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| 2. |
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| 3. |
- Griswold, Max G., et al.
(författare)
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Alcohol use and burden for 195 countries and territories, 1990-2016 : a systematic analysis for the Global Burden of Disease Study 2016
- 2018
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Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 392:10152, s. 1015-1035
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Tidskriftsartikel (refereegranskat)abstract
- Background: Alcohol use is a leading risk factor for death and disability, but its overall association with health remains complex given the possible protective effects of moderate alcohol consumption on some conditions. With our comprehensive approach to health accounting within the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we generated improved estimates of alcohol use and alcohol-attributable deaths and disability-adjusted life-years (DALYs) for 195 locations from 1990 to 2016, for both sexes and for 5-year age groups between the ages of 15 years and 95 years and older.Methods: Using 694 data sources of individual and population-level alcohol consumption, along with 592 prospective and retrospective studies on the risk of alcohol use, we produced estimates of the prevalence of current drinking, abstention, the distribution of alcohol consumption among current drinkers in standard drinks daily (defined as 10 g of pure ethyl alcohol), and alcohol-attributable deaths and DALYs. We made several methodological improvements compared with previous estimates: first, we adjusted alcohol sales estimates to take into account tourist and unrecorded consumption; second, we did a new meta-analysis of relative risks for 23 health outcomes associated with alcohol use; and third, we developed a new method to quantify the level of alcohol consumption that minimises the overall risk to individual health.Findings: Globally, alcohol use was the seventh leading risk factor for both deaths and DALYs in 2016, accounting for 2.2% (95% uncertainty interval [UI] 1.5-3.0) of age-standardised female deaths and 6.8% (5.8-8.0) of age-standardised male deaths. Among the population aged 15-49 years, alcohol use was the leading risk factor globally in 2016, with 3.8% (95% UI 3.2-4-3) of female deaths and 12.2% (10.8-13-6) of male deaths attributable to alcohol use. For the population aged 15-49 years, female attributable DALYs were 2.3% (95% UI 2.0-2.6) and male attributable DALYs were 8.9% (7.8-9.9). The three leading causes of attributable deaths in this age group were tuberculosis (1.4% [95% UI 1. 0-1. 7] of total deaths), road injuries (1.2% [0.7-1.9]), and self-harm (1.1% [0.6-1.5]). For populations aged 50 years and older, cancers accounted for a large proportion of total alcohol-attributable deaths in 2016, constituting 27.1% (95% UI 21.2-33.3) of total alcohol-attributable female deaths and 18.9% (15.3-22.6) of male deaths. The level of alcohol consumption that minimised harm across health outcomes was zero (95% UI 0.0-0.8) standard drinks per week.Interpretation: Alcohol use is a leading risk factor for global disease burden and causes substantial health loss. We found that the risk of all-cause mortality, and of cancers specifically, rises with increasing levels of consumption, and the level of consumption that minimises health loss is zero. These results suggest that alcohol control policies might need to be revised worldwide, refocusing on efforts to lower overall population-level consumption.
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| 4. |
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| 5. |
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| 6. |
- Gusev, A, et al.
(författare)
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Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation
- 2016
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7, s. 10979-
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Tidskriftsartikel (refereegranskat)abstract
- Although genome-wide association studies have identified over 100 risk loci that explain ∼33% of familial risk for prostate cancer (PrCa), their functional effects on risk remain largely unknown. Here we use genotype data from 59,089 men of European and African American ancestries combined with cell-type-specific epigenetic data to build a genomic atlas of single-nucleotide polymorphism (SNP) heritability in PrCa. We find significant differences in heritability between variants in prostate-relevant epigenetic marks defined in normal versus tumour tissue as well as between tissue and cell lines. The majority of SNP heritability lies in regions marked by H3k27 acetylation in prostate adenoc7arcinoma cell line (LNCaP) or by DNaseI hypersensitive sites in cancer cell lines. We find a high degree of similarity between European and African American ancestries suggesting a similar genetic architecture from common variation underlying PrCa risk. Our findings showcase the power of integrating functional annotation with genetic data to understand the genetic basis of PrCa.
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| 7. |
- Porth, Oliver, et al.
(författare)
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The Event Horizon General Relativistic Magnetohydrodynamic Code Comparison Project
- 2019
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Ingår i: Astrophysical Journal, Supplement Series. - : American Astronomical Society. - 1538-4365 .- 0067-0049. ; 243:2
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Tidskriftsartikel (refereegranskat)abstract
- Recent developments in compact object astrophysics, especially the discovery of merging neutron stars by LIGO, the imaging of the black hole in M87 by the Event Horizon Telescope, and high- precision astrometry of the Galactic Center at close to the event horizon scale by the GRAVITY experiment motivate the development of numerical source models that solve the equations of general relativistic magnetohydrodynamics (GRMHD). Here we compare GRMHD solutions for the evolution of a magnetized accretion flow where turbulence is promoted by the magnetorotational instability from a set of nine GRMHD codes: Athena++, BHAC, Cosmos++, ECHO, H-AMR, iharm3D, HARM-Noble, IllinoisGRMHD, and KORAL. Agreement among the codes improves as resolution increases, as measured by a consistently applied, specially developed set of code performance metrics. We conclude that the community of GRMHD codes is mature, capable, and consistent on these test problems.
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| 8. |
- Gowin, Krisstina, et al.
(författare)
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Survival following allogeneic transplant in patients with myelofibrosis
- 2020
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Ingår i: Blood Advances. - : AMER SOC HEMATOLOGY. - 2473-9529 .- 2473-9537. ; 4:9, s. 1965-1973
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Tidskriftsartikel (refereegranskat)abstract
- Allogeneic hematopoietic cell transplantation (HCT) is the only curative therapy for myelofibrosis (MF). In this large multicenter retrospective study, overall survival (OS) in MF patients treated with allogeneic HCT (551 patients) and without HCT (non-HCT) (1377 patients) was analyzed with Cox proportional hazards model. Survival analysis stratified by the Dynamic International Prognostic Scoring System (DIPSS) revealed that the first year of treatment arm assignment, due to upfront risk of transplant-related mortality (TRM), HCT was associated with inferior OS compared with non-HCT (non-HCT vs HCT: DIPSS intermediate 1 [Int-1]: hazard ratio [HR] = 0.26, P < .0001; DIPSS-Int-2 and higher: HR, 0.39, P < .0001). Similarly, in the DIPSS low-risk MF group, due to upfront TRM risk, OS was superior with non-HCT therapies compared with HCT in the first-year post treatment arm assignment (HR, 0.16, P = .006). However, after 1 year, OS was not significantly different (HR, 1.38, P = .451). Beyond 1 year of treatment arm assignment, an OS advantage with HCT therapy in Int-1 and higher DIPSS score patients was observed (non-HCT vs HCT: DIPSS-Int-1: HR, 2.64, P < .0001; DIPSS-Int-2 and higher: HR, 2.55, P < .0001). In conclusion, long-term OS advantage with HCT was observed for patients with Int-1 or higher risk MF, but at the cost of early TRM. The magnitude of OS benefit with HCT increased as DIPSS risk score increased and became apparent with longer follow-up.
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| 9. |
- Mehta, Rohtesh S., et al.
(författare)
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Composite GRFS and CRFS Outcomes After Adult Alternative Donor HCT
- 2020
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Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology (ASCO). - 0732-183X .- 1527-7755. ; 38:18, s. 2062-2076
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE There is no consensus on the best choice of an alternative donor (umbilical cord blood [UCB], haploidentical, one-antigen mismatched [7/8]-bone marrow [BM], or 7/8-peripheral blood [PB]) for hematopoietic cell transplantation (HCT) for patients lacking an HLA-matched related or unrelated donor.METHODS We report composite end points of graft-versus-host disease (GVHD)-free relapse-free survival (GRFS) and chronic GVHD (cGVHD)-free relapse-free survival (CRFS) in 2,198 patients who underwent UCB (n = 838), haploidentical (n = 159), 7/8-BM (n = 241), or 7/8-PB (n = 960) HCT. All groups were divided by myeloablative conditioning (MAC) intensity or reduced intensity conditioning (RIC), except haploidentical group in which most received RIC. To account for multiple testing, P < .0071 in multivariable analysis and P < .00025 in direct pairwise comparisons were considered statistically significant.RESULTS In multivariable analysis, haploidentical group had the best GRFS, CRFS, and overall survival (OS). In the direct pairwise comparison of other groups, among those who received MAC, there was no difference in GRFS or CRFS among UCB, 7/8-BM, and 7/8-PB with serotherapy (alemtuzumab or antithymocyte globulin) groups. In contrast, the 7/8-PB without serotherapy group had significantly inferior GRFS, higher cGVHD, and a trend toward worse CRFS (hazard ratio [HR], 1.38; 95% CI, 1.13 to 1.69; P = .002) than the 7/8-BM group and higher cGVHD and trend toward inferior CRFS (HR, 1.36; 95% CI, 1.14 to 1.63; P = .0006) than the UCB group. Among patients with RIC, all groups had significantly inferior GRFS and CRFS compared with the haploidentical group.CONCLUSION Recognizing the limitations of a registry retrospective analysis and the possibility of center selection bias in choosing donors, our data support the use of UCB, 7/8-BM, or 7/8-PB (with serotherapy) grafts for patients undergoing MAC HCT and haploidentical grafts for patients undergoing RIC HCT. The haploidentical group had the best GRFS, CRFS, and OS of all groups.
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| 10. |
- Radivoyevitch, Tomas, et al.
(författare)
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Risk of acute myeloid leukemia and myelodysplastic syndrome after autotransplants for lymphomas and plasma cell myeloma
- 2018
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Ingår i: Leukemia Research. - : Elsevier BV. - 0145-2126 .- 1873-5835. ; 74, s. 130-136
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Tidskriftsartikel (refereegranskat)abstract
- Background: Exposures to DNA-damaging drugs and ionizing radiations increase risks of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).Methods: 9028 recipients of hematopoietic cell autotransplants (1995-2010) for Hodgkin lymphoma (HL; n=916), non-Hodgkin lymphoma (NHL; n=3546) and plasma cell myeloma (PCM; n=4566), reported to the CIBMTR, were analyzed for risk of subsequent AML or MDS.Results: 335 MDS/ AML cases were diagnosed posttransplant (3.7%). Variables associated with an increased risk for AML or MDS in multivariate analyses were: (1) conditioning with total body radiation versus chemotherapy alone for HL (HR=4.0; 95% confidence interval [1.4, 11.6]) and NHL (HR=2.5 [1.1, 2.5]); (2) >= 3 versus 1 line of chemotherapy for NHL (HR=1.9 [1.3, 2.8]); and (3) subjects with NHL transplanted in 2005-2010 versus 1995-1999 (HR=2.1 [1.5, 3.1]). Using Surveillance, Epidemiology and End Results (SEER) data, we found risks for AML/ MDS in HL, NHL and PCM to be 5-10 times the background rate. In contrast, relative risks were 10-50 for AML and approximately 100 for MDS in the autotransplant cohort.Conclusions: There are substantial risks of AML and MDS after autotransplants for HL, NHL and PCM.
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| 11. |
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| 12. |
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| 13. |
- DeFilipp, Zachariah, et al.
(författare)
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Maintenance Tyrosine Kinase Inhibitors Following Allogeneic Hematopoietic Stem Cell Transplantation for Chronic Myelogenous Leukemia : A Center for International Blood and Marrow Transplant Research Study
- 2020
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Ingår i: Biology of blood and marrow transplantation. - : Elsevier. - 1083-8791 .- 1523-6536. ; 26:3, s. 472-479
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Tidskriftsartikel (refereegranskat)abstract
- It remains unknown whether the administration of tyrosine kinase inhibitors (TKIs) targeting BCR-ABL1 after allogeneic hematopoietic cell transplantation (HCT) is associated with improved outcomes for patients with chronic myelogenous leukemia (CML). In this registry study, we analyzed clinical outcomes of 390 adult patients with CML who underwent transplantation between 2007 and 2014 and received maintenance TKI following HCT (n = 89) compared with no TKI maintenance (n = 301), as reported to the Center for International Blood and Marrow Transplant Research. All patients received TKI therapy before HCT. The majority of patients had a disease status of first chronic phase at HCT (n = 240; 62%). The study was conducted as a landmark analysis, excluding patients who died, relapsed, had chronic graft-versus-host disease, or were censored before day +100 following HCT. Of the 89 patients who received TKI maintenance, 77 (87%) received a single TKI and the other 12 (13%) received multiple sequential TKIs. The most common TKIs used for maintenance were dasatinib (n = 50), imatinib (n = 27), and nilotinib (n = 27). As measured from day +100, the adjusted estimates for 5-year relapse (maintenance, 35% versus no maintenance, 26%; P = .11), leukemia-free survival (maintenance, 42% versus no maintenance, 44%; P = .65), or overall survival (maintenance, 61% versus no maintenance, 57%; P = .61) did not differ significantly between patients receiving TKI maintenance or no maintenance. These results remained unchanged in multivariate analysis and were not modified by disease status before transplantation. In conclusion, our data from this day +100 landmark analysis do not demonstrate a significant impact of maintenance TKI therapy on clinical outcomes. The optimal approach to TKI administration in the post-transplantation setting in patients with CML remains undetermined.
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| 14. |
- Hu, Bei, et al.
(författare)
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Timing of allogeneic hematopoietic cell transplantation (alloHCT) for chronic myeloid leukemia (CML) patients
- 2020
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Ingår i: Leukemia and Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 61:12, s. 2811-2820
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Tidskriftsartikel (refereegranskat)abstract
- While TKI are the preferred first-line treatment for chronic phase (CP) CML, alloHCT remains an important consideration. The aim is to estimate residual life expectancy (RLE) for patients initially diagnosed with CP CML based on timing of alloHCT or continuation of TKI in various settings: CP1 CML, CP2 + [after transformation to accelerated phase (AP) or blast phase (BP)], AP, or BP. Non-transplant cohort included single-institution patients initiating TKI and switched TKI due to failure. CIBMTR transplant cohort included CML patients who underwent HLA sibling matched (MRD) or unrelated donor (MUD) alloHCT. AlloHCT appeared to shorten survival in CP1 CML with overall mortality hazard ratio (HR) for alloHCT of 2.4 (95% CI 1.2-4.9;p = .02). In BP CML, there was a trend toward higher survival with alloHCT; HR = 0.7 (0.5-1.1;p = .099). AlloHCT in CP2 + [HR = 2.0 (0.8-4.9),p = .13] and AP [HR = 1.1 (0.6-2.1);p = .80] is less clear and should be determined on a case-by-case basis.
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| 15. |
- Lee, Catherine J., et al.
(författare)
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Late effects after ablative allogeneic stem cell transplantation for adolescent and young adult acute myeloid leukemia
- 2020
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Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 4:6, s. 983-992
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Tidskriftsartikel (refereegranskat)abstract
- There is marked paucity of data regarding late effects in adolescents and young adults (AYAs) who undergo myeloablative conditioning (MAC) allogeneic hematopoietic cell transplantation (HCT) for acute myeloid leukemia (AML). We evaluated late effects and survival in 826 1-year disease-free survivors of MAC HCT for AYA AML, with an additional focus on comparing late effects based upon MAC type (total body irradiation [TBI] vs high-dose chemotherapy only). The estimated 10-year cumulative incidence of subsequent neoplasms was 4% (95% confidence interval [CI], 2%-6%); 10-year cumulative incidence of nonmalignant late effects included gonadal dysfunction (10%; 95% CI, 8%-13%), cataracts (10%; 95% CI, 7%-13%), avascular necrosis (8%; 95% CI, 5%-10%), diabetes mellitus (5%; 95% CI, 3%-7%), and hypothyroidism (3%; 95% CI, 2%-5%). Receipt of TBI was independently associated with a higher risk of cataracts only (hazard ratio [HR], 4.98; P < .0001) whereas chronic graft-versus-host disease (cGVHD) was associated with an increased risk of cataracts (HR, 3.22; P = .0006), avascular necrosis (HR, 2.49; P = .006), and diabetes mellitus (HR, 3.36; P = .03). Estimated 10-year overall survival and leukemia-free survival were 73% and 70%, respectively, and did not differ on the basis of conditioning type. In conclusion, late effects among survivors of MAC HCT for AYA AML are frequent and are more closely linked to cGVHD than type of conditioning.
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| 16. |
- Norkin, Maxim, et al.
(författare)
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Characteristics of Late Fatal Infections after Allogeneic Hematopoietic Cell Transplantation
- 2019
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Ingår i: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 25:2, s. 362-368
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Tidskriftsartikel (refereegranskat)abstract
- We analyzed late fatal infections (LFIs) in allogeneic stem cell transplantation (HCT) recipients reported to the Center for International Blood and Marrow Transplant Research. We analyzed the incidence, infection types, and risk factors contributing to LFI in 10,336 adult and 5088 pediatric subjects surviving for ≥2 years after first HCT without relapse. Among 2245 adult and 377 pediatric patients who died, infections were a primary or contributory cause of death in 687 (31%) and 110 (29%), respectively. At 12 years post-HCT, the cumulative incidence of LFIs was 6.4% (95% confidence interval [CI], 5.8% to 7.0%) in adults, compared with 1.8% (95% CI, 1.4% to 2.3%) in pediatric subjects; P < .001). In adults, the 2 most significant risks for developing LFI were increasing age (20 to 39, 40 to 54, and ≥55 years versus 18 to 19 years) with hazard ratios (HRs) of 3.12 (95% CI, 1.33 to 7.32), 3.86 (95% CI, 1.66 to 8.95), and 5.49 (95% CI, 2.32 to 12.99) and a history of chronic graft-versus-host disease GVHD (cGVHD) with ongoing immunosuppression at 2 years post-HCT compared with no history of GVHD with (HR, 3.87; 95% CI, 2.59 to 5.78). In pediatric subjects, the 3 most significant risks for developing LFI were a history of cGVHD with ongoing immunosuppression (HR, 9.49; 95% CI, 4.39 to 20.51) or without ongoing immunosuppression (HR, 2.7; 95% CI, 1.05 to 7.43) at 2 years post-HCT compared with no history of GVHD, diagnosis of inherited abnormalities of erythrocyte function compared with diagnosis of acute myelogenous leukemia (HR, 2.30; 95% CI, 1.19 to 4.42), and age >10 years (HR, 1.92; 95% CI, 1.15 to 3.2). This study emphasizes the importance of continued vigilance for late infections after HCT and institution of support strategies aimed at decreasing the risk of cGVHD.
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| 17. |
- Percival, Mary-Elizabeth, et al.
(författare)
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Impact of depth of clinical response on outcomes of acute myeloid leukemia patients in first complete remission who undergo allogeneic hematopoietic cell transplantation
- 2021
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Ingår i: Bone Marrow Transplantation. - : Springer Nature. - 0268-3369 .- 1476-5365. ; 56:9, s. 2108-2117
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Tidskriftsartikel (refereegranskat)abstract
- Acute myeloid leukemia (AML) patients often undergo allogeneic hematopoietic cell transplantation (alloHCT) in first complete remission (CR). We examined the effect of depth of clinical response, including incomplete count recovery (CRi) and/or measurable residual disease (MRD), in patients from the Center for International Blood and Marrow Transplantation Research (CIBMTR) registry. We identified 2492 adult patients (1799 CR and 693 CRi) who underwent alloHCT between January 1, 2007 and December 31, 2015. The primary outcome was overall survival (OS). Multivariable analysis was performed to adjust for patient-, disease-, and transplant-related factors. Baseline characteristics were similar. Patients in CRi compared to those in CR had an increased likelihood of death (HR: 1.27; 95% confidence interval: 1.13-1.43). Compared to CR, CRi was significantly associated with increased non-relapse mortality (NRM), shorter disease-free survival (DFS), and a trend toward increased relapse. Detectable MRD was associated with shorter OS, shorter DFS, higher NRM, and increased relapse compared to absence of MRD. The deleterious effects of CRi and MRD were independent. In this large CIBMTR cohort, survival outcomes differ among AML patients based on depth of CR and presence of MRD at the time of alloHCT. Further studies should focus on optimizing post-alloHCT outcomes for patients with responses less than CR.
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| 18. |
- Chhabra, Saurabh, et al.
(författare)
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Myeloablative vs reduced-intensity conditioning allogeneic hematopoietic cell transplantation for chronic myeloid leukemia
- 2018
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Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 2:21, s. 2922-2936
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Tidskriftsartikel (refereegranskat)abstract
- Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment of chronic myeloid leukemia (CML). Optimal conditioning intensity for allo-HCT for CML in the era of tyrosine kinase inhibitors (TKIs) is unknown. Using the Center for International Blood and Marrow Transplant Research database, we sought to determine whether reduced-intensity/nonmyeloablative conditioning (RIC) allo-HCT and myeloablative conditioning (MAC) result in similar outcomes in CML patients. We evaluated 1395 CML allo-HCT recipients between the ages of 18 and 60 years. The disease status at transplant was divided into the following categories: chronic phase 1, chronic phase 2 or greater, and accelerated phase. Patients in blast phase at transplant and alternative donor transplants were excluded. The primary outcome was overall survival (OS) after allo-HCT. MAC (n = 1204) and RIC allo-HCT recipients (n = 191) from 2007 to 2014 were included. Patient, disease, and transplantation characteristics were similar, with a few exceptions. Multivariable analysis showed no significant difference in OS between MAC and RIC groups. In addition, leukemia-free survival and nonrelapse mortality did not differ significantly between the 2 groups. Compared with MAC, the RIC group had a higher risk of early relapse after allo-HCT (hazard ratio [HR], 1.85; P = .001). The cumulative incidence of chronic graft-versus-host disease (cGVHD) was lower with RIC than with MAC (HR, 0.77; P = .02). RIC provides similar survival and lower cGVHD compared with MAC and therefore may be a reasonable alternative to MAC for CML patients in the TKI era.
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| 19. |
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| 20. |
- Gerds, Aaron T., et al.
(författare)
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Outcomes after Umbilical Cord Blood Transplantation for Myelodysplastic Syndromes
- 2017
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Ingår i: Biology of blood and marrow transplantation. - : Elsevier. - 1083-8791 .- 1523-6536. ; 23:6, s. 971-979
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Tidskriftsartikel (refereegranskat)abstract
- For patients with hematologic malignancies undergoing allogeneic hematopoietic cell transplantation, umbilical cord blood transplantation (UCBT) has become an acceptable alternative donor source in the absence of a matched sibling or unrelated donor. To date, however, there have been few published series dedicated solely to describing the outcomes of adult patients with myelodysplastic syndrome (MDS) who have undergone UCBT. Between 2004 and 2013, 176 adults with MDS underwent UCBT as reported to the Center for International Blood and Marrow Transplant Research. Median age at the time of transplantation was 56 years (range, 18-73 years). The study group included 10% with very low, 23% with low, 19% with intermediate, 19% with high, and 13% with very high-risk Revised International Prognostic Scoring System (IPSS-R) scores. The 100-day probability of grade II-IV acute graft-versus-host disease (GVHD) was 38%, and the 3-year probability of chronic GVHD was 28%. The probabilities of relapse and transplantation-related mortality (TRM) at 3 years were 32% and 40%, respectively, leading to a 3-year disease-free survival (DFS) of 28% and an overall survival (OS) of 31%. In multivariate analysis, increasing IPSS-R score at the time of HCT was associated with inferior TRM (P = .0056), DFS (P = .018), and OS (P = .0082), but not with GVHD or relapse. The presence of pretransplantation comorbidities was associated with TRM (P = .001), DFS (P = .02), and OS (P = .001). Reduced intensity conditioning was associated with increased risk of relapse (relative risk, 3.95; 95% confidence interval, 1.78-8.75; P < .001), and although a higher proportion of myeloablative UCBTs were performed in patients with high-risk disease, the effect of conditioning regimen intensity was the same regardless of IPSS-R score. For some individuals who lack a matched sibling or unrelated donor, UCBT can result in long-term DFS; however, the success of UCBT in this population is hampered by a high rate of TRM. (C) 2017 American Society for Blood and Marrow Transplantation.
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| 21. |
- Hall, Laurie A, et al.
(författare)
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Characterizing dispersal patterns in a threatened seabird with limited genetic structure.
- 2009
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Ingår i: Molecular ecology. - 1365-294X.
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Genetic assignment methods provide an appealing approach for characterizing dispersal patterns on ecological time scales, but require sufficient genetic differentiation to accurately identify migrants and a large enough sample size of migrants to, for example, compare dispersal between sexes or age classes. We demonstrate that assignment methods can be rigorously used to characterize dispersal patterns in a marbled murrelet (Brachyramphus marmoratus) population from central California that numbers approximately 600 individuals and is only moderately differentiated (F(ST) approximately 0.03) from larger populations to the north. We used coalescent simulations to select a significance level that resulted in a low and approximately equal expected number of type I and II errors and then used this significance level to identify a population of origin for 589 individuals genotyped at 13 microsatellite loci. The proportion of migrants in central California was greatest during winter when 83% of individuals were classified as migrants compared to lower proportions during the breeding (6%) and post-breeding (8%) seasons. Dispersal was also biased toward young and female individuals, as is typical in birds. Migrants were rarely members of parent-offspring pairs, suggesting that they contributed few young to the central California population. A greater number of migrants than expected under equilibrium conditions, a lack of individuals with mixed ancestry, and a small number of potential source populations (two), likely allowed us to use assignment methods to rigorously characterize dispersal patterns for a population that was larger and less differentiated than typically thought required for the identification of migrants.
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| 22. |
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| 23. |
- Huerta, E. A., et al.
(författare)
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Enabling real-time multi-messenger astrophysics discoveries with deep learning
- 2019
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Ingår i: Nature reviews physics. - : Springer Science and Business Media LLC. - 2522-5820. ; 1:10, s. 600-608
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Forskningsöversikt (refereegranskat)abstract
- Multi-messenger astrophysics is a fast-growing, interdisciplinary field that combines data, which vary in volume and speed of data processing, from many different instruments that probe the Universe using different cosmic messengers: electromagnetic waves, cosmic rays, gravitational waves and neutrinos. In this Expert Recommendation, we review the key challenges of real-time observations of gravitational wave sources and their electromagnetic and astroparticle counterparts, and make a number of recommendations to maximize their potential for scientific discovery. These recommendations refer to the design of scalable and computationally efficient machine learning algorithms; the cyber-infrastructure to numerically simulate astrophysical sources, and to process and interpret multi-messenger astrophysics data; the management of gravitational wave detections to trigger real-time alerts for electromagnetic and astroparticle follow-ups; a vision to harness future developments of machine learning and cyber-infrastructure resources to cope with the big-data requirements; and the need to build a community of experts to realize the goals of multi-messenger astrophysics. A group of experts suggests ways in which deep learning can be used to enhance the potential for discovery in multi-messenger astrophysics.
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| 24. |
- Jacobs, Alan M., et al.
(författare)
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The Qualitative Transparency Deliberations : Insights and Implications
- 2021
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Ingår i: Perspectives on Politics. - 1537-5927 .- 1541-0986. ; 19:1, s. 171-208
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Tidskriftsartikel (refereegranskat)abstract
- In recent years, a variety of efforts have been made in political science to enable, encourage, or require scholars to be more open and explicit about the bases of their empirical claims and, in turn, make those claims more readily evaluable by others. While qualitative scholars have long taken an interest in making their research open, reflexive, and systematic, the recent push for overarching transparency norms and requirements has provoked serious concern within qualitative research communities and raised fundamental questions about the meaning, value, costs, and intellectual relevance of transparency for qualitative inquiry. In this Perspectives Reflection, we crystallize the central findings of a three-year deliberative process-the Qualitative Transparency Deliberations (QTD)-involving hundreds of political scientists in a broad discussion of these issues. Following an overview of the process and the key insights that emerged, we present summaries of the QTD Working Groups' final reports. Drawing on a series of public, online conversations that unfolded at www.qualtd.net, the reports unpack transparency's promise, practicalities, risks, and limitations in relation to different qualitative methodologies, forms of evidence, and research contexts. Taken as a whole, these reports-the full versions of which can be found in the Supplementary Materials-offer practical guidance to scholars designing and implementing qualitative research, and to editors, reviewers, and funders seeking to develop criteria of evaluation that are appropriate-as understood by relevant research communities-to the forms of inquiry being assessed. We dedicate this Reflection to the memory of our coauthor and QTD working group leader Kendra Koivu.(1)
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| 25. |
- Jimenez, Antonio M. Jimenez, et al.
(författare)
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An adapted European LeukemiaNet genetic risk stratification for acute myeloid leukemia patients undergoing allogeneic hematopoietic cell transplant. A CIBMTR analysis
- 2021
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Ingår i: Bone Marrow Transplantation. - : Springer Nature. - 0268-3369 .- 1476-5365. ; 56:12, s. 3068-3077
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Tidskriftsartikel (refereegranskat)abstract
- Cytogenetic and molecular abnormalities are known to influence post-transplant outcomes in acute myeloid leukemia (AML) but data assessing the prognostic value of combined genetic models in the HCT setting are limited. We developed an adapted European LeukemiaNet (aELN) risk classification based on available genetic data reported to the Center for International Blood and Marrow Transplant Research, to predict post-transplant outcomes in 2289 adult AML patients transplanted in first remission, between 2013 and 2017. Patients were stratified according to aELN into three groups: favorable (Fav, N = 181), intermediate (IM, N = 1185), and adverse (Adv, N = 923). Univariate analysis demonstrated significant differences in 2-year overall survival (OS) (Fav: 67.7%, IM: 64.9% and Adv: 53.9%; p < 0.001); disease-free survival (DFS) (Fav: 57.8%, IM: 55.5% and Adv: 45.3; p < 0.001) and relapse (Fav: 28%, IM: 27.5% and Adv: 37.5%; p < 0.001). Multivariate analysis (MVA) revealed no differences in outcomes between the Fav and IM groups, thus they were combined. On MVA, patients in the Adv risk group had the highest risk of relapse (HR 1.47 p <= 0.001) and inferior DFS (HR 1.35 p < 0.001) and OS (HR 1.39 p < 0.001), even using myeloablative conditioning or in those without the pre-HCT measurable-residual disease. Novel approaches to mitigate relapse in this high-risk group are urgently needed.
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| 26. |
- Menghrajani, Kamal, et al.
(författare)
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Risk classification at diagnosis predicts post-HCT outcomes in intermediate-, adverse-risk, and KMT2A-rearranged AML
- 2022
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Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 6:3, s. 828-847
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Tidskriftsartikel (refereegranskat)abstract
- Little is known about whether risk classification at diagnosis predicts post-hematopoietic cell transplantation (HCT) outcomes in patients with acute myeloid leukemia (AML). We evaluated 8709 patients with AML from the CIBMTR database, and after selection and manual curation of the cytogenetics data, 3779 patients in first complete remission were included in the final analysis: 2384 with intermediate-risk, 969 with adverse-risk, and 426 with KMT2A-rearranged disease. An adjusted multivariable analysis detected an increased risk of relapse for patients with KMT2A-rearranged or adverse-risk AML as compared to those with intermediate-risk disease (hazards ratio [HR], 1.27; P = .01; HR, 1.71; P < .001, respectively). Leukemia-free survival was similar for patients with KMT2A rearrangement or adverse risk (HR, 1.26; P = .002, and HR, 1.47; P < .001), as was overall survival (HR, 1.32; P < .001, and HR, 1.45; P < .001). No differences in outcome were detected when patients were stratified by KMT2A fusion partner. This study is the largest conducted to date on post-HCT outcomes in AML, with manually curated cytogenetics used for risk stratification. Our work demonstrates that risk classification at diagnosis remains predictive of post-HCT outcomes in AML. It also highlights the critical need to develop novel treatment strategies for patients with KMT2A-rearranged and adverse-risk disease.
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| 27. |
- Metheny, Leland, et al.
(författare)
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Allogeneic Transplantation to Treat Therapy-Related Myelodysplastic Syndrome and Acute Myelogenous Leukemia in Adults
- 2021
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Ingår i: Transplantation and Cellular Therapy. - : Elsevier. - 2666-6375 .- 2666-6367. ; 27:11, s. 923.e1-923.e12
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Tidskriftsartikel (refereegranskat)abstract
- Patients who develop therapy-related myeloid neoplasm, either myelodysplastic syndrome (t-MDS) or acute myelogenous leukemia (t-AML), have a poor prognosis. An earlier Center for International Blood and Marrow Transplant Research (CIBMTR) analysis of 868 allogeneic hematopoietic cell transplantations (allo-HCTs) performed between 1990 and 2004 showed a 5-year overall survival (OS) and disease-free survival (DFS) of 22% and 21%, respectively. Modern supportive care, graft-versus-host disease prophylaxis, and reduced-intensity conditioning (RIC) regimens have led to improved outcomes. Therefore, the CIBMTR analyzed 1531 allo-HCTs performed in adults with t-MDS (n = 759) or t-AML (n = 772) between and 2000 and 2014. The median age was 59 years (range, 18 to 74 years) for the patients with t-MDS and 52 years (range, 18 to 77 years) for those with tAML. Twenty-four percent of patients with t-MDS and 11% of those with t-AML had undergone a previous autologous (auto-) HCT. A myeloablative conditioning (MAC) regimen was used in 49% of patients with t-MDS and 61% of patients with t-AML. Nonrelapse mortality at 5 years was 34% (95% confidence interval [CI], 30% to 37%) for patients with t-MDS and 34% (95% CI, 30% to 37%) for those with t-AML. Relapse rates at 5 years in the 2 groups were 46% (95% CI, 43% to 50%) and 43% (95% CI, 40% to 47%). Five-year OS and DFS were 27% (95% CI, 23% to 31%) and 19% (95% CI, 16% to 23%), respectively, for patients with t-MDS and 25% (95% CI, 22% to 28%) and 23% (95% CI, 20% to 26%), respectively, for those with t-AML. In multivariate analysis, OS and DFS were significantly better in young patients with low-risk t-MDS and those with t-AML undergoing HCT with MAC while in first complete remission, but worse for those with previous auto-HCT, higher-risk cytogenetics or Revised International Prognostic Scoring System score, and a partially matched unrelated donor. Relapse remains the major cause of treatment failure, with little improvement seen over the past 2 decades. These data mandate caution when recommending allo-HCT in these conditions and indicate the need for more effective antineoplastic approaches before and after allo-HCT.
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| 28. |
- Myers, Regina M., et al.
(författare)
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Long-Term Outcomes Among 2-Year Survivors of Autologous Hematopoietic Cell Transplantation for Hodgkin and Diffuse Large B-Cell Lymphoma
- 2018
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Ingår i: Cancer. - : WILEY. - 0008-543X .- 1097-0142. ; 124:4, s. 816-825
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Autologous hematopoietic cell transplantation (auto-HCT) is a standard therapy for relapsed classic Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL); however, long-term outcomes are not well described.METHODS: This study analyzed survival, nonrelapse mortality, late effects, and subsequent malignant neoplasms (SMNs) in 1617 patients who survived progression-free for >= 2 years after auto-HCT for cHL or DLBCL between 1990 and 2008. The median age at auto-HCT was 40 years; the median follow-up was 10.6 years.RESULTS: The 5-year overall survival rate was 90% (95% confidence interval [CI], 87%-92%) for patients with cHL and 89% (95% CI, 87%-91%) for patients with DLBCL. The risk of late mortality in comparison with the general population was 9.6-fold higher for patients with cHL (standardized mortality ratio [SMR], 9.6) and 3.4-fold higher for patients with DLBCL (SMR, 3.4). Relapse accounted for 44% of late deaths. At least 1 late effect was reported for 9% of the patients. A total of 105 SMNs were confirmed: 44 in the cHL group and 61 in the DLBCL group. According to a multivariate analysis, older age, male sex, a Karnofsky score < 90, total body irradiation (TBI) exposure, and a higher number of lines of chemotherapy before auto-HCT were risk factors for overall mortality in cHL. Risk factors in DLBCL were older age and TBI exposure. A subanalysis of 798 adolescent and young adult patients mirrored the outcomes of the overall study population.CONCLUSIONS: Despite generally favorable outcomes, 2-year survivors of auto-HCT for cHL or DLBCL have an excess late-mortality risk in comparison with the general population and experience an assortment of late complications.
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| 29. |
- Palsboll, Per J., et al.
(författare)
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Inferring recent historic abundance from current genetic diversity
- 2013
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Ingår i: Molecular Ecology. - : Wiley. - 0962-1083 .- 1365-294X. ; 22:1, s. 22-40
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Forskningsöversikt (refereegranskat)abstract
- Recent historic abundance is an elusive parameter of great importance for conserving endangered species and understanding the pre-anthropogenic state of the biosphere. The number of studies that have used population genetic theory to estimate recent historic abundance from contemporary levels of genetic diversity has grown rapidly over the last two decades. Such assessments often yield unexpectedly large estimates of historic abundance. We review the underlying theory and common practices of estimating recent historic abundance from contemporary genetic diversity, and critically evaluate the potential issues at various estimation steps. A general issue of mismatched spatio-temporal scales between the estimation itself and the objective of the estimation emerged from our assessment; genetic diversitybased estimates of recent historic abundance represent long-term averages, whereas the objective typically is an estimate of recent abundance for a specific population. Currently, the most promising approach to estimate the difference between recent historic and contemporary abundance requires that genetic data be collected from samples of similar spatial and temporal duration. Novel genome-enabled inference methods may be able to utilize additional information of dense genome-wide distributions of markers, such as of identity-by-descent tracts, to infer recent historic abundance from contemporary samples only.
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| 30. |
- Peery, M. Zachariah, et al.
(författare)
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Characterizing source-sink dynamics with genetic parentage assignments
- 2008
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Ingår i: Ecology. - : Wiley. - 0012-9658 .- 1939-9170. ; 89:10, s. 2746-2759
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Tidskriftsartikel (refereegranskat)abstract
- Source-sink dynamics have been suggested to characterize the population structure of many species, but the prevalence of source-sink systems in nature is uncertain because of inherent challenges in estimating migration rates among populations. Migration rates are often difficult to estimate directly with demographic methods, and indirect genetic methods are subject to a variety of assumptions that are difficult to meet or to apply to evolutionary timescales. Furthermore, such methods cannot be rigorously applied to high-gene-flow species. Here, we employ genetic parentage assignments in conjunction with demographic simulations to infer the level of immigration into a putative sink population. We use individual-based demographic models to estimate expected distributions of parent offspring dyads under competing sink and closed-population models. By comparing the actual number of parent-offspring dyads (identified from multilocus genetic profiles) in a random sample of individuals taken from a population to expectations under these two contrasting demographic models, it is possible to estimate the rate of immigration and test hypotheses related to the role of immigration on population processes on an ecological timescale. The difference in the expected number of parent-offspring dyads between the two population models was greatest when immigration into the sink population was high, indicating that unlike traditional population genetic inference models, the highest degree of statistical power is achieved for the approach presented here when migration rates are high. We used the proposed genetic parentage approach to demonstrate that a threatened population of Marbled Murrelets (Brachyramphus marmotus) appears to be supplemented by a low level of immigration (similar to 2-6% annually) from other populations.
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| 31. |
- Peery, M Zachariah, et al.
(författare)
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Genetic analyses of historic and modern marbled murrelets suggest decoupling of migration and gene flow after habitat fragmentation.
- 2010
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Ingår i: Proceedings of the Royal Society of London. Biological Sciences. - : The Royal Society. - 0962-8452 .- 1471-2954. ; 277:1682, s. 697-706
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Tidskriftsartikel (refereegranskat)abstract
- The dispersal of individuals among fragmented populations is generally thought to prevent genetic and demographic isolation, and ultimately reduce extinction risk. In this study, we show that a century of reduction in coastal old-growth forests, as well as a number of other environmental factors, has probably resulted in the genetic divergence of marbled murrelets (Brachyramphus marmoratus) in central California, despite the fact that 7 per cent of modern-sampled murrelets in this population were classified as migrants using genetic assignment tests. Genetic differentiation appears to persist because individuals dispersing from northern populations contributed relatively few young to the central California population, as indicated by the fact that migrants were much less likely to be members of parent-offspring pairs than residents (10.5% versus 45.4%). Moreover, a recent 1.4 per cent annual increase in the proportion of migrants in central California, without appreciable reproduction, may have masked an underlying decline in the resident population without resulting in demographic rescue. Our results emphasize the need to understand the behaviour of migrants and the extent to which they contribute offspring in order to determine whether dispersal results in gene flow and prevents declines in resident populations.
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| 32. |
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| 33. |
- Stroncek, David F, et al.
(författare)
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Donor Experiences of Second Marrow or Peripheral Blood Stem Cell Collection Mirror the First, but CD34+ Yields Are Less
- 2018
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Ingår i: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 24:1, s. 175-184
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Tidskriftsartikel (refereegranskat)abstract
- Little is known about the experiences of individuals donating peripheral blood stem cells (PBSCs) or marrow for a second time. To study this, unrelated donors making a second donation through the National Marrow Donor Program between 2004 and 2013 were evaluated. Experiences of second-time donors giving marrow (n = 118: first donation was PBSC in 76 and marrow in 42) were compared with those making only 1 marrow donation (n = 5829). Experiences of second-time donors giving PBSCs (n = 602) (first donation was PBSCs in 362; marrow in 240) were compared to first-time PBSC donors (n = 16,095). For donors giving a second PBSC or marrow donation there were no significant differences in maximum skeletal pain, maximum symptoms measured by an established modified toxicity criteria, and recovery time compared with those who donated only once. Notably, the yield of marrow nucleated cells and PBSC CD34+ cells with second donations was less. As previously noted with single first-time donations, female (PBSCs and marrow) and obese donors (PBSCs) had higher skeletal pain and/or toxicity with a second donation. PBSC donors who experienced high levels of pain or toxicity with the first donation also experienced high levels of these symptoms with their second donation and slower recovery times. In conclusion, for most donors second donation experiences were similar to first donation experiences, but CD34+ yields were less. Knowledge of the donor's first experience and stem cell yields may help centers decide whether second donations are appropriate and institute measures to improve donor experiences.
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| 34. |
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| 35. |
- Zhou, Zheng, et al.
(författare)
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Reduced intensity conditioning for acute myeloid leukemia using melphalan- vs busulfan-based regimens : a CIBMTR report
- 2020
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Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 4:13, s. 3180-3190
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Tidskriftsartikel (refereegranskat)abstract
- There is a lack of large comparative study on the outcomes of reduced intensity conditioning (RIC) in acute myeloid leukemia (AML) transplantation using fludarabine/busulfan (FB) and fludarabine/melphalan (FM) regimens. Adult AML patients from Center for International Blood and Marrow Transplant Research who received first RIC allo-transplant between 2001 and 2015 were studied. Patients were excluded if they received cord blood or identical twin transplant, total body irradiation in conditioning, or graft-versus-host disease (GVHD) prophylaxis with in vitro T-cell depletion. Primary outcome was overall survival (OS), secondary end points were leukemia-free survival (LFS), nonrelapse mortality (NRM), relapse, and GVHD. Multivariate survival model was used with adjustment for patient, leukemia, and transplant-related factors. A total of 622 patients received FM and 791 received FB RIC. Compared with FB, the FM group had fewer transplant in complete remission (CR), fewer matched sibling donors, and less usage of anti-thymocyte globulin or alemtuzumab. More patients in the FM group received marrow grafts and had transplantation before 2005. OS was significantly lower within the first 3 months posttransplant in the FM group (hazard ratio [HR] = 1.82, P < .001), but was marginally superior beyond 3 months (HR = 0.87, P = .05). LFS was better with FM compared with FB (HR = 0.89, P = .05). NRM was significantly increased in the FM group during the first 3 months of posttransplant (HR = 3.85, P < .001). Long-term relapse was lower with FM (HR = 0.65, P < .001). Analysis restricted to patients with CR showed comparable results. In conclusion, compared with FB, the FM RIC showed a marginally superior long-term OS and LFS and a lower relapse rate. A lower OS early posttransplant within 3 months was largely the result of a higher early NRM.
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