1,703 research outputs found

    Control of construction costs during construction

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    The construction of a major project requires a vast amount of time, money, material and human resources. Proper coordination of these elements into an array of activities is crutial to the success of the project if it is to be built on time and within budget. As technology advances, the complexity of the project increases the resources to build them remain finite, and therefore, the project manager must seek methods to improve control on the construction project. This thesis provides an overall view of the relatively new and rapidly expanding field of cost engineering. Cost engineering may be defined as that field of engineering practice where engineering judgement and experience are utilized in the application of science principles and techniques to the areas of cost estimation and cost control. Cost estimation and cost control will be the main subject of this thesis. Although this area has tremendous impact on the economics of private industries and the goverment, cost estimating and cost control has usually underestimated. Virtually all decisions to construct a facility is based on economics, inturn, the economic study is based on the accuracy of an estimate. Once management has committed itself to the project, cost control protects its decision and holds expenditures within budget by constant monitoring and appraisal of cost performance of those responsible for executing the project. The text will provide the reader with the basic understanding of the nature of construction costs, the types and importance of estimates, budgeting procedures and implementation of a cost control system

    Effects of feeding phytogenic substances and phytase on growth performance and nutrient digestibility of young broilers

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    The effect of feeding phytogenic feed additive (Biostrong¼, BS510) and microbial phytase (Natuphos¼ 5000) on the growth performance and nutrient digestibility in broiler chickens was studied. A total of 280 male Ross broilers were raised from day old until 21 d of age under 3-tier cage system. The chicks were divided into 5 groups: Control—Basal diet; T1: Basal diet + phytase (using 100% matrix value of phytase); T2: Basal diet + BS510 (using 100% matrix value of BS510); T3: Basal diet + phytase (using 100% matrix value of phytase) + BS510 (without matrix) and T4: Basal diet + phytase (using 100% matrix value of phytase) + BS510 (using only 100% Ca, P matrix value of BS510). The birds fed with phytase or phytogenic substances or combinations had better growth performance than the control. The diets added with phytogenic substances and phytase had better digestibility of nutrients such as crude protein, phosphorus and calcium. It is concluded that both additives can be used in broiler chicken diet with advantage

    Discordant and heterogeneous clinically relevant genomic alterations in circulating tumor cells vs plasma DNA from men with metastatic castration resistant prostate cancer

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    Circulating tumor cell (CTC) and cellĂą free (cf) DNAĂą based genomic alterations are increasingly being used for clinical decisionĂą making in oncology. However, the concordance and discordance between paired CTC and cfDNA genomic profiles remain largely unknown. We performed comparative genomic hybridization (CGH) on CTCs and cfDNA, and lowĂą pass whole genome sequencing (lpWGS) on cfDNA to characterize genomic alterations (CNA) and tumor content in two independent prospective studies of 93 men with mCRPC treated with enzalutamide/abiraterone, or radiumĂą 223. Comprehensive analysis of 69 patient CTCs and 72 cfDNA samples from 93 men with mCRPC, including 64 paired samples, identified common concordant gains in FOXA1, AR, and MYC, and losses in BRCA1, PTEN, and RB1 between CTCs and cfDNA. Concordant PTEN loss and discordant BRCA2 gain were associated with significantly worse outcomes in Epic ARĂą V7 negative men with mCRPC treated with abiraterone/enzalutamide. We identified and externally validated CTCĂą specific genomic alternations that were discordant in paired cfDNA, even in samples with high tumor content. These CTC/cfDNAĂą discordant regions included key genomic regulators of lineage plasticity, osteomimicry, and cellular differentiation, including MYCN gain in CTCs (31%) that was rarely detected in cfDNA. CTC MYCN gain was associated with poor clinical outcomes in ARĂą V7 negative men and small cell transformation. In conclusion, we demonstrated concordance of multiple genomic alterations across CTC and cfDNA platforms; however, some genomic alterations displayed substantial discordance between CTC DNA and cfDNA despite the use of identical copy number analysis methods, suggesting tumor heterogeneity and divergent evolution associated with poor clinical outcomes.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153751/1/gcc22824.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153751/2/gcc22824_am.pd

    Continuing to Confront COPD International Patient Survey:Economic Impact of COPD in 12 Countries

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    BACKGROUND:The Continuing to Confront COPD International Patient Survey estimated the prevalence and burden of COPD across 12 countries. Using data from this survey we evaluated the economic impact of COPD. METHODS:This cross-sectional, population-based survey questioned 4,343 subjects aged 40 years and older, fulfilling a case definition of COPD based on self-reported physician diagnosis or symptomatology. Direct cost measures were based on exacerbations of COPD (treated and those requiring emergency department visits and/or hospitalisation), contacts with healthcare professionals, and COPD medications. Indirect costs were calculated from work loss values using the Work Productivity and Activity Impairment scale. Combined direct and indirect costs estimated the total societal costs per patient. RESULTS:The annual direct costs of COPD ranged from 504(SouthKorea)to504 (South Korea) to 9,981 (USA), with inpatient hospitalisations (5 countries) and home oxygen therapy (3 countries) being the key drivers of direct costs. The proportion of patients completely prevented from working due to their COPD ranged from 6% (Italy) to 52% (USA and UK) with 8 countries reporting this to be ≄20%. Total societal costs per patient varied widely from 1,721(Russia)to1,721 (Russia) to 30,826 (USA) but a consistent pattern across countries showed greater costs among those with increased burden of COPD (symptoms, health status and more severe disease) and a greater number of comorbidities. CONCLUSIONS:The economic burden of COPD is considerable across countries, and requires targeted resources to optimise COPD management encompassing the control of symptoms, prevention of exacerbations and effective treatment of comorbidities. Strategies to allow COPD patients to remain in work are important for addressing the substantial wider societal costs

    Sunitinib in relapsed or refractory diffuse large B-cell lymphoma: a clinical and pharmacodynamic phase II multicenter study of the NCIC Clinical Trials Group

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    There are limited effective therapies for most patients with relapsed diffuse large B-cell lymphoma (DLBCL). We conducted a phase II trial of the multi-targeted vascular endothelial growth factor receptor (VEGFR) kinase inhibitor, sunitinib, 37.5 mg given orally once daily in adult patients with relapsed or refractory DLBCL. Of 19 enrolled patients, 17 eligible patients were evaluable for toxicity and 15 for response. No objective responses were seen and nine patients achieved stable disease (median duration 3.4 months). As a result, the study was closed at the end of the first stage. Grades 3—4 neutropenia and thrombocytopenia were observed in 29% and 35%, respectively. There was no relationship between change in circulating endothelial cell numbers (CECs) and bidimensional tumor burden over time. Despite some activity in solid tumors, sunitinib showed no evidence of response in relapsed/refractory DLBCL and had greater than expected hematologic toxicity

    Deployable Laboratory Response to Influenza Pandemic; PCR Assay Field Trials and Comparison with Reference Methods

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    Background: The influenza A/H1N1/09 pandemic spread quickly during the Southern Hemisphere winter in 2009 and reached epidemic proportions within weeks of the official WHO alert. Vulnerable population groups included indigenous Australians and remote northern population centres visited by international travellers. At the height of the Australian epidemic a large number of troops converged on a training area in northern Australia for an international exercise, raising concerns about their potential exposure to the emerging influenza threat before, during and immediately after their arrival in the area. Influenza A/H1N1/09 became the dominant seasonal variant and returned to Australia during the Southern winter the following year. Methods: A duplex nucleic acid amplification assay was developed within weeks of the first WHO influenza pandemic alert, demonstrated in northwestern Australia shortly afterwards and deployed as part of the pathology support for a field hospital during a military exercise during the initial epidemic surge in June 2009. Results: The nucleic acid amplification assay was twice as sensitive as a point of care influenza immunoassay, as specific but a little less sensitive than the reference laboratory nucleic acid amplification assay. Repetition of the field assay with blinded clinical samples obtained during the 2010 winter influenza season demonstrated a 91.7% congruence with the reference laboratory method. Conclusions: Rapid in-house development of a deployable epidemic influenza assay allowed a flexible laboratory response, effective targeting of limited disease control resources in an austere military environment, and provided the public health laboratory service with a set of verification tools for resource-limited settings. The assay method was suitable for rapid deployment in time for the 2010 Northern winter

    Selective Expression of a Stable Cell Surface Molecule on Type 2 but Not Type 1 Helper T Cells

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    T helper cell type 1 (Th1) and 2 (Th2) are central to immune regulation. However, no stable cell surface marker capable of distinguishing and separating these two subsets of CD4+ cells has yet been found. Using differential display PCR, we have identified a gene encoding a cell membrane bound molecule, originally designated ST2L, T1, DER4, or Fit, expressed constitutively and stably on the surface of murine Th2s, but not Th1s even after stimulation with a range of immunological stimuli. Antibody against a peptide derived from ST2L strongly and stably labeled the surface of cloned Th2s but not Th1s, and Th2s but not Th1s derived from naive T cells of ovalbumin T cell receptor–α/ÎČ transgenic mice. Three-color single cell flow cytometric analysis shows that cell surface ST2L coexpressed with intracellular interleukin (IL)-4, but not with interferon (IFN)-Îł. The antibody selectively lysed Th2s in vitro in a complement-dependent manner. In vivo, it enhanced Th1 responses by increasing IFN-Îł production and decreasing IL-4 and IL-5 synthesis. It induced resistance to Leishmania major infection in BALB/c mice and exacerbated collagen-induced arthritis in DBA/1 mice. Thus, ST2L is a stable marker distinguishing Th2s from Th1s and is also associated with Th2 functions. Hence, it may be a target for therapeutic intervention

    Selective Expression and Functions of Interleukin 18 Receptor on T Helper (Th) Type 1 but not Th2 Cells

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    Interleukin (IL)-18 induces interferon (IFN)-Îł synthesis and synergizes with IL-12 in T helper type 1 (Th1) but not Th2 cell development. We report here that IL-18 receptor (IL-18R) is selectively expressed on murine Th1 but not Th2 cells. IL-18R mRNA was expressed constitutively and consistently in long-term cultured clones, as well as on newly polarized Th1 but not Th2 cells. IL-18 sustained the expression of IL-12RÎČ2 mRNA, indicating that IL-18R transmits signals that maintain Th1 development through the IL-12R complex. In turn, IL-12 upregulated IL-18R mRNA. Antibody against an IL-18R–derived peptide bound Th1 but not Th2 clones. It also labeled polarized Th1 but not Th2 cells derived from naive ovalbumin–T cell antigen receptor-αÎČ transgenic mice (D011.10). Anti–IL-18R antibody inhibited IL-18– induced IFN-Îł production by Th1 clones in vitro. In vivo, anti–IL-18R antibody reduced local inflammation and lipopolysaccharide-induced mortality in mice. This was accompanied by shifting the balance from Th1 to Th2 responses, manifest as decreased IFN-Îł and proinflammatory cytokine production and increased IL-4 and IL-5 synthesis. Therefore, these data provide a direct mechanism for the selective effect of IL-18 on Th1 but not Th2 cells. They also show that the synergistic effect of IL-12 and IL-18 on Th1 development may be due to the reciprocal upregulation of their receptors. Furthermore, IL-18R is a cell surface marker distinguishing Th1 from Th2 cells and may be a therapeutic target

    Search for chargino-neutralino production with mass splittings near the electroweak scale in three-lepton final states in √s=13 TeV pp collisions with the ATLAS detector

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    A search for supersymmetry through the pair production of electroweakinos with mass splittings near the electroweak scale and decaying via on-shell W and Z bosons is presented for a three-lepton final state. The analyzed proton-proton collision data taken at a center-of-mass energy of √s=13  TeV were collected between 2015 and 2018 by the ATLAS experiment at the Large Hadron Collider, corresponding to an integrated luminosity of 139  fb−1. A search, emulating the recursive jigsaw reconstruction technique with easily reproducible laboratory-frame variables, is performed. The two excesses observed in the 2015–2016 data recursive jigsaw analysis in the low-mass three-lepton phase space are reproduced. Results with the full data set are in agreement with the Standard Model expectations. They are interpreted to set exclusion limits at the 95% confidence level on simplified models of chargino-neutralino pair production for masses up to 345 GeV
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