High resolution spectral-domain optical coherence tomography at 1.3 micron center wavelength using a broadband superluminescent diode light source

International audienceWe present an ultrahigh resolution spectral-domain optical coherence tomography imaging system using a broadband superluminescent diode light source emitting at a center wavelength of 1.3 mm. The light source consists of two spectrally shifted superluminescent diodes that are coupled together into a single mode fiber. The effective emission power spectrum has a full width at half maximum of 200 nm and the source output power is 10 mW. The imaging system has an axial resolution of 3.9 µm in air (3.0 µm in biological tissue), and a lateral resolution of 6.5 µm. The sensitivity and the maximum line rate are 95 dB and 46 kHz, respectively. Images of an infrared viewing card and a cornea from human eye suffering from glaucoma showing Schlemm's canal are presented to illustrate the performance of the system

Encontro Nacional Acadêmico de Secretariado Executivo - ENASEC: Um Estudo Bibliométrico

It is considered the National Meeting Academic Executive Secretariat - Enasec a very important event to the Executive Secretariat for allowing the discussion of issues of secretarial area, from the academic bias promoted by the Brazilian Association of Research Secretariat (ABPSEC). Therefore, this study, a quantitative approach, has as main objective to analyze the scientific production in a bibliometric way of authors in the annals Enasec, categorizing them by working groups. And the following objectives: identify areas of concentration of scientific production; check the evolution of the number of publications by the working group; raise the number of appearances of suits related to the secretarial area; and raise the recurrence of publications per institution in scientific production, the complete works in Enasec the proceedings. In this context, it has the question: what line of research possibilities Executive Secretariat, based on scientific production published in the annals of Enasec in the four editions of the event? It was concluded that it is not possible to infer about the lines of research due to the small number of publications in the event. Still, it is clear that for the secretariat area is consolidated as a science, productions need to be stimulated.Considera-se o Encontro Nacional Acadêmico de Secretariado Executivo - Enasec um evento bastante relevante ao Secretariado Executivo por permitir a discussão de temas da área secretarial, a partir do viés acadêmico promovido pela Associação Brasileira de Pesquisa em Secretariado (ABPSEC). Por isso, este estudo, de abordagem quantitativa, possui como objetivo geral: analisar bibliometricamente a produção científica dos autores nos anais do Enasec, categorizando-as por grupos de trabalho. E como objetivos específicos: identificar as áreas de concentração das produções científicas; verificar a evolução do número de publicações por grupo de trabalho; levantar o número de ocorrências dos termos relacionados à área secretarial; e levantar a reincidência de publicações por instituição nas produções científicas, dos trabalhos completos, nos anais do Enasec. Nesse contexto, tem como questionamento: quais as possibilidades de linha de pesquisa em secretariado executivo, com base nas produções científicas publicadas nos anais do Enasec nas quatro edições do evento? Concluiu-se que não é possível inferir sobre as linhas de pesquisas devido ao pequeno número de publicações existentes no evento. Ainda, verifica-se que, para que a área de secretariado se consolide como ciência, produções precisam ser estimuladas

Software livre como apoio à tomada de decisão no ensino e uso de tecnologias: estudo de caso para as escolas públicas municipais de Videira/SC

This paper describes the web tool to support the data analysis in the research project about the technological needs in the public schools from Videira city. At first, questionnaires were applied to teachers and students and then, the tool was created using free software allows the multidimensional data visualization, which means, in other words, different dimensions and levels of details which makes it easier to analyze data in the decision making process.Key-words: free software, decision making, technology.Neste artigo apresenta-se a ferramenta web desenvolvida para auxiliar na análise dos dados relacionados a uma pesquisa realizada sobre o uso e necessidade de tecnologias no ensino nas escolas públicas municipais urbanas de Videira-SC. Inicialmente foram aplicados questionários dirigidos aos alunos e aos professores e, posteriormente, foi desenvolvida a ferramenta usando software livre com o objetivo de permitir a visualização dos dados de forma multidimensional, ou seja, várias dimensões e diferentes níveis de detalhamento para facilitar a análise dos dados na tomada de decisão.Palavras-chave: software livre, tomada de decisão, tecnologia

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

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, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 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

Genome-wide association analyses identify new Brugada syndrome risk loci and highlight a new mechanism of sodium channel regulation in disease susceptibility.

Brugada syndrome (BrS) is a cardiac arrhythmia disorder associated with sudden death in young adults. With the exception of SCN5A, encoding the cardiac sodium channel Na1.5, susceptibility genes remain largely unknown. Here we performed a genome-wide association meta-analysis comprising 2,820 unrelated cases with BrS and 10,001 controls, and identified 21 association signals at 12 loci (10 new). Single nucleotide polymorphism (SNP)-heritability estimates indicate a strong polygenic influence. Polygenic risk score analyses based on the 21 susceptibility variants demonstrate varying cumulative contribution of common risk alleles among different patient subgroups, as well as genetic associations with cardiac electrical traits and disorders in the general population. The predominance of cardiac transcription factor loci indicates that transcriptional regulation is a key feature of BrS pathogenesis. Furthermore, functional studies conducted on MAPRE2, encoding the microtubule plus-end binding protein EB2, point to microtubule-related trafficking effects on Na1.5 expression as a new underlying molecular mechanism. Taken together, these findings broaden our understanding of the genetic architecture of BrS and provide new insights into its molecular underpinnings

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Chirurgie du segment antérieur de l'oeil et traitement du glaucome par laser femtoseconde et imagerie de tomographie par cohérence optique

My PhD project is closely related to the ANR project named "NOUGAT" which consists of developing a new tool for glaucoma surgery assisted by femtosecond laser and optical coherence tomography (OCT) [ANR-08-TECS-012]. This project is coordinated by the "Optics -Photonics - Health" group of the Laboratory of Applied Optics (LOA) and our partners are the Hôtel-Dieu hospital, the Charles Fabry Laboratory of the Institut d'Optique Graduate School and the company Amplitude Systèmes. Glaucoma is an ocular disease associated with an increase of the intraocular pressure. Surgical treatments consist in creating filtrating canals in deep sclera in order to lower the pressure; however benefits are often only temporary. Corneal grafting is indicated when reduced corneal transparency (visual acuity) is observed. This is the most common transplant but some limits of the laser procedure exist, especially when the incision has to be made in the depth of a pathological tissue. First, my PhD work consists in the characterization of the three main elements of the ocular anterior segment: the cornea, the sclera and the crystalline lens. The light scattering occurring into the cornea is now well understood and it can be quantified. Studies of the scleral tissue have also shown an optical transparency window around 1650 nm, and some preliminary experiments have been performed on the crystalline lens. Thanks to the optimization of laser sources already developed in the group, especially the optical parametric generator, new series of incisions on human corneas from the French eye bank (Paris), have been performed with wavelengths in the 1500 - 1800 nm spectral range. Analysis by histology and by transmission and scanning electronic microscopy of these new incisions confirm that the use of a longer wavelength in the 1600 - 1700 nm range greatly reduces the light scattering in the tissue compared to the one obtained with commercial systems (at 1000 nm). In addition, a new imaging system based on OCT has been developed in close collaboration with our colleagues from the Institut d'Optique Graduate School. Using a wavelength of 1315 nm, the system has a spatial resolution of 5 μm that is compatible with our medical application even if the acquisition rate stills quite low. Corneal structures have been imaged with three different available systems which makes the comparison of the specifications possible. Eventually, my PhD project leads to an optimization of laboratory surgical systems for the anterior segment of the eye and to the consolidation of knowledge on tissue optics, completing anterior studies conducted by my working group and opening new ways for future applications.Mon projet de thèse est étroitement lié au projet ANR NOUGAT, " Nouvel OUtil pour la chirurgie du Glaucome Assistée par laser femtoseconde et Tomographie par cohérence optique " (ANR-08-TECS-012), coordonné par le groupe " Optique, Photonique, Santé " (OPS) du Laboratoire d'Optique Appliquée (LOA), et dont les partenaires sont : l'hôpital Hôtel-Dieu de Paris, le laboratoire Charles Fabry de l'Institut d'Optique Graduate School, la société Amplitude Systèmes. Le glaucome est une maladie oculaire associée à une pression intraoculaire élevée. Les traitements chirurgicaux classiques visent à créer des canaux filtrants dans la sclère pour baisser la pression, mais les bénéfices ne sont souvent que temporaires. La greffe de cornée est indiquée lors d'opacités du tissu ou pathologies affectant la transparence cornéenne. Elle est largement pratiquée mais certaines limites existent, notamment lorsque la découpe doit se faire en profondeur d'un tissu pathologique. Mes travaux ont d'abord consisté à caractériser les trois principaux éléments constitutifs du segment antérieur de l'oeil : la cornée, la sclère et le cristallin. Suite aux recherches précédentes menées par notre équipe, la diffusion de la cornée est maintenant un phénomène compris et quantifiable. L'étude du tissu scléral a permis de mettre en évidence une fenêtre de relative transparence optique centrée à la longueur d'onde de 1650 nm ; des expériences préliminaires ont été menées sur le cristallin. Grâce à l'optimisation de sources laser existantes au sein de l'équipe, en particulier du générateur paramétrique optique, de nouvelles séries d'incisions ont ensuite été réalisées dans des cornées humaines (obtenues auprès de la Banque Française des Yeux), avec des longueurs d'onde situées entre 1500 et 1800 nm. Les analyses histologiques et par microscopie électronique en transmission et à balayage de ces découpes confirment que l'utilisation d'une longueur d'onde entre 1600 et 1700 nm réduit le phénomène de diffusion dans le tissu par rapport à la longueur d'onde appliquée dans les systèmes commerciaux (1000 nm). Par ailleurs, un dispositif d'imagerie par tomographie par cohérence optique (OCT) a été développé en étroite collaboration avec l'Institut d'Optique Graduate School. Utilisant une longueur d'onde de 1315 nm, ce dispositif a une résolution de l'ordre de 5 μm, ce qui est compatible avec notre application ; cependant, il présente encore une rapidité d'acquisition moyenne. Les structures cornéennes ont été imagées avec trois dispositifs OCT disponibles, ce qui a permis de comparer leurs avantages et leurs inconvénients en vue de la combinaison de ce système d'imagerie à la source laser et d'une éventuelle application clinique. Mes travaux de recherche ont finalement permis d'optimiser le développement de systèmes chirurgicaux pour les tissus du segment antérieur de l'oeil et d'approfondir nos connaissances sur l'optique de ces tissus, ce qui vient compléter les études antérieures réalisées au sein de mon équipe de travail et ouvre la voie à des applications futures

Chirurgie du segment antérieur de l’œil et traitement du glaucome assistés par laser femtoseconde et imagerie de tomographie par cohérence optique

Préparée au Laboratoire d’Optique AppliquéeENSTA ParisTech – École polytechnique – CNRS UMR 7639Palaiseau, FranceMy PhD project is closely related to the ANR project named “NOUGAT” which consists of developing a new tool for glaucoma surgery assisted by femtosecond laser and optical coherence tomography (OCT) [ANR-08-TECS-012]. This project is coordinated by the “Optics –Photonics – Health” group of the Laboratory of Applied Optics (LOA) and our partners are the Hôtel-Dieu hospital, the Charles Fabry Laboratory of the Institut d'Optique Graduate School and the company Amplitude Systèmes. Glaucoma is an ocular disease associated with an increase of the intraocular pressure. Surgical treatments consist in creating filtrating canals in deep sclera in order to lower the pressure; however benefits are often only temporary. Corneal grafting is indicated when reduced corneal transparency (visual acuity) is observed. This is the most common transplant but some limits of the laser procedure exist, especially when the incision has to be made in the depth of a pathological tissue. First, my PhD work consists in the characterization of the three main elements of the ocular anterior segment: the cornea, the sclera and the crystalline lens. The light scattering occurring into the cornea is now well understood and it can be quantified. Studies of the scleral tissue have also shown an optical transparency window around 1650 nm, and some preliminary experiments have been performed on the crystalline lens. Thanks to the optimization of laser sources already developed in the group, especially the optical parametric generator, new series of incisions on human corneas from the French eye bank (Paris), have been performed with wavelengths in the 1500 – 1800 nm spectral range. Analysis by histology and by transmission and scanning electronic microscopy of these new incisions confirm that the use of a longer wavelength in the 1600 – 1700 nm range greatly reduces the light scattering in the tissue compared to the one obtained with commercial systems (at 1000 nm). In addition, a new imaging system based on OCT has been developed in close collaboration with our colleagues from the Institut d'Optique Graduate School. Using a wavelength of 1315 nm, the system has a spatial resolution of 5 µm that is compatible with our medical application even if the acquisition rate stills quite low. Corneal structures have been imaged with three different available systems which makes the comparison of the specifications possible. Eventually, my PhD project leads to an optimization of laboratory surgical systems for the anterior segment of the eye and to the consolidation of knowledge on tissue optics, completing anterior studies conducted by my working group and opening new ways for future applications.Mon projet de thèse est étroitement lié au projet ANR NOUGAT, « Nouvel OUtil pour la chirurgie du Glaucome Assistée par laser femtoseconde et Tomographie par cohérence optique » (ANR-08-TECS-012), coordonné par le groupe « Optique, Photonique, Santé » (OPS) du Laboratoire d'Optique Appliquée (LOA), et dont les partenaires sont : l'hôpital Hôtel-Dieu de Paris, le laboratoire Charles Fabry de l'Institut d'Optique Graduate School, la société Amplitude Systèmes. Le glaucome est une maladie oculaire associée à une pression intraoculaire élevée. Les traitements chirurgicaux classiques visent à créer des canaux filtrants dans la sclère pour baisser la pression, mais les bénéfices ne sont souvent que temporaires. La greffe de cornée est indiquée lors d'opacités du tissu ou pathologies affectant la transparence cornéenne. Elle est largement pratiquée mais certaines limites existent, notamment lorsque la découpe doit se faire en profondeur d'un tissu pathologique. Mes travaux ont d'abord consisté à caractériser les trois principaux éléments constitutifs du segment antérieur de l'œil : la cornée, la sclère et le cristallin. Suite aux recherches précédentes menées par notre équipe, la diffusion de la cornée est maintenant un phénomène compris et quantifiable. L'étude du tissu scléral a permis de mettre en évidence une fenêtre de relative transparence optique centrée à la longueur d'onde de 1650 nm ; des expériences préliminaires ont été menées sur le cristallin. Grâce à l'optimisation de sources laser existantes au sein de l'équipe, en particulier du générateur paramétrique optique, de nouvelles séries d'incisions ont ensuite été réalisées dans des cornées humaines (obtenues auprès de la Banque Française des Yeux), avec des longueurs d'onde situées entre 1500 et 1800 nm. Les analyses histologiques et par microscopie électronique en transmission et à balayage de ces découpes confirment que l'utilisation d'une longueur d'onde entre 1600 et 1700 nm réduit le phénomène de diffusion dans le tissu par rapport à la longueur d'onde appliquée dans les systèmes commerciaux (1000 nm). Par ailleurs, un dispositif d'imagerie par tomographie par cohérence optique (OCT) a été développé en étroite collaboration avec l'Institut d'Optique Graduate School. Utilisant une longueur d'onde de 1315 nm, ce dispositif a une résolution de l'ordre de 5 µm, ce qui est compatible avec notre application ; cependant, il présente encore une rapidité d'acquisition moyenne. Les structures cornéennes ont été imagées avec trois dispositifs OCT disponibles, ce qui a permis de comparer leurs avantages et leurs inconvénients en vue de la combinaison de ce système d'imagerie à la source laser et d'une éventuelle application clinique. Mes travaux de recherche ont finalement permis d'optimiser le développement de systèmes chirurgicaux pour les tissus du segment antérieur de l'œil et d'approfondir nos connaissances sur l'optique de ces tissus, ce qui vient compléter les études antérieures réalisées au sein de mon équipe de travail et ouvre la voie à des applications futures