Immune DNA signature of T-cell infiltration in breast tumor exomes.

Tumor infiltrating lymphocytes (TILs) have been associated with favorable prognosis in multiple tumor types. The Cancer Genome Atlas (TCGA) represents the largest collection of cancer molecular data, but lacks detailed information about the immune environment. Here, we show that exome reads mapping to the complementarity-determining-region 3 (CDR3) of mature T-cell receptor beta (TCRB) can be used as an immune DNA (iDNA) signature. Specifically, we propose a method to identify CDR3 reads in a breast tumor exome and validate it using deep TCRB sequencing. In 1,078 TCGA breast cancer exomes, the fraction of CDR3 reads was associated with TILs fraction, tumor purity, adaptive immunity gene expression signatures and improved survival in Her2+ patients. Only 2/839 TCRB clonotypes were shared between patients and none associated with a specific HLA allele or somatic driver mutations. The iDNA biomarker enriches the comprehensive dataset collected through TCGA, revealing associations with other molecular features and clinical outcomes

Approche générationnelle des pratiques culturelles et médiatiques

L’approche par générations – c’est-à-dire par groupes d’individus nés au même moment et ayant par conséquent le même calendrier de vie – permet de distinguer les effets d’âge des effets de génération. Appliquée aux résultats des quatre vagues d’enquête sur les pratiques culturelles des Français (1973, 1981, 1988, 1997) cette approche confirme la nature générationnelle de la plupart des évolutions constatées depuis le début des années 1970 en montrant qu’elles ont été généralement initiées par une génération particulière, puis poursuivies et amplifiées par les suivantes. La montée en charge de l’audiovisuel par rapport à l’imprimé, par exemple, apparaît comme une mutation amorcée il y a trente ans par le recul de la lecture de la presse quotidienne, poursuivie par l’augmentation du temps passé devant le petit écran au moment de l’explosion du PAF et, un peu plus tard, par une relative désaffection pour la lecture de livre, puis enfin amplifiée ces dernières années par la généralisation des ordinateurs. L’analyse rétrospective confirme que la plupart des pratiques culturelles et médiatiques traditionnellement mesurées depuis le début des années 1970 semblent s’acheminer vers un déclin plus ou moins marqué au cours des prochaines années, à l’exception de l’écoute de la musique enregistrée. Cette tendance générale apparaît d’autant plus probable que ces dernières années ont été marquées par l’émergence d’une culture numérique que les jeunes générations ont massivement investie et dont on peut penser par conséquent qu’elle est amenée à se développer dans les années à venir du simple fait du renouvellement générationnel. Il est donc difficile, dans une perspective prospective, de ne pas penser que l’essor de cette culture numérique en devenir ne se fasse, au moins en partie, au détriment des pratiques culturelles et médiatiques antérieures, en raison de la concurrence qu’elle crée en termes de budget et de budgettemps, mais aussi en raison de la nature même de l’offre qu’elle propose, tant au plan des contenus culturels écrits, audio ou vidéo que des possibilités de diffusion pour les anciens médias (presse, radio, télevision)

Case Report Of Ganser Syndrome In A 14-year-old Girl: Another Face Of Depressive Disorder ?

International audienceABSTRACT: The Ganser syndrome is rare in children and in adolescents. A case of Ganser syndrome in a 14-year-old girl, with three of the four essential features, is presented. After rapid resolution in two weeks, Ganser symptoms reappear seven months later accompanied, this second time, by previous depressive symptoms. This report raises the possibility of Ganser syndrome as a manifestation of depressive disorder in adolescence

Can a two-hour lecture by a pharmacist improve the quality of prescriptions in a pediatric hospital? A retrospective cohort study

Background: A high rate of prescription errors exists in pediatric teaching hospitals, especially during initial training.Objectives: To determine the effectiveness of a two-hour lecture by a pharmacist on rates of prescription errors and quality of prescriptions.Methods: A two-hour lecture led by a pharmacist was provided to 11 junior pediatric residents (PGY-1) as part of a one-month immersion program. A control group included 15 residents without the intervention. We reviewed charts to analyze the first 50 prescriptions of each resident.Results: Data were collected from 1300 prescriptions involving 451 patients, 550 in the intervention group and 750 in the control group. The rate of prescription errors in the intervention group was 9.6% compared to 11.3% in the control group (p=0.32), affecting 106 patients. Statistically significant differences between both groups were prescriptions with unwritten doses (p=0.01) and errors involving overdosing (p=0.04). We identified many errors as well as issues surrounding quality of prescriptions.Conclusion: We found a 10.6% prescription error rate. This two-hour lecture seems insufficient to reduce prescription errors among junior pediatric residents. This study highlights the most frequent types of errors and prescription quality issues that should be targeted by future educational interventions

Semaine d'Etude Mathématiques et Entreprises 1 : Modèles de comparaison quantitative de matrices 3D

Air Liquide dispose de jeux de données représentant des champs de quantité de dépôt de particules sur les poumons. Ces données proviennent de mesures 3D (obtenues via SPECT, Single Photon Emission Computer Tomography) du dépôt d'un aérosol contenant des particules radio-labellisées préalablement inhalé par les patients étudiés. Le sujet proposé ici consiste à se demander quelles sont les méthodes permettant de comparer de façon quantitative et systématique les résultats des observations, qui sont donnés sous la forme de matrices 3D correspondant à la quantité de particules estimée dans chaque voxel

Adolescents' self-reported health status, behaviours and health issues addressed during routine school doctor consultations in Switzerland: an observational study

BACKGROUND We aimed to investigate the self-reported health status and behaviours of 7th-grade adolescents, associations with gender and educational track, as well as health issues addressed during routine school doctor consultations in Switzerland. METHODS Data on health status and behaviours, specifically general well-being, stimulant and addictive substance use, bullying/violence, exercise, nutrition and health protection, and puberty/sexuality, were drawn from routinely collected self-assessment questionnaires from 1076 (of a total of 1126) students from 14 schools in the Swiss canton of Zug in 2020. Data on health issues addressed in school doctor consultations were collected by nine school doctors (for 595 individual consultations). Multilevel logistic regression analyses were used to investigate the association of gender and educational track with unfavourable health status or behaviours. RESULTS Although 92% (n = 989) of the students reported being happy or satisfied overall, 21% (n = 215) often or almost always felt sad, and 5-10% had repeatedly been seriously physically hurt (n = 67), sexually harassed with words (n = 88) or experienced uncomfortable physical contact (n = 60). Female gender and a lower educational track were associated with unfavourable health status. In 90% (n = 533) of the school doctor consultations, at least one topic of disease prevention or health promotion was addressed, whereby the topics addressed depended strongly on the individual school doctors. CONCLUSIONS Our findings revealed that unfavourable health status and behaviours were prevalent among adolescents but the health topics addressed in school doctor consultations were not tailored to students' self-reported health issues. A school-based approach that strengthens adolescents' health literacy and provides opportunities for patient-centred counselling has the potential to improve the current and future health of adolescents and, ultimately, adults. To realise this potential, it is essential for school doctors to be sensitised and trained to address students' health concerns. Emphasis should be placed on the importance of patient-centred counselling, the high prevalence of bullying, and gender and educational differences

A Re-Examination of Hebbian-Covariance Rules and Spike Timing-Dependent Plasticity in Cat Visual Cortex in vivo

Spike timing-dependent plasticity (STDP) is considered as an ubiquitous rule for associative plasticity in cortical networks in vitro. However, limited supporting evidence for its functional role has been provided in vivo. In particular, there are very few studies demonstrating the co-occurrence of synaptic efficiency changes and alteration of sensory responses in adult cortex during Hebbian or STDP protocols. We addressed this issue by reviewing and comparing the functional effects of two types of cellular conditioning in cat visual cortex. The first one, referred to as the “covariance” protocol, obeys a generalized Hebbian framework, by imposing, for different stimuli, supervised positive and negative changes in covariance between postsynaptic and presynaptic activity rates. The second protocol, based on intracellular recordings, replicated in vivo variants of the theta-burst paradigm (TBS), proven successful in inducing long-term potentiation in vitro. Since it was shown to impose a precise correlation delay between the electrically activated thalamic input and the TBS-induced postsynaptic spike, this protocol can be seen as a probe of causal (“pre-before-post”) STDP. By choosing a thalamic region where the visual field representation was in retinotopic overlap with the intracellularly recorded cortical receptive field as the afferent site for supervised electrical stimulation, this protocol allowed to look for possible correlates between STDP and functional reorganization of the conditioned cortical receptive field. The rate-based “covariance protocol” induced significant and large amplitude changes in receptive field properties, in both kitten and adult V1 cortex. The TBS STDP-like protocol produced in the adult significant changes in the synaptic gain of the electrically activated thalamic pathway, but the statistical significance of the functional correlates was detectable mostly at the population level. Comparison of our observations with the literature leads us to re-examine the experimental status of spike timing-dependent potentiation in adult cortex. We propose the existence of a correlation-based threshold in vivo, limiting the expression of STDP-induced changes outside the critical period, and which accounts for the stability of synaptic weights during sensory cortical processing in the absence of attention or reward-gated supervision

Formation and Thermal Stability of sub-10 nm Carbon Templates on Si(100)

We report a lithographic process for creating high-resolution (<10 nm) carbon templates on Si(100). A scanning electron microscope, operating under low vacuum (10E-6 mbar), produces a carbon-containing deposit ("contamination resist") on the silicon surface via electron-stimulated dissociation of ambient hydrocarbons, water and other adsorbed molecules. Subsequent annealing at temperatures up to 1320 K in ultra-high vacuum removes SiO2 and other contaminants, with no observable change in dot shape. The annealed structures are compatible with subsequent growth of semiconductors and complex oxides. Carbon dots with diameter as low as 3.5 nm are obtained with a 200 us electron-beam exposure time.Comment: 13 pages, 4 figure

APOE Isoforms Control Pathogenic Subretinal Inflammation in Age-Related Macular Degeneration

International audienc