| 1. |
- Finzell, Thomas, et al.
(author)
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A Detailed Observational Analysis of V1324 Sco, the Most Gamma-Ray-luminous Classical Nova to Date
- 2018
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In: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 852:2
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Journal article (peer-reviewed)abstract
- It has recently been discovered that some, if not all, classical novae emit GeV gamma-rays during outburst, but the mechanisms involved in the production ofgamma-rays are still not well understood. We present here a comprehensive multiwavelength data set - from radio to X-rays - for the most gamma-ray-luminous classical nova to date, V1324 Sco. Using this data set, we show that V1324 Sco is a canonical dusty Fe ii-type nova, with a maximum ejecta velocity of 2600 km s-1 and an ejecta mass of a few × 10-5 M⊙. There is also evidence for complex shock interactions, including a double-peaked radio light curve which shows high brightness temperatures at early times. To explore why V1324 Sco was so gamma-ray luminous, we present a model of the nova ejecta featuring strong internal shocks and find that higher gamma-ray luminosities result from higher ejecta velocities and/or mass-loss rates. Comparison of V1324 Sco with other gamma-ray-detected novae does not show clear signatures of either, and we conclude that a larger sample of similarly well-observed novae is needed to understand the origin and variation of gamma-rays in novae.
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| 2. |
- Chomiuk, Laura, et al.
(author)
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Classical Novae at Radio Wavelengths
- 2021
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In: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 257:2
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Journal article (peer-reviewed)abstract
- We present radio observations (1-40 GHz) for 36 classical novae, representing data from over five decades compiled from the literature, telescope archives, and our own programs. Our targets display a striking diversity in their optical parameters (e.g., spanning optical fading timescales, t (2) = 1-263 days), and we find a similar diversity in the radio light curves. Using a brightness temperature analysis, we find that radio emission from novae is a mixture of thermal and synchrotron emission, with nonthermal emission observed at earlier times. We identify high brightness temperature emission (T ( B ) > 5 x 10(4) K) as an indication of synchrotron emission in at least nine (25%) of the novae. We find a class of synchrotron-dominated novae with mildly evolved companions, exemplified by V5589 Sgr and V392 Per, that appear to be a bridge between classical novae with dwarf companions and symbiotic binaries with giant companions. Four of the novae in our sample have two distinct radio maxima (the first dominated by synchrotron and the later by thermal emission), and in four cases the early synchrotron peak is temporally coincident with a dramatic dip in the optical light curve, hinting at a common site for particle acceleration and dust formation. We publish the light curves in a machine-readable table and encourage the use of these data by the broader community in multiwavelength studies and modeling efforts.
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| 3. |
- Huynh, Thao, et al.
(author)
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The Pre-Hospital Fibrinolysis Experience in Europe and North America and Implications for Wider Dissemination
- 2011
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In: JACC-CARDIOVASCULAR INTERVENTIONS. - : Elsevier. - 1936-8798 .- 1876-7605. ; 4:8, s. 877-883
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Journal article (peer-reviewed)abstract
- Objectives The primary objective of this report was to describe the infrastructures and processes of selected European and North American pre-hospital fibrinolysis (PHL) programs. A secondary objective is to report the outcome data of the PHL programs surveyed. less thanbrgreater than less thanbrgreater thanBackground Despite its benefit in reducing mortality in patients with ST-segment elevation myocardial infarction, PHL remained underused in North America. Examination of existing programs may provide insights to help address barriers to the implementation of PHL. less thanbrgreater than less thanbrgreater thanMethods The leading investigators of PHL research projects/national registries were invited to respond to a survey on the organization and outcomes of their affiliated PHL programs. less thanbrgreater than less thanbrgreater thanResults PHL was successfully deployed in a wide range of geographic territories (Europe: France, Sweden, Vienna, England, and Wales; North America: Houston, Edmonton, and Nova Scotia) and was delivered by healthcare professionals of varying expertise. In-hospital major adverse outcomes were rare with mortality of 3% to 6%, reinfarction of 2% to 5%, and stroke of andlt;2%. less thanbrgreater than less thanbrgreater thanConclusions Combining formal protocols for PHL for some patients with direct transportation of others to a percutaneous coronary intervention hospital for primary percutaneous coronary intervention would allow for tailored reperfusion therapy for patients with ST-segment elevation myocardial infarction. Insights from a variety of international settings may promote widespread use of PHL and increase timely coronary reperfusion worldwide.
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| 4. |
- O'Connor, Antoinette, et al.
(author)
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Plasma amyloid-β ratios in autosomal dominant Alzheimer's disease: the influence of genotype.
- 2021
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In: Brain : a journal of neurology. - : Oxford University Press (OUP). - 1460-2156. ; 144:10, s. 2964-2970
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Journal article (peer-reviewed)abstract
- In vitro studies of autosomal dominant Alzheimer's disease implicate longer amyloid-β peptides in disease pathogenesis; however, less is known about the behaviour of these mutations in vivo. In this cross-sectional cohort study, we used liquid chromatography-tandem mass spectrometry to analyse 66 plasma samples from individuals who were at risk of inheriting a mutation or were symptomatic. We tested for differences in amyloid-β (Aβ)42:38, Aβ42:40 and Aβ38:40 ratios between presenilin 1 (PSEN1) and amyloid precursor protein (APP) carriers. We examined the relationship between plasma and in vitro models of amyloid-β processing and tested for associations with parental age at onset. Thirty-nine participants were mutation carriers (28 PSEN1 and 11 APP). Age- and sex-adjusted models showed marked differences in plasma amyloid-β between genotypes: higher Aβ42:38 in PSEN1 versus APP (P<0.001) and non-carriers (P<0.001); higher Aβ38:40 in APP versus PSEN1 (P<0.001) and non-carriers (P<0.001); while Aβ42:40 was higher in both mutation groups compared to non-carriers (both P<0.001). Amyloid-β profiles were reasonably consistent in plasma and cell lines. Within the PSEN1 group, models demonstrated associations between Aβ42:38, Aβ42:40 and Aβ38:40 ratios and parental age at onset. In vivo differences in amyloid-β processing between PSEN1 and APP carriers provide insights into disease pathophysiology, which can inform therapy development.
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| 5. |
- Paterson, Ross W, et al.
(author)
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Cerebrospinal fluid in the differential diagnosis of Alzheimer's disease: clinical utility of an extended panel of biomarkers in a specialist cognitive clinic
- 2018
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In: Alzheimer's research & therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 10, s. 1-11
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Journal article (peer-reviewed)abstract
- Cerebrospinal fluid (CSF) biomarkers are increasingly being used to support a diagnosis of Alzheimer's disease (AD). Their clinical utility for differentiating AD from non-AD neurodegenerative dementias, such as dementia with Lewy bodies (DLB) or frontotemporal dementia (FTD), is less well established. We aimed to determine the diagnostic utility of an extended panel of CSF biomarkers to differentiate AD from a range of other neurodegenerative dementias.We used immunoassays to measure conventional CSF markers of amyloid and tau pathology (amyloid beta (Aβ)1-42, total tau (T-tau), and phosphorylated tau (P-tau)) as well as amyloid processing (AβX-38, AβX-40, AβX-42, soluble amyloid precursor protein (sAPP)α, and sAPPβ), large fibre axonal degeneration (neurofilament light chain (NFL)), and neuroinflammation (YKL-40) in 245 patients with a variety of dementias and 30 controls. Patients fulfilled consensus criteria for AD (n=156), DLB (n=20), behavioural variant frontotemporal dementia (bvFTD; n=45), progressive non-fluent aphasia (PNFA; n=17), and semantic dementia (SD; n=7); approximately 10% were pathology/genetically confirmed (n=26). Global tests based on generalised least squares regression were used to determine differences between groups. Non-parametric receiver operating characteristic (ROC) curves and area under the curve (AUC) analyses were used to quantify how well each biomarker discriminated AD from each of the other diagnostic groups (or combinations of groups). CSF cut-points for the major biomarkers found to have diagnostic utility were validated using an independent cohort which included causes of AD (n=104), DLB (n=5), bvFTD (n=12), PNFA (n=3), SD (n=9), and controls (n=10).There were significant global differences in Aβ1-42, T-tau, T-tau/Aβ1-42 ratio, P-tau-181, NFL, AβX-42, AβX-42/X-40 ratio, APPα, and APPβ between groups. At a fixed sensitivity of 85%, AβX-42/X-40 could differentiate AD from controls, bvFTD, and SD with specificities of 93%, 85%, and 100%, respectively; for T-tau/Aβ1-42 these specificities were 83%, 70%, and 86%. AβX-42/X-40 had similar or higher specificity than Aβ1-42. No biomarker or ratio could differentiate AD from DLB or PNFA with specificity >50%. Similar sensitivities and specificities were found in the independent validation cohort for differentiating AD and other dementias and in a pathology/genetically confirmed sub-cohort.CSF AβX-42/X-40 and T-tau/Aβ1-42 ratios have utility in distinguishing AD from controls, bvFTD, and SD. None of the biomarkers tested had good specificity at distinguishing AD from DLB or PNFA.
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| 6. |
- Sawcer, Stephen, et al.
(author)
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Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
- 2011
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 476:7359, s. 214-219
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Journal article (peer-reviewed)abstract
- Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.
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| 7. |
- Weston, David J., et al.
(author)
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The Sphagnome Project : enabling ecological and evolutionary insights through a genus-level sequencing project
- 2018
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In: New Phytologist. - : Wiley. - 0028-646X .- 1469-8137. ; 217:1, s. 16-25
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Journal article (other academic/artistic)abstract
- Considerable progress has been made in ecological and evolutionary genetics with studies demonstrating how genes underlying plant and microbial traits can influence adaptation and even 'extend' to influence community structure and ecosystem level processes. Progress in this area is limited to model systems with deep genetic and genomic resources that often have negligible ecological impact or interest. Thus, important linkages between genetic adaptations and their consequences at organismal and ecological scales are often lacking. Here we introduce the Sphagnome Project, which incorporates genomics into a long-running history of Sphagnum research that has documented unparalleled contributions to peatland ecology, carbon sequestration, biogeochemistry, microbiome research, niche construction, and ecosystem engineering. The Sphagnome Project encompasses a genus-level sequencing effort that represents a new type of model system driven not only by genetic tractability, but by ecologically relevant questions and hypotheses.
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