| 1. |
- Tabiri, S, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 2. |
- Bravo, L, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
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| 4. |
- Vogel, Jacob W., et al.
(författare)
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Four distinct trajectories of tau deposition identified in Alzheimer’s disease
- 2021
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 27:5, s. 871-881
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Tidskriftsartikel (refereegranskat)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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| 5. |
- Thoma, B, et al.
(författare)
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An international, interprofessional investigation of the self-reported podcast listening habits of emergency clinicians: A METRIQ Study
- 2020
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Ingår i: CJEM. - : Springer Science and Business Media LLC. - 1481-8043 .- 1481-8035. ; 22:1, s. 112-117
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesPodcasts are increasingly being used for medical education. A deeper understanding of usage patterns would inform both producers and researchers of medical podcasts. We aimed to determine how and why podcasts are used by emergency medicine and critical care clinicians.MethodsAn international interprofessional sample (medical students, residents, physicians, nurses, physician assistants, and paramedics) was recruited through direct contact and a multimodal social media (Twitter and Facebook) campaign. Each participant completed a survey outlining how and why they utilize medical podcasts. Recruitment materials included an infographic and study website.Results390 participants from 33 countries and 4 professions (medicine, nursing, paramedicine, physician assistant) completed the survey. Participants most frequently listened to medical podcasts to review new literature (75.8%), learn core material (75.1%), and refresh memory (71.8%). The majority (62.6%) were aware of the ability to listen at increased speeds, but most (76.9%) listened at 1.0 x (normal) speed. All but 25 (6.4%) participants concurrently performed other tasks while listening. Driving (72.3%), exercising (39.7%), and completing chores (39.2%) were the most common. A minority of participants used active learning techniques such as pausing, rewinding, and replaying segments of the podcast. Very few listened to podcasts multiple times.ConclusionsAn international cohort of emergency clinicians use medical podcasts predominantly for learning. Their listening habits (rarely employing active learning strategies and frequently performing concurrent tasks) may not support this goal. Further exploration of the impact of these activities on learning from podcasts is warranted.
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| 6. |
- Zhou, XP, et al.
(författare)
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Non-coding variability at the APOE locus contributes to the Alzheimer's risk
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 3310-
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Tidskriftsartikel (refereegranskat)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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| 7. |
- Baden, Susanne P., 1952, et al.
(författare)
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Between-individual variation in haemocyanin concentrations in the Norway lobster Nephrops norvegicus following exposure to hypoxia and manganese
- 2003
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Ingår i: Marine Biology. - 0025-3162. ; 143:2, s. 267-273
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Tidskriftsartikel (refereegranskat)abstract
- Environmental hypoxia and the release of reduced manganese (Mn) are often combined stress factors in marine sediments. Previous investigations have shown that hypoxia induces variable responses in the concentration of the respiratory pigment haemocyanin (Hc) of crustaceans. A recent study demonstrated that the magnitude and direction of the changes was dependent on the initial level of Hc in individuals of the Norway lobster Nephrops norvegicus. The changes also took place within 24 h rather than days as suggested by previous studies. In this present study we investigated changes of Hc in individual N. norvegicus in uncontaminated sea water after exposure to and release from realistic hypoxic stress (PO2 = 6.0 kPa). Furthermore we investigated how concomitant exposure to realistic concentrations of manganese (20 mg 1(-1)) modified the responses we observed. We confirmed a between-individual variation in response and a change in Hc towards an optimum level after hypoxia, but also showed that changes that took place post-hypoxic exposure occurred over a timescale similar to that of the hypoxic response itself. Manganese exposure resulted in no significant changes in Hc whereas Mn exposure combined with hypoxia resulted in a significant decrease (15%) in all individuals independent of initial Hc. N. norvegicus was thus unable to compensate for the effects of hypoxia by synthesis of Hc after exposure to naturally occurring Mn concentrations.
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| 8. |
- Bednarsek, N., et al.
(författare)
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Synthesis of Thresholds of Ocean Acidification Impacts on Echinoderms
- 2021
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Ingår i: Frontiers in Marine Science. - : Frontiers Media SA. - 2296-7745. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Assessing the vulnerability of marine invertebrates to ocean acidification (OA) requires an understanding of critical thresholds at which developmental, physiological, and behavioral traits are affected. To identify relevant thresholds for echinoderms, we undertook a three-step data synthesis, focused on California Current Ecosystem (CCE) species. First, literature characterizing echinoderm responses to OA was compiled, creating a dataset comprised of >12,000 datapoints from 41 studies. Analysis of this data set demonstrated responses related to physiology, behavior, growth and development, and increased mortality in the larval and adult stages to low pH exposure. Second, statistical analyses were conducted on selected pathways to identify OA thresholds specific to duration, taxa, and depth-related life stage. Exposure to reduced pH led to impaired responses across a range of physiology, behavior, growth and development, and mortality endpoints for both larval and adult stages. Third, through discussions and synthesis, the expert panel identified a set of eight duration-dependent, life stage, and habitat-dependent pH thresholds and assigned each a confidence score based on quantity and agreement of evidence. The thresholds for these effects ranged within pH from 7.20 to 7.74 and duration from 7 to 30 days, all of which were characterized with either medium or low confidence. These thresholds yielded a risk range from early warning to lethal impacts, providing the foundation for consistent interpretation of OA monitoring data or numerical ocean model simulations to support climate change marine vulnerability assessments and evaluation of ocean management strategies. As a demonstration, two echinoderm thresholds were applied to simulations of a CCE numerical model to visualize the effects of current state of pH conditions on potential habitat.
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| 9. |
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| 10. |
- Jacobson, A, et al.
(författare)
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Expression of human hyaluronan synthases in response to external stimuli.
- 2000
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Ingår i: Biochemical Journal. - 0264-6021 .- 1470-8728. ; 348 Pt 1, s. 29-35
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Tidskriftsartikel (refereegranskat)abstract
- In the present study we have investigated the expression of mRNAs for hyaluronan synthase isoforms (HAS1, HAS2 and HAS3) in different cells in response to various stimuli. Human mesothelial cells, which synthesize large amounts of hyaluronan, express mRNAs encoding all three HAS isoforms, whereas their transformed counterparts, mesothelioma cells, which produce only minute amounts of hyaluronan, express only HAS3 mRNA. Human lung fibroblasts and the glioma cell line U-118 MG express only the HAS2 and HAS3 genes. The expression of the transcripts was higher in subconfluent than in confluent cultures and was well correlated with the production of hyaluronan by the cells. Stimulation of mesothelial cells with platelet-derived growth factor-BB induced an up-regulation of mRNA for HAS2 to a maximum after 6 h of stimulation; HAS1 and HAS3 genes were only induced slightly. Transforming growth factor-beta1 reduced HAS2 mRNA slightly, and hydrocortisone reduced it strongly, within 6 h of stimulation in mesothelial cell cultures but did not significantly affect the expression of mRNAs for HAS1 and HAS3. Induction of HAS1 and HAS2 protein levels in response to the stimuli above correlated with HAS transcript levels. Thus the expression of the three HAS isoforms is more prominent in growing cells than in resting cells and is differentially regulated by various stimuli suggesting distinct functional roles of the three proteins.
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