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Aim: We describe the epidemiology of a community outbreak of Meningococcal C disease in Northland in 2011, and national trends in serogroup C disease in New Zealand., Methods: Notification data from EpiSurv for all meningococcal C cases were analysed for 2011 for Northland and for the period 2001-2011 nationally., Results: In 2011, the rate of group C meningococcal disease for the population in the Whangarei district aged less than 20 years was 27.6 cases per 100,000 population (6 cases) compared with 17.6 cases per 100,000 population under 20 years (8 cases) in the Northland District Health Board (DHB). All except one case were under 20 years of age. The case fatality rate was 33%. Nationally the rate of meningococcal C disease has fluctuated over the last decade, with an increasing trend apparent since 2007. There has been a noticeable increase over the last 3 years of group C cases infected with the C:P1.5-1,10-8 strain (including all of the Northland cases). This strain has also been associated with a higher case fatality rate (16% in the period 2007-2011)., Conclusion: Meningococcal C disease in New Zealand, although still less common than group B, is poorly understood. The relationships between carriage, invasive disease and community outbreaks deserve greater study. Active monitoring of surveillance data is warranted to ensure timely funded introduction of the highly effective meningococcal C conjugate vaccine on to the national immunisation schedule when appropriate, given increasing disease rates, the high case fatality rate and significant Maori non-Maori inequities in disease incidence.

Object: Fluorescence imaging has the potential to significantly improve neurosurgical resection of oncologic lesions through improved differentiation between normal and cancerous tissue at the tumor margins. In order to successfully mark glioma tissue a fluorescent tracer must have the ability to penetrate through the blood brain barrier (BBB) and provide delineation in the tumor periphery where heterogeneously intact BBB may exist. In this study it was hypothesized that, due to its smaller size, fluorescently labeled anti-EGFR Affibody protein (∼7 kDa) would provide a more clear delineation of the tumor margin than would fluorescently labeled cetuximab, a full antibody (∼150 kDa) to the epidermal growth factor receptor (EGFR)., Methods: Cetuximab and anti-EGFR targeted Affibody were conjugated to two different fluorescent dyes (both emitting in the near-infrared) and injected intravenously into 6 athymic mice which were inoculated orthotopically with green fluorescent protein (GFP) expressing human U251 glioma cells. Each mouse was sacrificed at 1-h post injection, at which time brains were removed, snap frozen, sectioned and quantitatively analyzed for fluorescence distribution., Results: Ex vivo analysis showed on average, nearly equal concentrations of cetuximab and Affibody within the tumor (on average Affibody made up 49±6% of injected protein), however, the cetuximab was more confined to the center of the tumor with Affibody showing significantly higher concentrations at the tumor periphery (on average Affibody made up 72±15% of injected protein in the outer 50 um of the tumor). Further ex vivo analysis of detection studies showed that the Affibody provided superior discrimination for differentiation of tumor from surrounding normal brain., Conclusions: The present study indicates that fluorescently labeled anti-EGFR Affibody can provide significantly better delineation of tumor margins than a fluorescently labeled anti-EGFR antibody and shows considerable potential for guiding margin detection during neurosurgery.

A cluster of salmonellosis cases caused by Salmonella Typhimurium phage type 42 (STM42) emerged in New Zealand in October 2008. STM42 isolates from a wheat-based poultry feed raw material (broll; i.e., product containing wheat flour and particles of grain) had been identified in the 2 months prior to this cluster. Initial investigations indicated that eating uncooked baking mixture was associated with illness. A case-control study was conducted to test the hypothesis that there was an association between STM42 cases and consumption of raw flour or other baking ingredients. Salmonella isolates from human and non-human sources were compared using pulsed-field gel electrophoresis (PFGE) and multiple-locus variable number tandem repeat analysis (MLVA). Environmental investigations included testing flour and other baking ingredients from case homes, unopened bags of flour purchased from retail stores, and inspection of an implicated flour mill. A case-control study of 39 cases and 66 controls found cases had 4.5 times the odds of consuming uncooked baking mixture as controls (95% confidence interval [CI] 1.6-12.5, p-value 0.001). Examination of individual baking ingredients found that, after adjusting for eggs, flour had an odds ratio (OR) of 5.7 (95% CI 1.1-29.1, p-value 0.035). After adjusting for flour, eggs had an OR of 0.8 (95% CI 0.2-3.4, p-value 0.762). PFGE patterns were identical for all STM42 isolates tested; however, MLVA distinguished isolates that were epidemiologically linked to the cluster. STM42 was recovered from flour taken from four cases' homes, two unopened packs purchased from retail stores and packs from three batches of retrieved (recalled) product. This outbreak was associated with the consumption of uncooked baking mixture containing flour contaminated with STM42. The implicated flour mill initiated a voluntary withdrawal from sale of all batches of flour thought to be contaminated. Media releases informed the public about implicated flour brands and the risks of consuming uncooked baking mixture.

Biomarkers of organochlorine pesticides were measured in both venous and umbilical cord blood from 35 pregnant Hispanic women living in Brownsville, Texas, USA. Gas chromatography with an electron capture detector was used to analyze specimens for 30 individual pesticides or their metabolites. Results indicate that blood concentrations were relatively low for most individual compounds, but that high-end (upper 10th percentile) values for total DDT were comparatively high. Although health effects associated with measured blood concentrations are uncertain, there is concern that fetal exposure to low levels of these OC compounds, either individually or in combination, might contribute to subsequent health problems, including neurodevelopmental effects, cancer, endocrine disruption, obesity and diabetes.

Biomarkers of polychlorinated biphenyls (PCB) were measured in both maternal and umbilical cord blood from 35 pregnant Hispanic women living in Brownsville, TX. Gas chromatography with an electron capture detector (GC/ECD) was used to analyze for 22 PCB analytes. Results indicated that both pregnant mothers and their fetuses were exposed to a variety of PCB at relatively low levels (≤ 0.2 ng/ml), and that concentrations in maternal and cord blood were similar. Concentrations of total PCB (sum or all PCB congeners) averaged more than 2.5 ng/ml, with highest values exceeding 3 ng/ml. Although health implications are uncertain, reports in the literature of PCB-related health effects raise concerns about possible future health consequences, especially obesity and diabetes, in this potentially vulnerable population.

Context: Exposure to ambient particulate air pollution is associated with increased cardiovascular and respiratory morbidity and mortality. It is necessary to understand causal pathways driving the observed health effects, particularly if they are differentially associated with particle size., Objectives: To investigate the effect of different size ranges of ambient particulate matter (PM) on gene and protein expression in an in vitro model., Materials and Methods: Normal human tracheobronchial epithelium (NHTBE) three-dimensional cell constructs were exposed for 24 h to washed ambient PM of different sizes (size 1: 7-615 nm; size 2: 616 nm-2.39 µm; size 3: 2.4-10 µm) collected from a residential street. A human stress and toxicity PCR array was used to investigate gene expression and iTRAQ was used to perform quantitative proteomics., Results: Eighteen different genes of the 84 on the PCR array were significantly dysregulated. Treatment with size 2 PM resulted in the greatest number of genes with altered expression, followed by size 1 and lastly size 3. ITRAQ identified 317 proteins, revealing 20 that were differentially expressed. Enrichment for gene ontology classification revealed potential changes to various pathways., Discussion and Conclusions: Different size fractions of ambient PM are associated with dysregulatory effects on the cellular proteome and on stress and toxicity genes of NHTBE cells. This approach not only provides an investigative tool to identify possible causal pathways but also permits the relationship between particle size and responses to be explored.

Purpose: Cellular receptor targeted imaging agents present the potential to target extracellular molecular expression in cancerous lesions; however, the image contrast in vivo does not reflect the magnitude of overexpression expected from in vitro data. Here, the in vivo delivery and binding kinetics of epidermal growth factor receptor (EGFR) was determined for normal pancreas and AsPC-1 orthotopic pancreatic tumors known to overexpress EGFR., Procedures: EGFR in orthotopic xenograft AsPC-1 tumors was targeted with epidermal growth factor (EGF) conjugated with IRDye800CW. The transfer rate constants (k(e), K₁₂, k₂₁, k₂₃, and k₃₂) associated with a three-compartment model describing the vascular delivery, leakage rate and binding of targeted agents were determined experimentally. The plasma excretion rate, k (e), was determined from extracted blood plasma samples. K₁₂, k₂₁, and k₃₂ were determined from ex vivo tissue washing studies at time points ≥ 24 h. The measured in vivo uptake of IRDye800CW-EGF and a non-targeted tracer dye, IRDye700DX-carboxylate, injected simultaneously was used to determined k₂₃., Results: The vascular exchange of IRDye800CW-EGF in the orthotopic tumor (K₁₂ and k₂₁) was higher than in the AsPC-1 tumor as compared to normal pancreas, suggesting that more targeted agent can be taken up in tumor tissue. However, the cellular associated (binding) rate constant (k₂₃) was slightly lower for AsPC-1 pancreatic tumor (4.1 × 10(-4) s(-1)) than the normal pancreas (5.5 × 10(-4) s(-1)), implying that less binding is occurring., Conclusions: Higher vascular delivery but low cellular association in the AsPC-1 tumor compared to the normal pancreas may be indicative of low receptor density due to low cellular content. This attribute of the AsPC-1 tumor may indicate one contributing cause of the difficulty in treating pancreatic tumors with cellular targeted agents.

The purpose of this study is to apply the Human Security Index (HSI) as a tool to detect social and economic cumulative risk burden at a county-level in the state of Texas. The HSI is an index comprising a network of three sub-components or "fabrics"; the Economic, Environmental, and Social Fabrics. We hypothesized that the HSI will be a useful instrument for identifying and analyzing socioeconomic conditions that contribute to cumulative risk burden in vulnerable counties. We expected to identify statistical associations between cumulative risk burden and (a) ethnic concentration and (b) geographic proximity to the Texas-Mexico border. Findings from this study indicate that the Texas-Mexico border region did not have consistently higher total or individual fabric scores as would be suggested by the high disease burden and low income in this region. While the Economic, Environmental, Social Fabrics (including the Health subfabric) were highly associated with Hispanic ethnic concentration, the overall HSI and the Crime subfabric were not. In addition, the Education, Health and Crime subfabrics were associated with African American racial composition, while Environment, Economic and Social Fabrics were not. Application of the HSI to Texas counties provides a fuller and more nuanced understanding of socioeconomic and environmental conditions, and increases awareness of the role played by environmental, economic, and social factors in observed health disparities by race/ethnicity and geographic region.

The purpose of this study is to determine whether Hispanic ethnic concentration is associated with a higher prevalence of obesity and, if this relationship exists, whether it is affected by the socioeconomic environment. The study uses the Texas Behavioral Risk Factor Surveillance System (BRFSS) linked to 2000 census data to access the relationship between prevalence of obesity, Hispanic ethnic concentration, poverty and level of education at a county-level. The findings suggest that the association of Hispanic ethnic concentration and obesity varies by socioeconomic environment. Although little influence was observed for % poverty, the relationship between Hispanic ethnic concentration and obesity differed by county-level educational attainment. High proportion of residents with a bachelor's degree is associated with a low prevalence of obesity; counties with both high % Hispanic and high % with Bachelor's degrees had the lowest prevalence of obesity. Our results suggest that promoting and improving education, perhaps including training on healthful living, may serve as an effective means of curbing current obesity trends and associated health problems in Hispanic and possibly other ethnic communities.

Systematic evaluation of cumulative health risks from the combined effects of multiple environmental stressors is becoming a vital component of risk-based decisions aimed at protecting human populations and communities. This article briefly examines the historical development of cumulative risk assessment as an analytical tool, and discusses current approaches for evaluating cumulative health effects from exposure to both chemical mixtures and combinations of chemical and nonchemical stressors. A comparison of stressor-based and effects-based assessment methods is presented, and the potential value of focusing on viable risk management options to limit the scope of cumulative evaluations is discussed. The ultimate goal of cumulative risk assessment is to provide answers to decision-relevant questions based on organized scientific analysis; even if the answers, at least for the time being, are inexact and uncertain.

Longitudinal measurements of biomarkers for metals, phthalates, environmental tobacco smoke, organochlorine and organophosphate pesticides, polychlorinated biphenyls, and volatile organic compounds were made in blood and/or urine from a stratified, random sample of more than 100 elementary school-aged children living in an inner-city section of Minneapolis. Repeated measures of 31 exposure biomarkers indicate that between-child variance (B-CV) was greater than within-child variance (W-CV) for 8 compounds, B-CV was a significant proportion of total variance for 9 compounds, and variances were homogeneous for 14 compounds. Among siblings living in the same household, positive correlations were observed for biomarker concentrations of polychlorinated biphenyls, organochlorine pesticides, metals, and volatile organic chemicals in blood, and total cotinine in urine. Biologic markers confirm that children from a low-income, ethnically diverse neighborhood experienced concurrent exposure to a variety of hazardous environmental chemicals during their everyday activities. Future monitoring studies should examine the nature and magnitude of children's cumulative exposure to both chemical and non-chemical stressors, especially in disadvantaged populations.

Objective: The objectives of the study were to detect high-risk areas and to examine how racial and ethnic status affect the geographic distribution of female breast cancer mortality in Texas. Analyses were based on county-level data for the years from 2000 to 2008., Materials and Methods: Breast cancer mortality data were obtained from the Texas Cancer Registry, and the Spatial Scan Statistics method was used to run Purely Spatial Analyses using the Discrete Poisson, Bernoulli, and Multinomial models., Results and Conclusions: Highest rates of female breast cancer mortality in Texas have shifted over time from southeastern areas towards northern and eastern areas, and breast cancer mortality at the county level is distributed heterogeneously based on racial/ethnic status. Non-Hispanic blacks were at highest risk in the northeastern region and lowest risk in the southern region, while Hispanics were at highest risk in the southern region along the border with Mexico and lowest risk in the northeastern region.

In the absence of scientific consensus on an appropriate theoretical framework, cumulative risk assessment and related research have relied on speculative conceptual models. We argue for the importance of theoretical backing for such models and discuss 3 relevant theoretical frameworks, each supporting a distinctive "family" of models. Social determinant models postulate that unequal health outcomes are caused by structural inequalities; health disparity models envision social and contextual factors acting through individual behaviors and biological mechanisms; and multiple stressor models incorporate environmental agents, emphasizing the intermediary role of these and other stressors. The conclusion is that more careful reliance on established frameworks will lead directly to improvements in characterizing cumulative risk burdens and accounting for disproportionate adverse health effects.

Cumulative risk assessment is a science policy tool for organizing and analyzing information to examine, characterize, and possibly quantify combined threats from multiple environmental stressors. We briefly survey the state of the art regarding cumulative risk assessment, emphasizing challenges and complexities of moving beyond the current focus on chemical mixtures to incorporate nonchemical stressors, such as poverty and discrimination, into the assessment paradigm. Theoretical frameworks for integrating nonchemical stressors into cumulative risk assessments are discussed, the impact of geospatial issues on interpreting results of statistical analyses is described, and four assessment methods are used to illustrate the diversity of current approaches. Prospects for future progress depend on adequate research support as well as development and verification of appropriate analytic frameworks.

Historically, it has been challenging to go beyond epidemiology to investigate the pathogenic changes caused by tobacco smoking. The EpiAirway-100 (MatTek Corp., Ashland, MA) was employed to investigate the effects of cigarette smoke components. Exposure at the air-liquid-interface represented particle and vapour phase components of cigarette smoke. A proteomic study utilising iTRAQ labelling compared expression profiles. The correlative histopathology revealed focal regions of hyperplasia, hypertrophy, cytolysis and necrosis. We identified 466 proteins, 250 with a parameter of two or more peptides. Four of these proteins are potential markers of lung injury and three are related to mechanistic pathways of disease.

Endocrine therapy in patients with breast cancer can be limited by the problem of resistance. Preclinical studies suggest that complete blockade of the estrogen receptor (ER) combined with inhibition of the epidermal growth factor receptor can overcome endocrine resistance. We tested this hypothesis in a phase II neoadjuvant trial of anastrozole and fulvestrant combined with gefitinib in postmenopausal women with newly diagnosed ER-positive breast cancer. After a baseline tumor core biopsy, patients were randomized to receive anastrozole and fulvestrant or anastrozole, fulvestrant, and gefitinib (AFG) for 3 weeks. After a second biopsy at 3 weeks, all patients received AFG for 4 months and surgery was done if the tumor was operable. The primary endpoint was best clinical response by RECIST criteria and secondary endpoints were toxicity and change in biomarkers. The study closed after 15 patients were enrolled because of slow accrual. Median patient age was 67 years and median clinical tumor size was 7 cm. Four patients had metastatic disease present. Three patients withdrew before response was assessed. In the remaining 12 patients, there were two complete clinical responses (17%), three partial responses (25%), five had stable disease (41%), and two (17%) had progressive disease. Most common adverse events were rash in four patients, diarrhea in four, joint symptoms in three, and abnormal liver function tests in three. There were no grade 4 toxicities and all toxicities were reversible. At 3 weeks, cell proliferation as measured by Ki-67 was significantly reduced in the AFG group (P value = 0.01), with a parallel reduction in the expression of the Cyclin D1 (P value = 0.02). RNA microarray data showed a corresponding decrease in the expression of cell cycle genes. These results suggest that AFG was an effective neoadjuvant therapy and consistently reduced proliferation in ER-positive tumors.

Venous blood was drawn from 35 pregnant Hispanic women living in Brownsville, Texas, and matched cord blood was collected at birth. Gas chromatography/mass spectrometry was used to measure concentrations of 55 individual PAHs or groups of PAHs. Results indicate that these women and their fetuses were regularly exposed to multiple PAHs at comparatively low concentrations, with levels in cord blood generally exceeding levels in paired maternal blood. While the possibility of related adverse effects on the fetus is uncertain, these exposures in combination with socioeconomically-disadvantaged and environmentally-challenging living conditions raise legitimate public health concerns.

1,3-Butadiene (BD) is a common environmental contaminant classified as "carcinogenic to humans." Formation of BD-induced DNA adducts plays a major role in its carcinogenicity. BD is also an epigenotoxic agent (i.e., it affects DNA and histone methylation in the liver). We used a panel of genetically diverse inbred mice (NOD/LtJ, CAST/EiJ, A/J, WSB/EiJ, PWK/PhJ, C57BL/6J, and 129S1/SvImJ) to assess whether BD-induced genotoxic and epigenotoxic events may be subject to interstrain differences. Mice (male, 7 weeks) were exposed via inhalation to 0 or 625 ppm BD for 6 h/day and 5 days/week for 2 weeks and liver BD-DNA adducts, epigenetic alterations, and liver toxicity were assessed. N-7-(2,3,4-trihydroxybut-1-yl)-guanine adducts were detected in all strains after exposure, yet BD-induced DNA damage in CAST/EiJ mice was two to three times lower. Epigenetic effects of BD were most prominent in C57BL/6J mice where loss of global DNA methylation and loss of trimethylation of histone H3 lysine 9, histone H3 lysine 27, and histone H4 lysine 20, accompanied by dysregulation of liver gene expression indicative of hepatotoxicity, were found. Interestingly, we observed an increase in histone methylation in the absence of changes in gene expression and DNA methylation in CAST/EiJ strain. We hypothesized that mitigated genotoxicity of BD in CAST/EiJ mice may be due to chromatin condensation. Indeed, we show that in response to BD exposure, chromatin condensation occurs in CAST/EiJ, whereas the opposite effect is observed in C57BL/6J mice. These findings demonstrate that interstrain susceptibility to genotoxicity by a well-known environmental carcinogen may be due to strain-specific epigenetic events in response to the exposure.

Marking human saphenous vein graft (HSV) with a surgical skin marker to prevent twisting on implantation is a common practice in peripheral and coronary artery bypass procedures. This study is designed to examine the effects of surgical skin markers on the HSV smooth muscle and endothelial functional responses. De-identified HSV remnants were collected during peripheral and coronary artery bypass procedures. Physiologic responses of the HSV were measured using a muscle bath. Veins that were marked with surgical skin markers intraoperatively generated significantly less contractile force to depolarizing KCl (110 mM) and receptor-mediated contractile agonists than unmarked HSV, suggesting that surgical skin markers impaired HSV smooth muscle contractility. To directly access the effects of chemical components in the surgical skin markers, unmarked HSV was exposed to isopropyl alcohol (a solvent commonly used in surgical skin markers) or methylene blue (a dye). Smooth muscle contractility was significantly reduced by isopropyl alcohol and methylene blue. Endothelial-dependent relaxation to carbachol was significantly reduced after exposure to surgical skin markers. Our data demonstrated that marking HSV with surgical skin markers reduces smooth muscle and endothelial functional viability.

Background: 1,3-Butadiene (BD) is a high-volume industrial chemical and a known human carcinogen. The main mode of BD carcinogenicity is thought to involve formation of genotoxic epoxides., Objectives: In this study we tested the hypothesis that BD may be epigenotoxic (i.e., cause changes in DNA and histone methylation) and explored the possible molecular mechanisms for the epigenetic changes., Methods and Results: We administered BD (6.25 and 625 ppm) to C57BL/6J male mice by inhalation for 2 weeks (6 hr/day, 5 days a week) and then examined liver tissue from these mice for signs of toxicity using histopathology and gene expression analyses. We observed no changes in mice exposed to 6.25 ppm BD, but glycogen depletion and dysregulation of hepatotoxicity biomarker genes were observed in mice exposed to 625 ppm BD. We detected N-7-(2,3,4-trihydroxybut-1-yl)guanine (THB-Gua) adducts in liver DNA of exposed mice in a dose-responsive manner, and also observed extensive alterations in the cellular epigenome in the liver, including demethylation of global DNA and repetitive elements and a decrease in histone H3 and H4 lysine methylation. In addition, we observed down-regulation of DNA methyltransferase 1 (Dnmt1) and suppressor of variegation 3-9 homolog 1, a histone lysine methyltransferase (Suv39h1), and up-regulation of the histone demethylase Jumonji domain 2 (Jmjd2a), proteins responsible for the accurate maintenance of the epigenetic marks. Although the epigenetic effects were most pronounced in the 625-ppm exposure group, some effects were evident in mice exposed to 6.25 ppm BD., Conclusions: This study demonstrates that exposure to BD leads to epigenetic alterations in the liver, which may be important contributors to the mode of BD carcinogenicity.

Daily activity levels were investigated as related to sleep quality in young adult college students aged 18 to 30 years. 85 participants (20 men, 65 women) completed the Young Adult Daily Activity Scale (YADAS). This 37-item checklist has 34 items based on focus group discussion points of college students' typical daily activities and three blank items for students to include their daily activities if not in the listing. The tabulation of type and amount of waking daily activities represents a unique measurement of factors that may affect sleep quality. The participants also rated their typical sleep quality using a standard 5-point scale (low indicating poor sleep). Correlations of sleep ratings and activities were not significant.

Concern is mounting that children from disadvantaged, low-income neighborhoods are likely to be both more exposed to chemical hazards and more susceptible to related adverse health effects. This article reports measurements of >75 individual biomarkers spanning 7 chemical/pollutant classes in blood and urine from more than 100 children living in a socioeconomically disadvantaged and ethnically diverse area of south Minneapolis, MN. Results indicate that a significant proportion of children in the study were at the high end of the exposure distribution compared to national reference ranges for a variety of environmental chemicals and/or their metabolites, including phthalates, organochlorine pesticides, organophosphate pesticides, metals, polychlorinated biphenyls, and volatile organic compounds. In addition, levels of cotinine in urine indicate that more than half the children were regularly exposed to environmental tobacco smoke, with the upper 10th percentile exposed to relatively high concentrations.

This study quantifies the national burden of disease attributed to particulate matter (PM) and ozone (O(3)) in ambient air in the United Arab Emirates (UAE), a rapidly growing nation in which economic development and climatic conditions pose important challenges for air quality management. Estimates of population exposure to these air pollutants are based on observed air quality data from fixed-site monitoring stations. We divide the UAE into small grid cells and use spatial-statistical methods to estimate the ambient pollutant concentrations in each cell based on the observed data. Premature deaths attributed to PM and O(3) are computed for each grid cell and then aggregated across grid cells and over a year to estimate the total number of excess deaths attributable to ambient air pollution. Our best estimate is that approximately 545 (95% CI: 132-1224) excess deaths in the UAE in the year 2007 are attributable to PM in ambient air. These excess deaths represent approximately 7% (95% CI: 2-17%) of the total deaths that year. We attribute approximately 62 premature deaths (95% CI: 17-127) to ground-level O(3) for the year 2007. Uncertainty in the natural background level of PM, due to the frequent dust storms occurring in the region, has significant impacts on the attributed mortality estimates. Despite the uncertainties associated with the integrated assessment framework, we conclude that anthropogenic ambient air pollution, in particular PM, causes a considerable public health impact in the UAE in terms of premature deaths. We discuss important uncertainties and scientific hypotheses to be investigated in future work that might help reduce the uncertainties in the burden of disease estimates., (Copyright © 2010 Elsevier B.V. All rights reserved.)

There is strong presumptive evidence that people living in poverty and certain racial and ethnic groups bear a disproportionate burden of environmental health risk. Many have argued that conducting formal assessments of the health risk experienced by affected communities is both unnecessary and counterproductive-that instead of analyzing the situation our efforts should be devoted to fixing obvious problems and rectifying observable wrongs. We contend that formal assessment of cumulative health risks from combined effects of chemical and nonchemical stressors is a valuable tool to aid decision makers in choosing risk management options that are effective, efficient, and equitable. If used properly, cumulative risk assessment need not impair decision makers' discretion, nor should it be used as an excuse for doing nothing in the face of evident harm. Good policy decisions require more than good intentions; they necessitate analysis of risk-related information along with careful consideration of economic issues, ethical and moral principles, legal precedents, political realities, cultural beliefs, societal values, and bureaucratic impediments. Cumulative risk assessment can provide a systematic and impartial means for informing policy decisions about environmental justice.

A novel nonsteroidal androgen receptor antagonist, (R)-4-(1-benzyl-4,4-dimethyl-2-oxopyrrolidin-3-yloxy)-2-(trifluoromethyl)benzonitrile (1), for the topical control of sebum production is reported. This compound, which is potent, selective, and efficacious in the clinically validated golden Syrian hamster ear animal model, was designed to be delivered to the pilosebaceous unit, the site of action, preferentially by the follicular route.

TNF-like protein 1A (TL1A), a TNF superfamily cytokine that binds to death receptor 3 (DR3), is highly expressed in macrophage foam cell-rich regions of atherosclerotic plaques, although its role in foam cell formation has yet to be elucidated. We investigated whether TL1A can directly stimulate macrophage foam cell formation in both THP-1 and primary human monocyte-derived macrophages with the underlying mechanisms involved. We demonstrated that TL1A promotes foam cell formation in human macrophages in vitro by increasing both acetylated and oxidized low-density lipoprotein uptake, by enhancing intracellular total and esterified cholesterol levels and reducing cholesterol efflux. This imbalance in cholesterol homeostasis is orchestrated by TL1A-mediated changes in the mRNA and protein expression of several genes implicated in the uptake and efflux of cholesterol, such as scavenger receptor A and ATP-binding cassette transporter A1. Furthermore, through the use of virally delivered DR3 short-hairpin RNA and bone marrow-derived macrophages from DR3 knockout mice, we demonstrate that DR3 can regulate foam cell formation and contributes significantly to the action of TL1A in this process in vitro. We show, for the first time, a novel proatherogenic role for both TL1A and DR3 that implicates this pathway as a target for the therapeutic intervention of atherosclerosis.

Urban air particulate matter (PM) has previously been associated with a variety of adverse health effects. It is now believed that the smallest particles, ultrafine or nanoparticles, are linked to the greatest health effects. The physicochemistry of these particles is likely to provide information regarding their toxicity. Therefore, the aim of this study was to further the understanding of the heterogeneous and changing particle concentrations in urban air, in conjunction with gaining an understanding of the physicochemistry of the particles. A Dekati electrical low-pressure impactor was used to collect the particles and real-time data in a busy traffic corridor in Swansea, Wales, over a period of 10 nonconsecutive weeks. Particle concentrations in the street canyon were analyzed and particle physicochemistries investigated using a variety of techniques. Particle number concentrations were found to vary both diurnally and from day to day in the traffic corridor. Of all particles, the nano to fine size fraction was consistently identified in the highest concentrations (maximum: 140,000 particles cm(-3)). Particle physicochemistry was found to vary as a function of size, with larger particles exhibiting a greater variety of morphologies (and consequently particle types) and associated metals.

Aim: To describe and quantify laboratory testing of faecal samples for enteric pathogens as a component of the reporting pyramid of acute gastrointestinal illness (AGI) in New Zealand., Method: Postal survey of community and hospital laboratories throughout New Zealand conducted in mid-2006, requesting data from the 2005 calendar year., Results: Of the 47 laboratories eligible for the survey, responses were received from 35 (74%, 16 hospital laboratories, 12 community laboratories, five hospital and community laboratories, and two Public Health Laboratories). Based on survey data and extrapolation it was estimated that approximately 250,000 faecal samples were received by New Zealand laboratories in 2005. The majority of these (77%) were requested by primary healthcare providers on people in the community. Routine testing of these samples would include bacteria (Salmonella, Shigella, Campylobacter, Yersinia) and parasites (Cryptosporidium, Giardia) and (depending principally on the age of the patient) rotavirus. Testing for other pathogens was comparatively infrequent. The frequency of detection of a pathogen in community samples was estimated as approximately 20%., Conclusion: The positivity rate of 20% for faecal samples from people in the community is consistent with overseas results. Although there was considerable variation in the testing methods employed by the laboratories the methods were considered appropriate based on consultation with ESR Public Health and Reference Laboratory staff. These data on the number and type of samples, and positivity rate , will assist in the determination of a reporting pyramid for AGI in New Zealand.

Purpose: Previous gene expression profiling studies of breast cancer have focused on the entire genome to identify genes differentially expressed between estrogen receptor (ER) alpha-positive and ER-alpha-negative cancers., Experimental Design: Here, we used gene expression microarray profiling to identify a distinct kinase gene expression profile that identifies ER-negative breast tumors and subsets ER-negative breast tumors into four distinct subtypes., Results: Based on the types of kinases expressed in these clusters, we identify a cell cycle regulatory subset, a S6 kinase pathway cluster, an immunomodulatory kinase-expressing cluster, and a mitogen-activated protein kinase pathway cluster. Furthermore, we show that this specific kinase profile is validated using independent sets of human tumors and is also seen in a panel of breast cancer cell lines. Kinase expression knockdown studies show that many of these kinases are essential for the growth of ER-negative, but not ER-positive, breast cancer cell lines. Finally, survival analysis of patients with breast cancer shows that the S6 kinase pathway signature subtype of ER-negative cancers confers an extremely poor prognosis, whereas patients whose tumors express high levels of immunomodulatory kinases have a significantly better prognosis., Conclusions: This study identifies a list of kinases that are prognostic and may serve as druggable targets for the treatment of ER-negative breast cancer.

Pulmonary fibrosis is a debilitating disease affecting up to 2 million people worldwide, with a median survival rate of only 3 years after diagnosis. The aim of this study was to evaluate a potential protein biomarker (Cocoacrisp, CC) to identify the onset of pulmonary fibrosis. A model of fibrosis was induced via intratracheal instillation of bleomycin, and samples were collected during the early phase of the disease. Immunohistochemical identification of CC was carried out in lung tissue from the bleomycin model. Quantification by image analysis showed CC levels were doubled (p <0.0003), after a single bleomycin dose, but not after double instillation. Microscopic analysis revealed that CC signal was primarily detected on the alveolar surface. The secretion of the novel protein CC during the early stages of bleomycin-induced injury may have the potential to be utilized as a clinical biomarker for the early stages of fibrosis, particularly as it may be detectable in bronchoalveolar lavage fluid.

The risk of Henoch-Schönlein purpura (HSP) following vaccination with a group B meningococcal vaccine was assessed through active hospital safety monitoring. There was no increase in the relative incidence of HSP within 30 days after vaccination nor recurrence in HSP cases who received one or more further vaccine doses (re-challenge).

Background: Associations between smoking and the development of tobacco-related diseases in humans have historically been assessed by epidemiological studies. These studies are further complicated by the number of chemicals used in tobacco and individual smoking habits. An alternative approach is required to assess the biological responses., Objective: Toxicogenomics was carried out to identify early molecular markers for events in pulmonary injury resulting from tobacco smoke components (TSC) exposure., Materials and Methods: EpiAirway-100 cells were exposed at the air/liquid interface to representative particle (nicotine; cadmium) and vapour phase [formaldehyde (FA) and ethyl carbamate] components of cigarette smoke. Microarray technology was used to compare expression profiles of human genes associated with toxicity and drug resistance, from control and TSC-treated respiratory epithelium (n=5/dose)., Results: Using the GEArray 'toxicology and drug resistance' microarray followed by significance analysis of microarray analysis, 42 mRNA transcripts were found to be significantly altered by the TSC exposure. The vapour [ethyl carbamate, FA and particle (nicotine, cadmium)] phase TSC exhibited differential transcriptional responses that could not be attributed to their chemical phase. The transcriptional changes could be classified according to a functional family, where ethyl carbamate, FA and cadmium classified as carcinogens, demonstrated the highest gene homology when compared with the noncarcinogen, nicotine., Discussion: Analysis of the microarray data and further confirmation (reverse transcriptase-PCR) identified three potential biomarkers for TSC-induced injury. These three genes (CYP7A1, HMOX1 and PTGS1) are highly upregulated and have been linked with mechanistic pathways of disease.

During the southern hemisphere winter of 2006 New Zealand experienced a significant increase in the number of reported cases of Campylobacter infection. In total, 112 Campylobacter isolates from eight district health boards (DHBs) located across New Zealand were submitted for PFGE, MLST and Penner serotyping analysis. Distinct clusters of Campylobacter isolates were identified, several of which were composed of isolates from up to five different DHBs located on both the North and South islands of New Zealand. One sequence type, ST-474, was identified in 32 of the 112 isolates and may represent an endemic sequence type present in New Zealand. The spatial pattern of genotypes, combined with the generalized increase in notifications throughout the country is consistent with a common source epidemic, most likely from a source contaminated with the dominant sequence types ST-474 and ST-190 and may also represent widely distributed stable clones present in New Zealand.

Air toxics are of particular concern in Greater Houston, home to one of the world's largest petrochemical complexes and a quarter ofthe nation's refining capacity. Much of this complex lies along a navigable ship channel that flows 50 miles from east of the central business district through Galveston Bay and into the Gulf of Mexico. Numerous communities, including both poor and affluent neighborhoods, are located in close proximity to the 200 facilities along this channel. Our aim is to examine the spatial distribution of cumulative, air-pollution-related cancer risks in Houston and Harris County, with particular emphasis on identifying ethnic, economic, and social disparities. We employ exposure estimates from NATA-1999 and census data to assess whether the cumulative cancer risks from air toxics in Houston (and Harris County) fall disproportionately on certain ethnicities and on the socially and economically disadvantaged. The cancer risk burden across Harris County census tracts increases with the proportion of residents who are Hispanic and with key indicators of relative social disadvantage. Aggregate disadvantage grows at each higher level of cancer risk. The highest cancer risk in Harris County is concentrated along a corridor flanking the ship channel. These high-risk neighborhoods, however, vary markedly in relative disadvantage, as well as in emission source mix. Much of the risk they face appears to be driven by only a few hazardous air pollutants. Results provide evidence of risk disparities from hazardous air pollution based on ethnicity and social disadvantage. At the highest levels of risk the pattern is more complex, arguing for a neighborhood level of analysis, especially when proximity to high-emissions industries is a substantial contributor to cumulative cancer risk.

Aim: To describe and investigate epidemic strain serogroup B meningococcal disease in recipients of the meningococcal vaccine, MeNZB., Method: Epidemic strain meningococcal disease cases in vaccine recipients were identified by matching disease notification and laboratory data against the National Immunisation Register. Descriptive analyses were undertaken for disease cases aged under 20 years and vaccine breakthrough cases (epidemic strain meningococcal disease cases with onset 28 or more days after receipt of the third MeNZB dose). Questionnaires were sent to hospital clinicians requesting medical histories and laboratory test results for vaccine breakthrough cases. A committee reviewed this information to assess immune competence in these cases., Results: From the start of the meningococcal B immunisation programme in July 2004 to the end of 2006, 34 vaccine breakthrough cases were identified. No underlying host factors were identified that explained disease occurrence for the 30 cases (88.2%) for whom questionnaires were completed. For 12 (35.3%) cases all requested laboratory tests to assess immune competence were performed and these subjects were judged to be immune competent., Conclusion: While epidemic strain meningococcal disease incidence has fallen dramatically with the introduction of the vaccine, these early results confirm the expectation that vaccine breakthrough cases will occur in immune competent individuals given the anticipated vaccine effectiveness of approximately 75%.

Previously, we had identified gene expression patterns that predicted response to neoadjuvant docetaxel. Other studies have validated that a high Recurrence Score (RS) by the 21-gene RT-PCR assay is predictive of worse prognosis but better response to chemotherapy. We investigated whether tumor expression of these 21 genes and other candidate genes can predict response to docetaxel. Core biopsies from 97 patients were obtained before treatment with neoadjuvant docetaxel (4 cycles, 100 mg/m2 q3 weeks). Three 10-microm FFPE sections were submitted for quantitative RT-PCR assays of 192 genes that were selected from our previous work and the literature. Of the 97 patients, 81 (84%) had sufficient invasive cancer, 80 (82%) had sufficient RNA for QRTPCR assay, and 72 (74%) had clinical response data. Mean age was 48.5 years, and the median tumor size was 6 cm. Clinical complete responses (CR) were observed in 12 (17%), partial responses in 41 (57%), stable disease in 17 (24%), and progressive disease in 2 patients (3%). A significant relationship (P<0.05) between gene expression and CR was observed for 14 genes, including CYBA. CR was associated with lower expression of the ER gene group and higher expression of the proliferation gene group from the 21 gene assay. Of note, CR was more likely with a high RS (P=0.008). We have established molecular profiles of sensitivity to docetaxel. RT-PCR technology provides a potential platform for a predictive test of docetaxel chemosensitivity using small amounts of routinely processed material.

One of the first lines of defence to inhaled toxins is the barrier formed by the tracheobronchial epithelium, making this the ideal region for studying the toxicity of inhaled substances. This study utilises a highly differentiated, three-dimensional, in vitro model of human upper respiratory tract epithelium (EpiAirway-100) to measure the acute toxicological responses to well-characterised tobacco smoke components. To determine the suitability of this model for screening inhaled toxicants, the EpiAirway tissue model (ETM) was treated apically with tobacco smoke components (nicotine, formaldehyde, cadmium, urethane) which are known to induce a variety of toxic effects (e.g. cytotoxic, thrombogenic, carcinogenic). A range of concentrations were used to model different mechanisms and severity of toxicity which were then compared to known in vivo responses. Similar trends in stress response occurred, with distinct alterations to the tissue in response to all four toxins. At high concentrations, cell viability decreased and tight junctions were degraded, but at sub-toxic concentrations epithelial resistance (indicating tissue integrity) increased 20-60% from control. This peak in resistance coincided with an increase in secreted protein levels, elevated cytokine release and goblet cell hyperplasia and hypertrophy. In conclusion, acute exposure to tobacco smoke components induces measurable toxic responses within human respiratory epithelium. Sub-toxic concentrations appear to illicit a protective response by increasing mucus secretion and mediating immune responses via cytokine release. These responses are comparable to human in vivo responses, indicating potential for the ETM as a tool for screening the toxicity of inhaled compounds.

Twenty-four hour average fine particle concentrations of 23 trace elements (TEs) were measured concurrently in (a) ambient air in three urban neighborhoods (Battle Creek-BCK; East St. Paul-ESP; and Phillips-PHI), (b) air inside residences of participants, and (c) personal air near the breathing zone of healthy, non-smoking adults. The outdoor (O), indoor (I), and personal (P) samples were collected in the Minneapolis/St. Paul metropolitan area over three seasons (Spring, Summer, Fall) using either the federal reference (O) or inertial impactor (I,P) inlets to collect PM(2.5). In addition to descriptive statistics, a hierarchical, mixed-effects statistical model was used to estimate the mutually adjusted effects of monitor location, community, and season on mean differences between monitoring locations while accounting for within-subject and within-monitoring period correlation. The relationships among P, I, and O concentrations varied across TEs. The O concentrations were usually higher than P or I for elements like Ca and Al that originate mainly from entrained crustal material, while P concentrations were often highest for other elements with non-crustal sources. Unadjusted mixed model results demonstrated that O monitors more frequently underestimated than overestimated P TE exposures for elements associated with non-crustal sources. This finding was true even though the O TE measurements were taken in the same neighborhoods as the P and I measurements. Further adjustment for community or season effects in the mixed models reduced the number of significant O-P and O-I differences compared to unadjusted models, but still indicated a tendency for underestimation of personal and indoor TE exposures by central site monitors, particularly in the PHI community. These results indicate that community and season are important covariates for developing long term TE exposure estimates, and that personal exposure to trace elements in PM(2.5) is likely to be underestimated by outdoor central site monitors.

1. The general term 'nanoparticle' (NP) is used to define any particle less than 100 nm in at least one dimension and NPs are generally classified as natural, anthropogenic or engineered in origin. Anthropogenic, also referred to as 'ultrafine' particles (UFPs), are predominately combustion derived and are characterized by having an equivalent spherical diameter less than 100 nm. 2. These particles, considered to be 'combustion-derived nanoparticles' (CDNPs), are of toxicological interest given their nanosized dimensions, with properties not displayed by their macroscopic counterparts. 3. The pulmonary deposition efficiency of inhaled UFPs, along with their large surface areas and bound transition metals, is considered important in driving the emerging health effects linked to respiratory toxicity. 4. The toxicology of CDNPs is currently used to predict the health outcomes in humans following exposure to manufactured NPs. Their similar physicochemistry would suggest similar adverse health effects (i.e. pulmonary (and perhaps cardiac) toxicity). As such, it is essential to fully understand CDNP nanotoxicology in order to minimize occupational and environmental exposure.

Background: Airborne emissions from numerous point, area, and mobile sources, along with stagnant meteorologic conditions, contribute to frequent episodes of elevated air pollution in Houston, Texas. To address this problem, decision makers must set priorities among thousands of individual air pollutants as they formulate effective and efficient mitigation strategies., Objectives: Our aim was to compare and rank relative health risks of 179 air pollutants in Houston using an evidence-based approach supplemented by the expert judgment of a panel of academic scientists., Methods: Annual-average ambient concentrations by census tract were estimated from the U.S. Environmental Protection Agency's National-scale Air Toxics Assessment and augmented with measured levels from the Houston monitoring network. Each substance was assigned to one of five risk categories (definite, probable, possible, unlikely, uncertain) based on how measured or monitored concentrations translated into comparative risk estimates. We used established unit risk estimates for carcinogens and/or chronic reference values for noncarcinogens to set thresholds for each category. Assignment to an initial risk category was adjusted, as necessary, based on expert judgment about the quality and quantity of information available., Results: Of the 179 substances examined, 12 (6.7%) were deemed definite risks, 9 (5.0%) probable risks, 24 (13.4%) possible risks, 16 (8.9%) unlikely risks, and 118 (65.9%) uncertain risks., Conclusions: Risk-based priority setting is an important step in the development of cost-effective solutions to Houston's air pollution problem.

New Zealand introduced a new outer membrane vesicle vaccine in 2004 to combat an epidemic of group B meningococcal disease. An Independent Safety Monitoring Board oversaw intensive safety monitoring, which included hospital surveillance, health professional reporting (passive and active) and mortality monitoring. With over three million doses administered to individuals aged under 20 years, the monitoring results provide consistent evidence supporting the vaccine's safety.

Background: Leptin is strongly associated with adiposity and few studies have investigated its role in Mexican-Americans. The aims of this study were to examine the association of serum leptin concentration with adiposity and body fat distribution in Mexican-Americans and to develop a predictive model of serum leptin concentration for this ethnic group., Methods: Three hundred fifty-two college students (242 women, 110 men; age 18-30 years) were evaluated in this cross-sectional study. Body fat content was assessed using bioelectrical impedance analysis. Correlation between serum leptin levels and several markers of adiposity and body fat distribution were examined in both men and women. Multiple regression analysis was performed to create the predictive model., Results: Women had higher serum leptin concentrations than men for the same levels of adiposity. After controlling for gender and body fat, only fat mass (FM) expressed in kg, was significantly correlated with serum leptin concentration in men (partial rho = 0.811, p <0.001), whereas body mass index (BMI), hip circumference (HC), and FM expressed in kg, were significantly correlated with serum leptin concentration in women (partial rho = 0.214, p <0.001; partial rho = 0.201, p <0.01; and partial rho = 0.818, p <0.001, respectively). Percent body fat (PBF) was the only significant predictor of serum leptin concentration among men, explaining 42% of the variance in serum leptin concentration. In addition to PBF, waist circumference (WC) and HC were significant predictors of serum leptin concentration among women explaining 65% of the variance in serum leptin concentration., Conclusions: Serum leptin concentration is a function of adiposity as determined by PBF in both Mexican-American men and women. HC and WC are associated with serum leptin concentration in Mexican-American women but not in men. BMI alone should not be used in evaluating the association of serum leptin concentration with body fatness in Mexican-Americans.

Cumulative risk refers to the combined threats from exposure via all relevant routes to multiple stressors including biological, chemical, physical, and psychosocial entities. Cumulative risk assessment is a tool for organizing and analyzing information to examine, characterize, and possibly quantify the combined adverse effects on human health or ecologic resources from multiple environmental stressors. The U.S. Environmental Protection Agency (EPA) has initiated a long-term effort to develop future guidelines for cumulative risk assessment, including publication in 2003 of a framework that describes important features of the process and discusses theoretical issues, technical matters, and key definitions. The framework divides the process of cumulative risk assessment into three interrelated phases: a) planning, scoping, and problem formulation; b) analysis; and c) interpretation and risk characterization. It also discusses the additional complexities introduced by attempts to analyze cumulative risks from multiple stressors and describes some of the theoretical approaches that can be used. The development of guidelines for cumulative risk assessment is an essential element in the transition of the U.S. EPA risk assessment methodology from a narrow focus on a single stressor, end point, source, pathway, and exposure route to a broader, more holistic approach involving analysis of combined effects of cumulative exposure to multiple stressors via all relevant sources, pathways, and routes.

Differential exposure to mixtures of environmental agents, including biological, chemical, physical, and psychosocial stressors, can contribute to increased vulnerability of human populations and ecologic systems. Cumulative risk assessment is a tool for organizing and analyzing information to evaluate the probability and seriousness of harmful effects caused by either simultaneous and/or sequential exposure to multiple environmental stressors. In this article we focus on elucidating key challenges that must be addressed to determine whether and to what degree differential exposure to environmental mixtures contributes to increased vulnerability of exposed populations. In particular, the emphasis is on examining three fundamental and interrelated questions that must be addressed as part of the process to assess cumulative risk: a) Which mixtures are most important from a public health perspective? and b) What is the nature (i.e., duration, frequency, timing) and magnitude (i.e., exposure concentration and dose) of relevant cumulative exposures for the population of interest? c) What is the mechanism (e.g., toxicokinetic or toxicodynamic) and consequence (e.g., additive, less than additive, more than additive) of the mixture's interactive effects on exposed populations? The focus is primarily on human health effects from chemical mixtures, and the goal is to reinforce the need for improved assessment of cumulative exposure and better understanding of the biological mechanisms that determine toxicologic interactions among mixture constituents.

This study examined the differences between nurses' (N = 3,337) scores on organizational support, workload, satisfaction, and intent to stay between Magnet, Magnet-aspiring, and non-Magnet hospitals. The study was conducted using the Individual Workload Perception Scale, a valid and reliable tool with 32 Likert scale items, with nurses from 11 states, 15 institutions, and 292 diverse units. Results indicate that nurses at Magnet hospitals had significantly better scores on all subscales. Furthermore, nurses from Magnet-aspiring hospitals had better scores than did nurses from non-Magnet facilities. Conclusions of the study indicate that the Magnet program is meeting its intended goal: to provide a professional practice environment for staff nurses. Nurse executives may consider using the Individual Workload Perception Scale as a way to assess their organization's culture as it relates to professional practice of the registered nurse.

An assessment study examining the relationship between sleep quality and personality style in individuals presenting to a sleep clinic with symptoms of insomnia was conducted. The protocol entailed standard clinical interviews conducted by a board certified sleep physician and licensed clinical psychologist. Participants were then assessed using a standard interview and the Millon Clinical Multi-axial Inventory III (MCMI-III) A follow-up appointment was conducted to provide interpretation and treatment recommendations from the interview and testing data. The results from a review of 210 cases are presented in terms of their sleep quality and dominant MCMI-III patterns. Preliminary multivariate analyses indicated two common profiles that correspond to the presentation of insomnia symptomology. These clusters were termed "avoidant" and "anxious" profiles, accordingly. Item content analyses were conducted via the Noteworthy Item classification in the MCMI-III manual to determine the viability of a category determined by the authors called Sleep Behavior Preoccupation. Of this sample 17% fit into the category.

Objective: Adjuvant chemotherapy in premenopausal women with breast cancer may induce amenorrhea, which can affect fertility, choice of hormonal therapy, and increase the risk of late toxicity. The incidence of chemotherapy-induced amenorrhea (CIA) resulting from doxorubicin and cyclophosphamide (AC) followed by a taxane (T) is poorly characterized., Methods: We retrospectively surveyed women who were premenopausal and less than age 50 at initiation of chemotherapy to determine the rates of CIA in women receiving AC followed by T compared with AC alone., Results: One hundred ninety-one eligible women completed the survey. The rate of CIA in women who received AC followed by T was 64% (95% confidence interval [CI] = 55-72%) compared with 55% (95% CI = 43-66%) in AC alone. As expected, CIA rates were higher in older than younger women (82% vs. 55%, P = 0.004). Multivariate logistic regression analysis revealed that age >40 was associated with a 4.6-fold increased risk of CIA (95% CI = 1.7-12.1, P = 0.002). It also revealed that receiving T after AC was associated with an odds ratio of 1.9 for CIA as compared with receiving AC alone (95% CI = 1.0-3.5, P = 0.05). Despite > or =6 months of amenorrhea, many women < or =40 resumed menses (40%). CIA was more likely to be irreversible in those >40. The addition of taxanes did not alter the rate of reversibility for the group as a whole (P = 0.36)., Conclusions: Older age and the addition of taxane to AC increased the risk of CIA and the amenorrhea was more likely to be irreversible for women >40. Women < or =40 often resume menstruation even after 6 months of amenorrhea, and the addition of T does not play a role. Subsequent resumption of menstrual function must be considered when initiating appropriate hormonal therapy.

Repeated measures of personal exposure to 14 volatile organic compounds (VOC) were obtained over 3 seasons for 70 healthy, nonsmoking adults living in Minneapolis-St. Paul. Matched data were also available for participants' time-activity patterns, and measured VOC concentrations outdoors in the community and indoors in residences. A novel modeling approach employing hierarchical Bayesian techniques was used to estimate VOC concentrations (posterior mode) and variability (credible intervals) in five microenvironments: (1) indoors at home; (2) indoors at work/school; (3) indoors in other locations; (4) outdoors in any location; and (5) in transit. Estimated concentrations tended to be highest in "other" indoor microenvironments (e.g., grocery stores, restaurants, shopping malls), intermediate in the indoor work/school and residential microenvironments, and lowest in the outside and in-transit microenvironments. Model estimates for all 14 VOC were reasonable approximations of measured median concentrations in the indoor residential microenvironment. The largest predicted contributor to cumulative (2-day) personal exposure for all 14 VOC was the indoor residential environment. Model-based results suggest that indoors-at-work/school and indoors-at-other-location microenvironments were the second or third largest contributors for all VOC, while the outside-in-any-location and in-transit microenvironments appeared to contribute negligibly to cumulative personal exposure. Results from a mixed-effects model indicate that being in or near a garage increased personal exposure to o-xylene, m/p-xylene, benzene, ethylbenzene, and toluene, and leaving windows and doors at home open for 6 h or more decreased personal exposure to 13 of 14 VOC, all except trichloroethylene.