602 research outputs found
How safe are clinical systems?
Th is study was commissioned by the Health Foundation to examine the extent, type and causes of failures in reliability in different healthcare systems: failures which have the potential to create risk or cause patient harm
Simulation-Based Design of Bicuspidization of the Aortic Valve
Objective: Severe congenital aortic valve pathology in the growing patient
remains a challenging clinical scenario. Bicuspidization of the diseased aortic
valve has proven to be a promising repair technique with acceptable durability.
However, most understanding of the procedure is empirical and retrospective.
This work seeks to design the optimal gross morphology associated with surgical
bicuspidization with simulations, based on the hypothesis that modifications to
the free edge length cause or relieve stenosis.
Methods: Model bicuspid valves were constructed with varying free edge
lengths and gross morphology. Fluid-structure interaction simulations were
conducted in a single patient-specific model geometry. The models were
evaluated for primary targets of stenosis and regurgitation. Secondary targets
were assessed and included qualitative hemodynamics, geometric height,
effective height, orifice area and prolapse.
Results: Stenosis decreased with increasing free edge length and was
pronounced with free edge length less than or equal to 1.3 times the annular
diameter d. With free edge length 1.5d or greater, no stenosis occurred. All
models were free of regurgitation. Substantial prolapse occurred with free edge
length greater than or equal to 1.7d.
Conclusions: Free edge length greater than or equal to 1.5d was required to
avoid aortic stenosis in simulations. Cases with free edge length greater than
or equal to 1.7d showed excessive prolapse and other changes in gross
morphology. Cases with free edge length 1.5-1.6d have a total free edge length
approximately equal to the annular circumference and appeared optimal. These
effects should be studied in vitro and in animal studies
Randomized phase II study investigating pazopanib versus weekly paclitaxel in relapsed or progressive urothelial cancer
Purpose:
Two previous single-arm trials have drawn conflicting conclusions regarding the activity of pazopanib in urothelial cancers after failure of platinum-based chemotherapy.
Patients and Methods:
This randomized (1:1) open-label phase II trial compared the efficacy of pazopanib 800 mg orally with paclitaxel (80 mg/m2 days 1, 8, and 15 every 28 days) in the second-line setting. The primary end point was overall survival (OS).
Results:
Between August 2012 and October 2014, 131 patients, out of 140 planned, were randomly assigned. The study was terminated early on the recommendation of the independent data monitoring committee because of futility. Final analysis after the preplanned number of deaths (n = 110) occurred after a median follow-up of 18 months. One hundred fifteen deaths had occurred at the final data extract presented here. Median OS was 8.0 months for paclitaxel (80% CI, 6.9 to 9.7 months) and 4.7 months for pazopanib (80% CI, 4.2 to 6.4 months). The hazard ratio (HR) adjusted for baseline stratification factors was 1.28 (80% CI, 0.99 to 1.67; one-sided P = .89). Median progression-free survival was 4.1 months for paclitaxel (80% CI, 3.0 to 5.6 months) and 3.1 months for pazopanib (80% CI, 2.7 to 4.6 months; HR, 1.09; 80% CI, 0.85 to 1.40; one-sided P = .67). Discontinuations for toxicity occurred in 7.8% and 23.1% for paclitaxel and pazopanib, respectively.
Conclusion:
Pazopanib did not have greater efficacy than paclitaxel in the second-line treatment of urothelial cancers. There was a trend toward superior OS for paclitaxel
ColabFit Exchange: open-access datasets for data-driven interatomic potentials
Data-driven (DD) interatomic potentials (IPs) trained on large collections of
first principles calculations are rapidly becoming essential tools in the
fields of computational materials science and chemistry for performing
atomic-scale simulations. Despite this, apart from a few notable exceptions,
there is a distinct lack of well-organized, public datasets in common formats
available for use with IP development. This deficiency precludes the research
community from implementing widespread benchmarking, which is essential for
gaining insight into model performance and transferability, while also limiting
the development of more general, or even universal, IPs. To address this issue,
we introduce the ColabFit Exchange, the first database providing open access to
a large collection of systematically organized datasets from multiple domains
that is especially designed for IP development. The ColabFit Exchange is
publicly available at \url{https://colabfit.org/}, providing a web-based
interface for exploring, downloading, and contributing datasets. Composed of
data collected from the literature or provided by community researchers, the
ColabFit Exchange consists of 106 datasets spanning nearly 70,000 unique
chemistries, and is intended to continuously grow. In addition to outlining the
software framework used for constructing and accessing the ColabFit Exchange,
we also provide analyses of data, quantifying the diversity and proposing
metrics for assessing the relative quality and atomic environment coverage of
different datasets. Finally, we demonstrate an end-to-end IP development
pipeline, utilizing datasets from the ColabFit Exchange, fitting tools from the
KLIFF software package, and validation tests provided by the OpenKIM framework
Critical Exponents for Diluted Resistor Networks
An approach by Stephen is used to investigate the critical properties of
randomly diluted resistor networks near the percolation threshold by means of
renormalized field theory. We reformulate an existing field theory by Harris
and Lubensky. By a decomposition of the principal Feynman diagrams we obtain a
type of diagrams which again can be interpreted as resistor networks. This new
interpretation provides for an alternative way of evaluating the Feynman
diagrams for random resistor networks. We calculate the resistance crossover
exponent up to second order in , where is the spatial
dimension. Our result verifies a
previous calculation by Lubensky and Wang, which itself was based on the
Potts--model formulation of the random resistor network.Comment: 27 pages, 14 figure
Nanometer-scale mapping of irreversible electrochemical nucleation processes on solid Li-ion electrolytes
Electrochemical processes associated with changes in structure, connectivity or composition typically proceed via new phase nucleation with subsequent growth of nuclei. Understanding and controlling reactions requires the elucidation and control of nucleation mechanisms. However, factors controlling nucleation kinetics, including the interplay between local mechanical conditions, microstructure and local ionic profile remain inaccessible. Furthermore, the tendency of current probing techniques to interfere with the original microstructure prevents a systematic evaluation of the correlation between the microstructure and local electrochemical reactivity. In this work, the spatial variability of irreversible nucleation processes of Li on a Li-ion conductive glass-ceramics surface is studied with ~30 nm resolution. An increased nucleation rate at the boundaries between the crystalline AlPO4 phase and amorphous matrix is observed and attributed to Li segregation. This study opens a pathway for probing mechanisms at the level of single structural defects and elucidation of electrochemical activities in nanoscale volumes
Presence of acyl-homoserine lactones in 57 members of the Vibrionaceae family
Aims: The aim of this study was to use a sensitive method to screen and
quantify 57 Vibrionaceae strains for the production of acyl-homoserine lactones
(AHLs) and map the resulting AHL profiles onto a host phylogeny.
Methods and Results: We used a high-performance liquid chromatography–
tandem mass spectrometry (HPLC-MS/MS) protocol to measure AHLs in
spent media after bacterial growth. First, the presence/absence of AHLs
(qualitative analysis) was measured to choose internal standard for subsequent
quantitative AHL measurements. We screened 57 strains from three genera
(Aliivibrio, Photobacterium and Vibrio) of the same family (i.e. Vibrionaceae).
Our results show that about half of the isolates produced multiple AHLs,
typically at 25–5000 nmol l-1
.
Conclusions: This work shows that production of AHL quorum sensing
signals is found widespread among Vibrionaceae bacteria and that closely
related strains typically produce similar AHL profiles.
Significance and Impact of the Study: The AHL detection protocol presented
in this study can be applied to a broad range of bacterial samples and may
contribute to a wider mapping of AHL production in bacteria, for example, in
clinically relevant strains
Robotic bronchoscopy for peripheral pulmonary lesions: A multicenter pilot and feasibility study (BENEFIT)
BACKGROUND: The diagnosis of peripheral pulmonary lesions (PPL) continues to present clinical challenges. Despite extensive experience with guided bronchoscopy, the diagnostic yield has not improved significantly. Robotic-assisted bronchoscopic platforms have been developed potentially to improve the diagnostic yield for PPL. Presently, limited data exist that evaluate the performance of robotic systems in live human subjects.
RESEARCH QUESTION: What is the safety and feasibility of robotic-assisted bronchoscopy in patients with PPLs?
STUDY DESIGN AND METHODS: This was a prospective, multicenter pilot and feasibility study that used a robotic bronchoscopic system with a mother-daughter configuration in patients with PPL 1 to 5 cm in size. The primary end points were successful lesion localization with the use of radial probe endobronchial ultrasound (R-EBUS) imaging and incidence of procedure related adverse events. Robotic bronchoscopy was performed in patients with the use of direct visualization, electromagnetic navigation, and fluoroscopy. After the use of R-EBUS imaging, transbronchial needle aspiration was performed. Rapid on-site evaluation (ROSE) was used on all cases. Transbronchial needle aspiration alone was sufficient when ROSE was diagnostic; when ROSE was not diagnostic, transbronchial biopsy was performed with the use of the robotic platform, followed by conventional guided bronchoscopic approaches at the discretion of the investigator.
RESULTS: Fifty-five patients were enrolled at five centers. One patient withdrew consent, which left 54 patients for data analysis. Median lesion size was 23 mm (interquartile range, 15 to 29 mm). R-EBUS images were available in 53 of 54 cases. Lesion localization was successful in 51 of 53 patients (96.2%). Pneumothorax was reported in two of 54 of the cases (3.7%); tube thoracostomy was required in one of the cases (1.9 %). No additional adverse events occurred.
INTERPRETATION: This is the first, prospective, multicenter study of robotic bronchoscopy in patients with PPLs. Successful lesion localization was achieved in 96.2% of cases, with an adverse event rate comparable with conventional bronchoscopic procedures. Additional large prospective studies are warranted to evaluate procedure characteristics, such as diagnostic yield.
CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT03727425; URL: www.clinicaltrials.gov
Molecular imaging of atherosclerotic plaque targeted to oxidized LDL receptor LOX-1 using magnetic resonance
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