Associations of sitting behaviours with all-cause mortality over a 16-year follow-up: the Whitehall II study.

PublishedJournal ArticleBACKGROUND: Sitting behaviours have been linked with increased risk of all-cause mortality independent of moderate to vigorous physical activity (MVPA). Previous studies have tended to examine single indicators of sitting or all sitting behaviours combined. This study aims to enhance the evidence base by examining the type-specific prospective associations of four different sitting behaviours as well as total sitting with the risk of all-cause mortality. METHODS: Participants (3720 men and 1412 women) from the Whitehall II cohort study who were free from cardiovascular disease provided information on weekly sitting time (at work, during leisure time, while watching TV, during leisure time excluding TV, and at work and during leisure time combined) and covariates in 1997-99. Cox proportional hazards models were used to investigate prospective associations between sitting time (h/week) and mortality risk. Follow-up was from date of measurement until (the earliest of) death, date of censor or July 31 2014. RESULTS: Over 81 373 person-years of follow-up (mean follow-up time 15.7 ± 2.2 years) a total of 450 deaths were recorded. No associations were observed between any of the five sitting indicators and mortality risk, either in unadjusted models or models adjusted for covariates including MVPA. CONCLUSIONS: Sitting time was not associated with all-cause mortality risk. The results of this study suggest that policy makers and clinicians should be cautious about placing emphasis on sitting behaviour as a risk factor for mortality that is distinct from the effect of physical activity.The Whitehall II study is supported by grants from the Medical Research Council (G0902037), British Heart Foundation (RG/07/008/23674), Stroke Association, National Heart Lung and Blood Institute (5RO1 HL036310) and National Institute on Aging (5RO1AG13196 and 5RO1AG034454). This report is independent research arising partly from a Career Development Fellowship supported by the National Institute for Health Research between 2011 and 2014 (to E.S.). The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health. Open Access publication was funded by grants from the BHF and MRC

OXSR1 inhibits inflammasome activation by limiting potassium efflux during mycobacterial infection.

Pathogenic mycobacteria inhibit inflammasome activation to establish infection. Although it is known that potassium efflux is a trigger for inflammasome activation, the interaction between mycobacterial infection, potassium efflux, and inflammasome activation has not been investigated. Here, we use Mycobacterium marinum infection of zebrafish embryos and Mycobacterium tuberculosis infection of THP-1 cells to demonstrate that pathogenic mycobacteria up-regulate the host WNK signalling pathway kinases SPAK and OXSR1 which control intracellular potassium balance. We show that genetic depletion or inhibition of OXSR1 decreases bacterial burden and intracellular potassium levels. The protective effects of OXSR1 depletion are at least partially mediated by NLRP3 inflammasome activation, caspase-mediated release of IL-1β, and downstream activation of protective TNF-α. The elucidation of this druggable pathway to potentiate inflammasome activation provides a new avenue for the development of host-directed therapies against intracellular infections

Rising adiposity curbing decline in the incidence of myocardial infarction: 20-year follow-up of British men and women in the Whitehall II cohort

Aims To estimate the contribution of risk factor trends to 20-year declines in myocardial infarction (MI) incidence in British men and women. Methods and results From 1985 to 2004, 6379 men and 3074 women in the Whitehall II cohort were followed for incident MI and risk factor trends. Over 20 years, the age-sex-adjusted hazard of MI fell by 74% (95% confidence interval 48-87%), corresponding to an average annual decline of 6.5% (3.2-9.7%). Thirty-four per cent (20-76%) of the decline in MI hazard could be statistically explained by declining non-HDL cholesterol levels, followed by increased HDL cholesterol (17%, 10-32%), reduced systolic blood pressure (13%, 7-24%), and reduced cigarette smoking prevalence (6%, 2-14%). Increased fruit and vegetable consumption made a non-significant contribution of 7% (-1-20%). In combination, these five risk factors explained 56% (34-112%). Rising body mass index (BMI) was counterproductive, reducing the scale of the decline by 11% (5-23%) in isolation. The MI decline and the impact of the risk factors appeared similar for men and women. Conclusion In men and women, over half of the decline in MI risk could be accounted for by favourable risk factor time trends. The adverse role of BMI emphasizes the importance of addressing the rising population BMI

Alcohol Consumption and Common Carotid Intima-Media Thickness: The USE-IMT Study

AIMS: Epidemiological evidence indicates a protective effect of light to moderate alcohol consumption compared to non-drinking and heavy drinking. Although several mechanisms have been suggested, the effect of alcohol on atherosclerotic changes in vessel walls is unclear. Therefore, we explored the relationship between alcohol consumption and common carotid intima media thickness, a marker of early atherosclerosis in the general population. METHODS: Individual participant data from eight cohorts, involving 37,494 individuals from the USE-IMT collaboration were used. Multilevel age and sex adjusted linear regression models were applied to estimate mean differences in common carotid intima-media thickness (CIMT) with alcohol consumption. RESULTS: The mean age was 57.9 years (SD 8.6) and the mean CIMT was 0.75 mm (SD 0.177). About, 40.5% reported no alcohol consumed, and among those who drank, mean consumption was 13.3 g per day (SD 16.4). Those consuming no alcohol or a very small amount (10 g per day, after adjusting for a range of confounding factors. CONCLUSION: In this large CIMT consortium, we did not find evidence to support a protective effect of alcohol on CIMT

Integrating isotopes and documentary evidence : dietary patterns in a late medieval and early modern mining community, Sweden

We would like to thank the Archaeological Research Laboratory, Stockholm University, Sweden and the Tandem Laboratory (Ångström Laboratory), Uppsala University, Sweden, for undertaking the analyses of stable nitrogen and carbon isotopes in both human and animal collagen samples. Also, thanks to Elin Ahlin Sundman for providing the δ13C and δ15N values for animal references from Västerås. This research (Bäckström’s PhD employment at Lund University, Sweden) was supported by the Berit Wallenberg Foundation (BWS 2010.0176) and Jakob and Johan Söderberg’s foundation. The ‘Sala project’ (excavations and analyses) has been funded by Riksens Clenodium, Jernkontoret, Birgit and Gad Rausing’s Foundation, SAU’s Research Foundation, the Royal Physiographic Society of Lund, Berit Wallenbergs Foundation, Åke Wibergs Foundation, Lars Hiertas Memory, Helge Ax:son Johnson’s Foundation and The Royal Swedish Academy of Sciences.Peer reviewedPublisher PD

Radiological staging in breast cancer: which asymptomatic patients to image and how.

BACKGROUND: Approximately 4% of patients diagnosed with early breast cancer have occult metastases at presentation. Current national and international guidelines lack consensus on whom to image and how. METHODS: We assessed practice in baseline radiological staging against local guidelines for asymptomatic newly diagnosed breast cancer patients presenting to the Cambridge Breast Unit over a 9-year period. RESULTS: A total of 2612 patients were eligible for analysis; 91.7% were appropriately investigated. However in the subset of lymph node negative stage II patients, only 269 out of 354 (76.0%) investigations were appropriate. No patients with stage 0 or I disease had metastases; only two patients (0.3%) with stage II and or =4 positive lymph nodes), III and IV disease, respectively. CONCLUSION: These results prompted us to propose new local guidelines for staging asymptomatic breast cancer patients: only clinical stage III or IV patients require baseline investigation. The high specificity and convenience of computed tomography (chest, abdomen and pelvis) led us to recommend this as the investigation of choice in breast cancer patients requiring radiological staging

The Atacama Cosmology Telescope: Two-Season ACTPol Spectra and Parameters

We present the temperature and polarization angular power spectra measured by the Atacama Cosmology Telescope Polarimeter (ACTPol). We analyze night-time data collected during 2013-14 using two detector arrays at 149 GHz, from 548 deg$^2$ of sky on the celestial equator. We use these spectra, and the spectra measured with the MBAC camera on ACT from 2008-10, in combination with Planck and WMAP data to estimate cosmological parameters from the temperature, polarization, and temperature-polarization cross-correlations. We find the new ACTPol data to be consistent with the LCDM model. The ACTPol temperature-polarization cross-spectrum now provides stronger constraints on multiple parameters than the ACTPol temperature spectrum, including the baryon density, the acoustic peak angular scale, and the derived Hubble constant. Adding the new data to planck temperature data tightens the limits on damping tail parameters, for example reducing the joint uncertainty on the number of neutrino species and the primordial helium fraction by 20%.Comment: 23 pages, 25 figure

The Effect of Testing on the Retention of Coherent and Incoherent Text Material

Research has shown that testing during learning can enhance the long-term retention of text material. In two experiments, we investigated the testing effect with a fill-in-the-blank test on the retention of text material. In Experiment 1, using a coherent text, we found no retention benefit of testing compared to a restudy (control) condition. In Experiment 2, text coherence was disrupted by scrambling the order of the sentences from the text. The material was subsequently presented as a list of facts as opposed to connected discourse. For the incoherent version of the text, testing slowed down the rate of forgetting compared to a restudy (control) condition. The results suggest that the connectedness of materials can play an important role in determining the magnitude of testing benefits for long-term retention. Testing with a completion test seems most beneficial for unconnected materials and less so for highly structured materials

Genetic variation in human NPY expression affects stress response and emotion

Understanding inter- individual differences in stress response requires the explanation of genetic influences at multiple phenotypic levels, including complex behaviours and the metabolic responses of brain regions to emotional stimuli. Neuropeptide Y ( NPY) is anxiolytic(1,2) and its release is induced by stress(3). NPY is abundantly expressed in regions of the limbic system that are implicated in arousal and in the assignment of emotional valences to stimuli and memories(4-6). Here we show that haplotype- driven NPY expression predicts brain responses to emotional and stress challenges and also inversely correlates with trait anxiety. NPY haplotypes predicted levels of NPY messenger RNA in postmortem brain and lymphoblasts, and levels of plasma NPY. Lower haplotype- driven NPY expression predicted higher emotion- induced activation of the amygdala, as well as diminished resiliency as assessed by pain/ stress- induced activations of endogenous opioid neurotransmission in various brain regions. A single nucleotide polymorphism ( SNP rs16147) located in the promoter region alters NPY expression in vitro and seems to account for more than half of the variation in expression in vivo. These convergent findings are consistent with the function of NPY as an anxiolytic peptide and help to explain inter- individual variation in resiliency to stress, a risk factor for many diseases.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62768/1/nature06858.pd

Pros and cons of estimating the reproduction number from early epidemic growth rate of influenza A (H1N1) 2009

<p>Abstract</p> <p>Background</p> <p>In many parts of the world, the exponential growth rate of infections during the initial epidemic phase has been used to make statistical inferences on the reproduction number, <it>R</it>, a summary measure of the transmission potential for the novel influenza A (H1N1) 2009. The growth rate at the initial stage of the epidemic in Japan led to estimates for <it>R </it>in the range 2.0 to 2.6, capturing the intensity of the initial outbreak among school-age children in May 2009.</p> <p>Methods</p> <p>An updated estimate of <it>R </it>that takes into account the epidemic data from 29 May to 14 July is provided. An age-structured renewal process is employed to capture the age-dependent transmission dynamics, jointly estimating the reproduction number, the age-dependent susceptibility and the relative contribution of imported cases to secondary transmission. Pitfalls in estimating epidemic growth rates are identified and used for scrutinizing and re-assessing the results of our earlier estimate of <it>R</it>.</p> <p>Results</p> <p>Maximum likelihood estimates of <it>R </it>using the data from 29 May to 14 July ranged from 1.21 to 1.35. The next-generation matrix, based on our age-structured model, predicts that only 17.5% of the population will experience infection by the end of the first pandemic wave. Our earlier estimate of <it>R </it>did not fully capture the population-wide epidemic in quantifying the next-generation matrix from the estimated growth rate during the initial stage of the pandemic in Japan.</p> <p>Conclusions</p> <p>In order to quantify <it>R </it>from the growth rate of cases, it is essential that the selected model captures the underlying transmission dynamics embedded in the data. Exploring additional epidemiological information will be useful for assessing the temporal dynamics. Although the simple concept of <it>R </it>is more easily grasped by the general public than that of the next-generation matrix, the matrix incorporating detailed information (e.g., age-specificity) is essential for reducing the levels of uncertainty in predictions and for assisting public health policymaking. Model-based prediction and policymaking are best described by sharing fundamental notions of heterogeneous risks of infection and death with non-experts to avoid potential confusion and/or possible misuse of modelling results.</p