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

The ecological fallacy of the role of age in chronic disease and hospital demand

Objective: To examine the relationship between age and all-cause hospital utilization in the years preceding and following a diagnosis in hospital of heart failure, type 2 diabetes, or chronic obstructive pulmonary disease (COPD). Research Design: A cohort study of all patients in Western Australia who have had a principal diagnosis of heart failure, type 2 diabetes, or COPD, upon admission to hospital. All-cause hospital utilization 6 years preceding and 4 years following cardinal events, that is, a disease-specific diagnosis upon hospital admission, where such an event has not occurred in the previous 2 years, are examined in specific age groups. Results: Six years preceding a cardinal event, all-cause emergency department (ED) presentations are similar in all age groups, from under 55 to over 85 years of age, except in COPD where ED presentation rates are higher in younger groups. All-cause hospital inpatient days are transiently higher in the years preceding and following a cardinal event in older age groups, yet return to similar levels across all age cohorts after 4 years. ED presentations are significantly higher in the 4 years following cardinal events in younger compared with older groups. Conclusions: Longitudinal analysis of utilization around cardinal events overcomes the confounding effect of differences in chronic disease rates between age groups, avoiding a source of ecologic bias that erroneously attributes increasing utilization in individuals with chronic disease to age. Programs designed to reduce hospital demand in patients with chronic disease should possibly focus on younger, rather than older, individuals

Prenatal Insecticide Exposures and Birth Weight and Length among an Urban Minority Cohort

We reported previously that insecticide exposures were widespread among minority women in New York City during pregnancy and that levels of the organophosphate chlorpyrifos in umbilical cord plasma were inversely associated with birth weight and length. Here we expand analyses to include additional insecticides (the organophosphate diazinon and the carbamate propoxur), a larger sample size (n = 314 mother–newborn pairs), and insecticide measurements in maternal personal air during pregnancy as well as in umbilical cord plasma at delivery. Controlling for potential confounders, we found no association between maternal personal air insecticide levels and birth weight, length, or head circumference. For each log unit increase in cord plasma chlorpyrifos levels, birth weight decreased by 42.6 g [95% confidence interval (CI), −81.8 to −3.8, p = 0.03] and birth length decreased by 0.24 cm (95% CI, −0.47 to −0.01, p = 0.04). Combined measures of (ln)cord plasma chlorpyrifos and diazinon (adjusted for relative potency) were also inversely associated with birth weight and length (p < 0.05). Birth weight averaged 186.3 g less (95% CI, −375.2 to −45.5) among newborns with the highest compared with lowest 26% of exposure levels (p = 0.01). Further, the associations between birth weight and length and cord plasma chlorpyrifos and diazinon were highly significant (p ≤ 0.007) among newborns born before the 2000–2001 U.S. Environmental Protection Agency’s regulatory actions to phase out residential use of these insecticides. Among newborns born after January 2001, exposure levels were substantially lower, and no association with fetal growth was apparent (p > 0.8). The propoxur metabolite 2-isopropoxyphenol in cord plasma was inversely associated with birth length, a finding of borderline significance (p = 0.05) after controlling for chlorpyrifos and diazinon. Results indicate that prenatal chlorpyrifos exposures have impaired fetal growth among this minority cohort and that diazinon exposures may have contributed to the effects. Findings support recent regulatory action to phase out residential uses of the insecticides

Spatio-temporal challenges in representing wildlife disturbance within a GIS

Assessing the potential environmental impacts of disturbance on protected species during and after the development process is a legislative requirement in most nations. However, the restrictions that this legislation places on developers are often based on limited ecological understanding, over-simplified methodologies, less-than-robust data and the subjective interpretations of field ecologists. Consequently, constraints may be imposed with no transparent methodology behind them to the frustration of, and occasionally large expense to, developers. Additionally, protected species numbers continue to decline and biodiversity continues to be threatened. This paper describes a GIS conceptual model for assessing ecological disturbance vulnerability, based upon a case study development in Scotland. First, uncertainties in traditional methods of recording and representing ecological features with GIS are reviewed such that they may be better accounted for in the disturbance model. Second, by incorporating temporal fluctuations in ecological behaviour into the disturbance susceptibility concept, it is argued that it is possible to synchronise development with conservation requirements. Finally, a method is presented to account for disturbance tolerances at the scale of the individual animal. It is anticipated that this model will enable environmental impact assessors to produce more robust analyses of wildlife disturbance risk and facilitate synchronisation between development and wildlife vulnerability to minimise disturbance and better avoid delays to the works programme

International Studies of Prenatal Exposure to Polycyclic Aromatic Hydrocarbons and Fetal Growth

OBJECTIVES: Polycyclic aromatic hydrocarbons (PAHs) are ubiquitously distributed human mutagens and carcinogens. However, lack of adequate air monitoring data has limited understanding of the effects of airborne PAHs on fetal growth. To address this gap in knowledge, we examined the association between prenatal exposure to airborne PAHs and birth weight, birth length, and birth head circumference, respectively, in Krakow, Poland, and New York City (NYC). METHODS: The parallel prospective cohort studies enrolled nonsmoking, healthy, and nonoccupationally exposed women and their newborns. Personal air monitoring of pregnant women was conducted over 48 hr. To control for maternal environmental tobacco smoke (ETS) exposure, we excluded those with umbilical cord plasma cotinine concentrations > 25 ng/mL. Mean cord plasma cotinine concentrations in both ethnic groups were ≤ 0.5 ng/mL. RESULTS: Prenatal PAH exposure was 10-fold higher in Krakow than in NYC. Prenatal PAH exposure was associated with significantly reduced birth weight in both Krakow Caucasians (p < 0.01) and in NYC African Americans (p < 0.01), controlling for known and potential confounders, but not in NYC Dominicans. Within the lower exposure range common to the two cities (1.80–36.47 ng/m(3)), the effect per unit PAH exposure on birth weight was 6-fold greater for NYC African Americans than for Krakow Caucasians (p = 0.01). CONCLUSIONS: These results confirm the adverse reproductive effect of relatively low PAH concentrations in two populations and suggest increased susceptibility of NYC African Americans. Fetal growth impairment has been linked to child developmental and health problems. Thus, substantial health benefits would result from global reduction of PAH emissions

Assessment of Benzo(a)pyrene-equivalent Carcinogenicity and Mutagenicity of Residential Indoor versus Outdoor Polycyclic Aromatic Hydrocarbons Exposing Young Children in New York City

The application of benzo(a)pyrene (BaP)-toxic equivalent factor to polycyclic aromatic hydrocarbons (PAH) concentrations can provide a more accurate risk assessment from environmental exposure to PAH. We hypothesized that BaP-equivalent toxicity determined following residential air monitoring among young urban children may vary by season. Residential indoor and outdoor air levels of PAH measured over two-weeks in a cohort of 5–6 year old children (n = 260) in New York City were normalized to the cancer and mutagen potency equivalent factor of BaP (BaP = 1). Data are presented as carcinogenic equivalents (BaP-TEQ) and mutagenic equivalents (BaP-MEQ) for the sum of 8 PAH (∑8PAH; MW ³ 228) and individual PAH and compared across heating versus nonheating seasons. Results show that heating compared to nonheating season was associated significantly with higher (BaP-TEQ)∑8PAH and (BaP-MEQ)∑8PAH both indoors and outdoors (p less than 0.001). Outdoor (BaP-TEQ)∑8PAH and (BaP-MEQ)∑8PAH were significantly higher than the corresponding indoor measures during the heating season (p less than 0.01). These findings suggest that at levels encountered in New York City air, especially during the heating season, residential exposure to PAH may pose an increased risk of cancer and mutation

Resolving the Broccoli Problem: Identifying Optimal Computational Algorithms for the Accuracy Assessment of Tree Delineations from Remotely-sensed Data

For many different investigative purposes, trees and forests are aerially scanned using light detection and ranging (LiDAR). Often, this also requires the manual measurement of ground reference (GR) plots within the LiDAR scan. Upon analysis, there is regularly a mismatch between the alignment of GR and LiDAR tree locations, crown areas and tree heights. This anomaly is frequently overlooked and under-reported in the current literature. This study investigates the suitability of match pairing algorithms for the quantification of misalignment errors between two datasets representing GR and LiDAR data, and recommends an algorithm for accurately quantifying match-pairing differences