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The Nottingham recovery from COVID-19 research platform (NoRCoRP): Functional, clinical and patient-reported outcomes in adults referred to a post-COVID respiratory service
Full text linkAimsTo characterise symptoms, function and patient-reported outcome measures (PROMs), and identify associated factors in adults with persisting respiratory symptoms post-COVID.MethodsCross-sectional analysis of 210 non-hospitalised adults referred to a post-COVID respiratory clinic (December 2020-July 2024) who consented to research. Assessments included demographics, symptoms, lung function, chest CT, and several PROMs: MRC dyspnoea score, Nijmegen Questionnaire score (NQ), Hospital Anxiety and Depression Scale, Chalder Fatigue Scale, Short Physical Performance Battery (SPPB) and Fried Frailty Index. Multivariate logistic regression examined key exposure-outcome associations.ResultsAmong participants (mean age 49.4 years; 68% female; median 13.3 months since COVID-19 diagnosis), 95% reported shortness of breath, 54% had clinically significant breathlessness (MRC ≥ 3), 68% had an NQ score (>23) consistent with dysregulated breathing, 32% had a low SPPB score (<10), and 77% were classed as frail/pre-frail, despite the majority being of working age. Nearly half (47%) of those employed pre-infection had not returned to previous hours. Spirometry and CT abnormalities were not common. Higher body mass index (odds ratio = 1.10, 95% confidence interval = 1.05–1.16, n in model = 190) and depression (2.25, 1.13–4.56, n = 164) were associated with MRC ≥ 3. Dysregulated breathing was associated with female sex (3.63, 1.77–7.60, n = 186), current/ex-smoker (2.56, 1.25–5.47, n = 186), fatigue (8.87, 2.59–37.0, n = 162), anxiety (3.57, 1.70–7.69, n = 162) and depression (5.70, 2.59–13.40, n = 162). A low SPPB score was associated with female sex, current smoking, depression, clinically significant breathlessness, dysregulated breathing, and greater deprivation.ConclusionIn non-hospitalised patients with persistent respiratory symptoms post-COVID, dysregulated breathing, deconditioning and psychological distress were key factors linked with symptom burden. These findings suggest a multidisciplinary approach should be considered to optimise recovery
Toward high-efficiency solid oxide fuel cells: A comprehensive review of hybrid integration techniques
No full textSolid oxide fuel cells (SOFCs) have emerged as highly effective and eco-friendly technologies for electricity generation, featuring high fuel flexibility and scalability. However, individual units of SOFCs face significant issues like high operating temperatures, degradation of materials, and slow transient response. To counter challenges and increase operational efficiencies, hybrid integration schemes have received considerable scholarly attentions. This review presents an exhaustive and critical assessment of advanced hybrid SOFC configurations and their implications in enhancing system performance, efficiency, and lifespan. The manuscript examines different hybrid approaches, such as SOFC-gas turbine (SOFC-GT) hybrid schemes, combination of heat and power (SOFC-CHP), double hybrid cycles (SOFC-CC), trigeneration (CCHP), and hybrid models of SOFC-battery. The integration strategy of each of these approaches is compared relative to design architecture, thermodynamic synergy, fuel utilization, waste heat recovery, and environmental aspects. The assessment is further extended to emerging energy ideas like CO2 capture, simultaneous hydrogen production, and biomass-based hybrid schemes with the goal of supporting long-term sustainability, enabling low-carbon energy transitions and decarbonization. The conclusions of this review outline considerable technological challenges, such as thermal management challenges, sealing problems, material interactions, and system control complexity. By synthesizing cutting-edge model studies, experimentation, and techno-economic studies, this manuscript outlines promising avenues to boost hybrid SOFC technologies. The results suggest outstanding enhancement of electrical efficiency (70 %) and overall system efficiency (90 %) attainable by hybridization. Finally, this review provides an essential source and guideline to promote transition to clean energy technologies of the future by maximizing advantages of hybrid SOFC platforms
Do remote clinical trials offer carbon savings while maintaining research quality? Experiences from the Eczema Bathing Study
No full textBackgroundTraditional clinical trials contribute significantly to the carbon footprint of healthcare. They are also expensive and take a long time to complete. Remote trials could offer part of the solution. They are a type of decentralized trial that use digital innovations to move all activities to participants’ homes or online. This gives them the potential to speed up recruitment, reduce overall trial duration, improve geographical inclusion and reduce the trial’s carbon footprint.ObjectivesTo assess whether a remote trial could reduce a trial’s carbon footprint, while maintaining the research quality needed to answer the scientific questions. The primary objective was to calculate the carbon footprint of a remote eczema trial and compare it with traditional and hybrid trials; the secondary objective was to assess quality indicators of remote, hybrid and traditional eczema trials in terms of speed of recruitment, retention and adherence to interventions.MethodsCarbon footprinting of the remote Eczema Bathing Study (n = 438, 4 weeks’ duration) was completed using the National Institute for Health and Care Research (NIHR)-funded detailed guidance and method to calculate the carbon footprint of a clinical trial. This footprint was compared with footprints of previously published publicly funded trials. Recruitment, retention and adherence metrics were compared between the Eczema Bathing Study and eight other NIHR-funded eczema treatment trials.ResultsThe carbon footprint of the Eczema Bathing Study was 14 tonnes CO2e. The most carbon-intensive activity was staff commuting. The mean speed of recruitment for remote, hybrid and traditional trials was 52, 27 and 13 participants per month, respectively. Mean retention for remote, hybrid and traditional trials was 90%, 95% and 95%, respectively. Adherence was defined individually for each study, making comparison difficult.ConclusionsThe Eczema Bathing Study’s lower carbon footprint in comparison with the other clinical trials mentioned in this study was largely due to online recruitment methods, reduced need for patient and staff travel, and reduced overall trial duration. Adherence and retention were slightly lower than for traditional trials but remained within predefined limits for the study’s size calculations. In situations where remote assessment of diagnosis and outcomes is possible, and where advertising direct to participants is appropriate, running trials completely online has the potential to improve speed of recruitment, reduce overall trial duration and reduce carbon emissions
The human DDX52 protein is a nucleic acid helicase and strand annealase that promotes cell migration
Full text linkDExD-box (DDX) proteins are essential for RNA metabolism and are targets for treatment of cancers and neurodevelopmental disorders. The biochemical mechanisms of many DDX proteins remain unclear, including human DDX52. DDX52 is essential for cell survival and is an emerging biomarker for the onset of metastatic melanoma. In this work, we identified that human DDX52 is an ATP-dependent translocase with 3'-5' polarity, which can unwind DNA duplexes and DNA/RNA hybrids. Further, DDX52 is a nucleic acid annealase, an activity that requires an N-terminal intrinsically disordered protein region. DDX52 becomes hyperactive at DNA annealing if DDX52 helicase activity is inactivated by mutagenesis. Using CRISPR-Cas9 genetic editing, we generated U2OS cell lines heterozygous for DDX52 (DDX52+/-), which exhibit growth defects and impaired cell migration, providing direct support for previous suggestions that DDX52 may promote cancer cell metastasis and C-myc regulation
The impact of derivative use on default probability among non-financial firms: Evidence from European firms
Full text linkThis paper examines how institutional environments shape the effectiveness of derivative hedging in reducing corporate default risk. Using hand-collected data from non-financial firms across nine European countries and various econometric methods to control for endogeneity, we provide novel evidence that the risk-reducing benefits of derivative usage are significantly enhanced in stronger creditor rights settings. Additionally, we document that the default risk-reducing effect of derivatives diminishes in countries with lower economic risk. We also find that for firms in severe financial distress, hedging does not reduce default likelihood. Regarding types of derivatives, we show that interest rate derivatives have a stronger default risk reducing effect than foreign exchange and commodity derivatives
The Ontogeny of the Generalization of Avoidance Behavior
No full textThe developmental trajectory of the generalization of avoidance has received limited research attention, despite generalization and avoidance being key features of anxiety disorders. This study used a gamified avoidance task to investigate generalization in 96 children aged 5–11years old.The task was an adaptation of the classic “Space Invaders” video game, in which participants have to shoot at spaceships to win points while also avoiding being shot by a large spaceship (i.e., aversive outcome). The appearance of the large spaceship (the outcome; which resulted in loss of points) was signaled by colored sensors at the top of the screen. One sensor predicted the outcome (CS+; an aqua-colored sensor), and a second did not (CS−; red). Participants could avoid the loss of points by moving into the safe areas of the screen in anticipation of the large spaceship. Following avoidance training, we then presented six generalization stimuli varying along the blue–green dimension of the CS+ to assess generalization. Our findings revealed that age significantly influenced generalization gradients, with younger children (5–8) exhibiting broader gradients compared to older children (9–11). Regression analyses indicated that age was a significant predictor of generalization. These results underscore the impact of ontogenetic changes on the generalization of avoidance behavior and highlight the importance of including young children in research to better understand the mechanisms underlying generalization and factors leading to anxiety disorders
Exploring the effects of pH, ionic strength, and temperature on bisulfide sorption onto bentonite via experiments and numerical modelling
Full text linkThe long-term performance of the Canadian deep geologic repository (DGR) relies significantly on bentonite clay, as sealing materials intended for use in the engineered barrier system (EBS). One particular safety concern is microbiologically influenced corrosion of the used fuel containers (UFCs) which may occur if bisulfide (HS−) transports through the bentonite buffer to reach the UFC surface and corrode the copper coating. Understanding HS− sorption onto bentonite is therefore an important aspect of this problem, as HS− sorption can reduce the extent of copper corrosion. However, sorption dynamics onto bentonite are not yet well-understood. As such, this study performed laboratory batch experiments to investigate HS− sorption onto bentonite slurries as a function of temperature (10–40 °C), pH (9–11), and ionic strength (0.01 M–1 M NaCl). These conditions were aimed to reflect the range of possible DGR geochemical conditions. The experimental results showed that HS− sorption onto bentonite increased with increasing temperature but decreased with increasing pH and ionic strength. A 3-way ANOVA (analysis of variance) showed that the variables' individual and 2-way interaction effects are statistically significant, which implies that they should be incorporated into a sorption mechanism. A thermodynamic-based sorption model was also developed in PHREEQC assuming that sorption was driven by three key processes: (i) redox reaction with the structural Fe3+ sites, (ii) surface precipitation as FeS (mackinawite), and (iii) surface complexation reactions with surface hydroxyl group (OH) at the edge sites of montmorillonite. The model successfully described the main experimental trends and provided valuable insights into the relative contribution of these processes to the total HS− sorption mechanism. Altogether, this study provides novel insights from experimental and numerical modelling findings that enhance the understanding of HS− sorption onto bentonite, in the context of Canadian DGR design as well as other nuclear repositories worldwide
Geriatric oncology in 2040: Exploring potential realities and challenges. A diverse perspective
Full text linkThe average global life expectancy is predicted to increase to approximately 80 years by 2040 [1]. Cancer is an ageing-related disease, and its prevalence will also increase with this ageing of the population [2]. This rise in older adults living with cancer will demand innovation in service delivery, multidisciplinary collaboration, and a renewed focus on compassionate, patient-centred care. We are therefore compelled to rethink how we approach cancer diagnosis, treatment, and survivorship. This white paper explores the potential realities and challenges through a multidimensional lens, addressing the intersection of demographic shifts, rapid technological advancements, and the evolving needs of older adults living with cancer. Key areas examined include the integration of precision medicine and digital health tools, the adaptation of healthcare delivery models, and the implications for workforce training and resource allocation.The discussion highlights disparities in care, the importance of personalised interventions, and strategies to enhance quality of life for older adults with cancer. By anticipating these developments, the paper offers critical insights for policymakers (who set the rules and goals and allocate funding), health system leaders (who manage the day-to-day operations), clinicians and allied health professionals (who are patient-facing), and patients and caregivers, aiming to promote equity, innovation, quality and resilience in the care of older adults with cancer as we approach the next decade.The paper seeks to consolidate and clarify the diverse issues and opportunities that will emerge as the global population ages and the burden of cancer among older adults rises. With average life expectancy predicted to approach 80 years by 2040, and cancer recognised as a disease closely linked to ageing [3], the paper brings together expert perspectives to provide a sector-wide synthesis of the impending challenges. Its purpose is not to offer a conventional systematic review, but rather to serve as a strategic resource for policymakers, health system leaders, clinicians, allied health professionals, patients, and caregivers, informing the response to demographic shifts, technological advances and evolving patient needs. By consolidating insights on disparities in care, the necessity for personalised interventions, and strategies to enhance quality of life, the paper aims to inform and inspire innovation, equity and resilience in geriatric oncology as we approach the next decade
Squeaking at soft–rigid frictional interfaces
Full text linkSqueaking is a constant companion in various aspects of our daily lives, whether we slide rubber-soled shoes across hardwood floors , scrape chalk on a blackboard, engage the brakes on a bicycle or walk with a hip replacement. When two rigid bodies slide over each other, squeaking is widely understood to result from self-excited stick–slip oscillations, triggered by a decrease in the friction coefficient with increasing slip velocity. However, sliding of extended interfaces can involve crack or slip-pulse propagation . This distinction is amplified when a soft body slides on a rigid one, in which large deformations and material mismatch can cause detachment by opening slip pulses. Previous studies focused mainly on slow sliding, in which pulses are slow and squeaking is absent. Although squeaking at soft–rigid interfaces has been linked to stick–slip oscillations, the mechanisms remain unclear. Here we experimentally investigate soft–rigid interfaces sliding at velocities that produce squeaking. High-speed imaging and acoustic analysis show that opening pulses propagate at approximately the shear wave speed of the soft material, mediating local slip across diverse materials. In flat samples, these pulses are irregular and generate broadband acoustic emissions. Introducing thin surface ridges confines pulse propagation, yielding a consistent repetition frequency matching the first shear mode of the sliding block and squeaking at that frequency. These findings show a structure-driven mechanism that stabilizes rupture in bimaterial friction. Geometric confinement suppresses competing modes, transforming irregular two-dimensional dynamics into coherent one-dimensional pulse trains, offering new insights into frictional rupture from engineered surfaces to geological faults
Tailoring cariprazine for dual disorders via secondary pharmacophore optimization
Full text linkCariprazine is an approved drug used to treat schizophrenia, bipolar disorder, and (more recently) major depression. These serious mental illnesses are often comorbid with psychostimulant use disorders, for which no pharmacotherapeutic is currently approved. Based on preclinical data and multiple case studies, cariprazine demonstrates significant potential as a treatment for such dual disorders. Notably, this drug acts as a high-affinity (Ki = 0.22 nM) partial agonist (Emax = 45.1%) of the dopamine D3 receptor (D3R), a molecular target implicated in a variety of substance use disorders. Unlike other atypical antipsychotics, cariprazine is 3.6-fold more selective for D3R than the homologous dopamine D2 receptor (D2R). Because patients with psychostimulant use disorders may be more susceptible to D2R-related side effects, we hypothesized that compounds with a higher D3R selectivity may offer a therapeutic advantage over cariprazine. By modifying part of the parent drug structure (i.e., secondary pharmacophore), analogues were developed that bind to D3R with similar affinity (Ki = 0.248–2.97 nM) and improved selectivity over D2R (5.0- to 39-fold). Compared to cariprazine, these derivatives behaved functionally as D3R partial agonists and retained a similar off-target profile; however, the most promising compounds also exhibited improved metabolic stability in rat liver microsomes (t1/2 ≥ 61.3 min). Taken together, our findings support further study of the lead candidate (8) for treating dual disorders that may have a reduced side effect profile
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