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Apert Syndrome
No full textApert syndrome (AS), alternatively known as Acrocephalocyndactyly type II, is an uncommon congenital condition resulting from fibroblast growth factor receptor 2 (FGFR2) gene mutations (Anderson et al. 1998). Although most reported patients with AS are de novo, autosomal dominant (AD) inheritance has been documented in some of the case report studies
NMR cryodiffusometry determination of pore utility differentials for liquid-phase diffusion within alumina, catalyst support pellets
No full textIntelligent design of optimal void spaces for diverse applications of porous media remains a still outstanding objective. The aim here was to predict the tortuosity for liquid-phase diffusion within complex, bidisperse, porous alumina pellets, and, thereby, assess the degree of control achieved via a porogen-based synthesis. NMR cryodiffusometry was used as a novel means to implement the so-called “sifting strategy” to identify the key aspects of the void space to include in a more efficient, minimalist, pore structural model for materials unsuited to a “brute-force” modelling approach. The cryodiffusometry showed, through the particular mathematical form of the data obtained, that the predominant geometry of the void space was a random cluster, but also detected the presence of some “dead volume” that provided little, or no, apparent contribution to the overall mass transport. This particular feature of the void space was corroborated by applying the concept of bound volume index to mercury porosimetry retraction data. A minimalist model, constructed incorporating these two key aspects of the void space, was found to be fully predictive of mass transport rates of water, or cyclohexane, within the alumina pellets. Seeded percolation analysis of gas sorption scanning curves demonstrated the dead volume was associated with particular pore space regions with low accessibility, which was consistent with previous Monte-Carlo simulations of self-diffusion on random cluster models and TEM data. The theoretical framework involving a random cluster with dead volume provided a more comprehensive account of the diverse experimental findings than a complementary critical path analysis-based approach
Non-Subtractive Arterial Spin Labeling-Based (NSASL) Renal Magnetic Resonance Angiography (MRA): Development and Clinical Feasibility Evaluation
Full text linkBackgroundNon-contrast renal MR angiography (MRA) is valuable for patients who cannot receive contrast agents or when avoiding radiation is desired. However, the conventional inflow inversion recovery (IFIR) method is limited by incomplete background suppression, venous contamination, and motion sensitivity.PurposeTo develop and evaluate a non-subtractive arterial spin labeling-based (NSASL) sequence for renal MRA and compare it with IFIR in healthy volunteers, with exploratory feasibility assessment relative to contrast-enhanced (CE)-MRA or computed tomography angiography (CTA) in patients.Study TypeProspective.SubjectsThirty healthy volunteers (10 male, 35.6 ±14.0 years) and six participants with renal diseases or high blood pressure (2 male, 62.7 ±9.03 years).Field Strength/Sequence1.5 T; 3D stack-of-stars balanced steady-state free precession (bSSFP) NSASL MRA, 3D Cartesian bSSFP IFIR MRA, and CE-MRA.AssessmentThree radiologists independently rated image quality (main and branch renal arteries visualization, motion artifacts, vessel-to-background contrast, diagnostic confidence) on a 5-point scale. SNR efficiency (or SNR and time) and contrast ratio (CR) were also measured.Statistical TestsIntraclass coefficient (ICC), Shapiro–Wilk's test, paired Student's t-test, and Wilcoxon signed-rank test with Bonferroni correction, with p < 0.05 considered statistically significant.ResultsICC was good to excellent (ICC = 0.61–0.89) for average subjective scores. Compared with IFIR, NSASL showed significantly better vessel-to-background contrast (approximately fivefold increase in CR, Cohen's |d| = 2.54; +1 subjective score, |r| = 0.88), improved renal arteries visualization (+0.7 points, |r| = 0.67, corrected p ≤ 0.003), fewer motion artifacts (+0.6 points, |r| = 0.67, corrected p = 0.002), and higher diagnostic confidence (+0.6 points, |r| = 0.80, corrected p < 0.001). Acquisition time was reduced from 267.3 ± 69.0 s to 240.2 ± 51.3 s (Cohen's |d| = 0.54, corrected p = 0.018) while SNR efficiency was moderately lower (~26%, Cohen's |d| = 1.99, corrected p = 0.002). In participants with disease, NSASL yielded similar diagnostic confidence to CE-MRA (n = 4, +0.7 points, p = 0.194) and to CTA (n = 2, −0.2 points, p = 0.317).Data ConclusionNSASL significantly outperformed IFIR, with improved background suppression, vessel conspicuity, motion tolerance, and scan time in healthy volunteers
Comparison of safety and efficacy of liberal versus restrictive red blood cell transfusion thresholds on the quality of life in patients with myelodysplastic syndromes: a systematic review and meta-analysis
Full text linkMyelodysplastic syndromes (MDS) are clonal stem cell disorders managed by risk stratification: lower-risk disease receives erythropoiesis-stimulating agents; higher-risk disease receives azacitidine. Red blood cell (RBC) transfusions manage symptomatic anaemia and improve quality of life (QoL) but carry risks of iron overload and alloimmunisation. No standardised transfusion strategy exists, requiring systematic evidence synthesis comparing liberal versus restrictive haemoglobin (Hb) thresholds for their effects on quality of life and transfusion-related complications. We performed a systematic review evaluating liberal versus restrictive RBC transfusion thresholds in adults with MDS not undergoing curative treatment such as stem cell transplantation. Primary outcome was health-related QoL measured by validated instruments. Secondary outcomes included mortality, transfusion reaction, iron overload, RBC utilisation and rise in ferritin level. Of 4,295 records screened, 212 articles underwent full-text review, with three RCTs meeting inclusion criteria. Liberal transfusion strategies were associated with improved QoL compared to restrictive approaches, with pooled standardised mean difference (Hedges g) of 0.54 (95% CI 0.06–1.02; p = 0.33; I²=9.7%). Subgroup analysis of EQ‑5D outcomes across studies revealed minimal but statistically significant difference between strategies (pooled mean difference 0.084; 95% CI: 0.033 to 0.134). Mortality (hazard ratio 0.913; 95% CI 0.167–4.98) and transfusion reactions (risk difference − 0.01; 95% CI-0.10 to 0.09) did not differ. Notably, liberal thresholds required average of 4 additional RBC units per patient (95% CI 1.43–6.79), raising concerns about iron overload (rise in ferritin; mean difference 868 µg/L; 95% CI 482–1255). Limited evidence suggests that liberal transfusion strategies in MDS may improve short-term QoL but at the cost of increased transfusion burden, with no clear impact on survival or safety. A patient-centred, multidisciplinary approach remains essential when tailoring transfusion thresholds
Guts, grit and God? Spiritual capital and entrepreneurial resilience in a turbulent environment
Full text linkEntrepreneurs operating in turbulent environments face significant uncertainty, resource constraints and institutional instability, requiring innovative coping mechanisms. Although resilience research has traditionally focused on tangible and network-based resources, the role of spiritual capital as a critical, yet largely unexplored, resource for entrepreneurial action remains insufficiently understood. This study addresses this gap by investigating how spiritual capital functions as a distinct yet complementary intangible resource alongside social capital in shaping entrepreneurial resilience. Using a cross-sectional survey of 622 entrepreneurs in Lagos, Nigeria, a setting marked by economic and political volatility, the study employs structural equation modelling (SEM) to assess the direct and mediating effects of spiritual capital on resilience. The findings indicate that spiritual capital significantly enhances entrepreneurial resilience, particularly in fostering psychological stability, perseverance and adaptive capacity. Moreover, the study reveals that although bonding social capital strengthens resilience through emotional and resource-based support, its effect is mediated by spiritual capital, which provides deeper existential motivation. Bridging social capital also plays a role but is less significant when spiritual capital is present, suggesting that in environments where external networks are weak or inaccessible, spiritual capital acts as a stabilizing force. The study contributes to the resource-based view (RBV) by demonstrating that resilience is shaped not only by firm-level resources but also by deeply embedded internally cultivated assets. Practically, the findings highlight the importance of integrating spirituality and psychological resilience mechanisms into entrepreneurship support programs, particularly in volatile institutional contexts
An extrapolative machine learning framework for forecasting nitrogen oxide mitigation in alcohol enhanced ammonia-methane blends
Full text linkAs carbon-free energy carrier, combustion of ammonia suffers from low burning rates, poor flame stability, and excessive nitrogen oxide (NOx) emissions. Although blending with hydrocarbon fuels such as methane alleviates some drawbacks, NOx formation remains a critical barrier. To address these challenges, we propose a hybrid framework combining reactive force field molecular dynamics (ReaxFF-MD) simulations with machine learning (ML). MD simulations at 2000-3000 K were performed for ammonia-methane blended combustion with 0-10% addition of ethanol or methanol. Adding alcohols suppressed the NOx formation by altering charge redistributions and redirecting nitrogen intermediates into stabilising pathways. Particularly at 3000 K, 10% ethanol and methanol reduced NOx by ∼39.5% and ∼30.1%, respectively. Both chemical and physical descriptors derived from MD were used to train ML models and successfully predicted NOx trends at intermediate compositions (2%, 7%, 12%) with <5% error for ethanol-rich mixtures, though predictions beyond 12% require further validation. This framework reduces reliance on costly simulations while providing mechanistic insights and predictive capability of designing alternative fuels
Nanoparticle-mediated antagonism of sustained endosomal signaling of the calcitonin receptor-like receptor provides enhanced and persistent relief of oral cancer pain
Full text linkBy improving the delivery and tumor retention of chemotherapeutics, nanomedicines hold potential for cancer treatment. The usefulness of nanoparticle (NP)-encapsulated analgesics for the cancer pain treatment is comparatively unexplored. We investigated whether NPs encapsulating olcegepant (OCP), an antagonist of the calcitonin receptor-like receptor (CLR) for the calcitonin gene-related peptide (CGRP), effectively relieved oral cancer pain in mice. Because persistent endosomal CLR signaling in Schwann cells mediates craniofacial pain, we reasoned that the predisposition of NPs to accumulate in endosomes could be leveraged to effectively relieve oral cancer pain. By expressing biosensors for activated CLR, Gα proteins and β-arrestins in HEK293T and Schwann cells, we found that CGRP activates CLR signaling first at the plasma membrane and then in early, late and recycling endosomes and the cis- and trans-Golgi apparatus. We synthesized biocompatible NPs encapsulating OCP and fluorophores by integrating hydrophobic ion pairing nanoformulation with Flash NanoPrecipitation. NPs slowly released OCP and accumulated in early endosomes, leading to sustained inhibition of endosomal CLR signaling in HEK293T and Schwann cells. Oral cancers were established in mice, which led to heightened pain-like responses. After intra-tumoral injection, NPs were retained in tumors for at least one week. OCP-loaded NPs almost completely reversed allodynia and hyperalgesia for a prolonged period, whereas unencapsulated OCP had small and transient effects. The NP accumulation in endosomal sites of pain signaling, the sustained release of antagonist, and the retention of NPs in tumors explain their beneficial actions. Thus, NP-encapsulation holds promise for the relief of painful cancers that are inadequately treated by opioids
Integration of the Global Water and Lake Sectors within the ISIMIP framework through scaling of streamflow inputs to lakes
Full text linkClimate change impacts both lakes and their surrounding catchments, leading to altered discharge and nutrient loading patterns from catchments to lakes, as well as modified thermal stratification and mixing dynamics within lakes. These alterations affect biogeochemical processes and water quality in lakes. Coupled catchment-lake modeling provides both a holistic evaluation of the effects of climate change on lakes and a framework for explicitly assessing the importance of how catchments effect lakes. The Inter-Sectoral Impact Model Intercomparison Project (ISIMIP) provides a framework for projecting the impacts of climate change across multiple sectors (e.g. water, lakes, energy, health) of the Earth System consistently, enabling integrated cross-sectoral assessments. However, climate impacts on lake dynamics are modeled in ISIMIP without consideration of the links between lakes and the surrounding catchments. This is a significant limitation, as it restricts assessments to only the direct impacts of climate change on lakes, overlooking the critical interactions between lakes and their catchment areas. In this study, we establish the first dynamic connection between the Global Water and Lake Sectors in ISIMIP, achieved by scaling the gridded modeled outputs of water fluxes from the Global Water Sector to the catchments of the representative lakes of the Lake Sector. The streamflow to the representative lake of each grid cell, as defined by the ISIMIP Global Lake Sector, was calculated based on runoff proportional to the catchment area of each representative lake. If the lake surface area was larger than the grid cell area, water from upstream grid cells was included as the corresponding proportion of river discharge. The methodology was applied to 70 lakes across Sweden covering a wide range of sizes, hydrological settings and catchment characteristics. The estimated streamflow was validated against both the streamflow outputs from the hydrological model HYPE and observed data. The comparison demonstrated good agreement in terms of long-term streamflow mean and seasonal pattern, indicating that the proposed approach is capable of producing reliable streamflow estimates without requiring high-resolution local models. This estimated streamflow, representing water flow into lakes, will provide a valuable dataset for the scientific community within the ISIMIP Lake Sector supporting hydrological and water quality modeling efforts aimed at understanding the impacts of climate change on lakes
Robotic end-effectors for manufacturing: Recent developments and future research challenges
No full textIndustrial robots excel at replicating human movements, with robotic arms mimicking the human arm and end-effectors replicating the hand. While robot arm designs offer versatility, end-effectors, typically designed for specific tasks, lack this flexibility. Despite numerous review papers focusing on specific applications or aspects of robotic end-effectors -such as agriculture, surgery, space, grinding, or control methods - a clear gap remains: the lack of a comprehensive review that integrates design, modeling, and control across diverse manufacturing applications. This paper reviews the state-of-the-art in robotic end-effectors, exploring their design variations and the enabling technologies that power them. The review categorises end-effectors based on their applications, including finishing, machining (traditional and non-traditional), additive manufacturing and grasping end-effectors. In each category we highlight the key design considerations for optimal performance. Beyond their application-specific designs, the paper explores the enabling technologies that shape end-effector capabilities. Sensors, the "eyes and ears," provide crucial information on the environment through force sensors and vision systems. Actuators, the "muscles," convert electrical signals into movement using pneumatics, hydraulics, or increasingly popular electric mechanisms. The paper concludes by discussing the modelling and control aspects of end-effectors. Kinematic, dynamic, and stiffness models are explored as crucial tools for designing and analysing these versatile tools, ensuring optimal functionality, accuracy, and efficiency. Finally, control tools act as the conductor, orchestrating the entire operation, and translating commands into real-time actions. This review emphasises the importance of end-effectors in expanding robot capabilities and highlights the intricate interplay of design and enabling technologies that drive their development
Evaluating training for occupational therapists and clinical psychologists to deliver vocational rehabilitation within a clinical trial: mixed-methods study
No full textBackground: Delayed return-to-work is common after serious injury. Vocational rehabilitation (VR) supports people to return to/remain in work. We developed training for occupational therapists (OTs) and clinical psychologists (CPs) to deliver a VR intervention (Return to Work After Trauma-ROWTATE) to UK trauma patients within a large-scale randomised controlled trial. Objectives: Evaluate the training, OT/CP competence and confidence to deliver ROWTATE, attitudes/confidence in evidence-based practice (EBP).Methods: Competency was assessed through Team Objective Structured Clinical Examination and two tasks (management plan, employer letter). Intraclass correlation coefficients (ICCs) estimated inter-rater reliability. Questionnaires measured EBP attitudes (EBPAS-36) and confidence (EPIC) pre and post-training and confidence in ROWTATE delivery post-training. Semi-structured interviews captured training experiences and confidence. Results: 47 OTs and 16 CPs completed training. Competency scores were high (OT range=27.5-37.5; CP range=28.5-37; maximum=38). Inter-rater reliability was moderate (OT ICC=0.56, 95%CI 0.18,0.77; CP ICC=0.73, 95%CI -0.22,0.93). EBPAS-36 scores were high pre and post-training with no significant increase post-training. OT confidence in applying evidence (P=0.01) and evaluating effect of their actions (P=0.04) increased significantly post-training. OTs and CPs had high confidence (80-100% across questions) in delivering ROWTATE. Conclusions: VR training resulted in high competency scores, improvements in EBP confidence and high confidence in delivering ROWTATE
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