68 research outputs found

    Voting with your wallet? Municipal budget policy and election results

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    In this research letter, we examine the impact of municipal budget policy on the percentage of votes for the incumbent majority parties in subsequent elections. We contribute to the academic literature by examining the combined influence of taxes, expenditures and debt. Based on data for Flanders (Belgium) between 1994 and 2012, we find no significant association between these budget variables and the actual election results

    Rer1p competes with APH-1 for binding to nicastrin and regulates γ-secretase complex assembly in the early secretory pathway

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    The γ-secretase complex, consisting of presenilin, nicastrin, presenilin enhancer-2 (PEN-2), and anterior pharynx defective-1 (APH-1) cleaves type I integral membrane proteins like amyloid precursor protein and Notch in a process of regulated intramembrane proteolysis. The regulatory mechanisms governing the multistep assembly of this “proteasome of the membrane” are unknown. We characterize a new interaction partner of nicastrin, the retrieval receptor Rer1p. Rer1p binds preferentially immature nicastrin via polar residues within its transmembrane domain that are also critical for interaction with APH-1. Absence of APH-1 substantially increased binding of nicastrin to Rer1p, demonstrating the competitive nature of these interactions. Moreover, Rer1p expression levels control the formation of γ-secretase subcomplexes and, concomitantly, total cellular γ-secretase activity. We identify Rer1p as a novel limiting factor that negatively regulates γ-secretase complex assembly by competing with APH-1 during active recycling between the endoplasmic reticulum (ER) and Golgi. We conclude that total cellular γ-secretase activity is restrained by a secondary ER control system that provides a potential therapeutic value

    Variations in follow-up services after inpatient stroke rehabilitation: A multicentre study

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    Background: Care after discharge from inpatient stroke rehabilitation units varies across Europe. The aim of this study was to compare service delivery after discharge. Methods: A total of 532 consecutive patients after stroke were recruited from 4 European rehabilitation centres in Germany, Switzerland, Belgium and the UK. At 2-month intervals, clinical assessments and structured interviews were carried out to document functional status and delivery of services after discharge. Significant factors for receiving follow-up services were analysed using a logistic generalized estimating equation model. Results: After controlling for case-mix, the results showed that Belgian patients were most likely to receive physical therapy but least likely to receive occupational therapy. German patients were least likely to receive nursing care. UK patients were less likely to receive medical care from their general practitioner compared with the other patient groups. Conclusion: Clinical characteristics did not explain the variations in service delivery after discharge from inpatient stroke rehabilitation. The decision-making processes involved in the provision of follow-up services need to be better documented. To improve our understanding of events post-discharge, the influence of non-clinical factors, such as healthcare regulations, should be explored further

    Thorough in silico and in vitro cDNA analysis of 21 putative BRCA1 and BRCA2 splice variants and a complex tandem duplication in BRCA2 allowing the identification of activated cryptic splice donor sites in BRCA2 exon 11

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    For 21 putative BRCA1 and BRCA2 splice site variants, the concordance between mRNA analysis and predictions by in silico programs was evaluated. Aberrant splicing was confirmed for 12 alterations. In silico prediction tools were helpful to determine for which variants cDNA analysis is warranted, however, predictions for variants in the Cartegni consensus region but outside the canonical sites, were less reliable. Learning algorithms like Adaboost and Random Forest outperformed the classical tools. Further validations are warranted prior to implementation of these novel tools in clinical settings. Additionally, we report here for the first time activated cryptic donor sites in the large exon 11 of BRCA2 by evaluating the effect at the cDNA level of a novel tandem duplication (5 breakpoint in intron 4; 3 breakpoint in exon 11) and of a variant disrupting the splice donor site of exon 11 (c.6841+1G>C). Additional sites were predicted, but not activated. These sites warrant further research to increase our knowledge on cis and trans acting factors involved in the conservation of correct transcription of this large exon. This may contribute to adequate design of ASOs (antisense oligonucleotides), an emerging therapy to render cancer cells sensitive to PARP inhibitor and platinum therapies

    The GEN-ERA toolbox: unified and reproducible workflows for research in microbial genomics

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    Microbial culture collections play a key role in taxonomy by studying the diversity of their strains and providing well-characterized biological material to the scientific community for fundamental and applied research. These microbial resource centers thus need to implement new standards in species delineation, including whole-genome sequencing and phylogenomics. In this context, the genomic needs of the Belgian Coordinated Collections of Microorganisms (BCCM) were studied, resulting in the GEN-ERA toolbox, a unified cluster of bioinformatic workflows dedicated to both bacteria and small eukaryotes (e.g., yeasts). This public toolbox is designed for researchers without a specific training in bioinformatics (launched by a single command line). Hence, it facilitates all steps from genome downloading and quality assessment, including genomic contamination estimation, to tree reconstruction. It also offers workflows for average nucleotide identity comparisons and metabolic modeling. All the workflows are based on Singularity containers and Nextflow to increase reproducibility. The GEN-ERA toolbox can be used to infer completely reproducible comparative genomic and metabolic analyses on prokaryotes and small eukaryotes. Although designed for routine bioinformatics of culture collections, it can also be used by all researchers interested in microbial taxonomy, as exemplified by our case study on Gloeobacterales (Cyanobacteria). This study is published at https://doi.org/10.1093/gigascience/giad022GENER

    The GEN-ERA toolbox: unified and reproducible workflows for research in microbial genomics.

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    peer reviewed[en] BACKGROUND: Microbial culture collections play a key role in taxonomy by studying the diversity of their strains and providing well-characterized biological material to the scientific community for fundamental and applied research. These microbial resource centers thus need to implement new standards in species delineation, including whole-genome sequencing and phylogenomics. In this context, the genomic needs of the Belgian Coordinated Collections of Microorganisms were studied, resulting in the GEN-ERA toolbox. The latter is a unified cluster of bioinformatic workflows dedicated to both bacteria and small eukaryotes (e.g., yeasts). FINDINGS: This public toolbox allows researchers without a specific training in bioinformatics to perform robust phylogenomic analyses. Hence, it facilitates all steps from genome downloading and quality assessment, including genomic contamination estimation, to tree reconstruction. It also offers workflows for average nucleotide identity comparisons and metabolic modeling. TECHNICAL DETAILS: Nextflow workflows are launched by a single command and are available on the GEN-ERA GitHub repository (https://github.com/Lcornet/GENERA). All the workflows are based on Singularity containers to increase reproducibility. TESTING: The toolbox was developed for a diversity of microorganisms, including bacteria and fungi. It was further tested on an empirical dataset of 18 (meta)genomes of early branching Cyanobacteria, providing the most up-to-date phylogenomic analysis of the Gloeobacterales order, the first group to diverge in the evolutionary tree of Cyanobacteria. CONCLUSION: The GEN-ERA toolbox can be used to infer completely reproducible comparative genomic and metabolic analyses on prokaryotes and small eukaryotes. Although designed for routine bioinformatics of culture collections, it can also be used by all researchers interested in microbial taxonomy, as exemplified by our case study on Gloeobacterales

    The organisation of physiotherapy for people with multiple sclerosis across Europe: a multicentre questionnaire survey

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    Background Understanding the organisational set-up of physiotherapy services across different countries is increasingly important as clinicians around the world use evidence to improve their practice. This also has to be taken into consideration when multi-centre international clinical trials are conducted. This survey aimed to systematically describe organisational aspects of physiotherapy services for people with multiple sclerosis (MS) across Europe. Methods Representatives from 72 rehabilitation facilities within 23 European countries completed an online web-based questionnaire survey between 2013 and 2014. Countries were categorised according to four European regions (defined by United Nations Statistics). Similarities and differences between regions were examined. Results Most participating centres specialized in rehabilitation (82 %) and neurology (60 %), with only 38 % specialising in MS. Of these, the Western based Specialist MS centres were predominately based on outpatient services (median MS inpatient ratio 0.14), whilst the Eastern based European services were mostly inpatient in nature (median MS inpatient ratio 0.5). In almost all participating countries, medical doctors - specialists in neurology (60 %) and in rehabilitation (64 %) - were responsible for referral to/prescription of physiotherapy. The most frequent reason for referral to/prescription of physiotherapy was the worsening of symptoms (78 % of centres). Physiotherapists were the most common members of the rehabilitation team; comprising 49 % of the team in Eastern countries compared to approximately 30 % in the rest of Europe. Teamwork was commonly adopted; 86 % of centres based in Western countries utilised the interdisciplinary model, whilst the multidisciplinary model was utilised in Eastern based countries (p = 0.046). Conclusion This survey is the first to provide data about organisational aspects of physiotherapy for people with MS across Europe. Overall, care in key organisational aspects of service provision is broadly similar across regions, although some variations, for example the models of teamwork utilised, are apparent. Organisational framework specifics should be considered anytime a multi-centre study is conducted and results from such studies are applied.PubMedWoSScopu

    Disciplinary power and the process of training informal carers on stroke units

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    This article examines the process of training informal carers on stroke units using the lens of power. Care is usually assumed as a kinship obligation but the state has long had an interest in framing the carer and caring work. Training carers in healthcare settings raises questions about the power of the state and healthcare professionals as its agents to shape expectations and practices related to the caring role. Drawing on Foucault's notion of disciplinary power, we show how disciplinary forms of power exercised in interactions between healthcare professionals and carers shape the engagement and resistance of carers in the process of training. Interview and observational field note extracts are drawn from a multi‐sited study of a training programme on stroke units targeting family carers of people with stroke to consider the consequences of subjecting caring to this intervention. We found that the process of training informal carers on stroke units was not simply a matter of transferring skills from professional to lay person, but entailed disciplinary forms of power intended to shape the conduct of the carer. We interrogate the extent to which a specific kind of carer is produced through such an approach, and the wider implications for the participation of carers in training in healthcare settings and the empowerment of carers

    Physical activity and cardiorespiratory fitness after stroke

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    Physical activity (PA) and cardiorespiratory fitness (CRF) are reduced after stroke. To enhance participation in daily activities and structured exercise training, longitudinal evaluation of the level and influencing factors of PA and CRF after stroke is crucial. These insights help to identify barriers of PA and to better delineate aerobicexercise interventions and maintain long-term benefits. Studies carried out within this PhD-project included the prevalence and determinants of stroke caregivers# strain in the first six months after stroke (chapter 1), the criterion validity of heart rate monitoring versus RT3-accelerometry and examination of the accuracy of Yamax-pedometers instroke survivors (chapter 2), the quantity of PA one year after stroke and its influencing factors (chapter 3), the evolution of CRF during thefirst year post-stroke and the influence of pre-stroke patients# characteristics and stroke-related factors on this evolution(chapter 4),and the identification of determinants of CRF at 3, 6 and 12 months post-stroke (chapter 5).In chapter 1, the prevalence and determinants of strain experienced by 90 stroke patients# caregivers at 2, 4 and 6 months post-stroke were presented. Demographic characteristics, physical and emotional performance of patients, caregivers# characteristics and service input were documented to identify determinants of the caregivers# strain. Nearly one out of three caregivers was under strain and no differences were seen between 2, 4 and 6 months post-stroke. Our results also indicated that in predicting strain, the patients# level of function andactivity played an important role in the subacute phase while the participation level increased in importance over time. These findings emphasized the importance of maximal physical recovery and optimal integration in the community. Providing services in which patients can participate, such as social activities, leisure and sport related activities might help to reduce caregivers# strain and to prevent socialisolation of the patient.In the validation study (chapter 2) nine stroke patients performed a standardised activity protocol wearing a Cosmed K4b² to measure oxygen consumption and heart rate (HR), a RT3-accelerometer and two Yamax SW-200 pedometers (hip- and knee-positioned). We concluded that the RT3-accelerometer showed poor validity for measuring PA in stroke patients. HR monitoring, however, can be used to make intra-individual comparisons through providing patients with information on exercise i ntensity. This study further revealed that the Yamax SW-200 pedometer provided accurate results during slow walking if positioned on the knee,but not when hip-positioned. In conclusion, HR monitoring and knee-positioned Yamax-pedometers seemed to be useful instruments to assess PA in stroke survivors and could be seen as a motivational strategy to enhance PA.Chapter 3 addressed the question whether stroke patients are active enough 1-year post-stroke to improve their physical health. Due to the unique attribute of absolute, relative, and self-reported measures, PA was quantified by a multifaceted approach in 16 mildly disabled stroke patients. Our results showed that on average, stroke patients spent 44±39 minutes a day in activities of moderate intensity and performed 6428 steps per day which is within the normative data (5900-6900 steps/day). However, none performed moderate activity at least three days per week and only 19% performed more than 10,000 steps/day, required to improve/maintain their health. Functional mobility, CRF, mood and participation had an influence on daily steps, but not on the time spent in moderately intense activities. We could conclude that discrepancies between absolute (daily steps) and relative (minutes moderate active) measures of PA exist with respect to the quantity achieved and its potential determinants.In chapter 4 the evolution of CRF of 33 stroke patients in a 1-year follow-up study were examined and the effect of pre-stroke patients# characteristics and stroke-related factors on this evolution were explored. Findings revealed that on average CRF was reduced from 3 to 12months post-stroke (values were 65% to 71% of the age- and sex-matched normative values in healthy sedentary persons) and did not significantlychange over time. These results suggest that conventional stroke rehabilitation is insufficient to obtain a cardiorespiratory training effect. It seems worthwhile to initiate exercise-based interventions of sufficient intensity, frequency and duration in the rehabilitation centre and continuation in the community. Stroke survivors at risk of deconditioning were pre-morbid less active at work or in sport activities, diabetic or initially more severely impaired. Statistically combining these factors revealed that older patients with stroke and diabetes were less likely to improve their VO2 peak and older, female, diabetic non-smokers improved less on log OUES. These results indicate that cardiovascular exercise training could be a therapeutic goal for these patients at risk and preferably be started as early as possible. Pre-morbid less active persons require extra stimulation to change theirsedentary lifestyle and guidance post-rehabilitation will be essential to retain long-term benefits.In chapter 5, CRF was predicted based on standardized measures along theseveral dimensions of the ICF model at 3, 6 and 12 months post-stroke in40 patients with stroke. Knee muscle strength was found the main predictor of CRF and explained variance increased over time from 41% to 72%. Functional mobility and mood affected CRF at 12 months post-stroke.These results may suggest that cardiorespiratory endurance training should be supplemented with strength-developing exercises of the lower limbs, especially on the weaker paretic side. Ambulation at moderate intensity and good mental health may further positively influence CRF.status: publishe

    Perspectieven en exclusieven voor competentieontwikkeling en levenslang leren van stakeholders in en om arbeidsorganisaties

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