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Autism spectrum disorder (ASD) is a multifactorial neurodevelopmental condition with several identified risk factors, both genetic and non-genetic. Among these, prenatal exposure to valproic acid (VPA) has been extensively associated with the development of the disorder. The zebrafish, a cost- and time-effective model, is useful for studying ASD features. Using validated VPA-induced ASD zebrafish models, we aimed to provide new insights into VPA exposure effects during embryonic development and to identify new potential biomarkers associated with ASD-like features. Dose–response analyses were performed in vivo to study larval phenotypes and mechanisms underlying neuroinflammation, mitochondrial dysfunction, oxidative stress, microglial cell status, and motor behaviour. Wild-type and transgenic Tg(mpeg1:EGFP) zebrafish were water-exposed to VPA doses (5 to 500 µM) from 6 to 120 h post-fertilisation (hpf). Embryos and larvae were monitored daily to assess survival and hatching rates, and numerous analyses and tests were conducted from 24 to 120 hpf. VPA doses higher than 50 µM worsened survival and hatching rates, while doses of 25 µM or more altered morphology, microglial status, and larval behaviours. VPA 50 µM also affected mRNA expression of inflammatory cytokines and neurogenesis-related genes, mitochondrial respiration, and reactive oxygen species accumulation. The study confirmed that VPA alters brain homeostasis, synaptic interconnections, and neurogenesis-related signalling pathways, contributing to ASD aetiopathogenesis. Further studies are essential to identify novel ASD biomarkers for developing new drug targets and tailored therapeutic interventions for ASD. [ABSTRACT FROM AUTHOR]

BackgroundCommunity Acute Bacterial Meningitis (CABM) is a rare infectious disease leading to important impairments. Our aim was to describe CABM survivors' quality of life (QOL) 12 months post-CABM and to assess its associations with CABM sequelae.MethodsPatients included in the CABM COMBAT cohort were evaluated one year after the CABM episode. Data were collected by questionnaire, via phone calls with the patients. The WHOQOL-BREF was used to measure CABM survivors' QOL. Hierarchical multivariate linear regressions were performed.ResultsStudy population was composed of 284 patients. At 12 months, 53.9% (153/284) reported at least incident headache/worsening headache intensity at 12 months post-CABM, and/or incident hearing impairment, and/or unfavourable disability outcome (GOS). Unfavourable disability outcome was associated with lower physical health QOL (B = -30.35, pConclusions12 month-CABM burden is heavy. Early detection and management of CABM impairments should be performed in clinical practice as early as possible to optimize patients' psychological and psychosocial functioning.Clinicaltrial. gov identification numberNCT01730690.

Cardiac magnetic resonance imaging (MRI) is an essential tool for the study of hypertrophic cardiomyopathies (HCM) and for differentiating HCM from conditions with increased ventricular wall thickness, such as cardiac storage diseases. Although cardiac MRI is already used for the diagnosis and characterization of some forms of storage diseases involving the myocardium, it has not yet been used to study myocardial involvement in neuronal ceroid lipofuscinosis (NCL). Here, we describe comprehensive cardiac MRI findings in a patient with the CLN3 form of NCL showing basal inferior interventricular septal hypertrophy with maintained indexed LV mass within reference values and low T1-native values. MRI findings support a finding of abnormal storage material within the myocardium in CLN3 disease. We recommend the possible routine use of cardiac MRI for early diagnosis of cardiac involvement in CLN3 disease (also termed juvenile NCL) and to monitor the effects of emerging CLN3 therapies on the myocardium as well.

Introduction Pharmacological and cognitive neuroenhancement refer to the non-medical use of prescription drugs, alcohol, illegal drugs, or the so-called soft enhancers, to enhance cognition, mood, work or school performance, or to promote pro-social behaviour. Literature on the topic is meagre, and available data only partially enlightens their use. Objectives The aim of this paper is to review and comment on the available literature on pharmacological neuroenhancement and, secondary, on emotional enhancement. Methods A systematic review was conducted according to the PRISMA guidelines. Pubmed, Scopus, Embase, PsychInfo and Google Scholar databases were accessed to select English language articles, published from 1980 to April 2020. 11746 papers were initially selected and 123 papers were finally included. Results Available literature indicates a widespread and increasing use of different kinds of substances, drugs and food supplements mainly with neuroenhancing purposes, especially amongst specific populations of young healthy subjects. The evidence regarding their efficacy is controversial. Further, a limited or no awareness regarding the possible consequences of their abuse/misuse emerges amongst users. Conclusions Despite the limited evidence that some substances may improve cognitive functions in healthy subjects and neglecting their detrimental side effects and potential risk of misuse, abuse and addiction, there is an increasing worldwide use of the so-called neuroenhancers, especially in some categories of individuals, such as university students. Further studies are needed to collect reliable data on the effects of neuroenhancers in healthy subjects. Neuroenhancement puts into question the concept of authenticity, so that the problem requires to be analyzed within a complex ethical conceptual frame. Disclosure No significant relationships.

BackgroundKidney transplantation is the preferred treatment option for patients with end-stage renal disease. To maximize patient and graft survival, the allocation of donor organs to potential recipients requires careful consideration. ObjectiveThis study aimed to develop an innovative technological solution to enable better prediction of kidney transplant survival for each potential donor-recipient pair. MethodsWe used deidentified data on past organ donors, recipients, and transplant outcomes in the United States from the Scientific Registry of Transplant Recipients. To predict transplant outcomes for potential donor-recipient pairs, we used several survival analysis models, including regression analysis (Cox proportional hazards), random survival forests, and several artificial neural networks (DeepSurv, DeepHit, and recurrent neural network [RNN]). We evaluated the performance of each model in terms of its ability to predict the probability of graft survival after kidney transplantation from deceased donors. Three metrics were used: the C-index, integrated Brier score, and integrated calibration index, along with calibration plots. ResultsOn the basis of the C-index metrics, the neural network–based models (DeepSurv, DeepHit, and RNN) had better discriminative ability than the Cox model and random survival forest model (0.650, 0.661, and 0.659 vs 0.646 and 0.644, respectively). The proposed RNN model offered a compromise between the good discriminative ability and calibration and was implemented in a technological solution of technology readiness level 4. ConclusionsOur technological solution based on the RNN model can effectively predict kidney transplant survival and provide support for medical professionals and candidate recipients in determining the most optimal donor-recipient pair.

Rita Chammem,1,2 Serge Domi,2 Claire Della Vecchia,1 Thomas Gilbert,1,3 Anne-Marie Schott1,3 1University of Claude Bernard Lyon 1, HESPER Laboratory, Lyon, EA 7425, France; 2CRIFONDO, Caribbean Renaissance Initiative, Département de Gérontologie, Martinique, France; 3Hospices Civils De Lyon, Pôle De Santé Publique, Public Health, Lyon, FranceCorrespondence: Rita ChammemLaboratoire HESPER, Université Claude Bernard Lyon 1, Site Rockefeller, 8 Avenue Rockefeller, Lyon, 69008, FranceTel +33 676813256Email r.chammain@gmail.comRationale: Although the literature recognizes the importance of older individuals’ subjective perceptions about their living environments, past studies on the subject have been primarily restricted to nursing home settings.Objective: This study aimed to better understand the experiences, perceptions, coping mechanisms, and needs of older people living in Martinique who had to modify their living environment because of a decline of autonomy.Design: Qualitative study using content analysis.Methods: Semi-structured one-on-one interviews were conducted with older people living in three different types of environment i) at home with professional support, ii) in a foster care family, iii) in a nursing home. Interviews were conducted until data saturation was reached. A conventional content analysis approach was used.Results: Thirty-four participants were interviewed. Subjects perceived ageing as a factor leading to changes in their living environment. However, they did not spontaneously evoke their functional/structural impairments nor their activity limitations as if the change of living environment could reduce the perceived loss of autonomy by maintaining an acceptable participation. Participants mostly experienced change as both inevitable and as a relief as it took them out of isolation and domestic hardship. This reaction was somewhat facilitated by spiritual beliefs as the changes were interpreted as the will of spiritual forces. Family and social relationships appeared to be more important determinants of participants’ perception of changes in living environment than was health status. We found differences between the three groups regarding familial relationship, fear of death, acceptance of change, and unmet needs. Unmet needs were particularly expressed by those living in foster care. The concept of “feeling at home”, which emerged as essential for all participants, was lacking in foster care families.Conclusion: Perceived autonomy, including not only functional/structural impairments, but also, social interactions, should be carefully considered when developing support services for older individuals.Keywords: older people, nursing home, autonomy, quality of life, foster care family

We described changes caused by the COVID-19 pandemic in the frequency of Emergency Department (ED) visits for mental health disorders (MHDs) in adolescents on a wider temporal range—that is, not just “the waves” of the pandemic—and characterized the profile of the adolescent seeking emergency psychiatric care. We conducted a retrospective longitudinal study by analyzing ED visits for MHDs from 10 March 2019 to 10 March 2021. A total of 1407 ED visits for MHDs were registered: 702 in the pre-COVID-19 and 707 in the COVID-19 period. The cumulative incidence of ED visits for MHDs was 1.22% in the pre-COVID-19 period and 1.77% in the COVID-19 period, with a statistically significant difference (p < 0.001). The principal characteristics of the adolescent with MHDs during the pandemic period: the odds of comorbidities decreased by 26% (p = 0.02), and the odds of transfer from other hospitals decreased by 71% (p < 0.001), while the odds of the ED presentation as first psychiatric episode were twice greater (p < 0.001). The risk of hospitalization increased by 54% (p = 0.001). Regarding psychopathology, the likelihood of attempted suicide increased by 74% during the pandemic (p = 0.02). The rate of mood and eating disorders grew significantly during the COVID-19 pandemic period (p = 0.005 and p = 0.031, respectively). Monitoring ED visits for MHDs and understanding changes in the profile of adolescents presenting to ED helps to reinforce the role of ED in identifying special clinical needs for these vulnerable patients in case of a future public health crisis.

We assessed whether contemporary immunosuppression agents were associated with cancer among kidney transplant recipients (KTR), and if this association varied by age and sex. We studied a retrospective province‐wide cohort of primary KTR (1997–2016). Employing multivariable Cox models, we estimated associations of cumulative doses of prednisone, mycophenolate and tacrolimus administered over the past 10 years, lagged by 2 years, with the incidence of primary malignant neoplasms (PMN). We assessed interactions with age and sex. To assess the impact of exposure recency, we used weighted cumulative exposure (WCE) modeling. Among 1064 KTR, 108 (10.2%) developed PMN over median follow‐up of 73 months (interquartile range: 32–120). Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) of 0.96 (0.64–1.43), 1.34 (0.96–1.86), and 1.06 (0.88–1.29) were estimated for cumulative daily doses of prednisone (5 mg), mycophenolate (1000 mg), and tacrolimus (2 mg) administered continuously over the past 10 years, respectively. PMN risk associated with cumulative tacrolimus exposure was modified by age (interaction p =.035) and was more pronounced in 15‐year and 30‐year‐old KTR (aHRs of 1.57 [1.08–2.28] and 1.31 [1.03–1.66], respectively) in comparison to older KTR. PMN risk increase associated with higher cumulative mycophenolate dose was more pronounced in females (aHR = 1.86 [1.15–3.00]) than in males (aHR = 1.16 [0.74–1.81]; interaction p =.131). WCE analyses suggested increased PMN risk the higher the mycophenolate doses taken 5–10 years ago. A trend toward increased PMN risk with long‐term mycophenolate exposure, particularly in females, and more pronounced risk with long‐term tacrolimus exposure in younger KTR, identify opportunities for tailored immunosuppression to mitigate cancer risk. [ABSTRACT FROM AUTHOR]

Changes in the chemistry of the pore fluid are known to have an impact on the hydro-mechanical behaviour of clays. Experimental evidence collected in recent decades has led to the formulation of constitutive chemo-mechanical models for expansive soils used in engineering practice for the containment of pollution, such as bentonite. Less attention has been paid to modelling the chemo-mechanical behaviour of non-expansive clays, which are less frequently used for geoenvironmental applications, but equally exposed to chemical changes. Key differences between the impact of salinity on the fabric of expansive and non-expansive clays are pointed out. At the macroscopic scale, an increase in salinity causes a translation of the normal compression line of non-expansive clays to higher void ratios, which in some cases is also accompanied by an increase in compressibility. The opposite occurs for expansive clays. Such experimental evidence provides the basis for a chemo-mechanical model formulated in the frame of elasto-plasticity with generalised hardening, whose yield surface expands with pore fluid concentration. The model is validated against experimental results, both original and from the literature. Simulation results compare very well with those of tests performed on reconstituted, compacted and intact samples. [ABSTRACT FROM AUTHOR]

Abstract Background Optimizing access to recanalization therapies in acute ischemic stroke patients is crucial. Our aim was to measure the short and long term effectiveness, at the acute phase and 1 year after stroke, of four sets of actions implemented in the Rhône County. Methods The four multilevel actions were 1) increase in stroke units bed capacity and development of endovascular therapy; 2) improvement in knowledge and skills of healthcare providers involved in acute stroke management using a bottom-up approach; 3) development and implementation of new organizations (transportation routes, pre-notification, coordination by the emergency call center physician dispatcher); and 4) launch of regional public awareness campaigns in addition to national campaigns. A before-and-after study was conducted with two identical population-based cohort studies in 2006–7 and 2015–16 in all adult ischemic stroke patients admitted to any emergency department or stroke unit of the Rhône County. The primary outcome criterion was in-hospital management times, and the main secondary outcome criteria were access to reperfusion therapy (either intravenous thrombolysis or endovascular treatment) and pre-hospital management times in the short term, and 12-month prognosis measured by the modified Rankin Scale (mRS) in the long term. Results Between 2015–16 and 2006–7 periods ischemic stroke patients increased from 696 to 717, access to reperfusion therapy increased from 9 to 23% (p

BackgroundThe field of mobile health (mHealth) is constantly expanding. Integrating mHealth apps and devices in clinical practice is a major and complex challenge. General practitioners (GPs) are an essential link in a patient’s care pathway. As they are patients’ preferred health care intermediaries, GPs play an important role in supporting patients’ transition to mHealth. ObjectiveThis study aims to identify the factors associated with the willingness of French GPs to prescribe mHealth apps and devices to their patients. MethodsThis study was part of the ApiAppS project whose overall objective was to help remove barriers GPs face when prescribing mHealth apps and devices by developing a custom-built platform to aid them. The study included GPs recruited from the general practice department of several medical faculties in France (Lyon, Nice, and Rouen) and mailing lists of academic GPs, health care professional associations, and social and professional networks. Participants were asked to complete a web-based questionnaire that collected data on various sociodemographic variables, indicators of their involvement in continued education programs and the amount of time they dedicated to promoting healthy behaviors during patient consultations, and indicators characterizing their patient population. Data on their perceptions of mHealth apps and devices were also collected. Finally, the questionnaire included items to measure GPs’ acceptability of prescribing mHealth apps and devices for several health-related dimensions. ResultsOf the 174 GPs, 129 (74.1%) declared their willingness to prescribe mHealth apps and devices to their patients. In multivariate analysis, involvement in continued education programs (odds ratio [OR] 6.17, 95% CI 1.52-28.72), a better patient base command of the French language (OR 1.45, 95% CI 1.13-1.88), GP-perceived benefits of mHealth apps and devices for both patients and their medical practice and GP-perceived drivers for mHealth apps and device implementation in their medical practice (OR 1.04, 95% CI 1.01-1.07), and validation of mHealth apps and devices through randomized clinical trials (OR 1.02, 95% CI 1.00-1.04) were all associated with GPs’ willingness to prescribe mHealth apps and devices. In contrast, older GPs (OR 0.95, 95% CI 0.91-0.98), female GPs (OR 0.26, 95% CI 0.09-0.69), and those who perceived risks for the patient or their medical practice (OR 0.96, 95% CI 0.94-0.99) were less inclined to prescribe mHealth apps and devices. ConclusionsmHealth apps and devices were generally seen by GPs as useful in general medicine and were, for the most part, favorable to prescribing them. Their full integration in general medicine will be conditioned by the need for conclusive certification, transparency (reliable and precise data concerning mHealth app and device methods of construction and clinical validation), software aids to assist GPs prescribe them, and dedicated training programs.

Marie Viprey,1,2 Maïlys Gouillet,3 Costanza Puppo,3 Anne Termoz,1,2 Claire Della Vecchia,2,3 Laurent Derex,2,4 Julie Haesebaert,1,2 Anne-Marie Schott,1,2 Marie Préau3 1Public Health Department, Hospices Civils de Lyon, Lyon, France; 2HESPER EA 7425, University of Lyon, University Claude Bernard Lyon 1, Lyon, France; 3GRePS, Lyon 2 University, Lyon, France; 4Comprehensive Stroke Center, Pierre Wertheimer Hospital, Hospices Civils de Lyon, Bron, FranceCorrespondence: Marie VipreyHospices Civils de Lyon, Pôle de Santé Publique, Bâtiment A, 6ème étage, 162, Avenue Lacassagne, Lyon 69003, FranceTel +33 4 72 11 53 02Email marie.viprey@chu-lyon.frPurpose: Secondary prevention medications (SPM) reduce the risk of ischemic stroke (IS) and transient ischemic attack (TIA) recurrence. However, approximately one-third of patients are estimated to be non-adherent. This qualitative study aimed to explore barriers and facilitators to adherence to SPM after IS or TIA.Patients and Methods: Thirty-six face-to-face semi-structured interviews were conducted with 14 TIA patients and 22 IS patients who self-administered their treatment 12 months after IS/TIA. A thematic analysis was performed.Results: Major facilitators to good adherence to SPM were the fear of stroke recurrence and the high level of trust in the prescribing physician. Barriers included a perceived lack and/or inappropriate timing of information about SPM, practical difficulties of taking some SPM (eg, inadequate packaging) and of implementing routines into their daily life.Conclusion: Information on SPM is inadequate in terms of quantity and timing both during the acute IS/TIA period and over the long term. Providing more tailor-made information at an opportune moment, in particular by promoting discussion with their general practitioner (GP) throughout the course of illness and recovery, is essential to ensure that patients are not left alone in the decision-making process regarding adherence to SPM.Keywords: medication adherence, stroke, transient ischemic attack, qualitative study

Abstract This paper reports the case of a 46‐year‐old woman suffering from bipolar disorder of type I with mixed features with initial fronto‐temporal atrophy. Although considered treatment‐resistant to conventional strategies, she successfully responded to a combination of rivastigmine, clozapine, and oxcarbazepine.

A stochastic scheme, namely, PLM-Lap, has recently been propounded, which relies on the profile likelihood (PL) constructed with a Laplace distribution for estimating muscle activation onsets (MAOs) in surface electromyographic (sEMG) data. The MAO detection accuracy and robustness of the PLM-Lap have been empirically shown to be better than those of several state-of-the-art approaches. The algorithm designates the data point index associated with the maximum of the PL function as an onset occurrence by regarding every sEMG data point as a candidate onset and hence exhaustively evaluating the objective function. This article concerns an expedient and faster approach premised on the discrete Fibonacci search (DFS) to locate the maximum of the discrete PL function. The experimental results support that both the exhaustive and DFS procedures are equivalent in a statistical sense, whereas the latter offers impressive computational savings by a factor of approximately 90. Owing to the speed-up, the accuracy of MAO estimation may further be enhanced by modeling the sEMG data with a set of PL functions, each one built using a suitable probability distribution, and picking the estimate from the best model. Three statistical criteria, i.e., Kolmogorov-Smirnov, Lilliefors, and Anderson-Darling test, for choosing the probability distribution are recommended. A freely downloadable MATLAB package, namely PROLIFIC, meant for sEMG onset detection is available on MATLAB File Exchange from the following link: https://www.mathworks.com/matlabcentral/fileexchange/76495-prolific-profile-likelihood-based-on-fibonacci-search.

The purpose of this paper is the evaluation of the aero-propulsive effects on a UAV wing model with distributed propulsion. An array of three propellers is placed ahead of the leading edge of a rectangular wing with flap. The investigation was performed with high-fidelity numerical analyses to provide insights into the phenomenology and to screen the interesting positions to be validated in the wind tunnel. The propellers’ array is moved into twelve different positions, allowing longitudinal and vertical translations. The wing has an untwisted and constant section profile, with a single slot trailing-edge flap that is deflected into three positions. The flap span is entirely covered by the propellers’ blowing. Results show an increment of lift, drag, and pitching moment coefficients with distributed propellers enabled. For a given thrust level, the magnitude of such increments depends on the propellers’ positions, the flap configuration, and the angle of attack. The lift enhancement sought in distributed propulsion applications comes at the expense of a significant increase in drag and pitching moment magnitude. In some combinations, the wing’s contribution to the aircraft longitudinal stability is severely affected. Conversely, the propellers’ inflow is altered such that thrust is increased in all the investigated configurations, with a small reduction of propulsive efficiency.