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Find video protocols related to scientific articles indexed in Pubmed.
Interactions Between Cigarette Smoking and Fine Particulate Matter in the Risk of Lung Cancer Mortality in Cancer Prevention Study II.
Am. J. Epidemiol.
PUBLISHED: 11-15-2014
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The International Agency for Research on Cancer recently classified outdoor air pollution and airborne particulate matter as carcinogenic to humans. However, there are gaps in the epidemiologic literature, including assessment of possible joint effects of cigarette smoking and fine particulate matter (particulate matter less than or equal to 2.5 µm in diameter) on lung cancer risk. We present estimates of interaction on the additive scale between these risk factors from Cancer Prevention Study II, a large prospective US cohort study of nearly 1.2 million participants recruited in 1982. Estimates of the relative excess risk of lung cancer mortality due to interaction, the attributable proportion due to interaction, and the synergy index were 2.19 (95% confidence interval (CI): -0.10, 4.83), 0.14 (95% CI: 0.00, 0.25), and 1.17 (95% CI: 1.00, 1.37), respectively, using the 25th and 75th percentiles as cutpoints for fine particulate matter. This suggests small increases in lung cancer risk among persons with both exposures beyond what would be expected from the sum of the effects of the individual exposures alone. Although reductions in cigarette smoking will achieve the greatest impact on lung cancer rates, these results suggest that attempted reductions in lung cancer risk through both tobacco control and air quality management may exceed expectations based on reducing exposure to either risk factor alone.
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Relationships Between Fine Particulate Air Pollution, Cardiometabolic Disorders and Cardiovascular Mortality.
Circ. Res.
PUBLISHED: 10-29-2014
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Rationale: Growing evidence suggests that long-term exposure to fine particulate matter (PM2.5) air pollution contributes to risk of cardiovascular disease (CVD) morbidity and mortality. There is uncertainty regarding who are most susceptible. Individuals with underlying cardiometabolic disorders, including hypertension, diabetes, and obesity, may be at greater risk. PM2.5 pollution may also contribute to cardiometabolic disorders, augmenting CVD risk. Objective: This analysis evaluates relationships between long-term PM2.5 exposure and cardiometabolic disease on risk of death from CVD and cardiometabolic conditions. Methods and Results: Data on 669,046 participants from the American Cancer Society, Cancer Prevention Study II cohort were linked to modeled PM2.5 concentrations at geocoded home addresses. Cox proportional hazards regression models were used to estimate adjusted hazards ratios (HR) for death from CVD and cardiometabolic diseases based on death-certificate information. Effect modification by pre-existing cardiometabolic risk factors on the PM2.5-CVD mortality association was examined. PM2.5 exposure was associated with CVD mortality, with the HR (95% CI) per 10 µg/m(3) increase in PM2.5 equal to 1.12 (1.10-1.15). Deaths linked to hypertension and/or diabetes (mentioned on death certificate as either primary or contributing cause of death) were also associated with PM2.5. There was no consistent evidence of effect modification by cardiometabolic disease risk factors on the PM2.5-CVD mortality association. Conclusions: Pollution-induced CVD mortality risk is observed for those with and without existing cardiometabolic disorders. Long-term exposure may also contribute to the development or exacerbation of cardiometabolic disorders, increasing risk of CVD and cardiometabolic disease mortality.
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Systematic review of potential health risks posed by pharmaceutical, occupational and consumer exposures to metallic and nanoscale aluminum, aluminum oxides, aluminum hydroxide and its soluble salts.
Crit. Rev. Toxicol.
PUBLISHED: 09-19-2014
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Abstract Aluminum (Al) is a ubiquitous substance encountered both naturally (as the third most abundant element) and intentionally (used in water, foods, pharmaceuticals, and vaccines); it is also present in ambient and occupational airborne particulates. Existing data underscore the importance of Al physical and chemical forms in relation to its uptake, accumulation, and systemic bioavailability. The present review represents a systematic examination of the peer-reviewed literature on the adverse health effects of Al materials published since a previous critical evaluation compiled by Krewski et al. (2007) . Challenges encountered in carrying out the present review reflected the experimental use of different physical and chemical Al forms, different routes of administration, and different target organs in relation to the magnitude, frequency, and duration of exposure. Wide variations in diet can result in Al intakes that are often higher than the World Health Organization provisional tolerable weekly intake (PTWI), which is based on studies with Al citrate. Comparing daily dietary Al exposures on the basis of "total Al"assumes that gastrointestinal bioavailability for all dietary Al forms is equivalent to that for Al citrate, an approach that requires validation. Current occupational exposure limits (OELs) for identical Al substances vary as much as 15-fold. The toxicity of different Al forms depends in large measure on their physical behavior and relative solubility in water. The toxicity of soluble Al forms depends upon the delivered dose of Al(+3) to target tissues. Trivalent Al reacts with water to produce bidentate superoxide coordination spheres [Al(O2)(H2O4)(+2) and Al(H2O)6 (+3)] that after complexation with O2(•-), generate Al superoxides [Al(O2(•))](H2O5)](+2). Semireduced AlO2(•) radicals deplete mitochondrial Fe and promote generation of H2O2, O2 (•-) and OH(•). Thus, it is the Al(+3)-induced formation of oxygen radicals that accounts for the oxidative damage that leads to intrinsic apoptosis. In contrast, the toxicity of the insoluble Al oxides depends primarily on their behavior as particulates. Aluminum has been held responsible for human morbidity and mortality, but there is no consistent and convincing evidence to associate the Al found in food and drinking water at the doses and chemical forms presently consumed by people living in North America and Western Europe with increased risk for Alzheimer's disease (AD). Neither is there clear evidence to show use of Al-containing underarm antiperspirants or cosmetics increases the risk of AD or breast cancer. Metallic Al, its oxides, and common Al salts have not been shown to be either genotoxic or carcinogenic. Aluminum exposures during neonatal and pediatric parenteral nutrition (PN) can impair bone mineralization and delay neurological development. Adverse effects to vaccines with Al adjuvants have occurred; however, recent controlled trials found that the immunologic response to certain vaccines with Al adjuvants was no greater, and in some cases less than, that after identical vaccination without Al adjuvants. The scientific literature on the adverse health effects of Al is extensive. Health risk assessments for Al must take into account individual co-factors (e.g., age, renal function, diet, gastric pH). Conclusions from the current review point to the need for refinement of the PTWI, reduction of Al contamination in PN solutions, justification for routine addition of Al to vaccines, and harmonization of OELs for Al substances.
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Intermediate CAG repeat expansion in the ATXN2 gene is a unique genetic risk factor for ALS--a systematic review and meta-analysis of observational studies.
PLoS ONE
PUBLISHED: 08-22-2014
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Amyotrophic lateral sclerosis (ALS) is a rare degenerative condition of the motor neurons. Over 10% of ALS cases are linked to monogenic mutations, with the remainder thought to be due to other risk factors, including environmental factors, genetic polymorphisms, and possibly gene-environmental interactions. We examined the association between ALS and an intermediate CAG repeat expansion in the ATXN2 gene using a meta-analytic approach. Observational studies were searched with relevant disease and gene terms from MEDLINE, EMBASE, and PsycINFO from January 2010 through to January 2014. All identified articles were screened using disease terms, gene terms, population information, and CAG repeat information according to PRISMA guidelines. The final list of 17 articles was further evaluated based on the study location, time period, and authors to exclude multiple usage of the same study populations: 13 relevant articles were retained for this study. The range 30-33 CAG repeats in the ATXN2 gene was most strongly associated with ALS. The meta-analysis revealed that the presence of an intermediate CAG repeat (30-33) in the ATXN2 gene was associated with an increased risk of ALS [odds ratio (OR)?=?4.44, 95%CI: 2.91-6.76)] in Caucasian ALS patients. There was no significant difference in the association of this CAG intermediate repeat expansion in the ATXN2 gene between familial ALS cases (OR?=?3.59, 1.58-8.17) and sporadic ALS cases (OR?=?3.16, 1.88-5.32). These results indicate that the presence of intermediate CAG repeat expansion in the ATXN2 gene is a specific genetic risk factor for ALS, unlike monogenic mutations with an autosomal dominant transmission mode, which cause a more severe phenotype of ALS, with a higher prevalence in familial ALS.
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Occupational exposure to extremely low-frequency magnetic fields and brain tumor risks in the INTEROCC study.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 06-16-2014
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Occupational exposure to extremely low-frequency magnetic fields (ELF) is a suspected risk factor for brain tumors, however the literature is inconsistent. Few studies have assessed whether ELF in different time windows of exposure may be associated with specific histologic types of brain tumors. This study examines the association between ELF and brain tumors in the large-scale INTEROCC study.
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Brain tumours and cigarette smoking: analysis of the INTERPHONE Canada case-control study.
Environ Health
PUBLISHED: 05-12-2014
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There is conflicting evidence regarding the associations between cigarette smoking and glioma or meningioma. Our purpose is to provide further evidence on these possible associations.
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A framework for the next generation of risk science.
Environ. Health Perspect.
PUBLISHED: 04-09-2014
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In 2011, the U.S. Environmental Protection Agency initiated the NexGen project to develop a new paradigm for the next generation of risk science.
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Statistical methods for active pharmacovigilance, with applications to diabetes drugs.
J Biopharm Stat
PUBLISHED: 04-05-2014
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Pharmacovigilance aims to identify adverse drug reactions using postmarket surveillance data under real-world conditions of use. Unlike passive pharmacovigilance, which is based on largely voluntary (and hence incomplete) spontaneous reports of adverse drug reactions with limited information on patient characteristics, active pharmacovigilance is based on electronic health records containing detailed information about patient populations, thereby allowing consideration of modifying factors such as polypharmacy and comorbidity, as well as sociodemographic characteristics. With the present shift toward active pharmacovigilance, statistical methods capable of addressing the complexities of such data are needed. We describe four such methods here, and demonstrate their application in the analysis of a large retrospective cohort of diabetics taking anti-hyperglycemic medications that may increase the risk of adverse cardiovascular events.
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Risk of heart failure following treatment with dopamine agonists in Parkinson's disease patients.
Expert Opin Drug Saf
PUBLISHED: 02-20-2014
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Dopamine agonists (DAs) are frequently used to treat early or advanced Parkinson's disease (PD) patients. They have been shown to be efficacious for the treatment of motor symptoms and for delaying levodopa-induced dyskinesias. However, their utilization is limited by the risk of adverse drug reactions, some of which affect the cardiovascular system. Recently, the US FDA identified a possible association between exposure to pramipexole and the risk of heart failure.
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Association between change of health care providers and pregnancy exposure to FDA category C, D and X drugs.
Chin. Med. J.
PUBLISHED: 02-19-2014
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Changing health care providers frequently breaks the continuity of care, which is associated with many health care problems. The purpose of this study was to examine the association between a change of health care providers and pregnancy exposure to FDA category C, D and X drugs.
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Association between labetalol use for hypertension in pregnancy and adverse infant outcomes.
Eur. J. Obstet. Gynecol. Reprod. Biol.
PUBLISHED: 01-07-2014
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Labetalol and methyldopa are the two antihypertensive drugs most frequently used to control blood pressure for hypertensive disorders of pregnancy. The objective of this study was to assess if labetalol is associated with poor infant outcomes.
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The MOBI-Kids Study Protocol: Challenges in Assessing Childhood and Adolescent Exposure to Electromagnetic Fields from Wireless Telecommunication Technologies and Possible Association with Brain Tumor Risk.
Front Public Health
PUBLISHED: 01-01-2014
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The rapid increase in mobile phone use in young people has generated concern about possible health effects of exposure to radiofrequency (RF) and extremely low frequency (ELF) electromagnetic fields (EMF). MOBI-Kids, a multinational case-control study, investigates the potential effects of childhood and adolescent exposure to EMF from mobile communications technologies on brain tumor risk in 14 countries. The study, which aims to include approximately 1,000 brain tumor cases aged 10-24?years and two individually matched controls for each case, follows a common protocol and builds upon the methodological experience of the INTERPHONE study. The design and conduct of a study on EMF exposure and brain tumor risk in young people in a large number of countries is complex and poses methodological challenges. This manuscript discusses the design of MOBI-Kids and describes the challenges and approaches chosen to address them, including: (1) the choice of controls operated for suspected appendicitis, to reduce potential selection bias related to low response rates among population controls; (2) investigating a young study population spanning a relatively wide age range; (3) conducting a large, multinational epidemiological study, while adhering to increasingly stricter ethics requirements; (4) investigating a rare and potentially fatal disease; and (5) assessing exposure to EMF from communication technologies. Our experience in thus far developing and implementing the study protocol indicates that MOBI-Kids is feasible and will generate results that will contribute to the understanding of potential brain tumor risks associated with use of mobile phones and other wireless communications technologies among young people.
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Spatial analysis of air pollution and mortality in California.
Am. J. Respir. Crit. Care Med.
PUBLISHED: 06-29-2013
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Although substantial scientific evidence suggests that chronic exposure to ambient air pollution contributes to premature mortality, uncertainties exist in the size and consistency of this association. Uncertainty may arise from inaccurate exposure assessment.
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Trends in using beta-blockers and methyldopa for hypertensive disorders during pregnancy in a Canadian population.
Eur. J. Obstet. Gynecol. Reprod. Biol.
PUBLISHED: 06-11-2013
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To describe trends in and patterns of antihypertensive drug use in a general obstetric population.
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Acute effects of ambient ozone on mortality in Europe and North America: results from the APHENA study.
Air Qual Atmos Health
PUBLISHED: 06-05-2013
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The "Air Pollution and Health: A Combined European and North American Approach" (APHENA) project is a collaborative analysis of multi-city time-series data on the association between air pollution and adverse health outcomes. The main objective of APHENA was to examine the coherence of findings of time-series studies relating short-term fluctuations in air pollution levels to mortality and morbidity in 125 cities in Europe, the US, and Canada. Multi-city time-series analysis was conducted using a two-stage approach. We used Poisson regression models controlling for overdispersion with either penalized or natural splines to adjust for seasonality. Hierarchical models were used to obtain an overall estimate of excess mortality associated with ozone and to assess potential effect modification. Potential effect modifiers were city-level characteristics related to exposure to other ambient air pollutants, weather, socioeconomic status, and the vulnerability of the population. Regionally pooled risk estimates from Europe and the US were similar; those from Canada were substantially higher. The pooled estimated excess relative risk associated with a 10 µg/m(3) increase in 1 h daily maximum O3 was 0.26 % (95 % CI, 0.15 %, 0.37 %). Across regions, there was little consistent indication of effect modification by age or other effect modifiers considered in the analysis. The findings from APHENA on the effects of O3 on mortality in the general population were comparable with previously reported results and relatively robust to the method of data analysis. Overall, there was no indication of strong effect modification by age or ecologic variables considered in the analysis.
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Exposure to environmental tobacco smoke (ETS) and risk of lung cancer in Montreal: a case-control study.
Environ Health
PUBLISHED: 04-28-2013
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The objective of the present study was to examine the association between environmental tobacco smoke (ETS) and risk of lung cancer among never smokers, defined as subjects who smoked less than 100 cigarettes in their lifetime.
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INTEROCC case-control study: lack of association between glioma tumors and occupational exposure to selected combustion products, dusts and other chemical agents.
BMC Public Health
PUBLISHED: 04-08-2013
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The aim was to investigate possible associations between glioma (an aggressive type of brain cancer) and occupational exposure to selected agents: combustion products (diesel and gasoline exhaust emissions, benzo(a)pyrene), dusts (animal dust, asbestos, crystalline silica, wood dust) and some other chemical agents (formaldehyde, oil mist, sulphur dioxide).
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Modeling seasonal behavior changes and disease transmission with application to chronic wasting disease.
J. Theor. Biol.
PUBLISHED: 02-14-2013
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Behavior and habitat of wildlife animals change seasonally according to environmental conditions. Mathematical models need to represent this seasonality to be able to make realistic predictions about the future of a population and the effectiveness of human interventions. Managing and modeling disease in wild animal populations requires particular care in that disease transmission dynamics is a critical consideration in the etiology of both human and animal diseases, with different transmission paradigms requiring different disease risk management strategies. Since transmission of infectious diseases among wildlife depends strongly on social behavior, mechanisms of disease transmission could also change seasonally. A specific consideration in this regard confronted by modellers is whether the contact rate between individuals is density-dependent or frequency-dependent. We argue that seasonal behavior changes could lead to a seasonal shift between density and frequency dependence. This hypothesis is explored in the case of chronic wasting disease (CWD), a fatal disease that affects deer, elk and moose in many areas of North America. Specifically, we introduce a strategic CWD risk model based on direct disease transmission that accounts for the seasonal change in the transmission dynamics and habitats occupied, guided by information derived from cervid ecology. The model is composed of summer and winter susceptible-infected (SI) equations, with frequency-dependent and density-dependent transmission dynamics, respectively. The model includes impulsive birth events with density-dependent birth rate. We determine the basic reproduction number as a weighted average of two seasonal reproduction numbers. We parameterize the model from data derived from the scientific literature on CWD and deer ecology, and conduct global and local sensitivity analyses of the basic reproduction number. We explore the effectiveness of different culling strategies for the management of CWD: although summer culling seems to be an effective disease eradication strategy, the total culling rate is limited by the requirement to preserve the herd.
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Allergy and brain tumors in the INTERPHONE study: pooled results from Australia, Canada, France, Israel, and New Zealand.
Cancer Causes Control
PUBLISHED: 02-07-2013
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A history of allergy has been inversely associated with several types of cancer although the evidence is not entirely consistent. We examined the association between allergy history and risk of glioma, meningioma, acoustic neuroma, and parotid gland tumors using data on a large number of cases and controls from five INTERPHONE study countries (Australia, Canada, France, Israel, New Zealand), to better understand potential sources of bias in brain tumor case-control studies and to examine associations between allergy and tumor sites where few studies exist.
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Radon and COPD mortality in the American Cancer Society Cohort.
Eur. Respir. J.
PUBLISHED: 10-17-2011
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Although radon gas is a known cause of lung cancer, the association between residential radon and mortality from non-malignant respiratory disease has not been well characterised. The Cancer Prevention Study-II is a large prospective cohort study of nearly 1.2 million Americans recruited in 1982. Mean county-level residential radon concentrations were linked to study participants residential address based on their ZIP code at enrolment (mean ± SD 53.5 ± 38.0 Bq · m(-3)). Cox proportional hazards regression models were used to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for non-malignant respiratory disease mortality associated with radon concentrations. After necessary exclusions, a total of 811,961 participants in 2,754 counties were included in the analysis. Throughout 2006, there were a total of 28,300 non-malignant respiratory disease deaths. Radon was significantly associated with chronic obstructive pulmonary disease (COPD) mortality (HR per 100 Bq · m(-3) 1.13, 95% CI 1.05-1.21). There was a significant positive linear trend in COPD mortality with increasing categories of radon concentrations (p<0.05). Findings suggest residential radon may increase COPD mortality. Further research is needed to confirm this finding and to better understand possible complex inter-relationships between radon, COPD and lung cancer.
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Long-term ambient fine particulate matter air pollution and lung cancer in a large cohort of never-smokers.
Am. J. Respir. Crit. Care Med.
PUBLISHED: 10-06-2011
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There is compelling evidence that acute and chronic exposure to ambient fine particulate matter (PM(2.5)) air pollution increases cardiopulmonary mortality. However, the role of PM(2.5) in the etiology of lung cancer is less clear, particularly at concentrations that prevail in developed countries and in never-smokers.
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A signal-to-noise crossover dose as the point of departure for health risk assessment.
Environ. Health Perspect.
PUBLISHED: 08-03-2011
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The U.S. National Toxicology Program (NTP) cancer bioassay database provides an opportunity to compare both existing and new approaches to determining points of departure (PoDs) for establishing reference doses (RfDs).
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Breast cancer risk in relation to alcohol consumption and BRCA gene mutations--a case-only study of gene-environment interaction.
Breast J
PUBLISHED: 07-15-2011
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The variable penetrance of the BRCA1 and BRCA2 genes suggests that other genetic or environmental factors may interact with these mutations to modify breast cancer risk. The objective of this study was to measure departures from multiplicative effects of alcohol consumption and BRCA gene mutations. A cohort of French-Canadian breast cancer patients was tested for BRCA gene mutations and completed a food frequency questionnaire. The case-only odds ratio (COR) was calculated. A total of 857 women, including 10 BRCA1 and 33 BRCA2 mutation carriers, participated in the study. No significant interaction between alcohol consumption and BRCA1 mutations was detected, although the interaction with wine consumption suggested a sub-multiplicative effect (COR = 0.38, 95% CI: 0.08-1.81). Consumption of alcohol other than wine interacted significantly with BRCA2 mutations (COR = 2.15, 95% CI: 1.03-4.49). Consumption of wine may protect against BRCA1-associated tumors, while women with BRCA2 mutations may be at greater risk of alcohol-induced breast cancer.
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Bias in the case-only design applied to studies of gene-environment and gene-gene interaction: a systematic review and meta-analysis.
Int J Epidemiol
PUBLISHED: 07-04-2011
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The case-only study, proposed as a design specifically for assessing departure from multiplicative gene-environment and gene-gene interactions, is of considerable potential value but there are concerns about its validity. The objective of this study was to evaluate the extent and sources of bias in the case-only design by means of a systematic review and meta-regression analysis.
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Principles, applications, risks and benefits of therapeutic hyperthermia.
Front Biosci (Elite Ed)
PUBLISHED: 05-31-2011
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Hyperthermia as a heat therapy is the procedure of raising the temperature of a part of or the whole body above normal for a certain period of time. Based largely on delivery methods, therapeutic hyperthermia falls under three major categories: local, regional, and whole-body. It may be applied alone or jointly with other modalities such as radiotherapy, chemotherapy, radiochemotherapy, and gene therapy. Because of the individual characteristics of each type of treatment, different types of heating systems have evolved. This paper provides an overview of possible mechanisms of heat-induced cell death and the way heating exerts its beneficial effect. It also discusses various heating devices as well as other modalities used with hyperthermia. The paper concludes with a summary of benefits and risks, obstacles encountered in the treatment process, and future research directions.
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Cobalt and chromium levels in blood and urine following hip resurfacing arthroplasty with the Conserve Plus implant.
J Bone Joint Surg Am
PUBLISHED: 05-06-2011
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The purpose of the present study was to determine cobalt and chromium ion levels in the blood and urine of patients in whom a modern-generation metal-on-metal hip resurfacing device had been implanted.
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Residential pesticides and childhood leukemia: a systematic review and meta-analysis.
Cien Saude Colet
PUBLISHED: 04-27-2011
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It is a systematic review and meta-analysis of previous observational epidemiologic studies examining the relationship between residential pesticide exposures during critical exposure time windows (preconception, pregnancy, and childhood) and childhood leukemia. Searches of Medline and other electronic databases were performed (1950-2009). Study selection, data abstraction, and quality assessment were performed by two independent reviewers. Random effects models were used to obtain summary odds ratios (ORs) and 95% confidence intervals (Cis). Of the 17 identified studies, 15 were included in the meta-analysis. Exposures during pregnancy to unspecified residential pesticides insecticides, and herbicides were positively associated with childhood leukemia. Exposures during childhood to unspecified residential pesticides and insecticides were also positively associated with childhood leukemia, but there was no association with herbicides. Positive associations were observed between childhood leukemia and residential pesticide exposures. Further work is needed to confirm previous findings based on self-report, to examine potential exposure-response relationships, and to assess specific pesticides and toxicologically related subgroups of pesticides in more detail.
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Lung cancer and cardiovascular disease mortality associated with ambient air pollution and cigarette smoke: shape of the exposure-response relationships.
Environ. Health Perspect.
PUBLISHED: 03-04-2011
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Lung cancer and cardiovascular disease (CVD) mortality risks increase with smoking, secondhand smoke (SHS), and exposure to fine particulate matter < 2.5 ?m in diameter (PM?.?) from ambient air pollution. Recent research indicates that the exposure-response relationship for CVD is nonlinear, with a steep increase in risk at low exposures and flattening out at higher exposures. Comparable estimates of the exposure-response relationship for lung cancer are required for disease burden estimates and related public health policy assessments.
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Detection of prion protein in urine-derived injectable fertility products by a targeted proteomic approach.
PLoS ONE
PUBLISHED: 02-10-2011
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Iatrogenic transmission of human prion disease can occur through medical or surgical procedures, including injection of hormones such as gonadotropins extracted from cadaver pituitaries. Annually, more than 300,000 women in the United States and Canada are prescribed urine-derived gonadotropins for infertility. Although menopausal urine donors are screened for symptomatic neurological disease, incubation of Creutzfeldt-Jakob disease (CJD) is impossible to exclude by non-invasive testing. Risk of carrier status of variant CJD (vCJD), a disease associated with decades-long peripheral incubation, is estimated to be on the order of 100 per million population in the United Kingdom. Studies showing infectious prions in the urine of experimental animals with and without renal disease suggest that prions could be present in asymptomatic urine donors. Several human fertility products are derived from donated urine; recently prion protein has been detected in preparations of human menopausal gonadotropin (hMG).
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Exposure to trimethoprim/sulfamethoxazole but not other FDA category C and D anti-infectives is associated with increased risks of preterm birth and low birth weight.
Int. J. Infect. Dis.
PUBLISHED: 01-18-2011
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To examine the association between trimethoprim/sulfamethoxazole, other US Food and Drug Administration (FDA) C and D anti-infectives, and non anti-infective FDA C, D, and X drugs used during pregnancy with preterm birth and low birth weight.
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New directions in toxicity testing.
Annu Rev Public Health
PUBLISHED: 01-12-2011
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In 2007, the U.S. National Research Council (NRC) published a groundbreaking report entitled Toxicity Testing in the 21st Century: A Vision and a Strategy. The purpose of this report was to develop a long-range strategic plan to update and advance the way environmental agents are tested for toxicity. The vision focused on the identification of critical perturbations of toxicity pathways that lead to adverse human health outcomes using modern scientific tools and technologies. This review describes how emerging scientific methods will move the NRC vision forward and improve the manner in which the potential health risks associated with exposure to environmental agents are assessed. The new paradigm for toxicity testing is compatible with the widely used four-stage risk assessment framework originally proposed by the NRC in 1983 in the so-called Red Book. The Nrf2 antioxidant pathway provides a detailed example of how relevant pathway perturbations will be identified within the context of the new NRC vision for the future of toxicity testing. The implications of the NRC vision for toxicity testing for regulatory risk assessment are also discussed.
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Expert elicitation for the judgment of prion disease risk uncertainties.
J. Toxicol. Environ. Health Part A
PUBLISHED: 01-11-2011
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There is a high level of uncertainty surrounding the potential for iatrogenic prion transmission through transplantation, medical instrument reuse, blood transfusion, and blood product use due to a lack of evidence-based research on this important risk issue. A group of specialists was enlisted to evaluate some of the knowledge gaps in this area using the "Classical Model," a structured elicitation procedure for weighting and pooling expert judgment. The elicitation exercise was undertaken in March 2009 with 11 transmissible spongiform encephalopathy (TSE) experts who were first calibrated using a series of seed questions for which the answers are known; they were then asked to answer a number of target questions that are important for risk assessment purposes, but for which there remains high uncertainty at this time. The target questions focused on variant Creutzfeldt-Jakob disease (vCJD) prevalence, incubation times for vCJD, genetic susceptibility to prion disease, blood infectivity, prion reduction of blood and blood products, surgical instrument risks, and interspecies transmission of TSEs. The experts were also asked to perform pairwise risk rankings for 12 different potential routes of infection. Dura mater transplantation was seen as having the highest risk, while dental tissue grafts were viewed as presenting the lowest risk of iatrogenic transmission. The structured elicitation procedure provides a rational, auditable, and repeatable basis for obtaining useful information on prion disease risk issues, for which data are sparse.
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Uncertainty beyond probabilities of BSE: appraisals predicting worry and coping strategies in the Canadian public.
J. Toxicol. Environ. Health Part A
PUBLISHED: 01-11-2011
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The impact of bovine spongiform encephalopathy (BSE) is not limited to the infection with the BSE agent but also affects psychosocial responses, such as worry and loss of confidence in public authorities. It was shown in past crises that these reactions depended upon the way the event was perceived by the public. Understanding the nature of the perceptions of BSE is therefore of great importance for risk management in all phases of the risk, including the period before the onset of a crisis, when BSE is still only a pending threat to human health. This study analyzed data from a representative national survey of Canadians (n = 1,517) on the perceived risk of prion diseases. Factor analysis revealed emerging dimensions of BSE appraisals and regression analysis identified variables that predicted worry and coping strategies. Results yielded three significant factors, each relating differently to reactions to BSE: (1) Perceived impact, which combined perceived risk for health and likelihood of occurrence of BSE crises, was the main predictor of worry about eating tainted beef; (2) perceived mastery, consisting of personal knowledge and control, predicted taking action to avoid the disease; and (3) perceived intricacy, composed of perceived complexity and uncertainty, uniquely predicted trying to ignore BSE-related risks. Further regression analysis and analysis of variance exposed a moderating role of perceived intricacy on the relationship between perceived impact of BSE crises and worry. The implications of these findings for risk communication and management are described.
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PrioNet Canada: a network of centres of excellence for research on prion diseases--ongoing and future research directions.
J. Toxicol. Environ. Health Part A
PUBLISHED: 01-11-2011
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It is PrioNets vision to build a network that shapes and sustains prion research in Canada, translating basic science into accessible socioeconomic benefits for global betterment. PrioNets research is developing surveillance measures, diagnostic tools, vaccines, and potential therapies and determining the various impacts of prion diseases on people. PrioNet seeks to integrate scientifically informed risk management strategies and to use this knowledge to address ongoing problems posed by bovine spongiform encephalopathy (BSE), the gathering crisis of chronic wasting disease (CWD), emerging issues of human prion disease, and basic scientific understanding of the nature of prions. PrioNet is strategically responding to prion threats by focusing its network of highly accomplished researchers and trainees to implement integrated risk management strategies that could not be supported by other mechanisms.
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Radon and lung cancer in the American Cancer Society cohort.
Cancer Epidemiol. Biomarkers Prev.
PUBLISHED: 01-06-2011
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Case-control studies conducted in North America, Europe, and Asia provided evidence of increased lung cancer risk due to radon in homes. Here, the association between residential radon and lung cancer mortality was examined in a large-scale cohort study.
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An exposure-response curve for copper excess and deficiency.
J Toxicol Environ Health B Crit Rev
PUBLISHED: 12-21-2010
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There is a need to define exposure-response curves for both Cu excess and deficiency to assist in determining the acceptable range of oral intake. A comprehensive database has been developed where different health outcomes from elevated and deficient Cu intakes were assigned ordinal severity scores to create common measures of response. A generalized linear model for ordinal data was used to estimate the probability of response associated with dose, duration and severity. The model can account for differences in animal species, the exposure medium (drinking water and feed), age, sex, and solubility. Using this model, an optimal intake level of 2.6 mg Cu/d was determined. This value is higher than the current U.S. recommended dietary intake (RDI; 0.9 mg/d) that protects against toxicity from Cu deficiency. It is also lower than the current tolerable upper intake level (UL; 10 mg/d) that protects against toxicity from Cu excess. Compared to traditional risk assessment approaches, categorical regression can provide risk managers with more information, including a range of intake levels associated with different levels of severity and probability of response. To weigh the relative harms of deficiency and excess, it is important that the results be interpreted along with the available information on the nature of the responses that were assigned to each severity score.
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Mining pharmacovigilance data using Bayesian logistic regression with James-Stein type shrinkage estimation.
J Biopharm Stat
PUBLISHED: 08-20-2010
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Spontaneous adverse event reporting systems are widely used to identify adverse reactions to drugs following their introduction into the marketplace. In this article, a James-Stein type shrinkage estimation strategy was developed in a Bayesian logistic regression model to analyze pharmacovigilance data. This method is effective in detecting signals as it combines information and borrows strength across medically related adverse events. Computer simulation demonstrated that the shrinkage estimator is uniformly better than the maximum likelihood estimator in terms of mean squared error. This method was used to investigate the possible association of a series of diabetic drugs and the risk of cardiovascular events using data from the Canada Vigilance Online Database.
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The future of toxicity testing.
J Toxicol Environ Health B Crit Rev
PUBLISHED: 06-25-2010
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In 2007, the U.S. National Research Council (NRC) released a report, "Toxicity Testing in the 21st Century: A Vision and a Strategy," that proposes a paradigm shift for toxicity testing of environmental agents. The vision is based on the notion that exposure to environmental agents leads to adverse health outcomes through the perturbation of toxicity pathways that are operative in humans. Implementation of the NRC vision will involve a fundamental change in the assessment of toxicity of environmental agents, moving away from adverse health outcomes observed in experimental animals to the identification of critical perturbations of toxicity pathways. Pathway perturbations will be identified using in vitro assays and quantified for dose response using methods in computational toxicology and other recent scientific advances in basic biology. Implementation of the NRC vision will require a major research effort, not unlike that required to successfully map the human genome, extending over 10 to 20 years, involving the broad scientific community to map important toxicity pathways operative in humans. This article provides an overview of the scientific tools and technologies that will form the core of the NRC vision for toxicity testing. Of particular importance will be the development of rapidly performed in vitro screening assays using human cells and cell lines or human tissue surrogates to efficiently identify environmental agents producing critical pathway perturbations. In addition to the overview of the NRC vision, this study documents the reaction by a number of stakeholder groups since 2007, including the scientific, risk assessment, regulatory, and animal welfare communities.
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Toxicity testing in the 21st century: a vision and a strategy.
J Toxicol Environ Health B Crit Rev
PUBLISHED: 06-25-2010
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With the release of the landmark report Toxicity Testing in the 21st Century: A Vision and a Strategy, the U.S. National Academy of Sciences, in 2007, precipitated a major change in the way toxicity testing is conducted. It envisions increased efficiency in toxicity testing and decreased animal usage by transitioning from current expensive and lengthy in vivo testing with qualitative endpoints to in vitro toxicity pathway assays on human cells or cell lines using robotic high-throughput screening with mechanistic quantitative parameters. Risk assessment in the exposed human population would focus on avoiding significant perturbations in these toxicity pathways. Computational systems biology models would be implemented to determine the dose-response models of perturbations of pathway function. Extrapolation of in vitro results to in vivo human blood and tissue concentrations would be based on pharmacokinetic models for the given exposure condition. This practice would enhance human relevance of test results, and would cover several test agents, compared to traditional toxicological testing strategies. As all the tools that are necessary to implement the vision are currently available or in an advanced stage of development, the key prerequisites to achieving this paradigm shift are a commitment to change in the scientific community, which could be facilitated by a broad discussion of the vision, and obtaining necessary resources to enhance current knowledge of pathway perturbations and pathway assays in humans and to implement computational systems biology models. Implementation of these strategies would result in a new toxicity testing paradigm firmly based on human biology.
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The vision of toxicity testing in the 21st century: moving from discussion to action.
Toxicol. Sci.
PUBLISHED: 06-23-2010
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Over the past year, a series on commentaries have appeared in the Toxicological Sciences Forum Series related to the 2007 National Research Council (NRC) publication, Toxicity Testing in the 21st Century: A Vision and A Strategy. The first article in the series provided an overview of the vision and was accompanied by an editorial by the three editors of Toxicological Sciences. During the past year, eight invited commentaries from the academic, industrial, and regulatory sectors have provided diverse perspectives on the vision, noted challenges to its implementation, and highlighted aspects of toxicity testing that were not addressed in the original NRC report. Here, we offer a summary of the main points raised by the commentators in tabular form, identify a number of common themes, and finish the series by providing our perspective on several key issues in charting the path forward to move from discussion to action.
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Alcohol consumption and the risk of breast cancer among BRCA1 and BRCA2 mutation carriers.
Breast
PUBLISHED: 03-10-2010
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Alcohol consumption increases the risk of breast cancer among women in the general population, but its effect on women who carry a BRCA gene mutation is unclear. We conducted a case-control study of 1925 matched pairs of predominantly premenopausal women who carry a BRCA1 or a BRCA2 mutation. Information on current alcohol consumption was obtained from a questionnaire administered during the course of genetic counselling or at the time of enrollment. A modest inverse association between breast cancer and reported current alcohol consumption was observed among women with a BRCA1 mutation (OR = 0.82, 95% CI 0.70-0.96), but not among women with a BRCA2 mutation (OR = 1.00; 95% CI 0.71-1.41). Compared to non-drinkers, exclusive consumption of wine was associated with a significant reduction in the risk of breast cancer among BRCA1 carriers (p-trend = 0.01). Alcohol consumption does not appear to increase breast cancer risk in women carrying a BRCA gene mutation.
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Risk assessment practice for essential metals.
J. Toxicol. Environ. Health Part A
PUBLISHED: 01-16-2010
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This article addresses the content of the workshop, including a panel discussion relevant to delineation of a path forward in relation to risk assessment of essential metals. The state of the art of risk assessment and associated issues for essential metals are outlined initially, followed by brief illustration by the case studies considered at the workshop (i.e., copper, zinc, and manganese). Approaches for the future testing strategies of essential metals are discussed in terms of options to increase efficiency and accuracy of assessments. Subsequently, recommendations for pragmatic next steps to advance progress and facilitate uptake by the regulatory risk assessment community are presented.
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Development of a copper database for exposure-response analysis.
J. Toxicol. Environ. Health Part A
PUBLISHED: 01-16-2010
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While its precise form has not yet been defined, it is assumed that the exposure-response curve for copper (Cu) is U-shaped, as both Cu deficiency and excess can produce adverse health effects. Exposure-response relationships provide the foundation for setting recommended levels of exposure to essential and nonessential substances. A group of toxicologists, biologists, and epidemiologists formed a working group in 2002 to review the literature on Cu excess and deficiency as well as possible exposure-response modeling strategies. It was decided that in order to conduct more complex modeling exercises with studies on Cu, the information had to be organized into a database for application of emerging analytical approaches in exposure-response assessment. The database would support both current as well as proposed methods for exposure-response assessment and accommodate a variety of reporting methods found in the literature. As there are multiple studies looking at a wide range of adverse health effects attributed to excess and deficiency, data were organized into ordered categories of severity to create a common measure of response. The present study (1) outlines the approach used to identify studies for the Cu database based on their quality and usefulness for exposure-response analyses; (2) provides an overview of the process used to define a common dose metric; and (3) describes the process used to categorize a diverse number of responses from Cu excess and deficiency to an ordinal severity score. Efforts are underway to use this database to define the exposure-response curve for Cu excess and deficiency; however, the comprehensive database can be used to carry out other in-depth analyses on Cu toxicity.
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The use of categorical regression in modeling copper exposure-response relationships.
J. Toxicol. Environ. Health Part A
PUBLISHED: 01-16-2010
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Characterization of the exposure-response relationship for copper (Cu) is an essential step in identifying a range of exposures that can prevent against toxicity from either excess or deficiency. Categorical regression is a exposure-response modeling technique that can be used to model data from multiple studies with diverse endpoints simultaneously by organizing the toxicity data into ordered categories of severity. This study describes how categorical regression can be used to model the exposure-response relationship for Cu and presents a preliminary analysis of the comprehensive database on Cu-induced toxicity due to either excess or deficiency. Categorical regression provides a useful tool for summarizing and describing the available data on Cu excess and deficiency, as well as in identifying data gaps in Cu exposure-response. This methodology also allows for a diverse database with considerable variability in animal species, strain, age, and study design to be analyzed in its entirety. The present application of the Cu toxicity database suggests that there is a lack of information on the potential adverse health effects from chronic exposure to Cu; there are also a limited number of studies using marginally excess and deficient levels of Cu. The database presently includes insufficient data to create a complex model that accounts for a large proportion of the heterogeneity in toxicity seen among the available studies on Cu-induced toxicity. The current Cu database is presently being updated in order to permit more comprehensive categorical regression analyses with finer stratification options. The resulting exposure-response model could be used to provide information in the determination of an acceptable range of oral intake for Cu.
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Residential pesticides and childhood leukemia: a systematic review and meta-analysis.
Environ. Health Perspect.
PUBLISHED: 01-09-2010
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We conducted a systematic review and meta-analysis of previous observational epidemiologic studies examining the relationship between residential pesticide exposures during critical exposure time windows (preconception, pregnancy, and childhood) and childhood leukemia.
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Conceptualizing the healthscape: contributions of time geography, location technologies and spatial ecology to place and health research.
Soc Sci Med
PUBLISHED: 12-04-2009
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Geomatics and related technologies allow for the application of integrated approaches to the analysis of individual spatial and temporal activities in the context of place and health research. The ability to track individuals as they make decisions and negotiate space may provide a fundamental advance. This paper introduces the need to move beyond conventional place-based perspectives in health research, and invokes the theoretical contributions of time geography and spatial ecology as opportunities to integrate human agency into contextual models of health. Issues around the geographical representation of place are reviewed, and the concept of the healthscape is introduced as an approach to operationalizing context as expressed by the spatial and temporal activities of individuals. We also discuss how these concepts have the potential to influence and contribute to empirical place and health research.
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Public health benefits of strategies to reduce greenhouse-gas emissions: health implications of short-lived greenhouse pollutants.
Lancet
PUBLISHED: 11-26-2009
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In this report we review the health effects of three short-lived greenhouse pollutants-black carbon, ozone, and sulphates. We undertook new meta-analyses of existing time-series studies and an analysis of a cohort of 352,000 people in 66 US cities during 18 years of follow-up. This cohort study provides estimates of mortality effects from long-term exposure to elemental carbon, an indicator of black carbon mass, and evidence that ozone exerts an independent risk of mortality. Associations among these pollutants make drawing conclusions about their individual health effects difficult at present, but sulphate seems to have the most robust effects in multiple-pollutant models. Generally, the toxicology of the pure compounds and their epidemiology diverge because atmospheric black carbon, ozone, and sulphate are associated and could interact with related toxic species. Although sulphate is a cooling agent, black carbon and ozone could together exert nearly half as much global warming as carbon dioxide. The complexity of these health and climate effects needs to be recognised in mitigation policies.
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Cardiovascular mortality and exposure to airborne fine particulate matter and cigarette smoke: shape of the exposure-response relationship.
Circulation
PUBLISHED: 08-31-2009
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Fine particulate matter exposure from both ambient air pollution and secondhand cigarette smoke has been associated with larger risks of cardiovascular mortality than would be expected on the basis of linear extrapolations of the relative risks from active smoking. This study directly assessed the shape of the exposure-response relationship between cardiovascular mortality and fine particulates from cigarette smoke and ambient air pollution.
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Recent advances in research on radiofrequency fields and health: 2004-2007.
J Toxicol Environ Health B Crit Rev
PUBLISHED: 08-28-2009
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The widespread use of wireless telecommunications devices, particularly mobile phones and wireless networks, has resulted in increased human exposure to radiofrequency (RF) fields. Although national and international agencies have established safety guidelines for exposure to RF fields, concerns remain about the potential for adverse health outcomes to occur in relation to RF field exposure. The extensive literature on RF fields and health was reviewed by a number of authorities, including the Royal Society of Canada (1999). This report is the third in a series of updates to the original report of the Royal Society of Canada, covering the period 2004-2007. In particular, the present study examined new data on (1) dosimetry and exposure assessment, (2) biological effects of RF fields such as enzyme induction, and (3) toxicological effects, including genotoxicity and carcinogenicity. Epidemiological studies of the potential health effects of RF exposure, particularly from mobile phones, were determined, along with human and animal studies of neurological and behavioural effects. Within the last 4 yrs investigators concluded that there is no clear evidence of adverse health effects associated with RF fields, although continued research is recommended to address specific areas of concern, including exposure to RF fields among children using mobile phones. The results of the ongoing 13-country World Health Organization INTERPHONE study of mobile phones may provide important new information on the potential cancer risks associated with mobile phone use.
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The psychosocial and socioeconomic consequences of bovine spongiform encephalopathy (BSE): a community impact study.
J. Toxicol. Environ. Health Part A
PUBLISHED: 08-22-2009
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The detection of the first indigenous case of bovine spongiform encephalopathy (BSE) in Canada on May 20, 2003, had significant consequences for the livestock industry. As a result, borders were closed by several trade partners, particularly the United States. The outbreak led to direct and indirect economic impacts to the "cattle" industry exceeding $6 billion. As a consequence of a number of risk management interventions implemented by the Canadian Food Inspection Agency (CFIA) and provincial agencies, the BSE outbreak appears to have been largely contained. The initial results from our study of the socioeconomic and psychosocial impact of BSE on the health and well-being of rural and farm families living in Canada, a topic that remains largely unexamined are presented. Our analysis of the outbreak raises a number of questions concerning the resulting consequences for farmers, their families, and their communities, including considerations from a social determinants of health perspective. In particular, our preliminary findings reveal that 5 years following the detection of the first indigenous case of BSE in Canada, ongoing uncertainty and stress resulting from unrecoverable financial losses continue to weigh heavily on the health and well-being of farmers, their families, and survival and sustainability of agricultural communities.
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Prionet Canada: a network of centres of excellence for research into prions and prion diseases.
J. Toxicol. Environ. Health Part A
PUBLISHED: 08-22-2009
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PrioNet Canadas strength in basic, applied, and social research is helping to solve the food, health safety, and socioeconomic problems associated with prion diseases. Prion diseases are transmissible, fatal neurodegenerative diseases of humans and animals. Examples of prion diseases include bovine spongiform encephalopathy (BSE, commonly known as "mad cow" disease), Creutzfeldt-Jakob disease in humans, and chronic wasting disease (CWD) in deer and elk. As of March 31, 2008, PrioNets interdisciplinary network included 62 scientific members, 5 international collaborators, and more than 150 students and young professionals working in partnership with 25 different government, nongovernment, and industry partners. PrioNets activities are developing strategies based on a sustained, rational approach that will mitigate, and ultimately control, prion diseases in Canada.
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Extended follow-up and spatial analysis of the American Cancer Society study linking particulate air pollution and mortality.
Res Rep Health Eff Inst
PUBLISHED: 07-25-2009
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We conducted an extended follow-up and spatial analysis of the American Cancer Society (ACS) Cancer Prevention Study II (CPS-II) cohort in order to further examine associations between long-term exposure to particulate air pollution and mortality in large U.S. cities. The current study sought to clarify outstanding scientific issues that arose from our earlier HEI-sponsored Reanalysis of the original ACS study data (the Particle Epidemiology Reanalysis Project). Specifically, we examined (1) how ecologic covariates at the community and neighborhood levels might confound and modify the air pollution-mortality association; (2) how spatial autocorrelation and multiple levels of data (e.g., individual and neighborhood) can be taken into account within the random effects Cox model; (3) how using land-use regression to refine measurements of air pollution exposure to the within-city (or intra-urban) scale might affect the size and significance of health effects in the Los Angeles and New York City regions; and (4) what exposure time windows may be most critical to the air pollution-mortality association. The 18 years of follow-up (extended from 7 years in the original study [Pope et al. 1995]) included vital status data for the CPS-II cohort (approximately 1.2 million participants) with multiple cause-of-death codes through December 31, 2000 and more recent exposure data from air pollution monitoring sites for the metropolitan areas. In the Nationwide Analysis, the influence of ecologic covariate data (such as education attainment, housing characteristics, and level of income; data obtained from the 1980 U.S. Census; see Ecologic Covariates sidebar on page 14) on the air pollution-mortality association were examined at the Zip Code area (ZCA) scale, the metropolitan statistical area (MSA) scale, and by the difference between each ZCA value and the MSA value (DIFF). In contrast to previous analyses that did not directly include ecologic covariates at the ZCA scale, risk estimates increased when ecologic covariates were included at all scales. The ecologic covariates exerted their greatest effect on mortality from ischemic heart disease (IHD), which was also the health outcome most strongly related with exposure to PM2.5 (particles 2.5 microm or smaller in aerodynamic diameter), sulfate (SO4(2-)), and sulfur dioxide (SO2), and the only outcome significantly associated with exposure to nitrogen dioxide (NO2). When ecologic covariates were simultaneously included at both the MSA and DIFF levels, the hazard ratio (HR) for mortality from IHD associated with PM2.5 exposure (average concentration for 1999-2000) increased by 7.5% and that associated with SO4(2-) exposure (average concentration for 1990) increased by 12.8%. The two covariates found to exert the greatest confounding influence on the PM2.5-mortality association were the percentage of the population with a grade 12 education and the median household income. Also in the Nationwide Analysis, complex spatial patterns in the CPS-II data were explored with an extended random effects Cox model (see Glossary of Statistical Terms at end of report) that is capable of clustering up to two geographic levels of data. Using this model tended to increase the HR estimate for exposure to air pollution and also to inflate the uncertainty in the estimates. Including ecologic covariates decreased the variance of the results at both the MSA and ZCA scales; the largest decrease was in residual variation based on models in which the MSA and DIFF levels of data were included together, which suggests that partitioning the ecologic covariates into between-MSA and within-MSA values more completely captures the sources of variation in the relationship between air pollution, ecologic covariates, and mortality. Intra-Urban Analyses were conducted for the New York City and Los Angeles regions. The results of the Los Angeles spatial analysis, where we found high exposure contrasts within the Los Angeles region, showed that air pollution-mortality risks were nearly 3 times greater than those reported from earlier analyses. This suggests that chronic health effects associated with intra-urban gradients in exposure to PM2.5 may be even larger between ZCAs within an MSA than the associations between MSAs that have been previously reported. However, in the New York City spatial analysis, where we found very little exposure contrast between ZCAs within the New York region, mortality from all causes, cardiopulmonary disease (CPD), and lung cancer was not elevated. A positive association was seen for PM2.5 exposure and IHD, which provides evidence of a specific association with a cause of death that has high biologic plausibility. These results were robust when analyses controlled (1) the 44 individual-level covariates (from the ACS enrollment questionnaire in 1982; see 44 Individual-Level Covariates sidebar on page 22) and (2) spatial clustering using the random effects Cox model. Effects were mildly lower when unemployment at the ZCA scale was included. To examine whether there is a critical exposure time window that is primarily responsible for the increased mortality associated with ambient air pollution, we constructed individual time-dependent exposure profiles for particulate and gaseous air pollutants (PM2.5 and SO2) for a subset of the ACS CPS-II participants for whom residence histories were available. The relevance of the three exposure time windows we considered was gauged using the magnitude of the relative risk (HR) of mortality as well as the Akaike information criterion (AIC), which measures the goodness of fit of the model to the data. For PM2.5, no one exposure time window stood out as demonstrating the greatest HR; nor was there any clear pattern of a trend in HR going from recent to more distant windows or vice versa. Differences in AIC values among the three exposure time windows were also small. The HRs for mortality associated with exposure to SO2 were highest in the most recent time window (1 to 5 years), although none of these HRs were significantly elevated. Identifying critical exposure time windows remains a challenge that warrants further work with other relevant data sets. This study provides additional support toward developing cost-effective air quality management policies and strategies. The epidemiologic results reported here are consistent with those from other population-based studies, which collectively have strongly supported the hypothesis that long-term exposure to PM2.5 increases mortality in the general population. Future research using the extended Cox-Poisson random effects methods, advanced geostatistical modeling techniques, and newer exposure assessment techniques will provide additional insight.
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Recall bias in the assessment of exposure to mobile phones.
J Expo Sci Environ Epidemiol
PUBLISHED: 07-03-2009
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Most studies of mobile phone use are case-control studies that rely on participants reports of past phone use for their exposure assessment. Differential errors in recalled phone use are a major concern in such studies. INTERPHONE, a multinational case-control study of brain tumour risk and mobile phone use, included validation studies to quantify such errors and evaluate the potential for recall bias. Mobile phone records of 212 cases and 296 controls were collected from network operators in three INTERPHONE countries over an average of 2 years, and compared with mobile phone use reported at interview. The ratio of reported to recorded phone use was analysed as measure of agreement. Mean ratios were virtually the same for cases and controls: both underestimated number of calls by a factor of 0.81 and overestimated call duration by a factor of 1.4. For cases, but not controls, ratios increased with increasing time before the interview; however, these trends were based on few subjects with long-term data. Ratios increased by level of use. Random recall errors were large. In conclusion, there was little evidence for differential recall errors overall or in recent time periods. However, apparent overestimation by cases in more distant time periods could cause positive bias in estimates of disease risk associated with mobile phone use.
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Health outcomes of low-dose ionizing radiation exposure among medical workers: a cohort study of the Canadian national dose registry of radiation workers.
Int J Occup Med Environ Health
PUBLISHED: 06-24-2009
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Medical workers can be exposed to low-dose ionizing radiation from various sources. The potential cancer risks associated with ionizing radiation exposure have been derived from cohort studies of Japanese atomic bomb survivors who had experienced acute, high-level exposure. Since such extrapolations are subject to uncertainty, direct information is needed on the risk associated with chronic low-dose occupational exposure to ionizing radiation.
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Does leptin play a role in obesity-asthma relationship?
Pediatr Allergy Immunol
PUBLISHED: 05-21-2009
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The increase of asthma has paralleled the rising obesity during the past decades. Obesity is characterized by the increase of leptin in the circulation. Leptin is an obesity gene product, and it can stimulate the production of pro-inflammatory mediators, such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 and interferon (IFN)-gamma. There is a link between leptin and asthma, especially in children. It remains unclear however, if leptin is in the pathway of obesity-asthma relationship and if it plays a distinctive role in asthma in obese vs. non-obese subjects. Since leptin is in a positive feedback loop with the pro-inflammatory cytokines such as TNF-alpha, there is a possibility that leptin is involved as a regulatory rather than an etiologic mechanism of asthma development. Weight loss is associated with decreased circulating leptin concentration in children. Weight control program may need to be considered in the treatment of asthma in obese children.
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Multi-jurisdictional expert opinion for improving childrens environmental health protection.
Int J Environ Health Res
PUBLISHED: 04-17-2009
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Expert opinion from Canada, the United States and European Union countries was solicited to examine the regulatory and non-regulatory approaches used to protect childrens environmental health. Thirty-five experts were interviewed by telephone from June 2004 to March 2005 using an open-ended survey questionnaire. Experts were asked to name legislative and non-legislative tools used to protect childrens environmental health in their jurisdiction as well as the effectiveness of approaches taken, barriers, facilitators, methods of evaluation, and recommendations for improving childrens health protection. A number of common themes were revealed by experts in different countries as well as novel approaches that could be used to improve childrens environmental health. Determining what types of governance and non-governance instruments are most effective based on experience from other jurisdictions, allows for the determination of common, effective, policy choice from shared childrens health environmental risks. It also provides a broad classification of different approaches that have been used for childrens environmental health. Three main areas suggested for strengthening childrens environmental health protection included: research and surveillance, institutional organization, and regulatory capacity.
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Air pollution and health: a European and North American approach (APHENA).
Res Rep Health Eff Inst
PUBLISHED: 04-02-2009
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This report provides the methodology and findings from the project: Air Pollution and Health: a European and North American Approach (APHENA). The principal purpose of the project was to provide an understanding of the degree of consistency among findings of multicity time-series studies on the effects of air pollution on mortality and hospitalization in several North American and European cities. The project included parallel and combined analyses of existing data. The investigators sought to understand how methodological differences might contribute to variation in effect estimates from different studies, to characterize the extent of heterogeneity in effect estimates, and to evaluate determinants of heterogeneity. The APHENA project was based on data collected by three groups of investigators for three earlier studies: (1) Air Pollution and Health: A European Approach (APHEA), which comprised two multicity projects in Europe. (Phase 1 [APHEA1] involving 15 cities, and Phase 2 [APHEA2] involving 32 cities); (2) the National Morbidity, Mortality, and Air Pollution Study (NMMAPS), conducted in the 90 largest U.S. cities; and (3) multicity research on the health effects of air pollution in 12 Canadian cities.
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Low dose ionizing radiation exposure and cardiovascular disease mortality: cohort study based on Canadian national dose registry of radiation workers.
Int J Occup Med Environ Health
PUBLISHED: 03-31-2009
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The purpose of our study was to assess the risk of cardiovascular disease (CVD) mortality in a Canadian cohort of 337 397 individuals (169 256 men and 168 141 women) occupationally exposed to ionizing radiation and included in the National Dose Registry (NDR) of Canada.
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Occupations and lung cancer: a population-based case-control study in British Columbia.
J. Toxicol. Environ. Health Part A
PUBLISHED: 03-25-2009
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An investigation based on a large population-based case-control study in British Columbia, Canada, was conducted to identify high-risk occupations for lung cancer by histological subtypes. Subjects were 14,755 male incident cancer cases for whom lifetime occupational histories and information on smoking and relevant covariates were collected. Occupational associations for 2998 lung cancer cases, including histological subtypes, were assessed by logistic regression using other cancer cases, excluding smoking-related cancers, as controls. An excess risk of lung cancer was found among workers in metal processing, bakers, and ship deck crew for all histological subtypes, and construction workers, chefs and cooks, and medical workers for specific histological subtypes. Occupational associations that are unique to histological subtypes of lung cancer were identified. Owing to a scarcity of literature in this area, future research needs to focus on confirming these histological associations, and identifying the risk from key exposures found within these occupations (e.g., medical radiation, electromagnetic fields, and cooking fumes).
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Long-term ozone exposure and mortality.
N. Engl. J. Med.
PUBLISHED: 03-13-2009
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Although many studies have linked elevations in tropospheric ozone to adverse health outcomes, the effect of long-term exposure to ozone on air pollution-related mortality remains uncertain. We examined the potential contribution of exposure to ozone to the risk of death from cardiopulmonary causes and specifically to death from respiratory causes.
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Toxicity testing in the 21st century: bringing the vision to life.
Toxicol. Sci.
PUBLISHED: 03-12-2009
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In 2007, the U.S. National Academy of Sciences released a report, Toxicity Testing in the 21st Century: A Vision and a Strategy, that envisions a not-so-distant future in which virtually all routine toxicity testing would be conducted in human cells or cell lines in vitro by evaluating cellular responses in a suite of toxicity pathway assays using high-throughput tests, that could be implemented with robotic assistance. Risk assessment based on results of these types of tests would shift towards the avoidance of significant perturbations of these pathways in exposed human populations. Dose-response modeling of perturbations of pathway function would be organized around computational systems biology models of the circuitry underlying each toxicity pathway. In vitro to in vivo extrapolations would rely on pharmacokinetic models to predict human blood and tissue concentrations under specific exposure conditions. All of the scientific tools needed to affect these changes in toxicity testing practices are either currently available or in an advanced state of development. A broad scientific discussion of this new vision for the future of toxicity testing is needed to motivate a departure from the traditional high dose animal-based toxicological tests, with its attendant challenges for dose and species extrapolation, towards a new approach more firmly grounded in human biology. The present paper, and invited commentaries on the report that will appear in Toxicological Sciences over the next year, are intended to initiate a dialog to identify challenges in implementing the vision and address obstacles to change.
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Recent oral contraceptive use and adverse birth outcomes.
Eur. J. Obstet. Gynecol. Reprod. Biol.
PUBLISHED: 02-23-2009
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To examine the possible association between oral contraceptive use and adverse birth outcomes.
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Health effects of radon: a review of the literature.
Int. J. Radiat. Biol.
PUBLISHED: 02-12-2009
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Radon is natural radioactive noble gas that can be found in soil, water, outdoor and indoor air. Exposure to radon accounts for more that 50% of the annual effective dose of natural radioactivity. The purpose of the current review is to summarize recent literature and evaluate the weight of evidence on the adverse health effects of radon.
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A multi-level analysis of risk factors for Schistosoma japonicum infection in China.
Int. J. Infect. Dis.
PUBLISHED: 02-04-2009
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The aim of this study was to explore the risk factors of schistosomiasis japonica in China, using a hierarchical multi-level model with individuals nested within villages.
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A literature review: the cardiovascular effects of exposure to extremely low frequency electromagnetic fields.
Int Arch Occup Environ Health
PUBLISHED: 01-26-2009
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The effects of exposure to extremely low frequency (ELF) electromagnetic fields (EMFs) on human cardiovascular parameters remain undetermined. Epidemiological studies have utilized dosimetry estimations of employee workplace exposure using altered heart rate variability (HRV) as predictive of certain cardiovascular pathologies. Laboratory studies have focused on macrocirculatory indicators including heart rate, HRV and blood pressure. Few studies have been conducted on the response of the microcirculatory system to EMF exposure. Attempts to replicate both epidemiological and laboratory studies have been mostly unsuccessful as study design, small sample populations and confounding variables have hampered progress to date. Identification of these problems, in the current context of international exposure guideline re-evaluation, is essential for future EMF studies. These studies should address the possible deleterious health effects of EMFs as well as the detection and characterization of subtle physiological changes they may induce. Recommendations for future work include investigating the macro- and microcirculatory relationship and the use of laboratory geomagnetic shielding.
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Toxicity testing in the 21st century: implications for human health risk assessment.
Risk Anal.
PUBLISHED: 01-16-2009
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At the request of the Environmental Protection Agency, the National Research Council (NRC) recently completed a major report entitled Toxicity Testing in the 21st Century: A Vision and a Strategy. The terms of reference for this report were to develop a long-range vision and strategic plan to advance the practices of toxicity testing and human health assessment of environmental agents. The report describes how current and anticipated scientific advances can be expected to transform toxicity testing to permit broader coverage of the universe of potentially toxic chemicals to which humans may be exposed, using more timely and more cost-effective methods for toxicity testing. The report envisages greatly expanded use of high- and medium-throughput in vitro screening assays, computational toxicology, and systems biology, along with other emerging high-content testing methodologies, such as functional genomics and transcriptomics. When fully implemented, the vision will transform the ways toxicity testing and chemical risk assessment are conducted, moving away from measuring apical health endpoints in experimental animals toward identification of significant perturbations of toxicity pathways using in vitro tests in human cells and cell lines. Population-based studies incorporating relevant biomarkers will also be useful in identifying pathway perturbations directly in humans and in interpreting the results of in vitro tests in the context of human health risk assessment. The present article summarizes and extends the NRC report and examines its implications for risk assessment practice.
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A systematic review and meta-analysis of childhood leukemia and parental occupational pesticide exposure.
Environ. Health Perspect.
PUBLISHED: 01-15-2009
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We conducted a systematic review and meta-analysis of childhood leukemia and parental occupational pesticide exposure.
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Radon and nonrespiratory mortality in the American Cancer Society cohort.
Am. J. Epidemiol.
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Radon is a known cause of human lung cancer. Previously, the authors observed a significant positive association between mean county-level residential radon concentrations and lung cancer mortality in the Cancer Prevention Study II (CPS-II), a large prospective study of nearly 1.2 million participants recruited in 1982 by the American Cancer Society. There was also a significant positive association with mortality from chronic obstructive pulmonary disease. Because it is unclear whether radon is associated with mortality from other malignant or nonmalignant disease, the authors examined the association between radon and nonrespiratory mortality in the CPS-II. Mean county-level residential radon concentrations (mean = 53.5 (standard deviation: 38.0) Bq/m(3)) were linked to participants by their zip code at enrollment. Cox proportional hazards regression models were used to estimate adjusted hazard ratios and 95% confidence intervals for all-cause (excluding lung cancer and respiratory mortality) and cause-specific mortality associated with radon concentrations. A total of 811,961 participants in 2,754 counties were analyzed, including 265,477 deaths through 2006. There were no clear associations between radon and nonrespiratory mortality in the CPS-II. These findings suggest that residential radon is not associated with any other mortality beyond lung cancer or chronic obstructive pulmonary disease.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.