Publications

Studies concerning whether exposure to low levels of maternal alcohol consumption during fetal development is related to child inattention and hyperactivity symptoms have shown conflicting results. We examine the contribution of covariates related to social adversity to resolve some inconsistencies in the extant research by conducting parallel analyses of three cohorts with varying alcohol consumption and attitudes towards alcohol use.We compare three population-based pregnancy-offspring cohorts within the Nordic Network on ADHD from Denmark and Finland. Prenatal data were gathered via self-report during pregnancy and birth outcomes were abstracted from medical charts. A total of 21,678 reports concerning inattention and hyperactivity symptoms in children were available from the Strengths and Difficulties Questionnaire or the Rutter Scale completed by parents and/or teachers.Drinking patterns differed cross-nationally. Women who had at least some social adversity (young, low education, or being single) were more likely to drink than those better off in the Finnish cohort, but the opposite was true for the Danish cohorts. Prenatal alcohol exposure was not related to risk for a high inattention-hyperactivity symptom score in children across cohorts after adjustment for covariates. In contrast, maternal smoking and social adversity during pregnancy were independently and consistently associated with an increase in risk of child symptoms.Low doses of alcohol consumption during pregnancy were not related to child inattention/hyperactivity symptoms once social adversity and smoking were taken into account.

Diffusion at the interface between two streams of liquids with different refractive indices, flowing laminarly, creates a controllable concentration gradient and a corresponding refractive index gradient. Using flow rate to change the time over which diffusion occurs in a liquid-liquid (L2) optical waveguide, we demonstrate an optical splitter and a wavelength filter. The optical splitter comprises two parallel L2 waveguides which smoothly merge into a single L2 waveguide by diffusion. The wavelength filter comprises an optical splitter in which the two L2 waveguides contain an absorbing dye.

Background: The optimal intake levels of fruit and vegetables for maintaining long-term health are uncertain. Methods: We followed 66 719 women from the Nurses’ Health Study (1984–2014) and 42 016 men from the Health Professionals Follow-up Study (1986–2014) who were free from cardiovascular disease (CVD), cancer, and diabetes at baseline. Diet was assessed using a validated semiquantitative food frequency questionnaire at baseline and updated every 2 to 4 years. We also conducted a dose-response meta-analysis, including results from our 2 cohorts and 24 other prospective cohort studies. Results: We documented 33 898 deaths during the follow-up. After adjustment for known and suspected confounding variables and risk factors, we observed nonlinear inverse associations of fruit and vegetable intake with total mortality and cause-specific mortality attributable to cancer, CVD, and respiratory disease (all P nonlinear <0.001). Intake of ≈5 servings per day of fruit and vegetables, or 2 servings of fruit and 3 servings of vegetables, was associated with the lowest mortality, and above that level, higher intake was not associated with additional risk reduction. In comparison with the reference level (2 servings/d), daily intake of 5 servings of fruit and vegetables was associated with hazard ratios (95% CI) of 0.87 (0.85–0.90) for total mortality, 0.88 (0.83–0.94) for CVD mortality, 0.90 (0.86–0.95) for cancer mortality, and 0.65 (0.59–0.72) for respiratory disease mortality. The dose-response meta-analysis that included 145 015 deaths accrued in 1 892 885 participants yielded similar results (summary risk ratio of mortality for 5 servings/d=0.87 [95% CI, 0.85–0.88]; P nonlinear <0.001). Higher intakes of most subgroups of fruits and vegetables were associated with lower mortality, with the exception of starchy vegetables such as peas and corn. Intakes of fruit juices and potatoes were not associated with total and cause-specific mortality. Conclusions: Higher intakes of fruit and vegetables were associated with lower mortality; the risk reduction plateaued at ≈5 servings of fruit and vegetables per day. These findings support current dietary recommendations to increase intake of fruits and vegetables, but not fruit juices and potatoes.

Rationale: Asthma has substantial morbidity and mortality and a strong genetic component, but identification of genetic risk factors is limited by availability of suitable studies. Objectives: To t ...

Genome-wide association studies have enabled identification of thousands of loci for hundreds of traits. Yet, for most human traits a substantial part of the estimated heritability is unexplained. This and recent advances in technology to produce high-dimensional data cost-effectively have led to method development beyond standard common variant analysis, including single-phenotype rare variant and multi-phenotype common variant analysis, with the latter increasing power for locus discovery and providing suggestions of pleiotropic effects. However, there are currently no optimal methods and tools for the combined analysis of rare variants and multiple phenotypes. We propose a user-friendly software tool MARV for Multi-phenotype Analysis of Rare Variants. The tool is based on a method that collapses rare variants within a genomic region and models the proportion of minor alleles in the rare variants on a linear combination of multiple phenotypes. MARV provides analyses of all phenotype combinations within one run and calculates the Bayesian Information Criterion to facilitate model selection. The running time increases with the size of the genetic data while the number of phenotypes to analyse has little effect both on running time and required memory. We illustrate the use of MARV with analysis of triglycerides (TG), fasting insulin (FI) and waist-to-hip ratio (WHR) in 4,721 individuals from the Northern Finland Birth Cohort 1966. The analysis suggests novel multi-phenotype effects for these metabolic traits at APOA5 and ZNF259, and at ZNF259 provides stronger support for association (P TG+FI = 1.8 × 10−9) than observed in single phenotype rare variant analyses (P TG = 6.5 × 10−8 and P FI = 0.27). MARV is a computationally efficient, flexible and user-friendly software tool allowing rapid identification of rare variant effects on multiple phenotypes, thus paving the way for novel discoveries and insights into biology of complex traits.

Objective The objective of this study was to evaluate the effect of skipping breakfast on body composition and cardiometabolic risk factors. Methods This study conducted a systematic review and meta‐analysis of randomized controlled trials (RCTs) evaluating breakfast skipping compared with breakfast consumption. Inclusion criteria included age ≥ 18, intervention duration ≥ 4 weeks, ≥ 7 participants per group, and ≥ 1 body composition measure. Random‐effects meta‐analyses of the effect of breakfast skipping on body composition and cardiometabolic risk factors were performed. Results Seven RCTs ( n = 425 participants) with an average duration of 8.6 weeks were included. Compared with breakfast consumption, breakfast skipping significantly reduced body weight (weighted mean difference [WMD] = −0.54 kg [95% CI: −1.05 to −0.03], P = 0.04 , I 2 = 21.4%). Percent body fat was reported in 5 studies and was not significantly different between breakfast skippers and consumers. Three studies reported on low‐density lipoprotein cholesterol (LDL), which was increased in breakfast skippers as compared with breakfast consumers (WMD = 9.24 mg/dL [95% CI: 2.18 to 16.30], P = 0.01). Breakfast skipping did not lead to significant differences in blood pressure, total cholesterol, high‐density lipoprotein (HDL) cholesterol, triglycerides, C‐reactive protein, insulin, fasting glucose, leptin, homeostatic model assessment of insulin resistance, or ghrelin. Conclusions Breakfast skipping may have a modest impact on weight loss and may increase LDL in the short term. Further studies are needed to provide additional insight into the effects of breakfast skipping.

No abstract is provided for this article.

Little is known about the potential adherence to and the effectiveness of a low-carbohydrate (LC) diet on weight loss and cardiometabolic risk factors in Chinese adults with a habitually high carbohydrate intake. In the present controlled feeding trial, fifty overweight or obese women (age 47·9 ( sem 0·9) years; BMI 26·7 ( sem 0·3) kg/m 2 ) were randomly assigned to a LC non-energy-restricted diet (initial carbohydrate intake 20 g/d, with a 10 g increase weekly) or an energy-restricted (ER) diet (carbohydrate intake 156–205 g/d, ER to 5021 or 6276 kJ/d, 35 % average energy reduction) for 12 weeks. Over the intervention period, the two diets had comparable compliance (96 %) and self-reported acceptability. At week 12, carbohydrate intake in the LC and ER groups contributed to 36·1 and 51·1 % of total energy, respectively ( P < 0·001). Although both diets showed similarly decreased mean body weight (LC − 5·27 (95 % CI − 6·08, − 4·46) kg; ER − 5·09 (95 % CI − 5·50, − 4·67) kg, P = 0·67) and percentage of fat mass measured by dual-energy X-ray absorptiometry (LC − 1·19 (95 % CI − 1·88, − 0·50) %; ER − 1·56 (95 % CI − 2·20, − 0·92) %, P = 0·42), participants in the LC group had greater reductions in the ratio of total cholesterol:HDL-cholesterol ( P = 0·03) and also in the ratio of TAG:HDL-cholesterol ( P = 0·01) than those in the ER group. The present 12-week diet trial suggested that both a LC non-energy-restricted diet and an ER diet were acceptable to Chinese women and both diets were equally effective in reducing weight and fat mass. Moreover, the LC diet showed beneficial effects on blood lipid profiles.

Background and Aims: We demonstrated in the randomized 18-month DIRECT PLUS trial (n = 294) that a Mediterranean (MED) diet, supplemented with polyphenol-rich Mankai duckweed, green tea, and walnuts and restricted in red/processed meat, caused substantial intrahepatic fat (IHF%) loss compared with 2 other healthy diets, reducing NAFLD by half, regardless of similar weight loss. Here, we investigated the baseline proteomic profile associated with IHF% and the changes in proteomics associated with IHF% changes induced by lifestyle intervention. Approach and Results: We calculated IHF% by proton magnetic resonance spectroscopy (normal IHF% <5% and abnormal IHF% ≥5%). We assayed baseline and 18-month samples for 95 proteomic biomarkers.Participants (age = 51.3 ± 10.8 y; 89% men; and body mass index = 31.3 ± 3.9 kg/m 2 ) had an 89.8% 18-month retention rate; 83% had eligible follow-up proteomics measurements, and 78% had follow-up proton magnetic resonance spectroscopy. At baseline, 39 candidate proteins were significantly associated with IHF% (false discovery rate <0.05), mostly related to immune function pathways (eg, hydroxyacid oxidase 1). An IHF% prediction based on the DIRECT PLUS by combined model ( R 2 = 0.47, root mean square error = 1.05) successfully predicted IHF% ( R 2 = 0.53) during testing and was stronger than separately inputting proteins/traditional markers ( R 2 = 0.43/0.44). The 18-month lifestyle intervention induced changes in 18 of the 39 candidate proteins, which were significantly associated with IHF% change, with proteins related to metabolism, extracellular matrix remodeling, and immune function pathways. Thrombospondin-2 protein change was higher in the green-MED compared to the MED group, beyond weight and IHF% loss ( p = 0.01). Protein principal component analysis revealed differences in the third principal component time distinct interactions across abnormal/normal IHF% trajectory combinations; p < 0.05 for all). Conclusions: Our findings suggest novel proteomic signatures that may indicate MRI-assessed IHF state and changes during lifestyle intervention. Specifically, carbonic anhydrase 5A, hydroxyacid oxidase 1, and thrombospondin-2 protein changes are independently associated with IHF% change, and thrombospondin-2 protein change is greater in the green-MED/high polyphenols diet.

Rapid advances in high performance computing (HPC) and the Internet are heralding a paradigm shift to network-based scientific software servers, libraries, repositories and problem solving environments. According to this new paradigm, vital pieces of software and information required for a computation are distributed across a network and need to be identified and 'linked' together at run time; this implies a 'net-centric' and collaborative scenario for scientific computing. This scenario requires the application to dynamically choose the best among several competing resources that can solve a given problem. For these systems to become ubiquitous, efficient mechanisms for collaboration and automatic inference of the abilities of multiple 'compute servers' need to be established. The authors demonstrate a methodology to facilitate collaborative scientific computing. Their idea is comprised of (i) a concept of 'reasonableness' to automatically generate exemplars for learning the mapping from problems to 'servers' and (ii) a neuro-fuzzy technique developed earlier by the authors that conducts supervised classification on the exemplars generated. The techniques work in an on-line manner and cater to mutually non-exclusive classes which are critical in the collaborative networked computing landscape.

OBJECTIVE Individuals with type 2 diabetes have high risk of late-life cognitive impairment, yet little is known about strategies to modify risk. Targeting insulin resistance and vascular complications—both associated with cognitive decline—may be a productive approach. We investigated whether dietary fat, which modulates glucose and lipid metabolism, might influence cognitive decline in older adults with diabetes. RESEARCH DESIGN AND METHODS Beginning in 1995–1999, we evaluated cognitive function in 1,486 Nurses' Health Study participants, aged ≥70 years, with type 2 diabetes; second evaluations were conducted 2 years later. Dietary fat intake was assessed regularly beginning in 1980; we considered average intake from 1980 (at midlife) through initial cognitive interview and also after diabetes diagnosis. We used multivariate-adjusted linear regression models to obtain mean differences in cognitive decline across tertiles of fat intake. RESULTS Higher intakes of saturated and trans fat since midlife, and lower polyunsaturated to saturated fat ratio, were each highly associated with worse cognitive decline in these women. On a global score averaging all six cognitive tests, mean decline among women in the highest trans fat tertile was 0.15 standard units worse than that among women in the lowest tertile (95% CI −0.24 to −0.06, P = 0.002); this mean difference was comparable with the difference we find in women 7 years apart in age. Results were similar when we analyzed diet after diabetes diagnosis. CONCLUSIONS These findings suggest that lower intakes of saturated and trans fat and higher intake of polyunsaturated fat relative to saturated fat may reduce cognitive decline in individuals with type 2 diabetes.