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The restoration and preservation of freshwater ecosystems is one of the prerequisites for a sustainable and fair future for all and therefore part of the United Nations Sustainable Development Goals (SDG 6). However, countries worldwide are facing a challenge to achieve this ambition by 2030. This paper focuses on the legal and governance challenges faced in the European context with regard to achieving water quality ambitions, using experiences from the Netherlands as a case study. Although many EU Member States (MS) are facing a challenge to meet the ambitions set by the Water Framework Directive (WFD) in 2027, literature on effectiveness of governance approaches in terms of actual water quality improvement, seems to be scarce. Based on interviews, a survey, expert panel discussions and literature we show that in the Netherlands, an important problem is that stakeholders, also within organisations, have different views on ambitions, achievements and necessary follow-up actions. This is problematic because for realising the water quality ambitions, cross-sectoral cooperation (e.g. from agriculture and spatial development) as well as strengthened interlinkages between these related policy fields is crucial. Moreover, there is a tendency to stick to the status quo. In order to increase effectiveness, a better understanding of the underlying mechanisms for this lock-in will be necessary. This will enable the development of practical tools and instruments to support cross-sectoral and multi-level collaboration. The sectoral implementation of the WFD in the Netherlands was chosen by many other MS, resulting in similar cross-sectoral challenges as we found in the Netherlands. Insight into how other MS deal with lock-in situations is needed to develop pathways to achieving WFD ambitions.

Background and aims: One of the objectives of the ESC-EORP EUROASPIRE V survey is to determine how well European guidelines on the management of dyslipidaemias are implemented in coronary patients. Methods: Standardized methods were used by trained technicians to collect information on 7824 patients from 130 centers in 27 countries, from the medical records and at a visit at least 6 months after hospitalization for a coronary event. All lipid measurements were performed in one central laboratory. Patients were divided into three groups: on high-intensity LDL-C-lowering-drug therapy (LLT), on low or moderate-intensity LLT and on no LLT. Results: At the time of the visit, almost half of the patients were on a high-intensity LLT. Between hospital discharge and the visit, LLT had been reduced in intensity or interrupted in 20.8% of the patients and had been started or increased in intensity in 11.7%. In those who had interrupted LLT or had reduced the intensity, intolerance to LLT and the advice of their physician were reported as the reason why in 15.8 and 36.8% of the cases, respectively. LDL-C control was better in those on a high-intensity LLT compared to those on low or moderate intensity LLT. LDL-C control was better in men than women and in patients with self-reported diabetes. Conclusions: The results of the EUROASPIRE V survey show that most coronary patients have a less than optimal management of LDL-C. More professional strategies are needed, aiming at lifestyle changes and LLT adapted to the need of the individual patient.

In neuroscience, the distribution of a decision time is modelled by means of a one-dimensional Fokker–Planck equation with time-dependent boundaries and space-time-dependent drift. Efficient approximation of the solution to this equation is required, e.g., for model evaluation and parameter fitting. However, the prescribed boundary conditions lead to a strong singularity and thus to slow convergence of numerical approximations. In this article we demonstrate that the solution can be related to the solution of a parabolic PDE on a rectangular space-time domain with homogeneous initial and boundary conditions by transformation and subtraction of a known function. We verify that the solution of the new PDE is indeed more regular than the solution of the original PDE and proceed to discretize the new PDE using a space-time minimal residual method. We also demonstrate that the solution depends analytically on the parameters determining the boundaries as well as the drift. This justifies the use of a sparse tensor product interpolation method to approximate the PDE solution for various parameter ranges. The predicted convergence rates of the minimal residual method and that of the interpolation method are supported by numerical simulations.

Behavioral control, the ability to manage one's exposure to a given stressor, influences the impacts of both the present and future stressors. Behavioral control over a stressor may decrease stress caused by the stressor, and promote resilience towards future stressors. A lack of behavioral control may exacerbate the stress response and lead to learned helplessness, a generalized view that one cannot control other, unrelated stressors in their environment. The ventromedial prefrontal cortex (vmPFC) may detect the presence of behavioral control over a stressor and communicate this to subcortical regions involved in stress responses, such as the nucleus accumbens (NAc). Building on previous research in animals and humans, we piloted a paradigm to investigate how behavioral control over a physical threat (electric shocks), generalized to responses for a subsequent social stressor (anticipation of public speaking). Our manipulation of behavioral control effected perceived control between groups, increased stress across but not between groups, and no effects generalized to the subsequent social stressor in behavioral, physiological, or neural responses. We discuss refinements to the paradigm to strengthen the manipulation, the potential impacts of statistical power on the present results, and metrics to measure the generalization of behavioral control in addition to vmPFC-subcortical connectivity.

Maize ( Zea mays ) is a major staple crop in Africa, where its yield and the livelihood of millions are compromised by the parasitic witchweed Striga . Germination of Striga is induced by strigolactones exuded from maize roots into the rhizosphere. In a maize germplasm collection, we identified two strigolactones, zealactol and zealactonoic acid, which stimulate less Striga germination than the major maize strigolactone, zealactone. We then showed that a single cytochrome P450, ZmCYP706C37, catalyzes a series of oxidative steps in the maize-strigolactone biosynthetic pathway. Reduction in activity of this enzyme and two others involved in the pathway, ZmMAX1b and ZmCLAMT1, can change strigolactone composition and reduce Striga germination and infection. These results offer prospects for breeding Striga -resistant maize.

The impact of the COVID-19 pandemic on mental health, well-being, and behavior is likely influenced by individual characteristics that determine one's capacity for resilience. In this exploratory study, we examined whether individual differences in working memory (WM) capacity and habit propensity (HP), measured before the outbreak, could predict variation in subsequent psychological coping efficacy (as operationalized by measures of depression, mental well-being, perceived stress, and loneliness) and behavioral adjustment (by evaluating compliance and self-reported automaticity of four COVID-19 guidelines) among Dutch older adults (n = 36) during the pandemic (measured April 25 to May 6, 2020). While we found elevated levels of depression and emotional loneliness, overall mental well-being, and perceived stress were not affected by the pandemic. Contrary to our expectations, we found no robust evidence for a protective role of WM in predicting these outcomes, although our findings hint at a positive relationship with perceived change in mental well-being. Interestingly, WM and HP were found to affect the self-reported automaticity levels of adherence to behavioral COVID-19 guidelines (i.e., washing hands, physical distancing), where a strong HP appeared beneficial when deliberate resources were less available (e.g., low WM capacity). These novel and preliminary findings offer new potential avenues for investigating individual differences in resilience in times of major life events or challenges.Supplementary Information: The online version contains supplementary material available at 10.1007/s10804-022-09404-9.

Background Recent paradigm shifts suggest that psychopathology manifests through dynamic interactions between individual symptoms. Aims To investigate the longitudinal relationships between symptoms in a transdiagnostic sample of patients with psychiatric disorders. Method A two-wave, cross-lagged panel network model of 15 nodes representing symptoms of depression, (social) anxiety and attenuated psychotic symptoms was estimated, using baseline and 1-year follow-up data of 222 individuals with psychiatric disorders. Centrality indices were calculated to determine important predictors and outcomes. Results Our results demonstrated that the strongest relationships in the network were between (a) more suicidal ideation predicting more negative self-view, and (b) autoregressive relationships of social anxiety symptoms positively reinforcing themselves. Negative self-view was the most predictable node in the network as it had the highest ‘in-expected influence’ centrality, and may be an important transdiagnostic outcome symptom. Conclusions The results give insight into longitudinal interactions between symptoms, which interact in ways that do not adhere to broader diagnostic categories. Our results suggest that self-view can also be a transdiagnostic outcome of psychopathology rather than just a predictor, as is normally posited, and may especially have an important relationship with suicidal ideation. Overall, our study demonstrates the dynamic complexity of psychopathology, and further supports the importance of investigating symptom interactions of different psychopathological dimensions over time and across disorders.

To effectively manipulate the electronic structure of the catalysts, we present here a simple bottom-up synthesis protocol for agglomerating palladium and cuprous oxide ultrasmall nanoclusters into single nanoparticles, forming so-called quantum dot assemblies (QDAs). Our synthesis is based on the galvanic displacement of copper with palladium cations under O2-free conditions, rendering the simultaneous and unique crystal growth of ∼3 nm Cu2O and Pd clusters. Such assemblies, comprising ultrasmall nanoconstitutes, offer much more phase boundaries, where the interfacial electronic effect becomes prominent in catalysis. This is demonstrated in the electrocatalytic oxidation of formaldehyde, ethanol, and glucose. In all three cases, the QDA catalyst, despite its similar Pd loading, outperforms the monometallic palladium catalyst. Indeed, complementing the experimental results with density functional theory calculations, we could confirm the sharply increased charge density at the Pd–Cu heterojunction and the decreased energy barrier of the formaldehyde oxidation on the QDA catalyst. Finally, we applied these catalysts in electroless copper deposition – an industrially relevant process for manufacturing printed circuit boards. The QDA catalysts gave uniform and robust copper wires at a rate that was three times faster than that of the monometallic Pd catalyst, showing their potential for real-life applications.

Objective: The COVID-19 pandemic has confronted young adults with an unprecedented mental health challenge. Yet, prospective studies examining protective factors are limited. Methods: In the present study, we focused on changes in mental health in a large sample (N = 685) of at-risk university students, which were measured before and during the pandemic. Network modeling was applied to 20 measured variables to explore intercorrelations between mental health factors, and to identify risk and protective factors. Latent change score modeling was used on a subset of variables. Results: The main findings indicate that (1) mental health problems increased at group level, especially depression-anxiety and loneliness; (2) emotional support during the COVID pandemic was associated with smaller increases in loneliness and depression-anxiety; (3) COVID-related stress predicted increases in depression-anxiety; (4) loneliness acted as a bridge construct between emotional support and changes in mental health. Conclusion: To mitigate the impact of the COVID-19 pandemic on the mental health of young adults, is it recommended to focus on interventions that strengthen internal resources (stress-regulating abilities) and reduce loneliness.

While functional magnetic resonance imaging (fMRI) at ultra-high field (7 T) promises a general increase in sensitivity compared to lower field strengths, the benefits may be most pronounced for specific applications. The current study aimed to evaluate the relative benefit of 7 over 3 T fMRI for the assessment of responses evoked in different brain regions by a well-controlled cognitive task. At 3 and 7 T, the same participants made challenging perceptual decisions about visual motion combined with monetary rewards for correct choices. Previous work on this task has extensively characterized the underlying cognitive computations and single-cell responses in cortical and subcortical structures. We quantified the evoked fMRI responses in extrastriate visual cortical areas, the striatum, and the brainstem during the decision interval and the post-feedback interval of the task. The dependence of response amplitudes on field strength during the decision interval differed between cortical, striatal, and brainstem regions, with a generally bigger 7 versus 3 T benefit in subcortical structures. We also found stronger responses during relatively easier than harder decisions at 7 T for dopaminergic midbrain nuclei, in line with reward expectation. Our results demonstrate the potential of 7 T fMRI for illuminating the contribution of small brainstem nuclei to the orchestration of cognitive computations in the human brain.

Diffusion models with constant boundaries and constant drift function have been successfully applied to model phenomena in a wide range of areas in psychology. In recent years, more complex models with time-dependent boundaries and space-time-dependent drift functions have gained popularity. One obstacle to the empirical and theoretical evaluation of these models is the lack of simple and efficient numerical algorithms for computing their first-passage time distributions. In the present work we use a known series expansion for the first-passage time distribution for models with constant drift function and constant boundaries to simplify the Kolmogorov backward equation for models with time-dependent boundaries and space-time-dependent drift functions. We show how a simple Crank–Nicolson scheme can be used to efficiently solve the simplified equation.

Memory B cells and antibody-secreting plasma cells are generated within germinal centers during affinity maturation in which B-cell proliferation, selection, differentiation, and self-renewal play important roles. The mechanisms behind memory B cell and plasma cell differentiation in germinal centers are not well understood. However, it has been suggested that cell fate is (partially) determined by asymmetric cell division, which involves the unequal distribution of cellular components to both daughter cells. To investigate what level and/or probability of asymmetric segregation of several fate determinant molecules, such as the antigen and transcription factors (BCL6, IRF4, and BLIMP1) recapitulates the temporal switch and DZ-to-LZ ratio in the germinal center, we implemented a multiscale model that combines a core gene regulatory network for plasma cell differentiation with a model describing the cellular interactions and dynamics in the germinal center. Our simulations show that BLIMP1 driven plasma cell differentiation together with coupled asymmetric division of antigen and BLIMP1 with a large segregation between the daughter cells results in a germinal center DZ-to-LZ ratio and a temporal switch from memory B cells to plasma cells that have been observed in experiments.

Feed-forward deep convolutional neural networks (DCNNs) are, under specific conditions, matching and even surpassing human performance in object recognition in natural scenes. This performance suggests that the analysis of a loose collection of image features could support the recognition of natural object categories, without dedicated systems to solve specific visual subtasks. Research in humans however suggests that while feedforward activity may suffice for sparse scenes with isolated objects, additional visual operations ('routines') that aid the recognition process (e.g. segmentation or grouping) are needed for more complex scenes. Linking human visual processing to performance of DCNNs with increasing depth, we here explored if, how, and when object information is differentiated from the backgrounds they appear on. To this end, we controlled the information in both objects and backgrounds, as well as the relationship between them by adding noise, manipulating background congruence and systematically occluding parts of the image. Results indicate that with an increase in network depth, there is an increase in the distinction between object- and background information. For more shallow networks, results indicated a benefit of training on segmented objects. Overall, these results indicate that, de facto, scene segmentation can be performed by a network of sufficient depth. We conclude that the human brain could perform scene segmentation in the context of object identification without an explicit mechanism, by selecting or “binding” features that belong to the object and ignoring other features, in a manner similar to a very deep convolutional neural network., Author summary To what extent do Deep Convolutional Neural Networks exhibit sensitivity to scene properties (e.g. object context) during object recognition, and how is this related to network depth? Linking human visual processing to performance of feed-forward DCNNs with increasing depth, our study explored if and how object information is differentiated from the backgrounds they appear on. We show that with an increase in network depth, there is a stronger selection of parts of the image that belong to the target object, compared to the rest of the image. In other words, network depth facilitates scene segmentation. Given that the operations of a very deep network can be performed by a recurrent network, we speculate that the human brain could perform scene segmentation, in the context of object identification, without an explicit mechanism using recurrent processing.

Background and purpose: It remains challenging to implement and sustain Interprofessional Training Units (ITUs) for equipping health professional students with competencies that are essential for providing collaborative patient-centered care. In this qualitative study, we aimed to identify types of motivation of IPE tutors, the factors that influence their motivation and how these factors can be used to facilitate implementation and sustenance of ITUs. Methods: We interviewed twelve midwifery and nursing tutors of an ITU on a maternity ward regarding their motivation for their role as tutors. Content analysis was performed on the data. Results: IPE tutors had various types of motivation for guiding interprofessional groups of healthcare students. Key factors influencing their motivation included appreciation for their role, perceived effectiveness of their guidance, learning from others, and a balance between their roles as health care professional (HCP) and tutor. Discussion and conclusion: HCPs serving as IPE tutors can be moved from controlled to autonomous motivation through enhancement of their feelings of autonomy, competence and relatedness, by providing tutors with operational support and professional development opportunities. Being a tutor also seems to foster the HCPs' professional identity. Further research is required to determine how tutors’ professional, interprofessional and tutor identities influence IPE outcomes for all stakeholders.

Forensic examination of fire debris evidence is a notoriously difficult analytical task due to the complexity and variability of sample composition. The use of comprehensive two-dimensional gas chromatography with mass spectrometry detection (GC × GC–MS) allows the coupling of orthogonal retention mechanisms and therefore a high peak capacity.We demonstrate recent innovations in combining chemometric techniques for data reduction and feature selection, with evaluation of the evidence for forensic questions pertaining to the detection and subsequent classification of ignitable liquid residue (ILR) in fire debris samples. Chromatograms are divided into non-overlapping spatially delimited regions; for each of these regions a Local Ion Signature (LIS) is computed by summing the intensities, per nominal mass/charge over all points contained within each region. This yields a reduced feature space representing the original data as a set of consolidated ion traces. Subsequent feature selection is performed by evaluating the individual efficacy of each feature using a univariate score-based likelihood ratio (LR) approach for discriminating between pairs of same or different type samples. The retained features are used to model each ILR class using linear discriminant analysis (LDA).Results are demonstrated for 155 arson samples containing a diversity of substrate compounds and several known ignitable liquids. ILR detection is performed at 84% accuracy with fewer than 1% false positives followed by subsequent classification. Likelihood ratio distributions are presented referring to both detection and classification tasks.

Background: The Clinical High Risk state for Psychosis (CHR-P) has become the cornerstone of modern preventive psychiatry. The next stage of clinical advancements rests on the ability to formulate a more accurate prognostic estimate at the individual subject level. Individual Participant Data Meta-Analyses (IPD-MA) are robust evidence synthesis methods that can also offer powerful approaches to the development and validation of personalized prognostic models. The aim of the study was to develop and validate an individualized, clinically based prognostic model for forecasting transition to psychosis from a CHR-P stage.Methods: A literature search was performed between January 30, 2016, and February 6, 2016, consulting PubMed, Psychinfo, Picarta, Embase, and ISI Web of Science, using search terms ("ultra high risk" OR "clinical high risk" OR "at risk mental state") AND [(conver* OR transition* OR onset OR emerg* OR develop*) AND psychosis] for both longitudinal and intervention CHR-P studies. Clinical knowledge was used to a priori select predictors: age, gender, CHR-P subgroup, the severity of attenuated positive psychotic symptoms, the severity of attenuated negative psychotic symptoms, and level of functioning at baseline. The model, thus, developed was validated with an extended form of internal validation.Results: Fifteen of the 43 studies identified agreed to share IPD, for a total sample size of 1,676. There was a high level of heterogeneity between the CHR-P studies with regard to inclusion criteria, type of assessment instruments, transition criteria, preventive treatment offered. The internally validated prognostic performance of the model was higher than chance but only moderate [Harrell's C-statistic 0.655, 95% confidence interval (CIs), 0.627-0.682]. Conclusion: This is the first IPD-MA conducted in the largest samples of CHR-P ever collected to date. An individualized prognostic model based on clinical predictors available in clinical routine was developed and internally validated, reaching only moderate prognostic performance. Although personalized risk prediction is of great value in the clinical practice, future developments are essential, including the refinement of the prognostic model and its external validation. However, because of the current high diagnostic, prognostic, and therapeutic heterogeneity of CHR-P studies, IPD-MAs in this population may have an limited intrinsic power to deliver robust prognostic models.

A new curriculum and examination programme for upper secondary school physics was recently introduced in the Netherlands. Models and modelling play an important role herein. But teachers need help in developing their PCK in this area. To this end we developed a modelling guide, which introduces physics teachers to the role of modelling in science and science education, the scientific base of teaching and learning routes of modelling in pre-university education, and curriculum relevant computer models. We discuss the design and contents of this guide, and teachers’ first impressions when it was presented to them in workshops.

Background: The oral cavity is a potential source of infectious complications in patients treated with myelosuppressive chemotherapy (CT). Pre-chemotherapy oral examination to identify foci of infection is recommended, but it is unclear whether this should include panoramic radiography. The present study aimed to evaluate the additional diagnostic merit of panoramic radiography as part of pre-CT oral screening. Methods: Patients with solid tumors scheduled to receive a myelosuppressive CT were eligible. The foci definition followed the guidelines of the Dutch Association of Maxillofacial Surgery. Oral foci assessed by clinical evaluation and panoramic radiography were compared. Results: In 33 out of 93 patients (35.5%), one or more foci were identified by clinical examination, whereas in 49.5% of patients, panoramic radiography showed pathology. In 19 patients, an oral focus was missed by clinical examination only, whereas in 11 patients, panoramic radiography indicated periodontal bone loss, but advanced periodontitis was not substantiated by clinical examination. Conclusions: Panoramic radiographs complement clinical examinations and have additional diagnostic value. Nevertheless, the additional merit seems small, and the clinical relevance may vary depending on the anticipated risk of developing oral complications and the need for detailed diagnosis and rigorous elimination of oral foci prior to the start of cancer therapy.

Background: The consequences of radial nerve palsy associated with a humeral shaft fracture are unclear. The aim of this study was to examine the functional recovery of radial nerve palsy, at presentation or postoperatively, in patients with a humeral shaft fracture. Methods: Data from patients who participated in the HUMeral shaft fractures: measuring recovery after operative versus non-operative treatment (HUMMER) study, a multicenter prospective cohort study including adults with a closed humeral shaft fracture Arbeitsgemeinschaft für Osteosynthesefragen (AO) type 12A or 12B, and had radial nerve palsy at presentation or postoperatively, were extracted from the HUMMER database. The primary outcome measure was clinically assessed recovery of motor function of the radial nerve. Secondary outcomes consisted of treatment, functional outcome (Disabilities of the Arm, Shoulder, and Hand and Constant–Murley Score), pain level, quality of life (Short Form-36 and EuroQoL-5D-3L), activity resumption, and range of motion of the shoulder and elbow joint at 12 months after trauma. Results: Three of the 145 nonoperatively treated patients had radial nerve palsy at presentation. One recovered spontaneously and 1 after osteosynthesis. Despite multiple surgical interventions, the third patient had no recovery after entrapment between fracture fragments. Thirteen of the 245 operatively treated patients had radial nerve palsy at presentation; all recovered. Nine other patients had postoperative radial nerve palsy; 8 recovered. One had ongoing recovery at the last follow-up, after nerve release and suture repair due to entrapment under the plate. At 12 months, the functional outcome scores of all patients suggested full recovery regarding functional outcome, pain, quality of life, activity resumption, and range of motion. Conclusion: Radial nerve palsy in patients with a humeral shaft fracture at presentation or postoperatively functionally recovers in 94% and 89%, respectively.

OBJECTIVE: Limited sampling strategies (LSS) lower the burden of pharmacokinetic (PK)-guided dosing, but an extensive evaluation of LSS for BAX 855 (Adynovi) is currently lacking. This study aimed to develop a LSS for BAX 855 and combine this with a LSS of a standard half-life (SHL) factor VIII (FVIII) concentrate in a clinical setting. METHODS: Individual PK parameters of BAX 855 were estimated for 10 000 virtual patients with severe hemophilia A using Monte Carlo simulations. Several LSS consisting of 2-6 samples were examined based on patient burden, bias and accuracy of clearance, elimination half-life, volume of distribution and trough levels at 72 h (C72). Analyses were performed separately for adults and children

Current diagnostic criteria for myelofibrosis are largely based on bone marrow (BM) biopsy results. However, these have several limitations, including sampling errors. Explorative studies have indicated that imaging might form an alternative for the evaluation of disease activity, but the heterogeneity in BM abnormalities complicates the choice for the optimal technique. In our prospective diagnostic pilot study, we aimed to visualize all BM abnormalities in myelofibrosis before and during ruxolitinib treatment using both PET/CT and MRI. A random sample of patients was scheduled for examinations at baseline and after 6 and 18 months of treatment, including clinical and laboratory examinations, BM biopsies, MRI (T1-weighted, Dixon, dynamic contrast-enhanced (DCE)) and PET/CT ([15O]water, [18F]NaF)). At baseline, all patients showed low BM fat content (indicated by T1-weighted MRI and Dixon), increased BM blood flow (as measured by [15O]water PET/CT), and increased osteoblastic activity (reflected by increased skeletal [18F]NaF uptake). One patient died after the baseline evaluation. In the others, BM fat content increased to various degrees during treatment. Normalization of BM blood flow (as reflected by [15O]water PET/CT and DCE-MRI) occurred in one patient, who also showed the fastest clinical response. Vertebral [18F]NaF uptake remained stable in all patients. In evaluable cases, histopathological parameters were not accurately reflected by imaging results. A case of sampling error was suspected. We conclude that imaging results can provide information on functional processes and disease distribution throughout the BM. Differences in early treatment responses were especially reflected by T1-weighted MRI. Limitations in the gold standard hampered the evaluation of diagnostic accuracy.

Aim Necrotizing enterocolitis (NEC) is the most lethal disease of the gastrointestinal tract of preterm infants. New and existing management strategies need clinical evaluation. Large heterogeneity exists in the selection, measurement, and reporting of outcome measures in NEC intervention studies. This hampers meta-analyses and the development of evidence-based management guidelines. We aim to develop a Core Outcome Set (COS) for NEC that includes the most relevant outcomes for patients and physicians, from moment of diagnosis into adulthood. This COS is designed for use in NEC treatment trials, in infants with confirmed NEC. Methods This study is designed according to COS-STAD (Core Outcome Set-STAndards for Development) recommendations and the COMET (Core Outcome Measures in Effectiveness Trials) Initiative Handbook. We obtained a waiver from the Ethics Review Board and prospectively registered this study with COMET (Study 1920). We will approach 125 clinicians and/or researchers from low-middle and high-income countries based on their scientific output (using SCIVAL, a bibliometric tool). Patients and parents will be approached through local patient organisations. Participants will be separated into three panels, to assess differences in priorities between former patients and parents (1. lay panel), clinicians and researchers involved in the neonatal period (2. neonatal panel) and after the neonatal period (3. post-neonatal panel). They will be presented with outcomes currently used in NEC research, identified through a systematic review, in a Delphi process. Eligible outcome domains are also identified from the patients and parents’ perspectives. Using a consensus process, including three online Delphi rounds and a final face-to-face consensus meeting, the COS will be finalised and include outcomes deemed essential to all stakeholders: health care professionals, parents and patients’ representatives. The final COS will be reported in accordance with the COS-Standards for reporting (COS-STAR) statement. Conclusions Development of an international COS will help to improve homogeneity of outcome measure reporting in NEC, will enable adequate and efficient comparison of treatment strategies, and will help the interpretation and implementation of clinical trial results. This will contribute to high-quality evidence regarding the best treatment strategy for NEC in preterm infants.

Background Binge eating disorder (BED), as the most prevalent eating disorder, is strongly related to obesity and other somatic and psychiatric morbidity. Despite evidence-based treatments a considerable number of BED patients fail to recover. There is preliminary evidence for the association between psychodynamic personality functioning and personality traits on treatment outcome. However, research is limited and results are still contradictory. Identifying variables associated with treatment outcome could improve treatment programs. The aim of the study was to explore whether personality functioning or personality traits are associated with Cognitive Behavioral Therapy (CBT) outcome in obese female patients with BED or subthreshold BED. Methods Eating disorder symptoms and clinical variables were assessed in 168 obese female patients with DSM-5 BED or subthreshold BED, referred to a 6-month outpatient CBT program in a pre-post measurement design. Personality functioning was assessed by the Developmental Profile Inventory (DPI), personality traits by the Temperament and Character Inventory (TCI). Treatment outcome was assessed by the Eating Disorder Examination-Questionnaire (EDE-Q) global score and self-reported binge eating frequency. According to the criteria of clinical significance, 140 treatment completers were categorized in four outcome groups (recovered, improved, unchanged, deteriorated). Results EDE-Q global scores, self-reported binge eating frequency and BMI significantly decreased during CBT, where 44.3% of patients showed clinically significant change in EDE-Q global score. Treatment outcome groups showed significant overall differences on the DPI Resistance and Dependence scales and the aggregated ‘neurotic’ scale. Significant overall differences were found between groups on TCI Harm avoidance, although post hoc t-tests were non-significant. Furthermore, multiple logistic regression analysis, controlling for mild to moderate depressive disorder and TCI harm avoidance showed that ‘neurotic’ personality functioning was a significant negative predictor of clinically significant change. Conclusion Maladaptive (‘neurotic’) personality functioning is significantly associated with a less favorable outcome after CBT in patients with binge eating. Moreover, ‘neurotic’ personality functioning is a predictor of clinically significant change. Assessment of personality functioning and personality traits could support indication for more specified or augmented care, tailored towards the patients’ individual strengths and vulnerabilities. Trial registration This study protocol was retrospectively evaluated and approved on 16-06-2022 by the Medical Ethical Review Committee (METC) of the Amsterdam Medical Centre (AMC). Reference number W22_219#22.271.

Purpose First, to assess the number of spinal cord anomalies (SCA), specifically tethered spinal cord (TSC) in patients with anorectal malformations (ARM), identified with spinal cord imaging (i.e. spinal cord US and/or MRI). Second, to report outcomes after TSC treatment. Methods A retrospective mono-center study was performed. All ARM patients born between January 2000 and December 2021 were included. Screening for SCA consisted of spinal cord US and/or MRI. Radiology reports were scored on presence of SCA. Data were presented with descriptive statistics. Results In total, 254 patients were eligible for inclusion, of whom 234 (92.1%) underwent spinal cord imaging. In total, 52 (22.2%) patients had a SCA, diagnosed with US (n = 20, 38.5%), MRI (n = 10, 19.2%), or both US and MRI (n = 22, 42.3%), of whom 12 (23.5%) with simple, 27 (52.7%) intermediate, and 12 (23.5%) complex ARM types. TSC was identified in 19 patients (8.1%), of whom 4 (21.1%) underwent uncomplicated neurosurgical intervention. Conclusions SCA were present in 22% of ARM patients both in simple, as well as more complex ARM types. TSC was present in 19 patients with SCA, of whom 4 underwent uncomplicated neurosurgical intervention. Therefore, screening for SCA seems to be important for all ARM patients, regardless of ARM type. Level of Evidence Level III.

Background Partial breast irradiation (PBI) is standard of care in low-risk breast cancer patients after breast-conserving surgery (BCS). Pre-operative PBI can result in tumor downstaging and more precise target definition possibly resulting in less treatment-related toxicity. This study aims to assess the pathologic complete response (pCR) rate one year after MR-guided single-dose pre-operative PBI in low-risk breast cancer patients. Methods The ABLATIVE-2 trial is a multicenter prospective single-arm trial using single-dose ablative PBI in low-risk breast cancer patients. Patients ≥ 50 years with non-lobular invasive breast cancer ≤ 2 cm, grade 1 or 2, estrogen receptor-positive, HER2-negative, and tumor-negative sentinel node procedure are eligible. A total of 100 patients will be enrolled. PBI treatment planning will be performed using a radiotherapy planning CT and -MRI in treatment position. The treatment delivery will take place on a conventional or MR-guided linear accelerator. The prescribed radiotherapy dose is a single dose of 20 Gy to the tumor, and 15 Gy to the 2 cm of breast tissue surrounding the tumor. Follow-up MRIs, scheduled at baseline, 2 weeks, 3, 6, 9, and 12 months after PBI, are combined with liquid biopsies to identify biomarkers for pCR prediction. BCS will be performed 12 months after radiotherapy or after 6 months, if MRI does not show a radiologic complete response. The primary endpoint is the pCR rate after PBI. Secondary endpoints are radiologic response, toxicity, quality of life, cosmetic outcome, patient distress, oncological outcomes, and the evaluation of biomarkers in liquid biopsies and tumor tissue. Patients will be followed up to 10 years after radiation therapy. Discussion This trial will investigate the pathological tumor response after pre-operative single-dose PBI after 12 months in patients with low-risk breast cancer. In comparison with previous trial outcomes, a longer interval between PBI and BCS of 12 months is expected to increase the pCR rate of 42% after 6–8 months. In addition, response monitoring using MRI and biomarkers will help to predict pCR. Accurate pCR prediction will allow omission of surgery in future patients. Trial registration The trial was registered prospectively on April 28th 2022 at clinicaltrials.gov (NCT05350722).

Objective Discussion remains on how to advise women with a past medical history of surgically corrected anorectal malformations (ARMs) regarding vaginal delivery. The aim of this review is to evaluate and review the reported obstetrical complications and outcomes after vaginal delivery for these women. Data sources A systematic search was performed from inception up to 25 July 2022 in PubMed, Embase.com and Clarivate Analytics/Web of Science Core Collection, with backward citation tracking. Study eligibility criteria/appraisal All articles reported on the outcomes of interest in women with a past medical history of surgically corrected anorectal malformation and had a vaginal delivery were included with the exception of editorial comments or invitational commentaries. Screening, data extraction and risk of bias assessment was done by two authors independently with a third and fourth reviewer in case of disagreement. Tool for Quality assessment depended on the type of article. As low quality evidence was expected no meta-analysis was performed. Results Only five of the 2377 articles screened were eligible for inclusion with a total of 13 attempted vaginal deliveries in eight women. In three patients complications were reported: failed vaginal delivery requiring urgent cesarean section in two patients, and vaginal tearing in one patient. Conclusion High quality evidence regarding outcomes and complications after vaginal delivery in women with a history of surgically corrected anorectal malformation is lacking. Therefore, based upon this systematic review no formal recommendation can be formulated regarding its safety. Future studies are essential to address this problem. Trial registration CRD42020201390. Date: 28–07-2020s.

IMPORTANCE\nAlthough numerous children receive methylphenidate hydrochloride for the treatment of attention-deficit/hyperactivity disorder (ADHD), little is known about age-dependent and possibly lasting effects of methylphenidate on the human dopaminergic system.\nOBJECTIVES\nTo determine whether the effects of methylphenidate on the dopaminergic system are modified by age and to test the hypothesis that methylphenidate treatment of young but not adult patients with ADHD induces lasting effects on the cerebral blood flow response to dopamine challenge, a noninvasive probe for dopamine function.\nDESIGN, SETTING, AND PARTICIPANTS\nA randomized, double-blind, placebo-controlled trial (Effects of Psychotropic Drugs on Developing Brain-Methylphenidate) among ADHD referral centers in the greater Amsterdam area in the Netherlands between June 1, 2011, and June 15, 2015. Additional inclusion criteria were male sex, age 10 to 12 years or 23 to 40 years, and stimulant treatment-naive status.\nINTERVENTIONS\nTreatment with either methylphenidate or a matched placebo for 16 weeks.\nMAIN OUTCOMES AND MEASURES\nChange in the cerebral blood flow response to an acute challenge with methylphenidate, noninvasively assessed using pharmacological magnetic resonance imaging, between baseline and 1 week after treatment. Data were analyzed using intent-to-treat analyses.\nRESULTS\nAmong 131 individuals screened for eligibility, 99 patients met DSM-IV criteria for ADHD, and 50 participants were randomized to receive methylphenidate and 49 to placebo. Sixteen weeks of methylphenidate treatment increased the cerebral blood flow response to methylphenidate within the thalamus (mean difference, 6.5; 95% CI, 0.4-12.6; P = .04) of children aged 10 to 12 years old but not in adults or in the placebo group. In the striatum, the methylphenidate condition differed significantly from placebo in children but not in adults (mean difference, 7.7; 95% CI, 0.7-14.8; P = .03).\nCONCLUSIONS AND RELEVANCE\nWe confirm preclinical data and demonstrate age-dependent effects of methylphenidate treatment on human extracellular dopamine striatal-thalamic circuitry. Given its societal relevance, these data warrant replication in larger groups with longer follow-up.\nTRIAL REGISTRATION\nidentifier: NL34509.000.10 and trialregister.nl identifier: NTR3103.

This second roundtable discussion was convened at the 56th European Society of Paediatric Radiology (ESPR) 2022 Annual Meeting in Marseille, France, to discuss controversial aspects of imaging in child abuse. The following topics were discussed: Fracture dating—the published literature is broadly similar with respect to the identification of the radiographic stages of bony healing. The non-expert/general radiologist is encouraged to use broad descriptors of fracture healing (acute, healing or old) within their reports, rather than attempting to date fractures. The more experienced/expert radiologist, who may provide a timeframe/range to assist the courts, should be aware that any published timeframes are not absolute and that recent research indicates that the rate of healing may differ according to the bone affected and the age of the patient. Whole spine imaging in suspected abusive head trauma—this is recommended to enable a complete assessment of the neuraxis when abusive head trauma is suspected or diagnosed, particularly in the presence of intracranial and cervical subdural haemorrhage and cervical ligamentous injury. Cranial imaging in suspected physical abuse—both computed tomography (CT) and magnetic resonance imaging (MRI) remain complimentary depending on the clinical context in which they are used with CT remaining first-line in the assessment of children with (suspected abusive) head trauma prior to an early MRI. MRI is superior in its assessment of parenchymal injury and may be employed as first-line in age appropriate asymptomatic siblings of a child with suspected physical abuse.

SamenvattingDoel van de studie was evaluatie van de beschikbare literatuur over de kans op succes van urinedeviaties al dan niet met cystectomie bij patiënten met bekkenpijnsyndroom / interstitiële cystitis. Er werden drie reviews gevonden en nul gerandomiseerde trials. In de 21 geselecteerde case series werden in totaal 475 patiënten geïncludeerd. De kans op succes van een urinedeviatie was 81%. Voorspellers voor de kans op succes (aanwezigheid van een Hunnerse laesie en kleine blaascapaciteit) konden niet worden bevestigd vanwege de heterogeniteit van de studies. Urinedeviatie in combinatie met verwijdering van de blaas was na cystectomie succesvol in 96% van de gevallen, na partiële cystectomie in 75% en na urinedeviatie en zonder cystectomie in 79% van de gevallen. Concluderend kan worden gesteld dat harde wetenschappelijke onderbouwing voor of tegen een urinedeviatie bij bekkenpijnsyndroom / interstitiële cystitis ontbreekt, omdat de (best goede) resultaten in de case series alleen kunnen worden geïnterpreteerd met inachtneming van (inclusie)bias. Op grond hiervan moeten therapiekeuzes nog steeds op individuele basis worden gemaakt.

In infants without a history of trauma, subdural haemorrhages should raise the concern for an abusive head injury, particularly when they are associated with bridging vein clotting/rupture or with septations. However, non-haemorrhagic, fluid-appearing subdural collections (also called hygromas) may also be the result of abuse. Subdural collections have also been uncommonly observed in patients with benign enlargement of the subarachnoid spaces (BESS) and a few large-scale studies accurately investigate the incidence and the significance. Currently, there is a wide variation of practices in children with BESS and subdural collections. Due to the social risks associated with abuse evaluation and the perceived risk of radiation exposure, there might be a reluctance to fully evaluate these children in some centres. The diagnosis of physical abuse cannot be substantiated nor safely excluded in infants with BESS and subdural collection(s), without investigation for concomitant traumatic findings. The exact prevalence of occult injuries and abuse in these infants is unknown. In macrocephalic infants with subdural collections and imaging features of BESS, thorough investigations for abuse are warranted and paediatricians should consider performing full skeletal surveys even when fundoscopy, social work consult, and detailed clinical evaluation are unremarkable.

van Doorn et al. (2021) outlined various questions that arise when conducting Bayesian model comparison for mixed effects models. Seven response articles offered their own perspective on the preferred setup for mixed model comparison, on the most appropriate specification of prior distributions, and on the desirability of default recommendations. This article presents a round-table discussion that aims to clarify outstanding issues, explore common ground, and outline practical considerations for any researcher wishing to conduct a Bayesian mixed effects model comparison.

Little is known about the safety and surgical outcomes of mastectomy after breast reduction in the trans male population. Several concerns have been voiced that performing mastectomy with prior breast reduction surgery, increases the risk for complications and revision surgery. All transgender men with a history of breast reduction, who underwent a mastectomy at our center between 01-1990 and 01-2021 were identified from our hospital registry. A retrospective chart study was conducted recording surgical characteristics, surgical complications, revision surgery, and clinical follow-up. A total of 1362 subcutaneous mastectomies were performed between 01-1990 and 01-2021. A total of 36 (2.6%) individuals were included (35 bilateral and 1 unilateral breast reduction). The mean age at mastectomy was 37 ? 10 years, and the median time between breast reduction and mastectomy was 6.3 years (range 1.0?31.1). Most individuals underwent a Wise-pattern breast reduction (91%) and a double incision mastectomy with free nipple grafts (86%). Following mastectomy, one acute reoperation was performed because of hemorrhage (3%). Partial pedicled nipple necrosis was seen in 7% and (partial) non-take of nipple grafts in 4%. Scar revisions were performed in 9%, dogear corrections in 20%, and both nipple corrections, and contour corrections in 6%. When comparing the outcomes in literature for surgical complications, scar revision, contour correction or nipple areolar complex revision, no clear disadvantage seems to be present when performing mastectomy after breast reduction. Mastectomy is a safe procedure in transgender men with a history of breast reduction.

Background Reducing radiation dose to the hippocampus with hippocampal avoidance prophylactic cranial irradiation (HA-PCI) is proposed to prevent cognitive decline. It has, however, not been investigated whether hippocampal atrophy is actually mitigated by this approach. Here, we determined whether HA-PCI reduces hippocampal atrophy. Additionally, we evaluated neurotoxicity of (HA-)PCI to other brain regions. Finally, we evaluated associations of hippocampal atrophy and brain neurotoxicity with memory decline. Methods High-quality research MRI scans were acquired in the multicenter, randomized phase 3 trial NCT01780675. Hippocampal atrophy was evaluated for 4 months (57 HA-PCI patients and 46 PCI patients) and 12 months (28 HA-PCI patients and 27 PCI patients) after (HA-)PCI. We additionally studied multimodal indices of brain injury. Memory was assessed with the Hopkins Verbal Learning Test–Revised (HVLT-R). Results HA-PCI reduced hippocampal atrophy at 4 months (1.8% for HA-PCI and 3.0% for PCI) and at 12 months (3.0% for HA-PCI and 5.8% for PCI). Both HA-PCI and PCI were associated with considerable reductions in gray matter and normal-appearing white matter, increases in white matter hyperintensities, and brain aging. There were no significant associations between hippocampal atrophy and memory. Conclusions HA-PCI reduces hippocampal atrophy at 4 and 12 months compared to regular PCI. Both types of radiotherapy are associated with considerable brain injury. We did not find evidence for excessive brain injury after HA-PCI relative to PCI. Hippocampal atrophy was not associated with memory decline in this population as measured with HVLT-R. The usefulness of HA-PCI is still subject to debate.

Objective: To assess facial esthetics and quality of life (QoL) as measure of success or failure after maxillomandibular advancement (MMA) surgery for obstructive sleep apnea (OSA). Methods: Visual analog scales (VAS) on facial esthetics and QoL survey, including EQ-5D3L, Epworth Sleepiness Scale (ESS), and Functional Outcome of Sleep Questionnaire (FOSQ) were collected. Outcomes were analyzed for surgical-success/failure after MMA. Results: Forty-one patients returned completed surveys (response: 66%). Mean VAS on facial esthetics was 57 ± 22 mm preoperative and 51 ± 24 mm postoperative (p = 0.217). When MMA was considered a surgical-failure, VAS was significantly more negative (40 ± 22 mm; p = 0.026). EQ-5D-3L showed an overall mean score of 73.2 ± 15.7, ESS was 6.3 ± 5.4, and FOSQ was 16.0 ± 3.3. Conclusion: No significant alteration of facial esthetics were reported after MMA; however, lower QoL was associated with surgical-failure; whereas, in surgical-success, QoL were higher.

After 20 years of testing a framework for affective user responses to artificial agents and robots, we compiled a full formalization of our findings so to make the agent respond affectively to its user. Silicon Coppelia as we dubbed our system works from the features of the observed other, appraises these in various domains (e.g., ethics and affordances), then compares them to goals and concerns of the agent, to finally reach a response that includes intentions to work with the user as well as a level of being engaged with the user. This ultimately results into an action that adds to or changes the situation both agencies are in. Unlike many other systems, Silicon Coppelia can deal with ambiguous emotions of its user and has ambiguous ‘feelings’ of itself, which makes its decisions quite human-like. In the current paper, we advance a fuzzy-sets approach and show the inner workings of our system through an elaborate example. We also present a number of simulation experiments, one of which showed decision behaviors based on biases when agent goals had low priorities. Silicon Coppelia is open to scrutiny and experimentation by way of an open-source implementation in Ptolemy.

In The Netherlands, post-war urban renewal policies have emerged under the influence of various welfare regimes. Corporatist and social democratic regimes promoted social justice, social cohesion, inclusion and redistribution of income; urban renewal policies stimulated social mix and area-based interventions. Both public and market partners and residents were involved. Liberal ideas became increasingly explicit from the 1990s, and became dominant after 2010. Individuality, ‘citizens own responsibility’, and cuts in public services were leading objectives. Private investors and entrepreneurs were leading the renewal, facilitated by the state. In this paper we focus on the most recent policies and their effects.

SamenvattingDoel van deze studie was de klinische toepasbaarheid van 3D-modellen onderzoeken in de preoperatieve planning van robotgeassisteerde radicale laparoscopische prostatectomie (RALP). Er werden 20 virtuele 3D-modellen en 3D-prints gemaakt, waarna 7 urologen op basis hiervan de mate van zijdespecifieke zenuwsparing bepaalden. Vervolgens werden de mate van zenuwsparing per zijde per modaliteit en de absolute overeenkomst in de geplande zenuwsparing tussen urologen geanalyseerd, waaruit bleek dat er tussen de urologen een klinisch-relevant verschil was in de mate van preoperatieve zijdespecifieke zenuwsparing tussen MRI en de virtuele modellen en MRI en de 3D-prints in 25 en 26% van de gevallen met een intraclasscorrelatiecoëfficient van 0,40 (95%-BI 0,28–0,55) voor MRI, van 0,52 (0,39–0,66) voor virtuele 3D-modellen en van 0,58 (0,45–0,71) voor 3D-prints. De conclusie is dat de 3D-modellen een klinisch-relevante impact hebben op de preoperatieve planning van zenuwsparing bij RALP.

BACKGROUND: Although curative treatment options are identical for male and female gastroesophageal cancer patients, access to care and survival may vary. This study aimed to compare treatment allocation and survival between male and female patients with potentially curable gastroesophageal cancer.; METHODS: Nationwide cohort study including all patients with potentially curable gastroesophageal squamous cell or adenocarcinoma diagnosed between 2006 and 2018 registered in the Netherlands Cancer Registry. The main outcome, treatment allocation, was compared between male and female patients with oesophageal adenocarcinoma (EAC), oesophageal squamous cell carcinoma (ESCC), and gastric adenocarcinoma (GAC). Additionally, 5-year relative survival with relative excess risk (RER), that is, adjusted for the normal life expectancy, was compared.; RESULTS: Among 27,496 patients (68.8% men), most were allocated to curative treatment (62.8%), although rates dropped to 45.6%>70 years. Curative treatment rates were comparable among younger male and female patients (≤70 years) with gastroesophageal adenocarcinoma, while older females with EAC were less frequently allocated to curative treatment than males (OR=0.85, 95%confidence interval [CI] 0.73-0.99). For those allocated to curative treatment, relative survival was superior for female patients with EAC (RER=0.88, 95%CI 0.80-0.96) and ESCC (RER=0.82, 95%CI 0.75-0.91), and comparable for males and females with GAC (RER=1.02, 95%CI 0.94-1.11).; CONCLUSIONS: While curative treatment rates were comparable between younger male and female patients with gastroesophageal adenocarcinoma, treatment disparities were present between older patients. When treated, the survival of females with EAC and ESCC was superior to males. The treatment and survival gaps between male and female patients with gastroesophageal cancer warrant further exploration and could potentially improve treatment strategies and survival. Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Objective: This study aimed to acquire insight into the perceived user friendliness, accessibility and inclusiveness of a personalized digital care pathway. Materials & methods: Usability of the tool was tested in an experimental setting. Mixed methods data collection consisted of scenario-based eye tracking tests in a web- or mobile-based prototype of the tool, followed by a questionnaire assessing user friendliness (System Usability Scale; SUS) and a structured interview. Inclusiveness was assessed by subgroup comparisons based on language proficiency, age and education level. Via purposive sampling a heterogeneous population of users (N = 24) was recruited. Eye tracking was used to measure gaze behavior. Results: Overall, participants were satisfied with the tool (scale 0–10, 7.5; SD = 1.29). User friendliness of the mobile version (68.3; SD = 21.6) was higher than the web version (50.9; SD = 17.3) measured by SUS score (0–100). With regard to accessibility, eye tracking scenarios showed that the menu bar was hard to find (17% mobile, 55% web). In all scenario's, information was found faster in the mobile version than the web version. Attention was easily drawn to images. Regarding inclusiveness of the tool, we found significantly longer completing time of the scenario tasks for low language proficiency (p-value = 0.029) and higher age subgroups (p-value = 0.049). Lower language proficiency scored a significant lower SUS score (p-value = 0.012). Conclusions: Overall, user friendliness and accessibility were positively evaluated. Assessment of inclusiveness emphasized the need for tailoring digital tools to those with low language proficiency and/or an older age. Co-creation of digital care tools with users is therefore important to match users’ needs, make tools easily understandable and accessible to all users, and ultimately result in better uptake and impact.

The need for a comparison between two proportions (sometimes called an A/B test) often arises in business, psychology, and the analysis of clinical trial data. Here we discuss two Bayesian A/B tests that allow users to monitor the uncertainty about a difference in two proportions as data accumulate over time. We emphasize the advantage of assigning a dependent prior distribution to the proportions (i.e., assigning a prior to the log odds ratio). This dependent-prior approach has been implemented in the open-source statistical software programs R and JASP. Several examples demonstrate how JASP can be used to apply this Bayesian test and interpret the results.

This study is to determine whether the volume and contact surface area (CSA) of a tumour with an adjacent prostate capsule on MRI in a three-dimensional (3D) model that can predict side-specific extraprostatic extension (EPE) at radical prostatectomy (RP). Patients with localised prostate cancer (PCa) who underwent robot-assisted RP between July 2015 and March 2021 were included in this retrospective study. MRI-based 3D prostate models incorporating the PCa volume and location were reconstructed. The tumour volume and surface variables were extracted. For the prostate-to-tumour and tumour-to-prostate CSAs, the areas in which the distances were ≤ 1, ≤ 2, ≤ 3, ≤ 4, and ≤ 5 mm were defined, and their surface (cm2) were determined. Differences in prostate sides with and without pathological EPE were analysed. Multivariable logistic regression analysis to find independent predictors of EPE. Overall, 75/302 (25%) prostate sides showed pathological EPE. Prostate sides with EPE had higher cT-stage, higher PSA density, higher percentage of positive biopsy cores, higher biopsy Gleason scores, higher radiological tumour stage, larger tumour volumes, larger prostate CSA, and larger tumour CSA (all p

Pitt-Hopkins syndrome (PTHS) is a rare neurodevelopmental disorder caused by mutations of the transcription factor 4 (Tcf4) gene. Individuals with PTHS often suffer from severe abdominal bloating and constipation. In this short communication, we discuss two individuals with PTHS who died unexpectedly due to gastrointestinal complications. We aim to increase awareness among healthcare professionals who care for individuals with PTHS, to ensure adequate screening and management of gastrointestinal symptoms in this population. Moreover, we discuss how fatal gastrointestinal complications may be related to PTHS and provide an overview of the literature.

Objective: : To develop an international Core Outcome Set (COS), a minimal collection of outcomes that should be measured and reported in all future clinical trials evaluating treatments of acute simple appendicitis in children.Summary Background Data: A previous systematic review identified 115 outcomes in 60 trials and systematic reviews evaluating treatments for children with appendicitis, suggesting the need for a COS.Methods: The development process consisted of four phases: (1) an updated systematic review identifying all previously reported outcomes, (2) a two-stage international Delphi study in which parents with their children and surgeons rated these outcomes for inclusion in the COS, (3) focus groups with young people to identify missing outcomes, and (4) international expert meetings to ratify the final COS.Results: The systematic review identified 129 outcomes which were mapped to 43 unique outcome terms for the Delphi survey. The first-round included 137 parents (eight countries) and 245 surgeons (10 countries), the second-round response rates were 61% and 85% respectively, with ten outcomes emerging with consensus. After two young peoples’ focus groups, two additional outcomes were added to the final COS (12): mortality, bowel obstruction, intra-abdominal abscess, recurrent appendicitis, complicated appendicitis, return to baseline health, readmission, reoperation, unplanned appendectomy, adverse events related to treatment, major and minor complications.Conclusion: An evidence-informed COS based on international consensus, including patients and parents has been developed. This COS is recommended for all future studies evaluating treatment of simple appendicitis in children, to reduce heterogeneity between studies and facilitate data synthesis and evidence-based decision-making.

Research has showed that aligning brand messages with topical events is a success formula for evoking positive consumer responses, in which ad creativity (i.e., originality, meaningfulness, and craftsmanship) and timing (i.e., the time between the start of an event and the appearance of a Topical Advertising message) play a pivotal role. This was demonstrated in the context of short, ending topical events. Less is known about the effects of aligning brand messages with enduring events that have no anticipated end date. Relying on news value theory and creativity literature, this paper explores the effects of Topical Advertising on engagement and the role of creativity and timing in the context of an enduring event: COVID-19. Based on a content analysis of 1,454 Twitter brand messages, the results showed positive effects of Topical Advertising for enduring events too. However, brands only benefited from chiming in at the start of an enduring event, considering that the positive effects on engagement declined as time progressed. Implications are discussed.

The greater wax moth, Galleria mellonella (L.) (Lepidoptera: Pyralidae), has gathered widespread interest in the biomedical research community as an alternative non-mammalian model to study bacterial and fungal infections in humans. Nevertheless, most laboratories rely on commercial breeding companies that grow these larvae in bulk. Variation in rearing conditions between these companies and shipping of the larvae affects the response of G. mellonella to infection, both decreasing the reproducibility and comparability of infection experiments across laboratories. To unlock the full potential of G. mellonella as an infection model, standardized rearing is essential to produce healthy larvae of uniform quality. To this end, we developed an optimized protocol using a high-nutritional artificial diet and cost-effective housing solutions to ensure optimal conditions during each stage of the G. mellonella life cycle. This resulted in the rapid generation of larvae with a short larval phase, large size, and increased weight compared to other protocols and commercial larvae. A survival analysis comparing the standardized larvae with commercially obtained larvae showed significantly higher survival of standardized reared larvae after infection with Candida albicans (CP Robin) Berkhout (Saccharomycetales), proving the higher quality of standardized reared larvae.

Although many studies have concluded that men and women engage in domestic violence at equal levels, existing studies have hardly focused on gender specific risk factors for domestic violence perpetration. Therefore, this study aimed to examine gender differences in criminogenic risk factors between Dutch male and female forensic outpatients who were referred to forensic treatment for domestic violence. Clinical structured assessments of criminogenic risk factors were retrieved for 366 male and 87 female outpatients. Gender differences were not only found in the prevalence and interrelatedness of criminogenic risk factors, but also in associations between criminogenic risk factors and treatment dropout. In men, risk factors related to the criminal history, substance abuse, and criminal attitudes were more prevalent than in women, whereas risk factors related to education/work, finances, and the living environment were more prevalent in women. Further, having criminal friends, having a criminal history, and drug abuse were associated with treatment dropout in men, whereas a problematic relationship with family members, housing instability, a lack of personal support, and unemployment were associated with treatment dropout in women. Finally, network analyses revealed gender differences in risk factor interrelatedness. The results provide important insights into gender specific differences in criminogenic risk factors for domestic violence, which support clinical professionals in tailoring treatment to the specific needs of male and female perpetrators of domestic violence.

Purpose: Brain metastases (BM) themselves and treatment with stereotactic radiosurgery (SRS) can influence neurocognitive functioning. This prospective study aimed to assess neurocognitive decline in patients with BM after SRS. Methods: A neuropsychological test battery was assessed yielding ten test outcomes. Neurocognitive decline at 3 and 6 months post SRS was compared to measurement prior to Gamma Knife (GK) or linear accelerator (LINAC) SRS. Reliable change indices with correction for practice effects were calculated to determine the percentage of neurocognitive decline (defined as decline on ≥ 2 test outcomes). Risk factors of neurocognitive decline were analyzed with binary logistic regression. Results: Of 194 patients pre-SRS, 40 GK and 29 LINAC patients had data accessible at 6 months. Compared to baseline, 38% of GK patients declined at 3 months, and 23% declined at 6 months. GK patients declined on attention, executive functioning, verbal memory, and fine motor skill. Of LINAC patients, 10% declined at 3 months, and 24% at 6 months. LINAC patients declined on executive functioning, verbal memory, and fine motor skills. Risk factors of neurocognitive decline at 3 months were high age, low education level and type of SRS (GK or LINAC). At 6 months, high age was a risk factor. Karnofsky Performance Scale, BM volume, number of BM, tumor progression and neurocognitive impairment pre-SRS were no risk factors. Conclusion: Neurocognitive decline occurs in a considerable proportion of patients with BM treated with GK or LINAC SRS. Overall, high age appears to be a risk factor for neurocognitive decline after SRS.

Sources of geophysical noise (such as wind, sea waves and earthquakes) or of anthropogenic noise impact ground-based gravitational-wave interferometric detectors, causing transient sensitivity worsening and gaps in data taking. During the one year-long third Observing Run (O3: from April 01, 2019 to March 27, 2020), the Virgo Collaboration collected a statistically significant dataset, used in this article to study the response of the detector to a variety of environmental conditions. We correlated environmental parameters to global detector performance, such as observation range, duty cycle and control losses. Where possible, we identified weaknesses in the detector that will be used to elaborate strategies in order to improve Virgo robustness against external disturbances for the next data taking period, O4, currently planned to start at the end of 2022. The lessons learned could also provide useful insights for the design of the next generation of ground-based interferometers., Comment: 49 pages, 27 figures. Published in Classical and Quantum Grav