103 research outputs found
Reference to index of Book 3. Poetry, 1891,Translation from Horace to Chloris: Ode XV - 'Thou of poor Ibycus the wife'.
Book 3. Poetry, 1891,Translation from Horace to Chloris: Ode XV - 'Thou of poor Ibycus the wife'
Tios: The Internet of Simulations. Turning Molecular Dynamics into a Data Streaming Web Application
The configuration of most current academic high-performance computing (HPC) resources tends to enforce ways of working with, and thinking about, molecular dynamics (MD) simulations that are not always optimal. For example, when the aim of the simulation(s) is to produce a representative sample of a Boltzmann weighted ensemble, the ideal scenario would be to be able to do just that—i.e. to tap into a running simulation of indefinite length, collect data from it in real time, and only terminate the simulation once the quality of a sample was assured. Current approaches, based on batch jobs of proscribed maximum length, and a postprocessing style of data analysis, inhibit this. In the spirit of the Internet of Things, we have developed Tios, a Python application that turns MD simulations into remotely discoverable and accessible streaming web applications to which researchers can connect and download data as they please. Tios is freely available, works with standard MD codes, and requires no modifications to them. In this paper we outline how Tios works and present a number of test cases that demonstrate its capabilities
Can the optimum artificial tear treatment for dry eye disease be predicted from presenting signs and symptoms?
PURPOSE: To assess dry eye treatment with four preservative-free dry eye artificial tear treatments to facilitate evidence-based prescribing. METHODS: A randomised, single masked crossover trial of Clinitas Soothe, Hyabak, Tears Again and TheraTears artificial tears was conducted on 50 symptomatic dry eye patients, aged 60.8±14.2years. At baseline and after trialling each treatment for 4 weeks, signs and symptoms were assessed using the Ocular Surface Disease Index (OSDI), non-invasive tear break-up time, fluorescein tear break-up time, tear meniscus height (TMH), Phenol Red test, lid-parallel conjunctival folds (LIPCOF), ocular surface staining, and lipid layer grading and osmolarity (baseline visit only). RESULTS: OSDI (p=0.002), LIPCOF (p=0.014) and conjunctival staining (p<0.001) significantly improved from baseline, however, the impact of each dry eye treatment on ocular symptoms and signs was similar. Clinitas Soothe and Hyabak were preferred by 34%/30% of participants, but only subjective comparison with the other drops influenced this choice. TheraTears was preferred (by 24%) by those with a lower baseline tear volume (p=0.01) and Tears Again (by 12%) by those with a thinner baseline lipid layer (p=0.04). The treatment that afforded the greatest improvement in clinical signs did not consistently match each individual's preferred treatment. CONCLUSIONS: If prescribed to a general dry eye population, the artificial tears performed similarly, improving symptoms and conjunctival signs. However, osmolarity balanced artificial tears were the preferred treatment in individuals with low baseline tear volume and lipisomal spray for individuals with a baseline lipid layer deficiency
How should initial fit inform soft contact lens prescribing
Purpose: To investigate how initial HEMA and silicone-hydrogel (SiHy) contact lens fit on insertion, which informs prescribing decisions, reflect end of day fit. Methods: Thirty participants (aged 22.9. ±. 4.9 years) were fitted contralaterally with HEMA and SiHy contact lenses. Corneal topography and tear break-up time were assessed pre-lens wear. Centration, lag, post-blink movement during up-gaze and push-up recovery speed were recorded after 5,10,20. min and 8. h of contact lens wear by a digital slit-lamp biomicroscope camera, along with reported comfort. Lens fit metrics were analysed using bespoke software. Results: Comfort and centration were similar with the HEMA and SiHy lenses (p > 0.05), but comfort decreased with time (p 0.05), but was slower with SiHy after 8. h wear (p = 0.016). Lens movement on blink and push-up recovery speed was predictive of the movement after 8. h of wear after 10-20. min SiHy wear, but after 5 to 20. min of HEMA lens wear. Conclusions: A HEMA or SiHy contact lens with poor movement on blink/push-up after at least 10. min after insertion should be rejected
Understanding patient non-transport decision theories in the pre-hospital setting: a narrative review
© 2023 The Author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/Background In pre-hospital emergency care, decisions regarding patient non-conveyance emerged as significant determinants of healthcare outcomes and resource utilization. These complex decisions became integral to the progress of emergency medical services, thus warranting an evolving exploration within the medical discourse. Objectives and methods This narrative review aimed to synthesize and critically evaluate various theoretical stances on patient non-conveyance in the pre-hospital emergency. The focus on studies published between January 2012 and August 2022 was intentional to capture contemporary practices and insights. PubMed and Google Scholar served as the primary databases for the investigation, while the AL-Rayyan® software facilitated a thorough screening process. Results and discussion Twenty-nine studies—encompassing articles, books, and theses—were discovered through our search, each presenting unique perspectives on patient non-transport, thus highlighting its criticality as a healthcare concern. Predominant factors influencing non-transport decisions were classified into patient-initiated refusals (PIR), clinician-initiated decisions (CID), and dispatcher-initiated decisions (DID). Conclusions The issue of patient non-conveyance to hospitals continues to pose a crucial challenge to the seamless operation of emergency healthcare systems, warranting increased attention from various healthcare entities. To comprehend and pinpoint potential areas of improvement, a comprehensive analysis of pre-hospital non-transport events is imperative. A well-informed, strategic approach could prevent resource waste while ensuring patients receive the required and definitive care.Peer reviewe
Development of fluorescent peptide G protein-coupled receptor activation biosensors for NanoBRET characterization of intracellular allosteric modulators
G protein-coupled receptors (GPCRs) are widely therapeutically targeted, and recent advances in allosteric modulator development at these receptors offer further potential for exploitation. Intracellular allosteric modulators (IAM) represent a class of ligands that bind to the receptor–effector interface (e.g., G protein) and inhibit agonist responses noncompetitively. This potentially offers greater selectivity between receptor subtypes compared to classical orthosteric ligands. However, while examples of IAM ligands are well described, a more general methodology for assessing compound interactions at the IAM site is lacking. Here, fluorescent labeled peptides based on the Gα peptide C terminus are developed as novel binding and activation biosensors for the GPCR-IAM site. In TR-FRET binding studies, unlabeled peptides derived from the Gαs subunit were first characterized for their ability to positively modulate agonist affinity at the β2-adrenoceptor. On this basis, a tetramethylrhodamine (TMR) labeled tracer was synthesized based on the 19 amino acid Gαs peptide (TMR-Gαs19cha18, where cha = cyclohexylalanine). Using NanoBRET technology to detect binding, TMR-Gαs19cha18 was recruited to Gs coupled β2-adrenoceptor and EP2 receptors in an agonist-dependent manner, but not the Gi-coupled CXCR2 receptor. Moreover, NanoBRET competition binding assays using TMR-Gαs19cha18 enabled direct assessment of the affinity of unlabeled ligands for β2-adrenoceptor IAM site. Thus, the NanoBRET platform using fluorescent-labeled G protein peptide mimetics offers novel potential for medium-throughput screens to identify IAMs, applicable across GPCRs coupled to a G protein class. Using the same platform, Gs peptide biosensors also represent useful tools to probe orthosteric agonist efficacy and the dynamics of receptor activation
Epidemiological Determinants of Patient Non-Conveyance to the Hospital in an Emergency Medical Service Environment
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/Background: The increasing prevalence of comorbidities worldwide has spurred the need for time-effective pre-hospital emergency medical services (EMS). Some pre-hospital emergency calls requesting EMS result in patient non-conveyance. Decisions for non-conveyance are sometimes driven by the patient or the clinician, which may jeopardize the patients’ healthcare outcomes. This study aimed to explore the distribution and determinants of patient non-conveyance to hospitals in a Middle Eastern national Ambulance Service that promotes the transportation of all emergency call patients and does not adopt clinician-based non-conveyance decision. Methods: Using R Language, descriptive, bivariate, and binary logistic regression analyses were conducted for 334,392 multi-national patient non-conveyance emergency calls from June 2018 to July 2022, from a total of 1,030,228 calls to which a response unit was dispatched. Results: After data pre-processing, 237,862 cases of patient non-conveyance to hospital were retained, with a monthly average of 41.96% (n = 8799) of the emergency service demands and a standard deviation of 5.49% (n = 2040.63). They predominantly involved South Asians (29.36%, n = 69,849); 64.50% (n = 153,427) were of the age category from 14 to 44 years; 61.22% (n = 145,610) were male; 74.59% (n = 177,424) from the urban setting; and 71.28% (n = 169,552) had received on-scene treatment. Binary logistic regression with full variables and backward methods identified the final models of the determinants of patient non-conveyance decisions with an Akaike information criterion prediction estimator, respectively, of (250,200) and (250,169), indicating no significant difference between both models (Chi-square test; p-value = 0.63). Conclusions: Despite exercising a cautious protocol by encouraging patient transportation to hospital, patient non-conveyance seems to be a problem in the healthcare system that strains the pre-hospital medical response teams’ resources. Policies and regulations should be adopted to encourage individuals to access other primary care centers when required rather than draining emergency services for non-emergency situations.Peer reviewe
A randomised controlled trial of laser scanning and casting for the construction of ankle foot orthoses
Study Design: Randomised controlled trial with blinding of orthotists and patients to the construction technique used. Background: Three-dimensional laser scanning has been used for patient measurement for cranial helmets and spinal braces. Ankle foot orthoses are commonly prescribed for children with orthopaedic conditions. This trial sought to compare ankle foot orthoses produced by laser scanning or traditional plaster casting. Objectives: Assessment of the effectiveness and efficiency of using laser scanning to produce AFOs. Methods: A randomised double blind trial comparing fabrication of AFOs from casts or laser scans. Results: The time spent in the rectification and moulding of scanned AFOs was around 50% less than for cast AFOs. A non-significant increase of 9 days was seen in the time to delivery to the patient for LSCAD/CAM. There was a higher incidence of problems with the scan-based AFOs at delivery of the device, but no difference in how long the AFOs lasted. Costs associated with laser scanning were not significantly different from traditional methods of AFO manufacture. Conclusions: Compared with conventional casting techniques laser scan based AFO manufacture neither significantly improved the quality of the final product nor delivered a useful saving in time
Rapid nano-gram scale screening method of micro-arrays to evaluate drug-polymer blends using high-throughput printing technology
A miniaturized, high-throughput assay was optimized to screen polymer-drug solid dispersions using a 2-D Ink-jet printer. By simply printing nanoliter amounts of polymer and drug solutions onto an inert surface, drug:polymer micro-dots of tunable composition were produced in an easily-addressable micro-array format. The amount of material printed for each dried spot ranged from 25 ng to 650 ng. These arrays were used to assess the stability of drug:polymer dispersions with respect to recrystallization, using polarized light microscopy. One array with a panel of 6 drugs formulated at different ratios with Poly (vinylpyrrolidone-vinyl acetate) copolymer (PVPVA) was developed to estimate a possible bulk (gram-scale) approximation threshold from the final printed nano amount of formulation. Another array was printed at a fixed final amount of material to establish a literature comparison of one drug formulated with different commercial polymers for validation. This new approach may offer significant efficiency in pharmaceutical formulation screening, with each experiment in the nano-micro-array format requiring from 3 up to 6 orders of magnitude lower amounts of sample than conventional screening methods
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