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Food security is a key facet of a sustainable society, while some threats, such as climate change and food riots may unsettle any society. Some aspects of food security such as food production and distribution are inherently spatial, thus requiring spatialized methods to study it. In this study, we introduce Discrete Ecosystem Evolution Rules (DEER), which is a spatial generalization of the EDEN framework developed in environmental sciences. Based on extensive expert knowledge and literature, we developed both spatially implicit and explicit models to assess the impacts of climate change on food security dynamics in a complex West-African social-ecological system (Dano, Burkina Faso). Comparing these two models allowed highlighting the role of spatial structure on food security degradation and recovery over the long term. Results showed that the impacts of climate change on food security were mediated by water availability and soil degradation. The spatial model provided a finer understanding of food security dynamics by highlighting unexpected sequences of events. These insights highlight the relevance of a spatial modeling framework to get a proper understanding of food security and, more generally, of social-ecological dynamics.

Purpose A persistant shortage of available organs for transplantation has driven French medical authorities to focus on organ retrieval from patients who die following the withdrawal of life-sustaining therapy. This study was designed to assess the theoretical eligibility of patients who have died in French intensive care units (ICUs) after a decision to withhold or withdraw life-sustaining therapy to organ donation. Methods This was an observational multi-center study in which data were collected on all consecutive patients admitted to any of the 43 participating ICUs during the study period who qualified for a withholding/withdrawal procedure according to French law. The theoretical organ donor eligibility of the patients once deceased was determined a posteriori according to current medical criteria for graft selection, as well as according to the withholding/withdrawal measures implemented and their impact on the time of death. Results A total of 5,589 patients were admitted to the ICU during the study period, of whom 777 (14 %) underwent withholding/withdrawal measures. Of the 557 patients who died following a foreseeable circulatory arrest, 278 (50 %) presented a contraindication ruling out organ retrieval. Of the 279 patients who would have been eligible as organ donors regardless of measures implemented, cardiopulmonary support was withdrawn in only 154 of these patients, 70 of whom died within 120 min of the withdrawal of life-sustaining treatment. Brain-injured patients accounted for 29 % of all patients who qualified for the withholding/withdrawal of treatment, and 57 % of those died within 120 min of the withdrawal/withholding of treatment. Conclusion A significant number of patients who died during the study period in French ICUs under withholding/withdrawal conditions would have been eligible for organ donation. Brain-injured patients were more likely to die in circumstances which would have been compatible with such practice.

Variability exists between ICUs in the limitations of therapy. Moreover practices may evolve over time. This single-center observational study aimed to compare withholding or withdrawing practices between 2012 and 2016. For each period and patient concerned by limitations, withholding “do-not start”, withholding “do-not-increase” and withdrawal measures were recorded. At a four-year interval, the rate of patients undergoing withholding or withdrawal rose from 10 to 23% and 4 to 7%, respectively. The proportion of patients dying in the ICU with previous limitations increased (53 to 89%), as did patients discharged alive despite withholding instructions (12 to 36%). The overall mortality (28%) was stable over time as the rate of failed resuscitation attempt declined (47 to 11%). In 2016 vs 2012, limitations started earlier following admission: 1 vs 7 days for withholding” do-not-start”, 4 vs 8 for withholding “do-not-increase”, 4 vs 7 for withdrawal. Notwithstanding the outcome and limitations applied, the median length of ICU stay of patients involved dropped from 13 days in 2012 to 8 days in 2016. A timely inclination to forego hopeless treatments resulted in a lower rate of failed resuscitations before death without change in global mortality. •Treatment limitations are increasingly common and occurred earlier during ICU stay.•Patient's wishes regarding end-of-life care should be better addressed by caregivers.•Advance care planning reduces both ICU stay and the rate of failed resuscitations.

PurposeTo assess the benefit-to-risk balance of bronchoalveolar lavage (BAL) in intensive care unit (ICU) patients.MethodsIn 16 ICUs, we prospectively collected adverse events during or within 24 h after BAL and assessed the BAL input for decision making in consecutive adult patients. The occurrence of a clinical adverse event at least of grade 3, i.e., sufficiently severe to need therapeutic action(s), including modification(s) in respiratory support, defined poor BAL tolerance. The BAL input for decision making was declared satisfactory if it allowed to interrupt or initiate one or several treatments.ResultsWe included 483 BAL in 483 patients [age 63 years (interquartile range (IQR) 53–72); female gender: 162 (33.5%); simplified acute physiology score II: 48 (IQR 37-61); immunosuppression 244 (50.5%)]. BAL was begun in non-intubated patients in 105 (21.7%) cases. Sixty-seven (13.9%) patients reached the grade 3 of adverse event or higher. Logistic regression showed that a BAL performed by a non-experienced physician (non-pulmonologist, or intensivist with less than 10 years in the specialty or less than 50 BAL performed) was the main predictor of poor BAL tolerance in non-intubated patients [OR: 3.57 (95% confidence interval 1.04–12.35); P = 0.04]. A satisfactory BAL input for decision making was observed in 227 (47.0%) cases and was not predictable using logistic regression.ConclusionsAdverse events related to BAL in ICU patients are not infrequent nor necessarily benign. Our findings call for an extreme caution, when envisaging a BAL in ICU patients and for a mandatory accompaniment of the less experienced physicians.

PurposeCardiac arrest may occur unexpectedly in intensive care units (ICU). We hypothesize that certain patient characteristics and treatments are associated with survival and long-term functional outcome following in-ICU cardiac arrest.MethodsOver a 12-month period, cardiac arrests with resuscitation attempts were prospectively investigated in 45 French ICUs. Survivors were followed for 6 months.ResultsIn total, 677 (2.16%) of 31,399 admitted patients had at least one in-ICU cardiac arrest with resuscitation attempt, 42% of which occurred on the day of admission. In 79% cases, one or more condition(s) likely to promote the occurrence of cardiac arrest was/were identified, including hypoxia (179 patients), metabolic disorders (122), hypovolemia (94), and adverse events linked to the life-sustaining devices in place (98). Return of spontaneous circulation was achieved in 478 patients, of whom 163 were discharged alive from ICU and 146 from hospital. Six-month survival with no or moderate functional sequel (118 of 125 patients alive) correlated with a number of organ failures ≤ 2 when cardiac arrest occurred (OR 4.17 [1.92–9.09]), resuscitation time ≤ 5 min (3.32 [2.01–5.47]), shockable rhythm cardiac arrests (2.13 [1.26–3.45]) or related to the life-sustaining devices in place (2.11 [1.22–3.65]), absence of preexisting disability (1.98 [1.09–3.60]) or disease deemed fatal within 5 years (1.70 [1.05–2.77]), and sedation (1.71 [1.06–2.75]).ConclusionOnly one in six patients with in-ICU cardiac arrest and resuscitation attempt was alive at 6 months with good functional status. Certain characteristics specific to cardiac arrests, resuscitation maneuvers, and the pathological context in which they happen may help clarify prognosis and inform relatives.

Glioblastoma is one of the most highly aggressive types of brain tumor in adults. With limited treatment options, current therapies remain insufficient due to its invasiveness and immune evasion, highlighting the urgent need for new treatments. Bifunctional molecules targeting multiple aspects of the disease could be promising to overcome drug resistance and tumor heterogeneity. Metformin has demonstrated protective effects against brain tumors but requires high doses for efficacy, making it of great interest for molecular optimization. In this context, we synthesized a series of nine metformin–phenolic molecules, combining the metformin guanidine framework with phenolic acids, which have well-established properties in inhibiting cancer cell migration and adhesion. Their impact on cytotoxicity, reactive oxygen species inhibition, and signaling pathways was investigated for glioma cell lines and stem cells. Two of these hybrids, 5a and 5h, particularly enhanced cytotoxicity in glioblastoma cells, selectively targeting cancer cells while sparing healthy ones. Their mechanism of action differed significantly from metformin. Unlike metformin, which mainly triggers metabolic stress, the hybrids broadly inhibit RTK–MAPK–PI3K signaling, leading to cell cycle arrest and apoptosis. The results suggest that these compounds could offer a more effective and synergistic approach for glioblastoma treatment.

Glioblastoma is one of the most highly aggressive types of brain tumor in adults. With limited treatment options, current therapies remain insufficient due to its invasiveness and immune evasion, highlighting the urgent need for new treatments. Bifunctional molecules targeting multiple aspects of the disease could be promising to overcome drug resistance and tumor heterogeneity. Metformin has demonstrated protective effects against brain tumors but requires high doses for efficacy, making it of great interest for molecular optimization. In this context, we synthesized a series of nine metformin–phenolic molecules, combining the metformin guanidine framework with phenolic acids, which have well-established properties in inhibiting cancer cell migration and adhesion. Their impact on cytotoxicity, reactive oxygen species inhibition, and signaling pathways was investigated for glioma cell lines and stem cells. Two of these hybrids, 5a and 5h, particularly enhanced cytotoxicity in glioblastoma cells, selectively targeting cancer cells while sparing healthy ones. Their mechanism of action differed significantly from metformin. Unlike metformin, which mainly triggers metabolic stress, the hybrids broadly inhibit RTK–MAPK–PI3K signaling, leading to cell cycle arrest and apoptosis. The results suggest that these compounds could offer a more effective and synergistic approach for glioblastoma treatment.

On November 11, 2019, a Mw 4.9 earthquake hit the region close to Montelimar (lower Rhône Valley, France), on the eastern margin of the Massif Central close to the external part of the Alps. Occuring in a moderate seismicity area, this earthquake is remarkable for its very shallow focal depth (between 1 and 3 km), its magnitude, and the moderate to large damages it produced in several villages. InSAR interferograms indicated a shallow rupture about 4 km long reaching the surface and the reactivation of the ancient NE-SW La Rouviere normal fault in reverse faulting in agreement with the present-day E-W compressional tectonics. The peculiarity of this earthquake together with a poor coverage of the epicentral region by permanent seismological and geodetic stations triggered the mobilisation of the French post-seismic unit and the broad French scientific community from various institutions, with the deployment of geophysical instruments (seismological and geodesic stations), geological field surveys, and field evaluation of the intensity of the earthquake. Within 7 days after the mainshock, 47 seismological stations were deployed in the epicentral area to improve the Le Teil aftershocks locations relative to the French permanent seismological network (RESIF), monitor the temporal and spatial evolution of microearthquakes close to the fault plane and temporal evolution of the seismic response of 3 damaged historical buildings, and to study suspected site effects and their influence in the distribution of seismic damage. This seismological dataset, completed by data owned by different institutions, was integrated in a homogeneous archive and distributed through FDSN web services by the RESIF data center. This dataset, together with observations of surface rupture evidences, geologic, geodetic and satellite data, will help to unravel the causes and rupture mechanism of this earthquake, and contribute to account in seismic hazard assessment for earthquakes along the major regional Cévenne fault system in a context of present-day compressional tectonics.

Melanoma is a highly metastatic and deadly form of cancer. Invasive melanoma cells overexpress integrin αvβ3, which is a well-known target for Arg-Gly-Asp-based (RGD) peptides. We developed a sophisticated method to synthetize milligram amounts of a targeted vector that allows the RGD-mediated targeting, internalization, and release of a mitochondria-disruptive peptide derived from the pro-apoptotic Bax protein. We found that 2.5 μM Bax[109-127] was sufficient to destabilize the mitochondria in ten different tumor cell lines, even in the presence of the anti-apoptotic Bcl2 protein, which is often involved in tumor resistance. This pore-forming peptide displayed antitumor activity when it was covalently linked by a disulfide bridge to the tetrameric RAFT-c[RGD]4-platform and after intravenous injection in a human melanoma tumor model established in humanized immuno-competent mice. In addition to its direct toxic effect, treatment with this combination induced the release of the immuno-stimulating factor monocyte chimoattractant protein 1 (MCP1) in the blood and a decrease in the level of the pro-angiogenic factor FGF2. Our novel multifunctional, apoptosis-inducing agent could be further customized and assayed for potential use in tumor-targeted therapy. We identified the shortest synthetic peptide derived from the fifth helix of Bax, a pro-apoptotic protein, capable of inducing mitochondrial depolarization. Using an original chemical procedure, we generated a c-[RGD]4-targeted toxic peptide capable of inducing tumor destruction after intravenous administration in a humanized-immunocompetent mice model of melanoma.

On November 11, 2019, a M\\(_{\\mathrm{w}}\\) 4.9 earthquake hit the region close to Montelimar (lower Rhône Valley, France), on the eastern margin of the Massif Central close to the external part of the Alps. Occuring in a moderate seismicity area, this earthquake is remarkable for its very shallow focal depth (between 1 and 3 km), its magnitude, and the moderate to large damages it produced in several villages. InSAR interferograms indicated a shallow rupture about 4 km long reaching the surface and the reactivation of the ancient NE–SW La Rouvière normal fault in reverse faulting in agreement with the present-day E–W compressional tectonics. The peculiarity of this earthquake together with a poor coverage of the epicentral region by permanent seismological and geodetic stations triggered the mobilisation of the French post-seismic unit and the broad French scientific community from various institutions, with the deployment of geophysical instruments (seismological and geodesic stations), geological field surveys, and field evaluation of the intensity of the earthquake. Within 7 days after the mainshock, 47 seismological stations were deployed in the epicentral area to improve the Le Teil aftershocks locations relative to the French permanent seismological network (RESIF), monitor the temporal and spatial evolution of microearthquakes close to the fault plane and temporal evolution of the seismic response of 3 damaged historical buildings, and to study suspected site effects and their influence in the distribution of seismic damage. This seismological dataset, completed by data owned by different institutions, was integrated in a homogeneous archive and distributed through FDSN web services by the RESIF data center. This dataset, together with observations of surface rupture evidences, geologic, geodetic and satellite data, will help to unravel the causes and rupture mechanism of this earthquake, and contribute to account in seismic hazard assessment for earthquakes along the major regional Cévenne fault system in a context of present-day compressional tectonics.