Estimating long-term health risks after breast cancer radiotherapy: merging evidence from low and high doses.

In breast cancer radiotherapy, substantial radiation exposure of organs other than the treated breast cannot be avoided, potentially inducing second primary cancer or heart disease. While distant organs and large parts of nearby ones receive doses in the mGy-Gy range, small parts of the heart, lung and bone marrow often receive doses as high as 50 Gy. Contemporary treatment planning allows for considerable flexibility in the distribution of this exposure. To optimise treatment with regards to long-term health risks, evidence-based risk estimates are required for the entire broad range of exposures. Here, we thus propose an approach that combines data from medical and epidemiological studies with different exposure conditions. Approximating cancer induction as a local process, we estimate organ cancer risks by integrating organ-specific dose-response relationships over the organ dose distributions. For highly exposed organ parts, specific high-dose risk models based on studies with medical exposure are applied. For organs or their parts receiving relatively low doses, established dose-response models based on radiation-epidemiological data are used. Joining the models in the intermediate dose range leads to a combined, in general non-linear, dose response supported by data over the whole relevant dose range. For heart diseases, a linear model consistent with high- and low-dose studies is presented. The resulting estimates of long-term health risks are largely compatible with rate ratios observed in randomised breast cancer radiotherapy trials. The risk models have been implemented in a software tool PASSOS that estimates long-term risks for individual breast cancer patients.

ProZES: the methodology and software tool for assessment of assigned share of radiation in probability of cancer occurrence.

ProZES is a software tool for estimating the probability that a given cancer was caused by preceding exposure to ionising radiation. ProZES calculates this probability, the assigned share, for solid cancers and hematopoietic malignant diseases, in cases of exposures to low-LET radiation, and for lung cancer in cases of exposure to radon. User-specified inputs include birth year, sex, type of diagnosed cancer, age at diagnosis, radiation exposure history and characteristics, and smoking behaviour for lung cancer. Cancer risk models are an essential part of ProZES. Linking disease and exposure to radiation involves several methodological aspects, and assessment of uncertainties received particular attention. ProZES systematically uses the principle of multi-model inference. Models of radiation risk were either newly developed or critically re-evaluated for ProZES, including dedicated models for frequent types of cancer and, for less common diseases, models for groups of functionally similar cancer sites. The low-LET models originate mostly from the study of atomic bomb survivors in Hiroshima and Nagasaki. Risks predicted by these models are adjusted to be applicable to the population of Germany and to different time periods. Adjustment factors for low dose rates and for a reduced risk during the minimum latency time between exposure and cancer are also applied. The development of the methodology and software was initiated and supported by the German Federal Ministry for the Environment, Nature Conservation and Nuclear Safety (BMU) taking up advice by the German Commission on Radiological Protection (SSK, Strahlenschutzkommission). These provide the scientific basis to support decision making on compensation claims regarding malignancies following occupational exposure to radiation in Germany.

LONG-TERM HEALTH RISK AFTER BREAST-CANCER RADIOTHERAPY: OVERVIEW OF PASSOS METHODOLOGY AND SOFTWARE.

Breast-cancer radiotherapy reduces the recurrence rates and improves patient survival. However, it also increases the incidence of second cancers and of heart disease. These radiation-induced long-term health risks become increasingly important with improved cure rates and prolonged patient survival. Radiation doses to nearby as well as distant organs strongly vary between different irradiation techniques and among individual patients. To provide personalized lifetime risk estimates, the German national project PASSOS combines individual anatomy, dosimetric estimates, organ-specific low- and high-dose risk models and personal risk factors such as smoking. A dedicated software tool is under development to assist clinical decision-making processes.

Dose-dependent expression of CLIP2 in post-Chernobyl papillary thyroid carcinomas.

A previous study on papillary thyroid carcinomas (PTC) in young patients who were exposed to (131)iodine from the Chernobyl fallout revealed an exclusive gain of chromosomal band 7q11.23 in exposed cases compared to an age-matched control cohort. CLIP2, a gene located within band 7q11.23 was shown to be differentially expressed between exposed and non-exposed cases at messenger RNA and protein level. Therefore, a standardized procedure for CLIP2 typing of PTCs has been developed in a follow-up study. Here we used CLIP2 typing data on 117 post-Chernobyl PTCs from two cohorts of exposed patients with individual dose estimates and 24 non-exposed controls to investigate a possible quantitative dose-response relationship of the CLIP2 marker. The 'Genrisk-T' cohort consisted of 45 PTCs and the 'UkrAm' cohort of 72 PTCs. Both cohorts differed in mean dose (0.59 Gy Genrisk-T, 1.2 Gy UkrAm) and mean age at exposure (AaE) (2 years Genrisk-T, 8 years UkrAm), whilst the median latency (16 years Genrisk-T, 18 years UkrAm) was comparable. We analyzed the association between the binary CLIP2 typing and continuous thyroid dose with logistic regression. A clear positive dose-response relationship was found for young PTC cases [age at operation (AaO) < 20 years, AaE < 5 years]. In the elder age group a higher proportion of sporadic tumors is assumed due to a negligible dose response, suggesting different molecular mechanisms in sporadic and radiation-induced cases. This is further supported by the association of elder patients (AaO > 20 years) with positivity for BRAF V600E mutation.

Toward reliable estimates of abundance: comparing index methods to assess the abundance of a Mammalian predator.

Due to time and financial constraints indices are often used to obtain landscape-scale estimates of relative species abundance. Using two different field methods and comparing the results can help to detect possible bias or a non monotonic relationship between the index and the true abundance, providing more reliable results. We used data obtained from camera traps and feces counts to independently estimate relative abundance of red foxes in the Black Forest, a forested landscape in southern Germany. Applying negative binomial regression models, we identified landscape parameters that influence red fox abundance, which we then used to predict relative red fox abundance. We compared the estimated regression coefficients of the landscape parameters and the predicted abundance of the two methods. Further, we compared the costs and the precision of the two field methods. The predicted relative abundances were similar between the two methods, suggesting that the two indices were closely related to the true abundance of red foxes. For both methods, landscape diversity and edge density best described differences in the indices and had positive estimated effects on the relative fox abundance. In our study the costs of each method were of similar magnitude, but the sample size obtained from the feces counts (262 transects) was larger than the camera trap sample size (88 camera locations). The precision of the camera traps was lower than the precision of the feces counts. The approach we applied can be used as a framework to compare and combine the results of two or more different field methods to estimate abundance and by this enhance the reliability of the result.

Space and habitat use by wild Bactrian camels in the Transaltai Gobi of southern Mongolia.

Wild Bactrian camels (Camela ferus) are listed as Critically Endangered by the International Union for Conservation of Nature (IUCN) and only persist in some of the most remote locations in northern China and southern Mongolia. Although the species has been recognized as an umbrella species for the fragile central Asian desert ecosystem and has been high on the conservation agenda, little is known about the species' habitat requirements, with most information coming from anecdotal sightings and descriptive studies. We compiled the only available telemetry data from wild camels worldwide. Seven wild camels, which were followed for 11-378 monitoring days, covered a total range of 28,410 km2, with individual annual ranges being >12,000 km2 for three animals followed over a year. Camels reacted strongly to capture events, moving up to 64 km from the capture site within a day, whereas normal average daily straight line distances were 3.0-6.4 km/day. Camels showed a preference for intermediate productivity values (NDVI, habitat type) and landscape parameters (distance to water, elevation) and an avoidance of steep slopes. Our telemetry results suggest that wild camels still range throughout the entire Great Gobi A Strictly Protected Area (SPA), are highly mobile, and very sensitive to human disturbance. Their habitat preference may be a trade-off between dietary and safety requirements. Small sample size did not allow the development of a full habitat model testing all variables simultaneously and we urgently call for more data from additional wild camels as a foundation for evidence driven conservation actions.

Decision-making behaviour during urban search and rescue: a case study of Germany.

The objective of assisting with tasks and decisions during incident response is to reduce the risks to victims and rescue personnel while increasing the efficiency of the rescue operation. Handling uncertain information during urban search and rescue (USAR) missions represents additional stress to the decision-maker. The aim of this study is to identify the decision-making behaviour of rescuers during USAR missions to pinpoint trapped or buried victims in debris in order to design assistance technologies and decision-support systems that meet their needs. In 2010, a survey was conducted among 10-15 per cent of all German rescue personnel specialised in search tasks. One of the major results of this survey is that a subjective assessment of the reliability of information available from heterogeneous sources influences the rescuers' actions and that there is no methodology for decision-making involving uncertain information. In addition, the study found that compliance with procedures does not require assistance.

Modified serum profiles of inflammatory and vasoconstrictive factors in patients with emotional stress-induced acute coronary syndrome during World Cup Soccer 2006.

OBJECTIVES: We sought to assess whether emotional stress-induced acute coronary syndrome (ACS) is mediated by increased inflammatory and vasoconstrictive mediators. BACKGROUND: The World Cup soccer 2006 has been shown to provoke levels of stress sufficient to increase the incidence of ACS. However, the mechanisms by which stress translates into vascular injury up to plaque rupture still remain elusive. METHODS: Serum levels of soluble CD40L (sCD40L), soluble vascular cell adhesion molecule (sVCAM)-1, monocyte chemoattractant protein (MCP)-1, tumor necrosis factor (TNF)-alpha, high-sensitivity C-reactive protein (hsCRP), regulated on activation, normal T-cell expressed and secreted (RANTES), and endothelin (ET)-1 were determined in patients who experienced an ACS during World Cup matches, in ACS reference patients (not associated with emotional stress), and in healthy volunteers. Correlations and receiver-operating characteristic curves were calculated to develop multivariable analysis and to investigate the diagnostic value of each parameter. RESULTS: The sCD40L, sVCAM-1, MCP-1, TNF-alpha, and ET-1 were significantly higher in study patients compared with the reference group. The hsCRP was similar in both groups, whereas RANTES was decreased in study patients. A positive correlation was found between ET-1 and soccer-induced enhanced levels of sCD40L, sVCAM-1, MCP-1, and TNF-alpha. Receiver-operating characteristic analysis displayed high performance of both MCP-1 and ET-1 as a measure to discriminate between stress-induced ACS and ACS controls. CONCLUSIONS: Stress-induced ACS is associated with a profound increase of inflammatory and vasoconstrictive mediators. The evaluation of a targeted drug delivery, such as anti-inflammatory agents, ET-1 receptor antagonists, or inhibition of endothelin-converting enzyme is warranted to reduce stress-mediated cardiovascular morbidity.

Cardiovascular events during World Cup soccer.

BACKGROUND: The Fédération Internationale de Football Association (FIFA) World Cup, held in Germany from June 9 to July 9, 2006, provided an opportunity to examine the relation between emotional stress and the incidence of cardiovascular events. METHODS: Cardiovascular events occurring in patients in the greater Munich area were prospectively assessed by emergency physicians during the World Cup. We compared those events with events that occurred during the control period: May 1 to June 8 and July 10 to July 31, 2006, and May 1 to July 31 in 2003 and 2005. RESULTS: Acute cardiovascular events were assessed in 4279 patients. On days of matches involving the German team, the incidence of cardiac emergencies was 2.66 times that during the control period (95% confidence interval [CI], 2.33 to 3.04; P<0.001); for men, the incidence was 3.26 times that during the control period (95% CI, 2.78 to 3.84; P<0.001), and for women, it was 1.82 times that during the control period (95% CI, 1.44 to 2.31; P<0.001). Among patients with coronary events on days when the German team played, the proportion with known coronary heart disease was 47.0%, as compared with 29.1% of patients with events during the control period. On those days, the highest average incidence of events was observed during the first 2 hours after the beginning of each match. A subanalysis of serious events during that period, as compared with the control period, showed an increase in the incidence of myocardial infarction with ST-segment elevation by a factor of 2.49 (95% CI, 1.47 to 4.23), of myocardial infarction without ST-segment elevation or unstable angina by a factor of 2.61 (95% CI, 2.22 to 3.08), and of cardiac arrhythmia causing major symptoms by a factor of 3.07 (95% CI, 2.32 to 4.06) (P<0.001 for all comparisons). CONCLUSIONS: Viewing a stressful soccer match more than doubles the risk of an acute cardiovascular event. In view of this excess risk, particularly in men with known coronary heart disease, preventive measures are urgently needed.