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Direct thermal imaging of domain wall hot spots in LiNbO<sub>3</sub>
No full textFerroelectric domain wall devices offer a promising route to low-voltage, reconfigurable nanoelectronics by confining currents to nanoscale conducting interfaces within an insulating bulk. However, the potential for resistive heating and unregulated temperature increases due to domain wall conduction remains unexplored. Here, scanning thermal microscopy is employed to directly image hot spots in thin-film lithium niobate domain wall devices. Piezoresponse force microscopy shows that the hot spots correlate with nanodomain structure, and thermal mapping reveals surface temperature rises of ≈20 K at most, levels that are unlikely to negatively affect device performance. This is due to the moderate electrical conductivity of domain walls, their voltage-tunable erasure, and distributed current pathways, which inherently limit power dissipation and peak temperatures. Finite element electrothermal modelling indicates that domain walls behave as pseudo-planar heat sources, distinct from the filament-based heating typically observed in resistive switching oxides. These findings highlight the potential for domain wall devices as an energy-efficient, thermally stable platform for emerging memory and logic applications
Mixed methods realist evaluation of a co-designed intervention to promote shared decision-making with frail older adults, planning discharge from hospital: a protocol
No full textBackgroundEffective planning for hospital discharge can best be achieved through shared decision-making (SDM): providing tailored, person-centred, strengths-based choice to allow for individuals to make fully informed decisions, with input from their relatives if they wish. Decisions such as care management, emergency planning and caregiver involvement. However, SDM is challenging for healthcare professionals and patients, particularly older people living with frailty. There is currently no consensus on the optimum way to achieve SDM, as the quality of evidence for interventions is minimal.AimThis protocol outlines a project that aims to co-design a multi-component intervention to prepare health professionals, patients, and patients’ carers to engage in SDM and to evaluate the feasibility of implementing the intervention using realist methods.MethodsThe research will be conducted in a health and social care trust in Northern Ireland with frail, older adults who are planning their discharge from hospital. The project will proceed in three stages. (1) Realist review of the literature will enable formulation of initial programme theory, including the impact of context and the identification of uncertainties. (2) Co-design of the intervention will ensure the inclusion of diverse stakeholders in the development of the intervention, with further development of the programme theory. (3) Implementation and feasibility testing of implementation processes, measurement of intervention costs, testing of outcome measures, and refinement of the programme theory.OutcomesIn line with MRC guidance for complex interventions we will seek insights to help refine the SDM intervention. The overall outcome evaluation will be guided by the ‘Quintuple Aim’ framework, which has five aims of seeking to advance health equity, enhance patient experience, improve health, reduce costs, and improve the work life of healthcare professionals.PROSPERO(International Prospective Register of Systematic Reviews) registration number CRD42024541455.<br/
Nrf2–Keap1 pathway and NLRP3 inflammasome in Parkinson’s disease: mechanistic crosstalk and therapeutic implications
No full textNeurodegenerative disorders such as Parkinson’s disease (PD) are characterized by the progressive degeneration of dopaminergic neurons, which is driven primarily by oxidative stress and chronic neuroinflammation. Central to the cellular antioxidant defense system is the nuclear factor erythroid 2–related factor 2 (Nrf2)–Kelch-like ECH-associated protein 1 (Keap1) pathway, which mitigates oxidative damage and preserves mitochondrial integrity. Concurrently, the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome acts as a key mediator of innate immune responses and has been increasingly implicated in neuroinflammatory cascades leading to neuronal loss in PD. Emerging evidence indicates a mechanistic interplay between the Nrf2–Keap1 axis and the NLRP3 inflammasome, wherein Nrf2 activation not only counteracts oxidative stress but also suppresses NLRP3-mediated inflammatory signaling. A comprehensive overview of the molecular crosstalk between the Nrf2 and NLRP3 pathways in the pathogenesis of PD, with emphasis on how impaired Nrf2 signaling exacerbates NLRP3 inflammasome activation, is provided. The preclinical and clinical findings on pharmacological agents that activate Nrf2 or inhibit NLRP3 as potential neuroprotective strategies in PD are also discussed. A growing body of evidence underscores the dual therapeutic benefit of targeting oxidative stress and inflammation via Nrf2 inducers and NLRP3 inhibitors. Nonetheless, obstacles such as restricted blood–brain barrier permeability, unintended effects, and variable clinical trial outcomes hinder the application of these findings in clinical settings. The advancement of disease-modifying therapies for PD hinges on continuous research aimed at deepening the mechanistic understanding of the Nrf2–NLRP3 axis and refining pharmacological strategies.<br/
Correction: Biocatalytic conversion of lignin model oligomer using a laccase-mediator system
No full text[This corrects the article DOI: 10.1039/D4GC01720J.]. [Abstract copyright: This journal is © The Royal Society of Chemistry.
Development of vismodegib-loaded PLGA nanoparticles for the treatment of pancreatic cancer: formulation and in vitro assessment in co-culture monolayers and spheroids
No full textThe desmoplastic tumour microenvironment (TME) is a defining feature of pancreatic cancer and serves as a major barrier to drug delivery and efficacy. Vismodegib is a clinically approved drug that targets the Hedgehog pathway via its receptor, Smoothened. This pathway is activated in cancer-associated fibroblasts (CAFs), one of the main cell types in the TME. In this study, vismodegib was loaded into PLGA nanoparticles to improve its solubility and enhance the efficacy of the chemotherapeutic drug gemcitabine. Vismodegib-loaded PLGA nanoparticles (Vis-PLGA NPs) were prepared and optimised based on PLGA polymer, drug to polymer ratio and formulation method. Vis-PLGA NPs formulated by the single emulsion method improved the encapsulation efficiency from 36% to 86% when compared to nanoprecipitation. More importantly, the drug release profile demonstrated a slower burst release, with sustained release for the single emulsion method at 35% vs. 86% for nanoprecipitation after 48 h. In pancreatic stellate cells, Vis-PLGA NP treatment selectively inhibited 2D co-cultured-induced Hh pathway activation via the effector glioma-associated protein 1 (Gli1) when compared to free vismodegib. More importantly, Vis-PLGA NPs enhanced gemcitabine efficacy as a sequential treatment by prolonging spheroid growth inhibition, combined with a higher apoptotic cell population compared to gemcitabine single treatment (10.3% vs. 7.5%). This increase in apoptosis was not observed with free vismodegib pre-treatment compared to gemcitabine alone. These promising results provide a platform for further in vitro characterisation and in vivo studies of Vis-PGLA NPs for pancreatic cancer treatment
Pelodera: cosmopolitan phoretic saprotrophs and neglected models for origins of nematode parasitism
No full textPelodera (A. Schneider, 1866) is a Clade V nematode genus of the Rhabditidae family and close relative of Caenorhabditis elegans. The genus comprises 26 species poised between free-living, commensal, and parasitic lifestyles, as well as species with underappreciated roles in soil nutrient cycling. Pelodera strongyloides, the type species, is a cause of follicular larva migrans among humans and other mammals but can be confused with hookworm folliculitis. With minimal genetic resources available, the capacity to identify and diagnose infectious species and strains of Pelodera are limited. Thus, the ecology of Pelodera species as both parasites and commensalists is likely underreported and possibly mischaracterised. Similarly, decomposition biome studies report Pelodera and other Rhabditidae as dominant taxa during decay but require greater genetic resources to classify species. To renew appreciation for these neglected model organisms, this review collates available literature to detail Pelodera associations across mammalian and invertebrate hosts and discusses traits that drive host association such as dauer formation, waving (nictation), phoresy, and tissue invasion. The potential for Pelodera as a satellite model to C. elegans is also discussed since Pelodera are readily culturable while having inducible parasitic forms. Research into Pelodera will not only improve understanding of their ecology and contribution to decomposition but may prove invaluable in identification of behaviours underpinning parasitism and parasite origins. Utilising Pelodera facultative parasites may be essential to triangulate and resolve differences between C. elegans and obligate nematode parasites with similar niches such as hookworms, lungworms, Strongyloides, and gastrointestinal nematodes of livestock.<br/
Enhancing diagnostic yield in functional seizures: A narrative review, design and implementation of a novel ictal testing battery for video telemetry
No full textEvaluation of behavioural impairment during functional seizures (FS) is critical for medical decision making, including accurate diagnosis, and future management recommendations. To date this type of behavioural evaluation in the setting of FS in an inpatient telemetry unit has not been closely reviewed. Here we perform a narrative review of the literature examining ictal testing and how best to improve diagnostic yield in the context of FS. We propose a novel ictal testing battery to obtain the most pertinent clinical information in people with functional seizures (PWFS). We then applied this novel ictal testing battery to patients as part of a service improvement project and compared it with the standard procedures in the video telemetry (VT) unit. This demonstrated significant improvement (Student's T-Statistic of 2.284 and a p-value of 0.014) in the amount of FS-specific information extracted as identified in the review, suggesting that such a battery is useful and can be utilised in the VT setting
Projected hospitalization cost impact of the selective cytopheretic device in pediatric acute kidney injury
No full textThe Selective Cytopheretic Device for Pediatrics (SCD-PED) is a cell-directed extracorporeal therapy approved by the Food and Drug Administration through the humanitarian device exemption pathway for patients≥10kg, age≤22 years with acute kidney injury due to sepsis or a septic condition requiring antibiotics and on continuous renal replacement therapy (CRRT). We leveraged the Kids' Inpatient Database (KID) and SCD-PED study data to estimate hospitalization costs with and without SCD-PED therapy. A cost regression model was built from KID hospitalizations (2019) that included patients aged 1-20 years with AKI receiving CRRT, total parenteral nutrition, KID mortality risk=4, KID severity=4, and hospital length of stay (LOS) ≤60 days. Data assessed as cost predictors included patient age, sex, vasopressor use, mechanical ventilation, sepsis, theoretical SCD-PED cost/number used, LOS, and death at hospital discharge. Differences in mean costs between a matched control cohort from the Prospective Pediatric CRRT registry (ppCRRT) and the SCD-PED study cohort were estimated from the model using SCD-PED study mortality rates and LOS reported in the SCD-PED studies. Modeled hospitalization costs were 389,451 in ppCRRT ( = 210). Median hospital LOS was lower in the SCD-PED group ( = 22): 28 days vs. 31 days in the control group, which despite the lower mortality rate, resulted in a lower estimated cost of 69,146 per hospitalization. The model in the current study compares patients using SCD-PED to an external control cohort with similar characteristics, because controls were not examined in the original clinical studies. This study is not intended to be predictive of costs in other patient types or larger populations. Additional study is needed. The SCD-PED is likely cost-beneficial in critically ill children with AKI requiring CRRT, including those with sepsis
Social‐symbolic work of engaging heterogeneous communities: participation work and entangled effects on organizations and communities
No full textCommunity participation is recognized as a crucial yet problematic element for addressing many issues in social development. Generating participation, however, is particularly challenging due to existing inequalities within heterogeneous communities, making it difficult for organizations to engage marginalized groups while letting go of their own control. We explore how organizations facilitate community participation through a qualitative comparative case study of two community radio stations in India. We find two approaches based on how organizations leverage three levels of influence: (1) open participation work leverages community members as audience and volunteers/staff by drawing on commonality between them. Furthermore, it defers decision making to community hierarchy; (2) protective participation work engages audience and volunteers/staff from marginalized groups, focusing on their differences from other community members, and defies community hierarchy in decision making. These two approaches led to contrasting outcomes: open participation work led to a pliable organization that invited the community in, but preserved community inequalities, and protective participation work led to a directive organization that restricted participation, but disrupted community inequalities. In unpacking these approaches, we extend the social‐symbolic work literature by theorizing how participation work creates entangled effects on the organization and community
