A Bayesian shared component model for genetic association studies

We present a novel approach to address genome association studies between single nucleotide polymorphisms (SNPs) and disease. We propose a Bayesian shared component model to tease out the genotype information that is common to cases and controls from the one that is specific to cases only. This allows to detect the SNPs that show the strongest association with the disease. The model can be applied to case-control studies with more than one disease. In fact, we illustrate the use of this model with a dataset of 23,418 SNPs from a case-control study by The Welcome Trust Case Control Consortium (2007) with 2,000 patients with diabetes type 1, 2,000 with diabetes type 2 and a control group with 3,000 individuals. We carry out a simulation study to assess the sensitivity and specificity of our model to detect SNPs with excess risk. Our results show that the method we propose here can be a very useful tool for this type of studies. The model has been implemented in the bayesGen library of the R statistical package

Estimation of treatment policy estimands for continuous outcomes using off treatment sequential multiple imputation

The estimands framework outlined in ICH E9 (R1) describes the components needed to precisely define the effects to be estimated in clinical trials, which includes how post-baseline "intercurrent" events (IEs) are to be handled. In late-stage clinical trials, it is common to handle intercurrent events like "treatment discontinuation" using the treatment policy strategy and target the treatment effect on all outcomes regardless of treatment discontinuation. For continuous repeated measures, this type of effect is often estimated using all observed data before and after discontinuation using either a mixed model for repeated measures (MMRM) or multiple imputation (MI) to handle any missing data. In basic form, both of these estimation methods ignore treatment discontinuation in the analysis and therefore may be biased if there are differences in patient outcomes after treatment discontinuation compared to patients still assigned to treatment, and missing data being more common for patients who have discontinued treatment. We therefore propose and evaluate a set of MI models that can accommodate differences between outcomes before and after treatment discontinuation. The models are evaluated in the context of planning a phase 3 trial for a respiratory disease. We show that analyses ignoring treatment discontinuation can introduce substantial bias and can sometimes underestimate variability. We also show that some of the MI models proposed can successfully correct the bias but inevitably lead to increases in variance. We conclude that some of the proposed MI models are preferable to the traditional analysis ignoring treatment discontinuation, but the precise choice of MI model will likely depend on the trial design, disease of interest and amount of observed and missing data following treatment discontinuation

Standalone direct pumping photovoltaic system or energy storage in batteries for supplying irrigation networks. Cost analysis

[EN] Solar photovoltaic systems have become one of the most popular topics in the water management industry. Moreover, irrigation networks are water- and energy-hungry, and utilitymanagers are likely to adaptwater consumption (and consequently energy demand) to the hours inwhich there is energy availability. In countries such as Spain (with high irradiance values), solar energy is an available green alternative characterised by zero electricity costs and significantly lower environmental impact. In this work, several types of irrigation scheduled programmes (according to different irrigation sectors) that minimise the number of photovoltaic solar panels to be installed are studied; moreover, the effects of the variable costs linked to energy (energy and emissions costs) are presented. Finally, the effect of incorporating batteries for storing energy to protect the system against emergencies, such as unfavourable weather, is proposed. The irrigation hours available to satisfywater demands are limited by sunlight; they are also limited by the condition that the irrigation schedule type has to be rigid (predetermined rotation) and that the pressure at any node has to be above minimumpressure required by standards. A real case study is performed, and the results obtained demonstrate that there is no universal solution; this is because the portfolio of alternatives is based on investments for purchasing equipment at present and also on future energy savings (revenues). Apart from these two values, there is an economic value (equivalent discontinuous discount rate), which also influences the final results.This work was supported by the research project “GESAEN” through the 2016 call of the Vicerrectorado de Investigación, Desarrollo e Innovación de la Universidad de Alicante GRE-16-08.Pardo Picazo, MA.; Manzano Juarez, J.; Valdes-Abellan, J.; Cobacho Jordán, R. (2019). Standalone direct pumping photovoltaic system or energy storage in batteries for supplying irrigation networks. Cost analysis. The Science of The Total Environment. 673:821-830. https://doi.org/10.1016/j.scitotenv.2019.04.050S82183067

Nonreferral of possible soft tissue sarcomas in adults: a dangerous omission in policy

Introduction. The aim of this study is to compare outcomes in three groups of STS patients treated in our specialist centre: patients referred immediately after an inadequate initial treatment, patients referred after a local recurrence, and patients referred directly, prior to any treatment. Patients and methods. We reviewed all our nonmetastatic extremity-STS patients with a minimum follow-up of 2 years. We compared three patient groups: those referred directly to our centre (group A), those referred after an inadequate initial excision (group B), and patients with local recurrence (group C). Results. The study included 174 patients. Disease-free survival was 73%, 76%, and 28% in groups A, B, and C, respectively (P < .001). Depth, size, and histologic grade influenced the outcome in groups A and B, but not in C. Conclusion. Initial wide surgical treatment is the main factor that determines local control, being even more important than the known intrinsic prognostic factors of tumour size, depth, and histologic grade. The influence on outcome of initial wide local excision (WLE), which is made possible by referral to a specialist centre, is paramount

Effectiveness of a multimodal intervention in functionally impaired older people with type 2 diabetes mellitus

Background: Type 2 diabetes, a highly prevalent chronic disease, is associated with increasing frailty and functional decline in older people. We aimed to evaluate the effectiveness of a multimodal intervention on functional performance in frail and pre-frail participants aged >= 70 years with type 2 diabetes mellitus. Methods: The MID-Frail study was a cluster-randomized multicenter clinical trial conducted in 74 trial sites across seven European countries. The trial recruited 964 participants who were aged >70 years [mean age in intervention group, 78.4 (SD 5.6) years, 49.2% male and 77.6 (SD 5.29) years, 52.4% male in usual care group], with type diabetes mellitus and determined to be frail or pre-frail using Fried's frailty phenotype. Participants were allocated by trial site to follow either usual care (UCG) or intervention procedures (IG). Intervention group participants received a multimodal intervention composed of (i) an individualized and progressive resistance exercise programme for 16 weeks; (ii) a structured diabetes and nutritional educational programme over seven sessions; and (iii) Investigator-linked training to ensure optimal diabetes care. Short Physical Performance Battery (SPPB) scores were used to assess change in functional performance at 12 months between the groups. An analysis of the cost-effectiveness of the intervention was undertaken using the incremental cost-effectiveness ratio (ICER). Secondary outcomes included mortality, hospitalization, institutionalization, quality of life, burden on caregivers, the frequency and severity of hypoglycaemia episodes, and the cost-effectiveness of the intervention. Results: After 12 months, IG participants had mean SPPB scores 0.85 points higher than those in the UCG (95% CI, 0.44 to 1.26, P < 0.0001). Dropouts were higher in frail participants and in the intervention group, but significant differences in SPPB between treatment groups remained consistent after sensitivity analysis. Estimates suggest a mean saving following intervention of 428.02 EUR (2016) per patient per year, with ICER analysis indicating a consistent benefit of the described health care intervention over usual care. No statistically significant differences between groups were detected in any of the other secondary outcomes. Conclusions: We have demonstrated that a 12 month structured multimodal intervention programme across several clinical settings in different European countries leads to a clinically relevant and cost-effective improvement in the functional status of older frail and pre-frail participants with type 2 diabetes mellitus

Methodologic issues and approaches to spatial epidemiology

Spatial epidemiology is increasingly being used to assess health risks associated with environmental hazards. Risk patterns tend to have both a temporal and a spatial component; thus, spatial epidemiology must combine methods from epidemiology, statistics, and geographic information science. Recent statistical advances in spatial epidemiology include the use of smoothing in risk maps to create an interpretable risk surface, the extension of spatial models to incorporate the time dimension, and the combination of individual- and area-level information. Advances in geographic information systems and the growing availability of modeling packages have led to an improvement in exposure assessment. Techniques drawn from geographic information science are being developed to enable the visualization of uncertainty and ensure more meaningful inferences are made from data. When public health concerns related to the environment arise, it is essential to address such anxieties appropriately and in a timely manner. Tools designed to facilitate the investigation process are being developed, although the availability of complete and clean health data, and appropriate exposure data often remain limiting factors

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

CARMENES: high-resolution spectra and precise radial velocities in the red and infrared

SPIE Astronomical Telescopes + Instrumentation (2018, Austin, Texas, United States

A giant exoplanet orbiting a very-low-mass star challenges planet formation models

Surveys have shown that super-Earth and Neptune-mass exoplanets are more frequent than gas giants around low-mass stars, as predicted by the core accretion theory of planet formation. We report the discovery of a giant planet around the very-low-mass star GJ 3512, as determined by optical and near-infrared radial-velocity observations. The planet has a minimum mass of 0.46 Jupiter masses, very high for such a small host star, and an eccentric 204-day orbit. Dynamical models show that the high eccentricity is most likely due to planet-planet interactions. We use simulations to demonstrate that the GJ 3512 planetary system challenges generally accepted formation theories, and that it puts constraints on the planet accretion and migration rates. Disk instabilities may be more efficient in forming planets than previously thought