Neuropsychological and functional outcomes in recent-onset major depression, bipolar disorder and schizophrenia-spectrum disorders: a longitudinal cohort study

Functional disability is the lead contributor to burden of mental illness. Cognitive deficits frequently limit functional recovery, although whether changes in cognition and disability are longitudinally associated in recent-onset individuals remains unclear. Using a prospective, cohort design, 311 patients were recruited and assessed at baseline. One hundred and sixty-seven patients met eligibility criteria (M = 21.5 years old, s.d. = 4.8) and returned for follow-up (M = 20.6 months later, s.d. = 7.8). Two-hundred and thirty participants were included in the final analysis, comprising clinically stable patients with major depression (n = 71), bipolar disorder (BD; n = 61), schizophrenia-spectrum disorders (n = 35) and 63 healthy controls. Neuropsychological functioning and self-rated functional disability were examined using mixed-design, repeated-measures analysis, across diagnoses and cognitive clusters, covarying for relevant confounds. Clinical, neuropsychological and functional changes did not differ between diagnoses (all P40.05). Three reliable neuropsychological subgroups emerged through cluster analysis, characterized by psychomotor slowing, improved sustained attention, and improved verbal memory. Controlling for diagnosis and changes in residual symptoms, clusters with improved neuropsychological functioning observed greater reductions in functional disability than the psychomotor slowing cluster, which instead demonstrated a worsening in disability (Po0.01). Improved sustained attention was independently associated with greater likelihood of follow-up employment (Po0.01). Diagnosis of BD uniquely predicted both follow-up employment and independent living. Neuropsychological course appears to be independently predictive of subjective and objective functional outcomes. Importantly, cognitive phenotypes may reflect distinct pathophysiologies shared across major psychiatric conditions, and be ideal targets for personalized early intervention

Climate and soil type together explain the distribution of microendemic species in a biodiversity hotspot

The grasshopper genus Caledonula, endemic to New Caledonia, was studied to understand the evolution of species distributions in relation to climate and soil types. Based on a comprehensive sampling of 80 locations throughout the island, the genus was represented by five species, four of which are new to science, of which three are described here. All the species have limited distributions in New Caledonia. Bioclimatic niche modelling shows that all the species were found in association with a wet climate and reduced seasonality, explaining their restriction to the southern half of the island. The results suggest that the genus was ancestrally constrained by seasonality. A molecular phylogeny was reconstructed using two mitochondrial and two nuclear markers. The partially resolved tree showed monophyly of the species found on metalliferous soils, and molecular dating indicated a rather recent origin for the genus. Adaptation to metalliferous soils is suggested by both morphological changes and radiation on these soils. The genus Caledonula is therefore a good model to understand the origin of microendemism in the context of recent and mixed influences of climate and soil type

Projet ITAC - L'accessibilité au cégep pour tous : informatique et technologies adaptées dans les cégeps pour les étudiants ayant des handicaps /

Bibliogr

Structure of the Cytoplasmic Loop between Putative Helices II and III of the Mannitol Permease of Escherichia coli: A Tryptophan and 5-Fluorotryptophan Spectroscopy Study

In this work, four single tryptophan (Trp) mutants of the dimeric mannitol transporter of Escherichia coli, EIImtl, are characterized using Trp and 5-fluoroTrp (5-FTrp) fluorescence spectroscopy. The four positions, 97, 114, 126, and 133, are located in a region shown by recent studies to be involved in the mannitol translocation process. To spectroscopically distinguish between the Trp positions in each subunit of dimeric EIImtl, 5-FTrp was biosynthetically incorporated because of its much simpler photophysics compared to those of Trp. The steady-state and time-resolved fluorescence methodologies used point out that all four positions are in structured environments, both in the absence and in the presence of a saturating concentration of mannitol. The fluorescence decay of all 5-FTrp-containing mutants was highly homogeneous, suggesting similar microenvironments for both probes per dimer. However, Stern-Volmer quenching experiments using potassium iodide indicate different solvent accessibilities for the two probes at positions 97 and 133. A 5 Å two-dimensional (2D) projection map of the membrane-embedded IICmtl dimer showing 2-fold symmetry is available. The results of this work are in better agreement with a 7 Å projection map from a single 2D crystal on which no symmetry was imposed.

Old lineage on an old island : Pixibinthus, a new cricket genus endemic to New Caledonia shed light on gryllid diversification in a hotspot of biodiversity

Few studies have focused on the early colonization of New Caledonia by insects, after the re-emergence of the main island, 37 Myr ago. Here we investigate the mode and tempo of evolution of a new endemic cricket genus, Pixibinthus, recently discovered in southern New Caledonia. First we formally describe this new monotypic genus found exclusively in the open shrubby vegetation on metalliferous soils, named 'maquis minier', unique to New Caledonia. We then reconstruct a dated molecular phylogeny based on five mitochondrial and four nuclear loci in order to establish relationships of Pixibinthus within Eneopterinae crickets. Pixibinthus is recovered as thesister clade of the endemic genus Agnotecous, mostly rainforest-dwellers. Dating results show that the island colonization by their common ancestor occurred around 34.7 Myr, shortly after New Caledonia re-emergence. Pixibinthus and Agnotecous are then one of the oldest insect lineages documented so far for New Caledonia. This discovery highlights for the first time two clear-cut ecological specializations between sister clades, as Agnotecous is mainly found in rainforests with 19 species, whereas Pixibinthus is found in open habitats with a single documented species. The preference of Pixibinthus for open habitats and of Agnotecous for forest habitats nicely fits an acoustic specialization, either explained by differences in body size or in acoustic properties of their respective habitats. We hypothesize that landscape dynamics, linked to major past climatic events and recent change in fire regimes are possible causes for both present-day low diversity and rarity in genus Pixibinthus. The unique evolutionary history of this old New Caledonian lineage stresses the importance to increase our knowledge on the faunal biodiversity of 'maquis minier', in order to better understand the origin and past dynamics of New Caledonian biota

SPIRAL2 RFQ prototype - First results

JACoW web site MOPCH103International audienceThe SPIRAL2 RFQ is designed to accelerate either 5 mA deuteron beam (Q/A=1/2) or a 1 mA of q/A=1/3 particle up to 0.75 MeV/A at 88 MHz. It is a CW machine which has to show stable operation, provide the required availability and reduce losses to a minimum in order to minimize the activation constraints. Extensive modelisation was done to ensure a good vane position under RF. The prototype of this 4-vane RFQ was built and tested in INFN-LNS Catania and then in IN2P3-LPSC Grenoble. It allowed us to measure the vacuum quality, the RF field by X-ray measurements, the cavity displacement and the real vane displacement during the RF injection. Different techniques were used, including an innovative CCD measurement with a 0.8 μm precision. This paper outlines the different results

Aurora kinase A drives the evolution of resistance to third-generation EGFR inhibitors in lung cancer.

Although targeted therapies often elicit profound initial patient responses, these effects are transient due to residual disease leading to acquired resistance. How tumors transition between drug responsiveness, tolerance and resistance, especially in the absence of preexisting subclones, remains unclear. In epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma cells, we demonstrate that residual disease and acquired resistance in response to EGFR inhibitors requires Aurora kinase A (AURKA) activity. Nongenetic resistance through the activation of AURKA by its coactivator TPX2 emerges in response to chronic EGFR inhibition where it mitigates drug-induced apoptosis. Aurora kinase inhibitors suppress this adaptive survival program, increasing the magnitude and duration of EGFR inhibitor response in preclinical models. Treatment-induced activation of AURKA is associated with resistance to EGFR inhibitors in vitro, in vivo and in most individuals with EGFR-mutant lung adenocarcinoma. These findings delineate a molecular path whereby drug resistance emerges from drug-tolerant cells and unveils a synthetic lethal strategy for enhancing responses to EGFR inhibitors by suppressing AURKA-driven residual disease and acquired resistance

17 ways to say yes:Toward nuanced tone of voice in AAC and speech technology

People with complex communication needs who use speech-generating devices have very little expressive control over their tone of voice. Despite its importance in human interaction, the issue of tone of voice remains all but absent from AAC research and development however. In this paper, we describe three interdisciplinary projects, past, present and future: The critical design collection Six Speaking Chairs has provoked deeper discussion and inspired a social model of tone of voice; the speculative concept Speech Hedge illustrates challenges and opportunities in designing more expressive user interfaces; the pilot project Tonetable could enable participatory research and seed a research network around tone of voice. We speculate that more radical interactions might expand frontiers of AAC and disrupt speech technology as a whole