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- Kuhle, J., et al.
(författare)
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Conversion from clinically isolated syndrome to multiple sclerosis: A large multicentre study
- 2015
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Ingår i: Multiple Sclerosis Journal. - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 21:8, s. 1013-1024
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Tidskriftsartikel (refereegranskat)abstract
- Background and objective: We explored which clinical and biochemical variables predict conversion from clinically isolated syndrome (CIS) to clinically definite multiple sclerosis (CDMS) in a large international cohort. Methods: Thirty-three centres provided serum samples from 1047 CIS cases with at least two years' follow-up. Age, sex, clinical presentation, T2-hyperintense lesions, cerebrospinal fluid (CSF) oligoclonal bands (OCBs), CSF IgG index, CSF cell count, serum 25-hydroxyvitamin D3 (25-OH-D), cotinine and IgG titres against Epstein-Barr nuclear antigen 1 (EBNA-1) and cytomegalovirus were tested for association with risk of CDMS. Results: At median follow-up of 4.31 years, 623 CIS cases converted to CDMS. Predictors of conversion in multivariable analyses were OCB (HR = 2.18, 95% CI = 1.71-2.77, p < 0.001), number of T2 lesions (two to nine lesions vs 0/1 lesions: HR = 1.97, 95% CI = 1.52-2.55, p < 0.001; >9 lesions vs 0/1 lesions: HR = 2.74, 95% CI = 2.04-3.68, p < 0.001) and age at CIS (HR per year inversely increase = 0.98, 95% CI = 0.98-0.99, p < 0.001). Lower 25-OH-D levels were associated with CDMS in univariable analysis, but this was attenuated in the multivariable model. OCB positivity was associated with higher EBNA-1 IgG titres. Conclusions: We validated MRI lesion load, OCB and age at CIS as the strongest independent predictors of conversion to CDMS in this multicentre setting. A role for vitamin D is suggested but requires further investigation.
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| 4. |
- Cheng, THT, et al.
(författare)
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Meta-analysis of genome-wide association studies identifies common susceptibility polymorphisms for colorectal and endometrial cancer near SH2B3 and TSHZ1
- 2015
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 5, s. 17369-
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Tidskriftsartikel (refereegranskat)abstract
- High-risk mutations in several genes predispose to both colorectal cancer (CRC) and endometrial cancer (EC). We therefore hypothesised that some lower-risk genetic variants might also predispose to both CRC and EC. Using CRC and EC genome-wide association series, totalling 13,265 cancer cases and 40,245 controls, we found that the protective allele [G] at one previously-identified CRC polymorphism, rs2736100 near TERT, was associated with EC risk (odds ratio (OR) = 1.08, P = 0.000167); this polymorphism influences the risk of several other cancers. A further CRC polymorphism near TERC also showed evidence of association with EC (OR = 0.92; P = 0.03). Overall, however, there was no good evidence that the set of CRC polymorphisms was associated with EC risk and neither of two previously-reported EC polymorphisms was associated with CRC risk. A combined analysis revealed one genome-wide significant polymorphism, rs3184504, on chromosome 12q24 (OR = 1.10, P = 7.23 × 10−9) with shared effects on CRC and EC risk. This polymorphism, a missense variant in the gene SH2B3, is also associated with haematological and autoimmune disorders, suggesting that it influences cancer risk through the immune response. Another polymorphism, rs12970291 near gene TSHZ1, was associated with both CRC and EC (OR = 1.26, P = 4.82 × 10−8), with the alleles showing opposite effects on the risks of the two cancers.
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| 6. |
- Vanzella, E., et al.
(författare)
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An extremely metal-poor star complex in the reionization era : Approaching Population III stars with JWST
- 2023
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Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 678
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Tidskriftsartikel (refereegranskat)abstract
- We present JWST/Near Infrared Spectrograph (NIRSpec) integral field spectroscopy (IFS) of a lensed Population III candidate stellar complex (dubbed Lensed And Pristine 1, LAP1), with a lensing-corrected stellar mass of ≲104 M⊙ and an absolute luminosity of MUV > −11.2 (mUV > 35.6), confirmed at redshift 6.639 ± 0.004. The system is strongly amplified (μ ≳ 100) by straddling a critical line of the Hubble Frontier Field galaxy cluster MACS J0416. Although the stellar continuum is currently not detected in the Hubble and JWST/Near Infrared Camera (NIRCam) and Near Infrared Imager and Slitless Spectrograph (NIRISS) imaging, arclet-like shapes of Lyman and Balmer lines, Lyα, Hγ, Hβ and Hα are detected with NIRSpec IFS with signal-to-noise ratios (S/N) of approximately 5 − 13 and large equivalent widths (> 300 − 2000 Å), along with a remarkably weak [O III]λλ4959, 5007 at S/N ≃ 4. LAP1 shows a large ionizing photon production efficiency, log(ξion[erg Hz−1]) > 26. From the metallicity indexes R23 = ([O III] + [O II])/Hβ ≲ 0.74 and R3 = ([O III]/Hβ) = 0.55 ± 0.14, we derive an oxygen abundance of 12 + log(O/H)≲6.3. Intriguingly, the Hα emission is also measured in mirrored subcomponents where no [O III] is detected, providing even more stringent upper limits on the metallicity if in situ star formation is ongoing in this region (12 + log(O/H) < 6). The formal stellar mass limit of the subcomponents would correspond to ∼103 M⊙ or MUV fainter than −10. Alternatively, this metal-free, pure line-emitting region could be the first case of a fluorescing H I gas region induced by transverse escaping ionizing radiation from a nearby star complex. The presence of large equivalent-width hydrogen lines and the deficiency of metal lines in such a small region make LAP1 the most metal-poor star-forming region currently known in the reionization era and a promising site that may host isolated, pristine stars.
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