A fast algorithm for sparse probability density function construction

A new sparse kernel density estimator is introduced. Our main contribution is to develop a recursive algorithm for the selection of significant kernels one at time using the minimum integrated square error (MISE) criterion for both kernel selection. The proposed approach is simple to implement and the associated computational cost is very low. Numerical examples are employed to demonstrate that the proposed approach is effective in constructing sparse kernel density estimators with competitive accuracy to existing kernel density estimators.

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.

Analyses of single nucleotide polymorphisms in selected nutrient-sensitive genes in weight-regain prevention: the DIOGENES study

BACKGROUND: Differences in the interindividual response to dietary intervention could be modified by genetic variation in nutrient-sensitive genes. OBJECTIVE: This study examined single nucleotide polymorphisms (SNPs) in presumed nutrient-sensitive candidate genes for obesity and obesity-related diseases for main and dietary interaction effects on weight, waist circumference, and fat mass regain over 6 mo. DESIGN: In total, 742 participants who had lost ≥ 8% of their initial body weight were randomly assigned to follow 1 of 5 different ad libitum diets with different glycemic indexes and contents of dietary protein. The SNP main and SNP-diet interaction effects were analyzed by using linear regression models, corrected for multiple testing by using Bonferroni correction and evaluated by using quantile-quantile (Q-Q) plots. RESULTS: After correction for multiple testing, none of the SNPs were significantly associated with weight, waist circumference, or fat mass regain. Q-Q plots showed that ALOX5AP rs4769873 showed a higher observed than predicted P value for the association with less waist circumference regain over 6 mo (-3.1 cm/allele; 95% CI: -4.6, -1.6; P/Bonferroni-corrected P = 0.000039/0.076), independently of diet. Additional associations were identified by using Q-Q plots for SNPs in ALOX5AP, TNF, and KCNJ11 for main effects; in LPL and TUB for glycemic index interaction effects on waist circumference regain; in GHRL, CCK, MLXIPL, and LEPR on weight; in PPARC1A, PCK2, ALOX5AP, PYY, and ADRB3 on waist circumference; and in PPARD, FABP1, PLAUR, and LPIN1 on fat mass regain for dietary protein interaction. CONCLUSION: The observed effects of SNP-diet interactions on weight, waist, and fat mass regain suggest that genetic variation in nutrient-sensitive genes can modify the response to diet. This trial was registered at clinicaltrials.gov as NCT00390637.

Association between FTO variant and change in body weight and its interaction with dietary factors: the DiOGenes study

Although FTO is an established obesity-susceptibility locus, it remains unknown whether it influences weight change in adult life and whether diet attenuates this association. Therefore, we investigated the association of FTO-rs9939609 with changes in weight and waist circumference (WC) during 6.8 years follow-up in a large-scale prospective study and examined whether these associations were modified by dietary energy percentage from fat, protein, carbohydrate, or glycemic index (GI). This study comprised data from five countries of European Prospective Investigation into Cancer and Nutrition (EPIC) and was designed as a case-cohort study for weight gain. Analyses included 11,091 individuals, of whom 5,584 were cases (age (SD), 47.6 (7.5) years), defined as those with the greatest unexplained annual weight gain during follow-up and 5,507 were noncases (48.0 (7.3) years), who were compared in our case-noncase (CNC) analyses. Furthermore, 6,566 individuals (47.9 (7.3) years) selected from the total sample (all noncases and 1,059 cases) formed the random subcohort (RSC), used for continuous trait analyses. Interactions were tested by including interaction terms in the models. In the RSC-analyses, FTO-rs9939609 was associated with BMI (β (SE), 0.17 (0.08) kg·m(-2)/allele; P = 0.034) and WC (0.47 (0.21) cm/allele; P = 0.026) at baseline, but not with weight change (5.55 (12.5) g·year(-1)/allele; P = 0.66) during follow up. In the CNC-analysis, FTO-rs9939609 was associated with increased risk of being a weight-gainer (OR: 1.1; P = 0.045). We observed no interaction between FTO-rs9939609 and dietary fat, protein and carbohydrate, and GI on BMI and WC at baseline or on change in weight and WC. FTO-rs9939609 is associated with BMI and WC at baseline, but association with weight gain is weak and only observed for extreme gain. Dietary factors did not influence the associations.

Genetic polymorphisms in the hypothalamic pathway in relation to subsequent weight change--the DiOGenes study

BACKGROUND: Single nucleotide polymorphisms (SNPs) in genes encoding the components involved in the hypothalamic pathway may influence weight gain and dietary factors may modify their effects. AIM: We conducted a case-cohort study to investigate the associations of SNPs in candidate genes with weight change during an average of 6.8 years of follow-up and to examine the potential effect modification by glycemic index (GI) and protein intake. METHODS AND FINDINGS: Participants, aged 20-60 years at baseline, came from five European countries. Cases ('weight gainers') were selected from the total eligible cohort (n = 50,293) as those with the greatest unexplained annual weight gain (n = 5,584). A random subcohort (n = 6,566) was drawn with the intention to obtain an equal number of cases and noncases (n = 5,507). We genotyped 134 SNPs that captured all common genetic variation across the 15 candidate genes; 123 met the quality control criteria. Each SNP was tested for association with the risk of being a 'weight gainer' (logistic regression models) in the case-noncase data and with weight gain (linear regression models) in the random subcohort data. After accounting for multiple testing, none of the SNPs was significantly associated with weight change. Furthermore, we observed no significant effect modification by dietary factors, except for SNP rs7180849 in the neuromedin β gene (NMB). Carriers of the minor allele had a more pronounced weight gain at a higher GI (P = 2 x 10⁻⁷). CONCLUSIONS: We found no evidence of association between SNPs in the studied hypothalamic genes with weight change. The interaction between GI and NMB SNP rs7180849 needs further confirmation.

Six new loci associated with body mass index highlight a neuronal influence on body weight regulation

Common variants at only two loci, FTO and MC4R, have been reproducibly associated with body mass index (BMI) in humans. To identify additional loci, we conducted meta-analysis of 15 genome-wide association studies for BMI (n > 32,000) and followed up top signals in 14 additional cohorts (n > 59,000). We strongly confirm FTO and MC4R and identify six additional loci (P < 5 x 10(-8)): TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 (where a 45-kb deletion polymorphism is a candidate causal variant). Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity.

Evaluating the Survey of Professional Forecasters probability distributions of expected inflation based on derived event probability forecasts

Techniques are proposed for evaluating forecast probabilities of events. The tools are especially useful when, as in the case of the Survey of Professional Forecasters (SPF) expected probability distributions of inflation, recourse cannot be made to the method of construction in the evaluation of the forecasts. The tests of efficiency and conditional efficiency are applied to the forecast probabilities of events of interest derived from the SPF distributions, and supplement a whole-density evaluation of the SPF distributions based on the probability integral transform approach.

Combining probability forecasts

We consider different methods for combining probability forecasts. In empirical exercises, the data generating process of the forecasts and the event being forecast is not known, and therefore the optimal form of combination will also be unknown. We consider the properties of various combination schemes for a number of plausible data generating processes, and indicate which types of combinations are likely to be useful. We also show that whether forecast encompassing is found to hold between two rival sets of forecasts or not may depend on the type of combination adopted. The relative performances of the different combination methods are illustrated, with an application to predicting recession probabilities using leading indicators.

Probability distributions or point predictions? Survey forecasts of US output growth and inflation

We consider whether survey respondents’ probability distributions, reported as histograms, provide reliable and coherent point predictions, when viewed through the lens of a Bayesian learning model. We argue that a role remains for eliciting directly-reported point predictions in surveys of professional forecasters.

Variation in genes related to hepatic lipid metabolism and changes in waist circumference and body weight.

We analysed single nucleotide polymorphisms (SNPs) tagging the genetic variability of six candidate genes (ATF6, FABP1, LPIN2, LPIN3, MLXIPL and MTTP) involved in the regulation of hepatic lipid metabolism, an important regulatory site of energy balance for associations with body mass index (BMI) and changes in weight and waist circumference. We also investigated effect modification by sex and dietary intake. Data of 6,287 individuals participating in the European prospective investigation into cancer and nutrition were included in the analyses. Data on weight and waist circumference were followed up for 6.9 ± 2.5 years. Association of 69 tagSNPs with baseline BMI and annual changes in weight as well as waist circumference were investigated using linear regression analysis. Interactions with sex, GI and intake of carbohydrates, fat as well as saturated, monounsaturated and polyunsaturated fatty acids were examined by including multiplicative SNP-covariate terms into the regression model. Neither baseline BMI nor annual weight or waist circumference changes were significantly associated with variation in the selected genes in the entire study population after correction for multiple testing. One SNP (rs1164) in LPIN2 appeared to be significantly interacting with sex (p = 0.0003) and was associated with greater annual weight gain in men (56.8 ± 23.7 g/year per allele, p = 0.02) than in women (-25.5 ± 19.8 g/year per allele, p = 0.2). With respect to gene-nutrient interaction, we could not detect any significant interactions when accounting for multiple testing. Therefore, out of our six candidate genes, LPIN2 may be considered as a candidate for further studies.

Association between Mediterranean and Nordic diet scores and changes in weight and waist circumference: influence of FTO and TCF7L2 loci

BACKGROUND: Several studies have shown that adherence to the Mediterranean Diet measured by using the Mediterranean diet score (MDS) is associated with lower obesity risk. The newly proposed Nordic Diet could hold similar beneficial effects. Because of the increasing focus on the interaction between diet and genetic predisposition to adiposity, studies should consider both diet and genetics. OBJECTIVE: We investigated whether FTO rs9939609 and TCF7L2 rs7903146 modified the association between the MDS and Nordic diet score (NDS) and changes in weight (Δweight), waist circumference (ΔWC), and waist circumference adjusted for body mass index (BMI) (ΔWCBMI). DESIGN: We conducted a case-cohort study with a median follow-up of 6.8 y that included 11,048 participants from 5 European countries; 5552 of these subjects were cases defined as individuals with the greatest degree of unexplained weight gain during follow-up. A randomly selected subcohort included 6548 participants, including 5496 noncases. Cases and noncases were compared in analyses by using logistic regression. Continuous traits (ie, Δweight, ΔWC, and ΔWCBMI) were analyzed by using linear regression models in the random subcohort. Interactions were tested by including interaction terms in models. RESULTS: A higher MDS was significantly inversely associated with case status (OR: 0.98; 95% CI: 0.96, 1.00), ΔWC (β = -0.010 cm/y; 95% CI: -0.020, -0.001 cm/y), and ΔWCBMI (β = -0.008; 95% CI:-0.015, -0.001) per 1-point increment but not Δweight (P = 0.53). The NDS was not significantly associated with any outcome. There was a borderline significant interaction between the MDS and TCF7L2 rs7903146 on weight gain (P = 0.05), which suggested a beneficial effect of the MDS only in subjects who carried 1 or 2 risk alleles. FTO did not modify observed associations. CONCLUSIONS: A high MDS is associated with a lower ΔWC and ΔWCBMI, regardless of FTO and TCF7L2 risk alleles. For Δweight, findings were less clear, but the effect may depend on the TCF7L2 rs7903146 variant. The NDS was not associated with anthropometric changes during follow-up.

Occurrence probability, width and number of steps of cusp precipitation for fully pulsed reconnection at the dayside magnetopause

We discuss the characteristics of magnetosheath plasma precipitation in the “cusp” ionosphere for when the reconnection at the dayside magnetopause takes place only in a series of pulses. It is shown that even in this special case, the low-altitude cusp precipitation is continuous, unless the intervals between the pulses are longer than observed intervals between magnetopause flux transfer event (FTE) signatures. We use FTE observation statistics to predict, for this case of entirely pulsed reconnection, the occurrence frequency, the distribution of latitudinal widths, and the number of ion dispersion steps of the cusp precipitation for a variety of locations of the reconnection site and a range of values of the local de-Hoffman Teller velocity. It is found that the cusp occurrence frequency is comparable with observed values for virtually all possible locations of the reconnection site. The distribution of cusp width is also comparable with observations and is shown to be largely dependent on the distribution of the mean reconnection rate, but pulsing the reconnection does very slightly increase the width of that distribution compared with the steady state case. We conclude that neither cusp occurrence probability nor width can be used to evaluate the relative occurrence of reconnection behaviors that are entirely pulsed, pulsed but continuous and quasi-steady. We show that the best test of the relative frequency of these three types of reconnection is to survey the distribution of steps in the cusp ion dispersion characteristics.

Probability functions to build composite indicators: a methodology to measure environmental impacts of genetically modified crops

There is an on-going debate on the environmental effects of genetically modified crops to which this paper aims to contribute. First, data on environmental impacts of genetically modified (GM) and conventional crops are collected from peer-reviewed journals, and secondly an analysis is conducted in order to examine which crop type is less harmful for the environment. Published data on environmental impacts are measured using an array of indicators, and their analysis requires their normalisation and aggregation. Taking advantage of composite indicators literature, this paper builds composite indicators to measure the impact of GM and conventional crops in three dimensions: (1) non-target key species richness, (2) pesticide use, and (3) aggregated environmental impact. The comparison between the three composite indicators for both crop types allows us to establish not only a ranking to elucidate which crop is more convenient for the environment but the probability that one crop type outperforms the other from an environmental perspective. Results show that GM crops tend to cause lower environmental impacts than conventional crops for the analysed indicators.

An evaluation of decadal probability forecasts from state-of-the-art climate models

While state-of-the-art models of Earth's climate system have improved tremendously over the last 20 years, nontrivial structural flaws still hinder their ability to forecast the decadal dynamics of the Earth system realistically. Contrasting the skill of these models not only with each other but also with empirical models can reveal the space and time scales on which simulation models exploit their physical basis effectively and quantify their ability to add information to operational forecasts. The skill of decadal probabilistic hindcasts for annual global-mean and regional-mean temperatures from the EU Ensemble-Based Predictions of Climate Changes and Their Impacts (ENSEMBLES) project is contrasted with several empirical models. Both the ENSEMBLES models and a “dynamic climatology” empirical model show probabilistic skill above that of a static climatology for global-mean temperature. The dynamic climatology model, however, often outperforms the ENSEMBLES models. The fact that empirical models display skill similar to that of today's state-of-the-art simulation models suggests that empirical forecasts can improve decadal forecasts for climate services, just as in weather, medium-range, and seasonal forecasting. It is suggested that the direct comparison of simulation models with empirical models becomes a regular component of large model forecast evaluations. Doing so would clarify the extent to which state-of-the-art simulation models provide information beyond that available from simpler empirical models and clarify current limitations in using simulation forecasting for decision support. Ultimately, the skill of simulation models based on physical principles is expected to surpass that of empirical models in a changing climate; their direct comparison provides information on progress toward that goal, which is not available in model–model intercomparisons.