3,271 research outputs found

    Clinical and Genomic Profile of Primary Cranial Neurolymphomatosis

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    Primary cranial neurolymphomatosis (PCNL) is a rare subtype of primary CNS lymphoma (PCNSL) in which infiltrative lymphomatous involvement is confined to cranial nerves. Here, we report a case of PCNL with successful genomic profiling. A 57-year-old male had a lengthy prediagnostic phase spanning approximately 30 months, characterized by multiple episodes of cranial neuropathies managed by steroids. At the time of diagnosis, the patient had right-sided cranial neuropathies involving cranial nerves (CN) V, VI, and VII. Pathological findings of the right cavernous lesion biopsy were consistent with large B-cell lymphoma-infiltrating nerve fibers. The clinical course was aggressive and refractory, characterized by relentless progression with the development of cervical spinal neurolymphomatosis, cerebrospinal fluid involvement, and ependymal and intraparenchymal cerebral involvement, despite multiple lines of therapy, including chemoimmunotherapy, Bruton\u27s tyrosine kinase inhibitor, radiation, autologous stem cell transplant, chimeric antigen receptor T-cell therapy (CAR-T), and whole-brain radiation. The patient survived for 22 months from the time of the initial diagnosis and 52 months after the first episode of cranial neuropathy. Next-generation sequencing identified mutations (MYD88, CD79b, and PIM1) that are frequently observed in PCNSL. The unusual findings included a total of 22 mutations involving PIM1, indicating a highly active aberrant somatic hypermutation and two missense CXCR4 mutations. CXCR4 mutations have never been described in PCNSL and may have implications for disease biology and therapeutic interventions. We provide a literature review to further elucidate PCNL

    Multiple component remediation of developmental reading disabilities: A Controlled factorial evaluation of the influence of IQ, socioeconomic status, and race on outcomes

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    Results from a controlled evaluation of remedial reading interventions are reported: 279 young disabled readers were randomly assigned to a program according to a 2 × 2 × 2 factorial design (IQ, socioeconomic status [SES], and race). The effectiveness of two multiple-component intervention programs for children with reading disabilities (PHAB + RAVE-O; PHAB + WIST) was evaluated against alternate (CSS, MATH) and phonological control programs. Interventions were taught an hour daily for 70 days on a 1:4 ratio at three different sites. Multiple-component programs showed significant improvements relative to control programs on all basic reading skills after 70 hours and at 1-year follow-up. Equivalent gains were observed for different racial, SES, and IQ groups. These factors did not systematically interact with program. Differential outcomes for word identification, fluency, comprehension, and vocabulary were found between the multidimensional pro- grams, although equivalent long-term outcomes and equal continued growth confirmed that different pathways exist to effective reading remediation

    Galactic structure from the Calar Alto Deep Imaging Survey (CADIS)

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    We used 1627 faint (15.5< R<23) stars in five fields of the Calar Alto Deep Imaging Survey (CADIS) to estimate the structure parameters of the Galaxy. The results were derived by applying two complementary methods: first by fitting the density distribution function to the measured density of stars perpendicular to the Galactic plane, and second by modelling the observed colors and apparent magnitudes of the stars in the field, using Monte Carlo simulations. The best-fitting model of the Galaxy is then determined by minimising the C-statistic, a modified chisquared. Our model includes a double exponential for the stellar disk with scaleheights h_1 and h_2 and a power law halo with exponent alpha. 24480 different parameter combinations have been simulated. Both methods yield consistent results: the best fitting parameter combination is alpha=3.0 (or alpha=2.5, if we allow for a flattening of the halo with an axial ratio of (c/a)=0.6), h_1=300 pc, h_2=900 pc, and the contribution of thick disk stars to the disk stars in the solar neighbourhood is found to be between 4 and 10%.Comment: 16 pages, 10 figures, submitted to Astronomy and Astrophysic

    Two neuroanatomical signatures in schizophrenia: Expression strengths over the first 2 years of treatment and their relationships to neurodevelopmental compromise and antipsychotic treatment

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    BACKGROUND AND HYPOTHESIS: Two machine learning derived neuroanatomical signatures were recently described. Signature 1 is associated with widespread grey matter volume reductions and signature 2 with larger basal ganglia and internal capsule volumes. We hypothesized that they represent the neurodevelopmental and treatment-responsive components of schizophrenia respectively. STUDY DESIGN: We assessed the expression strength trajectories of these signatures and evaluated their relationships with indicators of neurodevelopmental compromise and with antipsychotic treatment effects in 83 previously minimally treated individuals with a first episode of a schizophrenia spectrum disorder who received standardized treatment and underwent comprehensive clinical, cognitive and neuroimaging assessments over 24 months. Ninety-six matched healthy case-controls were included. STUDY RESULTS: Linear mixed effect repeated measures models indicated that the patients had stronger expression of signature 1 than controls that remained stable over time and was not related to treatment. Stronger signature 1 expression showed trend associations with lower educational attainment, poorer sensory integration, and worse cognitive performance for working memory, verbal learning and reasoning and problem solving. The most striking finding was that signature 2 expression was similar for patients and controls at baseline but increased significantly with treatment in the patients. Greater increase in signature 2 expression was associated with larger reductions in PANSS total score and increases in BMI and not associated with neurodevelopmental indices. CONCLUSIONS: These findings provide supporting evidence for two distinct neuroanatomical signatures representing the neurodevelopmental and treatment-responsive components of schizophrenia

    ESO Imaging Survey. The Stellar Catalogue in the Chandra Deep Field South

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    (abridged) Stellar catalogues in five passbands (UBVRI) over an area of approximately 0.3 deg^2, comprising about 1200 objects, and in seven passbands (UBVRIJK) over approximately 0.1 deg^2, comprising about 400 objects, in the direction of the Chandra Deep Field South are presented. The 90% completeness level of the number counts is reached at approximately U = 23.8, B = 24.0, V = 23.5, R = 23.0, I = 21.0, J = 20.5, K = 19.0. A scheme is presented to select point sources from these catalogues, by combining the SExtractor parameter CLASS_STAR from all available passbands. Probable QSOs and unresolved galaxies are identified by using the previously developed \chi^2-technique (Hatziminaoglou et al 2002), that fits the overall spectral energy distributions to template spectra and determines the best fitting template. The observed number counts, colour-magnitude diagrams, colour-colour diagrams and colour distributions are presented and, to judge the quality of the data, compared to simulations based on the predictions of a Galactic Model convolved with the estimated completeness functions and the error model used to describe the photometric errors of the data. The resulting stellar catalogues and the objects identified as likely QSOs and unresolved galaxies with coordinates, observed magnitudes with errors and assigned spectral types by the χ2\chi^2-technique are presented and are publicly available.Comment: Paper as it will appear in print. Complete figures and tables can be obtained from: http://www.eso.org/science/eis/eis_pub/eis_pub.html. Astronomy & Astrophysics, accepted for publicatio

    Bicontinuous minimal surface nanostructures for polymer blend solar cells

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    This paper presents the first examination of the potential for bicontinuous structures such as the gyroid structure to produce high efficiency solar cells based on conjugated polymers. The solar cell characteristics are predicted by a simulation model that shows how the morphology influences device performance through integration of all the processes occurring in organic photocells in a specified morphology. In bicontinuous phases, the surface de. ning the interface between the electron and hole transporting phases divides the volume into two disjoint subvolumes. Exciton loss is reduced because the interface at which charge separation occurs permeates the device so excitons have only a short distance to reach the interface. As each of the component phases is connected, charges will be able to reach the electrodes more easily. In simulations of the current-voltage characteristics of organic cells with gyroid, disordered blend and vertical rod (rods normal to the electrodes) morphologies, we find that gyroids have a lower than anticipated performance advantage over disordered blends, and that vertical rods are superior. These results are explored thoroughly, with geminate recombination, i.e. recombination of charges originating from the same exciton, identified as the primary source of loss. Thus, if an appropriate materials choice could reduce geminate recombination, gyroids show great promise for future research and applications

    Increased insolation threshold for runaway greenhouse processes on Earth like planets

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    Because the solar luminosity increases over geological timescales, Earth climate is expected to warm, increasing water evaporation which, in turn, enhances the atmospheric greenhouse effect. Above a certain critical insolation, this destabilizing greenhouse feedback can "runaway" until all the oceans are evaporated. Through increases in stratospheric humidity, warming may also cause oceans to escape to space before the runaway greenhouse occurs. The critical insolation thresholds for these processes, however, remain uncertain because they have so far been evaluated with unidimensional models that cannot account for the dynamical and cloud feedback effects that are key stabilizing features of Earth's climate. Here we use a 3D global climate model to show that the threshold for the runaway greenhouse is about 375 W/m2^2, significantly higher than previously thought. Our model is specifically developed to quantify the climate response of Earth-like planets to increased insolation in hot and extremely moist atmospheres. In contrast with previous studies, we find that clouds have a destabilizing feedback on the long term warming. However, subsident, unsaturated regions created by the Hadley circulation have a stabilizing effect that is strong enough to defer the runaway greenhouse limit to higher insolation than inferred from 1D models. Furthermore, because of wavelength-dependent radiative effects, the stratosphere remains cold and dry enough to hamper atmospheric water escape, even at large fluxes. This has strong implications for Venus early water history and extends the size of the habitable zone around other stars.Comment: Published in Nature. Online publication date: December 12, 2013. Accepted version before journal editing and with Supplementary Informatio

    A Keck/DEIMOS spectroscopic survey of the faint M31 satellites And IX, And XI, And XII, and And XIII

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    We present the first spectroscopic analysis of the faint M31 satellite galaxies, AndXI and AndXIII, and a reanalysis of existing spectroscopic data for two further faint companions, And IX and AndXII. By combining data obtained using the DEIMOS spectrograph mounted on the Keck II telescope with deep photometry from the Suprime-Cam instrument on Subaru, we have calculated global properties for the dwarfs, such as systemic velocities, metallicites and half-light radii.We find each dwarf to be very metal poor ([Fe/H] -2 both photometrically and spectroscopically, from their stacked spectrum), and as such, they continue to follow the luminosity-metallicity relationship established with brighter dwarfs. We are unable to resolve a dispersion for And XI due to small sample size and low S/N, but we set a one sigma upper limit of sigma-v <5 km/s. For And IX, And XII and And XIII we resolve velocity dispersions of v=4.5 (+3.4,-3.2), 2.6(+5.1,-2.6) and 9.7(+8.9,-4.5) km/s, and derive masses within the half light radii of 6.2(+5.3,-5.1)x10^6 Msun, 2.4 (+6.5,-2.4)x10^6 Msun and 1.1(+1.4,-0.7)x10^7 Msun respectively. We discuss each satellite in the context of the Mateo relations for dwarf spheroidal galaxies, and the Universal halo profiles established for Milky Way dwarfs (Walker et al. 2009). For both galaxies, this sees them fall below the Universal halo profiles of Walker et al. (2009). When combined with the findings of McConnachie & Irwin (2006a), which reveal that the M31 satellites are twice as extended (in terms of both half-light and tidal radii) as their Milky Way counterparts, these results suggest that the satellite population of the Andromeda system could inhabit halos that are significantly different from those of the Milky Way in terms of their central densities (abridged).Comment: 26 pages, 18 figures, MNRAS submitte

    Host‐derived population genomics data provides insights into bacterial and diatom composition of the killer whale skin

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    Recent exploration into the interactions and relationship between hosts and their microbiota has revealed a connection between many aspects of the host's biology, health and associated micro-organisms. Whereas amplicon sequencing has traditionally been used to characterize the microbiome, the increasing number of published population genomics data sets offers an underexploited opportunity to study microbial profiles from the host shotgun sequencing data. Here, we use sequence data originally generated from killer whale Orcinus orca skin biopsies for population genomics, to characterize the skin microbiome and investigate how host social and geographical factors influence the microbial community composition. Having identified 845 microbial taxa from 2.4 million reads that did not map to the killer whale reference genome, we found that both ecotypic and geographical factors influence community composition of killer whale skin microbiomes. Furthermore, we uncovered key taxa that drive the microbiome community composition and showed that they are embedded in unique networks, one of which is tentatively linked to diatom presence and poor skin condition. Community composition differed between Antarctic killer whales with and without diatom coverage, suggesting that the previously reported episodic migrations of Antarctic killer whales to warmer waters associated with skin turnover may control the effects of potentially pathogenic bacteria such as Tenacibaculum dicentrarchi. Our work demonstrates the feasibility of microbiome studies from host shotgun sequencing data and highlights the importance of metagenomics in understanding the relationship between host and microbial ecology
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