Fabrication of Polymer Optical Fiber Splitter Using Lapping Technique

This work involves in designing and developing a POF-based directional coupler/splitter using lapping technique and geometrical blocks. Two fiber strands were first tapered at the middle and they were attached to the geometrical blocks and lapped together. Design parameters that are used to develop this coupler/splitter are core diameter, Dc, etching length, Le, bending radius, Rc, coupling length, Lc and pressure, Fc. All the parameters were taken into account during characterization and analysis of the designed coupler in order to find the most optimum prototype coupler/splitter. Characterizations are done by experimental set-up to test the efficiency, splitting ratio, coupling ratio, excess loss and insertion loss for all the couplers/splitters. Through the characterization process and analysis, the optimized coupler with high splitting ratio and low excess loss were identified. Throughout the experimental process, some of the fibers were improved and renewed in order to realize the design and development of the coupler using this technique. The device can also be utilized as an optical tap and the applications of the device are not only limited in in-house network but also in automotive applications. By using a platform, several splitting ratio can be obtained by integrating different core-cladding thickness and bending radius in order to get the desired splitting ratio and excess loss

A Randomized Phase II Trial of Epigenetic Priming with Guadecitabine and Carboplatin in Platinum-resistant, Recurrent Ovarian Cancer.

PURPOSE: Platinum resistance in ovarian cancer is associated with epigenetic modifications. Hypomethylating agents (HMA) have been studied as carboplatin resensitizing agents in ovarian cancer. This randomized phase II trial compared guadecitabine, a second-generation HMA, and carboplatin (G+C) against second-line chemotherapy in women with measurable or detectable platinum-resistant ovarian cancer. PATIENTS AND METHODS: Patients received either G+C (guadecitabine 30 mg/m2 s.c. once-daily for 5 days and carboplatin) or treatment of choice (TC; topotecan, pegylated liposomal doxorubicin, paclitaxel, or gemcitabine) in 28-day cycles until progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS); secondary endpoints were RECIST v1.1 and CA-125 response rate, 6-month PFS, and overall survival (OS). RESULTS: Of 100 patients treated, 51 received G+C and 49 received TC, of which 27 crossed over to G+C. The study did not meet its primary endpoint as the median PFS was not statistically different between arms (16.3 weeks vs. 9.1 weeks in the G+C and TC groups, respectively; P = 0.07). However, the 6-month PFS rate was significantly higher in the G+C group (37% vs. 11% in TC group; P = 0.003). The incidence of grade 3 or higher toxicity was similar in G+C and TC groups (51% and 49%, respectively), with neutropenia and leukopenia being more frequent in the G+C group. CONCLUSIONS: Although this trial did not show superiority for PFS of G+C versus TC, the 6-month PFS increased in G+C treated patients. Further refinement of this strategy should focus on identification of predictive markers for patient selection

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Atherosclerosis Effects of the PPAR-␦ agonist MBX-8025 on atherogenic dyslipidemia

a b s t r a c t Objective: Determine the effects of treatment with a selective PPAR-␦ agonist ± statin on plasma lipoprotein subfractions in dyslipidemic individuals. Methods: Ion mobility analysis was used to measure plasma concentrations of subfractions of the full spectrum of lipoprotein particles in 166 overweight or obese dyslipidemic individuals treated with the PPAR-␦ agonist MBX-8025 (50 and 100 mg/d) ± atorvastatin (20 mg/d) in an 8-week randomized parallel arm double blind placebo controlled trial. Results: MBX-8025 at both doses resulted in reductions of small plus very small LDL particles and increased levels of large LDL, with a concomitant reduction in large VLDL, and an increase in LDL peak diameter. This translated to reversal of the small dense LDL phenotype (LDL pattern B) in ∼90% of the participants. Modest increases in HDL particles were confined to the smaller HDL fractions. Atorvastatin monotherapy resulted in reductions in particles across the VLDL-IDL-LDL spectrum, with a significantly smaller reduction in small and very small LDL vs. MBX-8025 100 mg/d (−24.5 ± 5.3% vs. −47.8 ± 4.9%), and, in combination with MBX-8025, a reversal of the increase in large LDL. Conclusion: PPAR-␦ and statin therapies have complementary effects in improving lipoprotein subfractions associated with atherogenic dyslipidemia

Kindy Moves: the feasibility of an intensive interdisciplinary programme on goal and motor outcomes for preschool-aged children with neurodisabilities requiring daily equipment and physical assistance

Objectives To determine the feasibility of an intensive interdisciplinary programme in improving goal and motor outcomes for preschool-aged children with non-progressive neurodisabilities. The primary hypothesis was that the intervention would be feasible.Design A single group feasibility study.Setting An Australian paediatric community therapy provider.Participants Forty children were recruited. Inclusion criteria were age 2–5 years with a non-progressive neurodisability, Gross Motor Function Classification System (GMFCS) levels III–V or equivalent, and goals relating to mobility, communication and upper limb function. Exclusion criteria included orthopaedic surgery in the past 6 months, unstable hip subluxation, uncontrolled seizure disorder or treadmill training in the past month.Intervention A goal-directed programme of three 2-hour sessions per week for 4 weeks (24 hours total). This consisted of treadmill and overground walking, communication practice, and upper limb tasks tailored by an interdisciplinary team.Primary and secondary outcome measures Limited-efficacy measures from preintervention (T1) to postintervention (T2) and 4-week follow-up (T3) included the Goal Attainment Scaling (GAS), Canadian Occupational Performance Measure (COPM), Gross Motor Function Measure (GMFM-66) and 10-Metre Walk Test (10MWT). Acceptability, demand, implementation and practicality were also explored.Results There were improvements at T2 compared with T1 for all limited-efficacy measures. The GAS improved at T2 (mean difference (MD) 27.7, 95% CI 25.8 to 29.5) as well as COPM performance (MD 3.2, 95% CI 2.8 to 3.6) and satisfaction (MD 3.3, 95% CI 2.8 to 3.8). The GMFM-66 (MD 2.3, 95% CI 1.0 to 3.5) and 10MWT (median difference −2.3, 95% CI −28.8 to 0.0) improved at T2. Almost all improvements were maintained at T3. Other feasibility components were also demonstrated. There were no adverse events.Conclusions An intensive interdisciplinary programme is feasible in improving goal and motor outcomes for preschool children with neurodisabilities (GMFCS III–V or equivalent). A randomised controlled trial is warranted to establish efficacy.Trial registration number ACTRN12619000064101