Methylation of NR3C1 is related to maternal PTSD, parenting stress and maternal medial prefrontal cortical activity in response to child separation among mothers with histories of violence exposure.

Prior research has shown that mothers with Interpersonal violence-related posttraumatic stress disorder (IPV-PTSD) report greater difficulty in parenting their toddlers. Relative to their frequent early exposure to violence and maltreatment, these mothers display dysregulation of their hypothalamic pituitary adrenal axis (HPA-axis), characterized by hypocortisolism. Considering methylation of the promoter region of the glucocorticoid receptor gene NR3C1 as a marker for HPA-axis functioning, with less methylation likely being associated with less circulating cortisol, the present study tested the hypothesis that the degree of methylation of this gene would be negatively correlated with maternal IPV-PTSD severity and parenting stress, and positively correlated with medial prefrontal cortical (mPFC) activity in response to video-stimuli of stressful versus non-stressful mother-child interactions. Following a mental health assessment, 45 mothers and their children (ages 12-42 months) participated in a behavioral protocol involving free-play and laboratory stressors such as mother-child separation. Maternal DNA was extracted from saliva. Interactive behavior was rated on the CARE-Index. During subsequent fMRI scanning, mothers were shown films of free-play and separation drawn from this protocol. Maternal PTSD severity and parenting stress were negatively correlated with the mean percentage of methylation of NR3C1. Maternal mPFC activity in response to video-stimuli of mother-child separation versus play correlated positively to NR3C1 methylation, and negatively to maternal IPV-PTSD and parenting stress. Among interactive behavior variables, child cooperativeness in play was positively correlated with NR3C1 methylation. Thus, the present study is the first published report to our knowledge, suggesting convergence of behavioral, epigenetic, and neuroimaging data that form a psychobiological signature of parenting-risk in the context of early life stress and PTSD.

The long-term development of avalanche risk in settlements considering the temporal variability of damage potential

Recent studies on the avalanche risk in alpine settlements suggested a strong dependency of the development of risk on variations in damage potential. Based on these findings, analyses on probable maximum losses in avalanche-prone areas of the municipality of Davos (CH) were used as an indicator for the long-term development of values at risk. Even if the results were subject to significant uncertainties, they underlined the dependency of today's risk on the historical development of land-use: Small changes in the lateral extent of endangered areas had a considerable impact on the exposure of values. In a second step, temporal variations in damage potential between 1950 and 2000 were compared in two different study areas representing typical alpine socio-economic development patterns: Davos (CH) and Galtür (A). The resulting trends were found to be similar; the damage potential increased significantly in number and value. Thus, the development of natural risk in settlements can for a major part be attributed to long-term shifts in damage potential.

Model for ranking freshwater fish farms according to their risk of infection and illustration for viral haemorrhagic septicaemia

We developed a model to calculate a quantitative risk score for individual aquaculture sites. The score indicates the risk of the site being infected with a specific fish pathogen (viral haemorrhagic septicaemia virus (VHSV); infectious haematopoietic necrosis virus, Koi herpes virus), and is intended to be used for risk ranking sites to support surveillance for demonstration of zone or member state freedom from these pathogens. The inputs to the model include a range of quantitative and qualitative estimates of risk factors organised into five risk themes (1) Live fish and egg movements; (2) Exposure via water; (3) On-site processing; (4) Short-distance mechanical transmission; (5) Distance-independent mechanical transmission. The calculated risk score for an individual aquaculture site is a value between zero and one and is intended to indicate the risk of a site relative to the risk of other sites (thereby allowing ranking). The model was applied to evaluate 76 rainbow trout farms in 3 countries (42 from England, 32 from Italy and 2 from Switzerland) with the aim to establish their risk of being infected with VHSV. Risk scores for farms in England and Italy showed great variation, clearly enabling ranking. Scores ranged from 0.002 to 0.254 (mean score 0.080) in England and 0.011 to 0.778 (mean of 0.130) for Italy, reflecting the diversity of infection status of farms in these countries. Requirements for broader application of the model are discussed. Cost efficient farm data collection is important to realise the benefits from a risk-based approach.

Childhood cancer and residential exposure to highways: a nationwide cohort study.

Children living near highways are exposed to higher concentrations of traffic-related carcinogenic pollutants. Several studies reported an increased risk of childhood cancer associated with traffic exposure, but the published evidence is inconclusive. We investigated whether cancer risk is associated with proximity of residence to highways in a nation-wide cohort study including all children aged <16 years from Swiss national censuses in 1990 and 2000. Cancer incidence was investigated in time to event analyses (1990-2008) using Cox proportional hazards models and incidence density analyses (1985-2008) using Poisson regression. Adjustments were made for socio-economic factors, ionising background radiation and electromagnetic fields. In time to event analysis based on 532 cases the adjusted hazard ratio for leukaemia comparing children living <100 m from a highway with unexposed children (≥500 m) was 1.43 (95 % CI 0.79, 2.61). Results were similar in incidence density analysis including 1367 leukaemia cases (incidence rate ratio (IRR) 1.57; 95 % CI 1.09, 2.25). Associations were similar for acute lymphoblastic leukaemia (IRR 1.64; 95 % CI 1.10, 2.43) and stronger for leukaemia in children aged <5 years (IRR 1.92; 95 % CI 1.22, 3.04). Little evidence of association was found for other tumours. Our study suggests that young children living close to highways are at increased risk of developing leukaemia.

Immunodeficiency and the risk of cervical intra-epithelial neoplasia 2/3 and cervical cancer: A nested case-control study in the Swiss HIV Cohort Study.

HIV-infected women are at increased risk of cervical intra-epithelial neoplasia (CIN) and invasive cervical cancer (ICC), but it has been difficult to disentangle the influences of heavy exposure to HPV infection, inadequate screening, and immunodeficiency. A case-control study including 364 CIN2/3 and 20 ICC cases matched to 1,147 controls was nested in the Swiss HIV Cohort Study (1985-2013). CIN2/3 risk was significantly associated with low CD4+ cell counts, whether measured as nadir (odds ratio (OR) per 100-cell/μL decrease=1.15, 95% CI: 1.08, 1.22), or at CIN2/3 diagnosis (1.10, 95% CI: 1.04, 1.16). An association was evident even for nadir CD4+ 200-349 versus ≥350 cells/μL (OR=1.57, 95% CI: 1.09, 2.25). After adjustment for nadir CD4+, a protective effect of >2-year cART use was seen against CIN2/3 (OR versus never cART use=0.64, 95% CI: 0.42, 0.98). Despite low study power, similar associations were seen for ICC, notably with nadir CD4+ (OR for 50 versus >350 cells/μL= 11.10, 95% CI: 1.24, 100). HPV16-L1 antibodies were significantly associated with CIN2/3, but HPV16-E6 antibodies were nearly exclusively detected in ICC. In conclusion, worsening immunodeficiency, even at only moderately decreased CD4+ cell counts (200-349 CD4+ cells/μL), is a significant risk factor for CIN2/3 and cervical cancer. This article is protected by copyright. All rights reserved.

At risk or not at risk? A meta-analysis of the prognostic accuracy of psychometric interviews for psychosis prediction

An accurate detection of individuals at clinical high risk (CHR) for psychosis is a prerequisite for effective preventive interventions. Several psychometric interviews are available, but their prognostic accuracy is unknown. We conducted a prognostic accuracy meta-analysis of psychometric interviews used to examine referrals to high risk services. The index test was an established CHR psychometric instrument used to identify subjects with and without CHR (CHR+ and CHR-). The reference index was psychosis onset over time in both CHR+ and CHR- subjects. Data were analyzed with MIDAS (STATA13). Area under the curve (AUC), summary receiver operating characteristic curves, quality assessment, likelihood ratios, Fagan's nomogram and probability modified plots were computed. Eleven independent studies were included, with a total of 2,519 help-seeking, predominately adult subjects (CHR+: N=1,359; CHR-: N=1,160) referred to high risk services. The mean follow-up duration was 38 months. The AUC was excellent (0.90; 95% CI: 0.87-0.93), and comparable to other tests in preventive medicine, suggesting clinical utility in subjects referred to high risk services. Meta-regression analyses revealed an effect for exposure to antipsychotics and no effects for type of instrument, age, gender, follow-up time, sample size, quality assessment, proportion of CHR+ subjects in the total sample. Fagan's nomogram indicated a low positive predictive value (5.74%) in the general non-help-seeking population. Albeit the clear need to further improve prediction of psychosis, these findings support the use of psychometric prognostic interviews for CHR as clinical tools for an indicated prevention in subjects seeking help at high risk services worldwide.

The independent role of prenatal and postnatal exposure to active and passive smoking on the development of early wheeze in children.

Maternal smoking during pregnancy increases childhood asthma risk, but health effects in children of nonsmoking mothers passively exposed to tobacco smoke during pregnancy are unclear. We examined the association of maternal passive smoking during pregnancy and wheeze in children aged ≤2 years.Individual data of 27 993 mother-child pairs from 15 European birth cohorts were combined in pooled analyses taking into consideration potential confounders.Children with maternal exposure to passive smoking during pregnancy and no other smoking exposure were more likely to develop wheeze up to the age of 2 years (OR 1.11, 95% CI 1.03-1.20) compared with unexposed children. Risk of wheeze was further increased by children's postnatal passive smoke exposure in addition to their mothers' passive exposure during pregnancy (OR 1.29, 95% CI 1.19-1.40) and highest in children with both sources of passive exposure and mothers who smoked actively during pregnancy (OR 1.73, 95% CI 1.59-1.88). Risk of wheeze associated with tobacco smoke exposure was higher in children with an allergic versus nonallergic family history.Maternal passive smoking exposure during pregnancy is an independent risk factor for wheeze in children up to the age of 2 years. Pregnant females should avoid active and passive exposure to tobacco smoke for the benefit of their children's health.

The impact of ABCC11 polymorphisms on the risk of early-onset fluoropyrimidine toxicity

A missense variant (c.1637C>T, T546M) in ABCC11 encoding the MRP8 (multidrug resistance protein 8), a transporter of 5-fluorodeoxyuridine monophosphate, has been associated with an increased risk of 5-fluorouracil-related severe leukopenia. To validate this association, we investigated the impact of the ABCC11 variants c.1637C>T, c.538G>A and c.395+1087C>T on the risk of early-onset fluoropyrimidine-related toxicity in 514 cancer patients. The ABCC11 variant c.1637C>T was strongly associated with severe leukopenia in patients carrying risk variants in DPYD, encoding the key fluoropyrimidine-metabolizing enzyme dihydropyrimidine dehydrogenase (odds ratio (OR): 71.0; 95% confidence interval (CI): 2.5-2004.8; Pc.1637C>T*DPYD=0.013). In contrast, in patients without DPYD risk variants, no association with leukopenia (OR: 0.95; 95% CI: 0.34-2.6) or overall fluoropyrimidine-related toxicity (OR: 1.02; 95% CI: 0.5-2.1) was observed. Our study thus suggests that c.1637C>T affects fluoropyrimidine toxicity to leukocytes particularly in patients with high drug exposure, for example, because of reduced fluoropyrimidine catabolism.

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 Associations Between Social, Behavioral, and Health Risk Factors on a High School Student’s Decision to Pursue Post High School Plans

Background: Due to the relationship between SES and health, pursuing post high-school plans can lead to better future health outcomes for the student. The current paper assesses how behavioral and health risk factors, and family and social support, effect a student’s decision to pursue post high school plans. Methods: Data from the Youth Behavioral Component of the 2007 Connecticut School Health Survey were analyzed. Composite measures of exposure to/participation in violent behavior, mental and physical health, family/social support and substance abuse were created. The effects of these domains on the decision to pursue post high-school plans were assessed using logistic regression. Data were stratified by socioeconomic status. Results: Low SES students were more likely than high SES students to be doubtful for post high-school plans. Cocaine abuse emerged as the risk factor that put low SES students at the highest odds of not pursuing post high-school plans, followed by involvement in violent/aggressive behavior, and receiving less family/social support than their peers. Similar findings regarding violence and family/social support were found in the high SES group. Findings regarding substance abuse in the high SES group were not statistically significant. Discussion: Prevention programs regarding violence and substance abuse may have the added benefit of increasing the likelihood that high school students will make post high school plans. Preventing cocaine use among low SES students may be of particular importance. Violence prevention measures should be tailored to the target group. Adequate family/social support emerged as an encouraging factor for post high school plans.

Is the Cheating Risk Always Higher in Online Instruction Compared to Face-to-Face Instruction?

This article analyzes the exposure to cheating risk of online courses relative to face-to-face courses at a single institution. For our sample of 20 online courses we report that the cheating risk is higher than for equivalent face-to-face courses because of reliance on un-proctored multiple choice exams. We conclude that the combination of a proctored final exam, and strategic use cheating deterrents in the administration of un-proctored multiple choice exams, would significantly reduce the cheating risk differential without substantially altering the assessment design of online instruction.

Contribution of activity and skin temperature to the risk of developing pressure ulcers in nursing facility residents

Purpose. The central concepts in pressure ulcer risk are exposure to external pressure caused by inactivity and tissue tolerance to pressure, a factor closely related to blood flow. Inactivity measures are effective in predicting pressure ulcer risk. The purpose of the study is to evaluate whether a physiological measure of skin blood flow improves pressure ulcer risk prediction. Skin temperature regularity and self-similarity, as proxy measures of blood flow, and not previously described, may be undefined pressure ulcer risk factors. The specific aims were to determine whether a sample of nursing facility residents at high risk of pressure ulcers classified using the Braden Scale for Pressure Sore Risk© differ from a sample of low risk residents according to (1) exposure to external pressure as measured by resident activity, (2) tissue tolerance to external pressure as measured by skin temperature, and (3) skin temperature fluctuations and recovery in response to a commonly occurring stressor, bathing and additionally whether (4) scores on the Braden Scale mobility subscale score are related to entropy and the spectral exponent. ^ Methods. A two group observational time series design was used to describe activity and skin temperature regularity and self-similarity, calculating entropy and the spectral exponent using detrended fluctuation analysis respectively. Twenty nursing facility residents wore activity and skin temperature monitors for one week. One bathing episode was observed as a commonly occurring stressor for skin temperature.^ Results. Skin temperature multiscale entropy (MSE), F(1, 17) = 5.55, p = .031, the skin temperature spectral exponent, F(1, 17) = 6.19, p = .023, and the activity mean MSE, F(1, 18) = 4.52, p = .048 differentiated the risk groups. The change in skin temperature entropy during bathing was significant, t(16) = 2.55, p = .021, (95% CI, .04-.40). Multiscale entropy for skin temperature was lowest in those who developed pressure ulcers, F(1, 18) = 35.14, p < .001.^ Conclusions. This study supports the tissue tolerance component of the Braden and Bergstrom conceptual framework and shows differences in skin temperature multiscale entropy between pressure ulcer risk categories, pressure ulcer outcome, and during a commonly occurring stressor. ^

Risk factors for Clostridium difficile nosocomial diarrhea in patients at the Michael E. Debakey Veterans Affairs Medical Center, Houston, Texas

Background. Clostridium difficile is the leading cause of hospital associated infectious diarrhea and colitis. About 3 million cases of Clostridium difficile diarrhea occur each year with an annual cost of $1 billion. ^ About 20% of patients acquire C. difficile during hospitalization. Infection with Clostridium difficile can result in serious complications, posing a threat to the patient's life. ^ Purpose. The aim of this research was to demonstrate the uniqueness in the characteristics of C. difficile positive nosocomial diarrhea cases compared with C. difficile negative nosocomial diarrhea controls admitted to a local hospital. ^ Methods. One hundred and ninety patients with a positive test and one hundred and ninety with a negative test for Clostridium difficile nosocomial diarrhea, selected from patients tested between January 1, 2002 and December 31, 2003, comprised the study population. Demographic and clinical data were collected from medical records. Logistic regression analyses were conducted to determine the associated odds between selected variables and the outcome of Clostridium difficile nosocomial diarrhea. ^ Results. For the antibiotic classes, cephalosporins (OR, 1.87; CI 95, 1.23 to 2.85), penicillins (OR, 1.57; CI 95, 1.04 to 2.37), fluoroquinolones (OR, 1.65; CI 95, 1.09 to 2.48) and antifungals (OR, 2.17; CI 95, 1.20 to 3.94), were significantly associated with Clostridium difficile nosocomial diarrhea Ceftazidime (OR, 1.95; CI 95, 1.25 to 3.03, p=0.003), gatifloxacin (OR, 1.97; CI 95, 1.31 to 2.97, p=0.001), clindamycin (OR, 3.13; CI 95, 1.99 to 4.93, p<0.001) and vancomycin (OR, 1.77; CI 95, 1.18 to 2.66, p=0.006, were also significantly associated with the disease. Vancomycin was not statistically significant when analyzed in a multivariable model. Other significantly associated drugs were, antacids, laxatives, narcotics and ranitidine. Prolong use of antibiotics and an increased number of comorbid conditions were also associated with C. difficile nosocomial diarrhea. ^ Conclusion. The etiology for C. difficile diarrhea is multifactorial. Exposure to antibiotics and other drugs, prolonged antibiotic usage, the presence and severity of comorbid conditions and prolonged hospital stay were shown to contribute to the development of the disease. It is imperative that any attempt to prevent the disease, or contain its spread, be done on several fronts. ^

Risk of adult-onset asthma in Mexican-American women employed in food preparation or food service

Existing literature examining the association between occupation and asthma has not been adequately powered to address this question in the food preparation or food service industries. Few studies have addressed the possible link between occupational exposure to cooking fumes and asthma. This secondary analysis of cohort study data aimed to investigate the association between adult-onset asthma and exposure to: (a) cooking fumes at work or (b) longest-held employment in food preparation or food service (e.g. waiters and waitresses, food preparation workers, non-restaurant food servers, etc.). Participants arose from a cohort of Mexican-American women residing in Houston, TX, recruited between July 2001 and June 2007. This analysis used Cox proportional-hazards regression to estimate the hazard ratio of adult-onset asthma given the exposures of interest, adjusting for age, BMI, smoking status, acculturation, and birthplace. We found a strong association between adult-onset asthma and occupational exposure to cooking fumes (hazard ratio [HR] = 1.77; 95% confidence interval [CI], 1.15, 2.72), especially in participants whose longest-held occupation was not in the food-related industry (HR = 2.12; 95% CI, 1.21, 3.60). In conclusion, adult-onset asthma is a serious public health concern for food industry workers. ^

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. ^