University of Tours

Background. Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare disease, predisposing to an increased risk of infection. A complete picture of these infections is lacking. Research question. Describe the characteristics and clinical outcomes of patients diagnosed with aPAP, and to identify risk factors associated with opportunistic infections. Methods. We conducted a retrospective cohort including all patients diagnosed with aPAP between 2008 and 2018 in France and Belgium. Data were collected using a standardised questionnaire including demographics, comorbidities, imaging features, outcomes and microbiological data. Results. We included 104 patients, 2/3 were men and median age at diagnosis was 45 years. With a median follow-up of 3.4 years (IQR 1.7–6.6 years), 60 patients (58%), developed at least one infection, including 23 (22%) with opportunistic infections. Nocardia spp was the main pathogen identified (n=10). Thirty-five (34%) patients were hospitalised due to infection. In univariate analysis, male gender was associated with opportunistic infections (p=0.04, OR=3.88; 95% CI (1.02 to 22.06)). Anti-granulocyte macrophage colony-stimulating factor antibody titre at diagnosis was significantly higher among patients who developed nocardiosis (1058 (316–1591) vs 580 (200–1190), p=0.01). Nine patients had died (9%), but only one death was related to infection. Interpretation. Patients with aPAP often presented with opportunistic infections, especially nocardiosis, which highlights the importance of systematic search for slow-growing bacteria in bronchoalveolar lavage or whole lung lavage.

Laryngeal chondrosarcoma is a rare tumor that mostly affects the cricoid cartilage. The aim of this study was to compare outcomes between the various treatments of this pathology as there are no official guidelines for this pathology. A retrospective analysis of the pathology database of nine French tertiary care centers was conducted. Outcomes of patients treated by total laryngectomy were compared with those treated by more conservative approaches (endoscopic debulking, median thyrotomy, partial laryngectomy). Two Kaplan–Meier survival analyses were performed: one to assess the overall survival rate and the other to assess laryngeal preservation over time. A total of 43 patients were enrolled: 12 with total laryngectomy as the initial treatment, and 31 who initially underwent laryngeal-preserving treatment. With conservative treatment, laryngeal function was preserved in 96% and 75% of patients at 1 and 5 years, respectively. Conservative treatment did not reduce the overall survival rate. These results suggest that laryngeal preservation should be considered as the initial treatment in cases of laryngeal chondrosarcoma.

Aims. The exposure-response relationship of bevacizumab may be confounded by various factors, i.e. baseline characteristics, time-dependent target engagement and recursive relationships between exposure and response. This work aimed at investigating the exposure-response relationships of bevacizumab in mCRC patients while mitigating potential sources of bias. Methods. Bevacizumab pharmacokinetics was described using target-mediated drug disposition (TMDD) modeling. The relationships between target kinetics, and progression-free (PFS) and overall (OS) survivals were assessed using joint pharmacokinetic and parametric hazard function models. Both potential biases due to prognostic-driven and response-driven of the concentration-effect relationship were mitigated. These models were used to evaluate the effect of increased antigen target levels and clearance, as well as intensified dosing regimen, on survival. Results. Estimated target-mediated pharmacokinetic parameters in 130 assessed patients were: baseline target levels (R0=8.4 nM), steady-state dissociation constant (KSS=10 nM) and antibody-target complexes elimination constant (kint=0.52 day-1). Distribution of R0 was significantly associated with an increased baseline CEA and circulating VEGF levels, and the presence of extra-hepatic metastases. Unbound target levels (R) significantly influenced both progression and death hazard functions. Increased R0 or CL values led to decreased bevacizumab unbound concentrations, increased R levels, and shortened PFS and OS, whereas increasing bevacizumab dose led to decreased R and longer survival. Conclusion. This study is the first to show the relationship between bevacizumab concentrations, target involvement and clinical efficacy by mitigating potential sources of bias. Most of target amount may be tumoral in mCRC. A more in-depth description of this relationship should be made in future studies.

The purpose of the eSMILE study was to explore social cognition (SC) in the two behavioural addictions (BAs) included in international classifications: gaming disorder and gambling disorder. In these disorders, cognitive functioning is involved in the development and maintenance of addiction. Nevertheless, SC have received less attention than other cognitive functions. The eSMILE study was conducted online and included 105 participants (gamers and gamblers). This study included: the Penn emotion recognition task, the Condensed and Revised Multifaced Empathy Test, the Interpersonal Reactivity Index, the Chicken Game, social metacognition questions, and the Toronto Alexithymia Scale. We analysed the relationships among SC measures, addiction levels, and behaviour frequency. For gamers, we showed that the higher their level of addiction was, the lower their self-confidence following the identification of basic emotions, although the more frequently they played, the better their performance on this task. Additionally, we found lower performance on the identification of more complex emotions by gamblers, which seems to be the result of their levels of addiction rather than the frequency of their gambling behaviour. This study contributes to our understanding of the cognitive processes underlying BAs. Additionally, working on SC abilities may be an additional management mode for BAs that could be added to existing treatments.

In 2022, the Greek Public Employment Service has launched a call for horizontal upskilling/reskilling programs for the unemployed. The action has been financed by European funds, and more specifically by the Recovery and Resilience Facility. This plan is initiated by the NextGenerationEU instrument and implements lifelong learning in green and digital skills. The study presented in this article, which is fully in line with this context, aims to discuss the initial results in terms of the social impact of the first four groups of trainees in the advanced computer-aided design program. The results show that the high percentage of university graduates reflects the current unemployment situation in Greece, and particularly in the prefecture of Attica. Strong social relationships developed between participants, irrespective of age, gender, economic and social status and level of education. The motivation for this program was not prior training, but rather, for most of the participants, the broadening of their field of knowledge with a view to seeking out new areas and sectors of employment.

Rivers are social-ecological systems. Yet, in urban contexts, they have often been degraded to lifeless conduits, failing to promote human-nature interactions. As a countermeasure, river restoration has progressively been implemented globally to improve rivers’ ecological quality and rejuvenate human-nature connections. In China, urban river restoration has been facilitated to improve river water quality and enhance nature-based recreation. Despite this nation-driven effort towards restoration, scholarly understanding of whether and how river restoration could align with societal preferences remains scarce. This study examined the social-ecological interactions associated with urban rivers with a social science methodology; a questionnaire survey was conducted at three Water Museums in three Chinese cities in summer 2022 and collected 654 responses from highly educated respondents. The results revealed an appreciation for rivers' environmental and recreational value among urban residents, with childhood experiences playing a role in shaping these evaluations and perceptions. Respondents generally preferred prioritizing biological elements in urban river restoration. They also stress the importance of a balanced approach, integrating nature conservation and recreational functionality while maintaining physical water access. These findings challenge the current approach of urban river restoration in the three Chinese cities, which tend to emphasize aesthetic and recreational aspects over comprehensive ecological considerations. The ANCOVA analysis further indicated that preferences for river restoration are influenced by individuals' perceptions of the positive and negative social-ecological impacts of rivers, emphasizing the need to enhance environmental awareness regarding river ecosystems. Finally, in alignment with China’s vision of promoting human-nature harmony, the study advocated for strategies that harmonize ecological functionality with societal needs in urban river management.

An ischemia-reperfusion injury (IRI) results from a prolonged ischemic insult followed by the restoration of blood perfusion, being a common cause of morbidity and mortality, especially in liver transplantation. At the maximum of the potential damage, IRI is characterized by 2 main phases. The first is the ischemic phase, where the hypoxia and vascular stasis induces cell damage and the accumulation of damage-associated molecular patterns and cytokines. The second is the reperfusion phase, where the local sterile inflammatory response driven by innate immunity leads to a massive cell death and impaired liver functionality. The ischemic time becomes crucial in patients with underlying pathophysiological conditions. It is possible to compare this process to a shooting gun, where the loading trigger is the ischemia period and the firing shot is the reperfusion phase. In this optic, this article aims at reviewing the main ischemic events following the phases of the surgical timeline, considering the consequent reperfusion damage.

Background Eosinophilic granulomatosis with polyangiitis (EGPA) is often associated with glucocorticoid-dependent asthma and/or ear, nose and throat (ENT) manifestations. When immunosuppressants and/or mepolizumab are ineffective, dupilumab could be an option. We describe the safety and efficacy of off-label use of dupilumab in relapsing and/or refractory EGPA. Patients and methods We conducted an observational multicentre study of EGPA patients treated with dupilumab. Complete response was defined by Birmingham Vasculitis Activity Score (BVAS)=0 and prednisone dose ≤4 mg/day, and partial response by BVAS=0 and prednisone dose >4 mg/day. Eosinophilia was defined as an eosinophil count >500/mm ³ . Results Fifty-one patients were included. The primary indication for dupilumab was disabling ENT symptoms in 92%. After a median follow-up of 13.1 months, 18 patients (35%) reported adverse events (AEs), including two serious AEs. Eosinophilia was reported in 34 patients (67%), with a peak of 2195/mm3 (IQR 1268–4501) occurring at 13 weeks (IQR 4–36) and was associated with relapse in 41%. Twenty-one patients (41%) achieved a complete response and 12 (24%) a partial response. Sixteen (31%) patients experienced an EGPA relapse while on dupilumab, which was associated with blood eosinophilia in 14/16 (88%) patients. The median eosinophil count at the start of dupilumab was significantly lower in relapsers than in non-relapsers, as was the median time between stopping anti-IL-5/IL-5R and switching to dupilumab. Conclusion These results suggest that dupilumab may be effective in treating patients with EGPA-related ENT manifestations. However, EGPA flares occurred in one-third of patients and were preceded by eosinophilia in 88%, suggesting that caution is required.

Combining the search and pursuit aspects of predator–prey interactions into a single game, where the payoff to the Searcher (predator) is the probability of finding and capturing the Hider (prey) within a fixed number of searches was proposed by Gal and Casas (J. R. Soc. Interface 11, 20140062 (doi:10.1098/rsif.2014.0062)). Subsequent models allowed the predator to continue its search (in another ‘round’) if the prey was found but escaped the chase. However, it is unrealistic to allow this pattern of prey relocation to go on forever, so here we introduce a limit of the total number of searches, in all ‘rounds’, that the predator can carry out. We show how habitat structural complexity affects the mean time until capture: the quality of the location with the lowest capture probability matters more than the number of hiding locations. Moreover, we observed that the parameter space defined by the capture probabilities in each location and the budget of the predator can be divided into distinct domains, defining whether the prey ought to play with pure or mixed hiding strategies.

A numerical model is proposed to predict the evolution of the tool temperature during a dry milling process using the finite volume method. This approach considers the secondary shear zone (tool-chip interface) and two distinct tertiary shear zones (tool-workpiece interfaces). Heat fluxes are calculated using experimentally measured cutting forces and linear velocity fields at the tool-chip and tool-workpiece interfaces, while considering the temperature dependent thermal properties of the tool’s substrate and coating. The simulated temperature results are compared to those measured in a previous experiment and the influence of the different interfaces on the evolution of the temperature field is studied.

Background Thrombotic microangiopathies (TMAs) are rare but can be severe in kidney transplant. recipients (KTR). Methods We analysed the epidemiology of adjudicated TMA in consecutive KTR during the. 2009–2021 period. Results TMA was found in 77/1644 (4.7%) KTR. Early TMA (n = 24/77 (31.2%); 1.5% of all KTR) occurred during the first two weeks ((median, IQR) 3 [1–8] days). Triggers included acute antibody-mediated rejection (ABMR, n = 4) and bacterial infections (n = 6). Graft survival (GS) was 100% and recurrence rate (RR) was 8%. Unexpected TMA (n = 31/77 (40.2%); 1.5/1000 patient-years) occurred anytime during follow-up (3.0 (0.5–6.2) years). Triggers included infections (EBV/CMV: n = 10; bacterial: n = 6) and chronic active ABMR (n = 5). GS was 81% and RR was 16%. Graft-failure associated TMA (n = 22/77 (28.6%); 2.2% of graft losses) occurred after 8.8 (4.9–15.5) years). Triggers included acute (n = 4) or chronic active (n = 14) ABMR, infections (viral: n = 6; bacterial: n = 5) and cancer (n = 6). 15 patients underwent transplantectomy. RR was 27%. Atypical (n = 6) and typical (n = 2) haemolytic and uremic syndrome, and isolated CNI toxicity (n = 4) were rare. Two-third of biopsies presented TMA features. Conclusions TMA are mostly due to ABMR and infections; causes of TMA are frequently combined. Management often is heterogenous. Our nosology based on TMA timing identifies situations with distinct incidence, causes and prognosis.

Maintaining the well-being of the older adults is a primary concern in gerontology. This study determined different profiles of well-being (WB) and compared the profiles in terms of successful aging (SA), personality, and sociodemographic variables. The study sample consisted of 856 adults aged 65 to 98 years. WB was taken into account in an eudemonic and hedonic approach. SA was measured by assessing the three distinct components of Rowe and Kahn's model (1997), personality by the Big Five Inventory, and sociodemographic variables. Latent class analyses (LCA) determined the number of WB profiles, and ANOVAs and Chi2 tests to compare them. The LCA revealed three WB profiles: Profile 1 (9.35%, n=80), Profile 2 (37.38%, n=320), and Profile 3 (53.27%, n=456) in which participants reported lower, intermediate, and higher WB scores. Our results confirm that a high level of WB (Profile 3) can be linked to the components of SA and socio-demographic characteristics (age, marital status, level of education, income). This raises questions about the injunctions concerning healthy aging that older people integrate. It's also interesting to note that the intermediate profile (profile 2) can be either close to the "lower WB" profile (Profile 1) in terms of openness, conscientiousness, and agreeableness or to the "higher WB" profile (Profile 3) in terms of extraversion. However the three profiles do not have the same level of neuroticism. These results also showed the importance of adapting the support offered to older people according to their health status and/or individual characteristics.

Aims Despite recommendations to initiate clozapine after two unsuccessful trials of antipsychotics, clozapine is underprescribed and initiated too late. The aim of this study was to describe different antipsychotic treatment sequences in the 36 months before the initiation of clozapine and to characterize clusters of treatment trajectories. Methods Using the French National Health Insurance database, a historical cohort study of the population in an area in western France was performed. The data from all new users of clozapine with a diagnosis of schizophrenia or schizoaffective disorder in the period of 2017–2018 were evaluated. All outpatient reimbursements for antipsychotics during the 36 months before clozapine initiation were analysed. Successive reimbursements for identical treatments were grouped into treatment trials (TTs), and different trajectories were clustered using a state sequence analysis. Results The results showed 1191 TTs for 287 individuals. The mean number of TTs per individual was 3.2. Risperidone, aripiprazole and haloperidol were the main treatments delivered. The frequencies of antipsychotics used differed between monotherapies and combination therapies. A three-cluster typology was identified: one cluster ( n = 133) of ‘less treated’ younger individuals with fewer TTs and shorter TT durations; a second cluster ( n = 53) of ‘more treated’ individuals with higher numbers of TTs and combinations of antipsychotics; and a third cluster ( n = 103) of ‘treatment-stable’ older individuals with longer TT durations. Conclusions The results indicate that the median number of TTs during the 36 months before clozapine prescription was higher than the two recommended. The different trajectories were associated with individual characteristics and treatment differences, suggesting that additional studies of clinical parameters are needed to understand barriers to clozapine prescription.

In the occupational field, the post-COVID-19 era is characterized by a deterioration of employees’ psychological health, and the “Great Resignation,” or “Big Quit,” leading to labor shortages in some activity sectors. In this context, identifying the factors of workers’ psychological health and staff retention on which organizations can act is therefore a crucial issue. The new integrative construct of virtuous organizational practices offers promising prospects to address this issue. The aims of this study were twofold. The first was to explore the relationships between virtuous organizational practices on the one hand, and employees’ need for recovery and turnover intentions on the other. The second was to test the mediating role of work ability between them. We conducted an empirical study with a sample of 521 individuals working in French organizations. Consistent with our assumptions, structural equation modeling revealed that virtuous organizational practices were negatively associated with employees’ need for recovery and turnover intentions. Resampling analyses showed that virtuous organizational practices could provide a protective effect by promoting work ability, which in turn could decrease the need for recovery and turnover intentions. Theoretical contributions, limitations, and practical implications are discussed.

Earwigs are often known for the forceps-like appendage at the end of their abdomen, urban legends about them crawling into human ears, and their roles as pest and biological control agents. However, they are much less known for their social life. This is surprising, as many of the 1,900 species of earwigs show social behaviors toward eggs, juveniles, and adults. These behaviors typically occur during family and group living, which may be obligatory or facultative, last up to several months, and involve only a few to several hundred related or unrelated individuals. Moreover, many individuals can alternate between solitary and group living during their life cycle, an ability that probably prevailed during the emergence of social life. In this review, I detail the diversity of group living and social behavior in earwigs and show how further developing this knowledge in Dermaptera can improve our general understanding of the early evolution of social life in insects. Expected final online publication date for the Annual Review of Entomology, Volume 69 is January 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Purpose Ejaculatory dysfunction is the most common side effect of benign prostatic hyperplasia surgery. Modified techniques have emerged with the aim of preserving antegrade ejaculation without compromising obstruction relief. None are standardized or validated. The PARTURP study is a randomized study investigating partial versus complete prostate resection. We conducted an investigator consensus meeting to define the ideal surgical technique to achieve both correct obstruction relief with ejaculation preservation. Methods An expert consensus meeting involving all investigators of the PARTURP study took place to define a common technique using the nominal group methodology. The objectives were to define the areas to be resected and the areas to be preserved; to define the criteria for proper obstruction relief; to define the criteria for proper ejaculation preservation. Results All investigators (n = 15) attended the consensus meeting, and agreement between all the participants was obtained. The anatomical landmarks to be preserved are located around the verumontanum and along the posterior part of the prostatic urethra. These structures must be preserved up to 2 cm from the verumontanum. The participants agreed on the need to preserve the urethral mucosa in all the areas to be preserved and to reach the enucleation plane in the areas of resection. Conclusions Anatomical landmarks for ejaculation-sparing surgery have been defined by the investigators of the PARTURP randomized study. These landmarks will be used during the study, and the clinical outcomes of this ejaculation-sparing technique will be compared with complete resection with up to 3 years follow-up.

The prevailing assumption has been that the human spermatozoon provides only one centriole to the zygote: the proximal centriole, with a canonical, cylinder-like shape. This overly simplistic view has come under challenge since discovering that the human spermatozoon provides a second, atypical centriole to the zygote. The study of human zygotes is challenging for ethical reasons, and bovine zygotes provide an important model due to a similarity in centrosome embryonic inherence and function. Detailed ultrastructural analyses by Uzbekov and colleagues identify the persistence of atypical centrioles in bovine early embryos, raising questions about the original single-centriole model. Whether the parental origin of nascent atypical centrioles or their wide structural diversity and deviation from the canonical centriolar form in blastomeres constitutes sufficient evidence to warrant a reconsideration of the single-centriole model is discussed herein. Because previous human studies identified only one canonical centriole in the zygote, atypical centrioles are likely present in the early human embryo; therefore, it is time to rethink the role of paternal centrioles in human development.

This paper investigates the impact of spatial heterogeneity on the interaction between similar strains in a dynamical system of coinfecting strains with spatial diffusion. The SIS model studied is a reaction–diffusion system with spatially heterogeneous coefficients. The study considers two limiting cases: asymptotically slow and fast diffusion coefficients. When the diffusion coefficient is small, the slow system is shown to be a semilinear system of “replicator equations,” describing the spatiotemporal evolution of the strains’ frequencies. This system is of the reaction–advection–diffusion type, with an additional advection term that explicitly involves the heterogeneity of the associated neutral system. In the case of fast diffusion, traditional methods of aggregating variables are used to reduce the spatialized SIS problem to a homogenized SIS system, on which the results of the non-spatial model can be applied directly.