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Abstract Bacterial extracellular vesicles (BEVs) enable communication between bacteria and their natural habitats, including multicellular organisms such as humans. Consequently, the study of BEVs has rapidly gained attention with recent research raising the prospect of developing BEVs as biomarkers and treatments to manage (mal)functioning of natural habitats. Although diverse technologies are available, the composition of their source, their heterogeneity in biophysical and biochemical features, and their multifaceted cargo composition challenges the analysis of BEVs. To map current practices in BEV research, we analyzed 845 publications released in 2015–2021, reporting 3338 BEV-related experiments. The extracted data are accessible via the publicly available EV-TRACK knowledgebase ( https://evtrack.org/ ). We identify the need for transparent reporting, delineate knowledge gaps, outline available best practices and define areas in need of guidance to ensure advances in BEV research and accelerate BEV applications.

Abstract Background Stakeholder engagement in evaluation of medical devices is crucial for aligning devices with stakeholders’ views, needs, and values. Methods for these engagements have however not been compared to analyse their relative merits for medical device evaluation. Therefore, we systematically compared these three methods in terms of themes, interaction, and time-investment. Methods We compared focus groups, interviews, and an online survey in a case-study on minimally invasive endoscopy-guided surgery for patients with intracerebral haemorrhage. The focus groups and interviews featured two rounds, one explorative focussing on individual perspectives, and one interactive focussing on the exchange of perspectives between participants. The comparison between methods was made in terms of number and content of themes, how participants interact, and hours invested by all researchers. Results The focus groups generated 34 themes, the interviews 58, and the survey 42. Various improvements for the assessment of the surgical procedure were only discussed in the interviews. In focus groups, participants were inclined to emphasise agreement and support, whereas the interviews consisted of questions and answers. The total time investment for researchers of focus groups was 95 h, of interviews 315 h, and survey 81 h. Conclusions Within the context of medical device evaluation, interviews appeared to be the most appropriate method for understanding stakeholder views since they provide a scope and depth of information that is not generated by other methods. Focus groups were useful to rapidly bring views together. Surveys enabled a quick exploration. Researchers should account for these methodological differences and select the method that is suitable for their research aim.

Abstract Ovarian cancer is the most lethal gynecologic malignancy, mainly due to late-stage diagnosis, frequent recurrences, and eventually therapy resistance. To identify potentially actionable genetic variants, sequencing data of 351 Belgian ovarian cancer patients were retrospectively captured from electronic health records. The cohort included 286 (81%) patients with high-grade serous ovarian cancer, 17 (5%) with low-grade serous ovarian cancer, and 48 (14%) with other histotypes. Firstly, an overview of the prevalence and spectrum of the BRCA1/2 variants highlighted germline variants in 4% (11/250) and somatic variants in 11% (37/348) of patients. Secondly, application of a multi-gene panel in 168 tumors revealed a total of 214 variants in 28 genes beyond BRCA1/2 with a median of 1 (IQR, 1–2) genetic variant per patient. The ten most often altered genes were (in descending order): TP53, BRCA1, PIK3CA, BRCA2, KRAS, ERBB2 (HER2), TERT promotor, RB1, PIK3R1 and PTEN. Of note, the genetic landscape vastly differed between the studied histotypes. Finally, using ESCAT the clinical evidence of utility for every genetic variant was scored. Only BRCA1/2 pathogenic variants were classified as tier-I. Nearly all patients (151/168; 90%) had an ESCAT tier-II variant, most frequently in TP53 (74%), PIK3CA (9%) and KRAS (7%). In conclusion, our findings imply that although only a small proportion of genetic variants currently have direct impact on ovarian cancer treatment decisions, other variants could help to identify novel (personalized) treatment options to address the poor prognosis of ovarian cancer, particularly in rare histotypes.

The significance of adaptive performance in today's rapidly evolving work environment cannot be overlooked. Despite its crucial nature, no validated scale exists for assessing adaptive performance in either English or Dutch. This project aims to rectify this deficiency by providing researchers with a reliable and validated instrument to measure adaptive performance. The French scale was translated into English and Dutch using forward and backward translation techniques and was pretested by healthcare professionals. A uniform interpretation of the translations was achieved, and the final questionnaires were distributed to healthcare professionals. We explored the dimensionality of the scales using factor analysis and tested for reliability and validity. Questionnaires were completed by 283 English-speaking and 306 Dutch-speaking respondents. Both questionnaires demonstrated good internal consistency (Cronbach's alpha 0.87) and convergent and discriminant validity. Minor issues were addressed. This analysis presents a dependable and legitimate tool for the further exploration of adaptive performance. The primary focus of this project was on healthcare professionals. Given that the original scale was evaluated across various occupations and the items were worded in general terms, the scale could be applied generally. This project successfully addressed the need for a scale on adaptive performance for researchers conducting studies with English or Dutch respondents.

BackgroundCervical cancer is the leading cause of cancer deaths among women in Kenya. In the context of the Global strategy to accelerate the elimination of cervical cancer as a public health problem, Kenya is currently implementing screening and treatment scale-up. For effectively tracking the scale-up, a baseline assessment of cervical cancer screening and treatment service availability and readiness was conducted in 25 priority counties. We describe the findings of this assessment in the context of elimination efforts in Kenya.MethodsThe survey was conducted from February 2021 to January 2022. All public hospitals in the target counties were included. We utilized healthcare workers trained in preparation for the scale-up as data collectors in each sub-county. Two electronic survey questionnaires (screening and treatment; and laboratory components) were used for data collection. All the health system building blocks were assessed. We used descriptive statistics to summarize the main service readiness indicators.ResultsOf 3,150 hospitals surveyed, 47.6% (1,499) offered cervical cancer screening only, while 5.3% (166) offered both screening and treatment for precancer lesions. Visual inspection with acetic acid (VIA) was used in 96.0% (1,599/1,665) of the hospitals as primary screening modality and HPV testing was available in 31 (1.0%) hospitals. Among the 166 hospitals offering treatment for precancerous lesions, 79.5% (132/166) used cryotherapy, 18.7% (31/166) performed thermal ablation and 25.3% (42/166) performed large loop excision of the transformation zone (LLETZ). Pathology services were offered in only 7.1% (17/238) of the hospitals expected to have the service (level 4 and above). Only 10.8% (2,955/27,363) of healthcare workers were trained in cervical cancer screening and treatment; of these, 71.0% (2,097/2,955) were offering the services. Less than half of the hospitals had cervical cancer screening and treatment commodities at time of survey. The main health system strength was presence of multiple screening points at hospitals, but frequent commodity stock-outs was a key weakness.ConclusionTraining, commodities, and diagnostic services are major gaps in the cervical cancer program in Kenya. To meet the 2030 elimination targets, the national and county governments should ensure adequate financing, training, and service integration, especially at primary care level.

Background and purpose: Chemoradiotherapy followed by brachytherapy is the standard of care for locally advanced cervical cancer (LACC). In this study, we postulate that omitting an iconographical unaffected uterus (+12 mm distance from the tumour) from the treatment volume is safe and that no tumour will be found in the non-targeted uterus (NTU) leading to reduction of high-dose volumes of surrounding organs at risk (OARs) Material and Methods: In this single-arm phase 2 study, two sets of target volumes were delineated: one standard-volume (whole uterus) and an EXIT-volume (exclusion of non-tumour-bearing parts of the uterus with a minimum 12 mm margin from the tumour). All patients underwent chemoradiotherapy targeting the EXIT-volume, followed by completion hysterectomy. In 15 patients, a plan comparison between two treatment plans (PTV vs PTV_EXIT) was performed. The primary endpoint was the pathological absence of tumour involvement in the non-targeted uterus (NTU). Secondary endpoints included dosimetric impact of target volume reduction on OARs, acute and chronic toxicity, overall survival (OS), locoregional recurrence-free survival (LRFS), and progression-free survival (PFS). Results: In all 21 (FIGO stage I: 2; II: 14;III: 3; IV: 2) patients the NTU was pathologically negative. Ssignificant reductions in Dmean in bladder, sigmoid and rectum; V15Gy in sigmoid and rectum, V30Gy in bladder, sigmoid and rectum; V40Gy and V45Gy in bladder, bowel bag, sigmoid and rectum; V50Gy in rectum were achieved. Median follow-up was 54 months (range 7–79 months). Acute toxicity was mainly grade 2 and 5 % grade 3 urinary. The 3y- OS, PFS and LRFS were respectively 76,2%, 64,9% and 81 %. Conclusion: MRI-based exclusion of the non-tumour-bearing parts of the uterus at a minimum distance of 12 mm from the tumour out of the target volume in LACC can be done without risk of residual disease in the NTU, leading to a significant reduction of the volume of surrounding OARS treated to high doses.

Summary: Perturbation of the apoptosis and necroptosis pathways critically influences embryogenesis. Receptor-associated protein kinase-1 (RIPK1) interacts with Fas-associated via death domain (FADD)-caspase-8-cellular Flice-like inhibitory protein long (cFLIPL) to regulate both extrinsic apoptosis and necroptosis. Here, we describe Ripk1-mutant animals (Ripk1R588E [RE]) in which the interaction between FADD and RIPK1 is disrupted, leading to embryonic lethality. This lethality is not prevented by further removal of the kinase activity of Ripk1 (Ripk1R588E K45A [REKA]). Both Ripk1RE and Ripk1REKA animals survive to adulthood upon ablation of Ripk3. While embryonic lethality of Ripk1RE mice is prevented by ablation of the necroptosis effector mixed lineage kinase-like (MLKL), animals succumb to inflammation after birth. In contrast, Mlkl ablation does not prevent the death of Ripk1REKA embryos, but animals reach adulthood when both MLKL and caspase-8 are removed. Ablation of the nucleic acid sensor Zbp1 largely prevents lethality in both Ripk1RE and Ripk1REKA embryos. Thus, the RIPK1-FADD interaction prevents Z-DNA binding protein-1 (ZBP1)-induced, RIPK3-caspase-8-mediated embryonic lethality, affected by the kinase activity of RIPK1.

Care providers in intellectual disability care use various health information systems (HIS) to document the care they provide. This generates a substantial amount of structured and unstructured data with significant potential for reuse, which is currently underexploited. To enhance data reuse, it is important to understand the architecture of health information systems in intellectual disability care, including their commonalities and variabilities (differences), as well as to identify related privacy and security issues. Our study adopts a multiple-case study approach, examining the architectures of four health information systems in the Netherlands. We conducted interviews with seven stakeholders from four HISs and reviewed multiple documents concerning system infrastructure. We identified commonalities and differences between these systems and outlined the primary challenges regarding privacy and security for data reuse. For each HIS, four architectural views were developed: a context diagram, decomposition view, layered view, and deployment view. The study discusses crucial security and privacy aspects for data reuse in intellectual disability care and highlights several challenges that must be addressed to unlock the full potential of this data. This research provides initial guidelines for overcoming these challenges.

Background There is a wide variety of participatory approaches to involve stakeholders in the development of medical devices, but there is no comprehensive overview of these approaches. We therefore studied what participatory approaches are used in the development of medical devices as well as the most important characteristics and challenges of these approaches.Methods We conducted a scoping review and searched PubMed, Embase and Web of Science for articles published between July 2014 and July 2019. Papers were included if they presented original research featuring any form of stakeholder participation in the development of medical devices. We used The Spectrum of Public Participation to categorise the approach of each paper. Subsequently, we described the characteristics of each approach: the stakeholders involved, data collection methods, and topics addressed. We also identified challenges of the approaches as reported by researchers.Results 277 papers were included, which could be categorised into three levels of participation: collaboration, involvement, and consultation. Patients and healthcare professionals are frequently engaged in all approaches. The most often used methods are workshops in the collaboration approach papers, and interviews in the involvement and consultation approach papers. Topics addressed in all approaches are: the problem, device requirements, design choices, testing, and procedural aspects of involvement. Reported challenges entail issues related to sampling, analysis, social dynamics, feasibility, and the limited number of topics that can be addressed.Conclusion Participatory approaches reported in literature can be categorised in three overarching approaches that have comparable methodological characteristics. This suggests that if researchers want to apply a participatory approach it is not necessary to adopt a pre-determined approach, such as ‘participatory action research’ (PAR). Instead, they can independently determine the degree of participation, stakeholders, methods, topics, and strategies to account for challenges, making sure the participatory approach fits their research question and context.

Abstract European rivers are disconnected by more than one million man-made barriers that physically limit aquatic species migration and contribute to modification of freshwater habitats. Here, a Conceptual Habitat Alteration Model for Ponding is developed to aid in evaluating the effects of impoundments on fish habitats. Fish communities present in rivers with low human impact and their broad environmental settings enable classification of European rivers into 15 macrohabitat types. These classifications, together with the estimated fish sensitivity to alteration of their habitat are used for assessing the impacts of six main barrier types (dams, weirs, sluices, culverts, fords, and ramps). Our results indicate that over 200,000 km or 10% of previously free-flowing river habitat has been altered due to impoundments. Although they appear less frequently, dams, weirs and sluices cause much more habitat alteration than the other types. Their impact is regionally diverse, which is a function of barrier height, type and density, as well as biogeographical location. This work allows us to foresee what potential environmental gain or loss can be expected with planned barrier management actions in rivers, and to prioritize management actions.

Dementia can be associated with social withdrawal, mood changes, and decreased interaction. Animal-assisted therapies and robotic companions have shown potential in enhancing well-being but come with limitations like high maintenance costs and complexity. This research presents an interactive digital aquarium called Mindful Waters, which was developed to promote social interaction and engagement among People with Dementia. The pilot study involved interactive sessions at a community center and a care facility, with situated observations, video and audio recordings, and interviews to assess user engagement motivation, behavior, and user experience with Mindful Waters. The study revealed that Mindful Waters functioned well with People with Dementia and stimulated conversational topics about aquariums through engagement. User feedback was generally positive, with participants appreciating the visual appeal and simplicity. However, some participants with advanced dementia found it challenging to interact due to their mobility limitations, cognitive impairments, and the limited duration of interaction sessions. The overall results suggest that Mindful Waters can benefit dementia care; further research is needed to optimize its design and functionality for long-term placement in care facilities.

Abstract Background While night shifts are crucial for patient care, they threaten doctors’ well-being and performance. Knowledge of how the impact of night shifts differs for doctors is needed to attenuate the adverse effects of night shifts. This study aimed to obtain more precise insight into doctors’ feelings surrounding night shift by: identifying profiles based on doctors’ alertness, contentedness and calmness scores before and after night shifts (research question (RQ) 1); assessing how doctors’ pre- and post-shift profiles change (RQ2); and determining associations of doctors’ demographics and shift circumstances with alertness, contentedness and calmness change (RQ3). Methods Latent Profile Analysis using doctors’ pre- and post-shift self-rated alertness, contentedness and calmness scores was employed to identify pre- and post-shift profiles (RQ1). A cross-tabulation revealed pre- and post-shift profile changes (RQ2). Multiple regressions determined associations of demographics (i.e. age, sex, specialty) and night shift circumstances (i.e. hours worked pre-call, hours awake pre-call, shift duration, number of consecutive shifts, total hours of sleep) with alertness, contentedness and calmness change (RQ3). Results In total, 211 doctors participated with a mean age of 39.8 ± 10 years; 47.4% was male. The participants included consultants (46.4%) and trainees (53.6%) of the specialties surgery (64.5%) and obstetrics/gynaecology (35.5%). Three pre-shift (Indifferent, Ready, Engaged) and four post-shift profiles (Lethargic, Tired but satisfied, Excited, Mindful) were found. Most doctors changed from Ready to Tired but satisfied, with alertness reducing most. Age, specialty, sleep, shift duration and the number of consecutive shifts associated with alertness, contentedness and calmness changes. Conclusions The results provided nuanced insight into doctors’ feelings before and after night shifts. Future research may assess whether specific subgroups benefit from tailored interventions.

Abstract Background Conducting a systematic review demands a significant amount of effort in screening titles and abstracts. To accelerate this process, various tools that utilize active learning have been proposed. These tools allow the reviewer to interact with machine learning software to identify relevant publications as early as possible. The goal of this study is to gain a comprehensive understanding of active learning models for reducing the workload in systematic reviews through a simulation study. Methods The simulation study mimics the process of a human reviewer screening records while interacting with an active learning model. Different active learning models were compared based on four classification techniques (naive Bayes, logistic regression, support vector machines, and random forest) and two feature extraction strategies (TF-IDF and doc2vec). The performance of the models was compared for six systematic review datasets from different research areas. The evaluation of the models was based on the Work Saved over Sampling (WSS) and recall. Additionally, this study introduces two new statistics, Time to Discovery (TD) and Average Time to Discovery (ATD). Results The models reduce the number of publications needed to screen by 91.7 to 63.9% while still finding 95% of all relevant records (WSS@95). Recall of the models was defined as the proportion of relevant records found after screening 10% of of all records and ranges from 53.6 to 99.8%. The ATD values range from 1.4% till 11.7%, which indicate the average proportion of labeling decisions the researcher needs to make to detect a relevant record. The ATD values display a similar ranking across the simulations as the recall and WSS values. Conclusions Active learning models for screening prioritization demonstrate significant potential for reducing the workload in systematic reviews. The Naive Bayes + TF-IDF model yielded the best results overall. The Average Time to Discovery (ATD) measures performance of active learning models throughout the entire screening process without the need for an arbitrary cut-off point. This makes the ATD a promising metric for comparing the performance of different models across different datasets.

Currently there is a global lack of consensus about the best treatment for asymptomatic congenital pulmonary airway malformation (CPAM) patients. The somatic KRAS mutations commonly found in adult lung cancer combined with mucinous proliferations are sometimes found in CPAM. For this risk of developing malignancy, 70% of paediatric surgeons perform a resection for asymptomatic CPAM. In order to stratify these patients into high- and low-risk groups for developing malignancy, a minimally invasive diagnostic method is needed, for example targeted molecular imaging. A prerequisite for this technique is a cell membrane bound target. The aim of this study was to review the literature to identify potential targets for molecular imaging in CPAM patients and perform a first step to validate these findings. A systematic search was conducted to identify possible targets in CPAM and adenocarcinoma in situ (AIS) patients. The most interesting targets were evaluated with immunofluorescent staining in adjacent lung tissue, KRAS+ CPAM tissue and KRAS– CPAM tissue. In 185 included studies, 143 possible targets were described, of which 20 targets were upregulated and membrane-bound. Six of them were also upregulated in lung AIS tissue (CEACAM5, E-cadherin, EGFR, ERBB2, ITGA2 and MUC1) and as such of possible interest. Validating studies showed that MUC1 is a potential interesting target. This study provides an extensive overview of all known potential targets in CPAM that might identify those patients at risk for malignancy and conducted the first step towards validation, identifying MUC1 as the most promising target.

Abstract Background Extracellular vesicles (EV) are extensively studied in human body fluids as potential biomarkers for numerous diseases. Major impediments of EV-based biomarker discovery include the specificity and reproducibility of EV sample preparation as well as intensive manual labor. We present an automated liquid handling workstation for the density-based separation of EV from human body fluids and compare its performance to manual handling by (in)experienced researchers. Results Automated versus manual density-based separation of trackable recombinant extracellular vesicles (rEV) spiked in PBS significantly reduces variability in rEV recovery as quantified by fluorescent nanoparticle tracking analysis and ELISA. To validate automated density-based EV separation from complex body fluids, including blood plasma and urine, we assess reproducibility, recovery, and specificity by mass spectrometry-based proteomics and transmission electron microscopy. Method reproducibility is the highest in the automated procedure independent of the matrix used. While retaining (in urine) or enhancing (in plasma) EV recovery compared to manual liquid handling, automation significantly reduces the presence of body fluid specific abundant proteins in EV preparations, including apolipoproteins in plasma and Tamm-Horsfall protein in urine. Conclusions In conclusion, automated liquid handling ensures cost-effective EV separation from human body fluids with high reproducibility, specificity, and reduced hands-on time with the potential to enable larger-scale biomarker studies. Graphical Abstract

Abstract Background Chemoradiotherapy (CRT) followed by brachytherapy (BT) is the standard treatment for locally advanced cervical cancer (LACC), but replacement of BT by surgery (CRT-S) could be an acceptable alternative. The main concern is the risk of operative morbidity. The aim is to report on therapeutic morbidity, OS, PC, and LC of CRT-S. Methods This was a single tertiary center retrospective cohort study in patients treated with CRT-S. A type II Wertheim hysterectomy was performed 6–8 weeks after CRT. Acute and chronic radiotherapy-related and surgical morbidity was classified according to the CTCAE v4.0. OS, and DFS, PC, and LC were calculated using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazard models were performed to determine variables with a prognostic role. Results A total of 130 consecutive LACC patients were treated with CRT, and 119 underwent completion surgery. The median follow-up was 53 months. Five-year OS rate, local control, pelvic control, and 5-year DFS rate were 73%, 93%, 90%, and 74%, respectively. The 5-year OS rate was 92%/72%/67%/56% for FIGO (2009) stage I/II/III/IV, respectively. The five-year OS rate was 79% and 71% for adenocarcinoma and squamous cell carcinoma (p > 0.05), respectively. There was no intra- and perioperative mortality. Intraoperative and early postoperative complication rates were 7% and 20% (3% ≥ G3), respectively; they resolved within 3 months. The late postoperative complication rate was 9% (7% ≥ G3). Acute/late radiotherapy-related G3 side effects were 5%/3% for gastrointestinal and 3%/7% for genitourinary side effects. Conclusions CRT-S is safe with an acceptable rate of complications for both the CRT and completion surgery and shows encouraging outcome data for stage III/IV and adenocarcinoma patients.

Abstract Background Physical activity (PA) is known to be beneficial for health, but adherence to international PA guidelines is low across different subpopulations. Interventions have been designed to stimulate PA of different target groups by influencing relevant psycho-social determinants, essentially based on a combination of the Integrated Model for Change, the Theory of Planned Behaviour, its successor the Reasoned Action Approach and the self-determination theory. The current study investigates the pathways through which interventions influence PA. Further, gender differences in pathways of change are studied. Methods An integrated dataset of five different randomised controlled trial intervention studies is analysed by estimating a Bayesian network. The data include measurements, at baseline and at 3, 6 (short-term), and 12 (long-term) months after the baseline, of important socio-cognitive determinants of PA, demographic factors, and PA outcomes. A fragment is extracted from the Bayesian network consisting of paths between the intervention variable, determinants, and short- and long-term PA outcomes. For each relationship between variables, a stability indicator and its mutual information are computed. Such a model is estimated for the full dataset, and in addition such a model is estimated based only on male and female participants’ data to investigate gender differences. Results The general model (for the full dataset) shows complex paths, indicating that the intervention affects short-term PA via the direct determinants of intention and habit and that self-efficacy, attitude, intrinsic motivation, social influence concepts, planning and commitment have an indirect influence. The model also shows how effects are maintained in the long-term and that previous PA behaviour, intention and attitude pros are direct determinants of long-term PA. The gender-specific models show similarities as well as important differences between the structures of paths for the male- and female subpopulations. For both subpopulations, intention and habit play an important role for short-term effects and maintenance of effects in the long-term. Differences are found in the role of self-efficacy in paths of behaviour change and in the fact that attitude is relevant for males, whereas planning plays a crucial role for females. The average of these differences in subpopulation mechanisms appears to be presented in the general model. Conclusions While previous research provided limited insight into how interventions influence PA through relevant determinants, the Bayesian network analyses show the relevance of determinants mentioned by the theoretical framework. The model clarifies the role that different determinants play, especially in interaction with each other. The Bayesian network provides new knowledge about the complex working mechanism of interventions to change PA by giving an insightful overview of influencing paths. Furthermore, by presenting subpopulation-specific networks, the difference between the influence structure of males and females is illustrated. These new insights can be used to improve interventions in order to enhance their effects. To accomplish this, we have developed a new methodology based on a Bayesian network analysis which may be applicable in various other studies.

In deze literatuurstudie is onderzocht hoe veranderlijk persoonlijkheidskenmerken en persoonlijkheidsstoornissen gedurende de levensloop zijn alsmede welke gevolgen dit heeft voor persoonlijkheidsonderzoek bij ouderen. Vijf longitudinale studies, gebaseerd op het vijf factorenmodel van Costa & McCrae, ondersteunen de veronderstelling dat persoonlijkheidskenmerken gedurende de gehele levensloop aan verandering onderhevig zijn. Neuroticisme, extraversie en openheid nemen met het stijgen van de leeftijd af. Altruïsme en consciëntieusheid daarentegen nemen met het ouder worden toe. Eén longitudinale en drie cross-sectionele studies naar persoonlijkheidspathologie wijzen op leeftijdspecifieke veranderingen in de uitingswijze van (mal)- adaptieve persoonlijkheidseigenschappen. Bovendien toont een grootschalig cross-sectioneel onderzoek dat ongeveer éénderde van de DSM-As-II criteria voor persoonlijkheidsstoornissen onvoldoende van toepassing zijn op ouderen. Derhalve compliceren de temporele instabiliteit van persoonlijkheidskenmerken en de beperkte validiteit van de As-II criteria persoonlijkheidsonderzoek bij ouderen. Oplossingen zouden gezocht kunnen worden in grootschalige normeringstudies van persoonlijkheidsvragenlijsten bij ouderen in de GGZ en V&V-sector. Ook ingrijpende veranderingen binnen de DSM, zoals een leeftijdsspecifieke, alsmede multidimensionale benadering van persoonlijkheidsstoornissen verdienen aanbeveling.

Advances in precision molecular imaging promise to transform our ability to detect, diagnose and treat disease. Here, we describe the engineering and validation of a new cystine knot peptide (knottin) that selectively recognizes human integrin αvβ6 with single-digit nanomolar affinity. We solve its 3D structure by NMR and x-ray crystallography and validate leads with 3 different radiolabels in pre-clinical models of cancer. We evaluate the lead tracer's safety, biodistribution and pharmacokinetics in healthy human volunteers, and show its ability to detect multiple cancers (pancreatic, cervical and lung) in patients at two study locations. Additionally, we demonstrate that the knottin PET tracers can also detect fibrotic lung disease in idiopathic pulmonary fibrosis patients. Our results indicate that these cystine knot PET tracers may have potential utility in multiple disease states that are associated with upregulation of integrin αvβ6.

Abstract Background Since the outbreak of the COVID-19 pandemic, physical distancing and hand washing have been used as effective means to reduce virus transmission in the Netherlands. However, these measures pose a societal challenge as they require people to change their customary behaviours in various contexts. The science of habit formation is potentially useful for informing policy-making in public health, but the current literature largely overlooked the role of habit in predicting and explaining these preventive behaviours. Our research aimed to describe habit formation processes of physical distancing and hand washing and to estimate the influences of habit strength and intention on behavioural adherence. Methods A longitudinal survey was conducted between July and November 2020 on a representative Dutch sample (n = 800). Respondents reported their intentions, habit strengths, and adherence regarding six context-specific preventive behaviours on a weekly basis. Temporal developments of the measured variables were visualized, quantified, and mapped onto five distinct phases of the pandemic. Regression models were used to test the effects of intention, habit strength, and their interaction on behavioural adherence. Results Dutch respondents generally had strong intentions to adhere to all preventive measures and their adherence rates were between 70% and 90%. They also self-reported to experience their behaviours as more automatic over time, and this increasing trend in habit strength was more evident for physical-distancing than for hand washing behaviours. For all six behaviours, both intention and habit strength predicted subsequent adherence (all ps < 2e-16). In addition, the predictive power of intention decreased over time and was weaker for respondents with strong habits for physical distancing when visiting supermarkets (B = -0.63, p

Primary thyroid lymphoma (PTL) is a rare malignancy of the thyroid gland which should be considered in patients with a rapidly growing cervical mass, especially in those with a history of Hashimoto’s thyroiditis. We present the case of a 53-year-old woman with a rapidly growing goitre with compressive symptoms. Computed tomography (CT) imaging was performed to examine the extent of disease and a biopsy showed B-cell non-Hodgkin lymphoma, stage I according to the Ann Arbor classification. The patient was immediately treated with high-dose prednisone for her compressive symptoms and after the diagnosis she received six cycles of R-CHOP (rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone) chemotherapy. The patient has now been in remission for 12 months. We present this case to demonstrate the importance of awareness of PTL. Up to 10% of cases can be missed with fine needle aspiration cytology (FNAC), making it important to obtain a histological biopsy in rapidly growing goitres. In addition, establishing the correct diagnosis can in most cases prevent unnecessary surgical intervention. The preferred treatment with the best overall survival is chemotherapy with or without radiation therapy.

The principal aim of the work presented here is to investigate and demonstrate that a forward tilted rowing blade would result in a more efficient and effective motion of the blade through the water that would result in a higher boat speed when an equal input power is provided. A 1:5 scaled rowing boat is used to determine the performance of rowing blades with different sizes and blade angles. This is used to validate the results of a previous study where the optimal blade angle of 15∘ with respect to the oar shaft was determined ( 1). The input power and speed of the rowing boat can be compared between original and modified oar blades. Measurements in a towing tank demonstrate that a modified rowing blade result in faster rowing by 0.4% at the same input power. Maintaining the same stroke rate, the improvement of the blade efficiency is compensated by using a 4–6% increased blade area to yield the same input power.

BackgroundA deliberative Citizen Forum ‘Choices in healthcare’ was held in the Netherlands to obtain insight into the criteria informed citizens would propose for the public reimbursement of healthcare. During 3 weekends, 24 citizens participated in evidence-informed deliberation on the basis of 8 case studies. The aim of this study was to assess how the opinions of 8 participants in the deliberative Citizens Forum changed and if so, why participants themselves believe their opinions have changed, whether participation influenced their perceived reasonableness of other participants in the forum and whether it influenced their opinions about involvement of citizens in decision-making.MethodsSemi-structured interviews were held with 8 participants before and after their participation in the Citizen Forum. Using the method of reconstructing interpretive frames opinions about the public reimbursement of healthcare were reconstructed.ResultsParticipants’ opinions changed over time; they became more aware of the complexity of decision-making and came to accept that there are limits to the available resources and accept cost as a criterion for reimbursement decisionmaking. Participants report that exchanging arguments and personal experiences with other participants made them change their initial opinions. Participants ascribed increases in the perceived reasonableness of other participants’ opinions to feelings of group-bonding and becoming more familiar with each other’s personal circumstances. Participants further believe that citizens represent an additional opinion to that of other stakeholders and believe their opinions should be considered in relation to those of other stakeholders, given they are provided with opportunities for critical discussion. ConclusionOrganized deliberation should allow for the exchange of arguments and the sharing of personal experiences which is linked to learning. On the one hand this is reflected in the uptake of new arguments and on the other hand in the revision, specification or expansion of personal argumentation. Providing opportunities for critical deliberation is key to prevent citizens from adhering to initial emotional reactions that remain unchallenged and which may no longer be supported after deliberation.