Controlled creation of a singular spinor vortex by circumventing the Dirac belt trick

Persistent topological defects and textures are particularly dramatic consequences of superfluidity. Among the most fascinating examples are the singular vortices arising from the rotational symmetry group SO(3), with surprising topological properties illustrated by Dirac’s famous belt trick. Despite considerable interest, controlled preparation and detailed study of vortex lines with complex internal structure in fully three-dimensional spinor systems remains an outstanding experimental challenge. Here, we propose and implement a reproducible and controllable method for creating and detecting a singular SO(3) line vortex from the decay of a non-singular spin texture in a ferromagnetic spin-1 Bose–Einstein condensate. Our experiment explicitly demonstrates the SO(3) character and the unique spinor properties of the defect. Although the vortex is singular, its core fills with atoms in the topologically distinct polar magnetic phase. The resulting stable, coherent topological interface has analogues in systems ranging from condensed matter to cosmology and string theory

Retinoid Signaling in Pancreatic Cancer, Injury and Regeneration

Background: Activation of embryonic signaling pathways quiescent in the adult pancreas is a feature of pancreatic cancer (PC). These discoveries have led to the development of novel inhibitors of pathways such as Notch and Hedgehog signaling that are currently in early phase clinical trials in the treatment of several cancer types. Retinoid signaling is also essential for pancreatic development, and retinoid therapy is used successfully in other malignancies such as leukemia, but little is known concerning retinoid signaling in PC. Methodology/Principal Findings: We investigated the role of retinoid signaling in vitro and in vivo in normal pancreas, pancreatic injury, regeneration and cancer. Retinoid signaling is active in occasional cells in the adult pancreas but is markedly augmented throughout the parenchyma during injury and regeneration. Both chemically induced and genetically engineered mouse models of PC exhibit a lack of retinoid signaling activity compared to normal pancreas. As a consequence, we investigated Cellular Retinoid Binding Protein 1 (CRBP1), a key regulator of retinoid signaling known to play a role in breast cancer development, as a potential therapeutic target. Loss, or significant downregulation of CRBP1 was present in 70% of human PC, and was evident in the very earliest precursor lesions (PanIN-1A). However, in vitro gain and loss of function studies and CRBP1 knockout mice suggested that loss of CRBP1 expression alone was not sufficient to induce carcinogenesis or to alter PC sensitivity to retinoid based therapies. Conclusions/Significance: In conclusion, retinoid signalling appears to play a role in pancreatic regeneration and carcinogenesis, but unlike breast cancer, it is not mediated directly by CRBP1

Protocol for north of England and Scotland study of tonsillectomy and adeno-tonsillectomy in children (NESSTAC). A pragmatic randomised controlled trial comparing surgical intervention with conventional medical treatment in children with recurrent sore throats

BACKGROUND: Uncertainties surrounding the effectiveness and cost-effectiveness of childhood tonsillectomy for recurrent sore throat led the NHS Health Technology Assessment Programme to commission this research to evaluate the effectiveness and cost-effectiveness of tonsillectomy and adeno-tonsillectomy in comparison with standard non-surgical management in children aged under 16 with recurrent throat infections. The aim is to evaluate if tonsillectomy and adeno-tonsillectomy reduces the number of episodes of sore throats among children to a clinically significant extent. METHODS/DESIGN: A simple prospective pragmatic randomised controlled trial with economic analysis and prospective cohort study of non-trial participants comparing surgical intervention with conventional medical treatment. The treatment arm will receive tonsillectomy and adeno-tonsillectomy while in the control arm non-surgical conventional medical treatment only will be used. The primary outcome measure will be reported number of episodes of sore throat over two years with secondary outcomes measures of reported number of episodes of sore throat, otitis media and upper respiratory tract infection which invoke a GP consultation; reported number of symptom-free days; reported severity of sore throats and surgical and anaesthetic morbidity. The study will take place in five hospitals in the UK. The trial population will be 406 children aged 4–15 on their last birthday with recurrent sore throat referred by primary care to the 5 otolaryngology departments. The duration of the study is seven years (July 2001- July 2008). DISCUSSION: As with all pragmatic randomised controlled trials it is impossible to control the external environment in which the research is taking place. Since this trial began a number of factors have arisen which could affect the outcome including; a reduction in the incidence of respiratory tract infections, marked socio-economic differences in consultation rates, the results from the National Prospective Tonsillectomy Audit and the Government's waiting list initiatives

Physical activity but not sedentary activity is reduced in primary Sjögren’s syndrome

The aim of the study was to evaluate the levels of physical activity in individuals with primary Sjögren’s syndrome (PSS) and its relationship to the clinical features of PSS. To this cross-sectional study, self-reported levels of physical activity from 273 PSS patients were measured using the International Physical Activity Questionnaire-short form (IPAQ-SF) and were compared with healthy controls matched for age, sex and body mass index. Fatigue and other clinical aspects of PSS including disease status, dryness, daytime sleepiness, dysautonomia, anxiety and depression were assessed using validated tools. Individuals with PSS had significantly reduced levels of physical activity [median (interquartile range, IQR) 1572 (594–3158) versus 3708 (1732–8255) metabolic equivalent of task (MET) × min/week, p < 0.001], but similar levels of sedentary activity [median (IQR) min 300 (135–375) versus 343 (223–433) (MET) × min/week, p = 0.532] compared to healthy individuals. Differences in physical activity between PSS and controls increased at moderate [median (IQR) 0 (0–480) versus 1560 (570–3900) MET × min/week, p < 0.001] and vigorous intensities [median (IQR) 0 (0–480) versus 480 (0–1920) MET × min/week, p < 0.001]. Correlation analysis revealed a significant association between physical activity and fatigue, orthostatic intolerance, depressive symptoms and quality of life. Sedentary activity did not correlate with fatigue. Stepwise linear regression analysis identified symptoms of depression and daytime sleepiness as independent predictors of levels of physical activity. Physical activity is reduced in people with PSS and is associated with symptoms of depression and daytime sleepiness. Sedentary activity is not increased in PSS. Clinical care teams should explore the clinical utility of targeting low levels of physical activity in PSS

A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes

dentification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined T1D+T2D GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 subjects with diabetes (18,582 with DKD). Analysis of specific DKD phenotypes identified a novel signal near GABRR1 (rs9942471, P = 4.5 x 10(-8)) associated with microalbuminuria in European T2D case subjects. However, no replication of this signal was observed in Asian subjects with T2D or in the equivalent T1D analysis. There was only limited support, in this substantially enlarged analysis, for association at previously reported DKD signals, except for those at UMOD and PRKAG2, both associated with estimated glomerular filtration rate. We conclude that, despite challenges in addressing phenotypic heterogeneity, access to increased sample sizes will continue to provide more robust inference regarding risk variant discovery for DKD.Peer reviewe

Occupant productivity and office indoor environment quality : a review of the literature

The purpose of this paper is to review the existing literature to draw an understanding of the relationship between indoor environmental quality and occupant productivity in an office environment. The study reviews over 300 papers from 67 journals, conference articles and books focusing on indoor environment, occupant comfort, productivity and green buildings. It limits its focus to the physical aspects of an office environment. The literature outlines eight Indoor Environmental Quality (IEQ) factors that influence occupant productivity in an office environment. It also discusses different physical parameters under each of the IEQ factors. It proposes a conceptual model of different factors affecting occupant productivity. The study also presents a review of the data collection methods utilised by the research studies that aim to investigate the relationship between IEQ and occupant productivity. The study presents a comprehensive discussion and analysis of different IEQ factors that affect occupant productivity. The paper provides a concise starting point for future researchers interested in the area of indoor environmental quality