Economic evaluation of using a genetic test to direct breast cancer chemoprevention in white women with a previous breast biopsy.

Background: Tamoxifen therapy reduces the risk of breast cancer but increases the risk of serious adverse events including endometrial cancer and thromboembolic events.

Objectives: The cost effectiveness of using a commercially available breast cancer risk assessment test (BREVAGen™) to inform the decision of which women should undergo chemoprevention by tamoxifen was modeled in a simulated population of women who had undergone biopsies but had no diagnosis of cancer.

Methods: A continuous time, discrete event, mathematical model was used to simulate a population of white women aged 40-69 years, who were at elevated risk for breast cancer because of a history of benign breast biopsy.

Daphnia predation on the amphibian chytrid fungus and its impacts on disease risk in tadpoles.

Direct predation upon parasites has the potential to reduce infection in host populations. For example, the fungal parasite of amphibians, Batrachochytrium dendrobatidis (Bd), is commonly transmitted through a free-swimming zoospore stage that may be vulnerable to predation. Potential predators of Bd include freshwater zooplankton that graze on organisms in the water column.

Cost-effectiveness of a genetic test for breast cancer risk.

Genetic testing of seven single-nucleotide polymorphisms (7SNP) can improve estimates of risk of breast cancer relative to the Gail risk test alone, for the purpose of recommending MRI screening for women at high risk. A simulation of breast cancer and health care processes was used to conduct a virtual trial comparing the use of the 7SNP test with the Gail risk test to categorize patients by risk. Average-risk patients received annual mammogram, whereas high-risk patients received annual MRI.

An estrogen model: the relationship between body mass index, menopausal status, estrogen replacement therapy, and breast cancer risk.

We present a mathematical model that lends support to the hypothesis that estrogen levels mediate the complex relationship between body mass index (BMI), menopausal status, estrogen-only hormone replacement therapy (HRT), and breast cancer risk. The model predicts a decrease in the relative risk of breast cancer of 3% per unit increase in BMI (kg/m(2)) for premenopausal women and an increase in the relative risk of 4% per unit increase in BMI for postmenopausal women who are not HRT users. When comparing postmenopausal women who use estrogen-only HRT to postmenopausal women who do not use HRT, the model predicts an increased risk of breast cancer associated with use of estrogen that diminishes with increasing BMI, with a relative risk of 1.

Cost-effectiveness of chemoprevention of breast cancer using tamoxifen in a postmenopausal US population.

Background: Previous cost-effectiveness analyses of tamoxifen therapy account for breast cancer risk reduction during active treatment but not for its persistent protective effect after active treatment.

Methods: A detailed, continuous time, mathematical model of breast cancer and healthcare processes was used to simulate a postmenopausal population aged <55 years in a virtual trial comparing tamoxifen treatment with no treatment for lifetime follow-up. Unlike previous work, the current model of tamoxifen therapy is based on a meta-analysis of 4 randomized, placebo-controlled chemoprevention trials with breast cancer risk reduction continuing for 10 years after treatment termination.

Acute toxicity of acidity in larvae and adults of four stream salamander species (Plethodontidae).

High levels of acid deposition have severely affected streamwater chemistry in the southern Appalachians. Plethodontid stream salamanders living in and around headwater streams rely on cutaneous respiration and are highly susceptible to changes in water quality. We examined the sensitivity to low pH conditions in four stream salamanders by monitoring the response to six pH treatments ranging from pH 2.

Nucleotide variation, haplotype structure, and association with end-stage renal disease of the human interleukin-1 gene cluster.

A dense gene-based SNP map was constructed across a 360-kb region containing the interleukin-1 gene cluster (IL1A, IL1B, and IL1RN), focusing on IL1RN. In total, 95 polymorphisms were confirmed or identified primarily by direct sequencing. Polymorphisms were precisely mapped to completed BAC and genomic sequences spanning this region.

Visualizing human leukocyte antigen class II risk haplotypes in human systemic lupus erythematosus.

Human leukocyte antigen (HLA) class I and class II alleles are implicated as genetic risk factors for many autoimmune diseases. However, the role of the HLA loci in human systemic lupus erythematosus (SLE) remains unclear. Using a dense map of polymorphic microsatellites across the HLA region in a large collection of families with SLE, we identified three distinct haplotypes that encompassed the class II region and exhibited transmission distortion.