Practice makes policy? The role of government and policy in shaping practices

Government and policy inevitably shape social practices. Both directly and indirectly, policy instruments can produce, configure, disperse and kill-off practices. How policy makers understand the nature of energy consumption crucially informs the design of policy interventions. The physical, technical and economic model (PTEM) of energy demand dominates policy, with little regard for how social norms, service expectations and always-changing practices influence the role of energy in everyday lif

New strategy, new accountability? The European Central Bank and the European Parliament after the strategy review

A striking asymmetry defines the European Central Bank (ECB)’s approach to democratic accountability. Although the post-2008 era saw the ECB move dramatically beyond the narrow role envisaged for it by the 1992 Maastricht Treaty, the central bank has continued to hew closely to its scarce accountability provisions.This article documents the much more complex and discretionary nature of today’s ECB policymaking by comparing the frameworks informing Governing Council deliberations according to the 1998, 2003 and 2021 strategies. It shows that the transformation of the ECB’s monetary policy strategy has not been matched with enhanced accountability arrangements between the ECB and the European Parliament. The article concludes with ambitious, but concrete policy proposals – both in substance and form – for new ways of informing the public about monetary policy, instruments to improve accountability and coordinating monetary policy with other European policymakers

Evaluation of the therapeutic potential of ant-TLR4-antibody MTS510 in experimental stroke and significa of different routes of application

Toll-like receptors (TLRs) are central sensors for the inflammatory response in ischemia-reperfusion injury. We therefore investigated whether TLR4 inhibition could be used to treat stroke in a standard model of focal cerebral ischemia. Anti-TLR4/MD2-antibody (mAb clone MTS510) blocked TLR4-induced cell activation in vitro, as reported previously. Here, different routes of MTS510 application in vivo were used to study the effects on stroke outcome up to 2d after occlusion of the middle cerebral artery (MCAO) for 45 min in adult male C57Bl/6 wild-type mice. Improved neurological performance, reduced infarct volumes, and reduced brain swelling showed that intravascular application of MTS510 had a protective effect in the model of 45 min MCAO. Evaluation of potential long-term adverse effects of anti-TLR4-mAb-treament revealed no significant deleterious effect on infarct volumes nor neurological deficit after 14d of reperfusion in a mild model of stroke (15 min MCAO). Interestingly, inhibition of TLR4 resulted in an altered adaptive immune response at 48 hours after reperfusion. We conclude that blocking TLR4 by the use of specific mAb is a promising strategy for stroke therapy. However, long-term studies with increased functional sensitivity, larger sampling sizes and use of other species are required before a clinical use could be envisaged

Quartet compatibility and the quartet graph

A collection P of leaf-labelled trees is compatible if there exists a single leaf-labelled tree that displays each of the trees in P. Despite its difficulty, determining the compatibility of P is a fundamental task in evolutionary biology. Attractive characterizations in terms of chordal graphs have been previously given for this problem as well as for the problems of (i) determining if there is a unique tree that displays each of the trees in P, that is 'P is definitive and (ii) determining if there is a tree that displays P and has the property that every other tree that displays P is a refinement of it, that is 'P identifies a leaf-labelled tree. In this paper, we describe new characterizations of each of these problems in terms of edge colourings. Furthermore, for an arbitrary leaf-labelled tree 'T, we also determine the minimum number of 'quartets' required to identify 'T, thus correcting a previously published result

Climate risks are real and need to become part of bank capital regulation

Climate risks are building up on banks’ balance sheets. Supervisory reviews show that banks are not well prepared. Yet, supervisors have been slow to include climate risks in minimum capital requirements. This column argues that doing so would speed up the transition to a low-carbon economy. Given the urgency of addressing the environmental risks that are now largely not accounted for, speed is of the essence

Integrative clinical transcriptome analysis reveals TMPRSS2-ERG dependency of prognostic biomarkers in prostate adenocarcinoma

In prostate adenocarcinoma (PCa), distinction between indolent and aggressive disease is challenging. Around 50% of PCa are characterized by TMPRSS2-ERG (T2E)-fusion oncoproteins defining two molecular subtypes (T2E-positive/negative). However, current prognostic tests do not differ between both molecular subtypes, which might affect outcome prediction. To investigate gene-signatures associated with metastasis in T2E-positive and T2E-negative PCa independently, we integrated tumor transcriptomes and clinicopathological data of two cohorts (total n = 783), and analyzed metastasis-associated gene- signatures regarding the T2E-status. Here, we show that the prognostic value of biomarkers in PCa critically depends on the T2E-status. Using gene-set enrichment analyses, we uncovered that metastatic T2E-positive and T2E-negative PCa arecharacterized by distinct gene-signatures. In addition, by testing genes shared by several functional gene-signatures for theirassociation with event-free survival in a validation cohort (n=272), we identifiedfive genes (ASPN,BGN,COL1A1,RRM2andTYMS)—three of which are included in commercially available prognostic tests—whose high expression was significantlyassociated with worse outcome exclusively in T2E-negative PCa. Among these genes,RRM2andTYMSwere validated byimmunohistochemistry in another validation cohort (n=135), and several of them proved to add prognostic information tocurrent clinicopathological predictors, such as Gleason score, exclusively for T2E-negative patients. No prognostic biomarkerswere identified exclusively for T2E-positive tumors. Collectively, our study discovers that the T2E-status, which ispersenot astrong prognostic biomarker, crucially determines the prognostic value of other biomarkers. Our data suggest that themolecular subtype needs to be considered when applying prognostic biomarkers for outcome prediction in PCa. What’s new? Genetic rearrangements involving androgen-regulated transmembrane protease serine 2 and genes from the ETS transcription factor family (T2E), most commonly ERG and ETV1, occur in half of prostate cancers but are currently not considered in risk predictions. The authors integrate clinical and transcriptomic data from multiple studies and show that the prognostic value of biomarkers critically depends on the T2E-status. They identify five biomarkers that predict negative outcome exclusively in T2E-negative prostate cancers, which has implications for outcome prediction based on the molecular subtype.Deutsche Forschungsgemeinschaft 391665916Deutsche Krebshilfe 70112257Dr Leopold and Carmen Ellinger FoundationDr Rolf M. Schwiete FoundationFriedrich-Baur FoundationGert and Susanna Mayer FoundationKind-Philipp FoundationMatthias-Lackas FoundationMehr LEBEN fur Krebskranke Kinder-Bettina-Brau-StiftungWilhelm Sander-Stiftung 2016.167.