| 61. |
- Marini, Sandro, et al.
(författare)
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17p12 Influences Hematoma Volume and Outcome in Spontaneous Intracerebral Hemorrhage
- 2018
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Ingår i: Stroke. - 0039-2499. ; 49:7, s. 1618-1625
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose-Hematoma volume is an important determinant of clinical outcome in spontaneous intracerebral hemorrhage (ICH). We performed a genome-wide association study (GWAS) of hematoma volume with the aim of identifying novel biological pathways involved in the pathophysiology of primary brain injury in ICH. Methods-We conducted a 2-stage (discovery and replication) case-only genome-wide association study in patients with ICH of European ancestry. We utilized the admission head computed tomography to calculate hematoma volume via semiautomated computer-Assisted technique. After quality control and imputation, 7 million genetic variants were available for association testing with ICH volume, which was performed separately in lobar and nonlobar ICH cases using linear regression. Signals with P<5×10- 8 were pursued in replication and tested for association with admission Glasgow coma scale and 3-month post-ICH dichotomized (0-2 versus 3-6) modified Rankin Scale using ordinal and logistic regression, respectively. Results-The discovery phase included 394 ICH cases (228 lobar and 166 nonlobar) and identified 2 susceptibility loci: A genomic region on 22q13 encompassing PARVB (top single-nucleotide polymorphism rs9614326: β, 1.84; SE, 0.32; P=4.4×10-8) for lobar ICH volume and an intergenic region overlying numerous copy number variants on 17p12 (top single-nucleotide polymorphism rs11655160: β, 0.95; SE, 0.17; P=4.3×10-8) for nonlobar ICH volume. The replication included 240 ICH cases (71 lobar and 169 nonlobar) and corroborated the association for 17p12 (P=0.04; meta-Analysis P=2.5×10-9; heterogeneity, P=0.16) but not for 22q13 (P=0.49). In multivariable analysis, rs11655160 was also associated with lower admission Glasgow coma scale (odds ratio, 0.17; P=0.004) and increased risk of poor 3-month modified Rankin Scale (odds ratio, 1.94; P=0.045). Conclusions-We identified 17p12 as a novel susceptibility risk locus for hematoma volume, clinical severity, and functional outcome in nonlobar ICH. Replication in other ethnicities and follow-up translational studies are needed to elucidate the mechanism mediating the observed association.
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| 62. |
- Mark, Daniel B., et al.
(författare)
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Comprehensive Quality-of-Life Outcomes With Invasive Versus Conservative Management of Chronic Coronary Disease in ISCHEMIA
- 2022
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Ingår i: Circulation. - : Ovid Technologies (Wolters Kluwer Health). - 0009-7322 .- 1524-4539. ; 145:17, s. 1294-1307
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) compared an initial invasive treatment strategy (INV) with an initial conservative strategy in 5179 participants with chronic coronary disease and moderate or severe ischemia. The ISCHEMIA research program included a comprehensive quality-of-life (QOL) substudy.METHODS: In 1819 participants (907 INV, 912 conservative strategy), we collected a battery of disease-specific and generic QOL instruments by structured interviews at baseline; at 3, 12, 24, and 36 months postrandomization; and at study closeout. Assessments included angina-related QOL (19-item Seattle Angina Questionnaire), generic health status (EQ-5D), depressive symptoms (Patient Health Questionnaire-8), and, for North American patients, cardiac functional status (Duke Activity Status Index).RESULTS: Median age was 67 years, 19.2% were female, and 15.9% were non-White. The estimated mean difference for the 19-item Seattle Angina Questionnaire Summary score favored INV (1.4 points [95% CI, 0.2-2.5] over all follow-up). No differences were observed in patients with rare/absent baseline angina (SAQ Angina Frequency score >80). Among patients with more frequent angina at baseline (SAQ Angina Frequency score <80, 744 patients, 41%), those randomly assigned to INV had a mean 3.7-point higher 19-item Seattle Angina Questionnaire Summary score than conservative strategy (95% CI, 1.6-5.8) with consistent effects across SAQ subscales: Physical Limitations 3.2 points (95% CI, 0.2-6.1), Angina Frequency 3.2 points (95% CI, 1.2-5.1), Quality of Life/Health Perceptions 5.3 points (95% CI, 2.8-7.8). For the Duke Activity Status Index, no difference was estimated overall by treatment, but in patients with baseline SAQ Angina Frequency scores <80, Duke Activity Status Index scores were higher for INV (3.2 points [95% CI, 0.6-5.7]), whereas patients with rare/absent baseline angina showed no treatment-related differences. Moderate to severe depression was infrequent at randomization (11.5%-12.8%) and was unaffected by treatment assignment.CONCLUSIONS: In the ISCHEMIA comprehensive QOL substudy, patients with more frequent baseline angina reported greater improvements in the symptom, physical functioning, and psychological well-being dimensions of QOL when treated with an invasive strategy, whereas patients who had rare/absent angina at baseline reported no consistent treatment-related QOL differences.
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| 63. |
- McCarthy, Shane, et al.
(författare)
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A reference panel of 64,976 haplotypes for genotype imputation
- 2016
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:10, s. 1279-1283
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Tidskriftsartikel (refereegranskat)abstract
- We describe a reference panel of 64,976 human haplotypes at 39,235,157 SNPs constructed using whole-genome sequence data from 20 studies of predominantly European ancestry. Using this resource leads to accurate genotype imputation at minor allele frequencies as low as 0.1% and a large increase in the number of SNPs tested in association studies, and it can help to discover and refine causal loci. We describe remote server resources that allow researchers to carry out imputation and phasing consistently and efficiently.
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| 64. |
- Meyer, Peter A., et al.
(författare)
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Data publication with the structural biology data grid supports live analysis
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Access to experimental X-ray diffraction image data is fundamental for validation and reproduction of macromolecular models and indispensable for development of structural biology processing methods. Here, we established a diffraction data publication and dissemination system, Structural Biology Data Grid (SBDG; data. sbgrid. org), to preserve primary experimental data sets that support scientific publications. Data sets are accessible to researchers through a community driven data grid, which facilitates global data access. Our analysis of a pilot collection of crystallographic data sets demonstrates that the information archived by SBDG is sufficient to reprocess data to statistics that meet or exceed the quality of the original published structures. SBDG has extended its services to the entire community and is used to develop support for other types of biomedical data sets. It is anticipated that access to the experimental data sets will enhance the paradigm shift in the community towards a much more dynamic body of continuously improving data analysis.
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| 65. |
- Miao, Kevin C., et al.
(författare)
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Electrically driven optical interferometry with spins in silicon carbide
- 2019
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Ingår i: Science Advances. - : AMER ASSOC ADVANCEMENT SCIENCE. - 2375-2548. ; 5:11
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Tidskriftsartikel (refereegranskat)abstract
- Interfacing solid-state defect electron spins to other quantum systems is an ongoing challenge. The ground-state spins weak coupling to its environment not only bestows excellent coherence properties but also limits desired drive fields. The excited-state orbitals of these electrons, however, can exhibit stronger coupling to phononic and electric fields. Here, we demonstrate electrically driven coherent quantum interference in the optical transition of single, basally oriented divacancies in commercially available 4H silicon carbide. By applying microwave frequency electric fields, we coherently drive the divacancys excited-state orbitals and induce Landau-Zener-Stuckelberg interference fringes in the resonant optical absorption spectrum. In addition, we find remarkably coherent optical and spin subsystems enabled by the basal divacancys symmetry. These properties establish divacancies as strong candidates for quantum communication and hybrid system applications, where simultaneous control over optical and spin degrees of freedom is paramount.
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| 66. |
- Milisavljevic, Dan, et al.
(författare)
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MULTI-WAVELENGTH OBSERVATIONS OF SUPERNOVA 2011ei : TIME-DEPENDENT CLASSIFICATION OF TYPE IIb AND Ib SUPERNOVAE AND IMPLICATIONS FOR THEIR PROGENITORS
- 2013
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 767:1, s. 71-
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Tidskriftsartikel (refereegranskat)abstract
- We present X-ray, UV/optical, and radio observations of the stripped-envelope, core-collapse supernova (SN) 2011ei, one of the least luminous SNe IIb or Ib observed to date. Our observations begin with a discovery within similar to 1 day of explosion and span several months afterward. Early optical spectra exhibit broad, Type II-like hydrogen Balmer profiles that subside rapidly and are replaced by Type Ib-like He-rich features on a timescale of one week. High-cadence monitoring of this transition suggests absorption attributable to a high-velocity (greater than or similar to 12,000 km s(-1)) H-rich shell, which is likely present in many Type Ib events. Radio observations imply a shock velocity of v approximate to 0.13 c and a progenitor star average mass-loss rate of (M) over dot approximate to 1.4 x 10(-5) M-circle dot yr(-1) (assuming wind velocity v(w) = 10(3) km s(-1)). This is consistent with independent constraints from deep X-ray observations with Swift-XRT and Chandra. Overall, the multi-wavelength properties of SN 2011ei are consistent with the explosion of a lower-mass (3-4 M-circle dot), compact (R-* less than or similar to 1 x 10(11) cm), He-core star. The star retained a thin hydrogen envelope at the time of explosion, and was embedded in an inhomogeneous circumstellar wind suggestive of modest episodic mass loss. We conclude that SN 2011ei's rapid spectral metamorphosis is indicative of time-dependent classifications that bias estimates of the relative explosion rates for Type IIb and Ib objects, and that important information about a progenitor star's evolutionary state and mass loss immediately prior to SN explosion can be inferred from timely multi-wavelength observations.
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| 67. |
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| 68. |
- Monk, Bradley J., et al.
(författare)
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A Randomized, Phase III Trial to Evaluate Rucaparib Monotherapy as Maintenance Treatment in Patients With Newly Diagnosed Ovarian Cancer (ATHENA-MONO/GOG-3020/ENGOT-ov45)
- 2022
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Ingår i: Journal of Clinical Oncology. - : Lippincott, Williams & Wilkins. - 0732-183X .- 1527-7755. ; 40:34, s. 3952-3964
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSEATHENA (ClinicalTrials.gov identifier: ) was designed to evaluate rucaparib first-line maintenance treatment in a broad patient population, including those without BRCA1 or BRCA2 (BRCA) mutations or other evidence of homologous recombination deficiency (HRD), or high-risk clinical characteristics such as residual disease. We report the results from the ATHENA-MONO comparison of rucaparib versus placebo.METHODSPatients with stage III-IV high-grade ovarian cancer undergoing surgical cytoreduction (R0/complete resection permitted) and responding to first-line platinum-doublet chemotherapy were randomly assigned 4:1 to oral rucaparib 600 mg twice a day or placebo. Stratification factors were HRD test status, residual disease after chemotherapy, and timing of surgery. The primary end point of investigator-assessed progression-free survival was assessed in a step-down procedure, first in the HRD population (BRCA-mutant or BRCA wild-type/loss of heterozygosity high tumor), and then in the intent-to-treat population.RESULTSAs of March 23, 2022 (data cutoff), 427 and 111 patients were randomly assigned to rucaparib or placebo, respectively (HRD population: 185 v 49). Median progression-free survival (95% CI) was 28.7 months (23.0 to not reached) with rucaparib versus 11.3 months (9.1 to 22.1) with placebo in the HRD population (log-rank P = .0004; hazard ratio [HR], 0.47; 95% CI, 0.31 to 0.72); 20.2 months (15.2 to 24.7) versus 9.2 months (8.3 to 12.2) in the intent-to-treat population (log-rank P < .0001; HR, 0.52; 95% CI, 0.40 to 0.68); and 12.1 months (11.1 to 17.7) versus 9.1 months (4.0 to 12.2) in the HRD-negative population (HR, 0.65; 95% CI, 0.45 to 0.95). The most common grade & GE; 3 treatment-emergent adverse events were anemia (rucaparib, 28.7% v placebo, 0%) and neutropenia (14.6% v 0.9%).CONCLUSIONRucaparib monotherapy is effective as first-line maintenance, conferring significant benefit versus placebo in patients with advanced ovarian cancer with and without HRD.
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| 69. |
- Myers, L. S., et al.
(författare)
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Compton scattering from C-12 using tagged photons in the energy range 65-115 MeV
- 2014
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 89:3
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Tidskriftsartikel (refereegranskat)abstract
- Elastic scattering of photons from C-12 has been investigated using quasimonoenergetic tagged photons with energies in the range 65-115 MeV at laboratory angles of 60 degrees, 120 degrees, and 150 degrees. at the Tagged-Photon Facility at the MAX IV Laboratory in Lund, Sweden. A phenomenological model was employed to provide an estimate of the sensitivity of the C-12(gamma,gamma)C-12 cross section to the bound- nucleon polarizabilities.
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| 70. |
- Nakamura, Rumi, et al.
(författare)
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Multiscale Currents Observed by MMS in the Flow Braking Region
- 2018
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Ingår i: Journal of Geophysical Research - Space Physics. - : AMER GEOPHYSICAL UNION. - 2169-9380 .- 2169-9402. ; 123:2, s. 1260-1278
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Tidskriftsartikel (refereegranskat)abstract
- We present characteristics of current layers in the off-equatorial near-Earth plasma sheet boundary observed with high time-resolution measurements from the Magnetospheric Multiscale mission during an intense substorm associated with multiple dipolarizations. The four Magnetospheric Multiscale spacecraft, separated by distances of about 50 km, were located in the southern hemisphere in the dusk portion of a substorm current wedge. They observed fast flow disturbances (up to about 500 km/s), most intense in the dawn-dusk direction. Field-aligned currents were observed initially within the expanding plasma sheet, where the flow and field disturbances showed the distinct pattern expected in the braking region of localized flows. Subsequently, intense thin field-aligned current layers were detected at the inner boundary of equatorward moving flux tubes together with Earthward streaming hot ions. Intense Hall current layers were found adjacent to the field-aligned currents. In particular, we found a Hall current structure in the vicinity of the Earthward streaming ion jet that consisted of mixed ion components, that is, hot unmagnetized ions, cold ExB drifting ions, and magnetized electrons. Our observations show that both the near-Earth plasma jet diversion and the thin Hall current layers formed around the reconnection jet boundary are the sites where diversion of the perpendicular currents take place that contribute to the observed field-aligned current pattern as predicted by simulations of reconnection jets. Hence, multiscale structure of flow braking is preserved in the field-aligned currents in the off-equatorial plasma sheet and is also translated to ionosphere to become a part of the substorm field-aligned current system.
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