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The Role of Resistance Exercise-Induced Local Metabolic Stress in Mediating Systemic Health and Functional Adaptations: Could Condensed Training Volume Unlock Greater Benefits Beyond Time Efficiency?
Get PDFThe majority of “specialised” exercise configurations (e.g., supersets, drop sets, blood flow restriction) are being assessed as “shortcuts” to hypertrophy and strength improvements. However, these advanced training techniques may also offer significant benefits for systemic health and functional outcomes across recreational and clinical populations via locally induced metabolic responses. Stress-regulating mechanisms are known to enhance the body’s resilience by facilitating allostasis, the process of coordinating adaptive processes in reaction to stressors such as physical training. Yet, the role of the local metabolic stress provoked by resistance exercise has not gained much research attention despite its wide potential. Positive effects are not only linked to improved muscular endurance, hypertrophy and strength via primary and secondary mechanisms, but also to the release of myokines, hormones, microRNAs, immune factors, inflammatory substances and other endocrine molecules that initiate numerous health-promoting modifications on a systemic level. Resistance exercise strategies that maximise the local accumulation of metabolites are not well defined, although high volume, close proximity to failure and shorter rests seem to be a necessity. Additionally, blood flow restriction training provides a potent alternative for inducing local acidosis, thereby triggering several pathways associated with improved immunity and physical function even in remote muscle tissues. Future research is warranted to further explore advanced resistance training techniques, as these approaches may offer comparable benefits for physical and mental health to those seen with other forms of exercise such as high-intensity interval training and heavy resistance training
Metformin for patients with metastatic prostate cancer starting androgen deprivation therapy: a randomised phase 3 trial of the STAMPEDE platform protocol
Get PDFBackground
Metformin is a widely used anti-diabetic drug. Several studies have suggested that metformin has anticancer activity in some malignancies, including prostate cancer. Metformin might also mitigate the adverse metabolic effects of androgen-deprivation therapy (ADT). We hypothesised that metformin might improve survival in patients with metastatic hormone-sensitive prostate cancer and reduce metabolic complications associated with ADT.
Methods
The STAMPEDE multi-arm, multi-stage, randomised phase 3 trial recruited patients with high-risk locally advanced or metastatic adenocarcinoma of the prostate staged by conventional imaging with isotope bone and CT scanning. This publication reports findings for the most recent STAMPEDE research question, testing the addition of metformin to standard of care for non-diabetic (glycated haemoglobin [HbA1c] <48 mmol/mol [equivalent to <6·5%]) patients with metastatic disease with adequate renal function (glomerular filtration rate ≥45 ml/min/1·73 m2) and WHO performance status 0–2. This trial recruited from 112 hospitals in the UK and Switzerland to the STAMPEDE protocol. Patients were randomly allocated (1:1) to standard of care or standard of care plus metformin 850 mg twice daily. Random assignment was by telephone using minimisation with a random element of 20% (developed and maintained by the MRC Clinical Trials Unit at UCL), stratified for randomising hospital, age (<70 years vs ≥70 years), WHO performance status (0 vs 1 or 2), type of ADT, regular long-term use of aspirin or non-steroidal anti-inflammatory drugs (NSAIDs; yes vs no), pelvic nodal status (positive vs negative), planned radiotherapy (yes vs no), and planned docetaxel or androgen receptor pathway inhibitor (ARPI) use (docetaxel vs abiraterone, enzalutamide, or apalutamide vs none). Standard of care comprised ADT with or without radiotherapy and with or without docetaxel or ARPI. The primary outcome measure was overall survival, defined as the time to death from any cause, assessed in the intention-to-treat population. Safety was assessed in patients who started treatment. The trial is registered with ClinicalTrials.gov, NCT00268476 and ISRCTN, ISRCTN78818544.
Findings
Between Sep 5, 2016, and Mar 31, 2023, 1874 patients with metastatic disease were randomly allocated to standard of care (n=938) or standard of care plus metformin (n=936). The median patient age was 69 years (IQR 63-73) and the median PSA was 84 ng/mL (24–352). 1758 (94%) of 1874 patients were newly diagnosed with metastatic disease and 116 (6%) were diagnosed with metachronous relapsing disease. 1543 (82%) of 1874 patients received ADT plus docetaxel and 52 (3%) received abiraterone, enzalutamide, or apalutamide. The median time to most recent case report form follow-up was 60 months (IQR 49–72). 473 deaths were reported in the standard of care group; median survival was 61·8 months (IQR 29·7 to not reached). There were 453 deaths in the metformin group; median survival was 67·4 months (32·5 to not reached; HR 0·91, 95% CI 0·80–1·03; p=0·15). Grade 3 or worse adverse events were reported in 487 (52%) of 938 patients in the standard of care group and 523 (57%) of 921 patients in the standard of care plus metformin group. 61 (7%) patients in the standard of care group and 84 (9%) patients in the standard of care plus metformin group reported at least one grade 3 or worse gastrointestinal adverse event; all other body systems showed no difference in grade 3 adverse events. There were six drug-related deaths in the standard of care group and one in the standard of care plus metformin group.
Interpretation
We did not find significant evidence of an overall survival benefit of adding metformin to standard of care in the overall population of patients with metastatic hormone-sensitive prostate cancer. The side-effect profile of metformin was as expected and consisted mainly of diarrhoea. Adverse metabolic side-effects of ADT were significantly reduced in the metformin group compared with the standard of care group
P79 Inflammatory bowel disease associated colorectal cancer: chemopreventive effects of 5-ASAs, immunomodulators, and biologics
No full textIntroduction The incidence and mortality of colorectal cancer (CRC) remains elevated in the inflammatory bowel disease (IBD) population. We aimed to examine the association between biologics, 5-aminosalicylates (5-ASAs), and immunomodulators, with the risk of CRC and/or dysplasia in patients with IBD in a contemporaneous systematic review and meta-analysis.
Methods We searched Web of Science, PubMed, MEDLINE, and EMBASE from inception to 15th June 2024 for all studies assessing the impact of biologics, 5-ASAs and immunomodulators on the occurrence of CRC or dysplasia in adults (≥16 years) with IBD. Data were pooled using a random effects model generating relative risk (RR) estimates with 95% confidence intervals (CIs). (PROSPERO registration number: CRD42024559501).
Results Eleven studies containing 8,721 cases of CRC in 447,637 patients with IBD, 32 studies containing 9,847 cases of CRC among 462,408 patients with IBD, and 35 studies containing 10,794 cases of CRC in 544,380 patients with IBD were analysed for biologics, 5-ASAs, and immunomodulators, respectively. Biologic therapies (RR 0.74; 95% CI 0.64-0.85, I2 =56.8%) and 5-ASAs (RR 0.78; 95% CI 0.70-0.86, I2 =52.1%) were associated with a reduced risk of CRC and/or dysplasia in patients with IBD. Immunomodulators were not associated with a reduced risk (RR 0.91; 95% CI 0.82-1.02, I2 =82.7%).
Conclusions The use of biologics and 5-ASAs, but not immunomodulators, is associated with a reduced risk of CRC and/or dysplasia in patients with IBD
What UK career guidance counsellors in high schools and further education think about nursing as a career for men
Get PDFAim: To identify why men in Western societies consistently make up between 9-11% of the nursing workforce and viable solutions to this Global recruitment issue.
Methods: A review of the literature was undertaken using Cinhal Ultimate, Embase and Nursing and Allied Health search engine databases. n=490 studies were retrieved, reduced to n=65 with a final n=21 appraised.
Findings: The identified themes were; promoting nursing in secondary school, and for career counsellors to suggest nursing as a career choice to adolescent boys.
Discussion: Significant others such as family members, and friends influence on adolescent boys had a positive impact on the choice of career, and exposure as a patient or visitor to what nurses do, and outreach work in schools help to support an interest in nursing as a career. Adult partners were found to be instrumental in supporting a change of career later in life. The issue of job security, promotional prospects, and leaning towards more technical roles in nursing were motivational themes when choosing a career path, with friendliness, feeling included, and low pay, considered key factors. Lastly, the specific role of career guidance counsellors (CGS’s) was found to be instrumental in widening the choices for a career in nursing, with differences in attitudes and expectations for boys seen in private and public education.
Conclusion: CGC’s can play a vital role in informing their male and female students about career opportunities in the caring profession although may need further support from industry experts. In addition, schools and colleges should be following benchmarks for good career guidance
Specialist domestic abuse training for emergency department clinical staff: A review of the literature
Get PDFAim: Emergency departments are often the first point of contact for women suffering from domestic abuse and identifying how healthcare staff can support women is important to tackle missed opportunities for timely intervention.
Method: A review of research studies was undertaken between 2012 and 2024 using electronic databases AMED, CINAHL Ultimate, MEDLINE, EBSCO, and the RCNi. The search words “emergency department, ED, accident and emergency, A & E, domestic abuse, domestic violence, intimate partner violence, family violence, staff- training education, development, learning” were used and retrieved n=93, reduced n=18, and finally n=7.
Findings: The findings identify a training and role-specific issue related to emergency department nursing, and the need to have a supportive environment for positive action to be taken on behalf of the victim and their families. Four themes were identified; “don’t ask,” “stereotyping,” moral distress” and “systemic support.” In ‘don’t ask’ the thread of conscious incompetence ensures staff reluctance to talk to women in case it opens a ‘can of worms.’
Discussion: The difficulties experienced by emergency nurses were compounded by staff being unaware of their departments policy on dealing with domestic abuse. Contrary to WHO recommendations, the evidence identified domestic abuse screening in most emergency departments happens on an ad-hoc basis and is subject to the experience and confidence of the individual clinician.
Conclusion: Training is required to myth bust the factors related to domestic abuse, yet training is not enough, there needs to be a shift in attitudes toward domestic abuse, and in an institutional context, staff should feel supported and empowered to respond to women appropriately
A Deep Q-Network Framework for Joint Optimization of EV Charging Station Placement and Vehicle Routing
Get PDFThe rapid adoption of electric vehicles (EVs) presents new challenges in designing efficient charging infrastructure and route planning mechanisms to ensure sustainable urban mobility. This paper introduces a novel two-stage optimization framework that leverages Deep Q-Networks (DQNs) for the intelligent placement of EV charging stations and real-time routing of vehicles. In the first stage, a DQN placement model learns to identify optimal charging station locations within a graph-represented road network, minimizing the expected energy consumption of future routing. In the second stage, a separate DQN routing model is trained to approximate cost-to-go functions and guide vehicles to the nearest stations efficiently. The models are evaluated against traditional methods, including Q-Learning, neural networks (NN), deep graph neural networks (DGNN), and Random Walk baselines. Simulation results across diverse network topologies demonstrate that our DQN approach consistently outperforms baselines in terms of average energy
consumption, travel time, and route success ratio. Specifically, the DQN placement strategy achieved the lowest average energy consumption of 1.2387 kWh and the most spatially equitable configuration (average distance: 6.34 km), while the DQN routing model recorded the best performance with 1.2587 kWh average energy, 1.98 hops, and a 96.67% success rate. These findings highlight the effectiveness of deep reinforcement learning in enhancing the scalability, reliability, and energy efficiency of EV infrastructure planning
Tourism and uncertainty: a machine learning approach
Get PDFIn this paper, we attempt to create a unique forecasting model to forecast out-of-sample the tourism demand in 24 European Union countries. The initial dataset included 34 relevant variables of annual frequency that span the period from 2010 to 2020 for 40 countries. A data prefiltering process resulted in a final set of 17 relevant variables for 24 countries. Additionally, in the effort to investigate the impact of uncertainty on international tourism, apart from the traditional factors that affect tourism, we also include variables that measure various forms of uncertainty: we use the World Pandemic Uncertainty (WPU) Index, the Global CBOE Volatility Index, the Political Globalisation Index, the Economic Globalisation Index, and the Political Stability Index. In the empirical part of our research, we employ and compare in terms of their forecasting accuracy a set of six state-of-the-art machine learning algorithms, the Support Vector Regression with both a linear and an RBF kernel, the Random Forests, the Decision Trees, the KNN, and gradient-boosting trees. The results show that the Gradient-Boosting Trees algorithm outperforms the other five models providing the most accurate forecasts with a MAPE of 0.10% and 1.36% in the training and the out-of-sample tests, respectively
Co-creating cultural narratives. TikTok’s role in enhancing museum engagement
No full textPurpose
This study aims to explore the crucial role of TikTok in enhancing museum visibility and digital engagement across social media brand communities. Specifically, the authors investigate social media users’ and creators’ mechanisms in driving the dissemination of museum-related content. We identify key dimensions of co-creation within the #museumtok landscape, extending the understanding of social media contribution to value co-creation in the cultural industry.
Design/methodology/approach
A qualitative approach based on mixed methods is used. In Study 1, content and thematic analysis are performed using NVivo 14 on nine TikTok videos, analysing 9,223 user comments to reveal recurring themes. In Study 2, sentiment analysis is conducted on Python’s Natural Language Toolkit and Vader Lexicon. Finally, engagement scores are calculated to assess user involvement.
Findings
We develop two critical dimensions of the digital museum experience: MuseumCriticism and MuseumStorytelling. These themes reflect a fundamental shift in museums’ role from mere exhibition spaces to vehicles for digital storytelling and ethical debates. TikTok enables social conversations, where content creators influence museums’ digital perceptions. Sentiment analysis shows a predominance of positive sentiments. It sheds light on the proactive role of content creators in enhancing the museum’s digital visibility. However, criticism-focused videos elicit negative sentiments, indicating a need for moderation when addressing ethical issues.
Originality/value
The study enhances the understanding of social media’s role in cultural heritage communication, offering managerial insights for leveraging digital platforms to engage younger audiences effectively. By outlining five distinct subdimensions of the phenomenon, the authors provide actionable strategies to build stronger connections with younger demographics
Changing Cultural Landscapes of South Korea
No full textThis book provides a comprehensive exploration of the profound transformations in the cultural and physical landscapes of South Korea, with an interdisciplinary approach that draws from anthropology, sociology, and human geography. The authors delve into the dynamic interplay between tradition and modernity in a nation that has experienced rapid development, technological innovation, and significant socio-cultural changes.
With contributions from experts across various fields, this book examines how South Korea’s distinctive path of modernisation is reshaping both the tangible and intangible aspects of its society. Organised around four key themes—Gender and the Media Landscape, Religion and Social Movements, the Ethno-racial Landscape, and the Traditional Landscape—it presents diverse perspectives on the interconnected forces driving rapid societal change. Together, these insights offer a nuanced understanding of one of the world’s most dynamic societies. This book is an essential resource for scholars, students, and practitioners in South Korean and East Asian studies, as well as the broader disciplines of cultural geography, anthropology, and sociology
SLICES-RI Pre-Operation Methodology and Services
No full textSLICES-RI is being developed as a scientific instrument, following established methodologies and best practices from the scientific community. This approach is increasingly essential to address the accelerating pace of data-driven research, which continuously generates a deluge of publications. The core mission of a scientific instrument is to provide a standardized and trusted reference, enabling direct performance comparisons of algorithms and ensuring reproducibility — thereby simplifying and strengthening the peer review process. To meet these goals, SLICES-RI adopts an intent-based design and generates tailored Blueprints for specific scientific questions. While it does not aim to be exhaustive, this approach significantly reduces the complexity involved in designing and executing experiments. In this presentation, we share the current deployment status of SLICES-RI as it entered its pre-operational phase. We illustrate its capabilities through the Post-5G and Federated Learning Blueprints. Additionally, we highlight MRS/DMI, a key feature of SLICES-RI, which offers an advanced data management framework aligned with the FAIR principles and fully integrated into the experimental workflow