Associations between diabetes and both cardiovascular disease and all-cause mortality are modified by grip strength: evidence from UK Biobank, a prospective population-based cohort study

OBJECTIVE Grip strength and diabetes are predictors of mortality and cardiovascular disease (CVD), but whether these risk factors interact to predispose to adverse health outcomes is unknown. This study determined the interactions between diabetes and grip strength and their association with health outcomes. RESEARCH DESIGN AND METHODS We undertook a prospective, general population cohort study by using UK Biobank. Cox proportional hazards models were used to explore the associations between both grip strength and diabetes and the outcomes of all-cause mortality and CVD incidence/mortality as well as to test for interactions between diabetes and grip strength. RESULTS 347,130 UK Biobank participants with full data available (mean age 55.9 years, BMI 27.2 kg/m2, 54.2% women) were included in the analysis, of which 13,373 (4.0%) had diabetes. Over a median follow-up of 4.9 years (range 3.3–7.8 years), 6,209 died (594 as a result of CVD), and 4,301 developed CVD. Participants with diabetes were at higher risk of all-cause and CVD mortality and CVD incidence. Significant interactions (P < 0.05) existed whereby the risk of CVD mortality was higher in participants with diabetes with low (hazard ratio [HR] 4.05 [95% CI 2.72, 5.80]) versus high (HR 1.46 [0.87, 2.46]) grip strength. Similar results were observed for all-cause mortality and CVD incidence. CONCLUSIONS Risk of adverse health outcomes among people with diabetes is lower in those with high grip strength. Low grip strength may be useful to identify a higher-risk subgroup of patients with diabetes. Intervention studies are required to determine whether resistance exercise can reduce risk

Sedimentological characterization of Antarctic moraines using UAVs and Structure-from-Motion photogrammetry

In glacial environments particle-size analysis of moraines provides insights into clast origin, transport history, depositional mechanism and processes of reworking. Traditional methods for grain-size classification are labour-intensive, physically intrusive and are limited to patch-scale (1m2) observation. We develop emerging, high-resolution ground- and unmanned aerial vehicle-based ‘Structure-from-Motion’ (UAV-SfM) photogrammetry to recover grain-size information across an moraine surface in the Heritage Range, Antarctica. SfM data products were benchmarked against equivalent datasets acquired using terrestrial laser scanning, and were found to be accurate to within 1.7 and 50mm for patch- and site-scale modelling, respectively. Grain-size distributions were obtained through digital grain classification, or ‘photo-sieving’, of patch-scale SfM orthoimagery. Photo-sieved distributions were accurate to <2mm compared to control distributions derived from dry sieving. A relationship between patch-scale median grain size and the standard deviation of local surface elevations was applied to a site-scale UAV-SfM model to facilitate upscaling and the production of a spatially continuous map of the median grain size across a 0.3 km2 area of moraine. This highly automated workflow for site scale sedimentological characterization eliminates much of the subjectivity associated with traditional methods and forms a sound basis for subsequent glaciological process interpretation and analysis

Jubilee mugs:the monarchy and the Sex Pistols

With rare exceptions sociologists have traditionally had little to say about the British monarchy. In the exceptional cases of the Durkheimian functionalism of Shills and Young (1953), the left humanism of Birnbaum (1955), or the archaic state/backward nation thesis of Nairn (1988), the British nation has been conceived as a homogenous mass. The brief episode of the Sex Pistols' Jubilee year song 'God Save the Queen' exposed some of the divisions within the national 'mass', forcing a re-ordering of the balance between detachment and belonging to the Royal idea. I argue that the song acted as a kind of 'breaching experiment'. Its wilful provocation of Royalist sentiment revealed the level of sanction available to the media-industrial complex to enforce compliance to British self-images of loyal and devoted national communicants

Disease-associated XMRV sequences are consistent with laboratory contamination

BACKGROUND: Xenotropic murine leukaemia viruses (MLV-X) are endogenous gammaretroviruses that infect cells from many species, including humans. Xenotropic murine leukaemia virus-related virus (XMRV) is a retrovirus that has been the subject of intense debate since its detection in samples from humans with prostate cancer (PC) and chronic fatigue syndrome (CFS). Controversy has arisen from the failure of some studies to detect XMRV in PC or CFS patients and from inconsistent detection of XMRV in healthy controls. RESULTS: Here we demonstrate that Taqman PCR primers previously described as XMRV-specific can amplify common murine endogenous viral sequences from mouse suggesting that mouse DNA can contaminate patient samples and confound specific XMRV detection. To consider the provenance of XMRV we sequenced XMRV from the cell line 22Rv1, which is infected with an MLV-X that is indistinguishable from patient derived XMRV. Bayesian phylogenies clearly show that XMRV sequences reportedly derived from unlinked patients form a monophyletic clade with interspersed 22Rv1 clones (posterior probability >0.99). The cell line-derived sequences are ancestral to the patient-derived sequences (posterior probability >0.99). Furthermore, pol sequences apparently amplified from PC patient material (VP29 and VP184) are recombinants of XMRV and Moloney MLV (MoMLV) a virus with an envelope that lacks tropism for human cells. Considering the diversity of XMRV we show that the mean pairwise genetic distance among env and pol 22Rv1-derived sequences exceeds that of patient-associated sequences (Wilcoxon rank sum test: p = 0.005 and p < 0.001 for pol and env, respectively). Thus XMRV sequences acquire diversity in a cell line but not in patient samples. These observations are difficult to reconcile with the hypothesis that published XMRV sequences are related by a process of infectious transmission. CONCLUSIONS: We provide several independent lines of evidence that XMRV detected by sensitive PCR methods in patient samples is the likely result of PCR contamination with mouse DNA and that the described clones of XMRV arose from the tumour cell line 22Rv1, which was probably infected with XMRV during xenografting in mice. We propose that XMRV might not be a genuine human pathogen

Noise Producing Toys and the Efficacy of Product Standard Criteria to Protect Health and Education Outcomes

An evaluation of 28 commercially available toys imported into New Zealand revealed that 21% of these toys do not meet the acoustic criteria in the ISO standard, ISO 8124-1:2009 Safety of Toys, adopted by Australia and New Zealand as AS/NZS ISO 8124.1:2010. While overall the 2010 standard provided a greater level of protection than the earlier 2002 standard, there was one high risk toy category where the 2002 standard provided greater protection. A secondary set of toys from the personal collections of children known to display atypical methods of play with toys, such as those with autism spectrum disorders (ASD), was part of the evaluation. Only one of these toys cleanly passed the 2010 standard, with the remainder failing or showing a marginal-pass. As there is no tolerance level stated in the standards to account for interpretation of data and experimental error, a value of +2 dB was used. The findings of the study indicate that the current standard is inadequate in providing protection against excessive noise exposure. Amendments to the criteria have been recommended that apply to the recently adopted 2013 standard. These include the integration of the new approaches published in the recently amended European standard (EN 71) on safety of toys

A Novel Method to Predict Carbohydrate and Energy Expenditure during Endurance Exercise Using Measures of Training Load

Background: Sports nutrition guidelines recommend carbohydrate (CHO) intake be individualized to the athlete and modulated according to changes in training load (TL). However, there are limited methods to assess CHO utilization during training sessions. Objectives: To 1) quantify bivariate relationships between both CHO and overall energy expenditure (EE) during exercise and commonly-used, non-invasive measures of TL across sessions of varying duration and intensity, and 2) build and evaluate prediction models to estimate CHO utilization and EE with the same TL measures and easily-quantified individual factors. Methods: This study was undertaken in two parts — a primary study, where participants performed four different laboratory-based cycle training sessions, and a validation study where different participants performed a single laboratory-based training session using one of three exercise modalities (cycling, running, or kayaking). The primary study included 15 cyclists (5 f; VdO2max, 52 ± 7 mL.kg-1.min-1), the validation study included 21 cyclists (7 f; VdO2max 53.5 ± 11.0 mL.kg-1.min-1), 20 runners (6 f; VdO2max 57.5 ± 7.2 mL.kg-1.min-1), and 17 kayakers (4 f; VdO2max 46.2 ± 4.1 mL.kg-1.min-1). Training sessions were quantified using six TL metrics: two using heart rate, three using power, and one using perceived exertion. CHO use and EE were determined separately for aerobic (gas exchange) and anaerobic (net lactate accumulation, body mass, and O2 lactate equivalent method) energy systems and summed. Repeated-measures correlations were used to examine relationships between TL and both CHO utilization and EE. General estimating equations were used to model CHO utilization and EE, using TL alongside measures of fitness and sex. Models were built in the primary study and tested in the validation study. Model performance is reported as the coefficient of determination (R2) and mean absolute error (MAE), with measures of calibration used for model evaluation and for sport-specific model re- calibration. Results: Very-large to near-perfect within-subject correlations (r = 0.76–0.96) were evident between all TL metrics and both CHO utilization and EE. In the primary study, all models explained a large amount of variance (R2 = 0.77–0.96) and displayed good accuracy (MAE; CHO = 16–21 g [10–14%], EE = 53–82 kcal [7–11%]). In the validation study the MAE ranged from 17–50 g [15– 45%] for CHO models and 53–178 kcal [9–30%] for EE models. The calibrated MAE ranged from 8–20 g [7–18%] for CHO models and 36–72 kcal [6–12%] for EE models. Conclusion: At the individual level, there are strong linear relationships between all measures of TL and both CHO utilization and EE during cycling. When combined with other measures of fitness, EE and CHO utilization during cycling can be estimated accurately. These models can be applied in running and kayaking when used with a calibration adjustment

Mulat-estetiek: ’n Analise van Adam Small se dramas

Opsomming In hierdie artikel word die dramakonvensies van Adam Small ondersoek met besondere aandag aan perspektiewe op die mulat as ’n sosiale gegewe. Hierdie element bied ’n gepaste invalshoek omdat dit enersyds ‘n verskynsel is wat Small in sy dramas en ander skryfwerk aansny en daar andersyds ’n uitgebreide literatuur bestaan waarin oor die dramatiese, lewensbeskoulike en literêr-teoretiese inkleding daarvan besin word. Die werk van onder andere Langston Hughes en Derek Walcott word ondersoek om ’n leesstrategie te ontwikkel waarmee die Small-teks geanaliseer kan word.Web of Scienc

The Scottish Early Rheumatoid Arthritis (SERA) Study:an inception cohort and biobank

Background: The Scottish Early Rheumatoid Arthritis (SERA) study is an inception cohort of rheumatoid (RA) and undifferentiated arthritis (UA) patients that aims to provide a contemporary description of phenotype and outcome and facilitate discovery of phenotypic and prognostic biomarkers Methods: Demographic and clinical outcome data are collected from newly diagnosed RA/UA patients every 6 months from around Scotland. Health service utilization data is acquired from Information Services Division, NHS National Services Scotland. Plain radiographs of hands and feet are collected at baseline and 12 months. Additional samples of whole blood, plasma, serum and filtered urine are collected at baseline, 6 and 12 months Results: Results are available for 1073 patients; at baseline, 76 % were classified as RA and 24 % as UA. Median time from onset to first review was 163 days (IQR97-323). Methotrexate was first-line DMARD for 75 % patients. Disease activity, functional ability and health-related quality of life improved significantly between baseline and 24 months, however the proportion in any employment fell (51 to 38 %, p = 0.0005). 24 % patients reported symptoms of anxiety and/or depression at baseline. 35/391 (9 %) patients exhibited rapid radiographic progression after 12 months. The SERA Biobank has accrued 60,612 samples Conclusions: In routine care, newly diagnosed RA/UA patients experience significant improvements in disease activity, functional ability and health-related quality of life but have high rates of psychiatric symptoms and declining employment rates. The co-existence of a multi-domain description of phenotype and a comprehensive biobank will facilitate multi-platform translational research to identify predictive markers of phenotype and prognosis

Translational models for vascular cognitive impairment: a review including larger species.

BACKGROUND: Disease models are useful for prospective studies of pathology, identification of molecular and cellular mechanisms, pre-clinical testing of interventions, and validation of clinical biomarkers. Here, we review animal models relevant to vascular cognitive impairment (VCI). A synopsis of each model was initially presented by expert practitioners. Synopses were refined by the authors, and subsequently by the scientific committee of a recent conference (International Conference on Vascular Dementia 2015). Only peer-reviewed sources were cited. METHODS: We included models that mimic VCI-related brain lesions (white matter hypoperfusion injury, focal ischaemia, cerebral amyloid angiopathy) or reproduce VCI risk factors (old age, hypertension, hyperhomocysteinemia, high-salt/high-fat diet) or reproduce genetic causes of VCI (CADASIL-causing Notch3 mutations). CONCLUSIONS: We concluded that (1) translational models may reflect a VCI-relevant pathological process, while not fully replicating a human disease spectrum; (2) rodent models of VCI are limited by paucity of white matter; and (3) further translational models, and improved cognitive testing instruments, are required

Mutational processes molding the genomes of 21 breast cancers

All cancers carry somatic mutations. The patterns of mutation in cancer genomes reflect the DNA damage and repair processes to which cancer cells and their precursors have been exposed. To explore these mechanisms further, we generated catalogs of somatic mutation from 21 breast cancers and applied mathematical methods to extract mutational signatures of the underlying processes. Multiple distinct single- and double-nucleotide substitution signatures were discernible. Cancers with BRCA1 or BRCA2 mutations exhibited a characteristic combination of substitution mutation signatures and a distinctive profile of deletions. Complex relationships between somatic mutation prevalence and transcription were detected. A remarkable phenomenon of localized hypermutation, termed "kataegis," was observed. Regions of kataegis differed between cancers but usually colocalized with somatic rearrangements. Base substitutions in these regions were almost exclusively of cytosine at TpC dinucleotides. The mechanisms underlying most of these mutational signatures are unknown. However, a role for the APOBEC family of cytidine deaminases is proposed