How to Sow and Reap as You Go: a Simple Model of Cyclical Endogenous Growth

In this paper, we present a simple endogenous growth model that allows for the occurrence of innovations that can develop into General Purpose Technologies (GPTs), which are the result of basic R&D. The model incorporates the main features of the Romer (1990) model and the Aghion and Howitt (1992) model by using multi-level Ethier functions on the one hand, and Poisson processes to describe the arrival of innovations produced by performing basic R&D and applied R&D. Through basic R&D the core of a potentially new GPT enters the economic system. This core offers the possibility for further expansion of the potential GPT through applied R&D by adding peripherals to this core. The characteristics of the new potential GPT that is represented by the core are randomly distributed. These characteristics include intrinsic profitability, scope for expansion, as well as R&D opportunities and efficiency of the corresponding applied R&D process. By using some illustrative simulations with the model, we show that the arrival of a successful GPT does indeed bring about a reallocation of R&D activities towards applied R&D, thus postponing the moment of arrival of the next GPT. Meanwhile, applied R&D raises the productivity of the GPT as a whole. But the profitability of finding the next/marginal peripheral falls in the process. This fall in marginal profits diminishes the incentives to engage in further applied R&D and increases the incentives to move into basic R&D activities again. Thus, we obtain a cyclical pattern in output growth that is not only partly driven by the arrival of the new potential GPTs but also by the continuing development of existing GPTs in the absence of the arrival of new ones. In periods that do not give rise to the arrival of new successful GPTs we find instances of alternating expansions of existing GPTs that have the character of a GPT-race.economic development an growth ;

SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues.

There is pressing urgency to understand the pathogenesis of the severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2), which causes the disease COVID-19. SARS-CoV-2 spike (S) protein binds angiotensin-converting enzyme 2 (ACE2), and in concert with host proteases, principally transmembrane serine protease 2 (TMPRSS2), promotes cellular entry. The cell subsets targeted by SARS-CoV-2 in host tissues and the factors that regulate ACE2 expression remain unknown. Here, we leverage human, non-human primate, and mouse single-cell RNA-sequencing (scRNA-seq) datasets across health and disease to uncover putative targets of SARS-CoV-2 among tissue-resident cell subsets. We identify ACE2 and TMPRSS2 co-expressing cells within lung type II pneumocytes, ileal absorptive enterocytes, and nasal goblet secretory cells. Strikingly, we discovered that ACE2 is a human interferon-stimulated gene (ISG) in vitro using airway epithelial cells and extend our findings to in vivo viral infections. Our data suggest that SARS-CoV-2 could exploit species-specific interferon-driven upregulation of ACE2, a tissue-protective mediator during lung injury, to enhance infection

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Influence of OSHV-1 oyster mortality episode on dissolved inorganic fluxes: An ex situ experiment at the individual scale

Ostreid herpesvirus 1 (OsHV-1 μvar) infection has caused significant mortalities in juvenile oysters (Crassostrea gigas). In contrast to the practices of other animal production industries, sick and dead oysters are not separated from live ones and are left to decay in the surrounding environment, with unknown consequences on fluxes of dissolved materials. A laboratory approach was used in this study to test the influence of oyster mortality episode on dissolved inorganic fluxes at the oyster interface, dissociating (i) the effect of viral infection on metabolism of juvenile oysters and (ii) the effect of flesh decomposition on oxygen consumption and nutrient releases at the individual scale. Nine batches of juvenile oysters (Individual Total wet weight 1 g) were infected via injection of OsHV-1 enriched inoculums at different viral loads (108 and 109 OsHV-1 DNA copies per oyster) to explore infection thresholds. Oysters injected with filtered seawater were used as controls (C). Oysters were maintained under standard conditions to avoid stress linked to hypoxia, starvation, or ammonia excess. Before, after the injection and during the mortality episode, i.e. at days 1, 3, 7, 10 and 14, nine oysters per treatment were incubated in individual metabolic chambers to quantify oxygen, ammonium and phosphate fluxes at the seawater-oyster interface. Nine empty chambers served as a reference. Injections of the two viral loads of OsHV-1 induced similar mortality rates (38%), beginning at day 3 and lasting until day 14. The observed mortality kinetics were slower than those reported in previous experimental pathology studies, but comparable to those observed in the field (Thau lagoon, France). This study highlights that oxygen and nutrient fluxes significantly varied during mortality episode. Indeed (i) OsHV-1 infection firstly modifies oyster metabolism, with significant decreases in oxygen consumption and ammonium excretion, and (ii) dead oysters lead to a strong increase of ammonium (6 fold) and phosphate (41 fold) fluxes and a decrease in the N/P ratio due to mineralisation of their flesh. The latter may modify the structure of the planktonic community in the field during mortality episode. This study is a first step of the MORTAFLUX program. The second step was to in situ confirm this abnormal nutrient loading during a mortality episode and show its impact on bacterio-, phyto- and protozoo-plankton

Marine ecological aquaculture: a successful Mediterranean integrated multi-trophic aquaculture case study of a fish, oyster and algae assemblage

International audienceInspired by agroecology, ecological aquaculture proposes an alternative model that uses ecology as a paradigm to develop innovative, more eco-friendly aquaculture with environmental, economic and social benefits. Integrated multi-trophic aquaculture (IMTA) is one application of this principle. Inspired by the natural trophic chain, it associates primary producers with primary or secondary consumers, providing a new source of biomass without requiring supplementary feed by recycling inorganic and organic wastes. Of these systems, land-based IMTAs demonstrate several advantages, especially easier control of nutrient flows, contaminants and/or predators. This study focused on a land-based marine IMTA, combining a recirculating aquaculture system for fish consecutively with a natural marine polyculture of microalgae and oyster cultivation. The objective was to assess the ability of the microalgal polyculture both to bioremediate fish nutrients and to sustain oyster growth. For the first time in a Mediterranean climate, we confirmed the feasibility of developing a microalgae community of interest for oysters maintained by fish effluent. Despite strong variability in microalgae production, this IMTA system resulted in significant oyster growth over the experimental period of one month, with growth results of the same order of magnitude as natural juvenile growth. In the conditions tested, this IMTA with reduced human intervention allowed a gain in recoverable biomass of 3.7 g of oyster produced per kg of fish feed distributed. By transforming waste into additional biomass, IMTAs offer a more promising, ecological avenue for aquaculture, based on a circular economy, which may in turn increase the social acceptability of fish farming

In situ characterisation of pathogen dynamics during a Pacific Oyster Mortality Syndrome episode

International audienceSignificant mortality of Crassostrea gigas juveniles is observed systematically every year worldwide. Pacific Oyster Mortality Syndrome (POMS) is caused by Ostreid Herpesvirus 1 (OsHV-1) infection leading to immune suppression, followed by bacteraemia caused by a consortium of opportunistic bacteria. Using an in-situ approach and pelagic chambers, our aim in this study was to identify pathogen dynamics in oyster flesh and in the water column during the course of a mortality episode in the Mediterranean Thau lagoon (France). OsHV-1 concentrations in oyster flesh increased before the first clinical symptoms of the disease appeared, reached maximum concentrations during the moribund phase and the mortality peak. The structure of the bacterial community associated with oyster flesh changed in favour of bacterial genera previously associated with oyster mortality including Vibrio, Arcobacter, Psychrobium, and Psychrilyobacter. During the oyster mortality episode, releases of OsHV-1 and opportunistic bacteria were observed, in succession, in the water surrounding the oyster lanterns. These releases may favour the spread of disease within oyster farms and potentially impact other marine species, thereby reducing marine biodiversity in shellfish farming area

Changes in planktonic microbial components in interaction with juvenile oysters during a mortality episode in the Thau lagoon (France)

Oysters modify the planktonic microbial community structure by their filtration and NH4 excretion activities. While many studies have been conducted on this subject with adult oysters, none had been carried out in situ with juveniles. Pacific oyster juveniles (Magallana gigas, previously Crassostrea gigas) died massively all over the world since 2008 in relation with OsHV-1 infection. During mortality episodes, sick and dead oysters are not separated from healthy live ones, and left to decay in the surrounding environment, with unknown consequences for the nutrient cycle and planktonic microbial components (PMC). The present study aimed to elucidate for the first time the interactions between oyster juveniles and PMC during a mortality episode. Innovative 425-L pelagic chambers were deployed weekly in situ around oyster lanterns along a stocking-density gradient in the Thau Mediterranean lagoon (France) before, during and after an oyster mortality episode, from April to May 2015. This study reveals (i) significant changes of planktonic microbial community structure during mortality episodes, with a proliferation of picoplankton (<3 μm) and ciliates (Balanion sp., Uronema sp.) within 2 weeks when mortality rates and numbers of moribund juvenile oysters were highest. These changes were probably induced by oyster tissue leaching, decomposition and mineralization, which probably began during the moribund period, as suggested by an increase of PO4 concentration and N:P ratio decrease, (ii) oyster juveniles mainly retained 3–20 μm plankton. In contrast to adults, picophytoplankton and small heterotrophic flagellates (<3 μm) were significantly depleted in the presence of oyster juveniles. Depletion of picoplankton occurred only at the starting of the mortality episode and during the moribund phase. (iii) Oyster juvenile filtration and mortality shifted the planktonic microbial structure toward a heterotrophic microbial system, where ciliates and heterotrophic flagellates acted as a trophic link between picoplankton and oysters. The next stage of our investigation is to examine the effect of a mortality episode on pathogen fluxes in the water column, exploring their relationships with planktonic components and dead oyster flesh

SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues.

There is pressing urgency to understand the pathogenesis of the severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2), which causes the disease COVID-19. SARS-CoV-2 spike (S) protein binds angiotensin-converting enzyme 2 (ACE2), and in concert with host proteases, principally transmembrane serine protease 2 (TMPRSS2), promotes cellular entry. The cell subsets targeted by SARS-CoV-2 in host tissues and the factors that regulate ACE2 expression remain unknown. Here, we leverage human, non-human primate, and mouse single-cell RNA-sequencing (scRNA-seq) datasets across health and disease to uncover putative targets of SARS-CoV-2 among tissue-resident cell subsets. We identify ACE2 and TMPRSS2 co-expressing cells within lung type II pneumocytes, ileal absorptive enterocytes, and nasal goblet secretory cells. Strikingly, we discovered that ACE2 is a human interferon-stimulated gene (ISG) in vitro using airway epithelial cells and extend our findings to in vivo viral infections. Our data suggest that SARS-CoV-2 could exploit species-specific interferon-driven upregulation of ACE2, a tissue-protective mediator during lung injury, to enhance infection

Observer, Analyser et Gérer la variabilité de la reproduction et du recrutement de l’huître creuse en France : Le Réseau Velyger. Rapport annuel 2013

La conchyliculture, et principalement l’élevage de l’huître creuse, Crassostrea gigas, constitue la principale activité aquacole française. Cette activité repose, en grande partie, sur le recrutement naturel de l’espèce qui assure 70% des besoins en jeunes huîtres (naissain) : cette activité de collecte s’appelle le captage. Les deux principaux centres de captage en France sont les bassins d’Arcachon et de Marennes-Oléron. Or, depuis une dizaine d'années, sur le bassin d'Arcachon, le captage devient très variable: à des années de captage nul (par exemple les années 2002, 2005, 2007) ou faible (2009, 2010, 2011) succèdent des années excellentes voire pléthoriques (les années 2003, 2006, 2008, 2012, 2013). A Marennes-Oléron, cette variabilité existe, mais s’avère beaucoup moins marquée. En outre, à la faveur du lent réchauffement des eaux, le captage peut désormais se pratiquer de plus en plus vers le nord. Ainsi, la baie de Bourgneuf, mais aussi la rade de Brest sont devenues, depuis quelques années, des secteurs où un nombre croissant d’ostréiculteurs pratiquent avec succès le captage, mais avec, là aussi, des irrégularités dans le recrutement qu’il convient de comprendre. Enfin, depuis la crise des mortalités de 2008, il se développe aussi sur l’étang de Thau une volonté de pratiquer le captage. Afin de mieux comprendre les facteurs de variations du captage, l’Ifremer a mis en place, à la demande du Comité National de la Conchyliculture, un réseau national de suivi de la reproduction : le Réseau VELYGER. Créé en 2008 sur fonds européens et financé désormais par la Direction des Pêches Maritimes et de l’Aquaculture, ce réseau apporte, chaque année, sur les écosystèmes cités précédemment, une série d’indicateurs biologiques (maturation, fécondité, date de ponte, abondance et survie larvaire, intensité du recrutement, survie du naissain) dont l’analyse croisée avec des indicateurs hydrologiques et climatiques permet progressivement de mieux appréhender les causes de variabilité du recrutement de l’huître creuse en France, modèle biologique et espèce clé de la conchyliculture française. Ce rapport présente donc les résultats 2013 de ce réseau d’observation et fait appel, pour la partie hydro-climatique, à des observations acquises par d’autres réseaux régionaux et nationaux. Il détaille toutes les caractéristiques par secteur du cycle de reproduction de l’huitre creuse : maturation et fécondité des adultes, période de ponte, abondance et survie des larves, intensité du captage et mortalités précoces. Il fournit ensuite une interprétation et une synthèse des résultats 2013 par secteur et à la lueur des résultats des années antérieures. Ainsi, pour l’année 2013, on retiendra les faits majeurs suivants : • L’année 2013 a été très contrastée. Un printemps particulièrement frais et généralement humide (mois de juin inclus) a fait suite à un hiver tardif alors que l’été a été ensoleillé et plutôt chaud. Les concentrations en phytoplancton ont été dans les normes avec toujours l’existence d’un gradient Nord-Sud : elles sont plutôt élevées en rade de Brest, baie de Bourgneuf et bassin de Marennes Oléron et plutôt faible dans le bassin d’Arcachon et l’étang de Thau. En outre, tout au long du printemps et jusqu’au mois de juillet, les températures de l’eau ont été toujours inférieures aux normales (excepté dans l’étang de Thau). • Ces conditions hydro-climatiques ont imprimé un gradient dans la maturation et la fécondité des huitres adultes avec un indice de condition très élevé en rade de Brest, en baie de Bourgneuf, et dans le bassin de Marennes Oléron et plutôt faible dans le bassin d’Arcachon et l’étang de Thau. En outre, le déficit thermique marqué jusqu’en juillet s’est traduit par une ponte très tardive sur l’ensemble des écosystèmes de la côte atlantique : par exemple, elle est survenue au 25 août en baie de Bourgneuf, ce qui constitue une valeur record. Malgré tout, quelques pontes partielles et asynchrones ont été observées sur certains écosystèmes en juillet. • Grâce à des températures très favorables en juillet et favorables en août, la plupart des cohortes larvaires présentes à cette période (rade de Brest, bassin d’Arcachon et étang de Thau) ont eu une survie normale à bonne (e.g. 0.2 à plus de 1 %), ce qui s’est traduit par un captage bon à excellent, avec une forte variabilité dans l’étang de Thau (cf paragraphe ci-dessous). Par contre, pour la baie de Bourgneuf et les pertuis Charentais, l’arrivée trop tardive des larves à la fin août dans une eau fraiche (< 20°C) n’a pas permis une survie favorable (autour de 0.01 %) ce qui s’est traduit par un captage tout juste modéré, faible voir nul selon les secteurs. • En conséquence, l’année 2013, se caractérise par un captage très variable géographiquement : « bon voire excellent » en rade de Brest (de 138 à 245 naissains/coupelle) et dans le bassin d’Arcachon (de 177 à 429 naissains/coupelle), modéré dans le bassin de Marennes-Oléron (de 25 à 52 naissains/coupelle) et faible en baie de Bourgneuf (< 5 naissains/coupelle). Ce rapport montre aussi que l’étang de Thau joue un rôle d’exception. Malgré une ponte d’intensité normale, des abondances de larves élevées et une bonne survie des cohortes, le captage 2013 y est très variable ce qui positionne l’étang de Thau en dehors du modèle de fonctionnement admis pour le cycle de reproduction de l’huître creuse sur la façade atlantique. Il semble que, sur ce site, la métamorphose constitue un verrou biologique qui peut être levé en utilisant des pratiques zootechniques adaptées à ce site particulier. Cette optimisation des pratiques zootechniques fait l’objet d’un projet régional : le projet PRONAMED