Mutations in the m-AAA proteases AFG3L2 and SPG7 are causing isolated dominant optic atrophy.

OBJECTIVE: To improve the genetic diagnosis of dominant optic atrophy (DOA), the most frequently inherited optic nerve disease, and infer genotype-phenotype correlations. METHODS: Exonic sequences of 22 genes were screened by new-generation sequencing in patients with DOA who were investigated for ophthalmology, neurology, and brain MRI. RESULTS: We identified 7 and 8 new heterozygous pathogenic variants in SPG7 and AFG3L2. Both genes encode for mitochondrial matricial AAA (m-AAA) proteases, initially involved in recessive hereditary spastic paraplegia type 7 (HSP7) and dominant spinocerebellar ataxia 28 (SCA28), respectively. Notably, variants in AFG3L2 that result in DOA are located in different domains to those reported in SCA28, which likely explains the lack of clinical overlap between these 2 phenotypic manifestations. In comparison, the SPG7 variants identified in DOA are interspersed among those responsible for HSP7 in which optic neuropathy has previously been reported. CONCLUSIONS: Our results position SPG7 and AFG3L2 as candidate genes to be screened in DOA and indicate that regulation of mitochondrial protein homeostasis and maturation by m-AAA proteases are crucial for the maintenance of optic nerve physiology

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Mesure de la température corporelle chez le patient de réanimation (évaluation des mesures par thermomètres électriques rectal, oesophagien, vésical, thermomètre à gallium axillaire et inguinal comparées à la température artérielle pulmonaire par cathétérisme artériel pulmonaire)

MONTPELLIER-BU Médecine UPM (341722108) / SudocPARIS-BIUM (751062103) / SudocMONTPELLIER-BU Médecine (341722104) / SudocSudocFranceF

Decision Fusion Of Spot6 And Multitemporal Sentinel2 Images For Urban Area Detection

Fusion of very high spatial resolution multispectral (VHR) images and lower spatial resolution image time series with more spectral bands can improve land cover classification, combining geometric and semantic advantages of both sources. This study presents a workflow to extract the extent of urban areas using decision-level fusion of individual classifications on Sentinel2 (S2) and SPOT6 satellite images. First, both sources are classified individually in five classes, using state-of-the-art supervised classification approaches and Convolutional Neural Networks. Obtained results are merged in order to extract buildings as accurately as possible. Then, detected buildings are merged again with the S2 classification to extract urban area; a prior to be in an urban area is derived from these building objects and merged with a binary classification derived from the original S2 classification. Both fusions involve a per pixel decision level fusion followed by a contrast sensitive regularization

FUSION TARDIVE D'IMAGES SPOT 6/7 ET DE DONNÉES MULTITEMPORELLES SENTINEL-2 POUR LA DÉTECTION DE LA TACHE URBAINE

International audienceLa fusion d'images multispectrales à très haute résolution spatiale (THR) avec des séries temporelles d'images moins résolues spatialement mais comportant plus de bandes spectrales permet d'améliorer la classification de l'occupation du sol. Elle permet en effet de tirer le meilleur parti des points forts, respectivement, géométriques et sémantiques de ces deux sources. Le travail proposé ici s'intéresse à un processus d'extraction automatique de la tache urbaine fondé sur la fusion tardive de classifications obtenues respectivement à partir d'images satellitaires Sentinel-2 et SPOT 6/7. Ces deux sources sont d'abord analysées indépendamment selon 5 classes, respectivement par Forêt Aléatoire et réseaux de neurones convolutifs. Les résultats sont alors fusionnés afin d'extraire les bâtiments le plus finement possible. Cette étape de fusion inclut une fusion au niveau pixellaire, suivie d'une étape de régularisation spatiale intégrant un terme lié au contraste de l'image. Le résultat obtenu connaît ensuite une seconde fusion afin d'en déduire la tache urbaine en elle-même : une mesure a priori de zone urbaine est calculée à partir des objets bâtiments détectés au préalable, puis fusionnée avec une classification binaire dérivée de la classification originale des données Sentinel-2. Les résultats montrent bien la complémentarité des deux sources de données ainsi que la pertinence de l'adoption d'une stratégie de fusion tardive. Abstract Fusion of very high spatial resolution multispectral (VHR) images with time series of lower spatial resolution images with more spectral bands can improve land cover classification, combining geometric and semantic advantages of both sources, respectively. This study presents a strategy to extract the urban footprint using decision-level fusion of individual classifications on Sentinel-2 and SPOT 6/7 satellite images. First, both sources are classified separately in five classes, using state-of-the-art supervised Random Forest classification and Convolutional Neural Networks. The two results are then merged in order to extract individual buildings with the highest spatial precision conceivable. Secondly, detected buildings are merged again with the Sentinel-2 classification so as to extract the artificialized areas ; the building labels from the regularization step are dilated in order to connect the building objects ; a binary classification is derived from the original Sentinel-2 classification before being reintroduced in a fusion and contrast sensitive regularization process so as to eventually retrieve the urban footprint. Results show well the complementary between both data sources as well as the relevance of the late fusion stategy

Parents’ and healthcare professionals’ perceptions of the use of live video recording in neonatal units: a focus group study

International audienceAbstract Background The emerging use of video in neonatology units raises ethical and practical questions. This study aims to gain a better understanding of the suitability, limitations and constraints concerning the use of live video as a tool in neonatal clinical practice. The perceptions of parents and healthcare professionals in regard to live video were examined. Methods Nine focus groups were conducted in four neonatal units involving 20 healthcare professionals and 19 parents. Data were triangulated using transcripts and field notes and analyzed using inductive and semantic thematic analysis. Results The seven major themes that emerged from the healthcare professionals focus groups were (i) the impact of video recording on healthcare professionals’ behavior; (ii) the impact on parents; (iii) forensic issues;(iv) guarantee of use; (v) benefits for the newborn; (vi) methodology of use; and (vii) technical considerations & feasibility. The five major themes that emerged from parents focus groups were (i) benefits for the newborn and care enhancement; (ii) impact on parents and potential benefits in case of newborn child/parent separation; (iii) informed consent and guarantee of use;(iv) concern about a possible disruptive impact on healthcare professionals; and (v) data protection. Conclusion Both parents and healthcare professionals found video recording useful and acceptable if measures were taken to protect the data and mitigate any negative impacts on healthcare professionals

Impact on disease mortality of clinical, biological, and virological characteristics at hospital admission and overtime in COVID‐19 patients

International audienc