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IntroductionWhite matter hyperintensities (WMH) are associated with key dementia etiologies, in particular arteriolosclerosis and amyloid pathology. We aimed to identify WMH locations associated with vascular risk or cerebral amyloid-β1-42 (Aβ42)-positive status.MethodsIndividual patient data (n = 3,132; mean age 71.5 ± 9 years; 49.3% female) from 11 memory clinic cohorts were harmonized. WMH volumes in 28 regions were related to a vascular risk compound score (VRCS) and Aß42 status (based on cerebrospinal fluid or amyloid positron emission tomography), correcting for age, sex, study site, and total WMH volume.ResultsVRCS was associated with WMH in anterior/superior corona radiata (B = 0.034/0.038, p

Abstract Background Tau-PET is a diagnostic tool with high sensitivity and specificity for discriminating Alzheimer’s disease (AD) dementia from other neurodegenerative disorders in well-controlled research environments. The role of tau-PET in real-world clinical practice, however, remains to be established. The aim of the TAP-TAU study is therefore to investigate the impact of tau-PET in clinical practice. Methods TAP-TAU is a prospective, longitudinal multi-center study in 300 patients (≥ 50 years old) with mild cognitive impairment or mild dementia across five Dutch memory clinics. Patients are eligible if diagnostic certainty is

IntroductionThe spatial distribution of white matter hyperintensities (WMH) on MRI is often considered in the diagnostic evaluation of patients with cognitive problems. In some patients, clinicians may classify WMH patterns as "unusual", but this is largely based on expert opinion, because detailed quantitative information about WMH distribution frequencies in a memory clinic setting is lacking. Here we report voxel wise 3D WMH distribution frequencies in a large multicenter dataset and also aimed to identify individuals with unusual WMH patterns.MethodsIndividual participant data (N = 3525, including 777 participants with subjective cognitive decline, 1389 participants with mild cognitive impairment and 1359 patients with dementia) from eleven memory clinic cohorts, recruited through the Meta VCI Map Consortium, were used. WMH segmentations were provided by participating centers or performed in Utrecht and registered to the Montreal Neurological Institute (MNI)-152 brain template for spatial normalization. To determine WMH distribution frequencies, we calculated WMH probability maps at voxel level. To identify individuals with unusual WMH patterns, region-of-interest (ROI) based WMH probability maps, rule-based scores, and a machine learning method (Local Outlier Factor (LOF)), were implemented.ResultsWMH occurred in 82% of voxels from the white matter template with large variation between subjects. Only a small proportion of the white matter (1.7%), mainly in the periventricular areas, was affected by WMH in at least 20% of participants. A large portion of the total white matter was affected infrequently. Nevertheless, 93.8% of individual participants had lesions in voxels that were affected in less than 2% of the population, mainly located in subcortical areas. Only the machine learning method effectively identified individuals with unusual patterns, in particular subjects with asymmetric WMH distribution or with WMH at relatively rarely affected locations despite common locations not being affected.DiscussionAggregating data from several memory clinic cohorts, we provide a detailed 3D map of WMH lesion distribution frequencies, that informs on common as well as rare localizations. The use of data-driven analysis with LOF can be used to identify unusual patterns, which might serve as an alert that rare causes of WMH should be considered.

Background: Kawasaki disease (KD) is a pediatric vasculitis, leading to coronary artery aneurysms (CAAs) in ~4–14%. Attention to the etiology and course of KD was generated by the close mimic of a SARS-CoV-2-induced phenotype, called multisystem inflammatory syndrome in children (MIS-C). Methods: A total of 1179 cases were collected from 2012 with ~50% of cases retrospectively included. Clinical characteristics were described and risk factors for CAA (persistence) were investigated. Phenotypic patterns of the prospectively included KD patients were evaluated. These patterns were also compared to the seronegative KD and seropositive MIS-C cases identified during the SARS-CoV-2 pandemic. Results: KD mostly affected boys and children < 5 years. IVIG resistance, CAAs, and giant CAAs occurred in 24.5%, 21.4%, and 6.6%, respectively. Giant CAAs were significantly more likely to normalize to a normal Z score in patients that were younger than 2.5 years old at the time of initial giant CAA (χ2 test p = 0.02). In our prospective (SARS-CoV-2-seronegative) KD series, there was a diminishing male predominance over time, whereas the proportions of incomplete presentations (p < 0.001) and patients with circulatory shock (p = 0.04) increased since the COVID-19 pandemic. Pre- and post-pandemic KD cases presented with different levels of C-reactive protein, thrombocyte counts, and hemoglobin levels over the years. Compared to pandemic KD, SARS-CoV-2-seropositive MIS-C patients were older (p < 0.001), and more often required intensive care admission (p < 0.001), with a gradual decrease over time between 2020 and 2022 (p = 0.04). KD carried a substantial risk of CAA development in contrast to MIS-C. Conclusion: the phenotypic changes seen over the last twelve years of our prospective follow-up study suggest a spectrum of hyperinflammatory states with potentially different triggering events within this clinical entity.

An unresolved dilemma facing many disciplines is how theory and practice can better work together to enhance the decision-making processes on the ground. This widely-known theory-practice gap often contributes to the misdiagnosis of problems and undermines the effectiveness of responses. Despite decades of research into why this gap remains, there is still a continuing and heated debate as to why it exists and how it could be resolved. This article examines the theory-practice gap through a systematic review that draws insights across diverse disciplines such as health, science, governance, and business. It builds a conceptual framework based on the findings, allowing for the analysis of the various drivers and solutions for addressing the gap. The findings show that to resolve this gap is necessary to change our perspective of the gap and understand it as a bilateral issue, where both theory and practice play a role in creating the gap. Thus, solutions to the gap need to follow a cyclical and integrative approach. As the gap may never be fully closed, the framework provides the tools to respond to it whenever it arises. Future research will be required to empirically test and advance the framework.

The first ever Global Stocktake is scheduled to conclude during COP28 and aims to assess progress on climate change mitigation, adaptation, and the means of implementation. However, the Global Stocktake runs the risk of overestimating progress by overlooking the symbolic dimensions of climate change adaptation policy.

Climate change has direct and indirect consequences for the military and defence sector. Direct impacts are for example the damaging of military infrastructure due to more extreme climatic conditions or the impact on operational capabilities when on missions. Indirect impacts include the increase of global instability and insecurity, or migration due to changing climatic conditions. Climate change risks are often seen as a threat multiplier. Whilst the impacts of climate change on the military and defence sector is gaining attention in both political and scientific realms, the way this sector adapts to these risks is, however, still pretty much unknown.This research aims to assess how the European Union member states’ military and defence sector are adapting to the impacts of climate change. We map and analyse the current policy actions by analysing the defence and climate policy documents (n = 63) and conducting interviews (n = 8) with civil servants of defence ministries across the EU. We find that almost none of the countries have a concrete climate change adaptation plan for their military. Whilst several frontrunner countries do mention climate change in their defence policy documents, they lack concrete policy goals and instruments. Moreover, concrete adaptation measures are not discussed by most of the countries. France is a notable exemption as it offers more detailed policies, but they too are at the groundwork stage. Hardly any reference to the military was found in the climate policy documents of the countries. The results show that the military and defence sector of the EU member states are not well prepared to the impacts of climate change and that concerted action is needed to close the adaptation gap adequately and effectively.

Summary: Background: Children with SARS-CoV-2 related Multisystem Inflammatory Syndrome in Children (MIS-C) often present with clinical features that resemble Kawasaki disease (KD). Disease severity in adult COVID-19 is associated to the presence of anti-cytokine autoantibodies (ACAAs) against type I interferons. Similarly, ACAAs may be implicated in KD and MIS-C. Therefore, we explored the immunological response, presence of ACAAs and disease correlates in both disorders. Methods: Eighteen inflammatory plasma protein levels and seven ACAAs were measured in KD (n = 216) and MIS-C (n = 56) longitudinally by Luminex and/or ELISA. Levels (up to 1 year post-onset) of these proteins were related to clinical data and compared with healthy paediatric controls. Findings: ACAAs were found in both patient groups. The presence of ACAAs lagged behind the inflammatory plasma proteins and peaked in the subacute phase. ACAAs were mostly directed against IFN-γ (>80%) and were partially neutralising at best. KD presented with a higher variety of ACAAs than MIS-C. Increased levels of anti-IL-17A (P = 0·02) and anti-IL-22 (P = 0·01) were inversely associated with ICU admission in MIS-C. Except for CXCL10 in MIS-C (P = 0·002), inflammatory plasma proteins were elevated in both KD and MIS-C. Endothelial angiopoietin-2 levels were associated with coronary artery aneurysms in KD (P = 0·02); and sCD25 (P = 0·009), angiopoietin-2 (P = 0·001), soluble IL-33-receptor (ST2, P = 0·01) and CXCL10 (P = 0·02) with ICU admission in MIS-C. Interpretation: Markers of endothelial activation (E-selectin, angiopoietin-2), and innate and adaptive immune responses (macrophages [CD163, G-CSF], neutrophils [lipocalin-2], and T cells [IFN-γ, CXCL10, IL-6, IL-17]), are upregulated in KD and MIS-C. ACAAs were detected in both diseases and, although only partly neutralising, their transient presence and increased levels in non-ICU patients may suggest a dampening role on inflammation. Funding: The Kawasaki study is funded by the Dutch foundation Fonds Kind & Handicap and an anonymous donor. The sponsors had no role in the study design, analysis, or decision for publication.

IntroductionThe Meta VCI Map consortium performs meta-analyses on strategic lesion locations for vascular cognitive impairment using lesion-symptom mapping. Integration of data from different cohorts will increase sample sizes, to improve brain lesion coverage and support comprehensive lesion-symptom mapping studies.MethodsCohorts with available imaging on white matter hyperintensities or infarcts and cognitive testing were invited. We performed a pilot study to test the feasibility of multicenter data processing and analysis and determine the benefits to lesion coverage.ResultsForty-seven groups have joined Meta VCI Map (stroke n = 7800 patients; memory clinic n = 4900; population-based n = 14,400). The pilot study (six ischemic stroke cohorts, n = 878) demonstrated feasibility of multicenter data integration (computed tomography/magnetic resonance imaging) and achieved marked improvement of lesion coverage.DiscussionMeta VCI Map will provide new insights into the relevance of vascular lesion location for cognitive dysfunction. After the successful pilot study, further projects are being prepared. Other investigators are welcome to join.

Rationale and objectiveImproving diet quality while decreasing environmental impacts is an important challenge for a healthy and sustainable food system. Therefore, this study aims to analyze the most common dietary patterns per female household member and explore the diet quality and environmental impacts of these patterns.MethodologyThe nationally representative General Nutrition Survey of 2009–2010 (n = 8,225 households) was used to derive dietary patterns using principal component analysis (PCA) based on 18 food groups as input variables. Quintiles of the highest adherence (Q5) and lowest adherence (Q1) were generated based on the factor score of each dietary pattern. Nutrient adequacy and dietary diversity scores (DDS) were calculated to measure diet quality, and greenhouse gas emission (GHGE) and blue water use (BWU) were selected as environmental impact indicators.ResultsUsing PCA, three distinct dietary patterns were identified: an Omnivorous, Traditional, and Pescatarian pattern. Compared to the Traditional pattern, the Omnivorous and Pescatarian patterns (Q5s) were associated with a higher nutrient adequacy, with mean probability of adequacy of 0.51 in both patterns, compared to 0.45 in the Traditional pattern. However, environmental impacts in terms of GHGE and BWU per 2,000 kcal were considerably higher in the Omnivorous pattern (6.14 kg CO2-eq. and 0.15 m3/kg) compared to all other pattern’s Q5s. The GHGE was lowest in the Traditional pattern (4.18 kg CO2-eq.) and the Pescatarian pattern has the lowest BWU (0.12 m3/kg).ConclusionDespite that diet quality was slightly better in all three patterns compared to the average diet of the total population, environmental impact was also higher. Therefore, future research is needed to develop a more optimal diet that considers both diet quality and environmental impact to explore the trade-offs between diet quality and environmental impact.

BackgroundA transition to healthy and sustainable diets has the potential to improve human and planetary health but diets need to meet requirements for nutritional adequacy, health, environmental targets, and be acceptable to consumers.ObjectiveThe objective of this study was to derive a nutritionally adequate and healthy diet that has the least deviation possible from the average observed diet of Danish adults while aiming for a greenhouse gas emission (GHGE) reduction of 31%, corresponding to the GHGE level of the Danish plant-rich diet, which lays the foundation for the current healthy and sustainable food-based dietary guidelines (FBDGs) in Denmark.MethodsWith an objective function minimizing the departure from the average observed diet of Danish adults, four diet optimizations were run using quadratic programming, with different combinations of diet constraints: (1) nutrients only (Nutri), (2) nutrients and health-based targets for food amounts (NutriHealth), (3) GHGE only (GHGE), and finally, (4) combined nutrient, health and GHGE constraints (NutriHealthGHGE).ResultsThe GHGE of the four optimized diets were 3.93 kg CO2-eq (Nutri), 3.77 kg CO2-eq (NutriHealth) and 3.01 kg CO2-eq (GHGE and NutriHealthGHGE), compared to 4.37 kg CO2-eq in the observed diet. The proportion of energy from animal-based foods was 21%–25% in the optimized diets compared to 34% in the observed diet and 18% in the Danish plant-rich diet. Moreover, compared to the average Danish diet, the NutriHealthGHGE diet contained more grains and starches (44 E% vs. 28 E%), nuts (+230%), fatty fish (+89%), eggs (+47%); less cheese (−73%), animal-based fats (−76%), total meat (−42%); and very limited amounts of ruminant meat, soft drinks, and alcoholic beverages (all-90%), while the amounts of legumes and seeds were unchanged. On average, the mathematically optimized NutriHealthGHGE diet showed a smaller deviation from the average Danish diet compared to the Danish plant-rich diet (38% vs. 169%, respectively).ConclusionThe final optimized diet presented in this study represents an alternative way of composing a nutritionally adequate and healthy diet that has the same estimated GHGE as a diet consistent with the climate-friendly FBDGs in Denmark. As this optimized diet may be more acceptable for some consumers, it might help to facilitate the transition toward more healthy and sustainable diets in the Danish population.

Abstract Objective This study investigates nutritional quality, environmental impact and costs of foods and drinks and their consumption in daily diets according to the degree of processing across the Dutch population. Design The NOVA classification was used to classify the degree of processing (ultra-processed foods (UPF) and ultra-processed drinks (UPD)). Food consumption data were derived from the Dutch National Food Consumption Survey 2012–2016. Indicators assessed were nutritional quality (saturated fatty acids (SFA), sodium, mono and disaccharides (sugar), fibre and protein), environmental impact (greenhouse gas (GHG) emissions and blue water use) and food costs. Setting The Netherlands. Participants Four thousand three hundred thirteen Dutch participants aged 1 to 79 years. Results Per 100 g, UPF were more energy-dense and less healthy than unprocessed or minimally processed foods (MPF); UPF were associated with higher GHG emissions and lower blue water use, and were cheaper. The energy and sugar content of UPD were similar to those of unprocessed or minimally processed drinks (MPD); associated with similar GHG emissions but blue water use was less, and they were also more expensive. In the average Dutch diet, per 2000 kcal, ultra-processed foods and drinks (UPFD) covered 29% (456 g UPF and 437 g UPD) of daily consumption and 61% of energy intake. UPFD consumption was higher among children than adults, especially for UPD. UPFD consumption determined 45% of GHG emissions, 23% of blue water use and 39% of expenses for daily food consumption. UPFD consumption contributed 54% to 72% to daily sodium, sugar and SFA intake. Conclusions Compared with unprocessed or minimally processed foods and drinks, UPF and UPD were found to be less healthy considering their high energy, SFA, sugar and sodium content. However, UPF were associated higher GHG emissions and with less blue water use and food costs. Therefore daily blue water use and food costs might increase if UPF are replaced by those unprocessed or minimally processed. As nutritional quality, environmental impacts and food costs relate differently to the NOVA classification, the classification is not directly applicable to identify win–win-wins of nutritional quality, environmental impact and costs of diets.