1,181 research outputs found
Construction and testing of self-drilled soil nails
Current standards and best practice guidance recognise that testing of self-drilled hollow bar soil nails can be problematic as conventional packers and debonded lengths cannot be constructed. As a result, this causes difficulty in testing and confirming the ultimate bond resistance within the passive zone of a soil-nailed slope, and thus the design soil nail lengths. This paper provides a summary and review of the various testing procedures adopted for a soil nail construction project in Scotland. The practical design considerations, and their validation through the installation and testing of 49 sacrificial test nails, are detailed. The construction issues associated with the nail installation and testing are also outlined and discussed in light of the results obtained using different testing approaches. The aim of this case study is to report on the experiences with installation and testing of hollow bar soil nails. The objectives are to develop an initial data base of available soil–grout bond strength of hollow bar soil nails based on the several practical installation procedures used in this project and to establish areas for improvement of installation, testing and quality control in order to perform comparable pullout tests on self-drilled hollow bar soil nails. </jats:p
Estrogenic activity, race/ethnicity, and Indigenous American ancestry among San Francisco Bay Area women.
Estrogens play a significant role in breast cancer development and are not only produced endogenously, but are also mimicked by estrogen-like compounds from environmental exposures. We evaluated associations between estrogenic (E) activity, demographic factors and breast cancer risk factors in Non-Latina Black (NLB), Non-Latina White (NLW), and Latina women. We examined the association between E activity and Indigenous American (IA) ancestry in Latina women. Total E activity was measured with a bioassay in plasma samples of 503 women who served as controls in the San Francisco Bay Area Breast Cancer Study. In the univariate model that included all women with race/ethnicity as the independent predictor, Latinas had 13% lower E activity (p = 0.239) and NLBs had 35% higher activity (p = 0.04) compared to NLWs. In the multivariable model that adjusted for demographic factors, Latinas continued to show lower E activity levels (26%, p = 0.026), but the difference between NLBs and NLWs was no longer statistically significant (p = 0.431). An inverse association was observed between E activity and IA ancestry among Latina women (50% lower in 0% vs. 100% European ancestry, p = 0.027) consistent with our previously reported association between IA ancestry and breast cancer risk. These findings suggest that endogenous estrogens and exogenous estrogen-like compounds that act on the estrogen receptor and modulate E activity may partially explain racial/ethnic differences in breast cancer risk
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Ca2+ waves coordinate purinergic receptor–evoked integrin activation and polarization
The integrin GPIIb/IIIa is highly abundant on the surface of platelets and can be activated by intracellular Ca2+ signaling in an “inside-out” manner to bind to the adhesive ligand fibrinogen. Bye et al. imaged intracellular Ca2+ signaling and fibrinogen binding events in primary rat megakaryocytes activated through the ADP-stimulated receptors P2Y1 and P2Y12. The authors found that signaling by both receptors was required for full integrin activation, which depended on P2Y1-stimulated Ca2+ signaling and P2Y12-stimulated activation of the kinase PI3K. In addition, fibrinogen binding became polarized in these cells in a manner dependent on the direction of ADP-stimulated Ca2+ waves
Leukemia-related chromosomal loss detected in hematopoietic progenitor cells of benzene-exposed workers.
Benzene exposure causes acute myeloid leukemia and hematotoxicity, shown as suppression of mature blood and myeloid progenitor cell numbers. As the leukemia-related aneuploidies monosomy 7 and trisomy 8 previously had been detected in the mature peripheral blood cells of exposed workers, we hypothesized that benzene could cause leukemia through the induction of these aneuploidies in hematopoietic stem and progenitor cells. We measured loss and gain of chromosomes 7 and 8 by fluorescence in situ hybridization in interphase colony-forming unit-granulocyte-macrophage (CFU-GM) cells cultured from otherwise healthy benzene-exposed (n=28) and unexposed (n=14) workers. CFU-GM monosomy 7 and 8 levels (but not trisomy) were significantly increased in subjects exposed to benzene overall, compared with levels in the control subjects (P=0.0055 and P=0.0034, respectively). Levels of monosomy 7 and 8 were significantly increased in subjects exposed to <10 p.p.m. (20%, P=0.0419 and 28%, P=0.0056, respectively) and ≥ 10 p.p.m. (48%, P=0.0045 and 32%, 0.0354) benzene, compared with controls, and significant exposure-response trends were detected (P(trend)=0.0033 and 0.0057). These data show that monosomies 7 and 8 are produced in a dose-dependent manner in the blood progenitor cells of workers exposed to benzene, and may be mechanistically relevant biomarkers of early effect for benzene and other leukemogens
Freedom of Information Act: scalpel or just a sharp knife?
The concluding statement of the Burns Commission, established to evaluate whether changes are needed to the Freedom of Information Act (FOIA), ruled no major legislative changes were required. As such Freedom of Information (FOI) legislation still enables anyone to obtain information from public authorities. In this brief report article we explore arguments regarding FOI as an instrument for healthcare research using an international research programme as a case study
Issues of Processing and Multiple Testing of SELDI-TOF MS Proteomic Data
A new data filtering method for SELDI-TOF MS proteomic spectra data is described. We examined technical repeats (2 per subject) of intensity versus m/z (mass/charge) of bone marrow cell lysate for two groups of childhood leukemia patients: acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). As others have noted, the type of data processing as well as experimental variability can have a disproportionate impact on the list of interesting proteins (see Baggerly et al. (2004)). We propose a list of processing and multiple testing techniques to correct for 1) background drift; 2) filtering using smooth regression and cross-validated bandwidth selection; 3) peak finding; and 4) methods to correct for multiple testing (van der Laan et al. (2005)). The result is a list of proteins (indexed by m/z) where average expression is significantly different among disease (or treatment, etc.) groups. The procedures are intended to provide a sensible and statistically driven algorithm, which we argue provides a list of proteins that have a significant difference in expression. Given no sources of unmeasured bias (such as confounding of experimental conditions with disease status), proteins found to be statistically significant using this technique have a low probability of being false positives
Assessing health risks from multiple environmental stressors: Moving from G×E to I×E.
Research on disease causation often attempts to isolate the effects of individual factors, including individual genes or environmental factors. This reductionist approach has generated many discoveries, but misses important interactive and cumulative effects that may help explain the broad range of variability in disease occurrence observed across studies and individuals. A disease rarely results from a single factor, and instead results from a broader combination of factors, characterized here as intrinsic (I) and extrinsic (E) factors. Intrinsic vulnerability or resilience emanates from a variety of both fixed and shifting biological factors including genetic traits, while extrinsic factors comprise all biologically-relevant external stressors encountered across the lifespan. The I×E concept incorporates the multi-factorial and dynamic nature of health and disease and provides a unified, conceptual basis for integrating results from multiple areas of research, including genomics, G×E, developmental origins of health and disease, and the exposome. We describe the utility of the I×E concept to better understand and characterize the cumulative impact of multiple extrinsic and intrinsic factors on individual and population health. New research methods increasingly facilitate the measurement of multifactorial and interactive effects in epidemiological and toxicological studies. Tiered or indicator-based approaches can guide the selection of potentially relevant I and E factors for study and quantification, and exposomics methods may eventually produce results that can be used to generate a response function over the life course. Quantitative data on I×E interactive effects should generate a better understanding of the variability in human response to environmental factors. The proposed I×E concept highlights the role for broader study design in order to identify extrinsic and intrinsic factors amenable to interventions at the individual and population levels in order to enhance resilience, reduce vulnerability and improve health
Clean subglacial access:Prospects for future deep hot-water drilling
Accessing and sampling subglacial environments deep beneath the Antarctic Ice Sheet presents several challenges to existing drilling technologies. With over half of the ice sheet believed to be resting on a wet bed, drilling down to this environment must conform to international agreements on environmental stewardship and protection, making clean hot-water drilling the most viable option. Such a drill, and its water recovery system, must be capable of accessing significantly greater ice depths than previous hot-water drills, and remain fully operational after connecting with the basal hydrological system. The Subglacial Lake Ellsworth (SLE) project developed a comprehensive plan for deep (greater than 3000 m) subglacial lake research, involving the design and development of a clean deep-ice hot-water drill. However, during fieldwork in December 2012 drilling was halted after a succession of equipment issues culminated in a failure to link with a subsurface cavity and abandonment of the access holes. The lessons learned from this experience are presented here. Combining knowledge gained from these lessons with experience from other hot-water drilling programmes, and recent field testing, we describe the most viable technical options and operational procedures for future clean entry into SLE and other deep subglacial access targets.</p
The NIEHS Superfund Research Program: 25 Years of Translational Research for Public Health
BACKGROUND: The Superfund Research Program (SRP) is an academically based, multidisciplinary, translational research program that for 25 years has sought scientific solutions to health and environmental problems associated with hazardous waste sites. SRP is coordinated by the National Institute of Environmental Health Sciences (NIEHS). It supports multi-project grants, undergraduate and postdoctoral training programs, individual research grants, and Small Business Innovation Research (SBIR) and Technology Transfer Research (STTR) grants.
RESULTS: SRP has had many successes: discovery of arsenic\u27s toxicity to the developing human central nervous system; documentation of benzene toxicity to hematologic progenitor cells in human bone marrow; development of novel analytic techniques such as the luciferase expression assay and laser fragmentation fluorescence spectroscopy; demonstration that PCBs can cause developmental neurotoxicity at low levels and alter the genomic characteristics of sentinel animals; elucidation of the neurodevelopmental toxicity of organophosphate insecticides; documentation of links between antimicrobial agents and alterations in hormone response; discovery of biological mechanisms through which environmental chemicals may contribute to obesity, atherosclerosis, diabetes, and cancer; tracking the health and environmental effects of the attacks on the World Trade Center and Hurricane Katrina; and development of novel biological and engineering techniques to facilitate more efficient and lower-cost remediation of hazardous waste sites.
CONCLUSION: SRP must continue to address the legacy of hazardous waste in the United States, respond to new issues caused by rapid advances in technology, and train the next generation of leaders in environmental health science while recognizing that most of the world\u27s worst toxic hot spots are now located in low- and middle-income countries
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