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Publication Pressure and Burn Out among Dutch Medical Professors: A Nationwide Survey
Joeri K. Tijdink, Anton C. M. Vergouwen, Yvo M. Smulders
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0073381
Abstract: Background Publication of scientific research papers is important for professionals working in academic medical centres. Quantitative measures of scientific output determine status and prestige, and serve to rank universities as well as individuals. The pressure to generate maximum scientific output is high, and quantitative aspects may tend to dominate over qualitative ones. How this pressure influences professionals’ perception of science and their personal well-being is unknown. Methods and Findings We performed an online survey inviting all medical professors (n = 1206) of the 8 academic medical centres in The Netherlands to participate. They were asked to fill out 2 questionnaires; a validated Publication Pressure Questionnaire and the Maslach Burnout Inventory. In total, 437 professors completed the questionnaires. among them, 54% judge that publication pressure ‘has become excessive’, 39% believe that publication pressure ‘affects the credibility of medical research’ and 26% judge that publication pressure has a ‘sickening effect on medical science’. The burn out questionnaire indicates that 24% of medical professors have signs of burn out. The number of years of professorship was significantly related with experiencing less publication pressure. Significant and strong associations between burn out symptoms and the level of perceived publication pressure were found. The main limitation is the possibility of response bias. Conclusion A substantial proportion of medical professors believe that publication pressure has become excessive, and have a cynical view on the validity of medical science. These perceptions are statistically correlated to burn out symptoms. Further research should address the effects of publication pressure in more detail and identify alternative ways to stimulate the quality of medical science.
No effect of epoprostenol on right ventricular diameter in patients with acute pulmonary embolism: a randomized controlled trial
Albertus J Kooter, Richard G IJzerman, Otto Kamp, Anco B Boonstra, Yvo M Smulders
BMC Pulmonary Medicine , 2010, DOI: 10.1186/1471-2466-10-18
Abstract: In a randomized, single-blind study, 14 patients with acute pulmonary embolism received epoprostenol or placebo infusion for 24 hours on top of conventional treatment. Effects on right ventricular end-diastolic diameter, systolic pulmonary artery pressure, right ventricle fractional area changeand tricuspid annular plane systolic excursion were assessed by serial echocardiography. Furthermore Troponin T and NT-proBNP were measured serially.Compared to placebo, epoprostenol was associated with a relative change from baseline in right ventricular end-diastolic diameter of +2% after 2.5 hours and -8% after 24 hours. Epoprostenol did not have a significant effect on systolic pulmonary artery pressure, right ventricular fractional area change and tricuspid annular plane systolic excursion, nor on biochemical parameters.In patients with acute pulmonary embolism and right ventricular overload, treatment with epoprostenol did not improve right ventricular dilatation or any other measured variables of right ventricular overload.Registration: URL: NCT01014156Medical ethical committee: Medisch-ethische toetsingscommissie (METc) from the VUmc (free university medical centre)Pulmonary embolism is a frequent and potentially fatal disorder. Despite immediate treatment with anticoagulants, morbidity and mortality are still high when hemodynamically stable patients with pulmonary embolism have echocardiographic signs of acute right ventricular overload [1-3].An acute increase in right ventricular afterload is the hallmark of severe pulmonary embolism, and is responsible for many of its clinical manifestations and complications. The traditional view is that mechanical obstruction by thrombus mass causes pulmonary hypertension. Therefore, treatment focusses on relieving mechanical obstruction, either by anticoagulation if patients are stable, or by thrombolytic therapy in case of hemodynamic instability [4]. The optimal treatment for haemodynamically stable patients with signs of righ
No Effect of Folic Acid Supplementation on Global DNA Methylation in Men and Women with Moderately Elevated Homocysteine
Audrey Y. Jung, Yvo Smulders, Petra Verhoef, Frans J. Kok, Henk Blom, Robert M. Kok, Ellen Kampman, Jane Durga
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0024976
Abstract: A global loss of cytosine methylation in DNA has been implicated in a wide range of diseases. There is growing evidence that modifications in DNA methylation can be brought about by altering the intake of methyl donors such as folate. We examined whether long-term daily supplementation with 0.8 mg of folic acid would increase global DNA methylation compared with placebo in individuals with elevated plasma homocysteine. We also investigated if these effects were modified by MTHFR C677T genotype. Two hundred sixteen participants out of 818 subjects who had participated in a randomized double-blind placebo-controlled trial were selected, pre-stratified on MTHFR C677T genotype and matched on age and smoking status. They were allocated to receive either folic acid (0.8 mg/d; n = 105) or placebo treatment (n = 111) for three years. Peripheral blood leukocyte DNA methylation and serum and erythrocyte folate were assessed. Global DNA methylation was measured using liquid chromatography-tandem mass spectrometry and expressed as a percentage of 5-methylcytosines versus the total number of cytosine. There was no difference in global DNA methylation between those randomized to folic acid and those in the placebo group (difference = 0.008, 95%CI = ?0.05,0.07, P = 0.79). There was also no difference between treatment groups when we stratified for MTHFR C677T genotype (CC, n = 76; CT, n = 70; TT, n = 70), baseline erythrocyte folate status or baseline DNA methylation levels. In moderately hyperhomocysteinemic men and women, long-term folic acid supplementation does not increase global DNA methylation in peripheral blood leukocytes. ClinicalTrials.gov NCT00110604
Life-Threatening Complications of Hormonal Contraceptives: A Case History
Saheed Khan,Yvo M. Smulders,Johanna I. P. de Vries,Angélique M. E. Spoelstra-de Man
Case Reports in Obstetrics and Gynecology , 2013, DOI: 10.1155/2013/186230
Abstract: We present a case with the rare combination of thrombotic and hemorrhagic complications of oral contraceptives. A healthy 40-year-old woman suffered from cardiac arrest due to massive pulmonary embolism, caused by oral contraceptives and immobilization during a flight. After successful resuscitation, obstructive shock necessitated thrombolysis and thereafter heparin. Anticoagulation was complicated by internal bleeding from contraceptive related hepatic adenoma. She underwent arterial embolisation, and anticoagulation was continued. On day 18, she was discharged in a good condition. Hepatic adenomas are a potential source of internal bleeding in women using oral contraceptives requiring anticoagulation. Signs of internal bleeding in such patients should prompt immediate abdominal ultrasound examination. 1. Introduction Oral contraceptives (OAC) are used worldwide and generally considered safe. Severe adverse events are rare and usually related to thromboembolism and neoplasm. The dose of the estrogen constituent and the type of progestin determine the risk of venous thromboembolism [1]. Another, less well-known complication is hepatic adenoma, which is related to the use of oral estrogens. We present a case with these two life-threatening complications of OAC at the same time, which confronted us with a therapeutic challenge. 2. Case A 40-year-old woman travelled by plane from Tanzania to the UK. She had an unremarkable medical history and only used a fourth generation OAC (Yasmin: ethinylestradiol/drospirenone). During a stopover in Amsterdam, she collapsed and was found to be pulseless. Basic life support was started immediately and when the paramedics arrived, she had pulseless electrical activity. After 55 minutes of resuscitation, spontaneous circulation returned. Upon arrival in our hospital, physical examination showed sinus tachycardia 150/min, blood pressure 90/60?mmHg with norepinephrine 0.4?mcg/kg/min, central venous pressure 22?mmHg, and oxygen saturation 92%. Relevant results of the blood examination are shown in Table 1. Table 1: Laboratory results on admission in hospital. After initial stabilisation, chest CT angiography revealed extensive bilateral pulmonary embolism. Despite the coagulation disorders, presumed to be due to disseminated intravascular coagulation, we administered recombinant tissue plasminogen activator (r-tPA), followed by heparin, because of persistent obstructive shock. Within a few hours, her hemodynamic condition improved. She was also treated with therapeutic hypothermia. After cessation of the sedation on day 3,
Plasma folate levels are associated with the lipoprotein profile: a retrospective database analysis
Alexander Semmler, Susanna Moskau, Andreas Grigull, Susan Farmand, Thomas Klockgether, Yvo Smulders, Henk Blom, Bernd Zur, Birgit Stoffel-Wagner, Michael Linnebank
Nutrition Journal , 2010, DOI: 10.1186/1475-2891-9-31
Abstract: In a retrospective single center approach, we analyzed the laboratory database (2003-2006) of the University Hospital Bonn, Germany, including 1743 individuals, in whom vitamin B12, folate and at least one lipoprotein parameter had been determined by linear multilogistic regression.Higher folate serum levels were associated with lower serum levels of low density lipoprotein cholesterol (LDL-C; Beta = -0.164; p < 0.001), higher levels of high density lipoprotein cholesterol (HDL-C; Beta = 0.094; p = 0.021 for trend) and a lower LDL-C-C/HDL-C-ratio (Beta = -0.210; p < 0.001). Using ANOVA, we additionally compared the individuals of the highest with those of the lowest quartile of folate. Individuals of the highest folate quartile had higher levels of HDL-C (1.42 ± 0.44 mmol/l vs. 1.26 ± 0.47 mmol/l; p = 0.005), lower levels of LDL-C (3.21 ± 1.04 mmol/l vs. 3.67 ± 1.10 mmol/l; p = 0.001) and a lower LDL-C/HDL-C- ratio (2.47 ± 1.18 vs. 3.77 ± 5.29; p = 0.002). Vitamin B12 was not associated with the lipoprotein profile.In our study sample, high folate levels were associated with a favorable lipoprotein profile. A reconfirmation of these results in a different study population with a well defined status of health, diet and medication is warranted.Increased homocysteine (Hcys) levels and altered plasma lipid levels are generally considered to be independent risk factors for the development of cardiovascular disease (CVD). However, lifestyle and nutrition may cause a coincidence of the homocysteine and lipoprotein status. Although of potential clinical and scientific relevance such a relationship is not generally acknowledged.Recent studies have already described an inverse relationship between folate and high-density lipoprotein cholesterol (HDL-C) levels and low folate levels have therefore been suggested to be a cardiovascular risk factor and that the subjects with lower folate levels should be recommended for dietary folic acid supplementation to HDL-C levels [1,2].Sev
Effect of B vitamin supplementation on plasma homocysteine levels in celiac disease
Muhammed Hadithi, Chris JJ Mulder, Frank Stam, Joshan Azizi, J Bart A Crusius, Amado Salvador Pe?a, Coen DA Stehouwer, Yvo M Smulders
World Journal of Gastroenterology , 2009,
Abstract: AIM: To investigate the effect of vitamin supplements on homocysteine levels in patients with celiac disease.METHODS: Vitamin B6, folate, vitamin B12, and fasting plasma homocysteine levels were measured in 51 consecutive adults with celiac disease [median (range) age 56 (18-63) years; 40% men, 26 (51%) had villous atrophy, and 25 (49%) used B-vitamin supplements] and 50 healthy control individuals matched for age and sex. Finally, the C677T polymorphism of 5,10-methylenetetrahydrofolate reductase (MTHFR) was evaluated in 46 patients with celiac disease and all control individuals.RESULTS: Patients with celiac disease and using vitamin supplements had higher serum vitamin B6 (P = 0.003), folate (P < 0.001), and vitamin B12 (P = 0.012) levels than patients who did not or healthy controls (P = 0.035, P < 0.001, P = 0.007, for vitamin B6, folate, and vitamin B12, respectively). Lower plasma homocysteine levels were found in patients using vitamin supplements than in patients who did not (P = 0.001) or healthy controls (P = 0.003). However, vitamin B6 and folate, not vitamin B12, were significantly and independently associated with homocysteine levels. Twenty-four (48%) of 50 controls and 23 (50%) of 46 patients with celiac disease carried the MTHFR thermolabile variant T-allele (P = 0.89).CONCLUSION: Homocysteine levels are dependent on Marsh classification and the regular use of B-vitamin supplements is effective in reduction of homocysteine levels in patients with celiac disease and should be considered in disease management.
Protein Arginine Methylation Is More Prone to Inhibition by S-Adenosylhomocysteine than DNA Methylation in Vascular Endothelial Cells
Ruben Esse, Monica S. Rocha, Madalena Barroso, Cristina Florindo, Tom Teerlink, Robert M. Kok, Yvo M. Smulders, Isabel Rivera, Paula Leandro, Pieter Koolwijk, Rita Castro, Henk J. Blom, Isabel Tavares de Almeida
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0055483
Abstract: Methyltransferases use S-adenosylmethionine (AdoMet) as methyl group donor, forming S-adenosylhomocysteine (AdoHcy) and methylated substrates, including DNA and proteins. AdoHcy inhibits most methyltransferases. Accumulation of intracellular AdoHcy secondary to Hcy elevation elicits global DNA hypomethylation. We aimed at determining the extent at which protein arginine methylation status is affected by accumulation of intracellular AdoHcy. AdoHcy accumulation in human umbilical vein endothelial cells was induced by inhibition of AdoHcy hydrolase by adenosine-2,3-dialdehyde (AdOx). As a measure of protein arginine methylation status, the levels of monomethylarginine (MMA) and asymmetric and symmetric dimethylated arginine residues (ADMA and SDMA, respectively) in cell protein hydrolysates were measured by HPLC. A 10% decrease was observed at a 2.5-fold increase of intracellular AdoHcy. Western blotting revealed that the translational levels of the main enzymes catalyzing protein arginine methylation, protein arginine methyl transferases (PRMTs) 1 and 5, were not affected by AdoHcy accumulation. Global DNA methylation status was evaluated by measuring 5-methylcytosine and total cytosine concentrations in DNA hydrolysates by LC-MS/MS. DNA methylation decreased by 10% only when intracellular AdoHcy concentration accumulated to 6-fold of its basal value. In conclusion, our results indicate that protein arginine methylation is more sensitive to AdoHcy accumulation than DNA methylation, pinpointing a possible new player in methylation-related pathology.
Local Open Innovation: How to Go from Ideas to Solutions
Oscar Smulders
Technology Innovation Management Review , 2013,
Abstract: Local open innovation can be used to create a powerful dynamic within a local multi-stakeholder environment. This article shares the experiences of setting up a collaborative innovation process in a regional initiative in the Netherlands. In the first phase of the process, a couple of interactive idea generating sessions have been organized. These so called Quest for Solutions sessions have not only generated a rich set of useful solutions, but they also created a positive vibe within the local community. Factors that have contributed to the success of the idea generation sessions are working around real-life problems involving people who are directly affected by the problem. The structure of the sessions with alternating phases of divergence, exploration, and convergence allowed for broad understanding of the problems, exploration of potential solutions, and working towards result-oriented value statements. Key challenges in translating the ideas into solutions have been determining the value case and dealing with intellectual property. Special attention is given to the notion of innovative contract design as a means of dealing with intellectual property in an environment of local open innovation.
E. van Blankenstein, Dr. M. van Blankenstein. Een Nederlands dagbladdiplomaat 1880-1964
E. Smulders
BMGN : Low Countries Historical Review , 2000,
Edge-Colored Graphs with Applications To Homogeneous Faults
Yongge Wang,Yvo Desmedt
Mathematics , 2012,
Abstract: In this paper, we use the concept of colored edge graphs to model homogeneous faults in networks. We then use this model to study the minimum connectivity (and design) requirements of networks for being robust against homogeneous faults within certain thresholds. In particular, necessary and sufficient conditions for most interesting cases are obtained. For example, we will study the following cases: (1) the number of colors (or the number of non-homogeneous network device types) is one more than the homogeneous fault threshold; (2) there is only one homogeneous fault (i.e., only one color could fail); and (3) the number of non-homogeneous network device types is less than five.
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