Phase Equilibria in Hydrocarbon Systems. II. Methane-Propane System

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Priming of microglia in a DNA-repair deficient model of accelerated aging

AbstractAging is associated with reduced function, degenerative changes, and increased neuroinflammation of the central nervous system (CNS). Increasing evidence suggests that changes in microglia cells contribute to the age-related deterioration of the CNS. The most prominent age-related change of microglia is enhanced sensitivity to inflammatory stimuli, referred to as priming. It is unclear if priming is due to intrinsic microglia ageing or induced by the ageing neural environment. We have studied this in Ercc1 mutant mice, a DNA repair-deficient mouse model that displays features of accelerated aging in multiple tissues including the CNS. In Ercc1 mutant mice, microglia showed hallmark features of priming such as an exaggerated response to peripheral lipopolysaccharide exposure in terms of cytokine expression and phagocytosis. Specific targeting of the Ercc1 deletion to forebrain neurons resulted in a progressive priming response in microglia exemplified by phenotypic alterations. Summarizing, these data show that neuronal genotoxic stress is sufficient to switch microglia from a resting to a primed state

Endovascular Stroke Treatment and Risk of Intracranial Hemorrhage in Anticoagulated Patients.

Background and Purpose- We aimed to determine the safety and mortality after mechanical thrombectomy in patients taking vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs). Methods- In a multicenter observational cohort study, we used multiple logistic regression analysis to evaluate associations of symptomatic intracranial hemorrhage (sICH) with VKA or DOAC prescription before thrombectomy as compared with no anticoagulation. The primary outcomes were the rate of sICH and all-cause mortality at 90 days, incorporating sensitivity analysis regarding confirmed therapeutic anticoagulation. Additionally, we performed a systematic review and meta-analysis of literature on this topic. Results- Altogether, 1932 patients were included (VKA, n=222; DOAC, n=98; no anticoagulation, n=1612); median age, 74 years (interquartile range, 62-82); 49.6% women. VKA prescription was associated with increased odds for sICH and mortality (adjusted odds ratio [aOR], 2.55 [95% CI, 1.35-4.84] and 1.64 [95% CI, 1.09-2.47]) as compared with the control group, whereas no association with DOAC intake was observed (aOR, 0.98 [95% CI, 0.29-3.35] and 1.35 [95% CI, 0.72-2.53]). Sensitivity analyses considering only patients within the confirmed therapeutic anticoagulation range did not alter the findings. A study-level meta-analysis incorporating data from 7462 patients (855 VKAs, 318 DOACs, and 6289 controls) from 15 observational cohorts corroborated these observations, yielding an increased rate of sICH in VKA patients (aOR, 1.62 [95% CI, 1.22-2.17]) but not in DOAC patients (aOR, 1.03 [95% CI, 0.60-1.80]). Conclusions- Patients taking VKA have an increased risk of sICH and mortality after mechanical thrombectomy. The lower risk of sICH associated with DOAC may also be noticeable in the acute setting. Improved selection might be advisable in VKA-treated patients. Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT03496064. Systematic Review and Meta-Analysis: CRD42019127464

Effects of the Training Dataset Characteristics on the Performance of Nine Species Distribution Models: Application to Diabrotica virgifera virgifera

Many distribution models developed to predict the presence/absence of invasive alien species need to be fitted to a training dataset before practical use. The training dataset is characterized by the number of recorded presences/absences and by their geographical locations. The aim of this paper is to study the effect of the training dataset characteristics on model performance and to compare the relative importance of three factors influencing model predictive capability; size of training dataset, stage of the biological invasion, and choice of input variables. Nine models were assessed for their ability to predict the distribution of the western corn rootworm, Diabrotica virgifera virgifera, a major pest of corn in North America that has recently invaded Europe. Twenty-six training datasets of various sizes (from 10 to 428 presence records) corresponding to two different stages of invasion (1955 and 1980) and three sets of input bioclimatic variables (19 variables, six variables selected using information on insect biology, and three linear combinations of 19 variables derived from Principal Component Analysis) were considered. The models were fitted to each training dataset in turn and their performance was assessed using independent data from North America and Europe. The models were ranked according to the area under the Receiver Operating Characteristic curve and the likelihood ratio. Model performance was highly sensitive to the geographical area used for calibration; most of the models performed poorly when fitted to a restricted area corresponding to an early stage of the invasion. Our results also showed that Principal Component Analysis was useful in reducing the number of model input variables for the models that performed poorly with 19 input variables. DOMAIN, Environmental Distance, MAXENT, and Envelope Score were the most accurate models but all the models tested in this study led to a substantial rate of mis-classification

Working with pain : sustainable work participation of workers with chronic nonspecific musculoskeletal pain

Dit proefschrift is een van de eerste studies specifiek gericht op mensen die blijven werken met chronische pijn aan het bewegingsapparaat. Unieke kennis over duurzame arbeidsparticipatie van werknemers met chronische pijn werd vergaard. Doel van dit promotieonderzoek was meer inzicht te krijgen in de groep mensen die werkt met pijn en te achterhalen hoe zij in staat zijn ondanks hun klachten te blijven werken. In het proefschrift staan kenmerken en determinanten beschreven van werknemers die doorwerken met chronische pijn, waardoor een completer beeld is ontstaan van arbeidsparticipatie bij mensen met chronische pijn aan het bewegingsapparaat. Uit de vergelijking van mensen die doorwerken ondanks chronische pijn en mensen met arbeidsverzuim die in revalidatiebehandeling komen met chronische pijn blijkt dat deze groepen op diverse factoren significant verschillen. In het onderzoek werd onder andere aangetoond dat de motivatie voor werk, zelfmanagementvaardigheden en het belang dat wordt toegekend aan pijn, belangrijke factoren zijn die werken met chronische pijn faciliteren. Chronische pijn op zichzelf is vaak niet de reden voor arbeidsverzuim, maar meestal spelen persoonlijke- en omgevingsfactoren daarin een beslissende rol. Deze factoren kunnen dienen als aangrijpingspunt voor het verhogen van duurzame inzetbaarheid en preventie van arbeidsverzuim van mensen met chronische pijn aan het bewegingsapparaat. De effectieve manier waarop deelnemende werknemers in het onderzoek met hun pijn omgingen en productief bleven, kan anderen inspireren aan het werk te blijven. Daarnaast biedt het onderzoek een nieuw referentiekader voor de bedrijfs-, verzekerings-, en revalidatiegeneeskunde. This thesis was one of the first studies that focused specifically on people who continued work with chronic nonspecific musculoskeletal pain (CMP), and collected (identified) unique data concerning sustainable work participation of workers with CMP. It provides a large range of characteristics of workers with CMP who continued work despite pain, which has added to our understanding of sustainable work participation in people suffering from CMP. Comparison of workers who continued work with CMP with sick listed workers with CMP admitted for rehabilitation revealed that these groups differ significantly on several factors. In this thesis, evidence was found that the workers’ motivation to work, self-management skills, and the attributed importance of pain on their (working) lives are important factors to manage staying at work with CMP. It is recommended to be aware of the fact that CMP standing on itself is often not the reason for sick leave and disability, but regularly personal and environmental factors play an additional decisive role. Because these factors can be influenced, they offer opportunity to promote staying at work. In the process of guiding workers back to work, the results of the project ‘Working with pain’ may be used. The findings of this thesis potentially contribute to promotion of sustained work participation and prevention of sick-leave in workers with CMP. The effective way workers in this project coped with CMP and remained productive, may inspire others in their efforts to stay work. Finally, this thesis offers a new reference for rehabilitation-, occupational-,and insurance medicine.

Integrating evidence in disability evaluation by social insurance physicians

The aim of this study was to explore applying the method of evidence-based medicine (EBM) to resolve common questions in the field of disability evaluation. We used three clinical questions corresponding to problems encountered by insurance physicians in daily practice to explore opportunities for and barriers to the application of EBM. The questions fell under two topics: the prognosis of work ability and the effectiveness of interventions to enhance work participation. We used the four-step EBM strategy: (i) formulation of a clinical question, (ii) searching the literature, (iii) appraisal of the evidence, and (iv) implementation of the findings into clinical practice. We restricted the searches to PubMed (Medline). For rheumatoid arthritis, we found evidence on the prognosis of work disability over a long-term period. For remaining sciatica after lumbar discectomy, we found evidence for the stability of the limitations at this stage. For depression with co-morbid alcoholism, we found evidence that treatment of both conditions would enhance work participation. The searches were effective and efficient. The interpretation of the findings was hampered by a lack of consensus in the literature about outcomes such as the concept of a poor prognosis of work ability. The EBM strategy and methods can be used by social insurance physicians to find and apply evidence for common questions in disability evaluation. The World Health Organization's International Classification of Functioning, Disability, and Health (ICF) model is instrumental in this, although more consensus on central outcome measures is needed. Further research is needed on the translation of evidence into practice. Development of valid specific search strategies for physicians in disability evaluation would improve the implementation of EB

Designing a new working method to support physicians’ (dis)ability prognosis evaluation

Introduction: Physicians performing disability assessments have to evaluate the prognosis of the (dis)abilities for work. This is a very complex task challenged by limited knowledge and skills of evidence-based medicine (EBM), time constraints, high quality demands and conflicting interests. Material and Methods: A new working method was developed to support physicians’ (dis)ability prognosis evaluation. The Intervention Mapping framework was used to identify content items, design features and considerations on implementation and evaluation of this working method. Results and Conclusions: The new working method consists of a stepwise EBM-approach to support physicians to gather available evidence, to review and weigh important prognostic aspects and to integrate these aspects into a transparent, tailored assessment. This working method is supported by a software tool, containing a database with links to evidence and other resources in order to facilitate searching, appraising and applying evidence-based information. An additional training program will further support the use of this working method. Physicians attending the training program will learn to apply the stepwise EBM-approach with support of the software tool and evaluate the prognosis of (dis)abilities in case scenarios based on daily practice. In a next phase limited efficacy, acceptability and practicality testing of the new working method is planned in a pilot study

Evaluation of a workshop on evidence-based medicine for social insurance physicians

BACKGROUND: Evidence-based medicine (EBM), a comprehensive method to support clinical decision making by using evidence, has been instrumental in clinical specialties but not yet in insurance medicine. AIMS: We developed and evaluated a workshop on EBM for Dutch social insurance physicians who perform disability evaluations. METHODS: Sixty-six social insurance physicians followed a 1-day introductory workshop that focused on teaching two EBM core skills: to ask answerable questions and to search for the best evidence. All outcomes were measured before, immediately after and 3 months after the workshop by means of self-assessment. The primary outcomes were knowledge, skills, attitude and intention to apply EBM in practice. The secondary outcomes were social influence, self-efficacy and behaviour. RESULTS: Immediately after the workshop, a marked and significant improvement was seen in self-assessed skills (mean difference 4.2, 95% CI 3.7-4.6) and in self-efficacy to apply EBM (mean difference 0.7, 95% CI 0.6-0.8). For attitude, knowledge and intention, the improvements were small. Three months after the workshop, the improvements in skills (mean difference 2.3, 95% CI 1.8-2.9) and self-efficacy (mean difference 0.5, 95% CI 0.3-0.6) remained significant. CONCLUSIONS: The workshop improved self-assessed EBM skills and self-efficacy both in the short and long term. The workshop also resulted in limited short-term improvements in self-assessed knowledge and in the intention to apply EBM in practice. The EBM approach can be successfully taught to social insurance physicians working in the field of disability evaluatio