151398 research outputs found
Sort by
Variation in attitudes to native kidney biopsy practice in the United States
No full textRationale & ObjectiveThere is substantial variation in kidney biopsy practices within and between countries; however, the reasons for this are unclear due to limited research among large diverse populations. The aim of this study was to explore variations in attitude to the indications and contraindications for native kidney biopsy in the United States (US).Study DesignA case-vignette questionnaire was developed. A propensity-to-biopsy score (0-44) was generated from responses to indications and contraindications, with a higher score indicating an increased likelihood to recommend biopsy. Dissemination of the questionnaire occurred by email, social media, and the National Kidney Foundation.Setting & ParticipantsA total of 295 nephrologists/fellows from 43 states within the US participated.ExposureAll participants completed an identical questionnaire on kidney biopsy practice.OutcomesResponses were collected on indications, contraindications, and attitudes to biopsy.Analytical ApproachAnonymized IP addresses were collected for comparison between US states. Data were also collected on the demographics of the individual and the type of institution in which the doctor was based.ResultsIn an adjusted multiple linear regression analysis, higher propensity-to-biopsy scores were demonstrated in US clinicians who were male, younger and more frequent performers of kidney biopsy (P = 0.05). There were significant differences between the 18 US states with 5 or more participants (P < 0.001) with the mean propensity-to-biopsy score ranging from 20.3 (Wisconsin) to 29.2 (New Jersey and Virginia). Increased biopsy propensity was also observed in US states with higher nephrologist density and lower statewide deprivation (P = 0.006).LimitationsThe condensed clinical scenarios may not accurately replicate real-world cases, and clinicians opted in often using social media, so generalizability is limited.ConclusionsAttitudes to kidney biopsy practice in the US are highly variable, and clinician or institutional characteristics do not fully explain these discrepancies. Further research is required to understand the factors that influence clinical decision making
Evaluating progesterone receptor agonist megestrol plus letrozole for women with early-stage estrogen-receptor-positive breast cancer: the window-of-opportunity, randomized, phase 2b, PIONEER trial
No full textThe use of progestogens in breast cancer has been controversial. Recent preclinical studies have shown that ligand-bound progesterone receptor interacts directly with the estrogen receptor (ER) and reprograms ER transcriptional activity. Progestogen cotreatment enhances the antitumor activity of antiestrogen therapy in mouse xenografts. We report PIONEER, a 198-participant, three-arm, randomized phase 2b window-of-opportunity study for women with early-stage ER breast cancer, which evaluated letrozole with or without megestrol at 40 mg or 160 mg daily. The primary endpoint was the change in tumor proliferation measured by Ki67 immunohistochemistry. Secondary and exploratory endpoints included a comparison of low versus higher dose of megestrol, safety, tolerability and biomarker subgroup analyses. The trial met its primary endpoint, with a greater reduction in proliferation seen when megestrol was added to letrozole. This effect was accompanied by reduced ER genomic binding at canonical binding sites in paired tumor biopsies, indicating reduced ER transcriptional activity. These results support further evaluation of low-dose megestrol, which has two mechanisms for potentially improving breast cancer outcomes in combination with standard antiestrogen therapy: alleviating hot flashes and thereby helping with treatment adherence, as well as a direct antiproliferative effect ( NCT03306472 )
Establishing a Memory Clinic Biobank Study
No full textBackgroundThe Northern Ireland Biobank was established to facilitate research access to quality-assured biological samples. Patients, with capacity to consent, are invited to give written consent for collection and retention of clinically surplus material for the purposes of research. In addition, blood can be collected for the purposes of biobanking.MethodSince May 2022 patients have been invited to donate clinically surplus cerebrospinal fluid (CSF) to the NI Biobank. Since March 2023 patients have been invited to donate blood for the purposes of biobanking. CSF is collected using the drip method into false-bottomed Starstedt tubes. Blood is collected, non-fasting, into two EDTA bottles. Both are transported at room temperature to Trust (CSF) and NI Biobank (blood) laboratories on the same day. CSF is frozen at -80C. Blood is processed within 24 hours and stored as plasma and buffy coat.ResultThus far, n = 37 participants have consented to the retention of their clinical surplus CSF. In addition, n = 105 participants have donated blood for the purposes of biobanking.The main barrier to recruitment has been the availability of staff time to facilitate the consent and sampling processes.ConclusionBiobanking of biological samples, with access to associated clinical data, provides opportunities to study real-world memory clinic cohorts. Researchers interested in accessing these samples should contact the authors
Biofilm communities above and below the cuff of endotracheal tubes are spatially homogenous
No full textBackgroundDuring mechanical ventilation, the inflated cuff of endotracheal tubes (ETTs) may help to minimise patient secretions containing microorganisms from reaching the lower trachea and distal ETT surface. The primary study aim was to determine if there were differences in biofilm formation above and below the cuff using microbial community profiling.MethodsIn this prospective observational study, ETTs were collected following extubation of mechanically ventilated critically ill adults. The biofilm community composition and structure on ETT segments were examined by culture-independent (Illumina MiSeq 16S rRNA marker-gene sequencing) and -dependent (extended-quantitative culture) methods and related to clinical variables.ResultsSixty-four participants were recruited following a median (IQR) of 3.77 (1.56–7.49) days intubation. Although participant-level differences in communities were observed, most had evidence of multispecies biofilm development on the ETT surface. Community profiling indicated that there was no difference in alpha- and beta-diversity metrics or density in paired segments from above and below the ETT cuff. Culture-independent analysis detected a greater biofilm richness and more often identified microorganisms reported with clinically-directed culture of respiratory secretions than extended-quantitative culture (82.35% vs. 52.94%). At extubation a higher community density was associated with increased richness (p = 0.01) and diversity (p = 0.03) and reduced evenness (p = 0.01) and dominance (p = 0.03), but not bacterial pathogen or yeast presence/abundance by culture. Participant characteristics were not associated with the extent of biofilm community density.ConclusionsBiofilm communities forming above and below the ETT cuff are highly individual but conserved suggesting that an inflated ETT cuff does not provide an effective microbial barrier
Demand-driven server deployment for green computing power networks: a multi-objective hierarchical optimization approach
No full textComputing Power Networks (CPNs) have become an essential network architecture for supporting emerging applications, where an efficient server deployment scheme is critical to meeting growing demands. However, existing studies on server deployment schemes overlook the significant spatiotemporal variations in renewable energy availability and electricity prices, and inadequately consider network paths and task characteristics, ultimately leading to suboptimal decisions. To bridge this gap, this paper proposes a demand-driven server deployment scheme enabled by a spatiotemporal task scheduling strategy. Firstly, for the task scheduling scheme, we leverage a demand response program to perform triple selection of computing resources, routing paths, and forwarding time. Then, for the server deployment scheme, we obtain the computing resource demand of each CPN node based on the optimized scheduling decisions and further select energy-efficient servers with low procurement costs. Due to the interdependence between the scheduling and deployment schemes, a Multi-Objective Evolutionary Algorithm (MOEA)-based hierarchical solution is developed to iteratively find the optimal deployment solution. Simulation results show that the proposed scheme significantly reduces carbon emissions and annual costs while increasing the proportion of green energy usage, outperforming benchmark methods. The findings demonstrate the effectiveness of integrating scheduling and deployment for building efficient and sustainable CPN infrastructures
Committee-structured games in a cooperative framework
No full textWe introduce the notion of committee-structured games (CSG) in a cooperative framework to analyze situations where committees affect players in generating their coalitional values. We represent the sets of committees by hypergraphs and obtain values as a function of both coalitions and hypergraphs. Based on how committee structures affect value generation, we present two models within the CSG framework. In the first model, the total value is generated by the committee set as a whole, while in the second model, it is obtained by aggregating contributions from all subsets of the set of committees. Accordingly, we define the Shapley value for the first model and the Aggregated Shapley value for the second, providing axiomatic characterizations for both. Further, we propose bidding mechanisms to show that the Shapley value and the Aggregated Shapley value for the class of CSG is a subgame perfect Nash equilibrium (SPNE) of the induced strategic game. Finally, we study an alternative Exchange Economy model by incorporating committees instead of commodities
A comprehensive review of nano-enhanced phase change materials for electric vehicle and power electronics thermal management
No full textNano-enhanced phase change materials (NEPCMs) are a novel small-scale passive technique for thermal management in electric-cars and high-power electronics. This paper summarises the innovations in materials, mechanistic-insights, and system-level performance of NEPCMs and quantifies reported advances to guide engineering execution. Nano-additives based on carbon, including graphene (40%–120%), carbon nanotubes (25%–80%), metal-oxide fillers (20%–60%) and MXenes (60%–150%), enable significant increases in thermal-conductivity, dependent on loading and dispersion-quality. The scalable-processing and low-temperature carbon-additive routes can reduce material-costs by 20%–35% compared to early laboratory-formulations and can thus match active cooling in cost-performance at moderate heat-fluxes. Performance enhancement approaches, such as hybrid PCMs, thermo-responsive and multi-functional PCMs, and their application in practical scenarios, especially in EV battery thermal control, power-electronics cooling and rapid charging are addressed. It also discusses the major issues of NEPCM implementation, including dispersion-stability, thermal-degradation and nanotoxicity, and suggests future research directions to mitigate these shortcomings.<br/
Ageing with cystic fibrosis: Challenges ahead
No full textAs life expectancy for people with cystic fibrosis continues to improve due to advances in care and CFTR modulator therapies, age-related comorbidities are emerging as new clinical challenges. This short review summarizes insights from a symposium focusing on ageing and CF at the 20th ECFS Basic Science Conference in March 2025 in Pisa, Italy. Mechanisms of ageing and their involvement in CF disease are first outlined. We then highlight two age-associated comorbidities in CF, cardiovascular disease and colorectal cancer, and outline future research directions to clarify how CF-specific and general ageing mechanisms intersect. Understanding these processes will be crucial for tailoring long-term care strategies in the ageing CF population.</p
Electrochemical synthesis of Ni-Co-W-Zr(P) quinary medium entropy alloy for enhanced hydrogen evolution reaction
No full textOver the course of history, the principles of alloying have evolved, with the past fifteen years witnessing the rise of high-entropy alloying theory, which has fundamentally transformed our approach to alloy design. Developing cost-effective and efficient electrocatalysts is critical for large-scale hydrogen production via water splitting. The Ni-Co-W-Zr-P alloy coating offers a promising alternative to noble metal-based electrocatalysts. In this study, we developed a Co-W-Zr-incorporated Ni(P) coating using the electroless plating method. The integration of Co-W-Zr into the Ni(P) matrix notably enhances the number of active sites during the hydrogen evolution reaction. Electrochemical studies revealed a low overpotential of 413.5 mV of the coating when the current density is at −10 mA cm −2 . Kinetic parameters were analyzed using EIS measurements, and a potential mechanism for the hydrogen evolution reaction (HER) was proposed. The coating demonstrated exceptional stability, with no surface degradation even after prolonged electrochemical testing, making it suitable for large or irregularly shaped electrodes required in industrial applications
Structurally and functionally optimized silk fibroin-alginate-based biomimetic scaffolds reinforced with nanobioceramics for bone tissue engineering applications
No full textIn this study, we prepared chemically crosslinked silk fibroin (SF) and sodium alginate (Alg) biomimetic scaffolds reinforced with bioceramic nanohydroxyapatite (nHAp) for bone tissue engineering (BTE) applications. The pore sizes of these scaffolds were effectively controlled by varying the composition of the SF/nHAp/Alg biocomposites. The scaffold prepared with a 40:20:40 SF: nHAp: Alg ratio exhibited excellent swelling properties, reaching over 1700% within 70 min. In vitro degradation studies demonstrated that these biomimetic scaffolds exhibited controlled degradation, taking over 30 days to achieve 50% degradation. The scaffolds also showed good mechanical properties; they maintained structural integrity and did not break, even under a load approximately 800 times their own weight. Additionally, scaffolds loaded with synthetic peptide salmon calcitonin effectively controlled initial burst release and enabled sustained therapeutics delivery for up to two weeks. The biocompatibility of the scaffolds was evaluated using in vitro cell viability and hemolysis assays, which revealed good safety for human dermal fibroblast cells and negligible toxicity to rabbit red blood cells. Importantly, the scaffolds promoted cell proliferation and alkaline phosphatase secretion in human bone marrow stem cells. Histological and immunological analyses in a scaffold-implanted mouse model have demonstrated biocompatibility, supporting osteoclastic resorption and osteoblastic mineralization by downregulating RANKL. Furthermore, the chick chorioallantoic membrane assay showed the excellent angiogenic properties of the scaffold. These results suggest that the bioceramic-reinforced SF/Alg biomimetic scaffold has significant potential for use in BTE