Grid tool integration within the eMinerals Project

In this article we describe the eMinerals mini grid, which is now running in production mode. Thisis an integration of both compute and data components, the former build upon Condor, PBS and thefunctionality of Globus v2, and the latter being based on the combined use of the Storage ResourceBroker and the CCLRC data portal. We describe how we have integrated the middleware components,and the different facilities provided to the users for submitting jobs within such an environment. We willalso describe additional functionality we found it necessary to provide ourselves

The Ethics of Belief

There is an ethics of thought, as well as of practice, and that ethics is the same outside religion as within it. We may not be able to control our beliefs directly, but we can control them indirectly. So we are accountable for the ways in which we form our beliefs. Some say that beliefs are private affairs, but our beliefs affect our actions, and our actions have consequences for others. Thus we are accountable for our beliefs. Religious traditions that promote unquestioning acceptance of belief without evidence are violating the ethics of belief. William James’ defense of belief without evidence is enticing, but ultimately unsuccessful.SUNY BrockportPhilosophic Exchang

Pancreatic insufficiency in patients with HIV infection: role of didanosine questioned.

OBJECTIVES: The aim of the study was to identify possible causes of pancreatic insufficiency in patients with HIV infection. METHODS: A retrospective analysis of 233 HIV-positive patients for whom faecal elastase measurement was available was performed to investigate potential associations with core demographic data, HIV infection characteristics, degree of immunosuppresion, exposure to antiretroviral therapy (ART), alcohol misuse, diabetes, hepatitis C virus (HCV) infection, triglyceride and cholesterol levels and symptomatology. The response to pancreatic enzyme replacement for patients with evidence of insufficiency was also evaluated. RESULTS: Of 233 patients, 104 (45%) had evidence of pancreatic exocrine insufficiency (faecal elastase < 200 mcg/g). A positive association with exocrine pancreatic insufficiency was found for HCV infection (P = 0.007), previous or current HCV treatment (P = 0.003), alcohol misuse history (P = 0.006) and the presence of steatorrhoea (P = 0.03). There was no demonstrated association between exocrine pancreatic insufficiency and didanosine (ddI) exposure (P = 0.43) or stavudine (d4T) exposure (P = 0.62). Seventy-seven per cent of patients who were treated with pancreatic enzymatic supplementation reported a subjective improvement in symptoms. CONCLUSIONS: Faecal elastase sampling should form part of the routine work-up for HIV-positive patients with chronic diarrhoea even in the absence of 'traditional' risk factors such as ddI exposure. In particular, if the patient has steatorrhoea, a history of alcohol exposure or their HCV serology is positive, they should be considered for investigation. Treatment with pancreatic enzyme supplementation appears to be effective in the treatment of chronic diarrhoea caused by pancreatic insufficiency in the majority of patients

Synthesis of recombinant antibacterial proteins in the Chlamydomonas reinhardtii chloroplast

The rise of antibiotic resistance and the decline in antibiotic discovery have been well publicised. These issues, in combination with a growing global reliance upon antibiotics for everyday modern life, urgently require the discovery of novel antibacterial drugs. Endolysins are one potential candidate to support, or replace, conventional antibiotics. Endolysins are lytic enzymes produced by bacteriophage in natura to enable the release of viral progeny from inside the host bacterium. When applied exogenously, endolysins can lyse Gram-positive bacteria, and thus could be used as a novel antibacterial for this group of pathogens. Biologically active endolysins have been successfully expressed as recombinants in the chloroplast of the green alga, Chlamydomonas reinhardtii. C. reinhardtii, and in particular the chloroplast, has several features as a cell factory which make it an attractive alternative to the traditional recombinant protein production platforms. C. reinhardtii is free of endotoxins, can be cultivated at low cost in photobioreactors, has GRAS status, and is genetically tractable. This study initially focuses upon improving the accumulation and activity of one endolysin, Cpl-1, targeting Streptococcus pneumoniae. Recombinant Cpl-1 has been shown previously in the Purton lab to accumulate to moderate levels in the C. reinhardtii chloroplast. Here we present two transgenic lines of C. reinhardtii that appear to accumulate recombinant Cpl-1 to higher levels – one through the incorporation of multiple expression cassettes, and one through codon pair optimization. To improve the activity of Cpl-1 as an enzyme, Cpl-1 binding site mutagenesis, Cpl-1 dimerization, and the production of a potentially synergistic holin protein were all attempted. Finally, an endolysin against Clostridium difficile, CD27L, was successfully produced in the C. reinhardtii chloroplast and shown to be active in vitro. Another endolysin, this time targeting Propionibacterium acnes, failed to express in C. reinhardtii, but was expressed in E. coli, albeit without obvious lytic activity

Atovaquone‐proguanil for treating uncomplicated Plasmodium falciparum malaria

Background The World Health Organization (WHO) in 2015 stated atovaquone‐proguanil can be used in travellers, and is an option in malaria‐endemic areas in combination with artesunate, as an alternative treatment where first‐line artemisinin‐based combination therapy (ACT) is not available or effective. This review is an update of a Cochrane Review undertaken in 2005. Objectives To assess the efficacy and safety of atovaquone‐proguanil (alone and in combination with artemisinin drugs) versus other antimalarial drugs for treating uncomplicated Plasmodium falciparum malaria in adults and children. Search methods The date of the last trial search was 30 January 2020. Search locations for published trials included the Cochrane Infectious Diseases Group Specialized Register, CENTRAL, MEDLINE, Embase, and LILACS. To include recently published and unpublished trials, we also searched ClinicalTrials.gov, the metaRegister of Controlled Trials and the WHO International Clinical Trials Registry Platform Search Portal. Selection criteria Randomized controlled trials (RCTs) reporting efficacy and safety data for atovaquone‐proguanil or atovaquone‐proguanil with a partner drug compared with at least one other antimalarial drug for treating uncomplicated Plasmodium falciparum infection. Data collection and analysis For this update, two review authors re‐extracted data and assessed certainty of evidence. We meta‐analyzed data to calculate risk ratios (RRs) with 95% confidence intervals (CI) for treatment failures between comparisons, and for safety outcomes between and across comparisons. Outcome measures include unadjusted treatment failures and polymerase chain reaction (PCR)‐adjusted treatment failures. PCR adjustment differentiates new infection from recrudescent infection. Main results Seventeen RCTs met our inclusion criteria providing 4763 adults and children from Africa, South‐America, and South‐East Asia. Eight trials reported PCR‐adjusted data to distinguish between new and recrudescent infection during the follow‐up period. In this abstract, we report only the comparisons against the three WHO‐recommended antimalarials which were included within these trials. There were two comparisons with artemether‐lumefantrine, one trial from 2008 in Ethiopia with 60 participants had two failures with atovaquone‐proguanil compared to none with artemether‐lumefantrine (PCR‐adjusted treatment failures at day 28). A second trial from 2012 in Colombia with 208 participants had one failure in each arm (PCR‐adjusted treatment failures at day 42). There was only one comparison with artesunate‐amodiaquine from a 2014 trial conducted in Cameroon. There were six failures with atovaquone‐proguanil at day 28 and two with artesunate‐amodiaquine (PCR‐adjusted treatment failures at day 28: 9.4% with atovaquone‐proguanil compared to 2.9% with artesunate‐amodiaquine; RR 3.19, 95% CI 0.67 to 15.22; 1 RCT, 132 participants; low‐certainty evidence), although there was a similar number of PCR‐unadjusted treatment failures (9 (14.1%) with atovaquone‐proguanil and 8 (11.8%) with artesunate‐amodiaquine; RR 1.20, 95% CI 0.49 to 2.91; 1 RCT, 132 participants; low‐certainty evidence). There were two comparisons with artesunate‐mefloquine from a 2012 trial in Colombia and a 2002 trial in Thailand where there are high levels of multi‐resistant malaria. There were similar numbers of PCR‐adjusted treatment failures between groups at day 42 (2.7% with atovaquone‐proguanil compared to 2.4% with artesunate‐mefloquine; RR 1.15, 95% CI 0.57 to 2.34; 2 RCTs, 1168 participants; high‐certainty evidence). There were also similar PCR‐unadjusted treatment failures between groups (5.3% with atovaquone‐proguanil compared to 6.6% with artesunate‐mefloquine; RR 0.8, 95% CI 0.5 to 1.3; 1 RCT, 1063 participants; low‐certainty evidence). When atovaquone‐proguanil was combined with artesunate, there were fewer treatment failures with and without PCR‐adjustment at day 28 (PCR‐adjusted treatment failures at day 28: 2.16% with atovaquone‐proguanil compared to no failures with artesunate‐atovaquone‐proguanil; RR 5.14, 95% CI 0.61 to 43.52; 2 RCTs, 375 participants, low‐certainty evidence) and day 42 (PCR‐adjusted treatment failures at day 42: 3.82% with atovaquone‐proguanil compared to 2.05% with artesunate‐atovaquone‐proguanil (RR 1.84, 95% CI 0.95 to 3.56; 2 RCTs, 1258 participants, moderate‐certainty evidence). In the 2002 trial in Thailand, there were fewer treatment failures in the artesunate‐atovaquone‐proguanil group compared to the atovaquone‐proguanil group at day 42 with PCR‐adjustment. Whilst there were some small differences in which adverse events were more frequent in the atovaquone‐proguanil groups compared to comparator drugs, there were no recurrent associations to suggest that atovaquone‐proguanil is strongly associated with any specific adverse event. Authors' conclusions Atovaquone‐proguanil was effective against uncomplicated P falciparum malaria, although in some instances treatment failure rates were between 5% and 10%. The addition of artesunate to atovaquone‐proguanil may reduce treatment failure rates. Artesunate‐atovaquone‐proguanil and the development of parasite resistance may represent an area for further researc

To meat or not to meat? New perspectives on Neanderthal ecology.

Neanderthals have been commonly depicted as top predators who met their nutritional needs by focusing entirely on meat. This information mostly derives from faunal assemblage analyses and stable isotope studies: methods that tend to underestimate plant consumption and overestimate the intake of animal proteins. Several studies in fact demonstrate that there is a physiological limit to the amount of animal proteins that can be consumed: exceeding these values causes protein toxicity that can be particularly dangerous to pregnant women and newborns. Consequently, to avoid food poisoning from meat-based diets, Neanderthals must have incorporated alternative food sources in their daily diets, including plant materials as well

A skirmish in the early reception of Karl Barth in Scotland: The exchange between Thomas F. Torrance and Brand Blanshard

With an introduction by Iain Torrance, this paper reproduces a series of letters in The Scotsman newspaper between T. F. Torrance and the distinguished American philosopher Brand Blanshard. This (at times highly contentious) exchange was occasioned by views expressed by Blanshard in his 1952 Gifford Lectures on Barth and Brunner and what he called their ‘theology of crisis’. The letters give a fascinating insight into the way this new theology was perceived in the English-speaking world at the time