Candidate genes for obesity-susceptibility show enriched association within a large genome-wide association study for BMI

Before the advent of genome-wide association studies (GWASs), hundreds of candidate genes for obesity-susceptibility had been identified through a variety of approaches. We examined whether those obesity candidate genes are enriched for associations with body mass index (BMI) compared with non-candidate genes by using data from a large-scale GWAS. A thorough literature search identified 547 candidate genes for obesity-susceptibility based on evidence from animal studies, Mendelian syndromes, linkage studies, genetic association studies and expression studies. Genomic regions were defined to include the genes ±10 kb of flanking sequence around candidate and non-candidate genes. We used summary statistics publicly available from the discovery stage of the genome-wide meta-analysis for BMI performed by the genetic investigation of anthropometric traits consortium in 123 564 individuals. Hypergeometric, rank tail-strength and gene-set enrichment analysis tests were used to test for the enrichment of association in candidate compared with non-candidate genes. The hypergeometric test of enrichment was not significant at the 5% P-value quantile (P = 0.35), but was nominally significant at the 25% quantile (P = 0.015). The rank tail-strength and gene-set enrichment tests were nominally significant for the full set of genes and borderline significant for the subset without SNPs at P < 10(-7). Taken together, the observed evidence for enrichment suggests that the candidate gene approach retains some value. However, the degree of enrichment is small despite the extensive number of candidate genes and the large sample size. Studies that focus on candidate genes have only slightly increased chances of detecting associations, and are likely to miss many true effects in non-candidate genes, at least for obesity-related traits.

Early modern Oxford bindings in twenty-first century markup

Purpose – The Bodleian Binders Book contains nearly 150 pages of seventeenth century library records, revealing information about the binders used by the library and the thousands of bindings they produced. The purpose of this paper is to explore a pilot project to survey and record bindings information contained in the Binders Book. Design/methodology/approach – A sample size of seven pages (91 works, 65 identifiable bindings) to develop a methodology for surveying and recording bindings listed in the manuscript. To create a successful product that would be useful to bindings researchers, it addressed questions of bindings terminology and the role of the library in the knowledge creation process within the context that text encoding is changing the landscape of library functions. Text encoding formats were examined, and a basic TEI (Text Encoding Initiative) transcription was produced. This facilitates tagging of names and titles and the display of transcriptions with text images. Findings – Encoding was found not only to make the manuscript content more accessible, but to allow for the construction of new knowledge: characteristic Oxford binding traits were revealed and bindings were matched to binders. Plans for added functionality were formed. Originality/value – This research presents a “big picture” analysis of Oxford bindings as a result of text encoding and the foundation for qualitative and statistical analysis. It exemplifies the benefits of interdisciplinary methods – in this case from Digital Humanities – to enhance access to and interpretation of specialist materials and the library's provenance record.

Are power calculations useful? A multicentre neuroimaging study

There are now many reports of imaging experiments with small cohorts of typical participants that precede large-scale, often multicentre studies of psychiatric and neurological disorders. Data from these calibration experiments are sufficient to make estimates of statistical power and predictions of sample size and minimum observable effect sizes. In this technical note, we suggest how previously reported voxel-based power calculations can support decision making in the design, execution and analysis of cross-sectional multicentre imaging studies. The choice of MRI acquisition sequence, distribution of recruitment across acquisition centres, and changes to the registration method applied during data analysis are considered as examples. The consequences of modification are explored in quantitative terms by assessing the impact on sample size for a fixed effect size and detectable effect size for a fixed sample size. The calibration experiment dataset used for illustration was a precursor to the now complete Medical Research Council Autism Imaging Multicentre Study (MRC-AIMS). Validation of the voxel-based power calculations is made by comparing the predicted values from the calibration experiment with those observed in MRC-AIMS. The effect of non-linear mappings during image registration to a standard stereotactic space on the prediction is explored with reference to the amount of local deformation. In summary, power calculations offer a validated, quantitative means of making informed choices on important factors that influence the outcome of studies that consume significant resources.

Identifying trends in domestic electricity consumption in Botswana

Data on electricity consumption patterns relating to different end uses in domestic houses in Botswana is virtually non-existent, despite the fact that the total electricity consumption patterns are available. This can be attributed to the lack of measured and quantified data and in other instances the lack of modern technology to perform such investigations. This paper presents findings from initial studies that are envisaged to bridge the gap. Electricity consumption patterns of 73 domestic households across three cities have been studied. This was carried out through a questionnaire survey, calculated national metering data and electricity measurements. All together nine appliance groups were identified. The results showed the mean electricity consumption for the households considering the calculated consumption from bills and the survey to be t = 4.23; p < 0.000067, two-tailed. The findings of this paper focus on a relatively small sample size (73). It would therefore not be wise to draw sweeping conclusions from the analysis or to make statements that would be aimed at influencing policies. However, the results presented forms a formidable base for further research, which is currently on going.

An investigation into knowledge acquisition idiosyncrasies in Ghanaian universities

Purpose This paper aims to fill the research and knowledge gap in knowledge management studies in Ghana. Knowledge acquisition is one of the unexploited areas in knowledge management literature, especially in the Ghanaian context. This study tries to ascertain the factors affecting knowledge acquisition in Ghanaian universities. Design/methodology/approach The study used the quantitative approach. The cross-sectional survey was adopted as the research design. A questionnaire consisting of Likert scale questions was used to collect data from the respondents. The items and the constructs were derived from the extant literature. The questionnaire was sent to 350 respondents, out of which 250 were returned fully completed. Data were quantitatively analysed using descriptive methods and factor analysis. Findings This study provides empirical evidence about the factors affecting knowledge acquisition in Ghanaian universities. Findings from the study show that programme content, lecturers’ competence, student academic background and attitude and facilities for teaching and learning influence knowledge acquisition in Ghanaian universities. Research limitations/implications Although the study seeks to generalize the findings, this should be cautiously done, as some scholars have advocated for large sample size. Nonetheless, there are some studies that have used sample size less than the one used in this study. Practical implications The study takes notice of the need for Ghanaian universities to use modern facilities and infrastructures such as electronic libraries and information technology equipment and also provide reading rooms to enhance teaching and learning. Originality/value Studies looking at knowledge acquisition in Ghanaian universities are virtually non-existent, and this study provides empirical findings on the factors affecting knowledge acquisition in Ghanaian universities.

Trends in domestic electricity consumption in Botswana

Data on electricity consumption patterns relating to different end uses in domestic houses in Botswana is virtually non-existent, despite the fact that the total electricity consumption patterns are available. This can be attributed to the lack of measured and quantified data and in other instances the lack of modern technology to perform such investigations. This paper presents findings from initial studies that are envisaged to bridge the gap. Electricity consumption patterns of 275 domestic households in Gaborone (the capital city of Botswana) have been studied. This was carried out through a questionnaire survey and electricity measurements. Households were categorized based on the number of people occupying the house. From the study, it was evident that the number of people influences the amount of energy a household use although this cannot be treated as an independent factor when assessing energy use. The study also indicated that heating, cooling and domestic hot water (DHW) account for over 30% of energy used in the home. This is worth considering in energy consumption reduction measures. Due to a small sample size, it would not be wise to draw sweeping conclusions from the analysis of this paper or to make statements that would be aimed at influencing policies. However, the results presented forms a formidable base for further research, which is currently on going.

Metrics for linking emissions of gases and aerosols to global precipitation changes

Recent advances in understanding have made it possible to relate global precipitation changes directly to emissions of particular gases and aerosols that influence climate. Using these advances, new indices are developed here called the Global Precipitation-change Potential for pulse (GPP_P) and sustained (GPP_S) emissions, which measure the precipitation change per unit mass of emissions. The GPP can be used as a metric to compare the effects of different emissions. This is akin to the global warming potential (GWP) and the global temperature-change potential (GTP) which are used to place emissions on a common scale. Hence the GPP provides an additional perspective of the relative or absolute effects of emissions. It is however recognised that precipitation changes are predicted to be highly variable in size and sign between different regions and this limits the usefulness of a purely global metric. The GPP_P and GPP_S formulation consists of two terms, one dependent on the surface temperature change and the other dependent on the atmospheric component of the radiative forcing. For some forcing agents, and notably for CO2, these two terms oppose each other – as the forcing and temperature perturbations have different timescales, even the sign of the absolute GPP_P and GPP_S varies with time, and the opposing terms can make values sensitive to uncertainties in input parameters. This makes the choice of CO2 as a reference gas problematic, especially for the GPP_S at time horizons less than about 60 years. In addition, few studies have presented results for the surface/atmosphere partitioning of different forcings, leading to more uncertainty in quantifying the GPP than the GWP or GTP. Values of the GPP_P and GPP_S for five long- and short-lived forcing agents (CO2, CH4, N2O, sulphate and black carbon – BC) are presented, using illustrative values of required parameters. The resulting precipitation changes are given as the change at a specific time horizon (and hence they are end-point metrics) but it is noted that the GPPS can also be interpreted as the time-integrated effect of a pulse emission. Using CO2 as a references gas, the GPP_P and GPP_S for the non-CO2 species are larger than the corresponding GTP values. For BC emissions, the atmospheric forcing is sufficiently strong that the GPP_S is opposite in sign to the GTP_S. The sensitivity of these values to a number of input parameters is explored. The GPP can also be used to evaluate the contribution of different emissions to precipitation change during or after a period of emissions. As an illustration, the precipitation changes resulting from emissions in 2008 (using the GPP_P) and emissions sustained at 2008 levels (using the GPP_S) are presented. These indicate that for periods of 20 years (after the 2008 emissions) and 50 years (for sustained emissions at 2008 levels) methane is the dominant driver of positive precipitation changes due to those emissions. For sustained emissions, the sum of the effect of the five species included here does not become positive until after 50 years, by which time the global surface temperature increase exceeds 1 K.

Methane cross-validation between three Fourier Transform Spectrometers: SCISAT ACE-FTS, GOSAT TANSO-FTS, and ground-based FTS measurements in the Canadian high Arctic

We present cross-validation of remote sensing measurements of methane profiles in the Canadian high Arctic. Accurate and precise measurements of methane are essential to understand quantitatively its role in the climate system and in global change. Here, we show a cross-validation between three datasets: two from spaceborne instruments and one from a ground-based instrument. All are Fourier Transform Spectrometers (FTSs). We consider the Canadian SCISAT Atmospheric Chemistry Experiment (ACE)-FTS, a solar occultation infrared spectrometer operating since 2004, and the thermal infrared band of the Japanese Greenhouse Gases Observing Satellite (GOSAT) Thermal And Near infrared Sensor for carbon Observation (TANSO)-FTS, a nadir/off-nadir scanning FTS instrument operating at solar and terrestrial infrared wavelengths, since 2009. The ground-based instrument is a Bruker 125HR Fourier Transform Infrared (FTIR) spectrometer, measuring mid-infrared solar absorption spectra at the Polar Environment Atmospheric Research Laboratory (PEARL) Ridge Lab at Eureka, Nunavut (80° N, 86° W) since 2006. For each pair of instruments, measurements are collocated within 500 km and 24 h. An additional criterion based on potential vorticity values was found not to significantly affect differences between measurements. Profiles are regridded to a common vertical grid for each comparison set. To account for differing vertical resolutions, ACE-FTS measurements are smoothed to the resolution of either PEARL-FTS or TANSO-FTS, and PEARL-FTS measurements are smoothed to the TANSO-FTS resolution. Differences for each pair are examined in terms of profile and partial columns. During the period considered, the number of collocations for each pair is large enough to obtain a good sample size (from several hundred to tens of thousands depending on pair and configuration). Considering full profiles, the degrees of freedom for signal (DOFS) are between 0.2 and 0.7 for TANSO-FTS and between 1.5 and 3 for PEARL-FTS, while ACE-FTS has considerably more information (roughly 1° of freedom per altitude level). We take partial columns between roughly 5 and 30 km for the ACE-FTS–PEARL-FTS comparison, and between 5 and 10 km for the other pairs. The DOFS for the partial columns are between 1.2 and 2 for PEARL-FTS collocated with ACE-FTS, between 0.1 and 0.5 for PEARL-FTS collocated with TANSO-FTS or for TANSO-FTS collocated with either other instrument, while ACE-FTS has much higher information content. For all pairs, the partial column differences are within ± 3 × 1022 molecules cm−2. Expressed as median ± median absolute deviation (expressed in absolute or relative terms), these differences are 0.11 ± 9.60 × 10^20 molecules cm−2 (0.012 ± 1.018 %) for TANSO-FTS–PEARL-FTS, −2.6 ± 2.6 × 10^21 molecules cm−2 (−1.6 ± 1.6 %) for ACE-FTS–PEARL-FTS, and 7.4 ± 6.0 × 10^20 molecules cm−2 (0.78 ± 0.64 %) for TANSO-FTS–ACE-FTS. The differences for ACE-FTS–PEARL-FTS and TANSO-FTS–PEARL-FTS partial columns decrease significantly as a function of PEARL partial columns, whereas the range of partial column values for TANSO-FTS–ACE-FTS collocations is too small to draw any conclusion on its dependence on ACE-FTS partial columns.

Cross-sector surveys assessing perceptions of key stakeholders towards barriers, concerns and facilitators to the appropriate use of adaptive designs in confirmatory trials

Background Appropriately conducted adaptive designs (ADs) offer many potential advantages over conventional trials. They make better use of accruing data, potentially saving time, trial participants, and limited resources compared to conventional, fixed sample size designs. However, one can argue that ADs are not implemented as often as they should be, particularly in publicly funded confirmatory trials. This study explored barriers, concerns, and potential facilitators to the appropriate use of ADs in confirmatory trials among key stakeholders. Methods We conducted three cross-sectional, online parallel surveys between November 2014 and January 2015. The surveys were based upon findings drawn from in-depth interviews of key research stakeholders, predominantly in the UK, and targeted Clinical Trials Units (CTUs), public funders, and private sector organisations. Response rates were as follows: 30(55 %) UK CTUs, 17(68 %) private sector, and 86(41 %) public funders. A Rating Scale Model was used to rank barriers and concerns in order of perceived importance for prioritisation. Results Top-ranked barriers included the lack of bridge funding accessible to UK CTUs to support the design of ADs, limited practical implementation knowledge, preference for traditional mainstream designs, difficulties in marketing ADs to key stakeholders, time constraints to support ADs relative to competing priorities, lack of applied training, and insufficient access to case studies of undertaken ADs to facilitate practical learning and successful implementation. Associated practical complexities and inadequate data management infrastructure to support ADs were reported as more pronounced in the private sector. For funders of public research, the inadequate description of the rationale, scope, and decision-making criteria to guide the planned AD in grant proposals by researchers were all viewed as major obstacles. Conclusions There are still persistent and important perceptions of individual and organisational obstacles hampering the use of ADs in confirmatory trials research. Stakeholder perceptions about barriers are largely consistent across sectors, with a few exceptions that reflect differences in organisations’ funding structures, experiences and characterisation of study interventions. Most barriers appear connected to a lack of practical implementation knowledge and applied training, and limited access to case studies to facilitate practical learning. Keywords: Adaptive designs; flexible designs; barriers; surveys; confirmatory trials; Phase 3; clinical trials; early stopping; interim analyses

Interim analyses and sequential designs in phase III studies

Recruitment of patients to a clinical trial usually occurs over a period of time, resulting in the steady accumulation of data throughout the trial's duration. Yet, according to traditional statistical methods, the sample size of the trial should be determined in advance, and data collected on all subjects before analysis proceeds. For ethical and economic reasons, the technique of sequential testing has been developed to enable the examination of data at a series of interim analyses. The aim is to stop recruitment to the study as soon as there is sufficient evidence to reach a firm conclusion. In this paper we present the advantages and disadvantages of conducting interim analyses in phase III clinical trials, together with the key steps to enable the successful implementation of sequential methods in this setting. Examples are given of completed trials, which have been carried out sequentially, and references to relevant literature and software are provided.

A comprehensive meta-analysis of common genetic variants in autism spectrum conditions

Background Autism spectrum conditions (ASC) are a group of neurodevelopmental conditions characterized by difficulties in social interaction and communication alongside repetitive and stereotyped behaviours. ASC are heritable, and common genetic variants contribute substantial phenotypic variability. More than 600 genes have been implicated in ASC to date. However, a comprehensive investigation of candidate gene association studies in ASC is lacking. Methods In this study, we systematically reviewed the literature for association studies for 552 genes associated with ASC. We identified 58 common genetic variants in 27 genes that have been investigated in three or more independent cohorts and conducted a meta-analysis for 55 of these variants. We investigated publication bias and sensitivity and performed stratified analyses for a subset of these variants. Results We identified 15 variants nominally significant for the mean effect size, 8 of which had P values below a threshold of significance of 0.01. Of these 15 variants, 11 were re-investigated for effect sizes and significance in the larger Psychiatric Genomics Consortium dataset, and none of them were significant. Effect direction for 8 of the 11 variants were concordant between both the datasets, although the correlation between the effect sizes from the two datasets was poor and non-significant. Conclusions This is the first study to comprehensively examine common variants in candidate genes for ASC through meta-analysis. While for majority of the variants, the total sample size was above 500 cases and 500 controls, the total sample size was not large enough to accurately identify common variants that contribute to the aetiology of ASC.

Assessing species’ habitat associations from occurrence records, standardised monitoring data and expert opinion: a test with British butterflies

Accurate knowledge of species’ habitat associations is important for conservation planning and policy. Assessing habitat associations is a vital precursor to selecting appropriate indicator species for prioritising sites for conservation or assessing trends in habitat quality. However, much existing knowledge is based on qualitative expert opinion or local scale studies, and may not remain accurate across different spatial scales or geographic locations. Data from biological recording schemes have the potential to provide objective measures of habitat association, with the ability to account for spatial variation. We used data on 50 British butterfly species as a test case to investigate the correspondence of data-derived measures of habitat association with expert opinion, from two different butterfly recording schemes. One scheme collected large quantities of occurrence data (c. 3 million records) and the other, lower quantities of standardised monitoring data (c. 1400 sites). We used general linear mixed effects models to derive scores of association with broad-leaf woodland for both datasets and compared them with scores canvassed from experts. Scores derived from occurrence and abundance data both showed strongly positive correlations with expert opinion. However, only for occurrence data did these fell within the range of correlations between experts. Data-derived scores showed regional spatial variation in the strength of butterfly associations with broad-leaf woodland, with a significant latitudinal trend in 26% of species. Sub-sampling of the data suggested a mean sample size of 5000 occurrence records per species to gain an accurate estimation of habitat association, although habitat specialists are likely to be readily detected using several hundred records. Occurrence data from recording schemes can thus provide easily obtained, objective, quantitative measures of habitat association.

Rejection thresholds (RjT) of sweet likers and dislikers

Sweetness is generally a desirable taste, however consumers can be grouped into sweet likers and dislikers according to optimally preferred sucrose concentrations. Understanding the levels of sweetness in products that are acceptable and unacceptable to both consumer groups is important to product development and for influencing dietary habits. The concentrations at which sucrose decreases liking (the rejection threshold; RjT) in liquid and semi-solid matrices were investigated in this study. Thirty six consumers rated their liking of 5 sucrose aqueous solutions; this identified 36% sweet likers (SL) whose liking ratings increased with increasing sucrose and 64% sweet dislikers (SD) whose liking ratings decreased above 6% (w/v) sucrose. We hypothesized that SL and SD would have different RjT for sucrose in products. This was tested by preparing 8 levels of sucrose in orange juice and orange jelly and presenting each against the lowest level in forced choice preference tests. In orange juice, as sucrose increased from 33g/L to 75g/L the proportion of people preferring the sweeter sample increased in both groups. However, at higher sucrose levels, the proportion of consumers preferring the sweet sample decreased. For SD, a RjT was reached at 380 g/L, whereas a significant RjT for SL was not reached. RjT in jelly were not reached as the sweetness in orange jelly was significantly lower than for orange juice (p<0.001). Despite statistically significant differences in rated sweetness between SL and SD (p=0.019), the extent of difference between the two groups was minor. The results implied that sweet liker status was not substantially related to differences in sweetness perception. Self-reported dietary intake of carbohydrate, sugars and sucrose were not significantly affected by sweet liker status. However the failure to find an effect may be due to the small sample size and future studies within a larger, more representative population sample are justifiable from the results of this study.

Ecological niche similarities of Peponapis bees and non-domesticated Cucurbita species

Peponapis bees are considered specialized pollinators of Cucurbita flowers, a genus that presents several species of economic value (squashes and pumpkins). Both genera originated in the Americas, and their diversity dispersion center is in Mexico. Ten species of Peponapis and ten species of Cucurbita (only non-domesticated species) were analyzed considering the similarity of their ecological niche characteristics with respect to climatic conditions of their occurrence areas (abiotic variables) and interactions between species (biotic variables). The similarity of climatic conditions (temperature and precipitation) was estimated through cluster analyses. The areas of potential occurrence of the most similar species were obtained through ecological niche modeling and summed with geographic information system tools. Three main clusters were obtained: one with species that shared potential occurrence areas mainly in deserts (P. pruinosa, P. timberlakei, C. digitata, C. palmata, C. foetidissima), another in moist forests (P. limitaris, P. atrata, C. lundelliana, C. o. martinezii) and a third mainly in dry forests (C. a. sororia, C. radicans, C. pedatifolia, P. azteca, P. smithi, P. crassidentata, P. utahensis). Some species with similar ecological niche presented potential shared areas that are also similar to their geographical distribution, like those occurring predominantly on deserts. However, some clustered species presented larger geographical areas, such as P. pruinosa and C. foetidissima suggesting other drivers than climatic conditions to shape their distributions. The domestication of Cucurbita and also the natural history of both genera were considered also as important factors. (C) 2011 Elsevier B.V. All rights reserved.

Vivipary in the cactus family: A reply to Ortega-Baes` et al. evaluation of 25 species from northwestern Argentina

This is a reply to Ortega-Baes` et al. (2010) survey of 25 Argentinean species of cacti evaluated for vivipary. We argue that the sample size and geographic area of the species investigated is insufficient to totally exclude the putative commonness of this condition in the Cactaceae. We indicate possible reasons why they did not find viviparous fruits in their survey. Failure to detect vivipary in cacti of NW Argentina may be correlated with limited taxonomic sampling and geographic region in addition to intrinsic and extrinsic plant factors, including different stages of fruit and seed development and genetic, ecological, and edaphic aspects, which, individually or in concert, control precocious germination. We uphold that viviparity is putatively frequent in this family and list 16 new cases for a total of 53 viviparous cacti, which make up ca. 4% incidence of viviparism in the Cactaceae, a substantially higher percentage than most angiosperm families exhibiting this condition. The Cactaceae ranks fourth in frequency of viviparity after the aquatic families of mangroves and seagrasses. We suggest the re-evaluation of cactus vivipary, primarily as a reproductive adaptation to changing environments and physiological stress with a secondary role as a reproductive strategy with limited offspring dispersal/survival and fitness advantages. (C) 2011 Elsevier Ltd. All rights reserved.