The design of collaborative projects : Language, metaphor, conversation and the systems approach

This thesis uses a systems approach to develop a model for Collaborative Project Design (CPD). Failure of the software process is the area of concern. The focus of the argument is, however, on the organizational environment of the software process. A central argument is that the analytic tools of standard software development methodologies are inappropriate for systems synthesis. They provide little assistance in coping with the loose complexity that is inherent in the organizational environment in which the software process is embedded. These analytic tools and the engineering language and metaphor which dominate the software process undermine collaboration and disempower business users. CPD was developed to enable viable collaboration that is necessary for the software process to succeed. The purpose of CPD is to provide a systemic model of causal influences and social process in order to guide a project designer when intervening in projects which call for acts of shared creation and/or discovery. CPD was developed through a combination of action research (in projects involving software development and organisational transformation) and theoretical readings focused on the philosophy of meaning, systems thinking, social process and the software process. CPD emphasises that a collaborative project requires careful design of its underlying languages, metaphors and conversations. It identifies three distinct types of conversation, namely communication, dialogue and collaboration. The thesis describes how these conversation types are utilised in transforming a project's network of commitments from loose complexity via shared meaning to cohesive simplicity. Associated with each conversation type is a set of project influences which are developed into a causal influence model in order to depict a collaborative project as a dynamic system of mutually interdependent influences. This causal influence model was used to synthesise the learning from action research and the theoretical readings. An appreciative systems framework was then derived in order to justify a collaborative project as a self-regulating social system and was overlaid onto the causal influence model in order to derive CPD in its final form. CPD proved beneficial when tested in practical projects as a framework to organise a project designer's mind when designing project interventions

Success of Agile Environment in Complex Projects

This paper discusses the impact of agile methodology in complex and modular interrelated projects based on the authors’ practical experience and observations. With the advancement of Web technologies and complex computer systems, business applications are able to transcend boundaries in order to fully meet business requirements and comply with the legislation, policies and procedures. The success of software development as well as software deployment of these complex applications is dependent upon the employed methodology and project management. This is so because employed methodology plays an important position in capturing and modeling of business requirements and project management helps to ensure delivery. Agile methods are rapidly becoming popular in the software development industry. This paper examines this crucial role of agile methodology in a software development and deployment environment

A framework for autonomic web service selection

Web services are a form of distributed computing. As applications accessible over standard internet protocols, web services allow access to disparate computational resources. Recently, with an increased commoditization of web services, there has been a greater interest in the problem of selection. If a web service client can be configured to use one of a number of different web services, which should it select? In this thesis, an approach based on examining the past quality of service (QoS) parameters of similar clients is presented. Standard web service clients are augmented to report their experiences, and can reason over both these and the experiences of others using a number of formal techniques, thereby arriving at an informed decision

Issues in Teaching Second Language Reading

Look through the window of any second or foreign language (L2) reading classroom and, invariably, you will see teacher and students seated with books open in front of them. This superficial similarity masks vast differences in teaching methodology, however. As the 20th century draws to a close, there are, around the world, at least four distinctive approaches to the teaching of L2 reading: grammar-translation, comprehension questions, skills and stategies, and extensive reading. After briei descriptions of the four approaches to teaching reading, this paper surveys a selection of recent articles and books that address important concems in L2 reading pedagogy. Finally, questions are raised about the relationship of theory, research, and teaching practice

The SOD2 C47T polymorphism influences NAFLD fibrosis severity: evidence from case-control and intra-familial allele association studies.

AIMS: Non-alcoholic fatty liver disease (NAFLD) is a complex disease trait where genetic variations and environment interact to determine disease progression. The association of PNPLA3 with advanced disease has been consistently demonstrated but many other modifier genes remain unidentified. In NAFLD, increased fatty acid oxidation produces high levels of reactive oxygen species. Manganese-dependent superoxide dismutase (MnSOD), encoded by the SOD2 gene, plays an important role in protecting cells from oxidative stress. A common non-synonymous polymorphism in SOD2 (C47T; rs4880) is associated with decreased MnSOD mitochondrial targeting and activity making it a good candidate modifier of NAFLD severity. METHODS: The relevance of the SOD2 C47T polymorphism to fibrotic NAFLD was assessed by two complementary approaches: we sought preferential transmission of alleles from parents to affected children in 71 family trios and adopted a case-control approach to compare genotype frequencies in a cohort of 502 European NAFLD patients. RESULTS: In the family study, 55 families were informative. The T allele was transmitted on 47/76 (62%) possible occasions whereas the C allele was transmitted on only 29/76 (38%) occasions, p=0.038. In the case control study, the presence of advanced fibrosis (stage>1) increased with the number of T alleles, p=0.008 for trend. Multivariate analysis showed susceptibility to advanced fibrotic disease was determined by SOD2 genotype (OR 1.56 (95% CI 1.09-2.25), p=0.014), PNPLA3 genotype (p=0.041), type 2 diabetes mellitus (p=0.009) and histological severity of NASH (p=2.0×10(-16)). CONCLUSIONS: Carriage of the SOD2 C47T polymorphism is associated with more advanced fibrosis in NASH

Transposon Insertion Sequencing Elucidates Novel Gene Involvement in Susceptibility and Resistance to Phages T4 and T7 in Escherichia coli O157.

Experiments using bacteriophage (phage) to infect bacterial strains have helped define some basic genetic concepts in microbiology, but our understanding of the complexity of bacterium-phage interactions is still limited. As the global threat of antibiotic resistance continues to increase, phage therapy has reemerged as an attractive alternative or supplement to treating antibiotic-resistant bacterial infections. Further, the long-used method of phage typing to classify bacterial strains is being replaced by molecular genetic techniques. Thus, there is a growing need for a complete understanding of the precise molecular mechanisms underpinning phage-bacterium interactions to optimize phage therapy for the clinic as well as for retrospectively interpreting phage typing data on the molecular level. In this study, a genomics-based fitness assay (TraDIS) was used to identify all host genes involved in phage susceptibility and resistance for a T4 phage infecting Shiga-toxigenic Escherichia coli O157. The TraDIS results identified both established and previously unidentified genes involved in phage infection, and a subset were confirmed by site-directed mutagenesis and phenotypic testing of 14 T4 and 2 T7 phages. For the first time, the entire sap operon was implicated in phage susceptibility and, conversely, the stringent starvation protein A gene (sspA) was shown to provide phage resistance. Identifying genes involved in phage infection and replication should facilitate the selection of bespoke phage combinations to target specific bacterial pathogens.IMPORTANCE Antibiotic resistance has diminished treatment options for many common bacterial infections. Phage therapy is an alternative option that was once popularly used across Europe to kill bacteria within humans. Phage therapy acts by using highly specific viruses (called phages) that infect and lyse certain bacterial species to treat the infection. Whole-genome sequencing has allowed modernization of the investigations into phage-bacterium interactions. Here, using E. coli O157 and T4 bacteriophage as a model, we have exploited a genome-wide fitness assay to investigate all genes involved in defining phage resistance or susceptibility. This knowledge of the genetic determinants of phage resistance and susceptibility can be used to design bespoke phage combinations targeted to specific bacterial infections for successful infection eradication.This work was supported by the Wellcome Trust (grant number WT098051). A.K.C. and C.J.B. were supported by the Medical Research Council (grant number G1100100/1). D.L.G. and A.S.L. were supported by BBSRC (UKRI) funding (programme number P013740)

Early-Season Avian Deaths from West Nile Virus as Warnings of Human Infection

An analysis of 2001 and 2002 West Nile virus (WNV) surveillance data shows that counties that report WNV-infected dead birds early in the transmission season are more likely to report subsequent WNV disease cases in humans than are counties that do not report early WNV-infected dead birds

Genome sequencing defines phylogeny and spread of methicillin-resistant Staphylococcus aureus in a high transmission setting.

Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of nosocomial infection. Whole-genome sequencing of MRSA has been used to define phylogeny and transmission in well-resourced healthcare settings, yet the greatest burden of nosocomial infection occurs in resource-restricted settings where barriers to transmission are lower. Here, we study the flux and genetic diversity of MRSA on ward and individual patient levels in a hospital where transmission was common. We repeatedly screened all patients on two intensive care units for MRSA carriage over a 3-mo period. All MRSA belonged to multilocus sequence type 239 (ST 239). We defined the population structure and charted the spread of MRSA by sequencing 79 isolates from 46 patients and five members of staff, including the first MRSA-positive screen isolates and up to two repeat isolates where available. Phylogenetic analysis identified a flux of distinct ST 239 clades over time in each intensive care unit. In total, five main clades were identified, which varied in the carriage of plasmids encoding antiseptic and antimicrobial resistance determinants. Sequence data confirmed intra- and interwards transmission events and identified individual patients who were colonized by more than one clade. One patient on each unit was the source of numerous transmission events, and deep sampling of one of these cases demonstrated colonization with a "cloud" of related MRSA variants. The application of whole-genome sequencing and analysis provides novel insights into the transmission of MRSA in under-resourced healthcare settings and has relevance to wider global health.The authors acknowledge financial support from the UKCRC Translational Infection Research (TIR) Initiative and the Medical Research Council (Grant number G1000803), with contributions to the grant from the Biotechnology and Biological Sciences Research Council, the National Institute for Health Research on behalf of the Department of Health, and the Chief Scientist Office of the Scottish Government Health Directorate (to Professor Peacock); from Wellcome Trust grant number 098051 awarded to the Wellcome Trust Sanger Institute; and the NIHR Cambridge Biomedical Research Centre (to Professor Peacock). S.Y.C.T. is an Australian National Health and Medical Research Council Career Development Fellow (1065736)This is the final version of the article. It first appeared at http://www.genome.org/cgi/doi/10.1101/gr.174730.114

PNPLA3 gene polymorphism is associated with predisposition to and severity of alcoholic liver disease

The genetic polymorphism with an isoleucine-to-methionine substitution at position 148 (rs738409 C>G) in the patatin-like phospholipase domain protein 3 (PNPLA3) gene confers risk of steatosis. PNPLA3 polymorphism is shown to be associated with alcoholic liver disease (ALD). We performed a systematic review and meta-analysis to examine association of this genetic polymorphism with ALD spectrum and its severity.METHODS:Medline, Embase, and Cochrane Library were searched for studies on association of PNPLA3 polymorphism and ALD spectrum: alcoholic fatty liver (AFL), alcoholic liver injury (ALI), alcoholic cirrhosis (AC), and hepatocellular carcinoma (HCC). Pooled data are reported as odds ratio (OR) with 95% confidence interval. Heterogeneity was assessed using the I 2 statistics and publication bias using Egger's test and Begg and Mazumdar's test. Individual participant data obtained from five studies were used for subgroup analyses.RESULTS:Among 10 studies included in this pooled analysis, compared with controls, OR for rs738409 CG and GG among ALI patients was 1.45 (1.24-1.69) and 2.22 (1.50-3.28), respectively, compared with CC. Respective OR among AC patients was 2.09 (1.79-2.44) and 3.37 (2.49-4.58) and among AC patients with HCC was 2.87 (1.61-5.10) and 12.41 (6.99-22.03). Data for AFL were inconsistent. Among ALD patients, OR of CG and GG genotypes was 2.62 (1.73-3.97) and 8.45 (2.52-28.37), respectively, for AC compared with fatty liver (FL) patients. Similar OR for AC compared with ALI was 1.98 (1.24-3.17) and 3.86 (1.18-12.60). The OR for CG and GG genotypes among AC patients for HCC occurrence was 1.43 (0.76-2.72) and 2.81 (1.57-5.01), respectively. Individual participant data analysis showed age to predispose to AC among ALI patients.CONCLUSIONS:PNPLA3 genetic polymorphism (rs738409 C>G) is associated with increased risk for the entire spectrum of ALD among drinkers including ALI, AC, and HCC. Studies are needed to clarify association of PNPLA3 polymorphism and steatosis in alcoholics. PNPLA3 gene may potentially be a therapeutic target in ALD

Novel Human Parechovirus 3 Diversity, Recombination, and Clinical Impact Across 7 Years: An Australian Story

BACKGROUND A novel human parechovirus 3 Australian recombinant (HPeV3-AR) strain emerged in 2013 and coincided with biennial outbreaks of sepsis-like illnesses in infants. We evaluated the molecular evolution of the HPeV3-AR strain and its association with severe HPeV infections. METHODS HPeV3-positive samples collected from hospitalized infants aged 5-252 days in 2 Australian states (2013-2020) and from a community-based birth cohort (2010-2014) were sequenced. Coding regions were used to conduct phylogenetic and evolutionary analyses. A recombinant-specific polymerase chain reaction was designed and utilized to screen all clinical and community HPeV3-positive samples. RESULTS Complete coding regions of 54 cases were obtained, which showed the HPeV3-AR strain progressively evolving, particularly in the 3' end of the nonstructural genes. The HPeV3-AR strain was not detected in the community birth cohort until the initial outbreak in late 2013. High-throughput screening showed that most (>75%) hospitalized HPeV3 cases involved the AR strain in the first 3 clinical outbreaks, with declining prevalence in the 2019-2020 season. The AR strain was not statistically associated with increased clinical severity among hospitalized infants. CONCLUSIONS HPeV3-AR was the dominant strain during the study period. Increased hospital admissions may have been from a temporary fitness advantage and/or increased virulence