128 resultados para success factor
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Objective: To describe new measures of risk from case-control and cohort studies, which are simple to understand and relate to numbers of the population at risk. Design: Theoretical development of new measures of risk. Setting: Review of literature and previously described measures. Main results: The new measures are: (1) the population impact number (PIN), the number of those in the whole population among whom one case is attributable to the exposure or risk factor (this is equivalent to the reciprocal of the population attributable risk),- (2) the case impact number (CIN) the number of people with the disease or outcome for whom one case will be attributable to the exposure or risk factor (this is equivalent to the reciprocal of the population attributable fraction); (3) the exposure impact number (EIN) the number of people with the exposure among whom one excess case is attributable to the exposure (this is equivalent to the reciprocal of the attributable risk); (4) the exposed cases impact number (ECIN) the number of exposed cases among whom one case is attributable to the exposure (this is equivalent to the reciprocal of the aetiological fraction). The impact number reflects the number of people in each population (the whole population, the cases, all those exposed, and the exposed cases) among whom one case is attributable to the particular risk factor. Conclusions: These new measures should help communicate the impact on a population, of estimates of risk derived from cohort or case-control studies.
Resumo:
Keratinocyte Growth factor (KGF) is an epithelial cell growth factor of the fibroblast growth factor family and is produced by fibroblasts and microvascular endothelium in response to proinflammatory cytokines and steroid hormones. KGF is a heparin binding growth factor that exerts effects on epithelial cells in a paracrine fashion through interaction with KGF receptors. Preclinical data has demonstrated that KGF can prevent lung and gastrointestinal toxicity following chemotherapy and radiation and preliminary clinical data in the later setting supports these findings. In the experimental allogeneic bone marrow transplant scenario KGF has shown significant ability to prevent graft-versus-host disease by maintaining gastrointestinal tract integrity and acting as a cytokine shield to prevent subsequent proinflammatory cytokine generation. Within this setting KGF has also shown an ability to prevent experimental idiopathic pneumonia syndrome by stimulating production of surfactant protein A, promoting alveolar epithelialization and attenuating immune-mediated injury. Perhaps most unexpectantly, KGF appears able to maintain thymic function during allogeneic stern cell transplantation and so promote T cell engraftment and reconstitution. These data suggest that KGF will find a therapeutic role in the prevention of epithelial toxicity following intensive chemotherapy and radiotherapy protocols and in allogeneic stem cell transplantation.
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This study explores several important aspects of the management of new product development (NPD) in the Chinese steel industry. Specifically it explores NPD success factors, the importance of management functions to new product success and measures of new product success from the perspective of the industry's practitioners. Based on a sample of 190 industrial practitioners from 18 Chinese steel companies, the study provides a mixed picture as China makes the transition from a centrally-controlled to market-based economy. On one hand, respondents ranked understanding users' needs as the most important factor influencing the performance of the new products. Further, formulating new product strategy and strengthening market research are perceived as the most important managerial functions in NPD. However, technical performance measures are regarded as more important and are more widely used in industry than market-based or financial measures of success.
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Streptococcus pyogenes (Group A streptococcus) interacts with host fibronectin via a number of distinct surface components. The streptococcal serum opacity factor (SOF) is a cell-surface protein of S. pyogenes which opalescence of human serum and mediates bacterial binding to fibronectin. In this study, hexahistidyl-tagged fusion proteins encompassing full-length SOF, and domains of SOF encompassing opacity factor activity and fibronectin-binding regions, were used in the characterization of the Aboriginal immune response to SOF. Anti-SOF serum IgG responses were found to be significantly higher (P
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During bacterial infections, the balance between resolution of infection and development of sepsis is dependent upon the macrophage response to bacterial products. We show that priming of murine bone marrow-derived macrophages (BMMs) with CSF-1 differentially regulates the response to two such stimuli, LPS and immunostimulatory (CpG) DNA. CSF-1 pretreatment enhanced IL-6, IL-12, and TNF-alpha production in response to LPS but suppressed the same response to CpG DNA. CSF-1 also regulated cytokine gene expression in response to CpG DNA and LPS; CpG DNA-induced IL-12 p40, IL-12 p35, and TNF-alpha mRNAs were all suppressed by CSF-1 pretreatment. CSF-1 pretreatment enhanced LPS-induced IL-12 p40 mRNA but not TNF-alpha and IL-12 p35 mRNAs, suggesting that part of the priming effect is posttranscriptional. CSF-1 pretreatment also suppressed CpG DNA-induced nuclear translocation of NF-kappaB and phosphorylation of the mitogen-activated protein kinases p38 and extracellular signal-related kinases-1/2 in BMMs, indicating that early events in CpG DNA signaling were regulated by CSF-1. Expression of Toll-like receptor (TLR)9, which is necessary for responses to CpG DNA, was markedly suppressed by CSF-1 in both BMMs and thioglycolate-elicited peritoneal macrophages. CSF-1 also down-regulated expression of TLR1, TLR2, and TLR6, but not the LPS receptor, TLR4, or TLR5. Hence, CSF-1 may regulate host responses to pathogens through modulation of TLR expression. Furthermore, these results suggest that CSF-1 and CSF-1R antagonists may enhance the efficacy of CpG DNA in vivo.
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Fibroblast growth factor receptors (FGFRs) undergo highly regulated spatial and temporal changes of expression during development. This study describes the use of quantitative reverse transcriptase-polymerase chain reaction and immunochemistry to assess the changes in expression of FGFR4 as compared to its FGFR4-17a and -17b isoforms in mouse tissues, from early embryogenesis through to adulthood. Compared to FGFR4, the expression of the isoforms is more restricted at all developmental stages tested. The reverse transcriptase-polymerase chain reaction demonstrated that FGFR4 is expressed in more tissue types than either of its isoforms: it was found predominantly in lung, liver, brain, skeletal muscle and kidney, whereas the FGFR4-17a form was detected in lung and skeletal muscle, and the FGFR4-17b form only in lung, liver, skeletal muscle and kidney. Immunohistochemistry confirmed strong FGFR4-17b expression in the postnatal lung. When combined, the results suggest that FGFR4 variants play important roles particularly in lung and skeletal muscle development.
Resumo:
We focus on mixtures of factor analyzers from the perspective of a method for model-based density estimation from high-dimensional data, and hence for the clustering of such data. This approach enables a normal mixture model to be fitted to a sample of n data points of dimension p, where p is large relative to n. The number of free parameters is controlled through the dimension of the latent factor space. By working in this reduced space, it allows a model for each component-covariance matrix with complexity lying between that of the isotropic and full covariance structure models. We shall illustrate the use of mixtures of factor analyzers in a practical example that considers the clustering of cell lines on the basis of gene expressions from microarray experiments. (C) 2002 Elsevier Science B.V. All rights reserved.
Resumo:
Marine reserves have been widely touted as a promising strategy for managing fisheries and protecting marine biodiversity. However, their establishment can involve substantial social conflict and may not produce the anticipated biological and economic benefits. A crucial factor associated with the success of marine reserves for enhancing fisheries and protecting biodiversity is the spatial distribution of fishing activity. Fishers may be attracted to the perimeter of a reserve in expectation of spillover of adult fishes. This concentration of effort can reduce spillover of fish to the surrounding fishery and has major implications for the effectiveness of reserves in achieving ecological and socioeconomic goals. We examined the spatial distribution of fishing activity relative to California's Big Creek Marine Ecological Reserve and found no aggregation near the reserve. We discuss the factors driving the spatial distribution of fishing activity relative to the reserve and the relevance of that distribution to the performance and evaluation of marine reserves.
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Background.-A number of extraneous factors have been implicated in the effectiveness of treatment of headache, including patient beliefs about aspects of the treatment or persons delivering the treatment. Objective.-The concept of external locus of control for headaches refers to patients with a high level of belief that headache and relief are influenced primarily by health care professionals. The aim of this study was to examine whether external locus of control is associated with a reduction in frequency of cervicogenic headaches among patients treated by a physiotherapist. Design.-A recent randomized controlled trial of the effectiveness of physiotherapy among 200 patients with headache enabled a test of this relationship. Treatment consisted of manipulative therapy, therapeutic exercise, or a combination of the 2. Analysis of relative change in headache frequency was conducted after 6 weeks of treatment and at 3- and 12-month follow-up appointments. Results.-Results of the analysis indicated that participants with relatively high external Headache-Specific Locus of Control scores were more likely to achieve a reduction in headache frequency if they received the combined manipulative therapy and exercise therapy, compared with those who received no treatment. This was not determined for the group who received manipulative therapy, which is a treatment received passively by the patient. Conclusions.-The interpretation of these findings is considered in the context of nongeneralization to the other physiotherapy treatment groups and sustained reduction in headache frequency following withdrawal of treatment. The pattern of findings suggests that characteristics of the therapy were more pertinent than characteristics of the therapist.
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In the toothless (tl/tl) osteopetrotic rat, teeth form but fail to erupt. Treatment of tl/tl rats with colony-stimulating factor-1 (CSF-1) activates bone resorption by osteoclasts, permits tooth eruption, and up-regulates the immunoreactivity of bone marrow mononuclear cells to growth hormone receptor (GHr) and insulin-like growth factor (IGF)-I. This study examined the distribution of tartrate-resistant acid phosphatase (TRAP) and immunoreactivity for GHr and IGF-I in osteoclast-like cells located on the alveolar bone margin, adjacent to the lower first molar crown, in 14-day-old normal and tl/tl rats, following treatment with CSF-1. Osteoclast-like cells demonstrated a positive reaction for TRAP, GHr, and IGF-I in all groups. However, in tl/tl tissue, osteoclast-like cells were generally negative for GHr. There was no significant difference in the total number of TRAP, GHr, and IGF-I-positive osteoclast-like cells on the adjacent bone margin in normal, normal treated with CSF-1, and tl/tl rats. CSF-1 treatment of the tl/tl rat significantly increased the total number of osteoclast-like cells, which were positive for TRAP (p < 0.001), GHr (p < 0.05) and IGF-I (P < 0.01).
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We show here that nerve growth factor (NGF), the canonical neurotrophic factor, is synthesized and released by breast cancer cells. High levels of NGF transcript and protein were detected in breast cancer cells by reverse transcription-PCR, Western blotting, ELISA assay and immunohistochemistry. Conversely, NGF production could not be detected in normal breast epithelial cells at either the transcriptional or protein level. Confocal analysis indicated the presence of NGF within classical secretion vesicles. Breast cancer cell-produced NGF was biologically active, as demonstrated by its ability to induce the neuronal differentiation of embryonic neural precursor cells. Importantly, the constitutive growth of breast cancer cells was strongly inhibited by either NGF-neutralizing antibodies or K-252a, a pharmacological inhibitor of NGF receptor TrkA, indicating the existence of an NGF autocrine loop. Together, our data demonstrate the physiological relevance of NGF in breast cancer and its potential interest as a marker and therapeutic target.