| 1. |
- Vogel, Jacob W., et al.
(author)
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Four distinct trajectories of tau deposition identified in Alzheimer’s disease
- 2021
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In: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 27:5, s. 871-881
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Journal article (peer-reviewed)abstract
- Alzheimer’s disease (AD) is characterized by the spread of tau pathology throughout the cerebral cortex. This spreading pattern was thought to be fairly consistent across individuals, although recent work has demonstrated substantial variability in the population with AD. Using tau-positron emission tomography scans from 1,612 individuals, we identified 4 distinct spatiotemporal trajectories of tau pathology, ranging in prevalence from 18 to 33%. We replicated previously described limbic-predominant and medial temporal lobe-sparing patterns, while also discovering posterior and lateral temporal patterns resembling atypical clinical variants of AD. These ‘subtypes’ were stable during longitudinal follow-up and were replicated in a separate sample using a different radiotracer. The subtypes presented with distinct demographic and cognitive profiles and differing longitudinal outcomes. Additionally, network diffusion models implied that pathology originates and spreads through distinct corticolimbic networks in the different subtypes. Together, our results suggest that variation in tau pathology is common and systematic, perhaps warranting a re-examination of the notion of ‘typical AD’ and a revisiting of tau pathological staging. © 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.
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| 2. |
- Zhou, XP, et al.
(author)
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Non-coding variability at the APOE locus contributes to the Alzheimer's risk
- 2019
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 3310-
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Journal article (peer-reviewed)abstract
- Alzheimer’s disease (AD) is a leading cause of mortality in the elderly. While the coding change of APOE-ε4 is a key risk factor for late-onset AD and has been believed to be the only risk factor in the APOE locus, it does not fully explain the risk effect conferred by the locus. Here, we report the identification of AD causal variants in PVRL2 and APOC1 regions in proximity to APOE and define common risk haplotypes independent of APOE-ε4 coding change. These risk haplotypes are associated with changes of AD-related endophenotypes including cognitive performance, and altered expression of APOE and its nearby genes in the human brain and blood. High-throughput genome-wide chromosome conformation capture analysis further supports the roles of these risk haplotypes in modulating chromatin states and gene expression in the brain. Our findings provide compelling evidence for additional risk factors in the APOE locus that contribute to AD pathogenesis.
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| 3. |
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| 4. |
- Pelttari, LM, et al.
(author)
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RAD51B in Familial Breast Cancer
- 2016
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In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 11:5, s. e0153788-
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Journal article (peer-reviewed)
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| 5. |
- Salloway, S, et al.
(author)
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A phase 2 multiple ascending dose trial of bapineuzumab in mild to moderate Alzheimer disease.
- 2009
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In: Neurology. - 1526-632X. ; 73:24, s. 2061-70
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Journal article (peer-reviewed)abstract
- BACKGROUND: Bapineuzumab, a humanized anti-amyloid-beta (Abeta) monoclonal antibody for the potential treatment of Alzheimer disease (AD), was evaluated in a multiple ascending dose, safety, and efficacy study in mild to moderate AD. METHODS: The study enrolled 234 patients, randomly assigned to IV bapineuzumab or placebo in 4 dose cohorts (0.15, 0.5, 1.0, or 2.0 mg/kg). Patients received 6 infusions, 13 weeks apart, with final assessments at week 78. The prespecified primary efficacy analysis in the modified intent-to-treat population assumed linear decline and compared treatment differences within dose cohorts on the Alzheimer's Disease Assessment Scale-Cognitive and Disability Assessment for Dementia. Exploratory analyses combined dose cohorts and did not assume a specific pattern of decline. RESULTS: No significant differences were found in the primary efficacy analysis. Exploratory analyses showed potential treatment differences (p < 0.05, unadjusted for multiple comparisons) on cognitive and functional endpoints in study "completers" and APOE epsilon4 noncarriers. Reversible vasogenic edema, detected on brain MRI in 12/124 (9.7%) bapineuzumab-treated patients, was more frequent in higher dose groups and APOE epsilon4 carriers. Six vasogenic edema patients were asymptomatic; 6 experienced transient symptoms. CONCLUSIONS: Primary efficacy outcomes in this phase 2 trial were not significant. Potential treatment differences in the exploratory analyses support further investigation of bapineuzumab in phase 3 with special attention to APOE epsilon4 carrier status. Classification of evidence: Due to varying doses and a lack of statistical precision, this Class II ascending dose trial provides insufficient evidence to support or refute a benefit of bapineuzumab.
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| 7. |
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| 8. |
- Crivillers, N, et al.
(author)
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Photoinduced work function changes by isomerization of a densely packed azobenzene-based SAM on Au: a joint experimental and theoretical study
- 2011
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In: Physical Chemistry, Chemical Physics - PCCP. - : Royal Society of Chemistry. - 1463-9076 .- 1463-9084. ; 13:32, s. 14302-14310
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Journal article (peer-reviewed)abstract
- Responsive monolayers are key building blocks for future applications in organic and molecular electronics in particular because they hold potential for tuning the physico-chemical properties of interfaces, including their energetics. Here we study a photochromic SAM based on a conjugated azobenzene derivative and its influence on the gold work function (Phi(Au)) when chemisorbed on its surface. In particular we show that the Phi(Au) can be modulated with external stimuli by controlling the azobenzene trans/cis isomerization process. This phenomenon is characterized experimentally by four different techniques, kelvin probe, kelvin probe force microscopy, electroabsorption spectroscopy and ultraviolet photoelectron spectroscopy. The use of different techniques implies exposing the SAM to different measurement conditions and different preparation methods, which, remarkably, do not alter the observed work function change (Phi(trans)-Phi(cis)). Theoretical calculations provided a complementary insight crucial to attain a deeper knowledge on the origin of the work function photo-modulation.
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| 9. |
- Frawley, Timothy H., et al.
(author)
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Self-governance mediates small-scale fishing strategies, vulnerability and adaptive response
- 2024
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In: Global Environmental Change. - 0959-3780 .- 1872-9495. ; 84
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Journal article (peer-reviewed)abstract
- As global change accelerates, natural resource-dependent communities must respond and adapt. Small-scale fisheries, essential for coastal livelihoods and food security, are considered among the most vulnerable of these coupled social-ecological systems. While previous studies have examined vulnerability and adaptation in fisheries at the individual, household, and community level, these scales of organization are inconsistent with many of the legal and regulatory frameworks that function in practice to mediate behavior, decision-making, and adaptation. Here, we use cooperative- and privately-owned fishing enterprises in Northwest Mexico as a case study to examine how different forms of marine self-governance experience and respond to climate shocks. Leveraging social-ecological network methods to examine changes in fisheries participation and vulnerability during a recent period of pronounced regional oceanographic change, our analysis suggests that: 1) different forms of SSF self-governance (and the fishing strategies and harvest portfolios with which they are associated) help determine the impacts of and response to environmental change; and 2) that there may be important tradeoffs between short-term responses which function to prevent or mitigate lost fishing revenue and long-term changes in climate vulnerability. In particular large fishing cooperatives, predicted to be highly vulnerable on the basis of network theoretic metrics, exceeded expectations (maintaining or increasing resource revenues) while demonstrating a degree of path dependency that may function to increase sensitivity and undermine resilience as climate change progresses. In providing an empirical evaluation of how self-governance arrangements characterized by different group sizes, access regimes and levels of cooperation respond to system perturbation, we aim to advance common pool resource theory while offering targeted guidance for the development of more nuanced and equitable climate adaptation policies.
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| 10. |
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| 11. |
- Lind, C. M., et al.
(author)
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Effectiveness and usability of real-time vibrotactile feedback training to reduce postural exposure in real manual sorting work
- 2023
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In: Ergonomics. - : Informa UK Limited. - 0014-0139 .- 1366-5847. ; 66:2, s. 198-216
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Journal article (peer-reviewed)abstract
- Vibrotactile feedback training may be used as a complementary strategy to reduce time in demanding postures in manual handling. This study evaluated the short- and medium-term effects of concurrent posture-correction vibrotactile feedback training on trunk inclination exposure in real manual sorting work. Fifteen warehouse workers completed the training and the follow-up sessions. Trunk inclination angles were recorded using the ambulatory Smart Workwear System. Questionnaires were used for assessing system usability, perceived physical exertion, and work ability. The results showed reduced time in trunk inclination >30°, >45°, and >60°, and reductions in the 90th, 95th, and 99th percentile trunk inclination angles, when receiving feedback and immediately after feedback withdrawal. No significant reduction was retained after one and three weeks. The wearer's comfort was scored high, and the feedback did not increase the perceived cognitive demands. No significant effects attributed to changed trunk inclination exposure were observed for perceived physical exertion or work ability. The training program has the potential of contributing to reduced trunk inclination exposure in the short term. Future studies are needed to evaluate if improvements in the feedback training can transfer the short-term results to retained median- and long-term effects. Practitioner summary: A two-day training program with concurrent posture-correction vibrotactile feedback can contribute to reduced exposure of trunk inclination in real manual sorting work in the short term. More research is needed on how to design the feedback training programs in order to be effective in the long term.
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| 12. |
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| 13. |
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| 14. |
- Zuiker, Rob G J A, et al.
(author)
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Kinetics of TH2 biomarkers in sputum of asthmatics following inhaled allergen.
- 2015
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In: European clinical respiratory journal. - : Informa UK Limited. - 2001-8525. ; 2
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Journal article (peer-reviewed)abstract
- Allergen-induced late airway response offers important pharmacodynamic targets, including T helper 2 (TH2) biomarkers. However, detection of inflammatory markers has been limited in dithiothreitol-processed sputum.
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| 15. |
- Colom-Cadena, Martí, et al.
(author)
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The clinical promise of biomarkers of synapse damage or loss in Alzheimer's disease.
- 2020
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In: Alzheimer's research & therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 12:1
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Journal article (peer-reviewed)abstract
- Synapse damage and loss are fundamental to the pathophysiology of Alzheimer's disease (AD) and lead to reduced cognitive function. The goal of this review is to address the challenges of forging new clinical development approaches for AD therapeutics that can demonstrate reduction of synapse damage or loss. The key points of this review include the following: Synapse loss is a downstream effect of amyloidosis, tauopathy, inflammation, and other mechanisms occurring in AD.Synapse loss correlates most strongly with cognitive decline in AD because synaptic function underlies cognitive performance.Compounds that halt or reduce synapse damage or loss have a strong rationale as treatments of AD.Biomarkers that measure synapse degeneration or loss in patients will facilitate clinical development of such drugs.The ability of methods to sensitively measure synapse density in the brain of a living patient through synaptic vesicle glycoprotein 2A (SV2A) positron emission tomography (PET) imaging, concentrations of synaptic proteins (e.g., neurogranin or synaptotagmin) in the cerebrospinal fluid (CSF), or functional imaging techniques such as quantitative electroencephalography (qEEG) provides a compelling case to use these types of measurements as biomarkers that quantify synapse damage or loss in clinical trials in AD.A number of emerging biomarkers are able to measure synapse injury and loss in the brain and may correlate with cognitive function in AD. These biomarkers hold promise both for use in diagnostics and in the measurement of therapeutic successes.
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| 16. |
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| 17. |
- Ek, M., et al.
(author)
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Probing Catalyst Surfaces at the Atomic-scale
- 2023
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In: Microscopy and microanalysis : the official journal of Microscopy Society of America, Microbeam Analysis Society, Microscopical Society of Canada. - 1435-8115. ; 29:1, s. 1291-1291
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Journal article (peer-reviewed)
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| 18. |
- Lagerholm, Vendela K., et al.
(author)
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Range shifts or extinction? Ancient DNA and distribution modelling reveal past and future responses to climate warming in cold-adapted birds
- 2017
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In: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 23:4, s. 1425-1435
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Journal article (peer-reviewed)abstract
- Global warming is predicted to cause substantial habitat rearrangements, with the most severe effects expected to occur in high-latitude biomes. However, one major uncertainty is whether species will be able to shift their ranges to keep pace with climate-driven environmental changes. Many recent studies on mammals have shown that past range contractions have been associated with local extinctions rather than survival by habitat tracking. Here, we have used an interdisciplinary approach that combines ancient DNA techniques, coalescent simulations and species distribution modelling, to investigate how two common cold-adapted bird species, willow and rock ptarmigan (Lagopus lagopus and Lagopus muta), respond to long-term climate warming. Contrary to previous findings in mammals, we demonstrate a genetic continuity in Europe over the last 20 millennia. Results from back-casted species distribution models suggest that this continuity may have been facilitated by uninterrupted habitat availability and potentially also the greater dispersal ability of birds. However, our predictions show that in the near future, some isolated regions will have little suitable habitat left, implying a future decrease in local populations at a scale unprecedented since the last glacial maximum.
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| 19. |
- Mohr, Friedrich W., et al.
(author)
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Coronary artery bypass graft surgery versus percutaneous coronary intervention in patients with three-vessel disease and left main coronary disease : 5-year follow-up of the randomised, clinical SYNTAX trial
- 2013
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In: The Lancet. - 0140-6736 .- 1474-547X. ; 381:9867, s. 629-638
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Journal article (peer-reviewed)abstract
- Background We report the 5-year results of the SYNTAX trial, which compared coronary artery bypass graft surgery (CABG) with percutaneous coronary intervention (PCI) for the treatment of patients with left main coronary disease or three-vessel disease, to confirm findings at 1 and 3 years. Methods The randomised, clinical SYNTAX trial with nested registries took place in 85 centres in the USA and Europe. A cardiac surgeon and interventional cardiologist at each centre assessed consecutive patients with de-novo three-vessel disease or left main coronary disease to determine suitability for study treatments. Eligible patients suitable for either treatment were randomly assigned (1: 1) by an interactive voice response system to either PCI with a first-generation paclitaxel-eluting stent or to CABG. Patients suitable for only one treatment option were entered into either the PCI-only or CABG-only registries. We analysed a composite rate of major adverse cardiac and cerebrovascular events (MACCE) at 5-year follow-up by Kaplan-Meier analysis on an intention-to-treat basis. This study is registered with ClinicalTrials.gov, number NCT00114972. Findings 1800 patients were randomly assigned to CABG (n=897) or PCI (n=903). More patients who were assigned to CABG withdrew consent than did those assigned to PCI (50 vs 11). After 5 years' follow-up, Kaplan-Meier estimates of MACCE were 26.9% in the CABG group and 37.3% in the PCI group (p<0.0001). Estimates of myocardial infarction (3.8% in the CABG group vs 9.7% in the PCI group; p<0.0001) and repeat revascularisation (13.7% vs 25.9%; p<0.0001) were significantly increased with PCI versus CABG. All-cause death (11.4% in the CABG group vs 13.9% in the PCI group; p=0.10) and stroke (3.7% vs 2.4%; p=0.09) were not significantly different between groups. 28.6% of patients in the CABG group with low SYNTAX scores had MACCE versus 32.1% of patients in the PCI group (p=0.43) and 31.0% in the CABG group with left main coronary disease had MACCE versus 36.9% in the PCI group (p=0.12); however, in patients with intermediate or high SYNTAX scores, MACCE was significantly increased with PCI (intermediate score, 25.8% of the CABG group vs 36.0% of the PCI group; p=0.008; high score, 26.8% vs 44.0%; p<0.0001). Interpretation CABG should remain the standard of care for patients with complex lesions (high or intermediate SYNTAX scores). For patients with less complex disease (low SYNTAX scores) or left main coronary disease (low or intermediate SYNTAX scores), PCI is an acceptable alternative. All patients with complex multivessel coronary artery disease should be reviewed and discussed by both a cardiac surgeon and interventional cardiologist to reach consensus on optimum treatment.
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