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Dominique A Cadilhac,1,2 Doreen Busingye,1 Jonathan C Li,3 Nadine E Andrew,1,4 Monique F Kilkenny,1,2 Amanda G Thrift,1 Vincent Thijs,2,5 Maree L Hackett,6,7 Ian Kneebone,8 Natasha A Lannin,9,10 Alana Stewart,11 Ida Dempsey,12 Jan Cameron,1,13 1Stroke and Ageing Research, Department of Medicine, School of Clinical Sciences at Monash Health, Monash University, Melbourne, VIC, Australia; 2Stroke Division, Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, VIC, Australia; 3Department of Electrical and Computer Systems Engineering, Monash University, Melbourne, VIC, Australia; 4Department of Medicine, Central Clinical School, Monash University, Melbourne, VIC, Australia; 5Department of Neurology, Austin Health, Melbourne, VIC, Australia; 6The George Institute for Global Health, University of New South Wales, Sydney, NSW, Australia; 7Faculty of Health and Wellbeing, University of Central Lancashire, Preston, UK; 8Graduate School of Health, University of Technology Sydney, Ultimo, NSW, Australia; 9College of Science, Health and Engineering, School of Allied Health, La Trobe University, Melbourne, VIC, Australia; 10Occupational Therapy Department, Alfred Health, Melbourne, VIC, Australia; 11Stroke Foundation, Melbourne, VIC, Australia; 12Consumer Representative, Melbourne, VIC, Australia; 13Australian Centre for Heart Health, Royal Melbourne Hospital, Melbourne, VIC, Australia Purpose: Worldwide, stroke is a leading cause of disease burden. Many survivors have unmet needs after discharge from hospital. Electronic communication technology to support post-discharge care has not been used for patients with stroke. In this paper, we describe the development of a novel electronic messaging system designed for survivors of stroke to support their goals of recovery and secondary prevention after hospital discharge. Participants and methods: This was a formative evaluation study. The design was informed by a literature search, existing data from survivors of stroke, and behavior change theories. We established two working groups; one for developing the electronic infrastructure and the other (comprising researchers, clinical experts and consumer representatives) for establishing the patient-centered program. Following agreement on the categories for the goal-setting menu, we drafted relevant messages to support and educate patients. These messages were then independently reviewed by multiple topic experts. Concurrently, we established an online database to capture participant characteristics and then integrated this database with a purpose-built messaging system. We conducted alpha testing of the approach using the first 60 messages. Results: The initial goal-setting menu comprised 26 subcategories. Following expert review, another 8 goal subcategories were added to the secondary prevention category: managing cholesterol; smoking; physical activity; alcohol consumption; weight management; medication management; access to health professionals, and self-care. Initially, 455 health messages were created by members of working group 2. Following refinement and mapping to different goals by the project team, 980 health messages across the health goals and 69 general motivational messages were formulated. Seventeen independent reviewers assessed the messages and suggested adding 73 messages and removing 16 (2%). Overall, 1,233 messages (18 administrative, 69 general motivation and 1,146 health-related) were created. Conclusion: This novel electronic self-management support system is ready to be pilot tested in a randomized controlled trial in patients with stroke. Keywords: stroke, e-health, self-management, health promotion, secondary prevention

Abstract Smart charging of electric vehicles can alleviate grid congestion and reduce charging costs. However, various electric vehicle models currently lack the technical capabilities to effectively implement smart charging since they cannot handle charging pauses or delays. These models enter sleep mode when charging is interrupted, preventing resumption afterwards. To avoid this, they should be continuously charged with their minimum charging power, even when a charging pause would be desirable, for instance with high electricity prices. This research examines this problem to inform various stakeholders, including policymakers and manufacturers, and stimulates the adoption of proactive measures that address this problem. Here, we demonstrate through technical charging tests that around one-third of tested car models suffer from this issue. Through model simulations we indicate that eliminating paused and delayed charging problems would double the smart charging potential for all applications. Lastly, we propose concrete legal and practical solutions to eliminate these problems.

BackgroundPatients with post–COVID-19 condition (PCC) experience a wide range of complaints (physical, cognitive, and mental), sometimes with high levels of disability in daily activities. Evidence of effective interdisciplinary rehabilitation treatment is lacking. A person-centered, biopsychosocial, interdisciplinary rehabilitation program, adapted to expert opinions and the patient’s needs, was therefore developed. ObjectiveThis study aims to present a study protocol for a clinical trial to evaluate the effect of a new, person-centered, interdisciplinary rehabilitation treatment for PCC. It is aimed at improving participation in society and health-related quality of life in patients with PCC who perceive a high level of disability in daily activities or participation. MethodsA total of 20 Dutch adults, aged 18 years or older, with high levels of disability in daily activities and participation in society will be included in this replicated and randomized single-case experimental design study, from October 2023 onward. The replicated and randomized single-case experimental design consists of 3 phases. The baseline phase is the observational period, in which no specific treatment will be given. In the intervention phase, patients will receive the new outpatient treatment 3 times a week for 12 weeks, followed by a 12-week follow-up phase. During the intervention phase, the treatment will be personalized according to the patient’s physical, mental, and cognitive symptoms and goals. The treatment team can consist of a rehabilitation physician, physiotherapist, occupational therapist, speech therapist, and psychologist. The primary outcomes of the study are daily diaries, which consist of 8 questions selected from validated questionnaires (Utrecht Scale for Evaluation of Rehabilitation-Participation, EQ-5D-5L, and the Hospital Anxiety and Depression Scale). The other primary outcome measurements are participation in society (Utrecht Scale for Evaluation of Rehabilitation-Participation) and health-related quality of life (EQ-5D-5L). The secondary outcomes are physical tests and validated questionnaires aimed at physical, mental, and cognitive complaints. Effect evaluation based on daily assessments will include visual analysis, calculation of effect sizes (Nonoverlap of All Pairs), randomization tests, and multilevel analysis. In addition, other analyses will be based on ANOVA or a 2-tailed Student t test. ResultsData collection for this study started in October 2023 and is planned to be completed in July 2024. The results will be published in peer-reviewed journals and presented at international conferences. ConclusionsThis is the first study investigating the effect of an interdisciplinary rehabilitation treatment with a person-centered, biopsychosocial approach in patients with PCC. Our findings will help to improve the treatment and support of patients with PCC. Trial RegistrationGerman Clinical Trials Register DRKS00032636; https://drks.de/search/en/trial/DRKS00032636 International Registered Report Identifier (IRRID)DERR1-10.2196/63951

Summary: Background: Traumatic brain injury is conventionally categorised as mild, moderate, or severe on the Glasgow Coma Scale (GCS). Recently developed biomarkers can provide more objective and nuanced measures of the extent of brain injury. Methods: Exposure–response relationships were investigated in 2479 patients aged ≥16 enrolled in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) prospective observational cohort study. Neurofilament protein-light (NFL), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and glial fibrillary acidic protein (GFAP) were assayed from serum sampled in the first 24 h; concentrations were divided into quintiles within GCS severity groups. Relationships with the Glasgow Outcome Scale-Extended were examined using modified Poisson regression including age, sex, major extracranial injury, time to sample, and log biomarker concentration as covariates. Findings: Within severity groups there were associations between biomarkers and outcomes after adjustment for covariates: GCS 13–15 and negative CT imaging (relative risks [RRs] from 1.28 to 3.72), GCS 13–15 and positive CT (1.21–2.81), GCS 9–12 (1.16–2.02), GCS 3–8 (1.09–1.94). RRs were associated with clinically important differences in expectations of prognosis. In patients with GCS 3 (RRs 1.51–1.80) percentages of unfavourable outcome were 37–51% in the lowest quintiles of biomarker levels and reached 90–94% in the highest quintiles. Similarly, for GCS 15 (RRs 1.83–3.79), the percentages were 2–4% and 19–28% in the lowest and highest biomarker quintiles, respectively. Interpretation: Conventional TBI severity classification is inadequate and underestimates heterogeneity of brain injury and associated outcomes. The adoption of circulating biomarkers can add to clinical assessment of injury severity. Funding: European Union 7th Framework program (EC grant 602150), Hannelore Kohl Stiftung, One Mind, Integra LifeSciences, Neuro-Trauma Sciences, NIHR Rosetrees Trust.

ABSTRACTIntroduction Given the complexity of teaching clinical reasoning to (future) healthcare professionals, the utilization of serious games has become popular for supporting clinical reasoning education. This scoping review outlines games designed to support teaching clinical reasoning in health professions education, with a specific emphasis on their alignment with the 8-step clinical reasoning cycle and the reflective practice framework, fundamental for effective learning.Methods A scoping review using systematic searches across seven databases (PubMed, CINAHL, ERIC, PsycINFO, Scopus, Web of Science, and Embase) was conducted. Game characteristics, technical requirements, and incorporation of clinical reasoning cycle steps were analyzed. Additional game information was obtained from the authors.Results Nineteen unique games emerged, primarily simulation and escape room genres. Most games incorporated the following clinical reasoning steps: patient consideration (step 1), cue collection (step 2), intervention (step 6), and outcome evaluation (step 7). Processing information (step 3) and understanding the patient’s problem (step 4) were less prevalent, while goal setting (step 5) and reflection (step 8) were least integrated.Conclusion All serious games reviewed show potential for improving clinical reasoning skills, but thoughtful alignment with learning objectives and contextual factors is vital. While this study aids health professions educators in understanding how games may support teaching of clinical reasoning, further research is needed to optimize their effective use in education. Notably, most games lack explicit incorporation of all clinical reasoning cycle steps, especially reflection, limiting its role in reflective practice. Hence, we recommend prioritizing a systematic clinical reasoning model with explicit reflective steps when using serious games for teaching clinical reasoning.

Introduction: Up to 50% of pulmonary embolism (PE) patients have perfusion defects or residual vascular obstruction during follow-up despite adequate anticoagulant treatment, and a similar percentage experience chronic functional limitations and/or dyspnoea post-PE. We aimed to evaluate the association between pulmonary perfusion defects or residual vascular obstruction and functional recovery after PE. Methods: We performed a systematic review and meta-analysis including studies assessing both the presence of perfusion defects or residual vascular obstruction and functional recovery (i.e. persistent symptoms, quality of life, exercise endurance). An odds ratio was pooled for perfusion defects or residual vascular obstruction and persistent symptoms using a random-effect model. Results: 12 studies were included totalling 1888 PE patients; at a median of 6 months after PE (range 2–72 months), 34% had perfusion defects or residual vascular obstruction and 37% reported persistent symptoms. Among patients with perfusion defects or residual vascular obstruction, 48% (95% CI 37–60%, I2=82%) remained symptomatic during follow-up, compared to 34% (95% CI 20–51%, I2=96%) of patients without such defects. Presence of perfusion defects or residual vascular obstruction was associated with persistent symptoms (OR 2.15, 95% CI 1.66–2.78; I2=0%, τ=0). Notably, there was no association between these defects and quality of life or cardiopulmonary exercise test parameters. Conclusion: While the odds of having persistent symptoms was higher in patients with perfusion defects or residual vascular obstruction after acute PE, a significant proportion of these patients reported no limitations. A possible causality between perfusion defects or residual vascular obstruction and residual functional limitation therefore remains to be proven.

IntroductionGrowing grass-legume mixtures for forage production improves both yield productivity and nutritional quality, while also benefiting the environment by promoting species biodiversity and enhancing soil fertility (through nitrogen fixation). Consequently, assessing legume proportions in grass-legume mixed swards is essential for breeding and cultivation. This study introduces an approach for automated classification and mapping of species in mixed grass-clover swards using object-based image analysis (OBIA).MethodsThe OBIA procedure was established for both RGB and ten band multispectral (MS) images capturedby an unmanned aerial vehicle (UAV). The workflow integrated structural (canopy heights) and spectral variables (bands, vegetation indices) along with a machine learning algorithm (Random Forest) to perform image segmentation and classification. Spatial k-fold cross-validation was employed to assess accuracy.Results and discussionResults demonstrated good performance, achieving an overall accuracy of approximately 70%, for both RGB and MS-based imagery, with grass and clover classes yielding similar F1 scores, exceeding 0.7 values. The effectiveness of the OBIA procedure and classification was examined by analyzing correlations between predicted clover fractions and dry matter yield (DMY) proportions. This quantification revealed a positive and strong relationship, with R2 values exceeding 0.8 for RGB and MS-based classification outcomes. This indicates the potential of estimating (relative) clover coverage, which could assist breeders but also farmers in a precision agriculture context.

Background: Due to the globally increasing demand for care, innovation is important to maintain quality, safety, effectiveness, patient sensitivity, and outcome orientation. Health care technologies could be a solution to innovate, maintain, or improve the quality of care and simultaneously decrease nurses’ workload. Currently, nurses are rarely involved in the design of health care technologies, mostly due to time constraints with clinical nursing responsibilities and limited exposure to technology and design disciplines. To ensure that health care technologies fit into nurses’ core and routine practice, nurses should be actively involved in the design process. Objective: The aim of the present study was to explore the main requirements for nurses’ active participation in the design of health care technologies. Design: An exploratory descriptive qualitative design was used which helps to both understand and describe a phenomenon. Participants: Twelve nurses from three academic hospitals in the Netherlands participated in this study. Method: Data were collected from semistructured interviews with hospital nurses experienced in design programs and thematically analysed. Results: Four themes were identified concerning the main requirements for nurses to participate in the design of health care technologies: (1) nurses’ motivations to participate, (2) the process of technology development, (3) required competence to participate (such as assertiveness, creative thinking, problem solving skills), and (4) facilitating and organizing nurses’ participation. Conclusion: Nurses experience their involvement in the design process as essential, distinctive, and meaningful but experience few possibilities to combine this work with their current workload, flows, routines, and requirements. To participate in the design of health care technologies nurses need motivation and specific competencies. Organizations should facilitate time for nurses to acquire the required competencies and to be intentionally involved in technology design and development activities.

This study investigates the influence of air exposure time on the erodibility of intertidal mud flats, emphasizing the role of evaporation in altering sediment strength and cohesion. Through a comprehensive approach combining laboratory experiments, fieldwork, and numerical modelling, it explores the dynamic interactions between sediment properties and environmental conditions. The research reveals that drying significantly reduces sediment erodibility, with pronounced effects observed during the initial hours of air exposure. Laboratory tests demonstrate a direct correlation between drying time and increased yield stress for both artificial and field-derived mud samples. Field observations further support these results, showing spatial and temporal variations in water content and shear strength across various locations on a tidal flat. The study emphasizes the critical impact of mud content on water retention and the subsequent effect on sediment stability. The incorporation of drying time into erosion formulations within a numerical model highlights the importance of considering evaporation processes in predicting the morphological evolution of tidal flats. This research contributes to a better understanding of sediment transport dynamics in intertidal zones, offering insights into the mechanisms driving the growth and stability of mud flats. It underscores the necessity of integrating evaporation effects into cohesive sediment transport models to enhance the accuracy of predictions concerning the erosion and accretion of intertidal environments.

Background/Objectives: The rise and spread of antimicrobial resistance complicates the treatment of bacterial wound pathogens, further increasing the need for newer, effective therapies. Azoles such as miconazole have shown promise as antibacterial compounds; however, they are currently only used as antifungals. Previous research has shown that combining azoles with quaternary ammonium compounds yields synergistic activity against fungal pathogens, but the effect on bacterial pathogens has not been studied yet. Methods: In this study, the focus was on finding active synergistic combinations of imidazoles and quaternary ammonium compounds against (multidrug-resistant) bacterial pathogens through checkerboard assays. Experimental evolution in liquid culture was used to evaluate the possible emergence of resistance against the most active synergistic combination. Results: Several promising synergistic combinations were identified against an array of Gram-positive pathogens: miconazole/domiphen bromide, ketoconazole/domiphen bromide, clotrimazole/domiphen bromide, fluconazole/domiphen bromide and miconazole/benzalkonium chloride. Especially, miconazole with domiphen bromide exhibits potential, as it has activity at a low concentration against a broad range of pathogens and shows an absence of strong resistance development over 11 cycles of evolution. Conclusions: This study provides valuable insight into the possible combinations of imidazoles and quaternary ammonium compounds that could be repurposed for (topical) wound treatment. Miconazole with domiphen bromide shows the highest application potential as a possible future wound therapy. However, further research is needed into the mode of action of these compounds and their efficacy and toxicity in vivo.

The impact of ecosystem conservation and restoration activities are rarely monitored from a global, multidimensional and multivariable perspective. Here we present an approach to quantify the environmental impact of landscape restoration using long-term and high-resolution satellite observations. For two restoration areas in Tanzania, we can likely attribute an increase in the amount of water retained by the soil (∼0.01 m³ m⁻³, ∼13% average increase), a soil temperature drop (∼-0.5°C) and an increase in surface greenness (∼50% average increase) in 3.5 years. These datasets illuminate the impact of restoration initiatives on the landscape and support the reporting of comprehensive metrics to donors and partners. Satellite observations from commercial providers and space agencies are now achieving the frequency, resolution, and accuracy that can allow for the effective evaluation of restoration activities.

Business models adopted by online platforms have enabled the proliferation of online hate speech. Platforms providing end-to-end encrypted (E2EE) services have been under increased scrutiny for hosting hate mongers. Legislators struggle to conceptualise the responsibilities of E2EE services to not host hate speech without infringing the users’ rights to freedom of expression, association, privacy, or data protection. This interdisciplinary article proposes a new legal minimum standard expanding corporate human rights responsibilities of E2EE services to mitigate a category of criminal hate speech - incitement to violence. We explore the regulation and application of metadata, hashing, and homomorphic encryption to disrupt incitement to violence in large groups on E2EE services in compliance with human rights.

We present the case of a 33-year-old patient with a rare combination of a right-sided aortic arch and occluded asymptomatic aberrant left subclavian artery diagnosed after the coincidental finding of an interarm blood pressure difference. Because there were no symptoms of local compression or subclavian steal, conservative management was suggested.

Bio-based and biodegradable polyhydroxyalkanoates (PHAs) have great potential as sustainable packaging materials. The incorporation of zinc oxide nanoparticles (ZnO NPs) could further improve their functional properties by providing enhanced barrier and antimicrobial properties, although current literature lacks details on how the characteristics of ZnO influence the structure–property relationships in PHA/ZnO nanocomposites. Therefore, commercial ZnO NPs with different morphologies (rod-like, spherical) and silane surface modification are incorporated into poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) via extrusion and compression molding. All ZnO NPs are homogeneously distributed in the PHBHHx matrix at 1, 3 and 5 wt.%, but finer dispersion is achieved with modified ZnO. No chemical interactions between ZnO and PHBHHx are observed due to a lack of hydroxyl groups on ZnO. The fabricated nanocomposite films retain the flexible properties of PHBHHx with minimal impact of ZnO NPs on crystallization kinetics and the degree of crystallinity (53 to 56%). The opacity gradually increases with ZnO loading, while remaining translucent up to 5 wt.% ZnO and providing an effective UV barrier. Improved oxygen barrier and antibacterial effects against S. aureus are dependent on the intrinsic characteristics of ZnO rather than its morphology. We conclude that PHBHHx retains its favorable processing properties while producing nanocomposite films that are suitable as flexible active packaging materials.

Abstract Background Healthcare professionals working in long-term care facilities reported heavy job demands and a lack of job resources during the 2019 coronavirus disease (COVID-19) pandemic. However, how job demands and resources in these facilities changed during the pandemic, and how possible changes affected professionals’ work-related well-being, remains unclear. Thus, we explored changes in job demands and resources in the face of surging COVID-19 infection rates, and investigated associations of these changes with changes in burnout and work engagement, among healthcare professionals working in long-term care facilities in the Netherlands. Methods This longitudinal study was conducted with healthcare professionals working in five long-term care facilities in the Netherlands. Data were collected in early and late 2021, when infection rates in long-term care facilities were low and high (mean, 29.1 and 275.4 infections/day), respectively. In total, 173 healthcare professionals completed the validated Job Demands and Resources Questionnaire, Copenhagen Burnout Inventory, and Utrecht Work Engagement Scale at both timepoints. We performed paired-samples t tests to examine changes in job demands and resources, and fixed-effects linear regression analyses to examine associations of within-person changes in job demands and resources with those in burnout and work engagement. Results Healthcare professionals perceived increased workloads, associated with increased burnout and decreased work engagement during the study period. Within-person increases in perceived collegial support were associated positively with work engagement and negatively with burnout symptoms. Conclusions Healthcare professionals in long-term care facilities perceived increased workloads in the wake of surging infection rates during the COVID-19 pandemic, resulting in increased burnout and decreased work engagement. These changes in burnout and work engagement were also perceived in response to declining collegial support. Efforts to protect the work-related well-being of healthcare professionals working in long-term care facilities in the pandemic context that focus on workload reduction and the promotion of collegial support may be most beneficial.

Abstract Microbe–plant interactions in the root zone not only shape crop performance in soil but also in hydroponic cultivation systems. The biological and physicochemical properties of the plant‐growing medium determine the root‐associated microbial community and influence bacterial inoculation effectiveness, which affects plant growth. This study investigated the combined impact of plant‐growing media composition and bacterial community inoculation on the root‐associated bacterial community of hydroponically grown lettuce (Lactuca sativa L.). Ten plant‐growing media were composed of varying raw materials, including black peat, white peat, coir pith, wood fibre, composted bark, green waste compost, perlite and sand. In addition, five different bacterial community inocula (BCI S1–5) were collected from the roots of lettuce obtained at different farms. After inoculation and cultivation inside a vertical farm, lettuce root‐associated bacterial community structures, diversity and compositions were determined by evaluating 16S rRNA gene sequences. The study revealed distinct bacterial community structures among experimental replicates, highlighting the influence of raw material variations on root‐associated bacterial communities, even at the batch level. However, bacterial community inoculation allowed modulation of the root‐associated bacterial communities independently from the plant‐growing medium composition. Bacterial diversity was identified as a key determinant of plant growth performance with green waste compost introducing Bacilli and Actinobacteria, and bacterial community inoculum S3 introducing Pseudomonas, which positively correlated with plant growth. These findings challenge the prevailing notion of hydroponic cultivation systems as sterile environments and highlight the significance of proper plant‐growing media raw material selection and bacterial community inoculation in shaping root‐associated microbiomes that provide stability through microbial diversity. This study supports the concept of creating bacterially enhanced plant‐growing media to promote plant growth in controlled environment agriculture.

We investigated a large outbreak of SARS-CoV-2 infections among passengers and crew members (60 cases in 132 persons) on a cruise ship sailing for 7 days on rivers in the Netherlands. Whole-genome analyses suggested a single or limited number of viral introductions consistent with the epidemiologic course of infections. Although some precautionary measures were taken, no social distancing was exercised, and air circulation and ventilation were suboptimal. The most plausible explanation for introduction of the virus is by persons (crew members and 2 passengers) infected during a previous cruise, in which a case of COVID-19 had occurred. The crew was insufficiently prepared on how to handle the situation, and efforts to contact public health authorities was inadequate. We recommend installing clear handling protocols, direct contacts with public health organizations, training of crew members to recognize outbreaks, and awareness of air quality on river-cruise ships, as is customary for most seafaring cruises.

Abstract Introduction Clinical practice guidelines (hereafter ‘guidelines’) are crucial in providing evidence‐based recommendations for physicians and multidisciplinary teams to make informed decisions regarding diagnostics and treatment in various diseases, including cancer. While guideline implementation has been shown to reduce (unwanted) variability and improve outcome of care, monitoring of adherence to guidelines remains challenging. Real‐world data collected from cancer registries can provide a continuous source for monitoring adherence levels. In this work, we describe a novel structured approach to guideline evaluation using real‐world data that enables continuous monitoring. This method was applied to endometrial cancer patients in the Netherlands and implemented through a prototype web‐based dashboard that enables interactive usage and supports various analyses. Method The guideline under study was parsed into clinical decision trees (CDTs) and an information standard was drawn up. A dataset from the Netherlands Cancer Registry (NCR) was used and data items from both instruments were mapped. By comparing guideline recommendations with real‐world data an adherence classification was determined. The developed prototype can be used to identify and prioritize potential topics for guideline updates. Results CDTs revealed 68 data items for recording in an information standard. Thirty‐two data items from the NCR were mapped onto information standard data items. Four CDTs could sufficiently be populated with NCR data. Conclusion The developed methodology can evaluate a guideline to identify potential improvements in recommendations and the success of the implementation strategy. In addition, it is able to identify patient and disease characteristics that influence decision‐making in clinical practice. The method supports a cyclical process of developing, implementing and evaluating guidelines and can be scaled to other diseases and settings. It contributes to a learning healthcare cycle that integrates real‐world data with external knowledge.

BackgroundThe peripartum period, defined as the period from the beginning of the gestation until 1 year after the delivery, has long been shown to be potentially associated with increased levels of stress and anxiety with regard to one’s transition to the status of parent and the accompanying parental tasks. Yet, no research to date has investigated changes in intrapersonal factors during the peripartum period in women at risk for pregnancy-induced hypertension (PIH). ObjectiveThe aim of this study is to explore and describe changes in intrapersonal factors in participants at risk for PIH. MethodsWe used an explorative design in which 3 questionnaires were sent by email to 110 participants the day following enrollment in the Pregnancy Remote Monitoring program for pregnant women at risk for PIH. Women were invited to complete the questionnaires at the beginning of their participation in the Pregnancy Remote Monitoring project (mostly at 14 weeks of gestation) and after approaching 32 weeks of gestational age (GA). The Generalized Anxiety Disorder-7 Scale (GAD-7) and the Patient Health Questionnaire-9 were used to assess anxiety and depression, and adaptation of the Pain Catastrophizing Scale was used to measure trait pain catastrophizing. ResultsScores were significantly higher at 32 weeks of GA than at the moment of enrollment (GAD-7 score=7, range 4-11 vs 5, range 3-8; P=.01; and Patient Health Questionnaire-9 score=6, range 4-10 vs 4, range 2-7; P10) was 13.3% (10/75) at enrollment and had increased to 35.6% (26/75) at 32 weeks of GA. ConclusionsThis study shows that pregnant women at risk for PIH have higher levels of stress and anxiety at 32 weeks of GA than at the moment of enrollment. Further research is recommended to investigate potential strategies to help pregnant women at risk for PIH manage feelings of stress and anxiety. Trial RegistrationClinicalTrials.gov NCT03246737; https://clinicaltrials.gov/study/NCT03246737

Summary: Background: Limited evidence existed on the comparative effectiveness of decompressive craniectomy (DC) versus craniotomy for evacuation of traumatic acute subdural hematoma (ASDH) until the recently published randomised clinical trial RESCUE-ASDH. In this study, that ran concurrently, we aimed to determine current practice patterns and compare outcomes of primary DC versus craniotomy. Methods: We conducted an analysis of centre treatment preference within the prospective, multicentre, observational Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (known as CENTER-TBI) and NeuroTraumatology Quality Registry (known as Net-QuRe) studies, which enrolled patients throughout Europe and Israel (2014–2020). We included patients with an ASDH who underwent acute neurosurgical evacuation. Patients with severe pre-existing neurological disorders were excluded. In an instrumental variable analysis, we compared outcomes between centres according to treatment preference, measured by the case-mix adjusted proportion DC per centre. The primary outcome was functional outcome rated by the 6-months Glasgow Outcome Scale Extended, estimated with ordinal regression as a common odds ratio (OR), adjusted for prespecified confounders. Variation in centre preference was quantified with the median odds ratio (MOR). CENTER-TBI is registered with ClinicalTrials.gov, number NCT02210221, and the Resource Identification Portal (Research Resource Identifier SCR_015582). Findings: Between December 19, 2014 and December 17, 2017, 4559 patients with traumatic brain injury were enrolled in CENTER-TBI of whom 336 (7%) underwent acute surgery for ASDH evacuation; 91 (27%) underwent DC and 245 (63%) craniotomy. The proportion primary DC within total acute surgery cases ranged from 6 to 67% with an interquartile range (IQR) of 12–26% among 46 centres; the odds of receiving a DC for prognostically similar patients in one centre versus another randomly selected centre were trebled (adjusted median odds ratio 2.7, p

Abstract Background Long-lasting crises, such as the COVID-19 pandemic, require proper interim evaluation in order to optimize response. The World Health Organization and the European Center for Disease Control have recently promoted the in(tra)-action review (IAR) method for this purpose. We systematically evaluated the added value of two IARs performed in the Dutch point of entry (PoE) setting. Methods Two online, 4-hour IAR meetings were organized in March 2021, for ports and airports respectively, to reflect on the ongoing COVID-19 response. Topics discussed were selected through a survey among participants. Participants were mainly self-selected by the (air)port public health service. Evaluation of the IAR method consisted of participant evaluation through a questionnaire, and hot and cold debriefs of the organizing team. Evaluation of the impact of the IAR was done through analysis of the meeting results, and a 3-month follow-up of the actions proposed during the meetings. Results Thirty-nine professionals joined the IAR meetings. In the participant evaluation (n = 18), 89% agreed or totally agreed the IAR made it possible to identify challenges and problems in the COVID-19 response at PoE. Participants especially appreciated the resulting insight in regional and national partners. Regarding the online setting of the meeting, participants suggested to choose accessible and familiar online tools. After 3 months, all national actions and actions for ports had been executed; some regional actions for airports required further attention. A major result was a new meeting structure for all ports and the participating national authorities in which remaining and newly occurring issues were discussed. Conclusions Based on the evaluations, we conclude that the IAR method can be of value during long-term crises, such as the COVID-19 pandemic response. Although it is challenging to dedicate time and effort to the organization and attendance of IAR meetings during crisis, the IAR method is feasible in an online setting if appropriate organizing and technical capacity is available. A participatory set-up supports the IAR method as a starting point for continuous exchange and learning during ongoing crises.

Abstract Background We assess whether social integration is associated with mental health among Somali refugees in the Netherlands, and how this association is shaped by perceived discrimination. Methods We performed linear regression and formal mediation analyses on Survey Integration Minorities data (n = 417) to assess whether the effects of two facets of social integration – Dutch language proficiency and informal contacts with natives – on mental health were mediated or suppressed by perceived discrimination. Results Dutch language proficiency was positively associated with mental health, but also with perceived discrimination. Informal contact with natives was not significantly associated with mental health or perceived discrimination. There was marginally significant evidence (p

Plain English Summary All major problems, including complex global problems such as air pollution and pandemics, require reliable data sharing between disciplines in order to respond effectively. Such problems require evidence-informed collaborative methods, multidisciplinary research and interventions in which the people who are affected are involved in every stage. However, there is currently no standardised way to share information about initiatives and problem-solving across and between fields such as health, environment, basic science, manufacturing, education, media and international development. A multi-disciplinary international team of over 100 citizens, experts and data-users has been involved in co-creating STARDIT to help everyone in the world share, find and understand information about collective human actions, which are referred to as ‘initiatives’. STARDIT is an open access data-sharing system to standardise the way that information about initiatives is reported, including information about which tasks were done by different people. Reports can be updated at all stages, from planning to evaluation, and can report impacts in many languages, using Wikidata. STARDIT is free to use, and data can be submitted by anyone. Report authors can be verified to improve trust and transparency, and data checked for quality. STARDIT can help create high-quality standardised information on initiatives trying to solve complex multidisciplinary global problems. Among its main benefits, STARDIT offers those carrying out research and interventions access to standardised information which enables well-founded comparisons of the effectiveness of different methods. This article outlines progress to date; current usage; information about submitting reports; planned next steps and how anyone can become involved.

Abstract Background Nipple fluid aspiration (NFA) is a technique to acquire nipple aspirate fluid (NAF), which is considered a rich source of breast-specific biomarkers. Originating directly from the mammary ducts, this liquid biopsy can offer insight into the process of carcinogenesis at its earliest stage and therefore could be of added value to the current imaging-based breast cancer screening tools. With that in mind, it is necessary to know how well NFA is tolerated. Aim To evaluate the participants’ tolerability of NFA compared to breast imaging screening methods and blood draws. Materials and methods Three cohorts of women underwent NFA: healthy women (n = 190), women diagnosed with breast cancer (n = 137) and women at high risk of developing breast cancer (n = 48). A 0–10 discomfort score of NFA, mammography, breast MRI and blood draws, was filled in at the study visits, which took place once or annually. Results The median discomfort rate of NFA was 1, which was significantly lower than the median discomfort of mammography and breast MRI (5 and 3, respectively, p

Abstract Temperature and strain are two vital parameters that play a significant role in wound diagnosis and healing. As periodic temperature measurements with a custom thermometer or strain measurements with conventional metallic gauges became less feasible for the modern competent health monitoring, individual temperature and strain measurement modalities incorporated into wearables and patches were developed. The proposed research in the article shows the development of a single sensor solution which can simultaneously measure both the above mentioned parameters. This work integrates a thermoelectric principle based temperature measurement approach into wearables, ensuring flexibility and bendability properties without affecting its thermo-generated voltage. The modified thermoelectric material helped to achieve stretchability of the sensor, thanks to its superior mechano-transduction properties. Moreover, the stretch-induced resistance changes become an additional marker for strain measurements so that both the parameters can be measured with the same sensor. Due to the independent measurement parameters (open circuit voltage and sensor resistance), the sensing model is greatly attractive for measurements without cross-sensitivity. The highly resilient temperature and strain sensor show excellent linearity, repeatability and good sensitivity. Besides, due to the compatibility of the fabrication scheme to low-temperature processing of the flexible materials and to mass volume production, printed fabrication methodologies were adopted to realize the sensor. This promises low-cost production and a disposable nature (single use) of the sensor patch. For the first time, this innovative temperature-strain dual parameter sensor concept has been tested on mice wounds in vivo. The preliminary experiments on mice wounds offer prospects for developing smart, i.e. sensorized, wound dressings for clinical applications.

BackgroundIn home care, eHealth implementation requires health care professionals and home care clients to change their behavior because they have to incorporate the use of eHealth into their daily routines. Knowledge of factors that influence the use of eHealth in home care is needed to optimize implementation strategies. However, a comprehensive overview of such factors is lacking. ObjectiveThe aims of this study were to (1) provide insight into the types of eHealth that are used and preferred in home care and (2) identify factors that influence the use of eHealth in home care according to health care professionals and home care clients. MethodsA scoping review and online, cross-sectional survey were conducted sequentially. The survey was conducted among Dutch health care professionals with a nursing background who were working for a home care organization at the time. The capability, opportunity, motivation, behavior (COM-B) model, which posits that for any behavior (B) to occur, a person must have the capability (C), opportunity (O), and motivation (M) to perform the behavior, was used to identify influencing factors. The use of a theoretical model may contribute to a better understanding of how to achieve and sustain behavior change in clinical practice. ResultsWe included 30 studies in the scoping review. The most frequently studied type of eHealth was a telecommunication/telemonitoring system. The survey was completed by 102 participants. The most frequently used types of eHealth were electronic health records, social alarms, and online client portals. A health app was the most frequently preferred type of eHealth. We identified 22 factors that influence the use of eHealth in home care according to health care professionals and home care clients. Influencing factors were organized into the components of the COM-B model, namely capability (n=6), opportunity (n=10), and motivation (n=6). We found that there is no single influencing factor that is key to the complexity of eHealth implementation. ConclusionsDifferent types of eHealth are used, and many types of eHealth are preferred by health care professionals. The identified factors that influence the use of eHealth in home care relate to all components of the COM-B model. These factors need to be addressed and embedded in implementation strategies of eHealth to optimize the use of eHealth in home care.

Abstract Background Breast cancer screening and improving imaging techniques have led to an increase in the detection rate of early, nonpalpable breast cancers. For early breast cancer, breast conserving surgery is an effective and safe treatment. Accurate intraoperative lesion localization during breast conserving surgery is essential for adequate surgical margins while sparing surrounding healthy tissue to achieve optimal cosmesis. Preoperative wire localization and radioactive seed localization are accepted standard methods to guide surgical excision of nonpalpable breast lesions. However, these techniques present significant limitations. Radiofrequency identification (RFID) technology offers a new, nonradioactive method for localizing nonpalpable breast lesions in patients undergoing breast conserving surgery. This study aims to evaluate the feasibility of RFID surgical guidance for nonpalpable breast lesions. Methods This multicenter prospective cohort study was approved by the Institutional Review Board of the University Medical Center Utrecht. Written informed consent is obtained from all participants. Women with nonpalpable, histologically proven in situ or invasive breast cancer, who can undergo breast conserving surgery with RFID localization are considered eligible for participation. An RFID tag is placed under ultrasound guidance, up to 30 days preoperatively. The surgeon localizes the RFID tag with a radiofrequency reader that provides audible and visual real-time surgical guidance. The primary study outcome is the percentage of irradical excisions and reexcision rate, which will be compared to standards of the National Breast Cancer Organisation Netherlands (NABON)(≤ 15% irradical excisions of invasive carcinomas). Secondary outcomes include user acceptability/experiences, learning curve, duration and ease of the placement- and surgical procedure and adverse events. Discussion This study evaluates the feasibility of RFID surgical guidance for nonpalpable breast lesions. Results may have implications for the future localization techniques in women with nonpalpable breast cancer undergoing breast conserving surgery. Trial registration Netherlands National Trial Register, NL8019 , registered on September 12th 2019.

Abstract Background Analysing distributed medical data is challenging because of data sensitivity and various regulations to access and combine data. Some privacy-preserving methods are known for analyzing horizontally-partitioned data, where different organisations have similar data on disjoint sets of people. Technically more challenging is the case of vertically-partitioned data, dealing with data on overlapping sets of people. We use an emerging technology based on cryptographic techniques called secure multi-party computation (MPC), and apply it to perform privacy-preserving survival analysis on vertically-distributed data by means of the Cox proportional hazards (CPH) model. Both MPC and CPH are explained. Methods We use a Newton-Raphson solver to securely train the CPH model with MPC, jointly with all data holders, without revealing any sensitive data. In order to securely compute the log-partial likelihood in each iteration, we run into several technical challenges to preserve the efficiency and security of our solution. To tackle these technical challenges, we generalize a cryptographic protocol for securely computing the inverse of the Hessian matrix and develop a new method for securely computing exponentiations. A theoretical complexity estimate is given to get insight into the computational and communication effort that is needed. Results Our secure solution is implemented in a setting with three different machines, each presenting a different data holder, which can communicate through the internet. The MPyC platform is used for implementing this privacy-preserving solution to obtain the CPH model. We test the accuracy and computation time of our methods on three standard benchmark survival datasets. We identify future work to make our solution more efficient. Conclusions Our secure solution is comparable with the standard, non-secure solver in terms of accuracy and convergence speed. The computation time is considerably larger, although the theoretical complexity is still cubic in the number of covariates and quadratic in the number of subjects. We conclude that this is a promising way of performing parametric survival analysis on vertically-distributed medical data, while realising high level of security and privacy.

Since the 1990s, sanctions senders like the European Union, the United States, and the United Nations have been imposing visa bans and asset freezes on individuals as a key element of their sanctions packages. Notwithstanding the growing centrality that individual sanctions have acquired in international sanctions practice, little is known about the impact of sanctions listings on designees. Some researchers have scrutinised targeting choices, while others have explored the effects of sanctions on designees. However, no study has yet examined the fit between targeting choices and impacts on designees. First, we interrogate the theory of targeted sanctions to identify the expectations that it generates. Second, we examine the effects on designees and contrast them with the targeting logic of the sender, in a bid to ascertain their fit. Our analysis of the cases of Côte d’Ivoire (2010–2011) and Zimbabwe (2002–2017) benefits from original interview material.

Dredged cohesive sediment is progressively being used for wetland construction. However, little is known about the effect of plant growth during the self-weight consolidation of this sediment. In order to check the feasibility of such a study, a new experimental setup has been constructed. As an example, the effect of Phragmites australis on the consolidation and drainage of dredged sediment from Lake Markermeer, the Netherlands was investigated. The changes in pore water pressures at 10 cm depth intervals during a 129-day period in a column with and without plants were measured, while the water level was fixed at a constant level. Water loss via evaporation and plant transpiration was measured using Mariotte bottles and the photosynthetic processes — including plant transpiration — were measured with a LI-COR photosynthesis system. The results show that several processes initiated by Phragmites australis interfere with the physical processes involved in sediment drainage and consolidation. Phragmites australis effectively altered the pore pressure gradient via water extraction, especially between 40 and 60 cm from the bottom of the column. In this zone, daily cycles in pore pressures were observed which could directly be linked to the diurnal cycle of stomatal gas exchange. On average, water loss via evaporation and transpiration of leaves of Phragmites australis amounted to 3.9 mm day−1, whereas evaporation of bare soil amounted on average to 0.6 mm day−1. The depth-averaged hydraulic conductivity increased on average by 40% in presence of Phragmites australis. This pilot experiment confirms that the pressures sensors coupled with the new set-up enable to study pore pressure development over time and to link the effect of plant growth with alterations in water pressures profiles. A more systematic study with this set-up will in the future enable to quantify the effects of plant growth on consolidation.

BackgroundTannins have demonstrated antibacterial and antibiofilm activity, but there are still unknown aspects on how the chemical properties of tannins affect their biological properties. We are interested in understanding how to modulate the antibiofilm activity of tannins and in delineating the relationship between chemical determinants and antibiofilm activity.Materials and methodsThe effect of five different naturally acquired tannins and their chemical derivatives on biofilm formation and planktonic growth of Salmonella Typhimurium, Pseudomonas aeruginosa, Escherichia coli and Staphylococcus aureus was determined in the Calgary biofilm device.ResultsMost of the unmodified tannins exhibited specific antibiofilm activity against the assayed bacteria. The chemical modifications were found to alter the antibiofilm activity level and spectrum of the tannins. A positive charge introduced by derivatization with higher amounts of ammonium groups shifted the anti-biofilm spectrum toward Gram-negative bacteria, and derivatization with lower amounts of ammonium groups and acidifying derivatization shifted the spectrum toward Gram-positive bacteria. Furthermore, the quantity of phenolic OH-groups per molecule was found to have a weak impact on the anti-biofilm activity of the tannins.ConclusionWe were able to modulate the antibiofilm activity of several tannins by specific chemical modifications, providing a first approach for fine tuning of their activity and antibacterial spectrum.

Abstract The phenylpropanoid cinnamic acid (CA) is a plant metabolite that can occur under a trans‐ or cis‐form. In contrast to the proven bioactivity of the cis‐form (c‐CA), the activity of trans‐CA (t‐CA) is still a matter of debate. We tested both compounds using a submerged rice coleoptile assay and demonstrated that they have opposite effects on cell elongation. Notably, in the tip of rice coleoptile t‐CA showed an inhibiting and c‐CA a stimulating activity. By combining transcriptomics and (untargeted) metabolomics with activity assays and genetic and pharmacological experiments, we aimed to explain the underlying mechanistic processes. We propose a model in which c‐CA treatment activates proton pumps and stimulates acidification of the apoplast, which in turn leads to the loosening of the cell wall, necessary for elongation. We hypothesize that c‐CA also inactivates auxin efflux transporters, which might cause a local auxin accumulation in the tip of the coleoptile. For t‐CA, the phenotype can partially be explained by a stimulation of cell wall polysaccharide feruloylation, leading to a more rigid cell wall. Metabolite profiling also demonstrated that salicylic acid (SA) derivatives are increased upon t‐CA treatment. As SA is a known antagonist of auxin, the shift in SA homeostasis provides an additional explanation of the observed t‐CA‐mediated restriction on cell growth.

Abstract Background Recent developments in machine learning have shown its potential impact for clinical use such as risk prediction, prognosis, and treatment selection. However, relevant data are often scattered across different stakeholders and their use is regulated, e.g. by GDPR or HIPAA. As a concrete use-case, hospital Erasmus MC and health insurance company Achmea have data on individuals in the city of Rotterdam, which would in theory enable them to train a regression model in order to identify high-impact lifestyle factors for heart failure. However, privacy and confidentiality concerns make it unfeasible to exchange these data. Methods This article describes a solution where vertically-partitioned synthetic data of Achmea and of Erasmus MC are combined using Secure Multi-Party Computation. First, a secure inner join protocol takes place to securely determine the identifiers of the patients that are represented in both datasets. Then, a secure Lasso Regression model is trained on the securely combined data. The involved parties thus obtain the prediction model but no further information on the input data of the other parties. Results We implement our secure solution and describe its performance and scalability: we can train a prediction model on two datasets with 5000 records each and a total of 30 features in less than one hour, with a minimal difference from the results of standard (non-secure) methods. Conclusions This article shows that it is possible to combine datasets and train a Lasso regression model on this combination in a secure way. Such a solution thus further expands the potential of privacy-preserving data analysis in the medical domain.

Bayesian state and parameter estimation are automated effectively in a variety of probabilistic programming languages. The process of model comparison on the other hand, which still requires error-prone and time-consuming manual derivations, is often overlooked despite its importance. This paper efficiently automates Bayesian model averaging, selection, and combination by message passing on a Forney-style factor graph with a custom mixture node. Parameter and state inference, and model comparison can then be executed simultaneously using message passing with scale factors. This approach shortens the model design cycle and allows for the straightforward extension to hierarchical and temporal model priors to accommodate for modeling complicated time-varying processes.

Background: There is an underuse of genetic testing in breast cancer patients with a lower level of education, limited health literacy or a migrant background. We aimed to study the effect of a health literacy training program for surgical oncologists and specialized nurses on disparities in referral to genetic testing. Methods: We conducted a multicenter study in a quasi-experimental pre-post (intervention) design. The intervention consisted of an online module and a group training for surgical oncologists and specialized nurses in three regions in the Netherlands. Six months pre- and 12 months post intervention, clinical geneticists completed a checklist with socio-demographic characteristics including the level of health literacy of each referred patient. We conducted univariate and logistic regression analysis to evaluate the effect of the training program on disparities in referral to genetic testing. Results: In total, 3179 checklists were completed, of which 1695 were from hospital referrals. No significant differences were found in educational level, level of health literacy and migrant background of patients referred for genetic testing by healthcare professionals working in trained hospitals before (n = 795) and after (n = 409) the intervention. The mean age of patients referred by healthcare professionals from trained hospitals was significantly lower after the intervention (52.0 vs. 49.8, P = 0.003). Conclusion: The results of our study suggest that the health literacy training program did not decrease disparities in referral to genetic testing. Future research in a more controlled design is needed to better understand how socio-demographic factors influence referral to breast cancer genetic testing and what other factors might contribute.

ObjectiveSpine injury is highly prevalent in patients with poly-trauma, but data on the co-occurrence of spine trauma in patients with traumatic brain injury (TBI) are scarce. In this study, we used the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) database to assess the prevalence, characteristics, and outcomes of patients with TBI and a concurrent traumatic spinal injury (TSI).MethodsData from the European multi-center CENTER-TBI study were analyzed. Adult patients with TBI (≥18 years) presenting with a concomitant, isolated TSI of at least serious severity (Abbreviated Injury Scale; AIS ≥3) were included. For outcome analysis, comparison groups of TBI patients with TSI and systemic injuries (non-isolated TSI) and without TSI were created using propensity score matching. Rates of mortality, unfavorable outcomes (Glasgow Outcome Scale Extended; GOSe < 5), and full recovery (GOSe 7–8) of all patients and separately for patients with only mild TBI (mTBI) were compared between groups at 6-month follow-up.ResultsA total of 164 (4%) of the 4,254 CENTER-TBI core study patients suffered from a concomitant isolated TSI. The median age was 53 [interquartile range (IQR): 37–66] years and 71% of patients were men. mTBI was documented in 62% of cases, followed by severe TBI (26%), and spine injuries were mostly cervical (63%) or thoracic (31%). Surgical spine stabilization was performed in 19% of cases and 57% of patients were admitted to the ICU. Mortality at 6 months was 11% and only 36% of patients regained full recovery. There were no significant differences in the 6-month rates of mortality, unfavorable outcomes, or full recovery between TBI patients with and without concomitant isolated TSI. However, concomitant non-isolated TSI was associated with an unfavorable outcome and a higher mortality. In patients with mTBI, a negative association with full recovery could be observed for both concomitant isolated and non-isolated TSI.ConclusionRates of mortality, unfavorable outcomes, and full recovery in TBI patients with and without concomitant, isolated TSIs were comparable after 6 months. However, in patients with mTBI, concomitant TSI was a negative predictor for a full recovery. These findings might indicate that patients with moderate to severe TBI do not necessarily exhibit worse outcomes when having a concomitant TSI, whereas patients with mTBI might be more affected.

Background: More than 300 cities including the city of Amsterdam in the Netherlands have joined the UNAIDS Fast-Track Cities initiative, committing to accelerate their HIV response and end the AIDS epidemic in cities by 2030. To support this commitment, we aimed to estimate the number and proportion of Amsterdam HIV infections that originated within the city, from Amsterdam residents. We also aimed to estimate the proportion of recent HIV infections during the 5-year period 2014–2018 in Amsterdam that remained undiagnosed. Methods: We located diagnosed HIV infections in Amsterdam using postcode data (PC4) at time of registration in the ATHENA observational HIV cohort, and used HIV sequence data to reconstruct phylogeographically distinct, partially observed Amsterdam transmission chains. Individual-level infection times were estimated from biomarker data, and used to date the phylogenetically observed transmission chains as well as to estimate undiagnosed proportions among recent infections. A Bayesian Negative Binomial branching process model was used to estimate the number, size, and growth of the unobserved Amsterdam transmission chains from the partially observed phylogenetic data. Results: Between 1 January 2014 and 1 May 2019, there were 846 HIV diagnoses in Amsterdam residents, of whom 516 (61%) were estimated to have been infected in 2014–2018. The rate of new Amsterdam diagnoses since 2014 (104 per 100,000) remained higher than the national rates excluding Amsterdam (24 per 100,000), and in this sense Amsterdam remained a HIV hotspot in the Netherlands. An estimated 14% [12–16%] of infections in Amsterdan MSM in 2014–2018 remained undiagnosed by 1 May 2019, and 41% [35–48%] in Amsterdam heterosexuals, with variation by region of birth. An estimated 67% [60–74%] of Amsterdam MSM infections in 2014–2018 had an Amsterdam resident as source, and 56% [41–70%] in Amsterdam heterosexuals, with heterogeneity by region of birth. Of the locally acquired infections, an estimated 43% [37–49%] were in foreign-born MSM, 41% [35–47%] in Dutch-born MSM, 10% [6–18%] in foreign-born heterosexuals, and 5% [2–9%] in Dutch-born heterosexuals. We estimate the majority of Amsterdam MSM infections in 2014–2018 originated in transmission chains that pre-existed by 2014. Conclusions: This combined phylogenetic, epidemiologic, and modelling analysis in the UNAIDS Fast-Track City Amsterdam indicates that there remains considerable potential to prevent HIV infections among Amsterdam residents through city-level interventions. The burden of locally acquired infection remains concentrated in MSM, and both Dutch-born and foreign-born MSM would likely benefit most from intensified city-level interventions. Funding: This study received funding as part of the H-TEAM initiative from Aidsfonds (project number P29701). The H-TEAM initiative is being supported by Aidsfonds (grant number: 2013169, P29701, P60803), Stichting Amsterdam Dinner Foundation, Bristol-Myers Squibb International Corp. (study number: AI424-541), Gilead Sciences Europe Ltd (grant number: PA-HIV-PREP-16-0024), Gilead Sciences (protocol numbers: CO-NL-276-4222, CO-US-276-1712, CO-NL-985-6195), and M.A.C AIDS Fund.

In several diseases, bone resorption by osteoclasts is dysregulated. Thus far, no simple technique for real-time measurement of resorption is available. Here, we introduce an impedimetric bioassay for real-time monitoring of resorption by making use of the electrical insulating properties of the resorbable substrate calcium phosphate. Different chemical stimuli were applied to (pre)osteoclasts cultured on a layer of calcium phosphate in multi-well plates containing electrodes. By this, osteoclast activity can be measured continuously over days, and the effects of stimulating or inhibiting factors can be quantified. When cells were cultured in the presence of an inflammatory factor such as IL-1β, the resorptive activity started earlier. The measured decline in resistance was higher at culture day 5 than at cultures with M-CSF or M-CSF + RANKL (M-CSF norm. Resistance = 1, M-CSF + RANKL = 0.7, M-CSF + RANKL + IL-1β = 0.5). However, at day 11, this difference had nearly disappeared. Likewise, bisphosphonates were shown to inhibit osteoclastic activity. Our findings illustrate the importance of real-time monitoring; wherefore, this method has high potential not only for the study of osteoclast resorptive activity in the context of osteoclast function and diseases but also could find application in high-throughput drug-testing studies.

A survey of plant-based wastes identified sunflower (Helianthus annuus) bark extract (SBE), produced via twin-screw extrusion, as a potential biostimulant. The addition of SBE to Arabidopsis (Arabidopsis thaliana) seedlings cultured in vitro showed a dose-dependent response, with high concentrations causing severe growth inhibition. However, when priming seeds with SBE, a small but significant increase in leaf area was observed at a dose of 0.5 g of lyophilized powder per liter. This optimal concentration of SBE in the culturing medium alleviated the growth inhibition caused by 100 mM NaCl. The recovery in shoot growth was accompanied by a pronounced increase in photosynthetic pigment levels and a stabilization of osmotic homeostasis. SBE-primed leaf discs also showed a similar protective effect. SBE mitigated salt stress by reducing the production of reactive oxygen species (ROS) (e.g., hydrogen peroxide) by about 30% and developing more expanded true leaves. This reduction in ROS levels was due to the presence of antioxidative agents in SBE and by activating ROS-eliminating enzymes. Polyphenols, carbohydrates, proteins, and other bioactive compounds detected in SBE may have contributed to the cellular redox homeostasis in salt-stressed plants, thus promoting early leaf development by relieving shoot apical meristem arrest. Sunflower stalks from which SBE is prepared can therefore potentially be valorized as a source to produce biostimulants for improving salt stress tolerance in crops.

Lignocellulosic biomass is recalcitrant toward deconstruction into simple sugars mainly due to the presence of lignin. By engineering plants to partially replace traditional lignin monomers with alternative ones, lignin degradability and extractability can be enhanced. Previously, the alternative monomer curcumin has been successfully produced and incorporated into lignified cell walls of Arabidopsis by the heterologous expression of DIKETIDE-CoA SYNTHASE (DCS) and CURCUMIN SYNTHASE2 (CURS2). The resulting transgenic plants did not suffer from yield penalties and had an increased saccharification yield after alkaline pretreatment. Here, we translated this strategy into the bio-energy crop poplar. Via the heterologous expression of DCS and CURS2 under the control of the secondary cell wall CELLULOSE SYNTHASE A8-B promoter (ProCesA8-B), curcumin was also produced and incorporated into the lignified cell walls of poplar. ProCesA8-B:DCS_CURS2 transgenic poplars, however, suffered from shoot-tip necrosis and yield penalties. Compared to that of the wild-type (WT), the wood of transgenic poplars had 21% less cellulose, 28% more matrix polysaccharides, 23% more lignin and a significantly altered lignin composition. More specifically, ProCesA8-B:DCS_CURS2 lignin had a reduced syringyl/guaiacyl unit (S/G) ratio, an increased frequency of p-hydroxyphenyl (H) units, a decreased frequency of p-hydroxybenzoates and a higher fraction of phenylcoumaran units. Without, or with alkaline or hot water pretreatment, the saccharification efficiency of the transgenic lines was equal to that of the WT. These differences in (growth) phenotype illustrate that translational research in crops is essential to assess the value of an engineering strategy for applications. Further fine-tuning of this research strategy (e.g., by using more specific promoters or by translating this strategy to other crops such as maize) might lead to transgenic bio-energy crops with cell walls more amenable to deconstruction without settling in yield.

Hippoboscid flies, also known as louse flies, are obligate blood-feeders ectoparasites of birds and mammals. By studying louse fly parasites of four Passeriformes species, Eurasian blackbird (Turdus merula), Eurasian blackcap (Sylvia atricapilla), common chaffinch (Fringilla coelebs) and European robin (Erithacus rubecula), with dissimilar time of colonization of Azores islands, we tested whether: (i) island host populations have lower parasite richness than the mainland one; (ii) island host populations undergo higher parasite prevalence, mean intensities and mean abundance than the mainland one; (iii) island parasite diversity are composed exclusively by specific parasites and (iv) parasite richness is positively correlated with the island area and proximity to the continent. For these purposes, 775 birds were sampled for presence of louse flies, by modified fumigation chamber method, from Azores Islands (São Miguel, Terceira and Flores) and Portugal mainland. Insular and mainland parasite assemblages were statistically compared. We record for the first time to Azores, Ornithomya fringillina and Icosta minor from Portugal mainland. Louse flies had highest prevalence and abundance from Azores Islands compared to those observed in mainland birds, especially blackbirds. The insular parasite diversity of Azores blackbirds, blackcaps and chaffinches was richer than the one observed in mainland population. None of the hippoboscid flies observed on the islands and mainland were host-specific. Thus, our findings provide an upgrade of parasite island syndromes knowledge, in the context of the ectoparasites, namely to the hippoboscid flies case.

Abstract Background This study assessed the extent to which persistent differences in self-rated health (SRH) between older immigrants and natives are attributable to negative and positive ageing perceptions. Methods The study was conducted with three population groups in Rotterdam, the Netherlands: native Dutch people aged ≥70 years (n = 1150), Turkish immigrants aged ≥65 years (n = 680) and Moroccan immigrants aged ≥65 years (n = 292). To assess participants’ internal ageing representations, we used the short Aging Perceptions Questionnaire, which distinguishes negative (consequences, chronic and cyclical timeline awareness, and emotional representations) and positive (positive consequences, positive and negative control) dimensions and has been validated in native and immigrant populations. We analysed differences in ageing perceptions between immigrants and natives and the associations of ageing perceptions with SRH. We used Karlson–Holm–Breen decomposition to assess ageing perceptions’ mediation of the relationship between migration background and SRH. Results Older immigrants had stronger negative and weaker positive ageing perceptions (excepting the positive consequences of ageing) than did Dutch natives. Ageing perceptions mediated the relationship between migration background and SRH. SRH differences between Turkish immigrants and native Dutch older persons were explained mainly by differences in negative consequences and cyclical timeline awareness. SRH differences between Moroccan immigrants and native Dutch older persons were attributable mainly to differences in negative consequences and positive control. Conclusions Differences in positive and negative ageing perceptions between older immigrants and natives in the Netherlands largely explained SRH differences between these population groups.

The technical feasibility and diagnostic potential of angiographic flat-detector perfusion imaging technique, combining digital subtraction angiography with a flat-detector computed tomography steady-state perfusion imaging, was explored in patients treated with direct or indirect revascularization surgery. This short communication is about an imaging modality with great potential for evaluation, comparison and grading of vascular perfusion territory areas and anatomical location selectively perfused by direct and indirect cerebral bypasses.

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With growing concern on climate change, widespread adoption of electric vehicles (EVs) is important. One of the main barriers to EV acceptance is range anxiety, which can be alleviated by fast charging (FC). The main technology constraints for enabling FC consist of high-charging-rate batteries, high-power-charging infrastructure, and grid impacts. Although these technical aspects have been studied in literature individually, there is no comprehensive review on FC involving all the perspectives. Moreover, the power quality (PQ) problems of fast charging stations (FCSs) and the mitigation of these problems are not clearly summarized in the literature. In this paper, the state-of-the-art technology, standards for FC (CHAdeMO, GB/T, CCS, and Tesla), power quality issues, IEEE and IEC PQ standards, and mitigation measures of FCSs are systematically reviewed.

Today's agriculture faces many concerns in maintaining crop yield while adapting to climate change and transitioning to more sustainable cultivation practices. The application of plant biostimulants (PBs) is one of the methods that step forward to address these challenges. The advantages of PBs have been reported numerous times. Yet, there is a general lack of quantitative assessment of the overall impact of PBs on crop production. Here we report a comprehensive meta-analysis on biostimulants (focus on non-microbial PBs) of over one thousand pairs of open-field data in a total of 180 qualified studies worldwide. Yield gains in open-field cultivation upon biostimulant application were compared across different parameters: biostimulant category, application method, crop species, climate condition, and soil property. The overall results showed that (1) the add-on yield benefit among all biostimulant categories is on average 17.9% and reached the highest potential via soil treatment; (2) biostimulant applied in arid climates and vegetable cultivation had the highest impact on crop yield; and (3) biostimulants were more efficient in low soil organic matter content, non-neutral, saline, nutrient-insufficient, and sandy soils. This systematic review provides general biostimulant application guidelines and gives consultants and growers insights into achieving an optimal benefit from biostimulant application.

The World Health Organisation has urged all governments to address rising rates of obesity by implementing population-based interventions, such as restrictions on the marketing to children of unhealthy food and beverage items. However, the relationship between unhealthy food advertisements and childhood obesity is disputed by industry-sponsored reports, which recommend promoting physical activity and weight loss campaigns rather than policies to limit exposure to advertisements. We aimed to elucidate this debate by providing a narrative review of the evidence on the relationship between unhealthy TV and online food advertisements, short-term food consumption and childhood obesity. We also examined the impact of unhealthy food advertisements on vulnerable groups and identified which policy interventions are supported by current evidence.We conducted a rapid overview of reviews published since 2006. From a synthesis of 18 reviews meeting the inclusion criteria, we conclude that exposure to unhealthy TV and online food advertising is a contributing factor to childhood obesity. Evidence of a relationship between exposure to unhealthy food advertisements and childhood obesity was evident at all stages of the causal pathway, including a clear dose-response relationship. The evidence base was particularly strong for children aged 3–12 years of age and for children from socio-economically disadvantaged and minority ethnic backgrounds.The introduction of statutory regulation is a potentially cost-effective policy option, in terms of healthcare savings outweighing the costs of implementing the policy, although voluntary codes were shown to be ineffective, with exposure to unhealthy food advertisements similar in countries before and after their introduction. Food advertising, however, is just one factor in the wider obesogenic environment and further advertising restrictions must be implemented alongside population-based interventions that aim to address systemic causes of poor diet.

Background The current study aimed to prospectively assess bodyweight change following the implementation of lockdown measures to contain the COVID-19 pandemic in the Netherlands and to explore the potentially moderating role of gender in this association.Design Using Dutch DNB Household Survey panel data collected between 1993 and 2020, we estimated fixed-effects regression models of bodyweight change. Models were stratified by gender and formal tests of gender differences in coefficient estimates were performed.Participants 4365 women and 4583 men aged 18–65 were included in the study. The total number of observations was 41 330.Outcome measures The outcome of interest was self-reported bodyweight in kilograms. Additional analyses were performed using body mass index (self-reported weight in kilograms divided by self-reported height in metres squared) as the outcome.Results The implementation of Dutch lockdown measures in 2020 was associated with bodyweight gain of approximately 800 g in working-age women compared with the 3 prior years. Bodyweight gain in 2020 relative to the prior years was significantly stronger for women than for men (F(4, 8947)=3.9, p

The Free Energy Principle (FEP) postulates that biological agents perceive and interact with their environment in order to minimize a Variational Free Energy (VFE) with respect to a generative model of their environment. The inference of a policy (future control sequence) according to the FEP is known as Active Inference (AIF). The AIF literature describes multiple VFE objectives for policy planning that lead to epistemic (information-seeking) behavior. However, most objectives have limited modeling flexibility. This paper approaches epistemic behavior from a constrained Bethe Free Energy (CBFE) perspective. Crucially, variational optimization of the CBFE can be expressed in terms of message passing on free-form generative models. The key intuition behind the CBFE is that we impose a point-mass constraint on predicted outcomes, which explicitly encodes the assumption that the agent will make observations in the future. We interpret the CBFE objective in terms of its constituent behavioral drives. We then illustrate resulting behavior of the CBFE by planning and interacting with a simulated T-maze environment. Simulations for the T-maze task illustrate how the CBFE agent exhibits an epistemic drive, and actively plans ahead to account for the impact of predicted outcomes. Compared to an EFE agent, the CBFE agent incurs expected reward in significantly more environmental scenarios. We conclude that CBFE optimization by message passing suggests a general mechanism for epistemic-aware AIF in free-form generative models.

Progressively, more dredged sediments are being reused for engineering projects. For example, the Marker Wadden is a new wetland constructed in lake Markermeer, the Netherlands, with dredged cohesive sediments originating from the bed of the lake. Such dredged sediments are often dominated by cohesive sediment particles with varying amounts of sand and organic matter. In addition, during and after the construction process, the material consolidates and is often compressed from a very loose state into a significantly denser condition. To assess the mechanical behavior of this material, the compressibility of the Markermeer dredged sediment samples with various sand and organic matter contents was analyzed with incremental loading oedometer tests, whereas the undrained shear strength was studied using the fall cone test. The behavior was theoretically analyzed assuming a fractal structure of the sediment and applying power law constitutive equations for effective stress, hydraulic conductivity, and undrained shear strength. These constitutive equations, usually used at low initial sediment densities, worked well at the relatively high initial densities studied and proved to be a useful tool to identify the transition fines content TFC. The constitutive equations were put in context with indicators traditionally used in soil mechanics. Samples, each with an identical composition of the fines fraction (particles< 63 μm), but with a sand content varying from 9 to 40%, showed the same compressibility and undrained shear strength behavior when considering the sand a filler material. For a natural sand content of 70%, the behavior was dominated by sand. The organic matter oxidation was observed to drastically decrease the compressibility and the shear strength, and even to decrease the amount of sand needed to exhibit sand-dominated behavior, showing the importance of the reactivity or state of organic matter on the TFC.