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| 3. |
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| 4. |
- Ostrom, Quinn T., et al.
(författare)
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Sex-specific glioma genome-wide association study identifies new risk locus at 3p21.31 in females, and finds sex-differences in risk at 8q24.21
- 2018
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Incidence of glioma is approximately 50% higher in males. Previous analyses have examined exposures related to sex hormones in women as potential protective factors for these tumors, with inconsistent results. Previous glioma genome-wide association studies (GWAS) have not stratified by sex. Potential sex-specific genetic effects were assessed in autosomal SNPs and sex chromosome variants for all glioma, GBM and non-GBM patients using data from four previous glioma GWAS. Datasets were analyzed using sex-stratified logistic regression models and combined using meta-analysis. There were 4,831 male cases, 5,216 male controls, 3,206 female cases and 5,470 female controls. A significant association was detected at rs11979158 (7p11.2) in males only. Association at rs55705857 (8q24.21) was stronger in females than in males. A large region on 3p21.31 was identified with significant association in females only. The identified differences in effect of risk variants do not fully explain the observed incidence difference in glioma by sex.
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| 5. |
- Agirre, Jon, et al.
(författare)
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The CCP4 suite: integrative software for macromolecular crystallography
- 2023
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Ingår i: Acta Crystallographica Section D. - : INT UNION CRYSTALLOGRAPHY. - 2059-7983. ; 79, s. 449-461
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Tidskriftsartikel (refereegranskat)abstract
- The Collaborative Computational Project No. 4 (CCP4) is a UK-led international collective with a mission to develop, test, distribute and promote software for macromolecular crystallography. The CCP4 suite is a multiplatform collection of programs brought together by familiar execution routines, a set of common libraries and graphical interfaces. The CCP4 suite has experienced several considerable changes since its last reference article, involving new infrastructure, original programs and graphical interfaces. This article, which is intended as a general literature citation for the use of the CCP4 software suite in structure determination, will guide the reader through such transformations, offering a general overview of the new features and outlining future developments. As such, it aims to highlight the individual programs that comprise the suite and to provide the latest references to them for perusal by crystallographers around the world.
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| 6. |
- Amirian, E. Susan, et al.
(författare)
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Approaching a Scientific Consensus on the Association between Allergies and Glioma Risk : a report from the Glioma International Case-Control Study
- 2016
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 25:2, s. 282-290
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Tidskriftsartikel (refereegranskat)abstract
- Background: Several previous studies have found inverse associations between glioma susceptibility and a history of allergies or other atopic conditions. Some evidence indicates that respiratory allergies are likely to be particularly relevant with regard to glioma risk. Using data from the Glioma International Case-Control Study (GICC), we examined the effects of respiratory allergies and other atopic conditions on glioma risk. Methods: The GICC contains detailed information on history of atopic conditions for 4,533 cases and 4,171 controls, recruited from 14 study sites across five countries. Using two-stage random-effects restricted maximum likelihood modeling to calculate meta-analysis ORs, we examined the associations between glioma and allergy status, respiratory allergy status, asthma, and eczema. Results: Having a history of respiratory allergies was associated with an approximately 30% lower glioma risk, compared with not having respiratory allergies (mOR, 0.72; 95% confidence interval, 0.58-0.90). This association was similar when restricting to high-grade glioma cases. Asthma and eczema were also significantly protective against glioma. Conclusion: A substantial amount of data on the inverse association between atopic conditions and glioma has accumulated, and findings from the GICC study further strengthen the existing evidence that the relationship between atopy and glioma is unlikely to be coincidental. Impact: As the literature approaches a consensus on the impact of allergies in glioma risk, future research can begin to shift focus to what the underlying biologic mechanism behind this association may be, which could, in turn, yield new opportunities for immunotherapy or cancer prevention. (C) 2016 AACR.
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| 7. |
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| 8. |
- Bellouin, N., et al.
(författare)
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Bounding Global Aerosol Radiative Forcing of Climate Change
- 2020
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Ingår i: Reviews of geophysics. - 8755-1209 .- 1944-9208. ; 58:1
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Forskningsöversikt (refereegranskat)abstract
- Aerosols interact with radiation and clouds. Substantial progress made over the past 40 years in observing, understanding, and modeling these processes helped quantify the imbalance in the Earth's radiation budget caused by anthropogenic aerosols, called aerosol radiative forcing, but uncertainties remain large. This review provides a new range of aerosol radiative forcing over the industrial era based on multiple, traceable, and arguable lines of evidence, including modeling approaches, theoretical considerations, and observations. Improved understanding of aerosol absorption and the causes of trends in surface radiative fluxes constrain the forcing from aerosol-radiation interactions. A robust theoretical foundation and convincing evidence constrain the forcing caused by aerosol-driven increases in liquid cloud droplet number concentration. However, the influence of anthropogenic aerosols on cloud liquid water content and cloud fraction is less clear, and the influence on mixed-phase and ice clouds remains poorly constrained. Observed changes in surface temperature and radiative fluxes provide additional constraints. These multiple lines of evidence lead to a 68% confidence interval for the total aerosol effective radiative forcing of -1.6 to -0.6Wm(-2), or -2.0 to -0.4Wm(-2) with a 90% likelihood. Those intervals are of similar width to the last Intergovernmental Panel on Climate Change assessment but shifted toward more negative values. The uncertainty will narrow in the future by continuing to critically combine multiple lines of evidence, especially those addressing industrial-era changes in aerosol sources and aerosol effects on liquid cloud amount and on ice clouds. Plain Language Summary Human activities emit into the atmosphere small liquid and solid particles called aerosols. Those aerosols change the energy budget of the Earth and trigger climate changes, by scattering and absorbing solar and terrestrial radiation and playing important roles in the formation of cloud droplets and ice crystals. But because aerosols are much more varied in their chemical composition and much more heterogeneous in their spatial and temporal distributions than greenhouse gases, their perturbation to the energy budget, called radiative forcing, is much more uncertain. This review uses traceable and arguable lines of evidence, supported by aerosol studies published over the past 40 years, to quantify that uncertainty. It finds that there are two chances out of three that aerosols from human activities have increased scattering and absorption of solar radiation by 14% to 29% and cloud droplet number concentration by 5 to 17% in the period 2005-2015 compared to the year 1850. Those increases exert a radiative forcing that offsets between a fifth and a half of the radiative forcing by greenhouse gases. The degree to which human activities affect natural aerosol levels, and the response of clouds, and especially ice clouds, to aerosol perturbations remain particularly uncertain.
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| 9. |
- Ostrom, Quinn T., et al.
(författare)
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Age‐specific genome‐wide association study in glioblastoma identifies increased proportion of 'lower grade glioma'‐like features associated with younger age
- 2018
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Ingår i: International Journal of Cancer. - : WILEY. - 0020-7136 .- 1097-0215. ; 143:10, s. 2359-2366
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Tidskriftsartikel (refereegranskat)abstract
- Glioblastoma (GBM) is the most common malignant brain tumor in the United States. Incidence of GBM increases with age, and younger age‐at‐diagnosis is significantly associated with improved prognosis. While the relationship between candidate GBM risk SNPs and age‐at‐diagnosis has been explored, genome‐wide association studies (GWAS) have not previously been stratified by age. Potential age‐specific genetic effects were assessed in autosomal SNPs for GBM patients using data from four previous GWAS. Using age distribution tertiles (18–53, 54–64, 65+) datasets were analyzed using age‐stratified logistic regression to generate p values, odds ratios (OR), and 95% confidence intervals (95%CI), and then combined using meta‐analysis. There were 4,512 total GBM cases, and 10,582 controls used for analysis. Significant associations were detected at two previously identified SNPs in 7p11.2 (rs723527 [p54–63 = 1.50x10−9, OR54–63 = 1.28, 95%CI54–63 = 1.18–1.39; p64+ = 2.14x10−11, OR64+ = 1.32, 95%CI64+ = 1.21–1.43] and rs11979158 [p54–63 = 6.13x10−8, OR54–63 = 1.35, 95%CI54–63 = 1.21–1.50; p64+ = 2.18x10−10, OR64+ = 1.42, 95%CI64+ = 1.27–1.58]) but only in persons >54. There was also a significant association at the previously identified lower grade glioma (LGG) risk locus at 8q24.21 (rs55705857) in persons ages 18–53 (p18–53 = 9.30 × 10−11, OR18–53 = 1.76, 95%CI18–53 = 1.49–2.10). Within The Cancer Genome Atlas (TCGA) there was higher prevalence of ‘LGG’‐like tumor characteristics in GBM samples in those 18–53, with IDH1/2 mutation frequency of 15%, as compared to 2.1% [54–63] and 0.8% [64+] (p = 0.0005). Age‐specific differences in cancer susceptibility can provide important clues to etiology. The association of a SNP known to confer risk for IDH1/2 mutant glioma and higher prevalence of IDH1/2 mutation within younger individuals 18–53 suggests that more younger individuals may present initially with ‘secondary glioblastoma.’
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| 10. |
- Garrard, S. L., et al.
(författare)
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Biological impacts of ocean acidification: a postgraduate perspective on research priorities
- 2013
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Ingår i: Marine Biology. - : Springer Science and Business Media LLC. - 0025-3162 .- 1432-1793. ; 160:8, s. 1789-1805
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Tidskriftsartikel (refereegranskat)abstract
- Research into the effects of ocean acidification (OA) on marine organisms has greatly increased during the past decade, as realization of the potential dramatic impacts has grown. Studies have revealed the multifarious responses of organisms to OA conditions, indicating a high level of intra- and interspecific variation in species' ability to accommodate these alterations. If we are to provide policy makers with sound, scientific input regarding the expected consequences of OA, we need a broader understanding of these predicted changes. As a group of 20 multi-disciplinary postgraduate students from around the globe, with a study focus on OA, we are a strong representation of 'next generation' scientists in this field. In this unique cumulative paper, we review knowledge gaps in terms of assessing the biological impacts of OA, outlining directions for future research.
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| 11. |
- Melin, Beatrice S., et al.
(författare)
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Genome-wide association study of glioma subtypes identifies specific differences in genetic susceptibility to glioblastoma and non-glioblastoma tumors
- 2017
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 49:5, s. 789-794
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have transformed our understanding of glioma susceptibility, but individual studies have had limited power to identify risk loci. We performed a meta-analysis of existing GWAS and two new GWAS, which totaled 12,496 cases and 18,190 controls. We identified five new loci for glioblastoma (GBM) at 1p31.3 (rs12752552; P = 2.04 x 10(-9), odds ratio (OR) = 1.22), 11q14.1 (rs11233250; P = 9.95 x 10(-10), OR = 1.24), 16p13.3 (rs2562152; P = 1.93 x 10-8, OR = 1.21), 16q12.1 (rs10852606; P = 1.29 x 10(-11), OR = 1.18) and 22q13.1 (rs2235573; P = 1.76 x 10(-10), OR = 1.15), as well as eight loci for non-GBM tumors at 1q32.1 (rs4252707; P = 3.34 x 10(-9), OR = 1.19), 1q44 (rs12076373; P = 2.63 x 10(-10), OR = 1.23), 2q33.3 (rs7572263; P = 2.18 x 10(-10), OR = 1.20), 3p14.1 (rs11706832; P = 7.66 x 10(-9), OR = 1.15), 10q24.33 (rs11598018; P = 3.39 x 10-8, OR = 1.14), 11q21 (rs7107785; P = 3.87 x 10(-10), OR = 1.16), 14q12 (rs10131032; P = 5.07 x 10(-11), OR = 1.33) and 16p13.3 (rs3751667; P = 2.61 x 10(-9), OR = 1.18). These data substantiate that genetic susceptibility to GBM and non-GBM tumors are highly distinct, which likely reflects different etiology.
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| 12. |
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| 13. |
- van der Spek, M., et al.
(författare)
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Uncertainty analysis in the techno-economic assessment of CO2 capture and storage technologies. Critical review and guidelines for use
- 2020
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Ingår i: International Journal of Greenhouse Gas Control. - : Elsevier BV. - 1750-5836 .- 1878-0148. ; 100
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Tidskriftsartikel (refereegranskat)abstract
- Uncertainty analysis is a key element of sound techno-economic analysis (TEA) of CO2 Capture and Storage (CCS) technologies and systems, and in the communication of TEA results. Many CCS technologies are relatively novel, with only few large-scale projects constructed and in operation to date. Therefore, uncertainties in technology performance and costs are often substantial, making it imperative that they be characterized and reported. Although uncertainty analysis itself is not novel, with some methods already frequently used by the CCS TEA community, a document that provides a comprehensive overview of methods and approaches, as well as guidance on their selection and use, is still lacking. Given its importance, we seek to fill this gap by providing a critical review of uncertainty analysis methods along with guidance on the selection and use of these methods for CCS TEAs, highlighting good practice and examples from the CCS literature. The paper starts by identifying the different audiences for CCS TEAs, the different modelling approaches available for CCS technology performance and cost analysis, and the different roles that uncertainty analysis may play. It then continues to discuss established, as well as emerging, uncertainty analysis methods and addresses how and when each method is best used, as well as common pitfalls. We argue that the most commonly used method of one-parameter-at-a-time ‘local’ sensitivity analysis may often be a suboptimal choice, and that other approaches may be more suitable or lead to more insight, especially since uncertainty analysis software is becoming more widespread and easier to use. Finally, the paper discusses the benefits of advanced uses of uncertainty analysis in, for instance, the design of CCS experiments or in the design and planning of CCS infrastructure. Sound uncertainty analysis has an important role to play in TEAs of CCS technologies and systems, and there are many opportunities to bring the use of uncertainty analysis to a higher level than currently practiced. This review of and guidance on available methods is intended to help accelerate continued methods development and their application to more robust and meaningful CCS performance and costing studies.
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| 14. |
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| 15. |
- Eckel-Passow, Jeanette E., et al.
(författare)
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Using germline variants to estimate glioma and subtype risks
- 2019
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Ingår i: Neuro-Oncology. - : Oxford University Press. - 1522-8517 .- 1523-5866. ; 21:4, s. 451-461
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Tidskriftsartikel (refereegranskat)abstract
- Background: Twenty-five single nucleotide polymorphisms (SNPs) are associated with adult diffuse glioma risk. We hypothesized that the inclusion of these 25 SNPs with age at diagnosis and sex could estimate risk of glioma as well as identify glioma subtypes.Methods: Case-control design and multinomial logistic regression were used to develop models to estimate the risk of glioma development while accounting for histologic and molecular subtypes. Case-case design and logistic regression were used to develop models to predict isocitrate dehydrogenase (IDH) mutation status. A total of 1273 glioma cases and 443 controls from Mayo Clinic were used in the discovery set, and 852 glioma cases and 231 controls from UCSF were used in the validation set. All samples were genotyped using a custom Illumina OncoArray.Results: Patients in the highest 5% of the risk score had more than a 14-fold increase in relative risk of developing an IDH mutant glioma. Large differences in lifetime absolute risk were observed at the extremes of the risk score percentile. For both IDH mutant 1p/19q non-codeleted glioma and IDH mutant 1p/19q codeleted glioma, the lifetime risk increased from almost null to 2.3% and almost null to 1.7%, respectively. The SNP-based model that predicted IDH mutation status had a validation concordance index of 0.85.Conclusions: These results suggest that germline genotyping can provide new tools for the initial management of newly discovered brain lesions. Given the low lifetime risk of glioma, risk scores will not be useful for population screening; however, they may be useful in certain clinically defined high-risk groups.
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| 16. |
- Hervey-Jumper, Shawn L, et al.
(författare)
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Interactive Effects of Molecular, Therapeutic, and Patient Factors on Outcome of Diffuse Low-Grade Glioma.
- 2023
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Ingår i: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. - 1527-7755. ; 41:11, s. 2029-2042
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Tidskriftsartikel (refereegranskat)abstract
- In patients with diffuse low-grade glioma (LGG), the extent of surgical tumor resection (EOR) has a controversial role, in part because a randomized clinical trial with different levels of EOR is not feasible.In a 20-year retrospective cohort of 392 patients with IDH-mutant grade 2 glioma, we analyzed the combined effects of volumetric EOR and molecular and clinical factors on overall survival (OS) and progression-free survival by recursive partitioning analysis. The OS results were validated in two external cohorts (n = 365). Propensity score analysis of the combined cohorts (n = 757) was used to mimic a randomized clinical trial with varying levels of EOR.Recursive partitioning analysis identified three survival risk groups. Median OS was shortest in two subsets of patients with astrocytoma: those with postoperative tumor volume (TV) > 4.6 mL and those with preoperative TV > 43.1 mL and postoperative TV ≤ 4.6 mL. Intermediate OS was seen in patients with astrocytoma who had chemotherapy with preoperative TV ≤ 43.1 mL and postoperative TV ≤ 4.6 mL in addition to oligodendroglioma patients with either preoperative TV > 43.1 mL and residual TV ≤ 4.6 mL or postoperative residual volume > 4.6 mL. Longest OS was seen in astrocytoma patients with preoperative TV ≤ 43.1 mL and postoperative TV ≤ 4.6 mL who received no chemotherapy and oligodendroglioma patients with preoperative TV ≤ 43.1 mL and postoperative TV ≤ 4.6 mL. EOR ≥ 75% improved survival outcomes, as shown by propensity score analysis.Across both subtypes of LGG, EOR beginning at 75% improves OS while beginning at 80% improves progression-free survival. Nonetheless, maximal resection with preservation of neurological function remains the treatment goal. Our findings have implications for surgical strategies for LGGs, particularly oligodendroglioma.
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| 17. |
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| 18. |
- McCoy, Isabel L., et al.
(författare)
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The hemispheric contrast in cloud microphysical properties constrains aerosol forcing
- 2020
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 117:32, s. 18998-19006
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Tidskriftsartikel (refereegranskat)abstract
- The change in planetary albedo due to aerosol-cloud interactions during the industrial era is the leading source of uncertainty in inferring Earth's climate sensitivity to increased greenhouse gases from the historical record. The variable that controls aerosol-cloud interactions in warm clouds is droplet number concentration. Global climate models demonstrate that the present-day hemispheric contrast in cloud droplet number concentration between the pristine Southern Hemisphere and the polluted Northern Hemisphere oceans can be used as a proxy for anthropogenically driven change in cloud droplet number concentration. Remotely sensed estimates constrain this change in droplet number concentration to be between 8 cm(-3) and 24 cm(-3). By extension, the radiative forcing since 1850 from aerosol-cloud interactions is constrained to be -1.2 W.m(-2) to -0.6 W.m(-2). The robustness of this constraint depends upon the assumption that pristine Southern Ocean droplet number concentration is a suitable proxy for preindustrial concentrations. Droplet number concentrations calculated from satellite data over the Southern Ocean are high in austral summer. Near Antarctica, they reach values typical of Northern Hemisphere polluted outflows. These concentrations are found to agree with several in situ datasets. In contrast, climate models show systematic underpredictions of cloud droplet number concentration across the Southern Ocean. Near Antarctica, where precipitation sinks of aerosol are small, the underestimation by climate models is particularly large. This motivates the need for detailed process studies of aerosol production and aerosol-cloud interactions in pristine environments. The hemispheric difference in satellite estimated cloud droplet number concentration implies preindustrial aerosol concentrations were higher than estimated by most models.
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| 19. |
- McCoy, M., et al.
(författare)
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ALMA Observations of the Physical and Chemical Conditions in Centaurus A
- 2017
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 851:2
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Tidskriftsartikel (refereegranskat)abstract
- Centaurus A, with its gas-rich elliptical host galaxy, NGC 5128, is the nearest radio galaxy at a distance of 3.8 Mpc. Its proximity allows us to study the interaction among an active galactic nucleus, radio jets, and molecular gas in great detail. We present ALMA observations of low-J transitions of three CO isotopologues, HCN, HCO+, HNC, CN, and CCH toward the inner projected 500 pc of NGC 5128. Our observations resolve physical sizes down to 40 pc. By observing multiple chemical probes, we determine the physical and chemical conditions of the nuclear interstellar medium of NGC 5128. This region contains molecular arms associated with the dust lanes and a circumnuclear disk (CND) interior to the molecular arms. The CND is approximately 400 pc by 200 pc and appears to be chemically distinct from the molecular arms. It is dominated by dense gas tracers while the molecular arms are dominated by (CO)-C-12 and its rare isotopologues. The CND has a higher temperature, elevated CN/HCN and HCN/HNC intensity ratios, and much weaker (CO)-C-13 and (CO)-O-18 emission than the molecular arms. This suggests an influence from the AGN on the CND molecular gas. There is also absorption against the AGN with a low velocity complex near the systemic velocity and a high velocity complex shifted by about 60 km s(-1). We find similar chemical properties between the CND in emission and both the low and high velocity absorption complexes, implying that both likely originate from the CND. If the HV complex does originate in the CND, then that gas would correspond to gas falling toward the supermassive black hole.
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| 20. |
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| 21. |
- Acharya, Shravan S., et al.
(författare)
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Diverse composites of metal-complexes and PEDOT facilitated by metal-free vapour phase polymerization
- 2017
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Ingår i: Reactive & functional polymers. - : Elsevier. - 1381-5148 .- 1873-166X. ; 116, s. 101-106
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Oxidative polymerization for the manufacture of conducting polymers such as poly(3,4-ethylenedioxy-thiophene) has traditionally employed iron(III) salts. Demonstrated in this study is vapour phase polymerization of 3,4-ethylenedio- xythiophene using a metal-free oxidant, ammonium persulfate, leading to films with an estimated conductivity of 75 S/cm. Additionally, a route for embedding active transition metal complexes into these poly(3,4-ethylenedioxythiophene)/-poly(styrene-4-sulfonate) (PEDOT/PSS) films via vapour assisted complexation is outlined. Here, the vapour pressure of solid ligands around their melting temperatures was exploited to ensure complexation to metal ions added into the oxidant mixture prior to polymerization of PEDOT. Four composite systems are discussed, viz. PEDOT/PSS embedded with tris(8-hydroxyquinolinato)cobalt(III), tris(2,2-bipyridine)cobalt(II), tris(1,10- phenanthroline)cobalt(II) and tris(8-hyd-roxyquinolinato)aluminium(III). Using these composites, electrochemical reduction of nitrite to ammonia with a faradaic efficiency of 61% was reported.
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| 22. |
- Appelgren, Anais S. C., et al.
(författare)
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Gene flow and adaptive potential in a generalist ectoparasite
- 2018
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Ingår i: BMC Evolutionary Biology. - : BMC. - 1471-2148. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- Background: In host-parasite systems, relative dispersal rates condition genetic novelty within populations and thus their adaptive potential. Knowledge of host and parasite dispersal rates can therefore help us to understand current interaction patterns in wild populations and why these patterns shift over time and space. For generalist parasites however, estimates of dispersal rates depend on both host range and the considered spatial scale. Here, we assess the relative contribution of these factors by studying the population genetic structure of a common avian ectoparasite, the hen flea Ceratophyllus gallinae, exploiting two hosts that are sympatric in our study population, the great tit Paws major and the collared flycatcher Ficedula albicollis. Previous experimental studies have indicated that the hen flea is both locally maladapted to great tit populations and composed of subpopulations specialized on the two host species, suggesting limited parasite dispersal in space and among hosts, and a potential interaction between these two structuring factors. Results: C gallinae fleas were sampled from old nests of the two passerine species in three replicate wood patches and were genotyped at microsatellite markers to assess population genetic structure at different scales (among individuals within a nest among nests and between host species within a patch and among patches). As expected, significant structure was found at all spatial scales and between host species, supporting the hypothesis of limited dispersal in this parasite. Clustering analyses and estimates of relatedness further suggested that inbreeding regularly occurs within nests. Patterns of isolation by distance within wood patches indicated that flea dispersal likely occurs in a stepwise manner among neighboring nests. From these data, we estimated that gene flow in the hen flea is approximately half that previously described for its great tit hosts. Conclusion: Our results fall in line with predictions based on observed patterns of adaptation in this host-parasite system, suggesting that parasite dispersal is limited and impacts its adaptive potential with respect to its hosts. More generally, this study sheds light on the complex interaction between parasite gene flow, local adaptation and host specialization within a single host-parasite system.
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| 23. |
- Eckel-Passow, Jeanette, et al.
(författare)
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USING GERMLINE VARIANTS TO PREDICT GLIOMA RISK AND IDENTIFY GLIOMA SUBTYPE PRE-OPERATIVELY
- 2018
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Ingår i: Neuro-Oncology. - : OXFORD UNIV PRESS INC. - 1522-8517 .- 1523-5866. ; 20, s. 82-82
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- To date, 25 single nucleotide polymorphisms (SNPs) have been shown to be associated with overall glioma risk or with risk of specific subtypes of glioma. We hypothesized that the inclusion of these 25 SNPs with patient age at diagnosis and sex could predict risk of glioma as well as predict IDH mutation status. Thus, case-control design and multinomial logistic regression were used to develop models to estimate the risk of glioma development while accounting for molecular subtypes. Case-case design and logistic regression were used to develop models to predict IDH mutation status. Each model included all 25 glioma risk SNPs, patient age at diagnosis and sex. A total of 1273 glioma cases and 443 controls from Mayo Clinic were used in the discovery set, and 852 glioma cases and 231 controls from UCSF were used in the validation set. All samples were genotyped using a custom Illumina OncoArray. We observed that patients in the highest 5% of the risk score had more than a 14-fold increased relative risk of developing an IDH-mutant glioma, compared to patients with median risk score. Large differences in lifetime absolute risk were observed at the extremes of the risk score percentile categories. For both IDH-mutated 1p/19q non-codeleted glioma and IDH-mutated 1p/19q-codeleted glioma, the lifetime risk increased from almost null to 2.3% and almost null to 1.7%, respectively. The SNP-based model that predicted IDH mutation status had a validation c-index of 0.85. These results suggest that germline genotyping has the potential to provide a new tool for clinicians for the initial management of newly-discovered brain lesions. Specifically, given the low lifetime risk of glioma, SNP-based risk scores should not be useful for general population screening. However, with further research these risk scores may be useful in certain clinically-defined high-risk groups.
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| 24. |
- McCoy, Daniel T., et al.
(författare)
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Aerosol midlatitude cyclone indirect effects in observations and high-resolution simulations
- 2018
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Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 18:8, s. 5821-5846
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Tidskriftsartikel (refereegranskat)abstract
- Aerosol-cloud interactions are a major source of uncertainty in inferring the climate sensitivity from the observational record of temperature. The adjustment of clouds to aerosol is a poorly constrained aspect of these aerosolcloud interactions. Here, we examine the response of midlatitude cyclone cloud properties to a change in cloud droplet number concentration (CDNC). Idealized experiments in high-resolution, convection-permitting global aquaplanet simulations with constant CDNC are compared to 13 years of remote-sensing observations. Observations and idealized aquaplanet simulations agree that increased warm conveyor belt (WCB) moisture flux into cyclones is consistent with higher cyclone liquid water path (CLWP). When CDNC is increased a larger LWP is needed to give the same rain rate. The LWP adjusts to allow the rain rate to be equal to the moisture flux into the cyclone along the WCB. This results in an increased CLWP for higher CDNC at a fixed WCB moisture flux in both observations and simulations. If observed cyclones in the top and bottom tercile of CDNC are contrasted it is found that they have not only higher CLWP but also cloud cover and albedo. The difference in cyclone albedo between the cyclones in the top and bottom third of CDNC is observed by CERES to be between 0.018 and 0.032, which is consistent with a 4.6-8.3Wm(-2) in-cyclone enhancement in upwelling shortwave when scaled by annualmean insolation. Based on a regression model to observed cyclone properties, roughly 60% of the observed variability in CLWP can be explained by CDNC and WCB moisture flux.
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| 25. |
- McCoy, Daniel T., et al.
(författare)
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Cloud feedbacks in extratropical cyclones : insight from long-term satellite data and high-resolution global simulations
- 2019
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Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 19:2, s. 1147-1172
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Tidskriftsartikel (refereegranskat)abstract
- A negative extratropical shortwave cloud feedback driven by changes in cloud optical depth is a feature of global climate models (GCMs). A robust positive trend in observed liquid water path (LWP) over the last two decades across the warming Southern Ocean supports the negative shortwave cloud feedback predicted by GCMs. This feature has been proposed to be due to transitions from ice to liquid with warming. To gain insight into the shortwave cloud feedback we examine extratropical cyclone variability and the response of extratropical cyclones to transient warming in GCM simulations. Multi-Sensor Advanced Climatology Liquid Water Path (MAC-LWP) microwave observations of cyclone properties from the period 1992-2015 are contrasted with GCM simulations, with horizontal resolutions ranging from 7 km to hundreds of kilometers. We find that inter-cyclone variability in LWP in both observations and models is strongly driven by the moisture flux along the cyclone's warm conveyor belt (WCB). Stronger WCB moisture flux enhances the LWP within cyclones. This relation-ship is replicated in GCMs, although its strength varies substantially across models. It is found that more than 80% of the enhancement in Southern Hemisphere (SH) extratropical cyclone LWP in GCMs in response to a transient 4K warming can be predicted based on the relationship between the WCB moisture flux and cyclone LWP in the historical climate and their change in moisture flux between the historical and warmed climates. Further, it is found that that the robust trend in cyclone LWP over the Southern Ocean in observations and GCMs is consistent with changes in the moisture flux. We propose two cloud feedbacks acting within extratropical cyclones: a negative feedback driven by Clausius-Clapeyron increasing water vapor path (WVP), which enhances the amount of water vapor available to be fluxed into the cyclone, and a feedback moderated by changes in the life cycle and vorticity of cyclones under warming, which changes the rate at which existing moisture is imported into the cyclone. Both terms contribute to increasing LWP within the cyclone. While changes in moisture flux predict cyclone LWP trends in the current climate and the majority of changes in LWP in transient warming simulations, a portion of the LWP increase in response to climate change that is unexplained by increasing moisture fluxes may be due to phase transitions. The variability in LWP within cyclone composites is examined to understand what cyclonic regimes the mixed-phase cloud feedback is relevant to. At a fixed WCB moisture flux cyclone LWP increases with increasing sea surface temperature (SST) in the half of the composite poleward of the low and decreases in the half equatorward of the low in both GCMs and observations. Cloud-top phase partitioning observed by the Atmospheric Infrared Sounder (AIRS) indicates that phase transitions may be driving increases in LWP in the poleward half of cyclones.
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| 27. |
- Robertson, Lindsay B, et al.
(författare)
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Survey of familial glioma and role of germline p16INK4A/p14ARF and p53 mutation
- 2010
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Ingår i: Familial Cancer. - : Springer Science and Business Media LLC. - 1389-9600 .- 1573-7292. ; 9:3, s. 413-421
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Tidskriftsartikel (refereegranskat)abstract
- There is increasing recognition of familial propensity to glioma as a distinct clinical entity beyond a few rare syndromes; however its genetic basis is poorly understood. The role of p16(INK4A)/p14(ARF) and p53 mutations in sporadic glioma provides a strong rationale for investigating germline mutations in these genes as a cause of familial glioma. To survey the familial glioma phenotype and examine the contribution of germline mutation in p16(INK4A)/p14(ARF) and p53 to the disease we have analyzed a series of 101 index familial cases collected through the GLIOGENE Consortium (http://braintumor.epigenetic.org/). There was little evidence for within family correlations for tumour histology, suggesting generic susceptibility to glial tumors. We did not detect any functional mutations in p16(INK4A) or p14(ARF). One index case with glioblastoma multiforme (GBM) diagnosed at age 54 and had a family history comprised of a paternal aunt with GBM at age 55, carried the p53 R158H mutation, which is predicted to be functional and has previously been implicated as a cause of Li-Fraumeni syndrome. Our findings provide no evidence that p16(INK4A)/p14(ARF) and p53 mutations contribute significantly to familial glioma.
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| 28. |
- van der Spek, Mijndert, et al.
(författare)
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Towards improved guidelines for uncertainty analysis of carbon capture and storage techno-economic studies
- 2021
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Ingår i: 15th Greenhouse Gas Control Technologies Conference 2021, GHGT 2021. - : International Energy Agency Greenhouse Gas, IEAGHG.
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Konferensbidrag (refereegranskat)abstract
- Uncertainty analysis is a key element of sound techno-economic analysis (TEA) of CO2 capture and storage (CCS) technologies and systems, and in the communication of TEA results. Many CCS technologies are novel concepts, that are still in the early (pre-commercial) stages of development. Therefore, uncertainties in their technology performance and cost are often substantial, making it imperative that they be characterized, and their impacts reported. Although uncertainty analysis itself is not novel, with some methods already frequently used by the CCS TEA community, a document that provides a comprehensive overview of methods and approaches, as well as guidance on their selection and use, is still lacking. Given its importance, we seek to fill this gap by providing a critical review of uncertainty analysis methods along with guidance on the selection and use of these methods for CCS TEAs, highlighting good practice and examples from the CCS literature. There are many opportunities to bring the use of uncertainty analysis to a higher level than currently practiced. This review of and guidance on available methods is intended to help accelerate continued methods development and their application to more robust and meaningful CCS performance and cost studies.
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