Sequential Injection Analysis for Automation and Evaluation of Drug Liberation Profiles: Clotrimazole Liberation Monitoring.
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ABSTRACT:
SUBMITTER: Sklenarova H
PROVIDER: S-EPMC8467677 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The goal of this work is to evaluate the effectiveness of Plan-Checker Tool (PCT) which was created to improve first-time plan quality, reduce patient delays, increase the efficiency of our electronic workflow, and standardize and automate the phys-ics plan review in the treatment planning system (TPS). PCT uses an application programming interface to check and compare data from the TPS and treatment management system (TMS). PCT includes a comprehensive checklist of automated and manual checks that are documented when performed by the user as part of a plan readiness check for treatment. Prior to and during PCT development, errors identified during the physics review and causes of patient treatment start delays were tracked to prioritize which checks should be automated. Nineteen of 33checklist items were automated, with data extracted with PCT. There was a 60% reduction in the number of patient delays in the six months after PCT release. PCT was suc-cessfully implemented for use on all external beam treatment plans in our clinic. While the number of errors found during the physics check did not decrease, automation of checks increased visibility of errors during the physics check, which led to decreased patient delays. The methods used here can be applied to any TMS and TPS that allows queries of the database.
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Project description:In the present study, we investigated the capabilities of a novel ultrasonic approach for real-time control of fibrinolysis under flow conditions. Ultrasonic monitoring was performed in a specially designed experimental in vitro system. Fibrinolytic agents were automatically injected at ultrasonically determined stages of the blood clotting. The following clots dissolution in the system was investigated by means of ultrasonic monitoring. It was shown, that clots resistance to fibrinolysis significantly increases during the first 5 minutes since the formation of primary micro-clots. The efficiency of clot lysis strongly depends on the concentration of the fibrinolytic agent as well as the delay of its injection moment. The ultrasonic method was able to detect the coagulation at early stages, when timely pharmacological intervention can still prevent the formation of macroscopic clots in the experimental system. This result serves as evidence that ultrasonic methods may provide new opportunities for real-time monitoring and the early pharmacological correction of thrombotic complications in clinical practice.
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Project description:BackgroundPrescription opioid misuse is an ongoing crisis and a risk factor for injection drug use (IDU). Few studies have evaluated strategies for preventing opioid or IDU initiation among adolescents. We evaluated changes in the proportion of adolescents reporting IDU before and after prescription drug monitoring program (PDMP) mandates were implemented in 18 states compared to 29 states without such mandates.Methods and findingsThis difference-in-differences analysis used biannual Youth Risk Behavioral Surveillance System (YRBSS) data representative of adolescents 17 to 18 years old across 47 states from 1995 to 2017. We compared changes in adolescent IDU in 18 states with and 29 states without PDMP mandates. Among 331,025 adolescents, 51.7% identified as male, 62.1% as non-Hispanic white, 17.4% as non-Hispanic black, and 14.6% as Hispanic. Overall, 3.5% reported IDU during the 2 years prior to PDMP mandates. In the final multivariable difference-in-differences model, we included individual age, sex, and race/ethnicity, as well as state and year as covariates from the YRBSS. We also included state- and year-specific poverty rates based on US Census Bureau data. Additionally, we controlled for state implementation of (non-mandated) PDMPs before states subsequently implemented mandates and pill mill laws. We conducted several sensitivity analyses, including repeating our main analysis using a logistic, rather than linear, model, and with a lead indicator on PDMP mandate implementation, a lag indicator, and alternative policy implementation dates. PDMP mandates were associated with a 1.5 percentage point reduction (95% CI -2.3 to -0.6 percentage points; p = 0.001) in adolescent IDU, on average over the years following mandate implementation, a relative reduction of 42.9% (95% CI -65.7% to -17.1%). The association of PDMP mandates with this reduction persisted at least 4 years beyond implementation. Sensitivity analyses were consistent with the main results. Limitations include the multi-stepped causal pathway from PDMP mandate implementation to changes in IDU and the potential for omitted state-level time-varying confounders.ConclusionsOur analysis indicated that PDMP mandates were associated with a reduction in adolescent IDU, providing empirical evidence that such mandates may prevent adolescents from initiating IDU. Policymakers might consider PDMP mandates as a potential strategy for preventing adolescent IDU.
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Project description:We present an Arduino-based automation system to control the streetlights based on solar rays and object's detection. We aim to design various systems to achieve the desired operations, which no longer require time-consuming manual switching of the streetlights. The proposed work is accomplished by using an Arduino microcontroller, a light dependent resistor (LDR) and infrared-sensors while, two main contributions are presented in this work. Firstly, we show that the streetlights can be controlled based on the night and object's detection. In which the streetlights automatically turn to DIM state at night-time and turn to HIGH state on object's detection, while during day-time the streetlights will remain OFF. Secondly, the proposed automated system is further extended to skip the DIM condition at night time, and streetlights turn ON based on the objects' detection only. In addition, an automatic door system is introduced to improve the safety measurements, and most importantly, a counter is set that will count the number of objects passed through the road. The proposed systems are designed at lab-scale prototype to experimentally validate the efficiency, reliability, and low-cost of the systems. We remark that the proposed systems can be easily tested and implemented under real conditions at large-scale in the near future, that will be useful in the future applications for automation systems and smart homes.
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Project description:Information about HBV sero-markers, infection stages and genotypes in HIV-1 infected and uninfected injection and non-injection drug users (IDUs) in Kenya remains elusive.A cross-sectional study examining HBV sero-marker, infection stages and genotypes was conducted among HIV-1 infected and uninfected, respectively, IDUs (n?=?157 and n?=?214) and non-IDUs (n?=?139 and n?=?48), and HIV-1 uninfected non-drug using controls (n?=?194) from coastal, Kenya. HBV sero-marker and infection stages were based on HBV 5-panel rapid test plasma sero-reactivity. DNA was extracted from acute and chronic plasma samples and genotypes established by nested-PCR and direct sequencing.HBsAg positivity was higher in HIV-1 infected IDUs (9.6%) relative to HIV-1 uninfected IDUs (2.3%), HIV-1 infected non-IDUs (3.6%), HIV-1 uninfected non-IDUs (0.0%) and non-drug users (2.6%; P?=?0.002). Contrastingly, HBsAb positivity was higher in HIV-1 uninfected IDUs (14.6%) and non-IDUs (16.8) in comparison to HIV-1 infected IDUs (8.3%), and non-IDUs (8.6%), and non-drug users (8.2%; P?=?0.023). HBcAb positivity was higher in HIV-1 infected IDUs (10.2%) compared to HIV-1 uninfected IDUs (3.3%), HIV-1 infected non-IDUs (6.5%), HIV-1 uninfected non-IDUs (2.1%) and non-drug users (4.6%; P?=?0.038). Acute (5.7%, 1.4%, 0.0%, 0.0% and 1.5%) and chronic (5.1%, 0.9%, 3.6%, 0.0% and 1.5%) stages were higher in HIV-1 infected IDUs, compared to HIV-1 uninfected IDUs, HIV-1 infected and uninfected non-IDUs and non-drug users, respectively. However, vaccine type response stage was higher in HIV-1 uninfected IDUs (15.4%) relative to HIV-1 infected IDUs (6.4%), and HIV-1 infected (6.5%), and uninfected (10.4%) non-IDUs, and non-drug users (5.7%; P?=?0.003). Higher resolved infection rates were also recorded in HIV-1 uninfected IDUs (11.2%) compared to HIV-1 infected IDUs (8.3%), and HIV-1 infected (7.2%), uninfected (6.3%) non-IDUs, and non-drug users (6.7%; P?=?0.479), respectively. Only A1 genotype showing minimal diversity was detected among the study participants.HBV sero-markers and infection staging are valuable in diagnosis and genotyping of HBV infections. Among IDUs, higher HBsAg and HBcAb positivity in HIV-1 infected and higher HBsAb positivity in HIV-1 negative IDUs suggests frequent exposure. Additionally, HBV genotype A is the dominant circulating genotype in both high and low risk populations of Kenya.
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Project description:The Swofford-Olsen-Waddell-Hillis (SOWH) test evaluates statistical support for incongruent phylogenetic topologies. It is commonly applied to determine if the maximum likelihood tree in a phylogenetic analysis is significantly different than an alternative hypothesis. The SOWH test compares the observed difference in log-likelihood between two topologies to a null distribution of differences in log-likelihood generated by parametric resampling. The test is a well-established phylogenetic method for topology testing, but it is sensitive to model misspecification, it is computationally burdensome to perform, and its implementation requires the investigator to make several decisions that each have the potential to affect the outcome of the test. We analyzed the effects of multiple factors using seven data sets to which the SOWH test was previously applied. These factors include a number of sample replicates, likelihood software, the introduction of gaps to simulated data, the use of distinct models of evolution for data simulation and likelihood inference, and a suggested test correction wherein an unresolved "zero-constrained" tree is used to simulate sequence data. To facilitate these analyses and future applications of the SOWH test, we wrote SOWHAT, a program that automates the SOWH test. We find that inadequate bootstrap sampling can change the outcome of the SOWH test. The results also show that using a zero-constrained tree for data simulation can result in a wider null distribution and higher p-values, but does not change the outcome of the SOWH test for most of the data sets tested here. These results will help others implement and evaluate the SOWH test and allow us to provide recommendations for future applications of the SOWH test. SOWHAT is available for download from https://github.com/josephryan/SOWHAT.
| S-EPMC4604836 | biostudies-literature
Project description:Background and aimsMorbidity and mortality from acute diarrheal disease remains high, particularly in developing countries and in cases of natural or man-made disasters. Previous work has shown that the small molecule clotrimazole inhibits intestinal Cl- secretion by blocking both cyclic nucleotide- and Ca(2+)-gated K(+) channels, implicating its use in the treatment of diarrhea of diverse etiologies. Clotrimazole, however, might also inhibit transporters that mediate the inwardly directed electrochemical potential for Na(+)-dependent solute absorption, which would undermine its clinical application. Here we test this possibility by examining the effects of clotrimazole on Na(+)-coupled glucose uptake.Materials and methodsShort-circuit currents (Isc) following administration of glucose and secretagogues were studied in clotrimazole-treated jejunal sections of mouse intestine mounted in Ussing chambers.ResultsTreatment of small intestinal tissue with clotrimazole inhibited the Cl- secretory currents that resulted from challenge with the cAMP-agonist vasoactive intestinal peptide (VIP) or Ca(2+)-agonist carbachol in a dose-dependent fashion. A dose of 30 μM was effective in significantly reducing the Isc response to VIP and carbachol by 50% and 72%, respectively. At this dose, uptake of glucose was only marginally affected (decreased by 14%, p = 0.37). There was no measurable effect on SGLT1-mediated sugar transport, as uptake of SGLT1-restricted 3-O-methyl glucose was equivalent between clotrimazole-treated and untreated tissue (98% vs. 100%, p = 0.90).ConclusionTreatment of intestinal tissue with clotrimazole significantly reduced secretory responses caused by both cAMP- and Ca(2+)-dependent agonists as expected, but did not affect Na(+)-coupled glucose absorption. Clotrimazole could thus be used in conjunction with oral rehydration solution as a low-cost, auxiliary treatment of acute secretory diarrheas.
| S-EPMC4583490 | biostudies-literature
Project description:BackgroundPosaconazole therapeutic drug monitoring (TDM) is increasingly used in clinical practice. However, the utility of posaconazole TDM and the target of posaconazole plasma concentration for clinical successful prophylaxis remain uncertain and controversial. The aim of this study was to evaluate posaconazole exposure-response relationship and determine an optimum posaconazole concentration for prophylaxis against invasive fungal infections (IFIs).MethodsBibliographic databases were searched (from inception to September 2017) to select studies including the clinical outcomes below and above concentration cut-off value of 0.5 mg/L and 0.7 mg/L. The reliability of the results were evaluated with trial sequential analysis (TSA).ResultsTwenty-eight studies with 1930 patients included were analyzed. The results of our pooled analysis demonstrated that patients with posaconazole plasma concentrations over 0.5 mg/L were twice more likely to achieve successful responses compared with those with lower concentrations (odds ratio, OR = 1.98, 95% confidence interval, CI 1.09-3.58, P = 0.02) while the threshold, 0.7 mg/L showed no significant difference (OR = 1.84, 95% CI 0.94-3.63, P = 0.08). The TSA results showed that there was sufficient information to support these findings.ConclusionsAn optimal posaconazole concentration target of 0.5 mg/L is suggested to ensure the clinical prophylactic efficacy and may help reduce the dosage and dose-dependent toxicity comparing with the target of 0.7 mg/L.
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