Walks4work: Rationale and study design to investigate walking at lunchtime in the workplace setting

Background: Following recruitment of a private sector company, an 8week lunchtime walking intervention was implemented to examine the effect of the intervention on modifiable cardiovascular disease risk factors, and further to see if walking environment had any further effect on the cardiovascular disease risk factors. Methods. For phase 1 of the study participants were divided into three groups, two lunchtime walking intervention groups to walk around either an urban or natural environment twice a week during their lunch break over an 8week period. The third group was a waiting-list control who would be invited to join the walking groups after phase 1. In phase 2 all participants were encouraged to walk during their lunch break on self-selecting routes. Health checks were completed at baseline, end of phase 1 and end of phase 2 in order to measure the impact of the intervention on cardiovascular disease risk. The primary outcome variables of heart rate and heart rate variability were measured to assess autonomic function associated with cardiovascular disease. Secondary outcome variables (Body mass index, blood pressure, fitness, autonomic response to a stressor) related to cardiovascular disease were also measured. The efficacy of the intervention in increasing physical activity was objectively monitored throughout the 8-weeks using an accelerometer device. Discussion. The results of this study will help in developing interventions with low researcher input with high participant output that may be implemented in the workplace. If effective, this study will highlight the contribution that natural environments can make in the reduction of modifiable cardiovascular disease risk factors within the workplace. © 2012 Brown et al.; licensee BioMed Central Ltd

A novel approach to simulate gene-environment interactions in complex diseases

Background: Complex diseases are multifactorial traits caused by both genetic and environmental factors. They represent the major part of human diseases and include those with largest prevalence and mortality (cancer, heart disease, obesity, etc.). Despite a large amount of information that has been collected about both genetic and environmental risk factors, there are few examples of studies on their interactions in epidemiological literature. One reason can be the incomplete knowledge of the power of statistical methods designed to search for risk factors and their interactions in these data sets. An improvement in this direction would lead to a better understanding and description of gene-environment interactions. To this aim, a possible strategy is to challenge the different statistical methods against data sets where the underlying phenomenon is completely known and fully controllable, for example simulated ones. Results: We present a mathematical approach that models gene-environment interactions. By this method it is possible to generate simulated populations having gene-environment interactions of any form, involving any number of genetic and environmental factors and also allowing non-linear interactions as epistasis. In particular, we implemented a simple version of this model in a Gene-Environment iNteraction Simulator (GENS), a tool designed to simulate case-control data sets where a one gene-one environment interaction influences the disease risk. The main aim has been to allow the input of population characteristics by using standard epidemiological measures and to implement constraints to make the simulator behaviour biologically meaningful. Conclusions: By the multi-logistic model implemented in GENS it is possible to simulate case-control samples of complex disease where gene-environment interactions influence the disease risk. The user has full control of the main characteristics of the simulated population and a Monte Carlo process allows random variability. A knowledge-based approach reduces the complexity of the mathematical model by using reasonable biological constraints and makes the simulation more understandable in biological terms. Simulated data sets can be used for the assessment of novel statistical methods or for the evaluation of the statistical power when designing a study

Functional divergence in the role of N-linked glycosylation in smoothened signaling

The G protein-coupled receptor (GPCR) Smoothened (Smo) is the requisite signal transducer of the evolutionarily conserved Hedgehog (Hh) pathway. Although aspects of Smo signaling are conserved from Drosophila to vertebrates, significant differences have evolved. These include changes in its active sub-cellular localization, and the ability of vertebrate Smo to induce distinct G protein-dependent and independent signals in response to ligand. Whereas the canonical Smo signal to Gli transcriptional effectors occurs in a G protein-independent manner, its non-canonical signal employs Gαi. Whether vertebrate Smo can selectively bias its signal between these routes is not yet known. N-linked glycosylation is a post-translational modification that can influence GPCR trafficking, ligand responsiveness and signal output. Smo proteins in Drosophila and vertebrate systems harbor N-linked glycans, but their role in Smo signaling has not been established. Herein, we present a comprehensive analysis of Drosophila and murine Smo glycosylation that supports a functional divergence in the contribution of N-linked glycans to signaling. Of the seven predicted glycan acceptor sites in Drosophila Smo, one is essential. Loss of N-glycosylation at this site disrupted Smo trafficking and attenuated its signaling capability. In stark contrast, we found that all four predicted N-glycosylation sites on murine Smo were dispensable for proper trafficking, agonist binding and canonical signal induction. However, the under-glycosylated protein was compromised in its ability to induce a non-canonical signal through Gαi, providing for the first time evidence that Smo can bias its signal and that a post-translational modification can impact this process. As such, we postulate a profound shift in N-glycan function from affecting Smo ER exit in flies to influencing its signal output in mice

Reduced functional measure of cardiovascular reserve predicts admission to critical care unit following kidney transplantation

Background: There is currently no effective preoperative assessment for patients undergoing kidney transplantation that is able to identify those at high perioperative risk requiring admission to critical care unit (CCU). We sought to determine if functional measures of cardiovascular reserve, in particular the anaerobic threshold (VO2AT) could identify these patients. Methods: Adult patients were assessed within 4 weeks prior to kidney transplantation in a University hospital with a 37-bed CCU, between April 2010 and June 2012. Cardiopulmonary exercise testing (CPET), echocardiography and arterial applanation tonometry were performed. Results: There were 70 participants (age 41.7614.5 years, 60% male, 91.4% living donor kidney recipients, 23.4% were desensitized). 14 patients (20%) required escalation of care from the ward to CCU following transplantation. Reduced anaerobic threshold (VO2AT) was the most significant predictor, independently (OR = 0.43; 95% CI 0.27–0.68; p,0.001) and in the multivariate logistic regression analysis (adjusted OR = 0.26; 95% CI 0.12–0.59; p = 0.001). The area under the receiveroperating- characteristic curve was 0.93, based on a risk prediction model that incorporated VO2AT, body mass index and desensitization status. Neither echocardiographic nor measures of aortic compliance were significantly associated with CCU admission. Conclusions: To our knowledge, this is the first prospective observational study to demonstrate the usefulness of CPET as a preoperative risk stratification tool for patients undergoing kidney transplantation. The study suggests that VO2AT has the potential to predict perioperative morbidity in kidney transplant recipients

Evolutionary connectionism: algorithmic principles underlying the evolution of biological organisation in evo-devo, evo-eco and evolutionary transitions

The mechanisms of variation, selection and inheritance, on which evolution by natural selection depends, are not fixed over evolutionary time. Current evolutionary biology is increasingly focussed on understanding how the evolution of developmental organisations modifies the distribution of phenotypic variation, the evolution of ecological relationships modifies the selective environment, and the evolution of reproductive relationships modifies the heritability of the evolutionary unit. The major transitions in evolution, in particular, involve radical changes in developmental, ecological and reproductive organisations that instantiate variation, selection and inheritance at a higher level of biological organisation. However, current evolutionary theory is poorly equipped to describe how these organisations change over evolutionary time and especially how that results in adaptive complexes at successive scales of organisation (the key problem is that evolution is self-referential, i.e. the products of evolution change the parameters of the evolutionary process). Here we first reinterpret the central open questions in these domains from a perspective that emphasises the common underlying themes. We then synthesise the findings from a developing body of work that is building a new theoretical approach to these questions by converting well-understood theory and results from models of cognitive learning. Specifically, connectionist models of memory and learning demonstrate how simple incremental mechanisms, adjusting the relationships between individually-simple components, can produce organisations that exhibit complex system-level behaviours and improve the adaptive capabilities of the system. We use the term “evolutionary connectionism” to recognise that, by functionally equivalent processes, natural selection acting on the relationships within and between evolutionary entities can result in organisations that produce complex system-level behaviours in evolutionary systems and modify the adaptive capabilities of natural selection over time. We review the evidence supporting the functional equivalences between the domains of learning and of evolution, and discuss the potential for this to resolve conceptual problems in our understanding of the evolution of developmental, ecological and reproductive organisations and, in particular, the major evolutionary transitions

A rapidly spinning supermassive black hole at the centre of NGC 1365

Broad X-ray emission lines from neutral and partially ionized iron observed in active galaxies have been interpreted as fluorescence produced by the reflection of hard X-rays off the inner edge of an accretion disk. In this model, line broadening and distortion result from rapid rotation and relativistic effects near the black hole, the line shape being sensitive to its spin. Alternative models in which the distortions result from absorption by intervening structures provide an equally good description of the data, and there has been no general agreement on which is correct. Recent claims that the black hole (2 × 10^6 solar masses) at the centre of the galaxy NGC 1365 is rotating at close to its maximum possible speed rest on the assumption of relativistic reflection. Here we report X-ray observations of NGC 1365 that reveal the relativistic disk features through broadened Fe-line emission and an associated Compton scattering excess of 10–30 kiloelectronvolts. Using temporal and spectral analyses, we disentangle continuum changes due to time-variable absorption from reflection, which we find arises from a region within 2.5 gravitational radii of the rapidly spinning black hole. Absorption-dominated models that do not include relativistic disk reflection can be ruled out both statistically and on physical grounds

Phenotypic Variation and Bistable Switching in Bacteria

Microbial research generally focuses on clonal populations. However, bacterial cells with identical genotypes frequently display different phenotypes under identical conditions. This microbial cell individuality is receiving increasing attention in the literature because of its impact on cellular differentiation, survival under selective conditions, and the interaction of pathogens with their hosts. It is becoming clear that stochasticity in gene expression in conjunction with the architecture of the gene network that underlies the cellular processes can generate phenotypic variation. An important regulatory mechanism is the so-called positive feedback, in which a system reinforces its own response, for instance by stimulating the production of an activator. Bistability is an interesting and relevant phenomenon, in which two distinct subpopulations of cells showing discrete levels of gene expression coexist in a single culture. In this chapter, we address techniques and approaches used to establish phenotypic variation, and relate three well-characterized examples of bistability to the molecular mechanisms that govern these processes, with a focus on positive feedback.

Assessment of multispectral and hyperspectral imaging systems for digitisation of a Russian icon

In a study of multispectral and hyperspectral reflectance imaging, a Round Robin Test assessed the performance of different systems for the spectral digitisation of artworks. A Russian icon, mass-produced in Moscow in 1899, was digitised by ten institutions around Europe. The image quality was assessed by observers, and the reflectance spectra at selected points were reconstructed to characterise the icon’s colourants and to obtain a quantitative estimate of accuracy. The differing spatial resolutions of the systems affected their ability to resolve fine details in the printed pattern. There was a surprisingly wide variation in the quality of imagery, caused by unwanted reflections from both glossy painted and metallic gold areas of the icon’s surface. Specular reflection also degraded the accuracy of the reconstructed reflectance spectrum in some places, indicating the importance of control over the illumination geometry. Some devices that gave excellent results for matte colour charts proved to have poor performance for this demanding test object. There is a need for adoption of standards for digitising cultural heritage objects to achieve greater consistency of system performance and image quality.This article arose out of a Short-Term Scientific Mission (STSM) conducted by Tatiana Vitorino when visiting University College London during a 2-week period in late October 2015. The research was carried out under the auspices of the European COST Action TD1201 Colour and Space in Cultural Heritage (COSCH). The project website is at http://www.cosch.info. Under the COST rules, TV received funding for travel and accommodation expenses, and all coauthors were able to claim travel expenses to attend the subsequent COSCH project meeting. No other funding was received from COSCH for labour or equipment and all work was done on a voluntary pro bono basis.info:eu-repo/semantics/publishedVersio

Overview of systematic reviews of therapeutic ranges : methodologies and recommendations for practice

BACKGROUND: Many medicines are dosed to achieve a particular therapeutic range, and monitored using therapeutic drug monitoring (TDM). The evidence base for a therapeutic range can be evaluated using systematic reviews, to ensure it continues to reflect current indications, doses, routes and formulations, as well as updated adverse effect data. There is no consensus on the optimal methodology for systematic reviews of therapeutic ranges. METHODS: An overview of systematic reviews of therapeutic ranges was undertaken. The following databases were used: Cochrane Database of Systematic Reviews (CDSR), Database of Abstracts and Reviews of Effects (DARE) and MEDLINE. The published methodologies used when systematically reviewing the therapeutic range of a drug were analyzed. Step by step recommendations to optimize such systematic reviews are proposed. RESULTS: Ten systematic reviews that investigated the correlation between serum concentrations and clinical outcomes encompassing a variety of medicines and indications were assessed. There were significant variations in the methodologies used (including the search terms used, data extraction methods, assessment of bias, and statistical analyses undertaken). Therapeutic ranges should be population and indication specific and based on clinically relevant outcomes. Recommendations for future systematic reviews based on these findings have been developed. CONCLUSION: Evidence based therapeutic ranges have the potential to improve TDM practice. Current systematic reviews investigating therapeutic ranges have highly variable methodologies and there is no consensus of best practice when undertaking systematic reviews in this field. These recommendations meet a need not addressed by standard protocols

Supporting the education and wellbeing of children looked-after: what is the role of the virtual school?

The Children and Families Act (2014) placed a statutory responsibility on local authorities in the United Kingdom to establish a Virtual School Headteacher with the role of championing the education of all children looked-after within that authority. The current research was designed to illuminate how Virtual Schools are currently supporting educational outcomes for children looked-after, not only through educational interventions, but also through supporting broader psychological factors that might impact on attainment such as attachment, relationships and mental health. Virtual School Head Teachers from 29 local authorities completed an online survey about the services they provided to three target groups – children looked-after, foster carers and schools – with a particular focus on the transition years from primary to secondary school, which have been identified as being a difficult time for children looked-after. Using inductive thematic analysis four overarching themes to service provision were identified: Enhanced learning opportunities; Specific Transition Support; Wellbeing and Relationships, and Raising Awareness. Direct work, interprofessional working and the development of supportive environments, particularly guided by attachment theory, were identified as important areas of practice. Practice is discussed in relation to resilience and ecological systems theory and suggestions for future research are identified