| 1. |
- Conti, David, V, et al.
(författare)
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Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction
- 2021
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:1, s. 65-75
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction. A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.
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| 2. |
- Wang, Anqi, et al.
(författare)
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Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
- 2023
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:12, s. 2065-2074
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Tidskriftsartikel (refereegranskat)abstract
- The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.
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| 3. |
- Andersson, Mikael, 1986, et al.
(författare)
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Control Rod Calculation in Axially-Heterogeneous Fast Reactors. Part I: Influence of the Absorber Environment
- 2017
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Ingår i: Nuclear Science and Engineering. - : Informa UK Limited. - 0029-5639 .- 1943-748X. ; 185:2, s. 263-276
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Tidskriftsartikel (refereegranskat)abstract
- In axially heterogeneous fast reactor concepts, such as the ASTRID CFVcore, the accurate neutronic prediction of control rods is a challenge. In suchcores, the performance of the classical 2D equivalence procedure, used forcontrol rod homogenization in homogeneous fast reactors, is questionable.In this work (Part I of II), a number of axially heterogeneous environ-ments, representative of a CFV-type core are investigated using 2D (X-Z )models, with the objective to distinguish regions where the classical equiva-lence procedure is valid from those where it is not.It is found that the environments that affect the control rod absorber themost, and are likely to invalidate the procedure, are the internal control rodinterfaces, such as the absorber/follower interface and the interface betweenzones of different boron enrichments. The range of the main spectral impactcould be seen within 0-10 cm from the material interfaces studied.In a companion Paper (Part II), a full core investigation is performed,which builds upon the results of this paper.
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| 4. |
- Andersson, Mikael, 1986, et al.
(författare)
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Control rod calculation in axially-heterogeneous fast reactors. Part II: Impact of 3D homogenization on core parameters
- 2017
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Ingår i: Nuclear Science and Engineering. - : Informa UK Limited. - 0029-5639 .- 1943-748X. ; 185:2, s. 277-293
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Tidskriftsartikel (refereegranskat)abstract
- Advanced sodium-cooled fast reactors with improved safety features, such asthe French ASTRID CFV-core concept, is characterized by an axial heteroge-neous core, which will present a challenge on the homogenization proceduresused today, taking into account all the different axial material transitions.Reliable modeling of the control rod and accurate prediction of the controlrod worth are essential to determine the shutdown margins and to ensuresafe operation.In this work (Part II of II), two different homogenization schemes are com-pared. One is based on the traditional reactivity-equivalence procedure in 2D,and the other a newly implemented 3D version of the reactivity-equivalenceprocedure, with approximations based on the results in a companion pa-pers (Part I). The deterministic results are compared with a Monte Carloreference.Both of the cross section sets, from the two homogenization schemes, yielded results within the requested 5% error margin in reactivity. Thelargest discrepancy was found for the classical procedure for the case with aslightly inserted control rod (normal operating conditions).Both sets of cross sections yielded similar power profiles in the fuel sub-assembly neighboring the control rod within the 2 Monte Carlo standarddeviation. Neither of the cross section sets were able to predict the largegradients in capture rates close to the internal control rod interfaces.The study showed that the traditional 2D reactivity-equivalence proce-dure produces homogenized cross sections which yield reliable results in aCFV-type core. One exception from this was found for slightly inserted con-trol rods, where the effect of the follower/absorber interface could not be fullycaptured by the 2D scheme, and for such cases, 3D modeling is recommended.
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| 6. |
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| 7. |
- Andersson, Mikael, 1986, et al.
(författare)
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Impact of Control Rod Position and Homogenization on Sodium Void Effect in CFV-type SFR
- 2016
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Ingår i: PHYSOR 2016. - 9781510825734 ; 4, s. 2658-2667
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Konferensbidrag (refereegranskat)abstract
- In complex innovative fast reactor concepts, fairly detailed core modeling is essential for reliable safety analysis during severe accident scenarios. The CFV core with its axially heterogeneous design, has a negative sodium void reactivity effect, a favorable feature wich increases the inherent system safety in case of sodium boiling. In this work, we studied the impact that the control rod homogenization model used, and the control rod position, have on the sodium void-reactivityeffect and the control rod worth, in the case of a voided CFV core. Three different control rodhomogenization models were studied, the traditional 2D equivalence procedure, and two models based on a 3D equivalence procedure, taking into account the axial heterogeneity of the CFV core.It was found that the impact of control rod homogenization has a negligible effect on the sodium void reactivity effect. However, between different control rod positions, a difference of up to 1$ in the sodium void reactivity effect was found, hence the control rod position has to be carefully considered when calculating the sodium void reactivity effect. For the control rod worth in a voidedCFV core, the traditional 2D procedure, could lead to discrepancies of up to 11% for control rod positions at the top of the core. These discrepancies could be much reduced by control rod homogenization with the 3D equivalence procedure. For the total control rod worth, all models andprocedures produced results within the desired error margin of 5%.
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| 8. |
- Andersson, Mikael, 1986, et al.
(författare)
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Influence of Local Spectral Variations on Control-Rod Homogenization in Fast Reactor Environments
- 2015
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Ingår i: Nuclear Science and Engineering. - 0029-5639 .- 1943-748X. ; 181:2, s. 204-215
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Tidskriftsartikel (refereegranskat)abstract
- Advanced fast reactor concepts, such as the CFV core (French acronym of "Coeur a Foible effet de Vide Sodium," meaning "low sodium void effect core"), are characterized by a heterogeneous axial core arrangement, with an inner fertile zone and a sodium plenum above the fuel. Such concepts represent a strong challenge for accurate predictions of the control-rod antireactivity effects, and the surrounding local fuel pin power. Classical equivalence procedures, which were developed for axially homogeneous cores, are put to the test when applied to such axially heterogeneous cores. In this work, we investigate the influence of variations in the local neutron spectra, for different control-rod environments, with the objective of understanding the impact of spectral variations in control-rod homogenization. This was conducted by considering a simple one-dimensional model of the equivalence procedure in which a transition zone between the fuel and control rod was introduced to represent different control-rod environments. Two types of situations were studied, one corresponding to softened neutron spectrum environments, for which the impact in the homogenized control-rod cross section was found to be smaller than 5%. The second situation was with wide elastic scattering resonances in the control-rod environment, which could locally lead to differences of up to 15% in the resulting equivalent cross sections. The reactivity effect of these changes was calculated to be less than 2%. In some cases, the numerical stability of the equivalence procedure was adversely affected, mainly in high-energy groups, due to the softening of the neutron spectra.
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| 9. |
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| 10. |
- Nguyen, Yann, et al.
(författare)
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Association Between Severe Nonadherence to Hydroxychloroquine and Systemic Lupus Erythematosus Flares, Damage, and Mortality in 660 Patients From the SLICC Inception Cohort
- 2023
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Ingår i: Arthritis and Rheumatology. - 2326-5191. ; 75:12, s. 2195-2206
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The goals of this study were to assess the associations of severe nonadherence to hydroxychloroquine (HCQ), objectively assessed by HCQ serum levels, and risks of systemic lupus erythematosus (SLE) flares, damage, and mortality rates over five years of follow-up. Methods: The Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort is an international multicenter initiative (33 centers throughout 11 countries). The serum of patients prescribed HCQ for at least three months at enrollment were analyzed. Severe nonadherence was defined by a serum HCQ level <106 ng/mL or <53 ng/mL for HCQ doses of 400 or 200 mg/day, respectively. Associations with the risk of a flare (defined as a Systemic Lupus Erythematosus Disease Activity Index 2000 increase ≥4 points, initiation of prednisone or immunosuppressive drugs, or new renal involvement) were studied with logistic regression, and associations with damage (first SLICC/American College of Rheumatology Damage Index [SDI] increase ≥1 point) and mortality with separate Cox proportional hazard models. Results: Of the 1,849 cohort participants, 660 patients (88% women) were included. Median (interquartile range) serum HCQ was 388 ng/mL (244–566); 48 patients (7.3%) had severe HCQ nonadherence. No covariates were clearly associated with severe nonadherence, which was, however, independently associated with both flare (odds ratio 3.38; 95% confidence interval [CI] 1.80–6.42) and an increase in the SDI within each of the first three years (hazard ratio [HR] 1.92 at three years; 95% CI 1.05–3.50). Eleven patients died within five years, including 3 with severe nonadherence (crude HR 5.41; 95% CI 1.43–20.39). Conclusion: Severe nonadherence was independently associated with the risks of an SLE flare in the following year, early damage, and five-year mortality. (Figure presented.).
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