Biomedical subjects

Paul Goldberg

Publications and source records attributed to Paul Goldberg.

4 recordsLinked to original sources

PubMed2007

Early Upper Paleolithic in Eastern Europe and implications for the dispersal of modern humans.

Radiocarbon and optically stimulated luminescence dating and magnetic stratigraphy indicate Upper Paleolithic occupation-probably representing modern humans-at archaeological sites on the Don River in Russia 45,000 to 42,000 years ago. The oldest levels at Kostenki underlie a volcanic ash horizon identified as the Campanian Ignimbrite Y5 tephra that is dated elsewhere to about 40,000 years ago. The occupation layers contain bone and ivory artifacts, including possible figurative art, and fossil shells imported more than 500 kilometers. Thus, modern humans appeared on the central plain of Eastern Europe as early as anywhere else in northern Eurasia.

Archaeology↗

PubMed2006

GSTM1 and GSTT1 polymorphisms as modifiers of age at diagnosis of hereditary nonpolyposis colorectal cancer (HNPCC) in a homogeneous cohort of individuals carrying a single predisposing mutation.

The variability in phenotype that occurs for so-called 'single-gene disorders' may be because of germline alterations in numerous primary and "modifier" genes. Within HNPCC families harbouring the same primary predisposing mutation, differences exist in the site of cancer, age of onset of disease symptoms and, consequently, survival until diagnosis of disease. The current study investigated a cohort of 129 individuals, from 13 different families, who harbour the identical nonsense mutation (C1528T) in the hMLH1 gene, predisposing them primarily to Lynch I syndrome. This cohort was screened for previously described polymorphisms in the glutathione-S-transferase genes, viz. GSTT1 and GSTM1. Male null carriers for both GSTT1 and GSTM1 were approximately three times more at risk of developing cancer at an earlier age when compared to non-null males. This work, particularly because of the relatively large "homogeneous" primary mutation cohort, provides evidence that genotypic changes distinct from the primary 'HNPCC-causing' mutation, influence the survival period until diagnosis of disease. It provides an impetus for expanding the study to include a wider range of candidate modifier genes. Such work may potentially lead to the development of individualised interval screening regimens for individuals with varying modifier genotypes--an attractive option in a resource-poor country.

Adolescent↗

PubMed2004

Identifying uniformly mutated segments within repeats.

Given a long string of characters from a constant size alphabet we present an algorithm to determine whether its characters have been generated by a single i.i.d. random source. More specifically, consider all possible n-coin models for generating a binary string S, where each bit of S is generated via an independent toss of one of the n coins in the model. The choice of which coin to toss is decided by a random walk on the set of coins where the probability of a coin change is much lower than the probability of using the same coin repeatedly. We present a procedure to evaluate the likelihood of a n-coin model for given S, subject a uniform prior distribution over the parameters of the model (that represent mutation rates and probabilities of copying events). In the absence of detailed prior knowledge of these parameters, the algorithm can be used to determine whether the a posteriori probability for n=1 is higher than for any other n>1. Our algorithm runs in time O(l4logl), where l is the length of S, through a dynamic programming approach which exploits the assumed convexity of the a posteriori probability for n. Our test can be used in the analysis of long alignments between pairs of genomic sequences in a number of ways. For example, functional regions in genome sequences exhibit much lower mutation rates than non-functional regions. Because our test provides means for determining variations in the mutation rate, it may be used to distinguish functional regions from non-functional ones. Another application is in determining whether two highly similar, thus evolutionarily related, genome segments are the result of a single copy event or of a complex series of copy events. This is particularly an issue in evolutionary studies of genome regions rich with repeat segments (especially tandemly repeated segments).

Algorithms↗

PubMedDate not supplied

An emergency medical services program of alternate destination of patient care.

OBJECTIVE: The emergency department (ED) is ideally reserved for urgent health needs. The ED, however, is often the site of care for nonurgent conditions. The authors investigated whether emergency medical technicians could decrease ED use by patients with nonurgent concerns who use 911 by appropriately identifying and triaging them to alternate care destinations. METHODS: From August 2000 through January 2001, two King County fire-based emergency medical services (EMS) agencies participated in an alternate care destination program for patients with specific low-acuity diagnosis codes (intervention group). Eligible patients were offered care at a clinic-based destination as an alternate to the ED (n = 1,016). The frequency of the destination of care (ED, clinic, or home) for the intervention group was compared with a matched control group that was comprised of a preintervention historical cohort of EMS encounters from the same two fire-based agencies and with the same acuity and diagnosis criteria and seasonal interval (n = 2,617). RESULTS: Compared with the preintervention group, a smaller proportion of patients in the intervention group received care in the ED (44.6% vs. 51.8%, p = 0.001), while a greater proportion of patients in the intervention group received clinic care (8.0% vs. 4.5%, p = 0.001) or home care (no transport) (47.4 vs. 43.7%, p = 0.043). Results were comparable when adjusted for other patient characteristics. Similar relationships were not evident among nonparticipating King County EMS agencies. Based on physician review and patient interview, the alternate care intervention appeared to be safe and satisfactory. CONCLUSION: An EMS-based program may represent one approach to limiting nonurgent ED use.

Adult↗