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- 2017
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Ingår i: Physical Review D. - 2470-0010 .- 2470-0029. ; 96:2
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Tidskriftsartikel (refereegranskat)
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| 2. |
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| 3. |
- Ahluwalia, T. S., et al.
(författare)
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Genome-wide association study of circulating interleukin 6 levels identifies novel loci
- 2021
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 30:5, s. 393-409
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Tidskriftsartikel (refereegranskat)abstract
- Interleukin 6 (IL-6) is a multifunctional cytokine with both pro- and anti-inflammatory properties with a heritability estimate of up to 61%. The circulating levels of IL-6 in blood have been associated with an increased risk of complex disease pathogenesis. We conducted a two-staged, discovery and replication meta genome-wide association study (GWAS) of circulating serum IL-6 levels comprising up to 67428 (n(discovery)=52654 and n(replication)=14774) individuals of European ancestry. The inverse variance fixed effects based discovery meta-analysis, followed by replication led to the identification of two independent loci, IL1F10/IL1RN rs6734238 on chromosome (Chr) 2q14, (P-combined=1.8x10(-11)), HLA-DRB1/DRB5 rs660895 on Chr6p21 (P-combined=1.5x10(-10)) in the combined meta-analyses of all samples. We also replicated the IL6R rs4537545 locus on Chr1q21 (P-combined=1.2x10(-122)). Our study identifies novel loci for circulating IL-6 levels uncovering new immunological and inflammatory pathways that may influence IL-6 pathobiology.
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| 4. |
- Dadaev, T, et al.
(författare)
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Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants
- 2018
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 2256-
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling.
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| 5. |
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| 6. |
- 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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| 7. |
- 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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| 8. |
- Arrillaga-Romany, Isabel, et al.
(författare)
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Performance of a Hospital Pathway for Patients With a New Single Brain Mass
- 2019
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Ingår i: JOURNAL OF ONCOLOGY PRACTICE. - : American Society of Clinical Oncology (ASCO). - 1554-7477. ; 15:3, s. e211-e218
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Tidskriftsartikel (refereegranskat)abstract
- WHAT WE FOUND:Length of stay and time to surgery were significantly reduced after implementation of this admission pathway. Readmission rate was not adversely affected by this change. The protocol also significantly reduced the number of unnecessary body computed tomography imaging studies obtained in this patient population.CONFOUNDING FACTORS/REAL-LIFE IMPLICATIONS:The results of this study should be interpreted with their retrospective nature in mind. Further, analysis of this admission pathway did not take into consideration patient perspective or cost implications. Finally, the authors recognize that the resources for such an operational shift may only be found in large, tertiary, referral centers.Optimized specialized care for patients with new single brain masses promotes improved health care outcomes. It may also predictively reduce health care costs and improve patient satisfaction. More research is needed in this field. Limitations to our study included the inherent limitations of a retrospective pre-post design that can make it difficult to separate the effect of a specific intervention from other factors that change over time. In addition, assessment of patient satisfaction, use of diagnostic tests beyond body imaging, and advanced cost analysis could have strengthened this study. Lastly, it should be noted that the applicability of our approach may be limited to major tertiary centers with enough resources to implement such a pathway.Purpose:To reduce care variation and improve the management of patients with newly identified single brain masses and no history of cancer, we implemented a dedicated admission protocol.Methods:We reviewed records of 206 patients who presented to our emergency department between January 2010 and May 2016 with a new single brain mass but no history of cancer. Patients admitted before the protocol implementation were designated the pre-implementation group (PRE), and those admitted after implementation were designated the post-implementation group (POST).Results:Ninety-six patients were in the PRE group and 110 in the POST group. Length of stay for POST patients was significantly shorter than for PRE patients (6 v 7 days, respectively; P = .042), and this effect was more robust after excluding the 66 patients who were discharged to rehabilitation, skilled nursing, or hospice facilities (5 v 7 days, respectively; P = .001). Additional comparison of POST with PRE patients showed that time to surgery was significantly reduced (2.7 v 3.5 days, respectively; P = .006) and that computed tomography scans of the chest, abdomen, and pelvis were reduced (12% v 47%, respectively; P < .001). No difference was found in the 30-day readmission rates. For patients with GBM, there also was no significant difference in time to initiation of chemoradiation or in median overall survival.Conclusion:Implementation of a specialized admission pathway for patients with a new single brain mass decreased average length of hospital stay and time to surgery and reduced unnecessary diagnostic imaging tests in patients with primary brain tumors.
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| 9. |
- Garg, K. B., et al.
(författare)
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Mechanism of quenching of superconductivity in the YBa2Cu3O7-delta system on substitution of Zn for Cu
- 2010
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Ingår i: International Journal of Modern Physics B. - 0217-9792. ; 24:14, s. 2135-2148
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Tidskriftsartikel (refereegranskat)abstract
- Substituting Zn for Cu is known to rapidly quench superconductivity in the doped perovskites but the mechanism behind it is still not clearly understood. Single phase YBa2(Cu1-xZnx)(3)O7-delta (x=0.0 to 0.06) samples were synthesized and characterized using XRD, wet titration, resistivity, and ac susceptibility. Angle-integrated Valence Band Photo emission and Zn K-edge XAFS results clearly show that their oxygen stoichiometry (delta) changes on Zn substitution, there by adversely affecting the density of free charge carriers and hence the normal state resistivity and the T-c. However, the observed changes in the two happen to be too large to be accounted for solely on the basis of changes in the oxygen stoichiometry delta. We find that the Zn cation acts as a strong "impurity" scattering centre in the YBCO lattice and causes local lattice distortion (LLD). It consequently induces local magnetic moment, seen in our dc susceptibility measurements. It is thus a composite of (Delta delta), LLD and possibly also magnetic pair-breaking that is responsible for the rapid quenching of the super conductivity observed with Zn doping in this system.
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| 10. |
- Singhal, Dhruv, et al.
(författare)
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Mapping the lymphatic system across body scales and expertise domains : A report from the 2021 National Heart, Lung, and Blood Institute workshop at the Boston Lymphatic Symposium
- 2023
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Ingår i: Frontiers in Physiology. - : Frontiers Media S.A.. - 1664-042X. ; 14
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Forskningsöversikt (refereegranskat)abstract
- Enhancing our understanding of lymphatic anatomy from the microscopic to the anatomical scale is essential to discern how the structure and function of the lymphatic system interacts with different tissues and organs within the body and contributes to health and disease. The knowledge of molecular aspects of the lymphatic network is fundamental to understand the mechanisms of disease progression and prevention. Recent advances in mapping components of the lymphatic system using state of the art single cell technologies, the identification of novel biomarkers, new clinical imaging efforts, and computational tools which attempt to identify connections between these diverse technologies hold the potential to catalyze new strategies to address lymphatic diseases such as lymphedema and lipedema. This manuscript summarizes current knowledge of the lymphatic system and identifies prevailing challenges and opportunities to advance the field of lymphatic research as discussed by the experts in the workshop.
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