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International audience; Apathy occurs in approximately one third of people after stroke. Despite its frequency and functional consequences, the determinants of apathy have only been partially defined. The major difficulty lies in disentangling the reduction in activity due to apathy itself from those secondary to comorbidities, such as depression, sensorimotor deficits, and cognitive impairment. Here, we aimed to examine the prevalence of apathy, identify confounding sources of hypoactivity, and define its neuroimaging determinants using multivariate voxel lesion symptom-mapping (mVLSM) analyses. We assessed apathy in a subgroup (n = 325, mean age: 63.8 ± 10.5 years, 91.1% ischemic stroke) of the GRECogVASC cohort using the validated Behavioral Dysexecutive Syndrome Inventory, interpreted using GREFEX criteria, as well as confounding factors (depression, anxiety, severity of the neurological deficit, and gait disorders). mVLSM analysis was used to define neuroimaging determinants and was repeated after controlling for confounding factors. Apathy was present for 120 patients (36.9%, 95% CI: 31.7-42.2). Stepwise linear regression identified three factors associated with apathy: depressive symptoms (R2 = .3, p = .0001), cognitive impairment (R2 = .015, p = .02), and neurological deficit (R2 = .110, p = .0001). Accordingly, only 9 (7.5%) patients had apathy without a confounding factor, i.e., isolated apathy. In conventional VLSM analysis, apathy was associated with a large number of subcortical lesions that were no longer considered after controlling for confounding factors. Strategic site analysis identified five regions associated with isolated apathy: the F3 orbitalis pars, left amygdala, left thalamus, left pallidum, and mesencephalon. mVLSM analysis identified four strategic sites associated with apathy: the right corticospinal tract (R2 = .11; p = .0001), left frontostriatal tract (R2 = .11; p = .0001), left thalamus (R2 = .04; p = .0001), and left amygdala (R2 = .01; p = .013). These regions remained significant after controlling for confounding factors but explained a lower amount of variance. These findings indicate that poststroke apathy is more strongly associated with depression, neurological deficit, and cognitive impairment than with stroke lesions locations, at least using VLSM analysis.

Background Gait disorders and cognitive impairments are prime causes of disability and institutionalization after stroke. We hypothesized that relative to single-task gait rehabilitation (ST GR), cognitive-motor dual-task (DT) GR initiated at the subacute stage would be associated with greater improvements in ST and DT gait, balance, and cognitive performance, personal autonomy, disability, and quality of life in the short, medium and long terms after stroke. Methods This multicenter (n=12), two-arm, parallel-group, randomized (1:1), controlled clinical study is a superiority trial. With p−1 gain in gait speed. Trial will include adult patients (18–90 years) in the subacute phase (0 to 6 months after a hemispheric stroke) and who are able to walk for 10 m (with or without a technical aid). Registered physiotherapists will deliver a standardized GR program (30 min three times a week, for 4 weeks). The GR program will comprise various DTs (phasic, executive function, praxis, memory, and spatial cognition tasks during gait) in the DT (experimental) group and gait exercises only in the ST (control) group. The primary outcome measure is gait speed 6 months after inclusion. The secondary outcomes are post-stroke impairments (National Institutes of Health Stroke Scale and the motor part of the Fugl-Meyer Assessment of the lower extremity), gait speed (10-m walking test), mobility and dynamic balance (timed up-and-go test), ST and DT cognitive function (the French adaptation of the harmonization standards neuropsychological battery, and eight cognitive-motor DTs), personal autonomy (functional independence measure), restrictions in participation (structured interview and the modified Rankin score), and health-related quality of life (on a visual analog scale). These variables will be assessed immediately after the end of the protocol (probing the short-term effect), 1 month thereafter (the medium-term effect), and 5 months thereafter (the long-term effect). Discussion The main study limitation is the open design. The trial will focus on a new GR program applicable at various stages after stroke and during neurological disease. Trial registration NCT03009773. Registered on January 4, 2017.

Some patients with subjective cognitive decline (SCD) progress to neurocognitive disorders (NCD), whereas others remain stable; however, the neuropsychological determinants of this progression have not been identified. Our objective was to examine baseline neuropsychological indicators that could discriminate between stable SCD Versus progression toward an NCD. We retrospectively included patients consulting for SCD at a university medical center's memory center (Amiens, France) who had undergone 3 or more neuropsychological assessments. Among the 80 patients with SCD, 11 had progressed to an NCD. The combination of age, memory, and speed scores at the baseline assessment predicted the progression of SCD with a sensitivity of 91%, and a negative predictive value of 98%. The present results constitute a first step (pending prospective studies) toward helping physicians to identify cases of SCD at risk of progression and, in particular, identifying patients with SCD who will not progress by examining baseline neuropsychological indicators. ClinicalTrials.gov ID: NCT04880252.

Background: Neurocognitive disorders (NCDs) are a part of the post-acute coronavirus disease (COVID-19) syndrome. No study has specifically evaluated NCDs in post-acute COVID-19 patients with cognitive complaints or their MRI determinants. Objective: To characterize NCDs in post-acute COVID-19 patients with cognitive complaints. The secondary objectives were to assess their clinical and MRI determinants. Methods: We included 46 patients with a post-acute COVID-19 cognitive complaint referred to the Amiens University Hospital Memory Center. They underwent a neuropsychological assessment and 36 had cerebral MRI. The G3 overall summary score was the sum of the mean z scores for the executive function, language, and action speed domains. Neuropsychological profiles were compared in a general linear model. Clinical determinants were analyzed by stepwise linear regression. White matter hyperintensities (WMH) masks were analyzed using parcel-based WMH symptom mapping to identify the locations of WMHs associated with cognitive performance. Results: Repeated ANOVA showed a group effect (p = 0.0001) due to overall lower performance for patients and a domain effect (p = 0.0001) due to a lower (p = 0.007) action speed score. The G3 overall summary score was significantly associated with solely the requirement for oxygen (R2 = 0.319, p = 0.031). WHMs were associated with the G3 overall summary score in the following structures, all right-sided (p

The aim of this study was to determine the contributions of background disorders responsible for participation restriction as indexed by a structured interview for the modified Rankin Scale (mRS-SI).A subset of 256 patients was assessed at 6 months after stroke using the National Institutes of Health Stroke Scale (NIHSS), gait score, comprehensive cognitive battery (yielding a global cognitive Z-score), behavioral dysexecutive disorders (DDs), anxiety and depressive symptoms, epilepsy, and headache. Following bivariate analyses, determinants of participation restriction were selected using ordinal regression analysis with partial odds.Poststroke participation restriction (mRS-SI score 1) was observed in 59% of the patients. In bivariate analyses, mRS-SI score was associated with prestroke mRS-SI score, 6-month NIHSS score, gait score, global cognitive Z-score, behavioral DDs, and presence of anxiety and depression (all: p = 0.0001; epilepsy: p =0.3; headache: p = 0.7). After logistic regression analysis, NIHSS score was associated with increasing mRS-SI score (p = 0.00001). Prestroke mRS-SI score (p = 0.00001), behavioral DDs (p = 0.0008) and global cognitive Z-score (p = 0.01) were associated with both mRS-SI score 1 and mRS-SI score 2. In addition, gait score was associated with mRS-SI score 2 (p = 0.00001). This model classified 85% of mRS-SI scores correctly (p = 0.001). Structural equation modeling showed the contributions of gait limitation (standardized coefficient [SC]: 0.68; p = 0.01), prestroke mRS-SI (SC: 0.41; p = 0.01), severity of neurological impairment (SC: 0.16; p = 0.01), global cognitive Z-score (SC: -0.14; p = 0.05), and behavioral DDs (SC: 0.13; p = 0.01).These results provide a statistical model of weights of determinants responsible for poststroke participation restriction and highlight a new independent determinant: behavioral DDs.

Although action slowing is the main cognitive impairment in stroke survivors, its mechanisms and determinants are still poorly understood. The objectives of the present study were to determine the mechanisms of post-stroke action slowing (using validated, highly specific simple reaction time (SRT) and tapping tests) and identify its imaging determinants (using multivariate lesion-symptom mapping (mLSM)).Action speed in the GRECogVASC cohort was assessed using finger tapping and SRT tests performed with both hands and analyzed using previously validated indices. Imaging determinants were identified using validated mLSM analyses and disconnection analysis and compared to those of an fMRI activation meta-analytic database.Both the tapping time and SRT were 10.7% slower for the 394 patients (p = 0.0001) than for the 786 controls, without a group × test interaction (p = 0.2). The intra-individual distribution curve was characterized by a rightward shift with an unaltered attentional peak. The mLSM analyses showed tapping to be associated with lesions in the frontostriatal tract (p = 0.0007). The SRT was associated with lesions in the frontostriatal tract (p = 0.04) and the orbital part of F3 (p = 0.0001). The SRT-tapping index was associated with lesions in the orbital part of F3 (p = 0.0001). All lesions were located in the right hemisphere only and were responsible for the disconnection of several structures involved in motor preparation, initiation, and speed. A comparison with fMRI activation meta-analytic data highlighted mostly the same regions, including the orbital part of F3, the ventral and dorsal parts of F1, and the premotor and cingulate regions in the right hemisphere.Our results confirm the marked impairment of action speed in stroke and show that the primary mechanism is motor slowing and that it is related to lesions in the right frontostriatal tract. A deficit in sustained alertness accounted for action slowing in the subgroup with lesions in the right orbital part of F3. Our SRT and mLSM results were in accordance with the fMRI activation data. Thus, stroke induces slowing in the broad network associated with SRT tasks by disrupting the frontostriatal tract and, to a lesser extent, other sites involved in attention.

Gene expression is regulated by promoters and enhancers marked by histone H3 lysine 27 acetylation (H3K27ac), which is established by the paralogous, multidomain-containing histone acetyltransferases (HAT) EP300 and CBP. These enzymes display overlapping regulatory roles in untransformed cells, but less characterized roles in cancer cells. We demonstrate that the majority of high-risk pediatric neuroblastoma (NB) depends on EP300, whereas CBP has a limited role. To disrupt EP300, we developed a proteolysis-targeting chimera (PROTAC) compound termed “JQAD1” that selectively targets EP300 for degradation. JQAD1 treatment causes loss of H3K27ac at the enhancers that regulate NB master transcription factors, and drives rapid NB apoptosis, with limited toxicity to untransformed cells where CBP may compensate. In parallel, we demonstrate that EP300 and CBP have subdomain-specific functions, with enriched activity for individual domains in distinct tumor lineages. These data provide a foundation for interrogation of these histone acetyltransferases in distinct tumor types and new strategies for therapeutic disruption of subdomain and scaffolding activities of these multidomain proteins in cancer. Citation Format: Adam D. Durbin, Noha Shendy, Audrey Mercier, Yang Zhang, Melissa J. Bikowitz, Logan H. Sigua, Sarah Robinson, Tingjian Wang, Barbara Jonchere, A. Thomas Look, Mark W. Zimmerman, Martine Roussel, Brian J. Abraham, Ernst Schonbrunn, Kimberly Stegmaier, Jun Qi. Targeting EP300 and CBP for therapeutic benefit in pediatric solid tumors. [abstract]. In: Proceedings of the AACR Special Conference: Cancer Epigenomics; 2022 Oct 6-8; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2022;82(23 Suppl_2):Abstract nr PR005.

Germline loss-of-function (LOF) mutations in Elongator complex protein 1 (ELP1) are found in 15-20% of childhood SHH medulloblastoma (MB) and are exceedingly rare in non-SHH-MB or other cancers. ELP1 germline carriers that develop SHH-MB harbor frequent somatic PTCH1 mutations and universally sustain loss-of-heterozygosity of the remaining ELP1 allele through chromosome 9q deletion. ELP1 functions as a scaffolding subunit of the Elongator complex that is required for posttranscriptional modification of tRNAs and maintenance of efficient translational elongation and protein homeostasis. However, the molecular, biochemical, and cellular mechanisms by which ELP1/Elongator LOF contribute to SHH-MB tumorigenesis remain largely unknown. Herein, we report that mice harboring germline Elp1 monoallelic loss (i.e., Elp1+/-) exhibit hallmark features of malignant predisposition in developing cerebellar granule neuron progenitors (GNPs), the lineage-of-origin for SHH-MB. Elp1+/- GNPs are characterized by increased replication stress-induced DNA damage, upregulation of the homologous recombination repair pathway, aberrant cell cycle, and attenuation of p53-dependent apoptosis. CRISPR/Cas9-mediated Elp1 and Ptch1 gene targeting in mouse GNPs reproduces highly penetrant SHH-MB tumors recapitulating the molecular and phenotypic features of patient tumors. Reactivation of the p53 pathway through MDM2 and PAK4 inhibitors promotes selective cell death in patient-derived xenograft tumors (PDX) harboring deleterious ELP1 mutations. Together, our findings reveal that germline Elp1 deficiency heightens genomic instability and survival in GNPs, providing a mechanistic model for the subgroup-restricted pattern of predisposition and malignancy associated with pathogenic ELP1 germline carriers. These results provide rationale for further preclinical studies evaluating drugs that overcome p53 pathway inhibition in ELP1-associated SHH-MB and a renewed outlook for improving treatment options for affected children and their families.*, # Contributed equally

The frequency of executive disorders in mild-to-moderate Alzheimer disease (AD) has been demonstrated by the application of a comprehensive battery. The present study analyzed data from 2 recent multicenter studies based on the same executive battery. The objective was to derive a shortened battery by using the GREFEX population as a training dataset and by cross-validating the results in the REFLEX population. A total of 102 AD patients of the GREFEX study (MMSE=23.2±2.9) and 72 patients of the REFLEX study (MMSE=20.8±3.5) were included. Tests were selected and receiver operating characteristic curves were generated relative to the performance of 780 controls from the GREFEX study. Stepwise logistic regression identified 3 cognitive tests (Six Elements Task, categorical fluency and Trail Making Test B error) and behavioral disorders globally referred as global hypoactivity (P=0.0001, all). This shortened battery was as accurate as the entire GREFEX battery in diagnosing dysexecutive disorders in both training group and the validation group. Bootstrap procedure confirmed the stability of AUC. A shortened battery based on 3 cognitive tests and 3 behavioral domains provides a high diagnosis accuracy of executive disorders in mild-to-moderate AD.

Background and Purpose- We aimed to define the neuroimaging determinants of poststroke cognitive performance and their relative contributions among a spectrum of magnetic resonance imaging markers, including lesion burden and strategic locations. Methods- We prospectively included patients with stroke from the GRECogVASC study (Groupe de Réflexion pour l'Évaluation Cognitive Vasculaire) who underwent 3-T magnetic resonance imaging and a comprehensive standardized battery of neuropsychological tests 6 months after the index event. An optimized global cognitive score and neuroimaging markers, including stroke characteristics, cerebral atrophy markers, and small vessel diseases markers, were assessed. Location of strategic strokes was determined using a specifically designed method taking into account stroke size and cerebral atrophy. A stepwise multivariable linear regression model was used to identify magnetic resonance imaging determinants of cognitive performance. Results- Data were available for 356 patients (mean age: 63.67±10.6 years; 326 [91.6%] of the patients had experienced an ischemic stroke). Six months poststroke, 50.8% of patients presented with a neurocognitive disorder. Strategic strokes (right corticospinal tract, left antero-middle thalamus, left arcuate fasciculus, left middle frontal gyrus, and left postero-inferior cerebellum; R

The contrast between memory versus executive function impairments is commonly used to differentiate between neurocognitive disorders (NCDs) due to Alzheimer's disease (AD) and vascular cognitive impairment (VCI). We reconsidered this question because of the current use of AD biomarkers and the recent revision of the criteria for AD, VCI, and dysexecutive syndrome.To establish and compare the neuropsychological profiles in AD (i.e., with positive CSF biomarkers) and in VCI.We included 62 patients with mild or major NCDs due to pure AD (with positive CSF biomarker assays), and 174 patients (from the GRECogVASC cohort) with pure VCI. The neuropsychological profiles were compared after stratification for disease severity (mild or major NCD). We defined a memory-executive function index (the mean z score for the third free recall and the delayed free recall in the Free and Cued Selective Reminding Test minus the mean z score for category fluency and the completion time in the Trail Making Test part B) and determined its diagnostic accuracy.Compared with VCI patients, patients with AD had significantly greater memory impairments (p = 0.001). Executive function was impaired to a similar extent in the two groups (p = 0.11). Behavioral executive disorders were more prominent in the AD group (p = 0.001). Although the two groups differed significant with regard to the memory-executive function index (p 0.001), the latter's diagnostic accuracy was only moderate (sensitivity: 63%, specificity: 87%).Although the contrast between memory and executive function impairments was supported at the group level it does not reliably discriminate between AD and VCI at the individual level.

Although most children with medulloblastoma (MB) are cured of their disease, SONIC HEDGEHOG (SHH) subgroup MB driven by TRP53 mutations is essentially lethal. Casein Kinase 1α (CK1α) phosphorylates and destabilizes GLI transcription factors, thereby inhibiting the key effectors of SHH signaling. We therefore tested a second-generation CK1α activator against, TRP53 mutant, MYCN amplified MB. Our novel CK1α activator inhibited SHH activity in vitro, acting downstream of the vismodegib target SMOOTHENED (SMO), and reduced the viability of sphere cultures derived from SHH MB. SSTC3 accumulated in the brain, inhibited growth of SHH MB tumors, and blocked metastases in a genetically-engineered vismodegib-resistant mouse model of SHH MB. Importantly, SSTC3 attenuated growth and metastasis of orthotopic patient-derived TRP53 mutant, MYCN amplified, SHH subgroup MB xenografts, increasing overall survival. Thus, a CK1α agonist penetrates into the brain, and shows efficacy against metastatic TRP53 mutant MB, which are resistant to existing therapies including the SMO inhibitors currently being evaluated clinically.

International audience; Hypertelescopes are large optical interferometric arrays, employing many small mirrors and a miniature pupildensifier before the focal camera, expected to produce direct images of celestial sources at high resolution. Their peculiar imaging properties, initially explored through analytical derivations, had been verified with simulations before testing a full-size testbed instrument. We describe several architectures and optical design solutions and present recent progress made on the Ubaye hypertelescope experiment. Arecibo-like versions with a fixed spherical primary meta-mirror, or an active aspheric one, have a suspended focal beam combiner equipped for pupil-drift accommodation, with a field-mosaic arrangement for observing multiple sources such as exoplanetary systems, globular clusters or active galactic nuclei. We have developed a cable suspension and drive system with tracking accuracy reaching a millimeter at 100m above ground.

Executive dysfunctions in Alzheimer's disease (AD) have been assessed using variable batteries and/or in selected populations.The primary objective of this observational study was to determine the prevalence and severity of executive dysfunction in AD patients using a previously validated battery. The secondary objective was to determine the characteristics including treatment outcomes of AD patients with severe executive dysfunction.The study included AD patients with mild-to-moderate dementia aged 60 or over, consulting in various clinical settings including memory clinics and requiring the introduction of an antidementia drug. Executive dysfunction was examined using a validated, shortened executive battery.381 patients were included. Executive dysfunctions were observed in 88.2% of the patients (95% CI: 84.9-91.4) and were severe (defined as ≥2/3 impaired scores) in 80.4% (95% CI: 76.9-84.8). Global hypoactivity with apathy was more frequent (p = 0.0001) than impairment in executive function tests. The 308 patients with severe executive dysfunction were older (p = 0.003) and had more severe dementia (p = 0.0001). Similarly, in the subset of 257 patients with mild dementia, individuals with severe executive dysfunction were older (p = 0.003) and had more severe dementia. Global hypoactivity was independently associated with difficulties in IADL and a higher caregiver burden (p = 0.0001 for both). The severity of executive dysfunction did not significantly influence the patients' outcomes at 6 months.Executive dysfunction is a very common disorder in a representative population of patients with mild-to-moderate AD. It was independently correlated with impaired autonomy and increased caregiver burden but did not significantly influence treatment outcomes.

Action slowing is frequently observed in multiple sclerosis (MS) patients. Several factors may account for response slowing: motor, perceptual, cognitive deficits, global mental slowing. Our objective was to examine mechanisms accounting for action slowing in MS patients.Twenty MS patients, free of visual impairment and of upper limbs sensory-motor deficit underwent previously validated reaction time (RT) tests using visual stimuli. Three tasks were used: (1) motor tapping, (2) simple reaction time (SRT) in a simple and dual task condition, and (3) choice RT (CRT) with varying response probabilities. Results were compared to those of 20 healthy matched subjects.MS patients had: (1) lower motor tapping frequency (p=0.02); (2) SRT lengthening (p=0.001) related to a lower proportion of fast responses (p=0.001) indicating attentional deficit whereas perceptuomotor index was spared (p=0.5), without higher sensitivity to dual task (p=0.9); and (3) CRT lengthening (p=0.001) with spared decision time (p=0.7).This study showed that action slowing of MS patient is mainly related to (1) attentional deficit resulting in inability to maintain high level of rapid actions, and (2) subtle motor slowing even in patients without motor deficit on clinical examination, whereas (3) divided attention and decisional process are preserved.

International audience

The aim of this study was to determine the neuropsychological consequences of a middle interhemispheric approach for the removal of tumors of the third or lateral ventricles. A retrospective analysis of eight callosotomized patients for ventricular tumors (three males/five females; mean age: 48.7 ± 11.2 years; education level: 11.9 ± 2.9 years) and eight healthy subjects was performed. An extensive neuropsychological test battery was used to evaluate global intellectual efficiency, memory capacities, executive functions, and interhemispheric transfer of a procedural learning task (serial reaction time task/SRTT). Neuropsychological results showed that: (1) five of eight patients operated through a middle transcallosal approach had disturbances of verbal or visual memory; (2) three of eight patients displayed a dysexecutive cognitive syndrome(two of eight of whom presenting with a deficit of verbal fluency); (3) two of eight patients presented a dysexecutive behavior syndrome; and (4) with regard to the SRTT, although all participants learned the task, in contrast to controls, the callosotomized patients showed an increase in reaction times and an absence of interhemispheric transfer of learning from one hand to the other. The transcallosal approach transects a large number of callosal fibers. This damage accounts for the deficits of memory, the dysexecutive cognitive and behavioral syndrome, and disturbances in interhemispheric transfer of learning.

Objective: Disorders of executive functions are among the most frequent cognitive deficits, but they remain poorly defined and are subject to heterogeneous assessment. To address this major issue, the Groupe de Reflexion sur l'Evaluation des Fonctions Executives (GREFEX) group has proposed criteria for behavioral and cognitive dysexecutive syndromes and has designed a battery including a specific heteroquestionnaire and 7 cognitive tests. We investigated the frequency of behavioral and cognitive dysexecutive disorders in patients suffering from various diseases and the association of these disorders with loss of autonomy. Methods: A total of 461 patients aged between 16 and 90 years with severe traumatic brain injury, stroke, mild cognitive impairment, Alzheimer disease, multiple sclerosis, and Parkinson disease were recruited into this prospective cohort study by 21 centers between September 2003 and June 2006. Behavioral and cognitive dysexecutive disorders were examined using the GREFEX battery. Results: A dysexecutive syndrome was observed in 60% of patients, concerning both behavioral and cognitive domains in 26% and dissociated in 34%. All behavioral and cognitive dysexecutive disorders discriminated (p ¼ 0.001, all) patients from controls. The pattern of cognitive syndrome differed (p ¼ 0.0001) according to the disease. Finally, behavioral (odds ratio (OR), 4.6; 95% confidence interval (CI), 2. 3-9.1; p ¼ 0.0001) and cognitive (OR, 3.36; 95% CI, 1.7-6.6; p ¼ 0.001) dysexecutive syndromes and Mini Mental State Examination score (OR, 0.79; 95% CI, 0.68-0.91; p ¼ 0.002) were independent predictors of loss of autonomy. Interpretation: This study provided criteria of dysexecutive syndrome and showed that both behavioral and cognitive syndromes contribute to loss of autonomy. Profiles vary across patients and diseases, and therefore systematic assessment of behavioral and cognitive disorders in reference to diagnostic criteria is needed. ANN NEUROL 2010;68:855-864

Introduction La dichotomisation manuelle des performances (normal vs pathologique), en fonction des criteres âge et de niveau socioculturel, d’un bilan neuropsychologique est couteuse en temps au regard des nombreux scores. Objectifs L’objectif du travail est de presenter un outil d’assistance informatise, « AMIENSCOG » et de montrer son interet lors de l’evaluation neuropsychologique et en particulier le gain de temps obtenu. Methodes L’interet de cet outil sera illustre en montrant qu’il permet de : – realiser automatiquement la dichotomisation des scores aux tests selon les donnees normatives ; – sauvegarder les donnees, en permettant de les consulter ou les modifier ; – d’exporter les scores et leur interpretation dichotomisee vers une base de donnees. Des analyses de comparaisons des temps de saisie et d’interpretation des scores aux bilans realises manuellement et avec « AMIENSCOG » ont ete effectuees. Resultats Durant la periode de 2008 a 2013, 4473 bilans ont ete effectues totalisant plus de 122000 scores qui ont ete rentres dans « AMIENSCOG » et automatiquement interpretes en normal vs pathologique. Les resultats de la comparaison entre les temps de saisie et l’interpretation des scores, montrent des temps pour « AMIENSCOG » (m = 284 ± 48 s) inferieurs ( p = 0,001) a ceux des bilans realises manuellement ( m = 284 ± 128 s). Discussion Ces resultats montrent que « AMIENSCOG » offre un gain de temps significatif sur la saisie et l’interpretation des scores mais aussi grâce a l’export automatique sur Excel. Il facilite et fiabilise le recueil et l’interpretation des scores automatiquement dichotomises en normal vs pathologique, en produisant une version papier synthetique regroupant les donnees cliniques et les scores en fonction des principales fonctions cognitive. Conclusion « AMIENSCOG » offre une aide precieuse au clinicien et chercheur en permettant un acces plus facile, plus rapide et plus fiable aux donnees neuropsychologiques disponibles avec un export possible vers une base de donnee. Informations complementaires Demonstration en direct possible du logiciel.

Macrophage infiltration of solid tumors correlates with poor prognosis for cancer patients. However, the tumor associated macrophage (TAM) phenotype appears complex and does not emulate the current in vitro paradigms of macrophage activation. To determine TAM phenotypes from a variety of solid tumors from distinct organ types, we analyzed global TAM gene expression profiles. > 90% of all gene expression was similar between TAMs isolated from gliomas, thymomas and spontaneously occurring neuroblastomas in mice, suggesting TAMs have a common phenotype regardless of tumor type or location. Importantly, many of the genes with the highest observed expression are involved in macrophage-mediated regulation of the inflammatory response. We have collected gene expression data from TAMs impaired in IL-1 and TLR signaling (Myd88-/-) and observed a MyD88-depedent regulation of multiple secreted proteins involved in Stat3 signaling (IL-6, IL-10, G-CSF) and T cell functional differentiation (IL-23p19, IL-12p40, IL-12p35). Harvesting macrophages from genetic mouse models, we have developed an in vitro neuroblastoma sphere/TAM tissue culture system to define the autocrine/paracrine mechanisms involved in both MyD88- and Stat3-dependent signaling networks, ultimately leading to defining their involvement in T cell differentiation and/or function. Our data will clarify the tumor/TAM relationship and potentially reveal TAM-specific targets for future therapeutic application.

Introduction. Le TOP 12 evalue la memoire collective au travers d'une serie de huit types de questions portant sur le souvenir de la vie de 12 celebrites nommement designees. La validation de tels tests est souvent envisagee dans le seul but de predire un critere externe au test (validation externe) ; la validation interne n'est quant a elle que tres rarement etudiee. Objectifs. Montrer comment les reponses obtenues peuvent mesurer une seule grandeur hypothetique (appelee aussi construit) : la capacite de la memoire collective. Methodes. L'echantillon est compose de 145 sujets (91 temoins, 32 patients presentant une maladie d'Alzheimer, 21 patients ayant un trouble cognitif leger de type amnesique, 1 patient ayant une demence semantique). Deux etapes sont necessaires : modeliser les reponses aux items a l'aide d'un modele de reponse a l'item a trois parametres et tester l'unidimensionnalite des scores estimes. Resultats. Les huit modeles s'ajustent etroitement aux donnees. L'analyse factorielle confirmatoire ne permet pas de rejeter l'idee selon laquelle les huit types de questions mesurent bien une seule et unique grandeur hypothetique. Conclusion. La modelisation psychometrique des donnees observees avec le TOP 12 indique qu'elles mesurent la capacite de la memoire collective. Mots cles : memoire collective * TOP 12 * validation interne * modelisation psychometrique * grandeur hypothetique