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Sökning: WFRF:(Barker Philip)

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1.
  • Meister, Philip, et al. (författare)
  • A global compilation of diatom silica oxygen isotope records from lake sediment - trends and implications for climate reconstruction
  • 2024
  • Ingår i: Climate of the Past. - 1814-9324. ; 20:2, s. 363-392
  • Tidskriftsartikel (refereegranskat)abstract
    • Oxygen isotopes in biogenic silica (δ18OBSi) from lake sediments allow for quantitative reconstruction of past hydroclimate and proxy-model comparison in terrestrial environments. The signals of individual records have been attributed to different factors, such as air temperature (Tair), atmospheric circulation patterns, hydrological changes, and lake evaporation. While every lake has its own local set of drivers of δ18O variability, here we explore the extent to which regional or even global signals emerge from a series of paleoenvironmental records. This study provides a comprehensive compilation and combined statistical evaluation of the existing lake sediment δ18OBSi records, largely missing in other summary publications (i.e. PAGES network). For this purpose, we have identified and compiled 71 down-core records published to date and complemented these datasets with additional lake basin parameters (e.g. lake water residence time and catchment size) to best characterize the signal properties. Records feature widely different temporal coverage and resolution, ranging from decadal-scale records covering the past 150 years to records with multi-millennial-scale resolution spanning glacial-interglacial cycles. The best coverage in number of records (NCombining double low line37) and data points (NCombining double low line2112) is available for Northern Hemispheric (NH) extratropical regions throughout the Holocene (roughly corresponding to Marine Isotope Stage 1; MIS 1). To address the different variabilities and temporal offsets, records were brought to a common temporal resolution by binning and subsequently filtered for hydrologically open lakes with lake water residence times <100 years. For mid- to high-latitude (>45°N) lakes, we find common δ18OBSi patterns among the lake records during both the Holocene and Common Era (CE). These include maxima and minima corresponding to known climate episodes, such as the Holocene Thermal Maximum (HTM), Neoglacial Cooling, Medieval Climate Anomaly (MCA) and the Little Ice Age (LIA). These patterns are in line with long-term air temperature changes supported by previously published climate reconstructions from other archives, as well as Holocene summer insolation changes. In conclusion, oxygen isotope records from NH extratropical lake sediments feature a common climate signal at centennial (for CE) and millennial (for Holocene) timescales despite stemming from different lakes in different geographic locations and hence constitute a valuable proxy for past climate reconstructions.
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2.
  • Barker, Philip A., et al. (författare)
  • Carbon cycling within an East African lake revealed by the carbon isotope composition of diatom silica: a 25-ka record from Lake Challa, Mt. Kilimanjaro
  • 2013
  • Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791. ; 66, s. 55-63
  • Tidskriftsartikel (refereegranskat)abstract
    • The carbon cycle of a lake is a balance between supply from the atmosphere and catchment, and the net demand exerted by primary producers, minus losses back to the atmosphere and to sediment storage. Evaluating the sum of these processes and reconstructing them from sediment records of lake history requires a range of methods and a multi-proxy approach. One promising technique is to explore the carbon-isotope composition (delta C-13(diatom)) of organic matter incorporated within the silica frustules of diatom algae. Here we present a 25,000-year record of delta C-13(diatom) from the sediments of crater Lake Challa on the eastern flank of Mt. Kilimanjaro, and along with other proxy data we make inferences about the three major phases in the history of the lake's carbon cycle. From 25 ka to 15.8 ka years BP, delta C-13(diatom) is positively correlated with the delta C-13 of bulk sediment organic matter (delta C-13(bulk)), indicating that high diatom productivity, as recorded by high % biogenic silica at this time, was preferentially removing C-12 and enriching the delta C-13 of lake-water dissolved inorganic carbon. From 15.8 to 5.5 ka the correlation between delta C-13(diatom) and delta C-13(bulk) breaks down, suggesting carbon supply to the lake satisfied or exceeded the demand from productivity. From 5.5 ka BP the positive correlation resumes, indicating an increase in the internal demand for carbon relative to external supply. Diatom frustule-bound carbon isotopes offer an original tool in examining long-term fluctuations in a lake's carbon budget and how the balance between supply and demand has changed through time. (C) 2012 Elsevier Ltd. All rights reserved.
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3.
  • Cammareri, Patrizia, et al. (författare)
  • Inactivation of TGFβ receptors in stem cells drives cutaneous squamous cell carcinoma
  • 2016
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • Melanoma patients treated with oncogenic BRAF inhibitors can develop cutaneous squamous cell carcinoma (cSCC) within weeks of treatment, driven by paradoxical RAS/RAF/MAPK pathway activation. Here we identify frequent TGFBR1 and TGFBR2 mutations in human vemurafenib-induced skin lesions and in sporadic cSCC. Functional analysis reveals these mutations ablate canonical TGFβ Smad signalling, which is localized to bulge stem cells in both normal human and murine skin. MAPK pathway hyperactivation (through Braf V600E or Kras G12D knockin) and TGFβ signalling ablation (through Tgfbr1 deletion) in LGR5 +ve stem cells enables rapid cSCC development in the mouse. Mutation of Tp53 (which is commonly mutated in sporadic cSCC) coupled with Tgfbr1 deletion in LGR5 +ve cells also results in cSCC development. These findings indicate that LGR5 +ve stem cells may act as cells of origin for cSCC, and that RAS/RAF/MAPK pathway hyperactivation or Tp53 mutation, coupled with loss of TGFβ signalling, are driving events of skin tumorigenesis.
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4.
  • Dand, Nick, et al. (författare)
  • Exome-wide association study reveals novel psoriasis susceptibility locus at TNFSF15 and rare protective alleles in genes contributing to type I IFN signalling
  • 2017
  • Ingår i: Human Molecular Genetics. - : OXFORD UNIV PRESS. - 0964-6906 .- 1460-2083. ; 26:21, s. 4301-4313
  • Tidskriftsartikel (refereegranskat)abstract
    • Psoriasis is a common inflammatory skin disorder for which multiple genetic susceptibility loci have been identified, but few resolved to specific functional variants. In this study, we sought to identify common and rare psoriasis-associated gene-centric variation. Using exome arrays we genotyped four independent cohorts, totalling 11 861 psoriasis cases and 28 610 controls, aggregating the dataset through statistical meta-analysis. Single variant analysis detected a previously unreported risk locus at TNFSF15 (rs6478108; P = 1.50 x 10(-8), OR = 1.10), and association of common protein-altering variants at 11 loci previously implicated in psoriasis susceptibility. We validate previous reports of protective low-frequency protein-altering variants within IFIH1 (encoding an innate antiviral receptor) and TYK2 (encoding a Janus kinase), in each case establishing a further series of protective rare variants (minor allele frequency amp;lt; 0.01) via gene-wide aggregation testing (IFIH1: p(burden) = 2.53 x 10(-7), OR = 0.707; TYK2: p(burden) = 6.17 x 10(-4), OR = 0.744). Both genes play significant roles in type I interferon (IFN) production and signalling. Several of the protective rare and low-frequency variants in IFIH1 and TYK2 disrupt conserved protein domains, highlighting potential mechanisms through which their effect may be exerted.
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5.
  • Dyverfeldt, Petter, et al. (författare)
  • 4D flow cardiovascular magnetic resonance consensus statement
  • 2015
  • Ingår i: Journal of Cardiovascular Magnetic Resonance. - : BioMed Central / Informa Healthcare. - 1097-6647 .- 1532-429X. ; 17:72
  • Forskningsöversikt (refereegranskat)abstract
    • Pulsatile blood flow through the cavities of the heart and great vessels is time-varying and multidirectional. Access to all regions, phases and directions of cardiovascular flows has formerly been limited. Four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) has enabled more comprehensive access to such flows, with typical spatial resolution of 1.5x1.5x1.5 - 3x3x3 mm(3), typical temporal resolution of 30-40 ms, and acquisition times in the order of 5 to 25 min. This consensus paper is the work of physicists, physicians and biomedical engineers, active in the development and implementation of 4D Flow CMR, who have repeatedly met to share experience and ideas. The paper aims to assist understanding of acquisition and analysis methods, and their potential clinical applications with a focus on the heart and greater vessels. We describe that 4D Flow CMR can be clinically advantageous because placement of a single acquisition volume is straightforward and enables flow through any plane across it to be calculated retrospectively and with good accuracy. We also specify research and development goals that have yet to be satisfactorily achieved. Derived flow parameters, generally needing further development or validation for clinical use, include measurements of wall shear stress, pressure difference, turbulent kinetic energy, and intracardiac flow components. The dependence of measurement accuracy on acquisition parameters is considered, as are the uses of different visualization strategies for appropriate representation of time-varying multidirectional flow fields. Finally, we offer suggestions for more consistent, user-friendly implementation of 4D Flow CMR acquisition and data handling with a view to multicenter studies and more widespread adoption of the approach in routine clinical investigations.
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7.
  • Jonsson, Christina E., 1965- (författare)
  • Holocene climate and atmospheric circulation changes in northern Fennoscandia : Interpretations from lacustrine oxygen isotope records
  • 2009
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • This thesis investigates how variations in the oxygen isotopic composition of lake waters in northern Fennoscandia are recorded in lake sediment archives, especially diatoms, and how these variations can be used to infer past changes in climate and atmospheric circulation. Results from analyses of the oxygen isotopic composition of lake water samples (δ18Olakew) collected between 2001 and 2006 show that δ18O of northern Fennoscandian lakes is mainly controlled by the isotopic composition of the precipitation (δ18Op). Changes in local δ18Op depend on variations in ambient air temperature and changes in atmospheric circulation that lead to changes in moisture source, vapour transport efficiency, or winter to summer precipitation distribution. This study demonstrates that the amount of isotopic variation in lake water δ18O is determined by a combination of the original δ18Olakew, the amount and timing of the snowmelt, the amount of seasonally specific precipitation and groundwater, any evaporation effects, and lake water residence time. The fact that the same isotope shifts have been detected in various δ18Olakew proxies, derived from hydrologically different lakes, suggests that these records reflect regional atmospheric circulation changes. The results indicate that diatom biogenic silica isotope (δ18Odiatom) records can provide important information about changes in atmospheric circulation that can help explain temperature and precipitation changes during the Holocene. The reconstructed long-term Holocene decreasing δ18Op trend was likely forced by a shift from strong zonal westerly airflow (relatively high δ18Op) in the early Holocene to a more meridional flow pattern (relatively low δ18Op). The large δ18Olakew depletion recorded in the δ18O records around ca. 500 cal yr BP (AD 1450) may be due to a shift to more intense meridional airflow over northern Fennoscandia resulting in an increasing proportion of winter precipitation from the north or southeast. This climate shift probably marks the onset of the so-called Little Ice Age in this region.
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8.
  • Kassebaum, Nicholas J., et al. (författare)
  • Global, regional, and national disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990-2015 : a systematic analysis for the Global Burden of Disease Study 2015
  • 2016
  • Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 388:10053, s. 1603-1658
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Healthy life expectancy (HALE) and disability-adjusted life-years (DALYs) provide summary measures of health across geographies and time that can inform assessments of epidemiological patterns and health system performance, help to prioritise investments in research and development, and monitor progress toward the Sustainable Development Goals (SDGs). We aimed to provide updated HALE and DALYs for geographies worldwide and evaluate how disease burden changes with development. Methods We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2015. We calculated DALYs by summing years of life lost (YLLs) and years of life lived with disability (YLDs) for each geography, age group, sex, and year. We estimated HALE using the Sullivan method, which draws from age-specific death rates and YLDs per capita. We then assessed how observed levels of DALYs and HALE differed from expected trends calculated with the Socio-demographic Index (SDI), a composite indicator constructed from measures of income per capita, average years of schooling, and total fertility rate. Findings Total global DALYs remained largely unchanged from 1990 to 2015, with decreases in communicable, neonatal, maternal, and nutritional (Group 1) disease DALYs off set by increased DALYs due to non-communicable diseases (NCDs). Much of this epidemiological transition was caused by changes in population growth and ageing, but it was accelerated by widespread improvements in SDI that also correlated strongly with the increasing importance of NCDs. Both total DALYs and age-standardised DALY rates due to most Group 1 causes significantly decreased by 2015, and although total burden climbed for the majority of NCDs, age-standardised DALY rates due to NCDs declined. Nonetheless, age-standardised DALY rates due to several high-burden NCDs (including osteoarthritis, drug use disorders, depression, diabetes, congenital birth defects, and skin, oral, and sense organ diseases) either increased or remained unchanged, leading to increases in their relative ranking in many geographies. From 2005 to 2015, HALE at birth increased by an average of 2.9 years (95% uncertainty interval 2.9-3.0) for men and 3.5 years (3.4-3.7) for women, while HALE at age 65 years improved by 0.85 years (0.78-0.92) and 1.2 years (1.1-1.3), respectively. Rising SDI was associated with consistently higher HALE and a somewhat smaller proportion of life spent with functional health loss; however, rising SDI was related to increases in total disability. Many countries and territories in central America and eastern sub-Saharan Africa had increasingly lower rates of disease burden than expected given their SDI. At the same time, a subset of geographies recorded a growing gap between observed and expected levels of DALYs, a trend driven mainly by rising burden due to war, interpersonal violence, and various NCDs. Interpretation Health is improving globally, but this means more populations are spending more time with functional health loss, an absolute expansion of morbidity. The proportion of life spent in ill health decreases somewhat with increasing SDI, a relative compression of morbidity, which supports continued efforts to elevate personal income, improve education, and limit fertility. Our analysis of DALYs and HALE and their relationship to SDI represents a robust framework on which to benchmark geography-specific health performance and SDG progress. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform financial and research investments, prevention efforts, health policies, and health system improvement initiatives for all countries along the development continuum.
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9.
  • Leebens-Mack, James H., et al. (författare)
  • One thousand plant transcriptomes and the phylogenomics of green plants
  • 2019
  • Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 574:7780, s. 679-
  • Tidskriftsartikel (refereegranskat)abstract
    • Green plants (Viridiplantae) include around 450,000-500,000 species(1,2) of great diversity and have important roles in terrestrial and aquatic ecosystems. Here, as part of the One Thousand Plant Transcriptomes Initiative, we sequenced the vegetative transcriptomes of 1,124 species that span the diversity of plants in a broad sense (Archaeplastida), including green plants (Viridiplantae), glaucophytes (Glaucophyta) and red algae (Rhodophyta). Our analysis provides a robust phylogenomic framework for examining the evolution of green plants. Most inferred species relationships are well supported across multiple species tree and supermatrix analyses, but discordance among plastid and nuclear gene trees at a few important nodes highlights the complexity of plant genome evolution, including polyploidy, periods of rapid speciation, and extinction. Incomplete sorting of ancestral variation, polyploidization and massive expansions of gene families punctuate the evolutionary history of green plants. Notably, we find that large expansions of gene families preceded the origins of green plants, land plants and vascular plants, whereas whole-genome duplications are inferred to have occurred repeatedly throughout the evolution of flowering plants and ferns. The increasing availability of high-quality plant genome sequences and advances in functional genomics are enabling research on genome evolution across the green tree of life.
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10.
  • Lozano, Rafael, et al. (författare)
  • Measuring progress from 1990 to 2017 and projecting attainment to 2030 of the health-related Sustainable Development Goals for 195 countries and territories: a systematic analysis for the Global Burden of Disease Study 2017
  • 2018
  • Ingår i: The Lancet. - : Elsevier. - 1474-547X .- 0140-6736. ; 392:10159, s. 2091-2138
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of “leaving no one behind”, it is increasingly important to examine the health-related SDGs beyond national-level estimates. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), we measured progress on 41 of 52 health-related SDG indicators and estimated the health-related SDG index for 195 countries and territories for the period 1990–2017, projected indicators to 2030, and analysed global attainment. Methods: We measured progress on 41 health-related SDG indicators from 1990 to 2017, an increase of four indicators since GBD 2016 (new indicators were health worker density, sexual violence by non-intimate partners, population census status, and prevalence of physical and sexual violence [reported separately]). We also improved the measurement of several previously reported indicators. We constructed national-level estimates and, for a subset of health-related SDGs, examined indicator-level differences by sex and Socio-demographic Index (SDI) quintile. We also did subnational assessments of performance for selected countries. To construct the health-related SDG index, we transformed the value for each indicator on a scale of 0–100, with 0 as the 2·5th percentile and 100 as the 97·5th percentile of 1000 draws calculated from 1990 to 2030, and took the geometric mean of the scaled indicators by target. To generate projections through 2030, we used a forecasting framework that drew estimates from the broader GBD study and used weighted averages of indicator-specific and country-specific annualised rates of change from 1990 to 2017 to inform future estimates. We assessed attainment of indicators with defined targets in two ways: first, using mean values projected for 2030, and then using the probability of attainment in 2030 calculated from 1000 draws. We also did a global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends. Using 2015 global averages of indicators with defined SDG targets, we calculated the global annualised rates of change required from 2015 to 2030 to meet these targets, and then identified in what percentiles the required global annualised rates of change fell in the distribution of country-level rates of change from 1990 to 2015. We took the mean of these global percentile values across indicators and applied the past rate of change at this mean global percentile to all health-related SDG indicators, irrespective of target definition, to estimate the equivalent 2030 global average value and percentage change from 2015 to 2030 for each indicator. Findings: The global median health-related SDG index in 2017 was 59·4 (IQR 35·4–67·3), ranging from a low of 11·6 (95% uncertainty interval 9·6–14·0) to a high of 84·9 (83·1–86·7). SDG index values in countries assessed at the subnational level varied substantially, particularly in China and India, although scores in Japan and the UK were more homogeneous. Indicators also varied by SDI quintile and sex, with males having worse outcomes than females for non-communicable disease (NCD) mortality, alcohol use, and smoking, among others. Most countries were projected to have a higher health-related SDG index in 2030 than in 2017, while country-level probabilities of attainment by 2030 varied widely by indicator. Under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria indicators had the most countries with at least 95% probability of target attainment. Other indicators, including NCD mortality and suicide mortality, had no countries projected to meet corresponding SDG targets on the basis of projected mean values for 2030 but showed some probability of attainment by 2030. For some indicators, including child malnutrition, several infectious diseases, and most violence measures, the annualised rates of change required to meet SDG targets far exceeded the pace of progress achieved by any country in the recent past. We found that applying the mean global annualised rate of change to indicators without defined targets would equate to about 19% and 22% reductions in global smoking and alcohol consumption, respectively; a 47% decline in adolescent birth rates; and a more than 85% increase in health worker density per 1000 population by 2030. Interpretation: The GBD study offers a unique, robust platform for monitoring the health-related SDGs across demographic and geographic dimensions. Our findings underscore the importance of increased collection and analysis of disaggregated data and highlight where more deliberate design or targeting of interventions could accelerate progress in attaining the SDGs. Current projections show that many health-related SDG indicators, NCDs, NCD-related risks, and violence-related indicators will require a concerted shift away from what might have driven past gains—curative interventions in the case of NCDs—towards multisectoral, prevention-oriented policy action and investments to achieve SDG aims. Notably, several targets, if they are to be met by 2030, demand a pace of progress that no country has achieved in the recent past. The future is fundamentally uncertain, and no model can fully predict what breakthroughs or events might alter the course of the SDGs. What is clear is that our actions—or inaction—today will ultimately dictate how close the world, collectively, can get to leaving no one behind by 2030.
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