Measurements and determinants of children's exposure to background gamma radiation in Switzerland.

Epidemiological studies of children's cancer risks associated with background gamma radiation exposure have used geographic exposure models to estimate exposure at their locations of residence. We measured personal exposure to background gamma radiation, and we investigated the extent to which it was associated with children's whereabouts. We collected data on whereabouts and exposure to background gamma radiation over a 5-day period among children aged 4-15 years in Switzerland. We used D-Shuttle dosimeters to measure children's exposure, and we asked parents to write their children's activities in diaries. We used Poisson mixed-effects and linear regression models to investigate the association of hourly and overall doses, respectively, with children's reported whereabouts. During the observed time, 149 participating children spent 66% indoors at home; 19% indoors away from home; and 15% outdoors. The mean personal exposure was 85.7 nSv/h (range 52.3 nSv/h-145 nSv/h). Exposure was 1.077 (95% CI 1.067, 1.087) times higher indoors than outdoors and varied by building material and (predicted) outdoor dose rates. Our study provides detailed information about children's patterns of exposure to background gamma radiation in Switzerland. Dwelling building materials and outdoor dose rates are important determinants of children's exposure. Future epidemiological studies may benefit from including information about building materials

Childhood cancer and traffic-related air pollution in Switzerland: A nationwide census-based cohort study.

Motor vehicle exhaust is a major contributor to air pollution, and exposure to benzene or other carcinogenic components may increase cancer risks. We aimed to investigate the association between traffic-related air pollution and risk of childhood cancer in a nationwide cohort study in Switzerland. We identified incident cases from the Swiss Childhood Cancer Registry diagnosed < 16 years of age between 1990 and 2015 and linked them probabilistically with the census-based Swiss National Cohort study. We developed land use regression models to estimate annual mean ambient levels of nitrogen dioxide (NO2) and benzene outside 1.4 million children's homes. We used risk-set sampling to facilitate the analysis of time-varying exposure and fitted conditional logistic regression models adjusting for neighborhood socio-economic position, level of urbanization, and background ionizing radiation. We included 2,960 cancer cases in the analyses. The adjusted hazard ratios (HR) and 95% confidence intervals for exposure to NO2 per 10 μg/m3 were 1.00 (95%-CI 0.88-1.13) for acute lymphoblastic leukemia (ALL) and 1.31 (95%-CI 1.00-1.71) for acute myeloid leukemia (AML). Using exposure lagged by 1 to 5 years instead of current exposure attenuated the effect for AML. The adjusted HR for exposure to benzene per 1 μg/m3 was 1.03 (95%-CI 0.86-1.23) for ALL and 1.29 (95%-CI 0.86-1.95) for AML. We also observed increased HRs for other diagnostic groups, notably non-Hodgkin lymphoma. Our study adds to the existing evidence that exposure to traffic-related air pollution is associated with an increased risk of childhood leukemia, particularly AML

Bayesian spatial modelling of terrestrial radiation in Switzerland

The geographic variation of terrestrial radiation can be exploited in epidemiological studies of the health effects of protracted low-dose exposure. Various methods have been applied to derive maps of this variation. We aimed to construct a map of terrestrial radiation for Switzerland. We used airborne $\gamma$-spectrometry measurements to model the ambient dose rates from terrestrial radiation through a Bayesian mixed-effects model and conducted inference using Integrated Nested Laplace Approximation (INLA). We predicted higher levels of ambient dose rates in the alpine regions and Ticino compared with the western and northern parts of Switzerland. We provide a map that can be used for exposure assessment in epidemiological studies and as a baseline map for assessing potential contamination.Comment: 27 pages, 10 figure

RITA modulates cell migration and invasion by affecting focal adhesion dynamics

RITA, the RBP-J interacting and tubulin-associated protein, has been reported to be related to tumor development, but the underlying mechanisms are not understood. Since RITA interacts with tubulin and coats microtubules of the cytoskeleton, we hypothesized that it is involved in cell motility. We show here that depletion of RITA reduces cell migration and invasion of diverse cancer cell lines and mouse embryonic fibroblasts. Cells depleted of RITA display stable focal adhesions (FA) with elevated active integrin, phosphorylated focal adhesion kinase, and paxillin. This is accompanied by enlarged size and disturbed turnover of FA. These cells also demonstrate increased polymerized tubulin. Interestingly, RITA is precipitated with the lipoma-preferred partner (LPP), which is critical in actin cytoskeleton remodeling and cell migration. Suppression of RITA results in reduced LPP and alpha-actinin at FA leading to compromised focal adhesion turnover and actin dynamics. This study identifies RITA as a novel crucial player in cell migration and invasion by affecting the turnover of FA through its interference with the dynamics of actin filaments and microtubules. Its deregulation may contribute to malignant progression

Temporal association between childhood leukaemia and population growth in Swiss municipalities.

The population mixing hypothesis proposes that childhood leukaemia (CL) might be a rare complication of a yet unidentified subclinical infection. Large population influxes into previously isolated rural areas may foster localised epidemics of the postulated infection causing a subsequent increase of CL. While marked population growth after a period of stability was central to the formulation of the hypothesis and to the early studies on population mixing, there is a lack of objective criteria to define such growth patterns. We aimed to determine whether periods of marked population growth coincided with increases in the risk of CL in Swiss municipalities. We identified incident cases of CL aged 0-15 years for the period 1985-2010 from the Swiss Childhood Cancer Registry. Annual data on population counts in Swiss municipalities were obtained for 1980-2010. As exposures, we defined (1) cumulative population growth during a 5-year moving time window centred on each year (1985-2010) and (2) periods of 'take-off growth' identified by segmented linear regression. We compared CL incidence across exposure categories using Poisson regression and tested for effect modification by degree of urbanisation. Our study included 1500 incident cases and 2561 municipalities. The incident rate ratio (IRR) comparing the highest to the lowest quintile of 5-year population growth was 1.18 (95 % CI 0.96, 1.46) in all municipalities and 1.33 (95 % CI 0.93, 1.92) in rural municipalities (p value interaction 0.36). In municipalities with take-off growth, the IRR comparing the take-off period (>6 % annual population growth) with the initial period of low or negative growth (<2 %) was 2.07 (95 % CI 0.95, 4.51) overall and 2.99 (1.11, 8.05) in rural areas (p interaction 0.52). Our study provides further support for the population mixing hypothesis and underlines the need to distinguish take-off growth from other growth patterns in future research

Survival rates and prognostic factors in right- and left-sided colon cancer stage I–IV: an unselected retrospective single-center trial

Purpose: Colorectal cancer revealed over the last decades a remarkable shift with an increasing proportion of a right- compared to a left-sided tumor location. In the current study, we aimed to disclose clinicopathological differences between right- and left-sided colon cancer (rCC and lCC) with respect to mortality and outcome predictors. Methods: In total, 417 patients with colon cancer stage I-IV were analyzed in the present retrospective single-center study. Survival rates were assessed using the Kaplan-Meier method and uni/multivariate analyses were performed with a Cox proportional hazards regression model. Results: Our study showed no significant difference of the overall survival between rCC and lCC stage I-IV (p = 0.354). Multivariate analysis revealed in the rCC cohort the worst outcome for ASA (American Society of Anesthesiologists) score IV patients (hazard ratio [HR]: 16.0; CI 95%: 2.1-123.5), CEA (carcinoembryonic antigen) blood level > 100 mu g/l (HR: 3.3; CI 95%: 1.2-9.0), increased lymph node ratio of 0.6-1.0 (HR: 5.3; CI 95%: 1.7-16.1), and grade 4 tumors (G4) (HR: 120.6; CI 95%: 6.7-2179.6) whereas in the lCC population, ASA score IV (HR: 8.9; CI 95%: 0.9-91.9), CEA blood level 20.1-100 mu g/l (HR: 5.4; CI 95%: 2.4-12.4), conversion to laparotomy (HR: 14.1; CI 95%: 4.0-49.0), and severe surgical complications (Clavien-Dindo III-IV) (HR: 2.9; CI 95%: 1.5-5.5) were identified as predictors of a diminished overall survival. Conclusion: Laterality disclosed no significant effect on the overall prognosis of colon cancer patients. However, group differences and distinct survival predictors could be identified in rCC and lCC patients

The impact of surgical site infection—a cost analysis

Purpose: Surgical site infection (SSI) occurs in up to 25% of patients after elective laparotomy. We aimed to determine the effect of SSI on healthcare costs and patients' quality of life. Methods: In this post hoc analysis based on the RECIPE trial, we studied a 30-day postoperative outcome of SSI in a single-center, prospective randomized controlled trial comparing subcutaneous wound irrigation with 0.04% polyhexanide to 0.9% saline after elective laparotomy. Total medical costs were analyzed accurately per patient with the tool of our corporate controlling team which is based on diagnosis-related groups in Germany. Results: Between November 2015 and May 2018, 456 patients were recruited. The overall rate of SSI was 28.2%. Overall costs of inpatient treatment were higher in the group with SSI: median 16.685 euro; 19.703 USD (IQR 21.638 euro; 25.552 USD) vs. median 11.235 euro; 13.276 USD (IQR 11.564 euro; 13.656 USD); p < 0.001. There was a difference in surgery costs (median 6.664 euro; 7.870 USD with SSI vs. median 5.040 euro; 5.952 USD without SSI; p = 0.001) and costs on the surgical ward (median 8.404 euro; 9.924 USD with SSI vs. median 4.690 euro; 5.538 USD without SSI; p < 0.001). Patients with SSI were less satisfied with the cosmetic result (4.3% vs. 16.2%; p < 0.001). Overall costs for patients who were irrigated with saline were median 12.056 euro; 14.237 USD vs. median 12.793 euro; 15.107 USD in the polyhexanide group (p = 0.52). Conclusion: SSI after elective laparotomy increased hospital costs substantially. This is an additional reason why the prevention of SSI is important. Overall costs for intraoperative wound irrigation with saline were comparable with polyhexanide