543 research outputs found

    Communicating the Value of Ergonomics to Management – Part 2: Ergonomics ROI Case Study Applications

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    More than ever, human factors engineers and ergonomists need to justify our practice’s value to management. How can we effectively communicate with management? How should we present a Return on Investment (ROI) that leadership will find useful that addresses company profits, cost savings, productivity, first time quality, and turnover? What else does management care about other than ROI? This second panel in a two panel series will specifically highlight case studies in which presenters give examples of situations in which ROI for ergonomics was investigated from a business value. The session will start with four case study lectures followed by a panel discussion led by the moderators. The audience will be encouraged to participate with their own questions and comments

    Pathological and molecular evaluation of pancreatic neoplasms

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    Pancreatic neoplasms are morphologically and genetically heterogeneous and include a wide variety of tumors ranging from benign to malignant with an extremely poor clinical outcome. Our understanding of these pancreatic neoplasms has improved significantly with recent advances in cancer sequencing. Awareness of molecular pathogenesis brings new opportunities for early detection, improved prognostication, and personalized gene-specific therapies. Here we review the pathological classification of pancreatic neoplasms from the molecular and genetic perspectives

    Aurora-A expressing tumour cells are deficient for homology-directed DNA double strand-break repair and sensitive to PARP inhibition.

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    The protein kinase Aurora-A is a major regulator of the cell cycle that orchestrates mitotic entry and is required for the assembly of a functional mitotic spindle. Overexpression of Aurora-A has been strongly linked with oncogenesis and this has led to considerable efforts at therapeutic targeting of the kinase activity of this protein. However, the exact mechanism by which Aurora-A promotes oncogenesis remains unclear. Here, we show that Aurora-A modulates the repair of DNA double-strand breaks (DSBs). Aurora-A expression inhibits RAD51 recruitment to DNA DSBs, decreases DSB repair by homologous recombination and sensitizes cancer cells to PARP inhibition. This impairment of RAD51 function requires inhibition of CHK1 by Polo-like kinase 1 (PLK1). These results identify a novel function of Aurora-A in modulating the response to DNA DSB that likely contributes to carcinogenesis and suggest a novel therapeutic approach to the treatment of cancers overexpressing this protein

    Comparison Between the Biomechanical Responses of the Hand and Foot When Exposed to Vertical Vibration

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    Workers can be exposed daily to foot-transmitted vibration (FTV) from standing on mobile equipment or vibrating platforms and surfaces. This results in a consistent risk of developing neurological, vascular, and musculoskeletal problems. To date, there are no international stand-ards describing procedures with which to evaluate the health risks deriving from long-term ex-posure to FTV. To study the applicability of hand–arm vibration (HAV) standards to the foot, the biomechanical responses of the hand and foot in terms of the frequency response function upon varying contact conditions were compared. Results evidenced similarities between the responses of the wrist and ankle, with differences in resonance for the fingers and toes. The study confirms that HAV standards are more suitable than whole-body vibration standards for evaluating higher frequency exposure to FTV

    Copy-Number Variants in Patients with a Strong Family History of Pancreatic Cancer

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    Copy-number variants such as germ-line deletions and amplifications are associated with inherited genetic disorders including familial cancer. The gene or genes responsible for the majority of familial clustering of pancreatic cancer have not been identified. We used representational oligonucleotide microarray analysis (ROMA) to characterize germ-line copy number variants in 60 cancer patients from 57 familial pancreatic cancer kindreds. Fifty-seven of the 60 patients had pancreatic cancer and three had nonpancreatic cancers (breast, ovary, ovary). A familial pancreatic cancer kindred was defined as a kindred in which at least two first-degree relatives have been diagnosed with pancreatic cancer. Copy-number variants identified in 607 individuals without pancreatic cancer were excluded from further analysis. A total of 56 unique genomic regions with copy-number variants not present in controls were identified, including 31 amplifications and 25 deletions. Two deleted regions were observed in two different patients, and one in three patients. The germ-line amplifications had a mean size of 662 Kb, a median size of 379 Kb (range 8.2 Kb to 2.5 Mb) and included 425 known genes. Examples of genes included in the germ-line amplifications include the MAFK, JunD and BIRC6 genes. The germ-line deletions had a mean size of 375Kb, a median size 151 Kb (range 0.4 Kb to 2.3 Mb) and included 81 known genes. In multivariate analysis controlling for region size, deletions were 90% less likely to involve a gene than were duplications (p < 0.01). Examples of genes included in the germ-line deletions include the FHIT, PDZRN3 and ANKRD3 genes. Selected deletions and amplifications were confirmed using real-time PCR, including a germ-line amplification on chromosome 19. These genetic copy-number variants define potential candidate loci for the familial pancreatic cancer gene

    Prognostic and therapeutic significance of carbohydrate antigen 19-9 as tumor marker in patients with pancreatic cancer

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    In pancreatic cancer ( PC) accurate determination of treatment response by imaging often remains difficult. Various efforts have been undertaken to investigate new factors which may serve as more appropriate surrogate parameters of treatment efficacy. This review focuses on the role of carbohydrate antigen 19- 9 ( CA 19- 9) as a prognostic tumor marker in PC and summarizes its contribution to monitoring treatment efficacy. We undertook a Medline/ PubMed literature search to identify relevant trials that had analyzed the prognostic impact of CA 19- 9 in patients treated with surgery, chemoradiotherapy and chemotherapy for PC. Additionally, relevant abstract publications from scientific meetings were included. In advanced PC, pretreatment CA 19- 9 levels have a prognostic impact regarding overall survival. Also a CA 19- 9 decline under chemotherapy can provide prognostic information for median survival. A 20% reduction of CA 19- 9 baseline levels within the first 8 weeks of chemotherapy appears to be sufficient to define a prognostic relevant subgroup of patients ('CA 19- 9 responder'). It still remains to be defined whether the CA 19- 9 response is a more reliable method for evaluating treatment efficacy compared to conventional imaging. Copyright (c) 2006 S. Karger AG, Basel

    Mesothelin-specific CD8+ T Cell Responses Provide Evidence of In Vivo Cross-Priming by Antigen-Presenting Cells in Vaccinated Pancreatic Cancer Patients

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    Tumor-specific CD8+ T cells can potentially be activated by two distinct mechanisms of major histocompatibility complex class I–restricted antigen presentation as follows: direct presentation by tumor cells themselves or indirect presentation by professional antigen-presenting cells (APCs). However, controversy still exists as to whether indirect presentation (the cross-priming mechanism) can contribute to effective in vivo priming of tumor-specific CD8+ T cells that are capable of eradicating cancer in patients. A clinical trial of vaccination with granulocyte macrophage–colony stimulating factor–transduced pancreatic cancer lines was designed to test whether cross-presentation by locally recruited APCs can activate pancreatic tumor-specific CD8+ T cells. Previously, we reported postvaccination delayed-type hypersensitivity (DTH) responses to autologous tumor in 3 out of 14 treated patients. Mesothelin is an antigen demonstrated previously by gene expression profiling to be up-regulated in most pancreatic cancers. We report here the consistent induction of CD8+ T cell responses to multiple HLA-A2, A3, and A24-restricted mesothelin epitopes exclusively in the three patients with vaccine-induced DTH responses. Importantly, neither of the vaccinating pancreatic cancer cell lines expressed HLA-A2, A3, or A24. These results provide the first direct evidence that CD8 T cell responses can be generated via cross-presentation by an immunotherapy approach designed to recruit APCs to the vaccination site

    Development of a two-dimensional dynamic model of the foot-ankle system exposed to vibration

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    Workers in mining, mills, construction and some types of manufacturing are exposed to vibration that enters the body through the feet. Exposure to foot-transmitted vibration (FTV) is associated with an increased risk of developing vibration-induced white foot (VIWFt). VIWFt is a vascular and neurological condition of the lower limb, leading to blanching in the toes and numbness and tingling in the feet, which can be disabling for the worker. This paper presents a two-dimensional dynamic model describing the response of the foot-ankle system to vibration using four segments and eight Kelvin-Voigt models. The parameters of the model have been obtained by minimizing the quadratic reconstruction error between the experimental and numerical curves of the transmissibility and the apparent mass of participants standing in a neutral position. The average transmissibility at five locations on the foot has been optimized by minimizing the difference between experimental data and the model prediction between 10 and 100 Hz. The same procedure has been repeated to fit the apparent mass measured at the driving point in a frequency range between 2 and 20 Hz. Monte Carlo simulations were used to assess how the variability of the mass, stiffness and damping matrices affect the overall data dispersion. Results showed that the 7 degree-of-freedom model correctly described the transmissibility: the average transmissibility modulus error was 0.1. The error increased when fitting the transmissibility and apparent mass curves: the average modulus error was 0.3. However, the obtained values were reasonable with respect to the average inter-participant variability experimentally estimated at 0.52 for the modulus. Study results can contribute to the development of materials and equipment to attenuate FTV and, consequently, lower the risk of developing VIWFt.INAI
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