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Abstract Background Persistent opioid use (POU) can occur with opioid use after surgery or trauma. Current systematic reviews include patients with previous exposure to opioids, meaning their findings may not be relevant to patients who are opioid naïve (i.e. Most recent exposure was from surgery or trauma). The aim of this review was to synthesise narratively the evidence relating to the incidence of, and risk factors for POU in opioid-naïve surgical or trauma patients. Method Structured searches of Embase, Medline, CINAHL, Web of Science, and Scopus were conducted, with final search performed on the 17th of July 2023. Searches were limited to human participants to identify studies that assessed POU following hospital admission due to surgery or trauma. Search terms relating to ‘opioid’, ‘analgesics’, ‘surgery’, ‘injury’, ‘trauma’ and ‘opioid-related disorder’ were combined. The Newcastle–Ottawa Scale for cohort studies was used to assess the risk of bias for studies. Results In total, 22 studies (20 surgical and two trauma) were included in the analysis. Of these, 20 studies were conducted in the United States (US). The incidence of POU for surgical patients 18 and over ranged between 3.9% to 14.0%, and for those under 18, the incidence was 2.0%. In trauma studies, the incidence was 8.1% to 10.5% among patients 18 and over. Significant risk factors identified across surgical and trauma studies in opioid-naïve patients were: higher comorbidity burden, having pre-existing mental health or chronic pain disorders, increased length of hospital stay during the surgery/trauma event, or increased doses of opioid exposure after the surgical or trauma event. Significant heterogeneity of study design precluded meta-analysis. Conclusion The quality of the studies was generally of good quality; however, most studies were of US origin and used medico-administrative data. Several risk factors for POU were consistently and independently associated with increased odds of POU, primarily for surgical patients. Awareness of these risk factors may help prescribers recognise the risk of POU after surgery or trauma, when considering continuing opioids after hospitalisation. The review found gaps in the literature on trauma patients, which represents an opportunity for future research. Trial registration PROSPERO registration: CRD42023397186.

The concept of nature positive has recently emerged from the widespread recognition of the global scale at which nature is being lost and the threat this poses to the collective survival of the human race. Much of the interest in nature positive reflects the initial commitment to it by conservation organisations and by a number of international political initiatives. However, the pursuit of nature positive approaches by businesses has received little attention in the business and management literature. Building upon an analysis of secondary sources, this entry paper first examines how three international organisations suggest a nature positive strategy could be pursued. This paper then focuses on two multinational companies and how they plan to pursue a nature positive approach to their business activities. This article identifies a number of critical factors in developing a nature positive strategy: incorporating suppliers in this strategy, assessing corporate dependencies and impacts on nature, and reporting on nature positive initiatives and outcomes. At the same time, this article raises concerns that nature positive approaches could be driven more by business imperatives rather than fundamental corporate concerns about biodiversity and that many business commitments to nature positive could be seen as mainly aspirational.

Background: Mobile phones, used in billions throughout the world, are high-touch devices subject to a dynamic contamination of microorganisms and rarely considered as an important fomite to sanitise systematically. The emergence of SARS-CoV-2 resulted in the COVID-19 pandemic, arguably the most impactful pandemic of the 21st century with millions of deaths and disruption of all facets of modern life globally. Aim: To perform a systematic review of the literature exploring SARS-CoV-2 presence as a contaminant on mobile phones. Methods: A systematic search (PubMed and Google Scholar) of literature was undertaken from December 2019 to March 2023 identifying English language studies. Studies included in this review specifically identified or tested for the contamination of the SARS-CoV-2 virus or genome on mobile phones while studies testing for SARS-COV-2 in environments and/or other fomites samples than but not mobile phones were excluded. Results: A total of 15 studies with reports of SARS-CoV-2 contamination on mobile phones between 2020 and 2023 were included. Amongst all studies, which encompassed ten countries, 511 mobile phones were evaluated for the presence of SARS-CoV-2 contamination and 45% (231/511) were positive for SARS-CoV-2. All studies were conducted in the hospital setting and two studies performed additional testing in residential isolation rooms and a patient’s house. Four studies (3 in 2020 and one in 2021) reported 0% contamination while two other studies (in 2020 and 2022) reported 100% of mobile phone contamination with SARS-COV-2. All other studies report mobile phones positive for the virus within a range of 4–77%. Conclusion: A total of 45% of mobile phones are contaminated with SARS-CoV-2 virus. These devices might be an important fomite vector for viral dissemination worldwide. Competent health authorities are advised/recommended to start a global implementation of mobile phone decontamination by introducing regulations and protocols in public health and health care settings such as the 6th moment of hand washing.

The term “metaverse” came to the fore in 2021 when Facebook rebranded its corporate identity to Meta and signalled its intention to invest at least USD 10 billion in developing the concepts and related products that year. However, there is still little consensus in defining what constitutes the metaverse, although there is a widespread, though not universal, agreement that it will bring a wide range of benefits across society. More specifically, the advent and continuing evolution of the metaverse has strategic and operational implications for, and impacts on, industry and business at large. Adopting an inductive, interpretivist approach, this exploratory research article presents case examples of the guidance on the responsible development of the metaverse provided by two IT business services companies. This article identifies the major risks and responsibilities associated with the metaverse and assesses how companies might address these responsibilities. Very little research has been published in this area, and this article attempts to make a small contribution to filling this gap in the literature. This article finds that these responsibilities are largely in line with those currently associated with corporate digital responsibility, and concludes that the strategic impact and extent of regulatory change will depend on the nature of the metaverse that materialises in the forthcoming decade.

Digital technologies bring a wide range of new opportunities, for both retailers and consumers, but retailers face, and may have to address, several new sets of responsibility issues as they progressively introduce these technologies. These responsibilities are increasingly being captured in the concept of corporate digital responsibility (CDR) but CDR within the retail industry has received little, or no attention, in the academic literature. This paper looks to make a small contribution to addressing that gap in the literature. The paper includes some definitions of CDR, an outline of the concept and scope of CDR, two cameo case studies which provide a simple illustration of some of the ways in which the Rewe Group and the Otto Group, two of Germany’s leading retailers, choose to publicly address CDR, and offers some reflections on retailers and CDR. The paper suggests that there are, potential tensions between the retailers’ management of the economic and the social dimensions of CDR, and that there are issues about whose best interests are served by CDR and the difficulties involved in making such judgements.

Abstract Process analytical technology (PAT) has demonstrated huge potential to enable the development of improved biopharmaceutical manufacturing processes by ensuring the reliable provision of quality products. However, the complexities associated with the manufacture of advanced therapy medicinal products have resulted in a slow adoption of PAT tools into industrial bioprocessing operations, particularly in the manufacture of cell and gene therapy products. Here we describe the applicability of a novel refractometry-based PAT system (Ranger system), which was used to monitor the metabolic activity of HEK293T cell cultures during lentiviral vector (LVV) production processes in real time. The PAT system was able to rapidly identify a relationship between bioreactor pH and culture metabolic activity and this was used to devise a pH operating strategy that resulted in a 1.8-fold increase in metabolic activity compared to an unoptimised bioprocess in a minimal number of bioreactor experiments; this was achieved using both pre-programmed and autonomous pH control strategies. The increased metabolic activity of the cultures, achieved via the implementation of the PAT technology, was not associated with increased LVV production. We employed a metabolic modelling strategy to elucidate the relationship between these bioprocess level events and HEK293T cell metabolism. The modelling showed that culturing of HEK293T cells in a low pH (pH 6.40) environment directly impacted the intracellular maintenance of pH and the intracellular availability of oxygen. We provide evidence that the elevated metabolic activity was a response to cope with the stress associated with low pH to maintain the favourable intracellular conditions, rather than being indicative of a superior active state of the HEK293T cell culture resulting in enhanced LVV production. Forecasting strategies were used to construct data models which identified that the novel PAT system not only had a direct relationship with process pH but also with oxygen availability; the interaction and interdependencies between these two parameters had a direct effect on the responses observed at the bioprocess level. We present data which indicate that process control and intervention using this novel refractometry-based PAT system has the potential to facilitate the fine tuning and rapid optimisation of the production environment and enable adaptive process control for enhanced process performance and robustness.

Modern slavery is an insidious problem in many sectors of the global economy, and it poses a challenge for the information technology industry. However, the issue of modern slavery in the information technology industry has received little or no attention in the business and management literature and this paper looks to provide an exploratory review of one of the ways in which the leading information and communication technology companies have addressed this issue, by reviewing their modern slavery statements. The findings reveal that five interlinked themes, namely, corporate commitment; risk assessments and due diligence in supply chains: codes of conduct; awareness, capability building, and training; and future plans and key performance indicators illustrated the spirit of the selected companies’ modern slavery statements. Identifying and tackling the risk of modern slavery within supply chains presents the major challenges for the information technology companies, and the paper concludes that the leading technology companies’ modern slavery statements can be best seen as a work in progress.

Unique aspects of New Zealand’s (NZ) health system allow for a novel pharmacoepidemiologic approach to conducting population-based clinical research. A defined cohort of surgical and trauma patients would facilitate future studies into opioid utilisation, outcomes, and other questions related to surgery and trauma. We aimed to describe all patients admitted to a NZ hospital with trauma or to undergo surgery between 1 January 2007 to 31 December 2019. This was a retrospective population-based study involving all hospital centres in NZ. We excluded patients with hospitalisation episodes for surgery or trauma one year before the event. We identified 1.78 million surgical only patients, 633,386 trauma only, and 250,800 trauma with surgery patients. Trauma only patients had the highest prevalence of death within one year of event (17.8%), history of opioid dispensing (18.3%), mental health disorders (17.0%) and chronic pain (2.3%). Moreover, trauma patients also had the highest prevalence of those with higher comorbidity burden. We plan to use this dataset for future research into the prevalence and outcomes of persistent opioid use, and to make our dataset available to other researchers upon request. Our findings of significant differences between cohorts suggest studies should treat surgical and trauma patients separately.

The causes of a pyrexia of unknown origin (PUO) are broadly spread across infectious, malignant, or inflammatory conditions. The authors report a case of a 43-year-old female who initially presented with hypoxia and fevers secondary to a presumed acute viral or bacterial infectious pulmonary insult. However, fevers persisted despite pulmonary imaging remaining normal. The case subsequently evolved into a PUO with multiple lines of investigation proving inconclusive. No definitive diagnosis was made at the time of discharge; however, cessation of hydralazine was noted to coincide with the last of the patient’s fevers. Following the discharge, her anti-histone antibodies returned a positive result, and the diagnosis of drug-induced lupus was made with hydralazine as the presumed trigger.

Abstract Advancements in technology and communication have revolutionised the twenty-first century with the introduction of mobile phones and smartphones. These phones are known to be platforms harbouring microbes with recent research shedding light on the abundance and broad spectrum of organisms they harbour. Mobile phone use in the community and in professional sectors including health care settings is a potential source of microbial dissemination. To identify the diversity of microbial genetic signature present on mobile phones owned by hospital medical staff. Twenty-six mobile phones of health care staff were swabbed. DNA extraction for downstream next generation sequencing shotgun metagenomic microbial profiling was performed. Survey questionnaires were handed to the staff to collect information on mobile phone usage and users’ behaviours. Each of the 26 mobile phones of this study was contaminated with microbes with the detection of antibiotic resistance and virulent factors. Taken together the sum of microbes and genes added together across all 26 mobile phones totalised 11,163 organisms (5714 bacteria, 675 fungi, 93 protists, 228 viruses, 4453 bacteriophages) and 2096 genes coding for antibiotic resistance and virulent factors. The survey of medical staff showed that 46% (12/26) of the participants used their mobile phones in the bathroom. Mobile phones are vectors of microbes and can contribute to microbial dissemination and nosocomial diseases worldwide. As fomites, mobile phones that are not decontaminated may pose serious risks for public health and biosecurity.

Introduction Evidence suggests a potentially causal role of interleukin 6 (IL-6), a pleiotropic cytokine that generally promotes inflammation, in the pathogenesis of psychosis. However, no interventional studies in patients with psychosis, stratified using inflammatory markers, have been conducted to assess the therapeutic potential of targeting IL-6 in psychosis and to elucidate potential mechanism of effect. Tocilizumab is a humanised monoclonal antibody targeting the IL-6 receptor to inhibit IL-6 signalling, licensed in the UK for treatment of rheumatoid arthritis. The primary objective of this study is to test whether IL-6 contributes to the pathogenesis of first episode psychosis and to examine potential mechanisms by which IL-6 affects psychotic symptoms. A secondary objective is to examine characteristics of inflammation-associated psychosis.Methods and analysis A proof-of-concept study employing a randomised, parallel-group, double-blind, placebo-controlled design testing the effect of IL-6 inhibition on anhedonia in patients with psychosis. Approximately 60 participants with a diagnosis of schizophrenia and related psychotic disorders (ICD-10 codes F20, F22, F25, F28, F29) with evidence of low-grade inflammation (IL-6≥0.7 pg/mL) will receive either one intravenous infusion of tocilizumab (4.0 mg/kg; max 800 mg) or normal saline. Psychiatric measures and blood samples will be collected at baseline, 7, 14 and 28 days post infusion. Cognitive and neuroimaging data will be collected at baseline and 14 days post infusion. In addition, approximately 30 patients with psychosis without evidence of inflammation (IL-6

This paper offers an exploratory review of how some of the major US and European food retailers have publicly addressed animal welfare. The findings reveal that six interlinked themes, namely, strategic corporate commitment, animal welfare as good business policy, a focus on supply chains, policies on specific categories of animals and animal products, antibiotics, and auditing, illustrated the food retailers’ approach to animal welfare. The authors raise a range of issues about the retailers’ approach to animal welfare, including the aspirational nature of their commitments, the emphasis on regular audits, the role of external assurance in the reporting process, pressure from animal welfare campaigns, and the impact of the COVID-19 pandemic. The paper offers an accessible review how some of the major US and European food retailers have publicly addressed the issue of animal welfare.

Objective To determine whether birth outside a level-3 centre (outborn) is associated with a difference in the combined outcome of mortality or moderate-to-severe neurological impairment at 5.5 years of age compared with birth in a level-3 centre (inborn) when antenatal steroids and gestational age (GA) are accounted for.Design Individual matched study nested within a prospective cohort. Each outborn infant was matched using GA and antenatal steroids with a maximum of four inborns. Conditional logistic regression was used to calculate ORs before being adjusted using maternal and birth characteristics. Analyses were carried out after multiple imputation for missing data.Setting EPIPAGE-2 French national prospective cohort including births up to 34 weeks GA inclusive.Patients Outborn and inborn control infants selected between 24 and 31 weeks GA were followed in the neonatal period and to 2 and 5.5 years. 3335 infants were eligible of whom all 498 outborns and 1235 inborn infants were included—equivalent to 2.5 inborns for each outborn.Main outcome measure Survival without moderate-to-severe neurodevelopmental impairment at 5.5 years.Results Chorioamnionitis, pre-eclampsia, caesarian birth and small-for-dates were more frequent among inborns, and spontaneous labour and antepartum haemorrhage among outborns. There was no difference in the main outcome measure at 5.5 years of age (adjusted OR 1.09, 95% CI 0.82 to 1.44); sensitivity analyses suggested improved outcomes at lower GAs for inborns.Conclusion In this GA and steroid matched cohort, there was no difference in survival without moderate-to-severe neurodevelopmental impairment to 5.5 years of age between inborn and outborn very preterm children. This suggests steroids might be important in determining outcomes.

Recent decades have witnessed increasing interest in the concept of the circular economy within both the business world and political circles. The circular economy spans the entire life cycle of products from product design through production, marketing, and consumption, to waste management, recycling, and re-use, and enthusiasm for putting the concept into practice has been identified across different sectors of the economy. This exploratory case study reviews how some of the leading companies in the paper and retail industries, have publicly addressed the circular economy. The case study outlines the nature of the circular economy, provides a cameo literature review of published work on the circular economy, describes the approach adopted for the case study, reports the findings of the review of how the leading companies in the paper and retail industries have addressed the circular economy, and discusses some wider issues.

Abstract Background Structured reporting is an efficient and replicable method of presenting diagnostic results that eliminates variability inherent in narrative descriptive reporting and may improve clinical decisions. Synoptic element reporting can generate discrete coded data that then may inform clinical decision support and trigger downstream actions in computerized electronic health records. Objective Limited evidence exists for use of synoptic reporting for computed tomography pulmonary arteriography (CTPA) among patients suspected of pulmonary embolism. We reported the accuracy of synoptic reporting for the outcome of pulmonary embolism among patients who presented to an integrated health care system with CTPA performed for suspected pulmonary embolism. Methods Structured radiology reports with embedded synoptic elements were implemented for all CTPA examinations on March 1, 2018. Four hundred CTPA reports between January 4, 2019 and July 30, 2020 (200 reports each for which synoptic reporting recorded the presence or absence of pulmonary embolism [PE]) were selected at random. One non‐diagnostic study was excluded from analysis. We then assessed the accuracy of synoptic reporting compared with the gold standard of manual chart review. Results Synoptic reporting and manual review agreed in 99.2% of patients undergoing CTPA for suspected PE, agreed on the presence of PE in 196 of 199 (98.5%) cases, the absence of PE in 200 of 200 (100%) cases with a sensitivity of 87.6% (76.1–96.1) a specificity of 99.9% (99.7%–100%), a positive predictive value of 99.5% (98.1–100), and a negative predictive value of 98% (95.7%–99.5%). Conclusion The overall rate of agreement was 99.2%, but we observed an unacceptable false‐negative rate for clinical reliance on synoptic element reporting in isolation from dictated reports.

As the digital era advances, many industries continue to expand their use of digital technologies to support company operations, notably at the customer interface, bringing new commercial opportunities and increased efficiencies. However, there are new sets of responsibilities associated with the deployment of these technologies, encompassed within the emerging concept of corporate digital responsibility (CDR), which to date has received little attention in the academic literature. This exploratory paper thus looks to make a small contribution to addressing this gap in the literature. The paper adopts a qualitative, inductive research method, employing an initial scoping literature review followed by two case studies. Based on the research findings, a simple model of CDR parameters is put forward. The article includes a discussion of a number of emergent issues—fair and equitable access, personal and social well-being, environmental implications, and cross-supply chain complexities—and a conclusion that summarises the main findings and suggests possible directions for future research.

Abstract There is increasing attention focussed on the risks associated with mobile phones possibly serving as ‘Trojan Horse’ fomites for microbial transmission in healthcare settings. However, little is reported on the presence of microbes on community derived mobile phones which in 2021, numbered in the billions in circulation with majority being used on a daily basis. Identify viable microbial organisms swabbed from smartphones on a university campus. Entire surfaces of 5 mobile phones were swabbed and examined for their microbial content using pre-agar-based growths followed by downstream DNA metagenomic next-generation sequencing analysis. All phones were contaminated with viable microbes. 173 bacteria, 8 fungi, 8 protists, 53 bacteriophages, 317 virulence factor genes and 41 distinct antibiotic resistant genes were identified. While this research represents a pilot study, the snapshot metagenomic analysis of samples collected from the surface of mobile phones has revealed the presence of a large population of viable microbes and an array of antimicrobial resistant factors. With billions of phones in circulation, these devices might be responsible for the rise of community acquired infections. These pilot results highlight the importance of public health authorities considering mobile phones as ‘Trojan Horse’ devices for microbial transmission and ensure appropriate decontamination campaigns are implemented.

Abstract An ever-increasing number of medical staff use mobile phones as a work aid, yet this may pose nosocomial diseases. To assess and report via a survey the handling practices and the use of phones by paediatric wards healthcare workers. 165 paediatric healthcare workers and staff filled in a questionnaire consisting of 14 questions (including categorical, ordinal and numerical data). Analysis of categorical data used non-parametric techniques such as the Chi-squared test. Although 98% of respondents (165 in total) report that their phones may be contaminated, 56% have never cleaned their devices. Of the respondents that clean their devices, 10% (17/165) had done so with alcohol swabs or disinfectant within that day or week; and an additional 12% respondents (20/165) within that month. Of concern, 52% (86/165) of the respondents use their phones in the bathroom, emphasising the unhygienic environments in which mobile phones/smartphones are constantly used. Disinfecting phones is a practice that only a minority of healthcare workers undertake appropriately. Mobile phones, present in billions globally, are therefore Trojan Horses if contaminated with microbes and potentially contributing to the spread and propagation of micro-organisms as per the rapid spread of SARS-CoV-2 virus in the world.

The Sustainable Development Goals (SDGs) agreed at a United Nations General Assembly in 2015 embrace an ambitious and wide-ranging set of global environmental, social and economic issues designed to effect a transition to a more sustainable future; the United Nations important role of the private sector in addressing the SDGs. The majority of Europe’s leading retailers have been pursuing sustainability strategies, and reporting on their achievements against their strategies, for some time and within the European retail community there is a recognition that retailers have a vital role to play in contributing to the achievement of the SDGs. This exploratory paper reviews and reflects on how seven of Europe’s leading retailers claim to be committed to addressing the SDGs. The findings revealed that all seven retailers reported on their commitment to contributing to the achievement of the SDGs, though the scale and the extent of their commitment varied. In reviewing the retailers’ approach to the SDGs, the authors drew attention to a number of issues namely, concentration on specific SDGs, issues of measurement and reporting and tensions between sustainability and economic growth

BackgroundMobile phones of healthcare workers (HCWs) can act as fomites in the dissemination of microbes. This study was carried out to investigate microbial contamination of mobile phones of HCWs and environmental samples from the hospital unit using a combination of phenotypic and molecular methods.MethodsThis point prevalence survey was carried out at the Emergency unit of a tertiary care facility. The emergency unit has two zones, a general zone for non-COVID-19 patients and a dedicated COVID-19 zone for confirmed or suspected COVID-19 patients. Swabs were obtained from the mobile phones of HCWs in both zones for bacterial culture and shotgun metagenomic analysis. Metagenomic sequencing of pooled environmental swabs was conducted. RT-PCR for SARS-CoV-2 detection was carried out.ResultsBacteria contamination on culture was detected from 33 (94.2%) mobile phones with a preponderance of Staphylococcus epidermidis (n/N = 18/35), Staphylococcus hominis (n/N = 13/35), and Staphylococcus haemolyticus (n/N = 7/35). Two methicillin-sensitive and three methicillin-resistant Staphylococcus aureus, and one pan-drug-resistant carbapenemase producer Acinetobacter baumannii were detected. Shotgun metagenomic analysis showed high signature of Pseudomonas aeruginosa in mobile phone and environmental samples with preponderance of P. aeruginosa bacteriophages. Malassezia and Aspergillus spp. were the predominant fungi detected. Fourteen mobile phones and one environmental sample harbored protists. P. aeruginosa antimicrobial resistance genes mostly encoding for efflux pump systems were detected. The P. aeruginosa virulent factor genes detected were related to motility, adherence, aggregation, and biofilms. One mobile phone from the COVID-19 zone (n/N = 1/5; 20%) had positive SARS-CoV-2 detection while all other phone and environmental samples were negative.ConclusionThe findings demonstrate that mobile phones of HCWs are fomites for potentially pathogenic and highly drug-resistant microbes. The presence of these microbes on the mobile phones and hospital environmental surfaces is a concern as it poses a risk of pathogen transfer to patients and dissemination into the community.

Abstract Regenerative medicine approaches to enhancing beta cell growth and survival represent potential treatments for diabetes. It is known that growth factors such as insulin, IGF-1 and HGF support beta cell growth and survival, but in people with type 2 diabetes the destructive effects of metabolic stress predominate and beta cell death or dysfunction occurs. In this study we explore the novel hypothesis that regulation of growth factor receptor trafficking can be used to promote islet beta cell survival. Growth factor signalling is dependent on the presence of cell surface receptors. Endosomal trafficking and subsequent recycling or degradation of these receptors is controlled by the Rab GTPase family of proteins. We show that Rab7a siRNA inhibition enhances IGF-1 and HGF signalling in beta cells and increases expression of the growth factor receptors IGF-1R and c-Met. Furthermore, Rab7a inhibition promotes beta cell growth and islet survival, and protects against activation of apoptosis and autophagy pathways under conditions of metabolic stress. This study therefore demonstrates that Rab7a-mediated trafficking of growth factor receptors controls beta cell survival. Pharmaceutical Rab7a inhibition may provide a means to promote beta cell survival in the context of metabolic stress and prevent the onset of type 2 diabetes.

Melanoma metastasis to the brain is one of the most frequent extracranial brain tumors. Cell surface gangliosides are elevated in melanoma metastasis; however, the metabolic regulatory mechanisms that govern these specific changes are poorly understood in melanoma particularly brain metastases (MBM) development. We found ganglioside GD3 levels significantly upregulated in MBM compared to lymph node metastasis (LNM) but not for other melanoma gangliosides. Moreover, we demonstrated an upregulation of ST8SIA1 (GD3 synthase) as melanoma progresses from melanocytes to MBM cells. Using RNA‐ISH on FFPE specimens, we evaluated ST8SIA1 expression in primary melanomas (PRM) (n = 23), LNM and visceral metastasis (n = 45), and MBM (n = 39). ST8SIA1 was significantly enhanced in MBM compared to all other specimens. ST8SIA1 expression was assessed in clinically well‐annotated melanoma patients from multicenters with AJCC stage III B‐D LNM (n = 58) with 14‐year follow‐up. High ST8SIA1 expression was significantly associated with poor overall survival (HR = 3.24; 95% CI, 1.19–8.86, P = 0.02). In a nude mouse human xenograft melanoma brain metastasis model, MBM variants had higher ST8SIA1 expression than their respective cutaneous melanoma variants. Elevated ST8SIA1 expression enhances levels of cell surface GD3, a phenotype that favors MBM development, hence associated with very poor prognosis. Functional assays demonstrated that ST8SIA1 overexpression enhanced cell proliferation and colony formation, whereby ST8SIA1 knockdown had opposite effects. Icaritin a plant‐derived phytoestrogen treatment significantly inhibited cell growth in high GD3‐positive MBM cells through targeting the canonical NFκB pathway. The study demonstrates GD3 phenotype associates with melanoma progression and poor outcome.

A 72-year-old man with coronary artery disease, statin intolerance, and chronic kidney disease stage IIIa was initiated on alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, and developed acute kidney injury. A kidney biopsy was performed and suggested acute tubular injury. The serum creatinine returned to baseline after discontinuation of alirocumab. (Level of Difficulty: Intermediate.)

Background Gaming is a potentially dysfunctional consequence of performance measurement and management systems in the health sector and more generally. In 2009, the New Zealand government initiated a Shorter Stays in Emergency Department (SSED) target in which 95% of patients would be admitted, discharged or transferred from an emergency department (ED) within 6 hours. The implementation of similar targets in England led to well-documented practices of gaming. Our research into ED target implementation sought to answer how and why gaming varies over time and between organisations. Methods We developed a mixed-methods approach. Four organisation case study sites were selected. ED lengths of stay (ED LOS) were collected over a 6-year period (2007-2012) from all sites and indicators of target gaming were developed. Two rounds of surveys with managers and clinicians were conducted. Interviews (n = 68) were conducted with clinicians and managers in EDs and the wider hospital in two phases across all sites. The interview data was used to develop explanations of the patterns of variation across time and across sites detected in the ED LOS data. Results Our research established that gaming behaviour – in the form of ‘clock-stopping’ and decanting patients to short-stay units (SSUs) or observation beds to avoid target breaches – was common across all 4 case study sites. The opportunity to game was due to the absence of independent verification of ED LOS data. Gaming increased significantly over time (2009-2012) as the means to game became more available, usually through the addition or expansion of short-stay facilities attached to EDs. Gaming varied between sites, but those with the highest levels of gaming differed substantially in terms of organisational dynamics and motives. In each case, however, high levels of gaming could be attributed to the strategies of senior management more than to the individual motivations of frontline staff. Conclusion Gaming of New Zealand’s ED target increased after the real benefits (in terms of process improvement) of the target were achieved. Gaming of ED targets could be minimised by eliminating opportunities to game through independent verification, or by monitoring and limiting the means and motivations to game.

The present special issue goes back to the online conference entitled Integrationism and Language Ideologies (March 15-20, 2021), which was organized by the Language Policy Group of the Federal University of Santa Catarina in conjunction with the International Association for the Integrational Study of Language and Communication (IAISLC). The contributions in this issue are for the most part revised versions of the conference papers presented at the event. The special issue also features an interview with integrationist David Bade as well as a Portuguese translation by Cristine Severo and Ana Cláudia Eltermann of one of Harris’ texts (‘The integrationist critique of orthodox linguistics’). The present volume introduces key ideas on Roy Harris’ integrational linguistics to a Lusophone readership by highlighting relevant issues in language ideology, linguistic methodology, decolonial linguistics and (socio)linguistic theory. The various contributions all underline the necessity to rethink (or ‘demythologize’) the semiological and philosophical foundations of orthodox linguistics and a need to develop a theory of communication in which language is treated as an integrated mode rather than a segregated object.

In this paper I wanted to give a personal view on where I believe integrationism (Harris, 1981, 1998) sits in the current field of linguistics and applied linguistics research. In doing so I hoped to try to clarify what I see as the distinctive contribution that the integrationist tradition may make in responding to the challenge that Alastair Pennycook and Sinfree Makoni (2020) have posed of a re-made linguistics which can learn from and do justice to the struggles for both social justice and equality across both the Global South and Global North as well as for harmonious and mutually beneficial relations with our world and the other beings that share it with us.

Behaviour on the road is ordered by a range of norms, rules, laws, and infrastructures. The introduction of self-driving vehicles onto the road opens a debate about the rules that should govern their actions and how these should be integrated with, or lead to the modification of, existing road rules. In this paper, we analyse the current rules of the road, with a particular focus on the UK's Highway Code, in order to inform future rulemaking. We consider the full range of laws, norms, infrastructures, and technologies that govern interactions on the road and where these came from. The rules have a long history and they contribute to a social order that privileges some modes of mobility over others, reinforcing a culture of automobility that shapes lives, livelihoods and places. The introduction of self-driving vehicles, and the digital code on which they depend, could reorder the culture and concrete of our roads, by flattening the multidimensional rules of the road, hardening rules that are currently soft and standardising across diverse contexts. Future rule changes to accommodate self-driving vehicles may enable increases in safety and accessibility, but the trade-offs demand democratic debate.

The twenty first century has witnessed wide-ranging changes in the banking industry and these changes have brought a number of challenges for customers and employees. Many banks have looked to employ storytelling as one way of trying to help both customers and employees to accommodate these changes and challenges. This exploratory paper looks provide a range of illustrations of the ways in which the UK’s leading banks have publicly employed stories on the Internet as part of their external and internal communication programmes and offers some reflections on the role of stories within such programmes. The paper reveals that the UK’s five leading banks all publicly employ stories, which address a number of issues including business successes and achievements, customers’ experiences, environmental and social commitments, career development, employees’ work experiences and the history of banks and their branches. The authors suggest that these themes collectively looked to reinforce the banks’ fundamental emphasis on trust, confidence, and customer relationships. At the same time, while the findings of the paper revealed that the stories are exclusively positive and are essentially scripted to cast banks in a favourable light, the authors counsel caution in that there is a danger that such stories may not always be fully representative of a bank’s relationships with its customers and employees.

Abstract Background Strategies to improve the effectiveness and quality of health and care have predominantly emphasised the implementation of new research and evidence into service organisation and delivery. A parallel, but less understood issue is how clinicians and service leaders stop existing practices and interventions that are no longer evidence based, where new evidence supersedes old evidence, or interventions are replaced with those that are more cost effective. The aim of this evidence synthesis is to produce meaningful programme theory and practical guidance for policy makers, managers and clinicians to understand how and why de-implementation processes and procedures can work. Methods and analysis The synthesis will examine the attributes or characteristics that constitute the concept of de-implementation. The research team will then draw on the principles of realist inquiry to provide an explanatory account of how, in what context and for whom to explain the successful processes and impacts of de-implementation. The review will be conducted in four phases over 18 months. Phase 1: develop a framework to map the preliminary programme theories through an initial scoping of the literature and consultation with key stakeholders. Phase 2: systematic searches of the evidence to develop the theories identified in phase 1. Phase 3: validation and refinement of programme theories through stakeholder interviews. Phase 4: formulating actionable recommendations for managers, commissioners and service leaders about what works through different approaches to de-implementation. Discussion This evidence synthesis will address gaps in knowledge about de-implementation across health and care services and ensure that guidance about strategies and approaches accounts for contextual factors, which may be operating at different organisational and decision-making levels. Through the development of the programme theory, which explains what works, how and under which circumstances, findings from the evidence synthesis will support managers and service leaders to make measured decisions about de-implementation. Systematic review registration PROSPERO CRD42017081030

Duchenne muscular dystrophy (DMD) is a devastating disease caused by mutations in the dystrophin gene that result in the complete absence of dystrophin protein. We have shown previously that recombinant mouse Galectin-1 treatment improves physiological and histological outcome measures in the mdx mouse model of DMD. Because recombinant human Galectin-1 (rHsGal1) will be used to treat DMD patients, we performed a dose-ranging study and intraperitoneal or intravenous delivery to determine the efficacy of rHsGal1 to improve preclinical outcome measures in mdx mice. Our studies showed that the optimal dose of rHsGal1 delivered intraperitoneally was 20 mg/kg and that this treatment improved muscle strength, sarcolemma stability, and capillary density in skeletal muscle. We next examined the efficacy of intravenous delivery and found that a dose of 2.5 mg/kg rHsGal1 was well tolerated and improved outcome measures in the mdx mouse model. Our studies identified that intravenous doses of rHsGal1 exceeding 2.5 mg/kg resulted in toxicity, indicating that dosing using this delivery mechanism will need to be carefully monitored. Our results support the idea that rHsGal1 treatment can improve outcome measures in the mdx mouse model and support further development as a potential therapeutic agent for DMD. Keywords: Duchenne muscular dystrophy, Galectin-1, protein therapeutic, biologic, vascularization

Real-time identification of venous thromboembolism (VTE), defined as deep vein thrombosis (DVT) and pulmonary embolism (PE), can inform a healthcare organization’s understanding of these events and be used to improve care. In a former publication, we reported the performance of an electronic medical record (EMR) interrogation tool that employs natural language processing (NLP) of imaging studies for the diagnosis of venous thromboembolism. Because we transitioned from the legacy electronic medical record to the Cerner product, iCentra, we now report the operating characteristics of the NLP EMR interrogation tool in the new EMR environment. Two hundred randomly selected patient encounters for which the imaging report assessed by NLP that revealed VTE was present were reviewed. These included one hundred imaging studies for which PE was identified. These included computed tomography pulmonary angiography—CTPA, ventilation perfusion—V/Q scan, and CT angiography of the chest/ abdomen/pelvis. One hundred randomly selected comprehensive ultrasound (CUS) that identified DVT were also obtained. For comparison, one hundred patient encounters in which PE was suspected and imaging was negative for PE (CTPA or V/Q) and 100 cases of suspected DVT with negative CUS as reported by NLP were also selected. Manual chart review of the 400 charts was performed and we report the sensitivity, specificity, positive and negative predictive values of NLP compared with manual chart review. NLP and manual review agreed on the presence of PE in 99 of 100 cases, the presence of DVT in 96 of 100 cases, the absence of PE in 99 of 100 cases and the absence of DVT in all 100 cases. When compared with manual chart review, NLP interrogation of CUS, CTPA, CT angiography of the chest, and V/Q scan yielded a sensitivity = 93.3%, specificity = 99.6%, positive predictive value = 97.1%, and negative predictive value = 99%.

Background: Health-care systems across the globe are facing increased pressures to balance the efficient use of resources and at the same time provide high-quality care. There is greater requirement for services to be evidence based, but practices that are of limited clinical effectiveness or cost-effectiveness still occur. Objectives: Our objectives included completing a concept analysis of de-implementation, surfacing decision-making processes associated with de-implementing through stakeholder engagement, and generating an evidence-based realist programme theory of ‘what works’ in de-implementation. Design: A realist synthesis was conducted using an iterative stakeholder-driven four-stage approach. Phase 1 involved scoping the literature and conducting stakeholder interviews to develop the concept analysis and an initial programme theory. In Phase 2, systematic searches of the evidence were conducted to test and develop this theory, expressed in the form of contingent relationships. These are expressed as context–mechanism–outcomes to show how particular contexts or conditions trigger mechanisms to generate outcomes. Phase 3 consisted of validation and refinement of programme theories through stakeholder interviews. The final phase (i.e. Phase 4) formulated actionable recommendations for service leaders. Participants: In total, 31 stakeholders (i.e. user/patient representatives, clinical managers, commissioners) took part in focus groups and telephone interviews. Data sources: Using keywords identified during the scoping work and concept analysis, searches of bibliographic databases were conducted in May 2018. The databases searched were the Cochrane Library, Campbell Collaboration, MEDLINE (via EBSCOhost), the Cumulative Index to Nursing and Allied Health Literature (via EBSCOhost), the National Institute for Health Research Journals Library and the following databases via the ProQuest platform: Applied Social Sciences Index and Abstracts, Social Services Abstracts, International Bibliography of the Social Sciences, Social Sciences Database and Sociological Abstracts. Alerts were set up for the MEDLINE database from May 2018 to December 2018. Online sources were searched for grey literature and snowballing techniques were used to identify clusters of evidence. Results: The concept analysis showed that de-implementation is associated with five main components in context and over time: (1) what is being de-implemented, (2) the issues driving de-implementation, (3) the action characterising de-implementation, (4) the extent that de-implementation is planned or opportunistic and (5) the consequences of de-implementation. Forty-two papers were synthesised to identify six context–mechanism–outcome configurations, which focused on issues ranging from individual behaviours to organisational procedures. Current systems can perpetuate habitual decision-making practices that include low-value treatments. Electronic health records can be designed to hide or remove low-value treatments from choice options, foregrounding best evidence. Professionals can be made aware of their decision-making strategies through increasing their attention to low-value practice behaviours. Uncertainty about diagnosis or patients’ expectations for certain treatments provide opportunities for ‘watchful waiting’ as an active strategy to reduce inappropriate investigations and prescribing. The emotional component of clinician–patient relationships can limit opportunities for de-implementation, requiring professional support through multimodal educational interventions. Sufficient alignment between policy, public and professional perspectives is required for de-implementation success. Limitations: Some specific clinical issues (e.g. de-prescribing) dominate the de-implementation evidence base, which may limit the transferability of the synthesis findings. Any realist inquiry generates findings that are essentially cumulative and should be developed through further investigation that extends the range of sources into, for example, clinical research and further empirical studies. Conclusions: This review contributes to our understanding of how de-implementation of low-value procedures and services can be improved within health-care services, through interventions that make professional decision-making more accountable and the prominence of a whole-system approach to de-implementation. Given the whole-system context of de-implementation, a range of different dissemination strategies will be required to engage with different stakeholders, in different ways, to change practice and policy in a timely manner. Study registration: This study is registered as PROSPERO CRD42017081030. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Services and Delivery Research programme and will be published in full in Health Services and Delivery Research; Vol. 9, No. 2. See the NIHR Journals Library website for further project information.

Introduction Opioid use has increased globally for the management of chronic non-cancer-related pain. There are concerns regarding the misuse of opioids leading to persistent opioid use and subsequent hospitalisation and deaths in developed countries. Hospital admissions related to surgery or trauma have been identified as contributing to the increasing opioid use internationally. There are minimal data on persistent opioid use and opioid-related harm in New Zealand (NZ), and how hospital admission for surgery or trauma contributes to this. We aim to describe rates and identify predictors of persistent opioid use among opioid-naïve individuals following hospital discharge for surgery or trauma.Methods and analysis This is a population-based, retrospective cohort study using linked data from national health administrative databases for opioid-naïve patients who have had surgery or trauma in NZ between January 2006 and December 2019. Linked data will be used to identify variables of interest including all types of hospital surgeries in NZ, all trauma hospital admissions, opioid dispensing, comorbidities and sociodemographic variables. The primary outcome of this study will be the prevalence of persistent opioid use. Secondary outcomes will include mortality, opioid-related harms and hospitalisation. We will compare the secondary outcomes between persistent and non-persistent opioid user groups. To compute rates, we will divide the total number of outcome events by total follow-up time. Multivariable logistic regression will be used to identify predictors of persistent opioid use. Multivariable Cox regression models will be used to estimate the risk of opioid-related harms and hospitalisation as well as all-cause mortality among the study cohort in a year following hospital discharge for surgery or trauma.Ethics and dissemination This study has been approved by the Auckland Health Research Ethics Committee (AHREC- AH1159). Results will be reported in accordance with the Reporting of studies Conducted using Observational Routinely collected health data statement (RECORD).

In a scientific career that spanned over three decades, Dr. Jeff Foote made seminal contributions to antibody humanization and the biophysical aspects of antibody recognition. In this Perspective, we discuss his life and work.

Introduction Ophthalmology education during medical school is often very limited. To provide exposure to areas beyond its standard curriculum, the University of Pittsburgh School of Medicine offers mini-elective courses in various disciplines. We developed such a course to provide instruction in the basics of clinical ophthalmology to interested preclinical medical students. Methods First- and second-year medical students electively enrolled in our course (mean number of students per year = 12), which included four sessions combining didactics and hands-on learning. Additionally, each student individually spent time with an ophthalmologist in the operating room. Our course was held each year from 2015 to 2019. Results Participants completed pre- (n = 25) and postsurveys (n = 20), reflecting increased comfort with the ophthalmologic history and physical examination. In 2019, participants also completed pre- and posttests, demonstrating increased knowledge of ophthalmology. Discussion The Ophthalmology Mini-Elective is a unique educational tool that introduces the principles of ophthalmology to preclinical medical students, addressing an area of medicine that is generally minimally included in the required curriculum.