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Design and rationale of aspirin versus aspirin and fondaparinux prior to early invasive strategy in patients with NSTEMI:The FOXY trial
No full textBackground: Current guidelines recommend a combination therapy with aspirin and a parenteral anticoagulant in patients with non-ST-elevation myocardial infarction (NSTEMI) prior to invasive assessment. However, these recommendations are based on clinical trials conducted at a time when NSTEMI patients were not routinely assessed invasively. Today, nearly all NSTEMI patients in Denmark undergo coronary angiography within 72 hours, and the necessity of routine anticoagulation remains uncertain. The FOXY trial aims to assess whether aspirin alone is noninferior to a combination therapy with aspirin and fondaparinux in preventing death, recurrent myocardial infarction, and refractory ischemia while lowering the risk of bleeding. Trial Design: The FOXY trial is a multicenter, open-label, noninferiority, randomized controlled trial enrolling 5,076 patients with NSTEMI. Participants will be randomized 1:1 to receive either aspirin alone or aspirin plus fondaparinux before invasive evaluation. The primary endpoint is a composite of 30-day mortality, recurrent MI, and refractory ischemia. Secondary outcomes include long-term ischemic events, cerebrovascular accidents, left ventricular function, hospital length of stay, and major bleeding. The study will be conducted across multiple cardiology centers, with the first patients enrolled in spring 2025. Conclusion and Perspective: The FOXY trial is the first study to investigate parenteral anticoagulant use in NSTEMI patients undergoing routine invasive management. By comparing aspirin alone to combination therapy, the study seeks to challenge current guideline recommendations and potentially simplify NSTEMI treatment. If noninferiority is demonstrated, the trial may support a shift toward a safer and more cost-effective management of NSTEMI patients. This could lead to a revision of clinical guidelines, minimizing bleeding risk, improving patient safety, and reducing healthcare costs. Trial registration: EU Trial Number: 2024-517229-18-00; ClinicalTrials.gov identifier: NCT06710184.</p
Electrochemical Energy Conversion Electrode Component and Process Multi-Scale Imaging
No full textBrintproduktion ved hjælp af protonudvekslingsmembran-vandelektrolysatorer (PEMWE) er en af de grønne teknologier, der imødekommer den stadigt stigende efterspørgsel efter energilagringssystemer. Disse energianordningers funktionalitet er baseret på vandspaltningsprocessen, der udnytter elektricitet fra elnettet, herunder vedvarende energikilder. Fordelen ved at bruge PEMWE er dens kompatibilitet medvedvarende energikilders intermitterende karakter på grund af hurtig dynamiskrespons samt dens høje ydeevne, mobilitet og sikre drift. Der er dog nogle udfordringer forbundet med at indføre PEMWE som en passende konkurrent til fossile elektrolysemetoder. I dette arbejde blev de vigtigste faktorer, der påvirker PEMWE's samlede ydeevne og holdbarhed, undersøgt ved hjælp af avancerede metoder, og der blev foreslået mulige løsninger i overensstemmelse hermed. Da bobledækning af katalytisk aktive steder er en af de primære flaskehalse i PEMWE, fokuserede den indledende forskning i dette arbejde på at forstå og foreslånye tilgange til at afbøde denne udfordring. Resultaterne viste, at kombinationen af metoder til fjernelse af bobler er afgørende for at udnytte det fulde potentiale af den elektrokatalysator, der anvendes i PEMWE. Derefter blev det andet mål for dette arbejde at finde egnede, billige keramiske alternativer til Pt/C-elektrokatalysatorer med fokus på at forbedre effektiviteten og samtidig tilbyde en enkel metode til relevante industrier. Som det tredje mål i dette ph.d.-arbejde kunne implementering af operando polariseret neutronbilleddannelse og neutronradiografi give os værdifuld indsigt i den midlertidige passivering af det Ti-baserede porøse transportlag (PTL) inde i en kørende PEMWE, hvilket baner vejen for forståelsen af dette komplicerede problem i PEMWE. Desuden er den kinetiske og transportmæssige betragtning af isotopeffekter i PEMWE til neutronundersøgelser et kritisk spørgsmål, som blev undersøgt grundigt som vores fjerde forskningsemne ved hjælp af flere operando teknikker, hvilket fremhævede forskelle i ydeevne og holdbarhed for disse enheder. Endelig var Ti-passiveringsproblemet i PEMWE beregnet til at håndtere en ny trinvisoptimering af PTL-platinering. Ved hjælp af den foreslåede elektrokemiske metodekunne yderligere forbedring af PTL målrettes mod højtydende, mere holdbare PEMWE.Hydrogen production using proton exchange membrane water electrolyzers (PEMWEs) is one of the green technologies to respond to the ever-growing demandfor energy storage systems. The functionality of these energy devices relies on thewater-splitting process, which utilizes electricity from the grid, including renewable sources. The advantage of using PEMWE is its compatibility with the intermittent nature of renewables due to rapid dynamic response, as well as its high performance, mobility, and safe operation. There are some challenges, however, to introduce PEMWE as a suitable competitor to fossil-based electrolysis methods. In the present work, major contributing issues affecting overall PEMWE performance and durability were investigated using state-of-the-art methods, and possible solutions were provided accordingly. As bubble coverage of catalytically active sites is one of the primary bottlenecks in PEMWE, the initial research in this work focused on understanding and proposing new approaches to mitigate this challenge. The results demonstrated that combining bubble removal methods is pivotal in accessing the full potential of the electrocatalyst used in PEMWEs. Afterwards, finding suitable, low-cost ceramicbased alternatives for Pt/C electrocatalysts was pursued as the second objective of this work, focusing on improving efficiency while offering a facile method for relevant industries.As the third objective in this PhD work, implementing operando polarized neutron imaging and neutron radiography could provide us with valuable insights regarding the temporary passivation of Ti-based porous transport layer (PTL) inside running PEMWE, paving the path for understanding this intricate issue in PEMWE. Furthermore, the kinetic and transport consideration of isotope effects in PEMWE for neutron studies is a critical matter that was investigated thoroughly as our fourth research by several operando techniques, highlighting performance and durability differences for these devices. Lastly, the Ti passivation issue in PEMWE was intended to deal with a novel step-by-step optimization of PTL platinization. Using the suggested electrochemical-based method, further advancement of PTL could be targeted for high-performance, more durable PEMWE
Physical work demands and risk of rheumatoid arthritis, systemic sclerosis, and systemic lupus erythematosus. A Danish longitudinal cohort study
No full textObjectivesThis study assesses the association between physical work demands and rheumatoid arthritis (RA), systemic sclerosis (SSc), and systemic lupus erythematosus (SLE) among men and women. MethodsThis nationwide, register-based study included more than 1.0 million women and 1.1 million men with employment born between 1960 and 1999 from the Danish Occupational Cohort with eXposure data (DOC∗X). Information on physical work demands was obtained from a job exposure matrix (JEM) and measured as recent physical work demands, accumulated physical work demands, and years with high physical work demands since workforce entry. The populations were followed from 1997 to 2018. Poisson regression models were used to estimate the IRRs for developing RA, SSc, and SLE, identified in the Danish National Patient Registry. ResultsMen in occupations with high recent physical work demands (4th quartile vs. 1st quartile: 1.36, 95 % CI 1.31–1.42), higher accumulated physical work demands, and more years with high physical work demands, had a higher risk of diagnosis of RA, while this was not the case for women. Accumulated physical work demands and more years with high physical work demands were associated with a small increased risk of diagnosis of SSc and SLE among men. In women, high physical work demands were associated with a reduced risk of diagnosis of SLE, while the results on SSc were inconsistent. ConclusionThese findings support an association between higher physical work demands and diagnosis of RA and possibly, albeit to a lesser extent, SLE and SSc in men, but not in women.</p
Optimising acute toxicity monitoring in prostate MR-guided radiotherapy workflow:Results from a prospective study using multiple electronic PRO assessments
No full textIntroduction Frequent electronic patient-reported outcomes (ePROs) may become an important tool for monitoring outcomes in ultrahypofractionated MRgRT for prostate cancer, enabling real-time remote tracking of toxicity. By integrating weekly ePROs and health-related quality of life (HRQoL) assessments into the early prostate MRgRT workflow, this study aimed to explore real-time acute symptom trajectories and the impact on HRQoL. Methods Two cohorts were followed: Patients receiving MRgRT for localised PCa (60Gy/20fx) or low-volume metastatic (M1) PCa (36Gy/6fx) and eligible to complete weekly ePROs and HRQoL measures (EQ-5D-5L, EORTC QLQ-C30) during and up to 24 weeks of follow-up. Linear mixed models were used to evaluate symptom changes over time. Results Of 76 included PCa patients, 42 had localised PCa and 34 low-volume M1 PCa. The linear model revealed significant changes in urinary symptoms from treatment week one, persisting 2 weeks post-MRgRT in the 36 Gy cohort, and 3–4 weeks in the 60 Gy cohort. Bowel symptoms increased early post-treatment in both cohorts, with diarrhoea being most frequent. Clinically relevant changes in HRQoL were observed during follow-up: patients in the 60 Gy cohort showed HRQoL improvements after 12 and 24 weeks. In the 36 Gy cohort, patients reported improved self-rated Global health status/QoL and emotional functioning. Conclusion Frequent ePROs during and after MRgRT provide critical insights into the timing, fluctuation and severity of acute toxicity, potentially missed with standard follow-up schedules. Integrating real-time ePROs into the MRgRT workflow is a feasible patient-centered method to systematically optimize the outcome assessments of MRgRT.</p
Review of current best practice in radiation oncology for older adults with cancer:Updates from the International Society of Geriatric Oncology (SIOG) Task Force
No full textRadiotherapy (RT) is a vital and effective cancer treatment that contributes to over 40 % of cancer cures. RT is also fundamental to palliation and improving quality of life in almost all advanced malignancies. The specialty of radiation oncology has undergone dramatic technological advances over the past decade with increasing sophistication of treatment planning and delivery leading to improved cure rates and reduced side effects. For older adults with cancer, RT represents an excellent treatment option due to its effectiveness, limited systemic toxicity, convenience, and tolerability. Advanced techniques such as stereotactic body radiotherapy (SBRT) and hypofractionated regimens are highly effective non-invasive treatment options that may avoid the need for hospital admission, the potential mortality and morbidity of surgery and/or the toxicities of systemic therapy. Historically, the role of RT for older adults has not been comprehensively assessed or defined due to the limited recruitment of older adults to clinical trials. Fortunately, the increasing number of RT trials tailored to specifically explore outcomes for older people is expanding the body of evidence for this priority research area. This updated expert position paper from the SIOG (International Society of Geriatric Oncology) Task Force seeks to provide an overview of the current role of RT in the management of older adults with cancer. The position paper is informed by the geriatric radiation oncology clinical expertise of the SIOG Task Force and emerging evidence in the field since the publication of the original 2014 position paper. Topics covered include the fundamentals of geriatric oncology as applied to radiation oncology, options for dose fractionation schedules and techniques across pre-defined tumor sites and appropriate individualised modifications of regimens in the setting of frailty, discussion of expected tolerability and toxicity (if any) in older adults, and the unique perspectives of care around older adults requiring RT in low- and middle-income countries.</p
Co-production of hydrogen, power, and liquid carbon dioxide in an integrated methane partial oxidation plant with zero-direct-emission:Thermodynamic and economic assessment
No full textThis study introduces a zero-emission cogeneration process that combines methane partial oxidation, recuperating organic Rankine cycle, CO2 capture and storage, and hydrogen-fueled steam Rankine cycle through cascade heat recovery. The process is modeled in Aspen HYSYS and analyzed using energy, exergy, and thermoeconomic methods. Under standard conditions, the plant consumes 25 MW of fuel, generates 1164 kW of net power, and produces 487.5 kg/h of H2 and 4851 kg/h of liquid CO2, with overall thermal and exergy efficiencies of 66.03 % and 64.58 %, respectively. The specific fuel consumption is 1.514, and the specific reboiler duty is 4.11 MJ/kg CO2, as the partial oxidation reactor supplies all solvent-regeneration heat with a heat-recovery efficiency of 83.78 %. Exergy analysis shows that the reforming unit and partial oxidation reactor account for about 66 % of total exergy destruction. Sensitivity analysis indicates that increasing the organic Rankine turbine inlet temperature to 600 °C and reducing oxygen flow to the partial oxidation reactor to 0.82 kg/s can boost exergy efficiency to 70 %, raise net power to 1,393 kW, and lower the energy cost from 1.354/kg H2, whereas Italy offers the shortest PBP, at approximately 4.7 years.</p
A Systematic Review With Meta-Analysis of Endogenous Opioid System Biomarkers in Patients With Chronic Axial Pain, Chronic Widespread Pain, and Fibromyalgia
No full textBackground: The opioid system is involved in the regulation of pain as well as stress homeostasis. Stress-induced opioid dysregulation has been proposed as a mechanism for pain development in patients with fibromyalgia (FM) and chronic low back pain (cLBP). However, the evidence to support this hypothesis is conflicting. Methods: We conducted a systematic literature search in MEDLINE, EMBASE, and the Cochrane Library database to investigate whether patients with FM or cLBP exhibit (1) different levels of endogenous opioids or anti-opioids in body fluids or tissue samples, or (2) altered levels of opioid receptor expression or availability compared to pain-free controls. Results: We identified 33 studies eligible for inclusion in the review, investigating 863 patients and 636 pain-free controls. Three meta-analyses of beta-endorphin levels in blood and cerebrospinal fluid (CSF) were performed, revealing no significant differences between patients with FM or cLBP and controls. However, the grading of the evidence was very low. Mu-opioid receptor (MOR) dysfunction emerged as a potential feature of FM, with some evidence suggesting reduced MOR binding in the brain and decreased MOR expression in immune cells. Conclusions: Current evidence does not support altered peripheral endorphin levels in FM or cLBP, while emerging PET findings indicate reduced central MOR availability in FM. These results suggest receptor-level dysregulation rather than peripheral opioid deficits. Limitations mainly arose from low sample sizes and inadequate study methodologies, underscoring the need for well-designed studies with larger sample sizes to clarify the role of endogenous opioid dysfunction in FM and cLBP. Significance: This systematic review highlights emerging evidence of mu-opioid receptor dysfunction in fibromyalgia, despite no consistent differences in beta-endorphin levels. The findings underscore significant methodological limitations in existing studies and point to the need for rigorous, well-powered research to clarify the role of endogenous opioid dysregulation in chronic pain.</p
Inverse correlation between plasma pyrophosphate hydrolysis and early growth of abdominal aortic aneurysm:a pilot study
No full textAbstract: Abdominal aortic aneurysm (AAA) is often associated with vascular calcification, the calcium-phosphate crystal deposition in the aortic wall, which could impact aneurysm progression and/or stability. Tissue-nonspecific alkaline phosphatase (TNAP) hydrolyzes pyrophosphate—a natural inhibitor of calcification—thereby promoting calcium deposition. This study analyzes phosphatase activity and pyrophosphate dynamics in the plasma of AAA patients, randomly selected from the whole VIVA cohort, including controls (n = 48, aortic diameter in < 30 mm) and small AAA patients (n = 96, aortic diameter 30–55 mm), which were stratified by growth rate (low < 2 mm/year or high > 2 mm/year, n = 48 in each group), initially adjusted by aortic diameter. The phosphatase activity was assessed at physiological (7.4) and optimal (10.5) pH levels. Phosphatase activity was significantly higher in AAA patients at physiological pH, a pattern absent at optimal pH, suggesting disease-specific alterations. Small AAA patients showed notably higher phosphatase activity and pyrophosphate hydrolysis than controls at physiological pH. An inverse correlation was also observed between phosphatase activity and aortic growth rate. Key messages: Increased alkaline phosphatase activity was detected in heparin-plasma samples from patients with abdominal aortic aneurysm at physiological pH (7.4), but not under optimal experimental conditions (pH 10.5), suggesting a disease-related effect that may reflect processes occurring in vivo. Concentrations of tissue-nonspecific alkaline phosphatase in heparin-plasma samples remained unchanged, despite increased hydrolysis of pyrophosphate, a key inhibitor of vascular calcification. Pyrophosphate hydrolysis in heparin-plasma samples correlated inversely with aortic growth rate in abdominal aortic aneurysm patients.</p
Enhancing Resilience and Efficiency in Low-Voltage Resistive AC Microgrids Through Distributed Control Strategies
No full textThis study focuses on islanded AC microgrids and addresses the dynamic stability challenges caused by renewable energy variability and uncertain load demand. The work specifically targets the secondary control layer, which plays a critical role in restoring voltage and frequency while ensuring accurate power sharing among distributed generators (DG). The primary control relies on conventional voltage–current (V–I) droop characteristics to provide decentralized operation, but this approach alone leads to steady-state deviations and limited power-sharing accuracy. To overcome these limitations, we propose an advanced distributed secondary control strategy based on consensus algorithms. At this layer, the two fundamental parameters of the droop characteristic—its slope and offset—are dynamically tuned in a coordinated manner. Active power sharing is improved by adjusting both the slope and the offset of the d-axis droop, while reactive power control is refined through modifications to the q-axis slope. This dual-parameter adaptation ensures robust proportional power sharing, precise voltage regulation at the point of common coupling, and resilience against communication delays. The effectiveness of the proposed secondary control scheme is validated through detailed simulations in MATLAB/Simulink, demonstrating enhanced stability, faster transient recovery, and improved power quality under varying load conditions.</p
Thoracic Ultrasound - EFSUMB Training Recommendations, a position paper
No full textA wide range of medical specialists increasingly use thoracic ultrasound and transthoracic ultrasound-guided interventions in their clinical practice. To ensure high quality and standardized practice across specialties, this position paper of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) describes the training requirements for thoracic ultrasound. The recommendations follow the three EFSUMB competency levels for medical ultrasound practice. Level 1 describes the skills required to perform basic thoracic ultrasound examinations and basic interventions independently, level 2 includes more advanced transthoracic ultrasound imaging and guided interventions, while level 3 involves the practice of high-level thoracic ultrasound and the use of advanced technologies. Previously, a predefined minimum number of ultrasound examinations was used to determine competence, but in recent years, a general shift towards competency-based training and assessment has been implemented. For each EFSUMB level, we outline the theoretical knowledge and practical skills needed for clinical practice.</p