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1.
  • Dornelas, M., et al. (författare)
  • BioTIME: A database of biodiversity time series for the Anthropocene
  • 2018
  • Ingår i: Global Ecology and Biogeography. - : Wiley. - 1466-822X .- 1466-8238. ; 27:7, s. 760-786
  • Tidskriftsartikel (refereegranskat)abstract
    • Motivation: The BioTIME database contains raw data on species identities and abundances in ecological assemblages through time. These data enable users to calculate temporal trends in biodiversity within and amongst assemblages using a broad range of metrics. BioTIME is being developed as a community-led open-source database of biodiversity time series. Our goal is to accelerate and facilitate quantitative analysis of temporal patterns of biodiversity in the Anthropocene. Main types of variables included: The database contains 8,777,413 species abundance records, from assemblages consistently sampled for a minimum of 2 years, which need not necessarily be consecutive. In addition, the database contains metadata relating to sampling methodology and contextual information about each record. Spatial location and grain: BioTIME is a global database of 547,161 unique sampling locations spanning the marine, freshwater and terrestrial realms. Grain size varies across datasets from 0.0000000158 km(2) (158 cm(2)) to 100 km(2) (1,000,000,000,000 cm(2)). Time period and grainBio: TIME records span from 1874 to 2016. The minimal temporal grain across all datasets in BioTIME is a year. Major taxa and level of measurement: BioTIME includes data from 44,440 species across the plant and animal kingdoms, ranging from plants, plankton and terrestrial invertebrates to small and large vertebrates.
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  • Fomalont, E. B., et al. (författare)
  • THE 2014 ALMA LONG BASELINE CAMPAIGN: AN OVERVIEW
  • 2015
  • Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 808:1
  • Tidskriftsartikel (refereegranskat)abstract
    • A major goal of the Atacama Large Millimeter/submillimeter Array (ALMA) is to make accurate images with resolutions of tens of milliarcseconds, which at submillimeter (submm) wavelengths requires baselines up to similar to 15 km. To develop and test this capability, a Long Baseline Campaign (LBC) was carried out from 2014 September to late November, culminating in end-to-end observations, calibrations, and imaging of selected Science Verification (SV) targets. This paper presents an overview of the campaign and its main results, including an investigation of the short-term coherence properties and systematic phase errors over the long baselines at the ALMA site, a summary of the SV targets and observations, and recommendations for science observing strategies at long baselines. Deep ALMA images of the quasar 3C 138 at 97 and 241 GHz are also compared to VLA 43 GHz results, demonstrating an agreement at a level of a few percent. As a result of the extensive program of LBC testing, the highly successful SV imaging at long baselines achieved angular resolutions as fine as 19 mas at similar to 350 GHz. Observing with ALMA on baselines of up to 15 km is now possible, and opens up new parameter space for submm astronomy.
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3.
  • Klionsky, Daniel J., et al. (författare)
  • Guidelines for the use and interpretation of assays for monitoring autophagy
  • 2012
  • Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
  • Forskningsöversikt (refereegranskat)abstract
    • In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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4.
  • Bosson, J. K., et al. (författare)
  • Psychometric Properties and Correlates of Precarious Manhood Beliefs in 62 Nations
  • 2021
  • Ingår i: Journal of Cross-Cultural Psychology. - : SAGE Publications. - 0022-0221 .- 1552-5422. ; 52:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Precarious manhood beliefs portray manhood, relative to womanhood, as a social status that is hard to earn, easy to lose, and proven via public action. Here, we present cross-cultural data on a brief measure of precarious manhood beliefs (the Precarious Manhood Beliefs scale [PMB]) that covaries meaningfully with other cross-culturally validated gender ideologies and with country-level indices of gender equality and human development. Using data from university samples in 62 countries across 13 world regions (N = 33,417), we demonstrate: (1) the psychometric isomorphism of the PMB (i.e., its comparability in meaning and statistical properties across the individual and country levels); (2) the PMB's distinctness from, and associations with, ambivalent sexism and ambivalence toward men; and (3) associations of the PMB with nation-level gender equality and human development. Findings are discussed in terms of their statistical and theoretical implications for understanding widely-held beliefs about the precariousness of the male gender role.
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7.
  • Shimwell, T. W., et al. (författare)
  • The LOFAR Two-metre Sky Survey: V. Second data release
  • 2022
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 659
  • Tidskriftsartikel (refereegranskat)abstract
    • In this data release from the ongoing LOw-Frequency ARray (LOFAR) Two-metre Sky Survey we present 120a 168 MHz images covering 27% of the northern sky. Our coverage is split into two regions centred at approximately 12h45m +44 30a and 1h00m +28 00a and spanning 4178 and 1457 square degrees respectively. The images were derived from 3451 h (7.6 PB) of LOFAR High Band Antenna data which were corrected for the direction-independent instrumental properties as well as direction-dependent ionospheric distortions during extensive, but fully automated, data processing. A catalogue of 4 396 228 radio sources is derived from our total intensity (Stokes I) maps, where the majority of these have never been detected at radio wavelengths before. At 6a resolution, our full bandwidth Stokes I continuum maps with a central frequency of 144 MHz have: a median rms sensitivity of 83 μJy beama 1; a flux density scale accuracy of approximately 10%; an astrometric accuracy of 0.2a; and we estimate the point-source completeness to be 90% at a peak brightness of 0.8 mJy beama 1. By creating three 16 MHz bandwidth images across the band we are able to measure the in-band spectral index of many sources, albeit with an error on the derived spectral index of > a ±a 0.2 which is a consequence of our flux-density scale accuracy and small fractional bandwidth. Our circular polarisation (Stokes V) 20a resolution 120a168 MHz continuum images have a median rms sensitivity of 95 μJy beama 1, and we estimate a Stokes I to Stokes V leakage of 0.056%. Our linear polarisation (Stokes Q and Stokes U) image cubes consist of 480a A a 97.6 kHz wide planes and have a median rms sensitivity per plane of 10.8 mJy beama 1 at 4a and 2.2 mJy beama 1 at 20a; we estimate the Stokes I to Stokes Q/U leakage to be approximately 0.2%. Here we characterise and publicly release our Stokes I, Q, U and V images in addition to the calibrated uv-data to facilitate the thorough scientific exploitation of this unique dataset.
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  • Shimwell, T. W., et al. (författare)
  • The LOFAR Two-metre Sky Survey: II. First data release
  • 2019
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 622
  • Forskningsöversikt (refereegranskat)abstract
    • The LOFAR Two-metre Sky Survey (LoTSS) is an ongoing sensitive, high-resolution 120-168 MHz survey of the entire northern sky for which observations are now 20% complete. We present our first full-quality public data release. For this data release 424 square degrees, or 2% of the eventual coverage, in the region of the HETDEX Spring Field (right ascension 10h45m00s to 15h30m00s and declination 45°00′00″ to 57°00′00″) were mapped using a fully automated direction-dependent calibration and imaging pipeline that we developed. A total of 325 694 sources are detected with a signal of at least five times the noise, and the source density is a factor of ∼10 higher than the most sensitive existing very wide-area radio-continuum surveys. The median sensitivity is S144 MHz = 71 μJy beam -1 and the point-source completeness is 90% at an integrated flux density of 0.45 mJy. The resolution of the images is 6″ and the positional accuracy is within 0.2″. This data release consists of a catalogue containing location, flux, and shape estimates together with 58 mosaic images that cover the catalogued area. In this paper we provide an overview of the data release with a focus on the processing of the LOFAR data and the characteristics of the resulting images. In two accompanying papers we provide the radio source associations and deblending and, where possible, the optical identifications of the radio sources together with the photometric redshifts and properties of the host galaxies. These data release papers are published together with a further ∼20 articles that highlight the scientific potential of LoTSS.
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10.
  • Hudson, Lawrence N, et al. (författare)
  • The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
  • 2017
  • Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
  • Tidskriftsartikel (refereegranskat)abstract
    • The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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11.
  • Fuchsberger, Christian, et al. (författare)
  • The genetic architecture of type 2 diabetes
  • 2016
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 536:7614, s. 41-47
  • Tidskriftsartikel (refereegranskat)abstract
    • The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.
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12.
  • Bellm, Eric C., et al. (författare)
  • The Zwicky Transient Facility : System Overview, Performance, and First Results
  • 2019
  • Ingår i: Publications of the Astronomical Society of the Pacific. - : IOP Publishing. - 0004-6280 .- 1538-3873. ; 131:995
  • Tidskriftsartikel (refereegranskat)abstract
    • The Zwicky Transient Facility (ZTF) is a new optical time-domain survey that uses the Palomar 48 inch Schmidt telescope. A custom-built wide-field camera provides a 47 deg(2) field of view and 8 s readout time, yielding more than an order of magnitude improvement in survey speed relative to its predecessor survey, the Palomar Transient Factory. We describe the design and implementation of the camera and observing system. The ZTF data system at the Infrared Processing and Analysis Center provides near-real-time reduction to identify moving and varying objects. We outline the analysis pipelines, data products, and associated archive. Finally, we present on-sky performance analysis and first scientific results from commissioning and the early survey. ZTF's public alert stream will serve as a useful precursor for that of the Large Synoptic Survey Telescope.
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  • Flannick, Jason, et al. (författare)
  • Data Descriptor : Sequence data and association statistics from 12,940 type 2 diabetes cases and controls
  • 2017
  • Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4
  • Tidskriftsartikel (refereegranskat)abstract
    • To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1-5%) non-coding variants in the whole-genome sequenced individuals and 99.7% of low-frequency coding variants in the whole-exome sequenced individuals. Each variant was tested for association with T2D in the sequenced individuals, and, to increase power, most were tested in larger numbers of individuals (> 80% of low-frequency coding variants in similar to ~82 K Europeans via the exome chip, and similar to ~90% of low-frequency non-coding variants in similar to ~44 K Europeans via genotype imputation). The variants, genotypes, and association statistics from these analyses provide the largest reference to date of human genetic information relevant to T2D, for use in activities such as T2D-focused genotype imputation, functional characterization of variants or genes, and other novel analyses to detect associations between sequence variation and T2D.
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15.
  • Gerds, Aaron T., et al. (författare)
  • Outcomes after Umbilical Cord Blood Transplantation for Myelodysplastic Syndromes
  • 2017
  • Ingår i: Biology of blood and marrow transplantation. - : Elsevier. - 1083-8791 .- 1523-6536. ; 23:6, s. 971-979
  • 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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16.
  • Ho, Anna Y. Q., et al. (författare)
  • Evidence for Late-stage Eruptive Mass Loss in the Progenitor to SN2018gep, a Broad-lined Ic Supernova : Pre-explosion Emission and a Rapidly Rising Luminous Transient
  • 2019
  • Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 887:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We present detailed observations of ZTF18abukavn (SN2018gep), discovered in high-cadence data from the Zwicky Transient Facility as a rapidly rising (1.4 +/- 0.1 mag hr(-1)) and luminous (M-g,M- peak = -20 mag) transient. It is spectroscopically classified as a broad-lined stripped-envelope supernova (Ic-BL SN). The high peak luminosity (L-bol greater than or similar to 3 x 10(44) erg s(-1)), the short rise time (t(rise) = 3 days in g band), and the blue colors at peak (g-r similar to -0.4) all resemble the high-redshift Ic-BL iPTF16asu, as well as several other unclassified fast transients. The early discovery of SN2018gep (within an hour of shock breakout) enabled an intensive spectroscopic campaign, including the highest-temperature (T-eff greater than or similar to 40,000 K) spectra of a stripped-envelope SN. A retrospective search revealed luminous (M-g similar to M-r approximate to -14 mag) emission in the days to weeks before explosion, the first definitive detection of precursor emission for a Ic-BL. We find a limit on the isotropic gamma-ray energy release E-gamma,E- iso < 4.9 x 10(48) erg, a limit on X-ray emission L-X < 10(40) erg s(-1), and a limit on radio emission nu L-v less than or similar to 10(37) erg s(-1). Taken together, we find that the early (< 10 days) data are best explained by shock breakout in a massive shell of dense circumstellar material (0.02 M-circle dot) at large radii (3 x 10(14) cm) that was ejected in eruptive pre-explosion mass-loss episodes. The late-time (> 10 days) light curve requires an additional energy source, which could be the radioactive decay of Ni-56.
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17.
  • Hu, Bei, et al. (författare)
  • Timing of allogeneic hematopoietic cell transplantation (alloHCT) for chronic myeloid leukemia (CML) patients
  • 2020
  • Ingår i: Leukemia and Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 61:12, s. 2811-2820
  • 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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  • Jencson, Jacob E., et al. (författare)
  • Discovery of an Intermediate-luminosity Red Transient in M51 and Its Likely Dust-obscured, Infrared-variable Progenitor
  • 2019
  • Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8205 .- 2041-8213. ; 880:2
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the discovery of an optical transient (OT) in Messier. 51, designated M51 OT2019-1 (also ZTF 19aadyppr, AT 2019abn, ATLAS19bz1), by the Zwicky Transient Facility (ZTF). The OT rose over 15. days to an observed luminosity of M-r = -13 (nu L-nu = 9 x 10(6) L-circle dot), in the luminosity gap between novae and typical supernovae (SNe). Spectra during the outburst show a red continuum, Balmer emission with a velocity width of approximate to 400 km s(-1), Ca II and [Ca II] emission, and absorption features characteristic of an F-type supergiant. The spectra and multiband light curves are similar to the so-called SN impostors and intermediate-luminosity red transients (ILRTs). We directly identify the likely progenitor in archival Spitzer Space Telescope imaging with a 4.5 mu m luminosity of M-[4.5] approximate to -12.2 mag and a [3.6]-[4.5] color redder than 0.74 mag, similar to those of the prototype ILRTs SN 2008S and NGC 300 OT2008-1. Intensive monitoring of M51 with Spitzer further reveals evidence for variability of the progenitor candidate at [ 4.5] in the years before the OT. The progenitor is not detected in pre-outburst Hubble Space Telescope optical and near-IR images. The optical colors during outburst combined with spectroscopic temperature constraints imply a higher reddening of E(B - V) approximate to 0.7 mag and higher intrinsic luminosity of M-r approximate to -14.9 mag (nu L-nu = 5.3 x 10(7) L-circle dot) near peak than seen in previous ILRT candidates. Moreover, the extinction estimate is higher on the rise than on the plateau, suggestive of an extended phase of circumstellar dust destruction. These results, enabled by the early discovery of M51. OT2019-1 and extensive pre-outburst archival coverage, offer new clues about the debated origins of ILRTs and may challenge the hypothesis that they arise from the electron-capture induced collapse of extreme asymptotic giant branch stars.
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  • Kim, Haesook T., et al. (författare)
  • Prognostic Score and Cytogenetic Risk Classification for Chronic Lymphocytic Leukemia Patients : Center for International Blood and Marrow Transplant Research Report
  • 2019
  • Ingår i: Clinical Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 1078-0432 .- 1557-3265. ; 25:16, s. 5143-5155
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: To develop a prognostic model and cytogenetic risk classification for previously treated patients with chronic lymphocytic leukemia (CLL) undergoing reduced intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT).Experimental Design: We performed a retrospective analysis of outcomes of 606 patients with CLL who underwent RIC allogeneic HCT between 2008 and 2014 reported to the Center for International Blood and Marrow Transplant Research.Results: On the basis of multivariable models, disease status, comorbidity index, lymphocyte count, and white blood cell count at HCT were selected for the development of prognostic model. Using the prognostic score, we stratified patients into low-, intermediate-, high-, and very-high-risk [4-year progression-free survival (PFS) 58%, 42%, 33%, and 25%, respectively, P < 0.0001; 4-year overall survival (OS) 70%, 57%, 54%, and 38%, respectively, P < 0.0001]. We also evaluated karyotypic abnormalities together with del(17p) and found that del(17p) or >= 5 abnormalities showed inferior PFS. Using a multivariable model, we classified cytogenetic risk into low, intermediate, and high (P < 0.0001). When the prognostic score and cytogenetic risk were combined, patients with low prognostic score and low cytogenetic risk had prolonged PFS (61% at 4 years) and OS (75% at 4 years).Conclusions: In this large cohort of patients with previously treated CLL who underwent RIC HCT, we developed a robust prognostic scoring system of HCT outcomes and a novel cytogenetic-based risk stratification system. These prognostic models can be used for counseling patients, comparing data across studies, and providing a benchmark for future interventions. For future study, we will further validate these models for patients receiving targeted therapies prior to HCT.
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  • Mahindra, Anuj, et al. (författare)
  • New Cancers after Autotransplantations for Multiple Myeloma
  • 2015
  • Ingår i: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 21:4, s. 738-745
  • Tidskriftsartikel (refereegranskat)abstract
    • We describe baseline incidence and risk factors for new cancers in 4161 persons receiving autotransplants for multiple myeloma in the United States from 1990 to 2010. Observed incidence of invasive new cancers was compared with expected incidence relative to the US population. The cohort represented 13,387 person-years at-risk. In total, 163 new cancers were observed, for a crude incidence rate of 1.2 new cancers per 100 person-years and cumulative incidences of 2.6% (95% confidence interval [CI], 2.09 to 3.17), 4.2% (95% CI, 3.49 to 5.00), and 6.1% (95% CI, 5.08 to 7.24) at 3, 5, and 7 years, respectively. The incidence of new cancers in the autotransplantation cohort was similar to age-, race-, and gender-adjusted comparison subjects with an observed/expected (O/E) ratio of 1.00 (99% CI, .81 to 1.22). However, acute myeloid leukemia and melanoma were observed at higher than expected rates with O/E ratios of 5.19 (99% CI, 1.67 to 12.04; P = .0004), and 3.58 (99% CI, 1.82 to 6.29; P < .0001), respectively. Obesity, older age, and male gender were associated with increased risks of new cancers in multivariate analyses. This large data set provides a baseline for comparison and defines the histologic type specific risk for new cancers in patients with MM receiving postautotransplantation therapies, such as maintenance.
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  • Manning, Alisa, et al. (författare)
  • A Low-Frequency Inactivating AKT2 Variant Enriched in the Finnish Population Is Associated With Fasting Insulin Levels and Type 2 Diabetes Risk
  • 2017
  • Ingår i: Diabetes. - : AMER DIABETES ASSOC. - 0012-1797 .- 1939-327X. ; 66:7, s. 2019-2032
  • Tidskriftsartikel (refereegranskat)abstract
    • To identify novel coding association signals and facilitate characterization of mechanisms influencing glycemic traits and type 2 diabetes risk, we analyzed 109,215 variants derived from exome array genotyping together with an additional 390,225 variants from exome sequence in up to 39,339 normoglycemic individuals from five ancestry groups. We identified a novel association between the coding variant (p.Pro50Thr) in AKT2 and fasting plasma insulin (FI), a gene in which rare fully penetrant mutations are causal for monogenic glycemic disorders. The low-frequency allele is associated with a 12% increase in FI levels. This variant is present at 1.1% frequency in Finns but virtually absent in individuals from other ancestries. Carriers of the FI-increasing allele had increased 2-h insulin values, decreased insulin sensitivity, and increased risk of type 2 diabetes (odds ratio 1.05). In cellular studies, the AKT2-Thr50 protein exhibited a partial loss of function. We extend the allelic spectrum for coding variants in AKT2 associated with disorders of glucose homeostasis and demonstrate bidirectional effects of variants within the pleckstrin homology domain of AKT2.
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24.
  • Qayed, Muna, et al. (författare)
  • Influence of Age on Acute and Chronic GVHD in Children Undergoing HLA-Identical Sibling Bone Marrow Transplantation for Acute Leukemia : Implications for Prophylaxis
  • 2018
  • Ingår i: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 24:3, s. 521-528
  • Tidskriftsartikel (refereegranskat)abstract
    • Relapse remains the major cause of mortality after hematopoietic cell transplantation (HCT) for pediatric acute leukemia. Previous research has suggested that reducing the intensity of calcineurin inhibitor-based graft-versus-host disease (GVHD) prophylaxis may be an effective strategy for abrogating the risk of relapse in pediatric patients undergoing matched sibling donor (MSD) HCT. We reasoned that the benefits of this strategy could be maximized by selectively applying it to those patients least likely to develop GVHD. We conducted a study of risk factors for GVHD, to risk-stratify patients based on age. Patients age <18 years with leukemia who received myeloablative, T cell-replete MSD bone marrow transplantation and calcineurin inhibitor-based GVHD prophylaxis between 2000 and 2013 and were entered into the Center for International Blood and Marrow Transplant Research registry were included. The cumulative incidence of grade II-IV acute GVHD (aGVHD) was 19%, that of grade II-IV aGVHD 7%, and that of chronic GVHD (cGVHD) was 16%. Compared with age 13 to 18 years, age 2 to 12 years was associated with a lower risk of grade II-IV aGVHD (hazard ratio [HR], .42; 95% confidence interval [CI], .26 to .70; P = .0008), grade II-IV aGVHD (HR, .24; 95% CI, .10 to .56; P = .001), and cGVHD (HR, .32; 95% CI, .19 to .54; P < .001). Compared with 2000-2004, the risk of grade II-IV aGVHD was lower in children undergoing transplantation in 2005-2008 (HR, .36; 95% CI, .20 to .65; P = .0007) and in 2009-2013 (HR, .24; 95% CI. .11 to .53; P = .0004). Similarly, the risk of grade III-IV aGVHD was lower in children undergoing transplantation in 2005-2008 (HR, .23; 95% CI, .08 to .65; P = .0056) and 2009-2013 (HR, .16; 95% CI, .04 to .67; P = .0126) compared with those doing so in 2000-2004. We conclude that aGVHD rates have decreased significantly over time, and that children age 2 to 12 years are at very low risk for aGVHD and cGVHD. These results should be validated in an independent analysis, because these patients with high-risk malignancies may be good candidates for trials of reduced GVHD prophylaxis.
  •  
25.
  • Ramirez, Kelly S., et al. (författare)
  • Detecting macroecological patterns in bacterial communities across independent studies of global soils
  • 2018
  • Ingår i: Nature Microbiology. - : NATURE PUBLISHING GROUP. - 2058-5276. ; 3:2, s. 189-196
  • Tidskriftsartikel (refereegranskat)abstract
    • The emergence of high-throughput DNA sequencing methods provides unprecedented opportunities to further unravel bacterial biodiversity and its worldwide role from human health to ecosystem functioning. However, despite the abundance of sequencing studies, combining data from multiple individual studies to address macroecological questions of bacterial diversity remains methodically challenging and plagued with biases. Here, using a machine-learning approach that accounts for differences among studies and complex interactions among taxa, we merge 30 independent bacterial data sets comprising 1,998 soil samples from 21 countries. Whereas previous meta-analysis efforts have focused on bacterial diversity measures or abundances of major taxa, we show that disparate amplicon sequence data can be combined at the taxonomy-based level to assess bacterial community structure. We find that rarer taxa are more important for structuring soil communities than abundant taxa, and that these rarer taxa are better predictors of community structure than environmental factors, which are often confounded across studies. We conclude that combining data from independent studies can be used to explore bacterial community dynamics, identify potential 'indicator' taxa with an important role in structuring communities, and propose hypotheses on the factors that shape bacterial biogeography that have been overlooked in the past.
  •  
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