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.

A genome-wide association meta-analysis identifies new childhood obesity loci

Multiple genetic variants have been associated with adult obesity and a few with severe obesity in childhood; however, less progress has been made in establishing genetic influences on common early-onset obesity. We performed a North American, Australian and European collaborative meta-analysis of 14 studies consisting of 5,530 cases (≥95th percentile of body mass index (BMI)) and 8,318 controls (<50th percentile of BMI) of European ancestry. Taking forward the eight newly discovered signals yielding association with P < 5 × 10(-6) in nine independent data sets (2,818 cases and 4,083 controls), we observed two loci that yielded genome-wide significant combined P values near OLFM4 at 13q14 (rs9568856; P = 1.82 × 10(-9); odds ratio (OR) = 1.22) and within HOXB5 at 17q21 (rs9299; P = 3.54 × 10(-9); OR = 1.14). Both loci continued to show association when two extreme childhood obesity cohorts were included (2,214 cases and 2,674 controls). These two loci also yielded directionally consistent associations in a previous meta-analysis of adult BMI(1).

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.

Evidence of increased net ecosystem productivity associated with a longer vegetated season in a deciduous forest in south-central Indiana, USA

Observations of net ecosystem exchange (NEE) of carbon and its biophysical drivers have been collected at the AmeriFlux site in the Morgan-Monroe State Forest (MMSF) in Indiana, USA since 1998. Thus, this is one of the few deciduous forest sites in the world, where a decadal analysis on net ecosystem productivity (NEP) trends is possible. Despite the large interannual variability in NEP, the observations show a significant increase in forest productivity over the past 10 years (by an annual increment of about 10 g C m−2 yr−1). There is evidence that this trend can be explained by longer vegetative seasons, caused by extension of the vegetative activity in the fall. Both phenological and flux observations indicate that the vegetative season extended later in the fall with an increase in length of about 3 days yr−1 for the past 10 years. However, these changes are responsible for only 50% of the total annual gain in forest productivity in the past decade. A negative trend in air and soil temperature during the winter months may explain an equivalent increase in NEP through a decrease in ecosystem respiration.

Beyond urban legends : an emerging framework of urban ecology, as illustrated by the Baltimore Ecosystem Study

The emerging discipline of urban ecology is shifting focus from ecological processes embedded within cities to integrative studies of large urban areas as biophysical-social complexes. Yet this discipline lacks a theory. Results from the Baltimore Ecosystem Study, part of the Long Term Ecological Research Network, expose new assumptions and test existing assumptions about urban ecosystems. The findings suggest a broader range of structural and functional relationships than is often assumed for urban ecological systems. We address the relationships between social status and awareness of environmental problems, and between race and environmental hazard. We present patterns of species diversity, riparian function, and stream nitrate loading. In addition, we probe the suitability of land-use models, the diversity of soils, and the potential for urban carbon sequestration. Finally, we illustrate lags between social patterns and vegetation, the biogeochemistry of lawns, ecosystem nutrient retention, and social-biophysical feedbacks. These results suggest a framework for a theory of urban ecosystems.

Low cost home ownership: legal issues of the shared ownership lease

Analysis of the decision in Richardson v Midland Heart Ltd (formally Focus Homes Options) [2008] L&TR 31

A comparison of methods for constructing confidence intervals after phase II/III clinical trials

Recently, in order to accelerate drug development, trials that use adaptive seamless designs such as phase II/III clinical trials have been proposed. Phase II/III clinical trials combine traditional phases II and III into a single trial that is conducted in two stages. Using stage 1 data, an interim analysis is performed to answer phase II objectives and after collection of stage 2 data, a final confirmatory analysis is performed to answer phase III objectives. In this paper we consider phase II/III clinical trials in which, at stage 1, several experimental treatments are compared to a control and the apparently most effective experimental treatment is selected to continue to stage 2. Although these trials are attractive because the confirmatory analysis includes phase II data from stage 1, the inference methods used for trials that compare a single experimental treatment to a control and do not have an interim analysis are no longer appropriate. Several methods for analysing phase II/III clinical trials have been developed. These methods are recent and so there is little literature on extensive comparisons of their characteristics. In this paper we review and compare the various methods available for constructing confidence intervals after phase II/III clinical trials.

Educational attainment in poor comprehenders

To date, only one study has investigated educational attainment in poor (reading) comprehenders, providing evidence of poor performance on national UK school tests at age 11 years relative to peers (Cain & Oakhill, 2006). In the present study, we adopted a longitudinal approach, tracking attainment on such tests from 11 years to the end of compulsory schooling in the UK (age 16 years). We aimed to investigate the proposal that educational weaknesses (defined as poor performance on national assessments) might become more pronounced over time, as the curriculum places increasing demands on reading comprehension. Participants comprised 15 poor comprehenders and 15 controls; groups were matched for chronological age, nonverbal reasoning ability and decoding skill. Children were identified at age 9 years using standardised measures of nonverbal reasoning, decoding and reading comprehension. These measures, along with a measure of oral vocabulary knowledge, were repeated at age 11 years. Data on educational attainment were collected from all participants (N = 30) at age 11 and from a subgroup (n = 21) at 16 years. Compared to controls, educational attainment in poor comprehenders was lower at ages 11 and 16 years, an effect that was significant at 11 years. When poor comprehenders were compared to national performance levels, they showed significantly lower performance at both time points. Low educational attainment was not evident for all poor comprehenders. Nonetheless, our findings point to a link between reading comprehension difficulties in mid to late childhood and poor educational outcomes at ages 11 and 16 years. At these ages, pupils in the UK are making key transitions: they move from primary to secondary schools at 11, and out of compulsory schooling at 16.

Development of a food-exchange model to replace saturated fat with MUFAS and n-6 PUFAS in adults at moderate cardiovascular risk

The recommendation to reduce saturated fatty acid (SFA) consumption to ≤10% of total energy (%TE) is a key public health target aimed at lowering cardiovascular disease (CVD) risk. Replacement of SFA with unsaturated fats may provide greater benefit than replacement with carbohydrates, yet the optimal type of fat is unclear. The aim was to develop a flexible food-exchange model to investigate the effects of substituting SFAs with monounsaturated fatty acids (MUFAs) or n-6 (ω-6) polyunsaturated fatty acids (PUFAs) on CVD risk factors. In this parallel study, UK adults aged 21-60 y with moderate CVD risk (50% greater than the population mean) were identified using a risk assessment tool (n = 195; 56% females). Three 16-wk isoenergetic diets of specific fatty acid (FA) composition (%TE SFA:%TE MUFA:%TE n-6 PUFA) were designed using spreads, oils, dairy products, and snacks as follows: 1) SFA-rich diet (17:11:4; n = 65); 2) MUFA-rich diet (9:19:4; n = 64); and 3) n-6 PUFA-rich diet (9:13:10; n = 66). Each diet provided 36%TE total fat. Dietary targets were broadly met for all intervention groups, reaching 17.6 ± 0.4%TE SFA, 18.5 ± 0.3%TE MUFA, and 10.4 ± 0.3%TE n-6 PUFA in the respective diets, with significant overall diet effects for the changes in SFA, MUFA, and n-6 PUFA between groups (P < 0.001). There were no differences in the changes of total fat, protein, carbohydrate, and alcohol intake or anthropometric measures between groups. Plasma phospholipid FA composition showed changes from baseline in the proportions of total SFA, MUFA, and n-6 PUFA for each diet group, with significant overall diet effects for total SFA and MUFA between groups (P < 0.001). In conclusion, successful implementation of the food-exchange model broadly achieved the dietary target intakes for the exchange of SFA with MUFA or n-6 PUFA with minimal disruption to the overall diet in a free-living population. This trial was registered at clinicaltrials.gov as NCT01478958.

Developing international business managers through international study visits to China

Globalization is a key factor in the success of business organizations today, impacting many aspects of management performance. Understanding the global business environment has therefore become a key objective in the teaching of international business on Executive MBA programs. Drawing on the theory of experiential learning, this study examines the relationship between program structure and learning activities of an international study visit (ISV) to China and the learning experience for Executive MBA students. The findings indicate that learning experience may be most effective where the structure of an ISV incorporates certain activities that promote experiential and deep-level learning. Educational implications are discussed.

Competitive fitness in coronaviruses is not correlated with size or number of double-membrane vesicles under reduced-temperature growth conditions

Positive-stranded viruses synthesize their RNA in membrane-bound organelles, but it is not clear how this benefits the virus or the host. For coronaviruses, these organelles take the form of double-membrane vesicles (DMVs) interconnected by a convoluted membrane network. We used electron microscopy to identify murine coronaviruses with mutations in nsp3 and nsp14 that replicated normally while producing only half the normal amount of DMVs. Viruses with mutations in nsp5 and nsp16 produced small DMVs but also replicated normally. Quantitative RT-PCR confirmed that the most strongly affected of these, the nsp3 mutant, produced more viral RNA than wild-type virus. Competitive growth assays were carried out in both continuous and primary cells to better understand the contribution of DMVs to viral fitness. Surprisingly, several viruses that produced fewer or smaller DMVs showed a higher relative fitness compared to wild-type virus, suggesting that larger and more numerous DMVs do not necessarily confer a competitive advantage in primary or continuous cell culture. For the first time, this directly demonstrates that replication and organelle formation may be, at least in part, studied separately during positive-stranded RNA virus infection.