48 research outputs found
Mycobacterium abscessus and Children with Cystic Fibrosis
We prospectively studied 298 patients with cystic fibrosis (mean age 11.3 years; range 2 months to 32 years; sex ratio, 0.47) for nontuberculous mycobacteria in respiratory samples from January 1, 1996, to December 31, 1999. Mycobacterium abscessus was by far the most prevalent nontuberculous mycobacterium: 15 patients (6 male, 9 female; mean age 11.9 years; range 2.5â22 years) had at least one positive sample for this microorganism (versus 6 patients positive for M. avium complex), including 10 with >3 positive samples (versus 3 patients for M. avium complex). The M. abscessus isolates from 14 patients were typed by pulsed-field gel electrophoresis: each of the 14 patients harbored a unique strain, ruling out a common environmental reservoir or person-to-person transmission. Water samples collected in the cystic fibrosis center were negative for M. abscessus. This major mycobacterial pathogen in children and teenagers with cystic fibrosis does not appear to be acquired nosocomially
CoNLL 2017 Shared Task : Multilingual Parsing from Raw Text to Universal Dependencies
The Conference on Computational Natural Language Learning (CoNLL) features a shared task, in which participants train and test their learning systems on the same data sets. In 2017, one of two tasks was devoted to learning dependency parsers for a large number of languages, in a real world setting without any gold-standard annotation on input. All test sets followed a unified annotation scheme, namely that of Universal Dependencies. In this paper, we define the task and evaluation methodology, describe data preparation, report and analyze the main results, and provide a brief categorization of the different approaches of the participating systems.Peer reviewe
SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues
Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to
genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility
and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component.
Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci
(eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene),
including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform
genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer
SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the
diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types
Genetic mechanisms of critical illness in COVID-19.
Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, PÂ =Â 1.65Â ĂÂ 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, PÂ =Â 2.3Â ĂÂ 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, PÂ =Â 3.98Â ĂÂ Â 10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, PÂ =Â 4.99Â ĂÂ 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice
Limits to reproduction and seed size-number trade-offs that shape forest dominance and future recovery
International audienceThe relationships that control seed production in trees are fundamental to understanding the evolution of forest species and their capacity to recover from increasing losses to drought, fire, and harvest. A synthesis of fecundity data from 714 species worldwide allowed us to examine hypotheses that are central to quantifying reproduction, a foundation for assessing fitness in forest trees. Four major findings emerged. First, seed production is not constrained by a strict trade-off between seed size and numbers. Instead, seed numbers vary over ten orders of magnitude, with species that invest in large seeds producing more seeds than expected from the 1:1 trade-off. Second, gymnosperms have lower seed production than angiosperms, potentially due to their extra investments in protective woody cones. Third, nutrient-demanding species, indicated by high foliar phosphorus concentrations, have low seed production. Finally, sensitivity of individual species to soil fertility varies widely, limiting the response of community seed production to fertility gradients. In combination, these findings can inform models of forest response that need to incorporate reproductive potential
Limits to reproduction and seed size-number tradeoffs that shape forest dominance and future recovery
The relationships that control seed production in trees are fundamental to understanding the evolution of forest species and their capacity to recover from increasing losses to drought, fire, and harvest. A synthesis of fecundity data from 714 species worldwide allowed us to examine hypotheses that are central to quantifying reproduction, a foundation for assessing fitness in forest trees. Four major findings emerged. First, seed production is not constrained by a strict trade-off between seed size and numbers. Instead, seed numbers vary over ten orders of magnitude, with species that invest in large seeds producing more seeds than expected from the 1:1 trade-off. Second, gymnosperms have lower seed production than angiosperms, potentially due to their extra investments in protective woody cones. Third, nutrient-demanding species, indicated by high foliar phosphorus concentrations, have low seed production. Finally, sensitivity of individual species to soil fertility varies widely, limiting the response of community seed production to fertility gradients. In combination, these findings can inform models of forest response that need to incorporate reproductive potential
RelatĂłrio de estĂĄgio em farmĂĄcia comunitĂĄria
RelatĂłrio de estĂĄgio realizado no Ăąmbito do Mestrado Integrado em CiĂȘncias FarmacĂȘuticas, apresentado Ă Faculdade de FarmĂĄcia da Universidade de Coimbr
L'accÚs à la parentalité des patientes souffrant d'un trouble bipolaire
Introduction : les troubles bipolaires sont des troubles de lâhumeur et se dĂ©finissent, le plus souvent, par lâalternance dâĂ©pisodes dĂ©pressifs caractĂ©risĂ©s, et dâexaltation pathologique (manie ou hypomanie) avec des intervalles de rĂ©mission, quâon appelle lâeuthymie. Ils apparaissent, en gĂ©nĂ©ral, au dĂ©but de lâĂąge adulte, Ăąge auquel le dĂ©sir dâenfant peut se manifester. Comment se dĂ©roule lâaccĂšs Ă la parentalitĂ© chez ces patientes ?MatĂ©riel et MĂ©thodes : nous avons rĂ©alisĂ© une revue de la littĂ©rature, sur lâaccĂšs Ă la parentalitĂ© chez les patientes souffrant dâun trouble bipolaire, grĂące au moteur de recherche PubMed. 63 articles sont retenus.RĂ©sultats : tout dâabord, une fĂ©conditĂ© rĂ©duite est constatĂ©e, par rapport Ă la population gĂ©nĂ©rale et les stigmatisations semblent aussi ĂȘtre un frein Ă lâaccĂšs Ă la parentalitĂ©. La gestion du trouble bipolaire durant la grossesse apparaĂźt complexe, en raison de lâabsence de recommandations prĂ©cises sur les thĂ©rapeutiques et de lâĂ©quilibre dĂ©licat entre le risque de rechute maternelle et la tĂ©ratogĂ©nicitĂ©. Les Ă©tudes prĂ©cisent que lâarrĂȘt du thymorĂ©gulateur majore le risque de dĂ©compensation thymique, durant la grossesse et le post-partum, pĂ©riodes de vulnĂ©rabilitĂ© psychique. Ensuite, la lecture de plusieurs travaux souligne une intrication entre dĂ©compensations psychiatriques maternelles, consommation de toxiques et complications nĂ©onatales. De plus, le risque de suicide est dĂ©crit dans le post-partum. Enfin, le retentissement du trouble bipolaire sur le dĂ©veloppement des enfants est notĂ© avec des troubles des interactions prĂ©coces, pouvant perturber lâattachement, on relĂšve peu de perturbations du dĂ©veloppement psychomoteur dans ces Ă©tudes, ainsi quâune hĂ©ritabilitĂ© marquĂ©e. Conclusion : lâaccĂšs Ă la parentalitĂ© des patientes bipolaires est un parcours difficile oĂč les enjeux sont multiples. Ainsi, nous avons Ă©tabli des conseils pratiques, afin dâessayer de mieux accompagner ces patientes, du projet de grossesse au post-partum, en impliquant le conjoint et en collaborant entre professionnels dâun rĂ©seau de soins Ă©largi
Diagnosis and treatment of invasive fungal infections- looking ahead
Improved standards of care depend on the development of new laboratory diagnostic and imaging procedures and the development of new antifungal compounds. Immunochromatography technologies have led to the development of lateral flow devices for the diagnosis of cryptococcal meningitis and invasive aspergillosis (IA). Similar devices are being developed for the detection of histoplasmosis that meet the requirements for speed (âŒ15âmin assay time) and ease of use for point-of-care diagnostics. The evolution of molecular tools for the detection of fungal pathogens has been slow but the introduction of new nucleic acid amplification techniques appears to be helpful, for example T2Candida. An Aspergillus proximity ligation assay has been developed for a rapid near-patient bedside diagnosis of IA. CT remains the cornerstone for radiological diagnosis of invasive pulmonary fungal infections. MRI of the lungs may be performed to avoid radiation exposure. MRI with T2-weighted turbo-spin-echo sequences exhibits sensitivity and specificity approaching that of CT for the diagnosis of invasive pulmonary aspergillosis. The final part of this review looks at new approaches to drug discovery that have yielded new classes with novel mechanisms of action. There are currently two new classes of antifungal drugs in Phase 2 study for systemic invasive fungal disease and one in Phase 1. These new antifungal drugs show promise in meeting unmet needs with oral and intravenous formulations available and some with decreased potential for drug-drug interactions. Novel mechanisms of action mean these agents are not susceptible to the common resistance mechanisms seen in Candida or Aspergillus. Modification of existing antifungal susceptibility testing techniques may be required to incorporate these new compounds