Background: In Alzheimer’s disease (AD), younger symptom onset is associated accelerated cognitive decline and tau spreading, yet the drivers of faster disease manifestation in patients with earlier symptom onset are unknown. Earlier symptom onset is associated with stronger tau pathology in fronto-parietal regions which typically harbor globally connected hubs that are central for cognition. Sinc

Framgången och kostnaderna för infrastrukturprojekt beror till stor del på tillförlitlig karakterisering av undermarken. Speciellt är information om grundvattnet avgörande för att skydda grundvattenresurserna och för att undvika stabilitetsproblem. För att fastställa de hydrogeologiska egenskaperna genomförs borrningar följt av hydrauliska tester som är tillförlitliga men dyra, och det ger endast The success and costs of infrastructure projects largely depend on reliable characterization of the subsoil, where information on groundwater is essential to protect groundwater resources and to avoid stability problems. To determine the hydrogeological characteristics, drilling is carried out followed by hydraulic tests which are reliable but expensive and provide limited information which, in so

Background: Pathological aggregation of tar DNA-binding protein 43 (TDP-43) in the brain is the primary cause of many cases of frontotemporal lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS) and limbic-predominant age-related TDP-43 encephalopathy (LATE). It is therefore imperative to establish empirical staging systems to characterize and distinguish stereotypical patterns and commo

People with kidney disease are disproportionately affected by atherosclerosis for unclear reasons. Soluble urokinase plasminogen activator receptor (suPAR) is an immune-derived mediator of kidney disease, levels of which are strongly associated with cardiovascular outcomes. We assessed suPAR’s pathogenic involvement in atherosclerosis using epidemiologic, genetic, and experimental approaches. We f

Background: Over the past decade, several PET tracers were developed to visualise and quantify tau pathology in vivo. However, all these tracers have distinct off-target binding, different dynamic ranges and likely different levels of non-specific binding resulting in large variability in semiquantification. We propose to standardise the sampling and the quantification across all available tau tra

Background: For optimal design of anti-amyloid-β (Aβ) and anti-tau clinical trials, it is important to understand how Aβ and soluble phosphorylated tau (p-tau) relate to the accumulation of tau aggregates assessed with positron emission tomography (PET) and subsequent cognitive decline across the Alzheimer's disease (AD) continuum. Method: We included 327 participants from the Swedish BioFINDER-2

This book casts new light on the application of the principle of proportionality in international law. Proportionality is claimed to play a central role in governing the exercise of public power in international law and has been presented as the ‘ultimate rule of law’. It has also been the subject of fierce criticism: it is argued that it leads to unreflexive and arbitrary application of the law a

Human gut microbiota produce a variety of molecules, some of which enter the bloodstream and impact health. Conversely, dietary or pharmacological compounds may affect the microbiota before entering the circulation. Characterization of these interactions is an important step towards understanding the effects of the gut microbiota on health. In this cross-sectional study, we used deep metagenomic s

By relying on theory from sociology of law and data feminism, this study showcases the norms guiding development in human-robot interaction. This qualitative study consists of an ethnography of the HRI conference 2021 and expert interviews which were merged and analysed using an ethnographic content analysis method on NVivo. The socio-legal data feminist lens enables to pinpoint the lack of clear

This paper summarises the contributions to our Topical Collection on indeterminacy and underdetermination. The collection includes papers in ethics, metaethics, logic, metaphysics, epistemology, philosophy of science, philosophy of language and philosophy of computation.

PURPOSETo provide precise age-specific risk estimates of cancers other than female breast and ovarian cancers associated with pathogenic variants (PVs) in BRCA1 and BRCA2 for effective cancer risk management.METHODSWe used data from 3,184 BRCA1 and 2,157 BRCA2 families in the Consortium of Investigators of Modifiers of BRCA1/2 to estimate age-specific relative (RR) and absolute risks for 22 first