Clinical effectiveness and cost-effectiveness of imatinib dose escalation for the treatment of unresectable and/or metastatic gastrointestinal stromal tumours that have progressed on treatment at a dose of 400 mg/day : a systematic review and economic evaluation

Peer reviewedPublisher PD

From Bugs to Decision Support – Leveraging Historical Issue Reports in Software Evolution

Software developers in large projects work in complex information landscapes and staying on top of all relevant software artifacts is an acknowledged challenge. As software systems often evolve over many years, a large number of issue reports is typically managed during the lifetime of a system, representing the units of work needed for its improvement, e.g., defects to fix, requested features, or missing documentation. Efficient management of incoming issue reports requires the successful navigation of the information landscape of a project. In this thesis, we address two tasks involved in issue management: Issue Assignment (IA) and Change Impact Analysis (CIA). IA is the early task of allocating an issue report to a development team, and CIA is the subsequent activity of identifying how source code changes affect the existing software artifacts. While IA is fundamental in all large software projects, CIA is particularly important to safety-critical development. Our solution approach, grounded on surveys of industry practice as well as scientific literature, is to support navigation by combining information retrieval and machine learning into Recommendation Systems for Software Engineering (RSSE). While the sheer number of incoming issue reports might challenge the overview of a human developer, our techniques instead benefit from the availability of ever-growing training data. We leverage the volume of issue reports to develop accurate decision support for software evolution. We evaluate our proposals both by deploying an RSSE in two development teams, and by simulation scenarios, i.e., we assess the correctness of the RSSEs' output when replaying the historical inflow of issue reports. In total, more than 60,000 historical issue reports are involved in our studies, originating from the evolution of five proprietary systems for two companies. Our results show that RSSEs for both IA and CIA can help developers navigate large software projects, in terms of locating development teams and software artifacts. Finally, we discuss how to support the transfer of our results to industry, focusing on addressing the context dependency of our tool support by systematically tuning parameters to a specific operational setting

Research and technology

Significant research and technology activities at the Johnson Space Center (JSC) during Fiscal Year 1990 are reviewed. Research in human factors engineering, the Space Shuttle, the Space Station Freedom, space exploration and related topics are covered

A transdisciplinary evaluation of forest retention policies and practices in the Australian context

The reduction or loss of habitat for conversion to extractive uses, urban development, or resource production is a key threat to biodiversity. Protected areas and vegetation management policy are essential mechanisms for abating species decline in the face of these compounding pressures. The thesis examines the effectiveness of policy responses for protected areas in Australia, and also evaluates key de facto arrangements that have a bearing on conservation outcomes, specifically, Environmental Impact Assessment (EIA). Stephanie Hernandez uses an interdisciplinary mixed-methods approach to investigate the complexities, effectiveness and future directions for conservation policy in Queensland, Australia. The overall goals of this thesis are to: 1) review policies and programs for retaining natural forested habitats in Australia; 2) estimate the impact of current protected areas in terms of preventing forest cover loss; 3) describe the impact of policy changes on vegetation 4) develop evidence-based recommendations for retaining Queensland's forests in the future. In addressing these respective knowledge gaps, this research provides an essential contribution to future protected area policy and the academic literature concerning conservation planning

Intervention or Collaboration?:Rethinking Information and Communication Technologies for Development

Over the past decades information system developers and knowledge engineers in ICT projects in wealthy regions of the world have come to realize that technical work can only be successful when situated in a broader organizational context. However, for low-resource environments (or example rural Africa), where contextual embedding is even more demanding given the complexity of these environments, practical, context-oriented methodologies how to "do" information systems engineering are still lacking. This book gives a basic but thorough insight how to develop information systems and services for people in low resource environments, from a socio-technical, information systems engineering perspective, presenting field-validated methods that cover the complete lifecycle of information systems engineering, with emphasis on context analysis, needs assessment, use case and requirements analysis and (business) sustainability analysis. Since technical development does not go without critical reflection, this book also investigates which (tacit) assumptions affect the way technologies are implemented in poor, low-resource environments. Linking collaborative sociotechnical development with theories of complexity and social networks of innovation, this book offers a reflective and critical approach to information and communication technologies for development

New Insights in Oral Health and Diets

The world of adult education needs information on instruments that provide behavioral changes and support the physical, emotional, and spiritual health of modern individuals. Under this scope, this Special Issue incorporates articles about modern perspectives on diet and coaching approaches that lead to new dietary habits

Natural Honey to Eradicate Nasal Methicillin resistant Staphylococcus aureus (MRSA) A Randomised Control Trial

Methicillin-resistant Staphylococcus aureus (MRSA) is an endemic pathogen of public health concern in Ireland, as in many other health systems. For the nasal clearance of MRSA, the site that is often colonised in humans, the antibiotic mupirocin remains one of the most successful topical antibiotics to date. However, increasing bacterial resistance to mupirocin and limited effective alternate antibiotic options necessitate the need for unconventional approaches to eradicate nasal MRSA. Colonisation is a precursor for infection, and infections due to MRSA are associated with a greater risk of treatment failure, increased patient mortality and higher costs. Natural honey has been used by many traditional systems of medicine as a healing agent. In modern medicine, it is used as a wound healing agent. A recent Cochrane review reports that honey appears to heal partial thickness burns more quickly than conventional treatment, and infected post-operative wounds more quickly than antiseptics and gauze. Interest in an alternative agent for nasal decolonisation of MRSA led the researcher to the pilot study that employed medical grade honey (MGH). The results of the pilot study were encouraging which lead to the conduct of a clinical study ‘Natural Honey to Eradicate Nasal MRSA (NHNMRSA) a Randomised Control Trial (RCT)’. Patients were recruited from Beaumont Hospital to the single centre open label RCT, which investigated the comparative efficacy of nasal decolonisation of MRSA using MGH and mupirocin 2% nasal application. Patient characteristics, including age, gender, comorbidity, dependency of care, presence of invasive and indwelling devices, skin integrity, colonisation with multi-resistant drug resistant organisms, MRSA status on study enrolment, past decolonisation attempts and mupirocin use, as well as infection prevention and control practices during the study period were assessed, to determine the impact if any, on the outcome of intervention on nasal MRSA. The data were then analysed to establish the correlation, if any, between the outcomes of the and between the intervention and control groups. The relationship between nasal as well as non-nasal MRSA colonisation was assessed, in addition to other factors that are previously reported as factors associated with failed decolonisation. Five specific objectives formed the foundation of the RCT, the key findings of which are summarised. The first objective a literature review on mupirocin resistance (MR), presented a comprehensive picture on the prevalence of MR, which ranges from 1% - 81%, associated chlorhexidine resistance, which ranges from 0.6% - 91%, as well as multi drug resistance among MRSA isolates. The emergence of high-level MR amongst coagulase negative Staphylococci (CoNS) isolates indicates an expanding reservoir of plasmids encoding MR, which can be transferred to other CoNS strains as well as to S. aureus including MRSA. HLMR and resistance to other antibiotics amongst CoNS curtails the oral antibiotic options for prolonged treatment of prosthetic infections with CoNS. Resistance to mupirocin and chlorhexidine limits the options for patients who may benefit from MRSA suppression or decolonisation therapy. Alternative agents such as octenidine dihydrochloride, polyhexanide, ethanol (70%), sodium hypochlorite, lysostaphin, omiganon pentahydrochloride, natural honey, tea tree oil, silver and bacteriophages have been investigated with varying success for MRSA decolonisation. However, therapeutic trials of alternative agents that show some promise must be further evaluated in clinical trials before they can be recommended for use in clinical practice. In the RCT, robust comparability of the study participants in the intervention and control groups was confirmed on univariate analysis. The univariate analysis also confirmed that none of the patient variables analysed was of statistical significance on the patient outcome, i.e. eradication of nasal MRSA. On an intention to treat (ITT) analysis, 18 (36%) in the intervention group and 25 (50%) in the control group were decolonised of nasal MRSA. A c2 test was performed to assess the difference in the rate of decolonisation of MRSA between the intervention and control group. There was no statistically significant difference between the two groups (c2=1.999, p=0.157). On a per-protocol (PP) analysis,in the intervention group 18 (43%) participants and in the control group 25 (57%) participants were decolonised of nasal MRSA, however, a c2- test showed no significant difference (c2=1.675, p=0.196). Based on the ITT and PP analysis, as there was no statistical significance difference in the outcome of nasal MRSA decolonisation between the intervention and control groups, the null hypothesis was not rejected. On multivariate logistic regression, concomitant non-nasal MRSA colonisation was significantly associated, (c2=7.241, p=0.008) with persistent nasal MRSA. In addition, altered skin integrity and the application of more than two courses of mupirocin 2% nasal ointment prior to RCT enrolment were also associated with persistent nasal carriage of MRSA. However the less than anticipated number of patients enrolled in the study impacted on the power to detect significant differences between the intervention and control groups. The third objective was to determine and compare bacterial susceptibility to mupirocin and changes over time from first identification to completion of the RCT. Of the historic, baseline and final isolates, mupirocin susceptibility (MS) was 91%, 88% and 77% respectively. The prevalence of MR progressively increased from the time initially identified to the end of the study, 8% on first time identification, 12% at study enrolment, and 23% at the end of study. New acquisition of MR amongst RCT participants was 10% and of all the cases who newly acquired MR, 75% were HLMR. The acquisition of MR necessitates the monitoring of MS amongst MRSA isolates, risk assessment, the judicious use of mupirocin as well as the use of alternative agents for MRSA decolonisation. Laboratory investigations of MRSA isolates and assays to determine antimicrobial efficacy of MGH together formed the fourth study objective. The MRSA isolates were characterised using spa typing and compared where available, at three time points; historic, baseline and on study completion. Of the baseline and persistent MRSA isolates (143), 26 different spa types were identified. The common spa types were; t032, 59 (41%), t515, 19 (13%), t127, 17 (11.8%) and t4599, 10 (7%). Based on the spa types, a sequence-type (ST) could be inferred for 110 (77%) isolates. The common STs were ST22, 91 (63.6%), followed by ST1, 17 (11.8%), and one isolate each of the ST5 and ST8 type. In summary, the spa type of the carriage isolates did not appear to influence the outcome of the nasal decolonisation. Persistent colonisation with the same spa type was evident even over relatively long time-spans. However, replacement of the colonising spa type was also identified. The minimum inhibition concentration (MIC) and minimum bactericidal concentration (MBC) of MGH (test honey) was determined using laboratory assays. The MIC determined using the agar well diffusion method demonstrated antibacterial activity of test honey at 5% and higher concentrations for the clinical and reference MRSA isolates. Using the broth micro-dilution method to differentiate bactericidal or bacteriostatic action, it was established that the MIC and MBC of the test honey were both 12.5% to the MRSA isolates tested. The findings are in concordance with reports by other investigators who have reported MIC at concentrations of 4% and higher to antibacterial honey. The participant’s perception on MRSA carriage and their experience following the use of MGH and mupirocin 2% was evaluated which formed the basis of the fifth objective. An adapted brief illness perception questionnaire (BIPQ) that composed of nine elements was utilised to collate patient perceptions of MRSA. In summary the participants perceived MRSA colonisation as a chronic condition and that it did not have serious consequences on their daily lives. They were in general emotionally detached from the condition and few had MRSA related symptoms. Although most participants felt they had limited or no control over carriage, decolonisation was considered beneficial, indicating the importance attached to treatment/control of MRSA. The survey result shows a sub-optimal understanding of MRSA among 40% of patients that necessitates measures to target improving knowledge about MRSA. Such an intervention should enable patients to understand MRSA acquisition and transmission as well as adherence to treatment/decolonisation, potentially leading to better outcomes. A Likert scale type rating was used in the product experience questionnaire (PEQ) to collate participants\u27 experiences of MGH cream and mupirocin nasal application. In the investigative group, most patients (95%) concurred that Medihoney™ Derma Cream was easy to apply, not sticky (90%), did not lead to a runny nose (85%) and they did not experience an unpleasant sensation (95%). Based on the participants’ response it could be inferred that Medihoney™ Derma Cream may be applied to the human nasal passages with minimal undesirable effects. In the control group, most respondents (87%) concurred that mupirocin 2% nasal ointment was easy to apply, but it was sticky (20%), and a runny nose was experienced by 33% of respondents. Almost all (95%) respondents agreed that they did not experience any unpleasant sensation following its application. Overall the patients’ preferred choice was a natural alternative to an antibiotic, if available, for MRSA decolonisation. The NHNMRSA RCT, I believe, is the first study that has used MGH for nasal MRSA decolonisation. The RCT results offer potential but larger and multisite studies must be conducted to confirm the results to facilitate the development of MGH as an alternate agent for nasal decolonisation of MRSA

Advances in Autism Research

This book represents one of the most up-to-date collections of articles on clinical practice and research in the field of Autism Spectrum Disorders (ASD). The scholars who contributed to this book are experts in their field, carrying out cutting edge research in prestigious institutes worldwide (e.g., Harvard Medical School, University of California, MIND Institute, King’s College, Karolinska Institute, and many others). The book addressed many topics, including (1) The COVID-19 pandemic; (2) Epidemiology and prevalence; (3) Screening and early behavioral markers; (4) Diagnostic and phenotypic profile; (5) Treatment and intervention; (6) Etiopathogenesis (biomarkers, biology, and genetic, epigenetic, and risk factors); (7) Comorbidity; (8) Adulthood; and (9) Broader Autism Phenotype (BAP). This book testifies to the complexity of performing research in the field of ASD. The published contributions underline areas of progress and ongoing challenges in which more certain data is expected in the coming years. It would be desirable that experts, clinicians, researchers, and trainees could have the opportunity to read this updated text describing the challenging heterogeneity of Autism Spectrum Disorder