Increase in soil erosion after agricultural intensification: evidence from a lowland basin in France

International audienceChanges in agricultural practices impact sediment transfer in catchments and rivers. Long term archives of sediment deposits in agricultural plains of northwestern Europe are rarely available, however, for reconstructing and quantifying erosion and sedimentation rates for the second half of the 20th century. In this context, a multi-parameter analysis was conducted on sedimentary deposits accumulated in a pond created in the 11th century and draining a 24 km2 cultivated catchment in western France. This catchment is representative of cultivated and drained lowland environments where agriculture has intensified during the last 60 years.High resolution seismic profiles and surface sediment samples (n = 74) were used to guide the collection of cores (n = 3) representative of the sequence of sediment accumulated in the pond. The cores were analysed to quantify and characterize the evolution of sediment dynamics in the pond.The first land consolidation period (1954-1960) was characterized by a dominance of allochtonous material input to the pond. This input represents an erosion of 1900 to 2300 t.km−2.yr−1 originating from the catchment. Then, between 1970-1990, the terrigenous input decreased progressively and tended to stabilize. Eutrophication and associated primary production increased in the pond. These processes generated the majority of material accumulated in the pond during this period. Further land consolidation programs conducted in 1992 generated a new increase in soil erosion and sediment input to the reservoir. For the last 10 years, terrigenous input to the pond corresponds to a catchment-wide erosion rate between 90 and 102 t.km−2.yr−1. While a strong decrease is observed, it still represents a 60-fold increase of the sediment flux compared to the pre-intensification period. These large temporal variations of sedimentation rates over a few decades underline the dynamics of sediment transfer and raise questions about the sustainability of soil resources in lowland temperate environments

Patient-safety incidents during COVID-19 health crisis in France: An exploratory sequential multi-method study in primary care.

BACKGROUND: The COVID-19 pandemic has resulted in the rapid reorganisation of health and social care services. Patients are already at significant risk of healthcare-associated harm and the wholesale disruption to service delivery during the pandemic stood to heighten those risks. OBJECTIVES: We explored the type and nature of patient safety incidents in French primary care settings during the COVID-19 first wave to make tentative recommendations for improvement. METHODS: A national patient safety incident reporting survey was distributed to General Practitioners (GPs) in France on 28 April 2020. Reports were coded using a classification system aligned to the WHO International Classification for Patient Safety (incident types, contributing factors, incident outcomes and severity of harm). Analysis involved data coding, processing, iterative generation of data summaries using descriptive statistical analysis. Clinicaltrials.gov: NCT04346121. RESULTS: Of 132 incidents, 58 (44%) related to delayed diagnosis, assessments and referrals. Cancellations of appointments, hospitalisations or procedures was reported in 22 (17%) of these incidents. Home confinement-related incidents accounted for 13 (10%) reports and inappropriate medication stopping for five (4%). Patients delayed attending or did not consult their general practitioner or other healthcare providers due to their fear of contracting COVID-19 infection at an in-person visit in 26 (10%) incidents or fear of burdening their GPs in eight (3%) incidents. CONCLUSION: Constraints from the first wave of the COVID-19 pandemic have contributed to patient safety incidents during non-COVID-19 care. Lessons from these incidents pinpoint where primary care services in France can focus resources to design safer systems for patients

Autocrine fibroblast growth factor-2 signaling contributes to altered endothelial phenotype in pulmonary hypertension.

Pulmonary vascular remodeling is key to the pathogenesis of idiopathic pulmonary arterial hypertension (IPAH). We recently reported that fibroblast growth factor (FGF)2 is markedly overproduced by pulmonary endothelial cells (P-ECs) in IPAH and contributes significantly to smooth muscle hyperplasia and disease progression. Excessive FGF2 expression in malignancy exerts pathologic effects on tumor cells by paracrine and autocrine mechanisms.We hypothesized that FGF2 overproduction contributes in an autocrine manner to the abnormal phenotype of P-ECs, characteristic of IPAH. In distal pulmonary arteries (PAs) of patients with IPAH, we found increased numbers of proliferating ECs and decreased numbers of apoptotic ECs, accompanied with stronger immunoreactivity for the antiapoptotic molecules, B-cell lymphoma (BCL)2, and BCL extra long (BCL-xL) compared with PAs from control patients. These in situ observations were replicated in vitro, with cultured P-ECs from patients IPAH exhibiting increased proliferation and diminished sensitivity to apoptotic induction with marked increases in the antiapoptotic factors BCL2 and BCL-xL and levels of phosphorylated extracellular signal-regulated (ERK)1/2 compared with control P-ECs. IPAH P-ECs also exhibited increased FGF2 expression and an accentuated proliferative and survival response to conditioned P-EC media or exogenous FGF2 treatment. Decreasing FGF2 signaling by RNA interference normalized sensitivity to apoptosis and proliferative potential in the IPAH P-ECs. Our findings suggest that excessive autocrine release of endothelial-derived FGF2 in IPAH contributes to the acquisition and maintenance of an abnormal EC phenotype, enhancing proliferation through constitutive activation of ERK1/2 and decreasing apoptosis by increasing BCL2 and BCL-xL.Comparative StudyJournal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Glacial Fluctuations and Exploitation of Copper Resources in High Mountain During the Late Neolithic and Bronze Age in the French Alps (2500-1500 BC)

International audienceDuring the late Neolithic – at the limit of the 4th and 3rd millennia BC – copper exploitation is growing in the southern of France (Fig. 1). On the southern edge of Massif Central southern edge of and the Pyrenees, the mining district and metallurgical processes develop extractive metallurgy of low-productivity metal. The diffusion of production is then transferred to local networks. The development of this metallurgy first contribution is mainly to areas of small and medium mountains. This model, which could be called "Neolithic system" is completed in the second half of the 3rd millennium, between the 25th and 24th century BC (Fig. 2), with the abandonment of mining operations, a modification of the terms of metal consumption and supply networks

Mitomycin-Induced Pulmonary Veno-Occlusive Disease: Evidence From Human Disease and Animal Models.

BACKGROUND: Pulmonary veno-occlusive disease (PVOD) is an uncommon form of pulmonary hypertension characterized by the obstruction of small pulmonary veins and a dismal prognosis. PVOD may be sporadic or heritable because of biallelic mutations of the EIF2AK4 gene coding for GCN2. Isolated case reports suggest that chemotherapy may be a risk factor for PVOD. METHODS AND RESULTS: We reported on the clinical, functional, and hemodynamic characteristics and outcomes of 7 cases of PVOD induced by mitomycin-C (MMC) therapy from the French Pulmonary Hypertension Registry. All patients displayed squamous anal cancer and were treated with MMC alone or MMC plus 5-fluoruracil. The estimated annual incidence of PVOD in the French population that have anal cancer is 3.9 of 1000 patients, which is much higher than the incidence of PVOD in the general population (0.5/million per year). In rats, intraperitoneal administration of MMC induced PVOD, as demonstrated by pulmonary hypertension at right-heart catheterization at days 21 to 35 and major remodeling of small pulmonary veins associated with foci of intense microvascular endothelial-cell proliferation of the capillary bed. In rats, MMC administration was associated with dose-dependent depletion of pulmonary GCN2 content and decreased smad1/5/8 signaling. Amifostine prevented the development of MMC-induced PVOD in rats. CONCLUSIONS: MMC therapy is a potent inducer of PVOD in humans and rats. Amifostine prevents MMC-induced PVOD in rats and should be tested as a preventive therapy for MMC-induced PVOD in humans. MMC-induced PVOD in rats represents a unique model to test novel therapies in this devastating orphan disease

Mitomycin-Induced Pulmonary Veno-Occlusive Disease

BACKGROUND: Pulmonary veno-occlusive disease (PVOD) is an uncommon form of pulmonary hypertension characterized by the obstruction of small pulmonary veins and a dismal prognosis. PVOD may be sporadic or heritable because of biallelic mutations of the EIF2AK4 gene coding for GCN2. Isolated case reports suggest that chemotherapy may be a risk factor for PVOD. METHODS AND RESULTS: We reported on the clinical, functional, and hemodynamic characteristics and outcomes of 7 cases of PVOD induced by mitomycin-C (MMC) therapy from the French Pulmonary Hypertension Registry. All patients displayed squamous anal cancer and were treated with MMC alone or MMC plus 5-fluoruracil. The estimated annual incidence of PVOD in the French population that have anal cancer is 3.9 of 1000 patients, which is much higher than the incidence of PVOD in the general population (0.5/million per year). In rats, intraperitoneal administration of MMC induced PVOD, as demonstrated by pulmonary hypertension at right-heart catheterization at days 21 to 35 and major remodeling of small pulmonary veins associated with foci of intense microvascular endothelial-cell proliferation of the capillary bed. In rats, MMC administration was associated with dose-dependent depletion of pulmonary GCN2 content and decreased smad1/5/8 signaling. Amifostine prevented the development of MMC-induced PVOD in rats. CONCLUSIONS: MMC therapy is a potent inducer of PVOD in humans and rats. Amifostine prevents MMC-induced PVOD in rats and should be tested as a preventive therapy for MMC-induced PVOD in humans. MMC-induced PVOD in rats represents a unique model to test novel therapies in this devastating orphan disease

Potassium Channel Subfamily K Member 3 (KCNK3) Contributes to the Development of Pulmonary Arterial Hypertension

International audienceBackground Mutations in the KCNK3 gene have been identified in some patients suffering from heritable pulmonary arterial hypertension (PAH). KCNK3 encodes an outward rectifier K+ channel, and each identified mutation leads to a loss of function. However, the pathophysiological role of potassium channel subfamily K member 3 (KCNK3) in PAH is unclear. We hypothesized that loss of function of KCNK3 is a hallmark of idiopathic and heritable PAH and contributes to dysfunction of pulmonary artery smooth muscle cells and pulmonary artery endothelial cells, leading to pulmonary artery remodeling: consequently, restoring KCNK3 function could alleviate experimental pulmonary hypertension (PH). Methods and Results We demonstrated that KCNK3 expression and function were reduced in human PAH and in monocrotaline-induced PH in rats. Using a patch-clamp technique in freshly isolated (not cultured) pulmonary artery smooth muscle cells and pulmonary artery endothelial cells, we found that KCNK3 current decreased progressively during the development of monocrotaline-induced PH and correlated with plasma-membrane depolarization. We demonstrated that KCNK3 modulated pulmonary arterial tone. Long-term inhibition of KCNK3 in rats induced distal neomuscularization and early hemodynamic signs of PH, which were related to exaggerated proliferation of pulmonary artery endothelial cells, pulmonary artery smooth muscle cell, adventitial fibroblasts, and pulmonary and systemic inflammation. Lastly, in vivo pharmacological activation of KCNK3 significantly reversed monocrotaline-induced PH in rats. Conclusions In PAH and experimental PH, KCNK3 expression and activity are strongly reduced in pulmonary artery smooth muscle cells and endothelial cells. KCNK3 inhibition promoted increased proliferation, vasoconstriction, and inflammation. In vivo pharmacological activation of KCNK3 alleviated monocrotaline-induced PH, thus demonstrating that loss of KCNK3 is a key event in PAH pathogenesis and thus could be therapeutically targeted

PACMAN trial protocol, Perioperative Administration of Corticotherapy on Morbidity and mortality After Non-cardiac major surgery: a randomised, multicentre, double-blind, superiority study

International audienceIntroduction Postoperative complications are major healthcare problems and are associated with a reduced short-term and long-term survival after surgery. An excessive postoperative inflammatory response participates to the development of postoperative infection and mortality. The aim of the Perioperative Administration of Corticotherapy on Morbidity and mortality After Non-cardiac surgery (PACMAN) study is to assess the effectiveness of perioperative administration of corticosteroid to reduce postoperative morbidity and mortality in patients undergoing major non-cardiac surgery.Methods and analysis The PACMAN is a multicentre, randomised, controlled, double-blind, superiority, two-arm trial of 1222 high-risk patients aged 50 years or older undergoing major non-cardiac surgery at 32 acute care hospital in France. Patients are randomly assigned to dexamethasone (0.2 mg/kg at the end of the surgical procedure and at day +1, n=611) or to placebo (n=611). The primary outcome is a composite of predefined 14-day major pulmonary complications and mortality. Secondary outcomes are surgical complications, infections, organ failures, critical care-free days, length of hospital stay and all-cause mortality at 28 days.Ethics and dissemination The PACMAN trial protocol has been approved by the ethics committee of Sud Mediterranée V, and will be carried out according to the Good Clinical Practice guidelines and the principles of the Declaration of Helsinki. The PACMAN trial is a randomised controlled trial powered to investigate whether perioperative administration of corticosteroids in patients undergoing non-cardiac major surgery reduces postoperative complications. The results of this study will be disseminated through presentation at scientific conferences and publication in peer-reviewed journals