Randomized Dose-Ranging Controlled Trial of AQ-13, a Candidate Antimalarial, and Chloroquine in Healthy Volunteers

OBJECTIVES: To determine: (1) the pharmacokinetics and safety of an investigational aminoquinoline active against multidrug–resistant malaria parasites (AQ-13), including its effects on the QT interval, and (2) whether it has pharmacokinetic and safety profiles similar to chloroquine (CQ) in humans. DESIGN: Phase I double-blind, randomized controlled trials to compare AQ-13 and CQ in healthy volunteers. Randomizations were performed at each step after completion of the previous dose. SETTING: Tulane–Louisiana State University–Charity Hospital General Clinical Research Center in New Orleans. PARTICIPANTS: 126 healthy adults 21–45 years of age. INTERVENTIONS: 10, 100, 300, 600, and 1,500 mg oral doses of CQ base in comparison with equivalent doses of AQ-13. OUTCOME MEASURES: Clinical and laboratory adverse events (AEs), pharmacokinetic parameters, and QT prolongation. RESULTS: No hematologic, hepatic, renal, or other organ toxicity was observed with AQ-13 or CQ at any dose tested. Headache, lightheadedness/dizziness, and gastrointestinal (GI) tract–related symptoms were the most common AEs. Although symptoms were more frequent with AQ-13, the numbers of volunteers who experienced symptoms with AQ-13 and CQ were similar (for AQ-13 and CQ, respectively: headache, 17/63 and 10/63, p = 0.2; lightheadedness/dizziness, 11/63 and 8/63, p = 0.6; GI symptoms, 14/63 and 13/63; p = 0.9). Both AQ-13 and CQ exhibited linear pharmacokinetics. However, AQ-13 was cleared more rapidly than CQ (respectively, median oral clearance 14.0–14.7 l/h versus 9.5–11.3 l/h; p ≤ 0.03). QTc prolongation was greater with CQ than AQ-13 (CQ: mean increase of 28 ms; 95% confidence interval [CI], 18 to 38 ms, versus AQ-13: mean increase of 10 ms; 95% CI, 2 to 17 ms; p = 0.01). There were no arrhythmias or other cardiac AEs with either AQ-13 or CQ. CONCLUSIONS: These studies revealed minimal differences in toxicity between AQ-13 and CQ, and similar linear pharmacokinetics

Novel Interleaved High Gain Boost Converter Using Switched Capacitor

The increase in global energy demand has led to increased research in harvesting solar energy. Solar energy is widely used in homes, electric vehicles and is a great solution to power remote areas. DC–DC converters are essential in extracting power from solar panels. One of the main problems in designing converters for solar energy applications is boosting the low output voltage of the solar panel to meaningful levels. While there are several topologies to achieve high gain, some of the problems faced by them are the extreme duty ratio, complex design and discontinuous input current. This paper presents a novel topology that uses an interleaved input, a voltage lift capacitor and a hybrid switched capacitor network to achieve high gain without an extreme duty ratio or bulky magnetics. The proposed converter is controlled using a microcontroller which regulates the output voltage. The voltage lift capacitor and the switched capacitor network enhances the voltage gain over a conventional boost converter without an extreme duty ratio. The analysis and design of the proposed converter are presented and verified with a 100 W prototype. The results show that the converter provides a gain of 10, at a duty ratio of 30%, while delivering the designed output power with considerably high efficiency

Non-Isolated Interleaved Hybrid Boost Converter for Renewable Energy Applications

DC-DC boost converters are necessary to extract power from solar panels. The output voltage from these panels is far lower than the utility voltage levels. One of the main functions of the boost converter is to provide a considerable step-up gain to interface the panel to the utility lines. There are several techniques used to boost the low panel voltage. Some of the issues faced by these topologies are a high duty ratio operation, complex design with multiple active switches and discontinuous input current that affects the power drawn from the panel. This paper presents a boost converter topology that combines the advantages of an interleaved structure, a voltage lift capacitor and a passive voltage multiplier network. A mathematical analysis of the proposed converter during its various modes of operation is presented. A 100 W prototype of the proposed converter is designed and tested. The prototype is controlled by a PIC16F18455 microcontroller. The converter is capable of achieving a gain of 10 without operating at extremely high duty ratios. The voltage stress of the switch is far lower than the maximum output voltage

Exploring DSSAT Model Genetic Coefficient Estimation Methodologies for Chickpea in Bundelkhand Region of Uttar Pradesh, India

In modern crop production, essential factors that contribute to narrowing yield gaps and minimizing production costs include making informed decisions about the selection of plant varieties, determining optimal sowing dates, determining appropriate plant populations, selecting suitable fertilizer rates, and implementing effective pest control methods. Two field experiments were conducted during the Rabi seasons of 2021 and 2022 at ICAR-Indian Institute of Pulses Research (IIPR), Kanpur using split-plot experimental design, where the main plots were three different sowing dates (20-25th October, November 10-15th, and 25th November-5th December), and the sub-plots were four chickpea cultivars (JG 16, RVG 202, IPC-07-66, and IPC-05-62), each with three replications. The genetic coefficients of the cultivars were estimated using both the iterative process (IP) and Generalized Likelihood Uncertainty Estimation (GLUE) methods in DSSAT v 4.7 to simulate the yields. Upon model validation, it was found that the average relative error (ARE) in predicting grain yield across the different sowing windows was between -25.7% to 29.1% when using the iterative process, while ARE was between -23.4% to 19% when using GLUE. The findings report more accurate simulations of chickpea growth and phenological development stages were recorded in normal sowings. And the model calibration suggest that GLUE provided superior estimates of genetic coefficients compared to the IP method. Therefore, it can be inferred that Glue is a more user-friendly and precise method

Anomalous superficial ulnar artery based flap

Upper limb shows a large number of arterial variations. This case report describes the presence of additional superficial ulnar artery which was used to raise a pedicle flap to cover an arm defect thus avoided using the main vessel of the forearm - radial or ulnar artery. Vascular anomalies occurring in the arm and forearm tend to increase the likelihood of damaging the superficial anomalous arteries during surgery. Superficial ulnar or radial arteries have been described to originate from the upper third of the brachial artery; here we report the origin of the anomalous superficial ulnar artery originating from the brachial artery at the level of elbow with the concomitant presence of normal deep radial and ulnar arteries

Pharmacokinetics in Animals and Humans of a First-in-Class Peptide Deformylase Inhibitor

BB-83698, a potent and selective inhibitor of peptide deformylase, was the first compound of this novel antibacterial class to progress to clinical trials. Single- and/or multiple-dose studies with doses ranging from 10 to 50 mg of BB-83698/kg of body weight were done with mice, rats, and dogs. Intravenous pharmacokinetics were characterized by low to moderate clearances and moderate volumes of distribution for all species. In dogs, but not in rodents, central nervous system (CNS) effects were dose limiting for intravenously administered BB-83698 and were suspected to be related to a high maximum concentration of the agent in plasma (C(max)) rather than to total systemic exposure. Controlled infusion studies with dogs demonstrated that CNS effects could be avoided without compromising systemic exposure by reducing the C(max). A randomized, double-blind, placebo-controlled, five-way-crossover, single-dose-escalation, phase I study to explore the safety, tolerability, and pharmacokinetics of intravenous BB-83698 at doses ranging from 10 to 475 mg was performed with healthy male volunteers. Systemic exposures were generally in linear relationships with administered doses in animals and humans. Pharmacokinetics were consistent, predictable, and exhibited good allometric scaling among all species (r(2) >0.98). Moreover, BB-83698 dosing in humans proceeded to a predicted efficacious exposure (the area under the concentration-time curve/MIC ratio, up to 184) without any clinically significant adverse effects