Intergenerational change and familial aggregation of body mass index

The relationship between parental BMI and that of their adult offspring, when increased adiposity can become a clinical issue, is unknown. We investigated the intergenerational change in body mass index (BMI) distribution, and examined the sex-specific relationship between parental and adult offspring BMI. Intergenerational change in the distribution of adjusted BMI in 1,443 complete families (both parents and at least one offspring) with 2,286 offspring (1,263 daughters and 1,023 sons) from the west of Scotland, UK, was investigated using quantile regression. Familial correlations were estimated from linear mixed effects regression models. The distribution of BMI showed little intergenerational change in the normal range (\25 kg/m2), decreasing overweightness (25– \30 kg/m2) and increasing obesity (C30 kg/m2). Median BMI was static across generations in males and decreased in females by 0.4 (95% CI: 0.0, 0.7) kg/m2; the 95th percentileincreased by 2.2 (1.1, 3.2) kg/m2 in males and 2.7 (1.4, 3.9) kg/m2 in females. Mothers’ BMI was more strongly associated with daughters’ BMI than was fathers’ (correlation coefficient (95% CI): mothers 0.31 (0.27, 0.36), fathers 0.19 (0.14, 0.25); P = 0.001). Mothers’ and fathers’ BMI were equally correlated with sons’ BMI (correlation coefficient: mothers 0.28 (0.22, 0.33), fathers 0.27 (0.22, 0.33). The increase in BMI between generations was concentrated at the upper end of the distribution. This, alongside the strong parent-offspring correlation, suggests that the increase in BMI is disproportionally greater among offspring of heavier parents. Familial influences on BMI among middle-aged women appear significantly stronger from mothers than father

The return of the bursts: Thermonuclear flashes from Circinus X-1

We report the detection of 15 X-ray bursts with RXTE and Swift observations of the peculiar X-ray binary Circinus X-1 during its May 2010 X-ray re-brightening. These are the first X-ray bursts observed from the source after the initial discovery by Tennant and collaborators, twenty-five years ago. By studying their spectral evolution, we firmly identify nine of the bursts as type I (thermonuclear) X-ray bursts. We obtain an arcsecond location of the bursts that confirms once and for all the identification of Cir X-1 as a type I X-ray burst source, and therefore as a low magnetic field accreting neutron star. The first five bursts observed by RXTE are weak and show approximately symmetric light curves, without detectable signs of cooling along the burst decay. We discuss their possible nature. Finally, we explore a scenario to explain why Cir X-1 shows thermonuclear bursts now but not in the past, when it was extensively observed and accreting at a similar rate.Comment: Accepted for publication in The Astrophysical Journal Letters. Tables 1 & 2 merged. Minor changes after referee's comments. 5 pages, 4 Figure

On the curvature of vortex moduli spaces

We use algebraic topology to investigate local curvature properties of the moduli spaces of gauged vortices on a closed Riemann surface. After computing the homotopy type of the universal cover of the moduli spaces (which are symmetric powers of the surface), we prove that, for genus g>1, the holomorphic bisectional curvature of the vortex metrics cannot always be nonnegative in the multivortex case, and this property extends to all Kaehler metrics on certain symmetric powers. Our result rules out an established and natural conjecture on the geometry of the moduli spaces.Comment: 25 pages; final version, to appear in Math.

The frequency and validity of self-reported diagnosis of Parkinson's Disease in the UK elderly: MRC CFAS cohort

BACKGROUND: Estimates of the incidence and prevalence of chronic diseases can be made using established cohort studies but these estimates may have lower reliability if based purely on self-reported diagnosis. METHODS: The MRC Cognitive Function & Ageing Study (MRC CFAS) has collected longitudinal data from a population-based random sample of 13004 individuals over the age of 65 years from 5 centres within the UK. Participants were asked at baseline and after a two-year follow-up whether they had received a diagnosis of Parkinson's disease. Our aim was to make estimates of the incidence and prevalence of PD using self-reporting, and then investigate the validity of self-reported diagnosis using other data sources where available, namely death certification and neuropathological examination. RESULTS: The self-reported prevalence of Parkinson's disease (PD) amongst these individuals increases with age from 0.7% (95%CI 0.5–0.9) for 65–75, 1.4% (95%CI 1.0–1.7) for 75–85, and 1.6% (95%CI 1.0–2.3) for 85+ age groups respectively. The overall incidence of self reported PD in this cohort was 200/100,000 per year (95%CI 144–278). Only 40% of the deceased individuals reporting prevalent PD and 35% of those reporting incident PD had diagnoses of PD recorded on their death certificates. Neuropathological examination of individuals reporting PD also showed typical PD changes in only 40%, with the remainder showing basal ganglia pathologies causing parkinsonism rather than true PD pathology. CONCLUSION: Self-reporting of PD status may be used as a screening tool to identify patients for epidemiological study, but inevitably identifies a heterogeneous group of movement disorders patients. Within this group, age, male sex, a family history of PD and reduced cigarette smoking appear to act as independent risk factors for self-reported PD

A lithium-isotope perspective on the evolution of carbon and silicon cycles

The evolution of the global carbon and silicon cycles is thought to have contributed to the long-term stability of Earth's climate. Many questions remain, however, regarding the feedback mechanisms at play, and there are limited quantitative constraints on the sources and sinks of these elements in Earth's surface environments. Here we argue that the lithium-isotope record can be used to track the processes controlling the long-term carbon and silicon cycles. By analysing more than 600 shallow-water marine carbonate samples from more than 100 stratigraphic units, we construct a new carbonate-based lithium-isotope record spanning the past 3 billion years. The data suggest an increase in the carbonate lithium-isotope values over time, which we propose was driven by long-term changes in the lithium-isotopic conditions of sea water, rather than by changes in the sedimentary alterations of older samples. Using a mass-balance modelling approach, we propose that the observed trend in lithium-isotope values reflects a transition from Precambrian carbon and silicon cycles to those characteristic of the modern. We speculate that this transition was linked to a gradual shift to a biologically controlled marine silicon cycle and the evolutionary radiation of land plants

Mathematical Evaluation of Community Level Impact of Combining Bed Nets and Indoor Residual Spraying upon Malaria Transmission in Areas where the main Vectors are Anopheles Arabiensis Mosquitoes.

Indoor residual insecticide spraying (IRS) and long-lasting insecticide treated nets (LLINs) are commonly used together even though evidence that such combinations confer greater protection against malaria than either method alone is inconsistent. A deterministic model of mosquito life cycle processes was adapted to allow parameterization with results from experimental hut trials of various combinations of untreated nets or LLINs (Olyset, PermaNet 2.0, Icon Life nets) with IRS (pirimiphos methyl, lambda cyhalothrin, DDT), in a setting where vector populations are dominated by Anopheles arabiensis, so that community level impact upon malaria transmission at high coverage could be predicted. Intact untreated nets alone provide equivalent personal protection to all three LLINs. Relative to IRS plus untreated nets, community level protection is slightly higher when Olyset or PermaNet 2.0 nets are added onto IRS with pirimiphos methyl or lambda cyhalothrin but not DDT, and when Icon Life nets supplement any of the IRS insecticides. Adding IRS onto any net modestly enhances communal protection when pirimiphos methyl is sprayed, while spraying lambda cyhalothrin enhances protection for untreated nets but not LLINs. Addition of DDT reduces communal protection when added to LLINs. Where transmission is mediated primarily by An. arabiensis, adding IRS to high LLIN coverage provides only modest incremental benefit (e.g. when an organophosphate like pirimiphos methyl is used), but can be redundant (e.g. when a pyrethroid like lambda cyhalothin is used) or even regressive (e.g. when DDT is used for the IRS). Relative to IRS plus untreated nets, supplementing IRS with LLINs will only modestly improve community protection. Beyond the physical protection that intact nets provide, additional protection against transmission by An. arabiensis conferred by insecticides will be remarkably small, regardless of whether they are delivered as LLINs or IRS. The insecticidal action of LLINs and IRS probably already approaches their absolute limit of potential impact upon this persistent vector so personal protection of nets should be enhanced by improving the physical integrity and durability. Combining LLINs and non-pyrethroid IRS in residual transmission systems may nevertheless be justified as a means to manage insecticide resistance and prevent potential rebound of not only An. arabiensis, but also more potent, vulnerable and historically important species such as Anopheles gambiae and Anopheles funestus

Celecoxib exerts protective effects in the vascular endothelium via COX-2-independent activation of AMPK-CREB-Nrf2 signalling

Although concern remains about the athero-thrombotic risk posed by cyclo-oxygenase (COX)-2-selective inhibitors, recent data implicates rofecoxib, while celecoxib appears equivalent to NSAIDs naproxen and ibuprofen. We investigated the hypothesis that celecoxib activates AMP kinase (AMPK) signalling to enhance vascular endothelial protection. In human arterial and venous endothelial cells (EC), and in contrast to ibuprofen and naproxen, celecoxib induced the protective protein heme oxygenase-1 (HO-1). Celecoxib derivative 2,5-dimethyl-celecoxib (DMC) which lacks COX-2 inhibition also upregulated HO-1, implicating a COX-2-independent mechanism. Celecoxib activated AMPKα(Thr172) and CREB-1(Ser133) phosphorylation leading to Nrf2 nuclear translocation. Importantly, these responses were not reproduced by ibuprofen or naproxen, while AMPKα silencing abrogated celecoxib-mediated CREB and Nrf2 activation. Moreover, celecoxib induced H-ferritin via the same pathway, and increased HO-1 and H-ferritin in the aortic endothelium of mice fed celecoxib (1000 ppm) or control chow. Functionally, celecoxib inhibited TNF-α-induced NF-κB p65(Ser536) phosphorylation by activating AMPK. This attenuated VCAM-1 upregulation via induction of HO-1, a response reproduced by DMC but not ibuprofen or naproxen. Similarly, celecoxib prevented IL-1β-mediated induction of IL-6. Celecoxib enhances vascular protection via AMPK-CREB-Nrf2 signalling, a mechanism which may mitigate cardiovascular risk in patients prescribed celecoxib. Understanding NSAID heterogeneity and COX-2-independent signalling will ultimately lead to safer anti-inflammatory drugs

Acceleration of generalized hypergeometric functions through precise remainder asymptotics

We express the asymptotics of the remainders of the partial sums {s_n} of the generalized hypergeometric function q+1_F_q through an inverse power series z^n n^l \sum_k c_k/n^k, where the exponent l and the asymptotic coefficients {c_k} may be recursively computed to any desired order from the hypergeometric parameters and argument. From this we derive a new series acceleration technique that can be applied to any such function, even with complex parameters and at the branch point z=1. For moderate parameters (up to approximately ten) a C implementation at fixed precision is very effective at computing these functions; for larger parameters an implementation in higher than machine precision would be needed. Even for larger parameters, however, our C implementation is able to correctly determine whether or not it has converged; and when it converges, its estimate of its error is accurate.Comment: 36 pages, 6 figures, LaTeX2e. Fixed sign error in Eq. (2.28), added several references, added comparison to other methods, and added discussion of recursion stabilit

Elevated surface chlorophyll associated with natural oil seeps in the Gulf of Mexico

Natural hydrocarbon seeps occur on the sea floor along continental margins, and account for up to 47% of the oil released into the oceans. Hydrocarbon seeps are known to support local benthic productivity, but little is known about their impact on photosynthetic organisms in the overlying water column. Here we present observations with high temporal and spatial resolution of chlorophyll concentrations in the northern Gulf of Mexico using in situ and shipboard flow-through fluorescence measurements from May to July 2012, as well as an analysis of ocean-colour satellite images from 1997 to 2007. All three methods reveal elevated chlorophyll concentrations in waters influenced by natural hydrocarbon seeps. Temperature and nutrient profiles above seep sites suggest that nutrient-rich water upwells from depth, which may facilitate phytoplankton growth and thus support the higher chlorophyll concentrations observed. Because upwelling occurs at natural seep locations around the world, we conclude that offshore hydrocarbon seeps, and perhaps other types of deep ocean vents and seeps at depths exceeding 1,000 m, may influence biogeochemistry and productivity of the overlying water column