Search

ObjectivesNo study has explored whether availability of endoscopic retrograde cholangiopancreatography (ERCP) is adequate and equitable across US children's hospitals. We hypothesized that ERCP availability and utilization differs by geography and patient factors.MethodsHealthcare encounter data from 2009 to 2019 on children with pancreatic and biliary diseases from the Pediatric Health Information System were analyzed. ERCP availability was defined as treatment at a hospital that performed pediatric ERCP during the year of service.ResultsFrom 2009 to 2019, 37,946 children (88,420 encounters) had a potential pancreatic or biliary indication for ERCP; 7066 ERCPs were performed. The commonest pancreatic diagnoses leading to ERCP were chronic (47.2%) and acute pancreatitis (43.2%); biliary diagnoses were calculus (68.3%) and obstruction (14.8%). No ERCP was available for 25.0% of pancreatic encounters and 8.1% of biliary encounters. In multivariable analysis, children with public insurance, rural residence, or of Black race were less likely to have pancreatic ERCP availability; those with rural residence or Asian race were less likely to have biliary ERCP availability. Black children or those with public insurance were less likely to undergo pancreatic ERCP where available. Among encounters for calculus or obstruction, those of Black race or admitted to hospitals in the West were less likely to undergo ERCP when available.ConclusionsOne-in-four children with pancreatic disorders and one-in-12 with biliary disorders may have limited access to ERCP. We identified racial and geographic disparities in availability and utilization of ERCP. Further studies are needed to understand these differences to ensure equitable care.

Background There has been a resurgence of research into the potential therapeutic benefits of psychedelics for neuropsychiatric disorders. Classic psychedelics, such as psilocybin, exert complex effects on higher cognitive functions such as perception and awareness, but their impact on motor function remains unexplored. Moreover, there is a theoretical rationale for using psychedelics to promote motor retraining in certain neuropsychiatric conditions associated with motor dysfunction. This protocol paper outlines the first study to investigate the feasibility and safety of performing movement tasks during the acute effects of psilocybin in healthy participants. The findings from this study will further our understanding of the impact of psychedelics on motor function, and inform future studies that combine classic psychedelics with motor retraining in clinical populations. Methods 12 healthy participants will each receive three doses of psilocybin (between 5 and 20 mg) in a randomized order, with each dose administered at least 1 week apart. Participants, the trial physiotherapists, and statisticians will remain blinded to the psilocybin dose. A battery of measures assessing motor function will be completed during the acute drug effects. In addition, measures of safety, pre‐ and post‐dose resting‐state brain activity via functional magnetic resonance imaging, and participants' subjective experience will be assessed.

Abstract The interplay between facial age and facial identity is evident from several scenarios experienced in daily life, such as when recognising a face several decades after the last exposure. However, the link between age and identity processing, and how age perception abilities might diverge in individuals with different face processing abilities, has scarcely been considered. Furthermore, the approach used to test age perception ability may also influence outcome, but the effect of different paradigms on performance is not yet known. Across three studies, we compare super-recognisers (SRs), people with developmental prosopagnosia (DPs), and a group of neurotypical controls, on three age perception paradigms. There were no differences on the numeric age estimation task (i.e. providing precise age estimates for a series of faces; Study 1), and numeric age estimation task with added noise-distortion to stimuli (Study 2). However, SRs were more accurate when instructed to classify ambient faces as either over- or under- the age of 18 compared to both DPs and controls (Study 3). Thus, there may be nuanced differences in age processing which can be tapped into using separate paradigms; however, given that the difference is only with SRs it remains unclear to what extent these are linked to facial identity processing.

Abstract Prostate cancer treatment resistance is a significant challenge facing the field. Genomic and transcriptomic profiling have partially elucidated the mechanisms through which cancer cells escape treatment, but their relation toward the tumor microenvironment (TME) remains elusive. Here we present a comprehensive transcriptomic landscape of the prostate TME at multiple points in the standard treatment timeline employing single-cell RNA-sequencing and spatial transcriptomics data from 120 patients. We identify club-like cells as a key epithelial cell subtype that acts as an interface between the prostate and the immune system. Tissue areas enriched with club-like cells have depleted androgen signaling and upregulated expression of luminal progenitor cell markers. Club-like cells display a senescence-associated secretory phenotype and their presence is linked to increased polymorphonuclear myeloid-derived suppressor cell (PMN-MDSC) activity. Our results indicate that club-like cells are associated with myeloid inflammation previously linked to androgen deprivation therapy resistance, providing a rationale for their therapeutic targeting.

The nickel-based superalloy is a critical material in aero-engines, where enhanced durability and resistance to stress relaxation are essential. This study evaluates the effectiveness of a high-energy composite modification technique, applied through dual surface friction methods, to induce residual stress and examines the stability of this stress under medium-temperature aging conditions. GH4169 was selected and a foundational study was conducted to quantify residual stress relaxation under medium-temperature aging treatment. The surface strengthening method used was a high-energy composite modification known for its significant post-treatment effects. The specific temperatures for medium-temperature aging treatment were 425 °C and 650 °C. The test results of the residual stress field confirmed the phenomenon of residual stress relaxation under the influence of temperature. Correspondingly, the different degrees of stress relaxation caused by varying aging treatment conditions are closely related to the microstructural changes within the material. Areas with a higher number of annealing twins exhibited a more pronounced degree of residual stress relaxation. By elucidating the link between stress relaxation and microstructural changes, this research offers a theoretical foundation for optimizing surface-strengthening processes and setting optimal operational temperatures for advanced structural materials.

Background: People with aphasia are vulnerable recipients of healthcare. The nature of the communicative environment and the communication disability can adversely impact access to timely and quality healthcare. Student healthcare professionals are often underprepared to interact successfully with people with aphasia and may benefit from communication partner training (CPT). Aims: To investigate the potential effectiveness and acceptability of a brief, two-part introductory Supported Conversation for Adults with Aphasia (SCA[superscript TM])-based CPT package, delivered to a sample of students across a diverse range of healthcare disciplines. Methods & Procedures: A pre-post-within group experimental design was used to investigate the potential effectiveness and acceptability of an online CPT package (50 minute module + 1 hour workshop) for healthcare students. The Aphasia Attitudes, Strategies and Knowledge (AASK) survey measured participants' knowledge of aphasia, facilitative communication strategies and attitudes towards people with aphasia. Data were collected pre-training, following the training module and following the workshop, and 6 weeks post-training. Statistical analysis was conducted on the AASK data. In addition, participant feedback (ratings and open text responses) was collected after the workshop. Ratings were analysed descriptively, and thematic content analysis was used for open text responses. Outcomes & Results: 236 participants completed the pre-training AASK and 106 completed the AASK at subsequent time points. Statistically significant gains were demonstrated from pre- to post-module completion. Between the end of the module and the end of the workshop, some gains were maintained and others showed further statistically significantly improvements. While all gains were not maintained at the 6-week follow-up, statistically significantly improvements from pre-training scores remained evident. Student feedback was predominantly positive, with suggested improvements for training content and length. Conclusions & Implications: The results provide preliminary evidence that a brief, online CPT package can support student healthcare professionals' knowledge and attitudes towards aphasia and communicating with people with aphasia. Online training was acceptable to students and feasible as an embedded or optional component of curriculum. Ongoing training (e.g., in the form of refresher sessions) and inclusion of a skills-based component are recommended to maximize communication skill development.

Abstract Ascomycetes, basidiomycetes and deuteromycetes can degrade wood, but less attention has been paid to basidiomycetes involved in Esca, a major Grapevine Trunk Disease. Using a wood sawdust microcosm system, we compared the wood degradation of three grapevine cultivars inoculated with Fomitiporia mediterranea M. Fisch, a basidiomycete responsible for white-rot development and involved in Esca disease. The grapevine cultivar Ugni blanc was more susceptible to wood degradation caused by F. mediterranea than the cultivars Cabernet Sauvignon and Merlot. Solid-state Nuclear Magnetic Resonance (NMR) spectroscopy showed that F. mediterranea preferentially degrades lignin and hemicellulose over cellulose (preferential, successive or sequential white-rot). In addition, co-inoculation of sawdust with two cellulolytic and xylanolytic bacterial strains of Paenibacillus (Nakamura) Ash ( Paenibacillus sp. (S231-2) and P. amylolyticus (S293)), enhanced F. mediterranea ability to degrade Ugni blanc. The NMR data further showed that the increase in Ugni blanc sawdust degradation products was greater when bacteria and fungi were inoculated together. We also demonstrated that these two bacterial strains could degrade the wood components of Ugni blanc sawdust. Genome analysis of these bacterial strains revealed numerous genes predicted to be involved in cellulose, hemicellulose, and lignin degradation, as well as several other genes related to bacteria-fungi interactions and endophytism inside the plant. The occurrence of this type of bacteria-fungus interaction could explain, at least in part, why necrosis develops extensively in certain grapevine varieties such as Ugni blanc.

BackgroundProstate cancer (PCa) is a clinically heterogeneous disease. The creation of an expression-based subtyping model based on prostate-specific biological processes was sought.MethodsUnsupervised machine learning of gene expression profiles from prospectively collected primary prostate tumors (training, n = 32,000; evaluation, n = 68,547) was used to create a prostate subtyping classifier (PSC) based on basal versus luminal cell expression patterns and other gene signatures relevant to PCa biology. Subtype molecular pathways and clinical characteristics were explored in five other clinical cohorts.ResultsClustering derived four subtypes: luminal differentiated (LD), luminal proliferating (LP), basal immune (BI), and basal neuroendocrine (BN). LP and LD tumors both had higher androgen receptor activity. LP tumors also had a higher expression of cell proliferation genes, MYC activity, and characteristics of homologous recombination deficiency. BI tumors possessed significant interferon γactivity and immune infiltration on immunohistochemistry. BN tumors were characterized by lower androgen receptor activity expression, lower immune infiltration, and enrichment with neuroendocrine expression patterns. Patients with LD tumors had less aggressive tumor characteristics and the longest time to metastasis after surgery. Only patients with BI tumors derived benefit from radiotherapy after surgery in terms of time to metastasis (hazard ratio [HR], 0.09; 95% CI, 0.01-0.71; n = 855). In a phase 3 trial that randomized patients with metastatic PCa to androgen deprivation with or without docetaxel (n = 108), only patients with LP tumors derived survival benefit from docetaxel (HR, 0.21; 95% CI, 0.09-0.51).ConclusionsWith the use of expression profiles from over 100,000 tumors, a PSC was developed that identified four subtypes with distinct biological and clinical features.Plain language summaryProstate cancer can behave in an indolent or aggressive manner and vary in how it responds to certain treatments. To differentiate prostate cancer on the basis of biological features, we developed a novel RNA signature by using data from over 100,000 prostate tumors-the largest data set of its kind. This signature can inform patients and physicians on tumor aggressiveness and susceptibilities to treatments to help personalize cancer management.

Not available.

The advancement of self-driving technologies facilitates the emergence of autonomous minibuses (ABs) in public transportation, which could provide flexible, reliable, and safe mobility services. This study develops an AB routing and scheduling model considering each passenger’s arrival reliability and travel risk. Firstly, to guarantee each passenger’s arrival on time, the arrival reliability (a predetermined threshold of on-time arrival probability of α ​= ​0.9) is included in the constraints. Secondly, three objectives, including system costs, greenhouse gas (GHG) emissions, and travel risk, are optimized in the model. To assess the travel risk of ABs, an enhanced method based on kernel density estimation (KDE) is proposed. Thirdly, an advanced multi-objective adaptive large neighborhood search algorithm (MOALNS) is designed to find the Pareto optimal set. Finally, experiments are conducted in Shanghai to validate model performance. Results show that it can decrease GHG emissions (−2.12%) and risk (−9.47%), while only increasing costs by 2.02%. Furthermore, the proposed arrival reliability constraint can improve an average of 14.70% of passengers to meet their arrival reliability requirement (α ​= ​0.9).