Equivalence Tests For Repeated Measures

Equivalence tests from the null hypothesis significance testing framework are appropriate alternatives to difference tests for demonstrating lack of difference. For determining equivalence among more than two repeated measurements, recently developed equivalence tests include the omnibus Hotelling T2, the pairwise standardized test, the pairwise unstandardized test, and the two one-sided test for negligible trend. With Monte Carlo simulations, the current research evaluated Type I error rates and power rates for these equivalence tests to inform an applied data analytic strategy. Because results suggest that there is no one statistical test that is optimal across all situations, I compare the tests’ statistical behaviours to provide guidance in test selection. Specifically, test selection should be informed by the measurement level of the repeated outcome, correlation structure, and precision

Identification of subgroups with differential treatment effects for longitudinal and multiresponse variables

We describe and evaluate a regression tree algorithm for finding subgroups with differential treatments effects in randomized trials with multivariate outcomes. The data may contain missing values in the outcomes and covariates, and the treatment variable is not limited to two levels. Simulation results show that the regression tree models have unbiased variable selection and the estimates of subgroup treatment effects are approximately unbiased. A bootstrap calibration technique is proposed for constructing confidence intervals for the treatment effects. The method is illustrated with data from a longitudinal study comparing two diabetes drugs and a mammography screening trial comparing two treatments and a control

The role of gap junctions in inflammatory and neoplastic disorders (Review).

Gap junctions are intercellular channels made of connexin proteins, mediating both electrical and biochemical signals between cells. The ability of gap junction proteins to regulate immune responses, cell proliferation, migration, apoptosis and carcinogenesis makes them attractive therapeutic targets for treating inflammatory and neoplastic disorders in different organ systems. Alterations in gap junction profile and expression levels are observed in hyperproliferative skin disorders, lymphatic vessel diseases, inflammatory lung diseases, liver injury and neoplastic disorders. It is now recognized that the therapeutic effects mediated by traditional pharmacological agents are dependent upon gap junction communication and may even act by influencing gap junction expression or function. Novel strategies for modulating the function or expression of connexins, such as the use of synthetic mimetic peptides and siRNA technology are considered.Dr Gary Tse received a BBSRC Doctoral Training Award at the University of Cambridge and is grateful to the Croucher Foundation for its support of his non‑clinical and clinical assistant professorships. Dr Yin Wah Fiona Chan was supported by the ESRC for her research at the University of Cambridge

Depresión infantil: una revisión bibliométrica

This work presents a review of the literature about childhood depression (CD), during the period from 2010 to 2018. The used method has been the analysis of documents on this subject, which were identified in the ProQuest, EBSCO databases, articles of Google academic and digital books. A form and content analysis was conducted with the information obtained, also reviewing the following concepts: depression, childhood depression and factors that cause it. In this way, it has been found that the research about this subject, in the period indicated above, is still limited, especially at the national level, which is why it is necessary to promote the research of childhood depression in Peru from different fields of studies.Este trabajo presenta una revisión de la literatura sobre la depresión infantil (DI) durante el período de 2010 hasta 2018. El método empleado ha sido el análisis de documentos sobre esta temática, los cuales fueron identificados en las bases de datos de PROQUEST, EBSCO, artículos de Google académico y libros digitales. Con la información obtenida se realizó un análisis de forma y contenido, revisando además los siguientes conceptos: depresión, depresión infantil y factores que la provocan. De esta manera, se ha encontrado que la investigación sobre este tema, en el periodo señalado líneas arriba, es aún escasa, sobre todo en el ámbito nacional, por lo cual se ve necesario promover la investigación de la DI en Perú desde los diferentes campos de estudios

Feasibility Study of Neoadjuvant Olaparib for Frontline BRCA Mutant Ovarian Cancer

https://openworks.mdanderson.org/sumexp22/1095/thumbnail.jp

Electrophysiological Mechanisms of Brugada Syndrome: Insights from Pre-clinical and Clinical Studies.

This is the final version of the article. It first appeared from Frontiers via https://doi.org/10.3389/fphys.2016.00467Brugada syndrome (BrS), is a primary electrical disorder predisposing affected individuals to sudden cardiac death via the development of ventricular tachycardia and fibrillation (VT/VF). Originally, BrS was linked to mutations in the SCN5A, which encodes for the cardiac Na+ channel. To date, variants in 19 genes have been implicated in this condition, with 11, 5, 3, and 1 genes affecting the Na+, K+, Ca2+, and funny currents, respectively. Diagnosis of BrS is based on ECG criteria of coved- or saddle-shaped ST segment elevation and/or T-wave inversion with or without drug challenge. Three hypotheses based on abnormal depolarization, abnormal repolarization, and current-load-mismatch have been put forward to explain the electrophysiological mechanisms responsible for BrS. Evidence from computational modeling, pre-clinical, and clinical studies illustrates that molecular abnormalities found in BrS lead to alterations in excitation wavelength (λ), which ultimately elevates arrhythmic risk. A major challenge for clinicians in managing this condition is the difficulty in predicting the subset of patients who will suffer from life-threatening VT/VF. Several repolarization risk markers have been used thus far, but these neglect the contributions of conduction abnormalities in the form of slowing and dispersion. Indices incorporating both repolarization and conduction and based on the concept of λ have recently been proposed. These may have better predictive values than the existing markers.GT received a BBSRC Doctoral CASE Studentship at the University of Cambridge and thanks the Croucher Foundation of Hong Kong for the support of his Clinical Assistant Professorship. YC is supported by the ESRC for her Ph.D. studies at the University of Cambridge. BY received funding from the Research Grant Council of Hong Kong for his research

The initiator methionine tRNA drives secretion of type II collagen from stromal fibroblasts to promote tumor growth and angiogenesis

Summary: Expression of the initiator methionine tRNA (tRNAi Met) is deregulated in cancer. Despite this fact, it is not currently known how tRNAi Met expression levels influence tumor progression. We have found that tRNAi Met expression is increased in carcinoma-associated fibroblasts, implicating deregulated expression of tRNAi Met in the tumor stroma as a possible contributor to tumor progression. To investigate how elevated stromal tRNAi Met contributes to tumor progression, we generated a mouse expressing additional copies of the tRNAi Met gene (2+tRNAi Met mouse). Growth and vascularization of subcutaneous tumor allografts was enhanced in 2+tRNAi Met mice compared with wild-type littermate controls. Extracellular matrix (ECM) deposited by fibroblasts from 2+tRNAi Met mice supported enhanced endothelial cell and fibroblast migration. SILAC mass spectrometry indicated that elevated expression of tRNAi Met significantly increased synthesis and secretion of certain types of collagen, in particular type II collagen. Suppression of type II collagen opposed the ability of tRNAi Metoverexpressing fibroblasts to deposit pro-migratory ECM. We used the prolyl hydroxylase inhibitor ethyl- 3,4-dihydroxybenzoate (DHB) to determine whether collagen synthesis contributes to the tRNAi Met-driven pro-tumorigenic stroma in vivo. DHB had no effect on the growth of syngeneic allografts in wild-type mice but opposed the ability of 2+tRNAi Met mice to support increased angiogenesis and tumor growth. Finally, collagen II expression predicts poor prognosis in high-grade serous ovarian carcinoma. Taken together, these data indicate that increased tRNAi Met levels contribute to tumor progression by enhancing the ability of stromal fibroblasts to synthesize and secrete a type II collagen-rich ECM that supports endothelial cell migration and angiogenesis

Animal models of atherosclerosis.

Atherosclerosis is a significant cause of morbidity and mortality globally. Many animal models have been developed to study atherosclerosis, and permit experimental conditions, diet and environmental risk factors to be carefully controlled. Pathophysiological changes can be produced using genetic or pharmacological means to study the harmful consequences of different interventions. Experiments using such models have elucidated its molecular and pathophysiological mechanisms, and provided platforms for pharmacological development. Different models have their own advantages and disadvantages, and can be used to answer different research questions. In the present review article, different species of atherosclerosis models are outlined, with discussions on the practicality of their use for experimentation.GT was supported by a BBSRC Doctoral Training Award and thanks the Croucher Foundation of Hong Kong for the generous support of his clinical assistant professorship. YC is supported by the ESRC