Parental occupational exposure to pesticides and risk of childhood cancer in Switzerland: a census-based cohort study.

Pesticide exposure is a suspected risk factor for childhood cancer. We investigated the risk of developing childhood cancer in relation to parental occupational exposure to pesticides in Switzerland for the period 1990-2015. From a nationwide census-based cohort study in Switzerland, we included children aged < 16 years at national censuses of 1990 and 2000 and followed them until 2015. We extracted parental occupations reported at the census closest to the birth year of the child and estimated exposure to pesticides using a job exposure matrix. Cox proportional hazards models, adjusted for potential confounders, were fitted for the following outcomes: any cancer, leukaemia, central nervous system tumours (CNST), lymphoma, non-CNS solid tumours. Analyses of maternal (paternal) exposure were based on approximately 15.9 (15.1) million-person years at risk and included 1891 (1808) cases of cancer, of which 532 (503) were leukaemia, 348 (337) lymphomas, 423 (399) CNST, and 588 (569) non-CNS solid tumours. The prevalence of high likelihood of exposure was 2.9% for mothers and 6.7% for fathers. No evidence of an association was found with maternal or paternal exposure for any of the outcomes, except for "non-CNS solid tumours" (High versus None; Father: adjusted HR [95%CI] =1.84 [1.31-2.58]; Mother: 1.79 [1.13-2.84]). No evidence of an association was found for main subtypes of leukaemia and lymphoma. A post-hoc analysis on frequent subtypes of "non-CNS solid tumours" showed positive associations with wide CIs for some cancers. Our study suggests an increased risk for solid tumours other than in the CNS among children whose parents were occupationally exposed to pesticides; however, the small numbers of cases limited a closer investigation of cancer subtypes. Better exposure assessment and pooled studies are needed to further explore a possible link between specific childhood cancers types and parental occupational exposure to pesticides

Methods comparison for detecting trends in herbicide monitoring time-series in streams

An inadvertent consequence of pesticide use is aquatic pesticide pollution, which has prompted the implementation of mitigation measures in many countries. Water quality monitoring programs are an important tool to evaluate the efficacy of these mitigation measures. However, large interannual variability of pesticide losses makes it challenging to detect significant improvements in water quality and to attribute these improvements to the application of specific mitigation measures. Thus, there is a gap in the literature that informs researchers and authorities regarding the number of years of aquatic pesticide monitoring or the effect size (e.g., loss reduction) that is required to detect significant trends in water quality. Our research addresses this issue by combining two exceptional empirical data sets with modelling to explore the relationships between the achieved pesticide reduction levels due to mitigation measures and the length of the observation period for establishing statistically significant trends. Our study includes both a large (Rhine at Basel, ∼36,300 km2) and small catchment (Eschibach, 1.2 km2), which represent spatial scales at either end of the spectrum that would be realistic for monitoring programs designed to assess water quality. Our results highlight several requirements in a monitoring program to allow for trend detection. Firstly, sufficient baseline monitoring is required before implementing mitigation measures. Secondly, the availability of pesticide use data helps account for the interannual variability and temporal trends, but such data are usually lacking. Finally, the timing and magnitude of hydrological events relative to pesticide application can obscure the observable effects of mitigation measures (especially in small catchments). Our results indicate that a strong reduction (i.e., 70–90 %) is needed to detect a change within 10 years of monitoring data. The trade-off in applying a more sensitive method for change detection is that it may be more prone to false-positives. Our results suggest that it is important to consider the trade-off between the sensitivity of trend detection and the risk of false positives when selecting an appropriate method and that applying more than one method can provide more confidence in trend detection

Bayesian spatial modelling of childhood cancer incidence in Switzerland using exact point data: a nationwide study during 1985-2015

BACKGROUND: The aetiology of most childhood cancers is largely unknown. Spatially varying environmental factors such as traffic-related air pollution, background radiation and agricultural pesticides might contribute to the development of childhood cancer. This study is the first investigation of the spatial disease mapping of childhood cancers using exact geocodes of place of residence. METHODS: We included 5947 children diagnosed with cancer in Switzerland during 1985-2015 at 0-15 years of age from the Swiss Childhood Cancer Registry. We modelled cancer risk using log-Gaussian Cox processes and indirect standardisation to adjust for age and year of diagnosis. We examined whether the spatial variation of risk can be explained by modelled ambient air concentration of NO$_{2}$, modelled exposure to background ionising radiation, area-based socio-economic position (SEP), linguistic region, duration in years of general cancer registration in the canton or degree of urbanisation. RESULTS: For all childhood cancers combined, the posterior median relative risk (RR), compared to the national level, varied by location from 0.83 to 1.13 (min to max). Corresponding ranges were 0.96 to 1.09 for leukaemia, 0.90 to 1.13 for lymphoma, and 0.82 to 1.23 for central nervous system (CNS) tumours. The covariates considered explained 72% of the observed spatial variation for all cancers, 81% for leukaemia, 82% for lymphoma and 64% for CNS tumours. There was weak evidence of an association of CNS tumour incidence with modelled exposure to background ionising radiation (RR per SD difference 1.17; 0.98-1.40) and with SEP (1.6; 1.00-1.13). CONCLUSION: Of the investigated diagnostic groups, childhood CNS tumours showed the largest spatial variation. The selected covariates only partially explained the observed variation of CNS tumours suggesting that other environmental factors also play a role

Detection of Septata intestinalis in Stool Specimens and Coprodiagnostic Monitoring of Successful Treatment with Albendazole

We describe two patients with AIDS and chronic diarrhea in whom the microsporidian Septata intestinalis was detected with use of light and electron microscopic coprodiagnostic techniques. The ultrastructure of the microsporidian spores found in their stool specimens was distinctly different from that of Enterocytozoon bieneusi, another intestinal microsporidian found in patients infected with human immunodeficiency virus. Electron microscopic examination of duodenal biopsy specimens available from one of the patients enabled identification of S. intestinalis and confirmed the similarity of spores found in feces and in duodenal tissue. Both patients' diarrhea stopped when they were treated with albendazole. Coprodiagnostic monitoring indicated disappearance of the parasites and allowed the diagnosis of a relapse in one patient, who responded well to a second course of treatmen

Long-term HIV infection and antiretroviral therapy are associated with bone microstructure alterations in premenopausal women

Summary: We evaluated the influence of long-term HIV infection and its treatment on distal tibia and radius microstructure. Premenopausal eumenorrheic HIV-positive women displayed trabecular and cortical microstructure alterations, which could contribute to increased bone fragility in those patients. Introduction: Bone fragility is an emerging issue in HIV-infected patients. Dual-energy X-ray absorptiometry (DXA) quantified areal bone mineral density (BMD) predicts fracture risk, but a significant proportion of fracture risk results from microstructural alterations. Methods: We studied the influence of long-term HIV infection on bone microstructure as evaluated by high-resolution peripheral quantitative computed tomography (HR-pQCT) in 22 HIV-positive (+ve) premenopausal eumenorrheic women and 44 age- and body mass index (BMI)-matched HIV-negative (−ve) controls. All subjects completed questionnaires regarding calcium/protein intakes and physical activity, and underwent DXA and HR-pQCT examinations for BMD and peripheral skeleton microstructure, respectively. A risk factor analysis of tibia trabecular density using linear mixed models was conducted. Results: In HIV+ve women on successful antiretroviral therapy (undetectable HIV-RNA, median CD4 cell count, 626), infection duration was 16.5 ± 3.5 (mean ± SD) years; median BMI was 22 (IQR, 21-26) kg/m2. More HIV+ve women were smokers (82 versus 50%, p = 0.013). Compared to controls, HIV+ve women had lower lumbar spine (spine T-score −0.70 vs −0.03, p = 0.014), but similar proximal femur BMD. At distal tibia, HIV+ve women had a 14.1% lower trabecular density and a 13.2% reduction in trabecular number compared to HIV−ve women (p = 0.013 and 0.029, respectively). HR-pQCT differences in distal radius were significant for cortical density (−3.0%; p = 0.029). Conclusions: Compared with HIV−ve subjects, premenopausal HIV+ve treated women had trabecular and cortical bone alterations. Adjusted analysis revealed that HIV status was the only determinant of between group tibia trabecular density differences. The latter could contribute to increased bone fragility in HIV+ve patient

Constitutive phosphorylation of MDC1 physically links the MRE11–RAD50–NBS1 complex to damaged chromatin

The MRE11–RAD50–Nijmegen breakage syndrome 1 (NBS1 [MRN]) complex accumulates at sites of DNA double-strand breaks (DSBs) in microscopically discernible nuclear foci. Focus formation by the MRN complex is dependent on MDC1, a large nuclear protein that directly interacts with phosphorylated H2AX. In this study, we identified a region in MDC1 that is essential for the focal accumulation of the MRN complex at sites of DNA damage. This region contains multiple conserved acidic sequence motifs that are constitutively phosphorylated in vivo. We show that these motifs are efficiently phosphorylated by caseine kinase 2 (CK2) in vitro and directly interact with the N-terminal forkhead-associated domain of NBS1 in a phosphorylation-dependent manner. Mutation of these conserved motifs in MDC1 or depletion of CK2 by small interfering RNA disrupts the interaction between MDC1 and NBS1 and abrogates accumulation of the MRN complex at sites of DNA DSBs in vivo. Thus, our data reveal the mechanism by which MDC1 physically couples the MRN complex to damaged chromatin

A simple asthma prediction tool for preschool children with wheeze or cough

BACKGROUND Many preschool children have wheeze or cough, but only some have asthma later. Existing prediction tools are difficult to apply in clinical practice or exhibit methodological weaknesses. OBJECTIVE We sought to develop a simple and robust tool for predicting asthma at school age in preschool children with wheeze or cough. METHODS From a population-based cohort in Leicestershire, United Kingdom, we included 1- to 3-year-old subjects seeing a doctor for wheeze or cough and assessed the prevalence of asthma 5 years later. We considered only noninvasive predictors that are easy to assess in primary care: demographic and perinatal data, eczema, upper and lower respiratory tract symptoms, and family history of atopy. We developed a model using logistic regression, avoided overfitting with the least absolute shrinkage and selection operator penalty, and then simplified it to a practical tool. We performed internal validation and assessed its predictive performance using the scaled Brier score and the area under the receiver operating characteristic curve. RESULTS Of 1226 symptomatic children with follow-up information, 345 (28%) had asthma 5 years later. The tool consists of 10 predictors yielding a total score between 0 and 15: sex, age, wheeze without colds, wheeze frequency, activity disturbance, shortness of breath, exercise-related and aeroallergen-related wheeze/cough, eczema, and parental history of asthma/bronchitis. The scaled Brier scores for the internally validated model and tool were 0.20 and 0.16, and the areas under the receiver operating characteristic curves were 0.76 and 0.74, respectively. CONCLUSION This tool represents a simple, low-cost, and noninvasive method to predict the risk of later asthma in symptomatic preschool children, which is ready to be tested in other populations

Detecting and describing heterogeneity in health care cost trajectories among asylum seekers.

The mechanism underlying the health care cost trajectories among asylum seekers is not well understood. In the canton of Vaud in Switzerland, a nurse-led health care and medical Network for Migrant Health ("Réseau santé et migration" RESAMI) has established a health care model focusing on the first year after arrival of asylum seekers, called the "community health phase". This model aims to provide tailored care and facilitate integration into the Swiss health care system. The aim of this study is to explore different health care cost trajectories among asylum seekers during this phase and identify the associated factors. We detected different patterns of health care cost trajectories using time-series clustering of longitudinal data of asylum seekers in the canton of Vaud in Switzerland. These data included all adult asylum seekers and recipients of emergency aid who entered the canton between 2012 and 2015 and were followed until 2018. The different clusters of health care cost trajectories were then described using a multinomial logistic regression model. We identified a concave, an upward trending, and a downward trending cluster of health care cost trajectories with different characteristics being associated with each cluster. The likelihood of being in the concave cluster is positively associated with coming from the Eastern Mediterranean region or Africa rather than Europe and with a higher share of consultations with an interpreter. The likelihood of being in the upward trending cluster, which accrued the highest costs, is positively associated with 20-24-year-olds rather than older individuals, coming from Europe than any other region and having a mental disorder. In contrast to the other two clusters, the likelihood of being in the downward trending cluster is positively associated with having contacted the RESAMI network within the first month after arrival, which might indicate the potential of early intervention. It is also positively associated with older age and living in a group lodge. Asylum seekers are heterogeneous in terms of health care cost trajectories. Exploring these differences can help point to possible ways to improve the care and supporting services provided to asylum seekers. Our findings could indicate that early and patient-centered interventions might be well-suited to this aim

Uncertainty in the reactive transport model response to analkaline perturbation in a clay formation

The mineral alteration in the concrete barrier and in the clay formation around long-lived intermediate-level radioactive waste in the French deep geological disposal concept is evaluated using numerical modeling. There are concerns that the mineralogical composition of the surrounded clay will not be stable under the high alkaline pore fluid conditions caused by concrete (pH {approx} 12). Conversely, the infiltration of CO{sub 2}-rich groundwater from the clay formation into initially unsaturated concrete, at the high temperature (T {approx} 70 C) produced from the decay of radionuclides, could cause carbonation, thereby potentially affecting critical performance functions of this barrier. This could also lead to significant changes in porosity, which would affect aqueous diffusive transport of long-lived radionuclides. All these processes are therefore intimately coupled and advanced reactive transport models are required for long-term performance assessment. The uncertainty in predictions of these models is one major question that must be answered. A mass-transfer model response to an alkaline perturbation in clay with standard model values is first simulated using the two-phase non-isothermal reactive transport code TOUGHREACT. The selection of input parameters is thereafter designed to sample uncertainties in a wide range of physico-chemical processes without making a priori assumptions about the relative importance of different feedbacks. This 'base-case' simulation is perturbed by setting a parameter to a minimum, intermediate or maximum value or by switching on/off a process. This sensitivity analysis is conducted using grid computing facilities of BRGM (http://iggi.imag.fr). Our evaluation of the preliminary results suggests that the resaturation and the heating of the near-field will be of long enough duration to cause a limited carbonation through all the width of the concrete barrier. Another prediction is the possibility of self-sealing at the concrete/clay interface. Further research is however required to discuss the effect of such evolution on the desirable performance function of both barriers