Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk

The timing of puberty is a highly polygenic childhood trait that is epidemiologically associated with various adult diseases. Using 1000 Genomes Project-imputed genotype data in up to similar to 370,000 women, we identify 389 independent signals (P <5 x 10(-8)) for age at menarche, a milestone in female pubertal development. In Icelandic data, these signals explain similar to 7.4% of the population variance in age at menarche, corresponding to similar to 25% of the estimated heritability. We implicate similar to 250 genes via coding variation or associated expression, demonstrating significant enrichment in neural tissues. Rare variants near the imprinted genes MKRN3 and DLK1 were identified, exhibiting large effects when paternally inherited. Mendelian randomization analyses suggest causal inverse associations, independent of body mass index (BMI), between puberty timing and risks for breast and endometrial cancers in women and prostate cancer in men. In aggregate, our findings highlight the complexity of the genetic regulation of puberty timing and support causal links with cancer susceptibility

A case study of an individual participant data meta-analysis of diagnostic accuracy showed that prediction regions represented heterogeneity well

The diagnostic accuracy of a screening tool is often characterized by its sensitivity and specificity. An analysis of these measures must consider their intrinsic correlation. In the context of an individual participant data meta-analysis, heterogeneity is one of the main components of the analysis. When using a random-effects meta-analytic model, prediction regions provide deeper insight into the effect of heterogeneity on the variability of estimated accuracy measures across the entire studied population, not just the average. This study aimed to investigate heterogeneity via prediction regions in an individual participant data meta-analysis of the sensitivity and specificity of the Patient Health Questionnaire-9 for screening to detect major depression. From the total number of studies in the pool, four dates were selected containing roughly 25%, 50%, 75% and 100% of the total number of participants. A bivariate random-effects model was fitted to studies up to and including each of these dates to jointly estimate sensitivity and specificity. Two-dimensional prediction regions were plotted in ROC-space. Subgroup analyses were carried out on sex and age, regardless of the date of the study. The dataset comprised 17,436 participants from 58 primary studies of which 2322 (13.3%) presented cases of major depression. Point estimates of sensitivity and specificity did not differ importantly as more studies were added to the model. However, correlation of the measures increased. As expected, standard errors of the logit pooled TPR and FPR consistently decreased as more studies were used, while standard deviations of the random-effects did not decrease monotonically. Subgroup analysis by sex did not reveal important contributions for observed heterogeneity; however, the shape of the prediction regions differed. Subgroup analysis by age did not reveal meaningful contributions to the heterogeneity and the prediction regions were similar in shape. Prediction intervals and regions reveal previously unseen trends in a dataset. In the context of a meta-analysis of diagnostic test accuracy, prediction regions can display the range of accuracy measures in different populations and settings

Rising rural body-mass index is the main driver of the global obesity epidemic in adults

Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities 1,2 . This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity 3�6 . Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55 of the global rise in mean BMI from 1985 to 2017�and more than 80 in some low- and middle-income regions�was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing�and in some countries reversal�of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories. © 2019, The Author(s)

Spectral variables, growth analysis and yield of sugarcane Variáveis espectrais e indicadores de desenvolvimento e produtividade da cana-de-açúcar

Spectral information is well related with agronomic variables and can be used in crop monitoring and yield forecasting. This paper describes a multitemporal research with the sugarcane variety SP80-1842, studying its spectral behavior using field spectroscopy and its relationship with agronomic parameters such as leaf area index (LAI), number of stalks per meter (NPM), yield (TSS) and total biomass (BMT). A commercial sugarcane field in Araras/SP/Brazil was monitored for two seasons. Radiometric data and agronomic characterization were gathered in 9 field campaigns. Spectral vegetation indices had similar patterns in both seasons and adjusted to agronomic parameters. Band 4 (B4), Simple Ratio (SR), Normalized Difference Vegetation Index (NDVI), and Soil Adjusted Vegetation Index (SAVI) increased their values until the end of the vegetative stage, around 240 days after harvest (DAC). After that stage, B4 reflectance and NDVI values began to stabilize and decrease because the crop reached ripening and senescence stages. Band 3 (B3) and RVI presented decreased values since the beginning of the cycle, followed by a stabilization stage. Later these values had a slight increase caused by the lower amount of green vegetation. Spectral variables B3, RVI, NDVI, and SAVI were highly correlated (above 0.79) with LAI, TSS, and BMT, and about 0.50 with NPM. The best regression models were verified for RVI, LAI, and NPM, which explained 0.97 of TSS variation and 0.99 of BMT variation.<br>A informação espectral tem boa relação com variáveis agronômicas e pode contribuir com informações para o monitoramento, acompanhamento e previsão de safras. O presente trabalho descreve a análise multitemporal do comportamento espectral da variedade de cana-de-açúcar SP80-1842 e a relação com variáveis agronômicas como índice de área foliar (IAF), número de perfilhos por metro (NPM), produtividade (TCH) e biomassa total (BMT). Nas safras 2000/2001 e 2001/2002, um talhão comercial, localizada no município de Araras/SP foi monitorado em nove campanhas de coleta de dados radiométricos e agronômicos. O comportamento temporal das variáveis espectrais acompanhou o comportamento das variáveis agronômicas. A banda 4 (B4), o índice de vegetação da razão simples (SR), o índice de vegetação por diferença normalizada (NDVI) e o índice de vegetação ajustado ao solo (SAVI) aumentaram seus valores até o fim da fase de crescimento vegetativo, aproximadamente até os 240 dias após o corte, a partir do qual os valores se estabilizaram e diminuíram em função da entrada da cultura na fase de maturação. A banda 3 (B3) e o índice de vegetação da razão (RVI) tiveram queda em seus valores desde o início do ciclo, com posterior estabilização e aumento em seus valores devido ao aumento da quantidade de palha e da queda da biomassa foliar. As variáveis espectrais B3, RVI, NDVI e SAVI tiveram correlações maiores que 0,79 com as variáveis IAF e BMT e de aproximadamente 0,50 com o NPM. Os melhores modelos de regressão linear múltipla foram os com RVI, IAF e NPM e explicaram 0,97 da variação da TCH e 0,99 da BMT

Orbital spectral variables, growth analysis and sugarcane yield Variáveis espectrais orbitais, indicadoras de desenvolvimento e produtividade da cana-de-açúcar

Temporal analysis of crop development in commercial fields requires tools for large area monitoring, such as remote sensing. This paper describes the temporal evolution of sugar cane biophysical parameters such as total biomass (BMT), yield (TSS), leaf area index (LAI), and number of plants per linear meter (NPM) correlated to Landsat data. During the 2000 and 2001 cropping seasons, a commercial sugarcane field in Araras, São Paulo state, Brazil, planted with the SP80-1842 sugarcane variety in the 4th and 5th cuts, was monitored using nine Landsat images. Spectral data were correlated with agronomic data, obtained simultaneously to the imagery acquisition. Two methodologies were used to collect spectral data from the images: four pixels (2 &#215; 2) window and average of total pixels in the field. Linear and multiple regression analysis was used to study the spectral behavior of the plants and to correlate with agronomic variables (days after harvest-DAC, LAI, NPM, BMT and TSS). No difference was observed between the methodologies to collect spectral data. The best models to describe the spectral crop development in relation to DAC were the quadratic and cubic models. Ratio vegetation index and normalized difference vegetation index demonstrated correlation with DAC, band 3 (B3) was correlated with LAI, and NDVI was well correlated with TSS and BMT. The best fit curves to estimate TSS and BMT presented r² between 0.68 and 0.97, suggesting good potential in using orbital spectral data to monitor sugarcane fields.<br>Dados de satélites são tradicionalmente utilizados em monitoramento de culturas. O presente trabalho busca contribuir no entendimento da evolução temporal de indicadores de crescimento da cana-de-açúcar como a biomassa total (BMT), produtividade (TSS), índice de área foliar (LAI) e número de plantas por metro (NPM) por meio de dados orbitais dos satélites Landsat 5 e 7, e verificar o seu potencial para o monitoramento desta. Durante as safras 2000 e 2001, uma área comercial em Araras, SP, cultivada com a variedade SP80-1842 no 4º e 5º cortes, foi acompanhada por imagens, buscando-se correlacionar dados espectrais com dados agronômicos. Os dados espectrais foram coletados de duas formas: uma com janelas de quatro pixels e outra com dados médios do talhão (DMt). Regressão linear e múltipla foram usadas para a análise temporal das bandas 3 e 4 e de índices de vegetação. As correlações e ajuste de modelos entre os dados espectrais orbitais e as variáveis agronômicas não apresentaram diferenças estatísticas. Os modelos quadráticos e cúbicos melhor descreveram o desenvolvimento temporal das variáveis espectrais, em função dos dias após o corte e apresentaram significância com os índices de vegetação da razão e por diferença normalizada (NDVI). As correlações entre os dados espectrais médios do talhão e as variáveis agronômicas foram significativas para banda3 e LAI, e entre NDVI e TSS/BMT. Os dados médios do talhão (DMt), para primeira safra (1ªS), para a segunda safra (2ªS) e ambas juntas geraram regressões múltiplas, com coeficientes determinação (r²) variando de 0,68 a 0,97 para a TSS e a BMT, mostrando que os dados espectrais orbitais estudados podem ser empregados no monitoramento da cultura da cana-de-açúcar