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OBJECTIVE: Endoscopic mucosal resection (EMR) is the preferred treatment for non-invasive large (=20?mm) non-pedunculated colorectal polyps (LNPCPs) but is associated with an early recurrence rate of up to 30%. We evaluated whether standardised EMR training could reduce recurrence rates in Dutch community hospitals. DESIGN: In this multicentre cluster randomised trial, 59 endoscopists from 30 hospitals were randomly assigned to the intervention group (e-learning and 2-day training including hands-on session) or control group. From April 2019 to August 2021, all consecutive EMR-treated LNPCPs were included. Primary endpoint was recurrence rate after 6 months. RESULTS: A total of 1412 LNPCPs were included; 699 in the intervention group and 713 in the control group (median size 30 mm vs 30 mm, 45% vs 52% size, morphology, site and access (SMSA) score IV, 64% vs 64% proximal location). Recurrence rates were lower in the intervention group compared with controls (13% vs 25%, OR 0.43; 95% CI 0.23 to 0.78; p=0.005) with similar complication rates (8% vs 9%, OR 0.93; 95% CI 0.64 to 1.36; p=0.720). Recurrences were more often unifocal in the intervention group (92% vs 76%; p=0.006). In sensitivity analysis, the benefit of the intervention on recurrence rate was only observed in the 20-40?mm LNPCPs (5% vs 20% in 20-29?mm, p=0.001; 10% vs 21% in 30-39?mm, p=0.013) but less evident in =40?mm LNPCPs (24% vs 31%; p=0.151). In a post hoc analysis, the training effect was maintained in the study group, while in the control group the recurrence rate remained high. CONCLUSION: A compact standardised EMR training for LNPCPs significantly reduced recurrences in community hospitals. This strongly argues for a national dedicated training programme for endoscopists performing EMR of =20?mm LNPCPs. Interestingly, in sensitivity analysis, this benefit was limited for LNPCPs =40?mm. TRIAL REGISTRATION NUMBER: NTR7477.

Purpose of review:In an attempt to reduce waiting list mortality in liver transplantation, less-than-ideal quality donor livers from extended criteria donors are increasingly accepted. Predicting the outcome of these organs remains a challenge. Machine perfusion provides the unique possibility to assess donor liver viability pretransplantation and predict postreperfusion organ function. Recent findings: Assessing liver viability during hypothermic machine perfusion remains challenging, as the liver is not metabolically active. Nevertheless, the levels of flavin mononucleotide, transaminases, lactate dehydrogenase, glucose and pH in the perfusate have proven to be predictors of liver viability. During normothermic machine perfusion, the liver is metabolically active and in addition to the perfusate levels of pH, transaminases, glucose and lactate, the production of bile is a crucial criterion for hepatocyte viability. Cholangiocyte viability can be determined by analyzing bile composition. The differences between perfusate and bile levels of pH, bicarbonate and glucose are good predictors of freedom from ischemic cholangiopathy. Summary:Although consensus is lacking regarding precise cut-off values during machine perfusion, there is general consensus on the importance of evaluating both hepatocyte and cholangiocyte compartments. The challenge is to reach consensus for increased organ utilization, while at the same time pushing the boundaries by expanding the possibilities for viability testing.

Acute myeloid leukemia (AML) driven by the activation of EVI1 due to chromosome 3q26/MECOM rearrangements is incurable. Because transcription factors such as EVI1 are notoriously hard to target, insight into the mechanism by which EVI1 drives myeloid transformation could provide alternative avenues for therapy. Applying protein folding predictions combined with proteomics technologies, we demonstrate that interaction of EVI1 with CTBP1 and CTBP2 via a single PLDLS motif is indispensable for leukemic transformation. A 4× PLDLS repeat construct outcompetes binding of EVI1 to CTBP1 and CTBP2 and inhibits proliferation of 3q26/MECOM rearranged AML in vitro and in xenotransplant models. This proof-of-concept study opens the possibility to target one of the most incurable forms of AML with specific EVI1-CTBP inhibitors. This has important implications for other tumor types with aberrant expression of EVI1 and for cancers transformed by different CTBP-dependent oncogenic transcription factors.

Industrial food processing and its possible adverse effects on health are widely debated in scientific literature and media. There is not much known about consumers’ attitudes towards the processing of foods. Therefore, a questionnaire (n = 463) was distributed and interviews (n = 11) were conducted with Dutch consumers to evaluate the attitudes and associations towards industrial food processing and to assess opinions about communications on food processing and health. The results showed that 51% of the respondents had a neutral, 23% had a positive, and 26% had a negative attitude towards food processing. Respondents with a background in food by profession or education (n = 159) had more frequently a positive attitude towards food processing (P = 0.008). Respondents and interviewees pointed out both positive and negative associations with industrial processing: additives, artificial, not fresh, low nutritional value, unnatural, but also palatability, food safety, shelf life, and convenience. The questionnaire showed that 70% of the respondents thought food processing had a (slightly) negative health effect. Most interviewees indicated that when doing groceries, food processing per se is not relevant in food choices, although some critically inspected the ingredients. Furthermore, interviewees indicated that communication about food and health is scattered and complex. They would like to gain easy and straightforward information from a central source. From the questionnaire respondents, 60% indicated that they would like to have more information about food processing. In conclusion, most Dutch consumers in this study have a neutral and nuanced attitude towards industrial food processing. A connection with food via profession or education showed a more positive attitude, which may indicate the importance of knowledge and the need for clear communication about nutrition, ingredients, and food processing.

This randomized, double-blind, placebo-controlled trial investigated the impact of 14-day Anaerobutyricum soehngenii L2-7 supplementation on postprandial glucose levels in 25 White Dutch males with type 2 diabetes (T2D) on stable metformin therapy. The primary endpoint was the effect of A. soehngenii versus placebo on glucose excursions and variability as determined by continuous glucose monitoring. Secondary endpoints were changes in ambulatory 24-h blood pressure, incretins, circulating metabolites and excursions of plasma short-chain fatty acids (SCFAs) and bile acids upon a standardized meal. Results showed that A. soehngenii supplementation for 14 days significantly improved glycemic variability and mean arterial blood pressure, without notable changes in SCFAs, bile acids, incretin levels, or anthropometric parameters as compared to placebo-treated controls. Although well-tolerated and effective in improving glycemic control in the intervention group, further research in larger and more diverse populations is needed to generalize these findings.

Gene expression can be highly plastic in response to environmental variation. However, we know little about how expression plasticity is shaped by natural selection and evolves in wild and domesticated species. We used genotypic selection analysis to characterize selection on drought-induced plasticity of over 7,500 leaf transcripts of 118 rice accessions (genotypes) from different environmental conditions grown in a field experiment. Gene expression plasticity was neutral for most gradually plastic transcripts, but transcripts with discrete patterns of expression showed stronger selection on expression plasticity. Whether plasticity was adaptive and co-gradient or maladaptive and counter-gradient varied among varietal groups. No transcripts that experienced selection for plasticity across environments showed selection against plasticity within environments, indicating a lack of evidence for costs of adaptive plasticity that may constrain its evolution. Selection on expression plasticity was influenced by degree of plasticity, transcript length and gene body methylation. We observed positive selection on plasticity of co-expression modules containing transcripts involved in photosynthesis, translation and responsiveness to abiotic stress. Taken together, these results indicate that patterns of selection on expression plasticity were context-dependent and likely associated with environmental conditions of varietal groups, but that the evolution of adaptive plasticity would likely not be constrained by opposing patterns of selection on plasticity within compared to across environments. These results offer a genome-wide view of patterns of selection and ecological constraints on gene expression plasticity and provide insights into the interplay between plastic and evolutionary responses to drought at the molecular level.

With Active Learning becoming more used in the context of data streams, there is also an increasing need to have an algorithm appropriate for this setting. As such, the active learner must be able to handle the challenges that arise in data stream-based settings. This research aims to determine if an optimal Active Learning algorithm can detect changes unsupervised, assess its performance, and be representative of the distribution of the data stream. When combined, a trade-off in the weighting of the different components also needs to be considered This master’s thesis proposes an active learning algorithm named IDEAL. IDEAL aims to operate in an evolving data stream where changes happen continuously based on three components. IDEAL aims to do this by Integrating the Detection of changes, Exploration of instance space, and Assessment of performance into Active Learning. One synthetic data set and three real-world benchmark datasets have been used to evaluate the performance of IDEAL. IDEAL performed quite well, but it was not the most accurate Active Learning algorithm. For future research, IDEAL is a good baseline for making a better Active Learning algorithm. The components’ weightings are scalable, and the option to add more or fewer components makes it easy to adjust the algorithm. More research into either the weightings between the three components or the Change Detector and Explorer components of IDEAL would be good.

Item does not contain fulltext, PURPOSE: The FLAME trial (NCT01168479) showed that isotoxic focal boosting to the intraprostatic lesion(s) in patients with intermediate- and high-risk prostate cancer improves 5-year disease-free survival (DFS). Although the near-minimum dose to the gross tumor volume (D98%) was associated with improved outcomes, a closer look suggested that this might not be the same for all patients. Therefore, we investigated whether risk factors that are associated with a benefit of focal boosting can be identified. METHODS AND MATERIALS: We described the distribution of clinical characteristics and the number of high-risk factors with respect to the D98% in 526 FLAME trial patients. We used penalized Cox regression to develop a prediction model. To investigate a potential benefit in patient subgroups, we compared the model-based predictions of 5-year DFS assuming standard whole-gland radiation therapy of 77 Gy to the predictions assuming an additional focal boost with D98% of 95 Gy. RESULTS: Patients with high-risk factors were well represented in the group of 120 patients that received D98% > 85 Gy and showed fewer recurrences compared with the group that received 77 Gy. Applying the model simulating a standard dose of 77 Gy, we predicted a high DFS for grade group (GG) 1 patients, whereas patients with high-risk characteristics appeared to show a low DFS. All risk groups showed a high level of DFS when simulating D98% of 95 Gy. CONCLUSIONS: Our results suggest that GG 1 patients already show a low level of failure at a standard dose of 77 Gy, limiting the additional benefit of focal boosting. In contrast, patients with high-risk characteristics, especially GG 4 or 5, show a low 5-year DFS, while focal boosting might improve this substantially. This suggests that reaching a high focal boost dose may be particularly beneficial for these patients.

EntreCompEdu is a professional development framework for educators, designed as a complement to the European Commission’s Entrepreneurship Competence Framework (EntreComp). The purpose of this chapter is to reflect upon EntreCompEdu’s potential to stimulate teachers’ entrepreneurial thinking and activity. The chapter is structured in three main sections. The first describe the policy context and the gap in teacher education that EntreCompEdu seeks to address. The second offers an overview of the framework’s main components. The third reflects on the pilot phase of implementation, focusing on two case studies to illustrate the factors that influence EntreCompEdu’s impact and future direction. The reflections are those of the lead author of EntreCompEdu, three of those who facilitated the professional development sessions and the project manager. We follow Borton’s ‘(1970) simple ‘What? So What? and Now What?’ model to shape our reflections. Our subjective narratives are based on specific professional experiences as we critically reflect on the framework’s implementation within the context of Covid-19 and other challenges associated with transnational projects. We conclude that EntreCompEdu can stimulate teachers’ entrepreneurial thinking, although its sustainability in school is contingent on a range of individual and organisational factors discussed.

Previous research indicated a need to improve pilot training with regard to understanding of autopilot logic and behavior, especially in non-routine situations. Therefore, we tested the effect of problem-based exploratory training on pilots’ understanding of autopilot functions. Using a moving-base flight simulator, general aviation pilots (n = 45) were trained to diagnose failures either without foreknowledge and guidance (exploratory group), without foreknowledge but with some guidance (exploratory-guidance group) or with foreknowledge and full guidance (control group). They subsequently performed six test scenarios in which their understanding of the effects of failures was tested by requiring them to deduce the failures and select autopilot modes that were still functioning. Those who received exploratory training with guidance were significantly more likely than the other groups to diagnose failures correctly. The exploratory training group also selected the most appropriate functioning autopilot modes significantly faster than the control group. The results suggest that exploratory training with an appropriate level of guidance is useful for gaining a practical understanding of autopilot logic and behavior. Exploratory training may help to improve transfer of training to operational practice, and prevent automation surprises and accidents., Control & Simulation, BUS/TNO STAFF

Novel therapies for multiple myeloma (MM) have improved patient survival, but their high costs strain healthcare budgets. End-of-life phases of treatment are generally the most expensive, however, these high costs may be less justifiable in the context of a less pronounced clinical benefit. To manage drug expenses effectively, detailed information on end-of-life drug administration and costs are crucial. In this retrospective study, we analysed treatment sequences and drug costs from 96 MM patients in the Netherlands who died between January 2017 and July 2019. Patients received up to 16 lines of therapy (median overall survival: 56.5 months), with average lifetime costs of €209 871 (€3111/month; range: €3942–€776 185) for anti-MM drugs. About 85% of patients received anti-MM treatment in the last 3 months before death, incurring costs of €20 761 (range: €70–€50 122; 10% of total). Half of the patients received anti-MM treatment in the last 14 days, mainly fully oral regimens (66%). End-of-life treatment costs are substantial despite limited survival benefits. The use of expensive treatment options is expected to increase costs further. These data serve as a reference point for future cost studies, and further research is needed to identify factors predicting the efficacy and clinical benefit of continuing end-of-life therapy.

Optimal treatment of infants with many renally cleared drugs must account for maturational differences in renal transporter (RT) activity. Pediatric physiologically-based pharmacokinetic (PBPK) models may incorporate RT activity, but this requires ontogeny profiles for RT activity in children, especially neonates, to predict drug disposition. Therefore, RT expression measurements from human kidney postmortem cortical tissue samples were normalized to represent a fraction of mature RT activity. Using these data, maximum likelihood estimated the distributions of RT activity across the pediatric age spectrum, including preterm and term neonates. PBPK models of four RT substrates (acyclovir, ciprofloxacin, furosemide, and meropenem) were evaluated with and without ontogeny profiles using average fold error (AFE), absolute average fold error (AAFE), and proportion of observations within the 5-95% prediction interval. Novel maximum likelihood profiles estimated ontogeny distributions for the following RT: OAT1, OAT3, OCT2, P-gp, URAT1, BCRP, MATE1, MRP2, MRP4, and MATE-2 K. Profiles for OAT3, P-gp, and MATE1 improved infant furosemide and neonate meropenem PBPK model AFE from 0.08 to 0.70 and 0.53 to 1.34 and model AAFE from 12.08 to 1.44 and 2.09 to 1.36, respectively, and improved the percent of data within the 5-95% prediction interval from 48% to 98% for neonatal ciprofloxacin simulations, respectively. Even after accounting for other critical population-specific maturational differences, novel RT ontogeny profiles substantially improved neonatal PBPK model performance, providing validated estimates of maturational differences in RT activity for optimal dosing in children.

Objective: We aimed to perform an early cost-effectiveness analysis of using a whole-genome sequencing-based tumor mutation burden (WGS-TMB), instead of programmed death-ligand 1 (PD-L1), for immunotherapy treatment selection in patients with non-squamous advanced/metastatic non-small cell lung cancer ineligible for targeted therapy, from a Dutch healthcare perspective. Methods: A decision-model simulating individual patients with metastatic non-small cell lung cancer was used to evaluate diagnostic strategies to select first-line immunotherapy only or the immunotherapy plus chemotherapy combination. Treatment was selected using PD-L1 [A, current practice], WGS-TMB [B], and both PD-L1 and WGS-TMB [C]. Strategies D, E, and F take into account a patient’s disease burden, in addition to PD-L1, WGS-TMB, and both PD-L1 and WGS-TMB, respectively. Disease burden was defined as a fast-growing tumor, a high number of metastases, and/or weight loss. A threshold of 10 mutations per mega-base was used to classify patients into TMB-high and TMB-low groups. Outcomes were discounted quality-adjusted life-years (QALYs) and healthcare costs measured from the start of first-line treatment to death. Healthcare costs includes drug acquisition, follow-up costs, and molecular diagnostic tests (i.e., standard diagnostic techniques and/or WGS for strategies involving TMB). Results were reported using the net monetary benefit at a willingness-to-pay threshold of €80,000/QALY. Additional scenario and threshold analyses were performed. Results: Strategy B had the lowest QALYs (1.84) and lowest healthcare costs (€120,800). The highest QALYs and healthcare costs were 2.00 and €140,400 in strategy F. In the base-case analysis, strategy A was cost effective with the highest net monetary benefit (€27,300), followed by strategy B (€26,700). Strategy B was cost effective when the cost of WGS testing was decreased by at least 24% or when immunotherapy results in an additional 0.5 year of life gain

In the Western Scheldt Estuary near the Belgian-Dutch border, middle to late Eocene strata crop out at the current seafloor. Most vertebrae of large Eocene basilosaurid taxa from this area were previously described in several papers. They represent three morphotypes: elongated vertebrae of a large species of Pachycetus (Morphotype 1b), a not-elongated vertebra of a large ‘dorudontid’ basilosaurid (Morphotype 2) and ‘shortened’ vertebrae of a new, unnamed taxon (Morphotype 3). This article deals with a still undescribed, smaller vertebra, NMR-16642, from this site. Our first aim was to date it by dinoflagellate cysts in adhering sediments. Yielding an age of about 38 Ma, it is one of the very few remains of basilosaurids from Europe, of which the age could be assessed with reasonable certainty. The vertebra, Morphotype 1a, is assigned to a small species of Pachycetus. High-quality CT scans are used to differentiate between NMR-16642, Morphotype 1a, and the large species of Pachycetus, Morphotype 1b. Another aim of this paper is to investigate the inner structure and vascularity of the study vertebra and that of the other morphotypes (1b, 2, 3) from this area by using high-quality CT scans. Notwithstanding differences in size, shape and compactness, the vertebral inner structure with a multi-layered cortex of periosteal bone, surrounding two cones of endosteal bone appears to be basically similar in all morphotypes. Apparently, this inner structure reflects the ontogenetic vertebral growth. An attempt to reconstruct the vascularity of the vertebrae reveals a remarkable pattern of interconnected vascular systems. From the dorsal and, if present, ventral foramina, vascular canals are running to a central vascular node. From this node a system of vascular canals goes to the epiphyseal ends, giving rise to separate systems for cortex and cones. It is the first time that the vascularity of vertebrae of archaeocetes is investigated.

Spinal muscular atrophy (SMA) is the leading genetic cause of infant mortality, characterized by progressive neuromuscular degeneration resulting from mutations in the survival motor neuron (SMN1) gene. The availability of disease-modifying therapies for SMA therapies highlights the pressing need for easily accessible and cost-effective blood biomarkers to monitor treatment response and for better disease management. Additionally, the wide implementation of newborn genetic screening programs in Western countries enables presymptomatic diagnosis of SMA and immediate treatment administration. However, the absence of monitoring and prognostic blood biomarkers for neurodegeneration in SMA hinders effective disease management. Neurofilament light protein (NfL) is a promising biomarker of neuroaxonal damage in SMA and reflects disease progression in children with SMA undergoing treatment. Recently, the European Medicines Agency issued a letter of support endorsing the potential utilization of NfL as a biomarker of pediatric neurological diseases, including SMA. Within this review, we comprehensively assess the potential applications of NfL as a monitoring biomarker for disease severity and treatment response in pediatric-onset SMA. We provide reference ranges for normal levels of serum based NfL in neurologically healthy children aged 0-18 years. These reference ranges enable accurate interpretation of NfL levels in children and can accelerate the implementation of NfL into clinical practice.

Teclistamab and other B-cell maturation antigen (BCMA)-targeting bispecific antibodies (BsAbs) have substantial activity in patients with heavily pretreated multiple myeloma (MM) but are associated with a high rate of infections. BCMA is also expressed on normal plasma cells and mature B cells, which are essential for the generation of a humoral immune response. The aim of this study was to improve the understanding of the impact of BCMA-targeting BsAbs on humoral immunity. The impact of teclistamab on polyclonal immunoglobulins and B cell counts was evaluated in patients with MM who received onceweekly teclistamab 1.5 mg/kg subcutaneously. Vaccination responses were assessed in a subset of patients. Teclistamabinduced rapid depletion of peripheral blood B cells in patients with MM and eliminated normal plasma cells in ex vivo assays. In addition, teclistamab reduced the levels of polyclonal immunoglobulins (immunoglobulin G [IgG], IgA, IgE, and IgM), without recovery over time while receiving teclistamab therapy. Furthermore, response to vaccines against Streptococcus pneumoniae, Haemophilus influenzae type B, and severe acute respiratory syndrome coronavirus 2 was severely impaired in patients treated with teclistamab compared with vaccination responses observed in patients with newly diagnosed MM or relapsed/refractory MM. Intravenous immunoglobulin (IVIG) use was associated with a significantly lower risk of serious infections among patients treated with teclistamab (cumulative incidence of infections at 6 months: 5.3% with IVIG vs 54.8% with observation only [P < .001]). In conclusion, our data show severe defects in humoral immunity induced by teclistamab, the impact of which can be mitigated by the use of immunoglobulin supplementation. This trial was registered at www.ClinicalTrials.gov as #NCT04557098.

Background and Aims: Although colorectal cancer (CRC) surveillance is embedded in clinical inflammatory bowel disease (IBD) practice, a subset of patients still develops advanced neoplasia (AN) (high-grade dysplasia [HGD] and/or CRC). We aimed to assess the impact of surveillance quality on AN risk in IBD. Methods:In this multicenter case-control study, we searched the Dutch nationwide pathology databank to identify IBD cases with AN and controls with indefinite or low-grade dysplasia. The surveillance colonoscopy preceding the index lesion (first indefinite for dysplasia [IND]/low-grade dysplasia [LGD] or AN) was used to assess the impact of surveillance quality. We assessed intervals, bowel preparation, cecal intubation, and absence of inflammation as primary quality indicators. In addition, we assessed chromoendoscopy, endoscopist expertise, hospital setting, and biopsy strategy. Associations of quality indicators with AN risk were determined with multivariable logistic regression analyses with Firth's correction. Results: We included 137 cases and 138 controls. Delayed intervals (58.2% vs 39.6%) and active inflammation (65.3% vs 41.8%) were frequently present in cases and controls and were associated with AN (delayed interval: adjusted odds ratio [aOR], 2.00; 95% confidence interval [CI], 1.07–3.81; P = .03; active inflammation: aOR, 2.46; 95% CI, 1.33–4.61; P < .01). Surveillance compliant with primary quality indicators was associated with a reduced AN risk (aOR, 0.43; 95% CI, 0.22–0.91; P = .03), similar to chromoendoscopy (OR, 0.11; 95% CI, 0.01–0.89; P = .01). Other indicators were not significantly associated with AN. Conclusions: Surveillance compliant with primary quality indicators is associated with a reduced colitis-associated AN risk. Delayed surveillance intervals and active inflammation were associated with an increased AN risk. This underlines the importance of proc

Voorliggende samenvatting van het milieueffectrapport (MER) voor Kustontwikkeling Eemszijlen geeft een toelichting op het project, hoe de milieueffecten zijn onderzocht en wat de resultaten van de onderzoeken zijn.

Een Tiny Forest is een door de mens ontworpen en aangelegd ‘oerbosje’ ter grootte van een tennisveld, waarin 600 inheemse bomen van minimaal 25 verschillende soorten dicht opeen worden aangeplant zodat ze extra snel omhoog groeien. Het bladerdek zou zich dan binnen drie jaar sluiten. Na tien jaar zou, vanwege die gunstige omstandigheden en het aldus gecreëerde microklimaat, een volgroeid stadsbosje ontstaan. Tiny Forests vormen daarmee unieke en herkenbare minieme mozaïekstukjes in het grotere geheel van het stedelijk groen, het ‘urban forest’. Wat is het gedachtengoed achter deze Tiny Forests en wat is het verschil met een doorsnee bosplantsoen? En wat stelt een Tiny Forest eigenlijk voor in het grotere geheel van het urban forest?

In dit advies: 1. In de Duinen Den Helder-Callantsoog is verslechtering niet uit te sluiten, maar kan door gebrek aan informatie niet worden bepaald of verslechtering reeds is opgetreden. Hierdoor is het onzeker of met bestaande maatregelen de doelen gehaald worden. 2. De instandhoudings- en verbeterdoelen van de habitattypen in de Duinen Den Helder-Callantsoog moeten concreet (SMART) gemaakt worden. 3. Omdat maar een beperkte hoeveelheid gegevens is gebruikt en omdat ook gegevens niet altijd beschikbaar zijn, ontbreekt systeeminzicht. Er dient een volledige en integrale LESA opgesteld te worden om inzicht te verkrijgen in de toestand van het gebied en de ecologische condities die nodig zijn om de instandhoudingsdoelen te bereiken. 4. Om effectiviteit van maatregelen in beeld te brengen, maar ook abiotische gegevens te verzamelen die nu ontbreken, is monitoring benodigd. Het opstellen van een kennisprogramma geeft daarbij invulling aan nog niet opgeloste vraagstukken (leemten in kennis). 5. Maatregelen die snel genomen moeten worden zijn: het verminderen van stikstofbelasting, het bevorderen van verstuivingsdynamiek, op beperkte schaal omvormen naaldbos, (intensiever) bestrijden van exoten en verminderen van de harde scheiding met aangrenzende landbouwgebieden (bufferzones).

In dit advies: 1. In Zwanenwater & Pettemerduinen is verslechtering niet uit te sluiten, maar kan door gebrek aan informatie niet worden bepaald of verslechtering reeds is opgetreden. Hierdoor is het onzeker of met bestaande maatregelen de doelen gehaald worden. 2. Het is noodzakelijk om de instandhoudings- en verbeterdoelen van de habitattypen en leefgebieden van beschermde planten en vogels concreet (SMART) te maken. 3. Omdat maar een beperkte hoeveelheid gegevens is gebruikt en omdat ook gegevens niet altijd beschikbaar zijn, ontbreekt systeeminzicht. Er dient een volledige en integrale LESA opgesteld te worden om inzicht te verkrijgen in de toestand van het gebied en de ecologische condities die nodig zijn om de instandhoudingsdoelen te bereiken. 4. Om effectiviteit van maatregelen in beeld te brengen, maar ook abiotische gegevens te verzamelen die nu ontbreken, is monitoring benodigd. Het opstellen van een kennisprogramma geeft daarbij invulling aan nog niet opgeloste vraagstukken (leemten in kennis). 5. Maatregelen die snel genomen moeten worden zijn: het verminderen van stikstofbelasting, het bevorderen van verstuivingsdynamiek, (intensiever) bestrijden van exoten en verminderen van de harde scheiding met aangrenzende landbouwgebieden (bufferzones). 6. Daarnaast adviseert de Ecologische Autoriteit om onderzoek te verrichten naar de herkomst van gewasbeschermingsmiddelen die zijn aangetroffen in het gebied en, indien dit recente bronnen betreft, maatregelen te treffen hiertegen (zoals intensiveren toezicht en handhaving).

Stichting Het Flevo-landschap wil een gebied van 152 hectare in het project NoorderwoldEemvallei herontwikkelen. Ze wil onder andere 68,5 hectare (ha) moeras en 36 ha bos realiseren. Dit is compensatie van natuur die aangetast is door de verbreding van de A6 en de aanleg van het windpark Zeewolde. De gemeente Zeewolde wil in dit project ook ‘roodkavels’ realiseren: delen van het gebied waar verschillende functies mogelijk zijn, zoals woningbouw, infrastructuur en verharding. Het beoogde resultaat is een aaneengesloten en gevarieerd moeras- en boslandschap met een mix van natuur, landbouw en bebouwing. In een milieueffectrapport (MER) zijn twee alternatieven onderzocht om het gebied in te richten en zijn de effecten op de leefomgeving in beeld gebracht. De gemeente heeft de Commissie voor de milieueffectrapportage (de Commissie) gevraagd om te adviseren over dit rapport. In haar voorlopige advies oordeelde de Commissie dat in het MER nog essentiële informatie ontbrak. Hierna heeft de gemeente het MER aangevuld. In dit advies spreekt de Commissie zich uit over de juistheid en de volledigheid van het MER en de aanvulling samen.

Background Mosquito-borne diseases are on the rise. While climatic factors have been linked to disease occurrences, they do not explain the non-random spatial distribution in disease outbreaks. Landscape-related factors, such as vegetation structure, likely play a crucial but hitherto unquantified role. Methods We explored how three critically important factors that are associated with mosquito-borne disease outbreaks: microclimate, mosquito abundance and bird communities, vary at the landscape scale. We compared the co-occurrence of these three factors in two contrasting habitat types (forest versus grassland) across five rural locations in the central part of the Netherlands between June and September 2021. Results Our results show that forest patches provide a more sheltered microclimate, and a higher overall abundance of birds. When accounting for differences in landscape characteristics, we also observed that the number of mosquitoes was higher in isolated forest patches. Conclusions Our findings indicate that, at the landscape scale, variation in tree cover coincides with suitable microclimate and high Culex pipiens and bird abundance. Overall, these factors can help understand the non-random spatial distribution of mosquito-borne disease outbreaks.

Stroke is a leading cause of disability worldwide which can cause significant and persistent upper limb (UL) impairment. It is difficult to predict UL motor recovery after stroke and to forecast the expected outcomes of rehabilitation interventions during the acute and subacute phases when using clinical data alone. Accurate prediction of response to treatment could allow for more timely and targeted interventions, thereby improving recovery, resource allocation, and reducing the economic impact of post-stroke disability. Initial motor impairment is currently the strongest predictor of post-stroke motor recovery. Despite significant progress, current prediction models could be refined with additional predictors, and an emphasis on the time dependency of patient-specific predictions of UL recovery profiles. In the current paper a panel of experts provide their opinion on additional predictors and aspects of the literature that can help advance stroke outcome prediction models. Potential strategies include close attention to post-stroke data collection timeframes and adoption of individual-computerized modeling methods connected to a patient’s health record. These models should account for the non-linear and the variable recovery pattern of spontaneous neurological recovery. Additionally, input data should be extended to include cognitive, genomic, sensory, neural injury, and function measures as additional predictors of recovery. The accuracy of prediction models may be further improved by including standardized measures of outcome. Finally, we consider the potential impact of refined prediction models on healthcare costs.

“De woningcrisis biedt kansen. De kans om een duurzaam en langdurig gezond woonklimaat te realiseren.” Woningnood is geen nieuw verschijnsel in ons land. Al in de negentiende eeuw leidde snelle bevolkingsgroei en verstedelijking tot een huisvestingstekort; de woningwet van 1901 moest daar een eind aan maken. In de wederopbouwjaren na de tweede wereldoorlog kwam de woningbouw maar langzaam op gang. En in de jaren 80 van de vorige eeuw was ‘geen woning, geen kroning’ de leus van demonstranten die aandacht vroegen voor woningnood., Real Estate Management, Environmental Technology and Design, Ethics & Philosophy of Technology, Architecture and the Built Environment, Integral Design & Management, Design Aesthetics, Architectural Technology, System Engineering, Urbanism, Support Architecture, Internal and External Communication

Background: Psoriatic arthritis (PsA) is an inflammatory arthritis associated with psoriasis. PsA disease involves flares, which are associated with increased joint inflammation and tissue remodeling. There is a need for identifying biomarkers related to PsA disease activity and flares to improve the management of PsA patients and decrease flares. The tissue turnover imbalance that occurs during the inflammatory and fibro-proliferative processes during flares leads to an increased degradation and/or reorganization of the extracellular matrix (ECM), where increased proteolysis plays a key role. Hence, protease-mediated fragments of inflammatory and tissue-remodeling components could be used as markers reflecting flares in PsA patients. Methods: A broad panel of protease-mediated biomarkers reflecting inflammation and tissue remodeling was measured in serum and synovial fluid (SF) obtained from PsA patients experiencing flares (acutely swollen joint[s], PsA-flare). In serum, biomarker levels assessed in PsA-flare patients were compared to controls and in early-diagnosed PsA patients not experiencing flares (referred to as PsA without flare). Furthermore, the biomarker levels assessed in SF from PsA-flare patients were compared to the levels in SF of osteoarthritis (OA) patients. Results: In serum, levels of the PRO-C3 and C3M, reflecting formation and degradation of the interstitial matrix, were found significantly elevated in PsA-flare compared to controls and PsA without flare. The remodeling marker of the basement membrane, PRO-C4, was significantly elevated in PsA-flare compared to PsA without flare. The inflammation and immune cell activity related markers, CRPM, VICM, and CPa9-HNE were significantly elevated in PsA-flare patients compared to controls and PsA without flare. In addition, VICM (AUC = 0.71), CPa9-HNE (AUC = 0.89), CRPM (AUC = 0.76), and PRO-C3 (AUC = 0.86) showed good discriminatory performance for separating PsA-flare from PsA without flare. In

Aims/hypothesis: The prevalence and severity of metabolic dysfunction-associated steatotic liver disease (MASLD) in type 1 diabetes remain unclear. Therefore, we investigated the prevalence and severity of MASLD in type 1 diabetes and assessed which clinical features are most important in predicting MASLD severity. Methods: A total of 453 individuals with type 1 diabetes (41.6 ± 15.0 years, 64% female, body mass index [BMI] 25.4 ± 4.2 kg/m2, and HbA1c 55.6 ± 12 mmol/mol) underwent vibration-controlled transient elastography (VCTE), with a controlled attenuation parameter (CAP) score for steatosis (≥280.0 dB/m) and a liver stiffness measurement (LMS) for fibrosis (≥8.0 kPa). A machine learning Extra-Trees classification model was performed to assess the predictive power of the clinical features associated with type 1 diabetes with respect to steatosis and fibrosis. Results: The prevalence of hepatic steatosis and fibrosis was 9.5% (95% CI, 6.8-12.2) and 3.5% (95% CI, 1.8-5.2). Higher LMS was associated with a longer duration of type 1 diabetes (median 30.5 [IQR 18.0-39.3] years vs 15.0 [IQR 6.0-27.0] years), and individuals were older, had a higher BMI (mean 27.8 ± 5.2 vs 25.3 ± 4.1 kg/m2), and a higher CAP score (mean 211.4 ± 51.7 dB/m vs 241.4 ± 75.6 dB/m). The most important predictive features of fibrosis were duration of type 1 diabetes, age, and systolic blood pressure, with a mean ± SD area under the curve of 0.73 ± 0.03. Conclusion: Individuals with type 1 diabetes and high blood pressure, older age, higher BMI, and longer duration of disease could be considered at high-risk for developing MASLD.