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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 ...

1,2-Diarylethenes and 1,2-diarylethynes are readily converted to the corresponding 1,2-diketones in high yield using the reagent iodine in dimethyl sulfoxide. Alkynes in these reactions are more reactive than alkenes.

After reaction of ICl and Ag 2 SO 4 in sulfuric acid and separation of resulting AgCl a stable solution is formed, containing very active forms of electrophilic iodine. This solution has a powerful iodination ability with respect to aromatic compounds. Deactivated arenes are iodinated easily and in mild conditions by action of this new reagent in generally good yields of the iodoarenes.Iodoarenes are valuable, versatile synthetic intermediates and have found wide applications in medicine and biochemistry. But the electrophilic nature of iodine is weaker than bromine and chlorine. For this and other reasons there are few methods for direct iodination of deactivated aromatics known. 1 Some arenes having electron-withdrawing substituents can be iodinated by the I 2 /Ag 2 SO 4 system in sulfuric acid. Under these conditions nitrobenzene (1a) is transformed into 3-iodonitrobenzene (2a) at 100 °C within 2-3 hours. 2 The use of iodine in 20% fuming sulfuric acid (oleum) for iodination of a range of aromatic nitro compounds was described. 3 In these conditions nitrobenzene (1a) can be iodinated to 3-iodonitrobenzene (2a) at room temperature and within 20 hours with 52% yield. Specific iodination of some deactivated arenes was achieved by using iodine with fluorine as the oxidant. 4 Probably nowadays the most active iodination agent is N-iodosuccinimide in CF 3 SO 3 H. 5 Deactivated arenes were found to react easily with this reagent giving iodoarenes with good yields. So, for example, nitrobenzene (1a) gives iodonitrobenzene 2a (86%) within two hours at room temperature. 5