Environmental Exposures during Puberty: Window of Breast Cancer Risk and Epigenetic Damage.

During puberty, a woman's breasts are vulnerable to environmental damage ("window of vulnerability"). Early exposure to environmental carcinogens, endocrine disruptors, and unhealthy foods (refined sugar, processed fats, food additives) are hypothesized to promote molecular damage that increases breast cancer risk. However, prospective human studies are difficult to perform and effective interventions to prevent these early exposures are lacking. It is difficult to prevent environmental exposures during puberty. Specifically, young women are repeatedly exposed to media messaging that promotes unhealthy foods. Young women living in disadvantaged neighborhoods experience additional challenges including a lack of access to healthy food and exposure to contaminated air, water, and soil. The purpose of this review is to gather information on potential exposures during puberty. In future directions, this information will be used to help elementary/middle-school girls to identify and quantitate environmental exposures and develop cost-effective strategies to reduce exposures

Assessing the health and environmental benefits associated with changes in transportation activities in near-road communities using low-cost sensors

Final ReportOn-road measurements of four pollutants (PM2.5, PM10, NO2, and O3) were continuously recorded by three U.S. EPA-certified FEM air pollution monitoring devices installed inside a vehicle traveling repeatedly on the same route in a near-road community. Spatio-temporal on-road air quality data were aggregated and compared to data collected at two fixed stations, one residence located 15 m from the frontage road adjacent to Interstate Highway I10, and another residential site 300 m from the frontage road. The first objective of this study is to assess the suitability of using the spatio-temporal on-road air monitoring data for representing community exposures to transportation-related air pollutants (TRAPs). While TRAP concentrations observed at a central state-operated site appear to be in good agreement with those observed in the near-road community, concentrations in the community may be better represented by spatio-temporal data generated by an on-road monitor. The second objective of evaluating the feasibility of using on-road air monitors instead of near-road monitors is supported by the facts that pollutants primarily emitted from sources other than traffic, such as PM10, display a different pattern than that of the other three pollutants. On-road monitors successfully detected PM10 concentrations near-road as well as in the community that are comparable to the regional background concentrations. PM2.5 and O3 detected by on-road monitors are also comparable to those detected near-road in the community. NO2 concentrations detected by the on-road monitors varied from the near-road monitors due to the complex interactions with ambient temperature, vehicle emissions, and atmospheric chemical reactions. It seems likely that community exposures to TRAPs can be represented by short-term spatio-temporal measurements using on-road monitors. On-road air pollution measurements provide a rapid assessment of the air quality in a community without installing multiple stationary sites.U.S. Department of Transportation 69A355174711

Using Transit Vehicles as Probes to Monitor Community Air Quality and Exposure

Final ReportThis project evaluates the feasibility of using transit vehicles traveling on fixed routes in a well-controlled residential community in El Paso for near-road exposure assessment. Continuous on-road measurements of four pollutants (PM2.5 , PM10, NO2, and O3) were recorded using U.S. EPA FEM-designated monitors in conjunction with a GPS device for coordinates and vehicle speed. Concurrent near-road measurements of the same air pollutants at two near-road stationary sites were used to develop relationships with the mobile data. It was found that pollutant concentrations measured by mobile air monitors agree well with that collected at stationary sites. On-road PM2.5 and PM10 concentrations closely resemble that measured at stationary sites. O3 concentration was found to be ubiquitous in the community whether it’s on-road, near-road, or in the community. On-road measurements of NO2 showed slightly higher values compared to near-road sites. Furthermore, concentrations of transportation related air pollutants at traffic intersections in an environment with less traffic and topological features were found to be indistinguishable from that measured on road segments away from the traffic intersections. This study demonstrates that mobile air monitoring in a less traveled community can accurately detect the exposure concentrations that are representative of the community and near-road receptors. Further research should focus on how the mobile data can be used in exposure and health assessment and how the technique can be applied to characterize exposure concentrations at locations that stationary monitoring is not allowed or possible.U.S. Department of Transportation 69A355174711

Assessing Children's Spatiotemporal Exposures to Transportation Pollutants in Near-Road Communities

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Assessing Children's Spatiotemporal Exposures to Transportation Pollutants in Near-road Communities

Final ReportTraffic-related air pollution has a profound impact on human health especially for residents living in near-road communities which are constantly exposed these air pollutants. A near-road community is expected to observe significant spatial and temporal variations in pollutant concentrations, as air pollution resulting from emissions from major highways decreases rapidly from the highway. This research conducted on-site traffic and air quality measurements on four critical transportations related air pollutants, PM2.5, PM10, NO2, O3, as well as emission and air dispersion modeling of transportation emission impacts in a near-road community. Using numerical models provided by the EPA, integrated with field measurements of both traffic and air quality, this research developed spatial and temporal pollutant concentration variation patterns in a near-road community using MOVES and AERMOD, EPA emissions and dispersion models. It was observed that modeled-to-monitored comparisons show that air quality impact in near-road communities resulting from traffic-related emissions are dominated by regional background concentrations. Additionally, the AERMOD predictions rendered highest concentration estimates at locations where the traffic volume is the highest and downwind of the prevailing winds. However, impacts of the traffic emissions on the air quality subside rapidly with increasing distance away from the highway, at around 200 meters. This research also apportioned the differences in exposure concentrations to background concentrations and those contributed from major highways. In the near-road community studied, traffic emissions from the highway were 4.8 times higher than the contributions made by local arterial roads. For better transportation air quality impact assessments, higher quality traffic data such as time-specific traffic volume and fleet information as well as meteorological data such as site-specific surface meteorological could help yield more accurate concentration predictions.U.S. Department of Transportation 69A355174711

Environmental Exposures during Puberty: Window of Breast Cancer Risk and Epigenetic Damage

During puberty, a woman’s breasts are vulnerable to environmental damage (“window of vulnerability”). Early exposure to environmental carcinogens, endocrine disruptors, and unhealthy foods (refined sugar, processed fats, food additives) are hypothesized to promote molecular damage that increases breast cancer risk. However, prospective human studies are difficult to perform and effective interventions to prevent these early exposures are lacking. It is difficult to prevent environmental exposures during puberty. Specifically, young women are repeatedly exposed to media messaging that promotes unhealthy foods. Young women living in disadvantaged neighborhoods experience additional challenges including a lack of access to healthy food and exposure to contaminated air, water, and soil. The purpose of this review is to gather information on potential exposures during puberty. In future directions, this information will be used to help elementary/middle-school girls to identify and quantitate environmental exposures and develop cost-effective strategies to reduce exposures

Odanacatib for the treatment of postmenopausal osteoporosis : Results of the LOFT multicentre, randomised, double-blind, placebo-controlled trial and LOFT Extension study

Background Odanacatib, a cathepsin K inhibitor, reduces bone resorption while maintaining bone formation. Previous work has shown that odanacatib increases bone mineral density in postmenopausal women with low bone mass. We aimed to investigate the efficacy and safety of odanacatib to reduce fracture risk in postmenopausal women with osteoporosis. Methods The Long-term Odanacatib Fracture Trial (LOFT) was a multicentre, randomised, double-blind, placebo-controlled, event-driven study at 388 outpatient clinics in 40 countries. Eligible participants were women aged at least 65 years who were postmenopausal for 5 years or more, with a femoral neck or total hip bone mineral density T-score between −2·5 and −4·0 if no previous radiographic vertebral fracture, or between −1·5 and −4·0 with a previous vertebral fracture. Women with a previous hip fracture, more than one vertebral fracture, or a T-score of less than −4·0 at the total hip or femoral neck were not eligible unless they were unable or unwilling to use approved osteoporosis treatment. Participants were randomly assigned (1:1) to either oral odanacatib (50 mg once per week) or matching placebo. Randomisation was done using an interactive voice recognition system after stratification for previous radiographic vertebral fracture, and treatment was masked to study participants, investigators and their staff, and sponsor personnel. If the study completed before 5 years of double-blind treatment, consenting participants could enrol in a double-blind extension study (LOFT Extension), continuing their original treatment assignment for up to 5 years from randomisation. Primary endpoints were incidence of vertebral fractures as assessed using radiographs collected at baseline, 6 and 12 months, yearly, and at final study visit in participants for whom evaluable radiograph images were available at baseline and at least one other timepoint, and hip and non-vertebral fractures adjudicated as being a result of osteoporosis as assessed by clinical history and radiograph. Safety was assessed in participants who received at least one dose of study drug. The adjudicated cardiovascular safety endpoints were a composite of cardiovascular death, myocardial infarction, or stroke, and new-onset atrial fibrillation or flutter. Individual cardiovascular endpoints and death were also assessed. LOFT and LOFT Extension are registered with ClinicalTrials.gov (number NCT00529373) and the European Clinical Trials Database (EudraCT number 2007-002693-66). Findings Between Sept 14, 2007, and Nov 17, 2009, we randomly assigned 16 071 evaluable patients to treatment: 8043 to odanacatib and 8028 to placebo. After a median follow-up of 36·5 months (IQR 34·43–40·15) 4297 women assigned to odanacatib and 3960 assigned to placebo enrolled in LOFT Extension (total median follow-up 47·6 months, IQR 35·45–60·06). In LOFT, cumulative incidence of primary outcomes for odanacatib versus placebo were: radiographic vertebral fractures 3·7% (251/6770) versus 7·8% (542/6910), hazard ratio (HR) 0·46, 95% CI 0·40–0·53; hip fractures 0·8% (65/8043) versus 1·6% (125/8028), 0·53, 0·39–0·71; non-vertebral fractures 5·1% (412/8043) versus 6·7% (541/8028), 0·77, 0·68–0·87; all p<0·0001. Combined results from LOFT plus LOFT Extension for cumulative incidence of primary outcomes for odanacatib versus placebo were: radiographic vertebral fractures 4·9% (341/6909) versus 9·6% (675/7011), HR 0·48, 95% CI 0·42–0·55; hip fractures 1·1% (86/8043) versus 2·0% (162/8028), 0·52, 0·40–0·67; non-vertebral fractures 6·4% (512/8043) versus 8·4% (675/8028), 0·74, 0·66–0·83; all p<0·0001. In LOFT, the composite cardiovascular endpoint of cardiovascular death, myocardial infarction, or stroke occurred in 273 (3·4%) of 8043 patients in the odanacatib group versus 245 (3·1%) of 8028 in the placebo group (HR 1·12, 95% CI 0·95–1·34; p=0·18). New-onset atrial fibrillation or flutter occurred in 112 (1·4%) of 8043 patients in the odanacatib group versus 96 (1·2%) of 8028 in the placebo group (HR 1·18, 0·90–1·55; p=0·24). Odanacatib was associated with an increased risk of stroke (1·7% [136/8043] vs 1·3% [104/8028], HR 1·32, 1·02–1·70; p=0·034), but not myocardial infarction (0·7% [60/8043] vs 0·9% [74/8028], HR 0·82, 0·58–1·15; p=0·26). The HR for all-cause mortality was 1·13 (5·0% [401/8043] vs 4·4% [356/8028], 0·98–1·30; p=0·10). When data from LOFT Extension were included, the composite of cardiovascular death, myocardial infarction, or stroke occurred in significantly more patients in the odanacatib group than in the placebo group (401 [5·0%] of 8043 vs 343 [4·3%] of 8028, HR 1·17, 1·02–1·36; p=0·029, as did stroke (2·3% [187/8043] vs 1·7% [137/8028], HR 1·37, 1·10–1·71; p=0·0051). Interpretation Odanacatib reduced the risk of fracture, but was associated with an increased risk of cardiovascular events, specifically stroke, in postmenopausal women with osteoporosis. Based on the overall balance between benefit and risk, the study's sponsor decided that they would no longer pursue development of odanacatib for treatment of osteoporosis