Abstract. Little quantitative knowledge is as yet available about the role of hydrological model complexity for climate change impact assessment. This study investigates and compares the varieties of different model response of three hydrological models (PROMET, Hydrotel, HSAMI), each representing a different model complexity in terms of process description, parameter space and spatial and temporal scale. The study is performed in the Ammer watershed, a 709 km 2 catchment in the Bavarian alpine forelands, Germany. All models are driven and validated by a 30-year time-series of observation data. It is expressed by objective functions, that all models, HSAMI and Hydrotel due to calibration, perform almost equally well for runoff simulation over the validation period. Some systematic deviances in the hydrographs and the spatial patterns of hydrologic variables are however quite distinct and thus further discussed.Virtual future climate (2071-2100) is generated by the Canadian Regional Climate Model (vers 3.7.1), driven by the Coupled Global Climate Model (vers. 2) based on an A2 emission scenario (IPCC 2007). The hydrological model performance is evaluated by flow indicators, such as flood frequency, annual 7-day and 30-day low flow and maximum seasonal flows. The modified climatic boundary conditions cause dramatic deviances in hydrologic model response. HSAMI shows tremendous overestimation of evapotranspiration, while Hydrotel and PROMET behave in comparable range. Still, their significant differences, like spatially explicit patterns of summerly water shortage or spring flood intensity, highlight the necessity to extend and quantify Correspondence to: R. Ludwig (r.ludwig@lmu.de) the uncertainty discussion in climate change impact analysis towards the remarkable effect of hydrological model complexity. It is obvious that for specific application purposes, water resources managers need to be made aware of this effect and have to take its implications into account for decision making. The paper concludes with an outlook and a proposal for future research necessities.

Predictive preventive personalized medicine Liver cancer is the fifth most common form of cancer worldwide [1], with an incidence rate almost equals the mortality rate and ranks 3 rd among causes of cancer related death [2]. The coexistence of two life threatening conditions, cancer and liver cirrhosis makes the staging challenging. However, there are some staging systems, e.g. the Barcelona staging system for Hepatocellular carcinoma (HCC) [3], that suggest treatment options and management. Whereas diagnosis in early stages gives hope for a curative outcome, the treatment regime for around 80 % [2] of the patients classified as severe stages only gears towards palliation [4]. An intra-arterial radiation approach, radioembolisation (RE) is ubiquitously applied as one of palliative approaches. Although, in general RE shows promising results in intermediate and advanced stage HCC [5], individual treatment outcomes are currently unpredictable. Corresponding stratification criteria are still unclear. We hypothesised that individual radioresistance/radiosensitivity may play a crucial role in treatment response towards RE strongly influencing individual outcomes. Further, HCC represents a highly heterogeneous group of patients which requires patient stratification according to clear criteria for treatment algorithms to be applied individually. Multilevel diagnostic approach (MLDA) is considered helpful to set-up optimal predictive and prognostic biomarker panel for individualised application of radioembolisation. Besides comprehensive medical imaging, our MLDA includes non-invasive multi-omics and sub-cellular imaging. Individual patient profiles are expected to give a clue to targeting shifted molecular pathways, individual RE susceptibility, treatment response. Hence, a dysregulation of the detoxification pathway (SOD2/Catalase) might indicate possible adverse effects of RE, and highly increased systemic activities of matrix metalloproteinases indicate an enhanced tumour aggressiveness and provide insights into molecular mechanisms/targets. Consequently, an optimal set-up of predictive and prognostic biomarker panels may lead to the changed treatment paradigm from untargeted "treat and wait" to the cost-effective predictive, preventive and personalised approach, improving the life quality and life expectancy of HCC patients. Keywords: Market access, Value, Strategy, Companion diagnostics, Cost-effectiveness, Reimbursement, Health technology assessment, Economic models, Predictive preventive personalized medicine Achieving and sustaining seamless "drug -companion diagnostic" market access requires a sound strategy throughout a product life cycle, which enables timely creation, substantiation and communication of value to key stakeholders [1, 2]. The study aims at understanding the root-cause of market access inefficiencies of companies by gazing at the "Rx-CDx" co-development process through the prism of "value", and developing a perfect co-development scenario based on the literature review and discussions with the ...

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The article presents main stages of the accommodation of the Federal Service for Supervision in the field of consumer rights protection and human well-being for a risk-oriented model of control and supervision activities. The main methodological approaches to the classification of the activities of legal entities and individual entrepreneurs on the potential risk of harm to human health in the case of non-compliance with mandatory sanitary and epidemiological requirements are described. When assessing the risk, the probable frequency of violations of legislative requirements, the associated indices of potential harm to human health and the population under the influence of the surveillance facility activity were shown to be taken into account. For the tasks of the risk-oriented model, there was formed a federal register of supervisory objects, supplemented by data from all 85 regions of the country. The results of categorization of more than 630 thousand objects of supervision, data on which are included in the federal register, indicate to the share of objects of extremely high and high risk of harm to amount about 7.5% of the total mass. About 40% of the facilities do not form significant risks for citizens and can be excluded from the planned supervision, which does not exclude unscheduled inspections of their activities on the grounds established by law. The classification system is dynamic, allows lowering or raising the category of the object of supervision, depending on the results and history of inspections. The ways of the development of the risk-oriented model of supervision are determined.

In the paper there are described examples of the practical implementation of methodological approaches to the assessment of evolution of the health risk under exposure to a set of environmental factors. In the hygienic assessment of the dynamics of health risks for citizens, residing near a major airport (about 500 takeoffs and landings per day), there were revealed high risks of disorders of the cardiovascular and nervous system. The difference between the risks emerging under the exposure and without the impact of the factors peculiar to the airport was shown to increase with the age significantly, accounting for 5-year period, 1,2% of the exposure; over 20 years - 8-10%, and during the period of 50 years - more than 20%. There were obtained results describing the dynamics of the gain of risks for the population of all ages, the structure of risks in the different periods of the human life. Outputs of evolutionary modeling allowed to identify critical periods of exposure to factors for which the qualitative changes of levels of risk take place. This is important in justifying the order ofpriorities and urgency of sanitary hygienic measures for risk management. The development of methodological approaches lies in the plane of the refinement of mathematical models, improvement of methods for the assessment of the intensity and duration of exposure, taking into account features of the combined impacts of hazard factors of different nature.