Neural correlates of evaluating hazards of high risk.

In personal and in society related context, people often evaluate the risk of environmental and technological hazards. Previous research addressing neuroscience of risk evaluation assessed particularly the direct personal risk of presented stimuli, which may have comprised for instance aspects of fear. Further, risk evaluation primarily was compared to tasks of other cognitive domains serving as control conditions, thus revealing general risk related brain activity, but not such specifically associated with estimating a higher level of risk. We here investigated the neural basis on which lay-persons individually evaluated the risk of different potential hazards for the society. Twenty healthy subjects underwent functional magnetic resonance imaging while evaluating the risk of fifty more or less risky conditions presented as written terms. Brain activations during the individual estimations of 'high' against 'low' risk, and of negative versus neutral and positive emotional valences were analyzed. Estimating hazards to be of high risk was associated with activation in medial thalamus, anterior insula, caudate nucleus, cingulate cortex and further prefrontal and temporo-occipital areas. These areas were not involved according to an analysis of the emotion ratings. In conclusion, we emphasize a contribution of the mentioned brain areas involved to signal high risk, here not primarily associated with the emotional valence of the risk items. These areas have earlier been reported to be associated with, beside emotional, viscerosensitive and implicit processing. This leads to assumptions of an intuitive contribution, or a "gut-feeling", not necessarily dependent of the subjective emotional valence, when estimating a high risk of environmental hazards.

Background Ionizing Radiation and the Risk of Childhood Cancer: A Census-Based Nationwide Cohort Study

BACKGROUND Exposure to medium or high doses of ionizing radiation is a known risk factor for cancer in children. The extent to which low dose radiation from natural sources contributes to the risk of childhood cancer remains unclear. OBJECTIVES In a nationwide census-based cohort study, we investigated whether the incidence of childhood cancer was associated with background radiation from terrestrial gamma and cosmic rays. METHODS Children aged <16 years in the Swiss National Censuses in 1990 and 2000 were included. The follow-up period lasted until 2008 and incident cancer cases were identified from the Swiss Childhood Cancer Registry. A radiation model was used to predict dose rates from terrestrial and cosmic radiation at locations of residence. Cox regression models were used to assess associations between cancer risk and dose rates and cumulative dose since birth. RESULTS Among 2,093,660 children included at census, 1,782 incident cases of cancer were identified including 530 with leukemia, 328 with lymphoma, and 423 with a tumor of the central nervous system (CNS). Hazard ratios for each mSv increase in cumulative dose of external radiation were 1.03 (95% CI: 1.01, 1.05) for any cancer, 1.04 (1.00, 1.08) for leukemia, 1.01 (0.96, 1.05) for lymphoma, and 1.04 (1.00, 1.08) for CNS tumors. Adjustment for a range of potential confounders had little effect on the results. CONCLUSIONS Our study suggests that background radiation may contribute to the risk of cancer in children including leukemia and CNS tumors.

Carriage of the PNPLA3 rs738409 C >G polymorphism confers an increased risk of non-alcoholic fatty liver disease associated hepatocellular carcinoma.

BACKGROUND & AIMS Subtle inter-patient genetic variation and environmental factors combine to determine disease progression in non-alcoholic fatty liver disease (NAFLD). Carriage of the PNPLA3 rs738409 c.444C >G minor allele (encoding the I148M variant) has been robustly associated with advanced NAFLD. Although most hepatocellular carcinoma (HCC) is related to chronic viral hepatitis or alcoholic liver disease, the incidence of NAFLD-related HCC is increasing. We examined whether rs738409 C >G was associated with HCC-risk in patients with NAFLD. METHODS PNPLA3 rs738409 genotype was determined by allelic discrimination in 100 European Caucasians with NAFLD-related HCC and 275 controls with histologically characterised NAFLD. RESULTS Genotype frequencies were significantly different between NAFLD-HCC cases (CC=28, CG=43, GG=29) and NAFLD-controls (CC=125, CG=117, GG=33) (p=0.0001). In multivariate analysis adjusted for age, gender, diabetes, BMI, and presence of cirrhosis, carriage of each copy of the rs738409 minor (G) allele conferred an additive risk for HCC (adjusted OR 2.26 [95% CI 1.23-4.14], p=0.0082), with GG homozygotes exhibiting a 5-fold [1.47-17.29], p=0.01 increased risk over CC. When compared to the UK general population (1958 British Birth Cohort, n=1476), the risk-effect was more pronounced (GC vs. CC: unadjusted OR 2.52 [1.55-4.10], p=0.0002; GG vs. CC: OR 12.19 [6.89-21.58], p<0.0001). CONCLUSIONS Carriage of the PNPLA3 rs738409 C >G polymorphism is not only associated with greater risk of progressive steatohepatitis and fibrosis but also of HCC. If validated, these findings suggest that PNPLA3 genotyping has the potential to contribute to multi-factorial patient-risk stratification, identifying those to whom HCC surveillance may be targeted.

A Multi-Breed Genome-Wide Association Analysis for Canine Hypothyroidism Identifies a Shared Major Risk Locus on CFA12.

Hypothyroidism is a complex clinical condition found in both humans and dogs, thought to be caused by a combination of genetic and environmental factors. In this study we present a multi-breed analysis of predisposing genetic risk factors for hypothyroidism in dogs using three high-risk breeds-the Gordon Setter, Hovawart and the Rhodesian Ridgeback. Using a genome-wide association approach and meta-analysis, we identified a major hypothyroidism risk locus shared by these breeds on chromosome 12 (p = 2.1x10-11). Further characterisation of the candidate region revealed a shared ~167 kb risk haplotype (4,915,018-5,081,823 bp), tagged by two SNPs in almost complete linkage disequilibrium. This breed-shared risk haplotype includes three genes (LHFPL5, SRPK1 and SLC26A8) and does not extend to the dog leukocyte antigen (DLA) class II gene cluster located in the vicinity. These three genes have not been identified as candidate genes for hypothyroid disease previously, but have functions that could potentially contribute to the development of the disease. Our results implicate the potential involvement of novel genes and pathways for the development of canine hypothyroidism, raising new possibilities for screening, breeding programmes and treatments in dogs. This study may also contribute to our understanding of the genetic etiology of human hypothyroid disease, which is one of the most common endocrine disorders in humans.

A Tort for Risk and Endogenous Bankruptcy

Conventional tort law bars victims of exposure to a toxic substance from filing suit until they actually develop symptoms of illness. Practically speaking, this rule often bars recovery due to bankruptcy and causal uncertainty. One solution is to allow victims to file at exposure for expected damages (a tort for risk). The trade-off is that such a rule may trigger a race to file among exposure victims, thereby itself inducing bankruptcy. This paper characterizes the conditions under which such a race will occur in equilibrium and examines the implications for social welfare.

The normal range of the leukocyte count: Implications for surveillance of occupational and environmental exposure and the practice of preventive medicine

Leukopenia, the leukocyte count, and prognosis of disease are interrelated; a systematic search of the literature was undertaken to ascertain the strength of the evidence. One hundred seventy-one studies were found from 1953 onward pertaining to the predictive capabilities of the leukocyte count. Of those studies, 42 met inclusion criteria. An estimated range of 2,200cells/μL to 7,000cells/μL was determined as that which indicates good prognosis in disease and indicates the least amount of risk to an individual overall. Tables of the evidence are included indicating the disparate populations examined and the possible degree of association. ^

An examination of the Gonorrhea Cases & Places study: An analysis of the Theory of Gender and Power, Situational/Environmental Variables Theory, and Sexual Script Theory as it relates to risky sexual behavior in African American adults

Objective. The purpose of the study is to provide a holistic depiction of behavioral & environmental factors contributing to risky sexual behaviors among predominantly high school educated, low-income African Americans residing in urban areas of Houston, TX utilizing the Theory of Gender and Power, Situational/Environmental Variables Theory, and Sexual Script Theory. ^ Methods. A cross-sectional study was conducted via questionnaires among 215 Houston area residents, 149 were women and 66 were male. Measures used to assess behaviors of the population included a history of homelessness, use of crack/cocaine among several other illicit drugs, the type of sexual partner, age of participant, age of most recent sex partner, whether or not participants sought health care in the last 12 months, knowledge of partner's other sexual activities, symptoms of depression, and places where partner's were met. In an effort to determine risk of sexual encounters, a risk index employing the variables used to assess condom use was created categorizing sexual encounters as unsafe or safe. ^ Results. Variables meeting the significance level of p<.15 for the bivariate analysis of each theory were entered into a binary logistic regression analysis. The block for each theory was significant, suggesting that the grouping assignments of each variable by theory were significantly associated with unsafe sexual behaviors. Within the regression analysis, variables such as sex for drugs/money, low income, and crack use demonstrated an effect size of ≥±1, indicating that these variables had a significant effect on unsafe sexual behavioral practices. ^ Conclusions. Variables assessing behavior and environment demonstrated a significant effect when categorized by relation to designated theories. ^

Environmental influences on self-reported leisure-time physical activity in the Austin/Travis County STEPS survey 2005--2009

This study was an examination of environmental and social correlates of physical inactivity in a socio-economically disadvantaged community. This study was a secondary analysis of data collected by the Austin/Travis County Department of Health and Human Services. The study included an analysis of perceived environmental influences (e.g. access to physical support features like sidewalks and streetlights). This study also investigated several features of the social environment (e.g. perceived neighborhood crime and social influence). Participants’ beliefs and attitudes about the neighborhood were investigated. Results included estimates of the association between neighborhood factors and physical inactivity controlling for age, gender and education. This study found significant associations for social and environmental variables with physical inactivity. The goal of this work was to identify factors that contribute to inactivity and address a number of environmental and neighborhood risk factors that contribute to sedentary behaviors in a population of relative social and economic disadvantage.^

Evaluation of environmental contamination of Clostridium difficile associated diarrhea in hospital rooms at St. Luke's Episcopal Hospital (SLEH) and review of literature on environmental sampling

The study was carried out at St. Luke's Episcopal Hospital to evaluate environmental contamination of Clostridium difficile in the infected patient rooms. Samples were collected from the high risk areas and were immediately cultured for the presence of Clostridium difficile . Lack of microbial typing prevented the study of molecular characterization of the Clostridium difficile isolates obtained led to a change in the study hypothesis. The study found a positivity of 10% among 50 Hospital rooms sampled for the presence of Clostridium difficile. The study provided data that led to recommendations that routine environmental sampling be carried in the hospital rooms in which patients with CDAD are housed and that effective environmental disinfection methods are used. The study also recommended molecular typing methods to allow characterization of the CD strains isolated from patients and environmental sampling to determine their type, similarity and origin.^

Hormone therapy and physical activity as predictors of lung cancer risk and survival: The California Teachers Study

Cigarette smoking is responsible for the majority of lung cancer cases worldwide; however, a proportion of never smokers still develop lung cancer over their lifetime, prompting investigation into additional factors that may modify lung cancer incidence, as well as mortality. Although hormone therapy (HT), physical activity (PA), and lung cancer have been previously examined, the associations remain unclear. This study investigated exposure to HT and PA that may modulate underlying mechanisms of lung cancer etiology and progression among women by using existing, de-identified data from the California Teachers Study (CTS).^ The CTS cohort, established in 1995–1996, has 133,479 active and retired female teachers and administrators, recruited through the California State Teachers Retirement System, and followed annually for cancer diagnosis, death, and change of address. Each woman enrolled in the CTS returned a questionnaire covering a wide variety of issues related to cancer risk and women's health, including recent and past HT use and physical activity, as well as active and environmental cigarette smoke exposure. Complete data to assess the associations between HT and lung cancer risk and survival were available for 60,592 postmenopausal women. Between 1995 and 2007, 727 of these women were diagnosed with invasive lung cancer; 441 of these died. Complete data to assess the associations between PA and lung cancer risk and survival were available for 118,513 women. Between 1995 and 2007, 853 of these women were diagnosed with invasive lung cancer; 516 of these died.^ After careful adjustment for smoking habits and other potential confounders, no measure of HT use was associated with lung cancer risk; however, any HT use (vs. no use) was associated with a decrease in lung-cancer-specific mortality. Specifically, among women who only used estrogen (E-only), decreases in lung cancer mortality were seen for recent use, but not for former use; no association was observed for estrogen plus progestin (E+P). Furthermore, among former users of HT, a statistically significant decrease in lung cancer mortality was observed for E-only use within 5 years prior to baseline, but not for E-only use >5 years prior to baseline. Neither long-term recreational PA nor recent recreational PA alone were associated with lung cancer risk; however, among women with a BMI<25 and ever smokers, high long-term moderate+strenuous PA was associated with a decrease in lung cancer risk. Women with non-local disease showed a decrease in lung cancer mortality associated with increasing duration of strenuous long-term activity, and 1.50-3.00 h/wk/y of recent moderate or recent strenuous PA. Long-term moderate PA was associated with decreased lung cancer mortality in never smokers, whereas recent moderate PA was associated with increased lung cancer mortality in current smokers. ^ Placing our findings in the context of the current literature, HT does not appear to be associated with lung cancer risk and previous studies reporting a protective effect of HT use on lung cancer risk may be subject to residual confounding by smoking. Looking at our findings regarding PA overall, the evidence still remains inconclusive regarding whether or not physical activity influence lung cancer risk or mortality. Our results suggest that recreational PA may associated with decreased lung cancer risk among women with BMI<25 and ever smoking-women; however, residual confounding by smoking should be strongly considered. To our knowledge, this is the first study to investigate lifetime recreational PA and lung cancer mortality among women. Our results contribute to the growing body of knowledge regarding non-smoking-related risk factors for lung cancer incidence and mortality among women. Given the potential clinical and interventional significance, further study and validation of these findings is warranted.^

Secondary data analysis of lead screening compliance in high-risk children

Introduction. Despite the ban of lead-containing gasoline and paint, childhood lead poisoning remains a public health issue. Furthermore, a Medicaid-eligible child is 8 times more likely to have an elevated blood lead level (EBLL) than a non-Medicaid child, which is the primary reason for the early detection lead screening mandate for ages 12 and 24 months among the Medicaid population. Based on field observations, there was evidence that suggested a screening compliance issue. Objective. The purpose of this study was to analyze blood lead screening compliance in previously lead poisoned Medicaid children and test for an association between timely lead screening and timely childhood immunizations. The mean months between follow-up tests were also examined for a significant difference between the non-compliant and compliant lead screened children. Methods. Access to the surveillance data of all childhood lead poisoned cases in Bexar County was granted by the San Antonio Metropolitan Health District. A database was constructed and analyzed using descriptive statistics, logistic regression methods and non-parametric tests. Lead screening at 12 months of age was analyzed separately from lead screening at 24 months. The small portion of the population who were also related were included in one analysis and removed from a second analysis to check for significance. Gender, ethnicity, age of home, and having a sibling with an EBLL were ruled out as confounders for the association tests but ethnicity and age of home were adjusted in the nonparametric tests. Results. There was a strong significant association between lead screening compliance at 12 months and childhood immunization compliance, with or without including related children (p<0.00). However, there was no significant association between the two variables at the age of 24 months. Furthermore, there was no significant difference between the median of the mean months of follow-up blood tests among the non-compliant and compliant lead screened population for at the 12 month screening group but there was a significant difference at the 24 month screening group (p<0.01). Discussion. Descriptive statistics showed that 61% and 56% of the previously lead poisoned Medicaid population did not receive their 12 and 24 month mandated lead screening on time, respectively. This suggests that their elevated blood lead level may have been diagnosed earlier in their childhood. Furthermore, a child who is compliant with their lead screening at 12 months of age is 2.36 times more likely to also receive their childhood immunizations on time compared to a child who was not compliant with their 12 month screening. Even though there was no statistical significant association found for the 24 month group, the public health significance of a screening compliance issue is no less important. The Texas Medicaid program needs to enforce lead screening compliance because it is evident that there has been no monitoring system in place. Further recommendations include a need for an increased focus on parental education and the importance of taking their children for wellness exams on time.^

An assessment of risk of osteogenic sarcoma from exposure to radium

The etiology of the vast majority of osteosarcoma deaths has not been explained. A possible explanation might be lifetime ingestion of radium from environmental sources which might give rise to differential risk. This study was an effort toward understanding the role of naturally occurring radium in the etiology of bone cancer. Furthermore, there was an interest in the interaction of between radionuclides and selenium; the latter believed to be a potential anticarcinogen.^ Two approaches were used to evaluate the association between environmental radium, selenium and osteogenic sarcoma: (1) spatial and temporal patterns of osteogenic sarcoma mortality in Texas were described for the period from 1969 to 1988; and (2) a case-control study was performed using 974 osteosarcoma deaths and category-matched controls selected from other deaths to evaluate the association between this disease and residency history as an indirect measure of radium and selenium exposures.^ Analyses and comparison of mortality in a population exposed to regions of elevated levels of radium 226,228 and elevated levels of selenium in drinking water with those in a matched control population have resulted in three observations: (1) there appeared to be a slight protective effect for residing in areas high in radium; (2) there were no significant differences between cases and controls when observed for length of residence or residence in urban/rural regions of high or low radium; and (3) although regions high in selenium appeared to have a decreased risk for bone cancer and urban areas in regions of elevated selenium showed an increased risk of bone cancer, these differences were not significant. ^

Planning and implementation efficacy as a determinant of health risk communication outcomes: Case studies of the U.S. Public Health Service (PHS)

This study was conducted under the auspices of the Subcommittee on Risk Communication and Education of the Committee to Coordinate Environmental Health and Related Programs (CCEHRP) to determine how Public Health Service (PHS) agencies are communicating information about health risk, what factors contributed to effective communication efforts, and what specific principles, strategies, and practices best promote more effective health risk communication outcomes.^ Member agencies of the Subcommittee submitted examples of health risk communication activities or decisions they perceived to be effective and some examples of cases they thought had not been as effective as desired. Of the 10 case studies received, 7 were submitted as examples of effective health risk communication, and 3, as examples of less effective communication.^ Information contained in the 10 case studies describing the respective agencies' health risk communication strategies and practices was compared with EPA's Seven Cardinal Rules of Risk Communication, since similar rules were not found in any PHS agency. EPA's rules are: (1) Accept and involve the public as a legitimate partner. (2) Plan carefully and evaluate your efforts. (3) Listen to the public's specific concerns. (4) Be honest, frank, and open. (5) Coordinate and collaborate with other credible sources. (6) Meet the needs of the media. (7) Speak clearly and with compassion.^ On the basis of case studies analysis, the Subcommittee, in their attempts to design and implement effective health risk communication campaigns, identified a number of areas for improvement among the agencies. First, PHS agencies should consider developing a focus specific to health risk communication (i.e., office or specialty resource). Second, create a set of generally accepted practices and guidelines for effective implementation and evaluation of PHS health risk communication activities and products. Third, organize interagency initiatives aimed at increasing awareness and visibility of health risk communication issues and trends within and between PHS agencies.^ PHS agencies identified some specific implementation strategies the CCEHRP might consider pursuing to address the major recommendations. Implementation strategies common to PHS agencies emerged in the following five areas: (1) program development, (2) building partnerships, (3) developing training, (4) expanding information technologies, and (5) conducting research and evaluation. ^