Nowadays, in the pharmaceutical industry, a growing concern with sustainability has become a strict consideration during the COVID-19 pandemic. There is a lack of good mathematical models in the field. In this research, a production–distribution–inventory–allocation–location problem in the sustainable medical supply chain network is designed to fill this gap. Also, the distribution of medicines related to COVID-19 patients and the periods of production and delivery of medicine according to the perishability of some medicines are considered. In the model, a multi-objective, multi-level, multi-product, and multi-period problem for a sustainable medical supply chain network is designed. Three hybrid meta-heuristic algorithms, namely, ant colony optimization, fish swarm algorithm, and firefly algorithm are suggested, hybridized with variable neighborhood search to solve the sustainable medical supply chain network model. Response surface method is used to tune the parameters since meta-heuristic algorithms are sensitive to input parameters. Six assessment metrics were used to assess the quality of the obtained Pareto frontier by the meta-heuristic algorithms on the considered problems. A real case study is used and empirical results indicate the superiority of the hybrid fish swarm algorithm with variable neighborhood search.

Objective To characterize the changes in brown adipose tissue (BAT) during puberty in boys and girls. Study design We examined the prevalence and the volume of BAT at different stages of sexual development in pediatric patients who underwent positron emission tomography/computer tomography (PET/CT) studies. Results Of the 73 patients, 43 (59%) had BAT depicted on PET/CT. Visualized BAT was significantly less prevalent in PET/CT studies of pre-pubertal (Tanner stage 1) children than pubertal (Tanner stages 2-5) subjects (15% vs. 75%). Values for the volume of BAT also increased during puberty, but the magnitude of the increase was substantially greater during the final two stages of puberty (Tanner stage 4 or 5) than in earlier stages of sexual development (Tanner stages 1, 2, and 3) (Boys: 499±246 vs. 50±36, p <0.0001, Girls: 286±139 vs. 36±29, p = 0.024). Changes in BAT volume were also significantly greater in boys than in girls (p = 0.004) and were closely related to muscle volume (r’s = 0.52, 0.64 and both p’s<0.01, for boys and girls, respectively). Conclusion The depiction and the volume of brown fat increase during puberty. Metabolic and hormonal events related to the achievement of sexual maturity are likely responsible for the rapid increase in brown fat that occurs during puberty.

Purpose Alisertib is an oral Aurora A kinase inhibitor with preclinical activity in neuroblastoma. Irinotecan and temozolomide have activity in patients with advanced neuroblastoma. The goal of this phase I study was to determine the maximum tolerated dose (MTD) of alisertib with irinotecan and temozolomide in this population. Patients and Methods Patients age 1 to 30 years with relapsed or refractory neuroblastoma were eligible. Patients received alisertib tablets at dose levels of 45, 60, and 80 mg/m2 per day on days 1 to 7 along with irinotecan 50 mg/m2 intravenously and temozolomide 100 mg/m2 orally on days 1 to 5. Dose escalation of alisertib followed the rolling six design. Samples for pharmacokinetic and pharmacogenomic testing were obtained. Results Twenty-three patients enrolled, and 22 were eligible and evaluable for dose escalation. A total of 244 courses were administered. The MTD for alisertib was 60 mg/m2, with mandatory myeloid growth factor support and cephalosporin prophylaxis for diarrhea. Thrombocytopenia and neutropenia of any grade were seen in the majority of courses (84% and 69%, respectively). Diarrhea in 55% of courses and nausea in 54% of courses were the most common nonhematologic toxicities. The overall response rate was 31.8%, with a 50% response rate observed at the MTD. The median number of courses per patient was eight (range, two to 32). Progression-free survival rate at 2 years was 52.4%. Pharmacokinetic testing did not show evidence of drug-drug interaction between irinotecan and alisertib. Conclusion Alisertib 60 mg/m2 per dose for 7 days is tolerable with a standard irinotecan and temozolomide backbone and has promising response and progression-free survival rates. A phase II trial of this regimen is ongoing.