Part 2: Making the "unproven" "proven"

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Aneurysmal disease is associated with lower carotid intima-media thickness than occlusive arterial disease

Objective: Patients with aneurysmal and occlusive arterial disease have overlapping cardiovascular risk profiles. The question remains how atherosclerosis is related to the formation of aortic aneurysms. Common carotid artery intima-media thickness (CIMT) is an easily accessible and objective marker of early atherosclerosis. The aim of the current study was to investigate whether there is a difference in atherosclerotic burden as measured by CIMT between patients with aneurysmal and those with occlusive arterial disease. Methods: From 2004 to 2011, the CIMT was measured using B-mode ultrasound scanning in patients undergoing vascular surgery for aortic aneurysmal or occlusive arterial disease at the Erasmus University Medical Center. Cardiovascular risk factors, comorbidities, and medication were recorded. Patients treated for combined aneurysmal and occlusive arterial disease and patients diagnosed with a genetic aneurysm syndrome were excluded. Univariable and multivariable analyses wer

An artificial neural network stratifies the risks of reintervention and mortality after endovascular aneurysm repair:a retrospective observational study

Background Lifelong surveillance after endovascular repair (EVAR) of abdominal aortic aneurysms (AAA) is considered mandatory to detect potentially life-threatening endograft complications. A minority of patients require reintervention but cannot be predictively identified by existing methods. This study aimed to improve the prediction of endograft complications and mortality, through the application of machine-learning techniques. Methods Patients undergoing EVAR at 2 centres were studied from 2004-2010. Pre-operative aneurysm morphology was quantified and endograft complications were recorded up to 5 years following surgery. An artificial neural networks (ANN) approach was used to predict whether patients would be at low- or high-risk of endograft complications (aortic/limb) or mortality. Centre 1 data were used for training and centre 2 data for validation. ANN performance was assessed by Kaplan-Meier analysis to compare the incidence of aortic complications, limb complications, and mortality; in patients predicted to be low-risk, versus those predicted to be high-risk. Results 761 patients aged 75 +/- 7 years underwent EVAR. Mean follow-up was 36+/- 20 months. An ANN was created from morphological features including angulation/length/areas/diameters/ volume/tortuosity of the aneurysm neck/sac/iliac segments. ANN models predicted endograft complications and mortality with excellent discrimination between a low-risk and high-risk group. In external validation, the 5-year rates of freedom from aortic complications, limb complications and mortality were 95.9% vs 67.9%; 99.3% vs 92.0%; and 87.9% vs 79.3% respectively (p0.001) Conclusion This study presents ANN models that stratify the 5-year risk of endograft complications or mortality using routinely available pre-operative data

Hollow-fibre affinity cell separation

The developing fields of cell and tissue engineering will require cost-effective technologies for delivery of cells to patients. Hollow-fibre affinity cell separation is a monoclonal antibody-based cell separation process whereby monoclonal antibody (ligand) is immobilised onto a stationary substrate, the luminal surface of a parallel array of hollow fibres. Deposited cells are fractionated on the basis of adhesion strength using hollow fibre geometry that generates a well-defined shear stress for cell recovery. In this chapter we present the biophysical basis for the process of ligand-mediated cell adhesion and relate this to the performance of affinity cell separation. We also discuss the hydrodynamics of hollow fibre arrays and the various approaches for modifying polymer substrates with protein ligands. One of the major limiting factors for large-scale epitope selective cell separation will be the prohibitive cost of these affinity processes. Hollow fibre systems offer the promise of providing flexibility and scalability for many of these applications

Scaling deterministic lateral displacement arrays for high throughput and dilution-free enrichment of leukocytes

A disposable device for fractionation of blood into its components that is simple to operate and provides throughput of greater than 1 mL min-1 is highly sought after in medical diagnostics and therapies. This paper describes a device with parallel deterministic lateral displacement devices for enrichment of leukocytes from blood. We show capture of 98% and approximately ten-fold enrichment of leukocytes in whole blood. We demonstrate scaling up through the integration of six parallel devices to achieve a flow rate of 115 νL of undiluted blood per minute per atmosphere of applied pressure.8 page(s

Susceptibility of Cell Populations to Transduction by Retroviral Vectors

Retroviral transduction efficiency is related to the multiplicity of infection and the physiological state of the target cells. It is generally not known what proportion of a cell population is susceptible to transduction. We used coinfection with two retroviral vectors containing the marker genes for green fluorescent protein and the truncated human nerve growth factor receptor. In the CD34(+) cell line TF-1 or human primary CD34(+) hematopoietic progenitor cells, it was found that cells transduced with one vector had a better than random chance of transduction by the other vector. A probability model was developed to estimate target cell susceptibility; susceptibility was calculated as the product of the proportions of transgene-positive cells divided by the proportion of double-positive cells. By using this relationship, it was found that susceptibility was related to the target cell type and culture conditions but not the retroviral titer or the retroviral packaging envelope protein used in this study. Cotransduction with two vectors is a relatively simple procedure that provides a means to assess the maximum transduction level possible in a given cell population

On-line detection and quantification of trace impurities in vaporisable samples by direct liquid introduction process mass spectrometry

A thermal vaporiser has been designed for analysis of liquid streams by a process mass spectrometer normally used for gas analysis. Concentrations of benzene, toluene and o-xylene at mg kg-1levels in ethanol were determined from continuous vaporisation of the liquid. Ions with m/z values of 39, 57, 73, 77, 78, 91, 92 and 106 were selected and the optimal regression model (multiple linear regression with mean-centring) was found using an automated design of experiments approach to calibration model selection. It was discovered that the linearity of the response allowed excellent calibration to be performed using only four standards (at 0 and 110 mg kg-1for each of the three analytes) and that there were minimal inter-analyte interferences. The detection limit of benzene, toluene and o-xylene was 0.5, 0.8 and 0.5 mg kg-1, respectively. Average differences between the actual and predicted concentrations, expressed as a percentage of the actual concentrations, for 27-82 mg kg-1of benzene, toluene and o-xylene were 0.5-1.4%, 0.0-0.4% and 0.3-1.6%, respectively, while the average relative standard deviations were 1.3-2.6%, 1.0-2.5% and 1.1-2.3%, respectively. Detection of 3 mg kg-1changes in the concentration of each of the analytes (at the 36 mg kg-1level) was also demonstrated, indicating the sensitivity of the technique and the potential ability of the procedure to detect minor deviations in the specification of process streams from continuous analysis