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Fibrosis is an excessive accumulation of the extracellular matrix within solid organs in response to injury and a common pathway that leads functional failure. No clinically approved agent is available to reverse or even prevent this process. Herein, we report a nanotechnology-based approach that utilizes a drug carrier to deliver a therapeutic cargo specifically to fibrotic kidneys, thereby improving the antifibrotic effect of the drug and reducing systemic toxicity. We first adopted in vitro-in vivo combinatorial phage display technology to identify peptide ligands that target myofibroblasts in mouse unilateral ureteral obstruction (UUO)-induced fibrotic kidneys. We then engineered lipid-coated poly(lactic-co-glycolic acid) nanoparticles (NPs) with fibrotic kidney-homing peptides on the surface and sorafenib, a potent antineoplastic multikinase inhibitor, encapsulated in the core. Sorafenib loaded in the myofibroblast-targeted NPs significantly reduced the infiltration of α-smooth muscle actin-expressing myofibroblasts and deposition of collagen I in UUO-treated kidneys and enhanced renal plasma flow measured by Technetium-99m mercaptoacetyltriglycine scintigraphy. This study demonstrates the therapeutic potential of the newly identified peptide fragments as anchors to target myofibroblasts and represents a strategic advance for selective delivery of sorafenib to treat renal fibrosis. SIGNIFICANCE STATEMENT: Renal fibrosis is a pathological feature accounting for the majority of issues in chronic kidney disease (CKD), which may progress to end-stage renal disease (ESRD). This manuscript describes a myofibroblast-targeting drug delivery system modified with phage-displayed fibrotic kidney-homing peptides. By loading the myofibroblast-targeting nanoparticles (NPs) with sorafenib, a multikinase inhibitor, the NPs could suppress collagen synthesis in cultured human myofibroblasts. When given intravenously to mice with UUO-induced renal fibrosis, sorafenib loaded in myofibroblast-targeting NPs significantly ameliorated renal fibrosis. This approach provides an efficient therapeutic option to renal fibrosis. The myofibroblast-targeting peptide ligands and nanoscale drug carriers may be translated into clinical application in the future.

Retinoblastoma, the most common pediatric intraocular malignancy, can develop during embryogenesis, with most children being diagnosed at 3-4 years of age. Multimodal therapies are typically associated with high levels of cytotoxicity and side effects. Therefore, the development of novel treatments with minimal side effects is crucial. Magnolol has a significant anti-tumor effect on various cancers. However, its antitumor effect on retinoblastoma remains unclear.The study aimed to determine the effects of magnolol on the regulation of EMT, migration, invasion, and cancer progression in retinoblastoma and the modulation of miR-200c-3p expression and the Wnt/ zinc finger E-box binding homeobox 1 (ZEB1)/E-cadherin axis in vivo and in vitro.The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay was used to evaluate magnolol-induced cell toxicity in the Y79 retinoblastoma cell line. Flow cytometry and immunostaining assays were performed to investigate the magnolol-regulated mitochondrial membrane potential and the intracellular and mitochondrial reactive oxygen species levels in Y79 retinoblastoma cells. Orthotopic and subcutaneous xenograft experiments were performed in eight-week-old male null mice to study retinoblastoma progression and metastasis. In situ hybridization and quantitative reverse transcription polymerase chain reaction (RT-qPCR) assays were performed to evaluate the level of the anti-cancer miRNA miR-200c-3p. The mRNA and protein levels of E-cadherin, β-catenin, α-smooth muscle actin (α-SMA), fibronectin-1, and ZEB1 were analyzed using RT-qPCR, immunoblot, immunocytochemistry, and immunohistochemistry assays in vitro and in vivo.Magnolol increased E-cadherin levels and reduced the activation of the EMT signaling pathway, EMT, tumor growth, metastasis, and cancer progression in the Y79 retinoblastoma cell line as well as in the orthotopic and subcutaneous xenograft animal models. Furthermore, magnolol increased the expression of miR-200c-3p. Our results demonstrate that miRNA-200c-3p inhibits EMT progression through the Wnt16/β-catenin/ZEB1/E-cadherin axis, and the ZEB1 silencing response shows that miR-200c-3p regulates ZEB1-mediated EMT in retinoblastoma.Magnolol has an antitumor effect by increasing E-cadherin and miRNA-200c-3p expression to regulate ZEB1-mediated EMT and cancer progression in retinoblastoma. The anti-tumor effect of magnolol by increasing E-cadherin and miRNA-200c-3p expression to regulate ZEB1-mediated EMT and cancer progression in retinoblastoma has been elucidated for the first time.

The liquid phase chemical enhanced oxidation (LPCEO) technique was applied to achieve planarized isolation of a high-indium-content In0.52Al0.48As/In0.8Ga0.2As metamorphic high-electron-mobility transistor (MHEMT). Through a simple, low-temperature process not requiring costly machinery, electrical isolation of components was accomplished. In addition, multiple advantages were gained, including the production of planarized surfaces, low pollution, and reduction in the subsequent disposal of wet etching solution and costs for dry etching or ion implantation. Because of the decrease in lateral defect density caused by wet or dry etching and the further decrease in gate leakage current owing to the isolated oxide film, the performance of devices, with improved DC characteristics, less flicker noise, and enhanced high-frequency performance, can be increased.

We conduct a cost-utility analysis of inotuzumab ozogamicin (INO) versus chemotherapy as the standard of care (SOC) for adults with relapsed or refractory B cell acute lymphoblastic leukemia. A Markov model incorporating transition probabilities between health states was applied to simulate disease progression. The model inputs, including overall survival, progression-free survival, and utility parameters, were obtained from the INO-VATE ALL trial and literatures. The Taiwan Cancer Registry Database and the Health and Welfare Database were utilized to identify the patient cohort and medical costs from the perspective of National Health Insurance Administration. The lifetime medical costs (in 2017 US dollars), quality-adjusted life years (QALYs) gained, and associated incremental cost-effectiveness ratio (ICER) were the main study outcomes. The lifetime medical costs for INO and SOC were $176,795 and $69,496, and the QALYs gained were 2.25 and 0.84, respectively. The ICER for INO versus SOC was $76,044 per QALY gained, which is slightly more than three times Taiwan’s gross domestic product per capita (i.e., $73,224). Favorable economic results for INO versus SOC were found with an increased time horizon for model simulation, less discounting for the future benefit, and higher stem cell transplantation (SCT) rate after INO treatment; and among patients aged less than 55 years, with no SCT history, or in the first salvage treatment. INO versus SOC has higher costs but is more effective. The use of INO is favorable for patients in the early treatment course and when more future benefit associated with INO is considered.

The accumulation of unknown polymorphic composites in the endocardium damages the endocardial endothelium (EE). However, the composition and role of unknown polymorphic composites in heart failure (HF) progression remain unclear. Here, we aimed to explore composite deposition during endocardium damage and HF progression. Adult male Sprague–Dawley rats were divided into two HF groups—angiotensin II-induced HF and left anterior descending artery ligation-induced HF. Heart tissues from patients who had undergone coronary artery bypass graft surgery (non-HF) and those with dilated cardiomyopathy (DCM) and ischemic cardiomyopathy (ICM) were collected. EE damage, polymorphic unknown composite accumulation, and elements in deposits were examined. HF progression reduced the expression of CD31 in the endocardium, impaired endocardial integrity, and exposed the myofibrils and mitochondria. The damaged endocardial surface showed the accumulation of unknown polymorphic composites. In the animal HF model, especially HF caused by myocardial infarction, the weight and atomic percentages of O, Na, and N in the deposited composites were significantly higher than those of the other groups. The deposited composites in the human HF heart section (DCM) had a significantly higher percentage of Na and S than the other groups, whereas the percentage of C and Na in the DCM and ICM groups was significantly higher than those of the control group. HF causes widespread EE dysfunction, and EndMT was accompanied by polymorphic composites of different shapes and elemental compositions, which further damage and deteriorate heart function.

Pulmonary artery hypertension (PAH) pathology involves extracellular matrix (ECM) remodeling in cardiac tissues, thus promoting cardiac fibrosis progression. miR-29a-3p reportedly inhibits lung progression and liver fibrosis by regulating ECM protein expression, however, its role in PAH-induced fibrosis remains unclear. In this study, we aimed to investigate the role of miR-29a-3p in cardiac fibrosis progression in PAH and its influence on ECM protein thrombospondin-2 (THBS2) expression. The diagnostic and prognostic values of miR-29a-3p and THBS2 in PAH were evaluated. The expressions and effects of miR-29a-3p and THBS2 were assessed in cell culture, monocrotaline-induced PAH mouse model, and patients with PAH. The levels of circulating miR-29a-3p and THBS2 in patients and mice with PAH decreased and increased, respectively. miR-29a-3p directly targets THBS2 and regulates THBS2 expression via a direct anti-fibrotic effect on PAH-induced cardiac fibrosis. The circulating levels of miR-29a-3p and THBS2 were correlated with PAH diagnostic parameters, suggesting their independent prognostic value. miR-29a-3p targeted THBS2 expression via a direct anti-fibrotic effect on PAH-induced cardiac fibrosis, indicating miR-29a-3p acts as a messenger with promising therapeutic effects.

Aims This study assessed the cost-effectiveness of long-acting insulin analogues (LAIAs) vs intermediate/long-acting human insulin (ILAHI) for patients with type 1 diabetes (T1D) in real-world clinical practice. Methods Individual-level analyses were conducted within a longitudinal population-based cohort of 540 propensity score-matched T1D patients (LAIAs, n = 270; ILAHI, n = 270) with over 10 years of follow-up using Taiwan's National Health Insurance Research Database, 2004-2013, from third-party payer and healthcare sector perspectives. The study outcomes included the number needed to treat (NNT) to prevent one case of clinical events (eg, hypoglycaemia, diabetes-related complications), medical costs, and cost per case of events prevented. Cost estimates are presented in 2013 British pounds (GBP, £). Results The NNTs using LAIAs vs ILAHI to avoid one case of hypoglycaemia requiring medical assistance, outpatient hypoglycaemia and any diabetes-related complications were 12, 9 and 10 for mean follow-up periods of 5.84, 6.02 and 3.62 years, respectively. From third-party payer and healthcare sector perspectives, using LAIAs instead of ILAHI saved GBP6924-GBP7116 per case of hypoglycaemia requiring medical assistance prevented, GBP5346-GBP5508 per case of outpatient hypoglycaemia prevented, and GBP3570-GBP3680 per case of any diabetes-related complications prevented. Sensitivity analyses considering sampling uncertainty showed that using LAIAs over ILAHI yields at least a 76% probability of cost-saving for avoiding one case of hypoglycaemia requiring medical assistance, outpatient hypoglycaemia or any diabetes-related complications. Conclusions This real-world evidence reveals that compared with ILAHI, the greater pharmaceutical costs associated with LAIAs for patients with T1D could be substantially offset by savings from averted hypoglycaemia or diabetes-related complications.

An individualized FEVTo evaluate the external validity of the LHS FEVWe used the sample of ever-smokers with spirometrically-confirmed COPD from the Canadian Cohort of Obstructive Lung Disease (CanCOLD), an ongoing prospective, longitudinal, multicenter population-based cohort study. We compared the mean predicted against the mean observed FEVThe final CanCOLD sample consisted of 360 ever-smoker COPD patients, contributing to 970 FEVThe model showed robust performance in predicting FEV

INTRODUCTION: Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in adults in the US. Sixty-seven percent of patients diagnosed with CLL are age 65 years or older. While new agents and treatment combinations have been approved for CLL and treatment guidelines take into consideration age, frailty, and comorbidity status, limited information exists on current prescribing patterns or the demographic and clinical characteristics of individuals receiving them. The objectives of this study were to: 1) characterize CLL treatment patterns and timing of treatment; 2) identify factors associated with the receipt of CLL treatment in the US Medicare population. METHODS: The study sample included Medicare beneficiaries diagnosed with CLL from 2017 to 2019 using the Chronic Conditions Data Warehouse. Medicare beneficiaries were identified using billing diagnosis codes. Patients who were not treated for CLL during a continuous 6-month period (i.e., baseline period), continuously enrolled in Medicare Parts A, B, and D at baseline with no evidence of enrollment in Medicare Advantage, and age 65 or older at the index date were included. The index date was defined as the date of the first claim with a CLL diagnosis code during the cohort identification period (7/1/2017-6/30/2019). Individuals were followed from the index date until loss of eligibility, death, or end of the study period on 12/31/2019, whichever occurred first. We characterized CLL treatments using National Comprehensive Cancer Network guidelines and grouped individuals based on the first treatment received. The CLL treatments included: rituximab monotherapy, ibrutinib monotherapy, bendamustine/rituximab (BR), obinutuzumab, and other treatments. We reported the proportion of individuals who received the first course of treatment (COT), the top-ranked regimens within the first COT, and the median time to starting the first COT. Time-to-initiation was calculated as the time (in days) from the index date until the first evidence of treatment receipt. We utilized EventFlow visual analytics software to characterize longitudinal patterns of CLL treatments received from the index date (Day 0) until the end of follow-up. EventFlow facilitates exploratory, visual analyses of temporal event sequences using patient-level information about single events (e.g., infusion date), interval events (prescription start and end date), and the end-of-study indicator. We characterized the sample using the following baseline measures: age, race/ethnicity, gender, Charlson Comorbidity Index score, and use of preventive health services, among other measures. We identified factors associated with receipt of CLL treatment using a logistic regression model and reported the covariate-adjusted odds ratio (AOR). An AOR RESULTS: After applying the inclusion/exclusion criteria, 3,440 CLL patients were identified. Sixteen percent (n=556) of individuals received CLL treatment and the median follow up time was 540 days. Overall, the mean (standard error) age was 77 (8); 49% male. Among the 556 treated patients, the distribution of first COT was 35% ibrutinib, 34% rituximab, 12% BR, 4% obinutuzumab, and 14% other treatment. The median (interquartile range, mean) time to receipt of CLL treatment was 61 (224, 166) days. The median time to receipt of ibrutinib, rituximab, BR, or obinutuzumab was 109, 49, 53, and 140 days, respectively. The EventFlow graphic (Figure 1) illustrates treatments received (prescriptions or chemotherapy administrations) post-index date and through the end of the study period. Less than half of the patients in the BR group completed six doses of BR. Compared to patients in the rituximab group, a larger proportion of patients in the ibrutinib and BR groups remained on the first COT over time. In the logistic regression model age (≥85 vs 65-74; AOR=0.69; 95% CI:0.53-0.91) and gender (male vs female; AOR=1.28; 95% CI: 1.06 - 1.54) were statically significant; no other statistically significant differences based on baseline measures were observed. CONCLUSIONS: Among Medicare beneficiaries diagnosed with CLL, less than 2 out of 10 patients received CLL treatment. The most common treatments administered during this time period were ibrutinib or rituximab. Younger age and male gender were factors associated with increased receipt of treatment. Figure 1 Figure 1. Disclosures Onukwugha: BeiGene, Ltd.: Research Funding; Sanofi Aventis: Other: Faculty mentor on a pre-doctoral fellowship. Cooke: BeiGene, Ltd.: Research Funding. Yang: BeiGene, Ltd.: Current Employment. Liu: BeiGene, Ltd.: Current Employment. Tang: BeiGene, Ltd.: Current Employment.

Aim We compared the effects of two types of basal insulin: long-acting insulin analogues vs. intermediate/long-acting human insulin, on diabetes-related complications in type 1 diabetes. Methods A total of 1188 patients with type 1 diabetes who had recently started on long-acting insulin analogues or intermediate/long-acting human insulin were identified in 2004–2008 and followed until death or the end of 2013. Clinical outcomes included acute (i.e. hyperglycaemia, hypoglycaemia) and chronic (i.e. nephropathy, retinopathy, neuropathy, cardiovascular diseases) complications. Diabetes-related complications were measured as a composite outcome which included acute and chronic complications. Cox proportional hazards models were used to assess the time to event hazard ratio. Three propensity score (PS) methods were applied to adjust for baseline imbalances between basal insulin groups, including the PS-matching approach (as the main analysis), standardized mortality ratio weighting (SMRW) and inverse probability of treatment weighting (IPTW). Results Long-acting insulin analogues vs. intermediate/long-acting human insulin had a lower risk for a composite of diabetes-related complications {adjusted hazards ratios [aHRs] [95% confidence interval (CI)] 0.782 [0.639, 0.956], 0.743 [0.598, 0.924] and 0.699 [0.577, 0.846] according to the PS-matching approach, SMRW and IPTW, respectively}. Compared with intermediate/long-acting human insulin, using long-acting insulin analogues had a lower hypoglycaemia risk: aHRs (95% CI) 0.681 (0.498, 0.930), 0.662 (0.466, 0.943) and 0.639 (0.471, 0.867) from the PS-matching approach, SMRW and IPTW, respectively. No statistical differences were found between two types of insulin on individual chronic complications. Conclusion A trend of lower diabetes-related complications associated with long-acting insulin analogues vs. intermediate/long-acting human insulin was observed. A reduced hypoglycaemia risk with long-acting insulin analogues was confirmed in this ‘real-world’ study.

The study investigated titanium dioxide (TiO2) on indium phosphide (InP) prepared by solution-gelation (sol-gel) process and application to InAlAs/InGaAs metal-oxide-semiconductor metamorphic high-electron-mobility transistor (MOS-MHEMT). The sol-gel TiO2 exhibits not only easy process and without plasma source, but also high dielectric constant to improve the interface state between metal and semiconductor. The InAlAs/InGaAs MHEMT with sol-gel processed TiO2 as gate oxide reveals superior electrical characteristics than the reference case. These electrical characteristics include better drain current density, larger turn-on voltage, improved reverse breakdown voltage, as well as smaller gate leakage current density. These results indicate the potentiality of the proposed sol-gel process TiO2 as gate oxide on InAlAs/InGaAs MHEMT for further power application.

With increasing of the development of smart grid and restructuring of the power industry, the efficient operation schedule for a time-of-use (TOU) rate industrial user may become a more important problem in smart cities. This paper develops a stochastic direct search method (SDSM) to solve the operating schedule of a TOU rate industrial user. To effectively overcome the coupling constraints of the operating schedule problem, the three-state dynamic programming (DP) is also incorporated into the SDSM to augment the direct stochastic search procedure. A TOU rate industrial customer of Taiwan Power Company (TPC) is used as an example to validate the feasibility of the SDSM algorithm for the application considered. Numerical experiments are included to illustrate the effects of battery energy storage system (BESS) on operating schedule and to assess the impact and economic benefits of the installation of renewable energy sources (RES) for the TOU rate industrial customer.

Background Although numerous health-related quality of life (HRQoL) instruments are available for patients with diabetes, the length of these measures may limit their feasibility to routine practice. Also, these measures do not distinguish items for generic and diabetes-specific HRQoL. This study was aimed to develop a diabetes-specific quality of life questionnaire module (DMQoL) to be in conjunction with the World Health Organization Quality of Life scale brief version (WHOQOL-BREF). Methods One hundred seventeen patients with diabetes were enrolled from a medical center in Taiwan. The item content of DMQoL was constructed based on an extensive review of existing HRQoL instruments for diabetes, expert discussions and patient interviews. A series of psychometric tests were conducted to ensure the reliability and validity of DMQoL. The WHOQOL-BREF served as an existing HRQoL measure for construct validity testing. The response scale of DMQoL was adopted from the 5-point Likert scale of WHOQOL-BREF. Results A total of 10 items without ceiling or floor effects were selected from 20 items. Exploratory factor analysis (EFA) with parallel analysis and Rasch analysis concluded that the 10 items were embedded in the same underlying concept. The corrected item-total correlations and factor loadings from EFA were all above 0.4. The internal consistency of the 10 items was satisfactory (Cronbach’s α = 0.84). The DMQoL total score was moderately correlated with that of WHOQOL-BREF (r = 0.48, p 8% (3.66 ± 0.47 vs. 3.41 ± 0.53; p = 0.037). Conclusions The DMQoL with only 10 items is developed and it is sensitive to the change of diabetes progression in early phases (e.g., glycemic changes). The combination of WHOQOL-BREF and DMQoL provides a comprehensive picture of overall HRQoL in patients with diabetes and enhance the instrument’s ability to detect clinically meaningful changes in diabetes. Electronic supplementary material The online version of this article (doi:10.1186/s12955-017-0744-3) contains supplementary material, which is available to authorized users.

Objective To estimate the incidence densities and cumulative incidence of diabetes-related complications in patients with type 1 diabetes for a maximum of 15-year follow-up. The estimations were further stratified by gender and age at diagnosis (ie, early onset: 0–12 years, late onset:≥13 years). Design A population-based retrospective longitudinal cohort study. Setting Taiwan’s National Health Insurance medical claims. Participants 4007 patients newly diagnosed with type 1 diabetes were identified during 1999–2012. Outcome measures Acute complications included diabetic ketoacidosis (DKA) and hypoglycaemia. Chronic complications were cardiovascular diseases (CVD), retinopathy, neuropathy and nephropathy. Results The incidence density of retinopathy was greatest (97.74 per 1000 person-years), followed by those of nephropathy (31.36), neuropathy (23.93) and CVD (4.39). Among acute complications, the incidence density of DKA was greatest (121.11 per 1000 person-years). The cumulative incidences of acute complications after 12 years following diagnosis were estimated to be 52.1%, 36.1% and 4.1% for DKA, outpatient hypoglycaemia and hospitalised hypoglycaemia, respectively. For chronic complications, the cumulative incidence of retinopathy after 12 years following diagnosis was greatest (65.2%), followed by those of nephropathy (30.2%), neuropathy (23.7%) and CVD (4.1%). Females with late-onset diabetes were greatly affected by advanced retinopathy (ie, sight-threatening diabetic retinopathy) and hospitalised hypoglycaemia, whereas those with early-onset diabetes were more vulnerable to DKA. Chronic complications were more commonly seen in late-onset diabetes, whereas early-onset diabetes were most affected by acute complications. Conclusions Ethnic Chinese patients with type 1 diabetes were greatly affected by DKA and retinopathy. The incidence of diabetes-related complications differed by age at diagnosis and sex.

We compared the effects of two types of basal insulin: long-acting insulin analogues vs. intermediate/long-acting human insulin, on diabetes-related complications in type 1 diabetes.A total of 1188 patients with type 1 diabetes who had recently started on long-acting insulin analogues or intermediate/long-acting human insulin were identified in 2004-2008 and followed until death or the end of 2013. Clinical outcomes included acute (i.e. hyperglycaemia, hypoglycaemia) and chronic (i.e. nephropathy, retinopathy, neuropathy, cardiovascular diseases) complications. Diabetes-related complications were measured as a composite outcome which included acute and chronic complications. Cox proportional hazards models were used to assess the time to event hazard ratio. Three propensity score (PS) methods were applied to adjust for baseline imbalances between basal insulin groups, including the PS-matching approach (as the main analysis), standardized mortality ratio weighting (SMRW) and inverse probability of treatment weighting (IPTW).Long-acting insulin analogues vs. intermediate/long-acting human insulin had a lower risk for a composite of diabetes-related complications {adjusted hazards ratios [aHRs] [95% confidence interval (CI)] 0.782 [0.639, 0.956], 0.743 [0.598, 0.924] and 0.699 [0.577, 0.846] according to the PS-matching approach, SMRW and IPTW, respectively}. Compared with intermediate/long-acting human insulin, using long-acting insulin analogues had a lower hypoglycaemia risk: aHRs (95% CI) 0.681 (0.498, 0.930), 0.662 (0.466, 0.943) and 0.639 (0.471, 0.867) from the PS-matching approach, SMRW and IPTW, respectively. No statistical differences were found between two types of insulin on individual chronic complications.A trend of lower diabetes-related complications associated with long-acting insulin analogues vs. intermediate/long-acting human insulin was observed. A reduced hypoglycaemia risk with long-acting insulin analogues was confirmed in this 'real-world' study.

Multifunctional polymer nanoparticles have been developed for cancer treatment because they could be easily designed to target cancer cells and to enhance therapeutic efficacy according to cancer hallmarks. In this study, we synthesized a pH-sensitive polymer, poly(methacrylic acid-co-histidine/doxorubicin/biotin) (HBD) in which doxorubicin (DOX) was conjugated by a hydrazone bond to encapsulate an immunotherapy drug, imiquimod (IMQ), to form dual cancer-targeting and dual drug-loaded nanoparticles. At low pH, polymeric nanoparticles could disrupt and simultaneously release DOX and IMQ. Our experimental results show that the nanoparticles exhibited pH-dependent drug release behavior and had an ability to target cancer cells via biotin and protonated histidine.

Many expect wind energy to continue increasing due to falling capital costs, market scalability, and its low environmental impact. As more wind turbine generators are connected to utility systems, it is becoming more important to study the impact of wind turbine generators (WTGs) on power system operations. Wind generation system will affect not only the economic operation of a power system but also the bus voltage and transmission losses due to different locations of wind generation system. Optimal power flow (OPF) program is a useful tool for power system operation and planning. This study proposes an Evolutionary Particle Swarm Optimization (EPSO) approach for the optimal power flow problem. The proposed model considers up-spinning reserves, down-spinning reserves and the operational constraints of the generation unit. The effects of wind generation on power system operation and planning are investigated. This study uses the load and unit data of a modified IEEE 30 bus power system to test the corrective of the new method. The OPF results in this study satisfy the operational requirements of a wind-thermal power system. This study also applies the developed OPF program to estimate the effects of wind generation on power system operation and the planning. Experiment results show that the developed OPF program is a useful tool for wind-thermal power system operation and the planning. The results of this study can serve as a reference for wind-thermal power system operation and the planning.

Wind power penetration in Taiwan power system faces significant barriers due to limited transmission capability. One of the most important future challenges seems to be the management of the integration of fluctuations in the electricity production from wind energy sources. The problem is further complicated by the generation dispatch imposed by the presence of transmission capacity limits. Several new important concepts about economic dispatch (ED) model are investigated in this paper for the large-scale wind capacity integration. A penalty function-hybrid direct search method (PF-HDSM) is also developed for the solution of multi-area wind-thermal coordination dispatch (MWCD) problem. Several important issues of wind capacity integration in the Taiwan power system are discussed by using the developed MWCD software. Numerical experiments are included to illustrate the impacts of transmission capacity limits on wind power penetration level in each area and to assess the impact and economic benefits of the installation of wind farms for the Taiwan power system.

Existing diabetes-specific health-related quality life measures. Appendix 2. Initial 20 items in DM module in Chinese (Bold items: 10 items retained in the final scale). Appendix 3. Initial 20 items in DM module in English (Bold items: 10 items retained in the final scale). (DOCX 30 kb)

Incremental cost-effectiveness ratio (ICER) under assumption that length of IV treatment for success and survival is 30 days. Figure S2. Incremental cost-effectiveness ratio (ICER) for comparison between echinocandins (anidulafungin as reference). Figure S3. Incremental cost-effectiveness ratio (ICER) based on efficacy data from Reboli et al.’s study [8]. Table S4. Summary of basic information on selected articles in Asia. Table S5. Summary of the results from systemic review and comparison to global data [25–31]. (DOCX 327 kb)

Background Cost-effectiveness studies of echinocandins for the treatment of invasive candidiasis, including candidemia, are rare in Asia. No study has determined whether echinocandins are cost-effective for both Candida albicans and non-albicans Candida species. There have been no economic evaluations that compare non-echinocandins with the three available echinocandins. This study was aimed to assess the cost-effectiveness of individual echinocandins, namely caspofungin, micafungin, and anidulafungin, versus non-echinocandins for C. albicans and non-albicans Candida species, respectively. Methods A decision tree model was constructed to assess the cost-effectiveness of echinocandins and non-echinocandins for invasive candidiasis. The probability of treatment success, mortality rate, and adverse drug events were extracted from published clinical trials. The cost variables (i.e., drug acquisition) were based on Taiwan’s healthcare system from the perspective of a medical payer. One-way sensitivity analyses and probability sensitivity analyses were conducted. Results For treating invasive candidiasis (all species), as compared to fluconazole, micafungin and caspofungin are dominated (less effective, more expensive), whereas anidulafungin is cost-effective (more effective, more expensive), costing US$3666.09 for each life-year gained, which was below the implicit threshold of the incremental cost-effectiveness ratio in Taiwan. For C. albicans, echinocandins are cost-saving as compared to non-echinocandins. For non-albicans Candida species, echinocandins are cost-effective as compared to non-echinocandins, costing US$652 for each life-year gained. The results were robust over a wide range of sensitivity analyses and were most sensitive to the clinical efficacy of antifungal treatment. Conclusions Echinocandins, especially anidulafungin, appear to be cost-effective for invasive candidiasis caused by C. albicans and non-albicans Candida species in Taiwan. Electronic supplementary material The online version of this article (doi:10.1186/s12879-017-2573-8) contains supplementary material, which is available to authorized users.

A novel approach based on the direct search method (DSM) is proposed for the solution of combined heat and power (CHP) dispatch problem. To deal with the mutual dependency of multiple-demand and heat–power capacity of cogeneration units, the penalty functions should be considered in DSM to enforce the corresponding violated constraints from the infeasible region into the feasible region. Many nonlinear characteristics of the generator can be handled properly in the direct search procedure. To increase the possibility of exploring the search space where the global optimal solution exists, another effective strategy based on a successive refinement search technique is also proposed to guarantee a possibly complete examination of the solution space. Numerical experiments are included to demonstrate the proposed direct search approach can obtain a higher quality solution than many existing techniques.

Wind farms installed on isolated systems are subject to significant restrictions, affecting their expected energy yield and, hence, the feasibility of investments. As wind power penetrations increase in isolated power systems, it is very important to understand how variations in wind plant outputs affect the operation of the isolated system on a day to day basis and what the associated added costs are. In this paper, a wind-Diesel coordination generation scheduling (WCGS) software is developed for appropriate assessment of the added cost to cover the unpredictable wind generator output variations. The developed WCGS software is also a useful tool for the system planner to predict the energy cost and the fuel saving from the expected new wind-Diesel systems. Several technique constraints are applied to determine the optimal proportion of wind generator capacity that can be integrated into the existing system. A simple benefit cost ratio (BCR) is used in this study to evaluate the investment effectiveness of the installation of wind farms for an isolated hybrid system. Numerical experiments are included to understand the wind generator output variations in system operating cost analysis and to assess the impact and economic benefits of the installation of wind farms.

This paper uses multi-pass iteration particle swarm optimization (MIPSO) to solve short term hydroelectric generation scheduling of a power system with wind turbine generators. MIPSO is a new algorithm for solving nonlinear optimal scheduling problems. A new index called iteration best (IB) is incorporated into particle swarm optimization (PSO) to improve solution quality. The concept of multi-pass dynamic programming is applied to modify PSO further and improve computation efficiency. The feasible operational regions of the hydro units and pumped storage plants over the whole scheduling time range must be determined before applying MIPSO to the problem. Wind turbine power generation then shaves the power system load curves. Next, MIPSO calculates hydroelectric generation scheduling. It begins with a coarse time stage and searching space and refines the time interval between two time stages and the search spacing pass by pass (iteration). With the cooperation of agents called particles, the near optimal solution of the scheduling problem can be effectively reached. The effects of wind speed uncertainty were also considered in this paper. The feasibility of the new algorithm is demonstrated by a numerical example, and MIPSO solution quality and computation efficiency are compared to those of other algorithms.

Polyethylene oxide/phenol formaldehyde silica composite hollow spheres were obtained from a fast silicification of a polymer blend, containing polyethylene oxide (PEO) as silica gelator and phenol formaldehyde (PF) polymer as carbon source, in a highly diluted silica solution at pH ≈ 5.0–6.0. The PF–PEO/silica hollow spheres can be feasibly converted to mesoporous silica hollow spheres by hydrothermal treatment and calcination, and to mesoporous carbon hollow spheres after pyrolysis under a nitrogen atmosphere and silica etching. Because the formation of the hollow spheres is kinetically controlled, the diameter of the hollow spheres is dependent on the molecular weight of the PEO polymer, pH value of the silica solution, and the PF content, and the size can be tuned within a range of a few micrometers to tens of nanometers. These mesoporous hollow spheres have high surface areas and large pore sizes and volumes. In practice, the mesoporous carbon hollow spheres with an interconnected mesostructure were used as a solid template to prepare different metal oxide hollow spheres. After impregnation of the proper metal oxide precursors and calcination, the γ-Al2O3, anatase-TiO2, α-Fe2O3, ZrO2, MgO, and CeO2 hollow spheres composed of nanoparticles were readily synthesize.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

Open reduction and internal fixation has been the gold standard for displaced fracture involving weightbearing dome and fractures with intra-articular fragments. However, extensile exposure can lead to complications. Fracture with minimal displacement can be fixed by a minimally invasive method. Percutaneous screwing for an anterior column fracture of acetabulum under conventional 2D fluoroscopy is a demanding technique. With fluoroscopic-based computerized navigation, we can determine the position of a screw real time intra-operatively with less exposure to radiation. We proposed that a fluoroscopy-based computerized navigational system would simplify operation procedures. The purpose of this study is to test the application of the fluoroscopy-based computerized navigational system for anterior column fracture of acetabulum.A prospective cohort study was conducted. Three patients with mildly displaced or non-displaced anterior column fracture of acetabulum were treated with a retrograde lag screw under a fluoroscopy-based computer navigation system. There were two males and one female with a mean age of 39 years and all patients were followed up for more than 1 year. Patients were allowed to perform joint movement exercises and to walk with partial weightbearing on the first day post-operatively.The mean operation time was 40 min (range 30-45 min) from the use of fluoroscopy to wound closure and the mean total fluoroscopy time was 38 s (range 35-45 s). Total blood loss was less than 10 ml. The patients were pain free 1 week after the operation and had good functional recovery thereafter. No complication was noted postoperatively.Though the indication for this procedure is limited, we think that there should be potential to apply the screw with less radiation by fluoroscopic-based computerized navigation. Once anatomic reduction can be achieved by the close method in the anterior column fracture of the acetabulum, percutaneous screw fixation under fluoroscopic-based computerized navigation could be a reliable method; however; validating the position of the guide pin and screw by fluoroscopy is suggested.

This paper presents a new algorithm for solving the optimal contract capacities of a time-of-use (TOU) rates industrial customer. This algorithm is named iteration particle swarm optimization (IPSO). A new index, called iteration best is incorporated into particle swarm optimization (PSO) to improve solution quality and computation efficiency. Expanding line construction cost and contract recovery cost are considered, as well as demand contract capacity cost and penalty bill, in the selection of the optimal contract capacities. The resulting optimal contract capacity effectively reaches the minimum electricity charge of TOU rates users. A significant reduction in electricity costs is observed. The effects of expanding line construction cost and contract recovery cost on the selection of optimal contract capacities can also be estimated. The feasibility of the new algorithm is demonstrated by a numerical example, and the IPSO solution quality and computation efficiency are compared to those of other algorithms.

This paper presents a new algorithm for solution of the nonlinear optimal scheduling problem. This algorithm is named the iteration particle swarm optimization (IPSO). A new index, called iteration best, is incorporated into particle swarm optimization (PSO) to improve the solution quality and computation efficiency. IPSO is applied to solve the unit commitment with probabilistic reserve problem of a power system. The outage cost as well as fuel cost of thermal units was considered in the unit commitment program to evaluate the level of spinning reserve. The optimal scheduling of on line generation units was reached while minimizing the sum of fuel cost and outage cost. A 48 unit power system was used as a numerical example to test the new algorithm. The optimal scheduling of on line generation units could be reached in the testing results while satisfying the requirement of the objective function.

As wind power penetrations increase in isolated power systems, more innovative and sophisticated approaches to system operation will need to be adopted due to the intermittency and unpredictability of wind power generation. Development of better wind-thermal coordination algorithms is necessary to determine the optimal proportion of wind generator capacity that can be integrated into the system for operating an isolated hybrid power system reliably and efficiently. In this paper, an iterative algorithm, which utilizes a direct search method (DSM) approach, is developed to coordinate the wind and thermal generation dispatch and to minimize the total production cost in the reserve constrained economic dispatch considering wind power generation. The effects of total wind power generation and system spinning reserve requirements are consistently reflected in the total production cost. Numerical experiments are included to understand the wind generator capacity in the production cost analysis and to provide valuable information for both operational and planning problems.

This paper presents an Ant Colony System (ACS) based optimization approach to solve the optimal spinning reserve problem for a power system. Unit commitment risk is used as an index to evaluate the level of spinning reserve. The outage cost and the fuel cost of thermal units were considered in the unit commitment program. The optimal spinning reserve and unit commitment risk were reached while the sum of fuel cost and outage cost was minimized. A 52 units power system was used as a numerical example to test the new algorithm. The optimal spinning reserve and unit commitment risk could be reached in the testing while satisfying the requirement of the objective function.

Isoequilibrium behavior arising from the temperature dependence of ΔG° of families of complexes containing phosphorus(III) ligands provides a diagnostic method for evaluating a model (used to describe ligand effects) and the associated set of stereoelectronic parameters. This evaluation is based not on the quality of a linear free energy relationship, but rather on the results of a thermodynamic argument. Studies of the temperature dependence of E°/T values for the η-Cp(CO)(L)Fe(COMe)+/η-Cp(CO)(L)Fe(COMe)0 couple, where L is a phosphorus(III) ligand, provide isoequilibrium data to test the ECW model for analysis of ligand effects. The ECW model fails this test. Therefore, we conclude that the ECW model is, in general, inadequate to describe the stereoelectronic properties of phosphorus(III) ligands.

This paper sets up a formulation to determine the optimal contract capacities and optimal sizes of battery energy storage systems for time-of-use rate customers. The advanced multi-pass dynamic programming and expert knowledge base rules are then applied to solve this problem. Two industrial customers of the Taiwan Power Company System are used as examples to test this algorithm. Results show that the optimal sizes of battery energy storage systems and the optimal contract capacities of customers during the life cycle of battery energy storage systems can be achieved by this algorithm; therefore the maximum economic benefits of battery energy storage systems for time-of-use rate customers can be estimated. >

It is widely recognized that a proper schedule of available generating units may save utilities millions of dollars per year in production costs. A novel particle swarm optimization (PSO) combined with the direct search method (DSM) is developed in this paper for the solution of economic dispatch (ED) problem with valve-point effect. A new inertia weight mechanism is incorporated into PSO to enhance its search capacity that leads to a higher probability of obtaining the global optimal solution. The main attractive feature of the proposed inertia weight mechanism is to monitor the weights of particles, which were linearly decreased in general applications, and to further provide a well-balanced mechanism between the global and local exploration abilities. The DSM algorithm is used as a fine tuning to determine the eventual global optimal solution with a reduced computing time. The validity, robustness, and effectiveness of the proposed approach is verified through numerical experiments for extended economic dispatch application.

This paper investigates the optimal capacity of a battery energy storage system in a power system. The Taiwan Power Company System is used as an example system to test this algorithm. Results show that the maximum economic benefit of battery energy storage in a power system can be achieved by this algorithm. >

Isoequilibrium behavior provides a method of determining stereoelectronic parameters, for use in linear free energy relationships. This method is based on thermodynamics and is different from the usual ways of assigning values to these parameters. Analysis of isoequilibrium behavior is done in terms of the three parameter QALE (quantitative analysis of ligand effects) model, with parameters χ, θ and Ear. We use this method to interpret new E°/T values of the η-Cp(CO)(L)Fe(COMe)+/0 couple (Cp = cyclopentadienyl, L = PPhiR3–i) and establish a way to calculate χ and Ear values for PPhiR3–i. In support of the validity of the method, we find that these calculated χ values agree well, except for PPh2Pri, with the values previously reported by Bartik. We also calculated a value for χ equal to 0.4 for P(NC4H8)3 for which a χ value had not been reported previously.