Vrije Universiteit Amsterdam

Background Preventing people from relapsing into unhealthy habits requires insight into predictors of relapse in weight loss maintenance behaviors. We aimed to explore predictors of relapse in physical activity and dietary behavior from the perspectives of health practitioners and persons who regained weight, and identify new predictors of relapse beyond existing knowledge. Methods We used concept mapping to collect data, by organizing eight concept mapping sessions among health practitioners (N=39, five groups) and persons who regained weight (N=21, three groups). At the start of each session, we collected participants’ ideas on potential predictors. Subsequently, participants individually sorted these ideas by relatedness and rated them on importance. We created concept maps using principal component analysis and cluster analysis. Results 43 predictors were identified, of which the majority belonged to the individual domain rather than the environmental domain. Although the majority of predictors were mentioned by both stakeholder groups, both groups had different opinions regarding their importance. Also, some predictors were mentioned by only one of the two stakeholder groups. Practitioners indicated change in daily structure, stress, maladaptive coping skills, habitual behavior, and lack of self-efficacy regarding weight loss maintenance as most important recurrent (mentioned in all groups) predictors. Persons who regained weight indicated lifestyle imbalance or experiencing a life event, lack of perseverance, negative emotional state, abstinence violation effect, decrease in motivation and indulgence as most important recurrent predictors. Conclusions For several predictors associations with relapse were shown in prior research; additionally, some new predictors were identified that have not been directly associated with relapse in weight loss maintenance behaviors. Our finding that both groups differed in opinion regarding the importance of predictors or identified different predictors, may provide an opportunity to enhance lifestyle coaching by creating more awareness of these possible discrepancies and including both points of view during coaching.

Background: Recent years have shown an increased application of prospective trajectory-oriented approaches to posttraumatic stress disorder (PTSD). Although women are generally considered at increased PTSD risk, sex and gender differences in PTSD symptom trajectories have not yet been extensively studied. Objective: To perform an in-depth investigation of differences in PTSD symptom trajectories across one-year post-trauma between men and women, by interpreting the general trends of trajectories observed in sex-disaggregated samples, and comparing within-trajectory symptom course and prevalence rates. Method: We included N = 554 participants (62.5% men, 37.5% women) from a multi-centre prospective cohort of emergency department patients with suspected severe injury. PTSD symptom severity was assessed at 1, 3, 6, and 12 months post-trauma, using the Clinician-Administered PTSD Scale for DSM-IV. Latent growth mixture modelling on longitudinal PTSD symptoms was performed within the sex-disaggregated whole samples. Bayesian modelling with informative priors was applied for reliable model estimation, considering the imbalanced prevalence of the expected latent trajectories. Results: In terms of general trends, the same trajectories were observed for men and women, i.e. resilient, recovery, chronic symptoms and delayed onset. Within-trajectory symptom courses were largely comparable, but resilient women had higher symptoms than resilient men. Sex differences in prevalence rates were observed for the recovery (higher in women) and delayed onset (higher in men) trajectories. Model fit for the sex-disaggregated samples was better than for the whole sample, indicating preferred application of sex-disaggregation. Analyses within the whole sample led to biased estimates of overall and sex-specific trajectory prevalence rates. Conclusions: Sex-disaggregated trajectory analyses revealed limited sex differences in PTSD symptom trajectories within one-year post-trauma in terms of general trends, courses and prevalence rates. The observed biased trajectory prevalence rates in the whole sample emphasize the necessity to apply appropriate statistical techniques when conducting sex-sensitive research.

The risk of recurrent dysplastic colonic lesions is increased following polypectomy. Yield of endoscopic surveillance after adenoma removal is low, while interval colorectal cancers occur. To longitudinally assess the dynamics of fecal microbiota and amino acids in the presence of adenomatous lesions and after their endoscopic removal. In this longitudinal case-control study, patients collected fecal samples prior to bowel preparation before scheduled colonoscopy and 3 months after this intervention. Based on colonoscopy outcomes, patients with advanced adenomas and nonadvanced adenomas (0.5-1.0 cm) who underwent polypectomy during endoscopy (n = 19) were strictly matched on age, body-mass index, and smoking habits to controls without endoscopic abnormalities (n = 19). Microbial taxa were measured by 16S RNA sequencing, and amino acids (AA) were measured by high-performance liquid chromatography (HPLC). Adenoma patients were discriminated from controls based on AA and microbial composition. Levels of proline (p = .001), ornithine (p = .02) and serine (p = .02) were increased in adenoma patients compared to controls but decreased to resemble those of controls after adenoma removal. These AAs were combined as a potential adenoma-specific panel (AUC 0.79(0.64-0.94)). For bacterial taxa, differences between patients with adenomas and controls were found (Bifidobacterium spp.↓, Anaerostipes spp.↓, Butyricimonas spp.↑, Faecalitalea spp.↑ and Catenibacterium spp.↑), but no alterations in relative abundance were observed after polypectomy. Furthermore, Faecalitalea spp. and Butyricimonas spp. were significantly correlated with adenoma-specific amino acids. We selected an amino acid panel specifically increased in the presence of adenomas and a microbial signature present in adenoma patients, irrespective of polypectomy. Upon validation, these panels may improve the effectiveness of the surveillance program by detection of high-risk individuals and determination of surveillance endoscopy timing, leading to less unnecessary endoscopies and less interval cancer.

The rapid increase in large-scale photovoltaic installations, or solar parks, causes a need to monitor their amount and allocation, and assess their impacts. While their spectral signature suggests that solar parks can be identified among other land covers, this detection is challenged by their low occurrence. Here, we develop an object-based random forest (RF) classification approach, using publicly available satellite imagery, which has the advantage of requiring relatively little training data and being easily extendable to large spatial extents and new areas. First, we segmented Sentinel-2 imagery into homogenous objects using a Simple Non-Iterative Clustering algorithm in Google Earth Engine. Thereafter, we calculated for each object the mean, standard deviation, and median for all 10- and 20-meter resolution bands of Sentinel-1 and Sentinel-2. These features are subsequently used to train and validate a range of RF models to select the most promising model setup. The training datasets consisted of subsampled presence/absence data, oversampled presence/ absence data, and multiple land-cover categories. The best-performing model used an oversampled dataset trained on all 10- and 20- meter resolution spectral bands and the radar backscatter properties of one period. Independent test results show an overall classification accuracy of 99.97% (Kappa: 0.90). For this result, the producer accuracy was 85.86% for solar park objects and 99.999% for non-solar park objects. The user accuracy was 92.39% for solar park objects and 99.999% for non-solar park objects. These high classification accuracies indicate that our approach is suitable for transfer learning and is able to detect solar parks in new study areas.

BACKGROUND : Accurate segmentation of head and neck squamous cell cancer (HNSCC) is important for radiotherapy treatment planning. Manual segmentation of these tumors is time-consuming and vulnerable to inconsistencies between experts, especially in the complex head and neck region. The aim of this study is to introduce and evaluate an automatic segmentation pipeline for HNSCC using a multi-view CNN (MV-CNN). Methods: The dataset included 220 patients with primary HNSCC and availability of T1-weighted, STIR and optionally contrast-enhanced T1-weighted MR images together with a manual reference segmentation of the primary tumor by an expert. A T1-weighted standard space of the head and neck region was created to register all MRI sequences to. An MV-CNN was trained with these three MRI sequences and evaluated in terms of volumetric and spatial performance in a cross-validation by measuring intra-class correlation (ICC) and dice similarity score (DSC), respectively. Results: The average manual segmented primary tumor volume was 11.8±6.70 cm3 with a median [IQR] of 13.9 [3.22-15.9] cm3. The tumor volume measured by MV-CNN was 22.8±21.1 cm3 with a median [IQR] of 16.0 [8.24-31.1] cm3. Compared to the manual segmentations, the MV-CNN scored an average ICC of 0.64±0.06 and a DSC of 0.49±0.19. Improved segmentation performance was observed with increasing primary tumor volume: the smallest tumor volume group (<3 cm3) scored a DSC of 0.26±0.16 and the largest group (>15 cm3) a DSC of 0.63±0.11 (p<0.001). The automated segmentation tended to overestimate compared to the manual reference, both around the actual primary tumor and in false positively classified healthy structures and pathologically enlarged lymph nodes. Conclusion: An automatic segmentation pipeline was evaluated for primary HNSCC on MRI. The MV-CNN produced reasonable segmentation results, especially on large tumors, but overestimation decreased overall performance. In further research, the focus should be on decreasing false positives and make it valuable in treatment planning.

The mission of academic excellence has resulted in a science system that incentivises publications within high impact, often basic science journals, and less in application-oriented journals. For the dental research field this so-called academic drift can result in a research portfolio that moves away from research that serves dental healthcare. Therefore, we examined if and how academic drift has changed the dental research field. Web of Science data were used to develop a network map for dental research containing journal clusters that show similar citation behavior. From the year 2000 up to 2015, we explored the intensity of knowledge exchange between the different clusters through citation relations. Next, we analyzed changes in research focus of dental research institutes in seven countries, in dental research, clinical medicine research, basic science, public health research and other fields . Within the citation network, 85.5% of all references in dental journals concern references to other dental journals. The knowledge contribution of non-dental research fields to dental research was limited during the studied period. At the same time, the share of output of dental research institutes in dental research has declined. The research activity of the dental research institutes increased mainly in basic science while the knowledge input from basic science into dental research did not increase. Our findings suggest that the dental research portfolio is influenced by academic drift. This academic drift has increased the disbalance towards basic science, and presents a challenge for the scientific progress in dental healthcare services.

Fractures of lower extremities are common trauma-related injuries, and have major impact on patients' functional status. A frequently used Patient-Reported Outcome Measure (PROM) to evaluate patients’ functional status with lower extremity fractures is the Lower Extremity Functional Scale (LEFS). However, there is no systematic review regarding content validity and other measurement properties of the LEFS in patients with lower extremity fractures. A search was performed in PubMed, Embase, Scopus, and Cochrane Library from inception until November 2020. Studies on development of the LEFS and/or the evaluation of one or more measurement properties of the LEFS in patients with lower extremity fractures were included, and independently assessed by two reviewers using COSMIN guidelines. Seven studies were included. Content validity of the LEFS was rated 'inconsistent', supported by very low quality of evidence. Structural validity was rated ‘insufficient’ supported by doubtful methodological quality. Internal consistency, measurement error, and responsiveness were rated 'indeterminate' supported by inadequate to adequate methodological quality. The methodological quality of the construct validity (hypotheses testing) assessment was rated as 'inadequate'. The LEFS has several shortcomings, the lack of sufficient content validity being the most important one as content validity is considered the most crucial measurement property of a PROM according to the COSMIN guidelines. In interpreting the outcomes, one should therefore be aware that not all relevant aspects of physical functioning may be accounted for in the LEFS. Further validation in a well-designed content validity study is needed, including a clearly defined construct and patient involvement during the assessment of different aspects of content validity. Bone fractures of the lower extremities are a common injury. During rehabilitation it is essential to evaluate how patients experience their physical functioning, in order to monitor the progress and to optimize treatment. To measure physical functioning often questionnaires (also known as Patient Reported Outcome Measures) are used, such as the Lower Extremity Functional Scale (LEFS). However, it is not clear if the LEFS actually measures physical function, and if its other measurement properties are sufficient for using this questionnaire among patients with fractures in the lower extremities. Therefore, we systematically searched and assessed scientific papers on the development of the LEFS (i.e., its ability to measure physical functioning), and papers on the performance of the LEFS with regard to several measurement properties to identify possible factors that may cause measurement errors. Hereby we have assessed the quality of the studies included. Our main finding was that the LEFS may not measure all aspects of physical function. Given the low quality of the papers included in our study, these findings come with considerable uncertainty. As the LEFS was developed more than 20 years ago, it may not represent physical functioning as we currently conceptualize this. Therefore, we recommend to perform a study in which the content of the LEFS will be evaluated by experts in the field as well as patients, and modify the questionnaire as needed.

Background Paralympic swimmers with vision impairment (VI) currently compete in one of the three classes depending on their visual acuity (VA) and/or visual field. However, there is no evidence to suggest that a three-class system is the most legitimate approach for classification in swimming, or that the tests of VA and visual field are the most suitable. An evidence-based approach is required to establish the relationship between visual function and performance in the sport. Therefore, the aim of this study was to establish the relationship between visual function and performance in VI Para swimming. The swimming performance of 45 elite VI swimmers was evaluated during international competitions by measuring the total race time, start time, clean swim velocity, ability to swim in a straight line, turn time, and finish time. Visual function was measured using a test battery that included VA, contrast sensitivity, light sensitivity, depth perception, visual search, and motion perception. Results Results revealed that VA was the best predictor of total race time ( r = 0.40, p < 0.01), though the relationship was not linear. Decision tree analysis suggested that only two classes were necessary for legitimate competition in VI swimming, with a single cut-off between 2.6 and 3.5 logMAR. No further significant association remained between visual function and performance in either of the two resulting classes (all | r s|< 0.11 and p s > 0.54). Conclusions Results suggest that legitimate competition in VI swimming requires one class for partially sighted and another for functionally blind athletes.

Background The development of accurate urinary biomarkers for non-invasive and cost-effective detection of primary and recurrent bladder tumours is recognized as one of the major clinical needs in bladder cancer diagnostics. The purposes of this study were (1) to validate the results of a previous technical comparison by determining the diagnostic performance of nine methylation markers in urine pellet compared to full void urine, and (2) to validate the diagnostic performance of the optimal marker panel GHSR/MAL from a previous exploratory study in a preclinical setting. Methods Urine samples of 108 patients with bladder cancer and 100 age- and gender-matched controls were prospectively collected for methylation analysis. Urinary methylation levels of the markers FAM19A4, GHSR, MAL, miR-129, miR-935, PHACTR3, PRDM14, SST and ZIC1 were determined with quantitative methylation-specific PCR in urine pellet. Area under the curves (AUCs) were determined for individual markers and the marker panel GHSR/MAL. The diagnostic performance of the marker panel GHSR/MAL was evaluated in the total study population and in different subgroups of patients with bladder cancer using the Chi-square test. The diagnostic accuracy was assessed by leave-one-out cross-validation. Results All nine urinary methylation markers (FAM19A4, GHSR, MAL, miR-129, miR-935, PHACTR3, PRDM14, SST and ZIC1) showed significantly higher methylation levels in bladder cancer patients than in controls (p < 0.001). Area under the curves (AUCs) of the nine methylation markers tested in urine pellet were similar to AUCs in full void urine of an independent previous cohort. GHSR/MAL reached an AUC of 0.89 (95% confidence interval [CI] 0.84–0.94), at 80% sensitivity and 93% specificity. Sensitivity of GHSR/MAL increased with higher tumour grades, higher tumour stages, in primary vs. recurrent tumours, and in males vs. females. Conclusions This technical validation supports the robustness of DNA methylation analysis in urine pellet and full void urine for the non-invasive detection of bladder cancer. Subsequent preclinical validation confirmed the diagnostic potential of GHSR/MAL. These findings underline the diagnostic potential of the marker panel GHSR/MAL for future bladder cancer diagnostics.

The chemical pollution crisis severely threatens human and environmental health globally. To tackle this challenge the establishment of an overarching international science–policy body has recently been suggested. We strongly support this initiative based on the awareness that humanity has already likely left the safe operating space within planetary boundaries for novel entities including chemical pollution. Immediate action is essential and needs to be informed by sound scientific knowledge and data compiled and critically evaluated by an overarching science–policy interface body. Major challenges for such a body are (i) to foster global knowledge production on exposure, impacts and governance going beyond data-rich regions (e.g., Europe and North America), (ii) to cover the entirety of hazardous chemicals, mixtures and wastes, (iii) to follow a one-health perspective considering the risks posed by chemicals and waste on ecosystem and human health, and (iv) to strive for solution-oriented assessments based on systems thinking. Based on multiple evidence on urgent action on a global scale, we call scientists and practitioners to mobilize their scientific networks and to intensify science–policy interaction with national governments to support the negotiations on the establishment of an intergovernmental body based on scientific knowledge explaining the anticipated benefit for human and environmental health.

Background Increased total tau (t-tau) in cerebrospinal fluid (CSF) is a key characteristic of Alzheimer’s disease (AD) and is considered to result from neurodegeneration. T-tau levels, however, can be increased in very early disease stages, when neurodegeneration is limited, and can be normal in advanced disease stages. This suggests that t-tau levels may be driven by other mechanisms as well. Because tau pathophysiology is emerging as treatment target for AD, we aimed to clarify molecular processes associated with CSF t-tau levels. Methods We performed a proteomic, genomic, and imaging study in 1380 individuals with AD, in the preclinical, prodromal, and mild dementia stage, and 380 controls from the Alzheimer’s Disease Neuroimaging Initiative and EMIF-AD Multimodality Biomarker Discovery study. Results We found that, relative to controls, AD individuals with increased t-tau had increased CSF concentrations of over 400 proteins enriched for neuronal plasticity processes. In contrast, AD individuals with normal t-tau had decreased levels of these plasticity proteins and showed increased concentrations of proteins indicative of blood–brain barrier and blood-CSF barrier dysfunction, relative to controls. The distinct proteomic profiles were already present in the preclinical AD stage and persisted in prodromal and dementia stages implying that they reflect disease traits rather than disease states. Dysregulated plasticity proteins were associated with SUZ12 and REST signaling, suggesting aberrant gene repression. GWAS analyses contrasting AD individuals with and without increased t-tau highlighted several genes involved in the regulation of gene expression. Targeted analyses of SNP rs9877502 in GMNC , associated with t-tau levels previously, correlated in individuals with AD with CSF concentrations of 591 plasticity associated proteins. The number of APOE-e4 alleles, however, was not associated with the concentration of plasticity related proteins. Conclusions CSF t-tau levels in AD are associated with altered levels of proteins involved in neuronal plasticity and blood–brain and blood-CSF barrier dysfunction. Future trials may need to stratify on CSF t-tau status, as AD individuals with increased t-tau and normal t-tau are likely to respond differently to treatment, given their opposite CSF proteomic profiles.

Background Anomalous phantom visual perceptions coupled to an aversion and discomfort to some visual patterns (especially grating in mid-range spatial frequency) have been associated with the hyperresponsiveness in migraine patients. Previous literature has found fluctuations of alpha oscillation (8-14 Hz) over the visual cortex to be associated with the gating of the visual stream. In the current study, we examined whether alpha activity was differentially modulated in migraineurs in anticipation of an upcoming stimulus as well as post-stimulus periods. Methods We used EEG to examine the brain activity in a group of 28 migraineurs (17 with aura /11 without) and 29 non-migraineurs and compared their alpha power in the pre/post-stimulus period relative to the onset of stripped gratings. Results Overall, we found that migraineurs had significantly less alpha power prior to the onset of the stimulus relative to controls. Moreover, migraineurs had significantly greater post-stimulus alpha suppression (i.e event-related desynchronization) induced by the grating in 3 cycles per degree at the 2nd half of the experiment. Conclusions These findings, taken together, provide strong support for the presence of the hyperresponsiveness of the visual cortex of migraine sufferers. We speculate that it could be the consequence of impaired perceptual learning driven by the dysfunction of GABAergic inhibitory mechanism.

Background Diaphragm ultrasonography is rapidly evolving in both critical care and research. Nevertheless, methodologically robust guidelines on its methodology and acquiring expertise do not, or only partially, exist. Therefore, we set out to provide consensus-based statements towards a universal measurement protocol for diaphragm ultrasonography and establish key areas for research. Methods To formulate a robust expert consensus statement, between November 2020 and May 2021, a two-round, anonymous and online survey-based Delphi study among experts in the field was performed. Based on the literature review, the following domains were chosen: “Anatomy and physiology”, “Transducer Settings”, “Ventilator Impact”, “Learning and expertise”, “Daily practice” and “Future directions”. Agreement of ≥ 68% (≥ 10 panelists) was needed to reach consensus on a question. Results Of 18 panelists invited, 14 agreed to participate in the survey. After two rounds, the survey included 117 questions of which 42 questions were designed to collect arguments and opinions and 75 questions aimed at reaching consensus. Of these, 46 (61%) consensus was reached. In both rounds, the response rate was 100%. Among others, there was agreement on measuring thickness between the pleura and peritoneum, using > 10% decrease in thickness as cut-off for atrophy and using 40 examinations as minimum training to use diaphragm ultrasonography in clinical practice. In addition, key areas for research were established. Conclusion This expert consensus statement presents the first set of consensus-based statements on diaphragm ultrasonography methodology. They serve to ensure high-quality and homogenous measurements in daily clinical practice and in research. In addition, important gaps in current knowledge and thereby key areas for research are established. Trial registration The study was pre-registered on the Open Science Framework with registration digital object identifier https://doi.org/10.17605/OSF.IO/HM8UG .

Background A high percentage of people dying at home, and a low percentage of people being admitted to hospital and dying there are regarded as indicators of appropriate care at the end of life. However, performance standards for these quality indicators are often lacking, which makes it difficult to state whether an indicator score falls between the ranges of good or poor quality care. The aim of this study was to assess quality indicators concerning place of death and hospital care utilization in people with diseases relevant for palliative care, and to establish best practice performance standards based on indicator scores in 31 regions in the Netherlands. Methods A retrospective nationwide population-based observational study was conducted, using routinely collected administrative data concerning persons who died in 2017 in the Netherlands with underlying causes relevant for palliative care ( N = 109,707). Data from four registries were linked for analysis. Scores on eight quality indicators concerning place of death and hospital care utilization were calculated, and compared across 31 healthcare insurance regions to establish relative benchmarks. Results On average, 36.4% of the study population died at home (range between regions 30.5%-42.6%) and 20.4% in hospital (range 16.6%-25.5%). Roughly half of the population who received hospital care at any time in the last year of life were found to (also) receive hospital care in the last month of life. In the last month, 32.0% of the study population were admitted to hospital (range 29.4-36.4%), 5.3% to an Intensive Care Unit (range 3.2-6.9%) and 23.9% visited an Emergency Department (range 21.0-27.4%). In the same time period, less than 1% of the study population was resuscitated in hospital or received tube or intravenous feeding in hospital. Conclusions The variation between regions points towards opportunities for practice improvement. The best practice performance standards as set in this study serve as ambitious but attainable targets for those regions that currently do not meet the standards. Policymakers, healthcare providers and researchers can use the suggested performance standards to further analyze causes of variance between regions and develop and test interventions that can improve practice.

The publication by Balsamo and colleagues describes a patient with Birt-Hogg-Dubé syndrome and hyperplastic polyposis throughout the gastro-intestinal tract. We question whether the diagnosis of BHD in this patient was justified. Using the previously proposed diagnostic criteria for establishing the diagnosis of BHD as a guideline, we systematically describe our concerns. In our opinion, the patient described by Balsamo and colleagues does not meet any of the proposed major and minor criteria for the diagnosis of Birt-Hogg-Dubé syndrome. Therefore, we believe that it is not justified to suggest a possible association between hyperplastic polyposis and Birt-Hogg-Dubé syndrome based on this patient, even though a higher risk for colorectal polyposis in Birt-Hogg-Dubé syndrome has not been excluded so far.