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| 2. |
- Sawcer, Stephen, et al.
(författare)
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Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
- 2011
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 476:7359, s. 214-219
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Tidskriftsartikel (refereegranskat)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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| 3. |
- Chen, T.-W., et al.
(författare)
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SN 2017ens : The Metamorphosis of a Luminous Broadlined Type Ic Supernova into an SN IIn
- 2018
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8205 .- 2041-8213. ; 867:2
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Tidskriftsartikel (refereegranskat)abstract
- We present observations of supernova (SN) 2017ens, discovered by the ATLAS survey and identified as a hot blue object through the GREAT program. The redshift z = 0.1086 implies a peak brightness of M-g = -21.1 mag, placing the object within the regime of superluminous supernovae. We observe a dramatic spectral evolution, from initially being blue and featureless, to later developing features similar to those of the broadlined Type Ic SN 1998bw, and finally showing 2000 km s(-1) wide H alpha and H beta emission. Relatively narrow Balmer emission (reminiscent of a SN IIn) is present at all times. We also detect coronal lines, indicative of a dense circumstellar medium. We constrain the progenitor wind velocity to similar to 50-60 km s(-1) based on P-Cygni profiles, which is far slower than those present in Wolf-Rayet stars. This may suggest that the progenitor passed through a luminous blue variable phase, or that the wind is instead from a binary companion red supergiant star. At late times we see the similar to 2000 km s(-1) wide H alpha emission persisting at high luminosity (similar to 3 x 10(40) erg s(-1)) for at least 100 day, perhaps indicative of additional mass loss at high velocities that could have been ejected by a pulsational pair instability.
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| 5. |
- Tartaglia, L., et al.
(författare)
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The Early Detection and Follow-up of the Highly Obscured Type II Supernova 2016ija/DLT16am
- 2018
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 853:1
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Tidskriftsartikel (refereegranskat)abstract
- We present our analysis of the Type II supernova DLT16am (SN 2016ija). The object was discovered during the ongoing D < 40 Mpc (DLT40) one-day cadence supernova search at r similar to 20.1 mag in the edge-on nearby (D = 20.0 +/- 4.0 Mpc) galaxy NGC 1532. The subsequent prompt and high-cadenced spectroscopic and photometric follow-up revealed a highly extinguished transient, with E(B - V) = 1.95 +/- 0.15 mag, consistent with a standard extinction law with R-V = 3.1 and a bright (M-V = -18.48 +/- 0.77 mag) absolute peak magnitude. A comparison of the photometric features with those of large samples of SNe II reveals a fast rise for the derived luminosity and a relatively short plateau phase, with a slope of S-50V = 0.84 +/- 0.04 mag/50 days, consistent with the photometric properties typical of those of fast-declining SNe II. Despite the large uncertainties on the distance and the extinction in the direction of DLT16am, the measured photospheric expansion velocity and the derived absolute V-band magnitude at similar to 50 days after the explosion match the existing luminosity-velocity relation for SNe II.
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| 6. |
- Tinyanont, S., et al.
(författare)
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Keck Infrared Transient Survey. I. Survey Description and Data Release 1
- 2024
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Ingår i: Publications of the Astronomical Society of the Pacific. - 0004-6280 .- 1538-3873. ; 136:1
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Tidskriftsartikel (refereegranskat)abstract
- We present the Keck Infrared Transient Survey, a NASA Key Strategic Mission Support program to obtain near-infrared (NIR) spectra of astrophysical transients of all types, and its first data release, consisting of 105 NIR spectra of 50 transients. Such a data set is essential as we enter a new era of IR astronomy with the James Webb Space Telescope (JWST) and the upcoming Nancy Grace Roman Space Telescope (Roman). NIR spectral templates will be essential to search JWST images for stellar explosions of the first stars and to plan an effective Roman SN Ia cosmology survey, both key science objectives for mission success. Between 2022 February and 2023 July, we systematically obtained 274 NIR spectra of 146 astronomical transients, representing a significant increase in the number of available NIR spectra in the literature. Here, we describe the first release of data from the 2022A semester. We systematically observed three samples: a flux-limited sample that includes all transients <17 mag in a red optical band (usually ZTF r or ATLAS o bands); a volume-limited sample including all transients within redshift z < 0.01 (D ≈ 50 Mpc); and an SN Ia sample targeting objects at phases and light-curve parameters that had scant existing NIR data in the literature. The flux-limited sample is 39% complete (60% excluding SNe Ia), while the volume-limited sample is 54% complete and is 79% complete to z = 0.005. Transient classes observed include common Type Ia and core-collapse supernovae, tidal disruption events, luminous red novae, and the newly categorized hydrogen-free/helium-poor interacting Type Icn supernovae. We describe our observing procedures and data reduction using PypeIt, which requires minimal human interaction to ensure reproducibility.
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| 7. |
- Beecham, Ashley H, et al.
(författare)
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Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis.
- 2013
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:11, s. 1353-60
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Tidskriftsartikel (refereegranskat)abstract
- Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10(-4)). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 × 10(-8)), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.
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| 8. |
- Labus, J. S., et al.
(författare)
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Acute tryptophan depletion alters the effective connectivity of emotional arousal circuitry during visceral stimuli in healthy women
- 2011
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Ingår i: Gut. - : BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288. ; 60:9, s. 1196-1203
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Alterations in serotonin signalling within the brain-gut axis have been implicated in the pathophysiology of irritable bowel syndrome (IBS) and is a treatment target. Acute tryptophan depletion (ATD) decreases brain serotonin (5-hydroxytryptamine; 5-HT) levels, and increases visceral perception and negative emotional bias in patients with IBS. The aim of the present study was to determine the effect of ATD on brain activity and connectivity during visceral stimuli in healthy women, and to compare the ATD-induced brain connectivity of an arousal circuit in female patients with IBS without ATD.METHODS: 12 healthy females (19-25 years) were studied under placebo (PLA) conditions and ATD. Functional MRI measurements were performed during a rectal barostat protocol, consisting of random non-painful and maximal tolerable distensions. Partial least squares analyses and structural equation modelling were used to evaluate the effect of ATD on functional and effective brain connectivity during distension. Results in healthy controls under ATD were compared with the effective connectivity of brain responses to 45 mm Hg rectal distension in 14 female patients with constipation-predominant IBS (IBS-C) (24-50 years).RESULTS: In healthy controls, ATD resulted in increased response of an extensive brain network to balloon distension, including the amygdala and nodes of emotional arousal and homeostatic afferent networks. The effect was greater during high inflation, suggesting greater engagement of the central serotonion system with more aversive visceral stimuli. Effective connectivity analysis revealed a profound effect of ATD on coupling between emotional arousal network nodes, resulting in loss of negative feedback inhibition of the amygdala. A near-identical pattern was identified in the patients with IBS-C.CONCLUSIONS: The findings are consistent with an ATD-induced disinhibition of and increased connectivity within an emotional arousal network during aversive stimulation. Together with the previous demonstration of ATD-induced visceral hyperalgesia in healthy controls, and the near-identical effective connectivity pattern observed in patients with IBS-C, these findings suggest that dysregulation of this brain network may play a role in central pain amplification and IBS pathophysiology.
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| 9. |
- Sandy, J, et al.
(författare)
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Why are multi-centre clinical observational studies still so difficult to run?
- 2011
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Ingår i: British Dental Journal. - 0007-0610 .- 1476-5373. ; 211:2, s. 59-61
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Tidskriftsartikel (refereegranskat)abstract
- Despite the introduction of IRAS, obtaining R&D approvals for multicentre studies is a major rate limiting step. Our experience with cleft research demonstrates that this approvals process must be drastically and rapidly improved if we wish to continue attract clinical research to the UK.
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