964 research outputs found

    Institutional relatedness and the emergence of renewable energy cooperatives in German districts

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    This paper analyses the evolution of renewable energy cooperatives, examining all such cooperatives founded in German districts between 2006 and 2016. The rise of the cooperative form in renewable energy production is a prominent example of the strong involvement of users in market formation. We investigate the effects of ‘institutional relatedness’, arguing that renewable energy cooperatives can leverage the organizational knowledge and the legitimacy gained by cooperatives active in other industries in the same district. Using an organizational ecology approach, we find that the local presence of cooperatives in other industries indeed supported the founding of renewable energy cooperatives

    Phase IB study of doxorubicin in combination with the multidrug resistance reversing agent S9788 in advanced colorectal and renal cell cancer.

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    S9788 is a new triazineaminopiperidine derivate capable of reversing multidrug resistance (MDR) in cells resistant to chemotherapeutic agents such as doxorubicin. It does not belong to a known class of MDR revertants, but its action involves the binding of P-glycoprotein. Thirty-eight evaluable patients with advanced colorectal or renal cell cancer were treated with doxorubicin alone (16 patients) followed after disease progression with combination treatment of doxorubicin plus S9788 (12 patients) or upfront with the combination of doxorubicin plus S9788 (22 patients). S9788 was given i.v. as a loading dose of 56 mg m-2 over 30 min followed by doxorubicin given at 50 mg m-2 as a bolus infusion. Thereafter, a 2-h infusion of S9788 was administered at escalating doses ranging from 24 to 120 mg m-2 in subsequent cohorts of 4-10 patients. Pharmacokinetic analysis demonstrated that concentrations of S9788 that are known to reverse MDR in vitro were achieved in patients at non-toxic doses. Compared with treatment with doxorubicin alone, treatment with the combination of doxorubicin and S9788 produced a significant increase in the occurrence of WHO grade 3-4 granulocytopenia. Treatment with S9788 was cardiotoxic as it caused a dose-dependent and reversible increase in corrected QT intervals as well as clinically non-significant arrhythmias on 24- or 48-h Holter recordings. Although clinically relevant cardiac toxicities did not occur, the study was terminated as higher doses of S9788 may increase the risk of severe cardiac arrhythmias. Twenty-nine patients treated with S9788 plus doxorubicin were evaluable for response, and one patient, who progressed after treatment with doxorubicin alone, achieved a partial response. We conclude that S9788 administered at the doses and schedule used in this study results in relevant plasma concentrations in humans and can safely be administered in combination with doxorubicin

    Standardising outcomes for clinical trials and systematic reviews

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    Fifteen years ago, what was to become OMERACT met for the first time in The Netherlands to discuss ways in which the multitude of outcomes in assessments of the effects of treatments for rheumatoid arthritis might be standardised. In Trials, Tugwell et al have described the need for, and success of, this initiative [1] and Cooney and colleagues have set out their plans for a corresponding initiative for ulcerative colitis [2]. Why do we need such initiatives? What\u27s the problem? And are these and other initiatives the solution

    Закономерности распределения аномальных концентраций гелия в палеозойских отложениях Донбасса

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    Підвищені концентрації гелію у вільних і розчинених газах у вугільно-породному масиві Донбасу приурочені до зон зчленування Донбасу з Приазовським і Воронезьким кристалічними масивами і Головної антикліналі. Диз'юнктивні тектонічні порушення глибокого закладення служили, ймовірно, шляхами транзиту гелію від кристалічних порід фундаменту в палеозойські відклади Донбасу, і підвищений вміст гелію може служити індикатором шляхів транзиту газів з глибоких горизонтів Донецького вугільного басейну.Elevated concentrations of helium in free and dissolved gases in coal-rock mass of the Donets Coal Basin are confined to the junction zones of the Donets Coal Basin with the Priazovie and Voronezh crystalline core-areas and Glavnaya (Principal) Anticline. Deep-laid disjunctive dislocations were probably the ways for transit of helium from crystalline basement rocks into Paleozoic deposits of the Basin. Elevated concentrations of helium can also serve as indicators of the ways for transit of gases from deep levels of the Donets Coal Basin

    Clarifying misconceptions of extinction risk assessment with the IUCN Red List

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    This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.The identification of species at risk of extinction is a central goal of conservation. As the use of data compiled for IUCN Red List assessments expands, a number of misconceptions regarding the purpose, application and use of the IUCN Red List categories and criteria have arisen. We outline five such classes of misconception; the most consequential drive proposals for adapted versions of the criteria, rendering assessments among species incomparable. A key challenge for the future will be to recognize the point where understanding has developed so markedly that it is time for the next generation of the Red List criteria. We do not believe we are there yet but, recognizing the need for scrutiny and continued development of Red Listing, conclude by suggesting areas where additional research could be valuable in improving the understanding of extinction risk among species

    Matrix Modulation of the Bioactivation of Estragole by Constituents of Different Alkenylbenzene-containing Herbs and Spices and Physiologically Based Biokinetic Modeling of Possible In Vivo Effects

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    The alkenylbenzene estragole is a constituent of several herbs and spices. It induces hepatomas in rodents at high doses following bioactivation by cytochrome P450s and sulfotransferases (SULTs) giving rise to the ultimate carcinogenic metabolite 1'-sulfooxyestragole which forms DNA adducts. Methanolic extracts from different alkenylbenzene-containing herbs and spices were able to inhibit SULT activity. Flavonoids including quercetin, kaempferol, myricetin, apigenin, and nevadensin were the major constituents responsible for this inhibition with Ki values in the nano to micromolar range. In human HepG2 cells exposed to the proximate carcinogen 1ʹ-hydroxyestragole, the various flavonoids were able to inhibit estragole DNA adduct formation and shift metabolism in favor of glucuronidation which is a detoxification pathway for 1ʹ-hydroxyestragole. In a next step, the kinetics for SULT inhibition were incorporated in physiologically based biokinetic (PBBK) models for estragole in rat and human to predict the effect of co-exposure to estragole and (mixtures of) the different flavonoids on the bioactivation in vivo. The PBBK-model-based predictions indicate that the reduction of estragole bioactivation in rat and human by co-administration of the flavonoids is dependent on whether the intracellular liver concentrations of the flavonoids can reach their Ki values. It is expected that this is most easily achieved for nevadensin which has a Ki value in the nanomolar range and is, due to its methyl ation, more metabolically stable than the other flavonoid

    Experience in implementing harvest strategies in Australia's south-eastern fisheries

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    The Southern and Eastern Scalefish and Shark Fishery (SESSF) is a complex multi-species fishery, with 34 stock units under quota management, for which a harvest strategy framework was developed in 2005. The framework involves the application of a set of tier-based harvest control rules (HCR) designed to provide a precautionary approach to management. The harvest strategy framework has been applied from 2005 to 2007, resulting in substantial reductions in quotas across the fishery. The experience in implementing the framework, both positive and negative, is described, and general lessons are drawn. Key lessons include the importance of formally testing such strategies using management strategy evaluation, the impact of external management drivers on implementation of the approach, the need to define strategies for setting "bycatch quotas" in multi-species fisheries, and the need for flexibility and pragmatism in the early stages of implementing such an approach

    Robustness of potential biological removal to monitoring, environmental, and management uncertainties

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    Support for this project was provided by the Lenfest Ocean Program.The potential biological removal (PBR) formula used to determine a reference point for human-caused mortality of marine mammals in the United States has been shown to be robust to several sources of uncertainty. This study investigates the consequences of the quality of monitoring on PBR performance. It also explores stochastic and demographic uncertainty, catastrophic events, sublethal effects of interactions with fishing gear, and the situation of a marine mammal population subject to bycatch in two fisheries, only one of which is managed. Results are presented for two pinniped and two cetacean life histories. Bias in abundance estimates and whether there is a linear relationship between abundance estimates and true abundance most influence conservation performance. Catastrophic events and trends in natural mortality have larger effects than environmental stochasticity. Managing only one of two fisheries with significant bycatch leads, as expected, to a lower probability of achieving conservation management goals, and better outcomes would be achieved if bycatch in all fisheries were managed. The results are qualitatively the same for the four life histories, but estimates of the probability of population recovery differ.Publisher PDFPeer reviewe
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