The concepts punitiveness and rehabilitation orientation in the general public are generally measured by rather broad attitude items that are not directly related to probation. In this study, two separate attitude scales were used that were tailor-made for the probation context and therefore have a high ecological validity. These ‘ecological scales’ were each analysed with the same predictor set. Cognitive emotive variables showed incremental prediction above demographics. Higher knowledge of probation and more satisfaction with society are related to a higher preference for rehabilitation. Less knowledge of probation and a higher feeling of victimization are related to a more punitive attitude.
Objective: To describe the discrimination and calibration of clinical prediction models, identify characteristics that contribute to better predictions and investigate predictors that are associated with unplanned hospital readmissions.Design: Systematic review and meta-analysis.Data source: Medline, EMBASE, ICTPR (for study protocols) and Web of Science (for conference proceedings) were searched up to 25 August 2020.Eligibility criteria for selecting studies: Studies were eligible if they reported on (1) hospitalised adult patients with acute heart disease; (2) a clinical presentation of prediction models with c-statistic; (3) unplanned hospital readmission within 6 months. Primary and secondary outcome measures: Model discrimination for unplanned hospital readmission within 6 months measured using concordance (c) statistics and model calibration. Meta-regression and subgroup analyses were performed to investigate predefined sources of heterogeneity. Outcome measures from models reported in multiple independent cohorts and similarly defined risk predictors were pooled.Results: Sixty studies describing 81 models were included: 43 models were newly developed, and 38 were externally validated. Included populations were mainly patients with heart failure (HF) (n=29). The average age ranged between 56.5 and 84 years. The incidence of readmission ranged from 3% to 43%. Risk of bias (RoB) was high in almost all studies. The c-statistic was <0.7 in 72 models, between 0.7 and 0.8 in 16 models and >0.8 in 5 models. The study population, data source and number of predictors were significant moderators for the discrimination. Calibration was reported for 27 models. Only the GRACE (Global Registration of Acute Coronary Events) score had adequate discrimination in independent cohorts (0.78, 95% CI 0.63 to 0.86). Eighteen predictors were pooled. Conclusion: Some promising models require updating and validation before use in clinical practice. The lack of independent validation studies, high RoB and low consistency in measured predictors limit their applicability.PROSPERO registration number: CRD42020159839.
MULTIFILE
Abstract Background: COVID-19 was first identified in December 2019 in the city of Wuhan, China. The virus quickly spread and was declared a pandemic on March 11, 2020. After infection, symptoms such as fever, a (dry) cough, nasal congestion, and fatigue can develop. In some cases, the virus causes severe complications such as pneumonia and dyspnea and could result in death. The virus also spread rapidly in the Netherlands, a small and densely populated country with an aging population. Health care in the Netherlands is of a high standard, but there were nevertheless problems with hospital capacity, such as the number of available beds and staff. There were also regions and municipalities that were hit harder than others. In the Netherlands, there are important data sources available for daily COVID-19 numbers and information about municipalities. Objective: We aimed to predict the cumulative number of confirmed COVID-19 infections per 10,000 inhabitants per municipality in the Netherlands, using a data set with the properties of 355 municipalities in the Netherlands and advanced modeling techniques. Methods: We collected relevant static data per municipality from data sources that were available in the Dutch public domain and merged these data with the dynamic daily number of infections from January 1, 2020, to May 9, 2021, resulting in a data set with 355 municipalities in the Netherlands and variables grouped into 20 topics. The modeling techniques random forest and multiple fractional polynomials were used to construct a prediction model for predicting the cumulative number of confirmed COVID-19 infections per 10,000 inhabitants per municipality in the Netherlands. Results: The final prediction model had an R2 of 0.63. Important properties for predicting the cumulative number of confirmed COVID-19 infections per 10,000 inhabitants in a municipality in the Netherlands were exposure to particulate matter with diameters <10 μm (PM10) in the air, the percentage of Labour party voters, and the number of children in a household. Conclusions: Data about municipality properties in relation to the cumulative number of confirmed infections in a municipality in the Netherlands can give insight into the most important properties of a municipality for predicting the cumulative number of confirmed COVID-19 infections per 10,000 inhabitants in a municipality. This insight can provide policy makers with tools to cope with COVID-19 and may also be of value in the event of a future pandemic, so that municipalities are better prepared.
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Huntington’s disease (HD) and various spinocerebellar ataxias (SCA) are autosomal dominantly inherited neurodegenerative disorders caused by a CAG repeat expansion in the disease-related gene1. The impact of HD and SCA on families and individuals is enormous and far reaching, as patients typically display first symptoms during midlife. HD is characterized by unwanted choreatic movements, behavioral and psychiatric disturbances and dementia. SCAs are mainly characterized by ataxia but also other symptoms including cognitive deficits, similarly affecting quality of life and leading to disability. These problems worsen as the disease progresses and affected individuals are no longer able to work, drive, or care for themselves. It places an enormous burden on their family and caregivers, and patients will require intensive nursing home care when disease progresses, and lifespan is reduced. Although the clinical and pathological phenotypes are distinct for each CAG repeat expansion disorder, it is thought that similar molecular mechanisms underlie the effect of expanded CAG repeats in different genes. The predicted Age of Onset (AO) for both HD, SCA1 and SCA3 (and 5 other CAG-repeat diseases) is based on the polyQ expansion, but the CAG/polyQ determines the AO only for 50% (see figure below). A large variety on AO is observed, especially for the most common range between 40 and 50 repeats11,12. Large differences in onset, especially in the range 40-50 CAGs not only imply that current individual predictions for AO are imprecise (affecting important life decisions that patients need to make and also hampering assessment of potential onset-delaying intervention) but also do offer optimism that (patient-related) factors exist that can delay the onset of disease.To address both items, we need to generate a better model, based on patient-derived cells that generates parameters that not only mirror the CAG-repeat length dependency of these diseases, but that also better predicts inter-patient variations in disease susceptibility and effectiveness of interventions. Hereto, we will use a staggered project design as explained in 5.1, in which we first will determine which cellular and molecular determinants (referred to as landscapes) in isogenic iPSC models are associated with increased CAG repeat lengths using deep-learning algorithms (DLA) (WP1). Hereto, we will use a well characterized control cell line in which we modify the CAG repeat length in the endogenous ataxin-1, Ataxin-3 and Huntingtin gene from wildtype Q repeats to intermediate to adult onset and juvenile polyQ repeats. We will next expand the model with cells from the 3 (SCA1, SCA3, and HD) existing and new cohorts of early-onset, adult-onset and late-onset/intermediate repeat patients for which, besides accurate AO information, also clinical parameters (MRI scans, liquor markers etc) will be (made) available. This will be used for validation and to fine-tune the molecular landscapes (again using DLA) towards the best prediction of individual patient related clinical markers and AO (WP3). The same models and (most relevant) landscapes will also be used for evaluations of novel mutant protein lowering strategies as will emerge from WP4.This overall development process of landscape prediction is an iterative process that involves (a) data processing (WP5) (b) unsupervised data exploration and dimensionality reduction to find patterns in data and create “labels” for similarity and (c) development of data supervised Deep Learning (DL) models for landscape prediction based on the labels from previous step. Each iteration starts with data that is generated and deployed according to FAIR principles, and the developed deep learning system will be instrumental to connect these WPs. Insights in algorithm sensitivity from the predictive models will form the basis for discussion with field experts on the distinction and phenotypic consequences. While full development of accurate diagnostics might go beyond the timespan of the 5 year project, ideally our final landscapes can be used for new genetic counselling: when somebody is positive for the gene, can we use his/her cells, feed it into the generated cell-based model and better predict the AO and severity? While this will answer questions from clinicians and patient communities, it will also generate new ones, which is why we will study the ethical implications of such improved diagnostics in advance (WP6).
Every year in the Netherlands around 10.000 people are diagnosed with non-small cell lung cancer, commonly at advanced stages. In 1 to 2% of patients, a chromosomal translocation of the ROS1 gene drives oncogenesis. Since a few years, ROS1+ cancer can be treated effectively by targeted therapy with the tyrosine kinase inhibitor (TKI) crizotinib, which binds to the ROS1 protein, impairs the kinase activity and thereby inhibits tumor growth. Despite the successful treatment with crizotinib, most patients eventually show disease progression due to development of resistance. The available TKI-drugs for ROS1+ lung cancer make it possible to sequentially change medication as the disease progresses, but this is largely a ‘trial and error’ approach. Patients and their doctors ask for better prediction which TKI will work best after resistance occurs. The ROS1 patient foundation ‘Stichting Merels Wereld’ raises awareness and brings researchers together to close the knowledge gap on ROS1-driven oncogenesis and increase the options for treatment. As ROS1+ lung cancer is rare, research into resistance mechanisms and the availability of cell line models are limited. Medical Life Sciences & Diagnostics can help to improve treatment by developing new models which mimic the situation in resistant tumor cells. In the current proposal we will develop novel TKI-resistant cell lines that allow screening for improved personalized treatment with TKIs. Knowledge of specific mutations occurring after resistance will help to predict more accurately what the next step in patient treatment could be. This project is part of a long-term collaboration between the ROS1 patient foundation ‘Stichting Merels Wereld’, the departments of Pulmonary Oncology and Pathology of the UMCG and the Institute for Life Science & Technology of the Hanzehogeschool. The company Vivomicx will join our consortium, adding expertise on drug screening in complex cell systems.
This project assists architects and engineers to validate their strategies and methods, respectively, toward a sustainable design practice. The aim is to develop prototype intelligent tools to forecast the carbon footprint of a building in the initial design process given the visual representations of space layout. The prediction of carbon emission (both embodied and operational) in the primary stages of architectural design, can have a long-lasting impact on the carbon footprint of a building. In the current design strategy, emission measures are considered only at the final phase of the design process once major parameters of space configuration such as volume, compactness, envelope, and materials are fixed. The emission assessment only at the final phase of the building design is due to the costly and inefficient interaction between the architect and the consultant. This proposal offers a method to automate the exchange between the designer and the engineer using a computer vision tool that reads the architectural drawings and estimates the carbon emission at each design iteration. The tool is directly used by the designer to track the effectiveness of every design choice on emission score. In turn, the engineering firm adapts the tool to calculate the emission for a future building directly from visual models such as shared Revit documents. The building realization is predominantly visual at the early design stages. Thus, computer vision is a promising technology to infer visual attributes, from architectural drawings, to calculate the carbon footprint of the building. The data collection for training and evaluation of the computer vision model and machine learning framework is the main challenge of the project. Our consortium provides the required resources and expertise to develop trustworthy data for predicting emission scores directly from architectural drawings.
