Swansea University

Qualitative content analysis and thematic analysis are two commonly used approaches in data analysis of nursing research, but boundaries between the two have not been clearly specified. In other words, they are being used interchangeably and it seems difficult for the researcher to choose between them. In this respect, this paper describes and discusses the boundaries between qualitative content analysis and thematic analysis and presents implications to improve the consistency between the purpose of related studies and the method of data analyses. This is a discussion paper, comprising an analytical overview and discussion of the definitions, aims, philosophical background, data gathering, and analysis of content analysis and thematic analysis, and addressing their methodological subtleties. It is concluded that in spite of many similarities between the approaches, including cutting across data and searching for patterns and themes, their main difference lies in the opportunity for quantification of data. It means that measuring the frequency of different categories and themes is possible in content analysis with caution as a proxy for significance.

BACKGROUND: Establishing cardiovascular safety of new therapies for type 2 diabetes is important. Safety data are available for the subcutaneous form of the glucagon-like peptide-1 receptor agonist semaglutide but are needed for oral semaglutide. METHODS: We assessed cardiovascular outcomes of once-daily oral semaglutide in an event-driven, randomized, double-blind, placebo-controlled trial involving patients at high cardiovascular risk (age of ≥50 years with established cardiovascular or chronic kidney disease, or age of ≥60 years with cardiovascular risk factors only). The primary outcome in a time-to-event analysis was the first occurrence of a major adverse cardiovascular event (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke). The trial was designed to rule out 80% excess cardiovascular risk as compared with placebo (noninferiority margin of 1.8 for the upper boundary of the 95% confidence interval for the hazard ratio for the primary outcome). RESULTS: A total of 3183 patients were randomly assigned to receive oral semaglutide or placebo. The mean age of the patients was 66 years; 2695 patients (84.7%) were 50 years of age or older and had cardiovascular or chronic kidney disease. The median time in the trial was 15.9 months. Major adverse cardiovascular events occurred in 61 of 1591 patients (3.8%) in the oral semaglutide group and 76 of 1592 (4.8%) in the placebo group (hazard ratio, 0.79; 95% confidence interval [CI], 0.57 to 1.11; P<0.001 for noninferiority). Results for components of the primary outcome were as follows: death from cardiovascular causes, 15 of 1591 patients (0.9%) in the oral semaglutide group and 30 of 1592 (1.9%) in the placebo group (hazard ratio, 0.49; 95% CI, 0.27 to 0.92); nonfatal myocardial infarction, 37 of 1591 patients (2.3%) and 31 of 1592 (1.9%), respectively (hazard ratio, 1.18; 95% CI, 0.73 to 1.90); and nonfatal stroke, 12 of 1591 patients (0.8%) and 16 of 1592 (1.0%), respectively (hazard ratio, 0.74; 95% CI, 0.35 to 1.57). Death from any cause occurred in 23 of 1591 patients (1.4%) in the oral semaglutide group and 45 of 1592 (2.8%) in the placebo group (hazard ratio, 0.51; 95% CI, 0.31 to 0.84). Gastrointestinal adverse events leading to discontinuation of oral semaglutide or placebo were more common with oral semaglutide. CONCLUSIONS: In this trial involving patients with type 2 diabetes, the cardiovascular risk profile of oral semaglutide was not inferior to that of placebo. (Funded by Novo Nordisk; PIONEER 6 ClinicalTrials.gov number, NCT02692716.).

BACKGROUND: Nivolumab, a programmed death 1 (PD-1) checkpoint inhibitor, was associated with encouraging overall survival in uncontrolled studies involving previously treated patients with advanced renal-cell carcinoma. This randomized, open-label, phase 3 study compared nivolumab with everolimus in patients with renal-cell carcinoma who had received previous treatment. METHODS: A total of 821 patients with advanced clear-cell renal-cell carcinoma for which they had received previous treatment with one or two regimens of antiangiogenic therapy were randomly assigned (in a 1:1 ratio) to receive 3 mg of nivolumab per kilogram of body weight intravenously every 2 weeks or a 10-mg everolimus tablet orally once daily. The primary end point was overall survival. The secondary end points included the objective response rate and safety. RESULTS: The median overall survival was 25.0 months (95% confidence interval [CI], 21.8 to not estimable) with nivolumab and 19.6 months (95% CI, 17.6 to 23.1) with everolimus. The hazard ratio for death with nivolumab versus everolimus was 0.73 (98.5% CI, 0.57 to 0.93; P=0.002), which met the prespecified criterion for superiority (P≤0.0148). The objective response rate was greater with nivolumab than with everolimus (25% vs. 5%; odds ratio, 5.98 [95% CI, 3.68 to 9.72]; P<0.001). The median progression-free survival was 4.6 months (95% CI, 3.7 to 5.4) with nivolumab and 4.4 months (95% CI, 3.7 to 5.5) with everolimus (hazard ratio, 0.88; 95% CI, 0.75 to 1.03; P=0.11). Grade 3 or 4 treatment-related adverse events occurred in 19% of the patients receiving nivolumab and in 37% of the patients receiving everolimus; the most common event with nivolumab was fatigue (in 2% of the patients), and the most common event with everolimus was anemia (in 8%). CONCLUSIONS: Among patients with previously treated advanced renal-cell carcinoma, overall survival was longer and fewer grade 3 or 4 adverse events occurred with nivolumab than with everolimus. (Funded by Bristol-Myers Squibb; CheckMate 025 ClinicalTrials.gov number, NCT01668784.).

UNLABELLED: A typical prokaryote population sequencing study can now consist of hundreds or thousands of isolates. Interrogating these datasets can provide detailed insights into the genetic structure of prokaryotic genomes. We introduce Roary, a tool that rapidly builds large-scale pan genomes, identifying the core and accessory genes. Roary makes construction of the pan genome of thousands of prokaryote samples possible on a standard desktop without compromising on the accuracy of results. Using a single CPU Roary can produce a pan genome consisting of 1000 isolates in 4.5 hours using 13 GB of RAM, with further speedups possible using multiple processors. AVAILABILITY AND IMPLEMENTATION: Roary is implemented in Perl and is freely available under an open source GPLv3 license from http://sanger-pathogens.github.io/Roary CONTACT: roary@sanger.ac.uk SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

INTRODUCTION: The SCARE Guidelines were first published in 2016 and were last updated in 2018. They provide a structure for reporting surgical case reports and are used and endorsed by authors, journal editors and reviewers, in order to increase robustness and transparency in reporting surgical cases. They must be kept up to date in order to drive forwards reporting quality. As such, we have updated these guidelines via a DELPHI consensus exercise. METHODS: The updated guidelines were produced via a DELPHI consensus exercise. Members were invited from the previous DELPHI group, as well as editorial board members and peer reviewers of the International Journal of Surgery Case Reports. The expert group completed an online survey to indicate their agreement with proposed changes to the checklist items. RESULTS: A total of 54 surgical experts agreed to participate and 53 (98%) completed the survey. The responses and suggested modifications were incorporated into the new 2020 guideline. There was a high degree of agreement amongst the SCARE Group, with all modified SCARE items receiving over 70% scores 7-9. CONCLUSION: A DELPHI consensus exercise was completed and an updated and improved SCARE Checklist is now presented.

BACKGROUND: Nivolumab combined with ipilimumab resulted in longer progression-free survival and a higher objective response rate than ipilimumab alone in a phase 3 trial involving patients with advanced melanoma. We now report 3-year overall survival outcomes in this trial. METHODS: We randomly assigned, in a 1:1:1 ratio, patients with previously untreated advanced melanoma to receive nivolumab at a dose of 1 mg per kilogram of body weight plus ipilimumab at a dose of 3 mg per kilogram every 3 weeks for four doses, followed by nivolumab at a dose of 3 mg per kilogram every 2 weeks; nivolumab at a dose of 3 mg per kilogram every 2 weeks plus placebo; or ipilimumab at a dose of 3 mg per kilogram every 3 weeks for four doses plus placebo, until progression, the occurrence of unacceptable toxic effects, or withdrawal of consent. Randomization was stratified according to programmed death ligand 1 (PD-L1) status, BRAF mutation status, and metastasis stage. The two primary end points were progression-free survival and overall survival in the nivolumab-plus-ipilimumab group and in the nivolumab group versus the ipilimumab group. RESULTS: At a minimum follow-up of 36 months, the median overall survival had not been reached in the nivolumab-plus-ipilimumab group and was 37.6 months in the nivolumab group, as compared with 19.9 months in the ipilimumab group (hazard ratio for death with nivolumab plus ipilimumab vs. ipilimumab, 0.55 [P<0.001]; hazard ratio for death with nivolumab vs. ipilimumab, 0.65 [P<0.001]). The overall survival rate at 3 years was 58% in the nivolumab-plus-ipilimumab group and 52% in the nivolumab group, as compared with 34% in the ipilimumab group. The safety profile was unchanged from the initial report. Treatment-related adverse events of grade 3 or 4 occurred in 59% of the patients in the nivolumab-plus-ipilimumab group, in 21% of those in the nivolumab group, and in 28% of those in the ipilimumab group. CONCLUSIONS: Among patients with advanced melanoma, significantly longer overall survival occurred with combination therapy with nivolumab plus ipilimumab or with nivolumab alone than with ipilimumab alone. (Funded by Bristol-Myers Squibb and others; CheckMate 067 ClinicalTrials.gov number, NCT01844505 .).

This chapter contains sections titled: Phenomenological aspects One-dimensional constitutive model General elastoplastic constitutive model Classical yield criteria Plastic flow rules Hardening laws

As far back as the industrial revolution, significant development in technical innovation has succeeded in transforming numerous manual tasks and processes that had been in existence for decades where humans had reached the limits of physical capacity. Artificial Intelligence (AI) offers this same transformative potential for the augmentation and potential replacement of human tasks and activities within a wide range of industrial, intellectual and social applications. The pace of change for this new AI technological age is staggering, with new breakthroughs in algorithmic machine learning and autonomous decision-making, engendering new opportunities for continued innovation. The impact of AI could be significant, with industries ranging from: finance, healthcare, manufacturing, retail, supply chain, logistics and utilities, all potentially disrupted by the onset of AI technologies. The study brings together the collective insight from a number of leading expert contributors to highlight the significant opportunities, realistic assessment of impact, challenges and potential research agenda posed by the rapid emergence of AI within a number of domains: business and management, government, public sector, and science and technology. This research offers significant and timely insight to AI technology and its impact on the future of industry and society in general, whilst recognising the societal and industrial influence on pace and direction of AI development.

BACKGROUND Nivolumab plus ipilimumab or nivolumab alone resulted in longer progression-free and overall survival than ipilimumab alone in a trial involving patients with advanced melanoma. We now report 5-year outcomes in the trial. METHODS We randomly assigned patients with previously untreated advanced melanoma to receive one of the following regimens: nivolumab (at a dose of 1 mg per kilogram of body weight) plus ipilimumab (3 mg per kilogram) every 3 weeks for four doses, followed by nivolumab (3 mg per kilogram every 2 weeks); nivolumab (3 mg per kilogram every 2 weeks) plus ipilimumab-matched placebo; or ipilimumab (3 mg per kilogram every 3 weeks for four doses) plus nivolumab-matched placebo. The two primary end points were progression-free survival and overall survival in the nivolumab-plus-ipilimumab group and in the nivolumab group, as compared with the ipilimumab group. RESULTS At a minimum follow-up of 60 months, the median overall survival was more than 60.0 months (median not reached) in the nivolumab-plus-ipilimumab group and 36.9 months in the nivolumab group, as compared with 19.9 months in the ipilimumab group (hazard ratio for death with nivolumab plus ipilimumab vs. ipilimumab, 0.52; hazard ratio for death with nivolumab vs. ipilimumab, 0.63). Overall survival at 5 years was 52% in the nivolumab-plus-ipilimumab group and 44% in the nivolumab group, as compared with 26% in the ipilimumab group. No sustained deterioration of health-related quality of life was observed during or after treatment with nivolumab plus ipilimumab or with nivolumab alone. No new late toxic effects were noted. CONCLUSIONS Among patients with advanced melanoma, sustained longterm overall survival at 5 years was observed in a greater percentage of patients who received nivolumab plus ipilimumab or nivolumab alone than in those who received ipilimumab alone, with no apparent loss of quality of life in the patients who received regimens containing nivolumab. (Funded by Bristol-Myers Squibb and others; CheckMate 067 ClinicalTrials.gov number, NCT01844505.).

Transformative artificially intelligent tools, such as ChatGPT, designed to generate sophisticated text indistinguishable from that produced by a human, are applicable across a wide range of contexts. The technology presents opportunities as well as, often ethical and legal, challenges, and has the potential for both positive and negative impacts for organisations, society, and individuals. Offering multi-disciplinary insight into some of these, this article brings together 43 contributions from experts in fields such as computer science, marketing, information systems, education, policy, hospitality and tourism, management, publishing, and nursing. The contributors acknowledge ChatGPT’s capabilities to enhance productivity and suggest that it is likely to offer significant gains in the banking, hospitality and tourism, and information technology industries, and enhance business activities, such as management and marketing. Nevertheless, they also consider its limitations, disruptions to practices, threats to privacy and security, and consequences of biases, misuse, and misinformation. However, opinion is split on whether ChatGPT’s use should be restricted or legislated. Drawing on these contributions, the article identifies questions requiring further research across three thematic areas: knowledge, transparency, and ethics; digital transformation of organisations and societies; and teaching, learning, and scholarly research. The avenues for further research include: identifying skills, resources, and capabilities needed to handle generative AI; examining biases of generative AI attributable to training datasets and processes; exploring business and societal contexts best suited for generative AI implementation; determining optimal combinations of human and generative AI for various tasks; identifying ways to assess accuracy of text produced by generative AI; and uncovering the ethical and legal issues in using generative AI across different contexts.

autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

Production of biochar (the carbon (C)-rich solid formed by pyrolysis of biomass) and its storage in soils have been suggested as a means of abating climate change by sequestering carbon, while simultaneously providing energy and increasing crop yields. Substantial uncertainties exist, however, regarding the impact, capacity and sustainability of biochar at the global level. In this paper we estimate the maximum sustainable technical potential of biochar to mitigate climate change. Annual net emissions of carbon dioxide (CO2), methane and nitrous oxide could be reduced by a maximum of 1.8 Pg CO2-C equivalent (CO2-Ce) per year (12% of current anthropogenic CO2-Ce emissions; 1 Pg=1 Gt), and total net emissions over the course of a century by 130 Pg CO2-Ce, without endangering food security, habitat or soil conservation. Biochar has a larger climate-change mitigation potential than combustion of the same sustainably procured biomass for bioenergy, except when fertile soils are amended while coal is the fuel being offset. The storage in soils of biochar, the product of biomass pyrolysis, has been proposed as an attractive option to mitigate climate change. Amonette and co-workers model the potential impact of biochar and find that it could eliminate more carbon from the atmosphere than using the same biomass for biofuel.

The metaverse has the potential to extend the physical world using augmented and virtual reality technologies allowing users to seamlessly interact within real and simulated environments using avatars and holograms. Virtual environments and immersive games (such as, Second Life, Fortnite, Roblox and VRChat) have been described as antecedents of the metaverse and offer some insight to the potential socio-economic impact of a fully functional persistent cross platform metaverse. Separating the hype and “meta…” rebranding from current reality is difficult, as “big tech” paints a picture of the transformative nature of the metaverse and how it will positively impact people in their work, leisure, and social interaction. The potential impact on the way we conduct business, interact with brands and others, and develop shared experiences is likely to be transformational as the distinct lines between physical and digital are likely to be somewhat blurred from current perceptions. However, although the technology and infrastructure does not yet exist to allow the development of new immersive virtual worlds at scale - one that our avatars could transcend across platforms, researchers are increasingly examining the transformative impact of the metaverse. Impacted sectors include marketing, education, healthcare as well as societal effects relating to social interaction factors from widespread adoption, and issues relating to trust, privacy, bias, disinformation, application of law as well as psychological aspects linked to addiction and impact on vulnerable people. This study examines these topics in detail by combining the informed narrative and multi-perspective approach from experts with varied disciplinary backgrounds on many aspects of the metaverse and its transformational impact. The paper concludes by proposing a future research agenda that is valuable for researchers, professionals and policy makers alike.

The use of the internet and social media have changed consumer behavior and the ways in which companies conduct their business. Social and digital marketing offers significant opportunities to organizations through lower costs, improved brand awareness and increased sales. However, significant challenges exist from negative electronic word-of-mouth as well as intrusive and irritating online brand presence. This article brings together the collective insight from several leading experts on issues relating to digital and social media marketing. The experts’ perspectives offer a detailed narrative on key aspects of this important topic as well as perspectives on more specific issues including artificial intelligence, augmented reality marketing, digital content management, mobile marketing and advertising, B2B marketing, electronic word of mouth and ethical issues therein. This research offers a significant and timely contribution to both researchers and practitioners in the form of challenges and opportunities where we highlight the limitations within the current research, outline the research gaps and develop the questions and propositions that can help advance knowledge within the domain of digital and social marketing.

Abstract A new error estimator is presented which is not only reasonably accurate but whose evaluation is computationally so simple that it can be readily implemented in existing finite element codes. The estimator allows the global energy norm error to be well estmated and alos gives a good evaluation of local errors. It can thus be combined with a full adaptive process of refinement or, more simply, provide guidance for mesh redesign which allows the user to obtain a desired accuracy with one or two trials. When combined with an automatic mesh generator a very efficient guidance process to analysis is avaiable. Estimates other than the energy norm have successfully been applied giving, for instance, a predetermined accuracy of stresses.

INTRODUCTION: Strengthening The Reporting Of Cohort Studies in Surgery (STROCSS) guidelines were developed in 2017 in order to improve the reporting quality of observational studies in surgery and updated in 2019. In order to maintain relevance and continue upholding good reporting quality among observational studies in surgery, we aimed to update STROCSS 2019 guidelines. METHODS: A STROCSS 2021 steering group was formed to come up with proposals to update STROCSS 2019 guidelines. An expert panel of researchers assessed these proposals and judged whether they should become part of STROCSS 2021 guidelines or not, through a Delphi consensus exercise. RESULTS: 42 people (89%) completed the DELPHI survey and hence participated in the development of STROCSS 2021 guidelines. All items received a score between 7 and 9 by greater than 70% of the participants, indicating a high level of agreement among the DELPHI group members with the proposed changes to all the items. CONCLUSION: We present updated STROCSS 2021 guidelines to ensure ongoing good reporting quality among observational studies in surgery.

Abstract. We present Bedmap2, a new suite of gridded products describing surface elevation, ice-thickness and the seafloor and subglacial bed elevation of the Antarctic south of 60° S. We derived these products using data from a variety of sources, including many substantial surveys completed since the original Bedmap compilation (Bedmap1) in 2001. In particular, the Bedmap2 ice thickness grid is made from 25 million measurements, over two orders of magnitude more than were used in Bedmap1. In most parts of Antarctica the subglacial landscape is visible in much greater detail than was previously available and the improved data-coverage has in many areas revealed the full scale of mountain ranges, valleys, basins and troughs, only fragments of which were previously indicated in local surveys. The derived statistics for Bedmap2 show that the volume of ice contained in the Antarctic ice sheet (27 million km3) and its potential contribution to sea-level rise (58 m) are similar to those of Bedmap1, but the mean thickness of the ice sheet is 4.6% greater, the mean depth of the bed beneath the grounded ice sheet is 72 m lower and the area of ice sheet grounded on bed below sea level is increased by 10%. The Bedmap2 compilation highlights several areas beneath the ice sheet where the bed elevation is substantially lower than the deepest bed indicated by Bedmap1. These products, along with grids of data coverage and uncertainty, provide new opportunities for detailed modelling of the past and future evolution of the Antarctic ice sheets.

All mammalian cells express 3 closely related Ras proteins, termed H-Ras, K-Ras, and N-Ras, that promote oncogenesis when they are mutationally activated at codon 12, 13, or 61. Although there is a high degree of similarity among the isoforms, K-Ras mutations are far more frequently observed in cancer, and each isoform displays preferential coupling to particular cancer types. We examined the mutational spectra of Ras isoforms curated from large-scale tumor profiling and found that each isoform exhibits surprisingly distinctive codon mutation and amino-acid substitution biases. These findings were unexpected given that these mutations occur in regions that share 100% amino-acid sequence identity among the 3 isoforms. Of importance, many of these mutational biases were not due to differences in exposure to mutagens, because the patterns were still evident when compared within specific cancer types. We discuss potential genetic and epigenetic mechanisms, as well as isoform-specific differences in protein structure and signaling, that may promote these distinct mutation patterns and differential coupling to specific cancers.

Abstract This is the first of two papers concerning superconvergent recovery techniques and a posteriori error estimation. In this paper, a general recovery technique is developed for determining the derivatives (stresses) of the finite element solutions at nodes. The implementation of the recovery technique is simple and cost effective. The technique has been tested for a group of widely used linear, quadratic and cubic elements for both one and two dimensional problems. Numerical experiments demonstrate that the recovered nodal values of the derivatives with linear and cubic elements are superconvergent. One order higher accuracy is achieved by the procedure with linear and cubic elements but two order higher accuracy is achieved for the derivatives with quadratic elements. In particular, an O ( h 4 ) convergence of the nodal values of the derivatives for a quadratic triangular element is reported for the first time. The performance of the proposed technique is compared with the widely used smoothing procedure of global L 2 projection and other methods. It is found that the derivatives recovered at interelement nodes, by using L 2 projection, are also superconvergent for linear elements but not for quadratic elements. Numerical experiments on the convergence of the recovered solutions in the energy norm are also presented. Higher rates of convergence are again observed. The results presented in this part of the paper indicate clearly that a new, powerful and economical process is now available which should supersede the currently used post‐processing procedures applied in most codes.

Leaders from the Canadian Society for Exercise Physiology convened representatives of national organizations, content experts, methodologists, stakeholders, and end-users who followed rigorous and transparent guideline development procedures to create the Canadian 24-Hour Movement Guidelines for Children and Youth: An Integration of Physical Activity, Sedentary Behaviour, and Sleep. These novel guidelines for children and youth aged 5-17 years respect the natural and intuitive integration of movement behaviours across the whole day (24-h period). The development process was guided by the Appraisal of Guidelines for Research Evaluation (AGREE) II instrument and systematic reviews of evidence informing the guidelines were assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Four systematic reviews (physical activity, sedentary behaviour, sleep, integrated behaviours) examining the relationships between and among movement behaviours and several health indicators were completed and interpreted by expert consensus. Complementary compositional analyses were performed using Canadian Health Measures Survey data to examine the relationships between movement behaviours and health indicators. A stakeholder survey was employed (n = 590) and 28 focus groups/stakeholder interviews (n = 104) were completed to gather feedback on draft guidelines. Following an introductory preamble, the guidelines provide evidence-informed recommendations for a healthy day (24 h), comprising a combination of sleep, sedentary behaviours, light-, moderate-, and vigorous-intensity physical activity. Proactive dissemination, promotion, implementation, and evaluation plans have been prepared in an effort to optimize uptake and activation of the new guidelines. Future research should consider the integrated relationships among movement behaviours, and similar integrated guidelines for other age groups should be developed.