| 1. |
- Stephens, Lucas, et al.
(författare)
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Archaeological assessment reveals Earth’s early transformation through land use
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science. - 0036-8075 .- 1095-9203. ; 365:6456, s. 897-902
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Tidskriftsartikel (refereegranskat)abstract
- Humans began to leave lasting impacts on Earth’s surface starting 10,000 to 8000 years ago. Through a synthetic collaboration with archaeologists around the globe, Stephens et al. compiled a comprehensive picture of the trajectory of human land use worldwide during the Holocene (see the Perspective by Roberts). Hunter-gatherers, farmers, and pastoralists transformed the face of Earth earlier and to a greater extent than has been widely appreciated, a transformation that was essentially global by 3000 years before the present.Science, this issue p. 897; see also p. 865Environmentally transformative human use of land accelerated with the emergence of agriculture, but the extent, trajectory, and implications of these early changes are not well understood. An empirical global assessment of land use from 10,000 years before the present (yr B.P.) to 1850 CE reveals a planet largely transformed by hunter-gatherers, farmers, and pastoralists by 3000 years ago, considerably earlier than the dates in the land-use reconstructions commonly used by Earth scientists. Synthesis of knowledge contributed by more than 250 archaeologists highlighted gaps in archaeological expertise and data quality, which peaked for 2000 yr B.P. and in traditionally studied and wealthier regions. Archaeological reconstruction of global land-use history illuminates the deep roots of Earth’s transformation and challenges the emerging Anthropocene paradigm that large-scale anthropogenic global environmental change is mostly a recent phenomenon.
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| 2. |
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| 3. |
- Hsu, David Fc, et al.
(författare)
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Studies of a Next Generation Silicon-Photomultiplier-Based Time-of-Flight PET/CT System
- 2017
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Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine and Molecular Imaging. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 58:9, s. 1511-1518
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Tidskriftsartikel (refereegranskat)abstract
- This article presents system performance studies of the Discovery MI PET/CT system, a new time-of-flight (TOF) system based on silicon photomultipliers. System performance and clinical imaging comparisons were made between this next-generation system and other commercially available PET/CT and PET/MR systems, as well as between different reconstruction algorithms. Methods: Spatial resolution, sensitivity, NECR, scatter fraction, count rate accuracy, and image quality were characterized with the NEMA NU-2 2012 standards. Energy and coincidence time resolution were measured. Tests were conducted independently and results were averaged on two Discovery MI scanners installed at Stanford and Uppsala University Hospitals. Back-to-back patient scans were also performed between the Discovery MI PET/CT, Discovery 690 PET/CT, and SIGNA PET/MR systems. Clinical images were reconstructed with both ordered-subset expectation maximization (OSEM) and the "Q.Clear" reconstruction algorithms, and examined qualitatively. Results: The averaged full-width half max (FWHM) of the radial/tangential/axial spatial resolution reconstructed with FBP at 1, 10, and 20 cm from the system center are, respectively, 4.10/4.19/4.48 mm, 5.47/4.49/6.01 mm, and 7.53/4.90/6.10 mm. The averaged sensitivity is 13.7 cps/kBq at the center of the FOV. Averaged peak noise equivalent count rate is 193.4 kcps at 21.9 kBq/mL with a scatter fraction of 40.6%. The averaged contrast recovery coefficients for the image quality phantom are 53.7/64.0/73.1/82.7/86.8/90.7 for the 10/13/17/22/28/37 mm diameter spheres. The average photopeak energy resolution is 9.40% FWHM and the average coincidence time resolution is 375.4 ps FWHM. Clinical image comparisons between the PET/CT systems demonstrate the high quality of the Discovery MI system. Comparisons between the Discovery MI and SIGNA systems show similar spatial resolution and overall imaging performance. Lastly, results indicate significant image quality and contrast-to-noise performance enhancement for the "Q.Clear" reconstruction algorithm when compared to OSEM. Conclusion: Excellent performance was achieved with the new Discovery MI system, including 375 ps FWHM coincidence time resolution and sensitivity of 14 cps/kBq. Comparisons between different image reconstruction algorithms and other multimodal SiPM and non-SiPM-based PET detector system designs indicate substantial performance enhancements are possible with this next-generation system.
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| 4. |
- Hsu, David, et al.
(författare)
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Studies of a Next Generation Silicon-Photomultiplier-Based Time-of-Flight PET/CT System
- 2017
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Ingår i: Journal of Nuclear Medicine. - 0161-5505 .- 1535-5667. ; 58:S1
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Objectives: This article presents studies performed with the Discovery MI PET/CT system, a new time-of-flight (TOF) system based on silicon photomultipliers. System performance was characterized according to the NEMA NU-2 2012 standards. Comparisons of performance and clinical images were also made between this next-generation system and other commercially available PET/CT and PET/MR systems, as well as between different image reconstruction algorithms.Methods: Spatial resolution, sensitivity, NECR, scatter fraction, count rate accuracy, and image quality were characterized according to the NEMA NU-2 2012 standards. In addition, energy and coincidence time resolution were measured using a line source at the center of the field-of-view (CFOV). Tests were conducted independently on two Discovery MI scanners installed at Stanford University Hospital and Uppsala University Hospital, and results were averaged between the two systems. In addition, back-to-back patient scans were performed between the Discovery MI PET/CT, Discovery 690 PET/CT, and SIGNA PET/MR systems. Clinical images were reconstructed with both ordered-subset expectation maximization (OSEM) reconstruction algorithms and the block-sequential regularized expectation maximization (BSREM) "Q.Clear" reconstruction algorithm, and examined qualitatively.Results: The averaged FWHM of the radial, tangential, and axial spatial resolution reconstructed with filtered backprojection (FBP) at 1/10/20 cm from the system center are, respectively, 4.10/4.19/4.48 mm, 5.47/4.49/6.01 mm, and 7.53/4.90/6.10 mm. The averaged sensitivity is 13.7 cps/kBq at the center and 13.4 cps/kBq at 10 cm radial offset from the center. Averaged peak noise equivalent count rate (NECR) is 193.4 kcps at 21.9 kBq/mL with a scatter fraction (SF) of 40.6%. The averaged contrast recovery (CR) coefficients for the image quality (IQ) phantom are 53.7/64.0/73.1/82.7/86.8/90.7 for the 10/13/17/22/28/37 mm diameter spheres over 3 separate acquisitions. The average photopeak energy resolution is 9.40% FWHM and the average coincidence time resolution is 375.4 ps FWHM. Clinical image comparisons between the PET/CT systems demonstrate the very high quality of the Discovery MI system. Comparisons between the Discovery MI PET/CT and SIGNA PET/MR systems, which contain identical detector architectures but with different detector diameters, show similar spatial resolution and overall imaging performance. Lastly, results indicate significant image quality and contrast-to-noise performance enhancement for the "Q.Clear" reconstruction algorithm when compared to OSEM.Conclusion: Excellent performance was achieved with the new Discovery MI system, including 375 ps FWHM coincidence time resolution and sensitivity of 14 cps/kBq. Comparisons between different image reconstruction algorithms and other multimodal SiPM and non-SiPM-based PET detector system designs indicate substantial performance enhancements are possible with this next-generation system. Research Support: None
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| 5. |
- Kovesdy, Csaba P, et al.
(författare)
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Past Decline Versus Current eGFR and Subsequent ESRD Risk
- 2016
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Ingår i: Journal of the American Society of Nephrology. - 1046-6673 .- 1533-3450. ; 27:8, s. 2447-2455
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Tidskriftsartikel (refereegranskat)abstract
- eGFR is a robust predictor of ESRD risk. However, the prognostic information gained from the past trajectory (slope) beyond that of the current eGFR is unclear. We examined 22 cohorts to determine the association of past slopes and current eGFR level with subsequent ESRD. We modeled hazard ratios as a spline function of slopes, adjusting for demographic variables, eGFR, and comorbidities. We used random effects meta-analyses to combine results across studies stratified by cohort type. We calculated the absolute risk of ESRD at 5 years after the last eGFR using the weighted average baseline risk. Overall, 1,080,223 participants experienced 5163 ESRD events during a mean follow-up of 2.0 years. In CKD cohorts, a slope of -6 versus 0 ml/min per 1.73 m(2) per year over the previous 3 years (a decline of 18 ml/min per 1.73 m(2) versus no decline) associated with an adjusted hazard ratio of ESRD of 2.28 (95% confidence interval, 1.88 to 2.76). In contrast, a current eGFR of 30 versus 50 ml/min per 1.73 m(2) (a difference of 20 ml/min per 1.73 m(2)) associated with an adjusted hazard ratio of 19.9 (95% confidence interval, 13.6 to 29.1). Past decline contributed more to the absolute risk of ESRD at lower than higher levels of current eGFR. In conclusion, during a follow-up of 2 years, current eGFR associates more strongly with future ESRD risk than the magnitude of past eGFR decline, but both contribute substantially to the risk of ESRD, especially at eGFR<30 ml/min per 1.73 m(2).
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| 6. |
- Patel, Riyaz S., et al.
(författare)
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Association of Chromosome 9p21 With Subsequent Coronary Heart Disease Events : A GENIUS-CHD Study of Individual Participant Data
- 2019
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Ingår i: Circulation. - 2574-8300. ; 12:4
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk.METHODS: A variant at chromosome 9p21 (rs1333049) was tested for association with subsequent events during follow-up in 103 357 Europeans with established CHD at baseline from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) Consortium (73.1% male, mean age 62.9 years). The primary outcome, subsequent CHD death or myocardial infarction (CHD death/myocardial infarction), occurred in 13 040 of the 93 115 participants with available outcome data. Effect estimates were compared with case/control risk obtained from the CARDIoGRAMplusC4D consortium (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics) including 47 222 CHD cases and 122 264 controls free of CHD.RESULTS: Meta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline (GENIUSCHD odds ratio, 1.02; 95% CI, 0.99-1.05). This contrasted with a strong association in CARDIoGRAMPlusC4D odds ratio 1.20; 95% CI, 1.18-1.22; P for interaction < 0.001 compared with the GENIUS-CHD estimate. Similarly, no clear associations were identified for additional subsequent outcomes, including all-cause death, although we found a modest positive association between chromosome 9p21 and subsequent revascularization (odds ratio, 1.07; 95% CI, 1.04-1.09).CONCLUSIONS: In contrast to studies comparing individuals with CHD to disease-free controls, we found no clear association between genetic variation at chromosome 9p21 and risk of subsequent acute CHD events when all individuals had CHD at baseline. However, the association with subsequent revascularization may support the postulated mechanism of chromosome 9p21 for promoting atheroma development.
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| 7. |
- Patel, Riyaz S., et al.
(författare)
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Subsequent Event Risk in Individuals With Established Coronary Heart Disease : Design and Rationale of the GENIUS-CHD Consortium
- 2019
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Ingår i: Circulation. - 2574-8300. ; 12:4
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The Genetics of Subsequent Coronary Heart Disease (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD.METHODS: The consortium currently includes 57 studies from 18 countries, recruiting 185 614 participants with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events.RESULTS: Enrollment into the individual studies took place between 1985 to present day with a duration of follow-up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (hazard ratio, 1.15; 95% CI, 1.14-1.16) per 5-year increase, male sex (hazard ratio, 1.17; 95% CI, 1.13-1.21) and smoking (hazard ratio, 1.43; 95% CI, 1.35-1.51) with risk of subsequent CHD death or myocardial infarction and differing associations with other individual and composite cardiovascular endpoints.CONCLUSIONS: GENIUS-CHD is a global collaboration seeking to elucidate genetic and nongenetic determinants of subsequent event risk in individuals with established CHD, to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators.
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| 8. |
- Unsalan, Ozan, et al.
(författare)
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The Sariçiçek howardite fall in Turkey : Source crater of HED meteorites on Vesta and impact risk of Vestoids
- 2019
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Ingår i: Meteoritics and Planetary Science. - Hoboken : John Wiley & Sons. - 1086-9379 .- 1945-5100. ; 54:5, s. 953-1008
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Tidskriftsartikel (refereegranskat)abstract
- The Sariçiçek howardite meteorite shower consisting of 343 documented stones occurred on September 2, 2015 in Turkey and is the first documented howardite fall. Cosmogenic isotopes show that Sariçiçek experienced a complex cosmic‐ray exposure history, exposed during ~12–14 Ma in a regolith near the surface of a parent asteroid, and that an ~1 m sized meteoroid was launched by an impact 22 ± 2 Ma ago to Earth (as did one‐third of all HED meteorites). SIMS dating of zircon and baddeleyite yielded 4550.4 ± 2.5 Ma and 4553 ± 8.8 Ma crystallization ages for the basaltic magma clasts. The apatite U‐Pb age of 4525 ± 17 Ma, K‐Ar age of ~3.9 Ga, and the U,Th‐He ages of 1.8 ± 0.7 and 2.6 ± 0.3 Ga are interpreted to represent thermal metamorphic and impact‐related resetting ages, respectively. Petrographic; geochemical; and O‐, Cr‐, and Ti‐isotopic studies confirm that Sariçiçek belongs to the normal clan of HED meteorites. Petrographic observations and analysis of organic material indicate a small portion of carbonaceous chondrite material in the Sariçiçek regolith and organic contamination of the meteorite after a few days on soil. Video observations of the fall show an atmospheric entry at 17.3 ± 0.8 km s−1 from NW; fragmentations at 37, 33, 31, and 27 km altitude; and provide a pre‐atmospheric orbit that is the first dynamical link between the normal HED meteorite clan and the inner Main Belt. Spectral data indicate the similarity of Sariçiçek with the Vesta asteroid family (V‐class) spectra, a group of asteroids stretching to delivery resonances, which includes (4) Vesta. Dynamical modeling of meteoroid delivery to Earth shows that the complete disruption of a ~1 km sized Vesta family asteroid or a ~10 km sized impact crater on Vesta is required to provide sufficient meteoroids ≤4 m in size to account for the influx of meteorites from this HED clan. The 16.7 km diameter Antionia impact crater on Vesta was formed on terrain of the same age as given by the 4He retention age of Sariçiçek. Lunar scaling for crater production to crater counts of its ejecta blanket show it was formed ~22 Ma ago.
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| 9. |
- Zweegman, Sonja, et al.
(författare)
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Melphalan, prednisone, and lenalidomide versus melphalan, prednisone, and thalidomide in untreated multiple myeloma.
- 2016
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 127:9, s. 1109-1116
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Tidskriftsartikel (refereegranskat)abstract
- The combination of melphalan, prednisone and thalidomide (MPT) is considered standard therapy for newly diagnosed patients with multiple myeloma (NDMM) who are ineligible for stem-cell transplantation. Long term treatment with thalidomide is hampered by neurotoxicity. Melphalan, prednisone and lenalidomide, followed by lenalidomide maintenance therapy showed promising results, without severe neuropathy emerging. We randomly assigned 668 NDMM patients, ineligible for stem-cell transplantation, between nine 4-weekly cycles of MPT followed by thalidomide maintenance until disease progression or unacceptable toxicity (MPT-T) and the same MP regimen with thalidomide being replaced by lenalidomide (MPR-R). This multicenter, open-label, randomised phase 3 trial was undertaken by HOVON and the NMSG. The primary endpoint was progression-free survival (PFS). The accrual for the study was completed in October 19, 2012. 318 patients were randomly assigned to receive MPT-T and 319 MPR-R. After a median follow up of 36 months PFS with MPT-T was 20 months (95% CI 18-23 months) versus 23 months (95% CI 19-27 months) with MPR-R (HR 0.87 [0.72-1.04], p=0.12). Response rates were similar, with ≥VGPR 47% and 45% respectively. Hematological toxicity was more pronounced with MPR-R, especially grade 3 and 4 neutropenia: 64 versus 27%. Neuropathy ≥ grade 3 was significantly higher in the MPT-T arm; 16% versus 2% in MPR-R, resulting in a significant shorter duration of maintenance therapy (5 versus 17 months in MPR-R), irrespective of age. MPR-R has no advantage over MPT-T concerning efficacy. The toxicity profile differed with clinically significant neuropathy during thalidomide maintenance versus myelosuppression with MPR.
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