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This open access book explores how medieval societies conversed about the city and citizen in texts, visual imagery and material culture. It adopts a long-term, interdisciplinary, and cross-cultural perspective, bringing together contributions on the early, high, and later Middle Ages, covering both the medieval East and West, and representing a wide variety of disciplinary angles and sources. The volume is first and foremost about medieval perceptions and their articulation in text, image and material form. The principal focus is not on cities or citizenship per se, but on those who used such concepts, wrote about them, and visualized and depicted them. At the same time, the book seeks to address why the city remained such a salient concept also in non-urban contexts – the periphery, the desert, the monastery – and how medieval thinking on the ideal city and civic community could involve denunciation of the earthly city and its institutional trappings. It thus pushes scholarly boundaries, but also seeks to escape deeply entrenched notions of citizenship as either a form of political participation or legal status.

Active learning can be used for optimizing and speeding up the screening phase of systematic reviews. Running simulation studies mimicking the screening process can be used to test the performance of different machine-learning models or to study the impact of different training data. This paper presents an architecture design with a multiprocessing computational strategy for running many such simulation studies in parallel, using the ASReview Makita workflow generator and Kubernetes software for deployment with cloud technologies. We provide a technical explanation of the proposed cloud architecture and its usage. In addition to that, we conducted 1140 simulations investigating the computational time using various numbers of CPUs and RAM settings. Our analysis demonstrates the degree to which simulations can be accelerated with multiprocessing computing usage. The parallel computation strategy and the architecture design that was developed in the present paper can contribute to future research with more optimal simulation time and, at the same time, ensure the safe completion of the needed processes.

Background: Drug repurposing (DR) refers to the practice of identifying new uses for existing drugs. This practice has the potential to provide a faster and less costly alternative to traditional de novo drug development. Despite the advantages, the adoption of DR by product developers is limited. Objective: The aim of this study was to identify the barriers and possible solution pathways for the repurposing of off-patent drugs, primarily within the context of the Dutch healthcare system. Method: Qualitative semi-structured interviews were conducted with a diverse group of stakeholders (e.g., experts in the field of drug regulation, health technology assessment, the pharmaceutical industry, clinical practice, and academic research) in the Netherlands between July 2023 and October 2023. Thematic analysis was used, building on verbatim transcripts. Results: Eleven stakeholders were interviewed. In general, interviewees emphasized the necessity for effective methods, strategies, and incentives to overcome overarching challenge that was identified: the lack of an adequate business case for product developers to invest in the repurposing of off-patent drugs. Significant barriers that were identified include costs and complexities of research, limited additional data exclusivity and market protection granted to marketing authorization holders, and limited outpatient reimbursement across various European member states for off-patent repurposed drugs. Identified potential solution pathways include facilitating partnerships between academia and industry, modifying fee structures for regulatory procedures, prolonging market and data exclusivity periods, intensifying the enforcement of second-medical use patents, and revising pricing and reimbursement models for off-patent repurposed drugs. Conclusion: The overarching challenge is the lack of an adequate business case for product developers to invest in the repurposing of off-patent drugs, due to multiple barriers across the d

Introduction: Pediatric open globe injuries are an important cause of non-congenital monocular visual acuity loss in children. In young children, who are still in their visual development, amblyopia is of great concern. Predicting the final visual outcome is important for proper counselling and management. The aim of this retrospective study is to investigate the epidemiology, aetiology, and the final visual acuity of traumatic open-globe injuries in children in a tertiary referral centre in the Netherlands. Secondly, potential factors for a poor final vision will be examined. Design: Retrospective cohort study Methods: Medical data of 45 children with open globe injuries who visited the UMC Utrecht between 2000 and 2021 where reviewed. Data was analysed and compared between patients with a final vision of ≥6/12 and patients with a final vision <6/12. Also, children in the amblyopic age group were analysed separately. Results: The median age was 7.5 years (range:1.5-18). Metal was the most prevalent type of material (36%). Involvement of the lens, iris and vitreous body were found to significant for a final vision of <6/12 (p=0.015, p=0.022, p=0.008). Endophthalmitis occurred in only one (2%) eye and a total of four (9%) eyes became non-functional. The most frequent secondary development were astigmatism (80%), and traumatic cataract (67%). A total of 22 (49%) eyes had a vision >6/12 of which 11 (55%) were of amblyopic age at trauma. The lens status showed to be significantly associated with the visual outcome (p=0.012). Conclusion: Our study is the first to explore pediatric open globe injuries in the Netherlands. The nature of the trauma and the anatomical structures involved have a major influence on the final vision. In addition, the preservation of one’s own lens makes for a better visual prognosis. About half of the children end up with a vision of less than 6/12, larger prospective research is needed. So that ultimately fewer children are left with an impaire

Senescent cells have detrimental effects on their tissue micro-environment and contribute to various diseases through the secretion of a the senescent-associated secretory phenotype (SASP). The composition of SASP varies based on cell types, senescence induction methods, and senescence types, complicating the understanding of its formation. Nevertheless, the SASP can be organized into a Core SASP, an NFkB- and P21-arm, a mitochondrion disfunction associated SASP (MIDAS) and P-21 associated secretory phenotype (PASP). The most common and consistently found SASP factors form a Core SASP. SASP has a distinct pro-inflammatory NFkB arm and a P21 regulated arm. MIDAS results from mitochondrial dysfunction during senescence, characterized by the conditional absence of an IL-1 cytokine arm and the presence of CCL27. PASP, activated through p21, is marked by the presence of CXCL14 and IL34. Post-translational modifications to high mobility group box 1 (HMGB1), particularly acetylation and oxidation, play a crucial role in regulating different SASP phenotypes. Acetylation is necessary for HMGB1 to interact with NF-kB and p53 leading secretion of the broad/core SASP. Oxidation induces PASP, and excessive acetylation leads to a pro-inflammatory MIDAS containing IL1. Focusing on Core SASP factors and differentiating between SASP phenotypes can expedite the identification of these phenotypes and uncover the underlying mechanisms, potentially aiding in the development of new therapeutic solutions for many diseases.

Contains fulltext : 305145.pdf (Publisher’s version ) (Open Access), To inform future Dutch COVID-19 testing policies we did an experimental vignette study to investigate whether inclusion of the less reliable lateral flow tests (self-tests) would change test-uptake sufficiently to improve population-level test sensitivity. A representative sample (n = 3,270) participated in a 2-by-2 online experiment to evaluate the effects of test-guidelines including self-testing advice (IV1), and the effects of self-test availability (IV2) on expected test uptake (PCR test, self-test or no test) and sensitivity of the overall test strategy (primary outcome). Across four scenarios, changing test advice did not affect expected testing behaviour. Self-test availability, however, increased the timeliness of testing, the number of people testing, and overall test strategy sensitivity. Based on these findings, we recommend that (national) policy facilitates a supply of self-tests at home, for example through free and pro-active distribution of test-kits during a pandemic. This could substantially enhance the chances of timely detecting and isolating patients.

SARS-CoV-2 prevention and control measures did not only impact SARS-CoV-2 circulation, but also the timing and prevalence of other seasonal respiratory viruses. Especially in children, information on exposure and infections to seasonal coronaviruses as well as SARS-CoV-2 in the first year of the pandemic is largely lacking. Therefore, we set up a one-year serological survey in a large tertiary hospital in the Netherlands. We show that seasonal coronavirus seroprevalence significantly decreased in 2021 in children less than one year, most likely due to COVID-19 control measures. The SARS-CoV-2 seroprevalence in children and adolescents increased from 0.4% to 11.3%, the highest in adolescents. This implies higher exposure rates in adolescents as compared to the general population (>18 years old). It is clear that there have been significant changes in the circulation and subsequent immunity against most respiratory pathogens as a result of the mitigation measures. The implications on shorter as well as longer term are still largely unknown, but the impact of the SARS-CoV-2 pandemic and subsequent control measures will continue to affect the dynamics of other pathogens.

Item does not contain fulltext, BACKGROUND: COVID-19 mitigation measures intend to protect public health, but their adverse psychological, social, and economic effects weaken public support. Less favorable trade-offs may especially weaken support for more restrictive measures. Support for mitigation measures may also differ between population subgroups who experience different benefits and costs, and decrease over time, a phenomenon termed "pandemic fatigue." METHODS: We examined self-reported support for COVID-19 mitigation measures in the Netherlands over 12 consecutives waves of data collection between April 2020 and May 2021 in an open population cohort study. Participants were recruited through community panels of the 25 regional public health services, and through links to the online surveys advertised on social media. The 54,010 unique participants in the cohort study on average participated in 4 waves of data collection. Most participants were female (65%), middle-aged [57% (40-69 years)], highly educated (57%), not living alone (84%), residing in an urban area (60%), and born in the Netherlands (95%). RESULTS: COVID-19 mitigation measures implemented in the Netherlands remained generally well-supported over time [all scores >3 on 5-point scale ranging 1 (low)-5 (high)]. During the whole period studied, support was highest for personal hygiene measures, quarantine and wearing face masks, high but somewhat lower for not shaking hands, testing and self-isolation, and restricting social contacts, and lowest for limiting visitors at home, and not traveling abroad. Women and higher educated people were more supportive of some mitigation measures than men and lower educated people. Older people were more supportive of more restrictive measures than younger people, and support for more socially restrictive measures decreased most over time in higher educated people or in younger people. CONCLUSIONS: This study found no support for pandemic fatigue in terms of a gradual decline in support for all

Item does not contain fulltext, OBJECTIVES: To assess the proportion of clinically significant (cs) prostate cancer (PCa) found during follow-up in patients with negative systematic biopsy (SB) followed by non-suspicious multiparametric magnetic resonance imaging (mpMRI) and persistent clinical suspicion of PCa compared to the general population. PATIENTS AND METHODS: A prospective study in a subgroup of patients from a multicentre randomized controlled trial was conducted between 2014 and 2017, including 665 men with prior negative SB with a persistent elevated prostate-specific antigen and/or suspicious digital rectal examination undergoing mpMRI. All patients with negative SB and Prostate Imaging-Reporting and Data System (PI-RADS) ≤2 on mpMRI entered biochemical follow-up. Follow-up data until December 2021 were collected by reviewing institutional hospital records and the Dutch Pathology Registry (PALGA). The primary outcome was the observed number of csPCa (Gleason ≥3 + 4/International Society of Urological Pathology grade group ≥2) cases during follow-up compared to the expected number in the general population (standardized incidence ratio [SIR]). RESULTS: In total, 431 patients had non-suspicious mpMRI and entered biochemical follow-up. After a median (interquartile range) follow-up of 41 (23-57) months, 38 patients were diagnosed with PCa, of whom 13 (3.0%) had csPCa. The SIR for csPCa was 4.3 (95% confidence interval 2.3-7.4; total excess of eight cases). A higher risk of a positive biopsy for (cs)PCa based on the European Randomized Study of Screening for Prostate Cancer risk calculator and a suspicious repeat MRI (PI-RADS ≥3) were significant predictive factors for csPCa. CONCLUSION: After negative prior biopsy and non-suspicious mpMRI the risk of csPCa is low. However, compared to the general population, the risk of csPCa is increased despite the high negative predictive value of mpMRI. More research focusing on biochemical and image-guided risk-adapted diagnostic surveillance strate

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Item does not contain fulltext, We investigated the determinants of daily PrEP use and coverage of condomless anal sex (CAS) by PrEP among men who have sex with men in Wales, UK. We measured PrEP use by electronic monitors and CAS by secure online surveys. We defined PrEP use based on daily medication cap openings and coverage as CAS episodes preceded by ≥ 3 days of PrEP use and followed by ≥ 2 days of PrEP use. We included 57 participants (5463 observations). An STI diagnosis was associated with lower PrEP use but also lower PrEP coverage. Older adults had higher PrEP use. A belief that other PrEP users took PrEP as prescribed was associated with lower PrEP coverage. An STI diagnosis is an important cue for an intervention, reflecting episodes of high-risk sexual behaviour and low PrEP coverage. Other results provide a basis for the development of an evidence-informed intervention for promoting coverage of PrEP.

Item does not contain fulltext, STUDY QUESTION: What is the evidence for over-the-counter antioxidant supplements for male infertility? SUMMARY ANSWER: Less than half of over-the-counter antioxidant supplements for male fertility patients have been tested in a clinical trial, and the available clinical trials are generally of poor quality. WHAT IS KNOWN ALREADY: The prevalence of male infertility is rising and, with this, the market for supplements claiming to improve male fertility is expanding. Up to now, there is limited data on the evidence for these over-the-counter supplements. STUDY DESIGN SIZE DURATION: Amazon, Google Shopping and other relevant shopping websites were searched on 24 June 2022 with the following terms: 'supplements', 'antioxidants', 'vitamins', AND 'male fertility', 'male infertility', 'male subfertility', 'fertility men', 'fertility man'. All supplements with a description of ingredients in English, Dutch, French, Spanish, or German were included. Subsequently, Pubmed and Google Scholar were searched for studies that included the supplements. PARTICIPANTS/MATERIALS SETTING METHODS: Inclusion criteria were supplements with antioxidant properties, of which the main purpose was to improve male fertility. Included supplements must be available without a doctor's prescription. Supplements containing plant extracts were excluded, as well as supplements of which the content or dosage was not clear. The ingredients, dosage, price and health claims of the supplements were recorded. We assessed whether substances in the supplements exceeded the recommended dietary allowance (RDA) or tolerable upper intake level (UL). All clinical trials and animal studies investigating included supplements were selected for this review. Clinical trials were assessed for risk of bias with a risk of bias tool appropriate for the study design. MAIN RESULTS AND THE ROLE OF CHANCE: There were 34 eligible antioxidant supplements found, containing 48 different active substances. The average price per 30 da

01 juli 2023, Item does not contain fulltext, Stigma may influence the use of HIV pre-exposure prophylaxis (PrEP). However, there is an absence of robust measures for PrEP-related stigma. We describe an adaptation of a HIV stigma scale for use in PrEP users and experiences of PrEP users in Wales (UK) with regards to PrEP-related stigma. A mixed methods study was conducted where PrEP users completed questionnaire items about PrEP-related stigma and a subset were interviewed about their experiences of taking PrEP. We adapted items from the HIV stigma scale and assessed construct validity and internal consistency. We analysed interview data using a framework approach, with themes focussing on enacted and anticipated stigma in order to identify areas for scale refinement. Our measure had good psychometric properties but additional items may be useful (e.g. specific instances of enacted stigma, concerns around homonegativity). Further work is needed to develop this scale and validate it in a larger sample.

Item does not contain fulltext, To meet surge capacity and to prevent hospitals from being overwhelmed with COVID-19 patients, a regional crisis task force was established during the first pandemic wave to coordinate the even distribution of COVID-19 patients in the Amsterdam region. Based on a preexisting regional management framework for acute care, this task force was led by physicians experienced in managing mass casualty incidents. A collaborative framework consisting of the regional task force, the national task force, and the region's hospital crisis coordinators facilitated intraregional and interregional patient transfers. After hospital admission rates declined following the first COVID-19 wave, a window of opportunity enabled the task forces to create, standardize, and optimize their patient transfer processes before a potential second wave commenced. Improvement was prioritized according to 3 crucial pillars: process standardization, implementation of new strategies, and continuous evaluation of the decision tree. Implementing the novel "fair share" model as a straightforward patient distribution directive supported the regional task force's decisionmaking. Standardization of the digital patient transfer registration process contributed to a uniform, structured system in which every patient transfer was verifiable on intraregional and interregional levels. Furthermore, the regional task force team was optimized and evaluation meetings were standardized. Lines of communication were enhanced, resulting in increased situational awareness among all stakeholders that indirectly provided a safety net and an improved integral framework for managing COVID-19 care capacities. In this article, we describe enhancements to a patient transfer framework that can serve as an exemplary system to meet surge capacity demands during current and future pandemics.