589 research outputs found

    Pengaruh Gross Profit Margin, Return On Asset, Return On Equity Dan Book Value Terhadap Harga Saham Pada Perusahaan Pertambangan Yang Terdaftar Di Bei Periode 2014-2017

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    Abstract This research is meant to test the influence of Gross Profit Margin, Return On Assets, Return On Equity and Book Value on Share Prices of mining companies listed on the Indonesia Stock Exchange Period 2014-2017. This research was conducted at a mining company listed on the Indonesia Stock Exchange (IDX). The number of samples taken were 19 companies from 22 listed mining companies during the 2014-2017 period. Data analysis method used is multiple linear regression. Based on the results of the F test statistic calculations, the calculated F value is 13,963 while the F table's value is 2.54, with a significance level of 0,000. Because the probability (0,000) is much smaller than 0.05, and F arithmetic (13,963)> F table (2.54) then the regression model can be used to predict GPM, ROA, ROE and BV together have a significant effect on price profitability Stock. Keywords : gross profit margin, return on assets, return on equity and book value

    A First-in-Human Study of Novel Cereblon Modulator Avadomide (CC-122) in Advanced Malignancies.

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    Purpose Avadomide is a novel, small-molecule therapeutic agent that modulates cereblon E3 ligase activity and exhibits potent antitumor and immunomodulatory activities. This first-in-human phase I study (NCT01421524) evaluated the safety and clinical activity of avadomide in patients with advanced solid tumors, non-Hodgkin lymphoma (NHL), and multiple myeloma.Patients and methods Thirty-four patients were treated with avadomide in 7 dose-escalation cohorts using a 3 + 3 design (0.5-3.5 mg, 28-day continuous dosing cycles). The primary objectives were to determine the dose-limiting toxicity (DLT), nontolerated dose (NTD), maximum tolerated dose (MTD), recommended phase II dose, and pharmacokinetics of avadomide. The secondary objective was to determine preliminary avadomide efficacy. Exploratory objectives included evaluation of pharmacodynamic effects of avadomide.Results DLTs were reported in 2 patients, and grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 14 patients (41%). The most common TEAEs (≥15%) were fatigue, neutropenia, and diarrhea. The NTD and MTD were 3.5 and 3.0 mg, respectively. Of 5 patients with NHL, 1 achieved a complete response, and 2 had partial responses. Although no objective responses were observed in patients with solid tumors, 5 of 6 patients with brain cancer experienced nonprogression of ≥6 months. A dose-dependent relationship between Aiolos degradation in peripheral B and T cells occurred within 5 hours of the first dose of avadomide administered, starting at 0.5 mg.Conclusions Avadomide monotherapy demonstrated acceptable safety and favorable pharmacokinetics in patients with solid tumors, NHL, and multiple myeloma. In addition, 3 objective responses were observed in NHL

    Nanobodies raised against monomeric alpha-synuclein inhibit fibril formation and destabilize toxic oligomeric species

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    BACKGROUND: The aggregation of the protein ɑ-synuclein (ɑS) underlies a range of increasingly common neurodegenerative disorders including Parkinson’s disease. One widely explored therapeutic strategy for these conditions is the use of antibodies to target aggregated ɑS, although a detailed molecular-level mechanism of the action of such species remains elusive. Here, we characterize ɑS aggregation in vitro in the presence of two ɑS-specific single-domain antibodies (nanobodies), NbSyn2 and NbSyn87, which bind to the highly accessible C-terminal region of ɑS. RESULTS: We show that both nanobodies inhibit the formation of ɑS fibrils. Furthermore, using single-molecule fluorescence techniques, we demonstrate that nanobody binding promotes a rapid conformational conversion from more stable oligomers to less stable oligomers of ɑS, leading to a dramatic reduction in oligomer-induced cellular toxicity. CONCLUSIONS: The results indicate a novel mechanism by which diseases associated with protein aggregation can be inhibited, and suggest that NbSyn2 and NbSyn87 could have significant therapeutic potential

    Fluoromycobacteriophages for rapid, specific, and sensitive antibiotic susceptibility testing of Mycobacterium tuberculosis

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    Rapid antibiotic susceptibility testing of Mycobacterium tuberculosis is of paramount importance as multiple- and extensively- drug resistant strains of M. tuberculosis emerge and spread. We describe here a virus-based assay in which fluoromycobacteriophages are used to deliver a GFP or ZsYellow fluorescent marker gene to M. tuberculosis, which can then be monitored by fluorescent detection approaches including fluorescent microscopy and flow cytometry. Pre-clinical evaluations show that addition of either Rifampicin or Streptomycin at the time of phage addition obliterates fluorescence in susceptible cells but not in isogenic resistant bacteria enabling drug sensitivity determination in less than 24 hours. Detection requires no substrate addition, fewer than 100 cells can be identified, and resistant bacteria can be detected within mixed populations. Fluorescence withstands fixation by paraformaldehyde providing enhanced biosafety for testing MDR-TB and XDR-TB infections. © 2009 Piuri et al

    Clofarabine and high-dose cytosine arabinoside in the treatment of refractory or relapsed acute myeloid leukaemia

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    Clofarabine (40 mg/m2/day × 5) and high-dose cytosine arabinoside (Ara-C, 1–2 g/m2/day × 5) were used in 10 men and 11 women, at a median age of 45 (22–62) years, with refractory (N = 4) and relapsed (N = 17) acute myeloid leukaemia, after a median of 3 (2–5) prior regimens. Grade 4 myelosuppression was observed in all cases, with two patients dying of bacterial sepsis. Nine patients achieved a complete remission. Disease status, number of prior therapies, and cytogenetic aberrations were not associated with the outcome. However, remission was only achieved with Ara-C at 2 g/m2/day and not 1 g/m2/day (9/15 versus 0/4, P = 0.03)

    Impact of lenalidomide dose on progression-free survival in patients with relapsed or refractory multiple myeloma

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    This analysis assessed the effect of lenalidomide on progression-free survival (PFS). Patients with relapsed or refractory multiple myeloma (RRMM) who received lenalidomide plus dexamethasone in the MM-009 and MM-010 trials were pooled and those who had not progressed and were still receiving lenalidomide at 12 months were included. The median follow-up of surviving patients was 48 months. Of 353 patients who received lenalidomide plus dexamethasone, 116 (33%) had not progressed. Overall, 52 patients (45%) had no dose reductions, 25 (22%) had dose reductions ⩾12 months and 39 (34%) had dose reductions before 12 months. Patients who had dose reductions ⩾12 months had a significantly longer median PFS than those who had reductions before 12 months (P=0.007) or no dose reductions (P=0.039) (not reached vs 28.0 vs 36.8 months, respectively). In a multivariate Cox regression model, dose reduction ⩾12 months was an independent predictor of improved PFS (hazard ratio, 0.47; 95% confidence interval, 0.23–0.98) after adjusting for patient characteristics. The data suggest that to achieve maximum PFS benefit, patients with RRMM should be treated for ⩾12 months with full-dose lenalidomide plus dexamethasone. Thereafter, patients may benefit from lower-dose continued therapy; prospective studies are needed to confirm these findings

    The mu - e Conversion in Nuclei, mu --> e gamma, mu --> 3e Decays and TeV Scale See-Saw Scenarios of Neutrino Mass Generation

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    We perform a detailed analysis of lepton flavour violation (LFV) within minimal see-saw type extensions of the Standard Model (SM), which give a viable mechanism of neutrino mass generation and provide new particle content at the electroweak scale. We focus, mainly, on predictions and constraints set on each scenario from mu --> e gamma, mu --> 3e and mu - e conversion in the nuclei. In this class of models, the flavour structure of the Yukawa couplings between the additional scalar and fermion representations and the SM leptons is highly constrained by neutrino oscillation measurements. In particular, we show that in some regions of the parameters space of type I and type II see-saw models, the Dirac and Majorana phases of the neutrino mixing matrix, the ordering and hierarchy of the active neutrino mass spectrum as well as the value of the reactor mixing angle theta_{13} may considerably affect the size of the LFV observables. The interplay of the latter clearly allows to discriminate among the different low energy see-saw possibilities.Comment: Expressions for the factors |C_{me}|^2 and |C_{mu3e}|^2 in the mu-e conversion and mu-->3e decay rates, eqs. (36) and (49), respectively, corrected; results in subsections 2.2 and 2.3 quantitatively changed, qualitatively remain the same; figures 2, 3, 4 and 5 replace

    Left atrial extension of metastatic lung tumor via pulmonary vein: report on the first case of Ewing sarcoma

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    Extension of metastatic lung tumors into the left atrium via pulmonary veins is rare. Here, we report the first case of Ewing sarcoma exhibiting such extension. A 31-year-old man with pulmonary metastasis from Ewing sarcoma presented with a mass in the left lung, extending to the left atrium through the left inferior pulmonary vein. As the patient was considered to be at risk of tumor embolism, the mass was excised surgically

    Does pre-operative psychological distress affect patient satisfaction after primary total hip arthroplasty?

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    <p>Abstract</p> <p>Background</p> <p>There are concerns that pre-operative psychological distress might be associated with reduced patient satisfaction after total hip replacement (THR).</p> <p>Methods</p> <p>We investigated this in a multi-centre prospective study between January 1999 and January 2002. We dichotomised the patients into the mentally distressed (MHS ≤ 56) and the not mentally distressed (MHS > 56) groups based on their pre-operative Mental Health Score (MHS) of SF36.</p> <p>Results</p> <p>448 patients (340 not distressed and 108 distressed) completed the patient satisfaction survey. Patient satisfaction rate at five year was 96.66% (415/448). There was no difference in patient satisfaction or willingness to have the surgery between the two groups. None of pre-operative variables predicted five year patient satisfaction in logistic regression.</p> <p>Conclusions</p> <p>Patient satisfaction after surgery may not be adversely affected by pre-operative psychological distress.</p
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