Case-control methods in the presence of multiple failure times and competing risks

The link between cohort and incident case-control studies has been considered by many authors. In particular, under the Cox proportional hazards model, follow-up data (implicit or explicit) can be analyzed as a case-control study by randomly selecting controls from the risk sets of each incident case, thereby obviating the necessity of working with the entire cohort when interest is primarily on exposure effects. This paper extends this linkage to competing risks and to diseases with multiple incidence or recurrence times by matching to each event (case) a sample of controls from the appropriate risk set. Illustrations are given.     

An impurity in phenol red opens an ion channel in cultured human cells

Summary Human fibroblast, bladder carcinoma, and breast carcinoma cells in commercial serum-free media or balanced salt solutions rapidly lose K⁺ and gain Na⁺. This rapid K⁺ loss is caused by one or more impurities in phenol red. Adding serum or albumin to media or to balanced salts prevents K⁺ loss. Quinine also prevents part of this loss in fibroblasts and breast carcinoma cells, suggesting that the impurity acts on an ion channel.     

Hormones and maternal behavior in the male rat

Castrate male rats were injected with estrogen, progesterone, and prolactin on the same schedule previously found to induce maternal behavior in ovariectomized nulliparous female rats. Males do not respond to the same dosage given females, but doubling either estrogen or progesterone significantly reduces the latency to maternal behavior. The results indicate a difference between male and female rats in sensitivity to the hormonal induction of maternal behavior.     

Epigenetic mechanisms in schizophrenia

Epidemiological research suggests that both an individual's genes and the environment underlie the pathophysiology of schizophrenia. Molecular mechanisms mediating the interplay between genes and the environment are likely to have a significant role in the onset of the disorder. Recent work indicates that epigenetic mechanisms, or the chemical markings of the DNA and the surrounding histone proteins, remain labile through the lifespan and can be altered by environmental factors. Thus, epigenetic mechanisms are an attractive molecular hypothesis for environmental contributions to schizophrenia. In this review, we first present an overview of schizophrenia and discuss the role of nature versus nurture in its pathology, where ‘nature’ is considered to be inherited or genetic vulnerability to schizophrenia, and ‘nurture’ is proposed to exert its effects through epigenetic mechanisms. Second, we define DNA methylation and discuss the evidence for its role in schizophrenia. Third, we define posttranslational histone modifications and discuss their place in schizophrenia. This research is likely to lead to the development of epigenetic therapy, which holds the promise of alleviating cognitive deficits associated with schizophrenia.