Pediatric drug safety signal detection: a new drug-event reference set for performance testing of data-mining methods and systems

BACKGROUND: Better evidence regarding drug safety in the pediatric population might be generated from existing data sources such as spontaneous reporting systems and electronic healthcare records. The Global Research in Paediatrics (GRiP)-Network of Excellence aims to develop pediatric-specific methods that can be applied to these data sources. A reference set of positive and negative drug-event associations is required. OBJECTIVE: The aim of this study was to develop a pediatric-specific reference set of positive and negative drug-event associations. METHODS: Considering user patterns and expert opinion, 16 drugs that are used in individuals aged 0-18 years were selected and evaluated against 16 events, regarded as important safety outcomes. A cross-table of unique drug-event pairs was created. Each pair was classified as potential positive or negative control based on information from the drug's Summary of Product Characteristics and Micromedex. If both information sources consistently listed the event as an adverse event, the combination was reviewed as potential positive control. If both did not, the combination was evaluated as potential negative control. Further evaluation was based on published literature. RESULTS: Selected drugs include ibuprofen, flucloxacillin, domperidone, methylphenidate, montelukast, quinine, and cyproterone/ethinylestradiol. Selected events include bullous eruption, aplastic anemia, ventricular arrhythmia, sudden death, acute kidney injury, psychosis, and seizure. Altogether, 256 unique combinations were reviewed, yielding 37 positive (17 with evidence from the pediatric population and 20 with evidence from adults only) and 90 negative control pairs, with the remainder being unclassifiable. CONCLUSION: We propose a drug-event reference set that can be used to compare different signal detection methods in the pediatric population

Finite element analysis of spot laser of steel welding temperature history

Laser welding process reduces the heat input to the work-piece which is the main goal in aerospace and electronics industries. A finite element model for axi-symmetric transient heat conduction has been used to predict temperature distribution through a steel cylinder subjected to CW laser beam of rectangular beam profile. Many numerical improvements had been used to reduce time of calculation and size of the program so as to achieve the task with minimum time required. An experimental determined absorptivity has been used to determine heat induced when laser interact with material. The heat affected zone and welding zone have been estimated to determine the effect of welding on material. The ratio of depth to width of the welding zone can be changed by proper selection of beam power to meet the specific production requirement. The temperature history obtained numerically has been compared with experimental data indicating good agreement

Understanding the Threshold Voltage Instability during OFF-State Stress in p-GaN HEMTs

© 1980-2012 IEEE. In this letter, we investigate by means of experimental results and TCAD simulations the threshold voltage instability due to OFF-state drain stress in p-GaN gate AlGaN/GaN-on-Si HEMTs. When the drain of the p-GaN HEMT is biased in the OFF-state the threshold voltage (Vth) shows a linear increase up to 40%. This increase saturates at drain bias voltages above 50 V. The positive Vth shift is attributed to the ionization of acceptor traps in the AlGaN region below the p-GaN gate with the source of these trapping sites suggested to be the p-GaN gate out-diffused Mg dopant atoms. The ionization of the Mg acceptors due to high electric field during OFF-state bias and the removal of the generated holes from the AlGaN region through the gate contact creates the charge conditions for a positive Vth shift. The sharp decrease in the gate drain capacitance (Cgd) for VD< 50 V, the simulated gate edge electric field reaching its peak for a drain voltage bias VD ∼ 50 V and the positive threshold voltage shift observed for negative gate stress further validate the proposed model

Effect of device layout on the switching of enhancement mode GaN HEMTs

In this study, a comparison of the on-state and switching performance of different die layout configurations of GaN HEMTs is given. Devices with different layout designs are shown to exhibit varying degrees of susceptibility to oscillatory behaviour when switching. This is demonstrated to be related to the level of source inductance and the unbalances of such inductances within the die rather than the package; this behaviour was quantified using a 3D electromagnetic simulation software. SPICE simulations were used to further support these findings

Reversal and remission of T2DM - an update for practitioners

Over the past 50 years, many countries around the world have faced an unchecked pandemic of obesity and type 2 diabetes (T2DM). As best practice treatment of T2DM has done very little to check its growth, the pandemic of diabesity now threatens to make health-care systems economically more difficult for governments and individuals to manage within their budgets. The conventional view has been that T2DM is irreversible and progressive. However, in 2016, the World Health Organization (WHO) global report on diabetes added for the first time a section on diabetes reversal and acknowledged that it could be achieved through a number of therapeutic approaches. Many studies indicate that diabetes reversal, and possibly even long-term remission, is achievable, belying the conventional view. However, T2DM reversal is not yet a standardized area of practice and some questions remain about long-term outcomes. Diabetes reversal through diet is not articulated or discussed as a first-line target (or even goal) of treatment by any internationally recognized guidelines, which are mostly silent on the topic beyond encouraging lifestyle interventions in general. This review paper examines all the sustainable, practical, and scalable approaches to T2DM reversal, highlighting the evidence base, and serves as an interim update for practitioners looking to fill the practical knowledge gap on this topic in conventional diabetes guidelines