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1.
  • Ederle, Joerg, et al. (author)
  • Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial
  • 2010
  • In: The Lancet. - 1474-547X. ; 375:9719, s. 985-997
  • Journal article (peer-reviewed)abstract
    • Background Stents are an alternative treatment to carotid endarterectomy for symptomatic carotid stenosis, but previous trials have not established equivalent safety and efficacy. We compared the safety of carotid artery stenting with that of carotid endarterectomy. Methods The International Carotid Stenting Study (ICSS) is a multicentre, international, randomised controlled trial with blinded adjudication of outcomes. Patients with recently symptomatic carotid artery stenosis were randomly assigned in a 1:1 ratio to receive carotid artery stenting or carotid endarterectomy. Randomisation was by telephone call or fax to a central computerised service and was stratified by centre with minimisation for sex, age, contralateral occlusion, and side of the randomised artery. Patients and investigators were not masked to treatment assignment. Patients were followed up by independent clinicians not directly involved in delivering the randomised treatment. The primary outcome measure of the trial is the 3-year rate of fatal or disabling stroke in any territory, which has not been analysed yet. The main outcome measure for the interim safety analysis was the 120-day rate of stroke, death, or procedural myocardial infarction. Analysis was by intention to treat (ITT). This study is registered, number ISRCTN25337470. Findings The trial enrolled 1713 patients (stenting group, n=855; endarterectomy group, n=858). Two patients in the stenting group and one in the endarterectomy group withdrew immediately after randomisation, and were not included in the ITT analysis. Between randomisation and 120 days, there were 34 (Kaplan-Meier estimate 4.0%) events of disabling stroke or death in the stenting group compared with 27 (3.2%) events in the endarterectomy group (hazard ratio [HR] 1.28, 95% CI 0.77-2.11). The incidence of stroke, death, or procedural myocardial infarction was 8.5% in the stenting group compared with 5.2% in the endarterectomy group (72 vs 44 events; HR 1.69, 1.16-2.45, p=0.006), Risks of any stroke (65 vs 35 events; HR 1.92, 1.27-2.89) and all-cause death (19 vs seven events; HR 2.76, 1.16-6.56) were higher in the stenting group than in the endarterectomy group. Three procedural myocardial infarctions were recorded in the stenting group, all of which were fatal, compared with four, all non-fatal, in the endarterectomy group. There was one event of cranial nerve palsy in the stenting group compared with 45 in the endarterectomy group. There were also fewer haematomas of any severity in the stenting group than in the endarterectomy group (31 vs 50 events; p=0.0197). Interpretation Completion of long-term follow-up is needed to establish the efficacy of carotid artery stenting compared with endarterectomy. In the meantime, carotid endarterectomy should remain the treatment of choice for patients suitable for surgery.
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  • Wang, Haidong, et al. (author)
  • Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015 : a systematic analysis for the Global Burden of Disease Study 2015
  • 2016
  • In: The Lancet. - 0140-6736 .- 1474-547X. ; 388:10053, s. 1459-1544
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015. These results informed an in-depth investigation of observed and expected mortality patterns based on sociodemographic measures.METHODS: We estimated all-cause mortality by age, sex, geography, and year using an improved analytical approach originally developed for GBD 2013 and GBD 2010. Improvements included refinements to the estimation of child and adult mortality and corresponding uncertainty, parameter selection for under-5 mortality synthesis by spatiotemporal Gaussian process regression, and sibling history data processing. We also expanded the database of vital registration, survey, and census data to 14 294 geography-year datapoints. For GBD 2015, eight causes, including Ebola virus disease, were added to the previous GBD cause list for mortality. We used six modelling approaches to assess cause-specific mortality, with the Cause of Death Ensemble Model (CODEm) generating estimates for most causes. We used a series of novel analyses to systematically quantify the drivers of trends in mortality across geographies. First, we assessed observed and expected levels and trends of cause-specific mortality as they relate to the Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility. Second, we examined factors affecting total mortality patterns through a series of counterfactual scenarios, testing the magnitude by which population growth, population age structures, and epidemiological changes contributed to shifts in mortality. Finally, we attributed changes in life expectancy to changes in cause of death. We documented each step of the GBD 2015 estimation processes, as well as data sources, in accordance with Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER).FINDINGS: Globally, life expectancy from birth increased from 61·7 years (95% uncertainty interval 61·4-61·9) in 1980 to 71·8 years (71·5-72·2) in 2015. Several countries in sub-Saharan Africa had very large gains in life expectancy from 2005 to 2015, rebounding from an era of exceedingly high loss of life due to HIV/AIDS. At the same time, many geographies saw life expectancy stagnate or decline, particularly for men and in countries with rising mortality from war or interpersonal violence. From 2005 to 2015, male life expectancy in Syria dropped by 11·3 years (3·7-17·4), to 62·6 years (56·5-70·2). Total deaths increased by 4·1% (2·6-5·6) from 2005 to 2015, rising to 55·8 million (54·9 million to 56·6 million) in 2015, but age-standardised death rates fell by 17·0% (15·8-18·1) during this time, underscoring changes in population growth and shifts in global age structures. The result was similar for non-communicable diseases (NCDs), with total deaths from these causes increasing by 14·1% (12·6-16·0) to 39·8 million (39·2 million to 40·5 million) in 2015, whereas age-standardised rates decreased by 13·1% (11·9-14·3). Globally, this mortality pattern emerged for several NCDs, including several types of cancer, ischaemic heart disease, cirrhosis, and Alzheimer's disease and other dementias. By contrast, both total deaths and age-standardised death rates due to communicable, maternal, neonatal, and nutritional conditions significantly declined from 2005 to 2015, gains largely attributable to decreases in mortality rates due to HIV/AIDS (42·1%, 39·1-44·6), malaria (43·1%, 34·7-51·8), neonatal preterm birth complications (29·8%, 24·8-34·9), and maternal disorders (29·1%, 19·3-37·1). Progress was slower for several causes, such as lower respiratory infections and nutritional deficiencies, whereas deaths increased for others, including dengue and drug use disorders. Age-standardised death rates due to injuries significantly declined from 2005 to 2015, yet interpersonal violence and war claimed increasingly more lives in some regions, particularly in the Middle East. In 2015, rotaviral enteritis (rotavirus) was the leading cause of under-5 deaths due to diarrhoea (146 000 deaths, 118 000-183 000) and pneumococcal pneumonia was the leading cause of under-5 deaths due to lower respiratory infections (393 000 deaths, 228 000-532 000), although pathogen-specific mortality varied by region. Globally, the effects of population growth, ageing, and changes in age-standardised death rates substantially differed by cause. Our analyses on the expected associations between cause-specific mortality and SDI show the regular shifts in cause of death composition and population age structure with rising SDI. Country patterns of premature mortality (measured as years of life lost [YLLs]) and how they differ from the level expected on the basis of SDI alone revealed distinct but highly heterogeneous patterns by region and country or territory. Ischaemic heart disease, stroke, and diabetes were among the leading causes of YLLs in most regions, but in many cases, intraregional results sharply diverged for ratios of observed and expected YLLs based on SDI. Communicable, maternal, neonatal, and nutritional diseases caused the most YLLs throughout sub-Saharan Africa, with observed YLLs far exceeding expected YLLs for countries in which malaria or HIV/AIDS remained the leading causes of early death.INTERPRETATION: At the global scale, age-specific mortality has steadily improved over the past 35 years; this pattern of general progress continued in the past decade. Progress has been faster in most countries than expected on the basis of development measured by the SDI. Against this background of progress, some countries have seen falls in life expectancy, and age-standardised death rates for some causes are increasing. Despite progress in reducing age-standardised death rates, population growth and ageing mean that the number of deaths from most non-communicable causes are increasing in most countries, putting increased demands on health systems.
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  • Khalil, Ibrahim, et al. (author)
  • Burden of Diarrhea in the Eastern Mediterranean Region, 1990-2013 : Findings from the Global Burden of Disease Study 2013
  • 2016
  • In: American Journal of Tropical Medicine and Hygiene. - : American Society of Tropical Medicine and Hygiene. - 1476-1645 .- 0002-9637. ; 95:6, s. 1319-1329
  • Journal article (peer-reviewed)abstract
    • Diarrheal diseases (DD) are leading causes of disease burden, death, and disability, especially in children in low-income settings. DD can also impact a child's potential livelihood through stunted physical growth, cognitive impairment, and other sequelae. As part of the Global Burden of Disease Study, we estimated DD burden, and the burden attributable to specific risk factors and particular etiologies, in the Eastern Mediterranean Region (EMR) between 1990 and 2013. For both sexes and all ages, we calculated disability-adjusted life years (DALYs), which are the sum of years of life lost and years lived with disability. We estimate that over 125,000 deaths (3.6% of total deaths) were due to DD in the EMR in 2013, with a greater burden of DD in low- and middle-income countries. Diarrhea deaths per 100,000 children under 5 years of age ranged from one (95% uncertainty interval [UI] = 0-1) in Bahrain and Oman to 471 (95% UI = 245-763) in Somalia. The pattern for diarrhea DALYs among those under 5 years of age closely followed that for diarrheal deaths. DALYs per 100,000 ranged from 739 (95% UI = 520-989) in Syria to 40,869 (95% UI = 21,540-65,823) in Somalia. Our results highlighted a highly inequitable burden of DD in EMR, mainly driven by the lack of access to proper resources such as water and sanitation. Our findings will guide preventive and treatment interventions which are based on evidence and which follow the ultimate goal of reducing the DD burden.
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  • Dramburg, S, et al. (author)
  • EAACI Molecular Allergology User's Guide 2.0
  • 2023
  • In: Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology. - 1399-3038. ; 3434 Suppl 28, s. e13854-
  • Journal article (peer-reviewed)
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  • Commins, Scott P, et al. (author)
  • Galactose-α-1,3-galactose-specific IgE is associated with anaphylaxis but not asthma.
  • 2012
  • In: American journal of respiratory and critical care medicine. - 1535-4970 .- 1073-449X. ; 185:7, s. 723-30
  • Journal article (peer-reviewed)abstract
    • IgE antibodies to the mammalian oligosaccharide galactose-α-1,3-galactose (α-gal) are common in the southeastern United States. These antibodies, which are induced by ectoparasitic ticks, can give rise to positive skin tests or serum assays with cat extract.
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  • Edger, P. P., et al. (author)
  • Subgenome dominance in an interspecific hybrid, synthetic allopolyploid, and a 140-Year-old naturally established neo-allopolyploid monkeyflower
  • 2017
  • In: Plant Cell. ; 29:9, s. 2150-2167
  • Journal article (peer-reviewed)abstract
    • Recent studies have shown that one of the parental subgenomes in ancient polyploids is generally more dominant, having retained more genes and being more highly expressed, a phenomenon termed subgenome dominance. The genomic features that determine how quickly and which subgenome dominates within a newly formed polyploid remain poorly understood. To investigate the rate of emergence of subgenome dominance, we examined gene expression, gene methylation, and transposable element (TE) methylation in a natural, <140-year-old allopolyploid (Mimulus peregrinus), a resynthesized interspecies triploid hybrid (M. robertsii), a resynthesized allopolyploid (M. peregrinus), and progenitor species (M. guttatus and M. luteus). We show that subgenome expression dominance occurs instantly following the hybridization of divergent genomes and significantly increases over generations. Additionally, CHH methylation levels are reduced in regions near genes and within TEs in the first-generation hybrid, intermediate in the resynthesized allopolyploid, and are repatterned differently between the dominant and recessive subgenomes in the natural allopolyploid. Subgenome differences in levels of TE methylation mirror the increase in expression bias observed over the generations following hybridization. These findings provide important insights into genomic and epigenomic shock that occurs following hybridization and polyploid events and may also contribute to uncovering the mechanistic basis of heterosis and subgenome dominance.
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  • Commins, Scott P., et al. (author)
  • The relevance of tick bites to the production of IgE antibodies to the mammalian oligosaccharide galactose-alpha-1,3-galactose
  • 2011
  • In: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 127:5, s. 1286-1293.e6
  • Journal article (peer-reviewed)abstract
    • Background: In 2009, we reported a novel form of delayed anaphylaxis to red meat that is related to serum IgE antibodies to the oligosaccharide galactose-alpha-1,3-galactose (alpha-gal). Most of these patients had tolerated meat for many years previously. The implication is that some exposure in adult life had stimulated the production of these IgE antibodies. Objectives: We sought to investigate possible causes of this IgE antibody response, focusing on evidence related to tick bites, which are common in the region where these reactions occur.Methods: Serum assays were carried out with biotinylated proteins and extracts bound to a streptavidin ImmunoCAP.Results: Prospective studies on IgE antibodies in 3 subjects after tick bites showed an increase in levels of IgE to alpha-gal of 20fold or greater. Other evidence included (1) a strong correlation between histories of tick bites and levels of IgE to alpha-gal (chi(2) = 26.8, P < .001), (2) evidence that these IgE antibodies are common in areas where the tick Amblyomma americanum is common, and (3) a significant correlation between IgE antibodies to alpha-gal and IgE antibodies to proteins derived from A americanum (r(s) = 0.75, P < .001).Conclusion: The results presented here provide evidence that tick bites are a cause, possibly the only cause, of IgE specific for alpha-gal in this area of the United States. Both the number of subjects becoming sensitized and the titer of IgE antibodies to alpha-gal are striking. Here we report the first example of a response to an ectoparasite giving rise to an important form of food allergy.
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  • Macgregor, Callum J., et al. (author)
  • Climate-induced phenology shifts linked to range expansions in species with multiple reproductive cycles per year
  • 2019
  • In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10
  • Journal article (peer-reviewed)abstract
    • Advances in phenology (the annual timing of species' life-cycles) in response to climate change are generally viewed as bioindicators of climate change, but have not been considered as predictors of range expansions. Here, we show that phenology advances combine with the number of reproductive cycles per year (voltinism) to shape abundance and distribution trends in 130 species of British Lepidoptera, in response to similar to 0.5 degrees C spring-temperature warming between 1995 and 2014. Early adult emergence in warm years resulted in increased within- and between-year population growth for species with multiple reproductive cycles per year (n = 39 multivoltine species). By contrast, early emergence had neutral or negative consequences for species with a single annual reproductive cycle (n = 91 univoltine species), depending on habitat specialisation. We conclude that phenology advances facilitate pole-wards range expansions in species exhibiting plasticity for both phenology and voltinism, but may inhibit expansion by less flexible species.
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  • Matricardi, PM, et al. (author)
  • EAACI Molecular Allergology User's Guide
  • 2016
  • In: Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology. - : Wiley. - 1399-3038. ; 2727 Suppl 23, s. 1-250
  • Journal article (peer-reviewed)
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  • Bunne, Joakim, et al. (author)
  • The Majority of Children Sensitized Before School-Age Develop Allergic Disease Before Adulthood: A Longitudinal Population-Based Study
  • 2022
  • In: Journal of Allergy and Clinical Immunology: In Practice. - : Elsevier BV. - 2213-2198 .- 2213-2201. ; 10:2
  • Journal article (peer-reviewed)abstract
    • Background: Allergic sensitization increases the risk of asthma and allergic rhinitis, but the impact of age at onset of sensitization is less studied. Objective: To examine the cumulative incidence of asthma and rhinitis up to age 19 years in relation to age at onset of sensitization to airborne allergens. Method: All children in grade 1 and 2 (median age, 8 years) in 2 municipalities in Northern Sweden were invited to undergo skin prick tests and answer a questionnaire about allergic diseases, and 88% participated. At ages 12 and 19 years, the protocol was repeated, and 1510 individuals participated in all 3 examinations. Specific IgE data were collected in a random sample at age 19 years (n = 770). Onset of sensitization was defined: 8 years or less, 8 to 12 years, 12 to 19 years, and never sensitized. Adjusted Poisson regression was used to calculate risk ratios (RRs). Results: At 19 years, those sensitized at 8 years of age or earlier had the highest risk of asthma (RR, 4.68; 95% CI, 3.15-6.97) and rhinitis (RR, 22.3; 95% CI, 13.3-37.6), and 84% had developed either asthma or rhinitis. The combination of sensitization at age 8 years or earlier and family history of allergic diseases rendered high risks for asthma (RR, 10.6; 95% CI, 6.71-16.7) and rhinitis (RR, 36.3; 95% CI, 18.9-69.7). Individuals sensitized at age 8 years or earlier showed significantly highest level of sensitization, as judged by number of positive skin test results and titers of specific IgE. Conclusions: Most individuals with sensitization at age 8 years or earlier developed asthma or rhinitis before young adulthood. The high level of sensitization in those sensitized early contributes to the high incidence of allergic airway conditions. © 2021 The Authors
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  • Carvalho, Alexandra T. P., et al. (author)
  • Understanding the structural and dynamic consequences of DNA epigenetic modifications : Computational insights into cytosine methylation and hydroxymethylation
  • 2014
  • In: Epigenetics. - : Informa UK Limited. - 1559-2294 .- 1559-2308. ; 9:12, s. 1604-1612
  • Journal article (peer-reviewed)abstract
    • We report a series of molecular dynamics (MD) simulations of up to a microsecond combined simulation time designed to probe epigenetically modified DNA sequences. More specifically, by monitoring the effects of methylation and hydroxymethylation of cytosine in different DNA sequences, we show, for the first time, that DNA epigenetic modifications change the molecule's dynamical landscape, increasing the propensity of DNA toward different values of twist and/or roll/tilt angles (in relation to the unmodified DNA) at the modification sites. Moreover, both the extent and position of different modifications have significant effects on the amount of structural variation observed. We propose that these conformational differences, which are dependent on the sequence environment, can provide specificity for protein binding.
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  • Charikinya, Edson, et al. (author)
  • Integration of mineralogical attributes in evaluating sustainability indicators of a magnetic separator
  • 2017
  • In: Minerals Engineering. - : Elsevier. - 0892-6875 .- 1872-9444. ; 107, s. 53-62
  • Journal article (peer-reviewed)abstract
    • Early integration of sustainability decisions and mineralogical attributes into the design of minerals processing units offers potential for reducing environmental impacts at mining and processing sites. The objective of this study is to demonstrate how the integration of sustainability indicators and mineralogical attributes could be achieved in developing an integrated modelling framework of a magnetic separator. A magnetic separator unit model based on existing literature was developed to include process stream mineralogical data and to output sustainability indicators. The overall sustainability of processing three ore types (low, medium and high grade iron ore) was evaluated using the developed model. Novel measures for evaluating magnetic separation (Grade Recovery Deviation Index (GRDI)) and energy efficiency (Rotational Energy Transfer Efficiency (RETE)) that incorporate the use of ore characteristics were developed in this study. These measures were used to calculate the separation and energy efficiency sustainability indicator ratings. In total eleven magnetic separator sustainability indicators were identified. Each indicator was assigned a weighting value out of 10 based on its importance. Of the 11 sustainability indicators identified; safety, reliability, Carbon dioxide (CO2) emissions, water use, noise and job creation ratings did not vary with changing mineralogical attributes of the feed ore. GRDI, RETE, electricity cost, particle emissions and waste generation ratings were observed to be dependent on the ore characteristics and therefore their values varied with different feed ore grades. The Analytic Hierarchy Process (AHP) and Weighted Sum Method (WSM) methods were applied to the sustainability indicator ratings and weightings to evaluate an overall sustainability cardinal score of processing a particular ore feed. Results of this study demonstrate the dependence of overall process sustainability indicators on feed ore mineralogical attributes. The results also provide an indication of the effect of ore variability (typical within a single deposit) on sustainability indicators.
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  • Cuni-Sanchez, Aida, et al. (author)
  • High aboveground carbon stock of African tropical montane forests
  • 2021
  • In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 596:7873, s. 536-542
  • Journal article (peer-reviewed)abstract
    • Tropical forests store 40–50per cent of terrestrial vegetation carbon. However, spatial variations in aboveground live tree biomass carbon (AGC) stocks remain poorly understood, in particular in tropical montane forests. Owing to climatic and soil changes with increasing elevation, AGC stocks are lower in tropical montane forests compared with lowland forests. Here we assemble and analyse a dataset of structurally intact old-growth forests (AfriMont) spanning 44 montane sites in 12 African countries. We find that montane sites in the AfriMont plot network have a mean AGC stock of 149.4megagrams of carbon per hectare (95% confidence interval 137.1–164.2), which is comparable to lowland forests in the African Tropical Rainforest Observation Network4 and about 70per cent and 32per cent higher than averages from plot networks in montane and lowland forests in the Neotropics, respectively. Notably, our results are two-thirds higher than the Intergovernmental Panel on Climate Change default values for these forests in Africa8. We find that the low stem density and high abundance of large trees of African lowland forests is mirrored in the montane forests sampled. This carbon store is endangered: we estimate that 0.8 million hectares of old-growth African montane forest have been lost since 2000. We provide country-specific montane forest AGC stock estimates modelled from our plot network to helpto guide forest conservation and reforestation interventions. Our findings highlight the need for conserving these biodiverse and carbon-rich ecosystems.
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  • Douglas, Gavin M., et al. (author)
  • Hybrid origins and the earliest stages of diploidization in the highly successful recent polyploid Capsella bursa-pastoris
  • 2015
  • In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 112:9, s. 2806-2811
  • Journal article (peer-reviewed)abstract
    • Whole-genome duplication (WGD) events have occurred repeatedly during flowering plant evolution, and there is growing evidence for predictable patterns of gene retention and loss following polyploidization. Despite these important insights, the rate and processes governing the earliest stages of diploidization remain poorly understood, and the relative importance of genetic drift, positive selection, and relaxed purifying selection in the process of gene degeneration and loss is unclear. Here, we conduct whole-genome resequencing in Capsella bursa-pastoris, a recently formed tetraploid with one of the most widespread species distributions of any angiosperm. Whole-genome data provide strong support for recent hybrid origins of the tetraploid species within the past 100,000-300,000 y from two diploid progenitors in the Capsella genus. Major-effect inactivating mutations are frequent, but many were inherited from the parental species and show no evidence of being fixed by positive selection. Despite a lack of large-scale gene loss, we observe a decrease in the efficacy of natural selection genome-wide due to the combined effects of demography, selfing, and genome redundancy from WGD. Our results suggest that the earliest stages of diploidization are associated with quantitative genome-wide decreases in the strength and efficacy of selection rather than rapid gene loss, and that non-functionalization can receive a head start through a legacy of deleterious variants and differential expression originating in parental diploid populations.
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  • Edger, Patrick P., et al. (author)
  • The butterfly plant arms-race escalated by gene and genome duplications
  • 2015
  • In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 112:27, s. 8362-8366
  • Journal article (peer-reviewed)abstract
    • Coevolutionary interactions are thought to have spurred the evolution of key innovations and driven the diversification of much of life on Earth. However, the genetic and evolutionary basis of the innovations that facilitate such interactions remains poorly understood. We examined the coevolutionary interactions between plants (Brassicales) and butterflies (Pieridae), and uncovered evidence for an escalating evolutionary arms-race. Although gradual changes in trait complexity appear to have been facilitated by allelic turnover, key innovations are associated with gene and genome duplications. Furthermore, we show that the origins of both chemical defenses and of molecular counter adaptations were associated with shifts in diversification rates during the arms-race. These findings provide an important connection between the origins of biodiversity, coevolution, and the role of gene and genome duplications as a substrate for novel traits.
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  • James, Hayley R, et al. (author)
  • IgE Antibodies to Mammalian Allergens Are a Major Risk Factor for Prevalence, Severity, and Persistence of Asthma in Northern Sweden
  • 2015
  • In: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 135:2, s. AB22-AB22
  • Journal article (other academic/artistic)abstract
    • IgE to mammalian allergens can contribute significantly to asthma risk. Studying the details of the relationship between animal sensitization and asthma is simpler in an environment where mite, fungal, and cockroach allergens make little or no contribution to asthma risk. Methods: Quantitative assays for IgE to eight allergens were carried out on 963 sera from 19-year-olds in a population-based cohort in northern Sweden, and associations with questionnaire data from ages 7, 12, and 19 on asthma symptoms, diagnosis, and treatment were tested. Results: Overall, 79 (53%) of the students with a physician diagnosis of asthma were positive to one or more of the mammalian allergens (cat, dog, or horse danders) tested. Of the allergens assessed, only mammalian allergens, birch, and timothy grass pollen showed a significant relationship with asthma diagnosis. Multivariate analysis showed that high titer (>17.5 IU/ml) IgE to any mammalian allergen had the strongest relationship with asthma at age 19 (odds ratio 5.1 [3.0-8.6]). Furthermore, IgE to mammalian allergens gave an odds ratio of 8.5 [4.9-15] for asthma that started before age 12 and was still present at age 19. Sensitization to Fel d 1 and Fel d 4 was strongly associated with asthma and significantly reduced in cat owners. Conclusions: Sensitization to cat and dog related allergens, and specifically to the components Fel d 1 and Fel d 4, is a major risk factor for the persistence and severity of asthma in an area where these are the only significant perennial allergens.
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  • Lawrence, Monica G, et al. (author)
  • Undetectable Serum IgE Is a Sensitive and Specific Marker of Common Variable Immunodeficiency (CVID)
  • 2015
  • In: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 135:2, s. AB275-AB275
  • Journal article (other academic/artistic)abstract
    • Common variable immunodeficiency (CVID) is characterized by antibody deficiency and recurrent infections as well as autoimmunity, lymphoproliferation, and hematologic malignancy. The current diagnostic criteria for CVID include reduction in serum immunoglobulin (Ig)G and either IgA or IgM and failure of antibody production. Serum IgE level is not currently considered in establishing the diagnosis of CVID. Methods: A cohort of 123 subjects from the University of Virginia Health Systems, Medical College of Wisconsin and Mount Sinai School of Medicine were diagnosed with CVID by an experienced immunologist on the basis of currently accepted diagnostic criteria, including clinical history, serum IgG, IgA and IgM, and antibody response to vaccinations. Serum IgE was measured in all of these subjects using the Phadia ImmunoCap system. Serum IgE was also measured in an unbiased control cohort of 963 healthy 17-18 year olds from northern Sweden. Results: The prevalence of undetectable (<2 IU/ml) total serum IgE in our cohort of 123 subjects with CVID was 84.6% and the prevalence of IgE <10 IU/ml was 97.6%. In comparison, IgE <2 IU/ml was found in only 3.8% of controls, in agreement with other published population estimates. Conclusions: The finding of an undetectable (<2 IU/ml) serum IgE has both a high sensitivity of 84.6% and a high specificity of 96.2% for the diagnosis of CVID. Based on this observation, measurement of serum IgE should be included as a part of the routine laboratory work-up for CVID, and an undetectable serum IgE included as a component of the diagnostic criteria.
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