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The aggregation of the 42-residue form of the amyloid-β peptide (Aβ42) is a pivotal event in Alzheimer's disease (AD). The use of chemical kinetics has recently enabled highly accurate quantifications of the effects of small molecules on specific microscopic steps in Aβ42 aggregation. Here, we exploit this approach to develop a rational drug discovery strategy against Aβ42 aggregation that uses as
We argue that the current system of agri-environment management in the European Common Agricultural Policy is ineffective at conserving biodiversity in part because it promotes fragmentation instead of collaboration of actors, thus hindering coordinated biodiversity management. Actor fragmentation is reinforced by the Common Agricultural Policy (CAP) in three ways: (1) through targeting individual
Flavonoids have been shown to inhibit colon cancer cell proliferation in vitro and protect against colorectal carcinogenesis in animal models. However, epidemiological evidence on the potential role of flavonoid intake in colorectal cancer (CRC) development remains sparse and inconsistent. We evaluated the association between dietary intakes of total flavonoids and their subclasses and risk of dev
Aims: Sudden cardiac arrest (SCA) accounts for 10% of adult mortality in Western populations. We aim to identify potential loci associated with SCA and to identify risk factors causally associated with SCA. Methods and results: We carried out a large genome-wide association study (GWAS) for SCA (n = 3939 cases, 25 989 non-cases) to examine common variation genome-wide and in candidate arrhythmia g
Introduction: Arterial stiffness is recognized as an intermediate phenotype and predictor of cardiovascular disease. Arterial stiffness is complex in origin with contributions from lifestyle and genetic factors. However, the association between single nucleotide polymorphisms (SNPs) and arterial stiffness remains unclear. Objective: The aim is to assess whether a multilocus genetic risk score (GRS
Bumblebees are important pollinators for a wide range of crops and wild plants. Performance of their colonies depends on pollen and nectar as food resources, but flowering plants are scarce in modern agricultural landscapes. It is well-known that semi-natural habitats can enhance floral resources and bumblebee abundance, but the impact of different crop types and their heterogeneity at the landsca
All-inorganic CsPbBr3 perovskite colloidal quantum dots have recently emerged as a promising material for a variety of optoelectronic applications, among others for multiphoton-pumped lasing. Nevertheless, high irradiance levels are generally required for such multiphoton processes. One strategy to enhance the multiphoton absorption is taking advantage of high local light intensities using photoni
In this trans-ethnic multi-omic study, we reinterpret the genetic architecture of blood pressure to identify genes, tissues, phenomes and medication contexts of blood pressure homeostasis. We discovered 208 novel common blood pressure SNPs and 53 rare variants in genome-wide association studies of systolic, diastolic and pulse pressure in up to 776,078 participants from the Million Veteran Program
Background: Alpha-1-antitrypsin (AAT) deficiency is a hereditary disorder that predisposes to emphysema. A cohort of severe (PiZZ) and moderate (PiSZ) AAT-deficient newborn infants was identified by the Swedish national neonatal AAT screening program in 1972–1974 and has been followed-up since birth. Our aim was to study whether the cohort has signs of emphysema in pulmonary function tests (PFTs)
Overall survival of patients with metastatic non-small cell lung cancer (NSCLC) has significantly improved with platinum-based salt treatments and recently with targeted therapies and immunotherapies. However, treatment failure occurs due to acquired or emerging tumor resistance. We developed a monoclonal antibody against the proform of neurotensin (LF-NTS mAb) that alters the homeostasis of tumor
The 2013 reform of the Common Agricultural Policy (CAP) introduced compulsory ‘greening’ measures with the goal to mitigate environmental degradation caused by intensive agriculture. This paper aims to investigate how the implementation of the Ecological Focus Areas (EFA) obligation will affect regional agricultural development, the economic performance of farms and land use (including choices of
Objective: To investigate whether inverse probability of participation weighting (IPPW) using register data on sociodemographic and disease history variables can improve external validity in a cohort study with selective participation. Study Design and Setting: We fitted various IPPW models by logistic regression using register data for the participants (n = 1,111) and nonparticipants (n = 1,132)
Objectives To conduct a comprehensive analysis of prospectively measured circulating high sensitivity C reactive protein (hsCRP) concentration and risk of lung cancer overall, by smoking status (never, former, and current smokers), and histological sub-type. Design Nested case-control study. setting 20 population based cohort studies in Asia, Europe, Australia, and the United States. ParticiPants
To identify genetic variants associated with diabetic retinopathy (DR), we performed a large multiethnic genome-wide association study. Discovery included eight European cohorts (n = 3,246) and seven African American cohorts (n = 2,611). We meta-analyzed across cohorts using inverse-variance weighting, with and without liability threshold modeling of glycemic control and duration of diabetes. Vari
The Common Agricultural Policy (CAP) affects about half of the land area of the EU and allocates close to 40% of the EU’s budget. Consequently, CAP has great potential to guide land management decisions towards multifunctional agricultural landscapes supporting both commodity production and biodiversity. The 2015 “greening” reform was an attempt to increase the multifunctionality of agricultural l
We examined farmers’ costs of providing public goods under the Common Agricultural Policy (CAP) and the expected impacts of the 2015 CAP “greening” reform on regional development and provisioning of public goods. Less than half of CAP spending Before the reform was justifiable in terms of the delivery of specific public goods; and predicted benefits from greening are low. We recommend re-allocatin
Background: To investigate changes in knee 3D bone shape over the first 5 years after acute anterior cruciate ligament (ACL) injury in participants of the randomized controlled KANON-trial. Methods: Serial MR images over 5 years from 121 young (32 women, mean age 26.1 years) adults with an acute ACL tear in a previously un-injured knee were analyzed using statistical shape models for bone. A match
Background & Aims: Evidence on the association between physical activity and risk of hepatobiliary cancers is inconclusive. We examined this association in the European Prospective Investigation into Cancer and Nutrition cohort (EPIC). Methods: We identified 275 hepatocellular carcinoma (HCC) cases, 93 intrahepatic bile duct cancers (IHBCs), and 164 non-gallbladder extrahepatic bile duct cance
Background: There is a lack of validated tools to assess potential disease progression and hospitalisation decisions in patients presenting to the emergency department (ED) with a suspected infection. This study aimed to identify suitable blood biomarkers (MR-proADM, PCT, lactate and CRP) or clinical scores (SIRS, SOFA, qSOFA, NEWS and CRB-65) to fulfil this unmet clinical need. Methods: An observ
