Search Results (55)

Background: There are a lot of advances that may affect the way treatment is delivered prehospital, including mobile stroke units and point-of-care diagnostics. These have the potential to affect populations differently and therefore affect the distribution of health outcomes. Objectives: We aimed to address the following research questions: (1) Which geographic and socioeconomic inequalities have been included when evaluating access to acute stroke treatment (including reperfusion therapies)? (2) How have the identified measures been considered/assessed/calculated? (3) We also report any methodological approaches that have been proposed that might further improve the way in which acute stroke care interventions are analysed, specified relating to inequalities. Methods: PubMed and Scopus electronic databases were searched for studies that included participants who underwent acute stroke treatment and included quantitative measures of geographic and/or socioeconomic inequalities or inequities in accessing/receiving treatment. Results: Overall, sixty-six studies were included in the review. Fifty-nine included at least one measure of geographic inequalities or inequities while thirty-six included at least one measure of socioeconomic inequalities or inequities. Twenty-eight of these studies included both a geographic and socioeconomic measure of inequalities or inequities. There were no commonalities in the methods of defining, categorising and measuring the inequalities or inequities. No study provided their definition of inequality or inequity or stated any normative judgements they had made. Conclusions: It is vital that the evaluation of programmes like acute stroke care consider impacts on inequality and inequity. Researchers and policy makers should work together to determine relevant measures of inequality/inequity and the most appropriate methods of measuring and categorising them. In addition, researchers should make it clear within their work how they are defining inequality and inequity and what (if any) normative judgements have been made. Full article

Predictive uncertainty analysis focuses on defensible variability in model projected values after estimation of the posterior parameter distribution. Inverse-style parameter estimation selects posterior parameters through history matching where parameters are varied and resulting model simulation values are compared to observations, and parameters are selected balancing goodness-of-fit between simulated and observed values and expert knowledge. When inverse-style parameter estimation approaches are used, parameter sensitivity, which is the change in simulated outputs relative to the change in parameter values, is an important consideration. Variation in null space parameters has a limited impact on history matching skill; however, these parameters become important when they impact predictions. A new null space sensitivity analysis for ensemble methods of data assimilation (DA) using observation error models is developed and implemented for an integrated hydrological model. Empirical parameter sensitivity is estimated by comparing the spreads of prior and posterior parameter distributions. Sensitivity analysis is generated by an ensemble of models with insensitive parameters varying across the prior parameter distribution and sensitive parameters fixed to best-fit model values. The result is identification of insensitive aquifer storage parameters that change storage-related model predictions by as much as two times. This null space analysis describes uncertainty from data insufficiency. Ensemble methods using observation error models also describe predictive uncertainty from noisy measurements and imperfect models. Full article

This paper presents an innovative approach to cultural heritage preservation through the development of an open framework that leverages RESTful APIs to make high-fidelity 3D models of cultural artifacts accessible to any application. Focusing on antique kitchenware utensils from the Nakhon Si Thammarat National Museum in Thailand, this research utilizes photogrammetry to create detailed 3D models, which are then made available on a web-based platform, accessible globally via standardized HTTP requests. The framework enables real-time access to 3D cultural content, overcoming the geographical and physical barriers that often limit access to cultural heritage. By integrating these 3D models into RESTful APIs, the project not only preserves delicate artifacts but also enhances their educational and cultural value through interactive accessibility. This system demonstrates the practical application of digital preservation technologies and sets a precedent for future initiatives aiming to digitize and disseminate cultural artifacts more broadly. The implications of this study extend beyond preservation to include enhanced global accessibility, enriched educational resources, and a more inclusive approach to cultural engagement. This project illustrates the transformative potential of digital technologies in preserving, accessing, and experiencing cultural heritage worldwide. Full article

Background/Objectives: Major surgery for gastrointestinal cancer carries a 50% risk of postoperative complications. Physiotherapists commonly provide interventions to patients undergoing gastrointestinal surgery for cancer with the intent of preventing complications and improving recovery. However, the evidence is unclear if physiotherapy is effective compared to providing no physiotherapy, nor if timing of service delivery during the perioperative pathway influences outcomes. The objective of this review is to evaluate and synthesise the evidence examining the effects of perioperative physiotherapy interventions delivered with prophylactic intent on postoperative outcomes compared to no treatment or early mobilisation alone. Methods: A protocol was prospectively registered with PROSPERO and a systematic review performed of four databases. Randomised controlled trials examining prophylactic physiotherapy interventions in adults undergoing gastrointestinal surgery for cancer were eligible for inclusion. Results: Nine publications from eight randomised controlled trials were included with a total sample of 1418 participants. Due to inconsistent reporting of other perioperative complications, meta-analysis of the effect of physiotherapy was only possible specific to postoperative pulmonary complications (PPCs). This found an estimated 59% reduction in risk with exposure to physiotherapy interventions (RR 0.41, 95%CI 0.23 to 0.73, p < 0.001). Sub-group analysis demonstrated that timing of delivery may be important, with physiotherapy delivered only in the preoperative phase or combined with a postoperative service significantly reducing PPC risk (RR 0.32, 95%CI 0.17 to 0.60, p < 0.001) and hospital length of stay (MD–1.4 days, 95%CI −2.24 to −0.58, p = 0.01), whilst the effect of postoperative physiotherapy alone was less certain. Conclusions: Preoperative-alone and perioperative physiotherapy is likely to minimise the risk of PPCs in patients undergoing gastrointestinal surgery for cancer. This challenges current traditional paradigms of providing physiotherapy only in the postoperative phase of surgery. A review with broader scope and component network analysis is required to confirm this. Full article

Background/Objectives: Overall survival for patients with Stage 3 pancreatic ductal adenocarcinoma (PDAC) remains limited, with a median survival of 12 to 15 months. Irreversible electroporation (IRE) is a local tumor ablation method that induces cancerous cell death by disrupting cell membrane homeostasis. The DIRECT Registry study was designed to assess the effectiveness and safety of IRE when combined with standard of care (SOC) treatment for Stage 3 PDAC versus SOC alone in a real-world setting after at least 3 months of induction chemotherapy; Methods: Patients with Stage 3 PDAC treated with IRE plus SOC or SOC alone were prospectively enrolled in a multicenter registry study. Enrollment required 3 months of active multi-agent chemotherapy with no progression before enrollment. Endpoints were 30- and 90-day mortality and adverse events (AEs). Results: Eighty-seven IRE and 27 SOC subjects were enrolled in the registry. Mean ages were 64.0 ± 8.4 and 66.4 ± 9.9 years, and mean anterior/posterior tumor diameters were 2.2 ± 0.7 cm and 3.2 ± 1.3 for the IRE and SOC groups respectively (p = 0.0066). All IRE procedures were performed using an open approach. The 90-day all-cause mortality was 5/83 (6.0%) and 2/27 (7.4%) for the IRE and SOC groups, respectively. Two subjects in the IRE group died from treatment-related complications, and one patient in the SOC group died due to chemotherapy-related complications. Conclusions: Initial results from the DIRECT registry study indicate the use of IRE for curative intent tumor ablation in combination with induction chemotherapy has equivalent morbidity and mortality rates when compared to standard-of-care chemotherapy alone. Full article

Lithium-ion batteries offer the highest energy density of any currently available portable energy storage technology. By using different anode materials, these batteries could have an even greater energy density. One material, tin, has a theoretical lithium capacity (994 mAh/g) over three-times higher than commercial carbon anode materials. Unfortunately, to achieve this high capacity, bulk tin undergoes a large volume expansion, and the material pulverizes during cycling, giving a rapid capacity fade. To mitigate this issue, tin must be scaled down to the nano-level to take advantage of unique micromechanics at the nanoscale. Synthesis techniques for Sn nanoparticle anodes are costly and overly complicated for commercial production. A novel one-step process for producing carbon-coated Sn nanoparticles via spark plasma erosion (SPE) shows great promise as a simple, inexpensive production method. The SPE method, characterization of the resulting particles, and their high-capacity reversible electrochemical performance as anodes are described. With only a 10% addition of these novel SPE carbon-coated Sn particles, one anode composition demonstrated a reversible capacity of ~460 mAh/g, achieving the theoretical capacity of that particular electrode formulation. These SPE carbon-coated Sn nanoparticles are drop-in ready for present commercial lithium-ion anode processing and would provide a ~10% increase in the total capacity of current commercial lithium-ion cells. Full article

Artificial intelligence (AI), including machine learning (ML) and deep learning (DL), learns by training and is restricted by the amount and quality of training data. Training involves a tradeoff between prediction bias and variance controlled by model complexity. Increased model complexity decreases prediction bias, increases variance, and increases overfitting possibilities. Overfitting is a significantly smaller training prediction error relative to the trained model prediction error for an independent validation set. Uncertain data generate risks for AI–ML because they increase overfitting and limit generalization ability. Specious confidence in predictions from overfit models with limited generalization ability, leading to misguided water resource management, is the uncertainty-related negative consequence. Improved data is the way to improve AI–ML models. With uncertain water resource data sets, like stream discharge, there is no quick way to generate improved data. Data assimilation (DA) provides mitigation for uncertainty risks, describes data- and model-related uncertainty, and propagates uncertainty to results using observation error models. A DA-derived mitigation example is provided using a common-sense baseline, derived from an observation error model, for the confirmation of generalization ability and a threshold identifying overfitting. AI–ML models can also be incorporated into DA to provide additional observations for assimilation or as a forward model for prediction and inverse-style calibration or training. The mitigation of uncertain data risks using DA involves a modified bias–variance tradeoff that focuses on increasing solution variability at the expense of increased model bias. Increased variability portrays data and model uncertainty. Uncertainty propagation produces an ensemble of models and a range of predictions. Full article

The Module-0 Demonstrator is a single-phase 600 kg liquid argon time projection chamber operated as a prototype for the DUNE liquid argon near detector. Based on the ArgonCube design concept, Module-0 features a novel 80k-channel pixelated charge readout and advanced high-coverage photon detection system. In this paper, we present an analysis of an eight-day data set consisting of 25 million cosmic ray events collected in the spring of 2021. We use this sample to demonstrate the imaging performance of the charge and light readout systems as well as the signal correlations between the two. We also report argon purity and detector uniformity measurements and provide comparisons to detector simulations. Full article

High density portable energy storage is desirable owing to the energy requirements of portable electronics and electric vehicles. The Li-ion battery’s high energy density could be even further improved through the utilization of alternative materials (instead of carbon) for the anode, such as Sn or Si. Nonetheless, the large volume expansion upon lithiation, up to ~300% for Li₂₂Si₅, causes pulverization and rapid capacity degradation during cycling. Sn also forms a Li₂₂Sn₅ compound with the equivalent stoichiometric Li capacity but with enhanced ductility. Nano-sized Si and Sn have demonstrated distinctive nanoscale properties, facilitating the retention of higher capacities, particularly when coated with carbon, which improves mechanical stability. To date, the methods of synthesizing coated Si, Sn, or Si-Sn alloyed nanoparticles are complicated, costly, and not readily scalable to meet the demands of cost-effective manufacturing. Spark plasma erosion in a hydrocarbon dielectric has been explored as a one-step process to produce Sn-Si alloy nanoparticles coated with a thin carbon film, offering a scalable and cost-effective processing route. The resulting Sn-Si particles exhibited a bi-modal size distribution at ~5 nm and ~500 nm and were carbon-coated, as intended, from the hydrocarbon dielectric breakdown. The spark-eroded nanoparticles were thoroughly characterized using TEM/EDS, XPS, AES, SSNMR, and TGA, and their improved electrochemical performance was assessed through half-cell experiments. Full article

ARID1A is the core DNA-binding subunit of the BAF chromatin remodeling complex and is mutated in about 8% of all cancers. The frequency of ARID1A loss varies between cancer subtypes, with clear cell ovarian carcinoma (CCOC) presenting the highest incidence at > 50% of cases. Despite a growing understanding of the consequences of ARID1A loss in cancer, there remains limited targeted therapeutic options for ARID1A-deficient cancers. Using a genome-wide CRISPR screening approach, we identify KEAP1 as a genetic dependency of ARID1A in CCOC. Depletion or chemical perturbation of KEAP1 results in selective growth inhibition of ARID1A-KO cell lines and edited primary endometrial epithelial cells. While we confirm that KEAP1-NRF2 signalling is dysregulated in ARID1A-KO cells, we suggest that this synthetic lethality is not due to aberrant NRF2 signalling. Rather, we find that KEAP1 perturbation exacerbates genome instability phenotypes associated with ARID1A deficiency. Together, our findings identify a potentially novel synthetic lethal interaction of ARID1A-deficient cells. Full article

Background: A universal infant free school meals (UIFSM) policy was introduced in 2014/15 in England and Scotland for schoolchildren aged 4–7 years; as a result, school meal uptake rose sharply. School food in the UK is known overall to be healthier and less processed than food brought from home (packed lunches), but it is unknown as to how UIFSM impacted the level and type of ultra-processed food (UPF) consumed. Therefore, this study aimed to evaluate the impact of the UIFSM policy on the processing levels of food consumed during the school lunchtime period among schoolchildren in England and Scotland. Methods: Data from the National Diet and Nutrition Study (NDNS), a nationally representative repeated cross-sectional survey, were used to conduct a difference-in-difference study. The average intake of UPF (% of total lunch grams and % total lunch Kcal) using the NOVA classification was calculated for each school lunch. The lunchtime intakes in the intervention group (4–7 years, n = 866) were compared to the control (8–11 years, n = 808) pre- (2008–2014) and post-intervention (2014–2019) using linear regression, adjusting for sociodemographic variables and total lunchtime intake (grams). Inverse probability weights were used to balance the characteristics across the intervention groups. Results: Before UIFSM, the consumption of UPFs as a proportion of total lunch energy (UPF % Kcal) was similar in the intervention and control groups (67% Kcal vs. 69% Kcal). After adjustment for covariates, UPF consumption decreased by 6.3 pp (95% CI −11.3, −1.3) after UIFSM. The findings were similar for UPF as the percentage of total lunch grams. These effects were driven by increases in minimally processed dairy and eggs and starchy foods and decreases in salty snacks and ultra-processed bread and drinks consumption. The greatest reduction in UPF consumption was in low-income children (−17.2% Kcal; 95% CI −26.5, −7.8), compared to mid- (0.5% Kcal; 95% CI −4.0, 1.0) or high-income children (−5.3% Kcal; 95% CI −13.6, 2.9). Conclusions: This study builds on previous evidence and shows that UIFSM improved children’s dietary intake at school by minimising exposure to UPFs. These results indicate that universal free school meal policies could be an important policy for long-term equitable improvements in children’s diet and subsequent health. Full article

This international multicenter cohort study included 30 centers. Patients with duodenal adenocarcinoma (DAC), intestinal-type (AmpIT) and pancreatobiliary-type (AmpPB) ampullary adenocarcinoma, distal cholangiocarcinoma (dCCA), and pancreatic ductal adenocarcinoma (PDAC) were included. The primary outcome was 30-day or in-hospital mortality, and secondary outcomes were major morbidity (Clavien-Dindo 3b≥), clinically relevant post-operative pancreatic fistula (CR-POPF), and length of hospital stay (LOS). Results: Overall, 3622 patients were included in the study (370 DAC, 811 AmpIT, 895 AmpPB, 1083 dCCA, and 463 PDAC). Mortality rates were comparable between DAC, AmpIT, AmpPB, and dCCA (ranging from 3.7% to 5.9%), while lower for PDAC (1.5%, p = 0.013). Major morbidity rate was the lowest in PDAC (4.4%) and the highest for DAC (19.9%, p < 0.001). The highest rates of CR-POPF were observed in DAC (27.3%), AmpIT (25.5%), and dCCA (27.6%), which were significantly higher compared to AmpPB (18.5%, p = 0.001) and PDAC (8.3%, p < 0.001). The shortest LOS was found in PDAC (11 d vs. 14–15 d, p < 0.001). Discussion: In conclusion, this study shows significant variations in perioperative mortality, post-operative complications, and hospital stay among different periampullary cancers, and between the ampullary subtypes. Further research should assess the biological characteristics and tissue reactions associated with each type of periampullary cancer, including subtypes, in order to improve patient management and personalized treatment. Full article

Supercritical carbon dioxide (sCO₂) can be mixed with dopants such as titanium tetrachloride (TiCl₄), hexafluoro-benzene (C₆F₆), and sulphur dioxide (SO₂) to raise the critical temperature of the working fluid, allowing it to condense at ambient temperatures in dry solar field locations. The resulting transcritical power cycles have lower compression work and higher thermal efficiency. This paper presents the aerodynamic flow path design of a utility-scale axial turbine operating with an 80–20% molar mix of CO₂ and SO₂. The preliminary design is obtained using a mean line turbine design method based on the Aungier loss model, which considers both mechanical and rotor dynamic criteria. Furthermore, steady-state 3D computational fluid dynamic (CFD) simulations are set up using the k-ω SST turbulence model, and blade shape optimisation is carried out to improve the preliminary design while maintaining acceptable stress levels. It was found that increasing the number of stages from 4 to 14 increased the total-to-total efficiency by 6.3% due to the higher blade aspect ratio, which reduced the influence of secondary flow losses, as well as the smaller tip diameter, which minimised the tip clearance losses. The final turbine design had a total-to-total efficiency of 92.9%, as predicted by the CFD results, with a maximum stress of less than 260 MPa and a mass flow rate within 1% of the intended cycle’s mass flow rate. Optimum aerodynamic performance was achieved with a 14-stage design where the hub radius and the flow path length are 310 mm and 1800 mm, respectively. Off-design analysis showed that the turbine could operate down to 88% of the design reduced mass flow rate with a total-to-total efficiency of 80%. Full article

Type 2 diabetes (T2D) is characterized by low-grade inflammation. Low-density neutrophils (LDNs) represent normally less than 2% of total neutrophils but increase in multiple pathologies, releasing inflammatory cytokines and neutrophil extracellular traps (NETs). We assessed the count and role of high-density neutrophils (HDNs), LDNs, and NET-related activities in patients with T2D. HDNs and LDNs were purified by fluorescence-activated cell sorting (FACS) and counted by flow cytometry. Circulating inflammatory and NETs biomarkers were measured by ELISA (Enzyme Linked Immunosorbent Assay). NET formation was quantified by confocal microscopy. Neutrophil adhesion onto a human extracellular matrix (hECM) was assessed by optical microscopy. We recruited 22 healthy volunteers (HVs) and 18 patients with T2D. LDN counts in patients with diabetes were significantly higher (160%), along with circulating NETs biomarkers (citrullinated H3 histone (H3Cit), myeloperoxidase (MPO), and MPO-DNA (137%, 175%, and 69%, respectively) versus HV. Circulating interleukins (IL-6 and IL-8) and C-Reactive Protein (CRP) were significantly increased by 117%, 171%, and 79%, respectively, in patients compared to HVs. Isolated LDNs from patients expressed more H3Cit, MPO, and NETs, formed more NETs, and adhered more on hECM compared to LDNs from HVs. Patients with T2D present higher levels of circulating LDN- and NET-related biomarkers and associated pro-inflammatory activities. Full article

Bacteria are identified in only 22% of critically ill children with respiratory infections treated with antimicrobial therapy. Once an organism is isolated, antimicrobial susceptibility results (phenotypic testing) can take another day. A rapid diagnostic test identifying antimicrobial resistance (AMR) genes could help clinicians make earlier, informed antimicrobial decisions. Here we aimed to validate a custom AMR gene TaqMan Array Card (AMR-TAC) for the first time and assess its feasibility as a screening tool in critically ill children. An AMR-TAC was developed using a combination of commercial and bespoke targets capable of detecting 23 AMR genes. This was validated using isolates with known phenotypic resistance. The card was then tested on lower respiratory tract and faecal samples obtained from mechanically ventilated children in a single-centre observational study of respiratory infection. There were 82 children with samples available, with a median age of 1.2 years. Major comorbidity was present in 29 (35%) children. A bacterial respiratory pathogen was identified in 13/82 (16%) of children, of which 4/13 (31%) had phenotypic AMR. One AMR gene was detected in 49/82 (60%), and multiple AMR genes were detected in 14/82 (17%) children. Most AMR gene detections were not associated with the identification of phenotypic AMR. AMR genes are commonly detected in samples collected from mechanically ventilated children with suspected respiratory infections. AMR-TAC may have a role as an adjunct test in selected children in whom there is a high suspicion of antimicrobial treatment failure. Full article