The diabeates project: Perceptual, affective and psychophysiological effects of music and music-video in a clinical exercise setting

Objectives The purpose of this study was to examine the effects of music and music-video on perceptual (attentional focus, rated perceived exertion), affective (affective valence and enjoyment) and psychophysiological (blood glucose, heart rate) variables in outpatients attending a diabetes exercise clinic. Methods Participants were 24 females (age = 66.0 ± 8.5 years) enrolled in a supervised exercise program for people with diabetes. They engaged in mixed-modality exercise sessions that included a standardized combination of flexibility, aerobic and resistance activities under conditions of music, music-video and control. Results Analyses revealed a main effect of condition on attentional focus and affect during aerobic exercise only. The music-video condition elicited the highest level of attentional dissociation, while affective valence was more positive in the 2 experimental conditions when compared to control. Rated perceived exertion and heart rate did not differ across conditions. Measures of exercise enjoyment indicated a main effect of condition wherein scores were higher with the music-video condition when compared to control. There was an acute glucose-lowering effect of exercise in all conditions. Conclusions Results lend support to the notion that auditory and visual stimuli can enhance affective responses to exercise in a clinical setting. This may have meaningful implications for adherence, given the link between affective judgements and future behaviour in an exercise context

Global Update and Trends of Hidden Hunger, 1995-2011: The Hidden Hunger Index

Background Deficiencies in essential vitamins and minerals–also termed hidden hunger–are pervasive and hold negative consequences for the cognitive and physical development of children. Methods This analysis evaluates the change in hidden hunger over time in the form of one composite indicator–the Hidden Hunger Index (HHI)–using an unweighted average of prevalence estimates from the Nutrition Impact Model Study for anemia due to iron deficiency, vitamin A deficiency, and stunting (used as a proxy indicator for zinc deficiency). Net changes from 1995–2011 and population weighted regional means for various time periods are measured. Findings Globally, hidden hunger improved (-6.7 net change in HHI) from 1995–2011. Africa was the only region to see a deterioration in hidden hunger (+1.9) over the studied time period; East Asia and the Pacific performed exceptionally well (-13.0), while other regions improved only slightly. Improvements in HHI were mostly due to reductions in zinc and vitamin A deficiencies, while anemia due to iron deficiency persisted and even increased. Interpretation This analysis is critical for informing and tracking the impact of policy and programmatic efforts to reduce micronutrient deficiencies, to advance the global nutrition agenda, and to achieve the Millennium Development Goals (MDGs). However, there remains an unmet need to invest in gathering frequent, nationally representative, high-quality micronutrient data as we renew our efforts to scale up nutrition, and as we enter the post-2015 development agenda. Funding Preparation of this manuscript was funded by Sight and Life. There was no funding involved in the study design, data collection, analysis, or decision to publish

Black hole microstate geometries from string amplitudes

In this talk we review recent calculations of the asymptotic supergravity fields sourced by bound states of D1 and D5-branes carrying travelling waves. We compute disk one-point functions for the massless closed string fields. At large distances from the branes, the effective open string coupling is small, even in the regime of parameters where the classical D1-D5-P black hole may be considered. The fields sourced by the branes differ from the black hole solution by various multipole moments, and have led to the construction of a new 1/8-BPS ansatz in type IIB supergravity.Comment: 14 pages, 3 figures, Contribution to the proceedings of the Black Objects in Supergravity School, Frascati, 201

The impact of population-based faecal occult blood test screening on colorectal cancer mortality:a matched cohort study

BACKGROUND: Randomised trials show reduced colorectal cancer (CRC) mortality with faecal occult blood testing (FOBT). This outcome is now examined in a routine, population-based, screening programme. METHODS: Three biennial rounds of the UK CRC screening pilot were completed in Scotland (2000–2007) before the roll out of a national programme. All residents (50–69 years) in the three pilot Health Boards were invited for screening. They received a FOBT test by post to complete at home and return for analysis. Positive tests were followed up with colonoscopy. Controls, selected from non-pilot Health Boards, were matched by age, gender, and deprivation and assigned the invitation date of matched invitee. Follow-up was from invitation date to 31 December 2009 or date of death if earlier. RESULTS: There were 379 655 people in each group (median age 55.6 years, 51.6% male). Participation was 60.6%. There were 961 (0.25%) CRC deaths in invitees, 1056 (0.28%) in controls, rate ratio (RR) 0.90 (95% confidence interval (CI) 0.83–0.99) overall and 0.73 (95% CI 0.65–0.82) for participants. Non-participants had increased CRC mortality compared with controls, RR 1.21 (95% CI 1.06–1.38). CONCLUSION: There was a 10% relative reduction in CRC mortality in a routine screening programme, rising to 27% in participants

Towards Accurate Estimation of the Proportion of True Null Hypotheses in Multiple Testing

BACKGROUND: Biomedical researchers are now often faced with situations where it is necessary to test a large number of hypotheses simultaneously, eg, in comparative gene expression studies using high-throughput microarray technology. To properly control false positive errors the FDR (false discovery rate) approach has become widely used in multiple testing. The accurate estimation of FDR requires the proportion of true null hypotheses being accurately estimated. To date many methods for estimating this quantity have been proposed. Typically when a new method is introduced, some simulations are carried out to show the improved accuracy of the new method. However, the simulations are often very limited to covering only a few points in the parameter space. RESULTS: Here I have carried out extensive in silico experiments to compare some commonly used methods for estimating the proportion of true null hypotheses. The coverage of these simulations is unprecedented thorough over the parameter space compared to typical simulation studies in the literature. Thus this work enables us to draw conclusions globally as to the performance of these different methods. It was found that a very simple method gives the most accurate estimation in a dominantly large area of the parameter space. Given its simplicity and its overall superior accuracy I recommend its use as the first choice for estimating the proportion of true null hypotheses in multiple testing

Multivariate discrimination and the Higgs + W/Z search

A systematic method for optimizing multivariate discriminants is developed and applied to the important example of a light Higgs boson search at the Tevatron and the LHC. The Significance Improvement Characteristic (SIC), defined as the signal efficiency of a cut or multivariate discriminant divided by the square root of the background efficiency, is shown to be an extremely powerful visualization tool. SIC curves demonstrate numerical instabilities in the multivariate discriminants, show convergence as the number of variables is increased, and display the sensitivity to the optimal cut values. For our application, we concentrate on Higgs boson production in association with a W or Z boson with H -> bb and compare to the irreducible standard model background, Z/W + bb. We explore thousands of experimentally motivated, physically motivated, and unmotivated single variable discriminants. Along with the standard kinematic variables, a number of new ones, such as twist, are described which should have applicability to many processes. We find that some single variables, such as the pull angle, are weak discriminants, but when combined with others they provide important marginal improvement. We also find that multiple Higgs boson-candidate mass measures, such as from mild and aggressively trimmed jets, when combined may provide additional discriminating power. Comparing the significance improvement from our variables to those used in recent CDF and DZero searches, we find that a 10-20% improvement in significance against Z/W + bb is possible. Our analysis also suggests that the H + W/Z channel with H -> bb is also viable at the LHC, without requiring a hard cut on the W/Z transverse momentum.Comment: 41 pages, 5 tables, 29 figure

Analysis of host responses to Mycobacterium tuberculosis antigens in a multi-site study of subjects with different TB and HIV infection states in sub-Saharan Africa.

BACKGROUND: Tuberculosis (TB) remains a global health threat with 9 million new cases and 1.4 million deaths per year. In order to develop a protective vaccine, we need to define the antigens expressed by Mycobacterium tuberculosis (Mtb), which are relevant to protective immunity in high-endemic areas. METHODS: We analysed responses to 23 Mtb antigens in a total of 1247 subjects with different HIV and TB status across 5 geographically diverse sites in Africa (South Africa, The Gambia, Ethiopia, Malawi and Uganda). We used a 7-day whole blood assay followed by IFN-γ ELISA on the supernatants. Antigens included PPD, ESAT-6 and Ag85B (dominant antigens) together with novel resuscitation-promoting factors (rpf), reactivation proteins, latency (Mtb DosR regulon-encoded) antigens, starvation-induced antigens and secreted antigens. RESULTS: There was variation between sites in responses to the antigens, presumably due to underlying genetic and environmental differences. When results from all sites were combined, HIV- subjects with active TB showed significantly lower responses compared to both TST(-) and TST(+) contacts to latency antigens (Rv0569, Rv1733, Rv1735, Rv1737) and the rpf Rv0867; whilst responses to ESAT-6/CFP-10 fusion protein (EC), PPD, Rv2029, TB10.3, and TB10.4 were significantly higher in TST(+) contacts (LTBI) compared to TB and TST(-) contacts fewer differences were seen in subjects with HIV co-infection, with responses to the mitogen PHA significantly lower in subjects with active TB compared to those with LTBI and no difference with any antigen. CONCLUSIONS: Our multi-site study design for testing novel Mtb antigens revealed promising antigens for future vaccine development. The IFN-γ ELISA is a cheap and useful tool for screening potential antigenicity in subjects with different ethnic backgrounds and across a spectrum of TB and HIV infection states. Analysis of cytokines other than IFN-γ is currently on-going to determine correlates of protection, which may be useful for vaccine efficacy trials

Small molecules restore the function of mutant CLC5 associated with Dent disease

Dent disease type 1 is caused by mutations in the CLCN5 gene that encodes CLC5, a 2Cl−/H+ exchanger. The CLC5 mutants that have been functionally analysed constitute three major classes based on protein expression, cellular localization and channel function. We tested two small molecules, 4‐phenylbutyrate (4PBA) and its analogue 2‐naphthoxyacetic acid (2‐NOAA), for their effect on mutant CLC5 function and expression by whole‐cell patch‐clamp and Western blot, respectively. The expression and function of non‐Class I CLC5 mutants that have reduced function could be restored by either treatment. Cell viability was reduced in cells treated with 2‐NOAA. 4PBA is a FDA‐approved drug for the treatment of urea cycle disorders and offers a potential therapy for Dent disease

Sodium channel Nav1.6 accumulates at the site of infraorbital nerve injury

<p>Abstract</p> <p>Background</p> <p>Sodium channel (NaCh) expressions change following nerve and inflammatory lesions and this change may contribute to the activation of pain pathways. In a previous study we found a dramatic increase in the size and density of NaCh accumulations, and a remodeling of NaChs at intact and altered myelinated sites at a location just proximal to a combined partial axotomy and chromic suture lesion of the rat infraorbital nerve (ION) with the use of an antibody that identifies all NaCh isoforms. Here we evaluate the contribution of the major nodal NaCh isoform, Na_v1.6, to this remodeling of NaChs following the same lesion. Sections of the ION from normal and ION lesioned subjects were double-stained with antibodies against Na_v1.6 and caspr (contactin-associated protein; a paranodal protein to identify nodes of Ranvier) and then z-series of optically sectioned images were captured with a confocal microscope. ImageJ (NIH) software was used to quantify the average size and density of Na_v1.6 accumulations, while additional single fiber analyses measured the axial length of the nodal gap, and the immunofluorescence intensity of Na_v1.6 in nodes and of caspr in the paranodal region.</p> <p>Results</p> <p>The findings showed a significant increase in the average size and density of Na_v1.6 accumulations in lesioned IONs when compared to normal IONs. The results of the single fiber analyses in caspr-identified typical nodes showed an increased axial length of the nodal gap, an increased immunofluorescence intensity of nodal Na_v1.6 and a decreased immunofluorescence intensity of paranodal caspr in lesioned IONs when compared to normal IONs. In the lesioned IONs, Na_v1.6 accumulations were also seen in association with altered caspr-relationships, such as heminodes.</p> <p>Conclusion</p> <p>The results of the present study identify Na_v1.6 as one isoform involved in the augmentation and remodeling of NaChs at nodal sites following a combined partial axotomy and chromic suture ION lesion. The augmentation of Na_v1.6 may result from an alteration in axon-Schwann cell signaling mechanisms as suggested by changes in caspr expression. The changes identified in this study suggest that the participation of Na_v1.6 should be considered when examining changes in the excitability of myelinated axons in neuropathic pain models.</p

Pulmonary Predictors of Incident Diabetes in Smokers.

BACKGROUND: Diabetes mellitus and its complications are a large and increasing burden for health care worldwide. Reduced pulmonary function has been observed in diabetes (both type 1 and type 2), and this reduction is thought to occur prior to diagnosis. Other measures of pulmonary health are associated with diabetes, including lower exercise tolerance, greater dyspnea, lower quality of life (as measured by the St. George's Respiratory Questionaire [SGRQ]) and susceptibility to lung infection and these measures may also predate diabetes diagnosis. METHODS: We examined 7080 participants in the COPD Genetic Epidemiology (COPDGene) study who did not report diabetes at their baseline visit and who provided health status updates during 4.2 years of longitudinal follow-up (LFU). We used Cox proportional hazards modeling, censoring participants at final LFU contact, reported mortality or report of incident diabetes to model predictors of diabetes. These models were constructed using known risk factors as well as proposed markers related to pulmonary health, forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC, respiratory exacerbations (RE), 6-minute walk distance (6MWD), pulmonary associated quality of life (as measured by the SGRQ), corticosteroid use, chronic bronchitis and dyspnea. RESULTS: Over 21,519 person years of follow-up, 392 of 7080 participants reported incident diabetes which was associated with expected predictors; increased body mass index (BMI), high blood pressure, high cholesterol and current smoking status. Age, gender and accumulated smoking exposure were not associated with incident diabetes. Additionally, preserved ratio with impaired spirometry (PRISm) pattern pulmonary function, reduced 6MWD and any report of serious pulmonary events were associated with incident diabetes. CONCLUSIONS: This cluster of pulmonary indicators may aid clinicians in identifying and treating patients with pre- or undiagnosed diabetes