Renormalized interactions with a realistic single particle basis

Neutron-rich isotopes in the sdpf space with Z < 15 require modifications to derived effective interactions to agree with experimental data away from stability. A quantitative justification is given for these modifications due to the weakly bound nature of model space orbits via a procedure using realistic radial wavefunctions and realistic NN interactions. The long tail of the radial wavefunction for loosely bound single particle orbits causes a reduction in the size of matrix elements involving those orbits, most notably for pairing matrix elements, resulting in a more condensed level spacing in shell model calculations. Example calculations are shown for 36Si and 38Si.Comment: 6 page

Competitive tenders on analogue hospital pharmaceuticals in Denmark 2017-2020

BACKGROUND: Competitive tenders on pharmaceuticals are one of the most effective cost-containment instruments in healthcare systems. Its effectiveness has been demonstrated, among other things, in markets for generic medicine and biosimilars. In Denmark, an internationally unique model for competitive tenders on analogue substitutable pharmaceuticals has been developed and implemented for all public hospitals. METHODS: We obtained data on all analogue competitive tenders carried out by the Danish Medicines Council from its foundation on January 1, 2017, to October 9, 2020. We calculated univariate descriptive statistics, pairwise correlations and made a multiple regression analysis on tender savings. RESULTS: Average annual saving on hospital pharmaceutical purchase prices was 44.1% ranging from 0.4% to 92.8% between therapeutic areas and areas of indication. There was a significant positive correlation between tender savings and the number of competitors participating in the tender, and a significant negative correlation between tender savings and the number of days since market authorization. CONCLUSIONS: This study finds analogue tenders to be similar in effect and mechanism to competitive tenders in markets for generic medicine and biosimilars. It supports the increasing number of empirical findings that competitive tendering has a high potential to generate substantial savings on healthcare budgets

Governance Struggles and Policy Processes in Disaster Risk Reduction: A Case Study from Nepal

In the neo-liberal climate of reduced responsibility for the state, alongside global platforms established to implement the Hyogo Framework for Action, a new arena opens for a multitude of stakeholders to engage in disaster risk reduction (DRR). The key role that the state can play in instituting effective DRR tends to receive little attention, yet in situations where the state apparatus is weak, such as in Nepal, it becomes evident that integrating DRR into development is a particularly challenging task. Due to the political situation in Nepal, progress has been stalled in providing a legislative context conducive to effective DRR. This paper traces the evolution of key DRR initiatives that have been developed in spite of the challenging governance context, such as the National Strategy for Disaster Risk Management and the Nepal Risk Reduction Consortium. Informed by in-depth interviews with key informants, the argument is made that the dedicated efforts of national and international non-governmental organisations, multilateral agencies and donors in mainstreaming DRR demonstrate that considerable progress can be made even where government departments are protective of their own interests and are slow to enact policies to support DRR. The paper suggests however, that without stronger engagement of key political actors the prospects for further progress in DRR may be limited. The findings have implications for other post-conflict countries or weak states engaging in DRR

Scenarios for use of biogas for heavy-duty vehicles in Denmark and related GHG emission impacts

Biogas may be a promising alternative fuel, mainly for heavy-duty vehicles, that can reduce CO2 emissions via substitution of fossil fuels and further reduce methane emissions from agricultural manure handling. However, as methane is a potent climate gas loss of methane from production to use of biogas is of concern. This study has analysed the potential biomass and biogas production from all Danish organic waste sources under different scenario assumptions for future scenario years. The analysis includes energy demand of the road transportation sector by means of transport and fuel types, and potential use of the limited biogas resource taking into account alternative fuel options available for transportation (electricity, hydrogen, biofuels). Further, the total differences in fuel consumption and GHG emissions due to the replacement of diesel-powered heavy-duty vehicles by gas-powered heavy-duty vehicles are estimated in a well-to-wheel perspective taking into account methane losses

Characterisation of cytotoxicity and DNA damage induced by the topoisomerase II-directed bisdioxopiperazine anti-cancer agent ICRF-187 (dexrazoxane) in yeast and mammalian cells

BACKGROUND: Bisdioxopiperazine anti-cancer agents are inhibitors of eukaryotic DNA topoisomerase II, sequestering this protein as a non-covalent protein clamp on DNA. It has been suggested that such complexes on DNA represents a novel form of DNA damage to cells. In this report, we characterise the cytotoxicity and DNA damage induced by the bisdioxopiperazine ICRF-187 by a combination of genetic and molecular approaches. In addition, the well-established topoisomerase II poison m-AMSA is used for comparison. RESULTS: By utilizing a panel of Saccharomyces cerevisiae single-gene deletion strains, homologous recombination was identified as the most important DNA repair pathway determining the sensitivity towards ICRF-187. However, sensitivity towards m-AMSA depended much more on this pathway. In contrast, disrupting the post replication repair pathway only affected sensitivity towards m-AMSA. Homologous recombination (HR) defective irs1SF chinese hamster ovary (CHO) cells showed increased sensitivity towards ICRF-187, while their sensitivity towards m-AMSA was increased even more. Furthermore, complementation of the XRCC3 deficiency in irs1SF cells fully abrogated hypersensitivity towards both drugs. DNA-PK(cs )deficient V3-3 CHO cells having reduced levels of non-homologous end joining (NHEJ) showed slightly increased sensitivity to both drugs. While exposure of human small cell lung cancer (SCLC) OC-NYH cells to m-AMSA strongly induced γH2AX, exposure to ICRF-187 resulted in much less induction, showing that ICRF-187 generates fewer DNA double strand breaks than m-AMSA. Accordingly, when yeast cells were exposed to equitoxic concentrations of ICRF-187 and m-AMSA, the expression of DNA damage-inducible genes showed higher levels of induction after exposure to m-AMSA as compared to ICRF-187. Most importantly, ICRF-187 stimulated homologous recombination in SPD8 hamster lung fibroblast cells to lower levels than m-AMSA at all cytotoxicity levels tested, showing that the mechanism of action of bisdioxopiperazines differs from that of classical topoisomerase II poisons in mammalian cells. CONCLUSION: Our results point to important differences in the mechanism of cytotoxicity induced by bisdioxopiperazines and topoisomerase II poisons, and suggest that bisdioxopiperazines kill cells by a combination of DNA break-related and DNA break-unrelated mechanisms