The Dutch system of education and training in radiation protection. Past, present and future

International Nuclear Information System (INIS)

Boersma, Hielke Freerk

2013-01-01

The earliest courses in 'Radiation Protection (RP) Education and Training in the Netherlands' date back to the late fifties, a time which saw major developments especially in both nuclear medicine and nuclear power. The Dutch Society for Radiation Protection (NVS - Nederlandse Vereinigung voor Strahlingshygiene), established in 1960, is in fact the result of one of the first RP courses for medical doctors. The current system of recognition of RP courses was implemented in 1984 in Dutch legislation, based on an advice of the Dutch Health Council from 1972 (.). The recognition system has fundamentally remained unchanged since then. Radiation protection courses in the Netherlands based on this system already started in the seventies. After many discussions in the past decade the system will change in the next years in close relation to the start of a system of registration of RPes. In this paper I will start with a short introduction of the Dutch system of RP education and training. I will consecutively describe the background of the future changes in our system. Finally the major changes will be given. In the end I hope to have convinced you of the fact that although we face some major changes in the near future, the basis of the current system of education and training in RP will remain. (orig.)

The Dutch system of education and training in radiation protection. Past, present and future

Energy Technology Data Exchange (ETDEWEB)

Boersma, Hielke Freerk [Groningen Univ. (Netherlands). Office of the Univ. Health, Safety and Environment

2013-09-01

The earliest courses in 'Radiation Protection (RP) Education and Training in the Netherlands' date back to the late fifties, a time which saw major developments especially in both nuclear medicine and nuclear power. The Dutch Society for Radiation Protection (NVS - Nederlandse Vereinigung voor Strahlingshygiene), established in 1960, is in fact the result of one of the first RP courses for medical doctors. The current system of recognition of RP courses was implemented in 1984 in Dutch legislation, based on an advice of the Dutch Health Council from 1972 (.). The recognition system has fundamentally remained unchanged since then. Radiation protection courses in the Netherlands based on this system already started in the seventies. After many discussions in the past decade the system will change in the next years in close relation to the start of a system of registration of RPes. In this paper I will start with a short introduction of the Dutch system of RP education and training. I will consecutively describe the background of the future changes in our system. Finally the major changes will be given. In the end I hope to have convinced you of the fact that although we face some major changes in the near future, the basis of the current system of education and training in RP will remain. (orig.)

Working as a locum GP: their professional role in organizational context.

NARCIS (Netherlands)

Batenburg, R.; Hassel, D. van; Velden, L. van der

2012-01-01

Context: The workforce of General Practitioners (GPs) in the Netherlands is closely monitored and planned to ensure their pivotal role in primary care and the Dutch health care system. While the majority of GPs have their own practice or are employed by other GP practices or health community

Cancer patients use hospital-based care until death: a further analysis of the Dutch Bone Metastasis Study.

Science.gov (United States)

Meeuse, Jan J; van der Linden, Yvette M; Post, Wendy J; Wanders, Rinus; Gans, Rijk O B; Leer, Jan Willem H; Reyners, Anna K L

2011-10-01

To describe health care utilization (HCU) at the end of life in cancer patients. These data are relevant to plan palliative care services, and to develop training programs for involved health care professionals. The Dutch Bone Metastasis Study (DBMS) was a nationwide study proving equal effectiveness of single fraction palliative radiotherapy compared with multiple fractions for painful bone metastases in 1157 patients. The 860 (74%) patients who died during follow-up were included in the current analysis. The main outcome was the frequency of hospital-based (outpatient contact or admission) and/or general practitioner (GP) contact during the last 12 weeks of life. Changes in HCU towards death were related to data on quality of life and pain intensity using a multilevel regression model. Hospital-based HCU was reported in 1801 (63%) returned questionnaires, whereas GP contact was stated in 1246 (43%). In 573 (20%) questionnaires, both types of HCU were reported. In multilevel regression analyses, the frequency of outpatient contacts remained constant during the weeks towards death, whereas the frequency of GP contacts increased. Lower valuation of quality of life was related to both GP- and hospital-based HCU. There was a high consumption of hospital-based HCU in the last 12 weeks of life of cancer patients with bone metastases. Hospital-based HCU did not decrease during the weeks towards death, despite an increase in GP contacts. Future planning of palliative care and training programs should encompass close collaboration between medical specialists and GPs to optimize end-of-life care.

Training in hospitals: what do GP specialist trainees think of workplace-based assessments?

Science.gov (United States)

Sabey, Abigail; Harris, Michael

2011-03-01

Workplace-based assessment (WBPA) was introduced in 2007 as a new approach to monitoring competence of GP specialist trainees (GPSTs). It includes a raft of assessments carried out in the workplace to assess what a trainee actually does in clinical practice. The assessment tools used are adapted from other contexts of doctors' training but little is known about how they function in day-to-day practice within GP training or how valid and useful they are found to be by trainees. To establish how the new system of WPBA is working in day-to-day practice for GPSTs in hospital posts. A mixed methods design including quantitative and qualitative phases of data collection. Two training locations within Severn Deanery. A questionnaire was completed by 52 GPSTs (67% response rate) currently in hospital posts. Twenty-two took part in focus groups and semi-structured interviews to explore key findings from the questionnaire in greater depth. There is value in the face-to-face contact between trainees and senior doctors. However, quality and depth of feedback are not consistent and there is evidence of poor use of the tools, reducing the value of the assessments. The system is further undermined by a clear perception of bias and lack of honesty in judgements which limit the scope for assessment to lead to learning. Overall, these weaknesses may impair the validity and usefulness of the system and its potential to improve the performance of doctors. General practice trainees in this study have a low opinion of how WPBA assessments function in the hospital setting. Changes are needed to optimise the potential of WPBA to improve the performance of doctors in training and to increase its credibility.

Alliances in the Dutch BeweegKuur lifestyle intervention

NARCIS (Netherlands)

Hartog-van den Esker, den F.G.; Wagemakers, A.; Vaandrager, L.; Dijk, van M.; Koelen, M.A.

2014-01-01

Objective: BeweegKuur (Exercise Therapy) is a Dutch lifestyle programme in which participants are referred by a general practitioner (GP) to a lifestyle advisor. To support participants, regional and local alliances are established. The present study explored the successes and challenges associated

Inequity in contraceptive care between refugees and other migrant women?: a retrospective study in Dutch general practice.

Science.gov (United States)

Raben, Liselotte A D; van den Muijsenbergh, Maria E T C

2018-01-17

Female refugees are at high risk of reproductive health problems including unmet contraceptive needs. In the Netherlands, the general practitioner (GP) is the main entrance to the healthcare system and plays a vital role in the prescription of contraceptives. Little is known about contraceptive care in female refugees in primary care. To get insight into GP care related to contraception in refugees and other migrants compared with native Dutch women. A retrospective descriptive study of patient records of refugees, other migrants and native Dutch women was carried out in five general practices in the Netherlands. The prevalence of discussions about contraception and prescriptions of contraceptives over the past 6 years was compared in women of reproductive age (15-49 years). In total, 104 refugees, 58 other migrants and 162 native Dutch women were included. GPs in our study (2 male, 3 female) discussed contraceptives significantly less often with refugees (51%) and other migrants (66%) than with native Dutch women (84%; P Dutch women (79%; P Dutch women (4% respectively 4%). Contraceptives were significantly less often discussed with and prescribed to refugees and other migrant women compared with native Dutch women. More research is needed to elicit the reproductive health needs and preferences of migrant women regarding GP's care and experiences in discussing these issues. Such insights are vital in order to provide equitable reproductive healthcare to every woman regardless of her background. © The Author(s) 2018. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Applying the trigger review method after a brief educational intervention: potential for teaching and improving safety in GP specialty training?

OpenAIRE

McKay, John; de Wet, Carl; Kelly, Moya; Bowie, Paul

2013-01-01

Background:\\ud The Trigger Review Method (TRM) is a structured approach to screening clinical records for undetected patient safety incidents (PSIs) and identifying learning and improvement opportunities. In Scotland, TRM participation can inform GP appraisal and has been included as a core component of the national primary care patient safety programme that was launched in March 2013. However, the clinical workforce needs up-skilled and the potential of TRM in GP training has yet to be teste...

Dutch virtual integration of healthcare information.

Science.gov (United States)

de Graaf, J C; Vlug, A E; van Boven, G J

2007-01-01

As information technology creates opportunities for cooperation which crosses the boundaries between healthcare institutions, it will become an integral part of the Dutch healthcare system. Along with many involved organizations in healthcare the National IT Institute for Healthcare in the Netherlands (NICTIZ) is working on the realization of a national IT infrastructure for healthcare and a national electronic patient record (EPR). An underlying national architecture is designed to enable the Dutch EPR virtually, not in a national database, nor on a patient's smartcard. The required secure infrastructure provides generic functions for healthcare applications: patient identification, authentication and authorization of healthcare professionals. The first national applications in the EPR program using a national index of where patient data is stored, are the electronic medication record and the electronic record for after hours GP services. The rollout of the electronic medication record and electronic record for after hours GP services has been started in 2007. To guarantee progress of electronic data exchange in healthcare in the Netherlands we have primarily opted for two healthcare applications: the electronic medication record and the electronic record for after hours GP services. The use of a national switch-point containing the registry of where to find what information, guarantees that the professional receives the most recent information and omits large databases to contain downloaded data. Proper authorization, authentication as well as tracing by the national switchpoint also ensures a secure environment for the communication of delicate information.

Exploring resilience in rural GP registrars ? implications for training

OpenAIRE

Walters, Lucie; Laurence, Caroline O.; Dollard, Joanne; Elliott, Taryn; Eley, Diann S.

2015-01-01

Background Resilience can be defined as the ability to rebound from adversity and overcome difficult circumstances. General Practice (GP) registrars face many challenges in transitioning into general practice, and additional stressors and pressures apply for those choosing a career in rural practice. At this time of international rural generalist medical workforce shortages, it is important to focus on the needs of rural GP registrars and how to support them to become resilient health care pr...

Attitudes towards obesity treatment in GP training practices: a focus group study

NARCIS (Netherlands)

Jochemsen-van der Leeuw, H. G. A.; van Dijk, N.; Wieringa-de Waard, M.

2011-01-01

Both patients and government expect the GP to treat obesity. Previous studies reported a negative attitude of GPs towards this task. Little is known about the attitude of GP trainees. To assess the attitude and other factors that influence the willingness and ability of GP trainees to provide

Factors with regard to computerisation of the Dutch and the Belgian national general practitioner sentinel networks: a comparative analysis.

NARCIS (Netherlands)

Schweikardt, C.; Casteren, V. van; Verheij, R.A.; Coppieters, Y.

2013-01-01

Background: A general practitioner (GP) sentinel network observes a sample of the population by supplying reports on the incidence and epidemiological characteristics of specific diseases and on procedures in primary health care. In the 1970s, the Dutch and the Belgian national GP sentinel networks

How can educators support general practice (GP) trainees to develop resilience to prevent burnout?

Science.gov (United States)

Sales, Bryony; Macdonald, Alexandra; Scallan, Samantha; Crane, Sue

2016-11-01

Burnout impacts adversely on professional and personal life, and holds implications for patient care. Current research on burnout mainly focuses on established general practitioners but it is unclear how early the signs of burnout really start. This work seeks to identify whether specific GP trainee groups are particularly at risk of burnout and the aspects of training they find stressful. A longitudinal cohort study, collecting qualitative and quantitative data through a single mode of data collection (questionnaire) took place with trainees from all GP training years (ST1-3), across a vocational training scheme (n = 48). Data gathered included the Oldenburg Burnout Inventory (OLBI). Higher than anticipated levels of burnout were displayed by all trainees. A sub-group self reporting higher levels of burnout comprised all-female, UK-trained-at-undergraduate GP trainees, with a partner but no children. Top reported stressors included knowledge/uncertainty, workload/time pressures and ePortfolio. Less than 50% of trainees perceived their burnout levels to be as high as their OLBI showing potential lack of insight. This research demonstrates that high levels of burnout are experienced in GP trainees as early as the first year of training. Early identification of burnout amongst trainees is essential by GP educators to help protect the future GP workforce.

GP Surgeons’ Experiences of Training in British Columbia and Alberta: A Case Study of Enhanced Skills for Rural Primary Care Providers

Directory of Open Access Journals (Sweden)

Jude Kornelsen

2012-04-01

Full Text Available Background: There has been a steady erosion of family physicians with enhanced surgical skills providing care for rural residents. This has been largely due to the lack of formal training avenues and continuing medical education (CME opportunities afforded to those interested and attrition of those currently practicing.. Methods: A qualitative study was undertaken using an exploratory policy framework to guide the collection of in-depth interview data on GP surgeons’ training experiences. A purposive sample of GP surgeons currently practicing in rural BC and Alberta communities yielded interviews with 62 participants in person and an additional 8 by telephone. Interviews were audio recorded and transcribed then subjected to a process analysis. Results: Participants thematically identified motivations for acquiring advanced skills training, resources required (primarily in the area of solid mentorship, the most efficacious context for a training program (structured and differences in mentorship between obstetricians and general surgeons. Conclusions: Mentors and role models were the most salient influencing factor in the trajectory of training for the participants in this study. Mentorship between specialists and generalists was constrained at times by inter-professional tensions and was accomplished more successfully within a cirriculum-based, structured environment as opposed to a learner-responsive training environment.

GP registrar well-being: a cross-sectional survey

OpenAIRE

Schattner, Peter; Mazalin, Dennis; Pier, Ciaran; Wainer, Jo; Ling, Mee Yoke

2010-01-01

Abstract Objectives To investigate the major stressors affecting GP registrars, how those at risk can be best identified and the most useful methods of managing or reducing their stress. Design, setting and participants Cross-sectional postal questionnaire of all GP registrars in one large regional training provider's catchment area. Main outcome measures The Depression, Anxiety and Stress Scale (DASS), a specifically developed Registrar Stressor Scale consisting of five subscales of potentia...

GP registrar well-being: a cross-sectional survey.

Science.gov (United States)

Schattner, Peter; Mazalin, Dennis; Pier, Ciaran; Wainer, Jo; Ling, Mee Yoke

2010-02-09

To investigate the major stressors affecting GP registrars, how those at risk can be best identified and the most useful methods of managing or reducing their stress. Cross-sectional postal questionnaire of all GP registrars in one large regional training provider's catchment area. The Depression, Anxiety and Stress Scale (DASS), a specifically developed Registrar Stressor Scale consisting of five subscales of potential stressors, plus closed questions on how to identify and manage stress in GP registrars. Survey response rate of 51% (102/199). Rural difficulties followed by achieving a work/life balance were the principal stressors. Ten percent of registrars were mildly or moderately depressed or anxious (DASS) and 7% mild to moderately anxious (DASS). Registrars preferred informal means of identifying those under stress (a buddy system and talks with their supervisors); similarly, they preferred to manage stress by discussions with family and friends, debriefing with peers and colleagues, or undertaking sport and leisure activities. This study supports research which confirms that poor psychological well-being is an important issue for a significant minority of GP trainees. Regional training providers should ensure that they facilitate formal and informal strategies to identify those at risk and assist them to cope with their stress.

Antibiotics in Dutch general practice: nationwide electronic GP database and national reimbursement rates.

NARCIS (Netherlands)

Akkerman, A.E.; Kuyvenhoven, M.M.; Verheij, T.J.M.; Dijk, L. van

2008-01-01

PURPOSE: In order to assess whether different databases generate information which can be reliable compared with each other, this study aimed to assess to which degree prescribing rates for systemic antibiotics from a nationwide electronic general practitioner (GP) database correspond with national

Child and adolescent mental health care in Dutch general practice: time trend analyses.

NARCIS (Netherlands)

Zwaanswijk, M.; Dijk, C.E. van; Verheij, R.A.

2011-01-01

Background: Because most children and adolescents visit their general practitioner (GP) regularly, general practice is a useful setting in which child and adolescent mental health problems can be identified, treated or referred to specialised care. Measures to strengthen Dutch primary mental health

The learner’s perspective in GP teaching practices with multi-level learners: a qualitative study

Science.gov (United States)

2014-01-01

Background Medical students, junior hospital doctors on rotation and general practice (GP) registrars are undertaking their training in clinical general practices in increasing numbers in Australia. Some practices have four levels of learner. This study aimed to explore how multi-level teaching (also called vertical integration of GP education and training) is occurring in clinical general practice and the impact of such teaching on the learner. Methods A qualitative research methodology was used with face-to-face, semi-structured interviews of medical students, junior hospital doctors, GP registrars and GP teachers in eight training practices in the region that taught all levels of learners. Interviews were audio-recorded and transcribed. Qualitative analysis was conducted using thematic analysis techniques aided by the use of the software package N-Vivo 9. Primary themes were identified and categorised by the co-investigators. Results 52 interviews were completed and analysed. Themes were identified relating to both the practice learning environment and teaching methods used. A practice environment where there is a strong teaching culture, enjoyment of learning, and flexible learning methods, as well as learning spaces and organised teaching arrangements, all contribute to positive learning from a learners’ perspective. Learners identified a number of innovative teaching methods and viewed them as positive. These included multi-level learner group tutorials in the practice, being taught by a team of teachers, including GP registrars and other health professionals, and access to a supernumerary GP supervisor (also termed “GP consultant teacher”). Other teaching methods that were viewed positively were parallel consulting, informal learning and rural hospital context integrated learning. Conclusions Vertical integration of GP education and training generally impacted positively on all levels of learner. This research has provided further evidence about the

The epidemiology of suicide and attempted suicide in Dutch general practice 1983-2003.

NARCIS (Netherlands)

Marquet, R.L.; Bartelds, A.I.M.; Kerkhof, A.J.F.M.; Schellevis, F.G.; Zee, J. van der

2005-01-01

BACKGROUND: Many patients attempting or committing suicide consult their general practitioner (GP) in the preceding period, indicating that GPs might play an important role in prevention. The aim of the present study was to analyse the epidemiology of suicidal behaviour in Dutch general practice in

How do trained raters take context factors into account when assessing GP trainee communication performance? An exploratory, qualitative study.

Science.gov (United States)

Essers, Geurt; Dielissen, Patrick; van Weel, Chris; van der Vleuten, Cees; van Dulmen, Sandra; Kramer, Anneke

2015-03-01

Communication assessment in real-life consultations is a complex task. Generic assessment instruments help but may also have disadvantages. The generic nature of the skills being assessed does not provide indications for context-specific behaviour required in practice situations; context influences are mostly taken into account implicitly. Our research questions are: 1. What factors do trained raters observe when rating workplace communication? 2. How do they take context factors into account when rating communication performance with a generic rating instrument? Nineteen general practitioners (GPs), trained in communication assessment with a generic rating instrument (the MAAS-Global), participated in a think-aloud protocol reflecting concurrent thought processes while assessing videotaped real-life consultations. They were subsequently interviewed to answer questions explicitly asking them to comment on the influence of predefined contextual factors on the assessment process. Results from both data sources were analysed. We used a grounded theory approach to untangle the influence of context factors on GP communication and on communication assessment. Both from the think-aloud procedure and from the interviews we identified various context factors influencing communication, which were categorised into doctor-related (17), patient-related (13), consultation-related (18), and education-related factors (18). Participants had different views and practices on how to incorporate context factors into the GP(-trainee) communication assessment. Raters acknowledge that context factors may affect communication in GP consultations, but struggle with how to take contextual influences into account when assessing communication performance in an educational context. To assess practice situations, raters need extra guidance on how to handle specific contextual factors.

GP registrar well-being: a cross-sectional survey

Directory of Open Access Journals (Sweden)

Schattner Peter

2010-02-01

Full Text Available Abstract Objectives To investigate the major stressors affecting GP registrars, how those at risk can be best identified and the most useful methods of managing or reducing their stress. Design, setting and participants Cross-sectional postal questionnaire of all GP registrars in one large regional training provider's catchment area. Main outcome measures The Depression, Anxiety and Stress Scale (DASS, a specifically developed Registrar Stressor Scale consisting of five subscales of potential stressors, plus closed questions on how to identify and manage stress in GP registrars. Results Survey response rate of 51% (102/199. Rural difficulties followed by achieving a work/life balance were the principal stressors. Ten percent of registrars were mildly or moderately depressed or anxious (DASS and 7% mild to moderately anxious (DASS. Registrars preferred informal means of identifying those under stress (a buddy system and talks with their supervisors; similarly, they preferred to manage stress by discussions with family and friends, debriefing with peers and colleagues, or undertaking sport and leisure activities. Conclusions This study supports research which confirms that poor psychological well-being is an important issue for a significant minority of GP trainees. Regional training providers should ensure that they facilitate formal and informal strategies to identify those at risk and assist them to cope with their stress.

Employees' views on home-based, after-hours telephone triage by Dutch GP cooperatives.

Science.gov (United States)

Backhaus, Ramona; van Exel, Job; de Bont, Antoinette

2013-11-04

Dutch out-of-hours (OOH) centers find it difficult to attract sufficient triage staff. They regard home-based triage as an option that might attract employees. Specially trained nurses are supposed to conduct triage by telephone from home for after-hours medical care. The central aim of this research is to investigate the views of employees of OOH centers in The Netherlands on home-based telephone triage in after-hours care. The study is a Q methodology study. Triage nurses, general practitioners (GPs) and managers of OOH centers ranked 36 opinion statements on home-based triage. We interviewed 10 participants to help develop and validate the statements for the Q sort, and 77 participants did the Q sort. We identified four views on home-based telephone triage. Two generally favor home-based triage, one highlights some concerns and conditions, and one opposes it out of concern for quality. The four views perceive different sources of credibility for nurse triagists working from home. Home-based telephone triage is a controversial issue among triage nurses, GPs and managers of OOH centers. By identifying consensus and dissension among GPs, triagists, managers and regulators, this study generates four perspectives on home-based triage. In addition, it reveals the conditions considered important for home-based triage.

The characteristics of general practice and the attractiveness of working as a GP: medical students' views.

Science.gov (United States)

Landstrom, Bjorn; Mattsson, Bengt; Nordin, Per; Rudebeck, Carl E

2014-03-15

The aim of the study was to investigate medical students' views on general practice based on their experiences in training, and to find out whether there were certain views associated with the intention to become a GP. A questionnaire, based on our earlier studies about GP working behaviour, was handed out to medical students in terms 1, 3, 5, 7, 10 and 11 of undergraduate studies in Gothenburg, Sweden. The analysis comprised statistical descriptions and comparisons. The students regarded general practice positively. They found the work environment good, the GP's awareness of patients' living conditions necessary, and that GP work requires medical breadth. The status of the GP in the medical profession was not considered high. One-fourth of the students strongly agreed with the possibility of a future as a GP. This attitude was statistically associated with support to the statements that general practice offers a good work environment and should be a major component in undergraduate training. Students with a negative attitude to working as GPs were also negative to having a major component of general practice in undergraduate training. Medical students with a positive stated attitude towards becoming GPs support changes in undergraduate training to include more general practice. The risk of increasing a negative attitude should be considered when changes are discussed.

Structures of Ebola virus GP and sGP in complex with therapeutic antibodies.

Science.gov (United States)

Pallesen, Jesper; Murin, Charles D; de Val, Natalia; Cottrell, Christopher A; Hastie, Kathryn M; Turner, Hannah L; Fusco, Marnie L; Flyak, Andrew I; Zeitlin, Larry; Crowe, James E; Andersen, Kristian G; Saphire, Erica Ollmann; Ward, Andrew B

2016-08-08

The Ebola virus (EBOV) GP gene encodes two glycoproteins. The major product is a soluble, dimeric glycoprotein (sGP) that is secreted abundantly. Despite the abundance of sGP during infection, little is known regarding its structure or functional role. A minor product, resulting from transcriptional editing, is the transmembrane-anchored, trimeric viral surface glycoprotein (GP). GP mediates attachment to and entry into host cells, and is the intended target of antibody therapeutics. Because large portions of sequence are shared between GP and sGP, it has been hypothesized that sGP may potentially subvert the immune response or may contribute to pathogenicity. In this study, we present cryo-electron microscopy structures of GP and sGP in complex with GP-specific and GP/sGP cross-reactive antibodies undergoing human clinical trials. The structure of the sGP dimer presented here, in complex with both an sGP-specific antibody and a GP/sGP cross-reactive antibody, permits us to unambiguously assign the oligomeric arrangement of sGP and compare its structure and epitope presentation to those of GP. We also provide biophysical evaluation of naturally occurring GP/sGP mutations that fall within the footprints identified by our high-resolution structures. Taken together, our data provide a detailed and more complete picture of the accessible Ebolavirus glycoprotein landscape and a structural basis to evaluate patient and vaccine antibody responses towards differently structured products of the GP gene.

Identification of nutrition communication styles and strategies: a qualitative study among Dutch GP's

NARCIS (Netherlands)

Dillen, van S.M.E.; Hiddink, G.J.; Koelen, M.A.; Graaf, de C.; Woerkum, van C.M.J.

2006-01-01

OBJECTIVE: The objectives of this study were to identify nutrition communication styles of Dutch GPs, their strategies regarding nutrition communication and nutrition information seeking behaviours. Another aim is to provide a hypothetical model for nutrition communication style, including

Consultation for and identification of child and adolescent psychological problems in Dutch general practice.

NARCIS (Netherlands)

Zwaanswijk, M.; Verhaak, P.F.M.; Ende, J. van der; Bensing, J.M.; Verhulst, F.C.

2005-01-01

BACKGROUND: Child and adolescent psychological problems are rarely brought to the attention of GPs. Children and adolescents with psychological problems who do visit their GP are seldom identified as such by GPs. OBJECTIVE: To investigate in a general population sample of 2,449 Dutch children and

Remembering Dutch-Moluccan radicalism

DEFF Research Database (Denmark)

Marselis, Randi Lorenz

2016-01-01

This article examines memory politics in relation to radical actions of young Dutch-Moluccans, more specifically a train hijacking in 1977 at the village of De Punt in the Netherlands. The article examines how these historical events were remembered in the drama-documentary television film, De Punt...... of the web debate examines how viewers reacted to this interpretation. The web debate functioned as a participatory forum, where collective and national memories and postcolonial history were intensely discussed, and the debate made room for some degree of reconciliation between viewers of Dutch......-Moluccan and of Dutch majority background...

Mutations in gp41 are correlated with coreceptor tropism but do not improve prediction methods substantially.

Science.gov (United States)

Thielen, Alexander; Lengauer, Thomas; Swenson, Luke C; Dong, Winnie W Y; McGovern, Rachel A; Lewis, Marilyn; James, Ian; Heera, Jayvant; Valdez, Hernan; Harrigan, P Richard

2011-01-01

The main determinants of HIV-1 coreceptor usage are located in the V3-loop of gp120, although mutations in V2 and gp41 are also known. Incorporation of V2 is known to improve prediction algorithms; however, this has not been confirmed for gp41 mutations. Samples with V3 and gp41 genotypes and Trofile assay (Monogram Biosciences, South San Francisco, CA, USA) results were taken from the HOMER cohort (n=444) and from patients screened for the MOTIVATE studies (n=1,916; 859 with maraviroc outcome data). Correlations of mutations with tropism were assessed using Fisher's exact test and prediction models trained using support vector machines. Models were validated by cross-validation, by testing models from one dataset on the other, and by analysing virological outcome. Several mutations within gp41 were highly significant for CXCR4 usage; most strikingly an insertion occurring in 7.7% of HOMER-R5 and 46.3% of HOMER-X4 samples (MOTIVATE 5.7% and 25.2%, respectively). Models trained on gp41 sequence alone achieved relatively high areas under the receiver-operating characteristic curve (AUCs; HOMER 0.713 and MOTIVATE 0.736) that were almost as good as V3 models (0.773 and 0.884, respectively). However, combining the two regions improved predictions only marginally (0.813 and 0.902, respectively). Similar results were found when models were trained on HOMER and validated on MOTIVATE or vice versa. The difference in median log viral load decrease at week 24 between patients with R5 and X4 virus was 1.65 (HOMER 2.45 and MOTIVATE 0.79) for V3 models, 1.59 for gp41-models (2.42 and 0.83, respectively) and 1.58 for the combined predictor (2.44 and 0.86, respectively). Several mutations within gp41 showed strong correlation with tropism in two independent datasets. However, incorporating gp41 mutations into prediction models is not mandatory because they do not improve substantially on models trained on V3 sequences alone.

A memory-based shallow parser for spoken Dutch

NARCIS (Netherlands)

Canisius, S.V.M.; van den Bosch, A.; Decadt, B.; Hoste, V.; De Pauw, G.

2004-01-01

We describe the development of a Dutch memory-based shallow parser. The availability of large treebanks for Dutch, such as the one provided by the Spoken Dutch Corpus, allows memory-based learners to be trained on examples of shallow parsing taken from the treebank, and act as a shallow parser after

'Just a GP': a mixed method study of undermining of general practice as a career choice in the UK.

Science.gov (United States)

Alberti, Hugh; Banner, Kimberley; Collingwood, Helen; Merritt, Kymberlee

2017-11-03

Failure to recruit sufficient applicants to general practice (GP) training has been a problem both nationally and internationally for many years and undermining of GP is one possible contributing factor. The aim of our study was to ascertain what comments, both negative and positive, are being made in UK clinical settings to GP trainees about GP and to further explore these comments and their influence on career choice. We conducted a mixed methods study. We surveyed all foundation doctors and GP trainees within one region of Health Education England regarding any comments they experienced relating to a career in GP. We also conducted six focus groups with early GP trainees to discuss any comments that they experienced and whether these comments had any influence on their or others career choice. Positive comments reported by trainees centred around the concept that choosing GP is a positive, family-focused choice which facilities a good work-life balance. Workload was the most common negative comment, alongside the notion of being 'just a GP'; the belief that GP is boring, a waste of training and a second-class career choice. The reasons for and origin of the comments are multifactorial in nature. Thematic analysis of the focus groups identified key factors such as previous exposure to and experience of GP, family members who were GPs, GP role models, demographics of the clinician and referral behaviour. Trainees perceived that negative comments may be discouraging others from choosing GP as a career. Our study demonstrates that negative comments towards GP as a career do exist within clinical settings and are having a potential impact on poor recruitment rates to GP training. We have identified areas in which further negative comments could be prevented by changing perceptions of GP as a career. Additional time spent in GP as undergraduates and postgraduates, and positive GP role models, could particularly benefit recruitment. We recommend that undermining of GP

Motivations and Training Needs of General Practitioner Preceptors

Science.gov (United States)

Ren, Wen; Hasenbieke, Nulanbieke; Liu, Ying; Qiu, Yan; Zhou, Zhao-Nong; Mao, Xiao-Yan; Ren, Jing-Jing

2017-01-01

Background: General practitioner (GP) preceptors play an important role in the cultivation of GPs. Many problems exist in the training of GP preceptors. This study aimed to explore the willingness and training needs of GP preceptors and compare the differences between preceptors from general practice and other specialties. Methods: A total of 375 questionnaire forms were sent to 375 GP preceptors from 11 different provinces, and 344 completed forms were returned. The main outcome included general information, teaching motivations, and training needs of GP preceptors. Results: The study showed that about 89.2% of GP preceptors were willing to be teachers. The majority of respondents strongly agreed that the motivation for becoming a GP supervisor was to learn from teaching. The most important capability they should master was clinical teaching (92.2%), followed by lecture (83.1%) and doctor–patient communication (83.1%). The top three preferred methods of GP preceptors training were case discussion (78.8%), workshop (57.6%), and classroom teaching (56.4%). The domains in which most GP preceptors wanted to acquire knowledge and skill were mental health (59.3%), rehabilitation (47.1%), pediatrics (41.0%), and obstetrics (37.5%). No significant differences were found in the willingness to train GPs (χ2 = 3.34, P > 0.05) and whether they would become or continue to become a GP supervisor after the training (χ2 = 1.106, P > 0.05). Conclusions: Although most preceptors were under on-the-job training, they were glad to train GPs. To be qualified, preceptors should be trained according to the actual needs of GP preceptors. PMID:28685719

Nature, frequency and determinants of prescription modifications in Dutch community pharmacies

Science.gov (United States)

Buurma, Henk; de Smet, Peter A G M; van den Hoff, Olga P; Egberts, Antoine C G

2001-01-01

Aims To examine the nature, frequency and determinants of prescription modifications in Dutch community pharmacies. Methods A prospective case-control study comparing modified prescriptions with nonmodified prescriptions was carried out in 141 Dutch community pharmacies. 2014 modified prescriptions (cases), collected in the selected pharmacies on a predetermined day in a specific period (25th February until 12th March 1999) and 2581 nonmodified prescriptions (controls) randomly selected on the same day were studied. The nature and frequency of prescription modifications and patient, drug and prescriber related determinants for a modified prescription were assessed. Results The overall incidence of prescription modifications was 4.3%, with a mean of 14.3 modifications per pharmacy per day. For prescription only medicines (POM) the incidence was 4.9%. The majority of POM modifications concerned a clarification (71.8%). In 22.2% a prescription could potentially have had clinical consequences when not altered; in more than half of the latter it concerned a dose error (13.7% of all cases). POM prescriptions of patients of 40–65 years had a significantly lower chance of modification compared with those of younger people (OR = 0.74 [0.64–0.86]). With respect to medication-class, we found a higher chance of POM modifications in the respiratory domain (OR = 1.48 [1.23-1.79]) and a decreased chance for nervous system POMs (OR = 0.71 [0.61–0.83]). With regard to prescriber-related determinants modifications were found three times more often in non printed prescriptions than in printed ones (OR = 3.30 [2.90-3.75]). Compared with prescriptions by the patient's own GP, prescriptions of specialists (OR = 1.82 [1.57-2.11]), other GP's (OR = 1.49 [1.02-2.17]) and other prescribers such as dentists and midwives (OR = 1.95 [1.06-3.57]) gave a higher probability of prescription modifications. When a GP had no on-line access to the computer of the pharmacy the chance of a

Using photography to enhance GP trainees’ reflective practice and professional development.

OpenAIRE

Rutherford,; Forde, Emer; Priego-Hernández, J.; Butcher, Aurelia; Wedderburn, Clare

2018-01-01

The capacity and the commitment to reflect are integral to the practice of medicine and are core components of most GP training programmes. Teaching through the Humanities is a growing area within medical education, but one which is often considered a voluntary ‘add on’ for the interested doctor. This article describes an evaluation of a highly innovative pedagogical project which used photography as a means to enhance GP trainees’ reflective capacity, self awareness and professional developm...

Educational CPD: how UK GP trainers develop themselves as teachers.

Science.gov (United States)

Waters, Mark; Wall, David

2007-09-01

There is little in the literature giving the perspective of UK General Practice (GP) trainers on their development as teachers. What motivates GP trainers develop themselves as teachers? What obstacles to their professional development do GP trainers perceive? A questionnaire to all GP trainers in the West Midlands Deanery in 2004. 360/444 (81%) questionnaires were returned. 56.6% of GP trainers had another educational role in addition to training GP Registrars in the practice. 15.8% of trainers possessed an educational qualification. 13 had completed a Certificate in Medical Education and 28 were engaged in study towards that qualification. Trainers wanted more time to spend on their development as teachers than they presently have, and would then be interested in a wider variety of learning methods. However, 56.6% of trainers would still not choose to undertake a university-accredited course. Female GP trainers perceived more difficulty in obtaining protected time for their development as teachers (Educational CPD) (p = 0.021), were significantly less sure of their partners' support for this development (p = 0.033), and were more likely to agree with trainers undertaking a Certificate in Medical Education (p = 0.003). Having an additional educational role did not affect trainers' ability to take protected time, but significantly increased the amount of time aspired to (p = 0.005). Nothing made more difference to trainers' perception of their ability to undertake Educational CPD than did the perceived attitude of their partners. Educational CPD was very important to GP trainers, but getting protected time was difficult. Consideration of the needs and opinions of partners was a very strong barrier to trainers taking sufficient protected time. Given more available time, GP trainers would be more likely to consider gaining academic qualifications in education. However, this was not be something that all trainers wanted.

Psychosocial factors in GP work: the effects of taking a GP position or leaving GP work.

Science.gov (United States)

Heponiemi, Tarja; Kouvonen, Anne; Aalto, Anna-Mari; Elovainio, Marko

2013-06-01

We examined the effects of leaving public sector general practitioner (GP) work and of taking a GP position on changes in work-related psychosocial factors, such as time pressure, patient-related stress, distress and work interference with family. In addition, we examined whether changes in time pressure and patient-related stress mediated the association of employment change with changes of distress and work interference with family. Participants were 1705 Finnish physicians (60% women) who responded to surveys in 2006 and 2010. Analyses of covariance were conducted to examine the effect of employment change to outcome changes adjusted for gender, age and response format. Mediational effects were tested following the procedures outlined by Baron and Kenny. Employment change was significantly associated with all the outcomes. Leaving public sector GP work was associated with substantially decreased time pressure, patient-related stress, distress and work interference with family. In contrast, taking a position as a public sector GP was associated with an increase in these factors. Mediation tests suggested that the associations of employment change with distress change and work interference with family change were partially explained by the changes in time pressure and patient-related stress. Our results showed that leaving public sector GP work is associated with favourable outcomes, whereas taking a GP position in the public sector is associated with adverse effects. Primary health-care organizations should pay more attention to the working conditions of their GPs, in particular, to time pressure and patient-related stress.

Blended learning in CME: the perception of GP trainers

NARCIS (Netherlands)

te Pas, E.; Meinema, J. G.; Visser, M. R. M.; van Dijk, N.

2016-01-01

Blended learning (the combination of electronic methods with traditional teaching methods) has the potential to combine the best of traditional education with the best of computer-mediated training. We chose to develop such an intervention for GP trainers who were undertaking a Continuing Medical

Using photography to enhance GP trainees' reflective practice and professional development.

Science.gov (United States)

Rutherford; Forde, Emer; Priego-Hernandez, Jacqueline; Butcher, Aurelia; Wedderburn, Clare

2018-02-08

The capacity and the commitment to reflect are integral to the practice of medicine and are core components of most general practitioners (GP) training programmes. Teaching through the humanities is a growing area within medical education, but one which is often considered a voluntary 'add-on' for the interested doctor. This article describes an evaluation of a highly innovative pedagogical project which used photography as a means to enhance GP trainees' reflective capacity, self-awareness and professional development. Photography was used as a tool to develop GP trainees' skills in recognising and articulating the attitudes, feelings and values that might impact on their clinical work and to enhance their confidence in their ability to deal with these concerns/issues. We submit that photography is uniquely well suited for facilitating insight and self-reflection because it provides the ability to record 'at the touch of a button' those scenes and images to which our attention is intuitively drawn without the need for-or the interference of-conscious decisions. This allows us the opportunity to reflect later on the reasons for our intuitive attraction to these scenes. These photography workshops were a compulsory part of the GP training programme and, despite the participants' traditional scientific backgrounds, the results clearly demonstrate the willingness of participants to accept-even embrace-the use of art as a tool for learning. The GP trainees who took part in this project acknowledged it to be beneficial for both their personal and professional development. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Development of out-of-hours primary care by general practitioners (GPs) in The Netherlands: from small-call rotations to large-scale GP cooperatives.

Science.gov (United States)

van Uden, Caro J T; Giesen, Paul H J; Metsemakers, Job F M; Grol, Richard P T M

2006-09-01

Over the last 10 years, care outside office hours by primary care physicians in The Netherlands has experienced a radical change. While Dutch general practitioners (GPs) formerly performed these services in small-call rotations, care is nowadays delivered by large-scale GP cooperatives. We searched the literature for relevant studies on the effect of the out-of-hours care reorganization in The Netherlands. We identified research that included before- and afterintervention studies, descriptive studies, and surveys. These studies focused on the consequences of reorganizing several aspects of out-of-hours care, such as patient and GP satisfaction, patient characteristics, utilization of care, and costs. Various studies showed that the reorganization has successfully addressed many of the critical issues that Dutch GPs were confronted with delivering these services. GPs' job satisfaction has increased, and patients seem to be satisfied with current out-of-hours care. Several aspects of out-of-hours care are discussed, such as telephone triage, self referrals, and future expectations, which should receive extra attention by researchers and health policy makers in the near future.

Implementing portfolio in postgraduate general practice training. Benefits and recommendations.

Science.gov (United States)

Alotaibi, Fawaz S

2012-10-01

This paper presents a review to explore the literature focusing on portfolio in postgraduate general practice (GP) training, and to examine the impact of implementation of portfolio on learning process, as well as proposing recommendations for its implementation in postgraduate GP training. An electronic search was carried out on several databases for studies addressing portfolio in postgraduate GP training. Six articles were included to address specifically the effectiveness of portfolio in postgraduate GP training. Five of them described successful experiences of portfolio-based learning implementation. Only one article addressed portfolio-based assessment in postgraduate GP training. The existing evidence provides various benefits of professional portfolio-based learning. It does appear to have advantages of stimulating reflective learning, promoting proactive learning, and bridging the hospital experiences of the learners to GP. Moreover, the challenges to implementation of portfolio-based learning are often based on orientation and training of stakeholders.

Is the role as gatekeeper still feasible? A survey among Dutch general practitioners.

Science.gov (United States)

Wammes, Joost Johan Godert; Jeurissen, Patrick Paulus Theodoor; Verhoef, Lise Maria; Assendelft, Willem J J; Westert, Gert P; Faber, Marjan J

2014-10-01

In the 2012 International Health Policy Survey by the Commonwealth Fund, 57% of Dutch GPs indicated that Dutch patients receive too much health care. This is an unexpected finding, given the clear gatekeeper role of Dutch GPs and recent efforts strengthening this role. The study aims to explore where perceived overuse of care prevails and to identify factors associated with too much care at the entry point of Dutch health care. An American survey exploring perceptions of the amount of care among primary care providers was modified for relevance to the Dutch health system. We further included additional factors possibly related to overuse based on 12 interviews with Dutch GPs. The survey was sent to a random sample of 600 GPs. Dutch GPs (N = 157; response rate 26.2%) indicated that patients receive (much) too much care in general hospitals, primary care, GP cooperatives as well as private clinics. The Dutch responding GPs showed a relatively demand-satisfying attitude, which contributed to the delivery of too much care, often leading to deviation from guidelines and professional norms. The increasing availability of diagnostic facilities was identified as an additional factor contributing to the provision of unnecessary care. Finally, funding gaps between primary care and hospitals impede cooperation and coordination, provoking unnecessary care. Our results--most notably regarding the demand-satisfying attitude of responding GPs--call into question the classical view of the guidance and gatekeeper role of GPs in the Dutch health care system. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The Dutch vocational education and training system

NARCIS (Netherlands)

Verhagen, A.M.C.

2014-01-01

The Dutch educational system is highly stratified from secondary education onwards3, and this also applies to MBO. Each MBO course can be followed in two different learning pathways, called the vocationally educating learning pathway (beroepsopleidende leerweg: BOL) and the vocationally guiding

Microsoft Dynamics GP 2013 implementation

CERN Document Server

Yudin, Victoria

2013-01-01

A step-by-step guide for planning and carrying out your Microsoft Dynamics GP 2013 implementation. Detailed descriptions and illustrations of setup screens and practical examples and advice are included for the Dynamics GP system and core modules.If you are a new or existing Microsoft Dynamics GP consultant or an end user who wants to implement, install, and set up core modules of Dynamics GP 2013, then this book is for you. A basic understanding of business management systems and either Dynamics GP or a similar application is recommended.

Patients' perceptions of GP non-verbal communication: a qualitative study.

Science.gov (United States)

Marcinowicz, Ludmila; Konstantynowicz, Jerzy; Godlewski, Cezary

2010-02-01

During doctor-patient interactions, many messages are transmitted without words, through non-verbal communication. To elucidate the types of non-verbal behaviours perceived by patients interacting with family GPs and to determine which cues are perceived most frequently. In-depth interviews with patients of family GPs. Nine family practices in different regions of Poland. At each practice site, interviews were performed with four patients who were scheduled consecutively to see their family doctor. Twenty-four of 36 studied patients spontaneously perceived non-verbal behaviours of the family GP during patient-doctor encounters. They reported a total of 48 non-verbal cues. The most frequent features were tone of voice, eye contact, and facial expressions. Less frequent were examination room characteristics, touch, interpersonal distance, GP clothing, gestures, and posture. Non-verbal communication is an important factor by which patients spontaneously describe and evaluate their interactions with a GP. Family GPs should be trained to better understand and monitor their own non-verbal behaviours towards patients.

Gp96 Peptide Antagonist gp96-II Confers Therapeutic Effects in Murine Intestinal Inflammation

Directory of Open Access Journals (Sweden)

Claudia A. Nold-Petry

2017-12-01

Full Text Available BackgroundThe expression of heat shock protein gp96 is strongly correlated with the degree of tissue inflammation in ulcerative colitis and Crohn’s disease, thereby leading us to the hypothesis that inhibition of expression via gp96-II peptide prevents intestinal inflammation.MethodsWe employed daily injections of gp96-II peptide in two murine models of intestinal inflammation, the first resulting from five daily injections of IL-12/IL-18, the second via a single intrarectal application of TNBS (2,4,6-trinitrobenzenesulfonic acid. We also assessed the effectiveness of gp96-II peptide in murine and human primary cell culture.ResultsIn the IL-12/IL-18 model, all gp96-II peptide-treated animals survived until day 5, whereas 80% of placebo-injected animals died. gp96-II peptide reduced IL-12/IL-18-induced plasma IFNγ by 89%, IL-1β by 63%, IL-6 by 43% and tumor necrosis factor (TNF by 70% compared to controls. The clinical assessment Disease Activity Index of intestinal inflammation severity was found to be significantly lower in the gp96-II-treated animals when compared to vehicle-injected mice. gp96-II peptide treatment in the TNBS model limited weight loss to 5% on day 7 compared with prednisolone treatment, whereas placebo-treated animals suffered a 20% weight loss. Histological disease severity was reduced equally by prednisolone (by 40% and gp96-II peptide (35%. Mice treated with either gp96-II peptide or prednisolone exhibited improved endoscopic scores compared with vehicle-treated control mice: vascularity, fibrin, granularity, and translucency scores were reduced by up to 49% by prednisolone and by up to 30% by gp96-II peptide. In vitro, gp96-II peptide reduced TLR2-, TLR4- and IL-12/IL-18-induced cytokine expression in murine splenocytes, with declines in constitutive IL-6 (54%, lipopolysaccharide-induced TNF (48%, IL-6 (81% and in Staphylococcus epidermidis-induced TNF (67% and IL-6 (81%, as well as IL-12/IL-18-induced IFNγ (75%. gp

MRSA Carriage in Community Outpatients: A Cross-Sectional Prevalence Study in a High-Density Livestock Farming Area along the Dutch-German Border.

Directory of Open Access Journals (Sweden)

John Paget

Full Text Available MRSA poses a considerable public health threat to the community. The objectives of this study were to assess the prevalence of MRSA carriage and determine factors that were associated with MRSA carriage among outpatients who had used antibiotics in the previous three months and who lived in a high-density livestock farming area along the Dutch-German border.Cross-sectional prevalence study carried out between November 2011 and June 2012. Nasal swabs and questionnaires were collected in patients (>4 years who had used antibiotics in the previous three months from twelve Dutch General Practitioners (GPs, seven German GPs and two German outpatient urologists. To assess nasal carriage, swabs were analyzed using selective MRSA agars after broth enrichment. MRSA positive samples were spa typed.Data were collected from 513 GP outpatients in the Netherlands, 261 GP outpatients in Germany and 200 urologist outpatients in Germany. The overall prevalence of MRSA carriage was 0.8%, 1.1% and 2.0%, respectively. In the GP outpatient populations, the prevalence was similar in both countries (0.8% and 1.1%, respectively, p = 0.879, all spa types were indicative for livestock-associated MRSA (4xt011 in the Netherlands; 2xt034 and t011 in Germany and being a farmer, living on or near (<5km to a farm were associated with MRSA carriage. In the urologist outpatient population, the prevalence was higher (2.0%, all spa types were indicative for healthcare-associated MRSA (t068, t032, t003, t10231 and being a farmer, living on or near to a farm were factors not associated with MRSA carriage.The prevalence of MRSA carriage in these community outpatient populations along the Dutch-German border was low. There were striking similarities in livestock-associated MRSA carriage and clonal spread in the outpatient populations seeing their GP in both countries. In contrast, urologist outpatients in Germany were colonized with spa types indicative of healthcare-associated MRSA.

An e-learning supported Train-the-Trainer program to implement a suicide practice guideline. Rationale, content and dissemination in Dutch mental health care.

NARCIS (Netherlands)

Groot, M. de; Beurs, D.P. de; Keijser, J. de; Kerkhof, A.F.J.M.

2015-01-01

An e-learning supported Train-the-Trainer program was developed to implement the Dutch suicide practice guideline inmental health care. Literature on implementation strategies has been restricted to the final reporting of studieswith little opportunity to describe relevant contextual, developmental

A comparative immunogenicity study in rabbits of disulfide-stabilized, proteolytically cleaved, soluble trimeric human immunodeficiency virus type 1 gp140, trimeric cleavage-defective gp140 and monomeric gp120

International Nuclear Information System (INIS)

Beddows, Simon; Franti, Michael; Dey, Antu K.; Kirschner, Marc; Iyer, Sai Prasad N.; Fisch, Danielle C.; Ketas, Thomas; Yuste, Eloisa; Desrosiers, Ronald C.; Klasse, Per Johan; Maddon, Paul J.; Olson, William C.; Moore, John P.

2007-01-01

The human immunodeficiency virus type 1 (HIV-1) surface envelope glycoprotein (Env) complex, a homotrimer containing gp120 surface glycoprotein and gp41 transmembrane glycoprotein subunits, mediates the binding and fusion of the virus with susceptible target cells. The Env complex is the target for neutralizing antibodies (NAbs) and is the basis for vaccines intended to induce NAbs. Early generation vaccines based on monomeric gp120 subunits did not confer protection from infection; one alternative approach is therefore to make and evaluate soluble forms of the trimeric Env complex. We have directly compared the immunogenicity in rabbits of two forms of soluble trimeric Env and monomeric gp120 based on the sequence of HIV-1 JR-FL . Both protein-only and DNA-prime, protein-boost immunization formats were evaluated, DNA-priming having little or no influence on the outcome. One form of trimeric Env was made by disrupting the gp120-gp41 cleavage site by mutagenesis (gp140 UNC ), the other contains an intramolecular disulfide bond to stabilize the cleaved gp120 and gp41 moieties (SOSIP.R6 gp140). Among the three immunogens, SOSIP.R6 gp140 most frequently elicited neutralizing antibodies against the homologous, neutralization-resistant strain, HIV-1 JR-FL . All three proteins induced NAbs against more sensitive strains, but the breadth of activity against heterologous primary isolates was limited. When antibodies able to neutralize HIV-1 JR-FL were detected, antigen depletion studies showed they were not directed at the V3 region but were targeted at other, undefined gp120 and also non-gp120 epitopes

Functional, interactive and critical health literacy: Varying relationships with control over care and number of GP visits.

Science.gov (United States)

van der Heide, Iris; Heijmans, Monique; Schuit, A Jantine; Uiters, Ellen; Rademakers, Jany

2015-08-01

The aim of this study is to examine the extent to which functional, interactive and critical health literacy are associated with patients' perceived control over care and frequency of GP visits. Data from the Dutch 'National Panel of People with Chronic Illness or Disability' was used (N=2508). Health literacy was assessed by the Functional, Communicative and Critical Health Literacy measure. Perceived control over care was indicated by perceived ability to organize care, interact with providers and to perform self-care. By multivariate linear and logistic regression analyses, associations between health literacy and perceived control over care and subsequently frequency of GP visits were studied. Mainly interactive health literacy was associated with patients' perceived ability to organize care, interact with healthcare providers and perform self-care, whereas only functional health literacy was associated with number of GP visits. The results imply that some patients' may be less able to exert control over their care because of lower health literacy. Functional, interactive and critical health literacy vary in their relevance for patients' ability to exert control. Initiatives for strengthening patients' role in healthcare may be improved by paying attention to patients' health literacy, specifically functional and interactive health literacy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Compatibility of scientific research and specialty training in general practice. A cross-sectional study.

Science.gov (United States)

Kötter, Thomas; Carmienke, Solveig; Herrmann, Wolfram J

2014-01-01

In many departments of General Practice (GP) in Germany, young doctors who are trainees also work as researchers. Often these trainees work part time at the university and part time as a trainee in clinical practice. However, little is known about the situation of the actors involved. The aim of the study was to investigate the perspectives of GP trainees, heads of departments and GP trainers regarding the combination of research and GP training. We conducted a web-based survey with the heads of all German departments of General Practice, GP trainees who also conduct research and their GP trainers. The questionnaires consisted of open and closed questions. The results were analyzed using descriptive statistics and qualitative methods. 28 heads of GP departments and 20 GP trainees responded. The trainees were mostly very satisfied with their situation as a trainee. However, the trainees considered the combination of research and GP training as difficult. The respondents name as problems the coordination of multiple jobs and the lack of credibility given to research in General Practice. They name as solutions research-enabling training programs and uniform requirements in training regarding research. The combination of GP training and scientific research activity is perceived as difficult. However, well-organized and designed programs can improve the quality of the combination.

Selecting, training and assessing new general practice community teachers in UK medical schools.

Science.gov (United States)

Hydes, Ciaran; Ajjawi, Rola

2015-09-01

Standards for undergraduate medical education in the UK, published in Tomorrow's Doctors, include the criterion 'everyone involved in educating medical students will be appropriately selected, trained, supported and appraised'. To establish how new general practice (GP) community teachers of medical students are selected, initially trained and assessed by UK medical schools and establish the extent to which Tomorrow's Doctors standards are being met. A mixed-methods study with questionnaire data collected from 24 lead GPs at UK medical schools, 23 new GP teachers from two medical schools plus a semi-structured telephone interview with two GP leads. Quantitative data were analysed descriptively and qualitative data were analysed informed by framework analysis. GP teachers' selection is non-standardised. One hundred per cent of GP leads provide initial training courses for new GP teachers; 50% are mandatory. The content and length of courses varies. All GP leads use student feedback to assess teaching, but other required methods (peer review and patient feedback) are not universally used. To meet General Medical Council standards, medical schools need to include equality and diversity in initial training and use more than one method to assess new GP teachers. Wider debate about the selection, training and assessment of new GP teachers is needed to agree minimum standards.

The importance of job characteristics in determining medical care-seeking in the Dutch working population, a longitudinal survey study.

Science.gov (United States)

Steenbeek, Romy

2012-08-31

The working population is ageing, which will increase the number of workers with chronic health complaints, and, as a consequence, the number of workers seeking health care. It is very important to understand factors that influence medical care-seeking in order to control the costs. I will investigate which work characteristics independently attribute to later care-seeking in order to find possibilities to prevent unnecessary or inefficient care-seeking. Data were collected in a longitudinal two-wave study (n = 2305 workers). The outcome measures were visits (yes/no and frequency) to a general practitioner (GP), a physical therapist, a medical specialist and/or a mental health professional. Multivariate regression analyses were carried out separately for men and women for workers with health complaints. In the Dutch working population, personal, health, and work characteristics, but not sickness absence, were associated with later care-seeking. Work characteristics independently attributed to medical care-seeking but only for men and only for the frequency of visits to the GP. Women experience more health complaints and seek health care more often than men. For women, experiencing a work handicap (health complaints that impede work performance) was the only work characteristic associated with more care-seeking (GP). For men, work characteristics that led to less care-seeking were social support by colleagues (GP frequency), high levels of decision latitude (GP frequency) and high levels of social support by the supervisor (medical specialist). Other work characteristics led to more care-seeking: high levels of engagement (GP), full time work (GP frequency) and experiencing a work handicap (physical therapist). We can conclude that personal and health characteristics are most important when explaining medical care-seeking in the Dutch working population. Work characteristics independently attributed to medical care-seeking but only for men and only for the

Association between patients' recommendation of their GP and their evaluation of the GP.

Science.gov (United States)

Vedsted, Peter; Heje, Hanne N

2008-01-01

Patient priorities and patient evaluations indicate that accessibility should receive more attention to increase quality in general practice. The definition of family medicine emphasizes the patient-centred approach, communication skills, continuity, and clinical skills. We aimed to explore the associations between the 23 items in the Europep questionnaire measuring patient evaluation of general practice and the patients' recommendation of their general practitioner (GP) to friends and to study the relationship of these items with the core competences of family medicine. Cross-sectional study where patients aged 18 years and over attending the practice were included. Patients completed the Danish version of the 23 item Europep questionnaire and an additional item about the degree to which they could recommend their GP to friends. Danish general practice (the DanPEP study). A total of 50 191 patients and 690 GPs were included in the analyses. For each item, associations were calculated between a positive answer and the degree to which the patient could recommend the GP. Analyses were made at patient and GP levels. We found 12 items that covered the 10 most strongly associated items from both analyses: four of six items from the "doctor-patient relationship", two of five items from "medical care", and all items from "information and support" and "organization of services". No items from "accessibility" were among the 12 items. Recommending the GP to others was most strongly associated with the "emphatic", "patient-oriented", "informative and coordinating", and "competent/skilled" GP and to a lesser degree with accessibility to general practice.

Blended learning in CME: the perception of GP trainers.

Science.gov (United States)

Te Pas, E; Meinema, J G; Visser, M R M; van Dijk, N

2016-05-01

Blended learning (the combination of electronic methods with traditional teaching methods) has the potential to combine the best of traditional education with the best of computer-mediated training. We chose to develop such an intervention for GP trainers who were undertaking a Continuing Medical Education (CME) course in evidence-based medicine (EBM). This study reports on our experience and investigated the factors influencing the perception on usefulness and logistics of blended learning for learners in CME. In total, 170 GP trainers participated in the intervention. We used questionnaires, observations during the four face-to-face meetings and evaluations in the e-course over one year. Additionally we organised focus groups to gain insight in some of the outcomes of the questionnaires and interpretations of the observations. The GP trainers found the design and the educational method (e-course in combination with meetings) attractive, instructive and complementary. Factors influencing their learning were (1) educational design, (2) educational method, (3) topic of the intervention, (4) time (planning), (5) time (intervention), (6) learning style, (7) technical issues, (8) preconditions and (9) level of difficulty. A close link between daily practice and the educational intervention was considered an important precondition for the success of the intervention in this group of learners. GP trainers were positive about blended learning: they found e-learning a useful way to gain knowledge and the meetings a pleasant way of transferring the knowledge into practice. Although some preconditions should be taken into consideration during its development and implementation, they would participate in similarly designed learning in the future.

Structure of HIV-1 gp120 with gp41-interactive region reveals layered envelope architecture and basis of conformational mobility.

Science.gov (United States)

Pancera, Marie; Majeed, Shahzad; Ban, Yih-En Andrew; Chen, Lei; Huang, Chih-chin; Kong, Leopold; Kwon, Young Do; Stuckey, Jonathan; Zhou, Tongqing; Robinson, James E; Schief, William R; Sodroski, Joseph; Wyatt, Richard; Kwong, Peter D

2010-01-19

The viral spike of HIV-1 is composed of three gp120 envelope glycoproteins attached noncovalently to three gp41 transmembrane molecules. Viral entry is initiated by binding to the CD4 receptor on the cell surface, which induces large conformational changes in gp120. These changes not only provide a model for receptor-triggered entry, but affect spike sensitivity to drug- and antibody-mediated neutralization. Although some of the details of the CD4-induced conformational change have been visualized by crystal structures and cryoelectron tomograms, the critical gp41-interactive region of gp120 was missing from previous atomic-level characterizations. Here we determine the crystal structure of an HIV-1 gp120 core with intact gp41-interactive region in its CD4-bound state, compare this structure to unliganded and antibody-bound forms to identify structurally invariant and plastic components, and use ligand-oriented cryoelectron tomograms to define component mobility in the viral spike context. Newly defined gp120 elements proximal to the gp41 interface complete a 7-stranded beta-sandwich, which appeared invariant in conformation. Loop excursions emanating from the sandwich form three topologically separate--and structurally plastic--layers, topped off by the highly glycosylated gp120 outer domain. Crystal structures, cryoelectron tomograms, and interlayer chemistry were consistent with a mechanism in which the layers act as a shape-changing spacer, facilitating movement between outer domain and gp41-associated beta-sandwich and providing for conformational diversity used in immune evasion. A "layered" gp120 architecture thus allows movement among alternative glycoprotein conformations required for virus entry and immune evasion, whereas a beta-sandwich clamp maintains gp120-gp41 interaction and regulates gp41 transitions.

Microsoft Dynamics GP 2013 financial management

CERN Document Server

Grieve, Ian

2013-01-01

A standard tutorial-based approach covering Microsoft Dynamics GP 2013 and its six financial modules. The book is intended to allow users to improve their system use and workflow by introducing new modules to assist in financial management.This book is for you if you're a Dynamics GP partner, or Dynamics GP user, primarily focused on delivering application optimizations. This book assumes that you have a working knowledge of Microsoft Dynamics GP and have an understanding of the requirements of financial management.

[Results from a general training hospital for the implementation of a diagnostic workup for pulmonary embolism according to the Dutch Institute for Health Care Improvement

NARCIS (Netherlands)

Kamphuisen, P.W.; Jacobs, E.M.G.; Mol, J.J.; Rijnders, A.J.; Ullmann, E.F.

2002-01-01

OBJECTIVE: To evaluate the active implementation of the Dutch Institute for Healthcare Improvement's guideline for the diagnostic work-up for pulmonary embolism in a general training hospital, and to analyse reasons for not following the guideline strategy. DESIGN: Partly retrospective and partly

On πgp-continuous functions in topological spaces

International Nuclear Information System (INIS)

Park, Jin Han; Park, Jin Keun

2004-01-01

The concept of πgp-closed sets was introduced by Park [On πgp-closed sets in topological spaces, Indian J. Pure Appl. Math., in press]. The aim of this paper is to consider and characterize πgp-irresolute and πgp-continuous functions via the concept of πgp-closed sets and to relate these concepts to the classes of πGPO-compact spaces and πGP-connected spaces

Vertical integration - Reducing the load on GP teachers.

Science.gov (United States)

Anderson, Katrina; Thomson, Jennifer

2009-11-01

With the increased medical student numbers in Australia there is an expectation that general practice will train students, junior doctors and registrars, and the teaching burden for busy general practitioners will rise. We discuss the model of vertical integration of general practice education set up at the Australian National University Medical School in the Australian Capital Territory and southeast New South Wales. This model of vertical integration is unique. It could be adapted in a range of vocational settings and spans medical student, prevocational doctor, registrar and international medical graduate teaching. A key aim of these strategies is to reduce the load on the clinical GP teacher as sustaining their contribution is crucial to the future of training in general practice.

GP supervisors--an investigation into their motivations and teaching activities.

Science.gov (United States)

Ingham, Gerard; O'Meara, Peter; Fry, Jennifer; Crothers, Natalie

2014-11-01

There is little empirical information on how general practitioner (GP) supervisors teach and the reasons for the variation in their teaching methods. Could the variation be due to differing motivations to teach? Supervisors from one regional training provider who attended educational workshops in 2013 were surveyed, seeking infor-mation on their motivation to become and remain a supervisor, and the frequency of use of selected teaching activities. The majority of respondents cited intrinsic motivators, including enjoying teaching (84%), contribution to the profession and community (82%), adding variety (78%) and workforce/succession planning (69%), as reasons for becoming GP supervisors. The expected relationships between motivations and teaching activities were not found. Variation in teaching activities used by supervisors does not appear to be associated with differing motivations. Measuring the use of teaching activities is not a mechanism to determine a supervisor's commitment to teaching.

Immunodiagnosis of paracoccidioidomycosis due to Paracoccidioides brasiliensis using a latex test: detection of specific antibody anti-gp43 and specific antigen gp43.

Directory of Open Access Journals (Sweden)

Priscila Oliveira Dos Santos

2015-02-01

Full Text Available Paracoccidioidomycosis (PCM is a life-threatening systemic disease and is a neglected public health problem in many endemic regions of Latin America. Though several diagnostic methods are available, almost all of them present with some limitations.A latex immunoassay using sensitized latex particles (SLPs with gp43 antigen, the immunodominant antigen of Paracoccidioides brasiliensis, or the monoclonal antibody mAb17c (anti-gp43 was evaluated for antibody or antigen detection in sera, cerebrospinal fluid (CSF, and bronchoalveolar lavage (BAL from patients with PCM due to P. brasiliensis. The gp43-SLPs performed optimally to detect specific antibodies with high levels of sensitivity (98.46%, 95% CI 91.7-100.0, specificity (93.94%, 95% CI 87.3-97.7, and positive (91.4% and negative (98.9% predictive values. In addition, we propose the use of mAb17c-SLPs to detect circulating gp43, which would be particularly important in patients with immune deficiencies who fail to produce normal levels of immunoglobulins, achieving good levels of sensitivity (96.92%, 95% CI 89.3-99.6, specificity (88.89%, 95% CI 81.0-94.3, and positive (85.1% and negative (97.8% predictive values. Very good agreement between latex tests and double immune diffusion was observed for gp43-SLPs (k = 0.924 and mAb17c-SLPs (k = 0.850, which reinforces the usefulness of our tests for the rapid diagnosis of PCM in less than 10 minutes. Minor cross-reactivity occurred with sera from patients with other fungal infections. We successfully detected antigens and antibodies from CSF and BAL samples. In addition, the latex test was useful for monitoring PCM patients receiving therapy.The high diagnostic accuracy, low cost, reduced assay time, and simplicity of this new latex test offer the potential to be commercialized and makes it an attractive diagnostic assay for use not only in clinics and medical mycology laboratories, but mainly in remote locations with limited laboratory infrastructure

stableGP

Data.gov (United States)

National Aeronautics and Space Administration — The code in the stableGP package implements Gaussian process calculations using efficient and numerically stable algorithms. Description of the algorithms is in the...

Characteristics and career intentions of Scottish rural and urban GP registrars: cause for concern?

Science.gov (United States)

Ross, S; Gillies, J C

1999-01-01

To investigate the differences between the characteristics and career intentions of GP registrars in urban and rural areas, and to make recommendations to reduce a potential work force crisis in rural practice. Postal survey. All general practices in Scotland. In February 1996, 40/196 (20%) of urban and 45/150 (30%) of rural GP registrar places available in Scotland, were vacant (chi 2 = 4.22, df = 1, p = 0.02). Postal questionnaires were sent to all 261 GP registrars in post. Of 235 respondents (90%), the majority wished to remain in general practice (63% of urban and 53% of rural registrars), but only 22% of urban and 18% of rural registrars intended to apply for principal posts immediately after training. Fewer urban (8%) than rural registrars (21%) stated an intention to go abroad to work after training. Rural registrars tended to want to work in rural areas, and vice versa. Part-time and job-sharing were attractive employment options for both groups, and more flexible career structures were favoured by over 80%. Though much more attention has been paid to recruitment in inner cities, the findings from this study suggest that in Scotland difficulties in finding principals may occur first in rural areas. As general practitioners have an extended role in rural areas, including that of emergency care, shortages could have a serious impact on patient care.

Yellow fever 17D-vectored vaccines expressing Lassa virus GP1 and GP2 glycoproteins provide protection against fatal disease in guinea pigs.

Science.gov (United States)

Jiang, Xiaohong; Dalebout, Tim J; Bredenbeek, Peter J; Carrion, Ricardo; Brasky, Kathleen; Patterson, Jean; Goicochea, Marco; Bryant, Joseph; Salvato, Maria S; Lukashevich, Igor S

2011-02-01

Yellow Fever (YF) and Lassa Fever (LF) are two prevalent hemorrhagic fevers co-circulating in West Africa and responsible for thousands of deaths annually. The YF vaccine 17D has been used as a vector for the Lassa virus glycoprotein precursor (LASV-GPC) or their subunits, GP1 (attachment glycoprotein) and GP2 (fusion glycoprotein). Cloning shorter inserts, LASV-GP1 and -GP2, between YF17D E and NS1 genes enhanced genetic stability of recombinant viruses, YF17D/LASV-GP1 and -GP2, in comparison with YF17D/LASV-GPC recombinant. The recombinant viruses were replication competent and properly processed YF proteins and LASV GP antigens in infected cells. YF17D/LASV-GP1 and -GP2 induced specific CD8+ T cell responses in mice and protected strain 13 guinea pigs against fatal LF. Unlike immunization with live attenuated reassortant vaccine ML29, immunization with YF17D/LASV-GP1 and -GP2 did not provide sterilizing immunity. This study demonstrates the feasibility of YF17D-based vaccine to control LF in West Africa. Copyright © 2010 Elsevier Ltd. All rights reserved.

Yellow fever 17D-vectored vaccines expressing Lassa virus GP1 and GP2 glycoproteins provide protection against fatal disease in guinea pigs

Science.gov (United States)

Jiang, Xiaohong; Dalebout, Tim J.; Bredenbeek, Peter J.; Carrion, Ricardo; Brasky, Kathleen; Patterson, Jean; Goicochea, Marco; Bryant, Joseph; Salvato, Maria S.; Lukashevich, Igor S.

2010-01-01

Yellow Fever (YF) and Lassa Fever (LF) are two prevalent hemorrhagic fevers co-circulating in West Africa and responsible for thousands of deaths annually. The YF vaccine 17D has been used as a vector for the Lassa virus glycoprotein precursor (LASV-GPC) or their subunits, GP1 (attachment glycoprotein) and GP2 (fusion glycoprotein). Cloning shorter inserts, LASV GP1 and GP2, between YF17D E and NS1 genes enhanced genetic stability of recombinant viruses, YF17D/LASV-GP1 and –GP2, in comparison with YF17D/LASV-GPC recombinant. The recombinant viruses were replication competent and properly processed YF and LASV GP proteins in infected cells. YF17D/LASV-GP1&GP2 induced specific CD8+ T cell responses in mice and protected strain 13 guinea pigs against fatal LF. Unlike immunization with live attenuated reassortant vaccine ML29, immunization with YF17D/LASV-GP1&GP2 did not provide sterilizing immunity. This study demonstrates the feasibility of YF17D-based vaccine to control LF in West Africa. PMID:21145373

Development of Classification Models for Identifying “True” P-glycoprotein (P-gp Inhibitors Through Inhibition, ATPase Activation and Monolayer Efflux Assays

Directory of Open Access Journals (Sweden)

Anna Maria Bianucci

2012-06-01

Full Text Available P-glycoprotein (P-gp is an efflux pump involved in the protection of tissues of several organs by influencing xenobiotic disposition. P-gp plays a key role in multidrug resistance and in the progression of many neurodegenerative diseases. The development of new and more effective therapeutics targeting P-gp thus represents an intriguing challenge in drug discovery. P-gp inhibition may be considered as a valid approach to improve drug bioavailability as well as to overcome drug resistance to many kinds of tumours characterized by the over-expression of this protein. This study aims to develop classification models from a unique dataset of 59 compounds for which there were homogeneous experimental data on P-gp inhibition, ATPase activation and monolayer efflux. For each experiment, the dataset was split into a training and a test set comprising 39 and 20 molecules, respectively. Rational splitting was accomplished using a sphere-exclusion type algorithm. After a two-step (internal/external validation, the best-performing classification models were used in a consensus predicting task for the identification of compounds named as “true” P-gp inhibitors, i.e., molecules able to inhibit P-gp without being effluxed by P-gp itself and simultaneously unable to activate the ATPase function.

A standardised questionnaire for evaluating hospital-based rotations in general practice vocational training.

Science.gov (United States)

Viniol, Annika; Lommler-Thamer, Martina; Baum, Erika; Banzhoff, Norbert Donner

2015-05-01

The residency period of vocational training is a fundamental component for a general practitioner's (GP's) qualification. During the residency, teaching is given by consultants and staff from different medical disciplines who do not necessarily know the GP registrar's training objectives. To develop a standardised feedback questionnaire to evaluate residency attachments and enable GP registrars and their supervisors to discuss the actual training environment and areas for improvement. A cross-sectional study was carried out to assess GP registrars' ratings of items preselected by an expert group to reflect important elements in high-quality vocational training. We recruited GP registrars in Germany via mailing lists and online discussion forums and used the importance-severity-score method to score the content and importance of the selected items. On the basis of these ratings, we eliminated 74 items. This version of the questionnaire then underwent an intra-observer-reliability evaluation by the same GP registrars after eight weeks. Items with a correlation of less than 0.4 (Pearson correlation coefficient) were dropped or rephrased. Our initial questionnaire featured 117 potential items. We reduced this to 43 items after the first study; two additional items were dropped following the reliability test. To our knowledge, this is the first standardised feedback questionnaire evaluating the residency period of vocational training. We hope our work will improve the quality of GPs' vocational training. The importance-severity-score method is a fast and efficient method for developing instruments using personal judgement to evaluate constructs.

Development and implementation of a lifestyle intervention to promote physical activity and healthy diet in the Dutch general practice setting: the BeweegKuur programme

Directory of Open Access Journals (Sweden)

de Vries Nanne K

2010-05-01

Full Text Available Abstract Background The number of patients with diabetes is increasing. BeweegKuur (Dutch for 'Exercise Therapy' is a Dutch lifestyle intervention which aims to effectively and feasibly promote physical activity and better dietary behaviour in primary health care to prevent diabetes. Methods The goal of this paper is to present the development process and the contents of the intervention, using a model of systematic health promotion planning. The intervention consists of a 1-year programme for diabetic and prediabetic patients. Patients are referred by their general practitioner (GP to a lifestyle advisor (LSA, usually the practice nurse or a physiotherapist. Based on specific inclusion criteria and in close collaboration with the patient, an individual exercise programme is designed and supervised by the LSA. This programme can be attended at existing local exercise facilities or (temporarily under the supervision of a specialized exercise coach or physiotherapist. All participants are also referred to a dietician and receive diet-related group education. In the first pilot year (2008, the BeweegKuur programme was implemented in 7 regions in the Netherlands (19 GP practices and health centres, while 14 regions (41 GP practices and health centres participated during the second year. The aim is to implement BeweegKuur in all regions of the Netherlands by 2012. Discussion The BeweegKuur programme was systematically developed in an evidence- and practice-based process. Formative monitoring studies and (controlled effectiveness studies are needed to examine the diffusion process and the effectiveness and cost-effectiveness of the intervention.

DutchParl: A corpus of parliamentary documents in Dutch

NARCIS (Netherlands)

Marx, M.; Schuth, A.

2010-01-01

A corpus called DutchParl is created which aims to contain all digitally available parliamentary documents written in the Dutch language. The first version of DutchParl contains documents from the parliaments of The Netherlands, Flanders and Belgium. The corpus is divided along three dimensions: per

CGP lil-gp 2.1;1.02 User's Manual

Science.gov (United States)

Janikow, Cezary Z.; DeWeese, Scott W.

1997-01-01

This document describes extensions provided to lil-gp facilitating dealing with constraints. This document deals specifically with lil-gp 1.02, and the resulting extension is referred to as CGP lil-gp 2.1; 1.02 (the first version is for the extension, the second for the utilized lil-gp version). Unless explicitly needed to avoid confusion, version numbers are omitted.

Medical students' and GP registrars' accommodation needs in the rural community: insight from a Victorian study.

Science.gov (United States)

Han, Gil-Soo; Wearne, Ben; O'Meara, Peter; McGrail, Matthew; Chesters, Janice

2003-01-01

Medical education in Australia is currently entering a new era, including support for the significant extension of medical students and general practitioner (GP) registrars' training programs in rural communities. This commitment to rural medical student and general practitioner recruitment and retention has made the provision of accommodation in rural communities a vital issue. This study has found that approximately half of all medical students on placement with rural GPs are currently accommodated with their GP supervisor or with other practice staff. This is a burden for many GPs and when the anticipated increase in the frequency and length of rural placements occurs what is currently a burden will become unsustainable. The changing gender and cultural demographics of medical students and rural general practitioners will also contribute to stresses on this accommodation system. It is important to have a systematic approach towards more appropriate and sustainable models of accommodation for both medical students and GP registrars.

Foreign Language Education Levels in the Dutch Population.

Science.gov (United States)

Oud-de Glas, Maria; Peels, Fons

1991-01-01

Reports on levels of foreign language education and foreign language competence among Dutch students, discussing the sharp decline in the teaching of French and German, a lack of foreign language training in technical education, where it is most needed, and the limitations of the data collected regarding foreign language attainment in the…

Identifying current training provision and future training needs in allergy available for UK general practice trainees: national cross-sectional survey of General Practitioner Specialist Training programme directors.

Science.gov (United States)

Ellis, Jayne; Rafi, Imran; Smith, Helen; Sheikh, Aziz

2013-03-01

There are ongoing concerns about the quality of care provision for allergy in primary care. To identify current training provision in allergy to GP trainees and to understand how this could be enhanced. A cross-sectional survey of GP Speciality Training (GPST) programme directors was undertaken. Programme directors of the 174 GPST schemes were sent an online questionnaire which was informed by the content of the Royal College of General Practitioners curriculum. Quantitative data were descriptively analysed and a thematic analysis was undertaken of free text responses. We obtained responses from 146 directors representing 106 training programmes. Responses indicated that two-thirds (62%, 95% CI 53.1 to 71.5) of programmes were providing at least some allergy training, with the remaining third stating that they either provided no training or were unsure. Overall, one-third (33%, 95% CI 22.7 to 42.2) of programme directors believed that all the relevant allergy-related curriculum requirements were being met. Where provided, this training was believed to be best for organ-specific allergic disorders but was thought to be poorer for systemic allergic disorders, particularly food allergy where 67% (95% CI 57.5 to 76.5) of respondents indicated that training was poor. There was considerable interest in increasing the allergy training provided, preferably through eLearning modules and problem-based learning materials supported by those with relevant specialist knowledge. This UK-wide survey has identified important gaps in the training of GP trainees in relation to allergy care. Addressing these gaps, particularly in the management of systemic allergic disorders, should help to improve delivery of primary care-based allergy care.

77 FR 19967 - Safety Zone, Port of Dutch Harbor; Dutch Harbor, AK

Science.gov (United States)

2012-04-03

...-AA00 Safety Zone, Port of Dutch Harbor; Dutch Harbor, AK AGENCY: Coast Guard, DHS. ACTION: Notice of proposed rulemaking. SUMMARY: The Coast Guard proposes temporary safety zones in the Port of Dutch Harbor... Dutch Harbor, Alaska, and the adjacent territorial sea due to additional vessel traffic associated with...

Structure and Recognition of a Novel HIV-1 gp120-gp41 Interface Antibody that Caused MPER Exposure through Viral Escape

Energy Technology Data Exchange (ETDEWEB)

Wibmer, Constantinos Kurt; Gorman, Jason; Ozorowski, Gabriel; Bhiman, Jinal N.; Sheward, Daniel J.; Elliott, Debra H.; Rouelle, Julie; Smira, Ashley; Joyce, M. Gordon; Ndabambi, Nonkululeko; Druz, Aliaksandr; Asokan, Mangai; Burton, Dennis R.; Connors, Mark; Abdool Karim, Salim S.; Mascola, John R.; Robinson, James E.; Ward, Andrew B.; Williamson, Carolyn; Kwong, Peter D.; Morris, Lynn; Moore, Penny L.; Desrosiers, Ronald C.

2017-01-11

A comprehensive understanding of the regions on HIV-1 envelope trimers targeted by broadly neutralizing antibodies may contribute to rational design of an HIV-1 vaccine. We previously identified a participant in the CAPRISA cohort, CAP248, who developed trimer-specific antibodies capable of neutralizing 60% of heterologous viruses at three years post-infection. Here, we report the isolation by B cell culture of monoclonal antibody CAP248-2B, which targets a novel membrane proximal epitope including elements of gp120 and gp41. Despite low maximum inhibition plateaus, often below 50% inhibitory concentrations, the breadth of CAP248-2B significantly correlated with donor plasma. Site-directed mutagenesis, X-ray crystallography, and negative-stain electron microscopy 3D reconstructions revealed how CAP248-2B recognizes a cleavage-dependent epitope that includes the gp120 C terminus. While this epitope is distinct, it overlapped in parts of gp41 with the epitopes of broadly neutralizing antibodies PGT151, VRC34, 35O22, 3BC315, and 10E8. CAP248-2B has a conformationally variable paratope with an unusually long 19 amino acid light chain third complementarity determining region. Two phenylalanines at the loop apex were predicted by docking and mutagenesis data to interact with the viral membrane. Neutralization by CAP248-2B is not dependent on any single glycan proximal to its epitope, and low neutralization plateaus could not be completely explained by N- or O-linked glycosylation pathway inhibitors, furin co-transfection, or pre-incubation with soluble CD4. Viral escape from CAP248-2B involved a cluster of rare mutations in the gp120-gp41 cleavage sites. Simultaneous introduction of these mutations into heterologous viruses abrogated neutralization by CAP248-2B, but enhanced neutralization sensitivity to 35O22, 4E10, and 10E8 by 10-100-fold. Altogether, this study expands the region of the HIV-1 gp120-gp41 quaternary interface that is a target for broadly neutralizing

Internalization and Axonal Transport of the HIV Glycoprotein gp120

Science.gov (United States)

Berth, Sarah; Caicedo, Hector Hugo; Sarma, Tulika; Morfini, Gerardo

2015-01-01

The HIV glycoprotein gp120, a neurotoxic HIV glycoprotein that is overproduced and shed by HIV-infected macrophages, is associated with neurological complications of HIV such as distal sensory polyneuropathy, but interactions of gp120 in the peripheral nervous system remain to be characterized. Here, we demonstrate internalization of extracellular gp120 in a manner partially independent of binding to its coreceptor CXCR4 by F11 neuroblastoma cells and cultured dorsal root ganglion neurons. Immunocytochemical and pharmacological experiments indicate that gp120 does not undergo trafficking through the endolysosomal pathway. Instead, gp120 is mainly internalized through lipid rafts in a cholesterol-dependent manner, with a minor fraction being internalized by fluid phase pinocytosis. Experiments using compartmentalized microfluidic chambers further indicate that, after internalization, endocytosed gp120 selectively undergoes retrograde but not anterograde axonal transport from axons to neuronal cell bodies. Collectively, these studies illuminate mechanisms of gp120 internalization and axonal transport in peripheral nervous system neurons, providing a novel framework for mechanisms for gp120 neurotoxicity. PMID:25636314

Structural Basis for Species Selectivity in the HIV-1 gp120-CD4 Interaction: Restoring Affinity to gp120 in Murine CD4 Mimetic Peptides

Directory of Open Access Journals (Sweden)

Kristin Kassler

2011-01-01

Full Text Available The first step of HIV-1 infection involves interaction between the viral glycoprotein gp120 and the human cellular receptor CD4. Inhibition of the gp120-CD4 interaction represents an attractive strategy to block HIV-1 infection. In an attempt to explore the known lack of affinity of murine CD4 to gp120, we have investigated peptides presenting the putative gp120-binding site of murine CD4 (mCD4. Molecular modeling indicates that mCD4 protein cannot bind gp120 due to steric clashes, while the larger conformational flexibility of mCD4 peptides allows an interaction. This finding is confirmed by experimental binding assays, which also evidenced specificity of the peptide-gp120 interaction. Molecular dynamics simulations indicate that the mCD4-peptide stably interacts with gp120 via an intermolecular β-sheet, while an important salt-bridge formed by a C-terminal lysine is lost. Fixation of the C-terminus by introducing a disulfide bridge between the N- and C-termini of the peptide significantly enhanced the affinity to gp120.

Increasing the general level of academic capacity in general practice: introducing mandatory research training for general practitioner trainees through a participatory research process

DEFF Research Database (Denmark)

Tulinius, Anne-Charlotte; Nielsen, Anni Brit Sternhagen; Hansen, Lars Jørgen

2012-01-01

skills, and through the development and implementation of the mandatory programme to gradually empower the GP community to achieve academic capacity by creating a link between the GP researchers and the GP training community. This was done by developing a faculty, giving teaching skills to GP academics...... of the planning phase. RESULTS: From 2006 to 2009, we built a teaching faculty of 25 teachers among clinical GPs and GP academics; developed the training programme; and delivered the programme to 95 GP trainees. Some of the GP trainees later showed an interest in more substantial research projects, and GP...... and teaching. There is, however, a generic barrier in the regulation of academia itself....

Lexicon Optimization for Dutch Speech Recognition in Spoken Document Retrieval

NARCIS (Netherlands)

Ordelman, Roeland J.F.; van Hessen, Adrianus J.; de Jong, Franciska M.G.

In this paper, ongoing work concerning the language modelling and lexicon optimization of a Dutch speech recognition system for Spoken Document Retrieval is described: the collection and normalization of a training data set and the optimization of our recognition lexicon. Effects on lexical coverage

Lexicon optimization for Dutch speech recognition in spoken document retrieval

NARCIS (Netherlands)

Ordelman, Roeland J.F.; van Hessen, Adrianus J.; de Jong, Franciska M.G.; Dalsgaard, P.; Lindberg, B.; Benner, H.

2001-01-01

In this paper, ongoing work concerning the language modelling and lexicon optimization of a Dutch speech recognition system for Spoken Document Retrieval is described: the collection and normalization of a training data set and the optimization of our recognition lexicon. Effects on lexical coverage

Cannabidiol changes P-gp and BCRP expression in trophoblast cell lines

Directory of Open Access Journals (Sweden)

Valeria Feinshtein

2013-09-01

Full Text Available Objectives. Marijuana is the most commonly used illicit drug during pregnancy. Due to high lipophilicity, cannabinoids can easily penetrate physiological barriers like the human placenta and jeopardize the developing fetus. We evaluated the impact of cannabidiol (CBD, a major non-psychoactive cannabinoid, on P-glycoprotein (P-gp and Breast Cancer Resistance Protein (BCRP expression, and P-gp function in a placental model, BeWo and Jar choriocarcinoma cell lines (using P-gp induced MCF7 cells (MCF7/P-gp for comparison. Study design. Following the establishment of the basal expression of these transporters in the membrane fraction of all three cell lines, P-gp and BCRP protein and mRNA levels were determined following chronic (24–72 h exposure to CBD, by Western Blot and qPCR. CBD impact on P-gp efflux function was examined by uptake of specific P-gp fluorescent substrates (calcein-AM, DiOC2(3 and rhodamine123(rh123. Cyclosporine A (CsA served as a positive control. Results. Chronic exposure to CBD resulted in significant changes in the protein and mRNA levels of both transporters. While P-gp was down-regulated, BCRP levels were up-regulated in the choriocarcinoma cell lines. CBD had a remarkably different influence on P-gp and BCRP expression in MCF7/P-gp cells, demonstrating that these are cell type specific effects. P-gp dependent efflux (of calcein, DiOC2(3 and rh123 was inhibited upon short-term exposure to CBD. Conclusions. Our study shows that CBD might alter P-gp and BCRP expression in the human placenta, and inhibit P-gp efflux function. We conclude that marijuana use during pregnancy may reduce placental protective functions and change its morphological and physiological characteristics.

Structural delineation of a quaternary, cleavage-dependent epitope at the gp41-gp120 interface on intact HIV-1 Env trimers.

Science.gov (United States)

Blattner, Claudia; Lee, Jeong Hyun; Sliepen, Kwinten; Derking, Ronald; Falkowska, Emilia; de la Peña, Alba Torrents; Cupo, Albert; Julien, Jean-Philippe; van Gils, Marit; Lee, Peter S; Peng, Wenjie; Paulson, James C; Poignard, Pascal; Burton, Dennis R; Moore, John P; Sanders, Rogier W; Wilson, Ian A; Ward, Andrew B

2014-05-15

All previously characterized broadly neutralizing antibodies to the HIV-1 envelope glycoprotein (Env) target one of four major sites of vulnerability. Here, we define and structurally characterize a unique epitope on Env that is recognized by a recently discovered family of human monoclonal antibodies (PGT151-PGT158). The PGT151 epitope is comprised of residues and glycans at the interface of gp41 and gp120 within a single protomer and glycans from both subunits of a second protomer and represents a neutralizing epitope that is dependent on both gp120 and gp41. Because PGT151 binds only to properly formed, cleaved trimers, this distinctive property, and its ability to stabilize Env trimers, has enabled the successful purification of mature, cleaved Env trimers from the cell surface as a complex with PGT151. Here we compare the structural and functional properties of membrane-extracted Env trimers from several clades with those of the soluble, cleaved SOSIP gp140 trimer. Copyright © 2014 Elsevier Inc. All rights reserved.

Ethnic identity, externalizing problem behaviour and the mediating role of self-esteem among Dutch, Turkish-Dutch and Moroccan-Dutch adolescents

NARCIS (Netherlands)

Wissink, I.B.; Deković, M.; Yağmur, S.; Stams, G.J.; de Haan, M.

2008-01-01

The present study examined whether self-esteem mediates the relationship between two aspects of ethnic identity (i.e. ethnic identity exploration and ethnic identity commitment-affirmation) and externalizing problem behaviour in Dutch, Turkish-Dutch and Moroccan-Dutch adolescents living in the

Are patients’ preferences regarding the place of treatment heard and addressed at the point of referral: an exploratory study based on observations of GP-patient consultations

Science.gov (United States)

2013-01-01

Background Today, in several north-western European countries, patients are encouraged to choose, actively, a healthcare provider. However, patients often visit the provider that is recommended by their general practitioner (GP). The introduction of patient choice requires GPs to support patients to be involved, actively, in the choice of a healthcare provider. We aim to investigate whether policy on patient choice is reflected in practice, i.e. what the role of the patient is in their choices of healthcare providers at the point of referral and to what extent GPs’ and patients’ healthcare paths influence the role that patients play in the referral decision. Methods In 2007–2008, we videotaped Dutch GP-patient consultations. For this study, we selected, at random, 72 videotaped consultations between 72 patients and 39 GPs in which the patient was referred to a healthcare provider. These were analysed using an observation protocol developed by the researchers. Results The majority of the patients had little or no input into the choice of a healthcare provider at the point of referral by their GP. Their GPs did not support them in actively choosing a provider and the patients often agreed with the provider that the GP proposed. Patients who were referred for diagnostic purposes seem to have had even less input into their choice of a provider than patients who were referred for treatment. Conclusions We found that the GP chooses a healthcare provider on behalf of the patient in most consultations, even though policy on patient choice expects from patients that they choose, actively, a provider. On the one hand, this could indicate that the policy needs adjustments. On the other hand, adjustments may be needed to practice. For instance, GPs could help patients to make an active choice of provider. However, certain patients prefer to let their GP decide as their agent. Even then, GPs need to know patients’ preferences, because in a principal-agent relationship

Are patients' preferences regarding the place of treatment heard and addressed at the point of referral: an exploratory study based on observations of GP-patient consultations.

Science.gov (United States)

Victoor, Aafke; Noordman, Janneke; Sonderkamp, Johan A; Delnoij, Diana M J; Friele, Roland D; van Dulmen, Sandra; Rademakers, Jany J D J M

2013-12-10

Today, in several north-western European countries, patients are encouraged to choose, actively, a healthcare provider. However, patients often visit the provider that is recommended by their general practitioner (GP). The introduction of patient choice requires GPs to support patients to be involved, actively, in the choice of a healthcare provider. We aim to investigate whether policy on patient choice is reflected in practice, i.e. what the role of the patient is in their choices of healthcare providers at the point of referral and to what extent GPs' and patients' healthcare paths influence the role that patients play in the referral decision. In 2007-2008, we videotaped Dutch GP-patient consultations. For this study, we selected, at random, 72 videotaped consultations between 72 patients and 39 GPs in which the patient was referred to a healthcare provider. These were analysed using an observation protocol developed by the researchers. The majority of the patients had little or no input into the choice of a healthcare provider at the point of referral by their GP. Their GPs did not support them in actively choosing a provider and the patients often agreed with the provider that the GP proposed. Patients who were referred for diagnostic purposes seem to have had even less input into their choice of a provider than patients who were referred for treatment. We found that the GP chooses a healthcare provider on behalf of the patient in most consultations, even though policy on patient choice expects from patients that they choose, actively, a provider. On the one hand, this could indicate that the policy needs adjustments. On the other hand, adjustments may be needed to practice. For instance, GPs could help patients to make an active choice of provider. However, certain patients prefer to let their GP decide as their agent. Even then, GPs need to know patients' preferences, because in a principal-agent relationship, it is necessary that the agent is fully

Perceived antecedents of marital satisfaction among Turkish, Turkish-Dutch, and Dutch couples.

Science.gov (United States)

Celenk, Ozgur; van de Vijver, Fons J R

2013-01-01

We studied mainstream couples in The Netherlands and Turkey as well as Turkish-Dutch immigrant couples to address cultural factors associated with marital satisfaction. A total of 13 Turkish (mainstream couples living in Turkey), 19 Turkish-Dutch (Turkish immigrant couples living in The Netherlands), and 17 Dutch (mainstream couples living in The Netherlands) married dyads (total of 98 individuals) were independently interviewed about positive and negative characteristics of marriages, determinants of general marital satisfaction and dissatisfaction, spousal communication, marital conflict, and marital roles. Multivariate tests revealed ethnic group differences on all marriage-related domains except the conflict resolution strategies. However, univariate analyses showed differences in few themes within domains; main differences were assessed between the Turkish/Turkish-Dutch (who put more emphasis on children and economical aspects) and Dutch couples (who put more emphasis on behavior, and personality of the spouse, reciprocity, emotional sharing, and psychological roles). Turkish-Dutch couples were more similar to Turkish than to Dutch couples. Results were discussed in light of the socioeconomic development and cultural value theories, which are believed to provide a useful framework for understanding the role of culture in marital satisfaction.

CFD simulation of train aerodynamics : train-induced wind conditions at an underground railroad passenger platform

NARCIS (Netherlands)

Khayrullina, A.; Blocken, B.J.E.; Janssen, W.D.; Straathof, J.

2015-01-01

The Dutch railways plan to increase the amount of trains and their running velocities to avoid overcrowded trains during rush hours. This can cause pedestrian wind discomfort or danger at the platforms as trains will be allowed to pass small railway stations at high speeds up to 140 km/h. A number

Anti-HIV double variable domain immunoglobulins binding both gp41 and gp120 for targeted delivery of immunoconjugates.

Directory of Open Access Journals (Sweden)

Ryan B Craig

Full Text Available BACKGROUND: Anti-HIV immunoconjugates targeted to the HIV envelope protein may be used to eradicate the latent reservoir of HIV infection using activate-and-purge protocols. Previous studies have identified the two target epitopes most effective for the delivery of cytotoxic immunoconjugates the CD4-binding site of gp120, and the hairpin loop of gp41. Here we construct and test tetravalent double variable domain immunoglobulin molecules (DVD-Igs that bind to both epitopes. METHODS: Synthetic genes that encode DVD-Igs utilizing V-domains derived from human anti-gp120 and anti-gp41 Abs were designed and expressed in 293F cells. A series of constructs tested different inter-V-linker domains and orientations of the two V domains. Antibodies were tested for binding to recombinant Ag and native Env expressed on infected cells, for neutralization of infectious HIV, and for their ability to deliver cytotoxic immunoconjugates to infected cells. FINDINGS: The outer V-domain was the major determinant of binding and functional activity of the DVD-Ig. Function of the inner V-domain and bifunctional binding required at least 15 AA in the inter-V-domain linker. A molecular model showing the spatial orientation of the two epitopes is consistent with this observation. Linkers that incorporated helical domains (A[EAAAK](nA resulted in more effective DVD-Igs than those based solely on flexible domains ([GGGGS](n. In general, the DVD-Igs outperformed the less effective parental antibody and equaled the activity of the more effective. The ability of the DVD-Igs to deliver cytotoxic immunoconjugates in the absence of soluble CD4 was improved over that of either parent. CONCLUSIONS: DVD-Igs can be designed that bind to both gp120 and gp41 on the HIV envelope. DVD-Igs are effective in delivering cytotoxic immunoconjugates. The optimal design of these DVD-Igs, in which both domains are fully functional, has not yet been achieved.

Ethnic Identity, Externalizing Problem Behaviour and the Mediating Role of Self-Esteem among Dutch, Turkish-Dutch and Moroccan-Dutch Adolescents

Science.gov (United States)

Wissink, Inge B.; Dekovic, Maja; Yagmur, Sengul; Stams, Geert Jan; de Haan, Mariette

2008-01-01

The present study examined whether self-esteem mediates the relationship between two aspects of ethnic identity (i.e. ethnic identity exploration and ethnic identity commitment-affirmation) and externalizing problem behaviour in Dutch, Turkish-Dutch and Moroccan-Dutch adolescents living in the Netherlands. A total number of 345 adolescents (115…

[Attrition and poor performance in general practice training: age, competence and knowledge play a role].

Science.gov (United States)

Vermeulen, Margit I; Kuyvenhoven, Marijke M; Zuithoff, N P A Peter; van der Graaf, Yolanda; Pieters, H M Ron

2011-01-01

To investigate which determinants are related to poor performance and forced attrition in the first year residency in general practice (GP). Observational retrospective cohort study. We collected data relating to personal characteristics such as age, sex and clinical experience from residents who started the GP training in Utrecht, the Netherlands, in the period March 2005-August 2007. We also collected competence scores from the domains 'medical expertise', 'doctor-patient communication' and 'professionalism', as well as scores on a national GP knowledge test. The outcome measures were 'poor performance' and 'forced attrition'. Multivariate logistic regression was used to analyse correlations between personal characteristics, competence scores on the 3 domains and knowledge scores in the first trimester on the one hand and poor performance or forced attrition on the other. 215 residents started the GP training. In the first trimester a quarter of the residents had an insufficient score in 1 or more of the domains. Competence scores were mutually correlated, but did not correlate with the knowledge score. 18 residents showed poor performance and 3 were forced to stop their training. Poor performance and forced attrition were correlated with age (adjusted odds ratio (OR): 1.1; 95% CI: 1.0-1.3), insufficient knowledge (adjusted OR: 8.9; 3.0-26.3) and medical expertise (adjusted OR: 2.1; 1.1-4.0) at the beginning of the training. Age, insufficient knowledge of general practice, and insufficient competence in the domain of 'medical expertise' at the beginning of the training are risk factors for poor performance by residents and attrition from their GP training.

Increase in prevalence of overweight in dutch children and adolescents: A comparison of nationwide growth studies in 1980, 1997 and 2009

NARCIS (Netherlands)

Schönbeck, Y.; Talma, H.; Dommelen, P. van; Bakker, B.; Buitendijk, S.E.; HiraSing, R.A.; Buuren, S. van

2011-01-01

To assess the prevalence of overweight and obesity among Dutch children and adolescents, to examine the 30-years trend, and to create new body mass index reference charts. Design: Nationwide cross-sectional data collection by trained health care professionals. Participants: 10,129 children of Dutch

Evaluating the effect of tax deductions on training

NARCIS (Netherlands)

Oosterbeek, H.; Leuven, E.

2004-01-01

Dutch employers can claim an extra tax deduction when they train employees older than age 40. This discontinuity in a firm's training cost is exploited to identify the tax deduction's effects on training participation and of training participation on wages. The results show that the training rate of

Cross-cultural training of general practitioner registrars: how does it happen?

Science.gov (United States)

Watt, Kelly; Abbott, Penny; Reath, Jenny

2016-01-01

An equitable multicultural society requires general practitioners (GPs) to be proficient in providing health care to patients from diverse backgrounds. GPs are required to have a certain attitudes, knowledge and skills known as cultural competence. Given its importance to registrar training, the aim of this study was to explore ways in which GP registrars are currently developing cultural competence. This study employed a survey design for GP registrars in Western Sydney. Training approaches to cultural competence that are relevant to the Australian General Practice setting include exposure to diversity, attitudes, knowledge and skills development. The 43 GP registrar respondents in Western Sydney are exposed to a culturally diverse patient load during training. Registrars report a variety of teachings related to cross-cultural training, but there is little consistency, with the most common approach entailing listening to patients' personal stories. Exposure to cultural diversity appears to be an important way in which cultural competency is developed. However, guidance and facilitation of skills development throughout this exposure is required and currently may occur opportunistically rather than consistently.

Gender shift in realisation of preferred type of GP practice: longitudinal survey over the last 25 years.

NARCIS (Netherlands)

Maiorova, T.; Stevens, F.; Velden, L. van der; Scherpbier, A.; Zee, J. van der

2007-01-01

Background: an increasing number of newly trained Dutch GPs prefer to work in a group practice and as a non-principal rather than in a single-handed practice. In view of the greater number of female doctors, changing practice preferences, and discussions on future workforce problems, the question is

[Dutch parliament legitimizes harmful quackery].

Science.gov (United States)

van Dam, Frits S A M; Renckens, Cees N M

2010-01-01

The Dutch parliament has recently accepted a tax law in which certain groups of alternative therapists can be exempt from VAT. To be eligible for this VAT exemption, the disciplines to which the therapists belong have to meet certain training requirements. In this article it is contended, in agreement with the Royal College of Physicians in the UK, that statutory regulation is inappropriate for disciplines whose therapies are neither of proved benefit nor appropriately tested. It legitimizes harmful therapies. This is illustrated by two serious accidents, previously described in this journal, caused by a chiropractor and a craniosacral therapist.

Musculoskeletal training: are GP trainees exposed to the right case mix for independent practice?

Science.gov (United States)

Goff, Iain; Wise, Elspeth Mary; Coady, David; Walker, David

2016-02-01

Musculoskeletal conditions are common in general practice, but clinicians express poor self confidence in dealing with them. Training in general practice relies on clinical exposure to a range of presentations in order to gain competence. It has been suggested that trainees are exposed to a different case mix from qualified general practices (GPs), due to seeing more minor illness and less chronic disease and that this may be responsible in part for their subsequent lack of confidence. The aims of this study were to analyse the case mix of musculoskeletal conditions encountered by general practice trainees and to compare this to the overall population consulting behaviour. This is a prospective observational study. Thirteen general practices in North East England were recruited. Musculoskeletal disorders encountered by 13 GP trainees (7 junior and 6 senior) were prospectively recorded using a handheld diary. Disorders were classified according to working diagnosis or body region if diagnosis was unclear. Musculoskeletal (MSK) disorders comprised 17 % of consultations, and the distribution of diagnoses of these was in proportion to epidemiological studies of MSK disorders in the UK as they present in primary care. Back pain was the most frequent label with 141 (29 %) consultations with a further 43 (9 %) for neck pain. Inflammatory arthritis accounted for the same number 43 (9 %). Individual joint problems were 115 (24 %) with knee being most common. A specific diagnosis was more likely to be applied when symptoms were more distal and less likely when axial. Trainees are exposed to the same spectrum of MSK disorders as are present in the population as a whole. Case mix does not appear to be a significant factor in low confidence levels in dealing with MSK disorders.

Prediction of the Secondary Structure of HIV-1 gp120

DEFF Research Database (Denmark)

Hansen, Jan; Lund, Ole; Nielsen, Jens O.

1996-01-01

Fourier transform infrared spectroscopy. The predicted secondary structure of gp120 compared well with data from NMR analysis of synthetic peptides from the V3 loop and the C4 region. As a first step towards modeling the tertiary structure of gp120, the predicted secondary structure may guide the design......The secondary structure of HIV-1 gp120 was predicted using multiple alignment and a combination of two independent methods based on neural network and nearest-neighbor algorithms. The methods agreed on the secondary structure for 80% of the residues in BH10 gp120. Six helices were predicted in HIV...

Understanding the use of email consultation in primary care using a retrospective observational study with data of Dutch electronic health records

Science.gov (United States)

Huygens, Martine W J; Swinkels, Ilse C S; Verheij, Robert A; Friele, Roland D; van Schayck, Onno C P; de Witte, Luc P

2018-01-01

Objectives It is unclear why the use of email consultation is not more widespread in Dutch general practice, particularly because, since 2006, its costs can be reimbursed. To encourage further implementation, it is needed to understand the current use of email consultations. This study aims to understand the use of email consultation by different patient groups, compared with other general practice (GP) consultations. Setting For this retrospective observational study, we used Dutch routine electronic health record data obtained from NIVEL Primary Care Database for the years 2010 and 2014. Participants 200 general practices were included in 2010 (734 122 registered patients) and 434 in 2014 (1 630 386 registered patients). Primary outcome measures The number and percentage of email consultations and patient characteristics (age, gender, neighbourhood socioeconomic status and diagnoses) of email consultation users were investigated and compared with those who had a telephone or face-to-face consultation. General practice characteristics were also taken into account. Results 32.0% of the Dutch general practices had at least one email consultation in 2010, rising to 52.8% in 2014. In 2014, only 0.7% of the GP consultations were by email (the others comprised home visits, telephone and face-to-face consultations). Its use highly varied among general practices. Most email consultations were done for psychological (14.7%); endocrine, metabolic and nutritional (10.9%); and circulatory (10.7%) problems. These diagnosis categories appeared less frequently in telephone and face-to-face consultations. Patients who had an email consultation were older than patients who had a telephone or face-to-face consultation. In contrast, patients with diabetes who had an email consultation were younger. Conclusion Even though email consultation was done in half the general practices in the Netherlands in 2014, the actual use of it is extremely low. Patients who had an email consultation

A multi-system approach assessing the interaction of anticonvulsants with P-gp.

Directory of Open Access Journals (Sweden)

David Dickens

Full Text Available 30% of epilepsy patients receiving antiepileptic drugs (AEDs are not fully controlled by therapy. The drug transporter hypothesis for refractory epilepsy proposes that P-gp is over expressed at the epileptic focus with a role of P-gp in extruding AEDs from the brain. However, there is controversy regarding whether all AEDs are substrates for this transporter. Our aim was to investigate transport of phenytoin, lamotrigine and carbamazepine by using seven in-vitro transport models. Uptake assays in CEM/VBL cell lines, oocytes expressing human P-gp and an immortalised human brain endothelial cell line (hCMEC/D3 were carried out. Concentration equilibrium transport assays were performed in Caco-2, MDCKII ±P-gp and LLC-PK1±P-gp in the absence or presence of tariquidar, an inhibitor of P-gp. Finally, primary porcine brain endothelial cells were used to determine the apparent permeability (Papp of the three AEDs in the absence or presence of P-gp inhibitors. We detected weak transport of phenytoin in two of the transport systems (MDCK and LLC-PK1 cells transfected with human P-gp but not in the remaining five. No P-gp interaction was observed for lamotrigine or carbamazepine in any of the seven validated in-vitro transport models. Neither lamotrigine nor carbamazepine was a substrate for P-gp in any of the model systems tested. Our data suggest that P-gp is unlikely to contribute to the pathogenesis of refractory epilepsy through transport of carbamazepine or lamotrigine.

The responsiveness of training participation to tax deductability

NARCIS (Netherlands)

Leuven, E.; Oosterbeek, H.

2006-01-01

To stimulate investment in training by individuals, the Dutch tax system allows a deduction of direct training expenditures from taxable income. This paper investigates to what extent the resulting cost reduction encourages training investments. Two different identification strategies are used. The

Extent, nature and covariates of multitasking of rail passengers in an urban corridor: a Dutch case study

NARCIS (Netherlands)

Waerden, van der P.J.H.J.; Timmermans, H.J.P.; Neerven, van R.

2009-01-01

A study of the frequency and nature of multitasking on Dutch trains is described. Descriptive and model analyses were carried out on the basis of field observations on intercity and regional trains. The most frequent task was "doing nothing," followed by "talking socially" and "reading a newspaper."

Beyond the Dutch Miracle? Challenges to and Responses of the Dutch Welfare System

NARCIS (Netherlands)

van Gerven-Haanpää, Minna Marja-Leena; Schubert, Klaus; de Villota, Paloma; Kuhlmann, Johanna

2016-01-01

This chapter explores how the Dutch welfare system has evolved in the last decade(s). It shows that the economic crisis and the process of demographic change have put the Dutch welfare system to the test. The surmounting pressures from 2007 onwards have revealed structural problems of the Dutch

Screening and Identification of ssDNA Aptamer for Human GP73

Directory of Open Access Journals (Sweden)

Jingchun Du

2015-01-01

Full Text Available As one tumor marker of HCC, Golgi Protein 73 (GP73 is given more promise in the early diagnosis of HCC, and aptamers have been developed to compete with antibodies as biorecognition probes in different detection system. In this study, we utilized GP73 to screen specific ssDNA aptamers by SELEX technique. First, GP73 proteins were expressed and purified by prokaryotic expression system and Nickle ion affinity chromatography, respectively. At the same time, the immunogenicity of purified GP73 was confirmed by Western blotting. The enriched ssDNA library with high binding capacity for GP73 was obtained after ten rounds of SELEX. Then, thirty ssDNA aptamers were sequenced, in which two ssDNA aptamers with identical DNA sequence were confirmed, based on the alignment results, and designated as A10-2. Furthermore, the specific antibody could block the binding of A10-2 to GP73, and the specific binding of A10-2 to GP73 was also supported by the observation that several tumor cell lines exhibited variable expression level of GP73. Significantly, the identified aptamer A10-2 could distinguish normal and cancerous liver tissues. So, our results indicate that the aptamer A10-2 might be developed into one molecular probe to detect HCC from normal liver specimens.

Planning the Dutch GP workforce.

NARCIS (Netherlands)

Batenburg, R.; Velden, L. van der; Greuningen, M. van

2010-01-01

CONTEXT: For a long time, shortages of health care personnel have been a major worldwide concern of health policy makers, professional bodies and patient organisations (cf. OECD, 2008). It is commonly acknowledged that manpower planning can be an important instrument to control shortages (and

Will Dutch Become Flemish? Autonomous Developments in Belgian Dutch

Science.gov (United States)

Van de Velde, Hans; Kissine, Mikhail; Tops, Evie; van der Harst, Sander; van Hout, Roeland

2010-01-01

In this paper a series of studies of standard Dutch pronunciation in Belgium and the Netherlands is presented. The research is based on two speech corpora: a diachronic corpus of radio speech (1935-1995) and a synchronic corpus of Belgian and Netherlandic standard Dutch from different regions at the turn of the millennium. It is shown that two…

Work-family balance by women GP specialist trainees in Slovenia: a qualitative study.

Science.gov (United States)

Petek, Davorina; Gajsek, Tadeja; Petek Ster, Marija

2016-01-28

Women physicians face many challenges while balancing their many roles: doctor, specialist trainee, mother and partner. The most opportune biological time for a woman to start a family coincides with a great deal of demands and requirements at work. In this study we explored the options and capabilities of women GP specialist trainees in coordinating their family and career. This is a phenomenological qualitative research. Ten GP specialist trainees from urban and rural areas were chosen by the purposive sampling technique, and semi-structured in-depth interviews were conducted, recorded, transcribed and analysed by using thematic analysis process. Open coding and the book of codes were formed. Finally, we performed the process of code reduction by identifying the themes, which were compared, interpreted and organised in the highest analytical units--categories. One hundred fifty-five codes were identified in the analysis, which were grouped together into eleven themes. The identified themes are: types, causes and consequences of burdens, work as pleasure and positive attitude toward self, priorities, planning and help, and understanding of superiors, disburdening and changing in specialisation. The themes were grouped into four large categories: burdens, empowerment, coordination and needs for improvement. Women specialist trainees encounter intense burdens at work and home due to numerous demands and requirements during their specialisation training. In addition, there is also the issue of the work-family conflict. There are many consequences regarding burden and strain; however, burnout stands out the most. In contrast, reconciliation of work and family life and needs can be successful. The key element is empowerment of women doctors. The foremost necessary systemic solution is the reinforcement of general practitioners in primary health care and their understanding of the specialisation training scheme with more flexible possibilities for time adaptations of

The Dutch Lifelong Learning scene : Continuing unresolved issues and two alternative perspectives

NARCIS (Netherlands)

van Dellen, Teije

2015-01-01

Lifelong learning (LLL) in the Netherlands is under debate in this article. The article shows the state of the art of the Dutch lifelong learning education, and training and development field. In particular the unfulfilled expectations of the field are shown in a polemic manner by discussing the

Innate immunity glycoprotein gp-340 variants may modulate human susceptibility to dental caries

Directory of Open Access Journals (Sweden)

Johansson Ingegerd

2007-06-01

Full Text Available Abstract Background Bacterial adhesion is an important determinant of colonization and infection, including dental caries. The salivary scavenger receptor cysteine-rich glycoprotein gp-340, which mediates adhesion of Streptococcus mutans (implicated in caries, harbours three major size variants, designated gp-340 I to III, each specific to an individual saliva. Here we have examined the association of the gp-340 I to III polymorphisms with caries experience and adhesion of S. mutans. Methods A case-referent study was performed in 12-year-old Swedish children with high (n = 19 or low (n = 19 caries experiences. We measured the gp-340 I to III saliva phenotypes and correlated those with multiple outcome measures for caries experience and saliva adhesion of S. mutans using the partial least squares (PLS multivariate projection technique. In addition, we used traditional statistics and 2-year caries increment to verify the established PLS associations, and bacterial adhesion to purified gp-340 I to III proteins to support possible mechanisms. Results All except one subject were typed as gp-340 I to III (10, 23 and 4, respectively. The gp-340 I phenotype correlated positively with caries experience (VIP = 1.37 and saliva adhesion of S. mutans Ingbritt (VIP = 1.47. The gp-340 II and III phenotypes tended to behave in the opposite way. Moreover, the gp-340 I phenotype tended to show an increased 2-year caries increment compared to phenotypes II/III. Purified gp-340 I protein mediated markedly higher adhesion of S. mutans strains Ingbritt and NG8 and Lactococcus lactis expressing AgI/II adhesins (SpaP or PAc compared to gp-340 II and III proteins. In addition, the gp-340 I protein appeared over represented in subjects positive for Db, an allelic acidic PRP variant associated with caries, and subjects positive for both gp-340 I and Db tended to experience more caries than those negative for both proteins. Conclusion Gp-340 I behaves as a caries

Dyslexia and early intervention: what did we learn from the Dutch Dyslexia Programme?

NARCIS (Netherlands)

van der Leij, A.

2013-01-01

Part of the Dutch Dyslexia Programme has been dedicated to early intervention. The question of whether the genetically affected learning mechanism of children who are at familial risk (FR) of developing dyslexia could be influenced by training phoneme awareness and letter-sound associations in the

The potential of in-train crowdsourcing

NARCIS (Netherlands)

van der Wees, Bernard; Moonen, Hans

2011-01-01

Nowadays railway operators are improving their services by offering IT-services within their trains. This paper reports on a design study we performed at Dutch Railways (Nederlandse Spoorwegen, NS) in order to research whether or not NS can crowdsource activities utilizing the novel in-train IT

Usefulness of a virtual community of practice and web 2.0 tools for general practice training: experiences and expectations of general practitioner registrars and supervisors.

Science.gov (United States)

Barnett, Stephen; Jones, Sandra C; Bennett, Sue; Iverson, Don; Bonney, Andrew

2013-01-01

General practice training is a community of practice in which novices and experts share knowledge. However, there are barriers to knowledge sharing for general practioner (GP) registrars, including geographic and workplace isolation. Virtual communities of practice (VCoP) can be effective in overcoming these barriers using social media tools. The present study examined the perceived usefulness, features and barriers to implementing a VCoP for GP training. Following a survey study of GP registrars and supervisors on VCoP feasibility, a qualitative telephone interview study was undertaken within a regional training provider. Participants with the highest Internet usage in the survey study were selected. Two researchers worked independently conducting thematic analysis using manual coding of transcriptions, later discussing themes until agreement was reached. Seven GP registrars and three GP supervisors participated in the study (average age 38.2 years). Themes emerged regarding professional isolation, potential of social media tools to provide peer support and improve knowledge sharing, and barriers to usage, including time, access and skills. Frequent Internet-using GP registrars and supervisors perceive a VCoP for GP training as a useful tool to overcome professional isolation through improved knowledge sharing. Given that professional isolation can lead to decreased rural work and reduced hours, a successful VCoP may have a positive outcome on the rural medical workforce.

Medical residents' perceptions of their competencies and training needs in health care management

DEFF Research Database (Denmark)

Berkenbosch, Lizanne; Schoenmaker, Suzanne Gerdien; Ahern, Susannah

2013-01-01

Previous research has shown that Dutch medical residents feel inadequate in certain management areas: 85% had a need for management training and reported preferences on the format of such training. Our objective was to explore if the perceived deficiencies and needs among Dutch residents were sim...... similar to those of their peers in other countries, and if a longer duration of the incorporation of the CanMEDS competency framework into curricula as well as management training had an influence on these perceptions....

Comprehensive functional analysis of N-linked glycans on Ebola virus GP1.

Science.gov (United States)

Lennemann, Nicholas J; Rhein, Bethany A; Ndungo, Esther; Chandran, Kartik; Qiu, Xiangguo; Maury, Wendy

2014-01-28

Ebola virus (EBOV) entry requires the virion surface-associated glycoprotein (GP) that is composed of a trimer of heterodimers (GP1/GP2). The GP1 subunit contains two heavily glycosylated domains, the glycan cap and the mucin-like domain (MLD). The glycan cap contains only N-linked glycans, whereas the MLD contains both N- and O-linked glycans. Site-directed mutagenesis was performed on EBOV GP1 to systematically disrupt N-linked glycan sites to gain an understanding of their role in GP structure and function. All 15 N-glycosylation sites of EBOV GP1 could be removed without compromising the expression of GP. The loss of these 15 glycosylation sites significantly enhanced pseudovirion transduction in Vero cells, which correlated with an increase in protease sensitivity. Interestingly, exposing the receptor-binding domain (RBD) by removing the glycan shield did not allow interaction with the endosomal receptor, NPC1, indicating that the glycan cap/MLD domains mask RBD residues required for binding. The effects of the loss of GP1 N-linked glycans on Ca(2+)-dependent (C-type) lectin (CLEC)-dependent transduction were complex, and the effect was unique for each of the CLECs tested. Surprisingly, EBOV entry into murine peritoneal macrophages was independent of GP1 N-glycans, suggesting that CLEC-GP1 N-glycan interactions are not required for entry into this important primary cell. Finally, the removal of all GP1 N-glycans outside the MLD enhanced antiserum and antibody sensitivity. In total, our results provide evidence that the conserved N-linked glycans on the EBOV GP1 core protect GP from antibody neutralization despite the negative impact the glycans have on viral entry efficiency. Filovirus outbreaks occur sporadically throughout central Africa, causing high fatality rates among the general public and health care workers. These unpredictable hemorrhagic fever outbreaks are caused by multiple species of Ebola viruses, as well as Marburg virus. While filovirus

Characterization of Human Colorectal Cancer MDR1/P-gp Fab Antibody

Directory of Open Access Journals (Sweden)

Xuemei Zhang

2013-01-01

Full Text Available In this study, the peptide sized 21 kDa covering P-gp transmembrane region was first prepared for generating a novel mouse monoclonal antibody Fab fragment with biological activity against multiple drug resistance protein P-gp21 by phage display technology. Phage-displayed antibody library prepared from mice spleen tissues was selected against the recombinant protein P-gp21 with five rounds of panning. A number of clones expressing Fab bound to P-gp21, showing neutralized activity in vitro, were isolated and screened by enzyme-linked immunosorbent assay based on its recognition properties to P-gp21 and human colorectal cancer tissue homogenate, resulting in identification of an optimal recombinant Fab clone (Number 29. Further characterization by recloning number 29 into an expression vector showed significant induction of the Fab antibody in the clone number 29 by Isopropyl β-D-1-thiogalactopyranoside (IPTG. After purified by HiTrap Protein L, the specificity of the Fab antibody to P-gp21 was also confirmed. Not only was the targeted region of this monoclonal Fab antibody identified as a 16-peptide epitope (ALKDKKELEGSGKIAT comprising residues 883–898 within the transmembrane (TM domain of human P-gp, but also the binding ability with it was verified. The clinical implication of our results for development of personalized therapy of colorectal cancer will be further studied.

Dutch School in Geneva

CERN Multimedia

2011-01-01

The Dutch School in Geneva organizes Dutch education for children in the primary and secondary school. For the school year 2011-2012 the Dutch School in Geneva is looking for qualified part time teachers Dutch for the primary and secondary school. If you are interested, please send your application and curriculum vitae in Dutch by email to the NTC coordinator, Mrs. Anne Saeys (anne.saeys@free.fr). More info : www.ntcgeneve.info De vereniging Nederlandse Taal en Cultuur De Taalfontein, kortweg NTC Genève, is een oudervereniging, die tot doel heeft de Nederlandse taal en de Nederlandse en Vlaamse cultuur in de regio Genève te stimuleren. Dit geschiedt d.m.v. het organiseren van Nederlandse les voor leerlingen zowel in het basisonderwijs als het voortgezet onderwijs. Voor het volgende schooljaar zoekt NTC parttime docenten (M/V) vanaf 2 uur per week, zowel voor het Primair Onderwijs als voor het Voortgezet Onderwijs, met name voor de IB-opleiding. Voor het Primair Onderwijs dienen ge&...

Gerontology and geriatrics in Dutch medical education.

Science.gov (United States)

Tersmette, W; van Bodegom, D; van Heemst, D; Stott, D; Westendorp, R

2013-01-01

The world population is ageing and healthcare services require trained staff who can address the needs of older patients. In this study we determined how current medical education prepares Dutch students of medicine in the field of Gerontology and Geriatrics (G&G). Using a checklist of the essentials of G&G, we assessed Dutch medical education on three levels. On the national level we analysed the latest National Blueprint for higher medical education (Raamplan artsopleiding 2009). On the faculty level we reviewed medical curricula on the basis of interviews with program directors and inspection of course materials. On the student level we assessed the topics addressed in the questions of the cross-institutional progress test (CIPT). The National Bluepr int contains few specific G&G objectives. Obligatory G&G courses in medical schools on average amount to 2.2% of the total curriculum measured as European Credit Transfer System units (ECTS). Only two out of eight medical schools have practical training during the Master phase in the form of a clerkship in G&G. In the CIPT, on average 1.5% of questions cover G&G. Geriatric education in the Netherlands does not seem to be in line with current demographic trends. The National Blueprint falls short of providing sufficiently detailed objectives for education on the care of older people. The geriatric content offered by medical schools is varied and incomplete, and students are only marginally tested on their knowledge of G&G in the CIPT.

Scotland's GP paediatric scholarship: an evaluation.

Science.gov (United States)

MacVicar, Ronald; Borland, Lyndsey; McHale, Sharon; Goh, Dayeel; Potter, Alex

2018-05-01

In a previous publication we described the implementation and early evaluation of general practice paediatric scholarships in Scotland. We suggested that it was too early to be able to determine whether this significant investment will produce a return for Scotland in terms of enhanced roles in providing, leading or developing children's services in primary care or at the primary care/secondary care interface. This paper presents the results of a survey of the impact of the scholarship for the first six cohorts of the scholarship (119 General Practitioners). The response rate was 76%. Of the 90 respondents, almost half (44) have developed roles or areas of special paediatric interest either within or out with the practice, or in three cases both within and out with the practice. A total of 37 (43%) of those that continue to work within general practice reported that they have developed areas of special interest of benefit to the practice. Qualitative analysis of free text questions suggested that scholars had benefited from their experience in terms of increased confidence in dealing with child health problems, developing links with secondary care colleagues, and personal gain with respect to role development. What is already known in this area: Changes in GP Training have been suggested in order to provide a workforce that can meet the needs of infants, children and young people. Studies have shown a positive impact of paediatric trainees and GP trainees learning together. Little attention has however been given to the potential to support trained GPs to develop their expertise in child health. What this work adds: Early evaluation of the Scottish Paediatric Scholarship suggested a high degree of satisfaction. This more robust evaluation suggests that almost half (44/90 respondents) have developed roles or areas of special paediatric interest either within or out with the practice, or in three cases both within and out with the practice. Suggestions for future

Transport inhibition of digoxin using several common P-gp expressing cell lines is not necessarily reporting only on inhibitor binding to P-gp.

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Annie Albin Lumen

Full Text Available We have reported that the P-gp substrate digoxin required basolateral and apical uptake transport in excess of that allowed by digoxin passive permeability (as measured in the presence of GF120918 to achieve the observed efflux kinetics across MDCK-MDR1-NKI (The Netherlands Cancer Institute confluent cell monolayers. That is, GF120918 inhibitable uptake transport was kinetically required. Therefore, IC50 measurements using digoxin as a probe substrate in this cell line could be due to inhibition of P-gp, of digoxin uptake transport, or both. This kinetic analysis is now extended to include three additional cell lines: MDCK-MDR1-NIH (National Institute of Health, Caco-2 and CPT-B2 (Caco-2 cells with BCRP knockdown. These cells similarly exhibit GF120918 inhibitable uptake transport of digoxin. We demonstrate that inhibition of digoxin transport across these cell lines by GF120918, cyclosporine, ketoconazole and verapamil is greater than can be explained by inhibition of P-gp alone. We examined three hypotheses for this non-P-gp inhibition. The inhibitors can: (1 bind to a basolateral digoxin uptake transporter, thereby inhibiting digoxin's cellular uptake; (2 partition into the basolateral membrane and directly reduce membrane permeability; (3 aggregate with digoxin in the donor chamber, thereby reducing the free concentration of digoxin, with concomitant reduction in digoxin uptake. Data and simulations show that hypothesis 1 was found to be uniformly acceptable. Hypothesis 2 was found to be uniformly unlikely. Hypothesis 3 was unlikely for GF120918 and cyclosporine, but further studies are needed to completely adjudicate whether hetero-dimerization contributes to the non-P-gp inhibition for ketoconazole and verapamil. We also find that P-gp substrates with relatively low passive permeability such as digoxin, loperamide and vinblastine kinetically require basolateral uptake transport over that allowed by +GF120918 passive permeability, while

Similar taste-nutrient relationships in commonly consumed Dutch and Malaysian foods.

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Teo, Pey Sze; van Langeveld, Astrid W B; Pol, Korrie; Siebelink, Els; de Graaf, Cees; Yan, See Wan; Mars, Monica

2018-06-01

Three recent studies showed that taste intensity signals nutrient content. However, current data reflects only the food patterns in Western societies. No study has yet been performed in Asian culture. The Malaysian cuisine represents a mixture of Malay, Chinese and Indian foods. This study aimed to investigate the associations between taste intensity and nutrient content in commonly consumed Dutch (NL) and Malaysian (MY) foods. Perceived intensities of sweetness, sourness, bitterness, umami, saltiness and fat sensation were assessed for 469 Dutch and 423 Malaysian commonly consumed foods representing about 83% and 88% of an individual's average daily energy intake in each respective country. We used a trained Dutch (n = 15) and Malaysian panel (n = 20) with quantitative sensory Spectrum™ 100-point rating scales and reference solutions, R1 (13-point), R2 (33-point) and R3 (67-point). Dutch and Malaysian foods had relatively low mean sourness and bitterness (Dutch foods (8-point). Positive associations were found between sweetness and mono- and disaccharides (R 2  = 0.67 (NL), 0.38 (MY)), between umami and protein (R 2  = 0.29 (NL), 0.26 (MY)), between saltiness and sodium (R 2  = 0.48 (NL), 0.27 (MY)), and between fat sensation and fat content (R 2  = 0.56 (NL), 0.17(MY)) in Dutch and Malaysian foods (all, p < 0.001). The associations between taste intensity and nutrient content are not different between different countries, except for fat sensation-fat content. The two dimensional basic taste-nutrient space, representing the variance and associations between tastes and nutrients, is similar between Dutch and Malaysian commonly consumed foods. Copyright © 2018 Elsevier Ltd. All rights reserved.

Study and preparation of 99Tcm-GP kit for lung ventilation imaging

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Zhu Lin; Meng Fanmin; Zhang Jihong; Hong Tao; Liu Yunzhong; Liu Xiujie

1997-01-01

The preparation of the lyophilizing reagent, D-glucose-l-phosphate (GP) kit and the method of using this kit to label 99 Tc m to form 99 Tc m -GP for lung ventilation imaging at room temperature in a simple, rapid procedure are described. The stability of the lyophilizing reagent kit under various stock conditions is examined. The results show that all of the 99 Tc m -GP yields by the lyophilizing reagent kit are above 95% at 4 degree C (cold), 20-25 degree C (room temperature) and 40 degree C (oven) for 180, 90 and 3 days, respectively. The clinical practice indicates that in comparison with 99 Tc m -DTPA, 99 Tc m -GP has remarkable difference (P 99 Tc m -GP is an ideal radioaerosol for SPECT studies of lung ventilation. It has high alveolar deposition rate but low adhesion in the major airways compared to those of 99 Tc m -DTPA. 99 Tc m -GP also features prolonged pulmonary clearance time

Reduction of cerebral glucose utilization by the HIV envelope glycoprotein Gp-120

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Kimes, A.S.; London, E.D.; Szabo, G.; Raymon, L.; Tabakoff, B. (Neuropharmacology Laboratory, National Institute on Drug Abuse, Baltimore, MD (USA))

1991-05-01

Gp-120 is a glycoprotein constituent of the human immunodeficiency virus (HIV) envelope. The effects of gp-120 on cerebral glucose utilization in rats were studied by the quantitative 2-deoxy-D-(1-14C) glucose method. Intracerebroventricular injection of gp-120 significantly reduced glucose utilization in the lateral habenula and the suprachiasmatic nucleus and decreased the global cerebral metabolic rate for glucose. The findings suggest that gp-120 and closely related peptides can alter neuronal function, thereby contributing to the sequelae of HIV infection.

Reduction of cerebral glucose utilization by the HIV envelope glycoprotein Gp-120

International Nuclear Information System (INIS)

Kimes, A.S.; London, E.D.; Szabo, G.; Raymon, L.; Tabakoff, B.

1991-01-01

Gp-120 is a glycoprotein constituent of the human immunodeficiency virus (HIV) envelope. The effects of gp-120 on cerebral glucose utilization in rats were studied by the quantitative 2-deoxy-D-[1-14C] glucose method. Intracerebroventricular injection of gp-120 significantly reduced glucose utilization in the lateral habenula and the suprachiasmatic nucleus and decreased the global cerebral metabolic rate for glucose. The findings suggest that gp-120 and closely related peptides can alter neuronal function, thereby contributing to the sequelae of HIV infection

Determinants of a GP visit and cervical cancer screening examination in Great Britain.

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Alexander Michael Labeit

Full Text Available In the UK, women are requested to attend a cervical cancer test every 3 years as part of the NHS Cervical Screening Programme. This analysis compares the determinants of a cervical cancer screening examination with the determinants of a GP visit in the same year and investigates if cervical cancer screening participation is more likely for women who visit their GP.A recursive probit model was used to analyse the determinants of GP visits and cervical cancer screening examinations. GP visits were considered to be endogenous in the cervical cancer screening examination. The analysed sample consisted of 52,551 observations from 8,386 women of the British Household Panel Survey.The analysis showed that a higher education level and a worsening self-perceived health status increased the probability of a GP visit, whereas smoking decreased the probability of a GP visit. GP visits enhanced the uptake of a cervical cancer screening examination in the same period. The only variables which had the same positive effect on both dependent variables were higher education and living with a partner. The probability of a cervical cancer screening examination increased also with previous cervical cancer screening examinations and being in the recommended age groups. All other variables had different results for the uptake of a GP visit or a cervical cancer screening examination.Most of the determinants of visiting a GP and cervical cancer screening examination differ from each other and a GP visit enhances the uptake of a smear test.

The Dutch gas policy: 'Dutch disease' or imaginary disease. CERI Studies Nr 11

International Nuclear Information System (INIS)

Crowley, John

1998-04-01

The Netherlands are the first European gas producer and exporter. The author proposes an analysis of the gas policy of this country. He first recalls some elements of context: peculiarities of energy as a domain of public policy, and characteristics of the Dutch political system. He recalls the historical development of the Dutch gas industry from the 1960's: political economics of natural gas and of competing fuels, development of the Groningen site as the keystone of the Dutch gas policy, and regulation of the industrial sector. In the next part, the author comments the emergence of energy as a topic of public debate from 1995, and how the Dutch gas policy has been put into question again: actors and interaction dynamics, stakes, present policy and perspectives

HIV-1 gp41 Fusion Intermediate: A Target for HIV Therapeutics

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Chungen Pan

2010-02-01

Full Text Available Human immunodeficiency virus (HIV-1 infection is initiated by the binding of gp120 envelope glyco-protein to its cell receptor (CD4 and a coreceptor (CXCR4 or CCR5, followed by a series of conformational changes in the gp41 transmembrane subunit. These changes include insertion of fusion peptide into the target cell membrane and association of C-heptad repeat (CHR peptide with the N-heptad repeat (NHR trimer, a pre-hairpin fusion intermediate. A stable six-helix bundle core is then formed, bringing the viral envelope and target cell membrane into close proximity for fusion. Peptides derived from the CHR region, such as T20 and C34, inhibit HIV-1 fusion by interacting with the gp41 fusion intermediate. A number of anti-HIV-1 peptides and small molecule compounds targeting the gp41 NHR-trimer have been identified. By combining HIV fusion/entry inhibitors targeting different sites in the gp41 fusion intermediate, a potent synergistic effect takes place, resulting in a potential new therapeutic strategy for the HIV infection/AIDS. Here, we present an overview of the current development of anti-HIV drugs, particularly those targeting the gp41 fusion intermediate.

Perceived antecedents of marital satisfaction among Turkish, Turkish-Dutch, and Dutch couples

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Celenk, O.; van de Vijver, F.J.R.

2013-01-01

We studied mainstream couples in The Netherlands and Turkey as well as Turkish-Dutch immigrant couples to address cultural factors associated with marital satisfaction. A total of 13 Turkish (mainstream couples living in Turkey), 19 Turkish-Dutch (Turkish immigrant couples living in The

Nurse telephone triage in out-of-hours GP practice: determinants of independent advice and return consultation

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Klazinga Niek S

2006-12-01

Full Text Available Abstract Background Nowadays, nurses play a central role in telephone triage in Dutch out-of-hours primary care. The percentage of calls that is handled through nurse telephone advice alone (NTAA appears to vary substantially between GP cooperatives. This study aims to explore which determinants are associated with NTAA and with subsequent return consultations to the GP. Methods For the ten most frequently presented problems, a two-week follow-up cohort study took place in one cooperative run by 25 GPs and 8 nurses, serving a population of 62,291 people. Random effects logistic regression analysis was used to study the determinants of NTAA and return consultation rates. The effect of NTAA on hospital referral rates was also studied as a proxy for severity of illness. Results The mean NTAA rate was 27.5% – ranging from 15.5% to 39.4% for the eight nurses. It was higher during the night (RR 1.63, CI 1.48–1.76 and lower with increasing age (RR 0.96, CI 0.93–0.99, per ten years or when the patient presented >2 problems (RR 0.65; CI 0.51–0.83. Using cough as reference category, NTAA was highest for earache (RR 1.49; CI 1.18–1.78 and lowest for chest pain (RR 0.18; CI 0.06–0.47. After correction for differences in case mix, significant variation in NTAA between nurses remained (p Conclusion Important inter-nurse variability may indicate differences in perception on tasks and/or differences in skill to handle telephone calls alone. Future research should focus more on modifiable determinants of NTAA rates.

GP and pharmacist inter-professional learning - a grounded theory study.

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Cunningham, David E; Ferguson, Julie; Wakeling, Judy; Zlotos, Leon; Power, Ailsa

2016-05-01

Practice Based Small Group Learning (PBSGL) is an established learning resource for primary care clinicians in Scotland and is used by one-third of general practitioners (GPs). Scottish Government and UK professional bodies have called for GPs and pharmacists to work more closely together to improve care. To gain GPs' and pharmacists' perceptions and experiences of learning together in an inter-professional PBSGL pilot. Qualitative research methods involving established GP PBSGL groups in NHS Scotland recruiting one or two pharmacists to join them. A grounded theory method was used. GPs were interviewed in focus groups by a fellow GP, and pharmacists were interviewed individually by two researchers, neither being a GP or a pharmacist. Interviews were audio-recorded, transcribed and analysed using grounded theory methods. Data saturation was achieved and confirmed. Three themes were identified: GPs' and pharmacists' perceptions and experiences of inter-professional learning; Inter-professional relationships and team-working; Group identity and purpose of existing GP groups. Pharmacists were welcomed into GP groups and both professions valued inter-professional PBSGL learning. Participants learned from each other and both professions gained a wider perspective of the NHS and of each others' roles in the organisation. Inter-professional relationships, communication and team-working were strengthened and professionals regarded each other as peers and friends.

'Burnout' among Dutch midwives.

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Bakker, R.H.C.; Groenewegen, P.P.; Jabaaij, L.; Meijer, W.; Sixma, H.; Veer, A. de

1996-01-01

OBJECTIVE: to determine the effect of workload on 'burnout' having considered work capacity. DESIGN: cross-sectional study. SETTING: Dutch community midwives in independent practice. PARTICIPANTS: 200 Dutch community midwives. MEASUREMENTS: three-week diary recordings, a questionnaire on practice

Enhancing field GP engagement in hospital-based studies. Rationale, design, main results and participation in the diagest 3-GP motivation study

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Berkhout Christophe

2012-06-01

Full Text Available Abstract Background Diagest 3 was a study aimed at lowering the risk of developing type 2 diabetes within 3 years after childbirth. Women with gestational diabetes were enrolled in the study. After childbirth, the subjects showed little interest in the structured education programme and did not attend workshops. Their general practitioners (GPs were approached to help motivate the subjects to participate in Diagest 3, but the GPs were reluctant. The present study aimed to understand field GPs’ attitudes towards hospital-based studies, and to develop strategies to enhance their involvement and reduce subject drop-out rates. Methods We used a three-step process: step one used a phenomenological approach exploring the beliefs, attitudes, motivations and environmental factors contributing to the GPs’ level of interest in the study. Data were collected in face-to-face interviews and coded by hand and with hermeneutic software to develop distinct GP profiles. Step two was a cross-sectional survey by questionnaire to determine the distribution of the profiles in the GP study population and whether completion of an attached case report form (CRF was associated with a particular GP profile. In step three, we assessed the impact of the motivation study on participation rates in the main study. Results Fifteen interviews were conducted to achieve data saturation. Theorisation led to the definition of 4 distinct GP profiles. The response rate to the questionnaire was 73%, but dropped to 52% when a CRF was attached. The link between GP profiles and the rate of CRF completion remains to be verified. The GPs provided data on the CRF that was of comparable quality to those collected in the main trial. Our analysis showed that the motivation study increased overall participation in the main study by 23%, accounting for 16% (24/152 of all final visits for 536 patients who were initially enrolled in the Diagest 3 study. Conclusions When a hospital-led study

Enhancing field GP engagement in hospital-based studies. Rationale, design, main results and participation in the Diagest 3-GP motivation study.

Science.gov (United States)

Berkhout, Christophe; Vandaele-Bétancourt, Marie; Robert, Stéphane; Lespinasse, Solène; Mitha, Gamil; Bradier, Quentin; Vambergue, Anne; Fontaine, Pierre

2012-06-21

Diagest 3 was a study aimed at lowering the risk of developing type 2 diabetes within 3 years after childbirth. Women with gestational diabetes were enrolled in the study. After childbirth, the subjects showed little interest in the structured education programme and did not attend workshops. Their general practitioners (GPs) were approached to help motivate the subjects to participate in Diagest 3, but the GPs were reluctant. The present study aimed to understand field GPs' attitudes towards hospital-based studies, and to develop strategies to enhance their involvement and reduce subject drop-out rates. We used a three-step process: step one used a phenomenological approach exploring the beliefs, attitudes, motivations and environmental factors contributing to the GPs' level of interest in the study. Data were collected in face-to-face interviews and coded by hand and with hermeneutic software to develop distinct GP profiles. Step two was a cross-sectional survey by questionnaire to determine the distribution of the profiles in the GP study population and whether completion of an attached case report form (CRF) was associated with a particular GP profile. In step three, we assessed the impact of the motivation study on participation rates in the main study. Fifteen interviews were conducted to achieve data saturation. Theorisation led to the definition of 4 distinct GP profiles. The response rate to the questionnaire was 73%, but dropped to 52% when a CRF was attached. The link between GP profiles and the rate of CRF completion remains to be verified. The GPs provided data on the CRF that was of comparable quality to those collected in the main trial. Our analysis showed that the motivation study increased overall participation in the main study by 23%, accounting for 16% (24/152) of all final visits for 536 patients who were initially enrolled in the Diagest 3 study. When a hospital-led study explores issues in primary care, its design must anticipate GP

Dutch elm disease

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James W. Walters

1992-01-01

Since its discovery in the United States in 1930, Dutch elm disease has killed thousands of native elms. The three native elms, American, slippery, and rock, have little or no resistance to Dutch elm disease, but individual trees within each species vary in susceptibility to the disease. The most important of these, American elm, is scattered in upland stands but is...

Spontaneous cure of American cutaneous leishmaniasis due to Leishmania naiffi in two Dutch infantry soldiers

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van der Snoek, E. M.; Lammers, A. M.; Kortbeek, L. M.; Roelfsema, J. H.; Bart, A.; Jaspers, C. A. J. J.

2009-01-01

We report two Dutch infantry soldiers who acquired American cutaneous leishmaniasis (ACL) during military jungle training in Surinam. The lesions had existed for 3 and 5 months, respectively, before the soldiers presented for treatment. The lesions occurred on the head and right thigh, and were

Emotions in primary care: Are there cultural differences in the expression of cues and concerns?

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Schouten, Barbara C; Schinkel, Sanne

2015-11-01

This study compared native-Dutch and Turkish-Dutch patients' expressions of emotional cues/concerns and GPs' responses to these cues/concerns. Relations between patient's cues/concerns and GPs' perceptions of the patient's health complaint were examined too. 82 audiotaped encounters with native-Dutch and 38 with Turkish-Dutch GP patients were coded using the VR-CoDES and VR-CoDES-P. Patients filled out a survey before each consultation to assess their cultural identification, Dutch language proficiency and health-related variables. GPs filled out a survey after each consultation to assess their perceptions of the patient's health complaint. Turkish-Dutch patients expressed more cues than native-Dutch patients, which was explained by higher worries about their health and worse perceived general health. GPs responded more often with space-providing responses to Turkish-Dutch patients compared to native-Dutch patients. Turkish-Dutch patients' cue expression strongly influenced GPs' perceptions about the presence of psychosocial problems. Migrant patient-related factors influence the amount of emotional cue expression in primary care. GPs perceive these cues as indicating the presence of psychosocial problems and provide space for patients to elaborate on their emotional distress. GPs should be trained in using more affective communication techniques to enhance elicitation of the underlying reasons for migrant patients' enhanced emotional cue expression. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

How to improve mental health competency in general practice training?--a SWOT analysis.

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van Marwijk, Harm

2004-06-01

It is quite evident there is room for improvement in the primary care management of common mental health problems. Patients respond positively when GPs adopt a more proactive role in this respect. The Dutch general practice curriculum is currently being renewed. The topics discussed here include the Strengths, Weaknesses, Opportunities and Threats (SWOT) of present primary mental healthcare teaching. What works well and what needs improving? Integrated teaching packages are needed to help general practice trainees manage various presentations of psychological distress. Such packages comprise training videotapes, in which models such as problem-solving treatment (PST) are demonstrated, as well as roleplaying material for new skills, self-report questionnaires for patients, and small-group video feedback of consultations. While GP trainees can effectively master such skills, it is important to query the level of proficiency required by registrars. Are these skills of use only to connoisseur GPs, or to all? More room for specialisation and differentiation among trainees may be the way forward. We have just developed a new curriculum for the obligatory three-month psychiatry housemanship. It is competency oriented, self-directed and assignment driven. This new curriculum will be evaluated in due course.

Marxism and the 'Dutch miracle': the Dutch Republic and the transition-debate

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Brandon, P.

2011-01-01

The Dutch Republic holds a marginal position in the debate on the transition from feudalism to capitalism, despite its significance in the early stage of the development of global capitalism. While the positions of those Marxists who did consider the Dutch case range from seeing it as the first

General practice education and training in southern China: recent development and ongoing challenges under the health care reform

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Wang Jia-Ji

2013-12-01

Full Text Available China has launched a general practice (GP-orientated primary care reform in 2009 to develop a more productive, coordinated, and cost-effective system to maintain and improve the health and wellbeing of one-fifth of the world population. The restructure of the health care system with a focus on primary care requires practitioners working on GP as gatekeepers for service delivery that is responsive to the needs of people. It is particularly prioritised to establish a sound education and training system to ensure that the competencies of practitioners are aligned with local health care needs. This article aims to provide a brief review of the development of GP, including exemplary model of education and training currently implemented in southern China, as well as the challenges to be addressed in the next step. There is a shortage of well-trained and qualified general practitioners in China where more than half of the licensed clinicians in primary care are educated below the undergraduate level. Although there is a stepwise increase in recognition that the capacity of GP is pivotal to the success of primary care development in China, challenges coming from resource restriction, rural and urban disparity, social attitude, and community involvement are highlighted as major bottlenecks that currently hinder the rapid development of GP in China. Supportive policy and guidelines are necessary to build up strong GP recognition and ensure adequate resources to underpin a robust primary care system to deliver affordable and effective health care services for the world’s largest population. It might share some similar experiences with other countries that are struggling to develop a GP-based primary care system.

General practice education and training in southern China: recent development and ongoing challenges under the health care reform.

Science.gov (United States)

Wang, H H X; Wang, J J; Zhou, Z H; Wang, X W; Xu, L

2013-01-01

China has launched a general practice (GP)-orientated primary care reform in 2009 to develop a more productive, coordinated, and cost-effective system to maintain and improve the health and well-being of one-fifth of the world population. The restructure of the health care system with a focus on primary care requires practitioners working on GP as gatekeepers for service delivery that is responsive to the needs of people. It is particularly prioritised to establish a sound education and training system to ensure that the competencies of practitioners are aligned with local health care needs. This article aims to provide a brief review of the development of GP, including exemplary model of education and training currently implemented in southern China, as well as the challenges to be addressed in the next step. There is a shortage of well-trained and qualified general practitioners in China where more than half of the licensed clinicians in primary care are educated below the undergraduate level. Although there is a stepwise increase in recognition that the capacity of GP is pivotal to the success of primary care development in China, challenges coming from resource restriction, rural and urban disparity, social attitude, and community involvement are highlighted as major bottlenecks that currently hinder the rapid development of GP in China. Supportive policy and guidelines are necessary to build up strong GP recognition and ensure adequate resources to underpin a robust primary care system to deliver affordable and effective health care services for the world's largest population. It might share some similar experiences with other countries that are struggling to develop a GP-based primary care system.

Crystallogenesis of bacteriophage P22 tail accessory factor gp26 at acidic and neutral pH

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Cingolani, Gino, E-mail: cingolag@upstate.edu; Andrews, Dewan [Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210 (United States); Casjens, Sherwood [Department of Pathology, Division of Cell Biology and Immunology, University of Utah Medical School, Salt Lake City, UT 84112 (United States); Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210 (United States)

2006-05-01

The crystallogenesis of bacteriophage P22 tail-fiber gp26 is described. To study possible pH-induced conformational changes in gp26 structure, native trimeric gp26 has been crystallized at acidic pH (4.6) and a chimera of gp26 fused to maltose-binding protein (MBP-gp26) has been crystallized at neutral and alkaline pH (7-10). Gp26 is one of three phage P22-encoded tail accessory factors essential for stabilization of viral DNA within the mature capsid. In solution, gp26 exists as an extended triple-stranded coiled-coil protein which shares profound structural similarities with class I viral membrane-fusion protein. In the cryo-EM reconstruction of P22 tail extracted from mature virions, gp26 forms an ∼220 Å extended needle structure emanating from the neck of the tail, which is likely to be brought into contact with the cell’s outer membrane when the viral DNA-injection process is initiated. To shed light on the potential role of gp26 in cell-wall penetration and DNA injection, gp26 has been crystallized at acidic, neutral and alkaline pH. Crystals of native gp26 grown at pH 4.6 diffract X-rays to 2.0 Å resolution and belong to space group P2{sub 1}, with a dimer of trimeric gp26 molecules in the asymmetric unit. To study potential pH-induced conformational changes in the gp26 structure, a chimera of gp26 fused to maltose-binding protein (MBP-gp26) was generated. Hexagonal crystals of MBP-gp26 were obtained at neutral and alkaline pH using the high-throughput crystallization robot at the Hauptman–Woodward Medical Research Institute, Buffalo, NY, USA. These crystals diffract X-rays to beyond 2.0 Å resolution. Structural analysis of gp26 crystallized at acidic, neutral and alkaline pH is in progress.

The pancreatic zymogen granule membrane protein, GP2, binds Escherichia coli type 1 Fimbriae

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Lowe Anson W

2009-07-01

Full Text Available Abstract Background GP2 is the major membrane protein present in the pancreatic zymogen granule, and is cleaved and released into the pancreatic duct along with exocrine secretions. The function of GP2 is unknown. GP2's amino acid sequence is most similar to that of uromodulin, which is secreted by the kidney. Recent studies have demonstrated uromodulin binding to bacterial Type 1 fimbria. The fimbriae serve as adhesins to host receptors. The present study examines whether GP2 also shares similar binding properties to bacteria with Type 1 fimbria. Commensal and pathogenic bacteria, including E. coli and Salmonella, express type 1 fimbria. Methods An in vitro binding assay was used to assay the binding of recombinant GP2 to defined strains of E. coli that differ in their expression of Type 1 fimbria or its subunit protein, FimH. Studies were also performed to determine whether GP2 binding is dependent on the presence of mannose residues, which is a known determinant for FimH binding. Results GP2 binds E. coli that express Type 1 fimbria. Binding is dependent on GP2 glycosylation, and specifically the presence of mannose residues. Conclusion GP2 binds to Type 1 fimbria, a bacterial adhesin that is commonly expressed by members of the Enterobacteriacae family.

Proteomics computational analyses suggest that baculovirus GP64 superfamily proteins are class III penetrenes

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Garry Robert F

2008-02-01

Full Text Available Abstract Background Members of the Baculoviridae encode two types of proteins that mediate virus:cell membrane fusion and penetration into the host cell. Alignments of primary amino acid sequences indicate that baculovirus fusion proteins of group I nucleopolyhedroviruses (NPV form the GP64 superfamily. The structure of these viral penetrenes has not been determined. The GP64 superfamily includes the glycoprotein (GP encoded by members of the Thogotovirus genus of the Orthomyxoviridae. The entry proteins of other baculoviruses, group II NPV and granuloviruses, are class I penetrenes. Results Class III penetrenes encoded by members of the Rhabdoviridae and Herpesviridae have an internal fusion domain comprised of beta sheets, other beta sheet domains, an extended alpha helical domain, a membrane proximal stem domain and a carboxyl terminal anchor. Similar sequences and structural/functional motifs that characterize class III penetrenes are located collinearly in GP64 of group I baculoviruses and related glycoproteins encoded by thogotoviruses. Structural models based on a prototypic class III penetrene, vesicular stomatitis virus glycoprotein (VSV G, were established for Thogoto virus (THOV GP and Autographa california multiple NPV (AcMNPV GP64 demonstrating feasible cysteine linkages. Glycosylation sites in THOV GP and AcMNPV GP64 appear in similar model locations to the two glycosylation sites of VSV G. Conclusion These results suggest that proteins in the GP64 superfamily are class III penetrenes.

Investigating the feasibility and acceptability of health psychology-informed obesity training for medical students.

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Chisholm, Anna; Hart, Jo; Mann, Karen; Perry, Mark; Duthie, Harriet; Rezvani, Leila; Peters, Sarah

2016-01-01

Health psychologists have succeeded in identifying theory-congruent behaviour change techniques (BCTs) to prevent and reduce lifestyle-related illnesses, such as cardiovascular disease, cancers and diabetes. Obesity management discussions between doctors and patients can be challenging and are often avoided. Despite a clear training need, it is unknown how best to tailor BCT research findings to inform obesity-management training for future healthcare professionals. The primary objective of this descriptive study was to gather information on the feasibility and acceptability of delivering and evaluating health psychology-informed obesity training to UK medical students. Medical students (n = 41) attended an obesity management session delivered by GP tutors. Sessions were audio-recorded to enable fidelity checks. Acceptability of training was explored qualitatively. Tutors consistently delivered training according to the intervention protocol; and students and tutors found the training highly acceptable. This psychology-informed training can be delivered successfully by GP tutors and further research is warranted to explore its efficacy.

Afrikaans and Dutch as closely-related languages: A comparison to West Germanic languages and Dutch dialects

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Wilbert Heeringa

2015-02-01

Full Text Available Following Den Besten’s (2009 desiderata for historical linguistics of Afrikaans, this article aims to contribute some modern evidence to the debate regarding the founding dialects of Afrikaans. From an applied perspective (i.e. human language technology, we aim to determine which West Germanic language(s and/or dialect(s would be best suited for the purposes of recycling speech resources for the benefit of developing speech technologies for Afrikaans. Being recognised as a West Germanic language, Afrikaans is first compared to Standard Dutch, Standard Frisian and Standard German. Pronunciation distances are measured by means of Levenshtein distances. Afrikaans is found to be closest to Standard Dutch. Secondly, Afrikaans is compared to 361 Dutch dialectal varieties in the Netherlands and North-Belgium, using material from the Reeks Nederlandse Dialectatlassen, a series of dialect atlases compiled by Blancquaert and Pée in the period 1925-1982 which cover the Dutch dialect area. Afrikaans is found to be closest to the South-Holland dialectal variety of Zoetermeer; this largely agrees with the findings of Kloeke (1950. No speech resources are available for Zoetermeer, but such resources are available for Standard Dutch. Although the dialect of Zoetermeer is significantly closer to Afrikaans than Standard Dutch is, Standard Dutch speech resources might be a good substitute.

Third Dutch Process Security Control Event

NARCIS (Netherlands)

Luiijf, H.A.M.

2009-01-01

On June 4th, 2009, the third Dutch Process Control Security Event took place in Amsterdam. The event, organised by the Dutch National Infrastructure against Cybercrime (NICC), attracted both Dutch process control experts and members of the European SCADA and Control Systems Information Exchange

77 FR 73635 - Northwest Storage GP, LLC; Notice of Application

Science.gov (United States)

2012-12-11

...) 1254 to a proposed 346-megawatt (MW) power plant located within the north industrial area of the Port...] Northwest Storage GP, LLC; Notice of Application Take notice that on November 21, 2012, Northwest Storage GP, LLC. (Northwest) filed with the Federal Energy Regulatory Commission an application under section 7 of...

Facilitators and barriers for GP-patient communication in palliative care: a qualitative study among GPs, patients, and end-of-life consultants.

Science.gov (United States)

Slort, Willemjan; Blankenstein, Annette H; Deliens, Luc; van der Horst, Henriëtte E

2011-04-01

Effective communication is considered to be essential for the delivery of high-quality care. Communication in palliative care may be particularly difficult, and there is still no accepted set of communication skills for GPs in providing palliative care. To obtain detailed information on facilitators and barriers for GP-patient communication in palliative care, with the aim to develop training programmes that enable GPs to improve their palliative care communication skills. Qualitative study with focus groups, interviews, and questionnaires. GPs with patients receiving palliative care at home, and end-of-life consultants in the Netherlands. GP (n = 20) focus groups discussing facilitators and barriers, palliative care patient (n = 6) interviews regarding facilitators, and end-of-life consultant (n = 22) questionnaires concerning barriers. Facilitators reported by both GPs and patients were accessibility, taking time, commitment, and listening carefully. GPs emphasise respect, while patients want GPs to behave in a friendly way, and to take the initiative to discuss end-of-life issues. Barriers reported by both GPs and end-of-life consultants were: difficulty in dealing with former doctors' delay and strong demands from patients' relatives. GPs report difficulty in dealing with strong emotions and troublesome doctor-patient relationships, while consultants report insufficient clarification of patients' problems, promises that could not be kept, helplessness, too close involvement, and insufficient anticipation of various scenarios. The study findings suggest that the quality of GP-patient communication in palliative care in the Netherlands can be improved. It is recommended that specific communication training programmes for GPs should be developed and evaluated.

Dutch voices: exploring the role of oral history in Dutch secondary history teaching

NARCIS (Netherlands)

Huijgen, Tim; Holthuis, Paul; Trškan, Danijela

2016-01-01

Oral history may enhance students’ historical content knowledge, historical reasoning competencies, and motivation to learn history. However, little is known regarding the role of oral history in Dutch history education. This study therefore explores the role of oral history in Dutch history

Effects of Kanjertraining (Topper Training) on Emotional Problems, Behavioural Problems and Classroom Climate

NARCIS (Netherlands)

Vliek, L.

2015-01-01

Reducing difficulties in social interactions and negative classroom climate at an early age may prevent escalation into severe problems that are harder to treat and save society from the associated costs and risks. Topper Training (Kanjertraining in Dutch) has been widely implemented in Dutch

Accurate and efficient gp120 V3 loop structure based models for the determination of HIV-1 co-receptor usage

Directory of Open Access Journals (Sweden)

Vaisman Iosif I

2010-10-01

Full Text Available Abstract Background HIV-1 targets human cells expressing both the CD4 receptor, which binds the viral envelope glycoprotein gp120, as well as either the CCR5 (R5 or CXCR4 (X4 co-receptors, which interact primarily with the third hypervariable loop (V3 loop of gp120. Determination of HIV-1 affinity for either the R5 or X4 co-receptor on host cells facilitates the inclusion of co-receptor antagonists as a part of patient treatment strategies. A dataset of 1193 distinct gp120 V3 loop peptide sequences (989 R5-utilizing, 204 X4-capable is utilized to train predictive classifiers based on implementations of random forest, support vector machine, boosted decision tree, and neural network machine learning algorithms. An in silico mutagenesis procedure employing multibody statistical potentials, computational geometry, and threading of variant V3 sequences onto an experimental structure, is used to generate a feature vector representation for each variant whose components measure environmental perturbations at corresponding structural positions. Results Classifier performance is evaluated based on stratified 10-fold cross-validation, stratified dataset splits (2/3 training, 1/3 validation, and leave-one-out cross-validation. Best reported values of sensitivity (85%, specificity (100%, and precision (98% for predicting X4-capable HIV-1 virus, overall accuracy (97%, Matthew's correlation coefficient (89%, balanced error rate (0.08, and ROC area (0.97 all reach critical thresholds, suggesting that the models outperform six other state-of-the-art methods and come closer to competing with phenotype assays. Conclusions The trained classifiers provide instantaneous and reliable predictions regarding HIV-1 co-receptor usage, requiring only translated V3 loop genotypes as input. Furthermore, the novelty of these computational mutagenesis based predictor attributes distinguishes the models as orthogonal and complementary to previous methods that utilize sequence

Biotechnology : A Dutch perspective

NARCIS (Netherlands)

Van Apeldoorn, J.H.F.

1981-01-01

Biotechnology: a Dutch Perspective assesses the future potential of biotechnology in the Netherlands. It has been published in English because it is felt that the Dutch case could be of relevance to other industrialised nations. Although the report is aimed primarily at policy planners and decision

Introducing a GP copayment in Australia: Who would carry the cost burden?

Science.gov (United States)

Elkins, Rosemary Kate; Schurer, Stefanie

2017-05-01

Recent policy changes designed to contain unsustainable health expenditure growth imply that many more Australians may soon be charged a copayment to consult a GP. We explore the distributional consequences associated with a range of hypothetical GP copayment scenarios using nationally-representative Australian survey data. For each scenario, we estimate the cost burden that individuals and households across the income distribution would need to absorb to maintain their current GP service utilisation. Even when concessional patients are charged a third or a quarter of the non-concessional copayment rate, the average estimated cost burden in the lowest income quartile is typically between three and six times that of the highest, and the average cost burden for women is significantly higher than for men within every income quartile. These disparities are intensified for those with a chronic illness. We conclude that the widespread implementation of GP copayments would disproportionately burden lower-income families, who experience higher rates of chronic illness, higher demand for GP services, and lower capacity to absorb price increases. The regressive nature of GP copayments is reduced when concessional and child patients are exempted entirely, highlighting the importance of supporting GPs-particularly in disadvantaged areas-to maintain bulk-billing arrangements for vulnerable patient groups. Copyright © 2017 Elsevier B.V. All rights reserved.

The Effects of IGF-1 on Trk Expressing DRG Neurons with HIV-gp120- Induced Neurotoxicity.

Science.gov (United States)

Li, Hao; Liu, Zhen; Chi, Heng; Bi, Yanwen; Song, Lijun; Liu, Huaxiang

2016-01-01

HIV envelope glycoprotein gp120 is the main protein that causes HIVassociated sensory neuropathy. However, the underlying mechanisms of gp120-induced neurotoxicity are still unclear. There are lack effective treatments for relieving HIV-related neuropathic symptoms caused by gp120-induced neurotoxicity. In the present study, tyrosine kinase receptor (Trk)A, TrkB, and TrkC expression in primary cultured dorsal root ganglion (DRG) neurons with gp120-induced neurotoxicity was investigated. The effects of IGF-1 on distinct Trk-positive DRG neurons with gp120-induced neurotoxicity were also determined. The results showed that gp120 not only dose-dependently induced DRG neuronal apoptosis and inhibited neuronal survival and neurite outgrowth, but also decreased distinct Trk expression levels. IGF-1 rescued DRG neurons from apoptosis and improved neuronal survival of gp120 neurotoxic DRG neurons in vitro. IGF-1 also improved TrkA and TrkB, but not TrkC, expression in gp120 neurotoxic conditions. The effects of IGF-1 could be blocked by preincubation with the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002. These results suggested that gp120 may have a wide range of neurotoxicity on different subpopulations of DRG neurons, while IGF-1 might only relieve some subpopulations of DRG neurons with gp120-induced neurotoxicity. These data provide novel information of mechanisms of gp120 neurotoxicity on primary sensory neurons and the potential therapeutic effects of IGF-1 on gp120-induced neurotoxicity.

Syntactic Atlas of the Dutch Dialects

NARCIS (Netherlands)

Barbiers, Sjef; Bennis, Hans; Vogelaer, De Gunther; Devos, Magda; Ham, van der Margreet

2005-01-01

Available in a Dutch and English Edition, the Syntactic Atlas of the Dutch Dialects (SAND) provides a detailed overview of the surprisingly rich syntactic variation found in 267 dialects of Dutch at the beginning of the 21th century. 200 full color maps show the geographic distribution of more than

Comparison between Dutch and German buildings

Energy Technology Data Exchange (ETDEWEB)

Lony, R.J.M.; Molenaar, D.J.; Rietkerk, J.; Schuiling, D.J.B.W.; Zeiler, W. [TU/e, Univ. of Technology Eindhoven (Netherlands); Brunk, M. [RWTH Aachen (Germany)

2006-07-01

German buildings are often seen as an example to Dutch architects and Dutch building services consultants. Goal of this article is to examine and to understand differences between the Dutch and German top office buildings. Objective is to examine to which extent these buildings were designed intelligently. An Intelligent Building is one that provides a productive cost effective environment through the optimisation of six basic elements; site, skin, systems, structures, services, space plan and staff and the interrelationship between them. Based on these six aspects the comparison is made between Dutch and German buildings. (orig.)

Dutch hi-tech companies exhibit at CERN

CERN Multimedia

Roberto Cantoni

2010-01-01

Twenty-seven Dutch companies will present the state of the art of their technological developments at the industrial exhibition Holland @ CERN from 8 to 11 November. The exhibition is designed to help strengthen the ties between fundamental science and Dutch industry.   The exhibition, supported by the Dutch Ministry of Economic Affairs and organised by the Netherlands National Institute for Subatomic Physics (Nikhef), in cooperation with the Foundation for Fundamental Research on Matter (FOM), the FOM Institute for Plasma Physics Rijnhuizen, and Dutch Scientific, an association of manufacturers of scientific equipment, will be held in the Main Building from 8 to11 November. “The last Holland @ CERN exhibition took place fifteen years ago”, says Robert Klöpping from Nikhef, Dutch Industrial Liaison Officer for CERN and Purchasing Advisor for Grenoble ESRF. “This kind of event is very important for Dutch industry as it allows us to show what Dutch companies c...

Validation of the Dutch version of the quick mild cognitive impairment screen (Qmci-D).

Science.gov (United States)

Bunt, Steven; O'Caoimh, Rónán; Krijnen, Wim P; Molloy, D William; Goodijk, Geert Pieter; van der Schans, Cees P; Hobbelen, Hans J S M

2015-10-02

Differentiating mild cognitive impairment (MCI) from dementia is important, as treatment options differ. There are few short (Dutch language. The Quick Mild Cognitive Impairment (Qmci) screen is sensitive and specific in differentiating MCI from NC and mild dementia. Given this, we adapted the Qmci for use in Dutch-language countries and validated the Dutch version, the Qmci-D, against the Dutch translation of the Standardised Mini-Mental State Examination (SMMSE-D). The Qmci was translated into Dutch with a combined qualitative and quantitative approach. In all, 90 participants were recruited from a hospital geriatric clinic (25 with dementia, 30 with MCI, 35 with NC). The Qmci-D and SMMSE-D were administered sequentially but randomly by the same trained rater, blind to the diagnosis. The Qmci-D was more sensitive than the SMMSE-D in discriminating MCI from dementia, with a significant difference in the area under the curve (AUC), 0.73 compared to 0.60 (p = 0.024), respectively, and in discriminating dementia from NC, with an AUC of 0.95 compared to 0.89 (p = 0.006). Both screening instruments discriminated MCI from NC with an AUC of 0.86 (Qmci-D) and 0.84 (SMMSE-D). The Qmci-D shows similar,(good) accuracy as the SMMSE-D in separating NC from MCI; greater,(albeit fair), accuracy differentiating MCI from dementia, and significantly greater accuracy in separating dementia from NC. Given its brevity and ease of administration, the Qmci-D seems a useful cognitive screen in a Dutch population. Further study with a suitably powered sample against more sensitive screens is now required.

'Just a lovely luxury?' What can public health attachments add to postgraduate general practice training?

Science.gov (United States)

Wills, Jane; Reynolds, Joanna; Swanwick, Tim

2009-07-01

Changing trends in the role of general practice and general practitioners (GPs), including a focus on commissioning and practice population health needs, were reflected in the specialty training curriculum published by the Royal College of General Practitioners (RCGP) in 2007. In response to these developments the London Deanery established training attachments to the public health departments of ten primary care trusts (PCTs) across London, incorporated into three-year GP specialty training programmes. These attachments were evaluated in 2008 by London South Bank University. The aims of the evaluation were to assess the attachment's suitability for addressing areas of the RCGP curriculum; and to explore perceptions of its value for GP training and for future practice. Semi-structured interviews were carried out with two cohorts of trainees towards the end of their public health attachment, and with public health trainers and GP training programme directors from participating schemes. The training attachments were generally considered to offer good opportunities for trainees to fulfil both public health competences and to address relevant areas of the RCGP curriculum, through a variety of types of work. However, this did not necessarily influence either the level of importance attributed to public health in comparison with other clinical training posts or the perceived impact of the attachment on the trainees' future practice as GPs. The reported learning outcomes and value of the attachment for the public health trainers and programme directors reflected the changing and perceived future demands on GPs, but these views were not generally shared by trainees. Public health attachments may offer general practice training programme opportunities for the development of skills and knowledge that are relevant to the changing nature of general practice. Yet, there still appears to be a barrier for trainee GPs in acknowledging their role in non-clinical, population

Waarnemers in beeld: diversiteit onder waarnemende huisartsen.

NARCIS (Netherlands)

Hassel, D. van; Batenburg, R.

2014-01-01

Diversity among GP locums.General practitioner (GP) locums are playing a pivotal role in sustaining flexibility on the Dutch labor market of GPs. In recent years their numbers have increased significantly. This group is hard to monitor as they have a dynamic career pattern. A survey among GP locums

Fisheries products export training Vietnam: On Risk assessment, HACCP auditing and EU legislation & monitoring

NARCIS (Netherlands)

Schelvis, R.; Poelman, M.

2012-01-01

IMARES and RIKILT developed a training program for fisheries inspectors and private sector quality controllers in Vietnam, in close cooperation with the Dutch Ministry of Economic Affairs, Agriculture and Innovation (EL&I) and the Dutch Ministry of Foreign Affairs (buza) and the Vietnamese fish

Validating glycoprotein non-metastatic melanoma B (gpNMB, osteoactivin), a new biomarker of Gaucher disease.

Science.gov (United States)

Murugesan, Vagishwari; Liu, Jun; Yang, Ruhua; Lin, Haiquin; Lischuk, Andrew; Pastores, Gregory; Zhang, Xiaokui; Chuang, Wei-Lien; Mistry, Pramod K

2018-02-01

In the spleens of Gaucher disease mice and patients, there is a striking elevation of expression of glycoprotein non-Metastatic Melanoma B (gpNMB). We conducted a study in a large cohort of patients with Gaucher disease to assess the utility of serum levels of soluble fragment of gpNMB as a biomarker of disease activity. There was >15-fold elevation of gpNMB in sera of untreated patients with Gaucher disease. gpNMB levels correlated with overall disease severity as well as the severity of individual organ compartments: liver, spleen, bone and hematological disease. Imiglucerase enzyme replacement therapy resulted in significant reduction of gpNMB. Serum levels of gpNMB were highly correlated with accumulation of bioactive lipid substrate of Gaucher disease, glucosylsphingosine as well as established biomarkers, chitotriosidase and chemokine, CCL18. Our results suggest utility of gpNMB as a biomarker of Gaucher disease to monitor individual patients and cohorts of patients for disease progression or response to therapy. Investigation of gpNMB in Gaucher disease pathophysiology is likely to illuminate our understanding disease mechanisms. Copyright © 2016 Elsevier Inc. All rights reserved.

The development and validation of testing materials for literacy, numeracy and digital skills in a Dutch context

NARCIS (Netherlands)

de Greef, Maurice; Segers, Mien; Nijhuis, Jan; Lam, Jo Fond; van Groenestijn, Mieke; van Hoek, Frans; van Deursen, Alexander Johannes Aloysius Maria; Bohnenn, Ella; Tubbing, Marga

2015-01-01

Besides work-oriented training, most Dutch adult learning courses of formal and non-formal education focus on three basic skills: literacy, numeracy and problem solving in technology-rich environments. In the Netherlands, the Ministry of Education, Culture and Science recently initiated the

Membrane insertion and assembly of epitope-tagged gp9 at the tip of the M13 phage

Directory of Open Access Journals (Sweden)

Kuhn Andreas

2011-09-01

Full Text Available Abstract Background Filamentous M13 phage extrude from infected Escherichia coli with a tip structure composed of gp7 and gp9. This tip structure is extended by the assembly of the filament composed of the major coat protein gp8. Finally, gp3 and gp6 terminate the phage structure at the proximal end. Up to now, gp3 has been the primary tool for phage display technology. However, gp7, gp8 and gp9 could also be used for phage display and these phage particles should bind to two different or more surfaces when the modified coat proteins are combined. Therefore, we tested here if the amino-terminal end of gp9 can be modified and whether the modified portion is exposed and detectable on the M13 phage particles. Results The amino-terminal region of gp9 was modified by inserting short sequences that encode antigenic epitopes. We show here that the modified gp9 proteins correctly integrate into the membrane using the membrane insertase YidC exposing the modified epitope into the periplasm. The proteins are then efficiently assembled onto the phage particles. Also extensions up to 36 amino acid residues at the amino-terminal end of gp9 did not interfere with membrane integration and phage assembly. The exposure of the antigenic tags on the phage was visualised with immunogold labelling by electron microscopy and verified by dot blotting with antibodies to the tags. Conclusions Our results suggest that gp9 at the phage tip is suitable for the phage display technology. The modified gp9 can be supplied in trans from a plasmid and fully complements M13 phage with an amber mutation in gene 9. The modified phage tip is very well accessible to antibodies.

Effect of early training on the jumping technique of horses

NARCIS (Netherlands)

Santamaría, Susana; Bobbert, Maarten F.; Back, Willem; Barneveld, Ab; van Weeren, P. Rene

Objective - To investigate the effects of early training for jumping by comparing the jumping technique of horses that had received early training with that of horses raised conventionally. Animals - 40 Dutch Warmblood horses. Procedure - The horses were analyzed kinematically during free jumping at

Engineering and exploitation of a fluorescent HIV-1 gp120 for live cell CD4 binding assays

Energy Technology Data Exchange (ETDEWEB)

Costantini, Lindsey M. [Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461 (United States); Irvin, Susan C. [Department of Pediatrics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461 (United States); Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461 (United States); Kennedy, Steven C. [Department of Pediatrics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461 (United States); Guo, Feng [Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461 (United States); Goldstein, Harris; Herold, Betsy C. [Department of Pediatrics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461 (United States); Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461 (United States); Snapp, Erik L., E-mail: erik-lee.snapp@einstein.yu.edu [Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461 (United States)

2015-02-15

The HIV-1 envelope glycoprotein, gp120, binds the host cell receptor, CD4, in the initial step of HIV viral entry and infection. This process is an appealing target for the development of inhibitory drugs and neutralizing antibodies. To study gp120 binding and intracellular trafficking, we engineered a fluorescent fusion of the humanized gp120 JRFL HIV-1 variant and GFP. Gp120-sfGFP is glycosylated with human sugars, robustly expressed, and secreted from cultured human cells. Protein dynamics, quality control, and trafficking can be visualized in live cells. The fusion protein can be readily modified with different gp120 variants or fluorescent proteins. Finally, secreted gp120-sfGFP enables a sensitive and easy binding assay that can quantitatively screen potential inhibitors of gp120-CD4 binding on live cells via fluorescence imaging or laser scanning cytometry. This adaptable research tool should aid in studies of gp120 cell biology and the development of novel anti-HIV drugs. - Highlights: • Development of fluorescent protein labeled HIV-1 envelope gp120. • Imaging of gp120 dynamics and trafficking in live cells. • Quantitative visual assay of antibody-mediated inhibition of gp120 binding to CD4 on live cells.

Engineering and exploitation of a fluorescent HIV-1 gp120 for live cell CD4 binding assays

International Nuclear Information System (INIS)

Costantini, Lindsey M.; Irvin, Susan C.; Kennedy, Steven C.; Guo, Feng; Goldstein, Harris; Herold, Betsy C.; Snapp, Erik L.

2015-01-01

The HIV-1 envelope glycoprotein, gp120, binds the host cell receptor, CD4, in the initial step of HIV viral entry and infection. This process is an appealing target for the development of inhibitory drugs and neutralizing antibodies. To study gp120 binding and intracellular trafficking, we engineered a fluorescent fusion of the humanized gp120 JRFL HIV-1 variant and GFP. Gp120-sfGFP is glycosylated with human sugars, robustly expressed, and secreted from cultured human cells. Protein dynamics, quality control, and trafficking can be visualized in live cells. The fusion protein can be readily modified with different gp120 variants or fluorescent proteins. Finally, secreted gp120-sfGFP enables a sensitive and easy binding assay that can quantitatively screen potential inhibitors of gp120-CD4 binding on live cells via fluorescence imaging or laser scanning cytometry. This adaptable research tool should aid in studies of gp120 cell biology and the development of novel anti-HIV drugs. - Highlights: • Development of fluorescent protein labeled HIV-1 envelope gp120. • Imaging of gp120 dynamics and trafficking in live cells. • Quantitative visual assay of antibody-mediated inhibition of gp120 binding to CD4 on live cells

The Dutch nuclear programme

International Nuclear Information System (INIS)

1986-01-01

Engineering Services Ltd. has, in fulfillment of its contractual commitment to the Dutch Industrial Council for Energy and Environment Technology (IREM), investigated the broad capability of the Dutch industry in playing a major role in the supply of goods and services for the construction of nuclear plants in the Netherlands. The findings are summarized in this document. 5 tabs

Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41

International Nuclear Information System (INIS)

Anastassopoulou, Cleo G.; Ketas, Thomas J.; Depetris, Rafael S.; Thomas, Antonia M.; Klasse, Per Johan; Moore, John P.

2011-01-01

Here, we describe the genetic pathways taken by a human immunodeficiency virus type 1 (HIV-1) isolate, D101.12, to become resistant to the small molecule CCR5 inhibitor, vicriviroc (VCV), in vitro. Resistant D101.12 variants contained at least one substitution in the gp120 V3 region (H308P), plus one of two patterns of gp41 sequence changes involving the fusion peptide (FP) and a downstream residue: G514V+V535M or M518V+F519L+V535M. Studies of Env-chimeric and point-substituted viruses in peripheral blood mononuclear cells (PBMC) and TZM-bl cells showed that resistance can arise from the cooperative action of gp120 and gp41 changes, while retaining CCR5 usage. Modeling the VCV inhibition data from the two cell types suggests that D101.12 discriminates between high- and low-VCV affinity forms of CCR5 less than D1/85.16, a resistant virus with three FP substitutions.

Performance of Dutch children on the Bayley III: a comparison study of US and Dutch norms.

Science.gov (United States)

Steenis, Leonie J P; Verhoeven, Marjolein; Hessen, Dave J; van Baar, Anneloes L

2015-01-01

The Bayley Scales of Infant and Toddler Development-third edition (Bayley-III) are frequently used to assess early child development worldwide. However, the original standardization only included US children, and it is still unclear whether or not these norms are adequate for use in other populations. Recently, norms for the Dutch version of the Bayley-III (The Bayley-III-NL) were made. Scores based on Dutch and US norms were compared to study the need for population-specific norms. Scaled scores based on Dutch and US norms were compared for 1912 children between 14 days and 42 months 14 days. Next, the proportions of children scoring Dutch norms fluctuated around values based on US norms on all subtests. The extent of the deviations differed across ages and subtests. Differences in means were significant across all five subtests (p Dutch norms resulted in over-referral regarding gross motor skills, and under-referral regarding cognitive, receptive communication, expressive communication, and fine motor skills. The Dutch norms differ from the US norms for all subtests and these differences are clinically relevant. Population specific norms are needed to identify children with low scores for referral and intervention, and to facilitate international comparisons of population data.

Induction of regulatory T cells by high-dose gp96 suppresses murine liver immune hyperactivation.

Directory of Open Access Journals (Sweden)

Xinghui Li

Full Text Available Immunization with high-dose heat shock protein gp96, an endoplasmic reticulum counterpart of the Hsp90 family, significantly enhances regulatory T cell (Treg frequency and suppressive function. Here, we examined the potential role and mechanism of gp96 in regulating immune-mediated hepatic injury in mice. High-dose gp96 immunization elicited rapid and long-lasting protection of mice against concanavalin A (Con A-and anti-CD137-induced liver injury, as evidenced by decreased alanine aminotransaminase (ALT levels, hepatic necrosis, serum pro-inflammatory cytokines (IFN-γ, TNF-α, and IL-6, and number of IFN-γ (+ CD4(+ and IFN-γ (+ CD8(+ T cells in the spleen and liver. In contrast, CD4(+CD25(+Foxp3(+ Treg frequency and suppressive function were both increased, and the protective effect of gp96 could be generated by adoptive transfer of Treg cells from gp96-immunized mice. In vitro co-culture experiments demonstrated that gp96 stimulation enhanced Treg proliferation and suppressive function, and up-regulation of Foxp3, IL-10, and TGF-β1 induced by gp96 was dependent on TLR2- and TLR4-mediated NF-κB activation. Our work shows that activation of Tregs by high-dose gp96 immunization protects against Con A- and anti-CD137-induced T cell-hepatitis and provides therapeutic potential for the development of a gp96-based anti-immune hyperactivation vaccine against immune-mediated liver destruction.

Insight derived from molecular dynamics simulations into molecular motions, thermodynamics and kinetics of HIV-1 gp120.

Directory of Open Access Journals (Sweden)

Peng Sang

Full Text Available Although the crystal structures of the HIV-1 gp120 core bound and pre-bound by CD4 are known, the details of dynamics involved in conformational equilibrium and transition in relation to gp120 function have remained elusive. The homology models of gp120 comprising the N- and C-termini and loops V3 and V4 in the CD4-bound and CD4-unbound states were built and subjected to molecular dynamics (MD simulations to investigate the differences in dynamic properties and molecular motions between them. The results indicate that the CD4-bound gp120 adopted a more compact and stable conformation than the unbound form during simulations. For both the unbound and bound gp120, the large concerted motions derived from essential dynamics (ED analyses can influence the size/shape of the ligand-binding channel/cavity of gp120 and, therefore, were related to its functional properties. The differences in motion direction between certain structural components of these two forms of gp120 were related to the conformational interconversion between them. The free energy calculations based on the metadynamics simulations reveal a more rugged and complex free energy landscape (FEL for the unbound than for the bound gp120, implying that gp120 has a richer conformational diversity in the unbound form. The estimated free energy difference of ∼-6.0 kJ/mol between the global minimum free energy states of the unbound and bound gp120 indicates that gp120 can transform spontaneously from the unbound to bound states, revealing that the bound state represents a high-probability "ground state" for gp120 and explaining why the unbound state resists crystallization. Our results provide insight into the dynamics-and-function relationship of gp120, and facilitate understandings of the thermodynamics, kinetics and conformational control mechanism of HIV-1 gp120.

Why are some patients in treatment for advanced cancer reluctant to consult their GP?

DEFF Research Database (Denmark)

Åbom, Birgit; Pfeiffer, Per

2009-01-01

and therefore consulted the doctor or the staff at the cancer treatment centre before seeking advice from their GP. Some patients found that the GP was not familiar enough with the treatments given; others that they did not want to inconvenience the busy GP with what they perceived to be minor non...

Estimating the risk of dengue transmission from Dutch blood donors travelling to Suriname and the Dutch Caribbean.

Science.gov (United States)

Oei, W; Lieshout-Krikke, R W; Kretzschmar, M E; Zaaijer, H L; Coutinho, R A; Eersel, M; Jubithana, B; Halabi, Y; Gerstenbluth, I; Maduro, E; Tromp, M; Janssen, M P

2016-05-01

The risk of dengue transmitted by travellers is known. Methods to estimate the transmission by transfusion (TT) risk from blood donors travelling to risk areas are available, for instance, the European Up-Front Risk Assessment Tool (EUFRAT). This study aimed to validate the estimated risk from travelling donors obtained from EUFRAT. Surveillance data on notified dengue cases in Suriname and the Dutch Caribbean islands (Aruba, Curaçao, St. Maarten, Bonaire, St. Eustatius and Saba) in 2001-2011 was used to calculate local incidence rates. Information on travel and donation behaviour of Dutch donors was collected. With the EUFRAT model, the TT risks from Dutch travelling donors were calculated. Model estimates were compared with the number of infections in Dutch travellers found by laboratory tests in the Netherlands. The expected cumulative number of donors becoming infected during travels to Suriname and the Dutch Caribbean from 2001 to 2011 was estimated at 5 (95% CI, 2-11) and 86 (45-179), respectively. The infection risk inferred from the laboratory-based study was 19 (9-61) and 28 (14-92). Given the independence of the data sources, these estimates are remarkably close. The model estimated that 0·02 (0·001-0·06) and 0·40 (0·01-1·4) recipients would have been infected by these travelling donors. The EUFRAT model provided an estimate close to actual observed number of dengue infections. The dengue TT risk among Dutch travelling donors can be estimated using basic transmission, travel and donation information. The TT risk from Dutch donors travelling to Suriname and the Dutch Caribbean is small. © 2016 International Society of Blood Transfusion.

Impact of Leishmania metalloprotease GP63 on macrophage signaling

Science.gov (United States)

Isnard, Amandine; Shio, Marina T.; Olivier, Martin

2012-01-01

The intramacrophage protozoan parasites of Leishmania genus have developed sophisticated ways to subvert the innate immune response permitting their infection and propagation within the macrophages of the mammalian host. Several Leishmania virulence factors have been identified and found to be of importance for the development of leishmaniasis. However, recent findings are now further reinforcing the critical role played by the zinc-metalloprotease GP63 as a virulence factor that greatly influence host cell signaling mechanisms and related functions. GP63 has been found to be involved not only in the cleavage and degradation of various kinases and transcription factors, but also to be the major molecule modulating host negative regulatory mechanisms involving for instance protein tyrosine phosphatases (PTPs). Those latter being well recognized for their pivotal role in the regulation of a great number of signaling pathways. In this review article, we are providing a complete overview about the role of Leishmania GP63 in the mechanisms underlying the subversion of macrophage signaling and functions. PMID:22919663

GPs' perceptions of resilience training: a qualitative study.

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Cheshire, Anna; Hughes, John; Lewith, George; Panagioti, Maria; Peters, David; Simon, Chantal; Ridge, Damien

2017-10-01

GPs are reporting increasing levels of burnout, stress, and job dissatisfaction, and there is a looming GP shortage. Promoting resilience is a key strategy for enhancing the sustainability of the healthcare workforce and improving patient care. To explore GPs' perspectives on the content, context, and acceptability of resilience training programmes in general practice, in order to build more effective GP resilience programmes. This was a qualitative study of the perspectives of GPs currently practising in England. GPs were recruited through convenience sampling, and data were collected from two focus groups ( n = 15) and one-to-one telephone interviews ( n = 7). A semi-structured interview approach was used and data were analysed using thematic analysis. Participants perceived resilience training to be potentially of value in ameliorating workplace stresses. Nevertheless, uncertainty was expressed regarding how best to provide training for stressed GPs who have limited time. Participants suspected that GPs most likely to benefit from resilience training were the least likely to engage, as stress and being busy worked against engagement. Conflicting views were expressed about the most suitable training delivery method for promoting better engagement. Participants also emphasised that training should not only place the focus on the individual, but also focus on organisation issues. A multimodal, flexible approach based on individual needs and learning aims, including resilience workshops within undergraduate training and in individual practices, is likely to be the optimal way to promote resilience. © British Journal of General Practice 2017.

Ethnic density is not associated with psychological distress in Turkish-Dutch, Moroccan-Dutch and Surinamese-Dutch ethnic minorities in the Netherlands.

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Schrier, Agnes C; Peen, Jaap; de Wit, Matty A S; van Ameijden, Erik J C; Erdem, Ozcan; Verhoeff, Arnoud P; Dekker, Jack J M; Beekman, Aartjan T F

2014-10-01

Ethnic density, the proportion of people of the same ethnic group in the neighbourhood, has been identified as a protective factor with regard to mental health in ethnic minorities. Research on the putative intermediating factors, exposure to discrimination and improved social support, has not yielded conclusive evidence. We investigated the association between ethnic density and psychological well-being in three ethnic minority groups in the Netherlands. We also assessed whether a protective ethnic density effect is related to the degree to which each group experiences discrimination and social support at group level. Using multi-level linear regression modelling, we studied the influence of ethnic density at neighbourhood level on psychological distress, measured with the Kessler Psychological Distress scale (K10), in 13,864 native Dutch, 1,206 Surinamese-Dutch, 978 Turkish-Dutch and 784 Moroccan-Dutch citizens of the four major cities in the Netherlands. Based on a nationwide survey among ethnic minorities on social integration, ethnic groups were ordered with respect to the intermediating factors. Ethnic density was not associated with psychological distress in any of the three ethnic minority groups. As a consequence, we found no support for either experiences of discrimination or for own-group social interactions at group level as intermediating factors. In all three ethnic minority groups, as well as in the native Dutch group, individual demographic and socio-economic factors emerged as the main explanations for individuals' mental well-being. These results suggest that individual demographic and socio-economic risk characteristics outweigh the influence of neighbourhood attributes on mental health.

CFD study on aerodynamics of a train passing an underground railroad platform

NARCIS (Netherlands)

Khayrullina, A.; Blocken, B.J.E.; Janssen, W.D.; Straathof, J.; Schlünzen, K.H.

2014-01-01

The Dutch railways provide transport for more than 1.2 million passengers a day, resulting in more than 5200 train rides. In order to avoid overcrowded trains during rush hours, it is planned to increase the amount of passenger and freight trains, and their running velocities. Pedestrian discomfort

Income smoothing by Dutch hospitals

NARCIS (Netherlands)

Boterenbrood, D.R.

2014-01-01

Research indicates that hospitals manage their earnings. However, these findings might be influenced by methodological issues. In this study, I exploit specific features of Dutch hospitals to study income smoothing while limiting these methodological issues. The managers of Dutch hospitals have the

65 nm LP/GP mix low cost platform for multi-media wireless and consumer applications

Science.gov (United States)

Tavel, B.; Duriez, B.; Gwoziecki, R.; Basso, M. T.; Julien, C.; Ortolland, C.; Laplanche, Y.; Fox, R.; Sabouret, E.; Detcheverry, C.; Boeuf, F.; Morin, P.; Barge, D.; Bidaud, M.; Biénacel, J.; Garnier, P.; Cooper, K.; Chapon, J. D.; Trouiller, Y.; Belledent, J.; Broekaart, M.; Gouraud, P.; Denais, M.; Huard, V.; Rochereau, K.; Difrenza, R.; Planes, N.; Marin, M.; Boret, S.; Gloria, D.; Vanbergue, S.; Abramowitz, P.; Vishnubhotla, L.; Reber, D.; Stolk, P.; Woo, M.; Arnaud, F.

2006-04-01

A complete 65 nm CMOS platform, called LP/GP Mix, has been developed employing thick oxide transistor (IO), Low Power (LP) and General Purpose (GP) devices on the same chip. Dedicated to wireless multi-media and consumer applications, this new triple gate oxide platform is low cost (+1mask only) and saves over 35% of dynamic power with the use of the low operating voltage GP. The LP/GP mix shows competitive digital performance with a ring oscillator (FO = 1) speed equal to 7 ps per stage (GP) and 6T-SRAM static power lower than 10 pA/cell (LP). Compatible with mixed-signal design requirements, transistors show high voltage gain, low mismatch factor and low flicker noise. Moreover, to address mobile phone demands, excellent RF performance has been achieved with FT = 160 GHz for LP and 280 GHz for GP nMOS transistors.

The Vicious Cycle of Stigma and Disclosure in "Self-Management": A Study Among the Dutch HIV Population.

Science.gov (United States)

de Vries, Daniel H; Koppen, Luca; Lopez, Adolfo Mejia; Foppen, Reina

2016-12-01

Though HIV has become a chronic disease, HIV-related stigma has remained. This article reports on a study that asked how Dutch people living with HIV-AIDS (PLWHA) experienced stigmatization and devised self-management strategies. We used qualitative findings from a survey questionnaire conducted among 468 Dutch HIV-positive people (3% of the population), using a stratified research sample. Findings show how respondents experience relatively high public (30%), self- (26%) and structural (15%) stigma. At the same time, results show the importance of selective disclosure as a self-management strategy. About half the respondents disclose selectively, while 16% does not disclose at all. We conclude that many Dutch PLHWA remain caught up in a vicious cycle of stigma and nondisclosure. To break the cycle, respondents point at the importance of stigma reduction campaigns using actual PLWHA. We highlight the importance of workplace programs and training of medical professionals.

Dutch Corporate Finance, 1602-1850

NARCIS (Netherlands)

A. de Jong (Abe); J. Jonker (Joost); A. Roëll (Ailsa)

2013-01-01

textabstractEarly Modern Dutch corporate finance had two notable features, a remarkable ease of raising large amounts of capital and a flexible legal framework. Having pioneered new corporate forms with two intercontinental trading companies, Dutch business adopted such forms on a wider scale only

Esters of the Marine-Derived Triterpene Sipholenol A Reverse P-GP-Mediated Drug Resistance

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Yongchao Zhang

2015-04-01

Full Text Available Our previous studies showed that several sipholane triterpenes, sipholenol A, sipholenone E, sipholenol L and siphonellinol D, have potent reversal effect for multidrug resistance (MDR in cancer cells that overexpressed P-glycoprotein (P-gp/ABCB1. Through comparison of cytotoxicity towards sensitive and multi-drug resistant cell lines, we identified that the semisynthetic esters sipholenol A-4-O-acetate and sipholenol A-4-O-isonicotinate potently reversed P-gp-mediated MDR but had no effect on MRP1/ABCC1 and BCRP/ABCG2-mediated MDR. The results from [3H]-paclitaxel accumulation and efflux studies suggested that these two triterpenoids were able to increase the intracellular accumulation of paclitaxel by inhibiting its active efflux. In addition, western blot analysis revealed that these two compounds did not alter the expression levels of P-gp when treated up to 72 h. These sipholenol derivatives also stimulated the ATPase activity of P-gp membranes, which suggested that they might be substrates of P-gp. Moreover, in silico molecular docking studies revealed the virtual binding modes of these two compounds into human homology model of P-gp. In conclusion, sipholenol A-4-O-acetate and sipholenol A-4-O-isonicotinate efficiently inhibit the P-gp and may represent potential reversal agents for the treatment of multidrug resistant cancers.

Market Imperfections and Firm-Sponsored Training

NARCIS (Netherlands)

Picchio, M.; van Ours, J.C.

2010-01-01

Recent human capital theories predict that labor market frictions and product market competition influence firm-sponsored training. Using matched worker-firm data from Dutch manufacturing, our paper empirically assesses the validity of these predictions. We find that a decrease in labor market

The Astringency of the GP Algorithm for Forecasting Software Failure Data Series

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Yong-qiang Zhang

2007-05-01

Full Text Available The forecasting of software failure data series by Genetic Programming (GP can be realized without any assumptions before modeling. This discovery has transformed traditional statistical modeling methods as well as improved consistency for model applicability. The individuals' different characteristics during the evolution of generations, which are randomly changeable, are treated as Markov random processes. This paper also proposes that a GP algorithm with "optimal individuals reserved strategy" is the best solution to this problem, and therefore the adaptive individuals finally will be evolved. This will allow practical applications in software reliability modeling analysis and forecasting for failure behaviors. Moreover it can verify the feasibility and availability of the GP algorithm, which is applied to software failure data series forecasting on a theoretical basis. The results show that the GP algorithm is the best solution for software failure behaviors in a variety of disciplines.

Early predictors of need for remediation in the Australian general practice training program: a retrospective cohort study.

Science.gov (United States)

Magin, Parker; Stewart, Rebecca; Turnock, Allison; Tapley, Amanda; Holliday, Elizabeth; Cooling, Nick

2017-10-01

Underperforming trainees requiring remediation may threaten patient safety and are challenging for vocational training programs. Decisions to institute remediation are high-stakes-remediation being resource-intensive and emotionally demanding on trainees. Detection of underperformance requiring remediation is particularly problematic in general (family) practice. We sought to establish early-training assessment instruments predictive of general practice (GP) trainees' subsequently requiring formal remediation. We conducted a retrospective cohort study of trainees from a large Australian regionally-based GP training organization. The outcome factor was requirement for formal remediation. Independent variables were demographic factors and a range of formative assessments conducted immediately prior to or during early-stage training. Analyses employed univariate and multivariate logistic regression of each predictor assessment modality with the outcome, adjusting for potential confounders. Of 248 trainees, 26 (10.5 %) required formal remediation. Performance on the Colleague Feedback Evaluation Tool (entailing feedback from a trainee's clinical colleagues on clinical performance, communication and probity) and External Clinical Teaching Visits (half-day sessions of the trainee's clinical consultations observed directly by an experienced GP), along with non-Australian primary medical qualification, were significantly associated with requiring remediation. There was a non-significant trend for association with performance on the Doctors Interpersonal Skills Questionnaire (patient feedback on interpersonal elements of the consultation). There were no significant associations with entry-selection scores or formative exam or assessment scores. Our finding that 'in vivo' assessments of complex behaviour, but not 'in vitro' knowledge-based assessments, predict need for remediation is consistent with theoretical understanding of the nature of remediation decision-making and

Consistency and reliability of judgements by assessors of case based discussions in general practice specialty training programmes in the United Kingdom.

Science.gov (United States)

Bodgener, Susan; Denney, Meiling; Howard, John

2017-01-01

Case based discussions (CbDs) are a mandatory workplace assessment used throughout general practitioner (GP) specialty training; they contribute to the annual review of competence progression (ARCP) for each trainee. This study examined the judgements arising from CbDs made by different groups of assessors and whether or not these assessments supported ARCP decisions. The trainees selected were at the end of their first year of GP training and had been identified during their ARCPs to need extra training time. CbDs were specifically chosen as they are completed by both hospital and GP supervisors, enabling comparison between these two groups. The results raise concern with regard to the consistency of judgements made by different groups of assessors, with significant variance between assessors of different status and seniority. Further work needs to be done on whether the CbD in its current format is fit for purpose as one of the mandatory WPBAs for GP trainees, particularly during their hospital placements. There is a need to increase the inter-rater reliability of CbDs to ensure a consistent contribution to subsequent decisions about a trainee's overall progress.

The role of women on Dutch farms

OpenAIRE

Meulen, van der, H.A.B.; Terluin, I.J.; Matser, I.A.

2015-01-01

In this paper an analysis is made of the contribution of women to labour input and management on Dutch farms. We used a written survey among the participants of the Dutch Farm Accountancy Data Network (FADN), in-depth interviews and a group discussion with farm women. Over half of the women on Dutch farms spend more than ten hours per week on agricultural activitieson the farm. More than 40% of women on Dutch farms have paid work off farm. The majority of the respondents’ farms is legally org...

The Dutch surgical colorectal audit

NARCIS (Netherlands)

van Leersum, N. J.; Snijders, H. S.; Henneman, D.; Kolfschoten, N. E.; Gooiker, G. A.; ten Berge, M. G.; Eddes, E. H.; Wouters, M. W. J. M.; Tollenaar, R. A. E. M.; Bemelman, W. A.; van Dam, R. M.; Elferink, M. A.; Karsten, Th M.; van Krieken, J. H. J. M.; Lemmens, V. E. P. P.; Rutten, H. J. T.; Manusama, E. R.; van de Velde, C. J. H.; Meijerink, W. J. H. J.; Wiggers, Th; van der Harst, E.; Dekker, J. W. T.; Boerma, D.

2013-01-01

In 2009, the nationwide Dutch Surgical Colorectal Audit (DSCA) was initiated by the Association of Surgeons of the Netherlands (ASN) to monitor, evaluate and improve colorectal cancer care. The DSCA is currently widely used as a blueprint for the initiation of other audits, coordinated by the Dutch

[A Matter of Balance: strategy for implementation in Dutch homecare organizations].

Science.gov (United States)

de Jonge, M C; van der Poel, A; van Haastregt, J C M; Du Moulin, M F T M; Zijlstra, G A R; Voordouw, I

2013-02-01

The Dutch version of A Matter of Balance (AMB-NL) is a cognitive behavioral group program to reduce fear of falling and related activity avoidance in community-living older persons. This paper presents the strategy for implementation of AMB-NL in Dutch homecare organizations and the outcomes of this implementation. The aim was to implement AMB-NL in at least 50 % of 64 homecare organizations in The Netherlands in 2009 and 2010. The implementation strategy was based on the four phases of the Replicating Effective Interventions: pre-conditions, pre-implementation, implementation, and maintenance and evolution. After preparing the implementation activities, such as identifying implementation barriers, consulting stakeholders, preparing the materials involved in the implementation, and training the facilitators of the program (n = 53), AMB-NL was implemented in 16 of the 64 homecare organizations (25 %). Another five homecare organizations indicated that they would shortly include AMB-NL in their care program. These organizations conducted the intervention 19 times to a total of 178 participants. After the implementation phase another 16 facilitators were trained, and program materials were successfully disseminated. The implementation of AMB-NL was well performed. The targeted aim is not fully reached within the two-year timeframe, but the program is well received by participants, trainers and homecare organizations. Further implementation and maintenance of AMB-NL in primary health care is recommended.

The role of women on Dutch farms

NARCIS (Netherlands)

Meulen, van der H.A.B.; Terluin, I.J.; Matser, I.A.

2015-01-01

In this paper an analysis is made of the contribution of women to labour input and management on Dutch farms. We used a written survey among the participants of the Dutch Farm Accountancy Data Network (FADN), in-depth interviews and a group discussion with farm women. Over half of the women on Dutch

Utility of learning plans in general practice vocational training: a mixed-methods national study of registrar, supervisor, and educator perspectives.

Science.gov (United States)

Garth, Belinda; Kirby, Catherine; Silberberg, Peter; Brown, James

2016-08-19

Learning plans are a compulsory component of the training and assessment requirements of general practice (GP) registrars in Australia. There is a small but growing number of studies reporting that learning plans are not well accepted or utilised in general practice training. There is a lack of research examining this apparent contradiction. The aim of this study was to examine use and perceived utility of formal learning plans in GP vocational training. This mixed-method Australian national research project utilised online learning plan usage data from 208 GP registrars and semi-structured focus groups and telephone interviews with 35 GP registrars, 12 recently fellowed GPs, 16 supervisors and 17 medical educators across three Regional Training Providers (RTPs). Qualitative data were analysed thematically using template analysis. Learning plans were used mostly as a log of activities rather than as a planning tool. Most learning needs were entered and ticked off as complete on the same day. Learning plans were perceived as having little value for registrars in their journey to becoming a competent GP, and as a bureaucratic hurdle serving as a distraction rather than an aid to learning. The process of learning planning was valued more so than the documentation of learning planning. This study provides creditable evidence that mandated learning plans are broadly considered by users to be a bureaucratic impediment with little value as a learning tool. It is more important to support registrars in planning their learning than to enforce documentation of this process in a learning plan. If learning planning is to be an assessed competence, methods of assessment other than the submission of a formal learning plan should be explored.

Dutch Colonial Nostalgia Across Decolonisation

NARCIS (Netherlands)

Bijl, P.

2013-01-01

This article argues that nostalgia for colonialism in the Netherlands, the so called tempo doeloe culture, is not a specifically postcolonial phenomenon caused by the collapse of the Dutch empire in Asia. In fact, nostalgia for the Dutch East Indies can be traced back to the nineteenth century, when

Family effects on the rurality of GP's work location: a longitudinal panel study.

Science.gov (United States)

McGrail, Matthew R; Russell, Deborah J; O'Sullivan, Belinda G

2017-10-19

Reduced opportunities for children's schooling and spouse's/partner's employment are identified internationally as key barriers to general practitioners (GPs) working rurally. This paper aims to measure longitudinal associations between the rurality of GP work location and having (i) school-aged children and (ii) a spouse/partner in the workforce. Participants included 4377 GPs responding to at least two consecutive annual surveys of the Medicine in Australia: Balancing Employment and Life (MABEL) national longitudinal study between 2008 and 2014. The main outcome, GP work location, was categorised by remoteness and population size. Five sequential binary school-age groupings were defined according to whether a GP had no children, only preschool children (aged 0-4 years), at least one primary-school child (aged 5-11 years), at least one child in secondary school (aged 12-18 years), and all children older than secondary school (aged ≥ 19). Partner in the workforce was defined by whether a GP had a partner who was either currently working or looking for work, or not. Separate generalised estimating equation models, which aggregated consecutive annual observations per GP, tested associations between work location and (i) educational stages and (ii) partner employment, after adjusting for key covariates. Male GPs with children in secondary school were significantly less likely to work rurally (inclusive of > 50 000 regional centres through to the smallest rural towns of locations were not significantly associated with the educational stage of their children. Having a partner in the workforce was not associated with work location for male GPs, whereas female GPs with a partner in the workforce were significantly less likely to work in smaller rural/remote communities (location is related to key family needs which differ according to GP gender and educational stages of children. Such non-professional factors are likely to be dynamic across the GP's lifespan and

CFD study on passenger and freight trains passing an underground railroad platform

NARCIS (Netherlands)

Khayrullina, A.; Blocken, B.J.E.; Janssen, W.D.; Straathof, J.

2014-01-01

The Dutch railways plan to increase the amount of trains and their running velocities to avoid overcrowded trains during rush hours. Pedestrian discomfort or danger at platforms can be caused by trains which are allowed to pass small railway stations at high speeds up to 140 km/h. A number of these

The Training Characteristics of the World's Most Successful Female Cross-Country Skier.

Science.gov (United States)

Solli, Guro S; Tønnessen, Espen; Sandbakk, Øyvind

2017-01-01

The main aim of this study was to investigate the training characteristics of the most successful female cross-country skier ever during the best period of her career. The participant won six gold medals at the Olympic Games, 18 gold medals at the World Championship, and 110 World Cup victories. Day-to-day training diary data, interviews, and physiological tests were analyzed. Training data was systemized by training form (endurance, strength, and speed), intensity [low- (LIT), moderate- (MIT), and high-intensity training (HIT)], and mode (running, cycling, and skiing/roller skiing), followed by a division into different periodization phases. Specific sessions utilized in the various periodization periods and the day-to-day periodization of training, in connection with altitude camps and tapering toward major championships, were also analyzed. Following a 12-year nonlinear increase in training load, the annual training volume during the five consecutive successful years stabilized at 937 ± 25 h, distributed across 543 ± 9 sessions. During these 5 years, total training time was distributed as 90.6% endurance-, 8.0% strength-, and 1.4% speed-training, with endurance-training time consisting of 92.3 ± 0.3% LIT, 2.9 ± 0.5% MIT, and 4.8 ± 0.5% HIT. Total LIT-time consisted of 21% warm-up, 14% sessions 90 min. While the total number of LIT sessions remained stable across phases (32 sessions), total LIT-time was reduced from GP (76 h/month) to SP (68 h/month) and CP (55 h/month). MIT-time decreased from GP (2.8 h/month) to SP (2.2 h/month) and CP (1 h/month). HIT-time increased from GP (2.8 h/month) to SP (3.2 h/month) and CP (4.7 h/month). Altitude training accounted for 18-25% of annual training volume and performed across relatively short training camps (≤16 days) with a clear reduction of HIT training, but increased total and LIT volume compared to sea-level training. Training before international championships included a 2-week increase in LIT and strength

Sexual harassment during clinical clerkships in Dutch medical schools.

Science.gov (United States)

Rademakers, Jany J D J M; van den Muijsenbergh, Maria E T C; Slappendel, Geerte; Lagro-Janssen, Antoine L M; Borleffs, Jan C C

2008-05-01

Sexual harassment of medical students has been the focus of many international studies. Prevalence rates from 18% to over 60% have been reported. However, a Dutch study at Nijmegen Medical School found the prevalence rate to be lower (13.3% in the total group; 20% among female students only). We aimed to identify whether Nijmegen constitutes a positive sample of Dutch medical schools or whether incidents of sexual harassment are less prevalent in the Netherlands than elsewhere, and to establish if and how these experiences impact the professional lives of students. Students received a semi-structured questionnaire containing questions about their experiences of sexual harassment during clerkships. The questions referred to students' reactions to any incidents, the possible consequences for their wellbeing or professional functioning and the way cases of sexual harassment were handled. The prevalence of sexual harassment was significantly higher in Utrecht than in Nijmegen. In both studies rates were relatively low compared with international data. Nevertheless, 1 in 3-5 Dutch female medical students had experienced unwelcome sexual attention from patients, colleagues or supervisors. Three of 10 students who had experienced such an incident stated that it had a negative impact on their functioning afterwards. Prevalence rates of sexual harassment in medical schools in the Netherlands are low compared with international rates. However, the number of women students who experience sexual harassment is still 1 in 3-5. The occurrence of and ways to deal with these incidents should be important topics in the training of medical students and supervisors.

HIV-1 specific IgA detected in vaginal secretions of HIV uninfected women participating in a microbicide trial in Southern Africa are primarily directed toward gp120 and gp140 specificities.

Directory of Open Access Journals (Sweden)

Kelly E Seaton

Full Text Available Many participants in microbicide trials remain uninfected despite ongoing exposure to HIV-1. Determining the emergence and nature of mucosal HIV-specific immune responses in such women is important, since these responses may contribute to protection and could provide insight for the rational design of HIV-1 vaccines.We first conducted a pilot study to compare three sampling devices (Dacron swabs, flocked nylon swabs and Merocel sponges for detection of HIV-1-specific IgG and IgA antibodies in vaginal secretions. IgG antibodies from HIV-1-positive women reacted broadly across the full panel of eight HIV-1 envelope (Env antigens tested, whereas IgA antibodies only reacted to the gp41 subunit. No Env-reactive antibodies were detected in the HIV-negative women. The three sampling devices yielded equal HIV-1-specific antibody titers, as well as total IgG and IgA concentrations. We then tested vaginal Dacron swabs archived from 57 HIV seronegative women who participated in a microbicide efficacy trial in Southern Africa (HPTN 035. We detected vaginal IgA antibodies directed at HIV-1 Env gp120/gp140 in six of these women, and at gp41 in another three women, but did not detect Env-specific IgG antibodies in any women.Vaginal secretions of HIV-1 infected women contained IgG reactivity to a broad range of Env antigens and IgA reactivity to gp41. In contrast, Env-binding antibodies in the vaginal secretions of HIV-1 uninfected women participating in the microbicide trial were restricted to the IgA subtype and were mostly directed at HIV-1 gp120/gp140.

Which positive factors determine the GP satisfaction in clinical practice? A systematic literature review.

Science.gov (United States)

Le Floch, B; Bastiaens, H; Le Reste, J Y; Lingner, H; Hoffman, R D; Czachowski, S; Assenova, R; Koskela, T H; Klemenc-Ketis, Z; Nabbe, P; Sowinska, A; Montier, T; Peremans, L

2016-09-13

Looking at what makes General Practitioners (GPs) happy in their profession, may be important in increasing the GP workforce in the future. The European General Practice Research Network (EGPRN) created a research team (eight national groups) in order to clarify the factors involved in GP job satisfaction throughout Europe. The first step of this study was a literature review to explore how the satisfaction of GPs had been studied before. The research question was "Which factors are related to GP satisfaction in Clinical Practice?" Systematic literature review according to the PRISMA statement. The databases searched were Pubmed, Embase and Cochrane. All articles were identified, screened and included by two separate research teams, according to inclusion or exclusion criteria. Then, a qualitative appraisal was undertaken. Next, a thematic analysis process was undertaken to capture any issue relevant to the research question. The number of records screened was 458. One hundred four were eligible. Finally, 17 articles were included. The data revealed 13 subthemes, which were grouped into three major themes for GP satisfaction. First there were general profession-related themes, applicable to many professions. A second group of issues related specifically to a GP setting. Finally, a third group was related to professional life and personal issues. A number of factors leading to GP job satisfaction, exist in literature They should be used by policy makers within Europe to increase the GP workforce. The research team needs to undertake qualitative studies to confirm or enhance those results.

Conformational alterations in the CD4 binding cavity of HIV-1 gp120 influencing gp120-CD4 interactions and fusogenicity of HIV-1 envelopes derived from brain and other tissues

Directory of Open Access Journals (Sweden)

Ramsland Paul A

2011-06-01

Full Text Available Abstract Background CD4-binding site (CD4bs alterations in gp120 contribute to HIV-1 envelope (Env mediated fusogenicity and the ability of gp120 to utilize low levels of cell-surface CD4. In a recent study, we constructed three-dimensional models of gp120 to illustrate CD4bs conformations associated with enhanced fusogenicity and enhanced CD4-usage of a modestly-sized panel of blood-derived HIV-1 Envs (n = 16. These conformations were characterized by a wider aperture of the CD4bs cavity, as constrained by the inner-most atoms at the gp120 V1V2 stem and the V5 loop. Here, we sought to provide further validation of the utility of these models for understanding mechanisms that influence Env function, by characterizing the structure-function relationships of a larger panel of Envs derived from brain and other tissues (n = 81. Findings Three-dimensional models of gp120 were generated by our recently validated homology modelling protocol. Analysis of predicted CD4bs structures showed correlations between the aperture width of the CD4bs cavity and ability of the Envs to mediate cell-cell fusion, scavenge low-levels of cell-surface CD4, bind directly to soluble CD4, and bind to the Env mAb IgG1b12 whose epitope overlaps the gp120 CD4bs. These structural alterations in the CD4bs cavity were associated with repositioning of the V5 loop. Conclusions Using a large, independent panel of Envs, we can confirm the utility of three-dimensional gp120 structural models for illustrating CD4bs alterations that can affect Env function. Furthermore, we now provide new evidence that these CD4bs alterations augment the ability of gp120 to interact with CD4 by increasing the exposure of the CD4bs.

Shouting in a Desert: Dutch missionary encounters with Javanese Islam, 1850-1910 : Dutch missionary encounters with Javanese Islam, 1850-1910

NARCIS (Netherlands)

M.J. Kruithof (Maryse)

2014-01-01

markdownabstract__Abstract__ ‘‘Shouting in a desert’ Dutch missionary encounters with Javanese Islam’ concentrates on the shifts and developments in the Dutch mission discourse within the period from 1850 to 1910. It explores the Dutch missionary encounter with local communities and is conducted

Do Dutch Musea Compete Or Cooperate?

OpenAIRE

Thomas De Graaff; Jaap Boter; Jan Rouwendal

2006-01-01

This paper looks into the effect of distance on market shares of Dutch museums. To this end, we assume a generic distance decay function for all museums. In addition, we allow for spatial dependence between museums to account for local competition or synergy effects. Using a unique transaction database with the visiting behavior of 80,821 museum cardholders to 108 Dutch museums, we are able to calculate market shares of each museum in all 484 Dutch municipalities. To account for possible meas...

Triage of febrile children at a GP cooperative : determinants of a consultation

NARCIS (Netherlands)

Monteny, Miriam; Berger, Marjolein Y.; van der Wouden, Johannes C.; Broekman, Berth J.; Koes, Bart W.

Background Most febrile children contacting a GP cooperative are seen by a GP, although the incidence of serious illness is low. The guidelines for triage might not be suitable in primary care. Aim To investigate the determinants related to the outcome of triage in febrile children. Design of study

The Implementation of the AIFMD in Dutch Tax Law

NARCIS (Netherlands)

Vermeulen, H.; Elink Schuurman, J.H.

2014-01-01

In this article, the authors explain the amendments to Dutch tax law as a result of the recent implementation of the Alternative Investment Fund Managers Directive. Changes were made to the Dutch Corporate Income Tax Act, the Dutch Dividend Withholding Tax Act and the Dutch General Tax Act. Given

Influences on GP coping and resilience: a qualitative study in primary care.

Science.gov (United States)

Cheshire, Anna; Ridge, Damien; Hughes, John; Peters, David; Panagioti, Maria; Simon, Chantal; Lewith, George

2017-06-01

'Neoliberal' work policies, austerity, NHS restructuring, and increased GP consultation rates provide the backdrop against increasing reports of GP burnout and an impending shortage of GPs. To explore GPs' experiences of workplace challenges and stresses, and their coping strategies, particularly focusing on understanding the impact of recent NHS workplace change. Study design was qualitative, with data collected from two focus groups and seven one-to-one telephone interviews. Focus groups and one-to-one telephone interviews explored the experiences of GPs currently practising in England, recruited through convenience sampling. Data were collected using a semi-structured interview approach and analysed using thematic analysis. There were 22 GP participants recruited: focus groups ( n = 15) and interviews ( n = 7). Interviewees understood GPs to be under intense and historically unprecedented pressures, which were tied to the contexts in which they work, with important moral implications for 'good' doctoring. Many reported that being a full-time GP was too stressful: work-related stress led to mood changes, sleep disruption, increases in anxiety, and tensions with loved ones. Some had subsequently sought ways to downsize their clinical workload. Workplace change resulted in little time for the things that helped GP resilience: a good work-life balance and better contact with colleagues. Although some GPs were coping better than others, GPs acknowledged that there was only so much an individual GP could do to manage their stress, given the external work issues they faced. GPs experience their emotional lives and stresses as being meaningfully shaped by NHS factors. To support GPs to provide effective care, resilience building should move beyond the individual to include systemic work issues. © British Journal of General Practice 2017.

How Effective is Anti-Phishing Training for Children? : (Distinguished Paper Award)

NARCIS (Netherlands)

Lastdrager, E.E.H.; Carvajal Gallardo, Inés Ramona; Hartel, Pieter H.; Junger, Marianne

2017-01-01

User training is a commonly used method for preventing victimization from phishing attacks. In this study, we focus on training children, since they are active online but often overlooked in interventions. We present an experiment in which children at Dutch primary schools received an anti-phishing

The Development and Validation of Testing Materials for Literacy, Numeracy and Digital Skills in a Dutch Context

Science.gov (United States)

de Greef, Maurice; Segers, Mien; Nijhuis, Jan; Lam, Jo Fond; van Groenestijn, Mieke; van Hoek, Frans; van Deursen, Alexander J. A. M.; Bohnenn, Ella; Tubbing, Marga

2015-01-01

Besides work-oriented training, most Dutch adult learning courses of formal and non-formal education focus on three basic skills: literacy, numeracy and problem solving in technology-rich environments. In the Netherlands, the Ministry of Education, Culture and Science recently initiated the development of a new adult education framework concerning…

Online Platform as a Tool to Support Postgraduate Training in General Practice – A Case Report

Science.gov (United States)

Dini, Lorena; Galanski, Claire; Döpfmer, Susanne; Gehrke-Beck, Sabine; Bayer, Gudrun; Boeckle, Martin; Micheel, Isabel; Novak, Jasminko; Heintze, Christoph

2017-01-01

Objective: Physicians in postgraduate training (PPT) in General Practice (GP) typically have very little interaction with their peers, as there is usually only one resident physician working in their respective department or GP office at a given time. Therefore, the online platform KOLEGEA, presented here, aims to support postgraduate training in general practice (PT in GP) in Germany through virtual interaction. Methodology: In 2012, the interdisciplinary research project KOLEGEA set up an online platform that any physicians in PT in GP can use for free after registration with their unitary continuous education number (Einheitliche Fortbildungsnummer, EFN). It offers problem-based learning and allows to discuss self-published anonymized patient cases with the community that can be classified and discussed with experienced mentors (specialists in general practice - GPs) in small virtual groups. Results: An anonymous online survey carried out as part of the 2014 project evaluation showed a good acceptance of the platform, even though shortage of time was mentioned as a limiting factor for its use. Data analysis showed that KOLEGEA was used by PPT in GP in all federal states. Patterns of passive use were predominant (90%). This report also describes the further development of the platform (in 2015 and 2016) that integrates an activity monitor as part of a gamification concept. Conclusions: Due to a low response rate of the 2014 online survey and the preliminary evaluations of usage patterns we could identify only initial trends regarding the role of KOLEGEA in supporting PPT. The platform was perceived as a helpful supplement to better structure PT in GP. PMID:29226227

Gender and personal breastfeeding experience of rural GP registrars in Australia--a qualitative study of their effect on breastfeeding attitudes and knowledge.

Science.gov (United States)

Brodribb, W E; Jackson, C; Fallon, A B; Hegney, D

2007-01-01

While most doctors believe they have a major role to play in breastfeeding promotion, and consider it worthwhile taking time to assist women to continue to breastfeed, it appears that gender and personal breastfeeding experience affect their attitude and confidence concerning breastfeeding issues. As doctors practicing in rural and regional areas may be expected to provide a greater degree of assistance and support for breastfeeding women, their views on these topics are of particular interest. This article reports the results of qualitative interviews with eight GP registrars from rural and regional Australia, and their views about the influence gender and personal experience have on their ability to assist breastfeeding women. The study is part of a larger project investigating the breastfeeding skills and knowledge of GP registrars as a basis for designing a tailored educational breastfeeding resource. This project uses mixed methods and triangulation of data. Semi-structured, one-on-one interviews were conducted with eight GP registrars from southern Queensland, Australia. The participants were chosen so that there were eight unique combinations of age ( or =34), gender (male or female) and breastfeeding experience (self or spouse had breastfed/had not breastfed) to ensure diversity of responses and increase the transferability of results. Demographics were collected from each participant, as well as information about: their attitudes to breastfeeding and to counselling breastfeeding women; their perception of breastfeeding knowledge needs and their confidence assisting breastfeeding women; and prior training about breastfeeding. Transcripts of the recorded interviews were returned to the participants for verification before analysis. Emergent themes were identified both within and between interviews following content analysis. Four male and four female registrars with a mean age of 35 years (range 28-43 years) were recruited. Two participants of each gender

Expression of HIV gp120 protein increases sensitivity to the rewarding properties of methamphetamine in mice

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Kesby, James P.; Hubbard, David T.; Markou, Athina; Semenova, Svetlana

2012-01-01

Methamphetamine abuse and human immunodeficiency virus (HIV) infection induce neuropathological changes in corticolimbic brain areas involved in reward and cognitive function. Little is known about the combined effects of methamphetamine and HIV infection on cognitive and reward processes. The HIV/gp120 protein induces neurodegeneration in mice, similar to HIV-induced pathology in humans. We investigated the effects of gp120 expression on associative learning, preference for methamphetamine and non-drug reinforcers, and sensitivity to the conditioned rewarding properties of methamphetamine in transgenic (tg) mice expressing HIV/gp120 protein (gp120-tg). gp120-tg mice learned the operant response for food at the same rate as non-tg mice. In the two-bottle choice procedure with restricted access to drugs, gp120-tg mice exhibited greater preference for methamphetamine and saccharin than non-tg mice, whereas preference for quinine was similar between genotypes. Under conditions of unrestricted access to methamphetamine, the mice exhibited a decreased preference for increasing methamphetamine concentrations. However, male gp120-tg mice showed a decreased preference for methamphetamine at lower concentrations than non-tg male mice. gp120-tg mice developed methamphetamine-induced conditioned place preference at lower methamphetamine doses compared with non-tg mice. No differences in methamphetamine pharmacokinetics were found between genotypes. These results indicate that gp120-tg mice exhibit no deficits in associative learning or reward/motivational function for a natural reinforcer. Interestingly, gp120 expression resulted in increased preference for methamphetamine and a highly palatable non-drug reinforcer (saccharin) and increased sensitivity to methamphetamine-induced conditioned reward. These data suggest that HIV-positive individuals may have increased sensitivity to methamphetamine, leading to high methamphetamine abuse potential in this population. PMID

Clinicopathological correlations of podoplanin (gp38 expression in rheumatoid synovium and its potential contribution to fibroblast platelet crosstalk.

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Manuel J Del Rey

Full Text Available Synovial fibroblasts (SF undergo phenotypic changes in rheumatoid arthritis (RA that contribute to inflammatory joint destruction. This study was undertaken to evaluate the clinical and functional significance of ectopic podoplanin (gp38 expression by RA SF.Expression of gp38 and its CLEC2 receptor was analyzed by immunohistochemistry in synovial arthroscopic biopsies from RA patients and normal and osteoarthritic controls. Correlation between gp38 expression and RA clinicopathological variables was analyzed. In patients rebiopsied after anti-TNF-α therapy, changes in gp38 expression were determined. Platelet-SF coculture and gp38 silencing in SF were used to analyze the functional contribution of gp38 to SF migratory and invasive properties, and to SF platelet crosstalk.gp38 was abundantly but variably expressed in RA, and it was undetectable in normal synovial tissues. Among clinicopathologigal RA variables, significantly increased gp38 expression was only found in patients with lymphoid neogenesis (LN, and RF or ACPA autoantibodies. Cultured synovial but not dermal fibroblasts showed strong constitutive gp38 expression that was further induced by TNF-α. In RA patients, anti-TNF-α therapy significantly reduced synovial gp38 expression. In RA synovium, CLEC2 receptor expression was only observed in platelets. gp38 silencing in cultured SF did not modify their migratory and invasive properties but reduced the expression of IL-6 and IL-8 genes induced by SF-platelet interaction.In RA, synovial expression of gp38 is strongly associated to LN and it is reduced after anti-TNF-α therapy. Interaction between gp38 and CLEC2 platelet receptor is feasible in RA synovium in vivo and can specifically contribute to gene expression by SF.

Prepayment Behavior of Dutch Mortgagors : An Empirical Analysis

NARCIS (Netherlands)

Charlier, E.; van Bussel, A.

2001-01-01

The booming Dutch mortgage market and the development of a promising secondary mortgage market in the Netherlands stress the need for an accurate mortgage prepayment model that incorporates typical Dutch market and contract characteristics.One of those typical Dutch features prescribes that each

Performance of Dutch children on the Bayley III: a comparison study of US and Dutch norms.

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Leonie J P Steenis

Full Text Available The Bayley Scales of Infant and Toddler Development-third edition (Bayley-III are frequently used to assess early child development worldwide. However, the original standardization only included US children, and it is still unclear whether or not these norms are adequate for use in other populations. Recently, norms for the Dutch version of the Bayley-III (The Bayley-III-NL were made. Scores based on Dutch and US norms were compared to study the need for population-specific norms.Scaled scores based on Dutch and US norms were compared for 1912 children between 14 days and 42 months 14 days. Next, the proportions of children scoring < 1-SD and < -2 SD based on the two norms were compared, to identify over- or under-referral for developmental delay resulting from non-population-based norms.Scaled scores based on Dutch norms fluctuated around values based on US norms on all subtests. The extent of the deviations differed across ages and subtests. Differences in means were significant across all five subtests (p < .01 with small to large effect sizes (ηp2 ranging from .03 to .26. Using the US instead of Dutch norms resulted in over-referral regarding gross motor skills, and under-referral regarding cognitive, receptive communication, expressive communication, and fine motor skills.The Dutch norms differ from the US norms for all subtests and these differences are clinically relevant. Population specific norms are needed to identify children with low scores for referral and intervention, and to facilitate international comparisons of population data.

Structural and functional characterization of EIAV gp45 fusion peptide proximal region and asparagine-rich layer

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Duan, Liangwei; Du, Jiansen [State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071 (China); Wang, Xuefeng; Zhou, Jianhua; Wang, Xiaojun [State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150001 (China); Liu, Xinqi, E-mail: liu2008@nankai.edu.cn [State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071 (China)

2016-04-15

Equine infectious anaemia virus (EIAV) and human immunodeficiency virus (HIV) are members of the lentiviral genus. Similar to HIV gp41, EIAV gp45 is a fusogenic protein that mediates fusion between the viral particle and the host cell membrane. The crystal structure of gp45 reported reveals a different conformation in the here that includes the fusion peptide proximal region (FPPR) and neighboring asparagine-rich layer compared with previous HIV-1 gp41 structures. A complicated hydrogen-bond network containing a cluster of solvent molecules appears to be critical for the stability of the gp45 helical bundle. Interestingly, viral replication was relatively unaffected by site-directed mutagenesis of EIAV, in striking contrast to that of HIV-1. Based on these observations, we speculate that EIAV is more adaptable to emergent mutations, which might be important for the evolution of EIAV as a quasi-species, and could potentially contribute to the success of the EIAV vaccine. - Highlights: • The crystal structure of EIAV gp45 was determined. • The fusion peptide proximal region adopts a novel conformation different to HIV-1. • The asparagine-rich layer includes an extensive hydrogen-bond network. • These regions of EIAV are highly tolerant to mutations. • The results provide insight into the mechanism of gp41/gp45-mediated membrane fusion.

Disentangling an Invisible Trade : state interventions in Dutch and Dutch-Curaçaoan single-mother families

NARCIS (Netherlands)

Verhallen, T.L.

2015-01-01

The doctoral thesis sheds light on the interactional and institutional processes through which child welfare and child protection practices are delivered to fifteen Dutch and fifteen Dutch-Curaçaoan single-mother families with multiple problems in the Netherlands in order to reveal structures of

The Dutch Economy 2009

International Nuclear Information System (INIS)

2010-09-01

In the series 'The Dutch Economy' the Dutch Statistical Office describes and analyzes annual developments in enterprises, households and governments, and with respect to employment and the environment. One of the subjects is 'Economy and Environment' with the sub-topics 'Resources and Energy', 'Emissions' and 'Environmental Taxes'. Furthermore, in articles on specific themes current economic issues are discussed. One of those themes has the title 'Share of renewable energy in the Netherlands is still small'. [nl

Subjective Oral Health in Dutch Adults

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Gijsbert H.W. Verrips

2013-05-01

Full Text Available Aim: To determine whether the subjective oral health (SOH of the Dutch adult population was associated with clinical and demographic variables. Methods: A clinical examination was conducted in a sample of 1,018 people from the Dutch city of ‘s-Hertogenbosch. SOH was measured using the Dutch translation of the short form of the Oral Health Impact Profile (OHIP-NL14. Results: The average score on the OHIP-NL14 was 2.8 ± 5.9 and 51% of the respondents had a score of 0. Dental status was the most important predictor of SOH. Conclusions:  The SOH in the Dutch adult population was much better than in groups of adults in Australia, the United Kingdom and New Zealand. Nevertheless, there were important variations in SOH related to dental and socio-economic status.

Mass media and GP statin prescribing.

NARCIS (Netherlands)

Verheij, R.A.; Kleijer, S.J.; Dijk, L. van; Schellevis, F.G.

2009-01-01

Background: In March 2007, a Dutch consumer affairs television programme (Radar) questioned the effectiveness of statins in reducing mortality and cardiovascular incidents. We investigated the effects of this television broadcasting on statin prescriptions by GPs in people with and without

Cognitive deficits associated with combined HIV gp120 expression and chronic methamphetamine exposure in mice

Science.gov (United States)

Kesby, James P.; Markou, Athina; Semenova, Svetlana

2014-01-01

Methamphetamine abuse is common among individuals infected by human immunodeficiency virus (HIV). Neurocognitive outcomes tend to be worse in methamphetamine users with HIV. However, it is unclear whether discrete cognitive domains are susceptible to impairment after combined HIV infection and methamphetamine abuse. The expression of HIV/gp120 protein induces neuropathology in mice similar to HIV-induced pathology in humans. We investigated the separate and combined effects of methamphetamine exposure and gp120 expression on cognitive function in transgenic (gp120-tg) and control mice. The mice underwent an escalating methamphetamine binge regimen and were tested in novel object/location recognition, object-in-place recognition, and Barnes maze tests. gp120 expression disrupted performance in the object-in-place test (i.e., similar time spent with all objects, regardless of location), indicating deficits in associative recognition memory. gp120 expression also altered reversal learning in the Barnes maze, suggesting impairments in executive function. Methamphetamine exposure impaired spatial strategy in the Barnes maze, indicating deficits in spatial learning. Methamphetamine-exposed gp120-tg mice had the lowest spatial strategy scores in the final acquisition trials in the Barnes maze, suggesting greater deficits in spatial learning than all of the other groups. Although HIV infection involves interactions between multiple proteins and processes, in addition to gp120, our findings in gp120-tg mice suggest that humans with the dual insult of HIV infection and methamphetamine abuse may exhibit a broader spectrum of cognitive deficits than those with either factor alone. Depending on the cognitive domain, the combination of both insults may exacerbate deficits in cognitive performance compared with each individual insult. PMID:25476577

Home Bias and Dutch Pension Funds’ Investment behaviour

NARCIS (Netherlands)

Verschoor, W.F.C.; Rubbaniy, G.; Lelyveld van, I.P.P.

2014-01-01

Using a panel data set of more than 600 Dutch pension funds (PFs) between 1992 and 2006, we investigate asset allocation behavior of Dutch PFs across multiple asset classes. We find that domestic investments, also known as home bias, in portfolio choices of Dutch institutional investors have fallen.

A review of a GP registrar-run mobile health clinic for homeless people.

Science.gov (United States)

O'Carroll, A; Irving, N; O'Neill, J; Flanagan, E

2017-08-01

Homeless people have excessively high morbidity and mortality rates, yet they face barriers accessing primary care. A mobile health clinic, staffed by GP registrars, was developed to provide services to homeless people, particularly rough sleepers and sex workers. The aims were to improve access to primary care and to challenge the stereotypes and prejudices of GP registrars through direct contact with homeless people. This was a qualitative study; questionnaires were completed on the mobile health clinic and two focus groups were conducted. All service users were asked to complete a questionnaire over a 3 month period. Two focus groups were conducted with 6 and 14 GP registrars who had worked on the bus. There was an 80% response rate (116 of 145). Fifty-two percent had no Medical Card meaning that they had no way to access the free primary care to which they are entitled. Had the clinic not been available, over half would not have sought further treatment and 16% would have gone to an Emergency Department. Ninety-one percent of users rated the service 10/10. The focus groups found that GP registrars who worked on the mobile health clinic had decreased negative stereotypes, increased empathy, and more knowledge of homeless issues. Furthermore, they intended to ensure that homeless people will not face discrimination in their future practice. A GP Registrar-run Mobile Health Clinic achieved its aims of improving access to primary care for rough sleepers and sex workers, and challenging stereotypes of GP Registrars.

Process mining approach for recovery of realized train paths and route conflict identification

NARCIS (Netherlands)

Kecman, P.; Goverde, R.M.P.

2012-01-01

Data records from train describer systems are a valuable source of information for analyzing railway operations performance and assessing railway timetable quality. This paper presents a tool based on process mining event data records from the Dutch train describer system TROTS. The underlying

Social relationships and GP use of middle-aged and older adults in Europe: a moderator analysis.

Science.gov (United States)

Bremer, Daniel; Lüdecke, Daniel; Vonneilich, Nico; von dem Knesebeck, Olaf

2018-04-07

This paper investigates (1) how social relationships (SRs) relate to the frequency of general practitioner (GP) visits among middle-aged and older adults in Europe, (2) if SRs moderate the association between self-rated health and GP visits, and (3) how the associations vary regarding employment status. Data stem from the Survey of Health, Ageing and Retirement in Europe project (wave 4, 56 989 respondents, 50 years or older). GP use was assessed by frequency of contacts with GPs in the last 12 months. Predictors were self-rated health and structural (Social Integration Index (SII), social contact frequency) and functional (emotional closeness) aspects of SR. Regressions were used to measure the associations between GP use and those predictors. Sociodemographic and socioeconomic factors were used as covariates. Additional models were computed with interactions. Analyses did not reveal significant associations of functional and structural aspects of SR with frequency of GP visits (SII: incidence rate ratio (IRR)=0.99, 95% CI 0.97 to 1.01, social contact frequency: IRR=1.04, 95% CI 1.00 to 1.07, emotional closeness: IRR=1.02, 95% CI 1.00 to 1.04). Moderator analyses showed that 'high social contact frequency people' with better health had more statistically significant GP visits than 'low social contact frequency people' with better health. Furthermore, people with poor health and an emotionally close network showed a significantly higher number of GP visits compared with people with same health, but less close networks. Three-way interaction analyses indicated employment status specific behavioural patterns with regard to SR and GP use, but coefficients were mostly not significant. All in all, the not employed groups showed a higher number of GP visits. Different indicators of SR showed statistically insignificantly associations with GP visits. Consequently, the relevance of SR may be rated rather low in quantitative terms for investigating GP use behaviour

Patient satisfaction with out-of-hours GP cooperatives: a longitudinal study.

Science.gov (United States)

Smits, Marleen; Huibers, Linda; Oude Bos, Anita; Giesen, Paul

2012-12-01

For over a decade, out-of-hours primary care in the Netherlands has been provided by general practitioner (GP) cooperatives. In the past years, quality improvements have been made and patients have become acquainted with the service. This may have increased patient satisfaction. The objective of this study was to examine changes in patient satisfaction with GP cooperatives over time. Longitudinal observational study. A validated patient satisfaction questionnaire was distributed in 2003-2004 (T1) and 2007-2008 (T2). Items were rated on a scale from 0 to 10 (1 = very bad; 10 = excellent). Eight GP cooperatives in the Netherlands. Stratified sample of 9600 patients. Response was 55% at T1 (n = 2634) and 51% at T2 (n = 2462). Expectations met; satisfaction with triage nurses, GPs, and organization. For most patients the care received at the GP cooperative met their expectations (T1: 86.1% and T2: 88.4%). Patients were satisfied with the triage nurses (overall grade T1: 7.73 and T2: 7.99), GPs (T1: 8.04 and T2: 8.25), and organization (overall grade T1: 7.60 and T2: 7.78). Satisfaction with triage nurses showed the largest increase over time. The quality and effectiveness of advice or treatment were given relatively low grades. Of all organizational aspects, the lowest grades were given for waiting times and information about the cooperative. In general, patients were initially satisfied with GP cooperatives and satisfaction had even increased four years later. However, there is room for improvement in the content of the advice, waiting times, and information supply. More research is needed into satisfaction of specific patient groups.

Alphavirus Replicon DNA Vectors Expressing Ebola GP and VP40 Antigens Induce Humoral and Cellular Immune Responses in Mice

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Shoufeng Ren

2018-01-01

Full Text Available Ebola virus (EBOV causes severe hemorrhagic fevers in humans, and no approved therapeutics or vaccine is currently available. Glycoprotein (GP is the major protective antigen of EBOV, and can generate virus-like particles (VLPs by co-expression with matrix protein (VP40. In this study, we constructed a recombinant Alphavirus Semliki Forest virus (SFV replicon vector DREP to express EBOV GP and matrix viral protein (VP40. EBOV VLPs were successfully generated and achieved budding from 293 cells after co-transfection with DREP-based GP and VP40 vectors (DREP-GP+DREP-VP40. Vaccination of BALB/c mice with DREP-GP, DREP-VP40, or DREP-GP+DREP-VP40 vectors, followed by immediate electroporation resulted in a mixed IgG subclass production, which recognized EBOV GP and/or VP40 proteins. This vaccination regimen also led to the generation of both Th1 and Th2 cellular immune responses in mice. Notably, vaccination with DREP-GP and DREP-VP40, which produces both GP and VP40 antigens, induced a significantly higher level of anti-GP IgG2a antibody and increased IFN-γ secreting CD8+ T-cell responses relative to vaccination with DREP-GP or DREP-VP40 vector alone. Our study indicates that co-expression of GP and VP40 antigens based on the SFV replicon vector generates EBOV VLPs in vitro, and vaccination with recombinant DREP vectors containing GP and VP40 antigens induces Ebola antigen-specific humoral and cellular immune responses in mice. This novel approach provides a simple and efficient vaccine platform for Ebola disease prevention.

Patient influences on satisfaction and loyalty for GP services.

Science.gov (United States)

Rundle-Thiele, Sharyn; Russell-Bennett, Rebekah

2010-04-01

Little is known about the influence that patients themselves have on their loyalty to a general practitioner (GP). Consequently, a theoretical framework that draws on diverse literature is proposed to suggest that along with satisfaction, patient loyalty is an important outcome for GPs. Comprising 174 Australian patients, this study identified that knowledgeable patients reported lower levels of loyalty while older patients and patients visiting a GP more frequently reported higher levels of loyalty. The results suggest that extending patient-centered care practices to encompass all patients may be warranted in order to improve patient satisfaction and loyalty. Further, future research opportunities abound, with intervention and dyadic research methodologies recommended.

Cloning of gp-340, a putative opsonin receptor for lung surfactant protein D

DEFF Research Database (Denmark)

Holmskov, U; Mollenhauer, J; Madsen, J

1999-01-01

in a soluble form and in association with the membranes of alveolar macrophages. The primary structure of gp-340 has been established by molecular cloning, which yielded a 7,686-bp cDNA sequence encoding a polypeptide chain of 2, 413 amino acids. The domain organization features 13 scavenger receptor cysteine...... in a way that suggested capping, whereas other macrophages showed strong intracellular staining within the phagosome/phagolysosome compartments. In some macrophages, SP-D and gp-340 were located in the same cellular compartment. Immunoreactive gp-340 was also found in epithelial cells of the small...

Training access, reciprocity, and expected retirement age

NARCIS (Netherlands)

Montizaan, R.M.; de Grip, A.; Fouarge, D.

2015-01-01

This paper investigates whether employers can induce employees to postpone retirement by offering access to training courses that maintain job proficiency. We use unique, matched employer-employee surveys for the Dutch public sector, which include detailed information on a wide range of HR practices

Investigation of the function of the putative self-association site of Epstein-Barr virus (EBV) glycoprotein 42 (gp42)

International Nuclear Information System (INIS)

Rowe, Cynthia L.; Matsuura, Hisae; Jardetzky, Theodore S.; Longnecker, Richard

2011-01-01

The Epstein-Barr virus (EBV) glycoprotein 42 (gp42) is a type II membrane protein essential for entry into B cells but inhibits entry into epithelial cells. X-ray crystallography suggests that gp42 may form dimers when bound to human leukocyte antigen (HLA) class II receptor (Mullen et al., 2002) or multimerize when not bound to HLA class II (Kirschner et al., 2009). We investigated this self-association of gp42 using several different approaches. We generated soluble mutants of gp42 containing mutations within the self-association site and found that these mutants have a defect in fusion. The gp42 mutants bound to gH/gL and HLA class II, but were unable to bind wild-type gp42 or a cleavage mutant of gp42. Using purified gp42, gH/gL, and HLA, we found these proteins associate 1:1:1 by gel filtration suggesting that gp42 dimerization or multimerization does not occur or is a transient event undetectable by our methods.

Crystal Structure of the Carboxy-Terminal Region of the Bacteriophage T4 Proximal Long Tail Fiber Protein Gp34

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Meritxell Granell

2017-06-01

Full Text Available Long tail fibers of bacteriophage T4 are formed by proteins gp34, gp35, gp36, and gp37, with gp34 located at the phage-proximal end and gp37 at the phage-distal, receptor-binding end. We have solved the structure of the carboxy-terminal region of gp34, consisting of amino acids 894–1289, by single-wavelength anomalous diffraction and extended the structure to amino acids 744–1289 using data collected from crystals containing longer gp34-fragments. The structure reveals three repeats of a mixed α-β fibrous domain in residues 744 to 877. A triple-helical neck connects to an extended triple β-helix domain (amino acids 900–1127 punctuated by two β-prism domains. Next, a β-prism domain decorated with short helices and extended β-helices is present (residues 1146–1238, while the C-terminal end is capped with another short β-helical region and three β-hairpins. The structure provides insight into the stability of the fibrous gp34 protein.

Is there a place for a holistic approach in surgical training?

Science.gov (United States)

Atayoglu, Timucin; Buchholz, Noor; Atayoglu, Ayten Guner; Caliskan, Mujgan

2014-03-01

The holistic approach in medicine is a framework that considers and treats all aspects of a patient's needs, as it relates to their health. The goal of such an approach is to prevent illness, and to maximise the well-being of individuals and families. Holistic medicine is also referred to as integrative, which has been interpreted by some professionals as the combination of evidence-based medicine and complementary medicine. The speciality of Family Medicine (FM) is often referred to as General Practice (GP), a terminology which emphasises the holistic nature of that discipline. Furthermore, GP/FM professional bodies in some countries have incorporated the holistic and integrative approach into curricula and guidelines for doctors in training, which reflects its acceptance as a component of medical training. However, despite this validation, and despite research showing the effectiveness of such strategies in enhancing the outcomes of surgery, a holistic framework or integrative approach has not been equally integrated into speciality training for would-be surgeons. We argue that it would be advisable to include holistic approaches into surgical training and help surgeons to recognise their role in the continuum of care.

A Critical View on In Vitro Analysis of P-glycoprotein (P-gp) Transport Kinetics.

Science.gov (United States)

Saaby, Lasse; Brodin, Birger

2017-09-01

Transport proteins expressed in the different barriers of the human body can have great implications on absorption, distribution, and excretion of drug compounds. Inhibition or saturation of a transporter can potentially alter these absorbtion, distribution, metabolism and elimination properties and thereby also the pharmacokinetic profile and bioavailability of drug compounds. P-glycoprotein (P-gp, ABCB1) is an efflux transporter which is present in most of the barriers of the body, including the small intestine, the blood-brain barrier, the liver, and the kidney. In all these tissues, P-gp may mediate efflux of drug compounds and may also be a potential site for drug-drug interactions. Consequently, there is a need to be able to predict the saturation and inhibition of P-gp and other transporters in vivo. For this purpose, Michaelis-Menten steady-state analysis has been applied to estimate kinetic parameters, such as K m and V max , for carrier-mediated transport, whereas half-maximal inhibitor concentration (IC 50 ) and the disassociation constant for an inhibitor/P-gp complex (K i ) have been determined to estimate P-gp inhibition. This review addresses in vitro methods commonly used to study P-gp transport kinetics and aims at providing a critical evaluation of the application of steady-state Michaelis-Menten analysis of kinetic parameters for substrate/P-gp interactions. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Curcumin improves synaptic plasticity impairment induced by HIV-1gp120 V3 loop

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Ling-ling Shen

2015-01-01

Full Text Available Curcumin has been shown to significantly improve spatial memory impairment induced by HIV-1 gp120 V3 in rats, but the electrophysiological mechanism remains unknown. Using extracellular microelectrode recording techniques, this study confirmed that the gp120 V3 loop could suppress long-term potentiation in the rat hippocampal CA1 region and synaptic plasticity, and that curcumin could antagonize these inhibitory effects. Using a Fura-2/AM calcium ion probe, we found that curcumin resisted the effects of the gp120 V3 loop on hippocampal synaptosomes and decreased Ca 2+ concentration in synaptosomes. This effect of curcumin was identical to nimodipine, suggesting that curcumin improved the inhibitory effects of gp120 on synaptic plasticity, ameliorated damage caused to the central nervous system, and might be a potential neuroprotective drug.

Conserved region at the COOH terminus of human immunodeficiency virus gp120 envelope protein contains an immunodominant epitope

International Nuclear Information System (INIS)

Palker, T.J.; Matthews, T.J.; Clark, M.E.

1987-01-01

A highly immunogenic epitope from a conserved COOH-terminal region of the human immunodeficiency virus (HIV) gp120 envelope protein has been identified with antisera from HIV-seropositive subjects and a synthetic peptide (SP-22) containing 15 amino acids from this region (Ala-Pro-Thr-Lys-Ala-Lys-Arg-Arg-Val-Val-Gln-Arg-Glu-Lys-Arg). Peptide SP-22 absorbed up to 100% of anti-gp120 antibody reactivity from select HIV + patient sera in immunoblot assays and up to 79% of serum anti-gp120 antibody reactivity in competition RIA. In RIA, 45% of HIV-seropositive subjects had antibodies that bound to peptide SP-22. Human anti-SP-22 antibodies that bound to and were eluted from an SP-22 affinity column reacted with gp120 in RIA and immunoblot assays but did not neutralize HIV or inhibit HIV-induced syncytium formation in vitro, even though these antibodies comprised 70% of all anti-gp120 antibodies in the test serum. In contrast, the remaining 30% of SP-22 nonreactive anti-gp120 antibodies did not react with gp120 in immunoblot assays but did react in RIA and neutralized HIV in vitro. Thus, ≅ 50% of HIV-seropositive patients make high titers of nonneutralizing antibodies to an immunodominant antigen on gp120 defined by SP-22. Moreover, the COOH terminus of gp120 contains the major antigen or antigens identified by human anti-gp120 antibodies in immunoblot assays

Gp120 stability on HIV-1 virions and Gag-Env pseudovirions is enhanced by an uncleaved Gag core

International Nuclear Information System (INIS)

Hammonds, Jason; Chen Xuemin; Ding Lingmei; Fouts, Timothy; De Vico, Anthony; Megede, Jan zur; Barnett, Susan; Spearman, Paul

2003-01-01

Human immunodeficiency virus type-1 (HIV-1) particles incorporate a trimeric envelope complex (Env) made of gp120 (SU) and gp41 (TM) heterodimers. It has been previously established that soluble CD4 (sCD4) interaction leads to shedding of gp120 from viral particles, and that gp120 may also be easily lost from virions during incubation or particle purification procedures. In the design of HIV particle or pseudovirion-based HIV vaccines, it may be important to develop strategies to maximize the gp120 content of particles. We analyzed the gp120 retention of HIV-1 laboratory-adapted isolates and primary isolates following incubation with sCD4 and variations in temperature. NL4-3 shed gp120 readily in a temperature- and sCD4-dependent manner. Surprisingly, inactivation of the viral protease led to markedly reduced shedding of gp120. Gp120 shedding was shown to vary markedly between HIV-1 strains, and was not strictly determined by whether the isolate was adapted to growth on immortalized T cell lines or was a primary isolate. Pseudovirions produced by expression of codon-optimized gag and env genes also demonstrated enhanced gp120 retention when an immature core structure was maintained. Pseudovirions of optimal stability were produced through a combination of an immature Gag protein core and a primary isolate Env. These results support the feasibility of utilizing pseudovirion particles as immunogens for the induction of humoral responses directed against native envelope structures

Effectiveness of feedback in a repeated spelling training

NARCIS (Netherlands)

Gruhn, C.M.S.; Segers, P.C.J.; Verhoeven, L.T.W.

2017-01-01

Effectiveness of feedback on strengthening lexical representations was investigated in a computerized spelling training by contrasting two different feedback conditions with a no feedback condition. Ninety-one Dutch fifth and sixth graders practiced spelling of 40 multisyllabic words with irregular

Binding kinetics of aptamers to gp120 derived from HIV-1 subtype C

CSIR Research Space (South Africa)

Millroy, L

2011-02-01

Full Text Available aptamers with specific and strong affinity to the HIV-1 envelope glycoprotein gp120 and act as novel HIV-1 entry inhibitor drugs or as targeted drug delivery systems to HIV-1 infected cells. Prior to any downstream applications, novel gp120 aptamers need...

Macronutrient Intakes in 553 Dutch Elite and Sub-Elite Endurance, Team, and Strength Athletes: Does Intake Differ between Sport Disciplines?

NARCIS (Netherlands)

Wardenaar, Floris; Brinkmans, Naomi; Ceelen, Ingrid; Rooij, Van Bo; Mensink, Marco; Witkamp, Renger; Vries, De Jeanne

2017-01-01

Web-based 24-h dietary recalls and questionnaires were obtained from 553 Dutch well-trained athletes. The total energy and macronutrient intake was compared between discipline-categories (endurance, team, and strength) within gender, and dietary inadequacy, i.e., too low or high intakes, according

CXCL10 Decreases GP73 Expression in Hepatoma Cells at the Early Stage of Hepatitis C Virus (HCV Infection

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Yuan Liu

2013-12-01

Full Text Available Golgi protein 73 (GP73, which is up-regulated in hepatocellular carcinoma (HCC, has recently been identified as a novel serum marker for HCC diagnosis. Several reports also noted the increased levels of GP73 expression in chronic liver disease in patients with acute hepatitis of various etiologies, chronic Hepatitis C virus (HCV infection and alcoholic liver disease. The molecular mechanisms of GP73 expression in HCV related liver disease still need to be determined. In this study, we aimed to evaluate the effect of HCV infection on GP73 expression. GP73 was highly expressed in Huh7, Hep3B, 293T and HUVEC cells, and was low-expressed in HepG2 cells. HCV infection led to down-regulation of GP73 in Huh7 and HepG2/CD81 cells at the early stage of infection. CXCL10 decreased GP73 expression in Huh7 and HepG2 cells. Up-regulation of GP73 was noted in hepatocytes with cytopathic effect at advanced stage of HCV infection, and further research is needed to determine the unknown factors affecting GP73 expression. In conclusion, our study provided additional evidence for the roles of GP73 in liver disease.

P-gp expression in brown trout erythrocytes: evidence of a detoxification mechanism in fish erythrocytes.

Science.gov (United States)

Valton, Emeline; Amblard, Christian; Wawrzyniak, Ivan; Penault-Llorca, Frederique; Bamdad, Mahchid

2013-12-05

Blood is a site of physiological transport for a great variety of molecules, including xenobiotics. Blood cells in aquatic vertebrates, such as fish, are directly exposed to aquatic pollution. P-gp are ubiquitous "membrane detoxification proteins" implicated in the cellular efflux of various xenobiotics, such as polycyclic aromatic hydrocarbons (PAHs), which may be pollutants. The existence of this P-gp detoxification system inducible by benzo [a] pyrene (BaP), a highly cytotoxic PAH, was investigated in the nucleated erythrocytes of brown trout. Western blot analysis showed the expression of a 140-kDa P-gp in trout erythrocytes. Primary cultures of erythrocytes exposed to increasing concentrations of BaP showed no evidence of cell toxicity. Yet, in the same BaP-treated erythrocytes, P-gp expression increased significantly in a dose-dependent manner. Brown trout P-gp erythrocytes act as membrane defence mechanism against the pollutant, a property that can be exploited for future biomarker development to monitor water quality.

N-terminal substitutions in HIV-1 gp41 reduce the expression of non-trimeric envelope glycoproteins on the virus

International Nuclear Information System (INIS)

Dey, Antu K.; David, Kathryn B.; Ray, Neelanjana; Ketas, Thomas J.; Klasse, Per J.; Doms, Robert W.; Moore, John P.

2008-01-01

The native, functional HIV-1 envelope glycoprotein (Env) complex is a trimer of two non-covalently associated subunits: the gp120 surface glycoprotein and the gp41 transmembrane glycoprotein. However, various non-functional forms of Env are present on virus particles and HIV-1-infected cells, some of which probably arise as the native complex decays. The aberrant forms include gp120-gp41 monomers and oligomers, as well as gp41 subunits from which gp120 has dissociated. The presence of non-functional Env creates binding sites for antibodies that do not recognize native Env complexes and that are, therefore, non-neutralizing. Non-native Env forms (monomers, dimers, tetramers and aggregates) can also arise when soluble gp140 proteins, lacking the cytoplasmic and transmembrane domains of gp41, are expressed for vaccine studies. We recently identified five amino acids in the gp41 N-terminal region (I535, Q543, S553, K567 and R588) that promote gp140 trimerization. We have now studied their influence on the function and antigenic properties of JR-FL Env expressed on the surfaces of pseudoviruses and Env-transfected cells. The 5 substitutions in gp41 reduce the expression of non-trimeric gp160s, without affecting trimer levels. Pseudovirions bearing the mutant Env are fully infectious with similar kinetics of Env-mediated fusion. Various non-neutralizing antibodies bind less strongly to the Env mutant, but neutralizing antibody binding is unaffected. Hence the gp41 substitutions do not adversely affect Env structure, supporting their use for making new Env-based vaccines. The mutant Env might also help in studies intended to correlate antibody binding to virus neutralization. Of note is that the 5 residues are much more frequent, individually or collectively, in viruses from subtypes other than B

Role for the disulfide-bonded region of human immunodeficiency virus type 1 gp41 in receptor-triggered activation of membrane fusion function

International Nuclear Information System (INIS)

Bellamy-McIntyre, Anna K.; Baer, Severine; Ludlow, Louise; Drummer, Heidi E.; Poumbourios, Pantelis

2010-01-01

The conserved disulfide-bonded region (DSR) of the human immunodeficiency virus type 1 (HIV-1) fusion glycoprotein, gp41, mediates association with the receptor-binding glycoprotein, gp120. Interactions between gp120, CD4 and chemokine receptors activate the fusion activity of gp41. The introduction of W596L and W610F mutations to the DSR of HIV-1 QH1549.13 blocked viral entry and hemifusion without affecting gp120-gp41 association. The fusion defect correlated with inhibition of CD4-triggered gp41 pre-hairpin formation, consistent with the DSR mutations having decoupled receptor-induced conformational changes in gp120 from gp41 activation. Our data implicate the DSR in sensing conformational changes in the gp120-gp41 complex that lead to fusion activation.

Nutritional status and food consumption in 10-11 year old Dutch boys (Dutch Nutrition Surveillance System)

NARCIS (Netherlands)

Poppel, G.van.; Schneijder, P.; Löwik, M.R.H.; Schrijver, J.; Kok, F.J.

1991-01-01

As part of the Dutch Nutrition Surveillance System, cardiovascular risk factors and food consumption (24 h recall) as well as haematological, Fe and vitamin status (A, B6, C) were assessed in 126 Dutch boys aged 10-11 years (response 71%). Body mass index (BMI) and the sum of four skinfolds were

The Training Characteristics of the World's Most Successful Female Cross-Country Skier

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Guro S. Solli

2017-12-01

Full Text Available The main aim of this study was to investigate the training characteristics of the most successful female cross-country skier ever during the best period of her career. The participant won six gold medals at the Olympic Games, 18 gold medals at the World Championship, and 110 World Cup victories. Day-to-day training diary data, interviews, and physiological tests were analyzed. Training data was systemized by training form (endurance, strength, and speed, intensity [low- (LIT, moderate- (MIT, and high-intensity training (HIT], and mode (running, cycling, and skiing/roller skiing, followed by a division into different periodization phases. Specific sessions utilized in the various periodization periods and the day-to-day periodization of training, in connection with altitude camps and tapering toward major championships, were also analyzed. Following a 12-year nonlinear increase in training load, the annual training volume during the five consecutive successful years stabilized at 937 ± 25 h, distributed across 543 ± 9 sessions. During these 5 years, total training time was distributed as 90.6% endurance-, 8.0% strength-, and 1.4% speed-training, with endurance-training time consisting of 92.3 ± 0.3% LIT, 2.9 ± 0.5% MIT, and 4.8 ± 0.5% HIT. Total LIT-time consisted of 21% warm-up, 14% sessions <90 min, and 65% long-duration sessions >90 min. While the total number of LIT sessions remained stable across phases (32 sessions, total LIT-time was reduced from GP (76 h/month to SP (68 h/month and CP (55 h/month. MIT-time decreased from GP (2.8 h/month to SP (2.2 h/month and CP (1 h/month. HIT-time increased from GP (2.8 h/month to SP (3.2 h/month and CP (4.7 h/month. Altitude training accounted for 18–25% of annual training volume and performed across relatively short training camps (≤16 days with a clear reduction of HIT training, but increased total and LIT volume compared to sea-level training. Training before international championships

Dutch word stress as pronounced by Indonesian students

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Lilie M. Roosman

2009-10-01

Full Text Available This study focuses on the way in which the Dutch monophthongal vowels are pronounced by Indonesian students. To investigate whether Indonesian students realize the Dutch vowels correctly, especially when they are stressed, I analysed duration and quality of stressed and unstressed Dutch vowels. Measurements were done on the duration and the formant frequencies of the vowels spoken by Indonesian students and by native speakers of Dutch as well. Statistical analysis showed that in general the differences in duration between vowels spoken by the Indonesian students and by the native speakers were not significant. However, the effect of stress on the lengthening of the vowels was stronger for the Indonesian students than for the native speakers. In addition, statistical analysis of the formant frequencies confirmed that the non-native speakers realized the Dutch vowels slightly differently from the Dutch native speakers. The Indonesian students pronounced the stressed vowels more clearly than their unstressed counterparts; yet their vowel diagram is smaller than the vowel diagram of the native speakers.

GP50 as a promising early diagnostic antigen for Taenia multiceps infection in goats by indirect ELISA.

Science.gov (United States)

Huang, Xing; Xu, Jing; Wang, Yu; Guo, Cheng; Chen, Lin; Gu, Xiaobin; Lai, Weimin; Peng, Xuerong; Yang, Guangyou

2016-12-01

Coenurosis is caused by coenurus, the metacestode of Taenia multiceps, which mainly parasitizes the brain and spinal cord of cattle, sheep and goats. To date, no widely-approved methods are available to identify early coenurus infection. In this study, we identified a full-length cDNA that encodes GP50 (TmGP50) from the transcriptome of T. multiceps, and then cloned and expressed in E. coli. The native proteins in adult stage and coenurus were located via immunofluorescence assays, while the potential of recombinant TmGP50 protein (rTmGP50) for indirect ELISA-based serodiagnostics was assessed using native goat sera. In addition, we orally infected 20 goats with mature T. multiceps eggs. Praziquantel (10%) was given to 10 of the goats 45 days post-infection (p.i.). Blood samples were collected for 17 weeks p.i. from the 20 goats and anti-rTmGP50 antibodies were evaluated using the indirect ELISA established here. The TmGP50 contains an 897 bp open reading frame, in which signal sequence resides in 1 ~ 48 sites and mature polypeptide consists of 282 amino acid residues. Immunofluorescence staining showed that native TmGP50 was localized to the microthrix and parenchymatous zone of the adult parasite and coenurus, and the coenurus cystic wall. The indirect ELISA based on rTmGP50 exhibited a sensitivity of 95.0% and a specificity of 92.6% when detecting GP50 antibodies in sera of naturally infected goats and sheep. In goats experimentally infected with T. multiceps, anti-TmGP50 antibody was detectable from 2 to 17 weeks p.i. in the control group, while the antibody fell below the cut-off value about 3 weeks after praziquantel treatment. Our results indicate that recombinant TmGP50 is a suitable early diagnostic antigen for coenurus infection in goats.

The Dutch private company: successfully relaunched?

NARCIS (Netherlands)

van der Elst, C.F.; Vermeulen, E.P.M.; De Cordt, Y.; Navez, E.J.

2014-01-01

This Chapter in a comparative book on private limited liability companies starts with an illustration of the former success of the Dutch limited liability company (BV). Next it addresses the competitive European legal environment within which the Dutch BV has to operate. The study shows how the

Improved Dutch Roll Approximation for Hypersonic Vehicle

Directory of Open Access Journals (Sweden)

Liang-Liang Yin

2014-06-01

Full Text Available An improved dutch roll approximation for hypersonic vehicle is presented. From the new approximations, the dutch roll frequency is shown to be a function of the stability axis yaw stability and the dutch roll damping is mainly effected by the roll damping ratio. In additional, an important parameter called roll-to-yaw ratio is obtained to describe the dutch roll mode. Solution shows that large-roll-to-yaw ratio is the generate character of hypersonic vehicle, which results the large error for the practical approximation. Predictions from the literal approximations derived in this paper are compared with actual numerical values for s example hypersonic vehicle, results show the approximations work well and the error is below 10 %.

Leishmania major surface protease Gp63 interferes with the function of human monocytes and neutrophils in vitro

DEFF Research Database (Denmark)

Sørensen, A L; Hey, A S; Kharazmi, A

1994-01-01

In the present study the effect of Leishmania major surface protease Gp63 on the chemotaxis and oxidative burst response of human peripheral blood monocytes and neutrophils was investigated. It was shown that prior incubation of cells with Gp63 inhibited chemotaxis of neutrophils but not monocytes...... towards the chemotactic peptide f-met-leu-phe. On the other hand, chemotaxis of both neutrophils and monocytes towards zymosan-activated serum containing C5a was inhibited by Gp63. Monocyte and neutrophil chemiluminescence response to opsonized zymosan was reduced by preincubation of the cells with Gp63...... in a concentration-dependent manner. Notably, monocytes were inhibited to a much greater degree than neutrophils by a given concentration of Gp63, and they were also inhibited at much lower concentrations of the protease. The inhibitory effect of Gp63 on chemotaxis and chemiluminescence was completely abolished...

Characterisation of different forms of the accessory gp3 canine coronavirus type I protein identified in cats.

Science.gov (United States)

d'Orengiani, Anne-Laure Pham-Hung d'Alexandry; Duarte, Lidia; Pavio, Nicole; Le Poder, Sophie

2015-04-16

ORF3 is a supplemental open reading frame coding for an accessory glycoprotein gp3 of unknown function, only present in genotype I canine strain (CCoV-I) and some atypical feline FCoV strains. In these latter hosts, the ORF3 gene systematically displays one or two identical deletions leading to the synthesis of truncated proteins gp3-Δ1 and gp3-Δ2. As deletions in CoV accessory proteins have already been involved in tissue or host switch, studies of these different gp3 proteins were conducted in canine and feline cell. All proteins oligomerise through covalent bonds, are N-glycosylated and are maintained in the ER in non-infected but also in CCoV-II infected cells, without any specific retention signal. However, deletions influence their level of expression. In canine cells, all proteins are expressed with similar level whereas in feline cells, the expression of gp3-Δ1 is higher than the two other forms of gp3. None of the gp3 proteins modulate the viral replication cycle of heterologous genotype II CCoV in canine cell line, leading to the conclusion that the gp3 proteins are probably advantageous only for CCoV-I and atypical FCoV strains. Copyright © 2015 Elsevier B.V. All rights reserved.

HIV-1 gp120 and drugs of abuse: interactions in the central nervous system.

Science.gov (United States)

Silverstein, Peter S; Shah, Ankit; Weemhoff, James; Kumar, Santosh; Singh, D P; Kumar, Anil

2012-07-01

HIV-1 infection is a global public health problem with more than 34 million people living with HIV infection. Although great strides have been made in treating this epidemic with therapeutic agents, the increase in patient life span has been coincident with an increase in the prevalence of HIV-associated neurocognitive disorders (HAND). HAND is thought to result from the neurotoxic effects of viral proteins that are shed from HIV-infected microglial cells. One of the primary neurotoxins responsible for this effect is the HIV-1 glycoprotein gp120. Exposure of neurons to gp120 has been demonstrated to cause apoptosis in neurons, as well as numerous indirect effects such as an increase in inflammatory cytokines, an increase in oxidative stress, and an increase in permeability of the blood-brain barrier. In many patients, the use of drugs of abuse (DOA) exacerbates the neurotoxic effects of gp120. Cocaine, methamphetamine and morphine are three DOAs that are commonly used by those infected with HIV-1. All three of these DOAs have been demonstrated to increase oxidative stress in the CNS as well as to increase permeability of the blood-brain barrier. Numerous model systems have demonstrated that these DOAs have the capability of exacerbating the neurotoxic effects of gp120. This review will summarize the neurotoxic effects of gp120, the deleterious effects of cocaine, methamphetamine and morphine on the CNS, and the combined effects of gp120 in the context of these drugs.

Comparative Glycoprofiling of HIV gp120 Immunogens by Capillary Electrophoresis and MALDI Mass Spectrometry

Science.gov (United States)

Guttman, Miklós; Váradi, Csaba; Lee, Kelly K.; Guttman, András

2015-01-01

The Human Immunodeficiency Virus (HIV) envelope glycoprotein (Env) is the primary antigenic feature on the surface of the virus and is of key importance in HIV vaccinology. Vaccine trials with the gp120 subunit of Env are ongoing with the recent RV144 trial showing moderate efficacy. gp120 is densely covered with N-linked glycans that are thought to help evade the host's humoral immune response. To assess how the global glycosylation patterns vary between gp120 constructs, the glycan profiles of several gp120s were examined by capillary electrophoresis with laser induced fluorescence detection and MALDI-MS. The glycosylation profiles were found to be similar for chronic vs. transmitter/founder isolates and only varied moderately between gp120s from different clades. This study revealed that the addition of specific tags, such as the gD tag used in the RV144 trial, had significant effects on the overall glycosylation patterns. Such effects are likely to influence the immunogenicity of various Env immunogens and should be considered for future vaccine strategies, emphasizing the importance of the glycosylation analysis approach described in this paper. PMID:25809283

Serological responses in chimpanzees inoculated with human immunodeficiency virus glycoprotein (gp120) subunit vaccine

International Nuclear Information System (INIS)

Arthur, L.O.; Pyle, S.W.; Nara, P.L.

1987-01-01

The major envelope glycoprotein of a human immunodeficiency virus (HIV) has been purified and was utilized as a prototype vaccine in chimpanzees. The 120,000-dalton glycoprotein (gp120) was purified from membranes of human T-lymphotropic virus (HTLV)-IIIB-infected cells and the final preparation contained low levels to no detectable HTLV-IIIB core antigen (p24) and low levels of endotoxin. Chimpanzees inoculated with gp120 responded by developing antibodies that precipitated radiolabeled gp120 and neutralized in vitro infection of HTLV-IIIB. Antibodies to HTLV-IIIB p24 were not detected in the gp120-immunized chimpanzees. Peripheral blood leukocytes from the vaccinated animals were examined for T4 + and T8 + cells, and no decrease in the T4/T8 ratio was found, indicating that immunization with a ligand (gp120) that binds to T4 has not detectable adverse effect on the population of T4 + cells. The only current animal model that can be reproducibly infected with HIV is the chimpanzee. Immunization of chimpanzees with HIV proteins will provide an experimental system for testing the effectiveness of prototype vaccines for preventing HIV infection in vivo

Management of the Dutch development cooperation

NARCIS (Netherlands)

Janssen, Lodevicus Johannes Henricus

2009-01-01

There is reason for concern about the Dutch development cooperation. A survey of some aid evaluations of the Dutch Ministry of Foreign Affairs (MFA) showed that the aid results are limited and that the goals of the programs are not achieved. Management concerns using an organisation's resources to

Similar associations between personality dimensions and anxiety or depressive disorders in a population study of Turkish-Dutch, Moroccan-Dutch, and native Dutch subjects.

Science.gov (United States)

Schrier, Agnes C; de Wit, Matty A S; Krol, Anneke; Fassaert, Thijs J L; Verhoeff, Arnoud P; Kupka, Ralph W; Dekker, Jack; Beekman, Aartjan T F

2013-05-01

It is well established that personality traits are associated with anxiety and depressive disorders in Western populations, but it is not known whether this is true also for people from non-Western cultures. In this study, we examined whether ethnicity moderates the association between personality dimensions and anxiety or depressive disorders or symptoms. In a random urban population sample, stratified by ethnicity, in Amsterdam, the Netherlands, we interviewed 309 native Dutch subjects, 203 Turkish-Dutch subjects, and 170 Moroccan-Dutch subjects. Dimensions of personality were measured using the NEO Five-Factor Inventory. Anxiety and depressive disorders and symptom levels were assessed with the Composite International Diagnostic Interview and the Symptom Checklist-90-Revised. The association between personality factors and disorders or symptoms of anxiety and depression was very similar in the three ethnic groups: all show the typical profile of high neuroticism and low extraversion, agreeableness, and conscientiousness.

Evaluating Hospice and Palliative Medicine Education in Pediatric Training Programs.

Science.gov (United States)

Singh, Arun L; Klick, Jeffrey C; McCracken, Courtney E; Hebbar, Kiran B

2017-08-01

Hospice and Palliative Medicine (HPM) competencies are of growing importance in training general pediatricians and pediatric sub-specialists. The Accreditation Council for Graduate Medical Education (ACGME) emphasized pediatric trainees should understand the "impact of chronic disease, terminal conditions and death on patients and their families." Currently, very little is known regarding pediatric trainee education in HPM. We surveyed all 486 ACGME-accredited pediatric training program directors (PDs) - 200 in general pediatrics (GP), 57 in cardiology (CARD), 64 in critical care medicine (CCM), 69 in hematology-oncology (ONC) and 96 in neonatology (NICU). We collected training program's demographics, PD's attitudes and educational practices regarding HPM. The complete response rate was 30% (148/486). Overall, 45% offer formal HPM curriculum and 39% offer a rotation in HPM for trainees. HPM teaching modalities commonly reported included conferences, consultations and bedside teaching. Eighty-one percent of all respondents felt that HPM curriculum would improve trainees' ability to care for patients. While most groups felt that a HPM rotation would enhance trainees' education [GP (96%), CARD (77%), CCM (82%) and ONC (95%)], NICU PDs were more divided (55%; p training, there remains a paucity of opportunities for pediatric trainees. Passive teaching methods are frequently utilized in HPM curricula with minimal diversity in methods utilized to teach HPM. Opportunities to further emphasize HPM in general pediatric and pediatric sub-specialty training remains.

Membrane binding properties of EBV gp110 C-terminal domain; evidences for structural transition in the membrane environment

International Nuclear Information System (INIS)

Park, Sung Jean; Seo, Min-Duk; Lee, Suk Kyeong; Lee, Bong Jin

2008-01-01

Gp110 of Epstein-Barr virus (EBV) mainly localizes on nuclear/ER membranes and plays a role in the assembly of EBV nucleocapsid. The C-terminal tail domain (gp110 CTD) is essential for the function of gp110 and the nuclear/ER membranes localization of gp110 is ruled by its C-terminal unique nuclear localization signal (NLS), consecutive four arginines. In the present study, the structural properties of gp110 CTD in membrane mimics were investigated using CD, size-exclusion chromatography, and NMR, to elucidate the effect of membrane environment on the structural transition and to compare the structural feature of the protein in the solution state with that of the membrane-bound form. CD and NMR analysis showed that gp110 CTD in a buffer solution appears to adopt a stable folding intermediate which lacks compactness, and a highly helical structure is formed only in membrane environments. The helical content of gp110 CTD was significantly affected by the negative charge as well as the size of membrane mimics. Based on the elution profiles of the size-exclusion chromatography, we found that gp110 CTD intrinsically forms a trimer, revealing that a trimerization region may exist in the C-terminal domain of gp110 like the ectodomain of gp110. The mutation of NLS (RRRR) to RTTR does not affect the overall structure of gp110 CTD in membrane mimics, while the helical propensity in a buffer solution was slightly different between the wild-type and the mutant proteins. This result suggests that not only the helicity induced in membrane environment but also the local structure around NLS may be related to trafficking to the nuclear membrane. More detailed structural difference between the wild-type and the mutant in membrane environment was examined using synthetic two peptides including the wild-type NLS and the mutant NLS

Awareness Trainings and Detecting Jihadists among Asylum Seekers: A Case Study from the Netherlands

NARCIS (Netherlands)

van Wijk, J.; Bolhuis, M.P.

2017-01-01

Dutch frontline professionals who work with asylum seekers receive awareness training to assist them in identifying possible signs of jihadist convictions. During these training sessions, they are provided with a complex, ambiguous, and multi-interpretable advice on how to detect such convictions.

Eumedion in the Dutch Corporate Governance and Sustainability Landscape

NARCIS (Netherlands)

Hermes, Niels; Hooghiemstra, Reggy; van Veen, Kees

2016-01-01

Eumedion is a Dutch foundation representing the interests of Dutch and foreign institutional investors with investments in Dutch listed companies. In particular, it represents the interests of these participants in the field of corporate governance and sustainability. The foundation was established

The Pathogenicity of Anti-β2GP1-IgG Autoantibodies Depends on Fc Glycosylation

Directory of Open Access Journals (Sweden)

Christoph Fickentscher

2015-01-01

Full Text Available To analyze the glycosylation of anti-β2GP1, we investigated purified IgG from healthy children, patients with APS, and asymptomatic adult carriers of antiphospholipid antibodies. We observed that in the sera of healthy children and of patients with APS, IgG3 and IgG2 were predominant, respectively. The potentially protective anti-β2GP1-IgM was lower in the sera of healthy children. Although anti-β2GP1-associated C1q did not differ between children and patients with antiphospholipid syndrome, the associated C3c was significantly higher in the sera of healthy children. This indicates a more efficient clearance of anti-β2GP1 immune complexes in the healthy children. This clearance is not accompanied by inflammation or coagulatory events. It is likely that the most important pathogenic factor of the anti-β2GP1-IgG is related to the different glycosylation observed in healthy and diseased individuals. We detected a significantly higher sialylation of anti-β2GP1-IgG isolated from the sera of healthy children and asymptomatic adults when compared with that of patients with clinically apparent antiphospholipid syndrome. Low sialylated IgG reportedly ameliorates inflammation and inflammation promotes hyposialylation. Thus, both reactions create a vicious circle that precipitates the pathology of the antiphospholipid syndrome including thrombus-formation. We conclude that the increased sialylation of anti-β2GP1-IgG of sera of healthy individuals limits their pathogenicity.

Dutch euthanasia revisited.

Science.gov (United States)

Fenigsen, R

1997-01-01

The results of a follow-up study of euthanasia by the Dutch government, five years after the first study, were published on November 26, 1996. This article provides a detailed review of the two reports comparing and contrasting the statistics cited therein. The author notes that the "rules of careful conduct" proposed by the courts and by the Royal Dutch Society of Medicine were frequently disregarded. Special topics included for the first time in the second study were the notification and non-prosecution procedure, euthanasia of newborns and infants, and assisted suicide in psychiatric practice. The authors of the follow-up report state that it would be desirable to reduce the number of "terminations of life without patients' request," but this must be the common responsibility of the doctor and the patient. They suggest that the person who does not wish to have his life terminated should declare this clearly, in advance, verbally and in writing, preferably in the form of a living will. Involuntary euthanasia was rampant in 1990 and equally rampant in 1995. The author concludes that Dutch doctors who practice euthanasia are not on the slippery slope. From the very beginning, they have been at the bottom.

Genome profiling (GP method based classification of insects: congruence with that of classical phenotype-based one.

Directory of Open Access Journals (Sweden)

Shamim Ahmed

Full Text Available Ribosomal RNAs have been widely used for identification and classification of species, and have produced data giving new insights into phylogenetic relationships. Recently, multilocus genotyping and even whole genome sequencing-based technologies have been adopted in ambitious comparative biology studies. However, such technologies are still far from routine-use in species classification studies due to their high costs in terms of labor, equipment and consumables.Here, we describe a simple and powerful approach for species classification called genome profiling (GP. The GP method composed of random PCR, temperature gradient gel electrophoresis (TGGE and computer-aided gel image processing is highly informative and less laborious. For demonstration, we classified 26 species of insects using GP and 18S rDNA-sequencing approaches. The GP method was found to give a better correspondence to the classical phenotype-based approach than did 18S rDNA sequencing employing a congruence value. To our surprise, use of a single probe in GP was sufficient to identify the relationships between the insect species, making this approach more straightforward.The data gathered here, together with those of previous studies show that GP is a simple and powerful method that can be applied for actually universally identifying and classifying species. The current success supported our previous proposal that GP-based web database can be constructible and effective for the global identification/classification of species.

Correlation between the GP78 Gene Polymorphism and Coronary Atherosclerotic Heart Disease

Directory of Open Access Journals (Sweden)

Long Wang

2018-01-01

Full Text Available Objective: To study the correlation between the GP78 gene polymorphism and blood fat, blood glucose, blood pressure and coronary atherosclerotic heart disease. Methods: A total of 72 patients with coronary atherosclerotic heart disease were selected as the observation group, and 68 healthy participants were selected as the control group. The gp78 gene polymorphism of both groups was studied via polymerase chain reaction-restriction fragment length polymorphism (RFLP. At the same time, the multiple expression quantities of the GP78 gene in the tissues of both groups were tested via fluorogenic quantitative PCR, enzyme-linked immunosorbent assay (ELISA and Western-blotting assay. Furthermore, the blood fat, blood glucose and blood pressure of subjects in both groups were tested. Results: The percentages of the gp78 gene polymorphisms of Arg/Arg, Arg/Gly and Gly/Gly at the 145 locus of the study subjects in the observation group were 12.3%, 43.2% and 44.5%, respectively, while those in the control group were 74.3%, 11.2% and 14.5%, respectively, and there were significant differences between both groups. Based on the test results of the blood fat, blood glucose and blood pressure of the objects in the observation group and control group, significant differences were found between the two groups (P<0.05. Conclusion: There was a significant correlation between the 145 locus of the gp89 gene and coronary atherosclerotic heart disease, indexes of blood fat, blood glucose and blood pressure. Keywords: blood fat, blood glucose, blood pressure, coronary sclerosis, heart disease

The Dutch National Research Agenda in Perspective

OpenAIRE

2017-01-01

The Dutch National Research Agenda is a set of national priorities that are set by scientists working in conjunction with corporations, civil society organisations, and interested citizens. The agenda consolidates the questions that scientific research will be focused on in the coming year. This book covers the current status of the Dutch National Research Agenda and considers what changes and adjustments may need to be made to the process in order to keep Dutch national research at the top o...

Fourth Dutch Process Security Control Event

NARCIS (Netherlands)

Luiijf, H.A.M.; Zielstra, A.

2010-01-01

On December 1st, 2009, the fourth Dutch Process Control Security Event took place in Baarn, The Netherlands. The security event with the title ‘Manage IT!’ was organised by the Dutch National Infrastructure against Cybercrime (NICC). Mid of November, a group of over thirty people participated in the

Losses on Dutch residential mortgage insurances

NARCIS (Netherlands)

Francke, M.K.; Schilder, F.P.W.

2014-01-01

Purpose - This paper aims to study the data on losses on mortgage insurance in the Dutch housing market to find the key drivers of the probability of loss. In 2013, 25 per cent of all Dutch homeowners were "under water": selling the property will not cover the outstanding mortgage debt. The

Lessons learned from an Internet GP information system.

Science.gov (United States)

Briggs, J S; Bradley, M P

1998-01-01

We describe the prototype of an application that in actual use would allow GPs to find out more information about consultants at hospitals. This would aid the GP in making the decision about which consultant a patient should be referred to. The requirements of the application from the GP's perspective are described, together with some of the issues that have to be resolved before hospitals can provide the necessary information in a standard format. The application is implemented as a client--server system using standard Internet technologies such as Java and HTML. This architecture has a number of advantages but also revealed some issues concerning security and the format of data, among other things. The project showed that there is a desire for such a system and that that desire can be fulfilled at a relatively low cost.

Determinants of Dutch general practitioners’ nutrition and physical activity guidance practices

NARCIS (Netherlands)

Hiddink, G.J.; Woerkum, van C.M.J.; Dillen, van S.M.E.

2013-01-01

Objective General practitioners (GP) are uniquely placed to guide their patients on nutrition and physical activity. The aims of the present study were to assess: (i) the extent to which GP guide on nutrition and physical activity; (ii) the determinants that cause GP to give guidance on nutrition

Oncostatin M induces heat hypersensitivity by gp130-dependent sensitization of TRPV1 in sensory neurons

Directory of Open Access Journals (Sweden)

Langeslag Michiel

2011-12-01

Full Text Available Abstract Oncostatin M (OSM is a member of the interleukin-6 cytokine family and regulates eg. gene activation, cell survival, proliferation and differentiation. OSM binds to a receptor complex consisting of the ubiquitously expressed signal transducer gp130 and the ligand binding OSM receptor subunit, which is expressed on a specific subset of primary afferent neurons. In the present study, the effect of OSM on heat nociception was investigated in nociceptor-specific gp130 knock-out (SNS-gp130-/- and gp130 floxed (gp130fl/fl mice. Subcutaneous injection of pathophysiologically relevant concentrations of OSM into the hind-paw of C57BL6J wild type mice significantly reduced paw withdrawal latencies to heat stimulation. In contrast to gp130fl/fl mice, OSM did not induce heat hypersensitivity in vivo in SNS-gp130-/- mice. OSM applied at the receptive fields of sensory neurons in in vitro skin-nerve preparations showed that OSM significantly increased the discharge rate during a standard ramp-shaped heat stimulus. The capsaicin- and heat-sensitive ion channel TRPV1, expressed on a subpopulation of nociceptive neurons, has been shown to play an important role in inflammation-induced heat hypersensitivity. Stimulation of cultured dorsal root ganglion neurons with OSM resulted in potentiation of capsaicin induced ionic currents. In line with these recordings, mice with a null mutation of the TRPV1 gene did not show any signs of OSM-induced heat hypersensitivity in vivo. The present data suggest that OSM induces thermal hypersensitivity by directly sensitizing nociceptors via OSMR-gp130 receptor mediated potentiation of TRPV1.

Quality assurance in postgraduate pathology training the Dutch way: regular assessment, monitoring of training programs but no end of training examination.

Science.gov (United States)

van der Valk, Paul

2016-01-01

It might seem self-evident that in the transition from a supervised trainee to an independent professional who is no longer supervised, formal assessment of whether the trainee knows his/her trade well enough to function independently is necessary. This would then constitute an end of training examination. Such examinations are practiced in several countries but a rather heterogeneous situation exists in the EU countries. In the Netherlands, the training program is not concluded by a summative examination and reasons behind this situation are discussed. Quality assurance of postgraduate medical training in the Netherlands has been developed along two tracks: (1) not a single testing moment but continuous evaluation of the performance of the trainee in 'real time' situations and (2) monitoring of the quality of the offered training program through regular site-visits. Regular (monthly and/or yearly) evaluations should be part of every self-respecting training program. In the Netherlands, these evaluations are formative only: their intention is to provide the trainee a tool by which he or she can see whether they are on track with their training schedule. In the system in the Netherlands, regular site-visits to training programs constitute a crucial element of quality assurance of postgraduate training. During the site-visit, the position and perceptions of the trainee are key elements. The perception by the trainee of the training program, the institution (or department) offering the training program, and the professionals involved in the training program is explicitly solicited and systematically assessed. With this two-tiered approach high-quality postgraduate training is assured without the need for an end of training examination.

Teaching the Dutch how to pronounce English

NARCIS (Netherlands)

Frans Hermans; Peter Sloep

2015-01-01

The Dutch overestimate their English speaking skills. Their pronunciation is not always convincing and certain pronunciation mistakes are easily recognised as being typical for Dutch speakers of English. Although intelligibility cannot exist without adequate pronunciation, teaching English

Teaching the Dutch how to pronounce English

NARCIS (Netherlands)

Hermans, Frans; Sloep, Peter

2018-01-01

The Dutch overestimate their English speaking skills. Their pronunciation is not always convincing, and certain pronunciation mistakes are easily recognised as being typical for Dutch speakers of English. Although intelligibility cannot exist without adequate pronunciation, teaching English

'I need her to be a doctor': patients' experiences of presenting health information from the internet in GP consultations.

Science.gov (United States)

Bowes, Parvathy; Stevenson, Fiona; Ahluwalia, Sanjiv; Murray, Elizabeth

2012-11-01

Patients are increasingly using the internet for health-related information and may bring this to a GP consultation. There is scant information about why patients do this and what they expect from their GP. The aim was to explore patients' motivation in presenting information, their perception of the GP's response and what they wanted from their doctor. Qualitative study based in North London involving patients with experience of bringing health information from the internet to their GP. Semi-structured face-to-face and telephone interviews using a critical incident technique, recorded, transcribed verbatim, and subjected to thematic analysis by a multidisciplinary team of researchers. Twenty-six interviews were completed. Participants reported using the internet to become better informed about their health and hence make best use of the limited time available with the GP and to enable the GP to take their problem more seriously. Patients expected their GP to acknowledge the information; discuss, explain, or contextualise it; and offer a professional opinion. Patients tended to prioritise the GP opinion over the internet information. However, if the GP appeared disinterested, dismissive or patronising patients reported damage to the doctor-patient relationship, occasionally to the extent of seeking a second opinion or changing their doctor. This is the first in-depth qualitative study to explore why patients present internet information to their GP within the consultation and what they want when they do this. This information should help GPs respond appropriately in such circumstances.

GPs' experiences with out-of-hours GP cooperatives: a survey study from the Netherlands.

Science.gov (United States)

Smits, Marleen; Keizer, Ellen; Huibers, Linda; Giesen, Paul

2014-09-01

Out-of-hours primary care has been provided by general practitioner (GP) cooperatives since the year 2000 in the Netherlands. Early studies in countries with similar organizational structures showed positive GP experiences. However, nowadays it is said that GPs experience a high workload at the cooperative and that they outsource a considerable part of their shifts. To examine positive and negative experiences of GPs providing out-of-hours primary care, and the frequency and reasons for outsourcing shifts. A cross-sectional observational survey among 688 GPs connected to six GP cooperatives in the Netherlands, using a web-based questionnaire. The response was 55% (n = 378). The main reasons for working in GP cooperatives were to retain registration as GP (79%) and remain experienced in acute care (74%). GPs considered the peak hours (81%) and the high number of patients (73%) as the most negative aspects. Most GPs chose to provide the out-of-hours shifts themselves: 85% outsourced maximally 25% of their shifts. The percentage of outsourced shifts increased with age. Main reasons for outsourcing were the desire to have more private time (76%); the high workload in daytime practice (71%); and less the workload during out-of-hours (46%). GPs are motivated to work in out-of-hours GP cooperatives, and they outsource few shifts. GPs consider the peak load and the large number of (non-urgent) help requests as the most negative aspects. To motivate and involve GPs for 7 × 24-h primary care, it is important to set limits on their workload.

Host-Primed Ebola Virus GP Exposes a Hydrophobic NPC1 Receptor-Binding Pocket, Revealing a Target for Broadly Neutralizing Antibodies.

Science.gov (United States)

Bornholdt, Zachary A; Ndungo, Esther; Fusco, Marnie L; Bale, Shridhar; Flyak, Andrew I; Crowe, James E; Chandran, Kartik; Saphire, Erica Ollmann

2016-02-23

The filovirus surface glycoprotein (GP) mediates viral entry into host cells. Following viral internalization into endosomes, GP is cleaved by host cysteine proteases to expose a receptor-binding site (RBS) that is otherwise hidden from immune surveillance. Here, we present the crystal structure of proteolytically cleaved Ebola virus GP to a resolution of 3.3 Å. We use this structure in conjunction with functional analysis of a large panel of pseudotyped viruses bearing mutant GP proteins to map the Ebola virus GP endosomal RBS at molecular resolution. Our studies indicate that binding of GP to its endosomal receptor Niemann-Pick C1 occurs in two distinct stages: the initial electrostatic interactions are followed by specific interactions with a hydrophobic trough that is exposed on the endosomally cleaved GP1 subunit. Finally, we demonstrate that monoclonal antibodies targeting the filovirus RBS neutralize all known filovirus GPs, making this conserved pocket a promising target for the development of panfilovirus therapeutics. Ebola virus uses its glycoprotein (GP) to enter new host cells. During entry, GP must be cleaved by human enzymes in order for receptor binding to occur. Here, we provide the crystal structure of the cleaved form of Ebola virus GP. We demonstrate that cleavage exposes a site at the top of GP and that this site binds the critical domain C of the receptor, termed Niemann-Pick C1 (NPC1). We perform mutagenesis to find parts of the site essential for binding NPC1 and map distinct roles for an upper, charged crest and lower, hydrophobic trough in cleaved GP. We find that this 3-dimensional site is conserved across the filovirus family and that antibody directed against this site is able to bind cleaved GP from every filovirus tested and neutralize viruses bearing those GPs. Copyright © 2016 Bornholdt et al.

[Expression and significance of P-gp/mdr1 mRNA, MRP and LRP in non-Hodgkin's lymphoma].

Science.gov (United States)

Li, Le; Su, Li-ping; Ma, Li; Zhao, Jin; Zhu, Lei; Zhou, Yong-an

2009-03-01

To explore the expression and clinical significance of P-glycoprotein (P-gp)/mdr1mRNA, multidrug resistance-associated protein (MRP) and lung resistance protein (LRP) in newly diagnosed non-Hodgkin's lymphoma. mdr1 mRNA of in 41 patients with non-Hodgkin's lymphoma was assayed by semi-quantitative RT-PCR. The expressions of P-gp, MRP and LRP proteins in lymph node viable blasts were identified by flow cytometry. The results were compared with those obtained from control cases, and the correlation of the changes with clinical outcomes was analyzed. (1) Among the 41 cases, the positive expression of P-gp protein was detected in 8 cases, MRP in 7 cases, LRP in 15 cases, and mdr 1 mRNA in 11 cases. (2) The P-gp and LRP levels in NHL were significantly higher than those in control group, but MRP wasn't. The P-gp over-expression was significantly associated with mdr1mRNA (r = 0.396, P = 0.01). No correlation was showed among the expressions of P-gp, MRP and LRP. (3) Patients with P-gp expression had a poorer outcome of chemotherapy than those with P-gp-negative (P = 0.005). P-gp expression was significantly associated with higher clinical stage (P = 0.046) and elevated serum lactate dehydrogenase level (P = 0.032), but not associated with malignant degree (P = 0.298). MRP had no impact on the outcome of chemotherapy (P = 0.212), and wasn't significantly associated with higher clinical stage (P = 0.369), elevated LDH (P = 0.762) and higher malignant degree (P = 0.451). Patients with LRP expression had a poorer outcome of chemotherapy than those LRP-negative (P = 0.012). LRP expression was significantly associated with higher clinical stage (P = 0.0019), elevated LDH (P = 0.02) and higher malignant degree (P = 0.01). The data of this study indicate that P-gp and LRP expressions but not MRP expression are important in the mechanism of drug resistance associated with a poor clinical outcome in previously untreated NHL.

N-acetylcysteine prevents HIV gp 120-related damage of human cultured astrocytes: correlation with glutamine synthase dysfunction

Directory of Open Access Journals (Sweden)

Costa Nicola

2007-12-01

Full Text Available Abstract Background HIV envelope gp 120 glycoprotein is released during active HIV infection of brain macrophages thereby generating inflammation and oxidative stress which contribute to the development of the AIDS-Dementia Complex (ADC. Gp120 has also been found capable to generate excitotoxic effect on brain tissue via enhancement of glutamatergic neurotransmission, leading to neuronal and astroglial damage, though the mechanism is still to be better understood. Here we investigated on the effect of N-acetylcysteine (NAC, on gp120-induced damage in human cultured astroglial cells and the possible contribution of gp120-related reacting oxygen species (ROS in the imbalanced activity of glutamine synthase (GS, the enzyme that metabolizes glutamate into glutamine within astroglial cells playing a neuroprotective role in brain disorders. Results Incubation of Lipari human cultured astroglial cells with gp 120 (0.1–10 nM produced a significant reduction of astroglial cell viability and apoptosis as evaluated by TUNEL reaction and flow cytometric analysis (FACS. This effect was accompanied by lipid peroxidation as detected by means of malondialdehyde assay (MDA. In addition, gp 120 reduced both glutamine concentration in astroglial cell supernatants and GS expression as detected by immunocytochemistry and western blotting analysis. Pre-treatment of cells with NAC (0.5–5 mM, dose-dependently antagonised astroglial apoptotic cell death induced by gp 120, an effect accompanied by significant attenuation of MDA accumulation. Furthermore, both effects were closely associated with a significant recovery of glutamine levels in cell supernatants and by GS expression, thus suggesting that overproduction of free radicals might contribute in gp 120-related dysfunction of GS in astroglial cells. Conclusion In conclusion, the present experiments demonstrate that gp 120 is toxic to astroglial cells, an effect accompanied by lipid peroxidation and by altered

Dutch Dwellings

NARCIS (Netherlands)

Vries, de B.; Zee, van der A.; Carp, J.C.; Soddu, C.

2004-01-01

Applying Generative Design (GD) for dwelling is not very common but it opens up the possibility to study whether GD systems can reproduce existing design typologies. Dutch dwellings as an exemplification of a design typology are analysed using the SAR methodology. Building regulations are used as

Does Media Use Result in More Active Communicators? Differences Between Native Dutch and Turkish-Dutch Patients in Information-Seeking Behavior and Participation During Consultations With General Practitioners.

Science.gov (United States)

Schinkel, Sanne; Van Weert, Julia C M; Kester, Jorrit A M; Smit, Edith G; Schouten, Barbara C

2015-08-01

This study investigates differences between native Dutch and Turkish-Dutch patients with respect to media usage before and patient participation during medical consultations with general practitioners. In addition, the authors assessed the relation between patient participation and communication outcomes. The patients were recruited in the waiting rooms of general practitioners, and 191 patients (117 native Dutch, 74 Turkish-Dutch) completed pre- and postconsultation questionnaires. Of this sample, 120 patients (62.8%; 82 native Dutch, 38 Turkish-Dutch) agreed to have their consultations recorded to measure patient participation. Compared with Turkish-Dutch patients of similar educational levels, results showed that native Dutch patients used different media to search for information, participated to a greater extent during their consultations and were more responsive to their general practitioner. With respect to the Turkish-Dutch patients, media usage was related to increased patient participation, which was correlated with having fewer unfulfilled information needs; however, these relations were not found in the native Dutch patient sample. In conclusion, interventions that enhance participation among ethnic minority patients will better fulfill informational needs when such interventions stimulate information-seeking behavior in that group before a medical consultation.

Between local governments and communities : Knowledge exchange and mutual learning in Dutch-Moroccan and Dutch-Turkish municipal partnerships

NARCIS (Netherlands)

van Ewijk, E.

2013-01-01

This PhD dissertation focuses on mutual learning processes of governmental and non-governmental actors involved in Dutch-Moroccan and Dutch-Turkish municipal partnerships in the period 2007-2011. These partnerships aim at strengthening local governance in Morocco and Turkey as well as in the

Marburg Virus Glycoprotein GP2: pH-Dependent Stability of the Ectodomain α-Helical Bundle†

Science.gov (United States)

Harrison, Joseph S.; Koellhoffer, Jayne F.; Chandran, Kartik; Lai, Jonathan R.

2012-01-01

Marburg virus (MARV) and Ebola virus (EBOV) constitute the family Filoviridae of enveloped viruses (filoviruses) that cause severe hemorrhagic fever. Infection by MARV is required for fusion between the host cell and viral membranes, a process that is mediated by the two subunits of the envelope glycoprotein GP1 (surface subunit) and GP2 (transmembrane subunit). Upon viral attachment and uptake, it is believed that the MARV viral fusion machinery is triggered by host factors and environmental conditions found in the endosome. Next, conformational rearrangements in the GP2 ectodomain result in the formation of a highly stable six-helix bundle; this refolding event provides the energetic driving force for membrane fusion. Both GP1 and GP2 from EBOV have been extensively studied, but there is little information available for the MARV glycoproteins. Here we have expressed two variants of the MARV GP2 ectodomain in Escherichia coli and analyzed their biophysical properties. Circular dichroism indicates that the MARV GP2 ectodomain adopts an α-helical conformation, and one variant sediments as a trimer by equilibrium analytical ultracentrifugation. Denaturation studies indicate the α-helical structure is highly stable at pH 5.3 (unfolding energy, ΔGunf H2O, of 33.4 ± 2.5 kcal/mol and melting temperature, Tm, of 75.3 ± 2.1 °C for one variant). Furthermore, we found the α-helical stability to be strongly dependent on pH with higher stability under lower pH conditions (Tm values ranging from ~92 °C at pH 4.0 to ~38 °C at pH 8.0). Mutational analysis suggests two glutamic acid residues (E579 and E580) are partially responsible for this pH-dependent behavior. Based on these results, we hypothesize that pH-dependent folding stability of the MARV GP2 ectodomain provides a mechanism to control conformational preferences such that the six-helix bundle ‘post-fusion’ state is preferred under conditions of appropriately matured endosomes. PMID:22369502

Patients' evaluation of quality of care in general practice: what are the cultural and linguistic barriers?

Science.gov (United States)

Harmsen, J A M; Bernsen, R M D; Bruijnzeels, M A; Meeuwesen, L

2008-07-01

Increased migration implies increased contacts for physicians with patients from diverse cultural backgrounds who have different expectations about healthcare. How satisfied are immigrant patients, and how do they perceive the quality of care? This study investigated which patient characteristics (such as cultural views and language proficiency) are related to patients' satisfaction and perceived quality of care. Patients (n=663) from 38 general practices in Rotterdam (The Netherlands) were interviewed. General satisfaction with the general practitioner (GP) was measured by a report mark. Perceived quality of care was measured using the 'Quote-mi' scale (quality of care through the patient's eyes-for migrants), which contains an ethnic-specific subscale and a communication process subscale. Using multilevel regression techniques, the relation between patient characteristics (ethnicity, age, education, Dutch language proficiency, cultural views) and satisfaction and perceived quality of care was analysed. In general, patients seemed fairly satisfied. Non-Western patients perceived less quality of care and were less satisfied than Dutch-born patients. The older the patients and the more modern cultural views they had, the more satisfied they were about the GP in general, as well as about the communication process. However, non-Western patients holding more modern views were the most critical regarding the ethnic-specific quality items. The poorer patients' Dutch language proficiency, the more negative they were about the communication process. It is concluded that next to communication aspects, especially when the patient's proficiency in Dutch is poor, physician awareness about the patient's cultural views is very important during the consultation. This holds especially true when the immigrant patient seems to be more or less acculturated. Medical students and physicians should be trained to become aware of the relevance of patients' different cultural backgrounds

Nuclear pore complex assembly and maintenance in POM121- and gp210-deficient cells

DEFF Research Database (Denmark)

Stavru, Fabrizia; Nautrup-Pedersen, Gitte; Cordes, Volker C

2006-01-01

So far, POM121 and gp210 are the only known anchoring sites of vertebrate nuclear pore complexes (NPCs) within the lipid bilayer of the nuclear envelope (NE) and, thus, are excellent candidates for initiating the NPC assembly process. Indeed, we demonstrate that POM121 can recruit several...... as depletion of POM121 from human fibroblasts, which do not express gp210, further suggest that NPCs can assemble or at least persist in a POM121- and gp210-free form. This points to extensive redundancies in protein-protein interactions within NPCs and suggests that vertebrate NPCs contain additional membrane...

Binding of radiolabeled asbestos fibers to guinea pig (gp) alveolar macrophages (AM)

International Nuclear Information System (INIS)

Giannotti, M.A.; Tewson, T.J.; Francsechini, M.P.; Scheule, R.K.; Holian, A.

1990-01-01

The mechanism by which fibrogenic particulates cause pulmonary fibrosis in humans is not understood, but is likely to involve the AM. Using two fibrogenic particulates, namely, chrysotile (CHR) and crocidolite (CRO) asbestos and gpAM as components of an in vitro model system, the authors have shown that CHR stimulates the gpAM to release superoxide anion, but CRO does not. To examine whether this difference in stimulatory abilities is a result of differences in cell-asbestos binding they have developed an efficient procedure that radiolabels asbestos fibers while retaining their bioactivity. The fibers are labeled with 68 Ge. The 68 Ge decays into 68 Ga, which then can be detected by its characteristic position emission. Both CHR and CRO asbestos were radiolabled successfully. Mild reaction conditions and short reaction times were found under which >90% of the added 68 Ge and 68 Ga bound to the fibers. The radiolabel was retained even after washing the fibers extensively with physiologic buffers. A density gradient procedure was developed to quantitate the binding of asbestos to gpAM in suspension. The binding of both fibers increased with time over one hr. Thus, these results indicate that although both CHR and CRO interact with the gpAM, only CHR interacts productively to stimulate superoxide anion release

77 FR 20807 - Northwest Pipeline GP; Notice of Application

Science.gov (United States)

2012-04-06

... diameter pipelines away from an adjacent surface coal mine west of Kemmerer, Wyoming. Northwest also... directed to Pam Barnes, Manager Certificates and Tariffs, Northwest Pipeline GP, 295 Chipeta Way, Salt Lake...

Determining the Structure of an Unliganded and Fully Glycosylated SIV gp120 Envelope Glycoprotein

Energy Technology Data Exchange (ETDEWEB)

Chen, Bing; Vogan, Erik M.; Gong, Haiyun; Skehel, John J.; Wiley, Don C.; Harrison, Stephen C. (Harvard-Med); (NIMR)

2010-07-13

HIV/SIV envelope glycoproteins mediate the first steps in viral infection. They are trimers of a membrane-anchored polypeptide chain, cleaved into two fragments known as gp120 and gp41. The structure of HIV gp120 bound with receptor (CD4) has been known for some time. We have now determined the structure of a fully glycosylated SIV gp120 envelope glycoprotein in an unliganded conformation by X-ray crystallography at 4.0 {angstrom} resolution. We describe here our experimental and computational approaches, which may be relevant to other resolution-limited crystallographic problems. Key issues were attention to details of beam geometry mandated by small, weakly diffracting crystals, and choice of strategies for phase improvement, starting with two isomorphous derivatives and including multicrystal averaging. We validated the structure by analyzing composite omit maps, averaged among three distinct crystal lattices, and by calculating model-based, SeMet anomalous difference maps. There are at least four ordered sugars on many of the thirteen oligosaccharides.

Commissioning of the iGp Feedback System at DAΦNE

International Nuclear Information System (INIS)

Drago, A.; Fox, J.D.; Teytelman, D.; Tobiyama, M.

2011-01-01

The iGp (Integrated Gigasample Processor) is an innovative digital bunch-by-bunch feedback system developed by a KEK / SLAC / INFN-LNF joint collaboration. The processing unit can sample at 500 MHz and compute the bunch-by-bunch output signal for up to ∼5000 bunches. The feedback gateware code is implemented inside just one FPGA (Field Programmable Gate Array) chip, a Xilinx Virtex-II. The FPGA implements two banks of 16-tap FIR (Finite Impulse Response) filters. Each filter is realtime programmable through the operator interface. At DAΦNE, the Frascati Φ-Factory, two iGp units have been commissioned in the April 2007. The iGp systems have substituted the previous betatron feedback systems. This insertion has been very fast and has shown no problems involving just a substitution of the old, less flexible, digital systems, letting unchanged the baseband analog frontend and backend. The commissioning has been very simple, due to the complete and powerful EPICS operator interface, working well in local and remote operations. The software includes also tools for analyzing post processor data. A description of the commissioning with the operations done is reported.

Aggression Replacement Training for Violent Young Men in a Forensic Psychiatric Outpatient Clinic

NARCIS (Netherlands)

Hornsveld, R.H.; Kraaimaat, F.W.; Muris, P.; Zwets, A.J.; Kanters, T.

2015-01-01

The effects of Aggression Replacement Training (ART) were explored in a group of Dutch violent young men aged 16 to 21 years, who were obliged by the court to follow a treatment program in a forensic psychiatric outpatient clinic. To evaluate the training, patients completed a set of self-report

The Strange Death of Dutch Tolerance: the Timing and Nature of the Pessimist Turn in the Dutch Migration Debate

NARCIS (Netherlands)

Lucassen, Leo; Lucassen, Jan

2015-01-01

In this article we explain why the Dutch nativist turn from the 1990s onwards was nourished both by the political left and the right and what the role was of specific Dutch developments in secularization and libertarian attitudes

Dutch taboo norms.

Science.gov (United States)

Roest, Sander A; Visser, Tessa A; Zeelenberg, René

2018-04-01

This article provides norms for general taboo, personal taboo, insult, valence, and arousal for 672 Dutch words, including 202 taboo words. Norms were collected using a 7-point Likert scale and based on ratings by psychology students from the Erasmus University Rotterdam in The Netherlands. The sample consisted of 87 psychology students (58 females, 29 males). We obtained high reliability based on split-half analyses. Our norms show high correlations with arousal and valence ratings collected by another Dutch word-norms study (Moors et al.,, Behavior Research Methods, 45, 169-177, 2013). Our results show that the previously found quadratic relation (i.e., U-shaped pattern) between valence and arousal also holds when only taboo words are considered. Additionally, words rated high on taboo tended to be rated low on valence, but some words related to sex rated high on both taboo and valence. Words that rated high on taboo rated high on insult, again with the exception of words related to sex many of which rated low on insult. Finally, words rated high on taboo and insult rated high on arousal. The Dutch Taboo Norms (DTN) database is a useful tool for researchers interested in the effects of taboo words on cognitive processing. The data associated with this paper can be accessed via the Open Science Framework ( https://osf.io/vk782/ ).

Interpreting The Chinese Wall knowing Dutch and ‘Dutchness'

NARCIS (Netherlands)

Forceville, C.

2015-01-01

Many film scholars equate "film" with "moving images." But, along with sound and music, language is often no less important for a film’s interpretation. This paper discusses how comprehension of the original Dutch affords subtle aspects of meaning unavailable to viewers who have to rely exclusively

The training of coaching skills: An implementation study

NARCIS (Netherlands)

Veenman, S.

1995-01-01

In this study, the implementation effects of a programme for the training of coaching skills with Dutch school counsellors are described. These school counsellors are expected to provide help and support to primary school teachers. Coaching is a form of in-class support intended to provide teachers

Automatic training of lemmatization rules that handle morphological changes in pre-, in- and suffixes alike

DEFF Research Database (Denmark)

Jongejan, Bart; Dalianis, Hercules

2009-01-01

We propose a method to automatically train lemmatization rules that handle prefix, infix and suffix changes to generate the lemma from the full form of a word. We explain how the lemmatization rules are created and how the lemmatizer works. We trained this lemmatizer on Danish, Dutch, English......, German, Greek, Icelandic, Norwegian, Polish, Slovene and Swedish full form-lemma pairs respectively. We obtained significant improvements of 24 percent for Polish, 2.3 percent for Dutch, 1.5 percent for English, 1.2 percent for German and 1.0 percent for Swedish compared to plain suffix lemmatization...... using a suffix-only lemmatizer. Icelandic deteriorated with 1.9 percent. We also made an observation regarding the number of produced lemmatization rules as a function of the number of training pairs....

Values of serum AFP, GGTⅡ and GP73 in diagnosis of primary hepatocellular carcinoma

Directory of Open Access Journals (Sweden)

ZHU Chen

2014-10-01

Full Text Available ObjectiveTo explore the early diagnostic values of serum alpha-fetoprotein (AFP, gamma-glutamyltransferase Ⅱ (GGTⅡ, and Golgi protein 73 (GP73 in patients with primary hepatocellular carcinoma (PHC. MethodsThe serum specimens of 100 patients with liver diseases (50 cases of hepatitis and liver cirrhosis and 50 cases of PHC and 50 healthy people were collected in our hospital from February 2013 to February 2014. Electrochemical luminescence technique, specific immuno-membrane adsorption assay, and enzyme-linked immunosorbent assay were used to measure the serum levels of AFP, GGTⅡ, and GP73. Comparison of continuous data between multiple groups was made by analysis of variance, and comparison between two groups was made by q test. The receiver operating characteristic (ROC curves of single or combined test results were made, and the areas under the ROC curves (AUCs were calculated. The sensitivity, specificity, and AUCs of AFP, GGTⅡ, GP73, and the combined test were analyzed and compared. ResultsThe level of serum GGTⅡ in the PHC group was significantly different compared with those in the other two groups (F=16.224, P＜0.05, but there was no significant difference between the normal group and the hepatitis and liver cirrhosis group (P＞0.05. Significant differences in serum levels of AFP and GP73 were observed by paired comparison between the PHC group, hepatitis and liver cirrhosis group, and normal group (F=193.128, F=20.231, P＜0.05 for both. When assayed alone, the specificities of GP73, GGTⅡ, and AFP were 69%, 64% and 51%, respectively, and the sensitivities were 92%, 84%, and 76%, respectively. In combined test, the specificity was 94.6% and the sensitivity was 98.8%. ConclusionThe GP73 test is the best performer in the single assays. Combined test of serum AFP, GGTⅡ, and GP73 shows a good diagnostic value for PHC with greatly improved specificity and sensitivity.

Antioxidant enzyme gene delivery to protect from HIV-1 gp120-induced neuronal apoptosis.

Science.gov (United States)

Agrawal, L; Louboutin, J-P; Reyes, B A S; Van Bockstaele, E J; Strayer, D S

2006-12-01

Human immunodeficiency virus-1 (HIV-1) infection in the central nervous system (CNS) may lead to neuronal loss and progressively deteriorating CNS function: HIV-1 gene products, especially gp120, induce free radical-mediated apoptosis. Reactive oxygen species (ROS), are among the potential mediators of these effects. Neurons readily form ROS after gp120 exposure, and so might be protected from ROS-mediated injury by antioxidant enzymes such as Cu/Zn-superoxide dismutase (SOD1) and/or glutathione peroxidase (GPx1). Both enzymes detoxify oxygen free radicals. As they are highly efficient gene delivery vehicles for neurons, recombinant SV40-derived vectors were used for these studies. Cultured mature neurons derived from NT2 cells and primary fetal neurons were transduced with rSV40 vectors carrying human SOD1 and/or GPx1 cDNAs, then exposed to gp120. Apoptosis was measured by terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assay. Transduction efficiency of both neuron populations was >95%, as assayed by immunostaining. Transgene expression was also ascertained by Western blotting and direct assays of enzyme activity. Gp120 induced apoptosis in a high percentage of unprotected NT2-N. Transduction with SV(SOD1) and SV(GPx1) before gp120 challenge reduced neuronal apoptosis by >90%. Even greater protection was seen in cells treated with both vectors in sequence. Given singly or in combination, they protect neuronal cells from HIV-1-gp120 induced apoptosis. We tested whether rSV40 s can deliver antioxidant enzymes to the CNS in vivo: intracerebral injection of SV(SOD1) or SV(GPx1) into the caudate putamen of rat brain yielded excellent transgene expression in neurons. In vivo transduction using SV(SOD1) also protected neurons from subsequent gp120-induced apoptosis after injection of both into the caudate putamen of rat brain. Thus, SOD1 and GPx1 can be delivered by SV40 vectors in vitro or in vivo. This approach may merit consideration for

A single amino acid substitution modulates low-pH-triggered membrane fusion of GP64 protein in Autographa californica and Bombyx mori nucleopolyhedroviruses

International Nuclear Information System (INIS)

Katou, Yasuhiro; Yamada, Hayato; Ikeda, Motoko; Kobayashi, Michihiro

2010-01-01

We have previously shown that budded viruses of Bombyx mori nucleopolyhedrovirus (BmNPV) enter the cell cytoplasm but do not migrate into the nuclei of non-permissive Sf9 cells that support a high titer of Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) multiplication. Here we show, using the syncytium formation assay, that low-pH-triggered membrane fusion of BmNPV GP64 protein (Bm-GP64) is significantly lower than that of AcMNPV GP64 protein (Ac-GP64). Mutational analyses of GP64 proteins revealed that a single amino acid substitution between Ac-GP64 H155 and Bm-GP64 Y153 can have significant positive or negative effects on membrane fusion activity. Studies using bacmid-based GP64 recombinant AcMNPV harboring point-mutated ac-gp64 and bm-gp64 genes showed that Ac-GP64 H155Y and Bm-GP64 Y153H substitutions decreased and increased, respectively, the multiplication and cell-to-cell spread of progeny viruses. These results indicate that Ac-GP64 H155 facilitates the low-pH-triggered membrane fusion reaction between virus envelopes and endosomal membranes.

Lexical preferences in Dutch verbal cluster ordering

NARCIS (Netherlands)

Bloem, J.; Bellamy, K.; Karvovskaya, E.; Kohlberger, M.; Saad, G.

2016-01-01

This study discusses lexical preferences as a factor affecting the word order variation in Dutch verbal clusters. There are two grammatical word orders for Dutch two-verb clusters, with no clear meaning difference. Using the method of collostructional analysis, I find significant associations

Surfactant protein D binds to human immunodeficiency virus (HIV) envelope protein gp120 and inhibits HIV replication

DEFF Research Database (Denmark)

Meschi, Joseph; Crouch, Erika C; Skolnik, Paul

2005-01-01

The envelope protein (gp120) of human immunodeficiency virus (HIV) contains highly conserved mannosylated oligosaccharides. These glycoconjugates contribute to resistance to antibody neutralization, and binding to cell surface lectins on macrophages and dendritic cells. Mannose-binding lectin (MBL......) binds to gp120 and plays a role in defence against the virus. In this study it is demonstrated that surfactant protein D (SP-D) binds to gp120 and inhibits HIV infectivity at significantly lower concentrations than MBL. The binding of SP-D was mediated by its calcium-dependent carbohydrate......-binding activity and was dependent on glycosylation of gp120. Native dodecameric SP-D bound to HIV gp120 more strongly than native trimeric SP-D. Since one common polymorphic form of SP-D is predominantly expressed as trimers and associated with lower blood levels, these individuals may have less effective innate...

Antigenicity and Immunogenicity of RV144 Vaccine AIDSVAX Clade E Envelope Immunogen Is Enhanced by a gp120 N-Terminal Deletion

Science.gov (United States)

Liao, Hua-Xin; Tomaras, Georgia D.; Bonsignori, Mattia; Tsao, Chun-Yen; Hwang, Kwan-Ki; Chen, Haiyan; Lloyd, Krissey E.; Bowman, Cindy; Sutherland, Laura; Jeffries, Thomas L.; Kozink, Daniel M.; Stewart, Shelley; Anasti, Kara; Jaeger, Frederick H.; Parks, Robert; Yates, Nicole L.; Overman, R. Glenn; Sinangil, Faruk; Berman, Phillip W.; Pitisuttithum, Punnee; Kaewkungwal, Jaranit; Nitayaphan, Sorachai; Karasavva, Nicos; Rerks-Ngarm, Supachai; Kim, Jerome H.; Michael, Nelson L.; Zolla-Pazner, Susan; Santra, Sampa; Letvin, Norman L.; Harrison, Stephen C.

2013-01-01

An immune correlates analysis of the RV144 HIV-1 vaccine trial revealed that antibody responses to the gp120 V1/V2 region correlated inversely with infection risk. The RV144 protein immunogens (A244-rp120 and MN-rgp120) were modified by an N-terminal 11-amino-acid deletion (Δ11) and addition of a herpes simplex virus (HSV) gD protein-derived tag (gD). We investigated the effects of these modifications on gp120 expression, antigenicity, and immunogenicity by comparing unmodified A244 gp120 with both Δ11 deletion and gD tag and with Δ11 only. Analysis of A244 gp120, with or without Δ11 or gD, demonstrated that the Δ11 deletion, without the addition of gD, was sufficient for enhanced antigenicity to gp120 C1 region, conformational V2, and V1/V2 gp120 conformational epitopes. RV144 vaccinee serum IgGs bound more avidly to A244 gp120 Δ11 than to the unmodified gp120, and their binding was blocked by C1, V2, and V1/V2 antibodies. Rhesus macaques immunized with the three different forms of A244 gp120 proteins gave similar levels of gp120 antibody titers, although higher antibody titers developed earlier in A244 Δ11 gp120-immunized animals. Conformational V1/V2 monoclonal antibodies (MAbs) gave significantly higher levels of blocking of plasma IgG from A244 Δ11 gp120-immunized animals than IgG from animals immunized with unmodified A244 gp120, thus indicating a qualitative difference in the V1/V2 antibodies induced by A244 Δ11 gp120. These results demonstrate that deletion of N-terminal residues in the RV144 A244 gp120 immunogen improves both envelope antigenicity and immunogenicity. PMID:23175357

Do practice nurse solve future GP capacity problems?

NARCIS (Netherlands)

Lamkaddem, M.; Haan, J. de; Bakker, D. de

2003-01-01

Background: Task delegation is viewed as an important policy instrument to counter foreseen future shortages in GP capacity in the Netherlands. Therefore, a national programme to introduce practice nurses in general practice was launched in 1998 by the National Association of General Practice. In

Potable Water Treatment Facility General Permit (PWTF GP) ...

Science.gov (United States)

2017-08-28

The Final PWTF GP establishes permit eligibility conditions, Notice of Intent (NOI) requirements, effluent limitations, standards, prohibitions, and best management practices for facilities that discharge to waters in the Commonwealth of Massachusetts (including both Commonwealth and Indian country lands) and the State of New Hampshire.

Specific assay measuring binding of /sup 125/I-Gp 120 from HIV to T4/sup +//CD4/sup +/ cells

Energy Technology Data Exchange (ETDEWEB)

Lundin, K.; Nygren, A.; Ramstedt, U.; Gidlund, M.; Wigzell, H.; Arthur, L.O.; Robey, W.G.; Morein, B.

1987-02-26

The HIV (HTLV-III) envelope glycoprotein, Gp120, was isolated from virus-infected tissue culture cells using affinity chromatography. A radioimmunoassay was developed to determine the degree of iodinated Gp120 to target CD4/sup +/ (T4/sup +/) cells. /sup 125/I-Gp120 could be shown to selectively bind to CD4/sup +/ cells only. The Gp120 remained bound to these cells after repeated washes. Monoclonal anti-CD4 antibodies block the binding of Gp120 to CD4/sup +/ cells. Monoclonal antibodies to other cell surface components do not interfere with /sup 125/I-Gp120 binding. All IgG antibodies from HIV seropositive donors tested block /sup 125/I-GP120 binding, though with variable titers. The authors believe that this assay provides further proof for the use of CD4 (T4) as a component of the receptor for HIV. It represents a safe, objective and sensitive method for the analysis of Gp120-CD4 interactions, as well as the potential of antibodies to interfere with this binding. (Auth.). 24 refs.; 2 figs.; 8 tabs.

Rewarding peak avoidance: the Dutch 'Spitsmijden' projects

NARCIS (Netherlands)

Knockaert, J.; Bakens, J.; Ettema, D.F.; Verhoef, E.

2011-01-01

The Dutch road network is becoming increasingly congested. In late 2006, a group of companies, universities and government institutions established the Spitsmijden project. ‘Spitsmijden’ is the Dutch term for ‘avoiding the peak’. This joint initiative aimed to identify and assess a short-term

Sustainable Entrepreneurship in the Dutch Construction Industry

NARCIS (Netherlands)

Klein Woolthuis, R.J.A.

2010-01-01

This article discusses the strategies that sustainable entrepreneurs use to interact with their environment in the Dutch construction industry. The Dutch construction industry is under great pressure to move towards sustainability, and entrepreneurs are believed to be able to play a large role in

Sustainable entrepreneurship in the Dutch construction industry

NARCIS (Netherlands)

Klein Woolthuis, R.J.A.

2010-01-01

This article discusses the strategies that sustainable entrepreneurs use to interact with their environment in the Dutch construction industry. The Dutch construction industry is under great pressure to move towards sustainability, and entrepreneurs are believed to be able to play a large role in

Analysis of purified gp96 preparations from rat and mouse livers using 2-D gel electrophoresis and tandem mass spectrometry.

Science.gov (United States)

Fairburn, B; Muthana, M; Hopkinson, K; Slack, L K; Mirza, S; Georgiou, A S; Espigares, E; Wong, C; Pockley, A G

2006-09-01

The stress protein gp96 exhibits a number of immunological activities, the majority of studies into which have used gp96 purified from a variety of tissues. On the basis of 1-D gel electrophoresis, the purity of these preparations has been reported to range between 70% and 99%. This study analyzed gp96 preparations from rat and mouse livers using 2-D gel electrophoresis and liquid chromatography electrospray ionization tandem mass spectrometry (MS-MS). The procedure for purifying gp96 was reproducible, as similar protein profiles were observed in replicate gels of gp96 preparations. The purity of the preparations was typically around 70%, with minor co-purified proteins of varying molecular weights and mobilities being present. Dominant bands at 95-100 kDa in preparations from Wistar rats and C57BL/6 mice were identified as gp96 by ECL Western blotting. Multiple bands having similar, yet distinct molecular weights and differing pI mobility on ECL Western blots were confirmed as being gp96 in preparations from Wistar rats using MS-MS. The most striking feature of the 2-D gel analysis was the presence of additional dominant bands at 55 kDa in preparations from Wistar rats, and at 75-90 kDa in preparations from C57BL/6 mice. These were identified as gp96 by ECL Western blotting and, in the case of preparations from Wistar rats, by MS-MS. Although the lower molecular weight, gp96-related molecules might be partially degraded gp96, their reproducible presence, definition and characteristics suggest that they are alternative, species-specific isoforms of the molecule. A 55 kDa protein which exhibited a lower pI value than gp96 was present in all preparations and this was identified as calreticulin, another putative immunoregulatory molecule. This study confirms the reproducibility of the gp96 purification protocol and reveals the presence of multiple gp96 isoforms, some of which likely result from post-translational modifications such as differential glycosylation and

The Gender Gap in Second Language Acquisition: Gender Differences in the Acquisition of Dutch among Immigrants from 88 Countries with 49 Mother Tongues.

Science.gov (United States)

van der Slik, Frans W P; van Hout, Roeland W N M; Schepens, Job J

2015-01-01

Gender differences were analyzed across countries of origin and continents, and across mother tongues and language families, using a large-scale database, containing information on 27,119 adult learners of Dutch as a second language. Female learners consistently outperformed male learners in speaking and writing proficiency in Dutch as a second language. This gender gap remained remarkably robust and constant when other learner characteristics were taken into account, such as education, age of arrival, length of residence and hours studying Dutch. For reading and listening skills in Dutch, no gender gap was found. In addition, we found a general gender by education effect for all four language skills in Dutch for speaking, writing, reading, and listening. Female language learners turned out to profit more from higher educational training than male learners do in adult second language acquisition. These findings do not seem to match nurture-oriented explanatory frameworks based for instance on a human capital approach or gender-specific acculturation processes. Rather, they seem to corroborate a nature-based, gene-environment correlational framework in which language proficiency being a genetically-influenced ability interacting with environmental factors such as motivation, orientation, education, and learner strategies that still mediate between endowment and acquiring language proficiency at an adult stage.

Study of coherence strain of GP II zones in an aged aluminum composite

International Nuclear Information System (INIS)

Hernández-Rivera, J.L.; Rivera, J.J. Cruz; Koch, C.T.; Özdöl, V.B.; Martínez-Sánchez, R.

2012-01-01

Highlights: ► Precipitation sequence was changed in 2024 Al alloy. ► Image artifacts ought to the mask size and shape increased the real strain value. ► The strain distribution around experimental GP area was non uniform and more complex than reference. ► The origin of this strain distribution are related to mechanisms by which GP precipitates lose coherence. - Abstract: Strain mapping using the geometric phase analysis (GPA) technique was applied to Al–GP II (Guinier–Preston) nanoscale precipitates, using both high resolution transmission electron microscopy (HRTEM) micrographs as well as the exit wave function (EWF) obtained by focal series reconstruction. The experimental strain results were compared with strain maps obtained from an atomic model which consisted of an Al supercell containing a GP II precipitate. It was built as a reference from literature data. The experimental results demonstrate a complex strain distribution and larger fluctuations than the reference strain maps. These differences were found to be partly a consequence of image artifacts produced by the technique as well as complex microstructural events which were present at the development stage studied.

Curcumin protects microglia and primary rat cortical neurons against HIV-1 gp120-mediated inflammation and apoptosis.

Directory of Open Access Journals (Sweden)

Luyan Guo

Full Text Available Curcumin is a molecule found in turmeric root that has anti-inflammatory, antioxidant, and anti-tumor properties and has been widely used as both an herbal drug and a food additive to treat or prevent neurodegenerative diseases. To explore whether curcumin is able to ameliorate HIV-1-associated neurotoxicity, we treated a murine microglial cell line (N9 and primary rat cortical neurons with curcumin in the presence or absence of neurotoxic HIV-1 gp120 (V3 loop protein. We found that HIV-1 gp120 profoundly induced N9 cells to produce reactive oxygen species (ROS, tumor necrosis factor-α (TNF-α and monocyte chemoattractant protein-1 (MCP-1. HIV-1 gp120 also induced apoptosis of primary rat cortical neurons. Curcumin exerted a powerful inhibitory effect against HIV-1 gp120-induced neuronal damage, reducing the production of ROS, TNF-α and MCP-1 by N9 cells and inhibiting apoptosis of primary rat cortical neurons. Curcumin may exert its biological activities through inhibition of the delayed rectification and transient outward potassium (K(+ current, as curcumin effectively reduced HIV-1 gp120-mediated elevation of the delayed rectification and transient outward K(+ channel current in neurons. We conclude that HIV-1 gp120 increases ROS, TNF-α and MCP-1 production in microglia, and induces cortical neuron apoptosis by affecting the delayed rectification and transient outward K(+ channel current. Curcumin reduces production of ROS and inflammatory mediators in HIV-1-gp120-stimulated microglia, and protects cortical neurons against HIV-1-mediated apoptosis, most likely through inhibition of HIV-1 gp120-induced elevation of the delayed rectification and transient outward K(+ current.

In vitro and in vivo evaluation of the effects of piperine on P-gp function and expression

International Nuclear Information System (INIS)

Han Yi; Chin Tan, Theresa May; Lim, Lee-Yong

2008-01-01

Piperine, a major component of black pepper, is used as spice and nutrient enhancer. The purpose of the present study was to evaluate the effects of acute and prolonged piperine exposure on cellular P-gp expression and function in vitro and in vivo. Piperine at concentrations ranging from 10 to 100 μM, determined by MTT assay to be non-cytotoxic, was observed to inhibit P-gp mediated efflux transport of [ 3 H]-digoxin across L-MDR1 and Caco-2 cell monolayers. The acute inhibitory effect was dependent on piperine concentration, with abolishment of [ 3 H]-digoxin polarized transport attained at 50 μM of piperine. In contrast, prolonged (48 and 72 h) co-incubation of Caco-2 cell monolayers with piperine (50 and 100 μM) increased P-gp activity through an up-regulation of cellular P-gp protein and MDR1 mRNA levels. The up-regulated protein was functionally active, as demonstrated by a higher degree of [ 3 H]-digoxin efflux across the cell monolayers, but the induction was readily reversed by the removal of the spice from the culture medium. Peroral administration of piperine at the dose of 112 μg/kg body weight/day to male Wistar rats for 14 consecutive days also led to increased intestinal P-gp levels. However, there was a concomitant reduction in the rodent liver P-gp although the kidney P-gp level was unaffected. Our data suggest that caution should be exercised when piperine is to be co-administered with drugs that are P-gp substrates, particularly for patients whose diet relies heavily on pepper

Energetics of dendrimer binding to HIV-1 gp120-CD4 complex and mechanismic aspects of its role as an entry-inhibitor

International Nuclear Information System (INIS)

Saurabh, Suman; Sahoo, Anil Kumar; Maiti, Prabal K.

2016-01-01

Experiments and computational studies have established that de-protonated dendrimers (SPL7013 and PAMAM) act as entry-inhibitors of HIV. SPL7013 based Vivagel is currently under clinical development. The dendrimer binds to gp120 in the gp120-CD4 complex, destabilizes it by breaking key contacts between gp120 and CD4 and prevents viral entry into target cells. In this work, we provide molecular details and energetics of the formation of the SPL7013-gp120-CD4 ternary complex and decipher modes of action of the dendrimer in preventing viral entry. It is also known from experiments that the dendrimer binds weakly to gp120 that is not bound to CD4. It binds even more weakly to the CD4-binding region of gp120 and thus cannot directly block gp120-CD4 complexation. In this work, we examine the feasibility of dendrimer binding to the gp120-binding region of CD4 and directly blocking gp120-CD4 complex formation. We find that the process of the dendrimer binding to CD4 can compete with gp120-CD4 binding due to comparable free energy change for the two processes, thus creating a possibility for the dendrimer to directly block gp120-CD4 complexation by binding to the gp120-binding region of CD4. (paper)

Energetics of dendrimer binding to HIV-1 gp120-CD4 complex and mechanismic aspects of its role as an entry-inhibitor

Science.gov (United States)

Saurabh, Suman; Sahoo, Anil Kumar; Maiti, Prabal K.

2016-10-01

Experiments and computational studies have established that de-protonated dendrimers (SPL7013 and PAMAM) act as entry-inhibitors of HIV. SPL7013 based Vivagel is currently under clinical development. The dendrimer binds to gp120 in the gp120-CD4 complex, destabilizes it by breaking key contacts between gp120 and CD4 and prevents viral entry into target cells. In this work, we provide molecular details and energetics of the formation of the SPL7013-gp120-CD4 ternary complex and decipher modes of action of the dendrimer in preventing viral entry. It is also known from experiments that the dendrimer binds weakly to gp120 that is not bound to CD4. It binds even more weakly to the CD4-binding region of gp120 and thus cannot directly block gp120-CD4 complexation. In this work, we examine the feasibility of dendrimer binding to the gp120-binding region of CD4 and directly blocking gp120-CD4 complex formation. We find that the process of the dendrimer binding to CD4 can compete with gp120-CD4 binding due to comparable free energy change for the two processes, thus creating a possibility for the dendrimer to directly block gp120-CD4 complexation by binding to the gp120-binding region of CD4.

Structural and biochemical characterization of phage λ FI protein (gpFI) reveals a novel mechanism of DNA packaging chaperone activity.

Science.gov (United States)

Popovic, Ana; Wu, Bin; Arrowsmith, Cheryl H; Edwards, Aled M; Davidson, Alan R; Maxwell, Karen L

2012-09-14

One of the final steps in the morphogenetic pathway of phage λ is the packaging of a single genome into a preformed empty head structure. In addition to the terminase enzyme, the packaging chaperone, FI protein (gpFI), is required for efficient DNA packaging. In this study, we demonstrate an interaction between gpFI and the major head protein, gpE. Amino acid substitutions in gpFI that reduced the strength of this interaction also decreased the biological activity of gpFI, implying that this head binding activity is essential for the function of gpFI. We also show that gpFI is a two-domain protein, and the C-terminal domain is responsible for the head binding activity. Using nuclear magnetic resonance spectroscopy, we determined the three-dimensional structure of the C-terminal domain and characterized the helical nature of the N-terminal domain. Through structural comparisons, we were able to identify two previously unannotated prophage-encoded proteins with tertiary structures similar to gpFI, although they lack significant pairwise sequence identity. Sequence analysis of these diverse homologues led us to identify related proteins in a variety of myo- and siphophages, revealing that gpFI function has a more highly conserved role in phage morphogenesis than was previously appreciated. Finally, we present a novel model for the mechanism of gpFI chaperone activity in the DNA packaging reaction of phage λ.

Characterization of humoral responses to soluble trimeric HIV gp140 from a clade A Ugandan field isolate.

Science.gov (United States)

Visciano, Maria Luisa; Tagliamonte, Maria; Stewart-Jones, Guillaume; Heyndrickx, Leo; Vanham, Guido; Jansson, Marianne; Fomsgaard, Anders; Grevstad, Berit; Ramaswamy, Meghna; Buonaguro, Franco M; Tornesello, Maria Lina; Biswas, Priscilla; Scarlatti, Gabriella; Buonaguro, Luigi

2013-07-08

Trimeric soluble forms of HIV gp140 envelope glycoproteins represent one of the closest molecular structures compared to native spikes present on intact virus particles. Trimeric soluble gp140 have been generated by several groups and such molecules have been shown to induce antibodies with neutralizing activity against homologous and heterologous viruses. In the present study, we generated a recombinant trimeric soluble gp140, derived from a previously identified Ugandan A-clade HIV field isolate (gp14094UG018). Antibodies elicited in immunized rabbits show a broad binding pattern to HIV envelopes of different clades. An epitope mapping analysis reveals that, on average, the binding is mostly focused on the C1, C2, V3, V5 and C5 regions. Immune sera show neutralization activity to Tier 1 isolates of different clades, demonstrating cross clade neutralizing activity which needs to be further broadened by possible structural modifications of the clade A gp14094UG018. Our results provide a rationale for the design and evaluation of immunogens and the clade A gp14094UG018 shows promising characteristics for potential involvement in an effective HIV vaccine with broad activity.

Arousing Discontent : Dutch Pornographic Plays, 1670-1800

NARCIS (Netherlands)

Leemans, I.B.

2012-01-01

n the second half of the seventeenth century, the Dutch Republic became the "sex shop" of Europe, printing large varieties of erotic works and distributing them through various reader groups. The production of pornographic works also inspired Dutch authors, who developed new forms of erotic prose

Leukemia: Derived heat shock protein gp96-peptide complex ...

African Journals Online (AJOL)

Jane

2011-06-27

Jun 27, 2011 ... Leukemia is a malignant clonal disease in hematopoietic stem cells that is typically treated with chemotherapy and radiotherapy. However ..... with autologous tumor-derived heatshock protein gp96 after liver resection for ...

The attitudes of Dutch fertility specialists towards the addition of genetic testing in screening of tubal factor infertility.

Science.gov (United States)

Malogajski, Jelena; Jansen, Marleen E; Ouburg, Sander; Ambrosino, Elena; Terwee, Caroline B; Morré, Servaas A

2017-06-01

This study aims to identify elements perceived by Dutch fertility specialists as barriers and facilitators for the introduction of genetic testing, and their attitudes towards the use of genetic information. The genetic test would be implemented in routine screening for tubal pathology and identifies SNPs relevant for the immune response causing tubal pathology. Experienced reproductive specialists working in Dutch Academic Hospitals were interviewed. Based on the results of four interviews a questionnaire was developed and used to survey medical doctors in six out of eight Dutch Academic hospitals. 60.4% (n=91) stated that the addition of genetic markers to the Chlamydia trachomatis antibody test (CAT) in screening for tubal pathology would increase screening accuracy. 68.2% (n=90) agreed they would require additional training on clinical genetics. Clinical utility (91.2%, n=91) and cost-effectiveness (95.6%, n=91) were recognized by the respondents as important factors in gaining support for the new screening strategy. In summary, respondents showed a positive attitude towards the implementation of a genetic test combined with CAT for tubal factor infertility (TFI) screening. To gain their support the majority of respondents agreed that clinical utility, specifically cost-effectiveness, is an important factor. Comprehensive research about economic implications and utility regarding the introduction of genomic markers should be the next step in the implementation strategy. Furthermore, education and training would need to be developed and offered to fertility care professionals about genetic markers, their interpretation, and implications for clinical decision-making. Copyright © 2017 Elsevier B.V. All rights reserved.

[The NHG guideline 'Sleep problems and sleeping pills'].

Science.gov (United States)

Damen-van Beek, Zamire; Lucassen, Peter L B J; Gorgels, Wim; Smelt, Antonette F H; Knuistingh Neven, Arie; Bouma, Margriet

2015-01-01

The Dutch College of General Practitioners' (NHG) guideline 'Sleep problems and sleeping pills' provides recommendations for the diagnosis and treatment of the most prevalent sleep problems and for the management of chronic users of sleeping pills. The preferred approach for sleeplessness is not to prescribe medication but to give information and behavioural advice. Practice assistants of the Dutch Association of Mental Health and Addiction Care are also expected to be able to undertake this management. The GP may consider prescribing sleeping pills for a short period only in cases of severe insomnia with considerable distress. Chronic users of sleeping pills should be advised by the GP to stop using them or to reduce the dose gradually (controlled dose reduction). The GP may refer patients with suspected obstructive sleep apnoea (OSA) to a pulmonary or ear, nose and throat specialist or neurologist for further diagnosis depending on the regional arrangements. The GP may then consider the cardiovascular risk factors commonly present with OSA. In patients with restless legs syndrome (RLS) who continue to experience major distress despite being given advice without the prescription of medication, the GP may consider prescribing a dopamine agonist.

HIV-gp120 and physical dependence to buprenorphine.

Science.gov (United States)

Palma, J; Abood, M E; Benamar, K

2015-05-01

Opioids are among the most effective and commonly used analgesics in clinical practice for severe pain. However, the use of opioid medications is clinically limited by several adverse properties including dependence. While opioid dependence is a complex health condition, the treatment of HIV-infected individuals with opioid dependence presents additional challenges. The goal of this study was to examine the physical dependence to buprenorphine in the context of HIV. Young adult male rats (Sprague-Dawley) were pretreated with HIV-1 envelope glycoprotein 120 (gp120) injected into the periaqueductal gray area (PAG) and we examined the impact on physical dependence to opioid. It was found that the physical dependence to methadone occurred earlier than that to buprenorphine, and that gp120 did not enhance or precipitate the buprenorphine withdrawal. The results suggest that buprenorphine could be the better therapeutic option to manage opioid dependence in HIV. Copyright © 2015. Published by Elsevier Ireland Ltd.

Studies on adsorptions of metallic ions in water by zirconium glyphosate (ZrGP): Behaviors and mechanisms

International Nuclear Information System (INIS)

Jia Yunjie; Zhang Yuejuan; Wang Runwei; Fan Faying; Xu Qinghong

2012-01-01

A new adsorbent named zirconium glyphosate [Zr(O 3 PCH 2 NHCH 2 COOH) 2 ·0.5H 2 O, denoted as ZrGP] and its selective adsorptions to Pb 2+ , Cd 2+ , Mg 2+ and Ca 2+ ions in water were reported in this paper. Compared to other zirconium adsorbents, such as zirconium phosphate [Zr(HPO 4 ) 2 ], ZrGP exhibited highly selective adsorption to Pb 2+ in solution which contained Pb 2+ , Cd 2+ , Mg 2+ and Ca 2+ ions. The loaded ZrGP with metallic ions can be efficaciously regenerated by aqueous solution of HCl (1.0 M) without any noticeable capacity loss, and almost all of it can be reused and recycled. The memory effect on structural regeneration of ZrGP was also found when Mg 2+ and Ca 2+ were adsorbed. To be specific, the structure of ZrGP was destroyed due to adsorbing these two ions, but it could be regenerated after the loaded materials were dipped in HCl solution (1.0 M) for several minutes to remove metallic ions.

Strategies for induction of catalytic antibodies toward HIV-1 glycoprotein gp120 in autoimmune prone mice.

Science.gov (United States)

Durova, Oxana M; Vorobiev, Ivan I; Smirnov, Ivan V; Reshetnyak, Andrew V; Telegin, Georgy B; Shamborant, Olga G; Orlova, Nadezda A; Genkin, Dmitry D; Bacon, Andrew; Ponomarenko, Natalia A; Friboulet, Alain; Gabibov, Alexander G

2009-11-01

Tremendous efforts to produce an efficient vaccine for HIV infection have been unsuccessful. The ability of HIV to utilize sophisticated mechanisms to escape killing by host immune system rises dramatic problems in the development of antiviral therapeutics. The HIV infection proceeds by interaction of coat viral glycoprotein gp120 trimer with CD4(+) receptor of the lymphocyte. Thus this surface antigen may be regarded as a favorable target for immunotherapy. In the present study, we have developed three different strategies to produce gp120-specific response in autoimmune prone mice (SJL strain) as potential tools for production "catalytic vaccine". Therefore (i) reactive immunization by peptidylphosphonate, structural part of the coat glycoprotein, (ii) immunization by engineered fused epitopes of gp120 and encephalogenic peptide, a part of myelin basic protein, and (iii) combined vaccination by DNA and corresponding gp120 fragments incorporated into liposomes were investigated. In the first two cases monoclonal antibodies and their recombinant fragments with amidolytic and gp120-specific proteolytic activities were characterized. In the last case, catalytic antibodies with virus neutralizing activity proved in cell line models were harvested.

Membrane topology analysis of HIV-1 envelope glycoprotein gp41

Directory of Open Access Journals (Sweden)

Xiao Dan

2010-11-01

Full Text Available Abstract Background The gp41 subunit of the HIV-1 envelope glycoprotein (Env has been widely regarded as a type I transmembrane protein with a single membrane-spanning domain (MSD. An alternative topology model suggested multiple MSDs. The major discrepancy between the two models is that the cytoplasmic Kennedy sequence in the single MSD model is assigned as the extracellular loop accessible to neutralizing antibodies in the other model. We examined the membrane topology of the gp41 subunit in both prokaryotic and mammalian systems. We attached topological markers to the C-termini of serially truncated gp41. In the prokaryotic system, we utilized a green fluorescent protein (GFP that is only active in the cytoplasm. The tag protein (HaloTag and a membrane-impermeable ligand specific to HaloTag was used in the mammalian system. Results In the absence of membrane fusion, both the prokaryotic and mammalian systems (293FT cells supported the single MSD model. In the presence of membrane fusion in mammalian cells (293CD4 cells, the data obtained seem to support the multiple MSD model. However, the region predicted to be a potential MSD is the highly hydrophilic Kennedy sequence and is least likely to become a MSD based on several algorithms. Further analysis revealed the induction of membrane permeability during membrane fusion, allowing the membrane-impermeable ligand and antibodies to cross the membrane. Therefore, we cannot completely rule out the possible artifacts. Addition of membrane fusion inhibitors or alterations of the MSD sequence decreased the induction of membrane permeability. Conclusions It is likely that a single MSD model for HIV-1 gp41 holds true even in the presence of membrane fusion. The degree of the augmentation of membrane permeability we observed was dependent on the membrane fusion and sequence of the MSD.

Cloning, expression and preliminary crystallographic analysis of the equine infectious anaemia virus (EIAV) gp45 ectodomain

International Nuclear Information System (INIS)

Sun, Pei-Long; Lv, Shu-Xia; Zhou, Jian-Hua; Liu, Xin-Qi

2011-01-01

The equine infectious anaemia virus gp45 ectodomain was cloned, expressed and crystallized. Preliminary crystallographic analysis showed that the protein belonged to space group P6 3 and contained one molecule per asymmetric unit. Like human immunodeficiency virus (HIV), equine infectious anaemia virus (EIAV) belongs to the lentivirus genus. The first successful lentiviral vaccine was developed for EIAV. Thus, EIAV may serve as a valuable model for HIV vaccine research. EIAV glycoprotein 45 (gp45) plays a similar role to gp41 in HIV by mediating virus–host membrane fusion. The gp45 ectodomain was constructed according to the structure of HIV gp41, with removal of the disulfide-bond loop region. The protein was expressed in Escherichia coli and crystallized following purification. However, most of the crystals grew as aggregates and could not be used for data collection. By extensively screening hundreds of crystals, a 2.7 Å resolution data set was collected from a single crystal. The crystal belonged to space group P6 3 , with unit-cell parameters a = b = 46.84, c = 101.61 Å, α = β = 90, γ = 120°. Molecular replacement was performed using the coordinates of various lengths of HIV gp41 as search models. A long bent helix was identified and a well defined electron-density map around the long helix was obtained. This primary model provided the starting point for further refinement

Functional, non-clonal IgMa-restricted B cell receptor interactions with the HIV-1 envelope gp41 membrane proximal external region.

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Laurent Verkoczy

Full Text Available The membrane proximal external region (MPER of HIV-1 gp41 has several features that make it an attractive antibody-based vaccine target, but eliciting an effective gp41 MPER-specific protective antibody response remains elusive. One fundamental issue is whether the failure to make gp41 MPER-specific broadly neutralizing antibodies like 2F5 and 4E10 is due to structural constraints with the gp41 MPER, or alternatively, if gp41 MPER epitope-specific B cells are lost to immunological tolerance. An equally important question is how B cells interact with, and respond to, the gp41 MPER epitope, including whether they engage this epitope in a non-canonical manner i.e., by non-paratopic recognition via B cell receptors (BCR. To begin understanding how B cells engage the gp41 MPER, we characterized B cell-gp41 MPER interactions in BALB/c and C57BL/6 mice. Surprisingly, we found that a significant (approximately 7% fraction of splenic B cells from BALB/c, but not C57BL/6 mice, bound the gp41 MPER via their BCRs. This strain-specific binding was concentrated in IgM(hi subsets, including marginal zone and peritoneal B1 B cells, and correlated with enriched fractions (approximately 15% of gp41 MPER-specific IgM secreted by in vitro-activated splenic B cells. Analysis of Igh(a (BALB/c and Igh(b (C57BL/6 congenic mice demonstrated that gp41 MPER binding was controlled by determinants of the Igh(a locus. Mapping of MPER gp41 interactions with IgM(a identified MPER residues distinct from those to which mAb 2F5 binds and demonstrated the requirement of Fc C(H regions. Importantly, gp41 MPER ligation produced detectable BCR-proximal signaling events, suggesting that interactions between gp41 MPER and IgM(a determinants may elicit partial B cell activation. These data suggest that low avidity, non-paratopic interactions between the gp41 MPER and membrane Ig on naïve B cells may interfere with or divert bnAb responses.

Phosphorylation of varicella-zoster virus glycoprotein gpI by mammalian casein kinase II and casein kinase I

International Nuclear Information System (INIS)

Grose, C.; Jackson, W.; Traugh, J.A.

1989-01-01

Varicella-zoster virus (VZV) glycoprotein gpI is the predominant viral glycoprotein within the plasma membranes of infected cells. This viral glycoprotein is phosphorylated on its polypeptide backbone during biosynthesis. In this report, the authors investigated the protein kinases which participate in the phosphorylation events. Under in vivo conditions, VZV gpI was phosphorylated on its serine and threonine residues by protein kinases present within lysates of either VZV-infected or uninfected cells. Because this activity was diminished by heparin, a known inhibitor of casein kinase II, isolated gpI was incubated with purified casein kinase II and shown to be phosphorylated in an in vitro assay containing [γ- 32 P]ATP. The same glycoprotein was phosphorylated when [ 32 P]GTP was substituted for [ 32 P]ATP in the protein kinase assay. They also tested whether VZV gpI was phosphorylated by two other ubiquitous mammalian protein kinases--casein kinase I and cyclic AMP-dependent kinase--and found that only casein kinase I modified gpI. When the predicted 623-amino-acid sequence of gpI was examined, two phosphorylation sites known to be optimal for casein kinase II were observed. In summary, this study showed that VZV gpI was phosphorylated by each of two mammalian protein kinases (casein kinase I and casein kinase II) and that potential serine-threonine phosphorylation sites for each of these two kinases were present in the viral glycoprotein

Host-Primed Ebola Virus GP Exposes a Hydrophobic NPC1 Receptor-Binding Pocket, Revealing a Target for Broadly Neutralizing Antibodies

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Zachary A. Bornholdt

2016-02-01

Full Text Available The filovirus surface glycoprotein (GP mediates viral entry into host cells. Following viral internalization into endosomes, GP is cleaved by host cysteine proteases to expose a receptor-binding site (RBS that is otherwise hidden from immune surveillance. Here, we present the crystal structure of proteolytically cleaved Ebola virus GP to a resolution of 3.3 Å. We use this structure in conjunction with functional analysis of a large panel of pseudotyped viruses bearing mutant GP proteins to map the Ebola virus GP endosomal RBS at molecular resolution. Our studies indicate that binding of GP to its endosomal receptor Niemann-Pick C1 occurs in two distinct stages: the initial electrostatic interactions are followed by specific interactions with a hydrophobic trough that is exposed on the endosomally cleaved GP1 subunit. Finally, we demonstrate that monoclonal antibodies targeting the filovirus RBS neutralize all known filovirus GPs, making this conserved pocket a promising target for the development of panfilovirus therapeutics.

CD4-binding site alterations in CCR5-using HIV-1 envelopes influencing gp120-CD4 interactions and fusogenicity

International Nuclear Information System (INIS)

Sterjovski, Jasminka; Churchill, Melissa J.; Roche, Michael; Ellett, Anne; Farrugia, William; Wesselingh, Steven L.; Cunningham, Anthony L.; Ramsland, Paul A.; Gorry, Paul R.

2011-01-01

CD4-binding site (CD4bs) alterations in gp120 contribute to different pathophysiological phenotypes of CCR5-using (R5) HIV-1 strains, but the potential structural basis is unknown. Here, we characterized functionally diverse R5 envelope (Env) clones (n = 16) to elucidate potential structural alterations within the gp120 CD4bs that influence Env function. Initially, we showed that the magnitude of gp120-CD4-binding correlates with increased fusogenicity and reduced CD4 dependence. Analysis of three-dimensional gp120 structural models revealed two CD4bs variants, D279 and N362, that were associated with reduced CD4 dependence. Further structural analysis showed that a wider aperture of the predicted CD4bs cavity, as constrained by the inner-most atoms at the gp120 V1V2 stem and the V5 loop, was associated with amino acid alterations within V5 and correlated with increased gp120-CD4 binding and increased fusogenicity. Our results provide evidence that the gp120 V5 loop may alter CD4bs conformation and contribute to increased gp120-CD4 interactions and Env fusogenicity.

A functional F analogue of AcMNPV GP64 is from the Agrotis segetum granulovirus

NARCIS (Netherlands)

Yin, F.; Wang, M.; Tan, Y.; Deng, F.; Vlak, J.M.; Hu, Z.H.; Wang, H.

2008-01-01

The envelope fusion protein F of Plutella xylostella granulovirus is a computational analogue of the GP64 envelope fusion protein of Autographa californica nucleopolyhedrovirus (AcMNPV). Granulovirus (GV) F proteins were thought to be unable to functionally replace GP64 in the AcMNPV pseudotyping

iP-gp , a novel cell line with tight barrier function and expression of human P-glycoprotein (ABCB1) for drug screening

DEFF Research Database (Denmark)

Brodin, Birger; Ozgür, Burak; Saaby, Lasse

that new API's are evaluated with respect to P-gp interactions.  Aim : The aim of the present work was to validate the suitability of the newly developed iP-gp cell line for investigating P-gp interactions with human P-gp. Methods: IPEC-J2 MDR1 (iP-gp) cells were cultured on permeable supports for 17......Background : The efflux transporter P-glycoprotein (P-gp, product of the MDR1/ABCB1 gene) hinders uptake of drug compounds to the brain, limits intestinal uptake, is a cause of resistance to chemoterapeutics and a potential "site" for drug-drug interaction. Regulatory agencies therefore recommend.......04 +/- 0.01 µM in transport experiments including digoxin and rhodamine 123, respectively. Summary/Conclusion : The iP-gp cell line may become a useful screening tool for interactions between drug compounds and human P-gp....

Selected Thermophysical Properties of 2,2 Dimethylcyclopentyl Methylphosphonofluoridate (GP) and 2,2 Dimethylcyclopentanol (DMCP)

Science.gov (United States)

2016-09-01

chromatography using a thermal conductivity detector (GC-TCD). Table 1. Sample Information for GP and DMCP Chemical Name Mole Fraction Purity...Proving Ground, MD, 1983; UNCLASSIFIED Report (ADC033491). 23. Weast, R.C. CRC Handbook of Chemistry and Physics, 53rd ed.; CRC Press: Boca Raton, FL...gas chromatography GD pinacolyl methylphosphonofluoridate GF cyclohexyl methylphosphonofluoridate GP 2,2-dimethylcyclopentyl

Dyslexia and early intervention: what did we learn from the Dutch Dyslexia Programme?

Science.gov (United States)

van der Leij, Aryan

2013-11-01

Part of the Dutch Dyslexia Programme has been dedicated to early intervention. The question of whether the genetically affected learning mechanism of children who are at familial risk (FR) of developing dyslexia could be influenced by training phoneme awareness and letter-sound associations in the prereading phase was investigated. The rationale was that intervention studies reveal insights about the weaknesses of the learning mechanisms of FR children. In addition, the studies aimed to gather practical insights to be used in the development of a system of early diagnosis and prevention. Focused on the last period of kindergarten before formal reading instruction starts in Grade 1, intervention methods with comparable samples and designs but differences in delivery mode (use of computer or manual), tutor (semi-professional or parent), location (at school or at home), and additional practices (serial rapid naming or simple word reading) have been executed to test the hypothesis that the incidence and degree of dyslexia can be reduced. The present position paper summarizes the Dutch Dyslexia Programme findings and relates them to findings of other studies. It is discussed that the Dutch studies provide evidence on why prevention of dyslexia is hard to accomplish. It is argued that effective intervention should not only start early but also be adapted to the individual and often long-lasting educational needs of children at risk of reading failure. Copyright © 2013 John Wiley & Sons, Ltd.

Th1-like human T-cell clones recognizing Leishmania gp63 inhibit Leishmania major in human macrophages

DEFF Research Database (Denmark)

Kemp, M; Hey, A S; Bendtzen, K

1994-01-01

The major surface protease of Leishmania major, gp63, has been suggested as a vaccine candidate for cutaneous leishmaniasis. In this study gp63 was purified from L. major promastigotes. A panel of human T-cell clones recognizing this protein were generated from individuals who had previously had...... resembling Th1 cells. Autologous mononuclear cells and Epstein-Barr virus-transformed B cell lines were equally efficient in presenting the antigen to the T cells. The gp63 reactive T cells induced resistance to infection in cultured human macrophages by L. major. The data confirm that human CD4+ T cells...... recognizing gp63 can take part in the host defence against L. major infections....

Seed bank characteristics of Dutch plant communities

NARCIS (Netherlands)

Bekker, RM; Schaminee, JHJ; Bakker, JP; Thompson, K

With the recent appearances of a new and well-documented classification of the Dutch plant communities (Schaminee et al 1995a,b; 1996) and a database on the seed longevity of plant species of North West Europe (Thompson ct al. 1997a) it was possible to investigate patterns of seed longevity in Dutch

‘British Capital, Industry and Perseverance’ versus Dutch ‘Old School’?: The Dutch Atlantic and the Takeover of Berbice, Demerara and Essequibo, 1750-1815

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Gert Oostindie

2012-12-01

Full Text Available Recent historiography has reconsidered the idea that the Dutch role in the early modern Atlantic was of little significance, particularly in comparison to the accomplishments of the Dutch East India Company (voc in Asia. Revisionist studies have emphasised that in spite of the limited and fragmented nature of the Dutch Atlantic ‘empire’, the Atlantic contribution to the Dutch economy was significant and possibly even greater than the voc’s share. Moreover, this scholarship stresses the vital role of Dutch Atlantic colonies (Curaçao and St Eustatius, (partly Jewish networks and individuals in connecting the various subempires of the Atlantic. While Oostindie subscribes to many of these conclusions, he argues against excessive revisionism. His analysis of the development of the lesser Dutch Guianas, adjacent to Suriname, is used as a counter-weight to this revisionist impulse. He demonstrates that the spectacular economic and demographic development of these colonies was due mainly to British and (British American involvement culminating in the eventual British takeover of ‘Guiana’.

Translation and validation of the Dutch new Knee Society Scoring System ©.

Science.gov (United States)

Van Der Straeten, Catherine; Witvrouw, Erik; Willems, Tine; Bellemans, Johan; Victor, Jan

2013-11-01

A new version of The Knee Society Knee Scoring System(©) (KSS) has recently been developed. Before this scale can be used in non-English-speaking populations, it has to be translated and validated for a particular population. We evaluated the construct and content validity, the test-retest reliability, and the internal consistency of the Dutch version of the New Knee Society KSS. A Dutch translation was performed using a forward-backward translation protocol. We tested the construct validity of the Dutch New KSS by comparing it with the Dutch versions of the WOMAC, Knee Injury and Osteoarthritis Outcome Score (KOOS), and SF-12 scores in 137 patients undergoing total knee arthroplasty (TKA). Content validity was assessed by comparing pre- and postoperative scores and by checking floor and ceiling effects. To evaluate test-retest reliability and consistency, 47 patients completed the questionnaire a second time with a mean of 8 days interval (range, 2-20 days) between tests. Construct validity was demonstrated because the Dutch New KSS correlated well with the Dutch WOMAC (r = -0.751; p Dutch KOOS (r = -0.723; p Dutch SF-12 (r = 0.569; p Dutch New KSS is an excellent instrument to evaluate TKA outcome in Dutch-speaking patients.

Classification as clustering: a Pareto cooperative-competitive GP approach.

Science.gov (United States)

McIntyre, Andrew R; Heywood, Malcolm I

2011-01-01

Intuitively population based algorithms such as genetic programming provide a natural environment for supporting solutions that learn to decompose the overall task between multiple individuals, or a team. This work presents a framework for evolving teams without recourse to prespecifying the number of cooperating individuals. To do so, each individual evolves a mapping to a distribution of outcomes that, following clustering, establishes the parameterization of a (Gaussian) local membership function. This gives individuals the opportunity to represent subsets of tasks, where the overall task is that of classification under the supervised learning domain. Thus, rather than each team member representing an entire class, individuals are free to identify unique subsets of the overall classification task. The framework is supported by techniques from evolutionary multiobjective optimization (EMO) and Pareto competitive coevolution. EMO establishes the basis for encouraging individuals to provide accurate yet nonoverlaping behaviors; whereas competitive coevolution provides the mechanism for scaling to potentially large unbalanced datasets. Benchmarking is performed against recent examples of nonlinear SVM classifiers over 12 UCI datasets with between 150 and 200,000 training instances. Solutions from the proposed coevolutionary multiobjective GP framework appear to provide a good balance between classification performance and model complexity, especially as the dataset instance count increases.

The role of membrane microdomains in transmembrane signaling through the epithelial glycoprotein Gp140/CDCP1

Science.gov (United States)

Alvares, Stacy M.; Dunn, Clarence A.; Brown, Tod A.; Wayner, Elizabeth E.; Carter, William G.

2008-01-01

Cell adhesion to the extracellular matrix (ECM) via integrin adhesion receptors initiates signaling cascades leading to changes in cell behavior. While integrin clustering is necessary to initiate cell attachment to the matrix, additional membrane components are necessary to mediate the transmembrane signals and the cell adhesion response that alter downstream cell behavior. Many of these signaling components reside in glycosphingolipid-rich and cholesterol-rich membrane domains such as Tetraspanin Enriched Microdomains (TEMs)/Glycosynapse 3 and Detergent-Resistant Microdomains (DRMs), also known as lipid rafts. In the following article, we will review examples of how components in these membrane microdomains modulate integrin adhesion after initial attachment to the ECM. Additionally, we will present data on a novel adhesion-responsive transmembrane glycoprotein Gp140/CUB Domain Containing Protein 1, which clusters in epithelial cell-cell contacts. Gp140 can then be phosphorylated by Src Family Kinases at tyrosine 734 in response to outside-in signals- possibly through interactions involving the extracellular CUB domains. Data presented here suggests that outside-in signals through Gp140 in cell-cell contacts assemble membrane clusters that associate with membrane microdomains to recruit and activate SFKs. Active SFKs then mediate phosphorylation of Gp140, SFK and PKCδ with Gp140 acting as a transmembrane scaffold for these kinases. We propose that the clustering of Gp140 and signaling components in membrane microdomains in cell-cell contacts contributes to changes in cell behavior. PMID:18269919

Broad and potent HIV-1 neutralization by a human antibody that binds the gp41-gp120 interface

Energy Technology Data Exchange (ETDEWEB)

Huang, Jinghe; Kang, Byong H.; Pancera, Marie; Lee, Jeong Hyun; Tong, Tommy; Feng, Yu; Imamichi, Hiromi; Georgiev, Ivelin S.; Chuang, Gwo-Yu; Druz, Aliaksandr; Doria-Rose, Nicole A.; Laub, Leo; Sliepen, Kwinten; van Gils, Marit J.; de la Peña, Alba Torrents; Derking, Ronald; Klasse, Per-Johan; Migueles, Stephen A.; Bailer, Robert T.; Alam, Munir; Pugach, Pavel; Haynes, Barton F.; Wyatt, Richard T.; Sanders, Rogier W.; Binley, James M.; Ward, Andrew B.; Mascola, John R.; Kwong, Peter D.; Connors, Mark [NIH

2015-10-15

The isolation of human monoclonal antibodies is providing important insights into the specificities that underlie broad neutralization of HIV-1 (reviewed in ref. 1). Here we report a broad and extremely potent HIV-specific monoclonal antibody, termed 35O22, which binds a novel HIV-1 envelope glycoprotein (Env) epitope. 35O22 neutralized 62% of 181 pseudoviruses with a half-maximum inhibitory concentration (IC₅₀) <50 μg ml^-1. The median IC₅₀ of neutralized viruses was 0.033 μg ml^-1, among the most potent thus far described. 35O22 did not bind monomeric forms of Env tested, but did bind the trimeric BG505 SOSIP.664. Mutagenesis and a reconstruction by negative-stain electron microscopy of the Fab in complex with trimer revealed that it bound to a conserved epitope, which stretched across gp120 and gp41. The specificity of 35O22 represents a novel site of vulnerability on HIV Env, which serum analysis indicates to be commonly elicited by natural infection. Binding to this new site of vulnerability may thus be an important complement to current monoclonal-antibody-based approaches to immunotherapies, prophylaxis and vaccine design.

Studies on adsorptions of metallic ions in water by zirconium glyphosate (ZrGP): Behaviors and mechanisms

Energy Technology Data Exchange (ETDEWEB)

Jia Yunjie; Zhang Yuejuan [State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Box. 98, No.15, Beisanhuan donglu, Beijing 100029 (China); Wang Runwei [State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, Jilin University, Changchun 130012 (China); Fan Faying [State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Box. 98, No.15, Beisanhuan donglu, Beijing 100029 (China); Xu Qinghong, E-mail: xuqh@mail.buct.edu.cn [State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Box. 98, No.15, Beisanhuan donglu, Beijing 100029 (China)

2012-01-15

A new adsorbent named zirconium glyphosate [Zr(O{sub 3}PCH{sub 2}NHCH{sub 2}COOH){sub 2}{center_dot}0.5H{sub 2}O, denoted as ZrGP] and its selective adsorptions to Pb{sup 2+}, Cd{sup 2+}, Mg{sup 2+} and Ca{sup 2+} ions in water were reported in this paper. Compared to other zirconium adsorbents, such as zirconium phosphate [Zr(HPO{sub 4}){sub 2}], ZrGP exhibited highly selective adsorption to Pb{sup 2+} in solution which contained Pb{sup 2+}, Cd{sup 2+}, Mg{sup 2+} and Ca{sup 2+} ions. The loaded ZrGP with metallic ions can be efficaciously regenerated by aqueous solution of HCl (1.0 M) without any noticeable capacity loss, and almost all of it can be reused and recycled. The memory effect on structural regeneration of ZrGP was also found when Mg{sup 2+} and Ca{sup 2+} were adsorbed. To be specific, the structure of ZrGP was destroyed due to adsorbing these two ions, but it could be regenerated after the loaded materials were dipped in HCl solution (1.0 M) for several minutes to remove metallic ions.

Attenuated Human Parainfluenza Virus Type 1 Expressing Ebola Virus Glycoprotein GP Administered Intranasally Is Immunogenic in African Green Monkeys.

Science.gov (United States)

Lingemann, Matthias; Liu, Xueqiao; Surman, Sonja; Liang, Bo; Herbert, Richard; Hackenberg, Ashley D; Buchholz, Ursula J; Collins, Peter L; Munir, Shirin

2017-05-15

The recent 2014-2016 Ebola virus (EBOV) outbreak prompted increased efforts to develop vaccines against EBOV disease. We describe the development and preclinical evaluation of an attenuated recombinant human parainfluenza virus type 1 (rHPIV1) expressing the membrane-anchored form of EBOV glycoprotein GP, as an intranasal (i.n.) EBOV vaccine. GP was codon optimized and expressed either as a full-length protein or as an engineered chimeric form in which its transmembrane and cytoplasmic tail (TMCT) domains were replaced with those of the HPIV1 F protein in an effort to enhance packaging into the vector particle and immunogenicity. GP was inserted either preceding the N gene (pre-N) or between the N and P genes (N-P) of rHPIV1 bearing a stabilized attenuating mutation in the P/C gene (C Δ170 ). The constructs grew to high titers and efficiently and stably expressed GP. Viruses were attenuated, replicating at low titers over several days, in the respiratory tract of African green monkeys (AGMs). Two doses of candidates expressing GP from the pre-N position elicited higher GP neutralizing serum antibody titers than the N-P viruses, and unmodified GP induced higher levels than its TMCT counterpart. Unmodified EBOV GP was packaged into the HPIV1 particle, and the TMCT modification did not increase packaging or immunogenicity but rather reduced the stability of GP expression during in vivo replication. In conclusion, we identified an attenuated and immunogenic i.n. vaccine candidate expressing GP from the pre-N position. It is expected to be well tolerated in humans and is available for clinical evaluation. IMPORTANCE EBOV hemorrhagic fever is one of the most lethal viral infections and lacks a licensed vaccine. Contact of fluids from infected individuals, including droplets or aerosols, with mucosal surfaces is an important route of EBOV spread during a natural outbreak, and aerosols also might be exploited for intentional virus spread. Therefore, vaccines that protect

Involvement of viral envelope GP2 in Ebola virus entry into cells expressing the macrophage galactose-type C-type lectin

International Nuclear Information System (INIS)

Usami, Katsuaki; Matsuno, Keita; Igarashi, Manabu; Denda-Nagai, Kaori; Takada, Ayato; Irimura, Tatsuro

2011-01-01

Highlights: → Ebola virus infection is mediated by binding to and fusion with the target cells. → Structural feature of the viral glycoprotein determines the infectivity. → Surface C-type lectin, MGL, of macrophages and dendritic cells mediate the infection. → GP2, one of glycoprotein subunits, plays an essential role in MGL-mediated infection. → There is a critical amino acid residue involved in high infectivity. -- Abstract: Ebola virus (EBOV) infection is initiated by the interaction of the viral surface envelope glycoprotein (GP) with the binding sites on target cells. Differences in the mortality among different species of the Ebola viruses, i.e., Zaire ebolavirus (ZEBOV) and Reston ebolavirus (REBOV), correspond to the in vitro infectivity of the pseudo-typed virus constructed with the GPs in cells expressing macrophage galactose-type calcium-type lectin (MGL/CD301). Through mutagenesis of GP2, the transmembrane-anchored subunit of GP, we found that residues 502-527 of the GP2 sequence determined the different infectivity between VSV-ZEBOV GP and -REBOV GP in MGL/CD301-expressing cells and a histidine residue at position 516 of ZEBOV GP2 appeared essential in the differential infectivity. These findings may provide a clue to clarify a molecular basis of different pathogenicity among EBOV species.

Involvement of viral envelope GP2 in Ebola virus entry into cells expressing the macrophage galactose-type C-type lectin

Energy Technology Data Exchange (ETDEWEB)

Usami, Katsuaki [Laboratory of Cancer Biology and Molecular Immunology, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033 (Japan); Matsuno, Keita; Igarashi, Manabu [Department of Global Epidemiology, Hokkaido University Research Center for Zoonosis Control, Sapporo 001-0020 (Japan); Denda-Nagai, Kaori [Laboratory of Cancer Biology and Molecular Immunology, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033 (Japan); Takada, Ayato [Department of Global Epidemiology, Hokkaido University Research Center for Zoonosis Control, Sapporo 001-0020 (Japan); Irimura, Tatsuro, E-mail: irimura@mol.f.u-tokyo.ac.jp [Laboratory of Cancer Biology and Molecular Immunology, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033 (Japan)

2011-04-01

Highlights: {yields} Ebola virus infection is mediated by binding to and fusion with the target cells. {yields} Structural feature of the viral glycoprotein determines the infectivity. {yields} Surface C-type lectin, MGL, of macrophages and dendritic cells mediate the infection. {yields} GP2, one of glycoprotein subunits, plays an essential role in MGL-mediated infection. {yields} There is a critical amino acid residue involved in high infectivity. -- Abstract: Ebola virus (EBOV) infection is initiated by the interaction of the viral surface envelope glycoprotein (GP) with the binding sites on target cells. Differences in the mortality among different species of the Ebola viruses, i.e., Zaire ebolavirus (ZEBOV) and Reston ebolavirus (REBOV), correspond to the in vitro infectivity of the pseudo-typed virus constructed with the GPs in cells expressing macrophage galactose-type calcium-type lectin (MGL/CD301). Through mutagenesis of GP2, the transmembrane-anchored subunit of GP, we found that residues 502-527 of the GP2 sequence determined the different infectivity between VSV-ZEBOV GP and -REBOV GP in MGL/CD301-expressing cells and a histidine residue at position 516 of ZEBOV GP2 appeared essential in the differential infectivity. These findings may provide a clue to clarify a molecular basis of different pathogenicity among EBOV species.

Tradeable emission permits in Dutch environmental policy. A utopia?

International Nuclear Information System (INIS)

Schuurman, S.J.

1997-01-01

Because of the lack of experience with permits in the Netherlands, and in view of the similarities between various other tradeable permit systems, the functioning of Dutch systems of tradeable fish, milk and manure quotas is discussed. Evaluation of these systems is based on criteria of effectiveness, target-group efficiency and government efficiency. These systems of tradeable permits appear to constitute a successful addition to the Dutch policy of direct regulation. Considering this, and the favorable American experience with the Emissions Trading Program, tradeable emission permits deserve a chance to be implemented in Dutch environmental policy. The question remains, however, whether the Dutch government is ready for such a step. 28 refs

Young Asian Dutch constructing Asianness: Understanding the role of Asian popular culture

OpenAIRE

Kartosen, R.A.

2016-01-01

This doctoral thesis is about young Asian Dutch, panethnic Asian identities and identifications, and Asian/Asian Dutch popular culture. It addresses several pressing questions, including: why do young Asian Dutch, who were born and/or raised in the Netherlands, identify as Asian and construct Asian identities? What is the content or meaning of these Asian identities and identifications young Asian Dutch imagine? And how do these relate to young Asian Dutch’ Dutch and homeland identities and i...

River scale model of an training dam using lightweight granulates

NARCIS (Netherlands)

Vermeulen, B.; Boersema, M.P.; Hoitink, A.J.F.; Sieben, J.; Sloff, C.J.; Wal, van der M.F.

2014-01-01

Replacing existing river groynes with longitudinal training dams is considered as a promising flood mitigation measure in the main Dutch rivers, which can also serve to guarantee navigability during low flows and to create conditions favourable for ecological development. Whereas the bed response in

Dutch ministerial visit

CERN Multimedia

2007-01-01

Dutch Minister of Education, Culture and Science R. Plasterk (third from left) in the ATLAS cavern with NIKHEF Director F. Linde, CERN Chief Scientific Officer J. Engelen, Ambassador J. van Eenennaam, ATLAS Collaboration Spokesperson P. Jenni, Mission Representative G. Vrielink and ATLAS Magnet Project Leader H. ten Kate.Minister of Education, Culture and Science from the Kingdom of the Netherlands, Ronald Plasterk, visited CERN on 25th October. With Jos Engelen, CERN Scientific Director, as his guide he visited Point 1 of the LHC tunnel and ATLAS, where Nikhef (the national institute for subatomic physics, a Dutch government and university collaboration) constructed all 96 of the largest muon drift chambers in the barrel as well as parts of the magnet system, the inner detector, the DAQ and triggering. Overall the Netherlands contribute 4.5% to the annual CERN budget and the minister’s visit celebrated the contributions of the 79 ...

Exploring provision of Innovative Community Education Placements (ICEPs) for junior doctors in training: a qualitative study.

Science.gov (United States)

Griffin, Ann; Jones, Melvyn M; Khan, Nada; Park, Sophie; Rosenthal, Joe; Chrysikou, Vasiliki

2016-02-09

Medical education in community settings is an essential ingredient of doctors' training and a key factor in recruiting general practitioners (GP). Health Education England's report 'Broadening the Foundation' recommends foundation doctors complete 4-month community placements. While Foundation GP schemes exist; other community settings, are not yet used for postgraduate training. The objective of this study was to explore how community-based training of junior doctors might be expanded into possible 'innovative community education placements' (ICEPs), examining opportunities and barriers to these developments. A qualitative study where semistructured interviews were undertaken and themes were generated deductively from the research questions, and iteratively from transcripts. UK community healthcare. Stakeholders from UK Community healthcare providers and undergraduate GP and community educators. Nine participants were interviewed; those experienced in delivering community-based undergraduate education, and others working in community settings that had not previously trained doctors. Themes identified were practicalities such as 'finance and governance', 'communication and interaction', 'delivery of training' and 'perceptions of community'. ICEPs were willing to train Foundation doctors. However, concerns were raised that large numbers and inadequate resources could undermine the quality of educational opportunities, and even cause reputational damage. Organisation was seen as a challenge, which might be best met by placing some responsibility with trainees to manage their placements. ICEP providers agreed that defined service contribution by trainees was required to make placements sustainable, and enhance learning. ICEPs stated the need for positive articulation of the learning value of placements to learners and stakeholders. This study highlighted the opportunities for foundation doctors to gain specialist and generalist knowledge in ICEPs from diverse clinical

Immunization With Fc-Based Recombinant Epstein–Barr Virus gp350 Elicits Potent Neutralizing Humoral Immune Response in a BALB/c Mice Model

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Bingchun Zhao

2018-05-01

Full Text Available Epstein–Barr virus (EBV was the first human virus proved to be closely associated with tumor development, such as lymphoma, nasopharyngeal carcinoma, and EBV-associated gastric carcinoma. Despite many efforts to develop prophylactic vaccines against EBV infection and diseases, no candidates have succeeded in effectively blocking EBV infection in clinical trials. Previous investigations showed that EBV gp350 plays a pivotal role in the infection of B-lymphocytes. Nevertheless, using monomeric gp350 proteins as antigens has not been effective in preventing infection. Multimeric forms of the antigen are more potently immunogenic than monomers; however, the multimerization elements used in previous constructs are not approved for human clinical trials. To prepare a much-needed EBV prophylactic vaccine that is potent, safe, and applicable, we constructed an Fc-based form of gp350 to serve as a dimeric antigen. Here, we show that the Fc-based gp350 antigen exhibits dramatically enhanced immunogenicity compared with wild-type gp350 protein. The complete or partial gp350 ectodomain was fused with the mouse IgG2a Fc domain. Fusion with the Fc domain did not impair gp350 folding, binding to a conformation-dependent neutralizing antibody (nAb and binding to its receptor by enzyme-linked immunosorbent assay and surface plasmon resonance. Specific antibody titers against gp350 were notably enhanced by immunization with gp350-Fc dimers compared with gp350 monomers. Furthermore, immunization with gp350-Fc fusion proteins elicited potent nAbs against EBV. Our data strongly suggest that an EBV gp350 vaccine based on Fc fusion proteins may be an efficient candidate to prevent EBV infection in clinical applications.

Pop and World Music in Dutch Music Education: Two Cases of Authentic Learning in Music Teacher Education and Secondary Music Education

Science.gov (United States)

Evelein, Frits

2006-01-01

Popular and world music play an important role in Dutch music education. This article examines two case studies that illustrate authentic music learning environments in which these types of music are prominently used. The first case follows a student during her training at the Rotterdam Academy for Music Education, in which her own musical and…

Construction and Characterization of a Humanized Anti-Epstein-Barr Virus gp350 Antibody with Neutralizing Activity in Cell Culture

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Jerome E. Tanner

2018-04-01

Full Text Available Acute Epstein-Barr virus (EBV infection in immunosuppressed transplant patients can give rise to a malignant B-cell proliferation known as post-transplant lymphoproliferative disease (PTLD. The EBV major virion surface glycoprotein (gp350 is a principal target of naturally occurring neutralizing antibodies and is viewed as the best target to prevent acute infection and PTLD in at-risk transplant recipients. We have constructed a humanized (hu version of the murine anti-gp350 neutralizing monoclonal antibody 72a1. The hu72a1 IgG1 antibody displayed no significant anti-mouse activity, recognized both gp350 and its splice variant gp220 as well as a gp350 peptide that was shown to constitute the principal EBV gp350 neutralizing epitope when tested in immunoassays. Hu72a1 antibody blocked in vitro EBV infection of B cells at a level which equaled that of a mouse-human chimeric 72a1 antibody construct. This work provides a further structural and immunological understanding of the 72a1 antibody interaction with EBV gp350, and constitutes a launch point for future anti-EBV therapeutic antibodies designed to block EBV infection and prevent PTLD while eliminating the deleterious antigenic murine features of the original 72a1 antibody.

Learning to read Dutch as a transparent orthography

NARCIS (Netherlands)

Verhoeven, L.T.W.

2017-01-01

The present longitudinal study investigated the growth of word reading fluency in Dutch as a transparent orthography as a function of meaning (words vs pseudowords) and orthographic complexity throughout the elementary school years. For a representative sample of 511 Dutch children, decoding

Human immunodeficiency virus envelope protein Gp120 induces proliferation but not apoptosis in osteoblasts at physiologic concentrations.

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Nathan W Cummins

Full Text Available Patients with HIV infection have decreased numbers of osteoblasts, decreased bone mineral density and increased risk of fracture compared to uninfected patients; however, the molecular mechanisms behind these associations remain unclear. We questioned whether Gp120, a component of the envelope protein of HIV capable of inducing apoptosis in many cell types, is able to induce cell death in bone-forming osteoblasts. We show that treatment of immortalized osteoblast-like cells and primary human osteoblasts with exogenous Gp120 in vitro at physiologic concentrations does not result in apoptosis. Instead, in the osteoblast-like U2OS cell line, cells expressing CXCR4, a receptor for Gp120, had increased proliferation when treated with Gp120 compared to control (P<0.05, which was inhibited by pretreatment with a CXCR4 inhibitor and a G-protein inhibitor. This suggests that Gp120 is not an inducer of apoptosis in human osteoblasts and likely does not directly contribute to osteoporosis in infected patients by this mechanism.

The GP problem: quantifying gene-to-phenotype relationships.

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Cooper, Mark; Chapman, Scott C; Podlich, Dean W; Hammer, Graeme L

2002-01-01

In this paper we refer to the gene-to-phenotype modeling challenge as the GP problem. Integrating information across levels of organization within a genotype-environment system is a major challenge in computational biology. However, resolving the GP problem is a fundamental requirement if we are to understand and predict phenotypes given knowledge of the genome and model dynamic properties of biological systems. Organisms are consequences of this integration, and it is a major property of biological systems that underlies the responses we observe. We discuss the E(NK) model as a framework for investigation of the GP problem and the prediction of system properties at different levels of organization. We apply this quantitative framework to an investigation of the processes involved in genetic improvement of plants for agriculture. In our analysis, N genes determine the genetic variation for a set of traits that are responsible for plant adaptation to E environment-types within a target population of environments. The N genes can interact in epistatic NK gene-networks through the way that they influence plant growth and development processes within a dynamic crop growth model. We use a sorghum crop growth model, available within the APSIM agricultural production systems simulation model, to integrate the gene-environment interactions that occur during growth and development and to predict genotype-to-phenotype relationships for a given E(NK) model. Directional selection is then applied to the population of genotypes, based on their predicted phenotypes, to simulate the dynamic aspects of genetic improvement by a plant-breeding program. The outcomes of the simulated breeding are evaluated across cycles of selection in terms of the changes in allele frequencies for the N genes and the genotypic and phenotypic values of the populations of genotypes.

Identification by Mass Spectrometry and Immune Response Analysis of Guinea Pig Cytomegalovirus (GPCMV Pentameric Complex Proteins GP129, 131 and 133

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Josephine S. Gnanandarajah

2014-02-01

Full Text Available Development of a vaccine against congenital infection with human cytomegalovirus (HCMV is a major public health priority. A potential vaccine target receiving considerable recent attention is the pentameric complex (PC of HCMV proteins consisting of gL, gH, UL128, UL130, and UL131, since some antibodies against these target proteins are capable of potently neutralizing virus at epithelial and endothelial cell surfaces. Recently, homologous proteins have been described for guinea pig cytomegalovirus (GPCMV, consisting of gH, gL, and the GPCMV proteins GP129, GP131, and GP133. To investigate these proteins as potential vaccine targets, expression of GP129-GP133 transcripts was confirmed by reverse-transcriptase PCR. Mass spectrometry combined with western blot assays demonstrated the presence of GP129, GP131, and GP133 proteins in virus particles. Recombinant proteins corresponding to these PC proteins were generated in baculovirus, and as GST fusion proteins. Recombinant proteins were noted to be immunoreactive with convalescent sera from infected animals, suggesting that these proteins are recognized in the humoral immune response to GPCMV infection. These analyses support the study of PC-based recombinant vaccines in the GPCMV congenital infection model.

Structure of the Epstein-Barr virus gp42 protein bound to the MHC class II recepter HLA-DR1

Energy Technology Data Exchange (ETDEWEB)

Mullen, M.; Haan, K.M.; Longnecker, R.; Jardetzky, T.

2010-03-08

Epstein-Barr virus (EBV) causes infectious mononucleosis, establishes long-term latent infections, and is associated with a variety of human tumors. The EBV gp42 glycoprotein binds MHC class II molecules, playing a critical role in infection of B lymphocytes. EBV gp42 belongs to the C-type lectin superfamily, with homology to NK receptors of the immune system. We report the crystal structure of gp42 bound to the human MHC class II molecule HLA-DR1. The gp42 binds HLA-DR1 using a surface site that is distinct from the canonical lectin and NK receptor ligand binding sites. At the canonical ligand binding site, gp42 forms a large hydrophobic groove, which could interact with other ligands necessary for EBV entry, providing a mechanism for coupling MHC recognition and membrane fusion.

Glial TNFα in the spinal cord regulates neuropathic pain induced by HIV gp120 application in rats

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Ouyang Handong

2011-05-01

Full Text Available Abstract Background HIV-associated sensory neuropathy (HIV-SN is one of the most common forms of peripheral neuropathy, affecting about 30% of people with acquired immune deficiency syndrome (AIDS. The symptoms of HIV-SN are dominated by neuropathic pain. Glia activation in the spinal cord has become an attractive target for attenuating chronic pain. This study will investigate the role of spinal TNFα released from glia in HIV-related neuropathic pain. Results Peripheral gp120 application into the rat sciatic nerve induced mechanical allodynia for more than 7 weeks, and upregulated the expression of spinal TNFα in the mRNA and the protein levels at 2 weeks after gp120 application. Spinal TNFα was colocalized with GFAP (a marker of astrocytes and Iba1 (a marker of microglia in immunostaining, suggesting that glia produce TNFα in the spinal cord in this model. Peripheral gp120 application also increased TNFα in the L4/5 DRG. Furthermore, intrathecal administration of TNFα siRNA or soluble TNF receptor reduced gp120 application-induced mechanical allodynia. Conclusions Our results indicate that TNFα in the spinal cord and the DRG are involved in neuropathic pain, following the peripheral HIV gp120 application, and that blockade of the glial product TNFα reverses neuropathic pain induced by HIV gp120 application.

Constrained Combinatorial Libraries of Gp2 Proteins Enhance Discovery of PD-L1 Binders.

Science.gov (United States)

Kruziki, Max A; Sarma, Vidur; Hackel, Benjamin J

2018-06-05

Engineered protein ligands are used for molecular therapy, diagnostics, and industrial biotechnology. The Gp2 domain is a 45-amino acid scaffold that has been evolved for specific, high-affinity binding to multiple targets by diversification of two solvent-exposed loops. Inspired by sitewise enrichment of select amino acids, including cysteine pairs, in earlier Gp2 discovery campaigns, we hypothesized that the breadth and efficiency of de novo Gp2 discovery will be aided by sitewise amino acid constraint within combinatorial library design. We systematically constructed eight libraries and comparatively evaluated their efficacy for binder discovery via yeast display against a panel of targets. Conservation of a cysteine pair at the termini of the first diversified paratope loop increased binder discovery 16-fold ( p libraries with conserved cysteine pairs, within the second loop or an interloop pair, did not aid discovery thereby indicating site-specific impact. Via a yeast display protease resistance assay, Gp2 variants from the loop one cysteine pair library were 3.3 ± 2.1-fold ( p = 0.005) more stable than nonconstrained variants. Sitewise constraint of noncysteine residues-guided by previously evolved binders, natural Gp2 homology, computed stability, and structural analysis-did not aid discovery. A panel of binders to programmed death ligand 1 (PD-L1), a key target in cancer immunotherapy, were discovered from the loop 1 cysteine constraint library. Affinity maturation via loop walking resulted in strong, specific cellular PD-L1 affinity ( K d = 6-9 nM).

Cost efficiency of waste management in Dutch municipalities

NARCIS (Netherlands)

de Groot, Hans; van Heezik, A.; Hollanders, D.; Felsö, F.

2011-01-01

This paper analyses the cost efficiency of waste management of Dutch municipalities. For the first time stochastic frontier analysis is applied to Dutch data, employing recent multi-year data (2005-2008). The preliminary findings confirm earlier results on the importance for cost efficiency of

Do Dutch nutrition and dietetics students meet nutritional requirements during education?

NARCIS (Netherlands)

van der Kruk, Joke; Jager, Harriët; Nieweg, Roos; van der Schans, Cees

2014-01-01

OBJECTIVES: To compare the dietary intakes of Dutch nutrition and dietetics students with the Dutch RDA and the Dutch National Food Consumption Survey (DNFCS), and to assess whether dietary intake changes during education.DESIGN: Cross-sectional and longitudinal research (2004-2010).SETTING: Data

Frequency and persistency of DNA vaccine encoding GP25 by oral on common carp

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Sri Nuryati

2015-05-01

Full Text Available ABSTRACT Koi herpesvirus (KHV is a major viral pathogen that infects common carp and koi. KHV disease outbreak is happened in almost all centre of common carp culture in Indonesia and caused mass mortality. Deoxyribonucleic acid (DNA vaccination method is one of ways to cope with KHV infection. Vaccines were commonly given by injection. The aim of this research was to get frequency and persistency of DNA vaccine encoding GP25 given by oral delivery method in common carp. This research would like to determine dose, frequency of vaccination, persistency of DNA vaccine and culture medium for the bacterial host. DNA vaccine persistency test was done by using polymerase chain reaction (PCR method with the specific primer for GP25 gene. The results showed that level of DNA vaccine that could be detected in feed was 7.56 ng (equal to 1.598×1010 copies. Efficient culture medium for Escherichia coli DH5α carrying DNA vaccine was LB triptone. Feeding fish with diet supplemented with 1 mL E. coli DH5α containing DNA vaccine for each fish and two times a week allowed persistence of DNA vaccine in kindney and spleen. Keywords: common carp, KHV, DNA vaccine, GP25, persistance  ABSTRAK Koi herpesvirus (KHV adalah virus patogen utama yang menginfeksi ikan mas dan ikan koi. Wabah penyakit KHV terjadi di hampir semua sentra budidaya ikan mas di Indonesia dan menyebabkan kematian massal ikan. Metode vaksinasi DNA merupakan salah satu cara yang dapat dilakukan untuk menanggulangi serangan KHV. Pemberian vaksin umumnya dilakukan dengan cara injeksi. Tujuan penelitian ini adalah untuk menguji frekuensi dan persistensi vaksin DNA GP25 antivirus KHV yang diberikan melalui oral pada ikan mas. Pada penelitian ini dilakukan uji dosis, frekuensi pemberian vaksin, persistensi vaksin DNA, dan media kultur bakteri inang. Persistensi vaksin DNA dianalisis menggunakan metode PCR dengan primer spesifik gen GP25. Hasil penelitian menunjukkan bahwa dosis vaksin DNA yang

The Influences of Glycosylation on the Antigenicity, Immunogenicity, and Protective Efficacy of Ebola Virus GP DNA Vaccines

National Research Council Canada - National Science Library

Dowling, William; Thompson, Elizabeth; Badger, Catherine; Mellquist, Jenny L; Garrison, Aura R; Smith, Jeffrey M; Paragas, Jason; Hogan, Robert J; Schmaljohn, Connie

2006-01-01

... or with deletions in the central hypervariable mucin region. We showed that mutation of one of the two N-linked GP2 glycosylation sites was highly detrimental to the antigenicity and immunogenicity of GP...

GP-9s are ubiquitous proteins unlikely involved in olfactory mediation of social organization in the red imported fire ant, Solenopsis invicta.

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Walter S Leal

Full Text Available The red imported fire ant (RIFA, Solenopsis invicta, is an invasive species, accidentally introduced in the United States that can cause painful (sometimes life-threatening stings to human, pets, and livestock. Their colonies have two social forms: monogyne and polygyne that have a single and multiple functional queens, respectively. A major gene (Gp-9, identified as a putative pheromone-binding protein on the basis of a modest amino acid sequence identity, has been suggested to influence the expression of colony social organization. Monogyne queens are reported to possess only the GP-9B alleles, whereas polygyne queens possess both GP-9B and GP-9b. Thus, both social forms are reported to express GP-9B, with GP-9b being a marker expressed in polygynes but it is absent in monogynes. Here, we report two types of polygyne colonies, one that does not express GP-9b (monogyne-like and the other expressing both proteins, GP-9B and GP-9b. Given their expression pattern, GP-9s are hemolymph proteins, which are more likely to be involved in the transport of lipids and small ligands within the homocoel. GP-9B existed in two forms, one of them is phosphorylated. The helical-rich content of the protein resembles the secondary structures of a beetle hemolymph protein and moth pheromone-binding proteins. An olfactory role is unlikely given the lack of specific expression in the sensillar lymph. In marked contrast to GP-9s, a chemosensory protein, SinvCSP, is demonstrated to be specifically expressed in the antennae. Within the antennae, expression of SinvCSP is restricted to the last two segments, which are known to house olfactory sensilla.

GP-initiated preconception counselling in a randomised controlled trial does not induce anxiety

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Neven A Knuistingh

2006-11-01

Full Text Available Abstract Background Preconception counselling (PCC can reduce adverse pregnancy outcome by addressing risk factors prior to pregnancy. This study explores whether anxiety is induced in women either by the offer of PCC or by participation with GP-initiated PCC. Methods Randomised trial of usual care versus GP-initiated PCC for women aged 18–40, in 54 GP practices in the Netherlands. Women completed the six-item Spielberger State Trait Anxiety Inventory (STAI before PCC (STAI-1 and after (STAI-2. After pregnancy women completed a STAI focusing on the first trimester of pregnancy (STAI-3. Results The mean STAI-1-score (n = 466 was 36.4 (95% CI 35.4 – 37.3. Following PCC there was an average decrease of 3.6 points in anxiety-levels (95% CI, 2.4 – 4.8. Mean scores of the STAI-3 were 38.5 (95% CI 37.7 – 39.3 in the control group (n = 1090 and 38.7 (95% CI 37.9 – 39.5 in the intervention group (n = 1186. Conclusion PCC from one's own GP reduced anxiety after participation, without leading to an increase in anxiety among the intervention group during pregnancy. We therefore conclude that GPs can offer PCC to the general population without fear of causing anxiety. Trial Registration: ISRCTN53942912

Professional development of teachers using a research based approach to clarify their challenges in multicultural classrooms: a case study of Dutch senior secondary vocational education

NARCIS (Netherlands)

Perry den Brok; dr.ir. Quinta Kools; Kennedy Tielman

2013-01-01

This research presents a descriptive study on regarding the use of a research-based approach by teachers to clarify problems they encountered in multicultural classrooms. It analyses the outcomes of a training in which seven teachers from a Dutch Senior Secondary Vocational Education school

The Tetherin Antagonism of the Ebola Virus Glycoprotein Requires an Intact Receptor-Binding Domain and Can Be Blocked by GP1-Specific Antibodies.

Science.gov (United States)

Brinkmann, Constantin; Nehlmeier, Inga; Walendy-Gnirß, Kerstin; Nehls, Julia; González Hernández, Mariana; Hoffmann, Markus; Qiu, Xiangguo; Takada, Ayato; Schindler, Michael; Pöhlmann, Stefan

2016-12-15

The glycoprotein of Ebola virus (EBOV GP), a member of the family Filoviridae, facilitates viral entry into target cells. In addition, EBOV GP antagonizes the antiviral activity of the host cell protein tetherin, which may otherwise restrict EBOV release from infected cells. However, it is unclear how EBOV GP antagonizes tetherin, and it is unknown whether the GP of Lloviu virus (LLOV), a filovirus found in dead bats in Northern Spain, also counteracts tetherin. Here, we show that LLOV GP antagonizes tetherin, indicating that tetherin may not impede LLOV spread in human cells. Moreover, we demonstrate that appropriate processing of N-glycans in tetherin/GP-coexpressing cells is required for tetherin counteraction by EBOV GP. Furthermore, we show that an intact receptor-binding domain (RBD) in the GP1 subunit of EBOV GP is a prerequisite for tetherin counteraction. In contrast, blockade of Niemann-Pick disease type C1 (NPC1), a cellular binding partner of the RBD, did not interfere with tetherin antagonism. Finally, we provide evidence that an antibody directed against GP1, which protects mice from a lethal EBOV challenge, may block GP-dependent tetherin antagonism. Our data, in conjunction with previous reports, indicate that tetherin antagonism is conserved among the GPs of all known filoviruses and demonstrate that the GP1 subunit of EBOV GP plays a central role in tetherin antagonism. Filoviruses are reemerging pathogens that constitute a public health threat. Understanding how Ebola virus (EBOV), a highly pathogenic filovirus responsible for the 2013-2016 Ebola virus disease epidemic in western Africa, counteracts antiviral effectors of the innate immune system might help to define novel targets for antiviral intervention. Similarly, determining whether Lloviu virus (LLOV), a filovirus detected in bats in northern Spain, is inhibited by innate antiviral effectors in human cells might help to determine whether the virus constitutes a threat to humans. The

Socialized choices: Labour market behaviour of Dutch mothers

NARCIS (Netherlands)

Ruitenberg, J.F.

2014-01-01

Dutch mothers display diverse labour market behaviour, though typically they work part-time, making modest use of childcare. It is generally assumed that Dutch women are free to make their own choices regarding employment. This narrative of 'choice' finds fertile ground in an era of general

Physical activity among Dutch workers-differences between occupations

NARCIS (Netherlands)

Proper, K.I.; Hildebrandt, V.H.

2006-01-01

Objective.: This study describes the total physical activity and the contribution of work to total physical activity among Dutch workers. The study was conducted in the Netherlands in the years 2000-2002. Methods.: 2,417 respondents of a cross-sectional survey representing the Dutch adult working

Preventing the Dutch Disease: The case of Indonesia

International Nuclear Information System (INIS)

Ramli, R.

1992-01-01

Indonesia has been more successful than other oil exporters in mitigating the effects of the Dutch Disease, the decline in non-oil production associated with an oil boom. Typically sharp increases in oil revenues promote the accumulation of international reserves, increasing monetization, and raising prices of non-traded relative to traded goods. The latter causes contraction of output and employment in the traded sector. This study analyzes the magnitude of the boom and its fiscal, monetary, and production effects. Proxies of the real exchange rate, defined as the relative price of traded to non-traded goods, were constructed. The effect of the exchange rate on the Dutch Disease problems were examined. The movement of the real exchange rate and the remarkable growth of production of traded goods indicate that the effects of the Dutch Disease on the Indonesian economy were remarkably limited. Structural and policy-induced factors, such as exchange rate protection and micro interventions, that mitigated the anticipated effects of the Dutch Disease are examined

Indonesianisasi of Dutch economic interests, 1930-1960 : The case of Internatio

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Jasper van der Kerkhof

2005-01-01

Full Text Available This article looks in detail into the process of indonesianisasi at Internatio, a major Dutch trading firm in Indonesia. I draw on Dutch archival records and the voluminous Dutch and international literature on the changing environment for Dutch private business in Indonesia in the 1950s. Internatio’s case is particularly instructive for the following reasons: – Internatio was a leading trading firm in Indonesia and regarded as a ‘trendsetter’ among the so-called ‘Big Five’, the leading Dutch import houses in the archipelago. – Successive Indonesian cabinets considered import trade crucial in the process of indonesianisasi, and for this reason the sector was targeted for policies aimed at wresting control from Dutch firms and encouraging the development of indigenous ones. – Internatio had a pivotal role in the Indonesian economy due to its extensive interests, not only in import trade but also in exports, estates, manufacturing, shipping, and insurance. The article is chronologically structured, distinguishing five periods: depression and diversification (1930-1940; the end of Dutch supremacy (1940-1945; revolution and rehabilitation (1945-1950; adjusting to new realities (1950- 1956; confrontation and nationalization (1956-1960.

Effects of local application of methylprednisolone delivered by the C/GP-hydrogel on the recovery of facial nerves.

Science.gov (United States)

Chao, Xiuhua; Fan, Zhaomin; Han, Yuechen; Wang, Yan; Li, Jianfeng; Chai, Renjie; Xu, Lei; Wang, Haibo

2015-01-01

Local administration of MP delivered by the C/GP-MP-hydrogel can improve the recovery of facial nerve following crush injury. The findings suggested that locally injected MP delivered by C/GP-hydrogel might be a promising treatment for facial nerve damage. In this study, the aim is to assess the effectiveness of locally administrating methylprednisolone(MP) loaded by chitosan-β-glycerophosphate hydrogel (C/GP-hydrogel) on the regeneration of facial nerve crush injury. After the crush of left facial nerves, Wistar rats were randomly divided into four different groups. Then, four different therapies were used to treat the damaged facial nerves. At the 1(st), 2(nd), 3(rd), and 4(th) week after injury, the functional recovery of facial nerves and the morphological changes of facial nerves were assessed. The expression of growth associated protein-43 (GAP-43) protein in the facial nucleus were also evaluated. Locally injected MP delivered by C/GP-hydrogel effectively accelerated the facial functional recovery. In addition, the regenerated facial nerves in the C/GP-MP group were more mature than those in the other groups. The expression of GAP-43 protein was also improved by the MP, especially in the C/GP-MP group.

Rhythms and Rhymes of Life. Music and Identification processes of Dutch-Moroccan youth

NARCIS (Netherlands)

Gazzah, M.

2008-01-01

Rhythms and Rhymes of Life: Music and Identification Processes of Dutch-Moroccan Youth is a comprehensive anthropological study of the social significance of music among Dutch-Moroccan youth. In the Netherlands, a Dutch-Moroccan music scene has emerged, including events and websites. Dutch-Moroccan

The effect of an e-learning supported Train-the-Trainer programme on implementation of suicide guidelines in mental health care.

NARCIS (Netherlands)

Beurs, D.P. de; Groot, M.H. de; Keijser, J. de; Mokkenstorm, J.; Duijn, E. van; Winter, R.F.P. de; Kerkhof, A.J.F.M.

2015-01-01

Background: Randomized studies examining the effect of training of mental health professionals in suicide prevention guidelines are scarce. We assessed whether professionals benefited from an e-learning supported Train-the-Trainer programme aimed at the application of the Dutch multidisciplinary

'A Dutch Miracle'

NARCIS (Netherlands)

Visser, Jelle; Hemerijck, Anton

1997-01-01

The Dutch polder model recently dubbed a 'success story' by Bill Clinton and Jacques Delors - plays a prominent role in current discussions about possibilities for a new 'capitalism with a social face', and appeals to experts all over the world. Just ten years ago the Swedish sociologist Goran

Risks of radicalization among Turkish-Dutch young adults?

NARCIS (Netherlands)

R.H.J.M. Staring (Richard)

2014-01-01

markdownabstract__Abstract__ Young adults heading for Syria to join the jihad and the safety risks associated with their return are currently a topic of debate in the Netherlands and in many other European countries. Around 120 Dutch citizens have gone abroad to join the jihad and the Dutch

The future of the Dutch egg processing industry

NARCIS (Netherlands)

Tacken, G.M.L.; Cotteleer, G.; Horne, van P.L.M.

2003-01-01

This research examines the competitiveness of the Dutch egg products industry, as well as the consequences of tightening up the laws concerning layer poultry on the competitive position of the Dutch egg production industry. A tightening of the laws has, in fact, the effect of raising the production

The Kenyan meat sector Opportunities for Dutch agribusiness

NARCIS (Netherlands)

Bergevoet, R.H.M.; Engelen, A.

2014-01-01

This study identifies opportunities for the Dutch agribusiness sector (industry as well as research and education) in Kenyan meat value chains at all levels. It can serve as a background document for Dutch agro-food business companies as well as other stakeholders. At the moment there is increased

The acquisition of the Dutch discourse particle wel

NARCIS (Netherlands)

Hogeweg, L.; Gerrevink, R.

2015-01-01

Dutch is known for its large inventory of discourse particles. Discourse particles are very frequent and highly important in conversation. Yet, not much research has been conducted on how children acquire them. In this paper we focus on the acquisition of the Dutch discourse particle wel. In earlier

Acquisition of Morpho-Phonology: the Dutch voicing alternation

NARCIS (Netherlands)

Kerkhoff, A.O.

2007-01-01

This dissertation investigates how and when the Dutch voicing alternation is acquired. In Dutch, final neutralisation of the voice contrast (or ‘final devoicing’) leads to alternations in singular - plural pairs such as bed ~ bedden ‘bed(s)’. In such pairs, the singular always ends in a voiceless

DNA unwinding by ring-shaped T4 helicase gp41 is hindered by tension on the occluded strand.

Science.gov (United States)

Ribeck, Noah; Saleh, Omar A

2013-01-01

The replicative helicase for bacteriophage T4 is gp41, which is a ring-shaped hexameric motor protein that achieves unwinding of dsDNA by translocating along one strand of ssDNA while forcing the opposite strand to the outside of the ring. While much study has been dedicated to the mechanism of binding and translocation along the ssDNA strand encircled by ring-shaped helicases, relatively little is known about the nature of the interaction with the opposite, 'occluded' strand. Here, we investigate the interplay between the bacteriophage T4 helicase gp41 and the ss/dsDNA fork by measuring, at the single-molecule level, DNA unwinding events on stretched DNA tethers in multiple geometries. We find that gp41 activity is significantly dependent on the geometry and tension of the occluded strand, suggesting an interaction between gp41 and the occluded strand that stimulates the helicase. However, the geometry dependence of gp41 activity is the opposite of that found previously for the E. coli hexameric helicase DnaB. Namely, tension applied between the occluded strand and dsDNA stem inhibits unwinding activity by gp41, while tension pulling apart the two ssDNA tails does not hinder its activity. This implies a distinct variation in helicase-occluded strand interactions among superfamily IV helicases, and we propose a speculative model for this interaction that is consistent with both the data presented here on gp41 and the data that had been previously reported for DnaB.

STS-9 payload specialist Merbold and backup Ockels in training session

Science.gov (United States)

1983-01-01

STS-9 payload specialist Ulf Merbold, right, a West German physicist and backup Wubbo Ockels, a Dutch scientist, are pictured in a training session in JSC's Shuttle mockup and integration laboratory. In this view Ockels appears to be showing Merbold how to operate a camera.

MOOC Introduction to Dutch

NARCIS (Netherlands)

den Hollander, Franciscus; Piersma, Kristien

Interview met Margriet Hidding, Birgit Lijmbach en Jeroen van Engen, medewerkers van het Talencentrum en de makers van de Massive Open Online Course (MOOC) Introduction to Dutch over het grote succes van deze cursus

Development of a novel, guinea pig-specific IFN-γ ELISPOT assay and characterization of guinea pig cytomegalovirus GP83-specific cellular immune responses following immunization with a modified vaccinia virus Ankara (MVA)-vectored GP83 vaccine.

Science.gov (United States)

Gillis, Peter A; Hernandez-Alvarado, Nelmary; Gnanandarajah, Josephine S; Wussow, Felix; Diamond, Don J; Schleiss, Mark R

2014-06-30

The guinea pig (Cavia porcellus) provides a useful animal model for studying the pathogenesis of many infectious diseases, and for preclinical evaluation of vaccines. However, guinea pig models are limited by the lack of immunological reagents required for characterization and quantification of antigen-specific T cell responses. To address this deficiency, an enzyme-linked immunospot (ELISPOT) assay for guinea pig interferon (IFN)-γ was developed to measure antigen/epitope-specific T cell responses to guinea pig cytomegalovirus (GPCMV) vaccines. Using splenocytes harvested from animals vaccinated with a modified vaccinia virus Ankara (MVA) vector encoding the GPCMV GP83 (homolog of human CMV pp65 [gpUL83]) protein, we were able to enumerate and map antigen-specific responses, both in vaccinated as well as GPCMV-infected animals, using a panel of GP83-specific peptides. Several potential immunodominant GP83-specific peptides were identified, including one epitope, LGIVHFFDN, that was noted in all guinea pigs that had a detectable CD8+ response to GP83. Development of a guinea pig IFN-γ ELISPOT should be useful in characterization of additional T cell-specific responses to GPCMV, as well as other pathogens. This information in turn can help focus future experimental evaluation of immunization strategies, both for GPCMV as well as for other vaccine-preventable illnesses studied in the guinea pig model. Copyright © 2014 Elsevier Ltd. All rights reserved.

Structure-based, targeted deglycosylation of HIV-1 gp120 and effects on neutralization sensitivity and antibody recognition

International Nuclear Information System (INIS)

Koch, Markus; Pancera, Marie; Kwong, Peter D.; Kolchinsky, Peter; Grundner, Christoph; Wang Liping; Hendrickson, Wayne A.; Sodroski, Joseph; Wyatt, Richard

2003-01-01

The human immunodeficiency virus (HIV-1) exterior envelope glycoprotein, gp120, mediates receptor binding and is the major target for neutralizing antibodies. Primary HIV-1 isolates are characteristically more resistant to broadly neutralizing antibodies, although the structural basis for this resistance remains obscure. Most broadly neutralizing antibodies are directed against functionally conserved gp120 regions involved in binding to either the primary virus receptor, CD4, or the viral coreceptor molecules that normally function as chemokine receptors. These antibodies are known as CD4 binding site (CD4BS) and CD4-induced (CD4i) antibodies, respectively. Inspection of the gp120 crystal structure reveals that although the receptor-binding regions lack glycosylation, sugar moieties lie proximal to both receptor-binding sites on gp120 and thus in proximity to both the CD4BS and the CD4i epitopes. In this study, guided by the X-ray crystal structure of gp120, we deleted four N-linked glycosylation sites that flank the receptor-binding regions. We examined the effects of selected changes on the sensitivity of two prototypic HIV-1 primary isolates to neutralization by antibodies. Surprisingly, removal of a single N-linked glycosylation site at the base of the gp120 third variable region (V3 loop) increased the sensitivity of the primary viruses to neutralization by CD4BS antibodies. Envelope glycoprotein oligomers on the cell surface derived from the V3 glycan-deficient virus were better recognized by a CD4BS antibody and a V3 loop antibody than were the wild-type glycoproteins. Absence of all four glycosylation sites rendered a primary isolate sensitive to CD4i antibody-mediated neutralization. Thus, carbohydrates that flank receptor-binding regions on gp120 protect primary HIV-1 isolates from antibody-mediated neutralization

Autographa californica multiple nucleopolyhedrovirus GP64 protein: Analysis of domain I and V amino acid interactions and membrane fusion activity

Energy Technology Data Exchange (ETDEWEB)

Yu, Qianlong [State Key Laboratory of Crop Stress Biology for Arid Areas, Key Laboratory of Northwest Loess Plateau Crop Pest Management of Ministry of Agriculture, College of Plant Protection, Northwest A& F University, Yangling, Shaanxi 712100 (China); Blissard, Gary W. [Boyce Thompson Institute, Cornell University, Ithaca, NY 14853, United State (United States); Liu, Tong-Xian [State Key Laboratory of Crop Stress Biology for Arid Areas, Key Laboratory of Northwest Loess Plateau Crop Pest Management of Ministry of Agriculture, College of Plant Protection, Northwest A& F University, Yangling, Shaanxi 712100 (China); Li, Zhaofei, E-mail: zhaofeili73@outlook.com [State Key Laboratory of Crop Stress Biology for Arid Areas, Key Laboratory of Northwest Loess Plateau Crop Pest Management of Ministry of Agriculture, College of Plant Protection, Northwest A& F University, Yangling, Shaanxi 712100 (China)

2016-01-15

The Autographa californica multiple nucleopolyhedrovirus GP64 is a class III viral fusion protein. Although the post-fusion structure of GP64 has been solved, its pre-fusion structure and the detailed mechanism of conformational change are unknown. In GP64, domain V is predicted to interact with two domain I segments that flank fusion loop 2. To evaluate the significance of the amino acids involved in these interactions, we examined 24 amino acid positions that represent interacting and conserved residues within domains I and V. In several cases, substitution of a single amino acid involved in a predicted interaction disrupted membrane fusion activity, but no single amino acid pair appears to be absolutely required. We identified 4 critical residues in domain V (G438, W439, T452, and T456) that are important for membrane fusion, and two residues (G438 and W439) that appear to be important for formation or stability of the pre-fusion conformation of GP64. - Highlights: • The baculovirus envelope glycoprotein GP64 is a class III viral fusion protein. • The detailed mechanism of conformational change of GP64 is unknown. • We analyzed 24 positions that might stabilize the post-fusion structure of GP64. • We identified 4 residues in domain V that were critical for membrane fusion. • Two residues are critical for formation of the pre-fusion conformation of GP64.

GP-Unet

DEFF Research Database (Denmark)

Dubost, Florian; Bortsova, Gerda; Adams, Hieab

2017-01-01

We propose a novel convolutional neural network for lesion detection from weak labels. Only a single, global label per image - the lesion count - is needed for training. We train a regression network with a fully convolutional architecture combined with a global pooling layer to aggregate the 3D ...

Between local governments and communities: Knowledge exchange and mutual learning in Dutch-Moroccan and Dutch-Turkish municipal partnerships

OpenAIRE

van Ewijk, E.

2013-01-01

This PhD dissertation focuses on mutual learning processes of governmental and non-governmental actors involved in Dutch-Moroccan and Dutch-Turkish municipal partnerships in the period 2007-2011. These partnerships aim at strengthening local governance in Morocco and Turkey as well as in the Netherlands. The research focuses on five case studies and indicate the partnerships lead to important forms of learning at both sides, including strengthening service delivery and working in multi-actor ...

Soluble rhesus lymphocryptovirus gp350 protects against infection and reduces viral loads in animals that become infected with virus after challenge.

Directory of Open Access Journals (Sweden)

Junji Sashihara

2011-10-01

Full Text Available Epstein-Barr virus (EBV is a human lymphocryptovirus that is associated with several malignancies. Elevated EBV DNA in the blood is observed in transplant recipients prior to, and at the time of post-transplant lymphoproliferative disease; thus, a vaccine that either prevents EBV infection or lowers the viral load might reduce certain EBV malignancies. Two major approaches have been suggested for an EBV vaccine- immunization with either EBV glycoprotein 350 (gp350 or EBV latency proteins (e.g. EBV nuclear antigens [EBNAs]. No comparative trials, however, have been performed. Rhesus lymphocryptovirus (LCV encodes a homolog for each gene in EBV and infection of monkeys reproduces the clinical, immunologic, and virologic features of both acute and latent EBV infection. We vaccinated rhesus monkeys at 0, 4 and 12 weeks with (a soluble rhesus LCV gp350, (b virus-like replicon particles (VRPs expressing rhesus LCV gp350, (c VRPs expressing rhesus LCV gp350, EBNA-3A, and EBNA-3B, or (d PBS. Animals vaccinated with soluble gp350 produced higher levels of antibody to the glycoprotein than those vaccinated with VRPs expressing gp350. Animals vaccinated with VRPs expressing EBNA-3A and EBNA-3B developed LCV-specific CD4 and CD8 T cell immunity to these proteins, while VRPs expressing gp350 did not induce detectable T cell immunity to gp350. After challenge with rhesus LCV, animals vaccinated with soluble rhesus LCV gp350 had the best level of protection against infection based on seroconversion, viral DNA, and viral RNA in the blood after challenge. Surprisingly, animals vaccinated with gp350 that became infected had the lowest LCV DNA loads in the blood at 23 months after challenge. These studies indicate that gp350 is critical for both protection against infection with rhesus LCV and for reducing the viral load in animals that become infected after challenge. Our results suggest that additional trials with soluble EBV gp350 alone, or in combination with

Dutch Building Decree

NARCIS (Netherlands)

Scholten, N.P.M.

2000-01-01

On the 1 October 1992 a change in the Dutch building legislation took effect: the revised Housing Act, the Building Decree and the technical documents related to this legislation came into force. This publication contains an English translation of the Building Decree. In order to give an idea of the

GP2 is selectively expressed by small intestinal CD103⁺CD11b⁺ cDC

DEFF Research Database (Denmark)

Müller-Luda, Katarzyna; Ahmadi, Fatemeh; Ohno, Hiroshi

DC in the small intestine. Moreover, GP2 expressing cDC in the small intestine were dramatically reduced in the setting of intestinal inflammation. We have previously shown that mice with an IRF4 deletion in CD11c+ cells (Cd11c-cre.Irf4 fl/fl mice) have reduced numbers of small intestinal CD103+CD11b+ c......DC. Interesting, we found that GP2+ CD103+CD11b+ cDC were dramatically reduced in these mice. Finally, to address the in vivo role of GP2 expression by cDC, we have generated mice with a selective deletion of GP2 in CD103+CD11b+ cDC (huLangerin-cre.gp2 fl/fl  mice). Results from these ongoing studies...

Selection of GP. Mur antigen-negative RBC for blood recipients with anti-'Mia ' records decreases transfusion reaction rates in Taiwan.

Science.gov (United States)

Yang, C-A; Lin, J-A; Chang, C-W; Wu, K-H; Yeh, S-P; Ho, C-M; Chang, J-G

2016-10-01

To evaluate the clinical significance of GP. Mur antigen-negative blood selection for transfusion in patients with anti-'Mi a ' records. The GP. Mur RBC phenotype is prevalent (7·3%) in Taiwan. Antibodies against GP. Mur (anti-'Mi a ') are identified in 1·24% of our population, and anti-'Mi a ' screening using GP. Mur RBC has been routine for Taiwan's blood banks. However, due to the lack of commercial antibodies, only cross-matching was used to prevent transfusion of GP. Mur-positive blood to patients with anti-'Mi a ' in most hospitals. There is still a risk of GP. Mur-positive RBC exposure and subsequent anti-'Mi a '-related transfusion reactions. Since February 2014, GP. Mur antigen-negative RBCs identified by reaction with anti-'Mi a '-positive serum were selected for blood recipients with anti-'Mi a ' records. The transfusion reactions between January 2013 and January 2014 were compared with those that occurred between February 2014 and July 2015. The transfusion reaction rate was significantly higher in anti-'Mi a '-positive blood recipients compared to total subjects receiving an RBC transfusion before GP. Mur-negative donor RBC selection. After antigen-negative RBC selection, the transfusion reaction frequency in subjects with anti-'Mi a ' became similar to total blood recipients. IgG form anti-'Mi a ' antibodies were present in all cases of probable anti-'Mi a '-related transfusion reactions. The time required for anti-'Mi a ' boosting after transfusion was around 4-21 days. Selection of GP. Mur-negative RBC for transfusion to patients with anti-'Mi a ' records could decrease the rate of transfusion reaction and antibody boosting. This procedure should be incorporated into blood bank routines in areas where anti-'Mi a ' is prevalent. © 2016 British Blood Transfusion Society.

Basso continuo sources from the Dutch Republic c. 1620-c1790

NARCIS (Netherlands)

Cok, Kathryn Meriel

2011-01-01

The results presented in this dissertation demonstrate the generous contribution that the Dutch Republic has made to the genre of basso continuo, including a survey of twenty-six Dutch sources from the 17th and 18th centuries. Focus has been made on the written record of the practice in the Dutch

Economic Impact of the Dutch Gas Hub Strategy on the Netherlands

International Nuclear Information System (INIS)

Harris, D.; Bazelon, C.; Humphreys, B.; Dickson, P.

2010-09-01

Since the discovery of the Groningen gas field in 1959, the Netherlands has been a key player in the European gas market. The Netherlands has built up a large onshore and offshore Exploration and Production sector, it has a highly developed gas transmission and distribution network, and is a major exporter of gas to other EU Member States. The Netherlands has considerable expertise in all parts of the gas supply chain, and is a world centre for Research and development in natural gas supply and use. More recently construction has begun on terminals to allow the import of Liquid Natural Gas to the Netherlands. However, Dutch gas reserves are now in decline, and the Netherlands will become a net importer of gas around 2025. The Dutch government wishes to capitalise on the existing industry and skills and sustain the Netherlands' place in the European gas industry beyond the life of the existing gas fields. In November 2009 the Minister of Economic Affairs published a paper describing the strategy of turning the Netherlands into a 'Gas Hub' or 'gas roundabout' for north-west Europe. The Dutch government intends that the gas hub would capitalise on the existing skills and industry, increase competition and security of supply in the Dutch gas market, create employment and make a significant contribution to the Dutch economy. The Dutch Ministry of Economic Affairs, Agriculture and Innovation has commissioned The Brattle Group to perform an analysis of the economic impact of the gas hub concept. The study has several aims including: To analyse the current contribution of the Dutch gas sector to the economy; To assess the Strengths, Weaknesses, Opportunities and Threats associated with the gas hub strategy; To quantify the benefits of the gas hub strategy to the Dutch economy. Note that the aim of the study is to define in more detail what a successful Dutch gas hub strategy would look like, to assess the strengths and weakness of the Dutch gas sector in achieving a

Upregulations of Clcn3 and P-Gp Provoked by Lens Osmotic Expansion in Rat Galactosemic Cataract

Directory of Open Access Journals (Sweden)

Lixia Ji

2017-01-01

Full Text Available Objective. Lens osmotic expansion, provoked by overactivated aldose reductase (AR, is the most essential event of sugar cataract. Chloride channel 3 (Clcn3 is a volume-sensitive channel, mainly participating in the regulation of cell fundamental volume, and P-glycoprotein (P-gp acts as its modulator. We aim to study whether P-gp and Clcn3 are involved in lens osmotic expansion of galactosemic cataract. Methods and Results. In vitro, lens epithelial cells (LECs were primarily cultured in gradient galactose medium (10–60 mM, more and more vacuoles appeared in LEC cytoplasm, and mRNA and protein levels of AR, P-gp, and Clcn3 were synchronously upregulated along with the increase of galactose concentration. In vivo, we focused on the early stage of rat galactosemic cataract, amount of vacuoles arose from equatorial area and scattered to the whole anterior capsule of lenses from the 3rd day to the 9th day, and mRNA and protein levels of P-gp and Clcn3 reached the peak around the 9th or 12th day. Conclusion. Galactosemia caused the osmotic stress in lenses; it also markedly leads to the upregulations of AR, P-gp, and Clcn3 in LECs, together resulting in obvious osmotic expansion in vitro and in vivo.

Dutch translation and cross-cultural adaptation of the PROMIS® physical function item bank and cognitive pre-test in Dutch arthritis patients.

Science.gov (United States)

Oude Voshaar, Martijn Ah; Ten Klooster, Peter M; Taal, Erik; Krishnan, Eswar; van de Laar, Mart Afj

2012-03-05

Patient-reported physical function is an established outcome domain in clinical studies in rheumatology. To overcome the limitations of the current generation of questionnaires, the Patient-Reported Outcomes Measurement Information System (PROMIS®) project in the USA has developed calibrated item banks for measuring several domains of health status in people with a wide range of chronic diseases. The aim of this study was to translate and cross-culturally adapt the PROMIS physical function item bank to the Dutch language and to pretest it in a sample of patients with arthritis. The items of the PROMIS physical function item bank were translated using rigorous forward-backward protocols and the translated version was subsequently cognitively pretested in a sample of Dutch patients with rheumatoid arthritis. Few issues were encountered in the forward-backward translation. Only 5 of the 124 items to be translated had to be rewritten because of culturally inappropriate content. Subsequent pretesting showed that overall, questions of the Dutch version were understood as they were intended, while only one item required rewriting. Results suggest that the translated version of the PROMIS physical function item bank is semantically and conceptually equivalent to the original. Future work will be directed at creating a Dutch-Flemish final version of the item bank to be used in research with Dutch speaking populations.

The predictive validity of a situational judgement test, a clinical problem solving test and the core medical training selection methods for performance in specialty training .

Science.gov (United States)

Patterson, Fiona; Lopes, Safiatu; Harding, Stephen; Vaux, Emma; Berkin, Liz; Black, David

2017-02-01

The aim of this study was to follow up a sample of physicians who began core medical training (CMT) in 2009. This paper examines the long-term validity of CMT and GP selection methods in predicting performance in the Membership of Royal College of Physicians (MRCP(UK)) examinations. We performed a longitudinal study, examining the extent to which the GP and CMT selection methods (T1) predict performance in the MRCP(UK) examinations (T2). A total of 2,569 applicants from 2008-09 who completed CMT and GP selection methods were included in the study. Looking at MRCP(UK) part 1, part 2 written and PACES scores, both CMT and GP selection methods show evidence of predictive validity for the outcome variables, and hierarchical regressions show the GP methods add significant value to the CMT selection process. CMT selection methods predict performance in important outcomes and have good evidence of validity; the GP methods may have an additional role alongside the CMT selection methods. © Royal College of Physicians 2017. All rights reserved.

Immunization with Hexon modified adenoviral vectors integrated with gp83 epitope provides protection against Trypanosoma cruzi infection.

Directory of Open Access Journals (Sweden)

Anitra L Farrow

2014-08-01

Full Text Available Trypanosoma cruzi is the causative agent of Chagas disease. Chagas disease is an endemic infection that affects over 8 million people throughout Latin America and now has become a global challenge. The current pharmacological treatment of patients is unsuccessful in most cases, highly toxic, and no vaccines are available. The results of inadequate treatment could lead to heart failure resulting in death. Therefore, a vaccine that elicits neutralizing antibodies mediated by cell-mediated immune responses and protection against Chagas disease is necessary.The "antigen capsid-incorporation" strategy is based upon the display of the T. cruzi epitope as an integral component of the adenovirus' capsid rather than an encoded transgene. This strategy is predicted to induce a robust humoral immune response to the presented antigen, similar to the response provoked by native Ad capsid proteins. The antigen chosen was T. cruzi gp83, a ligand that is used by T. cruzi to attach to host cells to initiate infection. The gp83 epitope, recognized by the neutralizing MAb 4A4, along with His6 were incorporated into the Ad serotype 5 (Ad5 vector to generate the vector Ad5-HVR1-gp83-18 (Ad5-gp83. This vector was evaluated by molecular and immunological analyses. Vectors were injected to elicit immune responses against gp83 in mouse models. Our findings indicate that mice immunized with the vector Ad5-gp83 and challenged with a lethal dose of T. cruzi trypomastigotes confer strong immunoprotection with significant reduction in parasitemia levels, increased survival rate and induction of neutralizing antibodies.This data demonstrates that immunization with adenovirus containing capsid-incorporated T. cruzi antigen elicits a significant anti-gp83-specific response in two different mouse models, and protection against T. cruzi infection by eliciting neutralizing antibodies mediated by cell-mediated immune responses, as evidenced by the production of several Ig isotypes

HIV gp120 binds to mannose receptor on vaginal epithelial cells and induces production of matrix metalloproteinases.

Directory of Open Access Journals (Sweden)

Sashaina E Fanibunda

Full Text Available BACKGROUND: During sexual transmission of HIV in women, the virus breaches the multi-layered CD4 negative stratified squamous epithelial barrier of the vagina, to infect the sub-epithelial CD4 positive immune cells. However the mechanisms by which HIV gains entry into the sub-epithelial zone is hitherto unknown. We have previously reported human mannose receptor (hMR as a CD4 independent receptor playing a role in HIV transmission on human spermatozoa. The current study was undertaken to investigate the expression of hMR in vaginal epithelial cells, its HIV gp120 binding potential, affinity constants and the induction of matrix metalloproteinases (MMPs downstream of HIV gp120 binding to hMR. PRINCIPAL FINDINGS: Human vaginal epithelial cells and the immortalized vaginal epithelial cell line Vk2/E6E7 were used in this study. hMR mRNA and protein were expressed in vaginal epithelial cells and cell line, with a molecular weight of 155 kDa. HIV gp120 bound to vaginal proteins with high affinity, (Kd = 1.2±0.2 nM for vaginal cells, 1.4±0.2 nM for cell line and the hMR antagonist mannan dose dependently inhibited this binding. Both HIV gp120 binding and hMR exhibited identical patterns of localization in the epithelial cells by immunofluorescence. HIV gp120 bound to immunopurified hMR and affinity constants were 2.9±0.4 nM and 3.2±0.6 nM for vaginal cells and Vk2/E6E7 cell line respectively. HIV gp120 induced an increase in MMP-9 mRNA expression and activity by zymography, which could be inhibited by an anti-hMR antibody. CONCLUSION: hMR expressed by vaginal epithelial cells has high affinity for HIV gp120 and this binding induces production of MMPs. We propose that the induction of MMPs in response to HIV gp120 may lead to degradation of tight junction proteins and the extracellular matrix proteins in the vaginal epithelium and basement membrane, leading to weakening of the epithelial barrier; thereby facilitating transport of HIV across the

Access to and utilisation of GP services among Burmese migrants in London: a cross-sectional descriptive study.

Science.gov (United States)

Aung, Nyein Chan; Rechel, Bernd; Odermatt, Peter

2010-10-12

An estimated 10,000 Burmese migrants are currently living in London. No studies have been conducted on their access to health services. Furthermore, most studies on migrants in the United Kingdom (UK) have been conducted at the point of service provision, carrying the risk of selection bias. Our cross-sectional study explored access to and utilisation of General Practice (GP) services by Burmese migrants residing in London. We used a mixed-method approach: a quantitative survey using self-administered questionnaires was complemented by qualitative in-depth interviews for developing the questionnaire and triangulating the findings of the survey. Overall, 137 questionnaires were received (a response rate of 57%) and 11 in-depth interviews conducted. The main outcome variables of the study included GP registration, barriers towards registration, GP consultations, barriers towards consultations, and knowledge on entitlements to health care. Quantitative data were analysed using descriptive statistics, association tests, and a multivariate analysis using logistic regression. The qualitative information was analysed using content analysis. The respondents were young, of roughly equal gender (51.5% female), well educated, and had a fair level of knowledge on health services in the UK. Although the GP registration rate was relatively high (80%, 109 out of 136), GP service utilisation during the last episode of illness, at 56.8% (54 out of 95), was low. The statistical analysis showed that age being younger than 35 years, lacking prior overseas experience, having an unstable immigration status, having a shorter duration of stay, and resorting to self-medication were the main barriers hindering Burmese migrants from accessing primary health care services. These findings were corroborated by the in-depth interviews. Our study found that having formal access to primary health care was not sufficient to ensure GP registration and health care utilisation. Some respondents faced

Access to and utilisation of GP services among Burmese migrants in London: a cross-sectional descriptive study

Directory of Open Access Journals (Sweden)

Rechel Bernd

2010-10-01

Full Text Available Abstract Background An estimated 10,000 Burmese migrants are currently living in London. No studies have been conducted on their access to health services. Furthermore, most studies on migrants in the United Kingdom (UK have been conducted at the point of service provision, carrying the risk of selection bias. Our cross-sectional study explored access to and utilisation of General Practice (GP services by Burmese migrants residing in London. Methods We used a mixed-method approach: a quantitative survey using self-administered questionnaires was complemented by qualitative in-depth interviews for developing the questionnaire and triangulating the findings of the survey. Overall, 137 questionnaires were received (a response rate of 57% and 11 in-depth interviews conducted. The main outcome variables of the study included GP registration, barriers towards registration, GP consultations, barriers towards consultations, and knowledge on entitlements to health care. Quantitative data were analysed using descriptive statistics, association tests, and a multivariate analysis using logistic regression. The qualitative information was analysed using content analysis. Results The respondents were young, of roughly equal gender (51.5% female, well educated, and had a fair level of knowledge on health services in the UK. Although the GP registration rate was relatively high (80%, 109 out of 136, GP service utilisation during the last episode of illness, at 56.8% (54 out of 95, was low. The statistical analysis showed that age being younger than 35 years, lacking prior overseas experience, having an unstable immigration status, having a shorter duration of stay, and resorting to self-medication were the main barriers hindering Burmese migrants from accessing primary health care services. These findings were corroborated by the in-depth interviews. Conclusions Our study found that having formal access to primary health care was not sufficient to ensure GP

Cultural Perspectives on Peer Conflicts in Multicultural Dutch Child Care Centres

Science.gov (United States)

Rourou, Amina; Singer, Elly; Bekkema, Nienke; De Haan, Dorian

2006-01-01

In this paper we discuss a study of cultural perspectives on peer conflicts in multicultural child care centres. On the level of child behaviour we did not find differences between native Dutch. Moroccan-Dutch and Antillean-Dutch children with regard to occurrence, duration and actions to solve peer conflicts. On the level of mother' opinions…

Development of the gas puff charge exchange recombination spectroscopy (GP-CXRS) technique for ion measurements in the plasma edge

International Nuclear Information System (INIS)

Churchill, R. M.; Theiler, C.; Lipschultz, B.; Dux, R.; Pütterich, T.; Viezzer, E.

2013-01-01

A novel charge-exchange recombination spectroscopy (CXRS) diagnostic method is presented, which uses a simple thermal gas puff for its donor neutral source, instead of the typical high-energy neutral beam. This diagnostic, named gas puff CXRS (GP-CXRS), is used to measure ion density, velocity, and temperature in the tokamak edge/pedestal region with excellent signal-background ratios, and has a number of advantages to conventional beam-based CXRS systems. Here we develop the physics basis for GP-CXRS, including the neutral transport, the charge-exchange process at low energies, and effects of energy-dependent rate coefficients on the measurements. The GP-CXRS hardware setup is described on two separate tokamaks, Alcator C-Mod and ASDEX Upgrade. Measured spectra and profiles are also presented. Profile comparisons of GP-CXRS and a beam based CXRS system show good agreement. Emphasis is given throughout to describing guiding principles for users interested in applying the GP-CXRS diagnostic technique

Development of the gas puff charge exchange recombination spectroscopy (GP-CXRS) technique for ion measurements in the plasma edge

Energy Technology Data Exchange (ETDEWEB)

Churchill, R. M.; Theiler, C.; Lipschultz, B. [MIT Plasma Science and Fusion Center, Cambridge, Massachusetts 02139 (United States); Dux, R.; Pütterich, T.; Viezzer, E. [Max-Planck-Institut für Plasmaphysik, EURATOM Association, Boltzmannstrasse 2, D-85748 Garching (Germany); Collaboration: Alcator C-Mod Team; ASDEX Upgrade Team

2013-09-15

A novel charge-exchange recombination spectroscopy (CXRS) diagnostic method is presented, which uses a simple thermal gas puff for its donor neutral source, instead of the typical high-energy neutral beam. This diagnostic, named gas puff CXRS (GP-CXRS), is used to measure ion density, velocity, and temperature in the tokamak edge/pedestal region with excellent signal-background ratios, and has a number of advantages to conventional beam-based CXRS systems. Here we develop the physics basis for GP-CXRS, including the neutral transport, the charge-exchange process at low energies, and effects of energy-dependent rate coefficients on the measurements. The GP-CXRS hardware setup is described on two separate tokamaks, Alcator C-Mod and ASDEX Upgrade. Measured spectra and profiles are also presented. Profile comparisons of GP-CXRS and a beam based CXRS system show good agreement. Emphasis is given throughout to describing guiding principles for users interested in applying the GP-CXRS diagnostic technique.

National Identification of Dutch Youth: An Exploratory Study

Science.gov (United States)

Oppenheimer, Louis

2011-01-01

246 Dutch participants aged 8, 10, 12, 14, and 16 years were presented with the Strength of Identification Scale (SoIS; Barrett, 2007) and the National Identity scale based on Cultural and Historical achievements (NICH; derived from the NATID, Keillor & Hult, 1999). The study aimed to examine the extent and nature of Dutch children and…

Gravity Probe-B (GP-B) Mission and Tracking, Telemetry and Control Subsystem Overview

Science.gov (United States)

Kennedy, Paul; Bell, Joseph L. (Technical Monitor)

2001-01-01

The National Aeronautics and Space Administration's (NASA) Marshall Space Flight Center (MSFC) in Huntsville, Alabama will launch the Gravity Probe B (GP-B) space experiment in the Fall of 2002. The GP-B spacecraft was developed to prove Einstein's theory of General Relativity. This paper will provide an overview of the GPB mission and will discuss the design, and test of the spacecraft Tracking, Telemetry and Control (TT&C) subsystem which incorporates NASA's latest generation standard transponder for use with the NASA Tracking and Data Relay Satellite System (TDRSS).

Practice variation in the Dutch long-term care and the role of supply-sensitive care: Is access to the Dutch long-term care equitable?

Science.gov (United States)

Duell, Daisy; Koolman, Xander; Portrait, France

2017-12-01

Universal access and generous coverage are important goals of the Dutch long-term care (LTC) system. It is a legal requirement that everyone eligible for LTC should be able to receive it. Institutional care (IC) made up for 90% of Dutch LTC spending. To investigate whether access to IC is as equitable as the Dutch government aspires, we explored practice variation in entitlements to IC across Dutch regions. We used a unique dataset that included all individual applications for Dutch LTC in January 2010-December 2013 (N = 3,373,358). This dataset enabled an accurate identification of the need for care. We examined the local variation in the probability of being granted long-term IC and in the intensity of the care granted given that individuals have applied for LTC. We also investigated whether the variation observed was related to differences in the local availability of care facilities. Although our analyses indicated the presence of some practice variation, its magnitude was very small by national and international standards (up to 3%). Only a minor part of the practice variation could be accounted for by local supply differences in care facilities. Overall, we conclude that, unlike many other developed countries, the Dutch system ensured equitable access to long-term IC. © 2017 The Authors. Health Economics Published by John Wiley & Sons Ltd.

Mimicking protein-protein interactions through peptide-peptide interactions: HIV-1 gp120 and CXCR4

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Andrea eGross

2013-09-01

Full Text Available We have recently designed a soluble synthetic peptide that functionally mimics the HIV-1 coreceptor CXCR4, which is a chemokine receptor that belongs to the family of seven-transmembrane GPCRs. This CXCR4 mimetic peptide, termed CX4-M1, presents the three extracellular loops (ECLs of the receptor. In binding assays involving recombinant proteins, as well as in cellular infection assays, CX4-M1 was found to selectively recognize gp120 from HIV-1 strains that use CXCR4 for cell entry (X4 tropic HIV-1. Furthermore, anti-HIV-1 antibodies modulate this interaction in a molecular mechanism related to that of their impact on the gp120-CXCR4 interaction. We could now show that the selectivity of CX4-M1 pertains not only to gp120 from X4 tropic HIV-1, but also to synthetic peptides presenting the V3 loops of these gp120 proteins. The V3 loop is thought to be an essential part of the coreceptor binding site of gp120 that contacts the second ECL of the coreceptor. We were able to experimentally confirm this notion in binding assays using substitution analogs of CX4-M1 and the V3 loop peptides, respectively, as well as in cellular infection assays. These results indicate that interactions of the HIV-1 Env with coreceptors can be mimicked by synthetic peptides, which may be useful to explore these interactions at the molecular level in more detail.

Striking HIV-1 Entry by Targeting HIV-1 gp41. But, Where Should We Target?

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Cátia Teixeira

Full Text Available HIV-1 gp41 facilitates the viral fusion through a conformational switch involving the association of three C-terminal helices along the conserved hydrophobic grooves of three N-terminal helices coiled-coil. The control of these structural rearrangements is thought to be central to HIV-1 entry and, therefore, different strategies of intervention are being developed. Herewith, we describe a procedure to simulate the folding of an HIV-1 gp41 simplified model. This procedure is based on the construction of plausible conformational pathways, which describe protein transition between non-fusogenic and fusogenic conformations. The calculation of the paths started with 100 molecular dynamics simulations of the non-fusogenic conformation, which were found to converge to different intermediate states. Those presenting defined criteria were selected for separate targeted molecular dynamics simulations, subjected to a force constant imposing a movement towards the gp41 fusogenic conformation. Despite significant diversity, a preferred sequence of events emerged when the simulations were analyzed in terms of the formation, breakage and evolution of the contacts. We pointed out 29 residues as the most relevant for the movement of gp41; also, 2696 possible interactions were reduced to only 48 major interactions, which reveals the efficiency of the method. The analysis of the evolution of the main interactions lead to the detection of four main behaviors for those contacts: stable, increasing, decreasing and repulsive interactions. Altogether, these results suggest a specific small cavity of the HIV-1 gp41 hydrophobic groove as the preferred target to small molecules.

Small-angle scattering from GP zones in Al–Cu alloy

Indian Academy of Sciences (India)

Administrator

ficial aging, which are extensively used in commercial practice. It is well established ... Cu system shows the variety of metastable states follow- ing the sequence SSS .... the model for spinodal decomposition of GP 1 zones in. Al–Cu system ...

Dutch Wholesale Power Market Review 2002. Executive Summary

International Nuclear Information System (INIS)

Vollebregt, T.; Rusch, H.

2002-01-01

Chapter 1 provides a background to the Dutch power market, covering generation, transmission, distribution, supply, and laws and regulations. Chapter 2 reviews the key market events during 2001 and early 2002, providing analysis and background on an important and tumultuous period in the Dutch market. Chapter 3 explains the structure and timing of the key market mechanisms (Amsterdam Power Exchange, interconnector capacity auctions, TenneT 15-minute balancing market). Chapter 4 briefly reviews fuel price developments and discusses their impact on the costs of generation. Chapter 5 contains a detailed review of the traded Dutch power markets (APX, OTC, interconnection), including the linkages between these markets and an analysis of arbitrage opportunities

The actual role of general practice in the Dutch health-care system: results of the Second Dutch National Survey of General Practice.

NARCIS (Netherlands)

Schellevis, F.G.; Westert, G.P.; Bakker, D.H. de

2005-01-01

A second Dutch National Survey of General Practice was carried out in 2001 with the aim of providing actual information about the role of general practice in the Dutch health-care system for researchers and policy makers. Data were collected on different levels (patients, general practitioners,

Inhibitory effects of herbal constituents on P-glycoprotein in vitro and in vivo: Herb–drug interactions mediated via P-gp

Energy Technology Data Exchange (ETDEWEB)

Li, Xue, E-mail: lixue@imm.ac.cn; Hu, Jinping, E-mail: hujp@imm.ac.cn; Wang, Baolian, E-mail: wangbaolian@imm.ac.cn; Sheng, Li, E-mail: shengli@imm.ac.cn; Liu, Zhihao, E-mail: liuzhihao@imm.ac.cn; Yang, Shuang, E-mail: yangsh@imm.ac.cn; Li, Yan, E-mail: yanli@imm.ac.cn

2014-03-01

Modulation of drug transporters via herbal medicines which have been widely used in combination with conventional prescription drugs may result in herb–drug interactions in clinical practice. The present study was designed to investigate the inhibitory effects of 50 major herbal constituents on P-glycoprotein (P-gp) in vitro and in vivo as well as related inhibitory mechanisms. Among these herbal medicines, four constituents, including emodin, 18β-glycyrrhetic acid (18β-GA), dehydroandrographolide (DAG), and 20(S)-ginsenoside F{sub 1} [20(S)-GF{sub 1}] exhibited significant inhibition (> 50%) on P-gp in MDR1-MDCKII and Caco-2 cells. Emodin was the strongest inhibitor of P-gp (IC{sub 50} = 9.42 μM), followed by 18β-GA (IC{sub 50} = 21.78 μM), 20(S)-GF{sub 1} (IC{sub 50} = 76.08 μM) and DAG (IC{sub 50} = 77.80 μM). P-gp ATPase activity, which was used to evaluate the affinity of substrates to P-gp, was stimulated by emodin and DAG with K{sub m} and V{sub max} values of 48.61, 29.09 μM and 71.29, 38.45 nmol/min/mg protein, respectively. However, 18β-GA and 20(S)-GF{sub 1} exhibited significant inhibition on both basal and verapamil-stimulated P-gp ATPase activities at high concentration. Molecular docking analysis (CDOCKER) further elucidated the mechanism for structure–inhibition relationships of herbal constituents with P-gp. When digoxin was co-administered to male SD rats with emodin or 18β-GA, the AUC{sub 0−t} and Cmax of digoxin were increased by approximately 51% and 58%, respectively. Furthermore, 18β-GA, DAG, 20(S)-GF{sub 1} and Rh{sub 1} at 10 μM significantly inhibited CYP3A4/5 activity, while emodin activated the metabolism of midazolam in human liver microsomes. In conclusion, four herbal constituents demonstrated inhibition of P-gp to specific extents in vitro and in vivo. Taken together, our findings provided the basis for the reliable assessment of the potential risks of herb–drug interactions in humans. - Highlights: • Emodin, 18

Inhibitory effects of herbal constituents on P-glycoprotein in vitro and in vivo: Herb–drug interactions mediated via P-gp

International Nuclear Information System (INIS)

Li, Xue; Hu, Jinping; Wang, Baolian; Sheng, Li; Liu, Zhihao; Yang, Shuang; Li, Yan

2014-01-01

Modulation of drug transporters via herbal medicines which have been widely used in combination with conventional prescription drugs may result in herb–drug interactions in clinical practice. The present study was designed to investigate the inhibitory effects of 50 major herbal constituents on P-glycoprotein (P-gp) in vitro and in vivo as well as related inhibitory mechanisms. Among these herbal medicines, four constituents, including emodin, 18β-glycyrrhetic acid (18β-GA), dehydroandrographolide (DAG), and 20(S)-ginsenoside F 1 [20(S)-GF 1 ] exhibited significant inhibition (> 50%) on P-gp in MDR1-MDCKII and Caco-2 cells. Emodin was the strongest inhibitor of P-gp (IC 50 = 9.42 μM), followed by 18β-GA (IC 50 = 21.78 μM), 20(S)-GF 1 (IC 50 = 76.08 μM) and DAG (IC 50 = 77.80 μM). P-gp ATPase activity, which was used to evaluate the affinity of substrates to P-gp, was stimulated by emodin and DAG with K m and V max values of 48.61, 29.09 μM and 71.29, 38.45 nmol/min/mg protein, respectively. However, 18β-GA and 20(S)-GF 1 exhibited significant inhibition on both basal and verapamil-stimulated P-gp ATPase activities at high concentration. Molecular docking analysis (CDOCKER) further elucidated the mechanism for structure–inhibition relationships of herbal constituents with P-gp. When digoxin was co-administered to male SD rats with emodin or 18β-GA, the AUC 0−t and Cmax of digoxin were increased by approximately 51% and 58%, respectively. Furthermore, 18β-GA, DAG, 20(S)-GF 1 and Rh 1 at 10 μM significantly inhibited CYP3A4/5 activity, while emodin activated the metabolism of midazolam in human liver microsomes. In conclusion, four herbal constituents demonstrated inhibition of P-gp to specific extents in vitro and in vivo. Taken together, our findings provided the basis for the reliable assessment of the potential risks of herb–drug interactions in humans. - Highlights: • Emodin, 18β-GA, DAG, and 20(S)-GF 1 significantly inhibited P-gp in vitro

Training healthcare professionals as moral case deliberation facilitators : evaluation of a Dutch training programme

NARCIS (Netherlands)

Plantinga, Mirjam; Molewijk, Bert; de Bree, Menno; Moraal, Marloes; Verkerk, Marian; Widdershoven, Guy A. M.

2012-01-01

Until recently, moral case deliberation (MCD) sessions have mostly been facilitated by external experts, mainly professional ethicists. We have developed a train the facilitator programme for healthcare professionals aimed at providing them with the competences needed for being an MCD facilitator.

Training healthcare professionals as moral case deliberation facilitators: evaluation of a Dutch training programme

NARCIS (Netherlands)

Plantinga, M.; Molewijk, A.C.; de Bree, M.; Moraal, M.; Verkerk, M.; Widdershoven, G.A.

2012-01-01

Until recently, moral case deliberation (MCD) sessions have mostly been facilitated by external experts, mainly professional ethicists. We have developed a train the facilitator programme for healthcare professionals aimed at providing them with the competences needed for being an MCD facilitator.

Quality assessment and improvement of post graduate family medicine training in the USA.

Science.gov (United States)

Hoekzema, Grant S; Maxwell, Lisa; Gravel, Joseph W; Mills, Walter W; Geiger, William; Honeycutt, J David

2016-09-01

In 2013, the World Organisation of Family Doctors published training standards for post-graduate medical education (GME) in Family Medicine/General Practice (FP/GP). GME quality has not been well-defined, other than meeting accreditation standards. In 2009, the Association of Family Medicine Residency Directors (AFMRD) developed a tool that would aid in raising the quality of family medicine residency training in the USA. We describe the development of this quality improvement tool, which we called the residency performance index (RPI), and its first three years of use by US family medicine residency (FMR) programmes. The RPI uses metrics specific to family medicine training in the USA to help programmes identify strengths and areas for improvement in their educational activities. Our review of three years of experience with the RPI revealed difficulties with collecting data, and lack of information on graduates' scope of practice. It also showed the potential usefulness of the tool as a programme improvement mechanism. The RPI is a nationwide, standardised, programme quality improvement tool for family medicine residency programmes in the USA, which was successfully launched as part of AFMRD's strategic plan. Although some initial challenges need to be addressed, it has the promise to aid family medicine residencies in their internal improvement efforts. This model could be adapted in other post-graduate training settings in FM/GP around the world.

Re-Audit of the Contents of GP Referral letters to General Adult Community Psychiatrists.

Science.gov (United States)

Odelola, Catherine; Jabbar, Farid

2017-09-01

The quality of information provided by referring general practitioners to secondary care mental health services are crucial elements in the effective management of patients. In order to establish effective communication, both primary and secondary care health professionals should contribute to planning and organising this process taking into account their different opinions and views. Anonymous questionnaire was designed to collect information on items that GPs and psychiatrist rated as most important items in GP referral letters to psychiatrists. The questionnaires were sent out electronically. Each item was scored using a rating scale where 0 was least important and 10 was most important. Items that scored 8 and above were agreed by all as the most important items. 76 GP letters were audited using a devised checklist of the identified most important items. Data was collected and analysed using a devised data collection tool. A re-audit was done 6months later. A response rate of 70% was obtained for both psychiatrists and GPs. Reasons for referral were described in almost all GP referral letters (95%). Only 24% referral letters had details about current physical health which improved to 59%. Concerns about risk were described in only 47% of letters and treatment provided by GP in 50% of letters. These improved in 79% and 71% of letters respectively in the re-audit. The involvement of professionals in devising a standardised approach for referral letters has improved communication in this re-audit between GPs and Psychiatrists. This is evident in the improvement in key aspects of the referral letters: past medical history, past psychiatric history, current physical health, treatment provided by GP. Efficient communication between GPs and psychiatrists improves the quality of health care for patients.

Increased Circulating Level of the Survival Factor GP88 (Progranulin in the Serum of Breast Cancer Patients When Compared to Healthy Subjects

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Katherine Rak Tkaczuk

2011-01-01

Full Text Available Introduction GP88 (PC-Cell Derived Growth Factor, progranulin is a glycoprotein overexpressed in breast tumors and involved in their proliferation and survival. Since GP88 is secreted, an exploratory study was established to compare serum GP88 level between breast cancer patients (BC and healthy volunteers (HV. Methods An IRB approved prospective study enrolled 189 stage 1–4 BC patients and 18 HV. GP88 serum concentration was determined by immunoassay. Results Serum GP88 level was 28.7+ 5.8 ng/ml in HV and increased to 40.7+ 16.0 ng/ml ( P = 0.007 for stage 1-3 and 45.3 +23.3 ng/ml ( P = 0.0007 for stage 4 BC patients. There was no correlation between the GP88 level and BC characteristics such as age, race, tumor grade, ER, PR and HER-2 expression. Conclusion These data suggest that serial testing of serum GP88 levels may have value as a circulating biomarker for detection, monitoring and follow up of BC.

Ten years of health workforce planning in the Netherlands: a tentative evaluation of GP planning as an example

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Van Greuningen Malou

2012-08-01

Full Text Available Abstract Introduction In many countries, health-care labour markets are constantly being challenged by an alternation of shortage and oversupply. Avoiding these cyclic variations is a major challenge. In the Netherlands, a workforce planning model has been used in health care for ten years. Case description Since 1970, the Dutch government has explored different approaches to determine the inflow in medical schools. In 2000, a simulation model for health workforce planning was developed to estimate the required and available capacity of health professionals in the Netherlands. In this paper, this model is explained, using the Dutch general practitioners as an example. After the different steps in the model are clarified, it is shown how elements can be added to arrive at different versions of the model, or ‘scenarios’. A comparison is made of the results of different scenarios for different years. In addition, the subsequent stakeholder decision-making process is considered. Discussion and evaluation Discussion of this paper shows that workforce planning in the Netherlands is a complex modelling task, which is sensitive to different developments influencing the balance between supply and demand. It seems plausible that workforce planning has resulted in a balance between supply and demand of general practitioners. Still, it remains important that the modelling process is accepted by the different stakeholders. Besides calculating the balance between supply and demand, there needs to be an agreement between the stakeholders to implement the advised training inflow. The Dutch simulation model was evaluated using six criteria to be met by models suitable for policy objectives. This model meets these criteria, as it is a comprehensive and parsimonious model that can include all relevant factors. Conclusion Over the last decade, health workforce planning in the Netherlands has become an accepted instrument for calculating the required supply of

The Dutch Are Missing in the American Curriculum

Science.gov (United States)

Claunch, Ann

2009-01-01

The Dutch are missing in any U.S. history textbook, in the content standards, and in the nationally endorsed curriculum. Outside of New York State history classes, there is almost no mention of the Dutch influence in early 17th-century America. Fleeting references to the Netherlands as a staging area for the Pilgrims' famous "Mayflower"…

CESAM: The CCSO annual model of the Dutch economy

NARCIS (Netherlands)

Jongbloed, Benjamin W.A.; Kuipers, S.K.; Kuper, G.H.; Sterken, E.

1990-01-01

This paper presents CESAM, a macroeconometric model of the Dutch economy based on annual data. CESAM can be characterized as a Keynesian expenditure model including a neoclassical production model and a post-Keynesian financial model. This characterization holds for most of the Dutch

Structure-based stabilization of HIV-1 gp120 enhances humoral immune responses to the induced co-receptor binding site.

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Barna Dey

2009-05-01

Full Text Available The human immunodeficiency virus type 1 (HIV-1 exterior envelope glycoprotein, gp120, possesses conserved binding sites for interaction with the primary virus receptor, CD4, and also for the co-receptor, generally CCR5. Although gp120 is a major target for virus-specific neutralizing antibodies, the gp120 variable elements and its malleable nature contribute to evasion of effective host-neutralizing antibodies. To understand the conformational character and immunogenicity of the gp120 receptor binding sites as potential vaccine targets, we introduced structure-based modifications to stabilize gp120 core proteins (deleted of the gp120 major variable regions into the conformation recognized by both receptors. Thermodynamic analysis of the re-engineered core with selected ligands revealed significant stabilization of the receptor-binding regions. Stabilization of the co-receptor-binding region was associated with a marked increase in on-rate of ligand binding to this site as determined by surface plasmon resonance. Rabbit immunization studies showed that the conformational stabilization of core proteins, along with increased ligand affinity, was associated with strikingly enhanced humoral immune responses against the co-receptor-binding site. These results demonstrate that structure-based approaches can be exploited to stabilize a conformational site in a large functional protein to enhance immunogenic responses specific for that region.

Antiviral Activity of HIV gp120 Targeting Bispecific T Cell Engager (BiTE®) Antibody Constructs.

Science.gov (United States)

Brozy, Johannes; Schlaepfer, Erika; Mueller, Christina K S; Rochat, Mary-Aude; Rampini, Silvana K; Myburgh, Renier; Raum, Tobias; Kufer, Peter; Baeuerle, Patrick A; Muenz, Markus; Speck, Roberto F

2018-05-02

Today's gold standard in HIV therapy is the combined antiretroviral therapy (cART). It requires strict adherence by patients and life-long medication, which can lower the viral load below detection limits and prevent HIV-associated immunodeficiency, but cannot cure patients. The bispecific T cell engaging (BiTE®) antibody technology has demonstrated long-term relapse-free outcomes in patients with relapsed and refractory acute lymphocytic leukemia. We here generated BiTE® antibody constructs that target the HIV-1 envelope protein gp120 (HIV gp120) using either the scFv B12 or VRC01, the first two extracellular domains (1+2) of human CD4 alone or joined to the single chain variable fragment (scFv) of the antibody 17b fused to an anti-human CD3ϵ scFv. These engineered human BiTE® antibody constructs showed engagement of T cells for redirected lysis of HIV gp120-transfected CHO cells. Furthermore, they substantially inhibited HIV-1 replication in PBMCs as well as in macrophages co-cultured with autologous CD8+ T-cells, the most potent being the human CD4(1+2) BiTE® antibody construct and the CD4(1+2)L17b BiTE® antibody construct. The CD4(1+2) h BiTE® antibody construct promoted HIV infection of human CD4-/CD8+ T cells. In contrast, the neutralizing B12 and the VRC01 BiTE® antibody constructs as well as the CD4(1+2)L17b BiTE® antibody construct did not. Thus, BiTE® antibody constructs targeting HIV gp120 are very promising for constraining HIV and warrant further development as novel antiviral therapy with curative potential. Importance HIV is a chronic infection well controlled with the current cART. However, we lack cure of HIV, and the HIV pandemic goes on. Here we showed in vitro and ex vivo t hat a bispecific T-cell engaging (BiTE®) antibody construct targeting HIV gp120 resulted in substantially reduced HIV replication. In addition, these BiTE® antibody constructs display efficient killing of gp120 expressing cells and inhibited replication in ex vivo

The Ixodes scapularis Salivary Protein, Salp15, Prevents the Association of HIV-1 gp120 and CD4

OpenAIRE

Juncadella, Ignacio J.; Garg, Renu; Bates, Tonya C.; Olivera, Elias R.; Anguita, Juan

2007-01-01

Ixodes scapularis salivary protein, Salp15, inhibits CD4+ T cell activation by binding to the most-extracellular domains of the CD4 molecule, potentially overlapping with the gp120-binding region. We now show that Salp15 inhibits the interaction of gp120 and CD4. Furthermore, Salp15 prevents syncytia formation between HL2/3 (a stable HeLa cell line expressing the envelope protein) and CD4-expressing cells. Salp15 prevented gp120-CD4 interaction at least partially through its direct interactio...

Dutch chemical producers pledge emissions cuts

International Nuclear Information System (INIS)

Chynoweth, E.; Schoenmakers, J.

1993-01-01

Dutch chemical producers have negotiated a long-term agreement with government ministries to reduce emissions of a wide range of chemicals. Industry association Vereniging van de Nederlandse Chemische Industrie (VNCI; Leidschendam) says implementing the commitment will cost companies Dfl 10 billion ($5.4 billion) between 1993 and 2000. VNCI technical director Wim Quik welcomes the accord, which he describes as a management contract, saying, Rather than have legislation, there is a certain adjustment available. Peter Santen, managing director of midsized chemicals player Cindu Chemicals (Uithoorn, the Netherlands) voices some concern about the details of the accord, but adds, we are flexible in trying to agree with the contents of the covenant [it] is better than having new rules from law. The Dutch government, traditionally eager for consensus, has struck a number of such deals with Dutch industries - including packaging, metal, and tire - to reduce emissions and set up environmental management programs. The effort is based on the government's National Environmental Policy Plans - NMP and NMP Plus. Targets for emissions reduction by the chemical industry were provided by a government-funded environmental research institute

Resource effects of training general practitioners in risk communication skills and shared decision making competences.

Science.gov (United States)

Cohen, David; Longo, M F; Hood, Kerenza; Edwards, Adrian; Elwyn, Glyn

2004-08-01

Involving patients more in decisions about their own care requires doctors to be trained in effective ways of communicating information and in developing competences to negotiate levels of patient involvement which are most appropriate for each case. The aim of this study was to determine the cost of such training and identify which service resource variables are subsequently affected. An explanatory cluster randomized crossover trial was carried out which involved training general practitioners (GPs) in the use of risk communication (RC) tools, shared decision making (SDM) competences or both. Continuing care by GPs of patients with one of four chronic conditions (menopausal symptoms, menorrhagia, atrial fibrillation, prostatism) was reviewed before and after training. Cost of training was assessed by prospective monitoring of resources used. Data on prescribing, referrals and investigations were collected via questionnaires to participating practitioners. Data on follow-up GP consultations were extracted from medical records. Three two-level logistic models were performed to investigate the probability of training having an effect on prescribing, referrals and investigations ordered at the review consultation. Training cost pound 1218 per practitioner which increased the cost of a consultation by pound 2.89. Training in SDM or combined with RC significantly affected the probability of a prescription being issued to women with menopausal symptoms and menorrhagia (although RC on its own had no effect) but did not significantly affect prescribing for patients with prostatism or atrial fibrillation. It did not significantly affect the probability of investigations, referrals or follow-up GP visits for any of the conditions. Unless training has a major influence on consultation length, it is unlikely to have any major impacts on cost.

Young Asian Dutch constructing Asianness: Understanding the role of Asian popular culture

NARCIS (Netherlands)

Kartosen, R.A.

2016-01-01

This doctoral thesis is about young Asian Dutch, panethnic Asian identities and identifications, and Asian/Asian Dutch popular culture. It addresses several pressing questions, including: why do young Asian Dutch, who were born and/or raised in the Netherlands, identify as Asian and construct Asian