Crediethypotheken

Het lijkt mij nuttig aan het einde van dit geschrift de belangrijkste conclusies nog eens onder elkaar te stellen. 1. Credietopening houdt een wederkerige overeenkomst tot verbruikleen in, welke is te beschouwen als een overeenkomst om te doen, nl. om leningen te sluiten. Op het tijdstip, waarop de crediethypotheek wordt ingeschreven, is de door haar te dekken schuld derhalve als toekomstig te kwalificeren. ... Zie: Samenvatting

Aanwezigheid van ascosporen van Sclerotinia sclerotiorum binnen en buiten besmette percelen

De aantasting van een gewas door Sclerotinia sclerotiorum hangt af van de aanwezigheid van ascosporen van deze schimmel in de lucht. In dit onderzoek dat gefinancierd wordt door PT en PA werd nagegaan in hoeverre de ascosporen van het eigen perceel afkomstig zijn of ook van een naburig perceel kunnen aanwaaien. In het eerste jaar van het onderzoek zijn aanwijzingen verkregen dat ascosporen in grote mate in de lucht aanwezig kunnen zijn zonder dat er duidelijk paddenstoelen in de omgeving aanwezig waren. Dat er niveauverschillen tussen percelen optreden wijst erop dat er per perceel toch meer of minder paddenstoelen aanwezig zijn. Afhankelijk van de situatie lijken er veel ascosporen van buiten het perceel te kunnen komen

Towards Personalized Treatment Strategies for Esophageal Adenocarcinoma; A Review on the Molecular Characterization of Esophageal Adenocarcinoma and Current Research Efforts on Individualized Curative Treatment Regimens

Simple Summary: Esophageal adenocarcinoma (EAC) is one of the two major subtypes of esophageal cancer. In early disease stage, many EAC patients are asymptomatic. Most patients will present with late-stage disease in case of dysphagia and/or weight loss. Patients who undergo treatment with curative intent, have 5-year survival rates rarely exceeding 30%. Currently, curative treatment consists of chemo- and radiotherapy combined with surgical resection. Despite differences between tumors at the molecular level, all patients receive similar treatment, which results in heterogeneous therapeutic response. The aim of this review is to discuss the current research on molecular characteristics in EAC, which may predict tumor response. Moreover, we also discuss the rationale and research on adjusted regimens for EAC with for instance chemoradiotherapy and surveillance instead of (immediate) surgical resection. In future, these findings will lead to more personalized treatment approaches for EAC.Esophageal cancers confer a major health challenge and are highly aggressive malignancies with poor prognosis. Esophageal adenocarcinoma (EAC) is one of the two major histopathological subtypes of esophageal cancer. Despite advances in treatment modalities, the prognosis of patients with EAC remains poor, with a 5-year survival rate that rarely exceeds 30% in patients treated with curative intent. Chemoradiotherapy followed by resection is the treatment of choice for EAC patients, which are deemed to be curable. Current patient stratification and treatments are based on outcomes from clinical trials. Unfortunately, the molecular heterogeneity of EAC which determines the chemo- and radiosensitivity of these cancers are not taken into account. A more personalized approach in the treatment of EAC could improve patient outcomes. This review aims at summarizing literature on translational and clinical research in the field of EAC which could be of importance to develop personalized approaches. As suggested by the TCGA, expression data features molecular classifications by different platforms, including miRNA, genomic mutations and reverse-phase protein arrays. Here, we summarize literature on transcriptomic, data-driven approaches to identify distinct subtypes of EAC associated with molecular features. These novel classifications may determine the responsiveness to chemo(radio)therapy and help to identify novel molecular targets within cell signaling pathways. Moreover, we discuss the current clinical research efforts on tailored treatment regimens for patients with EAC taking into account the heterogeneous response to chemoradiotherapy. We summarize the evidence regarding active surveillance instead of immediate surgical resection after application of neoadjuvant chemo(radio)therapy in EAC. We consider that in future patients with complete response to chemo(radio)therapy, predicted by (transcriptomic) biomarkers, might benefit most from this approach. Finally, challenges to overcome for current findings to be implemented in clinical practice and move the field forward are being discussed.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Corticostriatal connectivity fingerprints:Probability maps based on resting-state functional connectivity

Over the last decade, structure-function relationships have begun to encompass networks of brain areas rather than individual structures. For example, corticostriatal circuits have been associated with sensorimotor, limbic, and cognitive information processing, and damage to these circuits has been shown to produce unique behavioral outcomes in Autism, Parkinson's Disease, Schizophrenia and healthy ageing. However, it remains an open question how abnormal or absent connectivity can be detected at the individual level. Here, we provide a method for clustering gross morphological structures into subregions with unique functional connectivity fingerprints, and generate network probability maps usable as a baseline to compare individual cases against. We used connectivity metrics derived from resting-state fMRI (N = 100), in conjunction with hierarchical clustering methods, to parcellate the striatum into functionally distinct clusters. We identified three highly reproducible striatal subregions, across both hemispheres and in an independent replication dataset (N = 100) (dice-similarity values 0.40-1.00). Each striatal seed region resulted in a highly reproducible distinct connectivity fingerprint: the putamen showed predominant connectivity with cortical and cerebellar sensorimotor and language processing areas; the ventromedial striatum cluster had a distinct limbic connectivity pattern; the caudate showed predominant connectivity with the thalamus, frontal and occipital areas, and the cerebellum. Our corticostriatal probability maps agree with existing connectivity data in humans and non-human primates, and showed a high degree of replication. We believe that these maps offer an efficient tool to further advance hypothesis driven research and provide important guidance when investigating deviant connectivity in neurological patient populations suffering from e.g., stroke or cerebral palsy. Hum Brain Mapp 38:1478-1491, 2017. © 2016 Wiley Periodicals, Inc.status: publishe

Attribute Development and Level Selection for a Discrete Choice Experiment to Elicit Care Preferences of Older Adults and Informal Caregivers Aging in Place in The Netherlands

Background: The Netherlands reformed its long-term care policy to encourage older adults to age in place with the support of informal caregivers. It remains unclear whether the available care and support options align with the needs and preferences of older adults and caregivers. Discrete choice experiments (DCE) are increasingly used to identify individual preferences. This study describes the development of attributes (e.g., emotional support) and attribute levels (e.g., psychologist and case manager) for a DCE on aging-in-place preferences among older adults and informal caregivers in The Netherlands. Methods: Semi-structured interviews were conducted with older adults and informal caregivers to identify key components for successful aging in place. Interviews were transcribed, and reflexive thematic analysis identified patterns that led to a list of attributes. Visuals of these attributes were created and presented to a new sample of informal caregivers and older adults in focus groups to rank attributes and define attribute levels. Results: Attributes identified through the interviews (N = 28) included housing, personal care, household tasks, transportation, social activities, digital skills, and help navigating the healthcare system. Focus groups (N = 35) found that older adults prioritized housing, while informal caregivers prioritized navigating the healthcare system. Transportation and digital skills were ranked as the least important and were excluded from the final list of attributes. Conclusions: Our findings provide a detailed understanding of aging-in-place preferences of older adults and informal caregivers. These insights will inform a DCE to quantify preferences and provide evidence for policymakers. This study increases transparency about the process of attribute development and level selection, contributing to the quality of the final DCE study.</p

Recommendations for clinical research in children presenting to primary care out-of-hours services

BACKGROUND: Research in primary care is essential, but recruiting children in this setting can be complex and may cause selection bias. Challenges surrounding informed consent, particularly in an acute clinical setting, can undermine feasibility. The off-protocol use of an intervention nearing implementation has become common in pragmatic randomized controlled trials (RCTs) set in primary care. AIM: To describe how the informed consent procedure affects study inclusion and to assess how off-protocol medication prescribing affects participant selection in a paediatric RCT. DESIGN: A pragmatic RCT evaluating the cost-effectiveness of oral ondansetron in children diagnosed with acute gastroenteritis in primary care out-of-hours services and a parallel cohort study. METHOD: Consecutive children aged 6 months to 6 years attending primary care out-of-hours services with acute gastroenteritis were evaluated to assess the feasibility of obtaining informed consent, the off-protocol use of ondansetron, and other inclusion/exclusion criteria. RESULTS: The RCTs feasibility was reduced by the informed consent procedure because 39.0% (325/834) of children were accompanied by only one parent. General practitioners prescribed ondansetron off-protocol to 34 children (4.1%), whereof 19 children were eligible for the RCT. RCT-eligible children included in the parallel cohort had fewer risk factors for dehydration than children in the RCT despite similar dehydration assessments by general practitioners. CONCLUSION: The informed consent procedure and off-protocol use of study medication affect the inclusion rate but had little effect on selection. A parallel cohort study alongside the RCT can help evaluate selection bias, and a pilot study can reveal potential barriers to inclusion

Oral ondansetron for paediatric gastroenteritis in primary care:a randomised controlled trial

BACKGROUND: Acute gastroenteritis (AGE) affects almost all children aged ≤5 years. In secondary care, ondansetron was found to be effective at reducing vomiting. AIM: To determine the effectiveness of adding oral ondansetron to care as usual (CAU) to treat vomiting in children with AGE attending out-ofhours primary care (OOH-PC). DESIGN AND SETTING: A pragmatic randomised controlled trial at three OOH-PC centres in the north of the Netherlands (Groningen, Zwolle, and Assen), with a follow-up of 7 days. METHOD: Children were included if they were: aged 6 months–6 years; AGE diagnosed by a GP; ≥4 reported episodes of vomiting in the 24 hours before presentation; ≥1 reported episode of vomiting in the 4 hours before presentation; and written informed consent from both parents. Children were randomly allocated to either the control group or the intervention group. The control group received CAU, namely oral rehydration therapy. The intervention group received CAU plus one dose of oral ondansetron (0.1 mg/kg). RESULTS: In total, 194 children were included for randomisation. One dose of oral ondansetron decreased the proportion of children who continued vomiting within 4 hours from 42.9% to 19.5%, with an odds ratio of 0.37 (95% confidence interval [CI] = 0.20 to 0.72, number needed to treat: four). Ondansetron also decreased the number of vomiting episodes within 4 hours (incidence rate ratio 0.51 [95% CI = 0.29 to 0.88]) and improved overall parental satisfaction with treatment (P = 0.027). CONCLUSION: Children with AGE and increased risk of dehydration due to vomiting could be treated with ondansetron in primary care to stop vomiting more quickly and increase parental satisfaction with treatment. These results could be used to improve the quality and efficacy of general practice medicine