Combining Global and Marginal Tests to Compare Two Treatments on Multiple Endpoints

We consider the problem of comparing two treatments on multiple endpoints where the goal is to identify the endpoints that have treatment effects, while controlling the familywise error rate. Two current approaches for this are (i) applying a global test within a closed testing procedure, and (ii) adjusting individual endpoint p‐values for multiplicity. We propose combining the two current methods. We compare the combined method with several competing methods in a simulation study. It is concluded that the combined approach maintains higher power under a variety of treatment effect configurations than the other methods and is thus more power‐robust.     

Testing the Equality of the Intra‐Subject Treatment Covariance Matrices in a Crossover Study

In a 2 × 2 crossover bioavailability study, the sets of estimates of the pharmacokinetic parameters quite often have a symmetric covariance structure between the two treatments. For testing the equality of the intra‐subject covariance matrices for the two treatments in such studies, we suggest in this paper some statistical tests. When the response vectors are bivariate, we propose an exact test. Since the statistical procedures depend on the assumption of a symmetric covariance structure between the two treatments, we put forth some statistical tests for this assumption. We then apply the discussed tests to real data from a crossover bioavailability trial.     

Mendelian randomization analysis of the causal impact of body mass index and waist-hip ratio on rates of hospital admission

We analyze how measures of adiposity – body mass index (BMI) and waist hip ratio (WHR) – causally influence rates of hospital admission. Conventional analyses of this relationship are susceptible to omitted variable bias from variables that jointly influence both hospital admission and adipose status. We implement a novel quasi-Poisson instrumental variable model in a Mendelian randomization framework, identifying causal effects from random perturbations to germline genetic variation. We estimate the individual and joint effects of BMI, WHR, and WHR adjusted for BMI. We also implement multivariable instrumental variable methods in which the causal effect of one exposure is estimated conditionally on the causal effect of another exposure. Data on 310,471 participants and over 550,000 inpatient admissions in the UK Biobank were used to perform one-sample and two-sample Mendelian randomization analyses. The results supported a causal role of adiposity on hospital admissions, with consistency across all estimates and sensitivity analyses. Point estimates were generally larger than estimates from comparable observational specifications. We observed an attenuation of the BMI effect when adjusting for WHR in the multivariable Mendelian randomization analyses, suggesting that an adverse fat distribution, rather than a higher BMI itself, may drive the relationship between adiposity and risk of hospital admission.     

Reproductive fitness consequences of progenesis: Sex‐specific pay‐offs in safe and risky environments

Progenesis is considered to have an important role in evolution because it allows the retention of both a larval body size and shape in an adult morphology. However, the cost caused by the adoption of a progenetic process in both males and females remains to be explored to explain the success of progenesis and particularly its biased prevalence across the sexes and environments. Here, through an experimental approach, we used a facultative progenetic species, the palmate newt (Lissotriton helveticus) that can either mature at a small size and retain gills or mature after metamorphosis, to test three hypotheses for sex‐specific pay‐offs of progenesis in safe versus risky habitats. Goldfish were used because they caused a higher decline in progenetic than metamorphic newts. We determined that progenetic newts have a lower reproductive fitness than metamorphic newts. We also found that, when compared to metamorphs, progenetic males have lower reproductive activity than progenetic females and that predatory risk affects more progenetic than metamorphic newts. By identifying ultimate causes of the female‐biased sex ratios found in nature, these results support the male escape hypothesis, that is the higher metamorphosis rate of progenetic males. They also highlight that although progenesis is advantageous in advancing the age at first reproduction, it also brings an immediate fitness cost and this, particularly, in hostile predatory environments. This means that whereas some environmental constraints could favour facultative progenesis, some others, such as predation, can ultimately counter‐select progenesis. Altogether, these results improve our understanding of how developmental processes can affect the sexes differently and how species invasions can impair the success of alternative developmental phenotypes.     

Estimating mixtures of leaf functional types using continental-scale satellite and climatic data

Aim Recent research has shown that much of the variability in leaf gas exchange and leaf longevity can be related to variations in the surface : volume ratio of leaves. The aim of this paper was to develop a theoretical framework and a practical method to extend that result to the vegetation at the continental scale. Location The study was conducted in Australia. Methods We propose that vegetation is composed of a mixture of three basic leaf types, ‘turgor’ (T), ‘mesic’ (M) and ‘sclerophyll’ (S) leaves. Changes in the relative proportions of T, M and S leaves within a vegetation type are visualized using a ternary diagram and differences in vegetation structure are shown to be easily mapped onto the ternary diagram. We estimate the proportions of T, M and S leaves using readily available data. The total amount of PAR absorbed by the vegetation (fPAR) is estimated using continental‐scale satellite observations. The total fPAR is then decomposed into that absorbed by T, M and S leaves. The relative absorption of PAR by T leaves is estimated from the temporal dynamics in the satellite signal, while the relative proportions of M and S leaves are estimated using climatic (solar radiation, rainfall) data. Results When the availability of light, nutrients and water were near‐optimal, the vegetation was composed of predominantly M leaves. In low nutrient environments S leaves predominated. T leaves were dominant in disturbed environments. Conclusions The theoretical framework is used to predict that elevated atmospheric CO₂ would tend to increase the proportion of M and S leaves in an ecosystem and the resulting change means that the proportion of T leaves would decrease. In terms of the TMS scheme, this implies that elevated CO₂ has the same net effect on the vegetation as a decrease in disturbance.     

Phase separation of cholesterol from phosphatidylserine-cholesterol mixtures in the presence of the local anesthetic tetracaine

Addition of the local anesthetic tetracaine (TTC) to multilamellar dispersions of natural phosphatidylserine (PS) causes changes in the thermotropic properties of the membrane, which can be detected by differential scanning calorimetry, and in the structure of the membrane as detected by X-ray diffraction. At molar ratio [PS]/[TTC]8.5, the melting temperature of the phospholipid shifts downwards by approximately 2.5 °C. The melting endotherm is broadened; however, there is little change in the enthalpy of melting. In ternary mixtures (PS–TTC–cholesterol), the thermotropic changes are enhanced. At [PS]/[TTC]13, the onset of phase separation of cholesterol crystals from PS in the liquid crystalline state occurs at molar fraction cholesterol (X_chol)0.28, marginally smaller than that found in the absence of the anesthetic.     

Association of the variant rs2243421 of human DOC-2/DAB2 interactive protein gene (hDAB2IP) with gastric cancer in the Chinese Han population

Human DOC-2/DAB2 interactive protein (hDAB2IP) gene is a novel member of the Ras GTPase-activating family and has been demonstrated to be a tumor-suppressor gene that inhibits cell survival and proliferation and induces cell apoptosis. It was reported that the expression level of hDAB2IP in gastric cancer tissue was highly correlated with tumor progression, however, whether hDAB2IP genetic variants are associated with the risk of gastric cancer remains yet unknown. In this case–control study, we conducted a genetic analysis for hDAB2IP variants in 311 patients with gastric cancer and 425 controls from the Chinese Han population. We found that the SNP rs2243421 of hDAB2IP gene with the minor allele C significantly revealed strong association with decreased gastric cancer susceptibility (P = 0.007, adjusted odds ratio [OR] = 0.734, 95%CI = 0.586–0.919). Haplotypes rs2243421 and rs10985332 (HaploType: CC, P = 0.012, aOR = 0.760) and haplotypes rs2243421 and rs555996 (HaploType: CG, P = 0.034, aOR = 0.788) represented the decreased risk of gastric cancer, respectively. On the contrary, rs2243421 and rs555996 showed an elevated susceptibility (HaploType: TG, P = 0.010, aOR = 1.320). Our results for the first time provided new insight into susceptibility factors of hDAB2IP gene variants in carcinogenesis of gastric cancer.     

Documento de consenso para la detección y manejo de la enfermedad renal crónica

Chronic kidney disease (CKD) is an important global health problem, involving to 10% of the Spanish population, promoting high morbidity and mortality for the patient and an elevate consumption of the total health resources for the National Health System. This is a summary of an executive consensus document of ten scientific societies involved in the care of the renal patient, that actualizes the consensus document published in 2007. The central extended document can be consulted in the web page of each society. The aspects included in the document are: Concept, epidemiology and risk factors for CKD. Diagnostic criteria, evaluation and stages of CKD, albuminuria and glomerular filtration rate estimation. Progression factors for renal damage. Patient remission criteria. Follow-up and objectives of each speciality control. Nephrotoxicity prevention. Cardio-vascular damage detection. Diet, life-style and treatment attitudes: hypertension, dyslipidaemia, hyperglycemia, smoking, obesity, hyperuricemia, anemia, mineral and bone disorders. Multidisciplinary management for Primary Care, other specialities and Nephrology. Integrated management of CKD patient in haemodialysis, peritoneal dialysis and renal transplant patients. Management of the uremic patient in palliative care. We hope that this document may be of help for the multidisciplinary management of CKD patients by summarizing the most updated recommendations.