The EMSO-Azores deep sea observatory: 8 years of operation

The EMSO-Azores deep sea observatory is a component of the EMSO ERIC. It focuses on two main questions: What are the feedbacks between volcanism, deformation, seismicity, and hydrothermalism at a slow spreading mid-ocean ridge and how does the hydrothermal ecosystem couple with these sub-seabed processes? The infrastructure comprises 2 sea monitoring nodes, autonomous instruments and a set of site studies experiments. It has been deployed in 2010 in the Lucky Strike vent field and acquires multidisciplinary data since then.Peer Reviewe

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Movement-Based Control for Upper-Limb Prosthetics: Is the Regression Technique the Key to a Robust and Accurate Control?

Due to the limitations of myoelectric control (such as dependence on muscular fatigue and on electrodes shift, difficulty in decoding complex patterns or in dealing with simultaneous movements), there is a renewal of interest in the movement-based control approaches for prosthetics. The latter use residual limb movements rather than muscular activity as command inputs, in order to develop more natural and intuitive control techniques. Among those, several research works rely on the interjoint coordinations that naturally exist in human upper limb movements. These relationships are modeled to control the distal joints (e.g., elbow) based on the motions of proximal ones (e.g., shoulder). The regression techniques, used to model the coordinations, are various [Artificial Neural Networks, Principal Components Analysis (PCA), etc.] and yet, analysis of their performance and impact on the prosthesis control is missing in the literature. Is there one technique really more efficient than the others to model interjoint coordinations? To answer this question, we conducted an experimental campaign to compare the performance of three common regression techniques in the control of the elbow joint on a transhumeral prosthesis. Ten non-disabled subjects performed a reaching task, while wearing an elbow prosthesis which was driven by several interjoint coordination models obtained through different regression techniques. The models of the shoulder-elbow kinematic relationship were built from the recordings of fifteen different non-disabled subjects that performed a similar reaching task with their healthy arm. Among Radial Basis Function Networks (RBFN), Locally Weighted Regression (LWR), and PCA, RBFN was found to be the most robust, based on the analysis of several criteria including the quality of generated movements but also the compensatory strategies exhibited by users. Yet, RBFN does not significantly outperform LWR and PCA. The regression technique seems not to be the most significant factor for improvement of interjoint coordinations-based control. By characterizing the impact of the modeling techniques through closed-loop experiments with human users instead of purely offline simulations, this work could also help in improving movement-based control approaches and in bringing them closer to a real use by patients

The EGIM, EMSO generic instrument module, step towards standardization

Peer ReviewedPostprint (published version

A highly potent antibody effective against SARS-CoV-2 variants of concern.

Control of the ongoing SARS-CoV-2 pandemic is endangered by the emergence of viral variants with increased transmission efficiency, resistance to marketed therapeutic antibodies, and reduced sensitivity to vaccine-induced immunity. Here, we screen B cells from COVID-19 donors and identify P5C3, a highly potent and broadly neutralizing monoclonal antibody with picomolar neutralizing activity against all SARS-CoV-2 variants of concern (VOCs) identified to date. Structural characterization of P5C3 Fab in complex with the spike demonstrates a neutralizing activity defined by a large buried surface area, highly overlapping with the receptor-binding domain (RBD) surface necessary for ACE2 interaction. We further demonstrate that P5C3 shows complete prophylactic protection in the SARS-CoV-2-infected hamster challenge model. These results indicate that P5C3 opens exciting perspectives either as a prophylactic agent in immunocompromised individuals with poor response to vaccination or as combination therapy in SARS-CoV-2-infected individuals

The EMSO Generic Instrument Module (EGIM): Standardized and interoperable instrumentation for ocean observation

The oceans are a fundamental source for climate balance, sustainability of resources and life on Earth, therefore society has a strong and pressing interest in maintaining and, where possible, restoring the health of the marine ecosystems. Effective, integrated ocean observation is key to suggesting actions to reduce anthropogenic impact from coastal to deep-sea environments and address the main challenges of the 21st century, which are summarized in the UN Sustainable Development Goals and Blue Growth strategies. The European Multidisciplinary Seafloor and water column Observatory (EMSO), is a European Research Infrastructure Consortium (ERIC), with the aim of providing long-term observations via fixed-point ocean observatories in key environmental locations across European seas from the Arctic to the Black Sea. These may be supported by ship-based observations and autonomous systems such as gliders. In this paper, we present the EMSO Generic Instrument Module (EGIM), a deployment ready multi-sensor instrumentation module, designed to measure physical, biogeochemical, biological and ecosystem variables consistently, in a range of marine environments, over long periods of time. Here, we describe the system, features, configuration, operation and data management. We demonstrate, through a series of coastal and oceanic pilot experiments that the EGIM is a valuable standard ocean observation module, which can significantly improve the capacity of existing ocean observatories and provides the basis for new observatories. The diverse examples of use included the monitoring of fish activity response upon oceanographic variability, hydrothermal vent fluids and particle dispersion, passive acoustic monitoring of marine mammals and time series of environmental variation in the water column. With the EGIM available to all the EMSO Regional Facilities, EMSO will be reaching a milestone in standardization and interoperability, marking a key capability advancement in addressing issues of sustainability in resource and habitat management of the oceans

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

Abstract: Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and developm nt investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Contrôle de prothèses de bras à partir des mouvements de compensation de l'utilisateur

In recent years, the development of advanced mechatronics for upper-limb prostheses has led to technological improvements such as a better fixation system to the body with osseointegration or a larger number of degrees of freedom. However, providing these devices with a natural and efficient control is still a major challenge. Current approaches, such as myoelectric control, all show limitations, that can lead prosthetic users to abandon the active dimension of the device, use it as a rigid tool and perform the desired task with body compensations. To avoid such a behavior, we propose in this PhD thesis to employ body compensatory motions as an error signal to control the prosthetic device. With this concept, the human subject is in charge of the end-effector task, while the prosthesis is in charge of its user’s posture. This proposition is implemented and tested to control prosthetic wrist and elbow joints, individually and then simultaneously. The presented experiments first confirm that using body compensations as controller input does not enhance them. They then show the easy learning of the control scheme by naive subjects, its task-versatility and its scalability. A theoretical study completes this work and analyzes in details the human-robot coupling created. The foundations thus laid open exciting perspectives for an intuitive prosthesis control.Les récents progrès de la mécatronique pour les prothèses de bras ont permis divers avancées, comme un plus grand nombre de degrés de liberté contrôlables ou un meilleur système de fixation de la prothèse au corps de la personne via l’ostéointégration. Assurer un contrôle naturel et efficace de ces dispositifs de pointe reste néanmoins un défi majeur. Les approches actuelles présentent toutes des limites qui conduisent souvent les porteurs de prothèse à abandonner la dimension active de l’appareil. Ils vont l’utiliser comme un outil rigide et réaliser la tâche avec des mouvements compensatoires. Pour éviter cela, nous proposons d’utiliser ces mouvements comme un signal d’erreur pour contrôler la prothèse. L’humain est alors responsable de la réalisation de la tâche pendant que la prothèse est responsable de la posture de son porteur. Cette proposition est implémentée pour contrôler un poignet et un coude, individuellement puis simultanément. Les expériences confirment que l’utilisation des mouvements compensatoires en entrée du contrôleur prothétique ne les accroît pas. Elles montrent aussi la facilité de la prise en main, la polyvalence et la scalabilité du mode de contrôle proposé. Une étude théorique complète ce travail et analyse en détails le couplage homme-robot ainsi créé. Les résultats obtenus ouvrent d’intéressantes perspectives pour un contrôle intuitif de prothèse