.25–2.65), injuries as a result of the disaster (OR:1.80;CI:1.13–2.86), social functioning problems (OR:1.61;CI:1.05–2.44) and younger age (OR:0.98;CI:0.96–0.99) predicted MHS utilization within 18 months post-disaster. Furthermore, disaster intrusions and avoidance reactions (OR:2.29;CI:1.04–5.07) and hostility (OR:3.77;CI:1.51–9.40) predicted MHS utilization following 18 months post-disaster.</p> <p>Conclusion</p> <p>This study showed that several demographic and disaster-related variables and self-reported and physician diagnosed health problems predicted post-disaster MHS-use. The most important factors to predict post-disaster MHS utilization were disaster intrusions and avoidance reactions and symptoms of hostility (which can be identified as symptoms of PTSD) and pre-disaster chronic diseases.</p