Uncovering the heterogeneity and temporal complexity of neurodegenerative diseases with Subtype and Stage Inference

The heterogeneity of neurodegenerative diseases is a key confound to disease understanding and treatment development, as study cohorts typically include multiple phenotypes on distinct disease trajectories. Here we introduce a machine-learning technique\u2014Subtype and Stage Inference (SuStaIn)\u2014able to uncover data-driven disease phenotypes with distinct temporal progression patterns, from widely available cross-sectional patient studies. Results from imaging studies in two neurodegenerative diseases reveal subgroups and their distinct trajectories of regional neurodegeneration. In genetic frontotemporal dementia, SuStaIn identifies genotypes from imaging alone, validating its ability to identify subtypes; further the technique reveals within-genotype heterogeneity. In Alzheimer\u2019s disease, SuStaIn uncovers three subtypes, uniquely characterising their temporal complexity. SuStaIn provides fine-grained patient stratification, which substantially enhances the ability to predict conversion between diagnostic categories over standard models that ignore subtype (p = 7.18 7 10 124 ) or temporal stage (p = 3.96 7 10 125 ). SuStaIn offers new promise for enabling disease subtype discovery and precision medicine

Filocrono em batateira afetado pelo tamanho do tubérculo-semente e pela época de cultivo Phyllocrono in potato affected by tuber-seed size and growing season

O objetivo deste trabalho foi estimar o filocrono de plantas de batata da cultivar Asterix oriundas de diferentes tamanhos de tubérculos-semente, em duas épocas de cultivo em campo utilizando o conceito de graus-dia para o cálculo do filocrono. O experimento foi desenvolvido em Santa Maria (RS), na primavera de 2003 e no outono de 2004. Foram usados quatro tamanhos de tubérculos-semente da cultivar de batata Asterix: entre 2 e 4 cm, 4 e 6 cm, 6 e 8 cm e 8 e 10 cm. O filocrono (ºC dia folha-1) foi estimado pelo inverso do coeficiente angular da relação entre número de folhas na haste principal e a soma térmica calculada por três métodos: método 1 - considera apenas a temperatura base; método 2 - considera a temperatura base e a temperatura ótima, e método 3 - considera a temperatura base, a temperatura ótima e a temperatura máxima. O tamanho do tubérculo-semente não afetou o filocrono, mas o método de cálculo da soma térmica e a época de cultivo afetaram o filocrono da batateira cultivar Asterix. No método de cálculo da soma térmica a ser usado no filocrono da batateira cultivar Asterix, recomenda-se usar a temperatura base e a temperatura ótima, pois com este método, o filocrono foi similar entre as épocas de cultivo.<br>The objective of this study was to estimate the phyllochron of the potato cultivar Asterix in plants derived from different tuber seed sizes in two field growing seasons using the concept of degrees-days for calculating the phyllochron. The experiment was conducted in Santa Maria, RS, during Spring 2003 and Fall 2004. Four classes of tuber-seed diameter of the potato cultivar Asterix were used: 2-4 cm, 4-6 cm, 6-8 cm and 8-10 cm. The phyllochron was estimated as the inverse of the slope of the linear regression of main stem leaves number against the thermal time calculated with three methods: method 1 - considering only the base temperature, method 2 - considering the base temperature and the optimum temperature, and method 3 - considering the base temperature, the optimum temperature and the maximum temperature. Tuber-seed size did not affect the phyllochron of the potato cultivar Asterix, but the method of calculating thermal time and the planting date affected the phyllochron. For the method of calculating thermal time in the phyllochron of the potato cultivar Asterix, it is recommended to use the base temperature and the optimum temperature, because it produced similar phyllochron values in the two growing seasons

Simulating maize phenology as a function of air temperature with a linear and a nonlinear model Simulação da fenologia do milho em função da temperatura do ar por um modelo linear e um não linear

The objective of this study was to adapt a nonlinear model (Wang and Engel - WE) for simulating the phenology of maize (Zea mays L.), and to evaluate this model and a linear one (thermal time), in order to predict developmental stages of a field-grown maize variety. A field experiment, during 2005/2006 and 2006/2007 was conducted in Santa Maria, RS, Brazil, in two growing seasons, with seven sowing dates each. Dates of emergence, silking, and physiological maturity of the maize variety BRS Missões were recorded in six replications in each sowing date. Data collected in 2005/2006 growing season were used to estimate the coefficients of the two models, and data collected in the 2006/2007 growing season were used as independent data set for model evaluations. The nonlinear WE model accurately predicted the date of silking and physiological maturity, and had a lower root mean square error (RMSE) than the linear (thermal time) model. The overall RMSE for silking and physiological maturity was 2.7 and 4.8 days with WE model, and 5.6 and 8.3 days with thermal time model, respectively.<br>O objetivo deste trabalho foi adaptar um modelo não linear (Wang e Engel - WE), para simular a fenologia do milho (Zea mays L.), e avaliar esse modelo e um modelo linear (soma térmica), para estimar os estágios de desenvolvimento de uma variedade de milho cultivada em campo. Um experimento de dois anos, com sete datas anuais de semeadura cada ano, foi conduzido em Santa Maria, RS, durante os anos agrícolas 2005/2006 e 2006/2007. Foram registradas as datas de emergência, espigamento e maturação fisiológica da variedade de milho BRS Missões, em seis repetições, em cada data de semeadura. Os dados coletados no ano agrícola 2005/2006 foram usados para estimar os coeficientes dos dois modelos, e os dados coletados no ano agrícola 2006/2007 foram usados como dados independentes para avaliar os modelos. O modelo não linear (WE) estimou com precisão as datas de espigamento e maturação fisiológica e apresentou a raiz do quadrado médio do erro (RQME) menor que o modelo linear (soma térmica). A RQME geral para espigamento e maturação fisiológica foi 2,7 e 4,8 dias, com o modelo de WE, e 5,6 e 8,3 dias com o modelo da soma térmica, respectivamente