Family Characteristics as Risk Factors for Childhood Acute Lymphoblastic Leukemia: A Population-Based Case-Control Study

BACKGROUND: To date, few risk factors for childhood acute lymphoblastic leukemia (ALL) have been confirmed and the scientific literature is full of controversial "evidence." We examined if family characteristics, particularly maternal and paternal age and number of older siblings, were risk factors for childhood acute lymphoblastic leukemia (ALL). METHODOLOGY/PRINCIPAL FINDINGS: In this population-based nationwide matched case-control study, patients 0-14 years of age with ALL diagnosed 1991-2006 and registered in the Swiss Childhood Cancer Registry were linked with their census records of 1990 and 2000. Eight controls per case were selected from the census. The association between family characteristics and ALL was analyzed by conditional logistic regressions. We found that increasing maternal age was associated with incidence of ALL in the offspring (OR per 5-year increase in maternal age 1.18, 95% CI 1.05-1.31; p = 0.004), remaining stable (trend OR 1.14, 95% CI 0.99-1.31; p = 0.060) after adjustment for other risk factors. The association with paternal age was weaker (OR per 5-year increase 1.14, 95% CI 1.01-1.28, p = 0.032) and disappeared after adjustments. Number of older siblings was not associated with risk of ALL in the overall group of children aged 0-14 years at diagnosis. However, we found a negative trend between number of older siblings and ALL diagnosed at age 0-4 years (OR per sibling 0.85, 95% CI 0.68-1.06; p = 0.141) and a positive trend for ALL diagnosed at age 5-9 (OR 1.34, 95% CI 1.05-1.72; p = 0.019), with some evidence for an effect modification (p-value for interaction  = 0.040). CONCLUSIONS: As in other studies, increasing maternal, but not paternal age was associated with risk of ALL. We found only a weak association with the number of older siblings, suggesting a delay in disease manifestation rather than a decrease in incidence

Childhood leukaemia and socioeconomic status: what is the evidence?

The objectives of this systematic review are to summarise the current literature on socioeconomic status (SES) and the risk of childhood leukaemia, to highlight methodological problems and formulate recommendations for future research. Starting from the systematic review of Poole et al. (Socioeconomic status and childhood leukaemia: a review. Int. J. Epidemiol. 2006;35(2):370-384.), an electronic literature search was performed covering August 2002-April 2008. It showed that (1) the results are heterogeneous, with no clear evidence to support a relation between SES and childhood leukaemia; (2) a number of factors, most importantly selection bias, might explain inconsistencies between studies; (3) there is some support for an association between SES at birth (rather than later in childhood) and childhood leukaemia and (4) if there are any associations, these are weak, limited to the most extreme SES groups (the 10-20% most or least deprived). This makes it unlikely that they would act as strong confounders in research addressing associations between other exposures and childhood leukaemia. Future research should minimise case and control selection bias, distinguish between different SES measures and leukaemia subtypes and consider timing of exposures and cancer outcome

Der nacheiszeitliche Bergsturz im Kandertal (Schweiz): Alter und Auswirkungen auf die damalige Umwelt

Zusammenfassung.: Beim Bau des neuen AlpTransit Lötschberg Basistunnels wurden unter murgangartig verschwemmten Ablagerungen der alten Bergsturzmasse des Kandertals Stillwasserablagerungen mit zahlreichen organischen Resten und Torflagen gefunden. Die 14C-datierten Resultate der Pollen, Makrorest-, Holz- und Holzkohleanalysen ermöglichten eine Rekonstruktion der lokalen bis regionalen Umweltgeschichte. Ein Gewässer, vermutlich ein kleiner See, begann beim Tellenfeld in Frutigen um 8800 kal. Jahre v. Chr. zu verlanden. In der näheren Umgebung wuchs von 8800 v. Chr. bis 8000 v. Chr. ein Föhrenwald (Pinus silvestris), der reichlich mit Hasel (Corylus avellana) und anderen wärmeliebenden Gehölzen (Ulmen, Linden, Eichen; Ulmus, Tilia, Quercus) und Birken (Betula) durchsetzt war. Diese für die Nordalpen sehr frühe Bedeutung der Hasel ist durch 14C-datierte Corylus-Nussfragmente (9310±50 14C BP, 8722-8337 v. Chr.) belegt. Nach 8500 v. Chr. drängte die Hasel die Waldföhre allmählich zurück. Auf Grund der paläoökologischen Resultate muss angenommen werden, dass die Wälder um 7600 v. Chr. durch ein katastrophales Ereignis stark gestört wurden. Als Reaktion darauf kam es zu einer starken Zunahme der Waldbrände und es breiteten sich zuerst Farne und Gräser sowie wenig später Waldföhren aus. Das Gewässer wurde um 7100 v. Chr. durch verschwemmtes Bergsturzmaterial zerstört. Der geomorphologische Befund deutet darauf hin, dass diese Ereignisse in engem Zusammenhang mit dem Hauptbergsturz im Kandertal stehen, der aussergewöhnliche Ausmasse hatte (ca. 800 Millionen m3). Die Zerstörung der lokalen ökosysteme als Folge des Bergsturzes um 7600-7100 v. Chr. fiel in ein frühes holozänes Wärme- und Sonneneinstrahlungsmaximum, in dem es, wie vorgängige Untersuchungen in den Alpen und in anderen Gebirgen belegen, zu überdurchschnittlich vielen Hanginstabilitäten ka

Electrospray device

An electrospray device includes an electrospray emitter adapted to receive electrospray fluid; an extractor plate spaced from the electrospray emitter and having at least one aperture; and a power supply for applying a first voltage between the extractor plate and emitter for generating at least one Taylor cone emission through the aperture to create an electrospray plume from the electrospray fluid, the extractor plate as well as accelerator and shaping plates may include a porous, conductive medium for transporting and storing excess, accumulated electrospray fluid away from the aperture

Osteoradionecrosis of the Mandible: Minimized Risk Profile Following Intensity-Modulated Radiation Therapy (IMRT)

Background and Purpose:: Osteoradionecrosis (ON) of the mandible is a serious late complication of high-dose radiation therapy for tumors of the oropharynx and oral cavity. After doses between 60 and 72 Gy using standard fractionation, an incidence of ON between 5% and 15% is reported in a review from 1989, whereas in more recent publications using moderately accelerated or hyperfractionated irradiation and doses between 69 and 81 Gy, the incidence of ON is between 60 Gy for oropharyngeal or oral cavity cancer). 21/73 patients were treated in a postoperative setting, 52 patients underwent primary definitive irradiation. In 56 patients concomitant cisplatin-based chemotherapy was applied. Mean follow-up time was 22 months (12-46 months). Oral cavity including the mandible bone outside the planning target volume was contoured and dose-volume constraints were defined in order to spare bone tissue. Dose-volume histograms were obtained from contoured mandible in each patient and were analyzed and related to clinical mandible bone tolerance. Results:: Using IMRT with doses between 60 and 75 Gy (mean 67 Gy), on average 7.8, 4.8, 0.9, and 0.3 cm3 were exposed to doses > 60, 65, 70, and 75 Gy, respectively. These values are substantially lower than when using three-dimensional conformal radiotherapy. The difference has been approximately quantified by comparison with a historic series. Additional ON risk factors of the patients were also analyzed. Only one grade 3 ON of the lingual horizontal branch, treated with lingual decortication, was observed. Conclusion:: Using IMRT, only very small partial volumes of the mandibular bone are exposed to high radiation doses. This is expected to translate into a further reduction of ON and improved osseointegration of dental implant

Childhood cancer and nuclear power plants in Switzerland: a census-based cohort study

Background Previous studies on childhood cancer and nuclear power plants (NPPs) produced conflicting results. We used a cohort approach to examine whether residence near NPPs was associated with leukaemia or any childhood cancer in Switzerland. Methods We computed person-years at risk for children aged 0-15 years born in Switzerland from 1985 to 2009, based on the Swiss censuses 1990 and 2000 and identified cancer cases from the Swiss Childhood Cancer Registry. We geo-coded place of residence at birth and calculated incidence rate ratios (IRRs) with 95% confidence intervals (CIs) comparing the risk of cancer in children born 15 km away, using Poisson regression models. Results We included 2925 children diagnosed with cancer during 21 117 524 person-years of follow-up; 953 (32.6%) had leukaemia. Eight and 12 children diagnosed with leukaemia at ages 0-4 and 0-15 years, and 18 and 31 children diagnosed with any cancer were born 15 km away, the IRRs (95% CI) for leukaemia in 0-4 and 0-15 year olds were 1.20 (0.60-2.41) and 1.05 (0.60-1.86), respectively. For any cancer, corresponding IRRs were 0.97 (0.61-1.54) and 0.89 (0.63-1.27). There was no evidence of a dose-response relationship with distance (P > 0.30). Results were similar for residence at diagnosis and at birth, and when adjusted for potential confounders. Results from sensitivity analyses were consistent with main results. Conclusions This nationwide cohort study found little evidence of an association between residence near NPPs and the risk of leukaemia or any childhood cance

A prospective cohort analysis of residential radon and UV exposures and malignant melanoma mortality in the Swiss population.

BACKGROUND Radon is a radioactive noble gas naturally found in the earth crust that can accumulate in buildings. In addition to lung cancer, alpha particles emitted by radon may contribute to the risk of skin cancer. We evaluated the association between residential radon exposure and skin cancer mortality, over a fifteen year period, taking residential ultra-violet (UV) exposure into account. METHODS We included 4.9 million adults from the Swiss National Cohort. Hazard ratios for melanoma mortality were estimated using Cox proportional hazard models (20+ years old; follow-up 2001-2015). Long-term modelled residential radon and ambient UV exposures were assigned at baseline, and included together in the Cox models. With age as a time scale, models were adjusted for calendar time, sex, marital status, education, mother tongue, socioeconomic position, and occupational environment with potential for UV exposure. Age specific hazard ratios were derived. Effect modification, sensitivity analyses and the shape of the exposure response, as well as secondary analysis using other outcome definitions, were investigated. RESULTS During follow-up (average of 13.6 years), 3,979 melanoma deaths were observed. Associations declined with age, with an adjusted hazard ratio per 100 Bq/m3 radon at age 60 of 1.10 (95% CI: 0.99, 1.23). The dose-response showed an approximate linear trend between the minimum and mean radon exposure of 75 Bq/m3. Having outdoor occupation significantly increased the risk of melanoma mortality associated with UV exposure compared to indoor jobs. Analysis restricted to the last five years of follow-up showed similar results compared to the main analysis. Similar associations were found for mortality from melanoma and non-melanoma skin cancer combined. CONCLUSION With double the follow-up time, this study confirmed the previously observed association between residential radon exposure and melanoma and non-melanoma skin cancer mortality in Switzerland. Accumulation of radon indoors is preventable and of public health importance

Biomarkers of human gastrointestinal tract regions

Dysregulation of intestinal epithelial cell performance is associated with an array of pathologies whose onset mechanisms are incompletely understood. While whole-genomics approaches have been valuable for studying the molecular basis of several intestinal diseases, a thorough analysis of gene expression along the healthy gastrointestinal tract is still lacking. The aim of this study was to map gene expression in gastrointestinal regions of healthy human adults and to implement a procedure for microarray data analysis that would allow its use as a reference when screening for pathological deviations. We analyzed the gene expression signature of antrum, duodenum, jejunum, ileum, and transverse colon biopsies using a biostatistical method based on a multivariate and univariate approach to identify region-selective genes. One hundred sixty-six genes were found responsible for distinguishing the five regions considered. Nineteen had never been described in the GI tract, including a semaphorin probably implicated in pathogen invasion and six novel genes. Moreover, by crossing these genes with those retrieved from an existing data set of gene expression in the intestine of ulcerative colitis and Crohn's disease patients, we identified genes that might be biomarkers of Crohn's and/or ulcerative colitis in ileum and/or colon. These include CLCA4 and SLC26A2, both implicated in ion transport. This study furnishes the first map of gene expression along the healthy human gastrointestinal tract. Furthermore, the approach implemented here, and validated by retrieving known gene profiles, allowed the identification of promising new leads in both healthy and disease state