Implementation and evaluation of an antimicrobial stewardship programme in companion animal clinics: A stepped-wedge design intervention study
Hopman, Nonke E.M. ; Portengen, Lützen ; Hulscher, Marlies E.J.L. ; Heederik, Dick J.J. ; Verheij, T.J.M. ; Wagenaar, Jaap A. ; Prins, Jan M. ; Bosje, Tjerk ; Schipper, Louska ; Geijlswijk, Ingeborg M. Van; Broens, Els M. - \ 2019
PLoS ONE 14 (2019)11. - ISSN 1932-6203
Background To curb increasing resistance rates, responsible antimicrobial use (AMU) is needed, both in human and veterinary medicine. In human healthcare, antimicrobial stewardship programmes (ASPs) have been implemented worldwide to improve appropriate AMU. No ASPs have been developed for and implemented in companion animal clinics yet. Objectives The objective of the present study was to implement and evaluate the effectiveness of an ASP in 44 Dutch companion animal clinics. The objectives of the ASP were to increase awareness on AMU, to decrease total AMU whenever possible and to shift AMU towards 1st choice antimicrobials, according to Dutch guidelines on veterinary AMU. Methods The study was designed as a prospective, stepped-wedge, intervention study, which was performed from March 2016 until March 2018. The multifaceted intervention was developed using previous qualitative and quantitative research on current prescribing behaviour in Dutch companion animal clinics. The number of Defined Daily Doses for Animal (DDDAs) per clinic (total, 1st, 2nd and 3rd choice AMU) was used to quantify systemic AMU. Monthly AMU data were described using a mixed effect time series model with auto-regression. The effect of the ASP was modelled using a step function and a change in the (linear) time trend. Results A statistically significant decrease of 15% (7%-22%) in total AMU, 15% (5%-24%) in 1st choice AMU and 26% (17%-34%) in 2nd choice AMU was attributed to participation in the ASP, on top of the already ongoing time trends. Use of 3rd choice AMs did not significantly decrease by participation in the ASP. The change in total AMU became more prominent over time, with a 16% (4%-26%) decrease in (linear) time trend per year. Conclusions This study shows that, although AMU in Dutch companion animal clinics was already decreasing and changing, AMU could be further optimised by participation in an antimicrobial stewardship programme.
Salt inactivation of classical swine fever virus and African swine fever virus in porcine intestines confirms the existing in vitro casings model
Jelsma, Tinka ; Wijnker, Joris J. ; Smid, Bregtje ; Verheij, Eline ; Poel, Wim H.M. van der; Wisselink, Henk J. - \ 2019
Veterinary Microbiology 238 (2019). - ISSN 0378-1135
3D collagen matrix model - African swine fever - Classical swine fever - D-values - Intestine - Virus inactivation
Natural casings, to be used as sausage containers, are being traded worldwide and may be contaminated with contagious viruses. Standard processing of such natural casings is by salt treatment with a duration of 30 days before shipment. Since information is lacking about the efficacy of these virus inactivation procedures, an in vitro 3D collagen matrix model, mimicking natural casings, was developed previously to determine the efficacy of salt to inactivate specific viruses. To validate this model, a comparison in vivo experiment was performed using intestines of pigs experimentally infected with African swine fever virus (ASFV) and classical swine fever virus (CSFV). Decimal reduction (D) values, were determined at 4 °C, 12 °C, 20 °C and 25 °C. The standard salt processing procedure showed an efficient inactivation of ASFV and CSFV over time in a temperature dependent way. Dintestine values of both viruses, treated with the standard salt treatment, were in line with the Dcollagen values. It was concluded that these results underline the suitability of the 3D collagen matrix model to determine virus inactivation and to replace animal experiments. Furthermore, an increase in storage time for standard salt processed casings derived from CSFV endemic regions is highly recommended for an efficient inactivation of CSFV.
|Landelijk Coördinatiepunt Research Data Management Poditionering paper voor 2019 en verder
Verheul, Ingeborg ; Mordant, Annemie ; Ringersma, J. ; Sesink, Laurents ; Smeele, Ton ; Boiten, Jan Willem ; Bouwhuis, Maurice ; Dunning, Alastair ; Branchett, Susan ; Bijsterbos, Machiel ; Hoeksema, Bolinde ; Selm, Mariette van; Hoogen, Henk van der; Gankema, Hans ; Verheij, Marijke - \ 2019
Research Data Management
The effects of frozen storage on the chemical compositions, fermentability and palatability of temperate browse in zoos
Herk, Ellen van; Verheij, Martine ; Fens, Anouk ; Bionda, Thomas ; Idoe, Arun ; Bosch, G. - \ 2019
- p. 8 - 8.
The damage-associated molecular pattern HMGB1 is released early after clinical hepatic ischemia/reperfusion
Golen, Rowan F. van; Reiniers, Megan J. ; Marsman, Gerben ; Alles, Lindy K. ; Rooyen, Derrick M. van; Petri, Björn ; Mark, Vincent A. Van der; Beek, Adriaan A. van; Meijer, Ben ; Maas, Martinus A. ; Zeerleder, Sacha ; Verheij, Joanne ; Farrell, Geoffrey C. ; Luken, Brenda M. ; Teoh, Narci C. ; Gulik, Thomas M. van; Murphy, Michael P. ; Heger, Michal - \ 2019
Biochimica et Biophysica Acta. Molecular Basis of Disease 1865 (2019)6. - ISSN 0925-4439 - p. 1192 - 1200.
Antioxidants - Damage-associated molecular patterns - Intravital microscopy - Liver resection - Mitochondrial DNA - Sterile inflammation
Objective and background: Activation of sterile inflammation after hepatic ischemia/reperfusion (I/R) culminates in liver injury. The route to liver damage starts with mitochondrial oxidative stress and cell death during early reperfusion. The link between mitochondrial oxidative stress, damage-associate molecular pattern (DAMP) release, and sterile immune signaling is incompletely understood and lacks clinical validation. The aim of the study was to validate this relation in a clinical liver I/R cohort and to limit DAMP release using a mitochondria-targeted antioxidant in I/R-subjected mice. Methods: Plasma levels of the DAMPs high-mobility group box 1 (HMGB1), mitochondrial DNA, and nucleosomes were measured in 39 patients enrolled in an observational study who underwent a major liver resection with (N = 29) or without (N = 13) intraoperative liver ischemia. Circulating cytokine and neutrophil activation markers were also determined. In mice, the mitochondria-targeted antioxidant MitoQ was intravenously infused in an attempt to limit DAMP release, reduce sterile inflammation, and suppress I/R injury. Results: In patients, HMGB1 was elevated following liver resection with I/R compared to liver resection without I/R. HMGB1 levels correlated positively with ischemia duration and peak post-operative transaminase (ALT) levels. There were no differences in mitochondrial DNA, nucleosome, or cytokine levels between the two groups. In mice, MitoQ neutralized hepatic oxidative stress and decreased HMGB1 release by ±50%. MitoQ suppressed transaminase release, hepatocellular necrosis, and cytokine production. Reconstituting disulfide HMGB1 during reperfusion reversed these protective effects. Conclusion: HMGB1 seems the most pertinent DAMP in clinical hepatic I/R injury. Neutralizing mitochondrial oxidative stress may limit DAMP release after hepatic I/R and reduce liver damage.
Age-related distribution and dynamics of T-cells in blood and lymphoid tissues of goats
Baliu-Piqué, Mariona ; Kurniawan, Henry ; Ravesloot, Lars ; Verheij, Myrddin W. ; Drylewicz, Julia ; Lievaart-Peterson, Karianne ; Borghans, José A.M. ; Koets, Ad ; Tesselaar, Kiki - \ 2019
Developmental and Comparative Immunology 93 (2019). - ISSN 0145-305X - p. 1 - 10.
Deuterium - Development - Goat - Mathematical modelling - Neonatal adaptive immunity - Stable isotope labelling - T-cell turnover - T-lymphocytes
Neonatal mammals have increased disease susceptibility and sub-optimal vaccine responses. This raises problems in both humans and farm animals. The high prevalence of paratuberculosis in goats and the lack of an effective vaccine against it have a strong impact on the dairy sector, and calls for vaccines optimized for the neonatal immune system. We characterized the composition of the T-cell pool in neonatal kids and adult goats and quantified their turnover rates using in vivo deuterium labelling. From birth to adulthood, CD4+ T-cells were the predominant subset in the thymus and lymph nodes, while spleen and bone marrow contained mainly CD8+ lymphocytes. In blood, CD4+ T-cells were the predominant subset during the neonatal period, while CD8+ T-cells predominated in adults. We observed that thymic mass and cellularity increased during the first 5 months after birth, but decreased later in life. Deuterium labelling revealed that T-cell turnover rates in neonatal kids are considerably higher than in adult animals.
Short lifespans of memory T-cells in bone marrow, blood, and lymph nodes suggest that T-cell memory is maintained by continuous self-renewal of recirculating cells
Baliu-Piqué, Mariona ; Verheij, Myrddin W. ; Drylewicz, Julia ; Ravesloot, Lars ; Boer, Rob J. de; Koets, Ad ; Tesselaar, Kiki ; Borghans, José A.M. - \ 2018
Frontiers in Immunology 9 (2018)SEP. - ISSN 1664-3224
Bone marrow - Deuterium - Lifespan - Lymphocyte turnover - Mathematical modeling - Memory T-cells - Stable isotope labeling
Memory T-cells are essential to maintain long-term immunological memory. It is widely thought that the bone marrow (BM) plays an important role in the long-term maintenance of memory T-cells. There is controversy however on the longevity and recirculating kinetics of BM memory T-cells. While some have proposed that the BM is a reservoir for long-lived, non-circulating memory T-cells, it has also been suggested to be the preferential site for memory T-cell self-renewal. In this study, we used in vivo deuterium labeling in goats to simultaneously quantify the average turnover rates-and thereby expected lifespans-of memory T-cells from BM, blood and lymph nodes (LN). While the fraction of Ki-67 positive cells, a snapshot marker for recent cell division, was higher in memory T-cells from blood compared to BM and LN, in vivo deuterium labeling revealed no substantial differences in the expected lifespans of memory T-cells between these compartments. Our results support the view that the majority of memory T-cells in the BM are self-renewing as fast as those in the periphery, and are continuously recirculating between the blood, BM, and LN.
Validation of four real-time TaqMan PCRs for the detection of Ralstonia solanacearum and/or Ralstonia pseudosolanacearum and/or Clavibacter michiganensis subsp. sepedonicus in potato tubers using a statistical regression approach
Vreeburg, R.A.M. ; Zendman, A.J.W. ; Pol, A. ; Verheij, E. ; Nas, M. ; Kooman-Gersmann, M. - \ 2018
EPPO Bulletin 48 (2018)1. - ISSN 0250-8052 - p. 86 - 96.
A new DNA extraction method and a new multiplex real-time TaqMan PCR test for detection of Ralstonia solanacearum, Ralstonia pseudosolanacearum and Clavibacter michiganensis subsp. sepedonicus in asymptomatic potato tubers are presented. This new multiplex PCR and three published TaqMan PCRs for detection of R. solanacearum and/or R. pseudosolanacearum and/or R. syzygii spp. and/or C. michiganensis subsp. sepedonicus were validated using linear regression analysis for estimating the Ct values and its variation at 5 × 103 bacteria mL−1. The three published PCRs that have been validated are Massart et al. (2014, detecting R. solanacearum and C. michiganensis subsp. sepedonicus), Weller et al. (1999, detecting R. solanacearum, R. pseudosolanacearum and R. syzygii spp.) and Gudmestad et al. (2009, detecting C. michiganensis subsp. sepedonicus). All tested PCRs were fit for purpose for their target organisms. The PCR tests have different target genes, allowing one of the sets to be used as first screening test and another as second screening test for the detection of R. solanacearum and/or R. pseudosolanacearum and/or C. michiganensis subsp. sepedonicus in asymptomatic potato tubers.
Seaweed Competition: Ulva Sp. has the Potential to Produce the Betaine Lipid Diacylglyceryl-O-4’-(N,N,N,-Trimethyl) Homoserine (DGTS) in Order to Replace Phosphatidylcholine (PC) Under Phosphate-Limiting Conditions in the P-Limited Dutch Wadden Sea and Outcompete an Aggressive Non-Indigenous Gracilaria vermiculophylla Red Drift Algae Out of this Unique Unesco World Heritage Coastal Area
Ginneken, V.J.T. van; Gittenberger, A. ; Rensing, M. ; Vries, E. de; Peeters, E.T.H.M. ; Verheij, E. - \ 2017
Oceanography and Fisheries Open Access Journal 2 (2017)5. - ISSN 2476-0536 - 10 p.
The present study tested in the Western Dutch Wadden Sea (WDW) UNESCO World Heritage Site why an on a global scale the aggressive non-indigenous red drift alga Gracilaria vermiculophylla didn’t succeed to overgrow the WDC. In such a multifaceted complex ecosystem like the dynamic WDC it seems like unraveling a Gordian knob in order to describe the inextricable relationship between this seaweed invader suppression and its (a) biotic environment. However, we succeeded at the molecular level to give a convincing reasoning at first grounded in the awareness of a since 1987 river Rhine-North-Sea-WDC severely Phosphorus (P) restricted ecosystem. Our ecological datasets gave via final DCA (Detrended Correspondence Analysis) awareness of the very compelling interaction between Ulva sp. and G.vermiculophylla. Based on LCMS-techniques we discovered that Ulva sp. have the advantage to use the biochemical pathway solely rarely observed in some euckaryotes- to have the potential to produce the betaine lipid diacylglyceryl-O-4’-(N,N,N,-trimethyl)homoserine (DGTS) which replaces the plant/seaweed cell wall structure phosphatidylcholine (PC) “lecithine” under phosphate-limiting growth conditions. Also we hope this lipidomics based compound DGTS can serve as an ecological biomarker in order to protect vulnerable ecosystems like the Wadden Sea (UNESCO World Heritage).
Effect of structural animal health planning on antimicrobial use and animal health variables in conventional dairy farming in the Netherlands
Speksnijder, David C. ; Graveland, Haitske ; Eijck, Ineke A.J.M. ; Schepers, René W.M. ; Heederik, Dick J.J. ; Verheij, Theo J.M. ; Wagenaar, Jaap A. - \ 2017
Journal of Dairy Science 100 (2017)6. - ISSN 0022-0302 - p. 4903 - 4913.
Antimicrobial use - Continuous improvement - Facilitated animal health planning - Implementation
Widespread veterinary use of antimicrobials might contribute to the increasing burden of antimicrobial resistance. Despite many successful efforts to reduce veterinary antimicrobial use in the Netherlands, antimicrobial use on a substantial number of farms has remained relatively high over the past few years. Farm-specific solutions are required to further lower antimicrobial use on these farms. Reducing the burden of animal diseases at the farm level by means of a structured approach to animal health planning could be promising. This intervention study aimed to evaluate the main effects of an animal health planning program developed by an advisory team consisting of a dairy farmer, his veterinarian, and his feed adviser under the guidance of a professional facilitator. During an initial farm visit, the advisory team developed a farm-specific animal health planning program with support from the facilitator. After 1 yr, the effects of this program on animal health, production parameters, and antimicrobial use were evaluated and compared with control farms that did not have a facilitated animal health planning program. Antimicrobial use on intervention farms was significantly reduced between the start and the end of the study period; however, no significant differences in the rate of reduction between the intervention and control groups could be observed (-19% and -14%, respectively). Reduced antimicrobial use did not result in negative effects on animal health and production parameters during the study period in both groups. On intervention farms, a significant positive relationship was found between the percentage of completed action points at farm level and the percentage reduction in antimicrobial use. The level of compliance with action points and the quality of collaboration between farmer and advisers were positively associated with the accomplishment of corresponding objectives. However, the total number of objectives was negatively associated with the level of compliance with action points and tended to be negatively associated with the percentage reduction in antimicrobial use at farm level. Gradually reducing antimicrobial use without adverse effects on animal health and productivity is possible by adjusting management practices in a team effort. Fostering good collaboration among farmer, veterinarian, and feed adviser and focusing on a limited number of objectives have positive effects on the outcomes of the animal health planning program and antimicrobial use.
Hypothermic perfusion with retrograde outflow during right hepatectomy is safe and feasible
Reiniers, Megan J. ; Olthof, Pim B. ; Golen, Rowan F. van; Heger, Michal ; Beek, Adriaan A. van; Meijer, Ben ; Leen, René ; Kuilenburg, André B.P. van; Mearadji, Banafsche ; Bennink, Roelof J. ; Verheij, Joanne ; Gulik, Thomas M. van - \ 2017
Surgery 162 (2017)1. - ISSN 0039-6060 - p. 48 - 58.
Background: In situ hypothermic perfusion during liver resection performed under vascular inflow occlusion decreases hepatic ischemia-reperfusion injury, but technical limitations have restricted its widespread use. In situ hypothermic perfusion with retrograde outflow circumvents these impediments and thus could extend the applicability of in situ hypothermic perfusion. The safety and feasibility of in situ hypothermic perfusion with retrograde outflow were analyzed in selected patients undergoing right (extended) hepatectomy and compared to intermittent vascular inflow occlusion, the gold standard method, in this randomized pilot study. Methods: Patients were first screened for parenchymal liver disease (exclusion criteria: steatosis ≥30%, cirrhosis, or cholestasis). Study participants were randomized intraoperatively to undergo in situ hypothermic perfusion with retrograde outflow (n = 9) or intermittent vascular inflow occlusion (n = 9). The target liver core temperature during in situ hypothermic perfusion with retrograde outflow was 28°C. The primary end point was ischemia-reperfusion injury (expressed by peak postoperative transaminase levels). Secondary outcomes included functional liver regeneration (assessed by hepatobiliary scintigraphy) and clinical outcomes. Results: Peak transaminase levels, total bilirubin, and the international normalized ratio were similar between both groups, although a trend toward more rapid normalization of bilirubin levels was noted for the in situ hypothermic perfusion with retrograde outflow group. Functional liver regeneration as evaluated by hepatobiliary scintigraphy was improved on postoperative day 3 following in situ hypothermic perfusion with retrograde outflow but not after intermittent vascular inflow occlusion. Furthermore, in situ hypothermic perfusion with retrograde outflow (requiring continuous ischemia) was comparable to intermittent vascular inflow occlusion for all clinical outcomes, including postoperative complications and hospital stay. Conclusion: The use of in situ hypothermic perfusion with retrograde outflow appears to be safe and feasible in selected patients with healthy liver parenchyma and may benefit early functional liver regeneration. Future applications of in situ hypothermic perfusion with retrograde outflow include patients with damaged liver parenchyma who would require major hepatic resection with a prolonged vascular inflow occlusion duration.
Warm ischemia time-dependent variation in liver damage, inflammation, and function in hepatic ischemia/reperfusion injury
Olthof, Pim B. ; Golen, Rowan F. van; Meijer, Ben ; Beek, Adriaan A. van; Bennink, Roelof J. ; Verheij, Joanne ; Gulik, Thomas M. van; Heger, Michal - \ 2017
Biochimica et Biophysica Acta. Molecular Basis of Disease 1863 (2017)2. - ISSN 0925-4439 - p. 375 - 385.
Background Hepatic ischemia/reperfusion (I/R) injury is characterized by hepatocellular damage, sterile inflammation, and compromised postoperative liver function. Generally used mouse I/R models are too severe and poorly reflect the clinical injury profile. The aim was to establish a mouse I/R model with better translatability using hepatocellular injury, liver function, and innate immune parameters as endpoints. Methods Mice (C57Bl/6J) were subjected to sham surgery, 30 min, or 60 min of partial hepatic ischemia. Liver function was measured after 24 h using intravital microscopy and spectroscopy. Innate immune activity was assessed at 6 and 24 h of reperfusion using mRNA and cytokine arrays. Liver inflammation and function were profiled in two patient cohorts subjected to I/R during liver resection to validate the preclinical results. Results In mice, plasma ALT levels and the degree of hepatic necrosis were strongly correlated. Liver function was bound by a narrow damage threshold and was severely impaired following 60 min of ischemia. Severe ischemia (60 min) evoked a neutrophil-dominant immune response, whereas mild ischemia (30 min) triggered a monocyte-driven response. Clinical liver I/R did not compromise liver function and displayed a cytokine profile similar to the mild I/R injury model. Conclusions Mouse models using ≤ 30 min of ischemia best reflect the clinical liver I/R injury profile in terms of liver function dynamics and type of immune response. General significance This short duration of ischemia therefore has most translational value and should be used to increase the prospects of developing effective interventions for hepatic I/R.
The Relation between Non-adipose Muscle Fat and Hepatic Steatosis Studied with Localized 1H Magnetic Resonance Spectroscopy (1H MRS) and LC-MS Techniques
Ginneken, V.J.T. van; Booms, Ronald ; Verheij, Elwin ; Vries, Evert De ; Greef, Jan Van Der - \ 2016
Anatomy & Physiology 6 (2016). - ISSN 2161-0940
Aim/objective: In this study we investigated ectopic fat storage in the muscle and the liver using 1H Magnetic Resonance Spectroscopy (1H-MRS). The inability to store fat in adipose tissue leads to ectopic Triacylglycerol (TG) accumulation in muscle followed by the liver: the so called “overflow hypothesis”. It is assumed that when steatosis occurs in organs like the liver we can speak from “Metabolic Syndrome”. Methods: We compared the effects of two different diet interventions, 24 h-starvation and 40 days High-fat diet (+0.25% cholesterol and 45% energy from bovine lard) with control mice. Characterization of lipid molecular species in non-adipose muscle homogenate was performed by comparing the groups using liquid chromatography coupled to mass spectrometry (LC-MS) techniques following a Systems Biology lipidomics based approach. Reversed phase liquid chromatography coupled to mass spectrometry (LC-MS) were used to quantify and qualify the rearrangement and repartitioning of the triacylglycerol compound in the liver organ. Results: The major message of this manuscript is the interaction of remnant organ/tissue called “carcass” in the absorption capacity of lipids and the spill-over of these lipid compounds (mainly TG’s) to the liver. Our data suggest that if the remnant muscle compartment is saturated with lipids until ≈500 g/kg dry matter there is no TGs accumulation in the liver, but above this level there is a spill over in the plasma resulting in fat accumulation in the liver. Conclusion: We demonstrated in this study that fat can be stored in the muscle but when this compartment is saturated the liver takes over the function as a fat sink, the "overflow hypothesis" resulting finally in hepatic steatosis and ‘Metabolic Syndrome’.
Opinions of veterinarians on antimicrobial use in farm animals in Flanders and the Netherlands
Postma, M. ; Speksnijder, D.C. ; Jaarsma, A.D.C. ; Verheij, T.J.M. ; Wagenaar, J.A. ; Dewulf, J. - \ 2016
Veterinary Record 179 (2016)3. - ISSN 0042-4900
Veterinarians play an important role in the reduction of antimicrobial use in farm animals. This study aims to quantify opinions of veterinarians from the Netherlands and Flanders regarding antimicrobial use and resistance issues in farm animals. An online survey was sent out to 678 and 1100 farm animal veterinarians in Flanders and the Netherlands, of which 174 and 437 were returned respectively. Suboptimal climate conditions were regarded as the most important cause for high antimicrobial use in farm animals. Flemish veterinarians also regarded insufficient biosecurity measures and farmers' mentality as important determinants, while the Dutch respondents ranked insufficient immunity of young animals and economic considerations of farmers as major causes. The majority of Dutch respondents (63.8 per cent) supported the existing national policy, which aimed to halve veterinary antimicrobial use, while the Flemish (32.9 per cent) were less supportive of such a policy. Improvements in housing and climate conditions, biosecurity measures and strict control of specific infectious diseases were seen as important and promising measures to reduce antimicrobial use. To reduce antimicrobial use in farm animals, some shared approaches might be applicable in both countries. However, cultural, political and societal differences between Flanders and the Netherlands require differentiated approaches to reduce veterinary antimicrobial use.
|Osmanlı Döneminde Diyarbekir'de Toplumsal İlişkiler (1870-1915)
Jongerden, J.P. ; Verheij, Jelle ; Akgunduz, Emrullah ; Aydin, Suavi ; Gaunt, David ; Klein, Janet ; Özok-Gündoğan, Nilay ; Ümit Üngör, Uğur - \ 2016
Istanbul : Istanbul Bilgi Universitesi Yayinlari - ISBN 9786053994176 - 369 p.
Tarihi çok eskilere uzanan, Bereketli Hilal’in Dicle kıyısında kurulmuş Diyarbekir, tarih boyunca Amida adıyla Arami krallığı, Asur, Med, Pers, Roma ve Bizans imparatorluklarından sonra Osmanlı İmparatorluğu’nun bir parçası olmuş, sonunda modern Türkiye Cumhuriyeti’nin içinde bir il olarak kalmıştır. Bölgesel alanının sınırları ile idari örgütlenmesi sürekli değişen Diyarbekir; 1867’ye kadar Eyâlet-i Kürdistan olarak adlandırılmış, sonra büyük bir bölgeyi kapsayan vilayet haline getirilmiş, Cumhuriyet döneminde ise daralarak Diyarbakır adını almıştır.
Bu kitabın derleyenlerinin ifade ettiği gibi Diyarbekir’in tarihi “hiçbir zaman kendi başına bir alan olarak” araştırılmadı. Yapılan çalışmaların çoğu olayları, tarihsel olguları genel bir bağlamda ele alırken, resmi görüşlerin, egemen zihniyetin dışına çıkamadı.
Joost Jongerden ile Jelle Verheij’in derlediği ve konunun uzmanı birçok yazarın katkıda bulunduğu Osmanlı Döneminde Diyarbekir’de Toplumsal İlişkiler (1870-1915) adlı bu kitap ise Diyarbekir’in yüzyıllar boyunca geçirmiş olduğu toplumsal ilişkiler ağını, bunun sonuçları olan olgusal ilişkileri 19. yüzyılın sonundaki zaman dilimine yoğunlaştırarak, milliyetçi tarihyazımının dışına çıkıyor. Bu çalışmada yazarların temel yaklaşımı, alışılagelmiş merkez-çevre ilişkisini değil “çokmerkezlilik” ve bunun biçimlenmesini sağlayan farklı etkileşim biçimlerini temel alıyor.
Bu önemli çalışmada; değişik merkezlerde bulunan devlet çapında lider ve örgütlerle birlikte yerel liderler, Osmanlı bürokratları, çeşitli kuruluşlar, geleneksel ve modern alt gruplar, köylüler, aşiret liderleri ve üyeleri, milliyetçi gruplar, yörenin kültürel ve siyasal kişileri, şehirli alt gruplarla birlikte dinî tarikatlar, çeşitli etnik gruplar vb. ile dönemin Osmanlı Diyarbekir’inin karmaşık ve çok yüzlü tablosu ortaya çıkarken; devlet ve aşiret ilişkilerinden, Hamidiye Alayları’na, Ermeni soykırımından, Kürtlere, Süryanilere uzanan konular tüm ayrıntılarıyla inceleniyor.
Kitap bu yanıyla, Osmanlı’dan Cumhuriyet’e taşınan ve günümüzde de farklı veçheleriyle süregelen sorunlara yeni bir bakış açısı getirmektedir.
Determinants associated with veterinary antimicrobial prescribing in farm animals in the Netherlands : A qualitative study
Speksnijder, D.C. ; Jaarsma, A.D.C. ; Gugten, A.C. van der; Verheij, T.J.M. ; Wagenaar, J.A. - \ 2015
Zoonoses and Public Health 62 (2015)s1. - ISSN 1863-1959 - p. 39 - 51.
Antimicrobial resistance - Livestock - Public health - Qualitative methods - Veterinary medicine
Antimicrobial use in farm animals might contribute to the development of antimicrobial resistance in humans and animals, and there is an urgent need to reduce antimicrobial use in farm animals. Veterinarians are typically responsible for prescribing and overseeing antimicrobial use in animals. A thorough understanding of veterinarians' current prescribing practices and their reasons to prescribe antimicrobials might offer leads for interventions to reduce antimicrobial use in farm animals. This paper presents the results of a qualitative study of factors that influence prescribing behaviour of farm animal veterinarians. Semi-structured interviews with eleven farm animal veterinarians were conducted, which were taped, transcribed and iteratively analysed. This preliminary analysis was further discussed and refined in an expert meeting. A final conceptual model was derived from the analysis and sent to all the respondents for validation. Many conflicting interests are identifiable when it comes to antimicrobial prescribing by farm animal veterinarians. Belief in the professional obligation to alleviate animal suffering, financial dependency on clients, risk avoidance, shortcomings in advisory skills, financial barriers for structural veterinary herd health advisory services, lack of farmers' compliance to veterinary recommendations, public health interests, personal beliefs regarding the veterinary contribution to antimicrobial resistance and major economic powers are all influential determinants in antimicrobial prescribing behaviour of farm animal veterinarians. Interventions to change prescribing behaviour of farm animal veterinarians could address attitudes and advisory skills of veterinarians, as well as provide tools to deal with (perceived) pressure from farmers and advisors to prescribe antimicrobials. Additional (policy) measures could probably support farm animal veterinarians in acting as a more independent animal health consultant.
Attitudes and perceptions of Dutch veterinarians on their role in the reduction of antimicrobial use in farm animals
Speksnijder, David C. ; Jaarsma, Debbie A.C. ; Verheij, Theo J.M. ; Wagenaar, Jaap A. - \ 2015
Preventive Veterinary Medicine 121 (2015)3-4. - ISSN 0167-5877 - p. 365 - 373.
Antimicrobial resistance - Antimicrobial use - Farm animals - Prescribing behaviour - Prescribing determinants - Veterinary medicine
Little is known about attitudes of veterinarians towards antibiotic use and reduction opportunities, and their interaction with farmers herein. Therefore, a questionnaire was developed and sent out to Dutch farm animal veterinarians. The response rate was 40%. Categorical Principal Component Analysis (CATPCA) was conducted on statements measuring attitudes towards the use of antibiotics and reduction opportunities in farm animals, the veterinary pharmacy and the interaction of veterinarians with farmers in improving animal health. This resulted in 3 underlying dimensions. Additionally, possible explanatory variables (main farm animal species working with, years of experience in practice) were added to the CATPCA to identify differences between veterinarians. Veterinarians working with different animal species were comparable in their opinions towards the necessity to reduce veterinary antibiotic use and the current policy to halve veterinary antibiotic consumption. Veterinarians working with ruminants - "ruminant specialists" - and veterinarians working with several different animal species - "generalists" - reported to feel more uncertainty in acting independently from farmers' and significant others' (other advisors, colleagues) demands for antibiotics or opinions than veterinarians mainly working with intensively raised animals (pigs, poultry, veal calves) - "intensive specialists". Years of experience in practice was negatively related to feelings of uncertainty in acting independently. At the other hand, years of experience was associated with being less concerned about the possible contribution of veterinary antibiotic use to antimicrobial resistance, considering it more important to keep the right to prescribe and sell antibiotics, and being less hesitant to apply antibiotics to prevent (further dissemination of) animal diseases. Intensive specialists expected most from improving feed quality and benchmarking of antibiotic prescribing and use in reducing veterinary antibiotic use; ruminant specialists and generalists preferred improving housing and climate conditions and benchmarking. The by veterinarians perceived main reasons for farmers not to comply to veterinary advices to improve animal health were related to financial and time restrictions, although intensive specialists stressed the importance of conflicting advices from other advisors as a cause for non-compliance. The results showed that younger veterinarians might require additional support to act independently from farmers' and significant others'. Additionally, experienced veterinarians could be educated about possible risks related to veterinary overuse of antibiotics. Alternative approaches should be identified for veterinarians to preserve a decent income without pharmacy incomes. Especially in intensive farming, ways should be found to prevent contradictory advices as a barrier not to implement veterinary advices to improve animal health.
Groen en gebruik ADHD-medicatie door kinderen : de relatie tussen de hoeveelheid groen in de woonomgeving en de prevalentie van AD(H)D-medicatiegebruik bij 5- tot 12-jarigen
Vries, S. de; Verheij, R. ; Smeets, H. - \ 2015
Wageningen : Alterra, Wageningen-UR (Alterra 2672) - 23
kinderen - gezondheid van kinderen - aandachtstekort hyperactiviteitstoornis - natuur - omgevingspsychologie - milieu - lichamelijke activiteit - welzijn - gezondheid - beweging - children - child health - attention deficit hyperactivity disorder - nature - environmental psychology - environment - physical activity - well-being - health - movement
In deze studie is gekeken naar de relatie tussen de hoeveelheid groen in de woonomgeving en het gebruik van ADHD-medicatie door kinderen. De gegevens over het medicijngebruik zijn afkomstig uit de Achmea Health Database. Uit deze database zijn kinderen die in 2011 tussen de 5 en 12 jaar waren, geselecteerd, ongeacht of ze ADHD-medicatie gebruikten of niet. Hieraan zijn middels de 6-positie postcode van het woonadres gegevens over het groen in de woonomgeving (250 m en 500 m) gekoppeld alsmede enkele buurtkenmerken. Van de 274.698 kinderen in de database waren voor 248.270 kinderen alle gegevens beschikbaar. De uitval werd voornamelijk veroorzaakt door tussentijdse verhuizingen. Middels multilevel logistische regressieanalyse is de relatie tussen de hoeveelheid groen in de woonomgeving en het al dan niet gebruiken van een ADHD-medicijn geanalyseerd.
Bluetongue virus without NS3/NS3a expression is not virulent and protects against virulent bluetongue virus challenge.
Feenstra, F. ; Gennip, H.G.P. van; Maris-Veldhuis, M.A. ; Verheij, E. ; Rijn, P.A. van - \ 2014
Journal of General Virology 95 (2014)Pt. 9. - ISSN 0022-1317 - p. 2019 - 2029.
vaccinated animals - rna segment - serotype 8 - sheep - antibodies - particles - europe - cattle - ns3 - differentiation
Bluetongue is a disease in ruminants caused by the bluetongue virus (BTV), and is spread by Culicoides biting midges. Bluetongue outbreaks cause huge economic losses and death in sheep in several parts of the world. The most effective measure to control BTV is vaccination. However, both commercially available vaccines and recently developed vaccine candidates have several shortcomings. Therefore, we generated and tested next-generation vaccines for bluetongue based on the backbone of a laboratory-adapted strain of BTV-1, avirulent BTV-6 or virulent BTV-8. All vaccine candidates were serotyped with VP2 of BTV-8 and did not express NS3/NS3a non-structural proteins, due to induced deletions in the NS3/NS3a ORF. Sheep were vaccinated once with one of these vaccine candidates and were challenged with virulent BTV-8 3 weeks after vaccination. The NS3/NS3a knockout mutation caused complete avirulence for all three BTV backbones, including for virulent BTV-8, indicating that safety is associated with the NS3/NS3a knockout phenotype. Viraemia of vaccine virus was not detected using sensitive PCR diagnostics. Apparently, the vaccine viruses replicated only locally, which will minimize spread by the insect vector. In particular, the vaccine based on the BTV-6 backbone protected against disease and prevented viraemia of challenge virus, showing the efficacy of this vaccine candidate. The lack of NS3/NS3a expression potentially enables the differentiation of infected from vaccinated animals, which is important for monitoring virus spread in vaccinated livestock. The disabled infectious single-animal vaccine for bluetongue presented here is very promising and will be the subject of future studies.
Rapid emergence of a virulent PB2 E627K variant during adaptation of highly pathogenic avian influenza H7N7 virus to mice
Jong, M.C. de; Stockhofe-Zurwieden, N. ; Verheij, E.S. ; Boer-Luijtze, E.A. de; Ruiter, S.J.M. ; Leeuw, O.S. de; Cornelissen, A.H.M. - \ 2013
Virology journal 10 (2013). - ISSN 1743-422X
a virus - amino-acid - viral polymerase - molecular-basis - h5n1 viruses - host-range - mouse lung - humans - determinants - transmission
Background Highly pathogenic avian influenza (HPAI) viruses pose a potential human health threat as they can be transmitted directly from infected poultry to humans. During a large outbreak of HPAI H7N7 virus among poultry in The Netherlands in 2003, bird to human transmission was confirmed in 89 cases, of which one had a fatal outcome. Methods To identify genetic determinants of virulence in a mammalian host, we passaged an avian H7N7/03 outbreak isolate in mouse lungs and evaluated the phenotype of the mouse-adapted variant in animal models and in vitro. Results Three passages in mouse lungs were sufficient to select a variant that was highly virulent in mice. The virus had a MLD50 that was >4.3 logs lower than that of its non-lethal parental virus. Sequence analysis revealed a single mutation at position 627 in PB2, where the glutamic acid was changed to a lysine (E627K). The mouse-adapted virus has this mutation in common with the fatal human case isolate. The virus remained highly pathogenic for chickens after its passage in mice. In ferrets, the mouse-adapted virus induced more severe disease, replicated to higher titers in the lower respiratory tract and spread more efficiently to systemic organs compared with the parental virus. In vitro, the PB2 E627K mutation had a promoting effect on virus propagation in mammalian, but not in avian cells. Conclusions Our results show that the E627K mutation in PB2 alone can be sufficient to convert an HPAI H7N7 virus of low virulence to a variant causing severe disease in mice and ferrets. The rapid emergence of the PB2 E627K mutant during mouse adaptation and its pathogenicity in ferrets emphasize the potential risk of HPAI H7N7 viruses for human health.