Robust optimization utilizing the second-order design sensitivity information

This paper presents an effective methodology for robust optimization of electromagnetic devices. To achieve the goal, the method improves the robustness of the minimum of the objective function chosen as a design solution by minimizing the second-order sensitivity information, called a gradient index (GI) and defined by a function of gradients of performance functions with respect to uncertain variables. The constraint feasibility is also enhanced by adding a GI corresponding to the constraint value. The distinctive feature of the method is that it requires neither statistical information on design variables nor calculation of the performance reliability during the robust optimization process. The validity of the proposed method is tested with the TEAM Workshop Problem 2

The dark side of corporate social responsibility

The interests of employees take a back seat when firms mobilise resources for CSR, write Heung-Jun Jung and Dong-One Ki

Advanced Treatment of Intractable Childhood Epilepsy

Objectives: Up to one third of epilepsy patients have an unsatisfactory treatment with antiepileptic drugs (AEDs), but advance in neuroimaging, neurophysiologic investigation and treatment modalities have substantially improved the approaches and understanding of intractable childhood epilepsy. Methods: Journal papers, reports, books and government publications on epilepsy treatment were collected and reviewed in chronological order. Results: There are approximately more than 15 newer AEDs developed since 1990, highlighted by the novel mechanism of action with minimal adverse effect, thus they have been frequently used for those who are unresponsive to conventional AEDs. Non-pharmacologic therapies including diet therapy, epilepsy surgery, and neuromodulatory treatment are also effective and should be considered early in the disease course. Diet therapy began to reemerge in mid 1990s, and studies with large data collection allowed to overcome major concerns; its side effects, difficult compliance and doubts on efficacy. And more liberal forms of the diet therapy were introduced to benefit adults and patients in developing counties, where strict supervision is unavailable. The surgical treatment has become increasingly more valuable and it is now accepted for the management of drug resistant focal epilepsy due to major advances in presurgical investigation methods, and surgical techniques. Conclusions: The timely assessment of children with drug-resistant epilepsy and active application of advanced treatment modalities were necessary to prevent the effect of uncontrolled seizures on cognitive and behavioral development

Initial Experiences with Proton MR Spectroscopy in Treatment Monitoring of Mitochondrial Encephalopathy

PURPOSE: Mitochondrial encephalopathy (ME) is a rare disorder of energy metabolism. The disease course can roughly be evaluated by clinical findings. The purpose of this study was to evaluate metabolic spectral changes using proton MR spectroscopy (MRS), and to establish a way to monitor ME by neuroimaging. MATERIALS AND METHODS: Proton MRS data were retrospectively reviewed in 12 patients with muscle biopsy-confirmed ME (M : F = 7 : 5, Mean age = 4.8 years). All received 1H-MRS initially and also after a ketogenic diet and mitochondrial disease treatment cocktail (follow up average was 10.2 months). Changes of N-acetylaspartate/ creatine (NAA/Cr) ratio, choline/creatine (Cho/Cr) ratio, and lactate peak in basal ganglia at 1.2 ppm were evaluated before and after treatment. Findings on conventional T2 weighted MR images were also evaluated. RESULTS: On conventional MRI, increased basal ganglia T2 signal intensity was the most common finding with ME (n = 9, 75%), followed by diffuse cerebral atrophy (n = 8, 67%), T2 hyperintense lesions at pons and midbrain (n = 4, 33%), and brain atrophy (n = 2, 17%). Lactate peak was found in 4 patients; 2 had disappearance of the peak on follow up MRS. Quantitative analysis showed relative decrease of Cho/Cr ratio on follow up MRS (p = 0.0058, paired t-test, two-tailed). There was no significant change in NAA/Cr ratio. CONCLUSION: MRS is a useful tool for monitoring disease progression or improvement in ME, and decrease or disappearance of lactate peak and reduction of Cho/Cr fraction were correlated well with improvement of clinical symptoms.ope

Vagus Nerve Stimulation in Intractable Childhood Epilepsy: a Korean Multicenter Experience

We evaluated the long-term outcome of vagus nerve stimulation (VNS) in 28 children with refractory epilepsy. Of these 28 children, 15 (53.6%) showed a >50% reduction in seizure frequency and 9 (32.1%) had a >75% reduction. When we compared seizure reduction rates according to seizure types (generalized vs. partial) and etiologies (symptomatic vs. cryptogenic), we found no significant differences. In addition, there was no correlation between the length of the stimulation period and treatment effect. The seizure reduction rate, however, tended to be inversely related to the seizure duration before VNS implantation and age at the time of VNS therapy. VNS also improved quality of life in this group of patients, including improved memory in 9 (32.1%), improved mood in 12 (42.9%), improved behavior in 11 (39.3%), improved altertness in 12 (42.9%), improved achievement in 6 (21.4%), and improved verbal skills in 8 (28.6%). Adverse events included hoarseness in 7 patients, dyspnea at sleep in 2 patients, and wound infection in 1 patient, but all were transient and successfully managed by careful follow-up and adjustment of parameters. These results indicate that VNS is a safe and effective alternative therapy for pediatric refractory epilepsy, without significant adverse events

MR Findings of Fulminent Leukoencephalopathy in EBV-Associated Hemophagocytic Syndrome

Various manifestations of brain involvement for patients with virus-associated hemophagocytic syndrome have been reported. Here, we report on the sequential magnetic resonance (MR) findings of acute demyelination of the entire brain with subsequent brain atrophy in a follow-up study of a 25-month-old boy who was admitted with fever and then diagnosed with infectious mononucleosis and EBV-associated hemophagocytic syndrome. We also review other conditions that should be included in the differential diagnosis of this disease

Population pharmacokinetics of everolimus in patients with seizures associated with focal cortical dysplasia

Background: Everolimus is an inhibitor of mammalian target of rapamycin complex 1. As mutations in TSC1 and TSC2, which cause partial-onset seizures associated with TSC, were found in focal cortical dysplasia type Ⅱ (FCD Ⅱ) patients, a clinical trial has been performed to explore the efficacy and safety of everolimus in FCD patients. However, no dosage regimen was determined to treat FCD II. To recommend an optimal dose regimen for FCD patients, a population pharmacokinetic model of everolimus in FCD patients was developed.Methods: The data of everolimus were collected from September 2017 to May 2020 in a tertiary-level hospital in Korea. The model was developed using NONMEM® software version 7.4.1 (Icon Development Solutions, Ellicott City, MD, United States).Results: The population pharmacokinetics of everolimus was described as the one-compartment model with first-order absorption, with the effect of BSA on clearance. The final model was built as follows: TVCL = 12.5 + 9.71 × (BSA/1.5), TVV = 293, and TVKA = 0.585. As a result of simulation, a dose higher than 7 mg/m2 is needed in patients with BSA 0.5 m2, and a dose higher than 6 mg/m2 is needed in patients with BSA 0.7 m2. A dose of 4.5 mg/m2 is enough in the population with BSA higher than 1.5 m2 to meet the target trough range of 5–15 ng/mL.Conclusion: Based on the developed pharmacokinetics model, the optimal dose of everolimus in practice was recommended by considering the available strengths of Afinitor disperz®, 2 mg, 3 mg, and 5 mg