444 research outputs found

    Quickscan vraag en aanbod scholing voor multifunctionele ondernemers

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    Het doel van het onderzoek is inzicht te verkrijgen in het aanbod en de vraag naar scholing voor de multifunctionele ondernemersnetwerken. Daarnaast is er gekeken of er mogelijkheden zijn in vormen van samenwerking tussen de aanbieders van scholing en de ondernemersnetwerke

    Explainable haemoglobin deferral predictions using machine learning models: interpretation and consequences for the blood supply

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    BACKGROUND AND OBJECTIVES\nMATERIALS AND METHODS\nRESULTS\nCONCLUSION\nAccurate predictions of haemoglobin (Hb) deferral for whole-blood donors could aid blood banks in reducing deferral rates and increasing efficiency and donor motivation. Complex models are needed to make accurate predictions, but predictions must also be explainable. Before the implementation of a prediction model, its impact on the blood supply should be estimated to avoid shortages.\nDonation visits between October 2017 and December 2021 were selected from Sanquin's database system. The following variables were available for each visit: donor sex, age, donation start time, month, number of donations in the last 24 months, most recent ferritin level, days since last ferritin measurement, Hb at nth previous visit (n between 1 and 5), days since the nth previous visit. Outcome Hb deferral has two classes: deferred and not deferred. Support vector machines were used as prediction models, and SHapley Additive exPlanations values were used to quantify the contribution of each variable to the model predictions. Performance was assessed using precision and recall. The potential impact on blood supply was estimated by predicting deferral at earlier or later donation dates.\nWe present a model that predicts Hb deferral in an explainable way. If used in practice, 64% of non-deferred donors would be invited on or before their original donation date, while 80% of deferred donors would be invited later.\nBy using this model to invite donors, the number of blood bank visits would increase by 15%, while deferral rates would decrease by 60% (currently 3% for women and 1% for men).Algorithms and the Foundations of Software technolog

    Evaluating privacy of individuals in medical data

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    Algorithms and the Foundations of Software technolog

    Does Centralization of Radical Prostatectomy Reduce the Incidence of Postoperative Urinary Incontinence?

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    Background: On the basis of previous analyses of the incidence of urinary incontinence (UI) after radical prostatectomy (RP), the hospital RP volume threshold in the Netherlands was gradually increased from 20 per year in 2017, to 50 in 2018 and 100 from 2019 onwards. Objective: To evaluate the impact of hospital RP volumes on the incidence and risk of UI after RP (RP-UI). Design, setting, and participants: Patients who underwent RP during 2016–2020 were identified in the claims database of the largest health insurance company in the Netherlands. Incontinence was defined as an insurance claim for ≄1 pads/d. Outcome measurements and statistical analysis: The relationship between hospital RP volume (HV) and RP-UI was assessed via multivariable analysis adjusted for age, comorbidity, postoperative radiotherapy, and lymph node dissection. Results and limitations: RP-UI incidence nationwide and by RP volume category did not decrease significantly during the study period, and 5-yr RP-UI rates varied greatly among hospitals (19–85%). However, low-volume hospitals (≀120 RPs/yr) had a higher percentage of patients with RP-UI and higher variation in comparison to high-volume hospitals (&gt;120 RPs/yr). In comparison to hospitals with low RP volumes throughout the study period, the risk of RP-UI was 29% lower in hospitals shifting from the low-volume to the high-volume category (&gt;120 RPs/yr) and 52% lower in hospitals with a high RP volume throughout the study period (&gt;120 RPs/yr for 5 yr). Conclusions: A focus on increasing hospital RP volumes alone does not seem to be sufficient to reduce the incidence of RP-UI, at least in the short term. Measurement of outcomes, preferably per surgeon, and the introduction of quality assurance programs are recommended. Patient summary: In the Netherlands, centralization of surgery to remove the prostate (RP) because of cancer has not yet improved the occurrence of urinary incontinence (UI) after surgery. Hospitals performing more than 120 RP operations per year had better UI outcomes. However, there was a big difference in UI outcomes between hospitals.</p

    A truncated 14-amino-acid myelin protein-zero-targeting peptide for fluorescence-guided nerve-preserving surgery

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    Background: The occurrence of accidental nerve damage during surgery and the increasing application of image guidance during head-and-neck surgery have highlighted the need for molecular targeted nerve-sparing interventions. The implementation of such interventions relies on the availability of nerve-specific tracers. In this paper, we describe the development of a truncated peptide that has an optimized affinity for protein zero (P0), the most abundant protein in myelin. Methods and Materials: Further C- and N-terminal truncation was performed on the lead peptide Cy5-P0(101-125). The resulting nine Cy5-labelled peptides were characterized based on their photophysical properties, P0 affinity, and in vitro staining. These characterizations were combined with evaluation of the crystal structure of P0, which resulted in the selection of the optimized tracer Cy5-P0(112-125). A near-infrared Cy7-functionalized derivative (Cy7-P0(112-125)) was used to perform an initial evaluation of fluorescence-guided surgery in a porcine model. Results: Methodological truncation of the 26-amino-acid lead compound Cy5-P0(101-125) resulted in a size reduction of 53.8% for the optimized peptide Cy5-P0(112-125). The peptide design and the 1.5-fold affinity gain obtained after truncation could be linked to interactions observed in the crystal structure of the extracellular portion of P0. The near-infrared analogue Cy7-P0(112-125) supported nerve illumination during fluorescence-guided surgery in the head-and-neck region in a porcine model. Conclusions: Methodological truncation yielded a second-generation P0-specific peptide. Initial surgical evaluation suggests that the peptide can support molecular targeted nerve imaging.NWOTTW BGT16141Radiolog

    Developing mHealth Apps with researchers: multi-stakeholder design considerations

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    The authors have been involved with developing a number of mHealth smartphone Apps for use in health or wellness research in collaboration with researchers, clinicians and patient groups for clinical areas including Sickle Cell Disease, Attention Deficit Hyperactivity Disorder, asthma and infertility treatment. In these types of applications, end-users self-report their symptoms and quality of life or conduct psychometric tests. Physiological data may also be captured using sensors that are internal or external to the device. Following a discussion of the multiple stakeholders that are typically involved in small scale research projects involving end-user data collection, four Apps are used as case studies to explore the issue of non-functional requirements

    Influence of enzalutamide on cabazitaxel pharmacokinetics: A Drug–Drug interaction study in metastatic castration-resistant prostate cancer (mCRPC) patients

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    Purpose: In ongoing clinical research on metastatic castration-resistant prostate cancer (mCRPC) treatment, the potential enhanced efficacy of the combination of taxanes with AR-targeted agents, that is, enzalutamide and abiraterone, is currently being explored. Because enzalutamide induces the CYP3A4 enzyme and taxanes are metabolized by this enzyme, a potential drug–drug interaction needs to be investigated. Experimental Design: Therefore, we performed a pharmacokinetic cross-over study in mCRPC patients who were scheduled for treatment with cabazitaxel Q3W (25 mg/m2). Patients were studied for three consecutive cabazitaxel cycles. Enzalutamide (160 mg once daily) was administered concomitantly after the first cabazitaxel cycle, during 6 weeks. Primary endpoint was the difference in mean area under the curve (AUC) between the first (cabazitaxel monotherapy) and third cabazitaxel cycle, when enzalutamide was added. Results: A potential clinically relevant 22% (95% CI, 9%–34%; P ÂŒ 0.005) reduction in cabazitaxel exposure was found with concomitant enzalutamide use. The geometric mean AUC0–24h of cabazitaxel was 181 ngh/mL (95% CI, 150–219 ngh/mL) in cycle 3 and 234 ngh/mL (95% CI, 209–261 ngh/mL) in cycle 1. This combination did not result in excessive toxicity, whereas PSA response was promising. Conclusions: We found a significant decrease in cabazitaxel exposure when combined with enzalutamide. In an era of clinical trials on combination strategies for mCRPC, it is important to be aware of clinically relevant drug–drug interactions. Because recent study results support the use of a lower standard cabazitaxel dose of 20 mg/m2, the clinical relevance of this interaction may be substantial, because the addition of enzalutamide may result in subtherapeutic cabazitaxel exposure

    Human mesenchymal stromal cells in adhesion to cell-derived extracellular matrix and titanium: Comparative kinome profile analysis

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    The extracellular matrix (ECM) physically supports cells and influences stem cell behaviour, modulating kinase-mediated signalling cascades. Cell-derived ECMs have emerged in bone regeneration as they reproduce physiological tissue-architecture and ameliorate mesenchymal stromal cell (MSC) properties. Titanium scaffolds show good mechanical properties, facilitate cell adhesion, and have been routinely used for bone tissue engineering (BTE). We analyzed the kinomic signature of human MSCs in adhesion to an osteopromotive osteoblast-derived ECM, and compared it to MSCs on titanium. PamChip kinase-array analysis revealed 63 phosphorylated peptides on ECM and 59 on titanium, with MSCs on ECM exhibiting significantly higher kinase activity than on titanium. MSCs on the two substrates showed overlapping kinome profiles, with activation of similar signalling pathways (FAK, ERK, and PI3K signalling). Inhibition of PI3K signalling in cells significantly reduced adhesion to ECM and increased the number of nonadherent cells on both substrates. In summary, this study comprehensively characterized the kinase activity in MSCs on cell-derived ECM and titanium, highlighting the role of PI3K signalling in kinomic changes regulating osteoblast viability and adhesion. Kinome profile analysis represents a powerful tool to select pathways to better understand cell behaviour. Osteoblast-derived ECM could be further investigated as titanium scaffold-coating to improve BTE
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