| 1. |
- Brownstein, Catherine A., et al.
(författare)
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An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge
- 2014
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Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 15:3, s. R53-
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. Results: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. Conclusions: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups.
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| 2. |
- Soranno, Patricia A., et al.
(författare)
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LAGOS-NE : A multi-scaled geospatial and temporal database of lake ecological context and water quality for thousands of U.S. lakes
- 2017
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Ingår i: GigaScience. - : Oxford University Press (OUP). - 2047-217X. ; 6:12, s. 1-22
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the factors that affect water quality and the ecological services provided by freshwater ecosystems is an urgent global environmental issue. Predicting how water quality will respond to global changes not only requires water quality data, but also information about the ecological context of individual water bodies across broad spatial extents. Because lake water quality is usually sampled in limited geographic regions, often for limited time periods, assessing the environmental controls of water quality requires compilation of many data sets across broad regions and across time into an integrated database. LAGOS-NE accomplishes this goal for lakes in the northeastern-most 17 US states. LAGOS-NE contains data for 51101 lakes and reservoirs larger than 4 ha in 17 lake-rich US states. The database includes 3 datamodules for: lake location and physical characteristics for all lakes; ecological context (i.e., the land use, geologic, climatic, and hydrologic setting of lakes) for all lakes; and in situmeasurements of lake water quality for a subset of the lakes fromthe past 3 decades for approximately 2600–12 000 lakes depending on the variable. The database contains approximately 150000 measures of total phosphorus, 200 000 measures of chlorophyll, and 900 000 measures of Secchi depth. The water quality data were compiled from87 lake water quality data sets fromfederal, state, tribal, and non-profit agencies, university researchers, and citizen scientists. This database is one of the largest andmost comprehensive databases of its type because it includes both in situmeasurements and ecological context data. Because ecological context can be used to study a variety of other questions about lakes, streams, and wetlands, this database can also be used as the foundation for other studies of freshwaters at broad spatial and ecological scales
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| 3. |
- Holter-Chakrabarty, Jennifer L., et al.
(författare)
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The Sequence of Cyclophosphamide and Myeloablative Total Body Irradiation in Hematopoietic Cell Transplantation for Patients with Acute Leukemia
- 2015
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Ingår i: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 21:7, s. 1251-1257
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Tidskriftsartikel (refereegranskat)abstract
- Limited clinical data are available to assess whether the sequencing of cyclophosphamide (Cy) and total body irradiation (TBI) changes outcomes. We evaluated the sequence in 1769 (CyTBI, n = 948; TBICy, n = 821) recipients of related or unrelated hematopoietic cell transplantation who received TBI (1200 to 1500 cGY) for acute leukemia from 2003 to 2010. The 2 cohorts were comparable for median age, performance score, type of leukemia, first complete remission, Philadelphia chromosome positive acute lymphoblastic leukemia, HLA-matched siblings, stem cell source, antithymocyte globulin use, TBI dose, and type of graft-versus-host disease (GVHD) prophylaxis. The sequence of TBI did not significantly affect transplantation-related mortality (24% versus 23% at 3 years, P = .67; relative risk, 1.01; P = .91), leukemia relapse (27% versus 29% at 3 years, P = .34; relative risk,.89, P = .18), leukemia-free survival (49% versus 48% at 3 years, P = .27; relative risk,.93; P = .29), chronic GVHD (45% versus 47% at 1 year, P = .39; relative risk,.9; P = .11), or overall survival (53% versus 52% at 3 years, P = .62; relative risk,.96; P = .57) for CyTBI and TBICy, respectively. Corresponding cumulative incidences of sinusoidal obstruction syndrome were 4% and 6% at 100 days (P = .08), respectively. This study demonstrates that the sequence of Cy and TBI does not impact transplantation outcomes and complications in patients with acute leukemia undergoing hematopoietic cell transplantation with myeloablative conditioning.
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| 4. |
- Böhm, Johann, et al.
(författare)
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Mutation spectrum in the large GTPase dynamin 2, and genotype-phenotype correlation in autosomal dominant centronuclear myopathy.
- 2012
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Ingår i: Human mutation. - : Hindawi Limited. - 1098-1004 .- 1059-7794. ; 33:6, s. 949-59
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Tidskriftsartikel (refereegranskat)abstract
- Centronuclear myopathy (CNM) is a genetically heterogeneous disorder associated with general skeletal muscle weakness, type I fiber predominance and atrophy, and abnormally centralized nuclei. Autosomal dominant CNM is due to mutations in the large GTPase dynamin 2 (DNM2), a mechanochemical enzyme regulating cytoskeleton and membrane trafficking in cells. To date, 40 families with CNM-related DNM2 mutations have been described, and here we report 60 additional families encompassing a broad genotypic and phenotypic spectrum. In total, 18 different mutations are reported in 100 families and our cohort harbors nine known and four new mutations, including the first splice-site mutation. Genotype-phenotype correlation hypotheses are drawn from the published and new data, and allow an efficient screening strategy for molecular diagnosis. In addition to CNM, dissimilar DNM2 mutations are associated with Charcot-Marie-Tooth (CMT) peripheral neuropathy (CMTD1B and CMT2M), suggesting a tissue-specific impact of the mutations. In this study, we discuss the possible clinical overlap of CNM and CMT, and the biological significance of the respective mutations based on the known functions of dynamin 2 and its protein structure. Defects in membrane trafficking due to DNM2 mutations potentially represent a common pathological mechanism in CNM and CMT.
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| 5. |
- Read, Jordan S., et al.
(författare)
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Generating community-built tools for data sharing and analysis in environmental networks
- 2016
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Ingår i: Inland Waters. - 2044-2041 .- 2044-205X. ; 6:4, s. 637-644
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Tidskriftsartikel (refereegranskat)abstract
- Rapid data growth in many environmental sectors has necessitated tools to manage and analyze these data. The development of tools often lags behind the proliferation of data, however, which may slow exploratory opportunities and scientific progress. The Global Lake Ecological Observatory Network ( GLEON) collaborative model supports an efficient and comprehensive data-analysis-insight life cycle, including implementations of data quality control checks, statistical calculations/derivations, models, and data visualizations. These tools are community-built and openly shared. We discuss the network structure that enables tool development and a culture of sharing, leading to optimized output from limited resources. Specifically, data sharing and a flat collaborative structure encourage the development of tools that enable scientific insights from these data. Here we provide a cross-section of scientific advances derived from global-scale analyses in GLEON. We document enhancements to science capabilities made possible by the development of analytical tools and highlight opportunities to expand this framework to benefit other environmental networks.
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| 6. |
- Woolway, R. Iestyn, et al.
(författare)
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Geographic and temporal variations in turbulent heat loss from lakes : A global analysis across 45 lakes
- 2018
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Ingår i: Limnology and Oceanography. - : WILEY. - 0024-3590 .- 1939-5590. ; 63:6, s. 2436-2449
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Tidskriftsartikel (refereegranskat)abstract
- Heat fluxes at the lake surface play an integral part in determining the energy budget and thermal structure in lakes, including regulating how lakes respond to climate change. We explore patterns in turbulent heat fluxes, which vary across temporal and spatial scales, using in situ high-frequency monitoring data from 45 globally distributed lakes. Our analysis demonstrates that some of the lakes studied follow a marked seasonal cycle in their turbulent surface fluxes and that turbulent heat loss is highest in larger lakes and those situated at low latitude. The Bowen ratio, which is the ratio of mean sensible to mean latent heat fluxes, is smaller at low latitudes and, in turn, the relative contribution of evaporative to total turbulent heat loss increases toward the tropics. Latent heat transfer ranged from similar to 60% to > 90% of total turbulent heat loss in the examined lakes. The Bowen ratio ranged from 0.04 to 0.69 and correlated significantly with latitude. The relative contributions to total turbulent heat loss therefore differ among lakes, and these contributions are influenced greatly by lake location. Our findings have implications for understanding the role of lakes in the climate system, effects on the lake water balance, and temperature-dependent processes in lakes.
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| 7. |
- Woolway, R. Iestyn, et al.
(författare)
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Latitude and lake size are important predictors of over-lake atmospheric stability
- 2017
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Ingår i: Geophysical Research Letters. - : AMER GEOPHYSICAL UNION. - 0094-8276 .- 1944-8007. ; 44:17, s. 8875-8883
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Tidskriftsartikel (refereegranskat)abstract
- Turbulent fluxes across the air-water interface are integral to determining lake heat budgets, evaporation, and carbon emissions from lakes. The stability of the atmospheric boundary layer (ABL) influences the exchange of turbulent energy. We explore the differences in over-lake ABL stability using data from 39 globally distributed lakes. The frequency of unstable ABL conditions varied between lakes from 71 to 100% of the time, with average air temperatures typically several degrees below the average lake surface temperature. This difference increased with decreasing latitude, resulting in a more frequently unstable ABL and a more efficient energy transfer to and from the atmosphere, toward the tropics. In addition, during summer the frequency of unstable ABL conditions decreased with increasing lake surface area. The dependency of ABL stability on latitude and lake size has implications for heat loss and carbon fluxes from lakes, the hydrologic cycle, and climate change effects.
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