Genetic variants in hypothalamic-pituitary-adrenal axis genes and breast cancer risk in Caucasians and African Americans

Elevated circulating levels of the adrenal androgen dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) are associated with increased breast cancer risk in prospective studies. Genetic variants in hypothalamicpituitary- adrenal (HPA) axis genes may contribute to these circulating hormone levels, and consequently to breast cancer risk. No previous studies have examined the effects of genetic variants in HPA axis genes on breast cancer risk. We evaluated the associations of 49 single nucleotide polymorphisms (SNPs) in five HPA axis genes (NR3C1, NR3C2, CRH, CRHR1, and CRHBP) with the risk of breast cancer in the Women's Insights and Shared Experiences (WISE) Study of Caucasians (346 cases and 442 controls), as well as African Americans (149 cases and 246 controls). Of the 49 SNPs evaluated, one showed a nominal significant association (P for trend < 0.05) with breast cancer risk among Caucasians, and another two among African Americans. The age-adjusted additive odds ratio (OR) (95% confidence interval (95% CI)) of the SNP rs11747190[A] in the CRHBP gene for the risk of breast cancer among Caucasian women was 1.45 (1.09-1.94). The age-adjusted additive ORs (95% CIs) of two SNPs (CRHBP rs1700688[T] and CRHR1 rs17689471[C]) for the risk of breast cancer among African American women were 1.84 (1.13-2.98) and 2.48 (1.20-5.13), respectively. However, these SNPs did not show significant associations after correction for multiple testing. Our findings do not provide strong supportive evidence for the contribution of genetic variants in these HPA axis genes to the risk of developing breast cancer in either Caucasians or African Americans

Genetic variants in anti-Mullerian hormone and anti-Mullerian hormone receptor genes and breast cancer risk in Caucasians and African Americans

Anti-Mullerian hormone (AMH) regulates ovarian folliculogenesis by signaling via its receptors, and elevated serum AMH levels are associated with an increased risk of breast cancer. No previous studies have examined the effects of genetic variants in AMH-related genes on breast cancer risk. We evaluated the associations of 62 single nucleotide polymorphisms (SNPs) in AMH and its receptor genes, including AMH type 1 receptor (ACVR1) and AMH type 2 receptor (AMHR2), with the risk of breast cancer in the Women’s Insights and Shared Experiences (WISE) Study of Caucasians (346 cases and 442 controls), as well as African Americans (149 cases and 246 controls). Of the 62 SNPs evaluated, two showed a nominal significant association (P for trend < 0.05) with breast cancer risk among Caucasians, and another two among African Americans. The age-adjusted additive odds ratios (ORs) (95% confidence interval (95% CI)) of those two SNPs (ACVR1 rs12694937[C] and ACVR1 rs2883605[T]) for the risk of breast cancer among Caucasian women were 2.33 (1.20-4.52) and 0.68 (0.47-0.98), respectively. The age-adjusted additive ORs (95% CI) of those two SNPs (ACVR1 rs1146031[G] and AMHR2 functional SNP rs2002555[G]) for the risk of breast cancer among African American women were 0.63 (0.44-0.92) and 1.67 (1.10-2.53), respectively. However, these SNPs did not show significant associations after correction for multiple testing. Our findings do not provide strong supportive evidence for the contribution of genetic variants in AMH-related genes to the risk of developing breast cancer in either Caucasians or African Americans

Evaluation Of Football Shoulder Pads

The development of sports protective equipment has been largely the result of trial and error and, with the exception of foot and head protective devices, has not involved the research process. Claims related to football shoulder pad innovations have not typically been supported by relevant objective data. The purpose of this study was to develop procedures and instrumentation for comparison of the effectiveness of shoulder pads. The most important criterion for protective effectiveness was considered to be the prevention of high peak pressures on body parts and tissues underneath the pads. Phase I of the study was designed to determine player perceptions of high-pressure sites following performance of drills on the field using a variety of pads. Phase II involved the development of instrumentation and procedures to directly measure pressure on sites identified in phase I during a controlled blocking drill simulating field conditions. Pressure measurements were taken using twelve pressure sensing resistors (0.6 mm thick and 12 mm in diameter) attached to selected sites underneath the pads. Signal conditioning circuity was developed to provide output from these transducers proportional to pressure. The output was routed to a digital computer via an analog-todigital interface board for subsequent analysis. The measurement system was used to evaluate six sets of shoulder pads representing the use of conventional, closed-cell foam and the use of open-cell foam (one and three layers) with an air management system. Four experienced subjects used each set of pads to hit a blocking dummy several times. Results were consistent with subjects' perceptions of areas of greatest pressure, indicating that: 1) greatest peak forces for all pads were received on the portion of the superior portion of the deltoid, acromion, and superior portion of the trapezius; and 2) pads using open-cell foam with an air management system were superior to pads using closed-cell foam in preventing high peak pressures. This study was partially supported by the Kansas State University Research Foundation

Multidisciplinary Graduate Curriculum in Support of the Biobased Products Industry

The project had a dominant education component. The project involved revising curriculum to educate traditional engineering students in the emerging field of industrial biotechnology. New classes were developed and offered. As a result, the curriculum of the Colorado School of Mines was expanded to include new content. Roughly 100 undergraduates and about 10 graduate students each year benefit from this curricular expansion. The research associated with this project consisted of developing new materials and energy sources from renewable resources. Several significant advances were made, most importantly the heat distortion temperature of polylactide (PLA) was increased through the addition of cellulosic nanowhiskers. The resulting ecobionanocomposites have superior properties which enable the use of renewable resource based plastics in a variety of new applications. Significant amounts of petroleum are thereby saved and considerable environmental benefits also result. Effectiveness and economic feasibility of the project proved excellent. The educational activities are continuing in a sustainable fashion, now being supported by tuition revenues and the normal budgeting of the University. The PI will be teaching one of the newly developed classes will next Fall (Fall 2006), after the close of the DOE grant, and again repeatedly into the future. Now established, the curriculum in biobased products and energy will grow and evolve through regular teaching and revision. On the research side, the new plastic materials appear economically feasible and a new collaboration between the PI’s group and Sealed Air, a major food-packaging manufacturer, has been established to bring the new green plastics to market. Public benefits of the project are noteworthy in many respects. These include the development of a better educated workforce and citizenry capable of providing technological innovation as a means of growing the economy and providing jobs. In particular, the educational components addressing the production of bioethanol, biodiesel, and bioplastics provide graduates that can assist American industries in including greater renewable content in feedstocks for materials and fuels. Finally, the collaboration fostered by this grant led to the drafting of a new book entitled, Bioengineering for Sustainability: Materials and Fuels for the 21st Century. This text will be widely available to the public interested in learning more about these important areas of technology

The discovery of a novel antibiotic for the treatment of Clostridium difficile infections: a story of an effective academic-industrial partnership

Academic drug discovery is playing an increasingly important role in the identification of new therapies for a wide range of diseases. There is no one model that guarantees success. We describe here a drug discovery story where chance, the ability to capitalise on chance, and the assembling of a range of expertise, have all played important roles in the discovery and subsequent development of an antibiotic chemotype based on the bis-benzimidazole scaffold, with potency against a number of current therapeutically challenging diseases. One compound in this class, SMT19969, has recently entered Phase 2 human clinical trials for the treatment of Clostridium difficile infections

The effects of moderate alcohol supplementation on estrone sulfate and DHEAS in postmenopausal women in a controlled feeding study

BACKGROUND: We have demonstrated that moderate alcohol consumption (15 g/d, 30 g/d) for 8 weeks resulted in significantly increased levels of serum estrone sulfate and DHEAS in 51 postmenopausal women in a randomized, placebo-controlled trial. We now report on the relationships between serum estrone sulfate and dehydroepiandrosterone sulfate (DHEAS) levels after 4 weeks of moderate alcohol supplementation, and compare the results to the 8 weeks data to elucidate time-to-effect differences. METHODS: Postmenopausal women (n = 51) consumed 0 (placebo), 15 (1 drink), and 30 (2 drinks) g alcohol (ethanol)/ day for 8 weeks as part of a controlled diet in a randomized crossover design. Blood samples were drawn at baseline, at 4 weeks and at 8 weeks. Changes in estrone sulfate and DHEAS levels from placebo to 15 g and 30 g alcohol per day were estimated using linear mixed models. RESULTS AND DISCUSSION: At week 4, compared to the placebo, estrone sulfate increased an average 6.9% (P = 0.24) when the women consumed 15 g of alcohol per day, and 22.2% (P = 0.0006) when they consumed 30 g alcohol per day. DHEAS concentrations also increased significantly by an average of 8.0% (P < 0.0001) on 15 g of alcohol per day and 9.2% (P < 0.0001) when 30 g alcohol was consumed per day. Trend tests across doses for both estrone sulfate (P = 0.0006) and DHEAS (P < 0.0001) were significant. We found no significant differences between the absolute levels of serum estrone sulfate at week 4 versus week 8 (P = 0.32) across all doses. However, absolute DHEAS levels increased from week 4 to week 8 (P < 0.0001) at all three dose levels. CONCLUSIONS: These data indicate that the hormonal effects due to moderate alcohol consumption are seen early, within 4 weeks of initiation of ingestion

High-resolution computed tomography reconstructions of invertebrate burrow systems

The architecture of biogenic structures can be highly influential in determining species contributions to major soil and sediment processes, but detailed 3-D characterisations are rare and descriptors of form and complexity are lacking. Here we provide replicate high-resolution micro-focus computed tomography (μ-CT) data for the complete burrow systems of three co-occurring, but functionally contrasting, sediment-dwelling inter-tidal invertebrates assembled alone, and in combination, in representative model aquaria. These data (≤2,000 raw image slices aquarium−1, isotropic voxel resolution, 81 μm) provide reference models that can be used for the development of novel structural analysis routines that will be of value within the fields of ecology, pedology, geomorphology, palaeobiology, ichnology and mechanical engineering. We also envisage opportunity for those investigating transport networks, vascular systems, plant rooting systems, neuron connectivity patterns, or those developing image analysis or statistics related to pattern or shape recognition. The dataset will allow investigators to develop or test novel methodology and ideas without the need to generate a complete three-dimensional computation of exemplar architecture

Secondary Sex Ratio among Women Exposed to Diethylstilbestrol in Utero

BACKGROUND. Diethylstilbestrol (DES), a synthetic estrogen widely prescribed to pregnant women during the mid-1900s, is a potent endocrine disruptor. Previous studies have suggested an association between endocrine-disrupting compounds and secondary sex ratio. METHODS. Data were provided by women participating in the National Cancer Institute (NCI) DES Combined Cohort Study. We used generalized estimating equations to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the relation of in utero DES exposure to sex ratio (proportion of male births). Models were adjusted for maternal age, child's birth year, parity, and cohort, and accounted for clustering among women with multiple pregnancies. RESULTS. The OR for having a male birth comparing DES-exposed to unexposed women was 1.05 (95% CI, 0.95-1.17). For exposed women with complete data on cumulative DES dose and timing (33%), those first exposed to DES earlier in gestation and to higher doses had the highest odds of having a male birth. The ORs were 0.91 (95% C, 0.65-1.27) for first exposure at ≥ 13 weeks gestation to < 5 g DES; 0.95 (95% CI, 0.71-1.27) for first exposure at ≥ 13 weeks to ≥ 5 g; 1.16 (95% CI, 0.96-1.41) for first exposure at < 13 weeks to < 5 g; and 1.24 (95% CI, 1.04-1.48) for first exposure at < 13 weeks to ≥ 5 g compared with no exposure. Results did not vary appreciably by maternal age, parity, cohort, or infertility history. CONCLUSIONS. Overall, no association was observed between in utero DES exposure and secondary sex ratio, but a significant increase in the proportion of male births was found among women first exposed to DES earlier in gestation and to a higher cumulative dose.National Cancer Institute (N01-CP-21168, N01-CP-51017, N01-CP-01289