439 research outputs found

    Cyclin D1 overexpression is an indicator of poor prognosis in resectable non-small cell lung cancer

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    Cyclin D1 is one of the G1 cyclins that control cell cycle progression by allowing G1 to S transition. Overexpression of cyclin D1 has been postulated to play an important role in the development of human cancers. We have investigated the correlation between cyclin D1 overexpression and known clinicopathological factors and also its prognostic implication on resected non-small-cell lung cancer (NSCLC) patients. Formalin-fixed and paraffin-embedded tumour tissues resected from 69 NSCLC patients between stages I and IIIa were immunohistochemically examined to detect altered cyclin D1 expression. Twenty-four cases (34.8%) revealed positive immunoreactivity for cyclin D1. Cyclin D1 overexpression is significantly higher in patients with lymph node metastasis (50.0% vs 14.4%, P = 0.002) and with advanced pathological stages (I, 10%; II, 53.8%; IIIa, 41.7%, P = 0.048; stage I vs II, IIIa, P = 0.006). Twenty-four patients with cyclin D1-positive immunoreactivity revealed a significantly shorter overall survival than the patients with negativity (24.0 ± 3.9 months vs 50.1 ± 6.4 months, P = 0.0299). Among 33 patients between stages I and II, nine patients with cyclin D1-positive immunoreactivity had a much shorter overall survival (29.7 ± 6.1 months vs 74.6 ± 8.6 months, P = 0.0066). These results suggest that cyclin D1 overexpression is involved in tumorigenesis of NSCLCs from early stage and could be a predictive molecular marker for poor prognosis in resectable NSCLC patients, which may help us to choose proper therapeutic modalities after resection of the tumor. © 1999 Cancer Research Campaig

    Genome-Wide Association Analysis of Autoantibody Positivity in Type 1 Diabetes Cases

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    The genetic basis of autoantibody production is largely unknown outside of associations located in the major histocompatibility complex (MHC) human leukocyte antigen (HLA) region. The aim of this study is the discovery of new genetic associations with autoantibody positivity using genome-wide association scan single nucleotide polymorphism (SNP) data in type 1 diabetes (T1D) patients with autoantibody measurements. We measured two anti-islet autoantibodies, glutamate decarboxylase (GADA, n = 2,506), insulinoma-associated antigen 2 (IA-2A, n = 2,498), antibodies to the autoimmune thyroid (Graves') disease (AITD) autoantigen thyroid peroxidase (TPOA, n = 8,300), and antibodies against gastric parietal cells (PCA, n = 4,328) that are associated with autoimmune gastritis. Two loci passed a stringent genome-wide significance level (p<10(-10)): 1q23/FCRL3 with IA-2A and 9q34/ABO with PCA. Eleven of 52 non-MHC T1D loci showed evidence of association with at least one autoantibody at a false discovery rate of 16%: 16p11/IL27-IA-2A, 2q24/IFIH1-IA-2A and PCA, 2q32/STAT4-TPOA, 10p15/IL2RA-GADA, 6q15/BACH2-TPOA, 21q22/UBASH3A-TPOA, 1p13/PTPN22-TPOA, 2q33/CTLA4-TPOA, 4q27/IL2/TPOA, 15q14/RASGRP1/TPOA, and 12q24/SH2B3-GADA and TPOA. Analysis of the TPOA-associated loci in 2,477 cases with Graves' disease identified two new AITD loci (BACH2 and UBASH3A)

    Less is Different: Emergence and Reduction Reconciled

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    This is a companion to another paper. Together they rebut two widespread philosophical doctrines about emergence. The first, and main, doctrine is that emergence is incompatible with reduction. The second is that emergence is supervenience; or more exactly, supervenience without reduction. In the other paper, I develop these rebuttals in general terms, emphasising the second rebuttal. Here I discuss the situation in physics, emphasising the first rebuttal. I focus on limiting relations between theories and illustrate my claims with four examples, each of them a model or a framework for modelling, from well-established mathematics or physics. I take emergence as behaviour that is novel and robust relative to some comparison class. I take reduction as, essentially, deduction. The main idea of my first rebuttal will be to perform the deduction after taking a limit of some parameter. Thus my first main claim will be that in my four examples (and many others), we can deduce a novel and robust behaviour, by taking the limit, N goes to infinity, of a parameter N. But on the other hand, this does not show that that the infinite limit is "physically real", as some authors have alleged. For my second main claim is that in these same examples, there is a weaker, yet still vivid, novel and robust behaviour that occurs before we get to the limit, i.e. for finite N. And it is this weaker behaviour which is physically real. My examples are: the method of arbitrary functions (in probability theory); fractals (in geometry); superselection for infinite systems (in quantum theory); and phase transitions for infinite systems (in statistical mechanics).Comment: 75 p

    Parents’ marital status and child physical abuse potential: the mediation of depression symptoms

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    Informed by a social interactional framework of stress and parenting, the aim of this study was to examine the mediating effect of depression symptoms on the asso- ciation between parents’ marital status (married and divorced parents) and child physical abuse potential, in a Portuguese community sample. It was hypothesized that the possible observed differences between divorced and married parents in the child physical abuse potential would be explained by their depression symptoms. Parents (N = 892) were assessed in their marital status, severity of depression symptoms and child physical abuse potential. Results showed that, when compared with married parents, divorced parents had higher child physical abuse potential. However, parents’ depression symptomatology was found as a mediator of the effect of marital status differences on child physical abuse potential. The influence of the status of divorced parents on the increase of child physical abuse potential was explained by the increase of the parents’ depression symptoms. This finding suggested that parents’ divorced status had no longer an effect on child physical abuse potential when parents’ depression symptomatology was tested as a mediator vari- able. The present mediation model explained 47 % of the variability in the child physical abuse potential score. Prac- tical implications of these findings for prevention and psy- chological intervention are also discussed.info:eu-repo/semantics/publishedVersio

    Increased Diacylglycerols Characterize Hepatic Lipid Changes in Progression of Human Nonalcoholic Fatty Liver Disease; Comparison to a Murine Model

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    The spectrum of nonalcoholic fatty liver disease (NAFLD) includes steatosis, nonalcoholic steatohepatitis (NASH), and progression to cirrhosis. While differences in liver lipids between disease states have been reported, precise composition of phospholipids and diacylglycerols (DAG) at a lipid species level has not been previously described. The goal of this study was to characterize changes in lipid species through progression of human NAFLD using advanced lipidomic technology and compare this with a murine model of early and advanced NAFLD.Utilizing mass spectrometry lipidomics, over 250 phospholipid and diacylglycerol species (DAGs) were identified in normal and diseased human and murine liver extracts.Significant differences between phospholipid composition of normal and diseased livers were demonstrated, notably among DAG species, consistent with previous reports that DAG transferases are involved in the progression of NAFLD and liver fibrosis. In addition, a novel phospholipid species (ether linked phosphatidylinositol) was identified in human cirrhotic liver extracts.Using parallel lipidomics analysis of murine and human liver tissues it was determined that mice maintained on a high-fat diet provide a reproducible model of NAFLD in regards to specificity of lipid species in the liver. These studies demonstrated that novel lipid species may serve as markers of advanced liver disease and importantly, marked increases in DAG species are a hallmark of NAFLD. Elevated DAGs may contribute to altered triglyceride, phosphatidylcholine (PC), and phosphatidylethanolamine (PE) levels characteristic of the disease and specific DAG species might be important lipid signaling molecules in the progression of NAFLD

    Non-Take-Up of Student Financial Aid: A Microsimulation for Germany

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    This paper estimates the percentage of students who do not take up their federal need-based student financial aid entitlements and sheds light on determinants of this behavior. Against the background that educational mobility in Germany is low although extensive student financial aid for needy students is available, it is crucial to know whether students assert their claims for student aid at all. To investigate non-take-up, we set up a microsimulation model for the German Socio-Economic Panel Study 2002-2013 and estimate the respective aid amounts students would have received, had they filed an application for need-based aid. The results indicate that about 40% of the eligible low-income students do not take up their entitlements. We employ instrumental variable techniques and a sample selection model to consider several potential explanatory factors for this behavior. Our results suggest that non-take-up is inversely related to the level of benefits, though the elasticity is rather low. Apart from that, a shorter expected duration of benefit receipt is related to a higher non-take-up rate, whereas the possibility to draw upon older siblings' experience with completing the complex application for aid is associated with higher probabilities to claim. Moreover, we find robust evidence that significantly more students socialized in the former socialist East Germany choose to take up student aid than similar West German students. Finally, in line with behavioral economic theory, debt aversion of highly impulsive and impatient students is associated with higher rates of non-take-up
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