Background Metabolic syndrome (MS) is the simultaneous occurrence of a cluster of predefined cardiovascular risk factors. Although individual MS components are associated with increased risk of ...cancer, it is still unclear whether the association between MS and cancer differs from the association between individual MS components and cancer. The aim of this matched case-control study was to estimate the association of 13 types of cancer with (1) MS and (2) the diagnosis of 0, 1 or 2 individual MS components. Methods Cases included 183,248 patients ≥40 years from the SIDIAP database with incident cancer diagnosed between January 2008-December 2017. Each case was matched to four controls by inclusion date, sex and age. Adjusted conditional logistic regression models were used to evaluate the association between MS and cancer risk, comparing the effect of global MS versus having one or two individual components of MS. Results MS was associated with an increased risk of the following cancers: colorectal (OR: 1.28, 95%CI: 1.23–1.32), liver (OR: 1.93, 95%CI: 1.74–2.14), pancreas (OR: 1.79, 95%CI: 1.63–1.98), post-menopausal breast (OR: 1.10, 95%CI: 1.06–1.15), pre-menopausal endometrial (OR: 2.14, 95%CI: 1.74–2.65), post-menopausal endometrial (OR: 2.46, 95%CI: 2.20–2.74), bladder (OR: 1.41, 95%CI: 1.34–1.48), kidney (OR: 1.84, 95%CI: 1.69–2.00), non-Hodgkin lymphoma (OR: 1.23, 95%CI: 1.10–1.38), leukaemia (OR: 1.42, 95%CI: 1.31–1.54), lung (OR: 1.11, 95%CI: 1.05–1.16) and thyroid (OR: 1.71, 95%CI: 1.50–1.95). Except for prostate, pre-menopause breast cancer and Hodgkin and non-Hodgkin lymphoma, MS is associated with a higher risk of cancer than 1 or 2 individual MS components. Estimates were significantly higher in men than in women for colorectal and lung cancer, and in smokers than in non-smokers for lung cancer. Conclusion MS is associated with a higher risk of developing 11 types of common cancer, with a positive correlation between number of MS components and risk of cancer.
Background: Electronic health records are becoming an increasingly valuable resource for epidemiology but their data quality needs to be quantified. We aimed to validate twenty-five types of incident ...cancer cases in the Information System for Research in Primary Care (SIDIAP) in Catalonia with the population-based cancer registries of Girona and Tarragona as the gold-standard. Methods: We calculated the sensitivity, positive predictive values (PPV), and the time-difference between the date of diagnosis entered into the SIDIAP and into the registries. We added hospital discharge cancer diagnoses to the SIDIAP to assess sensitivity changes. Results: We identified 27,046 incident cancer diagnoses in the SIDIAP from 2009-2015 among the 949,841 residents of Girona and Tarragona. The cancer types with the highest sensitivity were breast (89%, 95% CI: 88-90%), colorectal (81%, 95% CI: 80-82%), and prostate (81%, 95% CI: 80-83%). Trachea, bronchus and lung cancers had the highest PPV (76%, 95% CI: 74%-78%) followed by stomach (72%, 95% CI: 68-75%) and pancreas (71%, 95% CI: 67-75%). Most cancer diagnoses were reported with less than three months of difference between the SIDIAP and the registries. More cases were registered first in the registries than in the SIDIAP. By adding cancer diagnoses based on hospital discharge data, sensitivity increased for all cancers, especially for gallbladder and biliary tract for which the sensitivity increased by 21%. Conclusion: The SIDIAP includes 76% of the cancer diagnoses in the cancer registries but includes a considerable number of cases that are not in the registries. The SIDIAP reports most of the cancer diagnoses within a three-month period difference from the date of diagnosis in the cancer registries. Our results support the use of the SIDIAP cancer diagnoses for epidemiological research when cancer is the outcome of interest. We recommend adding hospital discharge data to the SIDIAP to increase data quality, particularly for less frequent cancer types. Keywords: validation studies, cancer, electronic health records, primary health care, population-based cancer registries
Pigment epithelium derived factor (PEDF) is a potent antiangiogenic, neurotrophic, and neuroprotective molecule that is the endogenous inhibitor of vascular endothelial growth factor (VEGF) in the ...retina. An ex vivo gene therapy approach based on transgenic overexpression of PEDF in the eye is assumed to rebalance the angiogenic-antiangiogenic milieu of the retina, resulting in growth regression of choroidal blood vessels, the hallmark of neovascular age-related macular degeneration. Here, we show that rat pigment epithelial cells can be efficiently transfected with the PEDF-expressing non-viral hyperactive Sleeping Beauty transposon system delivered in a form free of antibiotic resistance marker miniplasmids. The engineered retinal and iris pigment epithelium cells secrete high (141 ± 13 and 222 ± 14 ng) PEDF levels in 72 hr in vitro. In vivo studies showed cell survival and insert expression during at least 4 months. Transplantation of the engineered cells to the subretinal space of a rat model of choroidal neovascularization reduces almost 50% of the development of new vessels.
Age-related macular degeneration (AMD) is a progressive retinal disorder characterized by imbalanced pro- and antiangiogenic signals. The aim of this study was to evaluate the effect of ex vivo ...cell-based gene therapy with stable expression of human pigment epithelium-derived factor (PEDF) release using the non-viral Sleeping Beauty (SB100X) transposon system delivered by miniplasmids free of antibiotic resistance markers (pFAR4). Retinal pigment epithelial (RPE) cells and iris pigment epithelial (IPE) cells were co-transfected with pFAR4-inverted terminal repeats (ITRs) CMV-PEDF-BGH and pFAR4-CMV-SB100X-SV40 plasmids. Laser-induced choroidal neovascularization (CNV) was performed in rats, and transfected primary cells (transfected RPE tRPE and transfected IPE tIPE cells) were injected into the subretinal space. The leakage and CNV areas, vascular endothelial growth factor (VEGF), PEDF protein expression, metalloproteinases 2 and 9 (MMP-2/9), and microglial/macrophage markers were measured. Injection with tRPE/IPE cells significantly reduced the leakage area at 7 and 14 days and the CNV area at 7 days. There was a significant increase in PEDF and the PEDF/VEGF ratio with tRPE cells and a reduction in the MMP-2 activity. Our data demonstrated that ex vivo non-viral gene therapy reduces CNV and could be an effective and safe therapeutic option for angiogenic retinal diseases.
The aim of COGNITVE CONTROL was to create cognitive automation systems with the capabilities automatic control performance monitoring (CPM), self-detection and automatic diagnosis of faults (sensors, ...actuators, controller) and self-adaptation in control system environments to optimise the product quality and minimise energy consumption in steel during the whole life cycle. In this project several software tools for online Control Performance Monitoring (CPM), monitoring energy efficiency, diagnosis of poor performance root-causes and control re-tuning for univariable and multivariable, linear and nonlinear processes were developed. The software tools were Graphical User Interface (GUI) that provided interface to access process data. The implemented methodologies were subsequently published as conference and journal papers. The methods were tested at hot strip mills, annealing furnaces and galvanizing lines.
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