A twelve-month follow-up of an information communication technology delivered intervention for children with autism spectrum disorder living in regional Australia

This study investigated the long-term follow-up of an information communication techonology based intervention, the Therapeutic Outcomes By You application, for children with autism spectrum disorder living in regional Australia. Fifteen participants who completed a three-month randomised controlled trial of the Therapeutic Outcomes By You were assessed at least 12 months post-intervention to determine the maintenance or continued improvement of their language and social communication skills. Findings demonstrate the receptive language, social skills, pragmatic language and playfulness of children with autism spectrum disorder improved during the three-month intervention period and were maintained at least 12 months after ceasing the Therapeutic Outcomes By You app intervention

A prospective cohort study assessing clinical referral management & workforce allocation within a UK regional medical genetics service

Abstract Ensuring patient access to genomic information in the face of increasing demand requires clinicians to develop innovative ways of working. This paper presents the first empirical prospective observational cohort study of UK multi-disciplinary genetic service delivery. It describes and explores collaborative working practices including the utilisation and role of clinical geneticists and non-medical genetic counsellors. Six hundred and fifty new patients referred to a regional genetics service were tracked through 850 clinical contacts until discharge. Referral decisions regarding allocation of lead health professional assigned to the case were monitored, including the use of initial clinical contact guidelines. Significant differences were found in the cases led by genetic counsellors and those led by clinical geneticists. Around a sixth, 16.8% (109/650) of referrals were dealt with by a letter back to the referrer or re-directed to another service provider and 14.8% (80/541) of the remaining patients chose not to schedule an appointment. Of the remaining 461 patients, genetic counsellors were allocated as lead health professional for 46.2% (213/461). A further 61 patients did not attend. Of those who did, 86% (345/400) were discharged after one or two appointments. Genetic counsellors contributed to 95% (784/825) of total patient contacts. They provided 93.7% (395/432) of initial contacts and 26.8% (106/395) of patients were discharged at that point. The information from this study informed a planned service re-design. More research is needed to assess the effectiveness and efficiency of different models of collaborative multi-disciplinary working within genetics services. Keywords (MeSH terms) Genetic Services, Genetic Counseling, Interdisciplinary Communication, Cohort Studies, Delivery of Healthcare, Referral and Consultation

Effects of eight neuropsychiatric copy number variants on human brain structure

Many copy number variants (CNVs) confer risk for the same range of neurodevelopmental symptoms and psychiatric conditions including autism and schizophrenia. Yet, to date neuroimaging studies have typically been carried out one mutation at a time, showing that CNVs have large effects on brain anatomy. Here, we aimed to characterize and quantify the distinct brain morphometry effects and latent dimensions across 8 neuropsychiatric CNVs. We analyzed T1-weighted MRI data from clinically and non-clinically ascertained CNV carriers (deletion/duplication) at the 1q21.1 (n = 39/28), 16p11.2 (n = 87/78), 22q11.2 (n = 75/30), and 15q11.2 (n = 72/76) loci as well as 1296 non-carriers (controls). Case-control contrasts of all examined genomic loci demonstrated effects on brain anatomy, with deletions and duplications showing mirror effects at the global and regional levels. Although CNVs mainly showed distinct brain patterns, principal component analysis (PCA) loaded subsets of CNVs on two latent brain dimensions, which explained 32 and 29% of the variance of the 8 Cohen’s d maps. The cingulate gyrus, insula, supplementary motor cortex, and cerebellum were identified by PCA and multi-view pattern learning as top regions contributing to latent dimension shared across subsets of CNVs. The large proportion of distinct CNV effects on brain morphology may explain the small neuroimaging effect sizes reported in polygenic psychiatric conditions. Nevertheless, latent gene brain morphology dimensions will help subgroup the rapidly expanding landscape of neuropsychiatric variants and dissect the heterogeneity of idiopathic conditions

A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Purpose Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the “ClinVar low-hanging fruit” reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion The “ClinVar low-hanging fruit” analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock

Evaluation du risque hémorragique chez les patients traités par aspirine en chirurgie de revascularisation coronarienne à coeur battant

La chirurgie de revascularisation coronarienne réalisée à coeur battant a permis de diminuer les pertes sanguines comparativement à la chirurgie avec circulation extracorporelle. Néanmoins le traitement par l'aspirine, qui est régulièrement poursuivi jusqu'à la veille de l'intervention chez le patient coronarien, peut majorer le saignement. Le but de cette étude rétrospective a été d'évaluer le risque hémorragique et transfusionnel des patients en fonction qu'ils étaient traités ou non par aspirine et opérés de pontages coronariens à cœur battant. Sur les 14 mois étudiés, 91 patients ont été inclus. Le groupe aspirine incluait 40 patients, le groupe sans aspirine incluait 51 patients. Tous les patients étaient opérés selon la technique du cœur battant. Le protocole anesthésique était le même pour tous les patients et comprenait systématiquement une dose unique d'aprotinine de 2.000.000 UIK. Les paramètres relatifs au saignement et à la transfusion étaient relevés en peropératoire et pendant les 48 premières heures postopératoires. Des critères cliniques et biologiques étaient recueillis durant les 48 premières heures de la prise en charge en réanimation nous permettant de déterminer l'incidence des évènements ischémiques myocardiques. Nous notions les durées de séjours hospitaliers et en réanimation. Enfin, nous relevions les décès survenus au cours du séjour hospitalier. Les deux populations étaient comparables. La transfusion peropératoire et durant les 48 premières heures postopératoires n'était pas différente dans les deux groupes de même que la quantité des pertes sanguines en réanimation et le nombre de reprises chirurgicales pour syndrome hémorragique. L'incidence des évènements secondaires était similaire dans les deux groupes. Le résultat principal de cette étude est que la prise d'aspirine n'est pas un facteur de risque transfusionnel en périodes per et postopératoires d'une chirurgie programmée de revascularisation coronarienne à coeur battant, dans le cadre d'un protocole avec aprotinine.ROUEN-BU Médecine-Pharmacie (765402102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Les maladies transmissibles du lapin de garenne (Oryctolagus cuniculus) en liberté

LYON1-BU Santé (693882101) / SudocTOULOUSE-EN Vétérinaire (315552301) / SudocSudocFranceF

Geochemistry of the Society and Pitcairn-Gambier mantle plumes: what they share and do not share

International audienceThe South Pacific Superswell in Polynesia is associated with a large seismic mantle anomaly at depth, the Polynesian dome, and it is characterized by the volcanic activity of five different hotspots giving birth to the Marquesas, Society, Pitcairn-Gambier, Cook-Austral and Arago island chains. Here we present new isotopic and major and trace element data in basalts from two of these chains, the Society and Pitcairn-Gambier chains, in order to examine the similarities and differences of their mantle source regions. In the Society chain the entire geochemical diversity of the archipelago exists at the scale of individual islands with no systematic trend over time. In contrast, a clear geochemical dichotomy exists along the Pitcairn-Gambier chain between the old volcanoes (Muru basalts from Mururoa, Fangataufa, Gambier, > 5 My) and their younger counterparts (Pitis basalts from Pitcairn Island and Seamounts, <1 My). The Muru group has high NbN/Nb* and Ce/Pb, low 87Sr/86Sr and define a steep trend in Nd-Hf isotopic space, features that call for old eclogite in their mantle source. The unradiogenic Pb isotopic ratios of Muru basalts, well below the values observed in HIMU (“high µ”’, or high 238U/204Pb) localities, are not easily explained by varying the age and composition of the eclogite and may call for the involvement of Pacific lower mantle in the source region. In contrast, the Pitis basalts share with the Society basalts low NbN/Nb* and radiogenic 87Sr/86Sr suggesting incorporation of continental material in their source region. While the Society source simply incorporates modern-like terrigenous sediments, the combination of low Ba/La, 143Nd/144Nd and 176Hf/177Hf and very high 208Pb*/206Pb* in Pitis basalts make the Pitis source unique and not sampled anywhere else on Earth. The Pitis source contains old, possibly Archean, material of unclear origin because it resembles neither modern lower continental crust nor modern pelagic sediments. Finally, the distribution of heterogeneities in the two mantle plumes is also very different: discrete filaments are randomly dispersed across the Society plume stem while eclogitic and continent-derived filaments are vertically separated under the Pitcairn-Gambier chain. By combining these results with those published for other Polynesian chains, we establish a snapshot of the composition, geometry and distribution of the crustal components present in the Polynesian dome

High-precision lead isotopes and stripy plumes: Revisiting the Society chain in French Polynesia

International audienceAn increasing number of geochemical studies looked for spatial organization of the isotopic variations along Pacific volcanic island chains (e.g., Hawaii, Marquesas, Samoa and Society Islands) in order to discuss the possible zoning of the plume conduits. Here, we reexamine the occurrence of isotopic stripes in the Society archipelago in French Polynesia, using new Sr-Nd-Hf-Pb isotope ratios of sixty-six lavas from six islands (Mehetia, Moorea, Maupiti, Huahine, Raiatea, Bora-Bora). We demonstrate that the Pb isotope variability observed using literature data is an analytical artifact related to the poor control of mass fractionation during Pb measurements by conventional TIMS technique. New MC-ICP-MS Pb data demonstrate that the isotopic stripes as previously defined disappear. They rather show that individual islands cover a significant part of the entire isotopic range of the chain. We suggest, therefore, that the dominant characteristic of the Society plume is small-scale heterogeneities, evenly distributed within the plume conduit. At a global scale, we show that some ocean island chains with similar geochemical and isotopic characteristics, such as Samoa and Society Islands, define different arrays when variations of Nd with high-precision Pb isotopes are considered. We proposed that this puzzling observation might record differences in recycling age of the basalt + sediment mixture subducted into the mantle and sampled by mantle plume