Meta-analysis of the INSIG2 association with obesity including 74,345 individuals: does heterogeneity of estimates relate to study design?

The INSIG2 rs7566605 polymorphism was identified for obesity (BMI> or =30 kg/m(2)) in one of the first genome-wide association studies, but replications were inconsistent. We collected statistics from 34 studies (n = 74,345), including general population (GP) studies, population-based studies with subjects selected for conditions related to a better health status ('healthy population', HP), and obesity studies (OB). We tested five hypotheses to explore potential sources of heterogeneity. The meta-analysis of 27 studies on Caucasian adults (n = 66,213) combining the different study designs did not support overall association of the CC-genotype with obesity, yielding an odds ratio (OR) of 1.05 (p-value = 0.27). The I(2) measure of 41% (p-value = 0.015) indicated between-study heterogeneity. Restricting to GP studies resulted in a declined I(2) measure of 11% (p-value = 0.33) and an OR of 1.10 (p-value = 0.015). Regarding the five hypotheses, our data showed (a) some difference between GP and HP studies (p-value = 0.012) and (b) an association in extreme comparisons (BMI> or =32.5, 35.0, 37.5, 40.0 kg/m(2) versus BMI<25 kg/m(2)) yielding ORs of 1.16, 1.18, 1.22, or 1.27 (p-values 0.001 to 0.003), which was also underscored by significantly increased CC-genotype frequencies across BMI categories (10.4% to 12.5%, p-value for trend = 0.0002). We did not find evidence for differential ORs (c) among studies with higher than average obesity prevalence compared to lower, (d) among studies with BMI assessment after the year 2000 compared to those before, or (e) among studies from older populations compared to younger. Analysis of non-Caucasian adults (n = 4889) or children (n = 3243) yielded ORs of 1.01 (p-value = 0.94) or 1.15 (p-value = 0.22), respectively. There was no evidence for overall association of the rs7566605 polymorphism with obesity. Our data suggested an association with extreme degrees of obesity, and consequently heterogeneous effects from different study designs may mask an underlying association when unaccounted for. The importance of study design might be under-recognized in gene discovery and association replication so far.

Environmental and ecological economics in the 21st century: an age adjusted citation analysis of the influential articles, journals, authors and institutions

We investigate the influence of articles, authors, journals and institutions in the field of environmental and ecological economics. We depart from studies that investigated the literature until 2001 and include a time period that has witnessed an enormous increase of importance in the field. We adjust for the age effect given the huge impact of the year of an article's publication on its influence and we show that this adjustment does make a substantial difference — especially for disaggregated units of analysis with diverse age characteristics such as articles or authors. We analyse 6597 studies on environmental and ecological economics published between 2000 and 2009. We provide rankings of the influential articles, authors, journals and institutions and find that Ecological Economics, Energy Economics and the Journal of Environmental Economics and Management have the most influential articles, they publish very influential authors and their articles are cited most. The University of Maryland, Resources for the Future, the University of East Anglia and the World Bank appear to be the most influential institutions in the field of environmental and ecological economics.

Controls on inorganic nitrogen leaching from Finnish catchments assessed using a sensitivity and uncertainty analysis of the INCA-N model

The semi-distributed, dynamic INCA-N model was used to simulate the behaviour of dissolved inorganic nitrogen (DIN) in two Finnish research catchments. Parameter sensitivity and model structural uncertainty were analysed using generalized sensitivity analysis. The Mustajoki catchment is a forested upstream catchment, while the Savijoki catchment represents intensively cultivated lowlands. In general, there were more influential parameters in Savijoki than Mustajoki. Model results were sensitive to N-transformation rates, vegetation dynamics, and soil and river hydrology. Values of the sensitive parameters were based on long-term measurements covering both warm and cold years. The highest measured DIN concentrations fell between minimum and maximum values estimated during the uncertainty analysis. The lowest measured concentrations fell outside these bounds, suggesting that some retention processes may be missing from the current model structure. The lowest concentrations occurred mainly during low flow periods; so effects on total loads were small.

Secondary structure analysis of the dissimilatory sulphite reductase in Desulfovibrio desulfuricans

The complete sequences of the dsrA and dsrB genes coding for the α− and β−subunits, respectively, of the sulphite reductase enzyme in Desulfovibrio desulfuricans were determined. Analyses of the amino acid sequences indicated a number of serohaem/Fe4S4 binding consensus sequences whilst predictive secondary structure analysis revealed a similar pattern of α−helix and β−strand structures between the two subunits which was indicative of gene duplication.

A multi-model analysis of the role of the ocean on the African and Indian monsoon during mid-Holocene

We investigate the role of the ocean feedback on the climate in response to insolation forcing during the mid-Holocene (6,000 year BP) using results from seven coupled ocean–atmosphere general circulation models. We examine how the dipole in late summer sea-surface temperature (SST) anomalies in the tropical Atlantic increases the length of the African monsoon, how this dipole structure is created and maintained, and how the late summer SST warming in the northwest Indian Ocean affects the monsoon retreat in this sector. Similar mechanisms are found in all of the models, including a strong wind evaporation feedback and changes in the mixed layer depth that enhance the insolation forcing, as well as increased Ekman transport in the Atlantic that sharpens the Atlantic dipole pattern. We also consider changes in interannual variability over West Africa and the Indian Ocean. The teleconnection between variations in SST and Sahelian precipitation favor a larger impact of the Atlantic dipole mode in this region. In the Indian Ocean, the strengthening of the Indian dipole structure in autumn has a damping effect on the Indian dipole mode at the interannual time scale

An enhanced model for small-signal analysis of the phase-shifted full-bridge converter

This paper presents an in-depth critical discussion and derivation of a detailed small-signal analysis of the Phase-Shifted Full-Bridge (PSFB) converter. Circuit parasitics, resonant inductance and transformer turns ratio have all been taken into account in the evaluation of this topology’s open-loop control-to-output, line-to-output and load-to-output transfer functions. Accordingly, the significant impact of losses and resonant inductance on the converter’s transfer functions is highlighted. The enhanced dynamic model proposed in this paper enables the correct design of the converter compensator, including the effect of parasitics on the dynamic behavior of the PSFB converter. Detailed experimental results for a real-life 36V-to-14V/10A PSFB industrial application show excellent agreement with the predictions from the model proposed herein.1

A comparative analysis of the accuracy and uncertainty in real estate and macroeconomic forecasts

We compare and contrast the accuracy and uncertainty in forecasts of rents with those for a variety of macroeconomic series. The results show that in general forecasters tend to be marginally more accurate in the case of macro-economic series than with rents. In common across all of the series, forecasts tend to be smoothed with forecasters under-estimating performance during economic booms, and vice-versa in recessions We find that property forecasts are affected by economic uncertainty, as measured by disagreement across the macro-forecasters. Increased uncertainty leads to increased dispersion in the rental forecasts and a reduction in forecast accuracy.

Analysis of the bacterial communities present in lungs of patients with cystic fibrosis from American and British centers

The aim of this study was to determine whether geographical differences impact the composition of bacterial communities present in the airways of cystic fibrosis (CF) patients attending CF centers in the United States or United Kingdom. Thirty-eight patients were matched on the basis of clinical parameters into 19 pairs comprised of one U.S. and one United Kingdom patient. Analysis was performed to determine what, if any, bacterial correlates could be identified. Two culture-independent strategies were used: terminal restriction fragment length polymorphism (T-RFLP) profiling and 16S rRNA clone sequencing. Overall, 73 different terminal restriction fragment lengths were detected, ranging from 2 to 10 for U.S. and 2 to 15 for United Kingdom patients. The statistical analysis of T-RFLP data indicated that patient pairing was successful and revealed substantial transatlantic similarities in the bacterial communities. A small number of bands was present in the vast majority of patients in both locations, indicating that these are species common to the CF lung. Clone sequence analysis also revealed that a number of species not traditionally associated with the CF lung were present in both sample groups. The species number per sample was similar, but differences in species presence were observed between sample groups. Cluster analysis revealed geographical differences in bacterial presence and relative species abundance. Overall, the U.S. samples showed tighter clustering with each other compared to that of United Kingdom samples, which may reflect the lower diversity detected in the U.S. sample group. The impact of cross-infection and biogeography is considered, and the implications for treating CF lung infections also are discussed.

Landscape change in central Latvia since the Iron Age: multi-proxy analysis of the vegetation impact of conflict, colonization and economic expansion during the last 2000 years

This study represents the first detailed multi-proxy palaeoenvironmental investigation associated with a Late Iron Age lake-dwelling site in the eastern Baltic. The main objective was to reconstruct the environmental and vegetation dynamics associated with the establishment of the lake-dwelling and land-use during the last 2,000 years. A lacustrine sediment core located adjacent to a Late Iron Age lake-dwelling, medieval castle and Post-medieval manor was sampled in Lake Āraiši. The core was dated using spheroidal fly-ash particles and radiocarbon dating, and analysed in terms of pollen, non-pollen palynomorphs, diatoms, loss-on-ignition, magnetic susceptibility and element geochemistry. Associations between pollen and other proxies were statistically tested. During ad 1–700, the vicinity of Lake Āraiši was covered by forests and human activities were only small-scale with the first appearance of cereal pollen (Triticum and Secale cereale) after ad 400. The most significant changes in vegetation and environment occurred with the establishment of the lake-dwelling around ad 780 when the immediate surroundings of the lake were cleared for agriculture, and within the lake there were increased nutrient levels. The highest accumulation rates of coprophilous fungi coincide with the occupation of the lake-dwelling from ad 780–1050, indicating that parts of the dwelling functioned as byres for livestock. The conquest of tribal lands during the crusades resulted in changes to the ownership, administration and organisation of the land, but our results indicate that the form and type of agriculture and land-use continued much as it had during the preceding Late Iron Age.

Are happy youth also satisfied adults? An analysis of the impact of childhood factors on adult life satisfaction

This paper aims to consider whether there is a link between youth happiness levels and adult life satisfaction. Our results are unequivocal that such a link exists both because demographic and socio-economic conditions are persistent over a lifetime and also because there is a persistence in personality effects. To test this link, we estimate a model of happiness for a sample of young people. This model provides us with a range of variables measuring socio-economic effects and personality effects amongst young people. These variables are then included in the adult life satisfaction model. The model is estimated using data from the British Household Panel Survey for 1994–2008. In addition to childhood happiness levels influencing adult life satisfaction significantly, we also find that the youthful personality trait for happiness has a larger effect on adult life satisfaction than demographic and socio-economic conditions.

An analysis of the accuracy of magnetopause reconnection rate variations deduced from cusp ion dispersion characteristics

We present an analysis of the accuracy of the method introduced by Lockwood et al. (1994) for the determination of the magnetopause reconnection rate from the dispersion of precipitating ions in the ionospheric cusp region. Tests are made by applying the method to synthesised data. The simulated cusp ion precipitation data are produced by an analytic model of the evolution of newly-opened field lines, along which magnetosheath ions are firstly injected across the magnetopause and then dispersed as they propagate into the ionosphere. The rate at which these newly opened field lines are generated by reconnection can be varied. The derived reconnection rate estimates are then compared with the input variation to the model and the accuracy of the method assessed. Results are presented for steady-state reconnection, for continuous reconnection showing a sine-wave variation in rate and for reconnection which only occurs in square wave pulses. It is found that the method always yields the total flux reconnected (per unit length of the open-closed field-line boundary) to within an accuracy of better than 5%, but that pulses tend to be smoothed so that the peak reconnection rate within the pulse is underestimated and the pulse length is overestimated. This smoothing is reduced if the separation between energy channels of the instrument is reduced; however this also acts to increase the experimental uncertainty in the estimates, an effect which can be countered by improving the time resolution of the observations. The limited time resolution of the data is shown to set a minimum reconnection rate below which the method gives spurious short-period oscillations about the true value. Various examples of reconnection rate variations derived from cusp observations are discussed in the light of this analysis.

Analysis of the regional pattern of sea level change due to ocean dynamics and density changes for 1993-2099 in observations and CMIP5 AOGCMs

Predictions of twenty-first century sea level change show strong regional variation. Regional sea level change observed by satellite altimetry since 1993 is also not spatially homogenous. By comparison with historical and pre-industrial control simulations using the atmosphere–ocean general circulation models (AOGCMs) of the CMIP5 project, we conclude that the observed pattern is generally dominated by unforced (internal generated) variability, although some regions, especially in the Southern Ocean, may already show an externally forced response. Simulated unforced variability cannot explain the observed trends in the tropical Pacific, but we suggest that this is due to inadequate simulation of variability by CMIP5 AOGCMs, rather than evidence of anthropogenic change. We apply the method of pattern scaling to projections of sea level change and show that it gives accurate estimates of future local sea level change in response to anthropogenic forcing as simulated by the AOGCMs under RCP scenarios, implying that the pattern will remain stable in future decades. We note, however, that use of a single integration to evaluate the performance of the pattern-scaling method tends to exaggerate its accuracy. We find that ocean volume mean temperature is generally a better predictor than global mean surface temperature of the magnitude of sea level change, and that the pattern is very similar under the different RCPs for a given model. We determine that the forced signal will be detectable above the noise of unforced internal variability within the next decade globally and may already be detectable in the tropical Atlantic.

Generation and analysis of the 2005 land cover map for Mexico using 250m MODIS data

Land cover plays a key role in global to regional monitoring and modeling because it affects and is being affected by climate change and thus became one of the essential variables for climate change studies. National and international organizations require timely and accurate land cover information for reporting and management actions. The North American Land Change Monitoring System (NALCMS) is an international cooperation of organizations and entities of Canada, the United States, and Mexico to map land cover change of North America's changing environment. This paper presents the methodology to derive the land cover map of Mexico for the year 2005 which was integrated in the NALCMS continental map. Based on a time series of 250 m Moderate Resolution Imaging Spectroradiometer (MODIS) data and an extensive sample data base the complexity of the Mexican landscape required a specific approach to reflect land cover heterogeneity. To estimate the proportion of each land cover class for every pixel several decision tree classifications were combined to obtain class membership maps which were finally converted to a discrete map accompanied by a confidence estimate. The map yielded an overall accuracy of 82.5% (Kappa of 0.79) for pixels with at least 50% map confidence (71.3% of the data). An additional assessment with 780 randomly stratified samples and primary and alternative calls in the reference data to account for ambiguity indicated 83.4% overall accuracy (Kappa of 0.80). A high agreement of 83.6% for all pixels and 92.6% for pixels with a map confidence of more than 50% was found for the comparison between the land cover maps of 2005 and 2006. Further wall-to-wall comparisons to related land cover maps resulted in 56.6% agreement with the MODIS land cover product and a congruence of 49.5 with Globcover.

Computational analysis of the LRRK2 interactome

LRRK2 was identified in 2004 as the causative protein product of the Parkinson’s disease locus designated PARK8. In the decade since then, genetic studies have revealed at least 6 dominant mutations in LRRK2 linked to Parkinson’s disease, alongside one associated with cancer. It is now well established that coding changes in LRRK2 are one of the most common causes of Parkinson’s. Genome-wide association studies (GWAs) have, more recently, reported single nucleotide polymorphisms (SNPs) around the LRRK2 locus to be associated with risk of developing sporadic Parkinson’s disease and inflammatory bowel disorder. The functional research that has followed these genetic breakthroughs has generated an extensive literature regarding LRRK2 pathophysiology; however, there is still no consensus as to the biological function of LRRK2. To provide insight into the aspects of cell biology that are consistently related to LRRK2 activity, we analysed the plethora of candidate LRRK2 interactors available through the BioGRID and IntAct data repositories. We then performed GO terms enrichment for the LRRK2 interactome. We found that, in two different enrichment portals, the LRRK2 interactome was associated with terms referring to transport, cellular organization, vesicles and the cytoskeleton. We also verified that 21 of the LRRK2 interactors are genetically linked to risk for Parkin- son’s disease or inflammatory bowel disorder. The implications of these findings are discussed, with particular regard to potential novel areas of investigation.

Analysis of the courtship behavior of the Navel Orangeworm, Amyelois transitella (Walker) (Lepidoptera: Pyralidae), with a commentary on methods for the analysis of sequences of behavioral transitions

The courtship behavior of the navel orangeworm, Amyelois transitella, was examined in a wind tunnel. Sixty nine courtship sequences were analyzed and successful sequences divided into two categories: rapid courtship sequences, which involved few breaks in contact, short or no periods of male/female chasing and lasted <10 s between initial contact and mating; and prolonged courtship sequences, which involved many breaks in contact, extended periods of male/female chasing and lasted >10 s. Fifty six (81%) courtships were successful (50.7% rapid courtship and 30.4% prolonged courtship); the remaining 13 (18.8%) sequences were failed courtships. Of failed courtships, 9 (13.0%) were due to males losing contact with females during courtship chases and 4 (5.8%) due to females flying away immediately after male contact. Of all courtship sequences involving a break in contact during a chase, 38.5% resulted in an unsuccessful mating attempt. These findings contrast with previous studies of the courtship behavior of the navel orangeworm, potentially indicating that the type of bioassay used to study courtship may have a large effect on the behavioral sequences displayed. We evaluate several diagnostic techniques for the analysis of sequences of behavioral transitions.