Experimental study of PLLA/INH slow release implant fabricated by three dimensional printing technique and drug release characteristics in vitro

BACKGROUND: Local slow release implant provided long term and stable drug release in the lesion. The objective of this study was to fabricate biodegradable slow release INH/PLLA tablet via 3 dimensional printing technique (3DP) and to compare the drug release characteristics of three different structured tablets in vitro. METHODS: Three different drug delivery systems (columnar-shaped tablet (CST), doughnut-shaped tablet (DST) and multilayer doughnut-shaped tablet (MDST)) were manufactured by the three dimensional printing machine and isoniazid was loaded into the implant. Dynamic soaking method was used to study the drug release characteristics of the three implants. MTT cytotoxicity test and direct contact test were utilized to study the biocompatibility of the implant. The microstructures of the implants’ surfaces were observed with electron microscope. RESULTS: The PLLA powder in the tablet could be excellently combined through 3DP without disintegration. Electron microscope observations showed that INH distributed evenly on the surface of the tablet in a “nest-shaped” way, while the surface of the barrier layer in the multilayer doughnut shaped tablet was compact and did not contain INH. The concentration of INH in all of the three tablets were still higher than the effective bacteriostasis concentration (Isoniazid: 0.025 ~ 0.05 μg/ml) after 30 day’s release in vitro. All of the tablets showed initial burst release of the INH in the early period. Drug concentration of MDST became stable and had little fluctuation starting from the 6th day of the release. Drug concentration of DST and CST decreased gradually and the rate of decrease in concentration was faster in DST than CST. MTT cytotoxicity test and direct contact test indicated that the INH-PLLA tablet had low cytotoxicity and favorable biocompatibility. CONCLUSIONS: Three dimensional printing technique was a reliable technique to fabricate complicated implants. Drug release pattern in MDST was the most stable among the three implants. It was an ideal drug delivery system for the antibiotics. Biocompatibility tests demonstrated that the INH-PLLA implant did not have cytotoxicity. The multilayer donut-shaped tablet provided a new constant slow release method after an initial burst for the topical application of the antibiotic

Towards Effective Bug Triage with Software Data Reduction Techniques

International audienceSoftware companies spend over 45 percent of cost in dealing with software bugs. An inevitable step of fixing bugs is bug triage, which aims to correctly assign a developer to a new bug. To decrease the time cost in manual work, text classification techniques are applied to conduct automatic bug triage. In this paper, we address the problem of data reduction for bug triage, i.e., how to reduce the scale and improve the quality of bug data. We combine instance selection with feature selection to simultaneously reduce data scale on the bug dimension and the word dimension. To determine the order of applying instance selection and feature selection, we extract attributes from historical bug data sets and build a predictive model for a new bug data set. We empirically investigate the performance of data reduction on totally 600,000 bug reports of two large open source projects, namely Eclipse and Mozilla. The results show that our data reduction can effectively reduce the data scale and improve the accuracy of bug triage. Our work provides an approach to leveraging techniques on data processing to form reduced and high-quality bug data in software development and maintenance

Development of FEB Configuration Test Board for ATLAS NSW Upgrade

The FEB(front end board) configuration test board is developed aiming at meeting the requirement of testing the new generation ASIC(application-specific integrated circuit) chips and its configuration system for ATLAS NSW(New Small Wheel) upgrade, In this paper, some functions are developed in terms of the configurations of the key chips on the FEB, VMM3 and TDS2 using GBT-SCA. Additionally, a flexible communication protocol is designed, verifying the whole data link. It provides technical reference for prototype FEB key chip configuration and data readout, as well as the final system configuration

ProtoEM: A Prototype-Enhanced Matching Framework for Event Relation Extraction

Event Relation Extraction (ERE) aims to extract multiple kinds of relations among events in texts. However, existing methods singly categorize event relations as different classes, which are inadequately capturing the intrinsic semantics of these relations. To comprehensively understand their intrinsic semantics, in this paper, we obtain prototype representations for each type of event relation and propose a Prototype-Enhanced Matching (ProtoEM) framework for the joint extraction of multiple kinds of event relations. Specifically, ProtoEM extracts event relations in a two-step manner, i.e., prototype representing and prototype matching. In the first step, to capture the connotations of different event relations, ProtoEM utilizes examples to represent the prototypes corresponding to these relations. Subsequently, to capture the interdependence among event relations, it constructs a dependency graph for the prototypes corresponding to these relations and utilized a Graph Neural Network (GNN)-based module for modeling. In the second step, it obtains the representations of new event pairs and calculates their similarity with those prototypes obtained in the first step to evaluate which types of event relations they belong to. Experimental results on the MAVEN-ERE dataset demonstrate that the proposed ProtoEM framework can effectively represent the prototypes of event relations and further obtain a significant improvement over baseline models.Comment: Work in progres

Egg consumption and risk of coronary heart disease and stroke: dose-response meta-analysis of prospective cohort studies

Objective: To investigate and quantify the potential dose-response association between egg consumption and risk of coronary heart disease and stroke. Design: Dose-response meta-analysis of prospective cohort studies. Data sources PubMed and Embase prior to June 2012 and references of relevant original papers and review articles. Eligibility criteria for selecting studies Prospective cohort studies with relative risks and 95% confidence intervals of coronary heart disease or stroke for three or more categories of egg consumption. Results: Eight articles with 17 reports (nine for coronary heart disease, eight for stroke) were eligible for inclusion in the meta-analysis (3 081 269 person years and 5847 incident cases for coronary heart disease, and 4 148 095 person years and 7579 incident cases for stroke). No evidence of a curve linear association was seen between egg consumption and risk of coronary heart disease or stroke (P=0.67 and P=0.27 for non-linearity, respectively). The summary relative risk of coronary heart disease for an increase of one egg consumed per day was 0.99 (95% confidence interval 0.85 to 1.15; P=0.88 for linear trend) without heterogeneity among studies (P=0.97, I2=0%). For stroke, the combined relative risk for an increase of one egg consumed per day was 0.91 (0.81 to 1.02; P=0.10 for linear trend) without heterogeneity among studies (P=0.46, I2=0%). In a subgroup analysis of diabetic populations, the relative risk of coronary heart disease comparing the highest with the lowest egg consumption was 1.54 (1.14 to 2.09; P=0.01). In addition, people with higher egg consumption had a 25% (0.57 to 0.99; P=0.04) lower risk of developing hemorrhagic stroke. Conclusions: Higher consumption of eggs (up to one egg per day) is not associated with increased risk of coronary heart disease or stroke. The increased risk of coronary heart disease among diabetic patients and reduced risk of hemorrhagic stroke associated with higher egg consumption in subgroup analyses warrant further studies

Aspirin for Primary Prevention of Cardiovascular Events: Meta-Analysis of Randomized Controlled Trials and Subgroup Analysis by Sex and Diabetes Status

Objective: To evaluate the benefits and harms of aspirin for the primary prevention of CVD and determine whether the effects vary by sex and diabetes status. Methods: We searched Medline, Embase, and Cochrane databases for randomized controlled trials comparing the effects of aspirin with placebo or control in people with no pre-existing CVD. Two investigators independently extracted data and assessed the study quality. Analyses were performed using Stata version 12. Results: Fourteen trials (107,686 participants) were eligible. Aspirin was associated with reductions in major cardiovascular events (risk ratio, 0.90; 95% confidence interval, 0.85–0.95), myocardial infarction (0.86; 0.75–0.93), ischemic stroke (0.86; 0.75–0.98) and all-cause mortality (0.94; 0.89–0.99). There were also increases in hemorrhagic stroke (1.34; 1.01–1.79) and major bleeding (1.55; 1.35–1.78) with aspirin. The number needed to treat to prevent 1 major cardiovascular event over a mean follow-up of 6.8 years was 284. By comparison, the numbers needed to harm to cause 1 major bleeding is 299. In subgroup analyses, pooled results demonstrated a reduction in myocardial infarction among men (0.71; 0.59–0.85) and ischemic stroke among women (0.77; 0.63–0.93). Aspirin use was associated with a reduction (0.65; 0.51–0.82) in myocardial infarction among diabetic men. In meta-regression analyses, the results suggested that aspirin therapy might be associated with a decrease in stroke among diabetic women and a decrease in MI among diabetic men and risk reductions achieved with low doses (75 mg/day) were as large as those obtained with higher doses (650 mg/day). Conclusions: The use of low-dose aspirin was beneficial for primary prevention of CVD and the decision regarding an aspirin regimen should be made on an individual patient basis. The effects of aspirin therapy varied by sex and diabetes status. A clear benefit of aspirin in the primary prevention of CVD in people with diabetes needs more trials