Fred Hutchinson Cancer Research Center

About: Fred Hutchinson Cancer Research Center is a nonprofit organization based out in Cape Town, South Africa. It is known for research contribution in the topics: Population & Transplantation. The organization has 12322 authors who have published 30954 publications receiving 2288772 citations. The organization is also known as: Fred Hutch & The Hutch.

Estimating medical costs from incomplete follow-up data.

Abstract: Estimation of the average total cost for treating patients with a particular disease is often complicated by the fact that the survival times are censored on some study subjects and their subsequent costs are unknown. The naive sample average of the observed costs from all study subjects or from the uncensored cases only can be severely biased, and the standard survival analysis techniques are not applicable. To minimize the bias induced by censoring, we partition the entire time period of interest into a number of small intervals and estimate the average total cost either by the sum of the Kaplan-Meier estimator for the probability of dying in each interval multiplied by the sample mean of the total costs from the observed deaths in that interval or by the sum of the Kaplan-Meier estimator for the probability of being alive at the start of each interval multiplied by an appropriate estimator for the average cost over the interval conditional on surviving to the start of the interval. The resultant estimators are consistent if censoring occurs solely at the boundaries of the intervals. In addition, the estimators are asymptotically normal with easily estimated variances. Extensive numerical studies show that the asymptotic approximations are adequate for practical use and the biases of the proposed estimators are small even when censoring may occur in the interiors of the intervals. An ovarian cancer study is provided.

A deletion of the human beta-globin locus activation region causes a major alteration in chromatin structure and replication across the entire beta-globin locus.

Abstract: Naturally occurring deletions that remove sequences located approximately 60 kb upstream of the human adult beta-globin gene result in the failure to transcriptionally activate the cis-linked globin genes in erythroid cells. In addition, transfection, transgenic, and somatic cell hybrid studies have revealed that sequences within this region are essential for the developmentally regulated high-level expression of cis-linked globin genes. This regulatory region located at the 5' end of the beta-globin locus has been termed the locus activation region (LAR). Using somatic cell hybrids, we have studied the chromatin structure and timing of DNA replication of the normal human beta-globin locus and a locus containing a de novo 25-kb deletion that removes elements of the LAR. As a result of this deletion, the entire beta-globin locus and sequences approximately 100 kb 5' and 3' of the adult beta-globin gene are DNase I-resistant and do not form characteristic distant hypersensitive sites. These sequences also replicate late in S phase in an erythroid cell background. In contrast, the sequences of the normal locus are DNase I sensitive and early replicating. These results suggest that the LAR is required for both the erythroid-specific chromatin structure and timing of DNA replication over a large physical distance.