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Securing raw materials, reagents, and consumable supplies in the academic bioproduction UNITC network: because the chain is only as strong as its weakest link
No full textInternational audienceAcademic autologous cell manufacturing offers key advantages, including cost-effectiveness, accessibility, and flexibility. However, the management of Raw Materials, Reagents, and Consumables (RMRCs) is essential for ensuring product purity, safety, and effectiveness. Variations in RMRC quality can increase production costs and result in batch failures. This work from the GMP-Bioproduction group of the French Consortium in Advancing Cancer Cell and Gene Therapy (UNITC) outlines a multicenter study conducted from 2022 to 2024 across all 11 French academic cell and gene therapy facilities producing Advanced Therapy Medicinal Products, evaluating current RMRC management practices. The study highlights significant challenges, including supply shortages, reference changes, and inconsistent quality controls. While RMRC-related non-conformities accounted for only 6.8% of total issues, they frequently required complex procedural adjustments, resulting in added financial and operational burdens. Despite differences in production scale and ATMP types, all centers consistently evaluated the criticality of RMRC, reflecting strong alignment in risk assessment practices. To address these issues, the study proposes recommendations, including a unified RMRC risk classification system, harmonized quality assurance processes. These actions aim to strengthen regulatory compliance, enhance collaboration across academic centers, and improve the overall resilience of academic decentralized CAR-T cells manufacturing in France
A Cerebral Origin for Retinal Degeneration in the Visual Form of Alzheimer's Disease?
No full textInternational audienceAlzheimer's disease ( AD ) manifests commonly as an amnestic syndrome (t AD ), but also as a rarer focal type, such as posterior cortical atrophy (PCA‐AD), which primarily impairs visuospatial functions. In addition to the brain atrophy, retinal degeneration has been demonstrated, associated with the accumulation of Ab and Tau protein in this tissue, which shares a common origin with the brain. Additionally, retrograde trans‐synaptic degeneration from the brain could affect the retina. We hypothesized that such dying‐back phenomenon would be more important in PCA‐ AD than in t AD and that this would be reflected on specific optical coherence tomography (OCT) measures. Twenty‐nine AD patients were categorized into 15 typical and 14 PCA forms. Complaints and symptoms were evaluated using a specific screening battery developed to detect PCA (Q‐ACP questionnaire, neuropsychological parietal and non‐parietal scales). Neuroimaging was performed to determine brain atrophy and its lateralization. OCT imaging allowed measuring the volumes of the macular ganglion cell layer (GCL) and the retinal nerve fibre layer (RNFL) of the optic nerve. While the global RNFL thickness and GCL volume were not statistically different, PCA‐ AD patients showed more thinning than tAD in the inferior temporal (IT) sector in both eyes. Moreover, the amount of thinning in this sector was correlated with the score on the Q‐ACP questionnaire and on the neuropsychological parietal scales. We propose that the thinning in the IT sector reflects the retrograde damage to the magnocellular pathway, which constitutes a major feed of the dorsal visual stream primarily damaged in PCA
Architecture
No full textLe Dictionnaire Nerval offre un panorama vivant et rigoureux de l’œuvre de Gérard de Nerval — poésie, nouvelles, théâtre, articles, récits de voyage, traductions. Il en propose des lectures éclairantes et les met en relation avec des écrivains, peintres et musiciens, afin de faire apparaître les sources d’inspiration et les traits essentiels de la pensée et de l’esthétique nervaliennes
Uneven tiredness. On some inequalities among the lyonnese streetcleaners
No full textInternational audienc
Donor Characteristics Associated With Graft Loss and Delayed Graft Function in Very-Aged Kidney Donors: An Observational Multicentric Study
No full textInternational audienceThis study explores the impact of using kidneys from very-aged donors to address the organ shortage, focusing on risk factors for graft loss and delayed graft function (DGF), independent of recipient factors. Data were sourced from the French multicentric prospective DIVAT cohort and retrospectively analyzed. The study included adult recipients transplanted between 2007 and 2018 receiving kidneys from brain-deceased donors over 70. The primary endpoint was death-censored graft survival, and secondary endpoint DGF. Among 1036 patients with a median follow-up of 3.96 years (2.01–6.31), donor hypertension (HR 1.46 95% CI (1.09–1.95), cold ischemia time (HR 1.03 per hour 95% CI (1.01–1.06) and HLA mismatches (after adjustment on DGF, HR 1.98 (1.45–2.71)) were significant risk factors for graft loss. Considering DGF, donor serum creatinine (HR 1.01 95% CI (1.01–1.01) per μmol/L), warm and cold ischemia times (HR 1.01 95% CI (1.0–1.01) per minute and HR 1.05 95% CI (1.02–1.08) per hour) and the use of SCOT preservation solution (HR 3.90 95% CI (1.26–11.84)) were deleterious, while hypothermic perfusion machine was protective (HR 0.65 95% CI (0.43–0.99)). The findings emphasize the paucity of modifiable variables associated with long-term outcomes in very-aged donors and the need for peri-transplant preservation strategies
Novel dimeric capsid assembly modulators as a unique class of highly potent anti-HBV agents
No full textInternational audienceApproximately 250 million people are chronic HBV carriers and are at high risk of developing hepatitis, cirrhosis, and hepatocellular carcinoma. Several drugs are currently approved, but because they do not cure, lifelong therapies are the norm. HBV Capsid Assembly Modulators (CAMs) have emerged as a promising option, as they lower several key markers of HBV replication. Novel dimeric structures (D-CAMs) were designed and evaluated. Their potency and mechanism of action compared to monomeric D-CAMs, such as GLP-26 wre studies. Among them, D-CAM-14 showed improved potency over GLP-26 and exhibited a unique and distinct effect on capsid morphology and kinetic assembly
Unraveling the complex rupture of the 2020 Mw 6.4 Petrinja Earthquake (Croatia): insights from joint inversion of geodetic benchmarks, InSAR and optical correlation data.
No full textInternational audienceThe Mw 6.4 Petrinja earthquake, which struck Croatia on December 29, 2020, is among the most powerful earthquakes recorded in the slowly deforming region of Eastern Europe. In areas of low tectonic strain, limited seismic monitoring and the sporadic occurrence of strong earthquakes often hinder detailed analyses of coseismic ruptures preventing the scientific community to fully understand the processes governing these moderate and destructive events. In particular, it's not clear whether those continental earthquakes follow the same scaling laws than the ones occurring on mature faults, hence the need to better understand the source of these events.Seismic source inversions and InSAR-based models from multiple studies indicate that the coseismic rupture of the Petrinja earthquake results from a single patch of right-lateral slip. On the other hand, we showed in a previous study that discontinuous surface ruptures and slip inversions of near-field geodetic benchmarks suggest rather along-strike complexities of the fault slip (Henriquet et al., 2023). To better constrain the slip distribution of the Petrinja earthquake, we leverage dense near field measurements from optical image correlation and numerous geodetic benchmarks together with InSAR data. We first assess the sensitivity of the model to each dataset to show that slip patterns are overall consistent to first order, although significant differences appear along dip, mainly depending on the distance between the fault trace and the considered measurements. We then jointly invert all the displacement data to provide a robust solution of the coseismic slip. The results confirm that the coseismic slip occurred on a near-vertical strike-slip fault at shallow depths, less than 10 km, with significant slip extending to the surface locally. It also indicates that fault bending near Kriz influenced the rupture propagation, as the largest slip, exceeding 3 meters, was concentrated in the northwestern section at depths of less than 5 km and that a deeper slip of smaller amplitude is required by the data to the southeast. This along-strike variation in slip depth and amplitude also correlates with changes in aftershocks rate and average depth (Herak et al., 2023), which confirms that the Petrinja fault is not a straight, mature fault system. This complexity in the slip distribution is in agreement with the large stress drop values obtained by seismological studies (Lončar et al., 2024). In conclusion, this study offers new insights into the seismogenic source of the Petrinja earthquake and highlights the value of combined displacement fields in improving source models of moderate intracontinental earthquakes
Baseline Chronic Pain Intensity and Long‐Term Depressive Symptoms in French Older Community‐Dwelling Adults: A 12‐Year Prospective Cohort Study
No full textInternational audienceABSTRACT Background Chronic pain (CP) in older adults was associated with depression in numerous cross‐sectional studies. However, the longitudinal link between CP characteristics and depressive symptoms in this population remains unsettled. We aimed to assess the prospective link between CP intensity and long‐term depressive symptoms in a population‐based cohort of older participants, considering numerous potential confounders. Methods The study sample was gathered from the PAQUID study, a prospective cohort study of community‐dwellers above 65. Information regarding CP characteristics was collected at the 3‐year follow‐up visit. The sample included the 742 participants who fulfilled this CP questionnaire. Three CP groups were distinguished: no ( n = 504), mild ( n = 101), and intense ( n = 137) CP. Depressive symptoms were assessed with the Center for Epidemiologic Studies Depression scale (CES‐D) every 2–3 years during 12 years (6 waves). The association between CP and the 12‐year CES‐D course (12 years after the 3‐year visit) was investigated using a multivariate latent process mixed model for curvilinear data. Results Compared with the participants without CP, those with moderate and intense CP had significantly higher CES‐D levels at baseline with a dose–response relationship as a function of pain intensity ( β = 0.366, p = 0.0308; 0.607, p < 0.0001, respectively). However, the time course was comparable in the three groups ( β = −0.003, p = 0.8351; −0.003, p = 0.8516, for mild and intense CP, respectively). Conclusion CP intensity is associated with higher levels of depressive symptoms persisting throughout the long period of follow‐up. This finding reinforces the importance of early treatment of CP in older adults to prevent its sustainable psychological consequences. Significance Statement Depression and chronic pain (CP) have been frequently associated in older adults. The longitudinal relationship between CP characteristics and the long‐term course of depressive symptoms in this population has yet to be specified. The present results showed that CP intensity is associated with higher levels of depressive symptoms persisting throughout a 15‐year follow‐up period, with a dose–response relationship. This finding reinforces the importance of early treatment of CP in the older population, in order to prevent its lasting psychological consequences
