294 research outputs found

    PCN185 A Multi-Country Retrospective Study of Patient Characteristics and Treatment Patterns in Chronic Myeloid Leukemia

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    Development and Validation of a Tokamak Skin Effect Transformer model

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    A control oriented, lumped parameter model for the tokamak transformer including the slow flux penetration in the plasma (skin effect transformer model) is presented. The model does not require detailed or explicit information about plasma profiles or geometry. Instead, this information is lumped in system variables, parameters and inputs. The model has an exact mathematical structure built from energy and flux conservation theorems, predicting the evolution and non linear interaction of the plasma current and internal inductance as functions of the primary coil currents, plasma resistance, non-inductive current drive and the loop voltage at a specific location inside the plasma (equilibrium loop voltage). Loop voltage profile in the plasma is substituted by a three-point discretization, and ordinary differential equations are used to predict the equilibrium loop voltage as function of the boundary and resistive loop voltages. This provides a model for equilibrium loop voltage evolution, which is reminiscent of the skin effect. The order and parameters of this differential equation are determined empirically using system identification techniques. Fast plasma current modulation experiments with Random Binary Signals (RBS) have been conducted in the TCV tokamak to generate the required data for the analysis. Plasma current was modulated in Ohmic conditions between 200kA and 300kA with 30ms rise time, several times faster than its time constant L/R\approx200ms. The model explains the most salient features of the plasma current transients without requiring detailed or explicit information about resistivity profiles. This proves that lumped parameter modeling approach can be used to predict the time evolution of bulk plasma properties such as plasma inductance or current with reasonable accuracy; at least in Ohmic conditions without external heating and current drive sources

    Economic burden of resected (stage IB-IIIA) non-small cell lung cancer in France, Germany and the United Kingdom: A retrospective observational study (LuCaBIS)

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    OBJECTIVES: New adjuvant treatments are being developed for patients with resected non-small cell lung cancer (NSCLC). Due to scarcity of real-world data available for treatment costs and resource utilization, health technology and cost-effectiveness assessments can be limited. We estimated the burden and cost-of-illness associated with completely resected stage IB-IIIA NSCLC in France, Germany and the United Kingdom (UK). MATERIALS AND METHODS: Eligible patients were aged ≥18 years with completely resected stage IB-IIIA NSCLC between August 2009 and July 2012. Patients (living or deceased) were enrolled at clinical sites by a systematic sampling method. Data were obtained from medical records and patient surveys. Direct, indirect and patient out-of-pocket expenses were estimated by multiplying resource use by country-specific unit costs. National annual costs were estimated based on disease prevalence data available from published sources. RESULTS: 39 centers provided data from 831 patients of whom patient surveys were evaluable in 306 patients. Median follow-up was 26 months. The mean total direct costs per patient during follow-up were: €19,057 (France), €14,185 (Germany), and €8377 (UK). The largest cost drivers were associated with therapies received (€12,375 France; €3694 UK), and hospitalization/emergency costs (€7706 Germany). Monthly direct costs per patient were the highest during the distant metastasis/terminal illness phase in France (€15,562) and Germany (€6047) and during the adjuvant treatment period in the UK (€2790). Estimated mean total indirect costs per patient were: €696 (France), €2476 (Germany), and €1414 (UK). Estimates for the annual national direct cost were €478.4 million (France), €574.6 million (Germany) and €325.8 million (UK). CONCLUSION: To our knowledge, this is the first comprehensive study describing the burden of illness for patients with completely resected stage IB-IIIA NSCLC. The economic burden was substantial in all three countries. Treatment of NSCLC is associated with large annual national costs, mainly incurred during disease progression

    Adjuvant treatment patterns and outcomes in patients with stage IB-IIIA non-small cell lung cancer in France, Germany, and the United Kingdom based on the LuCaBIS burden of illness study

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    OBJECTIVES: To inform health-technology assessments of new adjuvant treatments, we describe treatment patterns in patients with complete resection of stage IB-IIIA non-small cell lung cancer (NSCLC) in France, Germany, and the United Kingdom (UK). MATERIALS AND METHODS: Data were collected via medical record abstraction. Patients were aged ≥18 years with completely resected stage IB-IIIA NSCLC, diagnosed between 01 January 2009 and 31 December 2011. Median follow-up was 26 months. Adjuvant treatment patterns and clinical outcomes were summarized descriptively. RESULTS: Among the 831 patients studied, 239 (29%) had stage IB disease, 179 (22%) had stage IIA disease, 165 (20%) had stage IIB disease, and 248 (30%) had stage IIIA disease. Adjuvant systemic therapy was received by 402 patients (48.4%), (France, 61.8%; Germany, 51.9%; UK, 33.4%). Use of adjuvant therapy increased with increasing stage of disease. Cisplatin/vinorelbine and carboplatin/vinorelbine were the most frequently prescribed adjuvant regimens. Median disease-free survival was 48.0 months (95% confidence interval [CI] 42.3-not estimable); the 25th percentile was 13.2 months (95% CI, 11.0-15.3). 204 patients (24%) died during the follow-up period. The median overall survival was not reached, the 25th percentile was 31.2 months (95% CI 26.8-36.0 months). 272 patients (33%) had disease recurrence during the follow-up period. For 86 of those patients, the first recurrence was local or regional with no distant metastasis and 14 had further progression to metastatic disease during the follow-up time. For the other 186 patients, the first recurrence involved distant metastases. A total of 200 patients had metastatic disease at any time during study follow-up. CONCLUSIONS: Less than half the patients with stage IB-IIIA NSCLC in this observational study received adjuvant systemic therapy. A high rate of first recurrence with distant metastatic disease was observed, emphasising the need for more effective systemic adjuvant therapies in this population

    A Historiometric Examination of Machiavellianism and a New Taxonomy of Leadership

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    Although researchers have extensively examined the relationship between charismatic leadership and Machiavellianism (Deluga, 2001; Gardner & Avolio, 1995; House & Howell, 1992), there has been a lack of investigation of Machiavellianism in relation to alternative forms of outstanding leadership. Thus, the purpose of this investigation was to examine the relationship between Machiavellianism and a new taxonomy of outstanding leadership comprised of charismatic, ideological, and pragmatic leaders. Using an historiometric approach, raters assessed Machiavellianism via the communications of 120 outstanding leaders in organizations across the domains of business, political, military, and religious institutions. Academic biographies were used to assess twelve general performance measures as well as twelve general controls and five communication specific controls. The results indicated that differing levels of Machiavellianism is evidenced across the differing leader types as well as differing leader orientation. Additionally, Machiavellianism appears negatively related to performance, though less so when type and orientation are taken into account.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

    Integrating sequence and array data to create an improved 1000 Genomes Project haplotype reference panel

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    A major use of the 1000 Genomes Project (1000GP) data is genotype imputation in genome-wide association studies (GWAS). Here we develop a method to estimate haplotypes from low-coverage sequencing data that can take advantage of single-nucleotide polymorphism (SNP) microarray genotypes on the same samples. First the SNP array data are phased to build a backbone (or 'scaffold') of haplotypes across each chromosome. We then phase the sequence data 'onto' this haplotype scaffold. This approach can take advantage of relatedness between sequenced and non-sequenced samples to improve accuracy. We use this method to create a new 1000GP haplotype reference set for use by the human genetic community. Using a set of validation genotypes at SNP and bi-allelic indels we show that these haplotypes have lower genotype discordance and improved imputation performance into downstream GWAS samples, especially at low-frequency variants. © 2014 Macmillan Publishers Limited. All rights reserved

    New insights into the genetic etiology of Alzheimer's disease and related dementias

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    Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele
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