An empirical study of package coupling in Java open-source

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.Excessive coupling between object-oriented classes in systems is generally acknowledged as harmful and is recognised as a maintenance problem that can result in a higher propensity for faults in systems and a „stored up‟ future problem. Characterisation and understanding coupling at different levels of abstraction is therefore important for both the project manager and developer both of whom have a vested interest in software quality. In this Thesis, coupling trends are empirically investigated over multiple versions of seven Java open-source systems (OSS). The first investigation explores the trends in longitudinal changes to open-source systems given by six coupling metrics. Coupling trends are then explored from the perspective of: the relationship between removed classes and their coupling with other classes in the same package; the relationships between coupling and 'warnings’ in packages and the time interval between versions in Java OSS; the relationship between some of these coupling metrics are also explored. Finally, the existence of an 80/20 rule for the coupling metrics is inspected. Results suggest that developer activity comprises a set of high and low periods (peak and trough‟ effect) evident as a system evolves. Findings also demonstrate that addition of coupling may have beneficial effects on a system, particularly if they are added as new functionality through the package Java feature. The fan-in and fan-out coupling metrics reveal particular features and exhibited a wide range of traits in the classes depending on their high or low values; finally, we revealed that one metric (fan-in) is the only metric that appears consistently to exhibit an 80/20 (Pareto) relationship

Massively parallel next generation sequencing to investigate the cis- and trans-acting genetic modifiers of somatic instability in Huntington’s disease

Huntington disease (HD) is an extremely variable inherited neurodegenerative disorder caused by expansion of an unstable CAG trinucleotide repeat in the huntingtin gene (HTT). Somatic instability in HD exhibits an age-dependent, expansion-biased and tissue-specific pattern, and the highest level of somatic instability is found in tissues that are most susceptible to the disease pathology. Therefore, the aim of this project was to test the hypothesis that somatic instability of the HD CAG repeat plays a major role in disease pathology by quantifying somatic instability in the number of CAG repeats by next generation sequencing (NGS) technology in buccal cell DNA. We developed a method to sequence and genotype HTT alleles from blood and buccal swab DNA of the Scottish and Venezuelan populations respectively. A total of 210 individuals from the Scottish general population and 742 HD patients and unaffected individuals from the Venezuelan HD cohort were sequenced on the MiSeq platform. We established that it was possible to sequence and genotype the CAG repeats, the polymorphic CCG repeat and the flanking sequences. Our data highlight the utility of NGS technology as an approach to genotype HTT alleles, detect sequence variants and quantify somatic instability of the CAG repeat. Our data emphasise that the somatic instability in HD is age-dependent and expansion-biased, also could be a major factor in disease progression, and could be a potential therapeutic target in HD. We also investigated the possibility that there are trans-acting modifier factors involved in determining the degree of somatic instability in HD patients. We genotyped polymorphisms in candidate mismatch repair (MMR) genes and examined their effect, if any, on the residual variation of somatic instability. Individuals carrying the minor allele of rs3512 in FAN1 have a higher level of somatic instability than average, suggesting that some of the variations in HD somatic instability could be accounted for by genetic variation in the DNA mismatch repair pathway. The search for modifier genes might have consequences in understanding the pathological process in HD, and may therefore provide therapeutic targets for future investigations

Package Evolvability and its Relationship with Refactoring

In this paper, we address a set of research questions investigating trends in changes to an open-source system (OSS). An interesting âpeak and troughâ effect trend was found to exist in the system studied, suggesting that developer activity comprises of a set of high and low periods. Trends in overall changes applied to the system were complemented with empirical evidence in refactoring data for the same system; this showed a similar peak and trough effect but at different versions of the same system. This result suggests a contrasting motivation between regular maintenance practice and that of refactoring. Our analysis of high-level package trends informed some interesting cross-comparisons with refactoring practice, and some insights into why refactoring might be applied after a burst of regular change activity, rather than consistently. We use data extracted from seven Java OSS as a basis for our refactoring analysis

An empirical study of package coupling in Java open-source

Excessive coupling between object-oriented classes in systems is generally acknowledged as harmful and is recognised as a maintenance problem that can result in a higher propensity for faults in systems and a „stored up‟ future problem. Characterisation and understanding coupling at different levels of abstraction is therefore important for both the project manager and developer both of whom have a vested interest in software quality. In this Thesis, coupling trends are empirically investigated over multiple versions of seven Java open-source systems (OSS). The first investigation explores the trends in longitudinal changes to open-source systems given by six coupling metrics. Coupling trends are then explored from the perspective of: the relationship between removed classes and their coupling with other classes in the same package; the relationships between coupling and 'warnings’ in packages and the time interval between versions in Java OSS; the relationship between some of these coupling metrics are also explored. Finally, the existence of an 80/20 rule for the coupling metrics is inspected. Results suggest that developer activity comprises a set of high and low periods (peak and trough‟ effect) evident as a system evolves. Findings also demonstrate that addition of coupling may have beneficial effects on a system, particularly if they are added as new functionality through the package Java feature. The fan-in and fan-out coupling metrics reveal particular features and exhibited a wide range of traits in the classes depending on their high or low values; finally, we revealed that one metric (fan-in) is the only metric that appears consistently to exhibit an 80/20 (Pareto) relationship.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Knowledge, Attitude, and Practice of Complementary and Alternative Medicine among Program’s Residents in Tabuk, Saudi Arabia

BACKGROUND: Complementary and alternative medicine (CAM) focuses on stimulating the body’s ability to heal itself through energy alignment, herbal supplementation, and other balancing techniques. AIM: The objective of the study was to investigate and compare the Knowledge Attitude Practice (KAP) of CAM among program’s residents in Tabuk region. METHODS: A cross-sectional CAP study was conducted among program’s residents in Tabuk region. All program’s residents of all specialties in Tabuk region were included in the study. Data were collected by predesigned electronic questionnaire covering the needed items. Collected data were coded and analyzed using SPSS Inc., Chicago, Illinois, USA. The Chi-square test was used as a test of significance and p = 0.05 or less was considered statistically significant. RESULTS: Most (95.8%) of the participants have heard about CAM, 25% have used CAM in treatment before, and 72.3% of them reported beneficial outcome, 25.7% strongly agree and 48.6% agree that CAM is a useful complement to pharmacological medicine, 38.2% believed that the results of CAM are usually due to the placebo effect, and 52.1% recommended using CAM. On the other hand, 79.9% have knowledge about acupuncture, 54.9% spiritual healing and herbal medicine, 43.1% massage, 41% yoga, 70.8% bloodletting cupping, and 56.3% about cauterization. More than third (38.2%) of the participants agreed that the use of herbal products is a valid form of drugs which can be used for the treatment of variety of diseases, 48.6% agreed that CAM is a useful complement to pharmacological medicine, while 36.1% strongly agreed that CAM treatments are not tested in a scientifically recognized manner. CONCLUSION: In our study, the majority of program’s residents in Tabuk region agree that CAM is a useful complement to pharmacological medicine and recommended using CAM while reasonable percentage of them believed that the results of CAM are usually due to the placebo effect

Library preparation and MiSeq sequencing for the genotyping-by-sequencing of the Huntington disease HTT exon one trinucleotide repeat and the quantification of somatic mosaicism [Protocol]

Huntington disease (HD) is an autosomal dominant neurodegenerative disorder caused by the expansion of a CAG repeat in the first exon of the HTT gene. Affected individuals inherit more than 40 repeats and the CAG repeat is genetically unstable in both the germline and soma. Molecular diagnosis and genotyping of the CAG repeat is traditionally performed by estimation of PCR fragment size. However, this approach is complicated by the presence of an adjacent polymorphic CCG repeat and provides no information on the presence of variant repeats, flanking sequence variants or on the degree of somatic mosaicism. To overcome these limitations, we have developed an amplicon-sequencing protocol that allows the sequencing of hundreds of samples in a single MiSeq run. The composition of the HTT exon one trinucleotide repeat locus can be determined from the MiSeq sequencing reads generated. With sufficient sequencing depth, such MiSeq data can also be used to quantify the degree of somatic mosaicism of the HTT CAG repeat in the tissue analysed

A conceptual framework of the way forward to a community pharmacist- general practitioner collaborative medication therapy management model for chronic diseases in Malaysian primary care: a qualitative study

Background There is a growing global interest in interprofessional collaboration between community pharmacist (CP) and general practitioner (GP) in primary care. Objective To conceptualize a stakeholder driven framework to improve collaboration between the CP and the GP in Malaysian primary care to effectively manage medicines in chronic diseases. Design and Setting A qualitative study that involved individual semi structured interviews of the leadership of various associations, guilds, and societies representing CPs, GPs, and Nurses in Malaysia. Method This study collected and reported data in accordance with the Consolidated Criteria for Reporting of Qualitative Studies guidelines. Key informants were recruited based on purposive (expert) sampling. Interviews were transcribed verbatim and data were coded in NVivo based on the principles of thematic analysis. Result A total of twelve interviews (5 CPs, 5 GPs and 2 Nurses) were conducted. Five themes emerged: Theme-1 highlighted comparison of community pharmacy practice in Malaysia and developed countries; Theme-2 involved the current practices in Malaysian primary care; Theme- 3 encompassed the advantages of CP-GP collaboration in chronic diseases; Theme-4 highlighted the barriers which impede collaboration in Malaysian primary care; and, Theme-5 delineated the way forward for CP-GP collaboration in Malaysia. Conclusion The actionable insights obtained from the Malaysian stakeholders offered an outline of a framework to enhance collaboration between CP and GP in primary care. Generally, stakeholders were interested in CP-GP collaboration in primary care and viewed many positive roles of CPs including prescription review, adherence support and patient education. The framework of the way forward includes: separation of roles of the CP and the GP through a holistic revision of relevant legislation to grant an active role to the CPs in chronic care; definition of protocols for collaborative practices; incentivization of both stakeholders (CP and GP) and, Design and implementation of an effective regulatory mechanism where the Malaysian Ministry of Health may take a leading role

Role of Interventional Radiology in Management of Gastrointestinal Bleeding

Gastrointestinal bleeding is a common and potentially life-threatening condition that requires prompt and effective management. Interventional radiology has emerged as a valuable tool in the management of gastrointestinal bleeding, offering minimally invasive techniques that can rapidly control bleeding and improve patient outcomes. This review aims to provide an overview of the role of interventional radiology in the management of gastrointestinal bleeding, including its various techniques and their efficacy. The review discusses the different interventional radiology procedures that can be used to diagnose and treat gastrointestinal bleeding. It also highlights the advantages of techniques used in evaluation and management, including their ability to localize and control bleeding, as well as their low complication rates and shorter recovery times compared to traditional surgical approaches. Furthermore, the review addresses the specific indications for interventional radiology in the management of gastrointestinal bleeding, as well as the role of interventional radiology in the setting of underlying conditions. Overall, this review provides a comprehensive overview of the role of interventional radiology in the management of gastrointestinal bleeding, highlighting its effectiveness and potential benefits for patients. It also emphasizes the need for further research and collaboration between interventional radiologists and gastroenterologists to optimize the use of these techniques in clinical practice

Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial

Background Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH. Methods In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH,non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2–F3, or F1 with at least oneaccompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpointsfor the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2–F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6. Findings Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1–F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2–F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1–F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group). Interpretation Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10 years; 78.2% included were male with a median age of 37 years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020