Hypersensitive site 4 of the human β-globin locus control region.

The Locus Control Region (LCR) of the human beta globin gene domain is defined by four erythroid-specific DNasel hypersensitive sites (HSS) located upstream of this multigene cluster. The LCR confers copy number dependent high levels of erythroid specific expression to a linked transgene, independent of the site of integration. To assess the role of the individual hypersensitive sites of the LCR, we have localized HSS4 to a 280bp fragment that is functional both in murine erythroleukaemia (MEL) cells and in transgenic mice. This fragment coincides with the major area of hypersensitivity 'in vivo' and contains a number of DNasel footprints. Bandshift analysis shows that these footprints correspond to binding sites for the erythroid specific proteins GATA1 and NF-E2 and a number of ubiquitous proteins, including jun/fos, Sp1 and TEF2

Predictors of personal polycyclic aromatic hydrocarbon exposures among pregnant minority women in New York City.

As part of a multiyear birth-cohort study examining the roles of pre- and postnatal environmental exposures on developmental deficits and asthma among children, we measured personal exposures to polycyclic aromatic hydrocarbons (PAHs) among 348 pregnant women in northern Manhattan and the South Bronx, New York. Nonsmoking African-American or Dominican women were identified and recruited into the study. During the third trimester of pregnancy, each subject wore a personal air monitor for 48 hr to determine exposure levels to nine PAH compounds. In this study, we examined levels of exposures to PAHs and tested for associations with potential predictor variables collected from questionnaires addressing socioeconomic factors and day-to-day activities during pregnancy as well as activities and environmental exposures during the 48-hr monitoring period. Reliable personal monitoring data for women who did not smoke during the monitoring period were available for 344 of 348 subjects. Mean PAH concentrations ranged from 0.06 ng/m3 for dibenz[a,h]anthracene to 4.1 ng/m3 for pyrene; mean benzo[a]pyrene concentration was 0.50 ng/m3. As found in previous studies, concentrations of most PAHs were higher in winter than in summer. Multiple linear regression analysis revealed associations between personal PAH exposures and several questionnaire variables, including time spent outdoors, residential heating, and indoor burning of incense. This is the largest study to date characterizing personal exposures to PAHs, a ubiquitous class of carcinogenic air contaminants in urban environments, and is unique in its focus on pregnant minority women

Vulnerability as a Function of Individual and Group Resources in Cumulative Risk Assessment

BACKGROUND: The field of risk assessment has focused on protecting the health of individual people or populations of wildlife from single risks, mostly from chemical exposure. The U.S. Environmental Protection Agency recently began to address multiple risks to communities in the “Framework for Cumulative Risk Assessment” [EPA/630/P02/001F. Washington DC:Risk Assessment Forum, U.S. Environmental Protection Agency (2003)]. Simultaneously, several reports concluded that some individuals and groups are more vulnerable to environmental risks than the general population. However, vulnerability has received little specific attention in the risk assessment literature. OBJECTIVE: Our objective is to examine the issue of vulnerability in cumulative risk assessment and present a conceptual framework rather than a comprehensive review of the literature. In this article we consider similarities between ecologic and human communities and the factors that make communities vulnerable to environmental risks. DISCUSSION: The literature provides substantial evidence on single environmental factors and simple conditions that increase vulnerability or reduce resilience for humans and ecologic systems. This observation is especially true for individual people and populations of wildlife. Little research directly addresses the topic of vulnerability in cumulative risk situations, especially at the community level. The community level of organization has not been adequately considered as an end point in either human or ecologic risk assessment. Furthermore, current information on human risk does not completely explain the level of response in cumulative risk conditions. Ecologic risk situations are similarly more complex and unpredictable for cases of cumulative risk. CONCLUSIONS: Psychosocial conditions and responses are the principal missing element for humans. We propose a model for including psychologic and social factors as an integral component of cumulative risk assessment

Urinary Phthalate Metabolites in Relation to Preterm Birth in Mexico City

Background: Rates of preterm birth have been rising over the past several decades. Factors contributing to this trend remain largely unclear, and exposure to environmental contaminants may play a role. Objective: We investigated the relationship between phthalate exposure and preterm birth. Methods: Within a large Mexican birth cohort study, we compared third-trimester urinary phthalate metabolite concentrations in 30 women who delivered preterm (< 37 weeks of gestation) with those of 30 controls (≥ 37 weeks of gestation). Results: Concentrations of most of the metabolites were similar to those reported among U.S. females, although in the present study mono-n-butyl phthalate (MBP) concentrations were higher and monobenzyl phthalate (MBzP) concentrations lower. In a crude comparison before correcting for urinary dilution, geometric mean urinary concentrations were higher for the phthalate metabolites MBP, MBzP, mono(3-carboxylpropyl) phthalate, and four metabolites of di(2-ethyl-hexyl) phthalate among women who subsequently delivered preterm. These differences remained, but were somewhat lessened, after correction by specific gravity or creatinine. In multivariate logistic regression analysis adjusted for potential confounders, elevated odds of having phthalate metabolite concentrations above the median level were found. Conclusions: We found that phthalate exposure is prevalent among this group of pregnant women in Mexico and that some phthalates may be associated with preterm birth

Importance of globin gene order for correct developmental expression.

We have used transgenic mice to study the influence of position of the human globin genes relative to the locus control region (LCR) on their expression pattern during development. The LCR, which is located 5' of the globin gene cluster, is normally required for the activation of all the genes. When the human beta-globin gene is linked as a single gene to the LCR it is activated prematurely in the embryonic yolk sac. We show that the correct timing of beta gene activation is restored when it is placed farther from the LCR than a competing human gamma- or alpha-globin gene. Correct timing is not restored when beta is the globin gene closest to the LCR. Similarly, the human gamma-globin gene is silenced earlier when present farthest from the LCR. On the basis of this result, we propose a model of developmental gene control based on stage-specific elements immediately flanking the genes and on polarity in the locus. We suggest that the difference in relative distance to the LCR, which is a consequence of the ordered arrangement of the genes, results in nonreciprocal competition between the genes for activation by the LCR

A Multi-disciplinary Approach for the Precision Management of Lodging Risk

This paper describes how wind engineering, geospatial science and crop agronomy disciplines can be combined to provide a decision support system for farmers to manage lodging risk, using the Crop Failure Assessment due to Lodging Losses (CROPFALL) framework. CROPFALL calculates lodging risk using information about topography, land cover, soil type and meteorological data, combined with a mechanistic model of lodging, and crop parameters. The risk of lodging is calculated at regional, farm, field and sub-field scales. The impact of crop management changes on lodging risk is simulated, demonstrating that modest crop management changes can achieve large reductions in lodging risk

Scenario archetypes:converging rather than diverging themes

Future scenarios provide challenging, plausible and relevant stories about how the future could unfold. Urban Futures (UF) research has identified a substantial set (>450) of seemingly disparate scenarios published over the period 1997–2011 and within this research, a sub-set of >160 scenarios has been identified (and categorized) based on their narratives according to the structure first proposed by the Global Scenario Group (GSG) in 1997; three world types (Business as Usual, Barbarization, and Great Transitions) and six scenarios, two for each world type (Policy Reform—PR, Market Forces—MF, Breakdown—B, Fortress World—FW, Eco-Communalism—EC and New Sustainability Paradigm—NSP). It is suggested that four of these scenario archetypes (MF, PR, NSP and FW) are sufficiently distinct to facilitate active stakeholder engagement in futures thinking. Moreover they are accompanied by a well-established, internally consistent set of narratives that provide a deeper understanding of the key fundamental drivers (e.g., STEEP—Social, Technological, Economic, Environmental and Political) that could bring about realistic world changes through a push or a pull effect. This is testament to the original concept of the GSG scenarios and their development and refinement over a 16 year period

Evaluation and Inter-comparison of Acid Deposition Models for the UK

An evaluation has been made of a range of simple and complex atmospheric transport models, applied to estimate sulphur and nitrogen deposition in the UK in order to provide information to policy makers to support decisions on future model use. The models were evaluated by comparison with annually averaged measurements from the national monitoring networks. A number of statistical metrics were output to assess model performance and the models were compared graphically by plotting cross-country transects of concentrations in air

Enhancements to the UK Photochemical Trajectory Model for simulation of secondary inorganic aerosol

Particulate matter remains a challenging pollutant for air pollution control in the UK and across much of Europe. Particulate matter is a complex mixture of which secondary inorganic compounds (sulphates, nitrates) are a major component. This paper is concerned with taking a basic version of the UK Photochemical Trajectory Model and enhancing a number of features in the model in order to better represent boundary layer processes and to improve the description of secondary inorganic aerosol formation. The enhancements include an improved treatment of the boundary layer, deposition processes (both wet and dry), attenuation of photolysis rates by cloud cover, and inclusion of the aerosol thermodynamic model ISORROPIA II to account both for chemistry within the aerosol and between the particles and gas phase. Emissions inventories have been updated and are adjusted according to season, day of the week and hour of the day. Stack emissions from high level sources are now adjusted according to the height of the boundary layer and a scheme for generating marine aerosol has been included. The skill of the improved model has been evaluated through predictions of the concentrations of particulate chloride, nitrate and sulphate and the results show increased accuracy and lower mean bias. There is a much higher proportion of the values lying within a factor of 2 of the observed values compared to the basic model and Normalised Mean Bias has reduced by at least 89% for nitrate and sulphate. Similarly, the Index of Agreement between calculated and measured values has improved by ∼10%. Considering the contribution of each enhancement to the improvement in the performance metrics, the most significant enhancement was the replacement of the parameterisation of the boundary layer height, relative humidity and temperature by HYSPLIT values calculated for each trajectory. The second most significant enhancement was the parameterisation of the photolysis rates by values calculated by an off line database accounting for the dependence of photolysis rates on zenith angle, cloud cover, land surface type and column ozone. The inclusion of initial conditions which were dependent on the starting point of the trajectory and the modulation of stack emissions made the most significant improvement to sulphate. Furthermore, in order to assess the model's response to abatement scenarios, 30% abatements of either NH3, NOx or SO2 showed a reduction in the sum of chloride, nitrate and sulphate of between 3.1% and 8.5% (with a corresponding estimated reduction of 1.6–3.7% reduction in PM10). The largest reduction in this contribution is due to the abatement of NOx