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Pegunigalsidase alfa, a PEGylated α-galactosidase A enzyme replacement therapy (ERT) for Fabry disease, has a longer plasma half-life than other ERTs administered intravenously every 2 weeks (E2W). BRIGHT (NCT03180840) was a phase III, open-label study in adults with Fabry disease, previously treated with agalsidase alfa or beta E2W for ≥3 years, who switched to 2 mg/kg pegunigalsidase alfa every 4 weeks (E4W) for 52 weeks. Primary objective assessed safety, including number of treatment-emergent adverse events (TEAEs). Thirty patients were enrolled (24 males); 23 previously received agalsidase beta. Pegunigalsidase alfa plasma concentrations remained above the lower limit of quantification throughout the 4-week dosing interval. Thirty-three of 182 TEAEs (in 9 patients) were considered treatment-related; all were mild/moderate. No patients developed de novo anti-drug antibodies (ADAs). In the efficacy analysis (n = 29), median (inter-quartile range) eGFR change from baseline over 52 weeks was -1.9 (-5.9; 1.8) mL/min/1.73 m 2 (n = 28; males [n = 22]: -2.4 [-5.2; 3.2]; females [n = 6]: -0.7 [-9.2; 2.0]). Overall, median eGFR slope was -1.9 (-8.3; 1.9) mL/min/1.73 m 2 /year (ADA-negative [n = 20]: -1.2 [-6.4; 2.6]; ADA-positive [n = 9]: -8.4 [-11.6; -1.0]). Lyso-Gb3 concentrations were low and stable in females, with a slight increase in males (9/24 ADA-positive). The BRIGHT study results suggest that 2 mg/kg pegunigalsidase alfa E4W is tolerated well in stable adult patients with Fabry disease. Due to the low number of patients in this study, more research is needed to demonstrate the effects of pegunigalsidase alfa given E4W. Further evidence, outside of this clinical trial, should be factored in for physicians to prolong the biweekly ERT intervals to E4W. TAKE-HOME MESSAGE: Treatment with 2 mg/kg pegunigalsidase alfa every 4 weeks could offer a new treatment option for patients with Fabry disease., (© 2024 The Author(s). Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.)

Glioblastoma (GBM) is a deadly brain cancer. The prognosis of GBM patients has marginally improved over the last three decades. The response of GBMs to initial treatment is inevitably followed by relapse. Thus, there is an urgent need to identify and develop new therapeutics to target this cancer and improve both patient outcomes and long-term survival. Metabolic reprogramming is considered one of the hallmarks of cancers. However, cell-based studies fail to accurately recapitulate the in vivo tumour microenvironment that influences metabolic signalling and rewiring. Against this backdrop, we conducted global, untargeted metabolomics analysis of the G7 and R24 GBM 2D monolayers and 3D spheroid cultures under identical cell culture conditions. Our studies revealed that the levels of multiple metabolites associated with the vitamin B6 pathway were significantly altered in 3D spheroids compared to the 2D monolayer cultures. Importantly, we show that pharmacological intervention with hydralazine, a small molecule that reduces vitamin B6 levels, resulted in the cell death of 3D GBM spheroid cultures. Thus, our study shows that inhibition of the vitamin B6 pathway is a novel therapeutic strategy for the development of targeted therapies in GBMs.

A man in late adolescence of Asian descent was admitted with cardiac-sounding chest pain and a history of flu-like symptoms a week prior to presentation with negative screening for the SARS-CoV-2 virus. His ECG showed lateral T-wave changes and pre-excitation pattern suggestive of an accessory pathway. High-sensitivity troponin T peak was significantly elevated to 2550 ng/L (normal reference range 0-11). He was initially treated for a suspected perimyocarditis. Transthoracic echocardiography revealed moderate left ventricular systolic dysfunction with regional wall motion abnormalities suggestive of coronary artery disease. Cardiac magnetic resonance imaging showed subendocardial delayed gadolinium enhancement with ischaemia and viability in the left circumflex (LCx) territory. He was then sent for a CT coronary angiogram for a suspected spontaneous coronary artery dissection, and subsequently, he discussed with our team and accepted for immediate transfer. He underwent coronary angiography and intravascular ultrasound-guided percutaneous coronary intervention to his LCx artery with a drug-coated balloon. Following that, and after a discussion with the electrophysiology team, he had an attempt at ablating his accessory pathway with partial success. He was discharged home in a stable condition., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Autistic people are more likely to report gender dysphoric traits, and transgender and gender-expansive individuals frequently report higher scores on self-report measures of autistic traits. Despite the clear association between autism and gender diversity, there is a dearth of qualitative research exploring the lived experiences of autistic adults., Methods: This study contributes to the evidence base by exploring the strengths and challenges of the intersectional experiences of autism and gender diversity in adulthood. Twelve transgender/gender-expansive autistic people participated in an online semi-structured interview or an open-ended survey, and reflexive thematic analysis was used to analyze the data., Results: Three main themes were identified: (1) Navigating a gender journey, (2) The impact of social context on self, and (3) Provision of health care., Conclusion: The findings highlight the importance of acknowledging the unique experiences of being both an autistic and transgender/gender-expansive person to further understand the intersection between autism and gender diversity., (Copyright 2024, Mary Ann Liebert, Inc., publishers.)

Objectives: The last major UK survey of medical undergraduate rheumatology teaching was 25 years ago. This study aimed to describe current teaching practice, the perceptions of teachers and students and their engagement with Versus Arthritis teaching resources and future challenges and opportunities., Methods: Electronic surveys were distributed by e-mail and/or social media to relevant teachers and students identified within all 37 UK medical schools., Results: A total of 34/37 (91%) teacher and 30/37 (81%) student surveys were returned. Compared with the last survey, the proportion of schools delivering rheumatology-identifiable teaching has fallen from 100% to 86% and the mean number of teaching days from 30 to 10. Rheumatology teaching is now more dispersed throughout the curriculum. Students preferred active learning methods such as simulation and expert patient teaching, while teachers preferred small-group teaching, online learning and lectures. The Versus Arthritis resources appeared underutilized by students but were considered useful. Most students thought rheumatology careers were not promoted within their medical school., Conclusion: A decrease in dedicated rheumatology teaching time was noted since the last survey 25 years ago. Greater promotion of rheumatology as a speciality and future career is required to maintain its professional identity and prevent marginalization., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: Social welfare legal needs (matters of daily life, such as finances, housing and employment with legal rights, entitlements or protections) are prevalent towards end of life, creating significant difficulties for both patients and carers. Most people do not know where to go, although a range of services provide advice and support for addressing social welfare legal problems. Navigating this complex and fragmented system across health, social care and social welfare legal support is very challenging. Healthcare professionals are often the first contact for social welfare legal needs, although these are often overlooked and their impact on health and well-being unrecognised. Interprofessional learning can increase awareness of social welfare legal needs and build connections between service providers, offering a more holistic and cohesive multiagency response to the complex needs around end of life. The aim of the research was to co-create a robust foundation for cross-agency research investigating the impact of interprofessional learning on social welfare legal needs towards end of life in the North East England region., Objectives: Convene a research partnership group across academics, multiagency service providers and members of the public with lived experience. Consider and agree key issues for successful place-based multiagency research in this area. Co-create a complexity-appropriate research proposal with interprofessional learning as an intervention., Methods: A series of research activities was implemented to convene a multiagency partnership group and consider the key issues for successful place-based multiagency research. Data were collected from two online workshops, an optional reflective workbook, and a modified Delphi technique. Initial participants were selectively recruited from our established stakeholder and patient and public involvement groups. Increasing diversity of the partnership continued throughout the project, using contacts provided by group members. Representation of services supporting underserved groups was a priority., Results: All invited participants were recruited to the partnership, although contribution to research activities was variable. The partnership bridged knowledge gaps between services and united diverse perspectives, expertise and experience. A greater understanding of the barriers and opportunities for place-based multiagency working was generated, such as considering the importance of language in facilitating collaboration and responding to concerns around capacity. A non-hierarchical partnership was meaningful, with both personal and professional insights viewed as equally important. Facilitators to engagement with interprofessional learning were identified including the need for leadership endorsement. A non-traditional, mixed-method approach to interprofessional learning evaluation was favoured, with both qualitative and quantitative measures at three levels: patient and carer, professional learners and organisations. Important outcomes included raising awareness, connectedness and space to reflect., Limitations: The partnership group expanded throughout the course of the project. While this extended diversity, variable participation hindered depth of discussion, with participants engaging at different points and with different understanding levels of the project. Supplementary materials provided some mitigation. Capacity and funding constraints limited engagement for some participants., Conclusions: Convening a multiagency partnership generated insights into the benefits, barriers and facilitators to research co-design and potential measures of success of interprofessional learning., Future Work: Learning from this project has informed a complexity-appropriate research proposal to evaluate the impact of interprofessional learning as an intervention across different stakeholders., Funding: This article presents independent research funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme as award number NIHR135276.

Background: Clinical practice recommendations for macronutrient intake in Metabolic and Bariatric Surgery (MBS) are insufficiently grounded in the research, possibly due to a paucity of research in key areas necessary to support macronutrient recommendations. An initial scoping review, prior to any systematic review, was determined to be vital., Objectives: To identify topical areas in macronutrients and MBS with a sufficient evidence base to guide nutrition recommendations., Methods: PubMed, Cochrane, Ovid Medline, and Embase were initially searched in January 2019 (updated November 1, 2023) with terms encompassing current bariatric surgeries and macronutrients. Out of 757 records identified, 98 were included. A template was created. Five types of outcomes were identified for extraction: dietary intake, anthropometrics, adverse symptoms, health, and metabolic outcomes. All stages of screening and extraction were conducted independently by at least two authors and disagreements were resolved via team discussion. Macronutrient-related dietary treatments were classified as either innovative or standard of care. Descriptions of dietary arms were extracted in detail for a qualitatively generated typology of dietary or nutritional treatments. Heatmaps (treatments by outcomes) were produced to identify promising topics for further systematic analyses., Results: We identified protein supplementation and "food-focused" (e.g., portion-controlled meals, particular foods in the diet, etc.) topical areas in MBS nutrition care with potentially sufficient evidence to create specific MBS Macronutrients guidelines and identified topical areas with little research., Conclusions: Clinical practice regarding macronutrient intake remains guided by consensus and indirect evidence. We detail ways that leadership at the profession level may remedy this., (© 2024 The Author(s). Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

Background: Whether a conservative strategy of medical therapy alone or a strategy of medical therapy plus invasive treatment is more beneficial in older adults with non-ST-segment elevation myocardial infarction (NSTEMI) remains unclear., Methods: We conducted a prospective, multicenter, randomized trial involving patients 75 years of age or older with NSTEMI at 48 sites in the United Kingdom. The patients were assigned in a 1:1 ratio to a conservative strategy of the best available medical therapy or an invasive strategy of coronary angiography and revascularization plus the best available medical therapy. Patients who were frail or had a high burden of coexisting conditions were eligible. The primary outcome was a composite of death from cardiovascular causes (cardiovascular death) or nonfatal myocardial infarction assessed in a time-to-event analysis., Results: A total of 1518 patients underwent randomization; 753 patients were assigned to the invasive-strategy group and 765 to the conservative-strategy group. The mean age of the patients was 82 years, 45% were women, and 32% were frail. A primary-outcome event occurred in 193 patients (25.6%) in the invasive-strategy group and 201 patients (26.3%) in the conservative-strategy group (hazard ratio, 0.94; 95% confidence interval [CI], 0.77 to 1.14; P = 0.53) over a median follow-up of 4.1 years. Cardiovascular death occurred in 15.8% of the patients in the invasive-strategy group and 14.2% of the patients in the conservative-strategy group (hazard ratio, 1.11; 95% CI, 0.86 to 1.44). Nonfatal myocardial infarction occurred in 11.7% in the invasive-strategy group and 15.0% in the conservative-strategy group (hazard ratio, 0.75; 95% CI, 0.57 to 0.99). Procedural complications occurred in less than 1% of the patients., Conclusions: In older adults with NSTEMI, an invasive strategy did not result in a significantly lower risk of cardiovascular death or nonfatal myocardial infarction (the composite primary outcome) than a conservative strategy over a median follow-up of 4.1 years. (Funded by the British Heart Foundation; BHF SENIOR-RITA ISRCTN Registry number, ISRCTN11343602.)., (Copyright © 2024 Massachusetts Medical Society.)

English anatomical terminology has evolved over the long history of anatomical practice, with major influences from ancient Greek, classical Latin, Arabic, and post-classical Latin. Beginning in the nineteenth century, there have been various attempts to standardise and rationalise anatomical language, beginning in 1887, and culminating in the publication in 2019 of the second edition of the Terminologia Anatomica. This paper presents a brief historical overview of the development of anatomical terminology and usage in English, followed by a summary of the results of an anonymised survey of current practices that was sent out by email to anatomy educators at 45 medical schools in the United Kingdom. This is followed by personal reflections by six senior academics and/or clinicians, reviewing their extensive experience of teaching, researching, and communicating the language of anatomy within United Kingdom medical and clinical institutions., (© 2024. The Author(s), under exclusive licence to Japanese Association of Anatomists.)

Intervention by members of the public during an out of hospital cardiac arrest (OHAC) including resuscitation attempts and accessible automated external defibrillator (AED) has been shown to improve survival. This study aimed to investigate the OHCA and AED knowledge and confidence, and barriers to intervention, of the public of North East England, UK. This study used a face-to-face cross-sectional survey on a public high street in Newcastle, UK. Participants were asked unprompted to explain what they would do when faced with an OHCA collapse. Chi-Square analysis was used to test the association of the independent variables sex and first aid trained on the participants' responses. Of the 421 participants recruited to our study, 82.9% (n = 349) reported that they would know what to do during an OHCA collapse. The most frequent OHCA action mentioned was call 999 (64.1%, n = 270/421) and 58.2% (n = 245/421) of participants reported that they would commence CPR. However, only 14.3% (n = 60/421) of participants spontaneously mentioned that they would locate an AED, while only 4.5% (n = 19/421) recounted that they would apply the AED. Just over half of participants (50.8%, n = 214/421) were first aid trained, with statistically more females (57.3%, n = 126/220) than males (43.9%,  n = 87/198) being first aiders (p = 0.01 χ 2  = 7.41). Most participants (80.3%, n = 338/421) knew what an AED was, and 34.7% (n = 326/421) reported that they knew how to use one, however, only 11.9% (n = 50/421) mentioned that they would actually shock a patient. Being first aid trained increased the likelihood of freely recounting actions for OHCA and AED intervention. The most common barrier to helping during an OHCA was lack of knowledge (29.9%, n = 126/421). Although most participants reported they would know what to do during an OHCA and had knowledge of an AED, low numbers of participants spontaneously mentioned specific OHCA and AED actions. Improving public knowledge would help improve the public's confidence of intervening during an OHCA and may improve OHCA survival., (© 2024. The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI).)

Background & Aims: Postcolonoscopy colorectal cancer incidence and mortality rates are higher for endoscopists with low polyp detection rates. Using the UK's National Endoscopy Database (NED), which automatically captures real-time data, we assessed if providing feedback of case-mix-adjusted mean number of polyps (aMNP), as a key performance indicator, improved endoscopists' performance. Feedback was delivered via a theory-informed, evidence-based audit and feedback intervention., Methods: This multicenter, prospective, NED Automated Performance Reports to Improve Quality Outcomes Trial randomized National Health Service endoscopy centers to intervention or control. Intervention-arm endoscopists were e-mailed tailored monthly reports automatically generated within NED, informed by qualitative interviews and behavior change theory. The primary outcome was endoscopists' aMNP during the 9-month intervention., Results: From November 2020 to July 2021, 541 endoscopists across 36 centers (19 intervention; 17 control) performed 54,770 procedures during the intervention, and 15,960 procedures during the 3-month postintervention period. Comparing the intervention arm with the control arm, endoscopists during the intervention period: aMNP was nonsignificantly higher (7%; 95% CI, -1% to 14%; P = .08). The unadjusted MNP (10%; 95% CI, 1%-20%) and polyp detection rate (10%; 95% CI, 4%-16%) were significantly higher. Differences were not maintained in the postintervention period. In the intervention arm, endoscopists accessing NED Automated Performance Reports to Improve Quality Outcomes Trial webpages had a higher aMNP than those who did not (aMNP, 118 vs 102; P = .03)., Conclusions: Although our automated feedback intervention did not increase aMNP significantly in the intervention period, MNP and polyp detection rate did improve significantly. Engaged endoscopists benefited most and improvements were not maintained postintervention; future work should address engagement in feedback and consider the effectiveness of continuous feedback., Clinical Trials Registry:  www.isrctn.org ISRCTN11126923 ., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Latin America faces a significant public health challenge due to the high prevalence of obesity and its associated diseases. Metabolic and bariatric surgery is effective and safe to treat obesity when other treatments fail; however, its implementation in Latin America remains unsatisfactory. This review explores the current status, challenges, and innovations of metabolic and bariatric surgery in Latin America. We searched peer-reviewed journals in English and Spanish for relevant articles published between 1998 and 2023. We found that more than 20% of the Latin American population is affected by obesity. Unfortunately, only a limited number of patients have access to metabolic and bariatric surgery due to high cost, limited availability, and shortage of specialists. The review found that ongoing clinical trials are being conducted in Brazil, Mexico, Chile, and Venezuela, indicating some regional progress. However, published studies remain low in number compared with other regions. Furthermore, we summarized the clinical outcomes, risks, and perioperative assessments associated with metabolic and bariatric surgery. We discussed potential strategies to enhance the availability and affordability of this intervention. This review emphasizes the significance of metabolic and bariatric surgery in addressing the obesity pandemic, specifically for Latin America, and proposes directions for future research and innovation., (© 2024 World Obesity Federation.)

Helicobacter pylori ( H. pylori ) infection is a significant global health concern, affecting approximately 50% of the world's population and leading to gastric ulcers, gastritis, and gastric cancer. The increase in antibiotic resistance has compromised the efficacy of existing therapeutic regimens, necessitating novel approaches for effective eradication. This study aimed to develop a targeted liposomal drug delivery system incorporating furazolidone and N-acetylcysteine (NAC) to enhance mucopenetration and improve Helicobacter pylori eradication. Liposomes were formulated with furazolidone, NAC, and Pluronic F-127 using a modified reverse-phase evaporation technique. The formulations were categorized based on charge as neutral, negative, and positive and tested for mucopenetration using a modified silicon tube method with coumarin-6 as a fluorescent marker. The encapsulation efficiency and particle size were analyzed using HPLC and an Izon q-nano particle size analyzer. The results indicated that charged liposomes showed a higher encapsulation efficiency than neutral liposomes with Pluronic F-127. Notably, combining furazolidone with 1% NAC achieved complete eradication of H. pylori in 2.5 h, compared to six hours without NAC. The findings of this study suggest that incorporating NAC and Pluronic F-127 into liposomal formulations significantly enhances mucopenetration and antimicrobial efficacy.

Background: Dietary marine omega-3 fatty acids and phospholipids have individually shown favorable effects on skin barrier function. Krill oil offers a combination of omega-3 in phospholipid form which might enhance the efficacy in supporting skin health., Aims: The aim was to investigate the impact of two different doses of krill oil on skin transepidermal water loss (TEWL) in healthy adults. Secondary outcomes were skin hydration, elasticity and the omega-3 index., Methods: Two randomized, double-blind, placebo-controlled, pilot studies were conducted in healthy adults with a baseline TEWL of >10 and ≤24.9 g/m 2 /h. In study 1, 51 participants consumed 1 g of krill oil or placebo daily. In study 2, 50 participants consumed 2 g of krill oil or placebo daily. The outcomes were assessed at baseline, 6 and 12 weeks., Results: The krill oil supplemented groups significantly increased their omega-3 index versus placebo in both studies. Furthermore, the krill oil groups in both studies showed statistically significant beneficial reductions in TEWL (from 14.47 ± 3.65 to 13.83 ± 3.78 in study 1 and from 14.25 ± 3.21 to 13.02 ± 2.76 in study 2) and increases in hydration and elasticity when compared to placebo. There were significant linear relationships between changes in the omega-3 index and changes in TEWL, hydration and elasticity in both studies., Conclusions: Daily oral supplementation with 1 and 2 g of krill oil showed significant and dose-dependent improvements in skin TEWL, hydration, and elasticity compared to placebo that correlated with changes in the omega-3 index., (© 2024 Aker BioMarine Human Ingredients AS and The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Kink, often referred to as BDSM, is an important aspect of a sizable minority's sexual desires, practices, and personal relationships, yet there are few ways to assess kink engagement in a holistic manner. This study aimed to develop the Kink Orientation Scale (KOS), a novel short tool for measuring different aspects of kink sexuality. In phase one, 27 items were created and included in the initial scale based on a literature review and focus groups with kinky and non-kinky individuals. In phase two, the KOS was administered to 200 university students. Exploratory Factor Analyses (EFA) were used to determine the factor structure and dimensionality of the KOS, and we retained 18 items in the scale and identified five factors. In phase three, the 18 item KOS was administered to a kink sample of 1025 participants as a form of validation. Confirmatory Factor Analyses also identified five factors with a strong overlap to the EFA. The five factors were: kink identity; kink community; kink paraphernalia; kink practices; and sexual communication. The kink sample also provided higher scores on the KOS compared with the non-kink sample. This study shows the potential utility of the KOS in measuring kink engagement holistically.

Screening tools can help with the identification of intellectual disability, but little is known about who uses them. This study analysed anonymous information from 2691 users of an evidence-based, online, intellectual disability screening questionnaire for children and adolescents (CAIDS-Q) to explore the characteristics of the users and of those being screened. The users were split almost equally between parents/family members (48.6%) and professionals (49.9%), with the majority (63.8%) of the latter group being health staff. Significant differences in the characteristics of the children being screened were found, according to whether the user was a parent/family member or a professional, with the overall pattern suggesting that professionals screened children with greater complexity of needs, but about whom less was known. The screened children had a range of areas of difficulties that are common to those with intellectual disability. Implications for practice are discussed., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: The first author was a co-developer of the CAIDS-Q and receives a small payment for its use. The second and last authors are related to her.

Lay Abstract: Lots of people seek an autism diagnosis as an adult, and they often say that being diagnosed can be positively life-changing, but the experience of getting a diagnosis can be difficult. We often do not hear the views of people currently looking for a diagnosis, or talk to them about how diagnosis relates to their identity. In our study, we looked at experiences of people currently seeking an autism diagnosis in the UK. We used participatory methods, where six people seeking diagnosis were included as collaborators in the research. They took part in four different sessions, where they helped to shape the research, took part in interviews about their experiences and helped to analyse the patterns in all the interviews. We also used something called photovoice during the interviews, where they could use photos to show how they felt about navigating a diagnosis. We identified four common themes: (1) everyone had experienced some form of crisis before seeking diagnosis; (2) when they realised they were autistic, they felt seen; (3) the diagnostic process and criteria were not working, and they felt judged by clinicians and (4) there was limited support available after diagnosis. In another session, we identified actions that need to be taken which have implications for policy and practice, including improving the diagnostic process and criteria with autistic people, autistic people being listened to more by people like general practitioners and clinicians and diagnosis services needing to be more flexible and appreciate different aspects of someone's identity and neurodivergence., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Ecological risk management has emerged as a critical research and policy development area in energy and environmental economics. Sustained ecology is crucial for the standard of living and food security. As the adverse impacts of environmental degradation and climate change become increasingly apparent it is imperative to understand ecological risk and its interconnectedness with environmental pressure, clean energy, economic activity, globalization, and green technology. Ecological risk is assessed using the environmental performance index which is a holistic indicator of climate change, environmental pressures and human actions in which most of these indicators have spatial effects. This paper explores the multifaceted relationship between identified anthropogenic critical factors and their role in effectively managing ecological risk globally. This study has developed the second-generation dynamic panel quantile regression considering spatial effects of economic activities on ecology across borders of 55 countries between 1995 and 2022. This innovative hybrid estimation scheme that integrated theoretical and econometric aspects makes the model robust to major regression issues. Several implications ranked in decreasing order of its effectiveness are reducing environmental pressure, expediting energy transition, and embracing economic integration while there is a need to work on rejuvenating green technology and green growth., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: There is little international data on morbidity and mortality of surgery for perforated peptic ulcer (PPU). This study aimed to understand the global 30-day morbidity and mortality of patients undergoing surgery for PPU and to identify variables associated with these., Method: We performed an international study of adults (≥ 18 years) who underwent surgery for PPU from 1st January 2022 to 30th June 2022. Patients who were treated conservatively or had an underlying gastric cancer were excluded. Patients were divided into subgroups according to age (≤ 50 and > 50 years) and time from onset of symptoms to hospital presentation (≤ 24 and > 24 h). Univariate and Multivariate analyses were carried out to identify factors associated with higher 30-day morbidity and mortality., Results:  1874 patients from 159 centres across 52 countries were included. 78.3% (n = 1467) of the patients were males and the median (IQR) age was 49 years (25). Thirty-day morbidity and mortality were 48.5% (n = 910) and 9.3% (n = 174) respectively. Median (IQR) hospital stay was 7 (5) days. Open surgery was performed in 80% (n = 1505) of the cohort. Age > 50 years [(OR = 1.7, 95% CI 1.4-2), (OR = 4.7, 95% CI 3.1-7.6)], female gender [(OR = 1.8, 95% CI 1.4-2.3), (OR = 1.9, 95% CI 1.3-2.9)], shock on admission [(OR = 2.1, 95% CI 1.7-2.7), (OR = 4.8, 95% CI 3.2-7.1)], and acute kidney injury [(OR = 2.5, 95% CI 1.9-3.2), (OR = 3.9), 95% CI 2.7-5.6)] were associated with both 30-day morbidity and mortality. Delayed presentation was associated with 30-day morbidity [OR = 1.3, 95% CI 1.1-1.6], but not mortality., Conclusions: This study showed that surgery for PPU was associated with high 30-day morbidity and mortality rate. Age, female gender, and signs of shock at presentation were associated with both 30-day morbidity and mortality., (© 2024. Crown.)

GPS speed thresholds in women's rugby union are usually based on data derived from the men's game. However, evidence suggests the maximum speeds achieved by female players are 2-8 km.h -1 slower and the volume of high-intensity running (HIR) in women's rugby may be underestimated. The aim of the study was to examine the effect of adjusting absolute thresholds on the volume of high-intensity locomotion. GPS units recorded movement data from 58 players across 18 English Premier15 s matches. Distance in HIR and sprint (Spr) zones were calculated using male-derived criteria: Abs Male (HIR >18 km.h -1 ; Spr ≥21 km.h -1 ). Two alternative thresholds were compared: Abs FVmax (HIR >16 km.h -1 ; Spr ≥19 km.h -1 ); Abs Female (HIR >14 km.h -1 ; Spr ≥17 km.h -1 ). Data were analysed using one-way ANOVA and effect sizes to determine differences in distances between thresholds. Abs Male HIR and Spr distances were 63 ± 71 m and 30 ± 53 m. Significantly greater distances at higher-intensity speeds were observed with female-adjusted thresholds. Abs FVmax : HIR: 139 ± 116 m (p = 0.01, ES 0.80); Spr: 60 ± 90 m (p = 0.131, ES 0.41) and Abs Female : HIR: 239 ± 157 m (p < 0.01, ES 1.45); Spr: 137 ± 152 m (p < 0.01, ES 0.94). 24 players (41%) achieved speeds greater than the 21 km·h -1 threshold with the male-derived thresholds. At Abs FVmax threshold this increased to 44 (76%) and 100% at the Abs Female threshold. Existing male-derived thresholds appear to underestimate high-intensity locomotion of female players. With adjusted thresholds, specifically the Abs Female , the proportional volume of high-intensity activity in the women's game (8.2% total distance) aligns more closely to that observed during men's match-play., (© 2024 The Author(s). European Journal of Sport Science published by Wiley‐VCH GmbH on behalf of European College of Sport Science.)