Preface

The Marble (Maastricht Researched Based Learning for Excellence) programme at SBE facilitates the development of research projects for highly motivated and excellent undergraduate students. Students attending the bachelor programme of Econometrics and Operations Research join the Marble programme in the third year of their study. At the end of their bachelor they perform a short study which covers different applications of econometrical, mathematical and operations research techniques. The findings are presented at a mini symposium in June and documented in a research paper. This series is the second publication in the field of Econometrics and Operations Research and contains the best research papers in the academic year 2012/13

Preface

The Marble (Maastricht Researched Based Learning for Excellence) programme at SBE facilitates the development of research projects for highly motivated and excellent undergraduate students. Students attending the bachelor programme of Economics and International Business can join the Marble programme in the third year of their study. During the third year they perform a short research which deals with their specialization or major. The findings are presented at a mini symposium in December or June and documented in a research paper. This series contains the best research papers in the academic year 2012/13 and represent the different types of research in the programmes

Preface

The Marble (Maastricht Researched Based Learning for Excellence) programme at SBE facilitates the development of research projects for highly motivated and excellent undergraduate students. Students attending the bachelor programme of Econometrics and Operations Research join the Marble programme in the third year of their study. At the end of their bachelor they perform a short study which covers different applications of econometrical, mathematical and operations research techniques. The findings are presented at a mini symposium in June and documented in a research paper

Systemic neutrophil activation in COPD : Analysis of gene expression profiles and intracellular signaling

Granulocytes are thought to play an important role in the maintenance and progression of chronic diseases, such as COPD, allergic asthma, and rheumatoid arthritis. Despite the importance of granulocytes in these diseases surprisingly little is known about the processes occurring in vivo that regulate inappropriate granulocyte functioning. In this thesis, gene expression of neutrophils has been analyzed in vitro and in vivo, to characterize chronic systemic inflammation and identify mediators that are playing a role in the pathogenesis of COPD. To understand the finely tuned process of neutrophil functioning in vivo, it is also necessary to define components of the signaling pathways responsible for the priming and activation of effector functions in granulocytes. In this thesis, research questions were addressed, concerning granulocyte functioning in vitro and in vivo. Are changes in gene expression of peripheral blood neutrophils a result of the pathogenetic mechanisms underlying the development of COPD and can these gene profiles be used to define penotypes and severity of the disease? Exposure of neutrophils to cytokines or chemokines, results in their activation and changes in gene expression profiles. In Chapter 2, we utilise gene array technology and real time reverse trancriptase polymerase chain reaction to define the gene expression profiles of peripheral blood neutrophils of COPD patients compared with in vitro stimulated neutrophils. In Chapter 3, we use the same techniques, to investigate differences between peripheral blood neutrophils of COPD patients during a stable phase of their disease and during an exacerbation. Furthermore, we investigated the kinetics of activation of peripheral blood neutrophils in COPD patients in a longitudial setting. What is the role of Src kinases and small GTPase Rac in granulocyte functioning? To address this question, we use pharmacological inhibitors and a recently developed technique of protein transduction. In Chapter 5 we investigate the role of Src kinases in neutrophil functioning, whereas in Chapter 6 the role of Rac is investigated in peripheral blood eosinophil functioning by introducing a constitutively active mutant into these cells. In Chapter 7, we describe an ELISA technique developed for non-radioactive semi-quantitative analysis of the activation state of several kinases in adherent and suspension cells using phosphospecific antibodie

Urban dunes : Towards BwN design principles for dune formation along urbanized shores

Sandy shores worldwide suffer from coastal erosion due to a lack of sediment input and sea-level rise. In response, coastal sand nourishments are executed using ‘Building with Nature’ techniques (BwN), in which the sand balance is amplified and natural dynamics are instrumental in the redistribution of sand, cross- and alongshore. These nourishments contribute to the growth of beaches and dunes, serving various design objectives (such as flood safety, nature, and recreation). Nevertheless, human interference (such as buildings and traffic) along urbanized sandy shores may have significant, yet poorly understood, effects on beach and dune development. Better insight is required into the interplay of morphological, ecological and urban processes to support Aeolian BwN processes for dune formation and contribute to the sustainable design of urbanized coastal zones. This paper aims to bridge the gap between coastal engineering and urban design by formulating design principles for BwN along urbanized sandy shores, combining nourishments, natural dune formation and urban development on a local scale to strengthen the coastal buffer. The first part of the paper analyses sedimentation processes in the (built) sea-land interface and identifies spatial mechanisms that relate coastal occupation to dune formation. Hence a preliminary set of design principles is derived by manipulating wind-driven sediment transport for BwN dune formation after nourishment. In the second part of the paper, these principles are applied and contextualized in two case-studies to compare their capability for BwN in different coastal profiles: the vast, rural, geomorphologically high dynamic profile of a mega-nourishment (Sand Motor); versus the compact, highly urbanized, profile(s) of a coastal resort (Noordwijk). Conclusions reflect on the applicability of BwN design principles within different coastal settings (dynamics, urbanity) and spatial arrangements facilitating BwN dune formation

First Report on Real-World Outcomes with Evoked Compound Action Potential (ECAP)-Controlled Closed-Loop Spinal Cord Stimulation for Treatment of Chronic Pain

Introduction: A novel closed-loop spinal cord stimulation (SCS) system has recently been approved for use which records evoked compound action potentials (ECAPs) from the spinal cord and utilizes these recordings to automatically adjust the stimulation strength in real time. It automatically compensates for fluctuations in distance between the epidural leads and the spinal cord by maintaining the neural response (ECAP) at a determined target level. This data collection was principally designed to evaluate the performance of this first closed-loop SCS system in a ‘real-world’ setting under normal conditions of use in a single European center. Methods: In this prospective, single-center observational data collection, 22 patients were recruited at the outpatient pain clinic of the St. Antonius Hospital. All candidates were suffering from chronic pain in the trunk and/or limbs due to PSPS type 2 (persistent spinal pain syndrome). As standard of care, follow-up visits were completed at 3 months, 6 months, and 12 months post-device activation. Patient-reported outcome data (pain intensity, patient satisfaction) and electrophysiological and device data (ECAP amplitude, conduction velocity, current output, pulse width, frequency, usage), and patient interaction with their controller were collected at baseline and during standard of care follow-up visits. Results: Significant decreases in pain intensity for overall back or leg pain scores (verbal numerical rating score = VNRS) were observed between baseline [mean ± SEM (standard error of the mean); n = 22; 8.4 ± 0.2)], 3 months (n = 12; 1.9 ± 0.5), 6 months (n = 16; 2.6 ± 0.5), and 12 months (n = 20; 2.0 ± 0.5), with 85.0% of the patients being satisfied at 12 months. Additionally, no significant differences in average pain relief at 3 months and 12 months between the real-world data (77.2%; 76.8%) and the AVALON (71.2%; 73.6%) and EVOKE (78.1%; 76.7%) studies were observed. Conclusions: These initial ‘real-world’ data on ECAP-controlled, closed-loop SCS in a real-world clinical setting appear to be promising, as they provide novel insights of the beneficial effect of ECAP-controlled, closed-loop SCS in a real-world setting. The presented results demonstrate a noteworthy maintenance of pain relief over 12 months and corroborate the outcomes observed in the AVALON prospective, multicenter, single-arm study and the EVOKE double-blind, multicenter, randomized controlled trial. Trial Registration: The data collection is registered on the International Clinical Trials Registry Platform (Trial NL7889).</p

Significance of Gram's Stain in Rapid Intrapartum Screening for Maternal Carriership of Group B Streptococcus

Objective: Group B streptococcus (GBS, Streptococcus agalactiae) is an important cause of neonatal sepsis. Prevention is possible by intrapartum screening for maternal GBS carriership and antimicrobial treatment of colonized women with risk factors during labor. The conflicting results of diagnostic performance are reported both for the newly developed rapid GBS antigen tests and Gram's stain

HIV-1 protease inhibitor mutations affect the development of HIV-1 resistance to the maturation inhibitor bevirimat

<p>Abstract</p> <p>Background</p> <p>Maturation inhibitors are an experimental class of antiretrovirals that inhibit Human Immunodeficiency Virus (HIV) particle maturation, the structural rearrangement required to form infectious virus particles. This rearrangement is triggered by the ordered cleavage of the precursor Gag polyproteins into their functional counterparts by the viral enzyme protease. In contrast to protease inhibitors, maturation inhibitors impede particle maturation by targeting the substrate of protease (Gag) instead of the protease enzyme itself. Direct cross-resistance between protease and maturation inhibitors may seem unlikely, but the co-evolution of protease and its substrate, Gag, during protease inhibitor therapy, could potentially affect future maturation inhibitor therapy. Previous studies showed that there might also be an effect of protease inhibitor resistance mutations on the development of maturation inhibitor resistance, but the exact mechanism remains unclear. We used wild-type and protease inhibitor resistant viruses to determine the impact of protease inhibitor resistance mutations on the development of maturation inhibitor resistance.</p> <p>Results</p> <p>Our resistance selection studies demonstrated that the resistance profiles for the maturation inhibitor bevirimat are more diverse for viruses with a mutated protease compared to viruses with a wild-type protease. Viral replication did not appear to be a major factor during emergence of bevirimat resistance. In all <it>in vitro </it>selections, one of four mutations was selected: Gag V362I, A364V, S368N or V370A. The impact of these mutations on maturation inhibitor resistance and viral replication was analyzed in different protease backgrounds. The data suggest that the protease background affects development of HIV-1 resistance to bevirimat and the replication profiles of bevirimat-selected HIV-1. The protease-dependent bevirimat resistance and replication levels can be explained by differences in CA/p2 cleavage processing by the different proteases.</p> <p>Conclusions</p> <p>These findings highlight the complicated interactions between the viral protease and its substrate. By providing a better understanding of these interactions, we aim to help guide the development of second generation maturation inhibitors.</p

The Diagnostic Sensitivity for Ulnar Neuropathy at the Elbow Is Not Increased by Addition of Needle EMG of ADM and FDI When Nerve Conduction Studies Are Normal

Introduction: The main objective of this study was to investigate whether electromyography (EMG) has additional value in the confirmation of the clinical diagnosis of ulnar nerve entrapment at the elbow (UNE) if nerve conduction studies (NCS) are normal.Methods: A prospective cross-sectional cohort observational study was conducted among patients with the clinical suspicion of UNE. A total of 199 arms were included, who were examined according to a standard neurophysiological protocol, i.e., NCS and EMG relevant to the ulnar nerve.Results: NCS were normal in 76 (38.2%) arms. No abnormal spontaneous muscle fiber activity was found with EMG in any of these cases. In 9 arms with normal NCS (11.8%), isolated abnormal MUAP configurations were found with EMG. Of these nine arms one UNE was diagnosed clinically, in which additional ultrasound and repeated NCS/EMG were negative. One had already been diagnosed with neuralgic amyotrophy and one with CTS. The other 6 arms had additional diagnostics which did not reveal an UNE.Conclusion: EMG as part of the standard neurophysiological protocol exclusively in the confirmation of the clinical diagnosis of UNE has limited added value if NCS are normal in a high prior-odds setting. However, removing EMG may prevent detecting concomitant and/or additional differential diagnoses