| 11. |
- Ortiz-Fernandez, Lourdes, et al.
(författare)
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Identification of susceptibility loci for Takayasu arteritis through a large multi-ancestral genome-wide association study
- 2021
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Ingår i: American Journal of Human Genetics. - CAMBRIDGE, MA USA : Cell Press. - 0002-9297 .- 1537-6605. ; 108:1, s. 84-99
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Tidskriftsartikel (refereegranskat)abstract
- Takayasu arteritis is a rare inflammatory disease of large arteries. We performed a genetic study in Takayasu arteritis comprising 6,670 individuals (1,226 affected individuals) from five different populations. We discovered HLA risk factors and four non-HLA susceptibility loci in VPS8, SVEP1, CFL2, and chr13q21 and reinforced IL12B, PTK2B, and chr21q22 as robust susceptibility loci shared across ancestries. Functional analysis proposed plausible underlying disease mechanisms and pinpointed ETS2 as a potential causal gene for chr21q22 association. We also identified >60 candidate loci with suggestive association (p < 5 x 10(-s)) and devised a genetic risk score for Takayasu arteritis. Takayasu arteritis was compared to hundreds of other traits, revealing the closest genetic relatedness to inflammatory bowel disease. Epigenetic patterns within risk loci suggest roles for monocytes and B cells in Takayasu arteritis. This work enhances understanding of the genetic basis and pathophysiology of Takayasu arteritis and provides clues for potential new therapeutic targets.
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| 12. |
- Nicholl, M., et al.
(författare)
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On the diversity of superluminous supernovae : ejected mass as the dominant factor
- 2015
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 452:4, s. 3869-3893
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Tidskriftsartikel (refereegranskat)abstract
- We assemble a sample of 24 hydrogen-poor superluminous supernovae (SLSNe). Parameterizing the light-curve shape through rise and decline time-scales shows that the two are highly correlated. Magnetar-powered models can reproduce the correlation, with the diversity in rise and decline rates driven by the diffusion time-scale. Circumstellar interaction models can exhibit a similar rise-decline relation, but only for a narrow range of densities, which may be problematic for these models. We find that SLSNe are approximately 3.5 mag brighter and have light curves three times broader than SNe Ibc, but that the intrinsic shapes are similar. There are a number of SLSNe with particularly broad light curves, possibly indicating two progenitor channels, but statistical tests do not cleanly separate two populations. The general spectral evolution is also presented. Velocities measured from Fe II are similar for SLSNe and SNe Ibc, suggesting that diffusion time differences are dominated by mass or opacity. Flat velocity evolution in most SLSNe suggests a dense shell of ejecta. If opacities in SLSNe are similar to other SNe Ibc, the average ejected mass is higher by a factor 2-3. Assuming. = 0.1 cm(2) g(-1), we estimate a mean (median) SLSN ejecta mass of 10 M-circle dot (6 M-circle dot), with a range of 3-30 M-circle dot. Doubling the assumed opacity brings the masses closer to normal SNe Ibc, but with a high-mass tail. The most probable mechanism for generating SLSNe seems to be the core collapse of a very massive hydrogen-poor star, forming a millisecond magnetar.
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| 13. |
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| 14. |
- Scalzo, R. A., et al.
(författare)
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Early ultraviolet emission in the Type Ia supernova LSQ12gdj : No evidence for ongoing shock interaction
- 2014
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 445:1, s. 30-48
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Tidskriftsartikel (refereegranskat)abstract
- We present photospheric-phase observations of LSQ12gdj, a slowly declining, UV-bright Type Ia supernova. Classified well before maximum light, LSQ12gdj has extinction-corrected absolute magnitude M-B = -19.8, and pre-maximum spectroscopic evolution similar to SN 1991T and the super-Chandrasekhar-mass SN 2007if. We use ultraviolet photometry from Swift, ground-based optical photometry, and corrections from a near-infrared photometric template to construct the bolometric (1600-23 800 angstrom) light curve out to 45 d past B-band maximum light. We estimate that LSQ12gdj produced 0.96 +/- 0.07 M-circle dot of Ni-56, with an ejected mass near or slightly above the Chandrasekhar mass. As much as 27 per cent of the flux at the earliest observed phases, and 17 per cent at maximum light, is emitted bluewards of 3300 angstrom. The absence of excess luminosity at late times, the cutoff of the spectral energy distribution bluewards of 3000 angstrom and the absence of narrow line emission and strong Na I D absorption all argue against a significant contribution from ongoing shock interaction. However, similar to 10 per cent of LSQ12gdj's luminosity near maximum light could be produced by the release of trapped radiation, including kinetic energy thermalized during a brief interaction with a compact, hydrogen-poor envelope (radius < 10(13) cm) shortly after explosion; such an envelope arises generically in double-degenerate merger scenarios.
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| 15. |
- Dias, M M, et al.
(författare)
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The effect of the UGT1A1*28 allele on survival after irinotecan-based chemotherapy : a collaborative meta-analysis
- 2014
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Ingår i: The Pharmacogenomics Journal. - : Springer Science and Business Media LLC. - 1470-269X .- 1473-1150. ; 14:5, s. 424-431
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Tidskriftsartikel (refereegranskat)abstract
- To date, studies of irinotecan pharmacogenetics have mostly focused on the effect of the UGT1A1*28 allele on irinotecan-related toxicity. However, the clinical utility of routine UGT1A1*28 genotyping to pre-emptively adjust irinotecan dosage is dependent upon whether UGT1A1*28 also affects patient survival following irinotecan therapy. Previous observational studies evaluating the influence of UGT1A1*28 on survival have shown contradictory results. A systematic review and meta-analysis of both published and unpublished data were performed to summarize the available evidence of the relationship between the UGT1A1*28 allele and patient survival related to irinotecan therapy. Overall and progression-free survival meta-analysis data were available for 1524 patients and 1494 patients, respectively. The difference in the survival between patients of different UGT1A1*28 genotypes (homozygous, heterozygous or wild-type) who had received irinotecan was not found to be statistically significant. There was also no evidence of irinotecan dose, regimen or line of therapy having an impact on this association.
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| 16. |
- Polshaw, J., et al.
(författare)
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LSQ13fn : A type II-Plateau supernova with a possibly low metallicity progenitor that breaks the standardised candle relation
- 2016
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 588
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Tidskriftsartikel (refereegranskat)abstract
- We present optical imaging and spectroscopy of supernova (SN) LSQ13fn, a type II supernova with several hitherto-unseen properties. Although it initially showed strong symmetric spectral emission features attributable to He II, N III, and C III, reminiscent of some interacting SNe, it transitioned into an object that would fall more naturally under a type II-Plateau (IIP) classification. However, its spectral evolution revealed several unusual properties: metal lines appeared later than expected, were weak, and some species were conspicuous by their absence. Furthermore, the line velocities were found to be lower than expected given the plateau brightness, breaking the SN IIP standardised candle method for distance estimates. We found that, in combination with a short phase of early-time ejecta-circumstellar material interaction, metal-poor ejecta, and a large progenitor radius could reasonably account for the observed behaviour. Comparisons with synthetic model spectra of SNe IIP of a given progenitor mass would imply a progenitor star metallicity as low as 0.1 Z(circle dot). LSQ13fn highlights the diversity of SNe II and the many competing physical e ff ects that come into play towards the final stages of massive star evolution immediately preceding core-collapse.
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| 17. |
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| 18. |
- Gall, E. E. E., et al.
(författare)
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A comparative study of Type II-P and II-L supernova rise times as exemplified by the case of LSQ13cuw
- 2015
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 582
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Tidskriftsartikel (refereegranskat)abstract
- We report on our findings based on the analysis of observations of the Type II-L supernova LSQ13cuw within the framework of currently accepted physical predictions of core-collapse supernova explosions. LSQ13cuw was discovered within a day of explosion, hitherto unprecedented for Type II-L supernovae. This motivated a comparative study of Type II-P and II-L supernovae with relatively well-constrained explosion epochs and rise times to maximum (optical) light. From our sample of twenty such events, we find evidence of a positive correlation between the duration of the rise and the peak brightness. On average, SNe II-L tend to have brighter peak magnitudes and longer rise times than SNe II-P. However, this difference is clearest only at the extreme ends of the rise time versus peak brightness relation. Using two different analytical models, we performed a parameter study to investigate the physical parameters that control the rise time behaviour. In general, the models qualitatively reproduce aspects of the observed trends. We find that the brightness of the optical peak increases for larger progenitor radii and explosion energies, and decreases for larger masses. The dependence of the rise time on mass and explosion energy is smaller than the dependence on the progenitor radius. We find no evidence that the progenitors of SNe II-L have significantly smaller radii than those of SNe II-P.
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| 19. |
- Nduva, George M., et al.
(författare)
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Temporal trends and transmission dynamics of pre-treatment HIV-1 drug resistance within and between risk groups in Kenya, 1986–2020
- 2024
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Ingår i: Journal of Antimicrobial Chemotherapy. - 0305-7453. ; 79:2, s. 287-296
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Tidskriftsartikel (refereegranskat)abstract
- Background: Evidence on the distribution of pre-treatment HIV-1 drug resistance (HIVDR) among risk groups is limited in Africa. We assessed the prevalence, trends and transmission dynamics of pre-treatment HIVDR within and between MSM, people who inject drugs (PWID), female sex workers (FSWs), heterosexuals (HETs) and perinatally infected children in Kenya. Methods: HIV-1 partial pol sequences from antiretroviral-naive individuals collected from multiple sources between 1986 and 2020 were used. Pre-treatment reverse transcriptase inhibitor (RTI), PI and integrase inhibitor (INSTI) mutations were assessed using the Stanford HIVDR database. Phylogenetic methods were used to determine and date transmission clusters. Results: Of 3567 sequences analysed, 550 (15.4%, 95% CI: 14.2–16.6) had at least one pre-treatment HIVDR mutation, which was most prevalent amongst children (41.3%), followed by PWID (31.0%), MSM (19.9%), FSWs (15.1%) and HETs (13.9%). Overall, pre-treatment HIVDR increased consistently, from 6.9% (before 2005) to 24.2% (2016–20). Among HETs, pre-treatment HIVDR increased from 6.6% (before 2005) to 20.2% (2011–15), but dropped to 6.5% (2016–20). Additionally, 32 clusters with shared pre-treatment HIVDR mutations were identified. The majority of clusters had R0 ≥ 1.0, indicating ongoing transmissions. The largest was a K103N cluster involving 16 MSM sequences sampled between 2010 and 2017, with an estimated time to the most recent common ancestor (tMRCA) of 2005 [95% higher posterior density (HPD), 2000–08], indicating propagation over 12 years. Conclusions: Compared to HETs, children and key populations had higher levels of pre-treatment HIVDR. Introduction of INSTIs after 2017 may have abrogated the increase in pre-treatment RTI mutations, albeit in the HET population only. Taken together, our findings underscore the need for targeted efforts towards equitable access to ART for children and key populations in Kenya.
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| 20. |
- Yang, Xin, et al.
(författare)
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Cancer risks associated with germline PALB2 pathogenic variants : An international study of 524 families
- 2020
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Ingår i: Journal of Clinical Oncology. - 0732-183X. ; 38:7, s. 674-685
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE To estimate age-specific relative and absolute cancer risks of breast cancer and to estimate risks of ovarian, pancreatic, male breast, prostate, and colorectal cancers associated with germline PALB2 pathogenic variants (PVs) because these risks have not been extensively characterized. METHODS We analyzed data from 524 families with PALB2 PVs from 21 countries. Complex segregation analysis was used to estimate relative risks (RRs; relative to country-specific population incidences) and absolute risks of cancers. The models allowed for residual familial aggregation of breast and ovarian cancer and were adjusted for the family-specific ascertainment schemes. RESULTS We found associations between PALB2 PVs and risk of female breast cancer (RR, 7.18; 95% CI, 5.82 to 8.85; P = 6.5 × 10-76), ovarian cancer (RR, 2.91; 95% CI, 1.40 to 6.04; P = 4.1 × 10-3), pancreatic cancer (RR, 2.37; 95% CI, 1.24 to 4.50; P = 8.7 × 10-3), and male breast cancer (RR, 7.34; 95% CI, 1.28 to 42.18; P = 2.6 3 1022). There was no evidence for increased risks of prostate or colorectal cancer. The breast cancer RRs declined with age (P for trend = 2.0 × 10-3). After adjusting for family ascertainment, breast cancer risk estimates on the basis of multiple case families were similar to the estimates from families ascertained through population-based studies (P for difference = .41). On the basis of the combined data, the estimated risks to age 80 years were 53% (95% CI, 44% to 63%) for female breast cancer, 5% (95% CI, 2% to 10%) for ovarian cancer, 2%-3% (95% CI females, 1% to 4%; 95% CI males, 2% to 5%) for pancreatic cancer, and 1% (95% CI, 0.2% to 5%) for male breast cancer. CONCLUSION These results confirm PALB2 as a major breast cancer susceptibility gene and establish substantial associations between germline PALB2 PVs and ovarian, pancreatic, and male breast cancers. These findings will facilitate incorporation of PALB2 into risk prediction models and optimize the clinical cancer risk management of PALB2 PV carriers.
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