Application and Comparison of Optimal LQR Controllers for UPFC with wide range of Operating Conditions in Power System

This paper presents the design of Bryson, Bouderal multistage-based totally Linear Quadratic Regulator (LQR) optimal controllers to the Unified Power Flow Controller (UPFC) for mild, normal heavy loads to cowl huge range of running situations. The proposed controllers are applied and compared for the existing Phillips heffron model with UPFC installed using MATLAB/SIMULINK software

Oleic Acid Based Emulgel for Topical Delivery of Ofloxacin

The objective of the present study is to formulate and evaluate ofloxacin emulgel. Emulgel formulations of ofloxacin were prepared using different concentrations of gelling agent’s Carbopol-940 and Xanthum gum. Tween-80 and span-80 were used as emulsifiers and propylene glycol as a humectant in the preparation of emulgel. The effect of the concentration of gelling agent on the drug release from the prepared emulgel was investigated. The compatibility study was conducted using Fourier-transform infrared (FTIR). The formulated emulgel was characterized by their physical appearance, pH determination, viscosity, spreadability, drug content, microbial test and in vitro diffusion study. FTIR indicated that the drug and excipients used in the study are compatible with each other. All the prepared formulations showed acceptable physical properties, homogeneity, consistency, spreadability, viscosity, and pH value. Drug release from all the formulations depended upon the concentration of the polymer used. As the concentration of Carbopol 940 increased the spreadability and drug release was found to be decreased. Emulgels formulated with oleic acid gave a much higher release rate of ofloxacin than emulgels formulated with liquid paraffin. The release of drug from all the emulgels prepared followed Zero-order kinetics. The linear Higuchi plots indicated that the drug release from all the emulgels prepared followed diffusion kinetics. Emulgel formulated with oleic acid exhibited greater flux when compared with those formulated with liquid paraffin. The formulations were found to be stable during stability testing. It can be concluded that Carbopol 940 and oleic acid are recommended for the formulation and preparation of Ofloxacin emulgels for topical drug delivery. Key words: Ofloxacin, Emulgel, Spreadibility, Zone of inhibition

Strain-Temperature Discrimination Using a Single FBG at Cryogenic Region

A simple technique is presented to discriminate the Strain and Temperature with a single Fiber Bragg Grating (FBG) at cryogenic regime. The single FBG is divided into two parts, one half is without coating (FBG1) and other half is coated with Cyno-Acrylic Adhesive (FBG2). The measured temperature and strain sensitivities of the FBG1 are 4.05x10-6 /K and 2.13´10-6 /µε and FBG2 are 1.39 x 10-5 /K and 1.72 x 10-6 /µε respectively. FBG2 is more sensitive to low temperature and FBG1 is more sensitive to axial strain

Real-World Analysis Affirms the High Persistence and Adherence Observed with Diroximel Fumarate in Patients with Multiple Sclerosis

Abstract Introduction Adherence to disease-modifying therapies is key for achieving optimal outcomes in multiple sclerosis (MS). Diroximel fumarate (DRF) is an oral fumarate approved for treatment of relapsing forms of MS. It has the same pharmacologically active metabolite as dimethyl fumarate (DMF) and similar efficacy and safety profiles, but with demonstrated fewer gastrointestinal (GI) related adverse events (AEs). There are limited data characterizing persistence and adherence to DRF in the real world. Methods This retrospective analysis of the AcariaHealth Specialty Pharmacy Program included patients with MS initiating DRF from 1 December 2019 to 30 January 2021. This analysis evaluated persistence, measured as proportion of patients remaining on therapy; discontinuation rate due to GI AEs; and adherence measured by proportion of days covered (PDC). Results Overall, 1143 patients were included; 433 (37.9%) patients had been treated with prior DMF and switched to DRF. Persistence was high in both groups: the estimated proportion of patients remaining on DRF at 16 months was 82.3% [95% confidence internal (CI) 77.2–86.3%], and 90.1% (95% CI 82.2–94.6%) in the DMF to DRF group. Fifty-two (4.5%) patients overall and 15 (3.5%) in the DMF switch subgroup discontinued DRF due to GI AEs. Mean PDC was 90.8% (95% CI 89.2–92.5%), and 85.4% (95% CI 83.3–87.4%) of patients achieved PDC ≥ 80% in the overall population. In the DMF to DRF group, mean PDC was 90.7% (95% CI 88.0–93.5%), and 84.8% (95% CI 81.4–88.1%) of patients achieved PDC ≥ 80%. Conclusion In this analysis of  > 1000 patients treated with DRF in real-world clinical practice, overall persistence at 16 months was high, treatment discontinuation due to GI AEs was low, and patients were highly adherent to therapy. Of 433 patients who switched from DMF to DRF, most (> 90%) were able to tolerate and persist on DRF after switching. Graphical abstract available for this article. Graphical Abstrac

Systematic Review of Single-Fraction Stereotactic Body Radiation Therapy for Early Stage Non-Small-Cell Lung Cancer and Lung Oligometastases: How to Stop Worrying and Love One and Done

Adoption of single-fraction lung stereotactic body radiation therapy (SBRT) for patients with medically inoperable early stage non-small-cell lung cancer (NSCLC) or oligometastatic lung disease, even during the coronavirus disease 2019 (COVID-19) pandemic, was limited despite encouraging phase II trial results. Barriers to using single-fraction SBRT may include lack of familiarity with the regimen and lack of clarity about the expected toxicity. To address these concerns, we performed a systematic review of prospective literature on single-fraction SBRT for definitive treatment of early stage and oligometastatic lung cancer. A PubMed search of prospective studies in English on single-fraction lung SBRT was conducted. A systematic review was performed of the studies that reported clinical outcomes of single-fraction SBRT in the treatment of early stage non-small-cell lung cancer and lung oligometastases. The current prospective literature including nine trials supports the use of single-fraction SBRT in the definitive treatment of early stage peripheral NSCLC and lung oligometastases. Most studies cite local control rates of >90%, mild toxicity profiles, and favorable survival outcomes. Most toxicities reported were grade 1–2, with grade ≥3 toxicity in 0–17% of patients. Prospective trial results suggest potential consideration of utilizing single-fraction SBRT beyond the COVID-19 pandemic

Pomalidomide is effective for prevention and treatment of experimental skin fibrosis

OBJECTIVES: Tissue fibrosis is a major hallmark and a leading cause of death in systemic sclerosis (SSc). Here, we investigated the antifibrotic effects of pomalidomide, an analogue of thalidomide with potent immunomodulatory effects, in preclinical models of skin fibrosis. METHODS: We evaluated the antifibrotic effects of pomalidomide in preventive as well as therapeutic treatment regimes using bleomycin-induced dermal fibrosis as a model of early, inflammatory stages of fibrosis and the tight-skin mouse model as a model of later stages of fibrosis with endogenous activation of fibroblasts. RESULTS: Treatment with pomalidomide in doses from 0.3 to 30 mg/kd/day prevented skin fibrosis in Tsk-1 mice and in bleomycin-induced dermal fibrosis in a dose-dependent manner and reduced the expression of transforming growth factor (TGF) β-target genes such as PAI-1, CTGF and col 1a1. Pomalidomide was also effective in the setting of pre-established fibrosis and reduced dermal thickness, myofibroblast counts and hydroxyproline content below pretreatment levels. CONCLUSIONS: We demonstrate for the first time that pomalidomide exerts potent antifibrotic effects in different preclinical models of skin fibrosis. These findings lend preclinical support for the clinical studies of pomalidomide in SSc

Efficacy of Dimethyl Fumarate in Young Adults with Relapsing-Remitting Multiple Sclerosis: Analysis of the DEFINE, CONFIRM, and ENDORSE Studies

Abstract Introduction Dimethyl fumarate (DMF) showed favorable benefit-risk in patients with relapsing-remitting multiple sclerosis (MS) in phase 3 DEFINE and CONFIRM trials and in the ENDORSE extension study. Disease activity can differ in younger patients with MS compared with the overall population. Methods Randomized patients received DMF 240 mg twice daily or placebo (PBO; years 0–2 DEFINE/CONFIRM), then DMF (years 3–10; continuous DMF/DMF or PBO/DMF; ENDORSE); maximum follow-up (combined studies) was 13 years. This integrated post hoc analysis evaluated safety and efficacy of DMF in a subgroup of young adults aged 18–29 years. Results Of 1736 patients enrolled in ENDORSE, 125 were young adults, 86 treated continuously with DMF (DMF/DMF) and 39 received delayed DMF (PBO/DMF) in DEFINE/CONFIRM. Most (n = 116 [93%]) young adults completed DMF treatment in DEFINE/CONFIRM. Median (range) follow-up time in ENDORSE was 6.5 (2.0–10.0) years. Young adults entering ENDORSE who had been treated with DMF in DEFINE/CONFIRM had a model-based Annualized Relapse Rate (ARR; 95% CI) of 0.24 (0.16–0.35) vs. 0.56 (0.35–0.88) in PBO patients. ARR remained low in ENDORSE: 0.07 (0.01–0.47) at years 9–10 (DMF/DMF group). At year 10 of ENDORSE, EDSS scores were low in young adults: DMF/DMF, 1.9 (1.4); PBO/DMF, 2.4 (1.6). At ~ 7 years, the proportion of young adults with no confirmed disability progresion was 81% for DMF/DMF and 72% for PBO/DMF. Patient-reported outcomes (PROs) (SF-36 and EQ-5D) generally remained stable during ENDORSE. The most common adverse events (AEs) in young adults during ENDORSE were MS relapse (n = 53 [42%]). Most AEs were mild (n = 20 [23.3%], n = 7 [17.9%]) to moderate (n = 45 [52.3%], n = 23 [59.0%]) in the DMF/DMF and PBO/DMF groups, respectively. The most common serious AE (SAE) was MS relapse (n = 19 [15%]). Conclusion The data support a favorable benefit-risk profile of DMF in young adults, as evidenced by well-characterized safety, sustained efficacy, and stable PROs. Clinical Trial Information Clinical trials.gov, DEFINE (NCT00420212), CONFIRM (NCT00451451), and ENDORSE (NCT00835770)