A Critical Appraisal of Digitalization in City Administration

The improvement in technology infrastructure has paved way for creating web-portals, social media portals and space for suggestions within. This facility is well utilized by public to provide observations on development activities. For city administration, where development activities can take the help of technology to resolve social issues, it has given options in expressing opinions on different hash tags created by stakeholders for making structural decisions. The opinions posted are often random and at times critical to the issues in discussion. This paper brings out those observations posted in social media portals like twitter on urban development activities, analyzing statements to capture topics in discussion, the degree of relationship within the topics, and human emotions expressed as sentiments in the observations made for resolving social issues and innovative measures undertaken. The results indicate utmost positive sentiments expressed by public for measures and resolutions undertaken to deploy technology infrastructure in citie

Choice of Agile Methodologies in Software Development: A Vendor Perspective

The purpose of this research was to develop understanding about how vendor firms make choice about agile methodologies in software projects and their fit. Two analytical frameworks were developed from extant literature and the findings were compared with real world decisions. Framework 1 showed that the choice of XP for one project was not supported by the guidelines given by the framework. The choices of SCRUM for other two projects, were partially supported. Analysis using the framework 2 showed that except one XP project, all others had sufficient project management support, limited scope for adaptability and had prominence for rules

Fit of Development Methodologies in Software Projects

Software project outcomes characterized by meeting goal achievement and performance triad of budget, schedule and quality have been shown to be contingent upon project environment factors. However, choice of methodology and its implications on project outcomes still remain under- investigated. Following contingency theory, we empirically examine the effect of the fit between the choice of development methodology and project environment on the project outcome. We analysed a sample of 163 software development projects using PLS-SEM and our results show that the use of traditional methodology strongly countered the negative effect of requirement volatility on project outcome compared to agile methodologies and use of hybrid methodologies showed a stronger positive effect of project complexity on goal achievement. Further, for critical projects, use of agile methodologies favored goal achievement

Utility of B-type natriuretic peptide in predicting medium-term mortality in patients undergoing major non-cardiac surgery

We assessed the ability of pre-operative B-type natriuretic peptide (BNP) levels to predict medium-term mortality in patients undergoing major noncardiac surgery. During a median 654 days follow-up 33 patients from a total cohort of 204 patients (16%) died. The optimal cut-off in this cohort, determined using a receiver operating characteristic curve, was >35pg.mL-1. This was associated with a 3.47-fold increase in the hazard of death (p=0.001) and had a sensitivity of 70% and a specificity of 68% for this outcome. These findings extend recent work demonstrating that BNP levels obtained before major noncardiac surgery can be used to predict peri-operative morbidity, and indicate that they also forecast medium-term mortality.This work was supported by a grant from TENOVUS Scotland. The Health Services Research Unit is core-funded by the Chief Scientists Office of the Scottish Executive Health Department.Peer reviewedAuthor versio

Lysis-deficient phages as novel therapeutic agents for controlling bacterial infection

<p>Abstract</p> <p>Background</p> <p>Interest in phage therapy has grown over the past decade due to the rapid emergence of antibiotic resistance in bacterial pathogens. However, the use of bacteriophages for therapeutic purposes has raised concerns over the potential for immune response, rapid toxin release by the lytic action of phages, and difficulty in dose determination in clinical situations. A phage that kills the target cell but is incapable of host cell lysis would alleviate these concerns without compromising efficacy.</p> <p>Results</p> <p>We developed a recombinant lysis-deficient <it>Staphylococcus aureus </it>phage P954, in which the endolysin gene was rendered nonfunctional by insertional inactivation. P954, a temperate phage, was lysogenized in <it>S. aureus </it>strain RN4220. The native endolysin gene on the prophage was replaced with an endolysin gene disrupted by the chloramphenicol acetyl transferase (<it>cat</it>) gene through homologous recombination using a plasmid construct. Lysogens carrying the recombinant phage were detected by growth in presence of chloramphenicol. Induction of the recombinant prophage did not result in host cell lysis, and the phage progeny were released by cell lysis with glass beads. The recombinant phage retained the endolysin-deficient genotype and formed plaques only when endolysin was supplemented. The host range of the recombinant phage was the same as that of the parent phage. To test the <it>in vivo </it>efficacy of the recombinant endolysin-deficient phage, immunocompromised mice were challenged with pathogenic <it>S. aureus </it>at a dose that results in 80% mortality (LD₈₀). Treatment with the endolysin-deficient phage rescued mice from the fatal <it>S. aureus </it>infection.</p> <p>Conclusions</p> <p>A recombinant endolysin-deficient staphylococcal phage has been developed that is lethal to methicillin-resistant <it>S. aureus </it>without causing bacterial cell lysis. The phage was able to multiply in lytic mode utilizing a heterologous endolysin expressed from a plasmid in the propagation host. The recombinant phage effectively rescued mice from fatal <it>S. aureus </it>infection. To our knowledge this is the first report of a lysis-deficient staphylococcal phage.</p

A novel bacteriophage Tail-Associated Muralytic Enzyme (TAME) from Phage K and its development into a potent antistaphylococcal protein

<p>Abstract</p> <p>Background</p> <p><it>Staphylococcus aureus </it>is a major cause of nosocomial and community-acquired infections. However, the rapid emergence of antibiotic resistance limits the choice of therapeutic options for treating infections caused by this organism. Muralytic enzymes from bacteriophages have recently gained attention for their potential as antibacterial agents against antibiotic-resistant gram-positive organisms. Phage K is a polyvalent virulent phage of the <it>Myoviridae </it>family that is active against many <it>Staphylococcus </it>species.</p> <p>Results</p> <p>We identified a phage K gene, designated <it>orf</it>56, as encoding the phage tail-associated muralytic enzyme (TAME). The gene product (ORF56) contains a C-terminal domain corresponding to cysteine, histidine-dependent amidohydrolase/peptidase (CHAP), which demonstrated muralytic activity on a staphylococcal cell wall substrate and was lethal to <it>S. aureus </it>cells. We constructed N-terminal truncated forms of ORF56 and arrived at a 16-kDa protein (Lys16) that retained antistaphylococcal activity. We then generated a chimeric gene construct encoding Lys16 and a staphylococcal cell wall-binding SH3b domain. This chimeric protein (P128) showed potent antistaphylococcal activity on global clinical isolates of <it>S. aureus </it>including methicillin-resistant strains. In addition, P128 was effective in decolonizing rat nares of <it>S. aureus </it>USA300 in an experimental model.</p> <p>Conclusions</p> <p>We identified a phage K gene that encodes a protein associated with the phage tail structure. The muralytic activity of the phage K TAME was localized to the C-terminal CHAP domain. This potent antistaphylococcal TAME was combined with an efficient <it>Staphylococcus</it>-specific cell-wall targeting domain SH3b, resulting in the chimeric protein P128. This protein shows bactericidal activity against globally prevalent antibiotic resistant clinical isolates of <it>S. aureus </it>and against the genus <it>Staphylococcus </it>in general. <it>In vivo</it>, P128 was efficacious against methicillin-resistant <it>S. aureus </it>in a rat nasal colonization model.</p

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Platelet activation, biomarkers and troponin 1 release following major vascular surgery

Platelets have been implicated in the pathogenesis and progression of atherosclerosis in patients with peripheral arterial disease. These patients have been shown to have increased platelet activation as assessed by flow cytometry. P-selectin expression and fibrinogen binding as well as increased platelet aggregation. Platelet activation is also believed to play an important role in the pathogenesis of arterial thrombosis and related acute myocardial infarction. Platelet activity is increased in patients with acute coronary syndromes and in those with ST-segment elevation MI. Biomarkers like C-reactive protein (CRP), Interluekin-6 (IL-6), N Terminal –pro-B type Natriuretic Peptide (NT-pro-BNP) have been shown to be risk assessment tools in non-cardiac vascular surgical patients. This research study was prospectively conducted to see if platelet activation markers, aggregation tests and biomarkers mentioned above had any relationship to post-operative myocardial ischaemic events detected by Troponin-I elevation with or without electrocardiogram/ Holter detected ischaemic changes. 136 patients due to undergo repair for abdominal aortic aneurysm or lower extremity revascularisation for severe limb ischaemia were recruited for the study.EThOS - Electronic Theses Online ServiceGBUnited Kingdo