1,288 research outputs found

    Economic analysis of a transesophageal echocardiography-guided approach to cardioversion of patients with atrial fibrillation The ACUTE economic data at eight weeks

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    AbstractObjectivesThe aim of this study was to compare the relative cost of a transesophageal echocardiography (TEE)-guided strategy versus conventional strategy for patients with atrial fibrillation (AF) >2 days duration undergoing electrical cardioversion over an eight-week period.BackgroundThe Assessment of Cardioversion Using Transesophageal Echocardiography (ACUTE) trial found no difference in embolic rates between the two approaches. However, the TEE-guided strategy had a shorter time to cardioversion and a lower rate of composite bleeding. While similar clinical efficacy was concluded, the relative cost of these two strategies has not been explored.MethodsTwo economic approaches were employed in the ACUTE trial. The first approach was based on hospital charge data from complete hospital Universal Billing Code of 1992 forms, a detailed hospital charge questionnaire, or imputation. Regression analysis was used to investigate the added cost of adverse events. The second economic approach involved the development of an independent analytic model simulating treatment and actual ACUTE outcome costs as a validation of clinically derived data. Sensitivity analysis was performed on the analytic model to investigate the potential range in cost differences between the strategies.ResultsA total of 833 of the 1,222 patients were enrolled from 53 U.S. sites; TEE-guided (n = 420) and conventional (n = 413). At eight-week follow-up, total mean costs did not significantly differ between the two groups, respectively (6,508vs.6,508 vs. 6,239; difference of $269; p = 0.50). Cumulative costs were 24% higher in the conventional group, primarily due to increased incidence of bleeding and hospital costs associated with bleeding. A separate analytic model showed that treatment costs were higher for the TEE-guided strategy, but outcome costs were higher for the conventional strategy. Sensitivity analysis of the analytic model illustrated that varying the incidence and cost of major bleeding and the cost of TEE had the greatest impact on cost differences between the two groups.ConclusionsIn patients with AF >2 days duration undergoing electrical cardioversion, the TEE-guided group showed little difference in patient costs compared with the conventional group. The TEE strategy had higher initial treatment costs but lower outcome-associated costs. Cumulative costs were 24% higher in the conventional group, primarily due to bleeding. The TEE-guided strategy is an economically feasible approach compared with the conventional strategy

    Efficacy of a ML336 Derivative Against Venezuelan and Eastern Equine Encephalitis Viruses

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    Currently, there are no licensed human vaccines or antivirals for treatment of or prevention from infection with encephalitic alphaviruses. Because epidemics are sporadic and unpredictable, and endemic disease is common but rarely diagnosed, it is difficult to identify all populations requiring vaccination; thus, an effective post-exposure treatment method is needed to interrupt ongoing outbreaks. To address this public health need, we have continued development of ML336 to deliver a molecule with prophylactic and therapeutic potential that could be relevant for use in natural epidemics or deliberate release scenario for Venezuelan equine encephalitis virus (VEEV). We report findings from in vitro assessments of four analogs of ML336, and in vivo screening of three of these new derivatives, BDGR-4, BDGR-69 and BDGR-70. The optimal dosing for maximal protection was observed at 12.5 mg/kg/day, twice daily for 8 days. BDGR-4 was tested further for prophylactic and therapeutic efficacy in mice challenged with VEEV Trinidad Donkey (TrD). Mice challenged with VEEV TrD showed 100% and 90% protection from lethal disease when treated at 24 and 48 h post-infection, respectively. We also measured 90% protection for BDGR-4 in mice challenged with Eastern equine encephalitis virus. In additional assessments of BDGR-4 in mice alone, we observed no appreciable toxicity as evaluated by clinical chemistry indicators up to a dose of 25 mg/kg/day over 4 days. In these same mice, we observed no induction of interferon. Lastly, the resistance of VEEV to BDGR-4 was evaluated by next-generation sequencing which revealed specific mutations in nsP4, the viral polymerase

    Использование барий-стронциевого карбонатита при изготовлении сварочных флюсов на основе техногенных отходов металлургического производства

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    В данной работе рассмотрена возможность использования барий-стронциевого карбонатита при изготовлении сварочных флюсов на основе шлака производства силикомарганца, а так же на основе ковшевых электросталеплавильных шлаков, образованных при производстве рельсовых марок стали. В серии опытов в лабораторных условиях изготавливали и исследовали различные составы сварочных флюсов, были определены химические составы наплавленного металла, проведен металлографический анализ.In this paper the possibility of using barium-strontium carbonatite in the manufacture of welding fluxes on the basis of slag from the production of silicomanganese, and based on ladle steelmaking slags formed in the production of rail steel grades. In a series of experiments in the laboratory have produced and investigated different compositions of welding fluxes, were determined the chemical compositions of the weld metal metallographic analysis

    Dysphagia training for speech-language pathologists: implications for clinical practice

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    There are competency standards available in countries with established speech-language pathology services to guide basic dysphagia training with ongoing workplace mentoring for advanced skills development. Such training processes, however, are not as well established in countries where speech-language pathology training and practice is relatively new, such as Malaysia. The current study examines the extent of dysphagia training and workplace support available to speech-language pathologists (SLPs) in Malaysia and Queensland, Australia, and explores clinicians’ perceptions of the training and support provided, and of their knowledge, skills, and confidence. Using a matched cohort cross-sectional design, a purpose-built survey was administered to 30 SLPs working in Malaysian government hospitals and 30 SLPs working in Queensland Health settings in Australia. Malaysian clinicians were found to have received significantly less university training, less mentoring in the workplace, and were lacking key infrastructure needed to support professional development in dysphagia management. Over 90% of Queensland clinicians were confident and felt they had adequate skills in dysphagia management; in contrast, significantly lower levels of knowledge, skills, and confidence were observed in the Malaysian cohort. The findings identify a need for improved university training and increased opportunities for workplace mentoring, training, and support for Malaysian SLPs

    TIM-3 blockade in diffuse intrinsic pontine glioma models promotes tumor regression and antitumor immune memory

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    Diffuse intrinsic pontine glioma (DIPG) is an aggressive brain stem tumor and the leading cause of pediatric cancer-related death. To date, these tumors remain incurable, underscoring the need for efficacious therapies. In this study, we demonstrate that the immune checkpoint TIM-3 (HAVCR2) is highly expressed in both tumor cells and microenvironmental cells, mainly microglia and macrophages, in DIPG. We show that inhibition of TIM-3 in syngeneic models of DIPG prolongs survival and produces long-term survivors free of disease that harbor immune memory. This antitumor effect is driven by the direct effect of TIM-3 inhibition in tumor cells, the coordinated action of several immune cell populations, and the secretion of chemokines/cytokines that create a proinflammatory tumor microenvironment favoring a potent antitumor immune response. This work uncovers TIM-3 as a bona fide target in DIPG and supports its clinical translation

    Machine learning prediction of gestational age from metabolic screening markers resistant to ambient temperature transportation: Facilitating use of this technology in low resource settings of South Asia and East Africa.

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    BACKGROUND: Knowledge of gestational age is critical for guiding preterm neonatal care. In the last decade, metabolic gestational dating approaches emerged in response to a global health need; because in most of the developing world, accurate antenatal gestational age estimates are not feasible. These methods initially developed in North America have now been externally validated in two studies in developing countries, however, require shipment of samples at sub-zero temperature. METHODS: A subset of 330 pairs of heel prick dried blood spot samples were shipped on dry ice and in ambient temperature from field sites in Tanzania, Bangladesh and Pakistan to laboratory in Iowa (USA). We evaluated impact on recovery of analytes of shipment temperature, developed and evaluated models for predicting gestational age using a limited set of metabolic screening analytes after excluding 17 analytes that were impacted by shipment conditions of a total of 44 analytes. RESULTS: With the machine learning model using all the analytes, samples shipped in dry ice yielded a Root Mean Square Error (RMSE) of 1.19 weeks compared to 1.58 weeks for samples shipped in ambient temperature. Out of the 44 screening analytes, recovery of 17 analytes was significantly different between the two shipment methods and these were excluded from further machine learning model development. The final model, restricted to stable analytes provided a RMSE of 1.24 (95% confidence interval (CI) = 1.10-1.37) weeks for samples shipped on dry ice and RMSE of 1.28 (95% CI = 1.15-1.39) for samples shipped at ambient temperature. Analysis for discriminating preterm births (gestational age <37 weeks), yielded an area under curve (AUC) of 0.76 (95% CI = 0.71-0.81) for samples shipped on dry ice and AUC of 0.73 (95% CI = 0.67-0.78) for samples shipped in ambient temperature. CONCLUSIONS: In this study, we demonstrate that machine learning algorithms developed using a sub-set of newborn screening analytes which are not sensitive to shipment at ambient temperature, can accurately provide estimates of gestational age comparable to those from published regression models from North America using all analytes. If validated in larger samples especially with more newborns <34 weeks, this technology could substantially facilitate implementation in LMICs

    Direct Optimal Mapping Image Power Spectrum and its Window Functions

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    The key to detecting neutral hydrogen during the epoch of reionization (EoR) is to separate the cosmological signal from the dominating foreground radiation. We developed direct optimal mapping (Xu et al. 2022) to map interferometric visibilities; it contains only linear operations, with full knowledge of point spread functions from visibilities to images. Here we present an FFT-based image power spectrum and its window functions based on direct optimal mapping. We use noiseless simulation, based on the Hydrogen Epoch of Reionization Array (HERA) Phase I configuration, to study the image power spectrum properties. The window functions show <1011<10^{-11} power leakage from the foreground-dominated region into the EoR window; the 2D and 1D power spectra also verify the separation between the foregrounds and the EoR. Furthermore, we simulated visibilities from a uvuv-complete array and calculated its image power spectrum. The result shows that the foreground--EoR leakage is further suppressed below 101210^{-12}, dominated by the tapering function sidelobes; the 2D power spectrum does not show signs of the horizon wedge. The uvuv-complete result provides a reference case for future 21cm cosmology array designs.Comment: Submitted to Ap
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