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  • 1
    Publication Date: 2016-02-03
    Description: Background : The diagnosis-related group-based prospective payment programme was introduced in Korea in 1997 as a pilot programme to control health spending. In July 2013, the programme was implemented throughout the nation. The aim of our study is to evaluate the relationship between quality of care and market competition following the introduction of the new payment system in Korea. Methods : We conduct an observational analysis using National Health Insurance claim data from 2011 to 2014. We analyse data on readmission within 30 days, length of stay, and number of outpatient visits for 1742 hospitals and 821 912 cases. We use a generalized estimating equation model to evaluate readmission within 30 days and number of outpatient visits and a multi-level regression model to assess length of stay. Results : Total readmission within 30 days is 10 727 (1.3%). High competition areas present a lower risk of readmission [odds ratio (OR): 0.95, P : 0.0277], a longer length of stay (1%, P 〈 0.0001), and an increased number of outpatient visits (Relative Risk: 1.11, P : 0.0011) as compared with moderate competition areas. Risk of readmission is higher in low competition areas as compared with moderate competition areas (OR: 1.21, P 〈 0.0001). Conclusion: The effects of the introduction of the new payment system differed by degree of market competition. Thus, evaluation about the effect of new payment system on hospital performance should be measured in combination with the degree of hospital market structure.
    Print ISSN: 1101-1262
    Electronic ISSN: 1464-360X
    Topics: Medicine
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  • 2
    Publication Date: 2015-10-08
    Description: We present mid-infrared (MIR) luminosity functions (LFs) of local ( z  〈 0.3) star-forming (SF) galaxies in the AKARI 's North Ecliptic Pole (NEP)-Wide survey field. In order to derive more accurate LF, we used spectroscopic sample only. Based on the NEP-Wide point source catalogue containing a large number of infrared (IR) sources distributed over the wide (5.4 deg 2 ) field, we incorporated the spectroscopic redshift ( z ) data for ~1790 selected targets obtained by optical follow-up surveys with MMT/Hectospec and WIYN/Hydra. The AKARI 's continuous 2–24 μm wavelength coverage as well as photometric data from optical u * band to near-infrared H band with the spectroscopic redshifts for our sample galaxies enable us to derive accurate spectral energy distributions (SEDs) in the MIR. We carried out SED fit analysis and employed 1/ V max method to derive the MIR (e.g. 8, 12, and 15 μm rest-frame) LFs. We fit our 8 μm LFs to the double power-law with the power index of α = 1.53 and β = 2.85 at the break luminosity 4.95  x  10 9 L . We made extensive comparisons with various MIR LFs from several literatures. Our results for local galaxies from the NEP region are generally consistent with other works for different fields over wide luminosity ranges. The comparisons with the results from the NEP-Deep data as well as other LFs imply the luminosity evolution from higher redshifts towards the present epoch.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
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  • 3
    Publication Date: 2015-12-13
    Description: The scanning electron microscope is used in various fields to go beyond diffraction limits of the optical microscope. However, the electron pathway should be conducted in a vacuum so as not to scatter electrons. The pretreatment of the sample is needed for use in the vacuum. To directly observe large and fully hydrophilic samples without pretreatment, the atmospheric scanning electron microscope (ASEM) is needed. We developed an electron filter unit and an electron detector unit for implementation of the ASEM. The key of the electron filter unit is that electrons are transmitted while air molecules remain untransmitted through the unit. The electron detector unit collected the backscattered electrons. We conducted experiments using the selected materials with Havar foil, carbon film and SiN film.
    Print ISSN: 0022-0744
    Electronic ISSN: 1477-9986
    Topics: Electrical Engineering, Measurement and Control Technology , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2015-10-30
    Description: Abnormal accumulation of defective mitochondria is the hallmark of oncocytes, which are frequently observed in thyroid Hürthle cell lesions. Autophagy is an essential cellular catabolic mechanism for the degradation of dysfunctional organelles and has been implicated in several human diseases. It is yet unknown how autophagic turnover of defective mitochondria in Hürthle cell tumors is regulated. We characterized the expression patterns of molecular markers including Beclin1, LC3, PINK1 and Parkin, which are required for autophagy or mitophagy, in human oncocytic lesions of the thyroid. To undertake mechanistic studies, we investigated autophagy and mitophagy using XTC.UC1 cells, the only in vitro model of Hürthle cell tumors. Beclin1 and LC3 were highly expressed in oncocytes of Hürthle cell tumors. XTC.UC1 showed autophagic responses to starvation and rapamycin treatment, whereas they displayed ineffective activation of mitophagy, which is triggered by the coordinated action of PINK1 and Parkin in response to CCCP. This resulted in a decreased turnover of abnormal mitochondria. The mechanisms underlying defective mitophagy and mitochondrial turnover were investigated by genetic analysis of the PARK2 gene in XTC.UC1 and Hürthle cell tumor tissues. XTC.UC1 and several tumors harbored the V380L mutation, resulting in dysfunctional autoubiquitination and decreased E3 ligase activity. Consistently, oncocytes in Hürthle cell tumors displayed comparable expression of PINK1 but decreased Parkin expression in comparison to normal thyrocytes. The introduction of wild-type Parkin sensitized XTC.UC1 to death induced by CCCP. This study provides a possible etiological basis for oncocytic formation in heterogeneous Hürthle cell tumors through insufficient mitophagy leading to ineffective turnover of aberrant mitochondria caused by dysfunctional Parkin-mediated pathways of mitochondria quality control.
    Print ISSN: 0143-3334
    Electronic ISSN: 1460-2180
    Topics: Medicine
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  • 5
    Publication Date: 2015-11-17
    Description: Aims To investigate the impact of lesion angle on the incidence and distribution of acute vessel wall injuries and incomplete stent apposition (ISA) following second-generation drug-eluting stent (DES) implantation using optical coherence tomography (OCT). Several ex vivo studies demonstrated that angled arterial walls are exposed to imbalanced mechanical stress from deployed stents. Methods and results We included 243 lesions treated with a single DES (148 everolimus-eluting stent and 95 zotarolimus-eluting stent). Angled lesions were defined as lesions with angle ≥45° on an angiogram ( n = 58). The vessel wall injuries and ISA were evaluated by OCT. The results were compared with non-angled lesions (〈45°, n = 185). The incidence of instent dissection, thrombus, and ISA was significantly higher in the angled group than in the non-angled group (84.5 vs. 63.2%, P 〈 0.01; 55.2 vs. 35.1%, P 〈 0.01; 75.9 vs. 44.9%, P 〈 0.001, respectively). In the angled group, the normalized tissue protrusion volume around the centre of angle (6.59 ± 6.81, mm 3 x 10 2 ) was higher than in the distal sub-segment (2.21 ± 2.87, mm 3 x 10 2 , P 〈 0.001), in the proximal sub-segment (4.14 ± 5.34, mm 3 x 10 2 , P = 0.02), and in the non-angled group (3.30 ± 2.81, mm 3 x 10 2 , P 〈 0.001). The incidence of major adverse cardiac events within 12 months was similar between the groups. Conclusions Angled coronary lesions had a higher incidence rate of OCT-detected vessel wall injuries and ISA compared with non-angled lesions following second-generation DES implantation. Further studies are needed to understand the long-term clinical significance of these findings.
    Print ISSN: 1525-2167
    Electronic ISSN: 1532-2114
    Topics: Medicine
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  • 6
    Publication Date: 2016-03-01
    Description: Background Romidepsin, a histone deacetylase (HDAC) inhibitor, has been approved for the treatment of relapsed and refractory peripheral T-cell lymphoma. However, the efficacy and safety of romidepsin has never been studied in patients with relapsed or refractory extranodal natural killer (NK)/T-cell lymphoma (ENKTL). Patients and methods We conducted an open-label, prospective pilot study to evaluate the efficacy and feasibility of romidepsin in the treatment of patients with ENKTL. The treatment was intravenous infusion of romidepsin (14 mg/m 2 ) for 4 h on days 1, 8, and 15 of a 28-day cycle, and was repeated until disease progression or the occurrence of unacceptable toxicity. Results A total of five patients enrolled on to this pilot study. However, three patients developed fever and elevated liver enzyme and bilirubin levels immediately after their first administration of romidepsin. We suspected that these events were associated with Epstein–Barr virus (EBV) reactivation because of the rapidly elevated EBV DNA titers in blood from these patients. An in vitro study with the ENKTL cell line SNK-6 cells also showed that HDAC inhibitors including romidepsin increased the copy number of EBV DNA in a dose-dependent manner. These findings suggested that romidepsin-induced histone acetylation reversed the repressed state of the genes required for EBV reactivation and that romidepsin treatment may have caused EBV reactivation in EBV-infected tumor cells in ENKTL patients. Therefore, we discontinued the enrollment of patients into this pilot study. Conclusions Our study suggests that the use of romidepsin may cause severe EBV reactivation in patients with ENKTL.
    Print ISSN: 0923-7534
    Electronic ISSN: 1569-8041
    Topics: Medicine
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  • 7
    Publication Date: 2016-06-01
    Description: Motivation: Identification of altered pathways that are clinically relevant across human cancers is a key challenge in cancer genomics. Precise identification and understanding of these altered pathways may provide novel insights into patient stratification, therapeutic strategies and the development of new drugs. However, a challenge remains in accurately identifying pathways altered by somatic mutations across human cancers, due to the diverse mutation spectrum. We developed an innovative approach to integrate somatic mutation data with gene networks and pathways, in order to identify pathways altered by somatic mutations across cancers. Results: We applied our approach to The Cancer Genome Atlas (TCGA) dataset of somatic mutations in 4790 cancer patients with 19 different types of tumors. Our analysis identified cancer-type-specific altered pathways enriched with known cancer-relevant genes and targets of currently available drugs. To investigate the clinical significance of these altered pathways, we performed consensus clustering for patient stratification using member genes in the altered pathways coupled with gene expression datasets from 4870 patients from TCGA, and multiple independent cohorts confirmed that the altered pathways could be used to stratify patients into subgroups with significantly different clinical outcomes. Of particular significance, certain patient subpopulations with poor prognosis were identified because they had specific altered pathways for which there are available targeted therapies. These findings could be used to tailor and intensify therapy in these patients, for whom current therapy is suboptimal. Availability and implementation: The code is available at: http://www.taehyunlab.org . Contact: jhcheong@yuhs.ac or taehyun.hwang@utsouthwestern.edu or taehyun.cs@gmail.com Supplementary information: Supplementary data are available at Bioinformatics online.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
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  • 8
    Publication Date: 2016-10-08
    Description: Plant endomembranes are required for the biosynthesis and secretion of complex cell wall matrix polysaccharides, glycoproteins and proteoglycans. To define the biochemical roadmap that guides the synthesis and deposition of these cell wall components it is first necessary to outline the localization of the biosynthetic and modifying enzymes involved, as well as the distribution of the intermediate and final constituents of the cell wall. Thus far, a comprehensive understanding of cell wall matrix components has been hampered by the multiplicity of trafficking routes in the secretory pathway, and the diverse biosynthetic roles of the endomembrane organelles, which may exhibit tissue and development specific features. However, the recent identification of protein complexes producing matrix polysaccharides, and those supporting the synthesis and distribution of a grass-specific hemicellulose are advancing our understanding of the functional contribution of the plant secretory pathway in cell wall biosynthesis. In this review, we provide an overview of the plant membrane trafficking routes and report on recent exciting accomplishments in the understanding of the mechanisms underlying secretion with focus on cell wall synthesis in plants.
    Print ISSN: 0959-6658
    Electronic ISSN: 1460-2423
    Topics: Biology , Medicine
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  • 9
    Publication Date: 2016-03-23
    Description: Background Everolimus, an oral mTOR inhibitor, has single-agent activity against relapsed lymphomas. Thus, we carried out a phase II study of everolimus in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) as a first-line treatment for patients with peripheral T-cell lymphoma (PTCL) based on our phase I study results. Patients and methods Participants ( n = 30) received CHOP with 5 mg everolimus per day from day 1 to 14 every 21 days for a total of six cycles. The primary end point was the overall response rate (ORR), which included complete response (CR) and partial response (PR) to this regimen. Immunohistochemistry was used to evaluate the expression of phosphatase and tensin homology (PTEN) and phosphorylated S6 kinase (pS6K) as a response. Results The objective response rate was 90% with CR ( n = 17) and PR ( n = 10). The CR rate was different among subtypes; angioimmunoblastic T-cell lymphoma (AITL, n = 3) had a CR whereas PTCL–not-otherwise specified and ALK-negative anaplastic large-cell lymphoma (ALCL) patients showed 63% (12/19) and 29% (2/7) of CR rate, respectively. This difference in CR rate among subtypes was associated with PTEN loss because PTEN loss was not seen in AITL but 33% of ALCL patients. The most common toxicity was hematological, with 80% of patients experiencing at least one event of grade 3/4 neutropenia, and 60% of patients had grade 3/4 thrombocytopenia. Conclusion The everolimus plus CHOP was effective for PTCL patients, and its efficacy might be related with the preservation of PTEN.
    Print ISSN: 0923-7534
    Electronic ISSN: 1569-8041
    Topics: Medicine
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  • 10
    Publication Date: 2016-05-26
    Description: Background The use of imatinib combined with chemotherapy has demonstrated improved outcome in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL). However, a substantial proportion of patients continue to die as a result of disease progression. Patients and methods We assessed the minimal residual disease (MRD)-based effect and long-term outcome of first-line incorporation of dasatinib (100 mg once daily) into chemotherapy alternatively for adults with Ph-positive ALL. The primary end point was the major molecular response (MMR) rate by the end of the second dasatinib cycle. Patients with a donor proceeded to allogeneic stem cell transplantation (SCT) as early as possible. MRD monitoring was centrally evaluated by real-time quantitative polymerase chain reaction (4.5-log sensitivity) using bone marrow samples. Results Fifty-one patients (median age, 46 years) were enrolled and treated with this strategy. After the first dasatinib cycle, 50 patients (98.0%) achieved complete remission (CR). By the end of the second dasatinib cycle, 46 (93.9%) of 49 assessable patients had persistent CR, and 38 (77.6%) had MMR (32.7%) or undetectable MRD (44.9%). On the basis of the MRD kinetics by this time point, the numbers of early-stable, late, and poor molecular responders were 23 (46.9%), 15 (30.7%), and 11 (22.4%), respectively. Thirty-nine patients (76.5%) underwent allogeneic SCT in CR1. After a median follow-up of 54 months, the 4-year cumulative incidence of relapse and disease-free survival (DFS) rate for all patients were 30.0% and 52.0%, respectively, and the corresponding outcomes among those receiving allogeneic SCT in CR1 were 20.5% and 64.1%, respectively. Poor molecular responders had a higher risk of relapse and DFS than those of early-stable molecular responders. Conclusion This dasatinib-based protocol was effective for achieving a good quality molecular response and durable DFS in adults with Ph-positive ALL. Trial registration clinicaltrials.gov, NCT01004497.
    Print ISSN: 0923-7534
    Electronic ISSN: 1569-8041
    Topics: Medicine
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