Université Bordeaux-I

Objective: This study is a proof of concept that aims to measure the impacts of a human/cobot collaboration on the human and his task during a simulated chemistry assembly. Background: The 5th industrial revolution calls for refocusing work on the human operator, placing him or her at the center of the system. Thus, cobotic systems are increasingly implemented to support human work. In this research, we study the impact of a real-life cobot on the performance (e.g. number of errors, time completion), workload, risk exposure and acceptability of participants realizing an industrial-like assembly task. Method: Participants had to reproduce an assembly model with Duplos in collaboration with a cobot in a laboratory setting. The effect of the human expertise on the task (prior to the collaboration) and the level of cobot adaptation to human safety constraints on the performance at the task and on operator were tested. Results: The main results report that expert participants did less mistakes and were less exposed to risks than non-experts. However, both of them succeeded in the task thanks to the cobot adaptation. Also, the cobot was able to adapt to human safety constraints. This adaptation led participants to expose themselves to fewer risks. Also, contrary to previous findings, experts had a similar score of acceptability than non-experts. Conclusion: This laboratory experiment is a proof of concept demonstrating that using a cobotic solution could potentially assist humans in supporting high-risk work operations. Application: Cobotic system designers and work designers could benefit from this research's exploratory results when supporting the design of constraints in workstations for high-risk work operations.

257 Background: Disappearing liver metastases (DLMs) diagnosed on post-chemotherapy (Cx) computed tomography (CT) is a favorable prognostic factor in patients (pts) with colorectal liver metastases (CRLM). However, the optimal treatment of DLMs - whether they should be resected or left behind - is controversial. This is a prospective, multi-centred, international study examining the added value of MRI (DWI, T1/T2 and contrast-enhanced) to that of CT alone in accurate assessment of the viability of DLMs. Methods: Pts with initially unresectable CRLM downstaged to a planned liver resection after Cx were enrolled, based on the obligatory decision of a multidisciplinary team. Pts were imaged by both CT and MRI at baseline and presurgical timepoints. DLMs were defined as disappeared lesions diagnosed by CT alone, while confirmed DLMs (cDLMs) were defined as lesions that disappeared on both CT and MRI. cDLMs were either resected or followed-up for 2 years if not resected. All imaging scans were collected centrally for quality assurance. The primary endpoint was the negative predictive value (NPV) of MRI and CT in confirming the status of cDLMs using either pathological complete response or the absence of a local recurrence at the site of cDLMs during the 2 year follow up. The study was aimed at excluding a NPV ≤0.85 with a 1-sided alfa of 5% and power of 90% under the alternative that the NPV ≥0.95. The planned sample size was 92 evaluable (resected or left behind) cDLMs, assuming a within-patient correlation between cDLMs of 0.2 and an average number of 2 cDLMs per pt. Results: 233 pts were registered at 22 participating centres, and 112 were enrolled for analysis. A median of 8 cycles of Cx was delivered, and pts had a median of 7 CRLMs at baseline. A total of 203 cDLMs were identified while the number of DLMs diagnosed by CT was 296. Of these, 152 cDLMs and 227 DLMs, respectively, were evaluable according to the imaging protocol. Intraoperative ultrasound was performed for 195 cDLMs and, of these, 59 (30.2%) were still detected. The rate of R0/R1 resection was 95.5%. The NPV of evaluable cDLMs either resected or left behind was 62.5 % (95/152, 95% CI:50.8-74.2), which was lower than the prespecified threshold. The NPV of DLMs was 52.9% (119/227, 95% CI:42.7, 63.0). The NPV of resected cDLMs, and those left behind were 56.8% (50/88, 95% CI: 44.2, 69.5) and 70.3% (45/64, 95% CI: 48.6 -92.0), respectively. For DLMs, the NPV of resected DLMs and those left behind were 45.6% (72/158, 95% CI: 35.4-55.7) and 69.6% (48/69, 95% CI: 47.7-91.5), respectively. Conclusions: For pts with initially unresectable CRLM, cDLMs diagnosed by both CT and MRI do not correspond to tumor viability, even after highly effective chemotherapy. Ongoing survival analysis (to be presented at the annual meeting) may impact the treatment strategy of pts with DLMs. Clinical trial information: NCT02781935 .

Background and aims – Anadenanthera colubrina is a Neotropical native forest tree species with significant ecological importance in Seasonally Dry Tropical Forests. Developing genetic markers for this species is relevant for conservation, breeding, and evolutionary studies. Previously available genetic markers for A. colubrina consisted of a few microsatellites. Next-generation sequencing (NGS) strategies allow simple and cost-effective development of new SSR loci from low-coverage whole genome shotgun sequencing. The main aim was to develop microsatellite markers for sequence-based high-throughput genotyping (SSRseq) in the species and to characterize their information content against traditional capillary electrophoresis-based microsatellite data by estimating the amount of molecularly accessible size homoplasy of each locus. Additionally, the reliability of these markers for population genetic analysis was assessed by genotyping two age classes (reproductively mature trees and seedlings) in a typical location in Argentina. Key results – Sixty primer pairs targeting microsatellites were designed, of which 25 were validated with allelic error rates < 3% and genotype missingness < 20%. A significantly higher number of alleles per locus and heterozygosity was detected for SSRseq considering sequence polymorphisms compared to analysing the same data based on sequence size (length) only. Size homoplasy, calculated as the proportion of mismatches between datasets relative to the number of alleles differing in length, averaged 97.85% over all SSR loci. High levels of population genetic diversity were detected in adults and seedlings from Paranaense forests, exceeding those reported in previous studies of A. colubrina using traditional SSRs. The generated datasets increase the resolution of capillary-based microsatellite genotyping, allowing for more accurate inference of eco-evolutionary processes in non-model tree species.

PURPOSE Establishing an accurate prognosis remains challenging in older patients with cancer because of the population's heterogeneity and the current predictive models' reduced ability to capture the complex interactions between oncologic and geriatric predictors. We aim to develop and externally validate a new predictive score (the Geriatric Cancer Scoring System [GCSS]) to refine individualized prognosis for older patients with cancer during the first year after a geriatric assessment (GA). MATERIALS AND METHODS Data were collected from two French prospective multicenter cohorts of patients with cancer 70 years and older, referred for GA: ELCAPA (training set January 2007-March 2016) and ONCODAGE (validation set August 2008-March 2010). Candidate predictors included baseline oncologic and geriatric factors and routine biomarkers. We built predictive models using Cox regression, single decision tree (DT), and random survival forest (RSF) methods, comparing their predictive performance for 3-, 6-, and 12-month mortalities by computing time-dependent area under the receiver operator curve (tAUC). RESULTS A total of 2,012 and 1,397 patients were included in the training and validation set, respectively (mean age: 81 ± 6 years/78 ± 5 years; women: 47%/70%; metastatic cancer: 50%/34%; 12-month mortality: 43%/16%). Tumor site/metastatic status, cancer treatment, weight loss, ≥five prescription drugs, impaired functional status and mobility, abnormal G-8 score, low creatinine clearance, and elevated C-reactive protein (CRP)/albumin were identified as relevant predictors in the Cox model. DT and RSF identified more complex combinations of features, with G-8 score, tumor site/metastatic status, and CRP/albumin ratio contributing most to the predictions. The RSF approach gave the highest tAUC (12 months: 0.87 [RSF], 0.82 [Cox], 0.82 [DT]) and was retained as the final model. CONCLUSION The GCSS on the basis of a machine learning approach applied to two large French cohorts gave an accurate externally validated mortality prediction. The GCSS might improve decision making and counseling in older patients with cancer referred for pretherapeutic GA. GCSS's generalizability must now be confirmed in an international setting.

Intense sources of very cold neutrons (VCNs) would be beneficial for various neutron scattering techniques and low-energy particle physics experiments. Binary clathrate hydrates hosting deuterated tetrahydrofuran (THF-d) and dioxygen show promise as potential moderators for such sources due to a rich spectrum of localized low-energy excitations of the encaged guest molecules. In this article, we present a reliable manufacturing technique for such hydrates. Neutron diffraction data confirm their clathrate structure as type II (CS-II), determine their purity, and cage occupancy. Furthermore, we present data on the thermal expansivity of THF-d– and THF-d–O2clathrates, drawing attention to them as an interesting case study for the complex structure and dynamics of this class of material.

A pump‐probe shadowgraphy study of femtosecond laser percussion drilling on glass samples is reported applying three different operating regimes, which are the standard repetitive single pulse, the MHz‐ and the GHz‐burst modes. The comparison of pump‐probe imaging in the MHz‐burst and the GHz‐burst regimes is demonstrated for the first time to the best of knowledge. Synchronizing a single pulse probe with a pump operating in a burst regime constitutes a real novelty in femtosecond laser micromachining studies. By this means, a better understanding of the drilling process dynamics of the two burst regimes is provided and reveals the differences between these regimes. Especially, the process of through via drillings of different hole depths in the GHz‐burst regime is investigated in sodalime glass. The results of the pump‐probe shadowgraphy show that the ablation plume in the GHz‐burst regime has an essential role in the drilling process as it stops as soon as the plume escapes from the through hole explaining the final hole morphology observed for deep through via drillings.

We consider the Dirichlet-to-Neumann operator ${\mathcal {N}}$ associated with a general elliptic operator $\begin{aligned} {\mathcal {A}}u = - \sum _{k,l=1}^d \partial _k (c_{kl}\, \partial _l u) + \sum _{k=1}^d \Bigg ( c_k\, \partial _k u - \partial _k (b_k\, u) \Bigg ) +c_0\, u \in {\mathcal {D}}'(\Omega ) \end{aligned}$with possibly complex coefficients. We study three problems: (1) Boundedness on $C^\nu$ and on $L_p$ of the commutator $[{\mathcal {N}}, M_g]$, where $M_g$ denotes the multiplication operator by a smooth function g. (2) Hölder and $L_p$-bounds for the harmonic lifting associated with ${\mathcal {A}}$. (3) Poisson bounds for the heat kernel of ${\mathcal {N}}$. We solve these problems in the case where the coefficients are Hölder continuous and the underlying domain is bounded and of class $C^{1+\kappa }$ for some $\kappa > 0$. For the Poisson bounds we assume in addition that the coefficients are real-valued. We also prove gradient estimates for the heat kernel and the Green function G of the elliptic operator with Dirichlet boundary conditions.

Neocortical memory engrams are thought to stabilize and mature via enhanced interconnectivity during the so-called systems-consolidation process 1,2 . While synaptic plasticity of these engram connections is considered an important mechanism for storing memories 3,4 , it cannot fully account for the dynamic vividness of remote, cortically-based memories. Indeed, cell-intrinsic plasticity has been touted as the crucial early priming mechanism that renders nascent engram neurons susceptible to ongoing plastic processes while providing flexibility for later encoding events 5–7 . Here, we reveal that learning-related neuron-wide intrinsic excitability (IE) plasticity of nascent cortical engram neurons is a permissive mechanism for the formation and specificity of remote associative memories. Using a c-fos -dependent genetic and viral system for the targeted labeling of engram neurons in the anterior cingulate cortex (ACC) combined with ex vivo electrophysiology, we found that contextual fear learning triggered a time-dependent increase in their IE signature expressed over days during the early, but not late, phase of memory formation. Remarkably, chemogenetically hyperpolarizing engram neurons during this early plastic phase enhanced their maturation, increasing the strength and context-precision of consolidated memories and preventing memory disturbance caused by an interference event. Altogether, our findings identify cell-intrinsic plasticity within nascent ACC engram neurons as an essential tagging mechanism whose features determine the fate and dynamic content of remote memories.

Parkinson’s disease arises from the degeneration of dopaminergic neurons in the substantia nigra pars compacta, leading to motor symptoms such as akinesia, rigidity, and tremor at rest. The non-motor component of Parkinson’s disease includes increased neuropathic pain, the prevalence of which is 4 to 5 times higher than the general rate. By studying a mouse model of Parkinson’s disease induced by 6-hydroxydopamine, we assessed the impact of dopamine depletion on pain modulation. Mice exhibited mechanical hypersensitivity associated with hyperexcitability of neurons in the dorsal horn of the spinal cord (DHSC). Serotonin (5-HT) levels increased in the spinal cord, correlating with reduced tyrosine hydroxylase (TH) immunoreactivity in the nucleus raphe magnus (NRM) and increased excitability of 5-HT neurons. Selective optogenetic inhibition of 5-HT neurons attenuated mechanical hypersensitivity and reduced DHSC hyperexcitability. In addition, the blockade of 5-HT 2A and 5-HT 3 receptors reduced mechanical hypersensitivity. These results reveal, for the first time, that PD-like dopamine depletion triggers spinal-mediated mechanical hypersensitivity, associated with serotonergic hyperactivity in the NRM, opening up new therapeutic avenues for Parkinson’s disease-associated pain targeting the serotonergic systems.

In this paper, we report on the full classification of generic iso-edge subdivisions of six-dimensional translational lattices. We obtain a complete list of 55083357 affine types of iso-edge subdivisions. We report on the use of the method of canonical forms that allows us to apply hashing techniques used in modern databases.

In England, a vertical equity model of inclusive schooling is increasingly visible in both educational policy and school practices since the 2019 education reforms. Within this mixed model of provision, alongside and in complementarity to mainstream schooling, Alternative Provision (AP) and Special Educational Needs and Diversity (SEND) settings offer schooling for disabled or excluded children, as a significant part of the inclusion landscape. Within this national setting, a 2021-2022 study interviewed teachers in mainstream, AP and SEND schools about their views and experiences of training for inclusive pedagogies. Findings reveal similar problems for teachers across sectors, such as a lack of time for further training in inclusive pedagogies; and the difficulty of meeting the needs of all pupils (SEND and non-SEND). In response, both settings favour in-house training to promote specific skills, while AP and SEND settings would also like more sharing of best practice through inter-school networks. Both settings further identify a place for university-based training in supporting teachers’ understanding of diversity and inclusion, but as complementary to schools-based professional development. Teachers’ views suggest that initial teacher training (ITT) insufficiently prepares teachers for working with pupil diversity, and it is only by teaching in a school and “practising teaching” that effective skills are developed.

In this study, we report, for the first time, to the best of our knowledge, on in-volume glass modifications produced by GHz bursts of femtosecond pulses. We compare three distinct methods of energy deposition in glass, i.e., the single-pulse, MHz burst, and GHz burst regimes, and evaluate the resulting modifications. Specifically, we investigate in-volume modifications produced by each regime under varying parameters such as the pulse/burst energy, the scanning velocity, and the number of pulses in the burst, with the aim of establishing welding process windows for both sodalime and fused silica.

This work addresses the structural quantification of multiphase materials, here nanostructured polymer solid precursors and their micro/nano sized foamed counterparts. It is based on a strategy of contrast/edge enhancement, locally adaptive to image data in digital images of materials. The method allows to binarize straightforwardly the structures (the phases) in TEM and SEM images after edge identification, edge choice, and image virtual reconstruction. A detailed insight is brought into one‐step batch supercritical CO2 foaming of acrylic amorphous PMMA (polymethyl methacrylate) polymers, aided by the nanostructuration of block copolymers (BCP), here MAM (butyl acrylate center block methyl acrylate side blocks). The foaming conditions, i.e., pressure drop rate (PDR) and saturation temperature required for an actual one‐step procedure are specified and clarified, whereas previous works, dealing with “one‐step procedures”, are probably incurring in a two‐step procedure. The roles of the BCP content (and size) and saturation temperature are carefully analyzed and further clarified, more comprehensively than in previous literature. Thanks to the analysis of size distributions of foams and foam blend precursors (0.25, 0.5, 10 wt% MAM), bi modality of 10 wt% foams is for example revealed. A discussion of kinetics effects, i.e., evolutions of the effective sample temperature Tef(t), and the effective glass transition temperature Tg, ef(t). provides a new insight of “pseudo” one‐step VS “real” one‐step batch foaming.

During the cooking, processing, and storage of food products, a whole range of browning reactions occurs, initiated by the reaction of a carbohydrate with a compound possessing a free amino group. Melanoidins formed, influence food quality, mainly their colour, their flavour, and their antioxidant activities. Melanoidins are complex Maillard reaction products. We developed a method to isolate coffee melanoidins and melanoidins from toasted oak wood. We noted that coffee is richer in melanoidin compounds than oak wood. We presented a partial characterization of melanoidins fractions from toasted oak heartwood, and a comparison with melanoidins from roasted coffee. Mass spectra of the fractions isolated from toasted oak wood indicate the presence of pentose and hexose-based oligosaccharides with different degrees of polymerisation. The presence of the oligosaccharide moieties, as well as their degradation products found in the oak wood melanoidins, supports the postulated carbohydrate-based origin of melanoidins.

Among strategies to limit ischemia/reperfusion (IR) injuries in transplantation, cell therapy using stem cells to condition/repair transplanted organs appears promising. We hypothesized that using a cell therapy based on extracellular vesicles (EVs) derived from urine progenitor cells (UPCs) during hypothermic and normothermic machine perfusion can prevent IR‐related kidney damage. We isolated and characterized porcine UPCs and their extracellular vesicles (EVs). Then these were used in an ex vivo porcine kidney preservation model. Kidneys were subjected to warm ischemia (32 min) and then preserved by hypothermic machine perfusion (HMP) for 24 h before 5 h of normothermic machine perfusion (NMP). Three groups were performed (n = 5–6): Group 1 (G1): HMP/vehicle + NMP/vehicle, Group 2 (G2): HMP/EVs + NMP/vehicle, Group 3 (G3): HMP/EVs + NMP/EVs. Porcine UPCs were successfully isolated from urine and fully characterized as well as their EVs which were found of expected size/phenotype. EVs injection during HMP alone, NMP alone, or both was feasible and safe and did not impact perfusion parameters. However, cell damage markers (LDH, ASAT) were decreased in G3 compared with G1, and G3 kidneys displayed a preserved tissue integrity with reduced tubular dilatation and inflammation notably. However, renal function indicators such as creatinine clearance measured for 5 h of normothermic perfusion or NGAL perfusate's level were not modified by EVs injection. Regarding perfusate analysis, metabolomic analyses and cytokine quantification showed an immunomodulation signature in G3 compared with G1 and highlighted potential metabolic targets. In vitro, EVs as well as perfusates from G3 partially recovered endothelial cell metabolic activity after hypoxia. Finally, RNA‐seq performed on kidney biopsies showed different profiles between G1 and G3 with regulation of potential IR targets of EVs therapy. We showed the feasibility/efficacy of UPC‐EVs for hypothermic/normothermic kidney conditioning before transplantation, paving the way for combining machine perfusion with EVs‐based cell therapy for organ conditioning. Highlights ·UPCs from porcine urine can be used to generate a cell therapy product based on extracellular vesicles (pUPC‐EVs). ·pUPC‐EVs injection during HMP and NMP decreases cell damage markers and has an immunomodulatory effect. ·pUPC‐EVs‐treated kidneys have distinct biochemical, metabolic, and transcriptomic profiles highlighting targets of interest. ·Our results pave the way for combining machine perfusion with EV‐based cell therapy for kidney conditioning.

This paper presents a survey and critical analysis of the mathematical literature on modeling of dynamic populations living in a fluid medium. The present review paper is divided into two main parts: The first part deals with the multiscale derivation of deterministic and stochastic cross-diffusion systems governed by the incompressible Navier–Stokes equations. The derivation is obtained from the underlying description at the microscopic scale in kinetic theory models according to the micro–macro decomposition method. In the second part of this review, we are delighted to present a new variety of mathematical models describing different applications, namely, the pursuit–evasion dynamics, cancer invasion, and virus dynamics. Finally, critical analysis and future research perspectives are discussed.