151 research outputs found
Disentangling Human Error from the Ground Truth in Segmentation of Medical Images
Recent years have seen increasing use of supervised learning methods for
segmentation tasks. However, the predictive performance of these algorithms
depends on the quality of labels. This problem is particularly pertinent in the
medical image domain, where both the annotation cost and inter-observer
variability are high. In a typical label acquisition process, different human
experts provide their estimates of the 'true' segmentation labels under the
influence of their own biases and competence levels. Treating these noisy
labels blindly as the ground truth limits the performance that automatic
segmentation algorithms can achieve. In this work, we present a method for
jointly learning, from purely noisy observations alone, the reliability of
individual annotators and the true segmentation label distributions, using two
coupled CNNs. The separation of the two is achieved by encouraging the
estimated annotators to be maximally unreliable while achieving high fidelity
with the noisy training data. We first define a toy segmentation dataset based
on MNIST and study the properties of the proposed algorithm. We then
demonstrate the utility of the method on three public medical imaging
segmentation datasets with simulated (when necessary) and real diverse
annotations: 1) MSLSC (multiple-sclerosis lesions); 2) BraTS (brain tumours);
3) LIDC-IDRI (lung abnormalities). In all cases, our method outperforms
competing methods and relevant baselines particularly in cases where the number
of annotations is small and the amount of disagreement is large. The
experiments also show strong ability to capture the complex spatial
characteristics of annotators' mistakes
Molecular understanding of the serum antibody repertoires after seasonal influenza vaccination among different age cohorts
Numerous influenza vaccination studies based on bulk serology have indicated that the antibody responses to the vaccine markedly decrease in the elderly. However, whether such decline results from the changes in the overall quantity or the quality of the circulating antibodies in serum remains unknown. Utilizing novel antibody repertoire profiling technologies, combining tandem mass spectrometry (LC-MS/MS) and high-throughput sequencing, we investigated the influenza-specific serological repertoires of 10 donors ranging from 26 to 70 years old vaccinated with FluzoneÂź 2013-2014 and/or 2014-2015. In particular, we determined the serum antibodies that are specific to the H1 or H3 component of the vaccine or cross-reactive between the two (H1+H3) and examined their relative quantitative distributions. Our data indicate that the proportion of H1+H3 antibodies significantly increases in the elderly and that the somatic hypermutation rates of the influenza-specific antibodies are higher in the elderly. These results suggest that the repeated exposure to the different virus subtypes could have led to the prolonged selection of H1+H3 antibodies targeting highly conserved epitopes. To evaluate the potency of the antibodies circulating in different age groups, we recombinantly expressed a number of representative monoclonal antibodies isolated from the donors in different age groups for further characterizations. Overall, our analysis suggests that the influenza-specific repertoire in the elderly may converge toward shared epitopes but the quality of the antibodies can be superior in terms of cross-reactivity. However, because the antibody repertoire âshrinksâ as we age while targeting more conserved epitopes across different influenza subtypes, it is possible that the elderly is particularly susceptible to significantly altered strains. Collectively, profiling vaccine induced serological repertoires among different age cohorts can provide unprecedented insights regarding humoral immunity associated with age and a potential explanation for the vulnerability of the elderly
New Insight into the History of Domesticated Apple: Secondary Contribution of the European Wild Apple to the Genome of Cultivated Varieties
The apple is the most common and culturally important fruit crop of temperate areas. The elucidation of its origin and domestication history is therefore of great interest. The wild Central Asian species Malus sieversii has previously been identified as the main contributor to the genome of the cultivated apple (Malus domestica), on the basis of morphological, molecular, and historical evidence. The possible contribution of other wild species present along the Silk Route running from Asia to Western Europe remains a matter of debate, particularly with respect to the contribution of the European wild apple. We used microsatellite markers and an unprecedented large sampling of five Malus species throughout Eurasia (839 accessions from China to Spain) to show that multiple species have contributed to the genetic makeup of domesticated apples. The wild European crabapple M. sylvestris, in particular, was a major secondary contributor. Bidirectional gene flow between the domesticated apple and the European crabapple resulted in the current M. domestica being genetically more closely related to this species than to its Central Asian progenitor, M. sieversii. We found no evidence of a domestication bottleneck or clonal population structure in apples, despite the use of vegetative propagation by grafting. We show that the evolution of domesticated apples occurred over a long time period and involved more than one wild species. Our results support the view that self-incompatibility, a long lifespan, and cultural practices such as selection from open-pollinated seeds have facilitated introgression from wild relatives and the maintenance of genetic variation during domestication. This combination of processes may account for the diversification of several long-lived perennial crops, yielding domestication patterns different from those observed for annual species
2015 update of the evidence base:World Allergy Organization anaphylaxis guidelines
The World Allergy Organization (WAO) Guidelines for the assessment and management of anaphylaxis provide a unique global perspective on this increasingly common, potentially life-threatening disease. Recommendations made in the original WAO Anaphylaxis Guidelines remain clinically valid and relevant, and are a widely accessed and frequently cited resource. In this 2015 update of the evidence supporting recommendations in the Guidelines, new information based on anaphylaxis publications from January 2014 through mid- 2015 is summarized. Advances in epidemiology, diagnosis, and management in healthcare and community settings are highlighted. Additionally, new information about patient factors that increase the risk of severe and/or fatal anaphylaxis and patient co-factors that amplify anaphylactic episodes is presented and new information about anaphylaxis triggers and confirmation of triggers to facilitate specific trigger avoidance and immunomodulation is reviewed. The update includes tables summarizing important advances in anaphylaxis research. Keywords: Anaphylaxis, Epinephrine, Auto-injector, Food allergy, Stinging insect venom allergy, Drug allergy, Latex allergy, Exercise-induced anaphylaxis, Systemic allergic reaction, Adrenalin
Stroke genetics informs drug discovery and risk prediction across ancestries
Previous genome-wide association studies (GWASs) of stroke â the second leading cause of death worldwide â were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (Pâ<â0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries
Stroke genetics informs drug discovery and risk prediction across ancestries
Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry(1,2). Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis(3), and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach(4), we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry(5). Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.</p
Stroke genetics informs drug discovery and risk prediction across ancestries
Previous genome-wide association studies (GWASs) of stroke â the second leading cause of death worldwide â were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (Pâ<â0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries
Le parcours diagnostique des enfants atteints dâArthrogrypose Multiple CongĂ©nitale : description des pratiques actuelles Ă travers une cohorte monocentrique, et proposition de recommandations
Introduction: Arthrogryposis multiplex congenita (AMC) defines congenital contractures involving two or more body areas. The prevalence is estimated between 1/3000 and 1/12000. More than 400 conditions may lead to AMC through foetal hypo/a-kinesia, making the aetiological diagnosis challenging. The objective of this work was to describe the aetiological management of children with AMC and to propose recommendations in order to optimize clinical practices. Material and methods: We conducted a retrospective single centre observational study. Patients had been evaluated at least once at a paediatric age in Grenoble University Hospital from 2007 to 2019. After determining the diagnostic status of these patients, data on their diagnostic procedure were gathered. A literature review was performed for each paraclinical investigation to discuss their relevance in the light of patientsâ diagnoses, scientific knowledge, and benefit/risk or cost/benefit ratio. Results: 125 patients were included, 43% had Amyoplasia, 26% had distal arthrogryposis, and 31% had other forms. A definitive aetiological diagnosis was available for 63% of cases. We propose a two-time diagnostic process : first, non-invasive investigations that aim at classifying patients into one of the three groups, and then specific investigations targeting a subset of patients according to the expected yield and invasiveness. Conclusion: The diagnostic management of AMC patients has to result from a multidisciplinary approach. With the use of next generation sequencing, the aetiological assessment will be facilitated, but a relevant phenotyping will be paramount to guide their interpretation.Introduction : LâArthrogrypose Multiple CongĂ©nitale (AMC) correspond Ă des limitations articulaires touchant au moins deux niveaux. Sa prĂ©valence est estimĂ©e entre 1/3000 et 1/12000. Le diagnostic Ă©tiologique est difficile car il en existe plus de 400 causes. Lâobjectif de ce travail est de dĂ©crire le parcours diagnostique des enfants atteints dâAMC et de proposer des recommandations afin dâoptimiser les pratiques cliniques. MatĂ©riel et mĂ©thodes : Nous avons menĂ© une Ă©tude rĂ©trospective observationnelle monocentrique, incluant les enfants Ă©valuĂ©s au Centre Hospitalier Universitaire de Grenoble de 2007 Ă 2019. Nous avons collectĂ© les informations sur leur parcours diagnostique, puis avons menĂ© une revue de la littĂ©rature pour chaque investigation paraclinique afin dâen Ă©valuer la pertinence Ă la lumiĂšre du diagnostic final des patients, des connaissances scientifiques, de leur bĂ©nĂ©fices, risques et coĂ»ts. RĂ©sultats : Nous avons inclus un total de 125 patients, dont 43% cas dâAmyoplasie, 26% dâarthrogrypose distale et 31% dâautres formes. Un diagnostic Ă©tiologique Ă©tait posĂ© dans 63% des cas. Nous proposons une procĂ©dure diagnostique en deux temps: dâabord des investigations non invasives permettant dâorienter les patients vers lâun des trois groupes principaux, puis des investigations plus spĂ©cifiques avec des indications prĂ©cises, en fonction de leur rendement attendu et de leur caractĂšre invasif. Conclusion : Lâapproche diagnostique des enfants avec AMC doit rĂ©sulter dâun travail pluridisciplinaire. Lâutilisation croissante du sĂ©quençage de nouvelle gĂ©nĂ©ration facilitera cette dĂ©marche, mais le phĂ©notypage restera essentiel pour guider leur interprĂ©tation
Proposition dâune valeur limite biologique (VLB) du chrome urinaire dans une aciĂ©rie inoxydable
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