Phosphorylcholine Monoclonal Antibody Therapy Decreases Intraplaque Angiogenesis and Intraplaque Hemorrhage in Murine Vein Grafts

Funding: This work was supported by the European Union Program Grant CVDIMMUNE [037227], CARDIMMUN [601728] and Marie Sklodowska Curie Actions joint doctoral project MoGlyNet [675527]. Acknowledgments: We would like to thank Raghed Halawani with help of quantifying histological images.Peer reviewedPublisher PD

Influence of the molybdenum cofactor biosynthesis on anaerobic respiration, biofilm formation and motility in Burkholderia thailandensis

types: Journal Article; Research Support, Non-U.S. Gov'tCopyright © 2013 Institut Pasteur. Published by Elsevier Masson SAS.Elsevier. NOTICE: This is the author’s version of a work accepted for publication by Elsevier. Changes resulting from the publishing process, including peer review, editing, corrections, structural formatting and other quality control mechanisms, may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Research in Microbiology, 2014, Vol. 165, Issue 1, pp. 41 – 49 DOI: 10.1016/j.resmic.2013.10.009Burkholderia thailandensis is closely related to Burkholderia pseudomallei, a bacterial pathogen and the causative agent of melioidosis. B. pseudomallei can survive and persist within a hypoxic environment for up to one year and has been shown to grow anaerobically in the presence of nitrate. Currently, little is known about the role of anaerobic respiration in pathogenesis of melioidosis. Using B. thailandensis as a model, a library of 1344 transposon mutants was created to identify genes required for anaerobic nitrate respiration. One transposon mutant (CA01) was identified with an insertion in BTH_I1704 (moeA), a gene required for the molybdopterin biosynthetic pathway. This pathway is involved in the synthesis of a molybdopterin cofactor required for a variety of molybdoenzymes, including nitrate reductase. Disruption of molybdopterin biosynthesis prevented growth under anaerobic conditions, when using nitrate as the sole terminal electron acceptor. Defects in anaerobic respiration, nitrate reduction, motility and biofilm formation were observed for CA01. Mutant complementation with pDA-17:BTH_I1704 was able to restore anaerobic growth on nitrate, nitrate reductase activity and biofilm formation, but did not restore motility. This study highlights the potential importance of molybdoenzyme-dependent anaerobic respiration in the survival and virulence of B. thailandensis.BBSRC studentship (C. A. Andreae

Systematic analysis of the ability of Nitric Oxide donors to dislodge biofilms formed by Salmonella enterica and Escherichia coli O157:H7

Biofilms in the industrial environment could be problematic. Encased in extracellular polymeric substances, pathogens within biofilms are significantly more resistant to chlorine and other disinfectants. Recent studies suggest that compounds capable of manipulating nitric oxide-mediated signaling in bacteria could induce dispersal of sessile bacteria and provide a foundation for novel approaches to controlling biofilms formed by some microorganisms. In this work, we compared the ability of five nitric oxide donors (molsidomine, MAHMA NONOate, diethylamine NONOate, diethylamine NONOate diethylammonium salt, spermine NONOate) to dislodge biofilms formed by non-typhoidal Salmonella enterica and pathogenic E. coli on plastic and stainless steel surfaces at different temperatures. All five nitric oxide donors induced significant (35-80%) dispersal of biofilms, however, the degree of dispersal and the optimal dispersal conditions varied. MAHMA NONOate and molsidomine were strong dispersants of the Salmonella biofilms formed on polystyrene. Importantly, molsidomine induced dispersal of up to 50% of the pre-formed Salmonella biofilm at 4 degrees C, suggesting that it could be effective even under refrigerated conditions. Biofilms formed by E. coli O157:H7 were also significantly dispersed. Nitric oxide donor molecules were highly active within 6 hours of application. To better understand mode of action of these compounds, we identified Salmonella genomic region recA-hydN, deletion of which led to an insensitivity to the nitric oxide donors

Preparation and monitoring of small animals in renal MRI

Renal diseases remain devastating illnesses with unacceptably high rates of mortality and morbidity worldwide. Animal models are essential tools to better understand the pathomechanism of kidney-related illnesses and to develop new, successful therapeutic strategies. Magnetic resonance imaging (MRI) has been actively explored in the last decades for assessing renal function, perfusion, tissue oxygenation as well as the degree of fibrosis and inflammation. This chapter aims to provide an overview of the preparation and monitoring of small animals before, during, and after surgical interventions or MR imaging. Standardization of experimental settings such as body temperature or hydration of animals and minimizing pain and distress are essential for diminishing nonexperimental variables as well as for conducting ethical research.This publication is based upon work from the COST Action PARENCHIMA, a community-driven network funded by the European Cooperation in Science and Technology (COST) program of the European Union, which aims to improve the reproducibility and standardization of renal MRI biomarkers

Safety and immunogenicity of the two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in children in Sierra Leone: a randomised, double-blind, controlled trial

Background—Children account for a substantial proportion of cases and deaths from Ebola virus disease. We aimed to assess the safety and immunogenicity of a two-dose heterologous vaccine regimen, comprising the adenovirus type 26 vector-based vaccine encoding the Ebola virus glycoprotein (Ad26.ZEBOV) and the modified vaccinia Ankara vectorbased vaccine, encoding glycoproteins from the Ebola virus, Sudan virus, and Marburg virus, and the nucleoprotein from the Tai Forest virus (MVA-BN-Filo), in a paediatric population in Sierra Leone. Methods—This randomised, double-blind, controlled trial was done at three clinics in Kambia district, Sierra Leone. Healthy children and adolescents aged 1–17 years were enrolled in three age cohorts (12–17 years, 4–11 years, and 1–3 years) and randomly assigned (3:1), via computer-generated block randomisation (block size of eight), to receive an intramuscular injection of either Ad26.ZEBOV (5 × 1010 viral particles; first dose) followed by MVA-BN-Filo (1 × 108 infectious units; second dose) on day 57 (Ebola vaccine group), or a single dose of meningococcal quadrivalent (serogroups A, C, W135, and Y) conjugate vaccine (MenACWY; first dose) followed by placebo (second dose) on day 57 (control group). Study team personnel (except for those with primary responsibility for study vaccine preparation), participants, and their parents or guardians were masked to study vaccine allocation. The primary outcome was safety, measured as the occurrence of solicited local and systemic adverse symptoms during 7 days after each vaccination, unsolicited systemic adverse events during 28 days after each vaccination, abnormal laboratory results during the study period, and serious adverse events or immediate reportable events throughout the study period. The secondary outcome was immunogenicity (humoral immune response), measured as the concentration of Ebola virus glycoprotein-specific binding antibodies at 21 days after the second dose. The primary outcome was assessed in all participants who had received at least one dose of study vaccine and had available reactogenicity data, and immunogenicity was assessed in all participants who had received both vaccinations within the protocol-defined time window, had at least one evaluable post-vaccination sample, and had no major protocol deviations that could have influenced the immune response. This study is registered at ClinicalTrials.gov, NCT02509494. Findings—From April 4, 2017, to July 5, 2018, 576 eligible children or adolescents (192 in each of the three age cohorts) were enrolled and randomly assigned. The most common solicited local adverse event during the 7 days after the first and second dose was injection-site pain in all age groups, with frequencies ranging from 0% (none of 48) of children aged 1–3 years after placebo injection to 21% (30 of 144) of children aged 4–11 years after Ad26.ZEBOV vaccination. The most frequently observed solicited systemic adverse event during the 7 days was headache in the 12–17 years and 4–11 years age cohorts after the first and second dose, and pyrexia in the 1–3 years age cohort after the first and second dose. The most frequent unsolicited adverse event after the first and second dose vaccinations was malaria in all age cohorts, irrespective of the vaccine types. Following vaccination with MenACWY, severe thrombocytopaenia was observed in one participant aged 3 years. No other clinically significant laboratory abnormalities were observed in other study participants, and no serious adverse events related to the Ebola vaccine regimen were reported. There were no treatment-related deaths. Ebola virus glycoprotein-specific binding antibody responses at 21 days after the second dose of the Ebola virus vaccine regimen were observed in 131 (98%) of 134 children aged 12–17 years (9929 ELISA units [EU]/mL [95% CI 8172–12 064]), in 119 (99%) of 120 aged 4–11 years (10 212 EU/mL [8419–12 388]), and in 118 (98%) of 121 aged 1–3 years (22 568 EU/mL [18 426–27 642]). Interpretation—The Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen was well tolerated with no safety concerns in children aged 1–17 years, and induced robust humoral immune responses, suggesting suitability of this regimen for Ebola virus disease prophylaxis in children

Safety and long-term immunogenicity of the two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in adults in Sierra Leone: a combined open-label, non-randomised stage 1, and a randomised, double-blind, controlled stage 2 trial

Background The Ebola epidemics in west Africa and the Democratic Republic of the Congo highlight an urgent need for safe and effective vaccines to prevent Ebola virus disease. We aimed to assess the safety and long-term immunogenicity of a two-dose heterologous vaccine regimen, comprising the adenovirus type 26 vector-based vaccine encoding the Ebola virus glycoprotein (Ad26.ZEBOV) and the modified vaccinia Ankara vector-based vaccine, encoding glycoproteins from Ebola virus, Sudan virus, and Marburg virus, and the nucleoprotein from the Tai Forest virus (MVA-BN-Filo), in Sierra Leone, a country previously affected by Ebola. Methods The trial comprised two stages: an open-label, non-randomised stage 1, and a randomised, double-blind, controlled stage 2. The study was done at three clinics in Kambia district, Sierra Leone. In stage 1, healthy adults (aged ≥18 years) residing in or near Kambia district, received an intramuscular injection of Ad26.ZEBOV (5×1010 viral particles) on day 1 (first dose) followed by an intramuscular injection of MVA-BN-Filo (1×108 infectious units) on day 57 (second dose). An Ad26.ZEBOV booster vaccination was offered at 2 years after the first dose to stage 1 participants. The eligibility criteria for adult participants in stage 2 were consistent with stage 1 eligibility criteria. Stage 2 participants were randomly assigned (3:1), by computer-generated block randomisation (block size of eight) via an interactive web-response system, to receive either the Ebola vaccine regimen (Ad26.ZEBOV followed by MVA-BN-Filo) or an intramuscular injection of a single dose of meningococcal quadrivalent (serogroups A, C, W135, and Y) conjugate vaccine (MenACWY; first dose) followed by placebo on day 57 (second dose; control group). Study team personnel, except those with primary responsibility for study vaccine preparation, and participants were masked to study vaccine allocation. The primary outcome was the safety of the Ad26.ZEBOV and MVA-BN-Filo vaccine regimen, which was assessed in all participants who had received at least one dose of study vaccine. Safety was assessed as solicited local and systemic adverse events occurring in the first 7 days after each vaccination, unsolicited adverse events occurring in the first 28 days after each vaccination, and serious adverse events or immediate reportable events occurring up to each participant’s last study visit. Secondary outcomes were to assess Ebola virus glycoprotein-specific binding antibody responses at 21 days after the second vaccine in a per-protocol set of participants (ie, those who had received both vaccinations within the protocol-defined time window, had at least one evaluable post-vaccination sample, and had no major protocol deviations that could have influenced the immune response) and to assess the safety and tolerability of the Ad26.ZEBOV booster vaccination in stage 1 participants who had received the booster dose. This study is registered at ClinicalTrials.gov, NCT02509494. Findings Between Sept 30, 2015, and Oct 19, 2016, 443 participants (43 in stage 1 and 400 in stage 2) were enrolled; 341 participants assigned to receive the Ad26.ZEBOV and MVA-BN-Filo regimen and 102 participants assigned to receive the MenACWY and placebo regimen received at least one dose of study vaccine. Both regimens were well tolerated with no safety concerns. In stage 1, solicited local adverse events (mostly mild or moderate injection-site pain) were reported in 12 (28%) of 43 participants after Ad26.ZEBOV vaccination and in six (14%) participants after MVA-BN-Filo vaccination. In stage 2, solicited local adverse events were reported in 51 (17%) of 298 participants after Ad26.ZEBOV vaccination, in 58 (24%) of 246 after MVA-BN-Filo vaccination, in 17 (17%) of 102 after MenACWY vaccination, and in eight (9%) of 86 after placebo injection. In stage 1, solicited systemic adverse events were reported in 18 (42%) of 43 participants after Ad26.ZEBOV vaccination and in 17 (40%) after MVA-BN-Filo vaccination. In stage 2, solicited systemic adverse events were reported in 161 (54%) of 298 participants after Ad26.ZEBOV vaccination, in 107 (43%) of 246 after MVA-BN-Filo vaccination, in 51 (50%) of 102 after MenACWY vaccination, and in 39 (45%) of 86 after placebo injection. Solicited systemic adverse events in both stage 1 and 2 participants included mostly mild or moderate headache, myalgia, fatigue, and arthralgia. The most frequent unsolicited adverse event after the first dose was headache in stage 1 and malaria in stage 2. Malaria was the most frequent unsolicited adverse event after the second dose in both stage 1 and 2. No serious adverse event was considered related to the study vaccine, and no immediate reportable events were observed. In stage 1, the safety profile after the booster vaccination was not notably different to that observed after the first dose. Vaccine-induced humoral immune responses were observed in 41 (98%) of 42 stage 1 participants (geometric mean binding antibody concentration 4784 ELISA units [EU]/mL [95% CI 3736–6125]) and in 176 (98%) of 179 stage 2 participants (3810 EU/mL [3312–4383]) at 21 days after the second vaccination. Interpretation The Ad26.ZEBOV and MVA-BN-Filo vaccine regimen was well tolerated and immunogenic, with persistent humoral immune responses. These data support the use of this vaccine regimen for Ebola virus disease prophylaxis in adults

Towards a national system of teaching qualifications in higher education in The Netherlands

2005 6th Conference of the International Consortium for Educational Development Enhancing Academic Development Practice: International Perspectives 1. Contact Name: Hanno van Keulen 2. Title: Dr 3. Institution(s): Utrecht University 4. Department: IVLOS Institute of Education 5. Address for correspondence: PO Box 80127 6. Country: The Netherlands 7. Postcode/Zipcode: 3508 TC Utrecht 8. Telephone: +31 30 253 1718 (office) / +31 6 5213 8991 (GSM) 9. Email: [email protected] 10. Title and authors of other proposals in which you are involved: none 1. Session title: Towards a national system of teaching qualifications in Higher Education in The Netherlands 2. Conference theme Informing and responding to policy 3. Session Objectives/Learning Outcomes 1) A better understanding of how to design and approach consensus on a teaching qualification system with regard to: • Content (i.c. the teaching competencies); • Assessment (e.g. portfolio assessment) • Pathway (e.g. compulsory teacher training or more personalised approaches) 2) A better understanding of how to implement such a qualification system with regard to: • building a learning culture within institutions and departments; • influencing and engaging institutional and governmental policies and leaders; • respecting and building on local autonomous practices while maintaining a shared framework; 4. Intended audience Institutional management Educational consultants Staff developers Researchers on staff & educational development 5. Session Activities I would like to start with a short introduction into the current situation in The Netherlands (as outline below in the abstract), and then I would invite the audience to come up with suggestions informed by experience, research and theory. I suppose we in The Netherlands take a middle position: some countries, notably the UK, already have a national qualification system whereas many other countries are just opening up for this issue and want to learn how to start. My personal aim (and in this respect I represent the Dutch Network CRWO that is doing its best to influence the establishment of a national system) is to learn as much as possible from other experiences with the introduction and implementation of a qualification system: what are key factors and who are key stakeholders, both with regard to what to implement as to the process? I hope there will be some others who can benefit from discussing our experiences. I particularly want to discuss the strengths and weaknesses of compulsory training systems compared to systems based on the (direct or portfolio-based) assessment of capabilities at qualification level. And I would like to discuss the amount of local autonomy that would be beneficial to the process. 6. Abstract (revised version) Can and should we establish a nation-wide basic teaching qualification system in research-intensive universities? This workshop will discuss three themes: 1) Is it wise and necessary to establish a teaching qualification system in research-intensive universities? Or will this repel excellent researchers? If it is wise, which arguments will convince such stakeholders as vice chancellors, Faculty management and the staff? 2) If a basic teaching qualification system is to be established, should this be government driven and embedded in legislation, or is self-regulation between universities preferable, or should each university have its own system? Which are strategies to promote either of these goals? 3) Presume agreement on establishing a basic teaching qualification system, should this be based on (compulsory) training or on assessment of performance (portfolio model)? Participants are invited to contribute their experiences. In order to structure the interaction we will discuss some research findings and focus on the current situation in the Netherlands. Here, all teachers on all levels (primary, secondary, higher vocational) need teaching qualifications, except those who teach at (research) universities. In 1996 however, Utrecht University established a teaching qualification system: all staff need to have a Basic Teaching Qualification in order to get tenure. Essentially, this is a portfolio system: staff discuss their capabilities and document their performance; their portfolio is assessed. There is no compulsory training, although many staff development courses are provided. It is difficult to measure the effect of this policy on the quality of teaching or the quality and quantity of student learning, but there is some (circumstantial) evidence that the approach is successful: • national surveys on student satisfaction show higher and increasing satisfaction with teacher skills at Utrecht when compared with other universities; • the market share of Utrecht University is increasing; • staff satisfaction with teaching is increasing; • Utrecht consolidates its strong position as a research university; • in recent years, other universities started to copy the system. Government is under student pressure to give higher priority to the quality of teaching and is pondering upon legislation. Currently, vice-chancellors of all Dutch universities are discussing the implementation of a teaching qualification system; they reject legislation in favour of self-regulation. 7. Author(s) biography Dr Hanno van Keulen is researcher, trainer and consultant in higher education at IVLOS Institute of Education of Utrecht University, The Netherlands. He is a Board Member of the Dutch national network on Staff & Educational Develoment (CRWO) and represents CRWO in the ICED Board. He is editor of the Dutch journal Onderzoek van Onderwijs (Research in Education). Drs José van Alst is consultant, trainer and coach in higher education at IOWO – consultants in policy, organization and education of Radboud University, The Netherlands. Currently she is engaged in projects on staff development and quality assurance. She is member of the taskforce working towards agreement on a teaching qualification system among Dutch universities. Drs Riekje de Jong is consultant, trainer and coach in higher education at IOWO – consultants in policy, organization and education of Radboud University, The Netherlands. At this university she initiated compulsory training for junior teachers and portfolio assessment on basic and elaborated teaching qualifications. She is member of the taskforce working towards agreement on a teaching qualification system among Dutch universities. Drs Age Halma is senior HRM-officer at Utrecht University and responsible for staff development. At this university he is programme manager of the Center of Excellence in University Teaching, and of the Basic & Senior Teaching Qualification programmes. 8. References Gerritsen, R. J., R. d. Jong, et al. (2004). "Toetsen van docentcompetenties: professionaliseringsbeleid voor docenten." TH&MA 2004(5): 53-61. Keesen, F. (2005). "Onderwijsbeleid in een researchuniversiteit." TH&MA 2005(5): 9-15. Keesen, F., T. Wubbels, et al. (1996). "Preparing university teachers in The Netherlands: Issues and trends." International Journal for Academic Development 1(2): 8-16. Pilot, A. (2005). The teacher as a crucial factor in curriculum innovations. AERA 2005, Montreal (CN). Prebble, T., H. Hargraves, et al. (2004). Impact of student support services and academic development programmes on student outcomes in undergraduate tertiary study: a synthesis of the research. New Zealand: Ministry of Education. Trowler, P. and R. Bamber (2005). "Compulsory higher education teacher training: Joined-up policies, institutional architectures and enhancement cultures." International Journal for Academic Development 10(2): 79-93