Modelling mechanisms of change in crop populations

Computer -based simulation models of changes occurring within crop populations when subjected to agents of phenotypic change, have been developed for use on commonly available personal computer equipment. As an underlying developmental principle, the models have been designed as general -case, mechanistic, stochastic models, in contrast to the predominantly empirically- derived, system -specific, deterministic (predictive) models currently available. A modelling methodology has evolved, to develop portable simulation models, written in high - level, general purpose code, allowing for use, modification and continued development by biologists with little requirement for computer programming expertise.The initial subject of these modelling activities was the simulation of the effects of selection and other agents of genetic change in crop populations, resulting in the computer model, PSELECT. Output from PSELECT, specifically phenotypic and genotypic response to phenotypic truncation selection, conformed to expectation, as defined by results from established analogue modelling work. Validation of the model by comparison of output with the results from an experimental -scale plant breeding exercise was less conclusive, and, owing to the fact that the genetic basis of the phenotypic characters used in the selection programme was insufficiently defined, the validation exercise provided only broad qualitative agreement with the model output. By virtue of the predominantly subjective nature of plant breeding programmes, the development of PSELECT resulted in a model of theoretical interest, but with little current practical application.Modelling techniques from the development of the PSELECT model were applied to the simulation of plant disease epidemics, where the modelled system is well characterised, and simulation modelling is an area of active research. The model SATSUMA, simulating the spatial and temporal development of diseases within crop populations, was developed. The model generates output which conforms to current epidemiological theory, and is compatible with contemporary methods of temporal and spatial analysis of crop disease epidemics. Temporal disease progress in the simulations was accurately described by variations of a generalised logistic model. Analysis of the spatial pattern of simulated epidemics by frequency distribution fitting or distance class methods was found to give good qualitative agreement with observed biological systems.The mechanistic nature of SATSUMA and its deliberate design as a general case model make it especially suitable for the investigation of component processes in a generalised plant disease epidemic, and valuable as an educational tool. Subject to validation against observational data, such models can be utilised as predictive tools by the incorporation of information (concerning crop species, pathogen etc.) specifically relevant to the modelled system. In addition to its educational use, SATSUMA has been used as research tool for the examination of the effect of spatial pattern of disease and disease incidence on the efficiency of sampling protocols and in parameterising a general theoretical model for describing the spatio -temporal development of plant diseases

Two-year outcomes after transcatheter or surgical aortic-valve replacement.

BACKGROUND: The Placement of Aortic Transcatheter Valves (PARTNER) trial showed that among high-risk patients with aortic stenosis, the 1-year survival rates are similar with transcatheter aortic-valve replacement (TAVR) and surgical replacement. However, longer-term follow-up is necessary to determine whether TAVR has prolonged benefits. METHODS: At 25 centers, we randomly assigned 699 high-risk patients with severe aortic stenosis to undergo either surgical aortic-valve replacement or TAVR. All patients were followed for at least 2 years, with assessment of clinical outcomes and echocardiographic evaluation. RESULTS: The rates of death from any cause were similar in the TAVR and surgery groups (hazard ratio with TAVR, 0.90; 95% confidence interval [CI], 0.71 to 1.15; P=0.41) and at 2 years (Kaplan-Meier analysis) were 33.9% in the TAVR group and 35.0% in the surgery group (P=0.78). The frequency of all strokes during follow-up did not differ significantly between the two groups (hazard ratio, 1.22; 95% CI, 0.67 to 2.23; P=0.52). At 30 days, strokes were more frequent with TAVR than with surgical replacement (4.6% vs. 2.4%, P=0.12); subsequently, there were 8 additional strokes in the TAVR group and 12 in the surgery group. Improvement in valve areas was similar with TAVR and surgical replacement and was maintained for 2 years. Paravalvular regurgitation was more frequent after TAVR (P<0.001), and even mild paravalvular regurgitation was associated with increased late mortality (P<0.001). CONCLUSIONS: A 2-year follow-up of patients in the PARTNER trial supports TAVR as an alternative to surgery in high-risk patients. The two treatments were similar with respect to mortality, reduction in symptoms, and improved valve hemodynamics, but paravalvular regurgitation was more frequent after TAVR and was associated with increased late mortality. (Funded by Edwards Lifesciences; ClinicalTrials.gov number, NCT00530894.)

Both “illness and temptation of the enemy”: melancholy, the medieval patient and the writings of King Duarte of Portugal (r. 1433–38)

Recent historians have rehabilitated King Duarte of Portugal, previously maligned and neglected, as an astute ruler and philosopher. There is still a tendency, however, to view Duarte as a depressive or a hypochondriac, due to his own description of his melancholy in his advice book, the Loyal Counselor. This paper reassesses Duarte's writings, drawing on key approaches in the history of medicine, such as narrative medicine and the history of the patient. It is important to take Duarte's views on his condition seriously, placing them in the medical and theological contexts of his time and avoiding modern retrospective diagnosis. Duarte's writings can be used to explore the impact of plague, doubt and death on the life of a well-educated and conscientious late-medieval ruler

Additional file 17 of Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Additional file 17: Table S9. PheWAS UKB-MVP meta-analysis results for each index lipid variant at Bonferroni threshold for multiple testing

Additional file 27 of Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Additional file 27: Table S17. Sex-stratified effect sizes in UK Biobank considering all individuals or only those not on cholesterol lowering medications

Additional file 19 of Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Additional file 19: Table S11. Significant female-specific multi-ancestry meta-analysis results

Additional file 28 of Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Additional file 28: Table S18. Sex-participation association of the variants with significant sex-specific lipid results