Laboratory Detection of the Antiphospholipid Syndrome via Calibrated Automated Thrombography

Lupus anticoagulants (LAC) consist of anti phospholipid antibodies, detected via their anti coagulant properties in vitro. Strong LAC relate to thromboembolic events, a hallmark of the anti-phospholipid syndrome. We have analyzed whether detection of this syndrome would benefit from thrombin generation measurements. Therefore, calibrated automated thrombography was done in normal plasma (n=30) and LAC patient plasma (n=48 non-anticoagulated, n=12 on oral anti coagulants), diluted 1: 1 with a normal plasma pool. The anti-beta(2)-glycoprotein I monoclonal antibody 23H9, with known LAC properties, delayed the lag time and reduced the peak height during thrombin generation induction in normal plasma dose-dependently (0-150 mu g/ml). At variance, LAC patient 1: 1 plasma mixtures manifested variable lag time prolongations and/or peak height reductions. Coupling these two most informative thrombin generation parameters in a peak height/lag time ratio,and upon normalization versus the normal plasma pool, this ratio distributed normally and was reduced in the plasma mixtures, for 59/60 known LAC plasmas. The normalized peak height/lag time ratio correlated well with the normalized dilute prothrombin time,diluted Russell's viper venom time and silica clotting time, measured in 1: 1 plasma mixtures (correlation coefficients 0.59-0.72). The anticoagulant effects of activated protein C (0-7.5 nM) or 23H9 (0-150 mu g/ml), spiked in the 1: 1 LAC plasma mixtures were reduced for the majority of patients, compatible with functional competition between patient LAC and activated protein C and LAC and 23H9, respectively. Hence,the normalized thrombin gene ration-derived peak height/lag time ratio identifies LAC in plasma with high sensitivity in a single assay, irrespective of the patient's treatment with oral anticoagulants

Development of a WNT-selective oncolytic adenovirus for imaging the therapy of colorectal cancers.

PhDIntroduction: The concept of oncolytic adenoviruses has been validated in preclinical studies but clinical trials have demonstrated that the virus spread remains limited and the virus fails to infect all cancer cells in a tumour. Arming an oncolytic virus with a therapeutic trans gene would enhance the antitumour effect of these viruses by killing adjacent non-infected cells. The aim of this thesis is to test armed oncolytic adenoviruses targeting a constitutive activation of the Wnt signalling pathway in pre-clinical models of colorectal cancer. Methods: The Nail symporter was inserted into the genome of Wnt-selective oncolytic adenoviruses to visualise adenoviral spread in the tumour and assess image-guided radiotherapy. Results: In vitro testing of the virus has demonstrated that the Wnt-selectivity of the virus remains intact. The virus we generated has an equal or greater cytopathic effect than wild type adenovirus in Wnt-expressing cancer cell lines. The ability of the infected cells to take up iodine has been confirmed by iodine uptake assays. The virus has been injected into subcutaneous human tumour implants in nude mice. Images obtained with a SPECT/CT camera have demonstrated that viral propagation can be visualised in vivo. Finally, we have used the imaging data to determine the correct timing for the administration of therapeutic doses of 131 I. Conclusion: We have validated a non invasive method to image viral propagation and transgene expression in a preclinical model of colonic cancer. Sequential imaging can provide information on the ideal time point for therapeutic intervention. In pilot experiments, the aim was to exploit the potential of the Nail symporter for the concentration of radioactive iodine, but it did not lead to increased therapeutic efficacy in vivo in preclinical models. There is strong evidence that if these experiments were repeated, therapeutic efficacy could he demonstrated

A design method for parts picking zones in a manufacturing environment

This paper describes a method for the design of an order picking system in a manufacturing environment. Unlike order picking systems in warehouses, there is almost no literature available concerning order picking systems in a manufacturing environment. We start by defining the needed input parameters, followed by a parts classification method. This leads to the calculation of order specifications (order lines, volume, weight,…). The needed throughput, available floor space and associated costs then define the most appropriate order picking system under the given circumstances

A study of prospective surveillance for inhibitors among persons with haemophilia in the United States

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106128/1/hae12302.pd

Mild/moderate haemophilia A: new insights into molecular mechanisms and inhibitor development

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72987/1/j.1365-2516.2008.01730.x.pd

Healthcare resource utilization among haemophilia A patients in the United States

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91210/1/j.1365-2516.2011.02677.x.pd

Eliminating viral hepatitis C in Belgium: the micro-elimination approach

Background: Hepatitis C virus is one of the leading causes of chronic liver disease and liver-related deaths worldwide. The estimated prevalence of chronic hepatitis C viral infection among the general Belgian population was 0.57% (n = 64,000) in 2015. Although Belgium has had a ‘Hepatitis C Plan’ since 2014, elimination efforts are unclear. This study employs the best available data and modelling estimates to define the burden of hepatitis C viral infection among key subgroups in Belgium, identify information gaps and propose potential approaches to screening, linkage to care and treatment, and cure. Methods: We examined the peer-reviewed and grey literature since 2012 for data on the prevalence of hepatitis C viral infection in Belgium in key subgroups identified by national experts and in the literature. Ultimately, this research is primarily based on data provided by the key stakeholders themselves due to a lack of reliable data in the literature. Based on this, we modelled the treatment rates required to reach elimination of hepatitis C in several subgroups. Results: Eleven potential subgroups were identified. There were no data available for two subgroups: generational cohorts and men who have sex with men. In six subgroups, fewer than 3000 people were reported or estimated to have hepatitis C infection. Migrants and people who inject drugs were the most affected subgroups, and children were the least affected subgroup. Only two subgroups are on target to achieve elimination by 2030: patients living with haemophilia and transplant recipients. Conclusions: Removing Belgian treatment reimbursement restrictions in January 2019 was a big step towards eliminating HCV. In addition, increasing surveillance, including with a national registry, treatment prescription by other health-care providers and availability of treatment in local pharmacies are central to improving the current situation and getting on track to reach the 2030 WHO hepatitis C elimination targets in Belgium

Extracorporeal membrane oxygenator as a bridge to successful surgical repair of bronchopleural fistula following bilateral sequential lung transplantation: a case report and review of literature

<p>Abstract</p> <p>Background</p> <p>Lung transplantation (LTx) is widely accepted as a therapeutic option for end-stage respiratory failure in cystic fibrosis. However, airway complications remain a major cause of morbidity and mortality in these patients, serious airway complications like bronchopleural fistula (BPF) are rare, and their management is very difficult.</p> <p>Case presentation</p> <p>A 47-year-old man with end-stage respiratory failure due to cystic fibrosis underwent bilateral sequential lung transplantation. Severe post-operative bleeding occurred due to dense intrapleural adhesions of the native lungs. He was re-explored and packed leading to satisfactory haemostasis. He developed a bronchopleural fistula on the 14^thpost-operative day. The fistula was successfully repaired using pericardial and intercostal vascular flaps with veno-venous extracorporeal membrane oxygenator (VV-ECMO) support. Subsequently his recovery was uneventful.</p> <p>Conclusion</p> <p>The combination of pedicled intercostal and pericardial flaps provide adequate vascular tissue for sealing a large BPF following LTx. Veno-venous ECMO allows a feasible bridge to recovery.</p