Vitamin D deficiency is associated with tuberculosis disease in British children

Background53Basic science, epidemiological and interventional research supports a link between vitamin D and 54tuberculosis immunity, infection and disease. We evaluated the association between vitamin D 55levels and tuberculosis (TB) infection and disease in UK children recruited to the NIHR IGRA Kids 56Study (NIKS).57Methods58Children presenting between 2011-2014 were eligible if they had history of exposure to an adult 59case with sputum smear/culture-positive TB, or were referred and diagnosed with TB disease. 60Children were assessed at baseline and 6-8 weeks for immunological evidence of TB infection (IGRA 61and/or tuberculin skin test) and evidence of TB disease. Some centres routinely measured total 25-62hydroxy vitamin D levels.63Results64166 children were included. Median 25-hydroxy vitamin D levels were higher in uninfected children 65(45.5 nmol/l) compared to those with infection (36.2 nmol/l) and disease (20.0 nmol/l). The 66difference between TB infection and disease was statistically significant (p<0.001). By logistic 67regression, lower vitamin D levels were associated with TB disease among participants with 68infection/disease, with no evidence of confounding by age, sex, BCG status, ethnicity, non-contact 69referral, season or centre.70Conclusion71Children with TB disease had lower vitamin D levels than children with infection. Implications for 72prevention and treatment remain to be established

BEER - The Beamline for European Materials Engineering Research at the ESS

The Beamline for European Materials Engineering Research (BEER) will be built at the European Spallation Source (ESS). The diffractometer utilizes the high brilliance of the long-pulse neutron source and offers high instrument flexibility. It includes a novel chopper technique that extracts several short pulses out of the long pulse, leading to substantial intensity gain of up to an order of magnitude compared to pulse shaping methods for materials with high crystal symmetry. This intensity gain is achieved without compromising resolution. Materials of lower crystal symmetry or multi-phase materials will be investigated by additional pulse shaping methods. The different chopper set-ups and advanced beam extracting techniques offer an extremely broad intensity/resolution range. Furthermore, BEER offers an option of simultaneous SANS or imaging measurements without compromising diffraction investigations. This flexibility opens up new possibilities for in-situ experiments studying materials processing and performance under operation conditions. To fulfil this task, advanced sample environments, dedicated to thermo-mechanical processing, are foreseen

Development and validation of the predicted heat strain model

Abstract Eight laboratories participated in a concerted research project on the assessment of hot working conditions. The objectives were, among others, to co-ordinate the work of the main European research teams in the field of thermal factors and to improve the methods available to assess the risks of heat disorders at the workplace, and in particular the "Required Sweat Rate" model as presented in International Standard ISO 7933 Standard (1989). The scientific bases of this standard were thoroughly reviewed and a revised model, called "Predicted Heat Strain" (PHS), was developed. This model was then used to predict the minute by minute sweat rates and rectal temperatures during 909 laboratory and field experiments collected from the partners. The Pearson correlation coefficients between observed and predicted values were equal to 0.76 and 0.66 for laboratory experiments and 0.74 and 0.59 for field experiments, respectively, for the sweat rates and the rectal temperatures. The change in sweat rate with time was predicted more accurately by the PHS model than by the required sweat rate model. This suggests that the PHS model would provide an improved basis upon which to determine allowable exposure times from the predicted heat strain in terms of dehydration and increased core temperature

Adiposity, Dysmetabolic Traits, and Earlier Onset of Female Puberty in Adolescent Offspring of Women With Gestational Diabetes Mellitus: A Clinical Study Within the Danish National Birth Cohort

OBJECTIVE Offspring of pregnancies affected by gestational diabetes mellitus (GDM) are at increased risk of the development of type 2 diabetes. However, the extent to which these dysmetabolic traits may be due to offspring and/or maternal adiposity is unknown. We examined body composition and associated cardiometabolic traits in 561 9- to 16-year-old offspring of mothers with GDM and 597 control offspring. RESEARCH DESIGN AND METHODS We measured anthropometric characteristics; puberty status; blood pressure; and fasting glucose, insulin, C-peptide, and lipid levels; and conducted a DEXA scan in a subset of the cohort. Differences in the outcomes between offspring of mothers with GDM and control subjects were examined using linear and logistic regression models. RESULTS After adjustment for age and sex, offspring of mothers with GDM displayed higher weight, BMI, waist-to-hip ratio (WHR), systolic blood pressure, and resting heart rate and lower height. Offspring of mothers with GDM had higher total and abdominal fat percentages and lower muscle mass percentages, but these differences disappeared after correction for offspring BMI. The offspring of mothers with GDM displayed higher fasting plasma glucose, insulin, C-peptide, HOMA-insulin resistance (IR), and plasma triglyceride levels, whereas fasting plasma HDL cholesterol levels were decreased. Female offspring of mothers with GDM had an earlier onset of puberty than control offspring. Offspring of mothers with GDM had significantly higher BMI, WHR, fasting glucose, and HOMA-IR levels after adjustment for maternal prepregnancy BMI, and glucose and HOMA-IR remained elevated in the offspring of mothers with GDM after correction for both maternal and offspring BMIs. CONCLUSIONS In summary, adolescent offspring of women with GDM show increased adiposity, an adverse cardiometabolic profile, and earlier onset of puberty among girls. Increased fasting glucose and HOMA-IR levels among the offspring of mothers with GDM may be explained by the programming effects of hyperglycemia in pregnancy. </jats:sec

Helical Chirality: a Link between Local Interactions and Global Topology in DNA

DNA supercoiling plays a major role in many cellular functions. The global DNA conformation is however intimately linked to local DNA-DNA interactions influencing both the physical properties and the biological functions of the supercoiled molecule. Juxtaposition of DNA double helices in ubiquitous crossover arrangements participates in multiple functions such as recombination, gene regulation and DNA packaging. However, little is currently known about how the structure and stability of direct DNA-DNA interactions influence the topological state of DNA. Here, a crystallographic analysis shows that due to the intrinsic helical chirality of DNA, crossovers of opposite handedness exhibit markedly different geometries. While right-handed crossovers are self-fitted by sequence-specific groove-backbone interaction and bridging Mg2+ sites, left-handed crossovers are juxtaposed by groove-groove interaction. Our previous calculations have shown that the different geometries result in differential stabilisation in solution, in the presence of divalent cations. The present study reveals that the various topological states of the cell are associated with different inter-segmental interactions. While the unstable left-handed crossovers are exclusively formed in negatively supercoiled DNA, stable right-handed crossovers constitute the local signature of an unusual topological state in the cell, such as the positively supercoiled or relaxed DNA. These findings not only provide a simple mechanism for locally sensing the DNA topology but also lead to the prediction that, due to their different tertiary intra-molecular interactions, supercoiled molecules of opposite signs must display markedly different physical properties. Sticky inter-segmental interactions in positively supercoiled or relaxed DNA are expected to greatly slow down the slithering dynamics of DNA. We therefore suggest that the intrinsic helical chirality of DNA may have oriented the early evolutionary choices for DNA topology

Mapping children's presence in the neighbourhood

Within the work of Gert Biesta, public spaces are considered as the main fields where processes of civic learning can take place. Learning is always “in place and time”. Place matters, not only as a spatial background or set of conditions , but as a pedagogical process in itself. So in order to facilitate processes of civic learning we need to understand how spaces function as a co-educator in its own right.. In my PhD I studied how the neighbourhood can be understood as a co-educator. The processes through which children are socialised into a given order are not universal, nor neutral. One might state that children grow up into very different orders. The neighbourhood is an important factor into these diversified socialisation processes, but the neighbourhood is also made by its residents and users themselves, including children. This emphasises that socialisation is a relational process and not a functional oneway introduction of children into a prescribed social ordeIn this contribution, a methodological framework will be developed for understanding and studying the neighbourhood of children as a co-educator. The basis of this framework is formed by the synergy between spatial, social and personal dimensions of the neighbourhood

Behavior Modes, Pathways and Overall Trajectories: Eigenvector and Eigenvalue Analysis of Dynamic Systems

One of the most fundamental principles in system dynamics is the premise that the structure of the system will generate its behavior. Such philosophical position has fostered the development of a number of formal methods aimed at understanding the causes of model behavior. To most in the field of system dynamics, behavior is commonly understood as modes of behavior (e.g., exponential growth, exponential decay, and oscillation) because of their direct association with the feedback loops (e.g., reinforcing, balancing, and balancing with delays, respectively) that generate them. Hence, traditional research on formal model analysis has emphasized which loops cause a particular “mode” of behavior, with eigenvalues representing the most important link between structure and behavior. The main contribution of this work arises from a choice to focus our analysis in the overall trajectory of a state variable – a broader definition of behavior than that of a specific behavior mode. When we consider overall behavior trajectories, contributions from eigenvectors are just as central as those from eigenvalues. Our approach to understanding model behavior derives an equation describing overall behavior trajectories in terms of both eigenvalues and eigenvectors. We then use the derivatives of both eigenvalues and eigenvectors with respect to link (or loop) gains to measure how they affect overall behavior trajectories over time. The direct consequence of focusing on behavior trajectories is that system dynamics researchers' reliance on eigenvalue elasticities can be seen as too-narrow a focus on model behavior – a focus that has excluded the short term impact of a change in loop (or link) gain in its analysis

Implementation of an End-to-End Standards-based Patient Monitoring Solution

A proof-of-concept design of a patient monitoring solution for intensive care unit environments has been presented. It is end-to-end standard-based, using ISO/IEEE 11073 (X73) in the bedside environment and EN13606 to communicate the information to an electronic healthcare record (EHR) server. At the bedside end, the system is a plug-and-play sensor network communicating with a gateway that collects medical information and sends the data to a monitoring server. The monitoring server transforms this information into an EN13606 extract to be stored on the EHR server. The system has been implemented to comply with the last X73 and EN13606 available versions and tested in a laboratory environment to demonstrate the feasibility of an end-to-end standard-based solution

The proteoglycan osteoglycin/mimecan is correlated with arteriogenesis

Arteriogenesis or collateral growth is able to compensate for the stenosis of major arteries. Using differential display RT-PCR on growing and quiescent collateral arteries in a rabbit femoral artery ligation model, we cloned the rabbit full-length cDNA of osteoglycin/mimecan. Osteoglycin was present in the adventitia of collateral arteries as a glycosylated protein without keratan sulfate side chains, mainly produced by smooth muscle cells (SMCs) and perivascular fibroblasts. Northern blot, Western blot, and immunohistochemistry confirmed a collateral artery-specific downregulation of osteoglycin from 6 h to 3 weeks after the onset of arteriogenesis. Treatment of primary SMCs with the arteriogenic protein fibroblast growth factor-2 (FGF-2) resulted in a similar reduction of osteoglycin expression as observed in vivo. Application of the FGF-2 inhibitor polyanethole sulfonic acid (PAS) blocked the downregulation of osteoglycin and interfered with arteriogenesis. From our study we conclude that downregulation of osteoglycin is a fundamental requirement for proper arteriogenesis