Citations

Key Points Pomalidomide plus low-dose dexamethasone significantly improved PFS vs pomalidomide alone in relapsed and refractory multiple myeloma. Pomalidomide plus low-dose dexamethasone is an important new treatment option for RRMM patients who have received multiple prior therapies.

ABSTRACTMany important complex diseases are composed of a series of phenotypes, which makes the disease diagnosis and its genetic dissection difficult. The standard procedures to determine heritability in such complex diseases are either applied for single phenotype analyses or to compare findings across phenotypes or multidimensional reduction procedures, such as principal components analysis using all phenotypes. However each method has its own problems and the challenges are even more complex for extended family data and categorical phenotypes. In this paper, we propose a methodology to determine a scale for complex outcomes involving multiple categorical phenotypes in extended pedigrees using item response theory (IRT) models that take all categorical phenotypes into account, allowing informative comparison among individuals. An advantage of the IRT framework is that a straightforward joint heritability parameter can be estimated for categorical phenotypes. Furthermore, our methodology allows many possible extensions such as the inclusion of covariates and multiple variance components. We use Markov Chain Monte Carlo algorithm for the parameter estimation and validate our method through simulated data. As an application we consider the metabolic syndrome as the multiple phenotype disease using data from the Baependi Heart Study consisting of 1,696 individuals in 95 families. We adjust IRT models without covariates and include age and age squared as covariates. The results showed that adjusting for covariates yields a higher joint heritability () than without co variates () indicating that the covariates absorbed some of the error variance.

Sex refers to biological differences between men and women. Although sex is a fundamental aspect of human physiology that splits the population in two approximately equal halves, this essential biological variable is rarely considered in the design of basic physiological studies, in translating findings from basic science to clinical research, or in developing personalized medical strategies. Contrary to sex, gender refers to social and cultural factors related to being a man or a woman in a particular historical and cultural context. Unfortunately, gender is often used incorrectly by scientists and clinical investigators as synonymous with sex. This article clarifies the definition of sex and gender and reviews evidence showing how sex and gender interact with each other to influence etiology, presentation of disease, and treatment outcomes. In addition, strategies to improve the inclusion of female and male human beings in preclinical and clinical studies will be presented, and the importance of embedding concepts of sex and gender into postgraduate and medical curricula will be discussed. Also, provided is a list of resources for educators. In the history of medical concepts, physiologists have provided pivotal contributions to understanding health and disease processes. In the future, physiologists should provide the evidence for advancing personalized medicine and for reducing sex and gender disparities in health care.