Exposure to Political Violence in Northern Ireland and Outcome of First Episode Psychosis

The impact of political violence on individuals presenting with an episode of first episode psychosis has not been examined. Individuals were assessed for exposure to political violence in Northern Ireland (the “Troubles”) by asking for a response to 2 questions: one asked about the impact of violence “on your area”; the second about the impact of violence “on you or your family’s life.” The participants were separated into 2 groups (high and low impact) for each question. Symptom profiles and rates of substance misuse were compared across the groups at baseline and at 3-year follow up. Of the 178 individuals included in the study 66 (37.1%) reported a high impact of the “Troubles” on their life and 81 (45.5%) a high impact of the “Troubles” on their area. There were no significant differences in symptom profile or rates of substance misuse between high and low groups at presentation. At 3-year follow-up high impact of the “Troubles” on life was associated with higher Positive and Negative Symptom Scale (PANSS) Total (P = .01), PANSS-Positive (P < .05), and PANSS-General (P < .01) scores and lower global assessment of functioning disability (P < .05) scores, after adjusting for confounding factors. Impact of the “Troubles” on area was not associated with differences in symptom outcomes. This finding adds to the evidence that outcomes in psychosis are significantly impacted by environmental factors and suggests that greater attention should be paid to therapeutic strategies designed to address the impact of trauma.

Religious actions speak louder than words::exposure to credibilityenhancing displays predicts theism

One of the central aims of the cognitive science of religion (CSR) is to explain why supernatural agent beliefs are so widespread. A related but distinct aim is to explain why some individuals hold supernatural agent beliefs but others do not. Here, we aim to provide an initial test of the power of exposure to what Henrich calls “credibility enhancing displays” (or “CREDs”) in determining whether or not an individual holds explicit supernatural agent beliefs. We present evidence from two studies of Americans suggesting that exposure to CREDs, as measured by a scale we developed and validated, predicts current theism vs. non-theism, certainty of God’s existence/non-existence, and religiosity while controlling for overall religious socialization. These results are among the first to empirically support the theorized significance of CREDs for the acquisition of supernatural agent beliefs.

Challenging conventional risk assessment with respect to human exposure to multiple food contaminants in food: A case study using maize

Mycotoxins and heavy metals are ubiquitous in the environment and contaminate many foods. The widespread use of pesticides in crop production to control disease contributes further to the chemical contamination of foods. Thus multiple chemical contaminants threaten the safety of many food commodities; hence the present study used maize as a model crop to identify the severity in terms of human exposure when multiple contaminants are present. High Content Analysis (HCA) measuring multiple endpoints was used to determine cytotoxicity of complex mixtures of mycotoxins, heavy metals and pesticides. Endpoints included nuclear intensity (NI), nuclear area (NA), plasma membrane permeability (PMP), mitochondrial membrane potential (MMP) and mitochondrial mass (MM). At concentrations representing legal limits of each individual contaminant in maize (3. ng/ml ochratoxin A (OTA), 1. μg/ml fumonisin B1 (FB1), 2. ng/ml aflatoxin B1 (AFB1), 100. ng/ml cadmium (Cd), 150. ng/ml arsenic (As), 50. ng/ml chlorpyrifos (CP) and 5. μg/ml pirimiphos methyl (PM), the mixtures (tertiary mycotoxins plus Cd/As) and (tertiary mycotoxins plus Cd/As/CP/PM) were cytotoxic for NA and MM endpoints with a difference of up to 13.6% (. p≤. 0.0001) and 12% (. p≤. 0.0001) respectively from control values. The most cytotoxic mixture was (tertiary mycotoxins plus Cd/As/CP/PM) across all 4 endpoints (NA, NI, MM and MMP) with increases up to 61.3%, 23.0%, 61.4% and 36.3% (. p≤. 0.0001) respectively. Synergy was evident for two endpoints (NI and MM) at concentrations contaminating maize above legal limits, with differences between expected and measured values of (6.2-12.4% (. p≤. 0.05-. p≤. 0.001) and 4.5-12.3% (. p≤. 0.05-. p≤. 0.001) for NI and MM, respectively. The study introduces for the first time, a holistic approach to identify the impact in terms of toxicity to humans when multiple chemical contaminants are present in foodstuffs. Governmental regulatory bodies must begin to contemplate how to safeguard the population when such mixtures of contaminants are found in foods and this study starts to address this critical issue.

Breaking and Entering: Examining the role of stress and aerial exposure in predator-prey relationships between the common shore crab (Carcinus maenas) and cultivated blue mussels (Mytilus edulis).

During benthic cultivation Mytilus edulis (blue mussels) are subject to predation pressure from a number of predators including Carcinus maenas (shore crabs). This predator can be responsible for substantial losses of mussels from the fishery and a full understanding of the predator–prey relationship between M. edulis and C. maenas is required to ensure attempts that reduce predatory pressure and subsequent commercial loss are successful. Whilst much work has examined the prey–predator size relationships between C. maenas and M. edulis, far less research has investigated how stress, such as periods of extended aerial exposure, may affect these relationships. We tested whether profit in terms of calories gained by crabs consuming mussels stressed by aerial exposure for 48 h differed from that of mussels at ambient conditions and whether being stressed affected the mussel's likelihood of predation. We also tested whether the size relationship between predators and their prey differed when mussels were stressed. We found that the profitability of prey (calories gained per second of handling time) did not vary between stressed and unstressed mussels. Handling times for stressed and unstressed mussels were similar, even when crabs were presented with mussels of the maximum size that they are able to consume. Small crabs were more likely to reject a mussel of preferred size if it was unstressed, suggesting that crabs may be able to assess that these mussels would require extra effort to break into and consume. Our findings suggest that the predator–prey relationship between mussels and crabs is not altered when mussels are stressed. C. maenas remains a voracious predator and regardless of the condition of mussels laid on commercial beds there is a need to control this predator in attempt to reduce losses in the benthic fishery.

The use of erythropoiesis-stimulating agents with ruxolitinib in patients with myelofibrosis in COMFORT-II: an open-label, phase 3 study assessing efficacy and safety of ruxolitinib versus best available therapy in the treatment of myelofibrosis

BACKGROUND: Anemia is considered a negative prognostic risk factor for survival in patients with myelofibrosis. Most patients with myelofibrosis are anemic, and 35-54 % present with anemia at diagnosis. Ruxolitinib, a potent inhibitor of Janus kinase (JAK) 1 and JAK2, was associated with an overall survival benefit and improvements in splenomegaly and patient-reported outcomes in patients with myelofibrosis in the two phase 3 COMFORT studies. Consistent with the ruxolitinib mechanism of action, anemia was a frequently reported adverse event. In clinical practice, anemia is sometimes managed with erythropoiesis-stimulating agents (ESAs). This post hoc analysis evaluated the safety and efficacy of concomitant ruxolitinib and ESA administration in patients enrolled in COMFORT-II, an open-label, phase 3 study comparing the efficacy and safety of ruxolitinib with best available therapy for treatment of myelofibrosis. Patients were randomized (2:1) to receive ruxolitinib 15 or 20 mg twice daily or best available therapy. Spleen volume was assessed by magnetic resonance imaging or computed tomography scan.

RESULTS: Thirteen of 146 ruxolitinib-treated patients had concomitant ESA administration (+ESA). The median exposure to ruxolitinib was 114 weeks in the +ESA group and 111 weeks in the overall ruxolitinib arm; the median ruxolitinib dose intensity was 33 mg/day for each group. Six weeks before the first ESA administration, 10 of the 13 patients had grade 3/4 hemoglobin abnormalities. These had improved to grade 2 in 7 of the 13 patients by 6 weeks after the first ESA administration. The rate of packed red blood cell transfusions per month within 12 weeks before and after first ESA administration remained the same in 1 patient, decreased in 2 patients, and increased in 3 patients; 7 patients remained transfusion independent. Reductions in splenomegaly were observed in 69 % of evaluable patients (9/13) following first ESA administration.

CONCLUSIONS: Concomitant use of an ESA with ruxolitinib was well tolerated and did not affect the efficacy of ruxolitinib. Further investigations evaluating the effects of ESAs to alleviate anemia in ruxolitinib-treated patients are warranted (ClinicalTrials.gov identifier, NCT00934544; July 6, 2009).

Dietary exposure to aflatoxin and micronutrient status among young children from Guinea

SCOPE: Aflatoxin exposure coincides with micronutrient deficiencies in developing countries. Animal feeding studies have postulated that aflatoxin exposure may be exacerbating micronutrient deficiencies. Evidence available in human subjects is limited and inconsistent. The aim of the study was to investigate the relationship between aflatoxin exposure and micronutrient status among young Guinean children.

METHOD AND RESULTS: A total of 305 children (28.8 ± 8.4 months) were recruited at groundnut harvest (rainy season), of which 288 were followed up 6 months later post-harvest (dry season). Blood samples were collected at each visit. Aflatoxin-albumin adduct levels were measured by ELISA. Vitamin A, vitamin E and β-carotene concentrations were measured using HPLC methods. Zinc was measured by atomic absorption spectroscopy. Aflatoxin exposure and micronutrient deficiencies were prevalent in this population and were influenced by season, with levels increasing between harvest and post-harvest. At harvest, children in the highest aflatoxin exposure group, compared to the lowest, were 1.98 (95%CI: 1.00, 3.92) and 3.56 (95%CI: 1.13, 11.15) times more likely to be zinc and vitamin A deficient.

CONCLUSION: Although children with high aflatoxin exposure levels were more likely to be zinc and vitamin A deficient, further research is necessary to determine a cause and effect relationship. 

Impact of fractionation on out-of-field survival and DNA damage responses following exposure to intensity modulated radiation fields

To limit toxicity to normal tissues adjacent to the target tumour volume, radiotherapy is delivered using fractionated regimes whereby the total prescribed dose is given as a series of sequential smaller doses separated by specific time intervals. The impact of fractionation on out-of-field survival and DNA damage responses was determined in AGO-1522 primary human fibroblasts and MCF-7 breast tumour cells using uniform and modulated exposures delivered using a 225 kVp x-ray source. Responses to fractionated schedules (two equal fractions delivered with time intervals from 4 h to 48 h) were compared to those following acute exposures. Cell survival and DNA damage repair measurements indicate that cellular responses to fractionated non-uniform exposures differ from those seen in uniform exposures for the investigated cell lines. Specifically, there is a consistent lack of repair observed in the out-of-field populations during intervals between fractions, confirming the importance of cell signalling to out-of-field responses in a fractionated radiation schedule, and this needs to be confirmed for a wider range of cell lines and conditions.

Prying into the intimate secrets of animal lives; software beyond hardware for comprehensive annotation in 'Daily Diary' tags

BACKGROUND: Smart tags attached to freely-roaming animals recording multiple parameters at infra-second rates are becoming commonplace, and are transforming our understanding of the way wild animals behave. Interpretation of such data is complex and currently limits the ability of biologists to realise the value of their recorded information.

DESCRIPTION: This work presents Framework4, an all-encompassing software suite which operates on smart sensor data to determine the 4 key elements considered pivotal for movement analysis from such tags (Endangered Species Res 4: 123-37, 2008). These are; animal trajectory, behaviour, energy expenditure and quantification of the environment in which the animal moves. The program transforms smart sensor data into dead-reckoned movements, template-matched behaviours, dynamic body acceleration-derived energetics and position-linked environmental data before outputting it all into a single file. Biologists are thus left with a single data set where animal actions and environmental conditions can be linked across time and space.

CONCLUSIONS: Framework4 is a user-friendly software that assists biologists in elucidating 4 key aspects of wild animal ecology using data derived from tags with multiple sensors recording at high rates. Its use should enhance the ability of biologists to derive meaningful data rapidly from complex data.

Comorbidity in severe asthma requiring systemic corticosteroid therapy: cross-sectional data from the Optimum Patient Care Research Database and the British Thoracic Difficult Asthma Registry

Objective: To determine the prevalence of systemic corticosteroid-induced morbidity in severe asthma.
Design: Cross-sectional observational study.Setting The primary care Optimum Patient Care Research Database and the British Thoracic Society Difficult Asthma Registry.
Participants: Optimum Patient Care Research Database (7195 subjects in three age- and gender-matched groups)—severe asthma (Global Initiative for Asthma (GINA) treatment step 5 with four or more prescriptions/year of oral corticosteroids, n=808), mild/moderate asthma (GINA treatment step 2/3, n=3975) and non-asthma controls (n=2412). 770 subjects with severe asthma from the British Thoracic Society Difficult Asthma Registry (442 receiving daily oral corticosteroids to maintain disease control).
Main outcome measures: Prevalence rates of morbidities associated with systemic steroid exposure were evaluated and reported separately for each group.
Results: 748/808 (93%) subjects with severe asthma had one or more condition linked to systemic corticosteroid exposure (mild/moderate asthma 3109/3975 (78%), non-asthma controls 1548/2412 (64%); p<0.001 for severe asthma versus non-asthma controls). Compared with mild/moderate asthma, morbidity rates for severe asthma were significantly higher for conditions associated with systemic steroid exposure (type II diabetes 10% vs 7%, OR=1.46 (95% CI 1.11 to 1.91), p<0.01; osteoporosis 16% vs 4%, OR=5.23, (95% CI 3.97 to 6.89), p<0.001; dyspeptic disorders (including gastric/duodenal ulceration) 65% vs 34%, OR=3.99, (95% CI 3.37 to 4.72), p<0.001; cataracts 9% vs 5%, OR=1.89, (95% CI 1.39 to 2.56), p<0.001). In the British Thoracic Society Difficult Asthma Registry similar prevalence rates were found, although, additionally, high rates of osteopenia (35%) and obstructive sleep apnoea (11%) were identified.

Conclusions: Oral corticosteroid-related adverse events are common in severe asthma. New treatments which reduce exposure to oral corticosteroids may reduce the prevalence of these conditions and this should be considered in cost-effectiveness analyses of these new treatments.

Exposure to children and risk of active trachoma in Tanzanian women

The authors surveyed the trachoma status of 515 women aged 18-60 years and 527 children aged 1-7 years in the trachoma hyperendemic region of Kongwa, Tanzania, in 1989 to further describe the importance of exposure to young children as a risk factor for active trachoma in women. The women were identified as caretakers, who currently cared for children aged 1-7 years; noncaretakers, who lived with, but did not care for, children aged 1-7; or those without children aged 1-7 in the household. The age-adjusted odds ratios for active trachoma seemed to rise with greater exposure to young children, from 1.00 for women without such children, to 1.63 for noncaretakers and 2.43 for caretakers (trend test, p = 0.08). Among those who lived in households with young children, the prevalence of active trachoma in women increased with the total number of young children cared for and with the number of infected children cared for. The prevalence of active trachoma was 40% (6 of 15) for caretakers of three or more infected children, compared with 0 (0 of 88) for caretakers with no infected children (p < 0.0001). Caring for infected children also appeared to be associated with signs of chronic trachoma in caretakers. Noncaretakers who lived with infected children were not at a significantly increased risk for trachoma compared with noncaretakers who were not exposed to such children (5.4% (three of 56) vs. 5.6% (one of 18); p > 0.4). None of the facial signs observed in the children (flies on the face, nasal discharge, etc.) appeared to increase the odds ratio of active trachoma in caretakers beyond the increase associated with trachoma alone in the child. These data support the hypothesis that active disease in women is associated with direct caretaking of young children with active disease. Strategies that interrupt household transmission may affect the binding sequelae of trachoma in women.