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With the emergence of Alzheimer's disease (AD) disease-modifying therapies, identifying patients who could benefit from these treatments becomes critical. In this study, we evaluated whether a precise blood test could perform as well as established cerebrospinal fluid (CSF) tests in detecting amyloid-β (Aβ) plaques and tau tangles. Plasma %p-tau217 (ratio of phosporylated-tau217 to non-phosphorylated tau) was analyzed by mass spectrometry in the Swedish BioFINDER-2 cohort (n = 1,422) and the US Charles F. and Joanne Knight Alzheimer Disease Research Center (Knight ADRC) cohort (n = 337). Matched CSF samples were analyzed with clinically used and FDA-approved automated immunoassays for Aβ42/40 and p-tau181/Aβ42. The primary and secondary outcomes were detection of brain Aβ or tau pathology, respectively, using positron emission tomography (PET) imaging as the reference standard. Main analyses were focused on individuals with cognitive impairment (mild cognitive impairment and mild dementia), which is the target population for available disease-modifying treatments. Plasma %p-tau217 was clinically equivalent to FDA-approved CSF tests in classifying Aβ PET status, with an area under the curve (AUC) for both between 0.95 and 0.97. Plasma %p-tau217 was generally superior to CSF tests in classification of tau-PET with AUCs of 0.95-0.98. In cognitively impaired subcohorts (BioFINDER-2: n = 720; Knight ADRC: n = 50), plasma %p-tau217 had an accuracy, a positive predictive value and a negative predictive value of 89-90% for Aβ PET and 87-88% for tau PET status, which was clinically equivalent to CSF tests, further improving to 95% using a two-cutoffs approach. Blood plasma %p-tau217 demonstrated performance that was clinically equivalent or superior to clinically used FDA-approved CSF tests in the detection of AD pathology. Use of high-performance blood tests in clinical practice can improve access to accurate AD diagnosis and AD-specific treatments.

Abstract Alzheimer’s disease (AD) is a debilitating neurodegenerative disorder characterized by brain aggregation of β-amyloid (Aβ) peptides and phosphorylated tau (P-tau) proteins. Extracellular vesicles (EVs) can be isolated and studied for potential roles in disease. While several studies have tested plasma-derived EVs in AD, few have analyzed EVs from cerebrospinal fluid (CSF), which are potentially more closely related to brain changes. This study included 20 AD patients and 20 cognitively unimpaired (CU) participants. Using a novel EV isolation method based on acoustic trapping, we isolated and purified EVs from minimal CSF volumes. EVs were lysed and analyzed by immunoassays for P-tau217 and P-tau181. Isolation was confirmed through transmission electron microscopy and the presence of EV-specific markers (CD9, CD63, CD81, ATP1A3). Nanoparticle tracking analysis revealed a high variance in EV distribution. AD patients exhibited increased P-tau181 and decreased P-tau217 in EVs, leading to a higher EV P-tau181/P-tau217 ratio compared to CU. No significant differences in EV counts or sizes were observed between AD and CU groups. This study is the first to use acoustic trapping to isolate EVs from CSF and demonstrates differential P-tau content in AD-derived EVs, warranting further research to understand the relationship between these EV changes and brain pathology.

Abstract This paper considers the European transfer market for professional football players as a network to study the relation between a team’s position in this network and performance in its domestic league. Our analysis is centered on eight top European leagues. The market in each season is represented as a weighted directed network capturing the transfers of players to or from the teams in these leagues, and we also consider the cumulative network over the past 28 years. We find that the overall structure of this transfer market network has properties commonly observed in real-world networks, such as a skewed degree distribution, high clustering, and small-world characteristics. To assess football teams we first construct a measure of within-league performance that is comparable across leagues. Regression analysis is used to relate league performance with both the network position and level of engagement of the team in the transfer market, under two complimentary setups. Network position variables include, e.g., betweenness centrality, closeness centrality and node clustering coefficient, whereas market engagement variables capture a team’s activity in the transfer market, e.g., total number of player transfers and total paid for players. For the season snapshots, the number of transfers correspond to weighted in- and out-degree. Our analysis first corroborates several recent findings relating aspects of market engagement with teams’ league performance. A higher number of incoming transfers indicates worse performance and better resourced teams perform better. Then, and across specifications, we find that network position variables remain salient even when engagement variables are already considered. This substantiates the notion in the existing literature that a high degree corresponds to better team performance and suggests that network aspects of trading strategy may affect a team’s success in their respective domestic league (or vice versa). In this sense, the approach and findings presented in this paper may in the future guide team’s player acquisition policies.

Abstract Background Chronic lymphocytic leukemia (CLL) is a heterogeneous disease. Whereas some patients have an indolent disease, others experience an aggressive course and early death. Our aim was to investigate if modifiable and non‐modifiable medical history and lifestyle factors prior to diagnosis had an impact on the natural course of the disease. Method In 1154 CLL patients, we assessed if the weight, physical activity, smoking, and alcohol consumption or non‐modifiable characteristics including family history of lymphoid malignancy and medical history were associated with time‐to‐first‐treatment (TTFT) and adjusted all results for the CLL‐International Prognostic Index (CLL‐IPI). Results TTFT was shorter for patients with high/very high‐risk CLL‐IPI than those with low/intermediate risk CLL‐IPI. In the adjusted analysis we did not find additional impact on TTFT besides CLL‐IPI from any environmental characteristics assessed. Conclusions We found limited impact of environmental factors on the natural course of CLL (measured as the TTFT in treatment naïve patients) providing valuable knowledge, and potential relief, to share with patients at the time of diagnosis.

Abstract Background In Alzheimer’s disease (AD), the associations between tau pathology and brain atrophy and cognitive decline are well established, but imperfect. We investigate whether cerebrospinal fluid (CSF) biomarkers of biological processes (vascular, synaptic, and axonal integrity, neuroinflammation, neurotrophic factors) explain the disconnection between tau pathology and brain atrophy (brain resilience), and tau pathology and cognitive decline (cognitive resilience). Methods We included 428 amyloid positive participants (134 cognitively unimpaired (CU), 128 with mild cognitive impairment (MCI), 166 with AD dementia) from the BioFINDER-2 study. At baseline, participants underwent tau positron emission tomography (tau-PET), magnetic resonance imaging (MRI), cognitive testing, and lumbar puncture. Longitudinal data were available for MRI (mean (standard deviation) follow-up 26.4 (10.7) months) and cognition (25.2 (11.4) months). We analysed 18 pre-selected CSF proteins, reflecting vascular, synaptic, and axonal integrity, neuroinflammation, and neurotrophic factors. Stratifying by cognitive status, we performed linear mixed-effects models with cortical thickness (brain resilience) and global cognition (cognitive resilience) as dependent variables to assess whether the CSF biomarkers interacted with tau-PET levels in its effect on cortical atrophy and cognitive decline. Results Regarding brain resilience, interaction effects were observed in AD dementia, with vascular integrity biomarkers (VEGF-A (βinteraction = -0.009, pFDR = 0.047) and VEGF-B (βinteraction = -0.010, pFDR = 0.037)) negatively moderating the association between tau-PET signal and atrophy. In MCI, higher NfL levels were associated with more longitudinal cortical atrophy (β = -0.109, pFDR = 0.033) and lower baseline cortical thickness (β = -0.708, pFDR = 0.033) controlling for tau-PET signal. Cognitive resilience analyses in CU revealed interactions with tau-PET signal for inflammatory (GFAP, IL-15; βinteraction -0.073–-0.069, pFDR 0.001–0.045), vascular (VEGF-A, VEGF-D, PGF; βinteraction -0.099–-0.063, pFDR

Abstract Background The medial temporal lobe (MTL) is hypothesized to be relatively spared in early-onset Alzheimer’s disease (EOAD). Yet, detailed examination of MTL subfields and drivers of atrophy in amnestic EOAD is lacking. Methods BioFINDER-2 participants with memory impairment, abnormal amyloid-β and tau-PET were included. Forty-one amnestic EOAD individuals ≤65 years and, as comparison, late-onset AD (aLOAD, ≥70 years, n = 154) and amyloid-β-negative cognitively unimpaired controls were included. MTL subregions and biomarkers of (co-)pathologies were measured. Results AD groups showed smaller MTL subregions compared to controls. Atrophy patterns were similar across AD groups: aLOAD showed thinner entorhinal cortices than aEOAD; aEOAD showed thinner parietal regions than aLOAD. aEOAD showed lower white matter hyperintensities than aLOAD. No differences in MTL tau-PET or transactive response DNA binding protein 43-proxy positivity were found. Conclusions We found evidence for MTL atrophy in amnestic EOAD and overall similar levels to aLOAD of MTL tau pathology and co-pathologies.

Abstract Background The aim was to investigate the total prevalence of known and undiagnosed diabetes mellitus (DM), and the association of DM with perioperative complications following elective, infrarenal, open surgical (OSR) or endovascular (EVAR), Abdominal Aortic Aneurysm (AAA) repair. Methods In this Norwegian prospective multicentre study, 877 patients underwent preoperative screening for DM by HbA1c measurements from November 2017 to December 2020. Diabetes was defined as screening detected HbA1c ≥ 48 mmol/mol (6.5%) or previously diagnosed diabetes. The association of DM with in-hospital complications, length of stay, and 30-day mortality rate were evaluated using adjusted and unadjusted logistic regression models. Results The total prevalence of DM was 15% (95% CI 13%,17%), of which 25% of the DM cases (95% CI 18%,33%) were undiagnosed upon admission for AAA surgery. The OSR to EVAR ratio was 52% versus 48%, with similar distribution among DM patients, and no differences in the prevalence of known and undiagnosed DM in the EVAR versus the OSR group. Total 30-day mortality rate was 0.6% (5/877). Sixty-six organ-related complications occurred in 58 (7%) of the patients. DM was not statistically significantly associated with a higher risk of in-hospital organ-related complications (OR 1.23, 95% CI 0.57,2.39, p = 0.57), procedure-related complications (OR 1.48, 95% CI 0.79,2.63, p = 0.20), 30-day mortality (p = 0.09) or length of stay (HR 1.06, 95% CI 0.88,1.28, p = 0.54). According to post-hoc-analyses, organ-related complications were more frequent in patients with newly diagnosed DM (n = 32) than in non-DM patients (OR 4.92; 95% CI 1.53,14.3, p = 0.005). Conclusion Twenty-five percent of all DM cases were undiagnosed at the time of AAA surgery. Based on post-hoc analyses, undiagnosed DM seems to be associated with an increased risk of organ related complications following AAA surgery. This study suggests universal DM screening in AAA patients to reduce the number of DM patients being undiagnosed and to improve proactive diabetes care in this population. The results from post-hoc analyses should be confirmed in future studies.

Abstract Identifying concomitant Lewy body (LB) pathology through seed amplification assays (SAA) might enhance the diagnostic and prognostic work-up of Alzheimer’s disease (AD) in clinical practice and trials. This study examined whether LB pathology exacerbates AD-related disease progression in 795 cognitively impaired individuals (Mild Cognitive Impairment and dementia) from the longitudinal multi-center observational ADNI cohort. Participants were on average 75 years of age (SD = 7.89), 40.8% were female, 184 (23.1%) had no biomarker evidence of AD/LB pathology, 39 (4.9%) had isolated LB pathology (AD-LB+), 395 (49.7%) had only AD pathology (AD+LB-), and 177 (22.3%) had both pathologies (AD+LB+). The AD+LB+ group showed worst baseline performance for most cognitive outcomes and compared to the AD+LB− group faster global cognitive decline and more cortical hypometabolism, particularly in posterior brain regions. Neuropathological examination (n = 61) showed high sensitivity (26/27, 96.3%) and specificity (27/28, 96.4%) of the SAA-test. We showed that co-existing LB-positivity exacerbates cognitive decline and cortical brain hypometabolism in AD. In vivo LB pathology detection could enhance prognostic evaluations in clinical practice and could have implications for clinical AD trial design.

Introduction: Research has indicated that Physical Education (PE) is often characterized by teacher-centred teaching (e.g. Byra 2006; Tinning 2010), where the pupils follow instruction and perform pre-established movements (Karlefors and Larsson 2018). Pupils are expected to listen, do as they are told, and follow rules (Fitzpatrick and Russell 2015; Quennerstedt 2013). PE teaching has been described as an act of control (Quennerstedt 2013), and teachers face the dilemma of letting go of control and still having enough control to make sure that the lesson smoothly moves forward (Alfrey and O'Connor 2020). However, when the pupils are given more power and the teacher applies student-centred teaching, the pupils get to come up with ideas and make decisions (e.g. Byra 2006; Garrett and Wrench 2018; Mattsson and Larsson 2021). This is significant because it can develop PE and contribute to meaning making among pupils and their experiences of movement. This article aims to analyse the use of exploratory circus assignments in PE teaching and to discuss this in relation to current school norms. Biesta's ("The Beautiful Risk of Education" [Paradigm Publishers 2014]) concept of risk, which means not knowing the outcome, is used. The article problematizes pupils' own ideas and suggestions in relation to prevailing norms in school. What happens when pupils participate in teaching based on exploratory circus assignments? Exploration, playfulness, and expression were focused, and the lessons were characterized by the absence of primary focus on competitiveness as a counterweight to traditional PE content. Methods: A research teacher (a university teacher with experience teaching school PE and circus) conducted 10 lessons together with 20 pupils (aged 10) and their PE teacher using exploratory circus assignments. Data was collected through participant observation, video observation, and field diary. The data analysis generated three themes, Following instruction, Limited exploration, and Shared power, that were reviewed in relation to the theoretical framework. Results: The results show that the research teacher and the PE teacher resisted embracing risk in PE due to the prevailing norms and what Biesta (2014) describes as the practice of schooling. They focused on keeping the pupils in order rather than being flexible and open to unknown outcomes. The exploratory circus assignments involved risk to different extents, and the research teacher's tendency to embrace risk increased over time. Her letting go of control enabled her to embrace risk. It did not mean a total relinquishment of control, but rather not having exclusive control over the decision-making and meaning-making processes. When she shared the power with the pupils, new and other movements could be explored. The results show that pupils' actions can be more educative than what teachers initially consider. Conclusion: Teachers need to relinquish control to conduct teaching which embraces risk. Doing so enables them to share power with the pupils, which allows pupils to explore and discover different ways of moving and using the material. Exploratory circus assignments can enable risk embracement in PE and function as a way for teachers to reflect upon pedagogical considerations and practice the sharing of power with their pupils.

This study aims to contribute to the understanding of food for health as educational content in Home and Consumer Studies (HCS), specifically targeting three educational functions: (i) qualification, (ii) socialization, and (iii) subjectification. Data came from a comprehensive case study, where one school class and two HCS teachers were followed during one school year. Fourteen classroom observations and eight teacher interviews were included. It is shown how qualification functions comprise nutrition knowledge and cooking skills, how socialization functions entail, e.g., dichotomous values of food as "good" or "bad," and how conscious consumers who take personal responsibility for themselves and the environment become promoted subjects. Taken together, the results illustrate how educational content can have consequences beyond those intended. Based on the results, an argument is made about the relevance for HCS teachers to critically reflect on their teaching and its potential educational consequences.

This study aimed to analyse how school health team professionals in geographical areas with a long tradition of neo-Nazi activism discursively conceptualise the problem of racism. The participants do not consider racism or neo-Nazi mobilisation to be a central problem at their schools. At the same time, they cited several examples of obvious expressions of neo-Nazi convictions among students. This discrepancy is explained in different capacities. Firstly, as the students are understood to have a mill-town mentality, certain behaviours are expected and excused. Secondly, to be seen as a problem, racist expression is also expected to be visual. A third factor is that the problem is individualised, focusing on one incident at a time.