The origins of the trypanosome genome strains Trypanosoma brucei brucei TREU 927, T. b. gambiense DAL 972, T. vivax Y486 and T. congolense IL3000

The genomes of several tsetse-transmitted African trypanosomes (Trypanosoma brucei brucei, T. b. gambiense, T. vivax, T. congolense) have been sequenced and are available to search online. The trypanosome strains chosen for the genome sequencing projects were selected because they had been well characterised in the laboratory, but all were isolated several decades ago. The purpose of this short review is to provide some background information on the origins and biological characterisation of these strains as a source of reference for future users of the genome data. With high throughput sequencing of many more trypanosome genomes in prospect, it is important to understand the phylogenetic relationships of the genome strains

The PREDICTS database: a global database of how local terrestrial biodiversity responds to human impacts

Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species’ threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project – and avert – future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1% of the total number of all species described, and more than 1% of the described species within many taxonomic groups – including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems – www.predicts.org.uk). We make site-level summary data available alongside this article. The full database will be publicly available in 2015

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Mindful of the Love : The Holy Communion and daily Life

Londonxi, 132 p.; 20 c

Supervision of Instruction in Elementary Schools: An Inquiry Into the Theory of Supervision and the Reaction of Teachers to Supervisory Practices

Abstract not availabl

Frontiers Old and New

512 hal;ill;20 c

Globalisierung, Sicherheit und Wirtschaftspolitik

Die gegenwärtige Weltwirtschaftskrise hat die Diskussion um die Wirkungen der Globalisierung und einer kapitalistischen Wirtschaftsordnung neu entfacht, vielfach herrscht eine große Skepsis über die möglichen negativen Wirkungen der Globalisierung. Derartig motivierte Sorgen können sich durch radikale Kräfte instrumentalisieren lassen und Konflikte beziehungsweise Gewalt entfachen. Auf der anderen Seite kann Globalisierung friedensstiftend wirken, weil der Handel zum gegenseitigen Vorteil aus Fremden Partner macht. Vor diesem Hintergrund untersucht der Aufsatz die Evidenz und gibt einen Überblick über die relevante Literatur. Es zeigt sich, dass zwischenstaatliche Konflikte eindeutig durch internationale Arbeitsteilung reduziert werden. Für Terrorakte kann keine klare Evidenz gesehen werden. Daraus ist die wirtschaftspolitische Schlussfolgerung zu ziehen, die Märkte offen zu halten und die Kenntnisse über die Wirkungsmechanismen in breiten Kreisen der Bevölkerung zu verbessern. Abstract The current economic crisis has intensified the debate on globalisation. There is a widespread scepticism about it, which can be instrumentalised by extremist groups and thus may lead to violence and terror. On the other hand, globalisation and the international division of labour may well contribute to peace since it raises the opportunity cost of violence, terror and war. The paper investigates the empirical evidence, which is straightforward for international official conflicts: they are reduced by globalisation and trade. With respect to terror, the evidence is less clear: some studies claim a terror enhancing effect of globalisation, some the opposite. Therefore, it seems necessary to improve the knowledge about the effects of international trade, besides keeping markets open to further reduce the potential of international conflict. JEL Classifications: D7, F

Platinum Priority -Review -Prostate Cancer Treatment of the Primary Tumor in Metastatic Prostate Cancer: Current Concepts and Future Perspectives

Abstract Context: Multimodal treatment for men with locally advanced prostate cancer (PCa) using neoadjuvant/adjuvant systemic therapy, surgery, and radiation therapy is being increasingly explored. There is also interest in the oncologic benefit of treating the primary tumor in the setting of metastatic PCa (mPCa). Objective: To perform a review of the literature regarding the treatment of the primary tumor in the setting of mPCa. Evidence acquisition: Medline, PubMed, and Scopus electronic databases were queried for English language articles from January 1990 to September 2014. Prospective and retrospective studies were included. Evidence synthesis: There is no published randomized controlled trial (RCT) comparing local therapy and systemic therapy to systemic therapy alone in the treatment of mPCa. Prospective studies of men with locally advanced PCa and retrospective studies of occult node-positive PCa have consistently shown the addition of local therapy to a multimodal treatment regimen improves outcomes. Molecular and genomic evidence further suggests the primary tumor may have an active role in mPCa. Conclusions: Treatment of the primary tumor in mPCa is being increasingly explored. While preclinical, translational, and retrospective evidence supports local therapy in advanced disease, further prospective studies are under way to evaluate this multimodal approach and identify the patients most likely to benefit from the inclusion of local therapy in the setting of metastatic disease. Patient summary: In this review we explored preclinical and clinical evidence for treatment of the primary tumor in metastatic prostate cancer (mPCa). We found evidence to support clinical trials investigating mPCa therapy that includes local treatment of the primary tumor. Currently, treating the primary tumor in mPCa is controversial and lacks high-level evidence sufficient for routine recommendation.