Causal relationship between obesity and vitamin D status: bi-directional mendelian randomization analysis of multiple cohorts

BACKGROUND: Obesity is associated with vitamin D deficiency, and both are areas of active public health concern. We explored the causality and direction of the relationship between body mass index (BMI) and 25-hydroxyvitamin D [25(OH)D] using genetic markers as instrumental variables (IVs) in bi-directional Mendelian randomization (MR) analysis. METHODS AND FINDINGS: We used information from 21 adult cohorts (up to 42,024 participants) with 12 BMI-related SNPs (combined in an allelic score) to produce an instrument for BMI and four SNPs associated with 25(OH)D (combined in two allelic scores, separately for genes encoding its synthesis or metabolism) as an instrument for vitamin D. Regression estimates for the IVs (allele scores) were generated within-study and pooled by meta-analysis to generate summary effects. Associations between vitamin D scores and BMI were confirmed in the Genetic Investigation of Anthropometric Traits (GIANT) consortium (n = 123,864). Each 1 kg/m(2) higher BMI was associated with 1.15% lower 25(OH)D (p = 6.52×10⁻²⁷). The BMI allele score was associated both with BMI (p = 6.30×10⁻⁶²) and 25(OH)D (-0.06% [95% CI -0.10 to -0.02], p = 0.004) in the cohorts that underwent meta-analysis. The two vitamin D allele scores were strongly associated with 25(OH)D (p≤8.07×10⁻⁵⁷ for both scores) but not with BMI (synthesis score, p = 0.88; metabolism score, p = 0.08) in the meta-analysis. A 10% higher genetically instrumented BMI was associated with 4.2% lower 25(OH)D concentrations (IV ratio: -4.2 [95% CI -7.1 to -1.3], p = 0.005). No association was seen for genetically instrumented 25(OH)D with BMI, a finding that was confirmed using data from the GIANT consortium (p≥0.57 for both vitamin D scores). CONCLUSIONS: On the basis of a bi-directional genetic approach that limits confounding, our study suggests that a higher BMI leads to lower 25(OH)D, while any effects of lower 25(OH)D increasing BMI are likely to be small. Population level interventions to reduce BMI are expected to decrease the prevalence of vitamin D deficiency.

Influence of dietary protein intake and glycemic index on the association between TCF7L2 HapA and weight gain

BACKGROUND: Genetic polymorphisms of transcription factor 7-like 2 (TCF7L2) have been associated with type 2 diabetes and BMI. OBJECTIVE: The objective was to investigate whether TCF7L2 HapA is associated with weight development and whether such an association is modulated by protein intake or by the glycemic index (GI). DESIGN: The investigation was based on prospective data from 5 cohort studies nested within the European Prospective Investigation into Cancer and Nutrition. Weight change was followed up for a mean (±SD) of 6.8 ± 2.5 y. TCF7L2 rs7903146 and rs10885406 were successfully genotyped in 11,069 individuals and used to derive HapA. Multiple logistic and linear regression analysis was applied to test for the main effect of HapA and its interaction with dietary protein or GI. Analyses from the cohorts were combined by random-effects meta-analysis. RESULTS: HapA was associated neither with baseline BMI (0.03 ± 0.07 BMI units per allele; P = 0.6) nor with annual weight change (8.8 ± 11.7 g/y per allele; P = 0.5). However, a previously shown positive association between intake of protein, particularly of animal origin, and subsequent weight change in this population proved to be attenuated by TCF7L2 HapA (P-interaction = 0.01). We showed that weight gain becomes independent of protein intake with an increasing number of HapA alleles. Substitution of protein with either fat or carbohydrates showed the same effects. No interaction with GI was observed. CONCLUSION: TCF7L2 HapA attenuates the positive association between animal protein intake and long-term body weight change in middle-aged Europeans but does not interact with the GI of the diet.

Physical activity attenuates the body mass index-increasing influence of genetic variation in the FTO gene 1-3.

BACKGROUND: Intronic variation in the FTO (fat mass and obesity-associated) gene has been unequivocally associated with increased body mass index (BMI; in kg/m(2)) and the risk of obesity in populations of different ethnicity. OBJECTIVE: We examined whether this robust genetic predisposition to obesity can be attenuated by being more physically active. DESIGN: The FTO variant rs1121980 was genotyped in 20,374 participants (39-79 y of age) from the European Prospective Investigation into Cancer and Nutrition-Norfolk Study, an ethnically homogeneous population-based cohort. Physical activity (PA) was assessed with a validated self-reported questionnaire. The interaction between rs1121980 and PA on BMI and waist circumference (WC) was examined by including the interaction term in mixed-effect models. RESULTS: We confirmed that the risk (T) allele of rs1121980 was significantly associated with BMI (0.31-unit increase per allele; P < 0.001) and WC (0.77-cm increase per allele; P < 0.001). The PA level attenuated the effect of rs1121980 on BMI and WC; ie, whereas in active individuals the risk allele increased BMI by 0.25 per allele, the increase in BMI was significantly (P for interaction = 0.004) more pronounced (76%) in inactive individuals (0.44 per risk allele). We observed similar effects for WC (P for interaction = 0.02): the risk allele increased WC by 1.04 cm per allele in inactive individuals but by only 0.64 cm in active individuals. CONCLUSIONS: Our results showed that PA attenuates the effect of the FTO rs1121980 genotype on BMI and WC. This observation has important public health implications because we showed that a genetic susceptibility to obesity induced by FTO variation can be overcome, at least in part, by adopting a physically active lifestyle.

Basic theory behind parameterizing atmospheric convection

Last fall, a network of the European Cooperation in Science and Technology (COST), called “Basic Concepts for Convection Parameterization in Weather Forecast and Climate Models” (COST Action ES0905; see http://w3.cost.esf.org/index.php?id=205&action_number=ES0905), organized a 10-day training course on atmospheric convection and its parameterization. The aim of the workshop, held on the island of Brac, Croatia, was to help young scientists develop an in-depth understanding of the core theory underpinning convection parameterizations. The speakers also sought to impart an appreciation of the various approximations, compromises, and ansatz necessary to translate theory into operational practice for numerical models.

MODIS-based vegetation index has sufficient sensitivity to indicate stand-level intra-seasonal climatic stress in oak and beech forests

Context: Variation in photosynthetic activity of trees induced by climatic stress can be effectively evaluated using remote sensing data. Although adverse effects of climate on temperate forests have been subjected to increased scrutiny, the suitability of remote sensing imagery for identification of drought stress in such forests has not been explored fully. Aim: To evaluate the sensitivity of MODIS-based vegetation index to heat and drought stress in temperate forests, and explore the differences in stress response of oaks and beech. Methods: We identified 8 oak and 13 beech pure and mature stands, each covering between 4 and 13 MODIS pixels. For each pixel, we extracted a time series of MODIS NDVI from 2000 to 2010. We identified all sequences of continuous unseasonal NDVI decline to be used as the response variable indicative of environmental stress. Neural Networks-based regression modelling was then applied to identify the climatic variables that best explain observed NDVI declines. Results: Tested variables explained 84–97% of the variation in NDVI, whilst air temperature-related climate extremes were found to be the most influential. Beech showed a linear response to the most influential climatic predictors, while oak responded in a unimodal pattern suggesting a better coping mechanism. Conclusions: MODIS NDVI has proved sufficiently sensitive as a stand-level indicator of climatic stress acting upon temperate broadleaf forests, leading to its potential use in predicting drought stress from meteorological observations and improving parameterisation of forest stress indices.

Ionospheric and geomagnetic responses to changes in IMF B_Z: a superposed epoch study

Superposed epoch studies have been carried out in order to determine the ionospheric response at mid-latitudes to southward turnings of the interplanetary magnetic field (IMF). This is compared with the geomagnetic response, as seen in the indices K p, AE and Dst. The solar wind, IMF and geomagnetic data used were hourly averages from the years 1967–1989 and thus cover a full 22-year cycle in the solar magnetic field. These data were divided into subsets, determined by the magnitudes of the southward turnings and the concomitant increase in solar wind pressure. The superposed epoch studies were carried out using the time of the southward turning as time zero. The response of the mid-latitude ionosphere is studied by looking at the F-layer critical frequencies, f o F2, from hourly soundings by the Slough ionosonde and their deviation from the monthly median values, δf o F2. For the southward turnings with a change in B z of δB z > 11.5 nT accompanied by a solar wind dynamic pressure P exceeding 5 nPa, the F region critical frequency, f o F2, shows a marked decrease, reaching a minimum value about 20 h after the southward turning. This recovers to pre-event values over the subsequent 24 h, on average. The Dst index shows the classic storm-time decrease to about −60 nT. Four days later, the index has still to fully recover and is at about −25 nT. Both the K p and AE indices show rises before the southward turnings, when the IMF is strongly northward but the solar wind dynamic pressure is enhanced. The average AE index does register a clear isolated pulse (averaging 650 nT for 2 h, compared with a background peak level of near 450 nT at these times) showing enhanced energy deposition at high latitudes in substorms but, like K p, remains somewhat enhanced for several days, even after the average IMF has returned to zero after 1 day. This AE background decays away over several days as the Dst index recovers, indicating that there is some contamination of the currents observed at the AE stations by the continuing enhanced equatorial ring current. For data averaged over all seasons, the critical frequencies are depressed at Slough by 1.3 MHz, which is close to the lower decile of the overall distribution of δf o Fl values. Taking 30-day periods around summer and winter solstice, the largest depression is 1.6 and 1.2 MHz, respectively. This seasonal dependence is confirmed by a similar study for a Southern Hemisphere station, Argentine Island, giving peak depressions of 1.8 MHz and 0.5 MHz for summer and winter. For the subset of turnings where δB z > 11.5 nT and P ≤ 5 nPa, the response of the geomagnetic indices is similar but smaller, while the change in δf o F2 has all but disappeared. This confirms that the energy deposited at high latitudes, which leads to the geomagnetic and ionospheric disturbances following a southward turning of the IMF, increases with the energy density (dynamic pressure) of the solar wind flow. The magnitude of all responses are shown to depend on δB z . At Slough, the peak depression always occurs when Slough rotates into the noon sector. The largest ionospheric response is for southward turnings seen between 15–21 UT.

Preliminary leaf area index estimates from airborne small footprint full-waveform LiDAR data

This study has compared preliminary estimates of effective leaf area index (LAI) derived from fish-eye lens photographs to those estimated from airborne full-waveform small-footprint LiDAR data for a forest dataset in Australia. The full-waveform data was decomposed and optimized using a trust-region-reflective algorithm to extract denser point clouds. LAI LiDAR estimates were derived in two ways (1) from the probability of discrete pulses reaching the ground without being intercepted (point method) and (2) from raw waveform canopy height profile processing adapted to small-footprint laser altimetry (waveform method) accounting for reflectance ratio between vegetation and ground. The best results, that matched hemispherical photography estimates, were achieved for the waveform method with a study area-adjusted reflectance ratio of 0.4 (RMSE of 0.15 and 0.03 at plot and site level, respectively). The point method generally overestimated, whereas the waveform method with an arbitrary reflectance ratio of 0.5 underestimated the fish-eye lens LAI estimates.

Potential role of vegetation feedback in the climate sensitivity of high-latitude regions: a case study at 6000 years B.P.

Previous climate model simulations have shown that the configuration of the Earth's orbit during the early to mid-Holocene (approximately 10–5 kyr) can account for the generally warmer-than-present conditions experienced by the high latitudes of the northern hemisphere. New simulations for 6 kyr with two atmospheric/mixed-layer ocean models (Community Climate Model, version 1, CCMl, and Global ENvironmental and Ecological Simulation of Interactive Systems, version 2, GENESIS 2) are presented here and compared with results from two previous simulations with GENESIS 1 that were obtained with and without the albedo feedback due to climate-induced poleward expansion of the boreal forest. The climate model results are summarized in the form of potential vegetation maps obtained with the global BIOME model, which facilitates visual comparisons both among models and with pollen and plant macrofossil data recording shifts of the forest-tundra boundary. A preliminary synthesis shows that the forest limit was shifted 100–200 km north in most sectors. Both CCMl and GENESIS 2 produced a shift of this magnitude. GENESIS 1 however produced too small a shift, except when the boreal forest albedo feedback was included. The feedback in this case was estimated to have amplified forest expansion by approximately 50%. The forest limit changes also show meridional patterns (greatest expansion in central Siberia and little or none in Alaska and Labrador) which have yet to be reproduced by models. Further progress in understanding of the processes involved in the response of climate and vegetation to orbital forcing will require both the deployment of coupled atmosphere-biosphere-ocean models and the development of more comprehensive observational data sets

Comparative analysis of performance and stability among composite cross populations, variety mixtures and pure lines of winter wheat in organic and conventional cropping systems

This study investigated the effects of increased genetic diversity in winter wheat (Triticum aestivum L.), either from hybridization across genotypes or from physical mixing of lines, on grain yield, grain quality, and yield stability in different cropping environments. Sets of pure lines (no diversity), chosen for high yielding ability or high quality, were compared with line mixtures (intermediate level of diversity), and lines crossed with each other in composite cross populations (CCPn, high diversity). Additional populations containing male sterility genes (CCPms) to increase outcrossing rates were also tested. Grain yield, grain protein content, and protein yield were measured at four sites (two organically-managed and two conventionally-managed) over three years, using seed harvested locally in each preceding year. CCPn and mixtures out-yielded the mean of the parents by 2.4% and 3.6%, respectively. These yield differences were consistent across genetic backgrounds but partly inconsistent across cropping environments and years. Yield stability measured by environmental variance was higher in CCPn and CCPms than the mean of the parents. An index of yield reliability tended to be higher in CCPn, CCPms and mixtures than the mean of the parents. Lin and Binns’ superiority values of yield and protein yield were consistently and significantly lower (i.e. better) in the CCPs than in the mean of the parents, but not different between CCPs and mixtures. However, CCPs showed greater early ground cover and plant height than mixtures. When compared with the (locally non-predictable) best-yielding pure line, CCPs and mixtures exhibited lower mean yield and somewhat lower yield reliability but comparable superiority values. Thus, establishing CCPs from smaller sets of high-performing parent lines might optimize their yielding ability. On the whole, the results demonstrate that using increased within-crop genetic diversity can produce wheat crops with improved yield stability and good yield reliability across variable and unpredictable cropping environments.

Using E-Z Reader to examine the concurrent development of eye-movement control and reading skill

Compared to skilled adult readers, children typically make more fixations that are longer in duration, shorter saccades, and more regressions, thus reading more slowly (Blythe & Joseph, 2011). Recent attempts to understand the reasons for these differences have discovered some similarities (e.g., children and adults target their saccades similarly; Joseph, Liversedge, Blythe, White, & Rayner, 2009) and some differences (e.g., children’s fixation durations are more affected by lexical variables; Blythe, Liversedge, Joseph, White, & Rayner, 2009) that have yet to be explained. In this article, the E-Z Reader model of eye-movement control in reading (Reichle, 2011; Reichle, Pollatsek, Fisher, & Rayner, 1998) is used to simulate various eye-movement phenomena in adults versus children in order to evaluate hypotheses about the concurrent development of reading skill and eye-movement behavior. These simulations suggest that the primary difference between children and adults is their rate of lexical processing, and that different rates of (post-lexical) language processing may also contribute to some phenomena (e.g., children’s slower detection of semantic anomalies; Joseph et al., 2008). The theoretical implications of this hypothesis are discussed, including possible alternative accounts of these developmental changes, how reading skill and eye movements change across the entire lifespan (e.g., college-aged vs. elderly readers), and individual differences in reading ability.

A psychometric analysis of reliability and validity of the index of learning styles (ILS)

Prior literature showed that Felder and Silverman learning styles model (FSLSM) was widely adopted to cater to individual styles of learners whether in traditional or Technology Enhanced Learning (TEL). In order to infer this model, the Index of Learning Styles (ILS) instrument was proposed. This research aims to analyse the soundness of this instrument in an Arabic sample. Data were integrated from different courses and years. A total of 259 engineering students participated voluntarily in the study. The reliability was analysed by applying internal construct reliability, inter-scale correlation, and total item correlation. The construct validity was also considered by running factor analysis. The overall results indicated that the reliability and validity of perception and input dimensions were moderately supported, whereas processing and understanding dimensions showed low internal-construct consistency and their items were weakly loaded in the associated constructs. Generally, the instrument needs further effort to improve its soundness. However, considering the consistency of the produced results of engineering students irrespective of cross-cultural differences, it can be adopted to diagnose learning styles.

The atomic structure of low-index surfaces of the intermetallic compound InPd

The intermetallic compound InPd (CsCl type of crystal structure with a broad compositional range) is considered as a candidate catalyst for the steam reforming of methanol. Single crystals of this phase have been grown to study the structure of its three low-index surfaces under ultra-high vacuum conditions, using low energy electron diffraction (LEED), X-ray photoemission spectroscopy (XPS), and scanning tunneling microscopy (STM). During surface preparation, preferential sputtering leads to a depletion of In within the top few layers for all three surfaces. The near-surface regions remain slightly Pd-rich until annealing to ∼580 K. A transition occurs between 580 and 660 K where In segregates towards the surface and the near-surface regions become slightly In-rich above ∼660 K. This transition is accompanied by a sharpening of LEED patterns and formation of flat step-terrace morphology, as observed by STM. Several superstructures have been identified for the different surfaces associated with this process. Annealing to higher temperatures (≥750 K) leads to faceting via thermal etching as shown for the (110) surface, with a bulk In composition close to the In-rich limit of the existence domain of the cubic phase. The Pd-rich InPd(111) is found to be consistent with a Pd-terminated bulk truncation model as shown by dynamical LEED analysis while, after annealing at higher temperature, the In-rich InPd(111) is consistent with an In-terminated bulk truncation, in agreement with density functional theory (DFT) calculations of the relative surface energies. More complex surface structures are observed for the (100) surface. Additionally, individual grains of a polycrystalline sample are characterized by micro-spot XPS and LEED as well as low-energy electron microscopy. Results from both individual grains and “global” measurements are interpreted based on comparison to our single crystals findings, DFT calculations and previous literature.

Jump and variance risk premia in the S&P 500

We analyze the risk premia embedded in the S&P 500 spot index and option markets. We use a long time-series of spot prices and a large panel of option prices to jointly estimate the diffusive stock risk premium, the price jump risk premium, the diffusive variance risk premium and the variance jump risk premium. The risk premia are statistically and economically significant and move over time. Investigating the economic drivers of the risk premia, we are able to explain up to 63 % of these variations.