PubMed · 15064057
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Mike Fitzpatrick. 2004-04-03. The tablets.. https://doi.org/10.1016/s0140-6736(04)15926-6
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Excessive alcohol consumption is a major health and social issue in our society. Pharmacologic administration of the endocrine hormone fibroblast growth factor 21 (FGF21) suppresses alcohol consumption through actions in the brain in rodents, and genome-wide association studies have identified single nucleotide polymorphisms in genes involved with FGF21 signaling as being associated with increased alcohol consumption in humans. However, the neural circuit(s) through which FGF21 signals to suppress alcohol consumption are unknown, as are its effects on alcohol consumption in higher organisms. Here, we demonstrate that administration of an FGF21 analog to alcohol-preferring non-human primates reduces alcohol intake by 50%. Further, we reveal that FGF21 suppresses alcohol consumption through a projection-specific subpopulation of KLB-expressing neurons in the basolateral amygdala. Our results illustrate how FGF21 suppresses alcohol consumption through a specific population of neurons in the brain and demonstrate its therapeutic potential in non-human primate models of excessive alcohol consumption.
This article describes the characteristics of 3 dominant features of breast cancer epidemiology. These characteristics include the association of disease risk with childbearing, its relationship to ovarian activity and its international variation (particularly as the latter differs in the years before and after menopause). Equivocal tests of one hypothesis that reconciled some of these features through variations in levels of the fractions of estrogen are described. Other hypotheses with a similar objective are needed. The 3 known causes of human breast cancer, ionizing radiation, exogenous ovarian hormones and beverage alcohol, offer some preventive possibilities but do little to explain the epidemiologic features of the majority of cases of the disease that occur in their absence.
In this paper, we assess the performance of homogeneity tests for two or more kappa statistics when prevalence rates across reliability studies are assumed to be equal. The likelihood score method and the chi-square goodness-of-fit (GOF) test provide type 1 error rates that are satisfactorily close to the nominal level, but a Fleiss-like test is not satisfactory for small or moderate sample sizes. Simulations show that the score test is more powerful than the chi-square GOF test and the approximate sample size required for a specific power of the former is substantially smaller than the latter. In addition, the score test is robust to deviations from the equal prevalence assumption, while the GOF test is highly sensitive and it may give a grossly misleading type 1 error rate when the assumption of equal prevalence is violated. We conclude that the homogeneity score test is the preferred method.