Modelling Business Ownership in the Netherlands

Beschrijving van een empirisch model ter verklaring van het aantal zelfstandige ondernemingen in Nederland. Een dergelijk model voorziet in het maken van scenario’s gemaakt voor de toekomstige ontwikkeling van het aantal ondernemingen in Nederland. Het model onderscheidt effecten op lange en korte termijn en besteedt expliciet aandacht aan turbulentie (gemeten als de som van bedrijfstoetredingen en -beëindigingen) van de markt. Hierbij wordt gebruikgemaakt van econometrische tijdserietechnieken. Het aantal ondernemingen en het aantal toe- en uittredingen worden zodoende verklaard uit economische en demografische variabelen. Naast de invloeden van deze variabelen tendeert het aantal ondernemingen naar een evenwichtsniveau, dat geschat is voor de lange termijn.

Dark matter, fine-tuning and (g−2)μ(g-2)_μ in the pMSSM

In this paper we analyze spectra in the phenomenological supersymmetric Standard Model that simultaneously result in the right dark-matter relic density $\Omega_{\rm DM} h^2$, offer an explanation for the $(g-2)_{\mu}$ discrepancy $\Delta a_{\mu}$ and are minimally fine-tuned. We discuss the LHC phenomenology resulting from these spectra and the sensitivity of dark-matter direct detection experiments to these spectra. We find that the latter type of experiments with sensitivity to the spin-dependent dark-matter-nucleon scattering cross section $\sigma_{\rm SD,p}$ will probe all of our found solutions

935-38 Restenosis After Coronary Angioplasty is Associated with the Activation Status of Circulating Phagocytes Before Treatment

BackgroundThe purpose of this study was to identify biological risk factors for restenosis after PTCA, in order to predict the long-term outcome of PTCA before treatment.Methods and ResultsTo investigate whether blood granulocytes and monocytes could determine luminal renarrowing after PTCA, several characteristics of these phagocytes were assessed before angioplasty in 32 patients who underwent PTCA of one coronary artery and who had repeat angiograms at six months follow-up. The plasma levels 1L-1β, TNF-α, IL-6, fibrinogen, C-reactive protein and LP(a) before angioplasty were assessed as well. We found that the expression of the membrane antigens CD64, CD66 and CD67 by granulocytes was inversely associated with the luminal renarrowing normalized for vessel size (relative loss) at six months after PTCA. while the production of IL-1β by stimulated monocytes was positively associated with the relative loss. Next. these univariate predictors were corrected for the established clinical risk factors, dilation of the LAD, current smoking and angina class.Multiple linear regression analysis showed that luminal renarrowing could be predicted reliably (R2=0.65; P<0.0001) in this patients group on the basis of the vessel dilated and only two biological risk factors that reflect the activation status of blood phagocytes, i.e., the expression of CD66 by granulocytes and the production of IL-lβ by stimulated monocytes.ConclusionsThe results of the present study indicate that activated blood granulocytes prevent luminal renarrowing after PTCA, while activated blood monocytes promote restenosis. To validate this new finding further study in an independent patients group is required

Comparison of methods for in-house screening of HLA*B57:01 to prevent abacavir hypersensitivity in HIV-1 care

Abacavir is a nucleoside reverse transcriptase inhibitor used as part of combination antiretroviral therapy in HIV-1-infected patients. Because this drug can cause a hypersensitivity reaction that is correlated with the presence of the HLA-B*57:01 allotype, screening for the presence of HLA-B*57:01 is recommended before abacavir initiation. Different genetic assays have been developed for HLA-B*57:01 screening, each with specific sensitivity, turnaround time and assay costs. Here, a new real-time PCR (qPCR) based analysis is described and compared to sequence specific primer PCR with capillary electrophoresis (SSP PCR CE) on 149 patient-derived samples, using sequence specific oligonucleotide hybridization combined with high resolution SSP PCR as gold standard. In addition to these PCR based methods, a complementary approach was developed using flow cytometry with an HLA-B17 specific monoclonal antibody as a pre-screening assay to diminish the number of samples for genetic testing. All three assays had a maximum sensitivity of >99. However, differences in specificity were recorded, i.e. 84.3%, 97.2% and >99% for flow cytometry, qPCR and SSP PCR CE respectively. Our data indicate that the most specific and sensitive of the compared methods is the SSP PCR CE. Flow cytometry pre-screening can substantially decrease the number of genetic tests for HLA-B*57:01 typing in a clinical setting

Late Lumen Loss After Coronary Angioplasty Is Associated With the Activation Status of Circulating Phagocytes Before Treatment

Background The purpose of this pilot study was to identify biological risk factors for restenosis after percutaneous transluminal coronary angioplasty (PTCA) to predict the long-term outcome of PTCA before treatment. Methods and Results To investigate whether blood granulocytes and monocytes could determine luminal renarrowing after PTCA, several characteristics of these phagocytes were assessed before angioplasty in 32 patients who underwent PTCA of one coronary artery and who had repeat angiograms at 6-month follow-up. The plasma levels of interleukin (IL)-1ß, tumor necrosis factor-, IL-6, fibrinogen, C-reactive protein, and lipoprotein(a) before angioplasty were assessed as well. We found that the expression of the membrane antigens CD64, CD66, and CD67 by granulocytes was inversely associated with the luminal renarrowing normalized for vessel size (relative loss) at 6 months after PTCA, while the production of IL-1ß by stimulated monocytes was positively associated with the relative loss. Next, these univariate predictors were corrected for the established clinical risk factors of dilation of the left anterior descending coronary artery and current smoking, which were statistically significant classic predictors in our patient group. Only the expression of CD67 did not predict late lumen loss independent of these established clinical risk factors. Multiple linear regression analysis showed that luminal renarrowing could be predicted reliably (R2=.65; P<.0001) in this patient group on the basis of the vessel dilated and only two biological risk factors that reflect the activation status of blood phagocytes, ie, the expression of CD66 by granulocytes and the production of IL-1ß by stimulated monocytes. Conclusions The results of the present study indicate that activated blood granulocytes prevent luminal renarrowing after PTCA, while activated blood monocytes promote late lumen loss. To validate this new finding, further study in an independent patient group is required

Prorenin accumulation and activation in human endothelial cells: importance of mannose 6-phosphate receptors

ACE inhibitors improve endothelial dysfunction, possibly by blocking endothelial angiotensin production. Prorenin, through its binding and activation by endothelial mannose 6-phosphate (M6P) receptors, may contribute to this production. Here, we investigated this possibility as well as prorenin activation kinetics, the nature of the prorenin-activating enzyme, and M6P receptor-independent prorenin binding. Human umbilical vein endothelial cells (HUVECs) were incubated with wild-type prorenin, K/A-2 prorenin (in which Lys42 is mutated to Ala, thereby preventing cleavage by known proteases), M6P-free prorenin, and nonglycosylated prorenin, with or without M6P, protease inhibitors, or angiotensinogen. HUVECs bound only M6P-containing prorenin (K(d) 0.9+/-0.1 nmol/L, maximum number of binding sites [B(max)] 1010+/-50 receptors/cell). At 37 degrees C, because of M6P receptor recycling, the amount of prorenin internalized via M6P receptors was >25 times B(max). Inside the cells, wild-type and K/A-2 prorenin were proteolytically activated to renin. Renin was subsequently degraded. Protease inhibitors interfered with the latter but not with prorenin activation, thereby indicating that the activating enzyme is different from any of the known prorenin-activating enzymes. Incubation with angiotensinogen did not lead to endothelial angiotensin generation, inasmuch as HUVECs were unable to internalize angiotensinogen. Most likely, therefore, in the absence of angiotensinogen synthesis or endocytosis, M6P receptor-mediated prorenin internalization by endothelial cells represents prorenin clearance

Copper-Heparin Inhalation Therapy To Repair Emphysema: A Scientific Rationale

Current pharmacotherapy of chronic obstructive pulmonary disease (COPD) aims at reducing respiratory symptoms and exacerbation frequency. Effective therapies to reduce disease progression, however, are still lacking. Furthermore, COPD medications showed less favorable effects in emphysema than in other COPD phenotypes. Elastin fibers are reduced and disrupted, whereas collagen levels are increased in emphysematous lungs. Protease/antiprotease imbalance has historically been regarded as the sole cause of emphysema. However, it is nowadays appreciated that emphysema may also be provoked by perturbations in the sequential repair steps following elastolysis. Essentiality of fibulin-5 and lysyl oxidase-like 1 in the elastin restoration process is discussed, and it is argued that copper deficiency is a plausible reason for failing elastin repair in emphysema patients. Since copper-dependent lysyl oxidases crosslink elastin as well as collagen fibers, copper supplementation stimulates accumulation of both proteins in the extracellular matrix. Restoration of abnormal elastin fibers in emphysematous lungs is favorable, whereas stimulating pulmonary fibrosis formation by further increasing collagen concentrations and organization is detrimental. Heparin inhibits collagen crosslinking while stimulating elastin repair and might therefore be the ideal companion of copper for emphysema patients. Efficacy and safety considerations may lead to a preference of pulmonary administration of copper-heparin over systemic administration