Optimization of Inventory and Capacity in Large-Scale Assembly Systems Using Extreme-Value Theory

High-tech systems are typically produced in two stages: (1) production of components using specialized equipment and staff and (2) system assembly/integration. Component production capacity is subject to fluctuations, causing a high risk of shortages of at least one component, which results in costly delays. Companies hedge this risk by strategic investments in excess production capacity and in buffer inventories of components. To optimize these, it is crucial to characterize the relation between component shortage risk and capacity and inventory investments. We suppose that component production capacity and produce demand are normally distributed over finite time intervals, and we accordingly model the production system as a symmetric fork-join queueing network with N statistically identical queues with a common arrival process and independent service processes. Assuming a symmetric cost structure, we subsequently apply extreme value theory to gain analytic insights into this optimization problem. We derive several new results for this queueing network, notably that the scaled maximum of N steady-state queue lengths converges in distribution to a Gaussian random variable. These results translate into asymptotically optimal methods to dimension the system. Tests on a range of problems reveal that these methods typically work well for systems of moderate size

Rosuvastatin use increases plasma fibrinolytic potential: a randomised clinical trial

We conducted a study to assess the effect of rosuvastatin use on fibrinolysis in patients with previous venous thromboembolism (VTE). This was a post hoc analysis within the STAtins Reduce Thrombophilia (START) study (NCT01613794). Plasma fibrinolytic potential, fibrinogen, plasmin inhibitor, plasminogen activator inhibitor-1 (PAI-1) and thrombin-activatable fibrinolysis inhibitor (

A revised systematic review and meta-analysis on the effect of statins on D-dimer levels

Background: D-dimers are generated during endogenous fibrinolysis of a blood clot and have a central role in diagnostic algorithms to rule out venous thromboembolism. HMG-CoA reductase inhibitors, more commonly called statins, are known to have effects independent of LDL-cholesterol lowering, including antithrombotic properties. An effect of statins on D-dimer levels has been reported in a prior systematic review and meta-analysis, but methodological shortcomings might have led to an overestimated effect. To re-evaluate the association between statins and D-dimer levels, we systematically reviewed all published articles on the influence of statins on D-dimer levels and conducted a novel meta-analysis (PROSPERO registration number CRD42017058932). Materials and methods: We electronically searched EMBASE, Medline Epub, Cochrane, Web of Science and Google Scholar (100 top relevance) (d

Clinical effects of antiplatelet drugs and statins on D-dimer levels

Thrombosis and Hemostasi

Evaluation of Protocol Uniformity Concerning Laparoscopic Cholecystectomy in The Netherlands

Background: Iatrogenic bile duct injury remains a current complication of laparoscopic cholecystectomy. One uniform and standardized protocol, based on the "critical view of safety" concept of Strasberg, should red

Harmonization and standardization of nucleus pulposus cell extraction and culture methods

Background In vitro studies using nucleus pulposus (NP) cells are commonly used to investigate disc cell biology and pathogenesis, or to aid in the development of new therapies. However, lab-to-lab variability jeopardizes the much-needed progress in the field. Here, an international group of spine scientists collaborated to standardize extraction and expansion techniques for NP cells to reduce variability, improve comparability between labs and improve utilization of funding and resources. Methods The most commonly applied methods for NP cell extraction, expansion, and re-differentiation were identified using a questionnaire to research groups worldwide. NP cell extraction methods from rat, rabbit, pig, dog, cow, and human NP tissue were experimentally assessed. Expansion and re-differentiation media and techniques were also investigated. Results Recommended protocols are provided for extraction, expansion, and re-differentiation of NP cells from common species utilized for NP cell culture. Conclusions This international, multilab and multispecies study identified cell extraction methods for greater cell yield and fewer gene expression changes by applying species-specific pronase usage, 60–100 U/ml collagenase for shorter durations. Recommendations for NP cell expansion, passage number, and many factors driving successful cell culture in different species are also addressed to support harmonization, rigor, and cross-lab comparisons on NP cells worldwide

Harmonization and standardization of nucleus pulposus cell extraction and culture methods

Background: In vitro studies using nucleus pulposus (NP) cells are commonly used to investigate disc cell biology and pathogenesis, or to aid in the development of new therapies. However, lab‐to‐lab variability jeopardizes the much‐needed progress in the field. Here, an international group of spine scientists collaborated to standardize extraction and expansion techniques for NP cells to reduce variability, improve comparability between labs and improve utilization of funding and resources. Methods: The most commonly applied methods for NP cell extraction, expansion, and re‐differentiation were identified using a questionnaire to research groups worldwide. NP cell extraction methods from rat, rabbit, pig, dog, cow, and human NP tissue were experimentally assessed. Expansion and re‐differentiation media and techniques were also investigated. Results: Recommended protocols are provided for extraction, expansion, and re‐differentiation of NP cells from common species utilized for NP cell culture. Conclusions: This international, multilab and multispecies study identified cell extraction methods for greater cell yield and fewer gene expression changes by applying species‐specific pronase usage, 60–100 U/ml collagenase for shorter durations. Recommendations for NP cell expansion, passage number, and many factors driving successful cell culture in different species are also addressed to support harmonization, rigor, and cross‐lab comparisons on NP cells worldwide

Influence of (Co-)Medication on Haemostatic Biomarkers

We showed that the simplified diagnostic YEARS algorithm for suspected acute pulmonary embolism can be safely applied in patients presenting in the hospital, also in patients using statins or antiplatelet drugs, but that the diagnosis of VTE in schizophrenic patients remains difficult. Additionally, we showed that statins but not antiplatelet drugs and PCSK9 inhibitors influence D-dimer levels and that in participants with prior VTE, statin use led to an improved breakdown of blood clots compared to non-statin use