Search

Purpose The Utrecht Cardiovascular Cohort–Second Manifestations of Arterial Disease (UCC-SMART) Study is an ongoing prospective single-centre cohort study with the aim to assess important determinants and the prognosis of cardiovascular disease progression. This article provides an update of the rationale, design, included patients, measurements and findings from the start in 1996 to date.Participants The UCC-SMART Study includes patients aged 18–90 years referred to the University Medical Center Utrecht, the Netherlands, for management of cardiovascular disease (CVD) or severe cardiovascular risk factors. Since September 1996, a total of 14 830 patients have been included. Upon inclusion, patients undergo a standardised screening programme, including questionnaires, vital signs, laboratory measurements, an ECG, vascular ultrasound of carotid arteries and aorta, ankle-brachial index and ultrasound measurements of adipose tissue, kidney size and intima–media thickness. Outcomes of interest are collected through annual questionnaires and adjudicated by an endpoint committee.Findings to date By May 2022, the included patients contributed to a total follow-up time of over 134 000 person-years. During follow-up, 2259 patients suffered a vascular endpoint (including non-fatal myocardial infarction, non-fatal stroke and vascular death) and 2794 all-cause deaths, 943 incident cases of diabetes and 2139 incident cases of cancer were observed up until January 2020. The UCC-SMART cohort contributed to over 350 articles published in peer-reviewed journals, including prediction models recommended by the 2021 European Society of Cardiology CVD prevention guidelines.Future plans The UCC-SMART Study guarantees an infrastructure for research in patients at high cardiovascular risk. The cohort will continue to include about 600 patients yearly and follow-up will be ongoing to ensure an up-to-date cohort in accordance with current healthcare and scientific knowledge. In the near future, UCC-SMART will be enriched by echocardiography, and a food frequency questionnaire at baseline enabling the assessment of associations between nutrition and CVD and diabetes.

IntroductionDendritic cells (DC) are crucial for initiating and shaping immune responses. So far, little is known about the functional specialization of human DC subsets in (local) inflammatory conditions. We profiled conventional (c)DC1, cDC2 and monocytes based on phenotype, transcriptome and function from a local inflammatory site, namely synovial fluid (SF) from patients suffering from a chronic inflammatory condition, Juvenile Idiopathic Arthritis (JIA) as well as patients with rheumatoid arthritis (RA).MethodsPaired PB and SF samples from 32 JIA and 4 RA patients were collected for mononuclear cell isolation. Flow cytometry was done for definition of antigen presenting cell (APC) subsets. Cell sorting was done on the FACSAria II or III. RNA sequencing was done on SF APC subsets. Proliferation assays were done on co-cultures after CD3 magnetic activated cell sorting (MACS). APC Toll-like receptor (TLR) stimulation was done using Pam3CSK4, Poly(I:C), LPS, CpG-A and R848. Cytokine production was measured by Luminex.ResultscDC1, a relatively small DC subset in blood, are strongly enriched in SF, and showed a quiescent immune signature without a clear inflammatory profile, low expression of pathogen recognition receptors (PRRs), chemokine and cytokine receptors, and poor induction of T cell proliferation and cytokine production, but selective production of IFNλ upon polyinosinic:polycytidylic acid exposure. In stark contrast, cDC2 and monocytes from the same environment, showed a pro-inflammatory transcriptional profile, high levels of (spontaneous) pro-inflammatory cytokine production, and strong induction of T cell proliferation and cytokine production, including IL-17. Although the cDC2 and monocytes showed an overlapping transcriptional core profile, there were clear differences in the transcriptional landscape and functional features, indicating that these cell types retain their lineage identity in chronic inflammatory conditions.DiscussionOur findings suggest that at the site of inflammation, there is specific functional programming of human DCs, especially cDC2. In contrast, the enriched cDC1 remain relatively quiescent and seemingly unchanged under inflammatory conditions, pointing to a potentially more regulatory role.

The power of portfolios in enhancing student motivation is frequently emphasised. Portfolios are conceptualised as a tool to implement Assessment for Learning (AfL) in classroom practice. However, the relation between portfolios and AfL on the one hand, and student motivation on the other hand, is complex and subject to many assumptions. This study investigates whether portfolio use actually supports the integration of AfL in classroom practice and the relation with students' motivation. Questionnaires were administered to a total of 419 grade 4 to 6 students from seven Dutch elementary schools. The results of structural equation modelling did not confirm a direct relation between portfolio use and students' motivational orientation. The findings indicate that the relation between portfolios and motivational orientation is fully mediated by students' perceptions of AfL. The findings indicate that the tool portfolio is not related to students' motivation, however, AfL practices do affect motivation.

Abstract Background Radiomics is aimed at image-based tumor phenotyping, enabling application within clinical-decision-support-systems to improve diagnostic accuracy and allow for personalized treatment. The purpose was to identify predictive 18-fluor-fluoro-2-deoxyglucose (18F-FDG) positron-emission tomography (PET) radiomic features to predict recurrence, distant metastasis, and overall survival in patients with head and neck squamous cell carcinoma treated with chemoradiotherapy. Methods Between 2012 and 2018, 103 retrospectively (training cohort) and 71 consecutively included patients (validation cohort) underwent 18F-FDG-PET/CT imaging. The 434 extracted radiomic features were subjected, after redundancy filtering, to a projection resulting in outcome-independent meta-features (factors). Correlations between clinical, first-order 18F-FDG-PET parameters (e.g., SUVmean), and factors were assessed. Factors were combined with 18F-FDG-PET and clinical parameters in a multivariable survival regression and validated. A clinically applicable risk-stratification was constructed for patients’ outcome. Results Based on 124 retained radiomic features from 103 patients, 8 factors were constructed. Recurrence prediction was significantly most accurate by combining HPV-status, SUVmean, SUVpeak, factor 3 (histogram gradient and long-run-low-grey-level-emphasis), factor 4 (volume-difference, coarseness, and grey-level-non-uniformity), and factor 6 (histogram variation coefficient) (CI = 0.645). Distant metastasis prediction was most accurate assessing metabolic-active tumor volume (MATV)(CI = 0.627). Overall survival prediction was most accurate using HPV-status, SUVmean, SUVmax, factor 1 (least-axis-length, non-uniformity, high-dependence-of-high grey-levels), and factor 5 (aspherity, major-axis-length, inversed-compactness and, inversed-flatness) (CI = 0.764). Conclusions Combining HPV-status, first-order 18F-FDG-PET parameters, and complementary radiomic factors was most accurate for time-to-event prediction. Predictive phenotype-specific tumor characteristics and interactions might be captured and retained using radiomic factors, which allows for personalized risk stratification and optimizing personalized cancer care. Trial registration Trial NL3946 (NTR4111), local ethics commission reference: Prediction 2013.191 and 2016.498. Registered 7 August 2013, https://www.trialregister.nl/trial/3946

The understanding of the changes regulating gene expression relevant for the emergence of the human brain and its susceptibility to disease is limited. Here, the authors identified a set of regulatory elements that evolved in hominins affecting oligodendrocyte function, and link these to autism.

Background: Laparoscopic cruroplasty and fundoplication have become the gold standard in the treatment of hiatal hernia and gastro-oesophageal reflux disease (GERD). The use of a mesh-reinforcement of the cruroplasty has been proven effective; although, there is a lack of evidence considering which type of mesh is superior. The aim of this study was to compare recurrence rates after mesh reinforced cruroplasty using biological versus synthetic meshes. Methods: We performed a systematic review of all clinical trials published between January 2004 and September 2015 describing the application of a mesh in the hiatal hernia repair during Nissen fundoplication for both GERD and hiatal hernia. The primary outcome was the recurrence rate, and secondary outcomes were complication rate, mortality and symptomatic outcome. Results: We included 16 studies and extracted data regarding 1089 mesh operated patients of whom 385 received a biological mesh and 704 a synthetic mesh. The mean follow-up was 53.4 months. The recurrence rate in the synthetic mesh group was 6.8% compared to 16.1% in the biological mesh group (P < 0.05). The complication rate was 5.1% and 4.6% (P = 0.694), respectively, and there were 12 mesh-related complications. No mesh-related mortality was reported. Conclusion: Mesh reinforcement of hiatal hernia repair seems safe in the short-term follow-up. The available literature suggests no clear advantage of biological over synthetic meshes. Regarding cost-efficiency and short-term results, the use of synthetic nonabsorbable meshes might be advocated.

Introduction: Nissen fundoplication is the golden standard for surgical treatment of gastroesophageal reflux disease (GERD). Numerous studies report excellent short-term results. However, data regarding long-term quality of life are lacking. The aim of this study is to investigate the long-term quality of life after Nissen fundoplication in patients with GERD and to compare this with the short-term results. Patients and Methods: We retrospectively analysed all patients who underwent laparoscopic Nissen fundoplication for GERD between January 2004 and January 2016. All patients received a validated GERD-Health-Related Quality of Life questionnaire by mail to assess post-operative quality of life. Maximum quality of life is represented by a score of 75. Secondary outcome measures were complications and recurrence rate. Results: One hundred and seventy-five (77.1%) of the 227 operated patients returned the questionnaire. The median follow-up was 3.7 (0.1–10.3) years. Mean age was 51.6 (range 15–85) and 72 patients were male. We report an excellent quality of life with a median total score of 70 (range 2–75). Re-operation rate was 13.6% (23/169); the re-operation was due to recurrent reflux in 12 patients and due to persistent dysphagia in 11 patients. 91.3% of the re-operations were performed within the first 5 years after surgery. Mortality rate was zero. Conclusion: We report a large series of single-centre, single-surgeon laparoscopic Nissen fundoplication. Despite the re-operation rate of 13.6%, we found excellent long-term symptomatic outcome. There was no difference between short- and long-term results.

Abstract Background Considerable variation exists in diagnostic tests used for local response evaluation after chemoradiation in patients with advanced oropharyngeal cancer. The yield of invasive examination under general anesthesia (EUA) with biopsies in all patients is low and it may induce substantial morbidity. We explored four response evaluation strategies to detect local residual disease in terms of diagnostic accuracy and cost-effectiveness. Methods We built a decision-analytic model using trial data of forty-six patients and scientific literature. We estimated for four strategies the proportion of correct diagnoses, costs concerning diagnostic instruments and the proportion of unnecessary EUA indications. Besides a reference strategy, i.e. EUA for all patients, we considered three imaging strategies consisting of 18FDG-PET-CT, diffusion-weighted MRI (DW-MRI), or both 18FDG-PET-CT and DW-MRI followed by EUA after a positive test. The impact of uncertainty was assessed in sensitivity analyses. Results The EUA strategy led to 96% correct diagnoses. Expected costs were €468 per patient whereas 89% of EUA indications were unnecessary. The DW-MRI strategy was the least costly strategy, but also led to the lowest proportion of correct diagnoses, i.e. 93%. The PET-CT strategy and combined imaging strategy were dominated by the EUA strategy due to respectively a smaller or equal proportion of correct diagnoses, at higher costs. However, the combination of PET-CT and DW-MRI had the highest sensitivity. All imaging strategies considerably reduced (unnecessary) EUA indications and its associated burden compared to the EUA strategy. Conclusions Because the combined PET-CT and DW-MRI strategy costs only an additional €927 per patient, it is preferred over immediate EUA since it reaches the same diagnostic accuracy in detecting local residual disease while leading to substantially less unnecessary EUA indications. However, if healthcare resources are limited, DW-MRI is the strategy of choice because of lower costs while still providing a large reduction in unnecessary EUA indications.

Background: Assessment for Learning (AfL) is believed to create a rich learning environment in which students develop their cognitive and metacognitive strategies. Monitoring student growth and providing scaffolds that shed light on the next step in the learning process are hypothesized to be essential elements of AfL that enhance cognitive and metacognitive strategies. However, empirical evidence for the relation between AfL and students' strategy use is scarce. Aim: This study investigates the relation between AfL and elementary school students' use of cognitive and metacognitive strategies. Sample: The sample comprised 528 grade four to six students (9-to 12-year-olds) from seven Dutch elementary schools. Methods: Students' perceptions of AfL and their cognitive and metacognitive strategy use were measured by means of questionnaires. Structural equation modelling was used to investigate the relations among the variables. Results: The results reveal that monitoring activities that provide students an understanding of where they are in their learning process predict Students' task orientation and planning. Scaffolding activities that support students in taking the next step in their learning are positively related to the use of both surface and deep-level learning strategies and the extent to which they evaluate their learning process after performing tasks. Conclusions: The results underline the importance of assessment practices in ceding responsibility to students in taking control of their own learning.

The differential cross sections and unpolarized spin-density matrix elements for the reaction γp→pω were measured using the CBELSA/TAPS experiment for initial photon energies ranging from the reaction threshold to 2.5 GeV. These observables were measured from the radiative decay of the ω meson, ω→π0γ. The cross sections cover the full angular range and show the full extent of the t-channel forward rise. The overall shape of the angular distributions in the differential cross sections and unpolarized spin-density matrix elements are in fair agreement with previous data. In addition, for the first time, a beam of linearly-polarized tagged photons in the energy range from 1150 MeV to 1650 MeV was used to extract polarized spin-density matrix elements. These data were included in the Bonn–Gatchina partial wave analysis (PWA). The dominant contribution to ω photoproduction near threshold was found to be the 3/2+ partial wave, which is primarily due to the sub-threshold N(1720)3/2+ resonance. At higher energies, pomeron-exchange was found to dominate whereas π-exchange remained small. These t-channel contributions as well as further contributions from nucleon resonances were necessary to describe the entire dataset: the 1/2−, 3/2−, and 5/2+ partial waves were also found to contribute significantly.

Photoproduction of two neutral pions off the proton is studied using linearly polarized photons, and the polarization observables Is and Ic are measured for the first time. These two observables are unique to multi-meson final states; they characterize correlations between the linear photon polarization and the direction of outgoing single particles in photoproduction of three-body final states. The Is and Ic distributions suggest that, in the 1.8 to 2.0 GeV mass region, the N(1520)3/2−π intermediate state is reached with reaction dynamics consistent with a dominant JP=3/2+ wave. These data are included in the Bonn–Gatchina (BnGa) partial wave analysis which is based on a large variety of data; the analysis confirms a significant contribution from the reaction chain γp→N(1900)3/2+→N(1520)3/2−π0→pπ0π0. Keywords: Baryon spectroscopy, Double meson photoproduction, Polarization observables

Many innovations in education are not completed, even if they are well thought out in advance. One of the main causes is the organization's lack of learning ability, combined with a shortage of teachers' and students' ownership with respect to the renewal of ideas and design. In communities of learners, teachers and students collaborate and learn together in order to shape innovations in their daily practice. Their ability to learn collectively is a key factor in developing a learning organization. So far, insights into how processes of collective learning can be designed effectively, and which critical factors play a role, have been based on limited empirical research. This article's goal is to contribute to the development of these insights, using the results of a study based on 48 cases of collective learning in communities of learners in primary schools and teacher education institutes. The results suggest that although collective learning rarely takes place in most cases, many outcomes are created that affect all community members. This leads to the conclusion that some participants create outcomes, not only on behalf of themselves but also on behalf of others.