Multivariate neuroanatomical classification of cognitive subtypes in schizophrenia: A support vector machine learning approach

AbstractHeterogeneity in the structural brain abnormalities associated with schizophrenia has made identification of reliable neuroanatomical markers of the disease difficult. The use of more homogenous clinical phenotypes may improve the accuracy of predicting psychotic disorder/s on the basis of observable brain disturbances. Here we investigate the utility of cognitive subtypes of schizophrenia – ‘cognitive deficit’ and ‘cognitively spared’ – in determining whether multivariate patterns of volumetric brain differences can accurately discriminate these clinical subtypes from healthy controls, and from each other. We applied support vector machine classification to grey- and white-matter volume data from 126 schizophrenia patients previously allocated to the cognitive spared subtype, 74 cognitive deficit schizophrenia patients, and 134 healthy controls. Using this method, cognitive subtypes were distinguished from healthy controls with up to 72% accuracy. Cross-validation analyses between subtypes achieved an accuracy of 71%, suggesting that some common neuroanatomical patterns distinguish both subtypes from healthy controls. Notably, cognitive subtypes were best distinguished from one another when the sample was stratified by sex prior to classification analysis: cognitive subtype classification accuracy was relatively low (<60%) without stratification, and increased to 83% for females with sex stratification. Distinct neuroanatomical patterns predicted cognitive subtype status in each sex: sex-specific multivariate patterns did not predict cognitive subtype status in the other sex above chance, and weight map analyses demonstrated negative correlations between the spatial patterns of weights underlying classification for each sex. These results suggest that in typical mixed-sex samples of schizophrenia patients, the volumetric brain differences between cognitive subtypes are relatively minor in contrast to the large common disease-associated changes. Volumetric differences that distinguish between cognitive subtypes on a case-by-case basis appear to occur in a sex-specific manner that is consistent with previous evidence of disrupted relationships between brain structure and cognition in male, but not female, schizophrenia patients. Consideration of sex-specific differences in brain organization is thus likely to assist future attempts to distinguish subgroups of schizophrenia patients on the basis of neuroanatomical features

Transformation and patterning of supermicelles using dynamic holographic assembly

Although the solution self-assembly of block copolymers has enabled the fabrication of a broad range of complex, functional nanostructures, their precise manipulation and patterning remain a key challenge. Here we demonstrate that spherical and linear supermicelles, supramolecular structures held together by non-covalent solvophobic and coordination interactions and formed by the hierarchical self-assembly of block copolymer micelle and block comicelle precursors, can be manipulated, transformed and patterned with mediation by dynamic holographic assembly (optical tweezers). This allows the creation of new and stable soft-matter superstructures far from equilibrium. For example, individual spherical supermicelles can be optically held in close proximity and photocrosslinked through controlled coronal chemistry to generate linear oligomeric arrays. The use of optical tweezers also enables the directed deposition and immobilization of supermicelles on surfaces, allowing the precise creation of arrays of soft-matter nano-objects with potentially diverse functionality and a range of applications

Microfibres and macroscopic films from the coordination-driven hierarchical self-assembly of cylindrical micelles

Anisotropic nanoparticles prepared from block copolymers are of growing importance as building blocks for the creation of synthetic hierarchical materials. However, the assembly of these structural units is generally limited to the use of amphiphilic interactions. Here we report a simple, reversible coordination-driven hierarchical self-assembly strategy for the preparation of micron-scale fibres and macroscopic films based on monodisperse cylindrical block copolymer micelles. Coordination of Pd(0) metal centres to phosphine ligands immobilized within the soluble coronas of block copolymer micelles is found to induce intermicelle crosslinking, affording stable linear fibres comprised of micelle subunits in a staggered arrangement. The mean length of the fibres can be varied by altering the micelle concentration, reaction stoichiometry or aspect ratio of the micelle building blocks. Furthermore, the fibres aggregate on drying to form robust, self-supporting macroscopic micelle-based thin films with useful mechanical properties that are analogous to crosslinked polymer networks, but on a longer length scale

Abundances in Galactic Bulge Dwarfs and the Origin of the Elements in the Bulge

The Galactic Bulge has a very different chemical evolution history than the Milky Way disk or halo. The unique mix of supernovae and asymptotic giant branch stars that have contributed to the elements in the bulge offer the opportunity to identify or confirm the nucleosynthesis sites of elements. Abundance measurements based on the spectra of Galactic bulge dwarfs provide the only reliable measurements of the evolution of C and N in the Bulge, and have also been the source of the first measurements of S, K, Zn, Cu and Ba. We report on the use of gravitational microlensing to observe very faint Galactic bulge dwarfs and discuss the implications of these measurements for the origin of the elements. In particular, we argue that Type Ia SNe are unlikely to be important sources of Zn, but while the data on C and N suggest that asymptotic giant stars contributed to the chemical enrichment of the bulge, the data on Ba suggest that there was a delay before substantial AGB star production

Chemical evolution of the Galactic bulge as traced by microlensed dwarf and subgiant stars : V. Evidence for a wide age distribution and a complex MDF

Based on high-resolution spectra obtained during gravitational microlensing events we present a detailed elemental abundance analysis of 32 dwarf and subgiant stars in the Galactic bulge. Combined with the sample of 26 stars from the previous papers in this series, we now have 58 microlensed bulge dwarfs and subgiants that have been homogeneously analysed. The main characteristics of the sample and the findings that can be drawn are: (i) the metallicity distribution (MDF) is wide and spans all metallicities between [Fe/H] = -1.9 to +0.6; (ii) the dip in the MDF around solar metallicity that was apparent in our previous analysis of a smaller sample (26 microlensed stars) is no longer evident; instead it has a complex structure and indications of multiple components are starting to emerge. A tentative interpretation is that there could be different stellar populations at interplay, each with a different scale height: the thin disk, the thick disk, and a bar population; (iii) the stars with [Fe/H] ≤ -0.1 are old with ages between 10 and 12 Gyr; (iv) the metal-rich stars with [Fe/H] ≥ -0.1 show a wide variety of ages, ranging from 2 to 12 Gyr with a distribution that has a dominant peak around 4-5 Gyr and a tail towards higher ages; (v) there are indications in the [α/Fe]-[Fe/H] abundance trends that the "knee" occurs around [Fe/H] = -0.3to -0.2, which is a slightly higher metallicity as compared to the "knee" for the local thick disk. This suggests that the chemical enrichment of the metal-poor bulge has been somewhat faster than what is observed for the local thick disk. The results from the microlensed bulge dwarf stars in combination with other findings in the literature, in particular the evidence that the bulge has cylindrical rotation, indicate that the Milky Way could be an almost pure disk galaxy. The bulge would then just be a conglomerate of the other Galactic stellar populations (thin disk, thick disk, halo, and.?), residing together in the central parts of the Galaxy, influenced by the Galactic bar

The K20 survey. VI. The Distribution of the Stellar Masses in Galaxies up to z~2

We present a detailed analysis of the stellar mass content of galaxies up to z=2.5 in the K20 galaxy sample, that has a 92% spectroscopic completeness and a complete $UBVRIzJK_s$ multicolor coverage. We find that the M/L ratio decreases with redshift: in particular, the average M/L ratio of early type galaxies decreases with $z$, with a scatter that is indicative of a range of star--formation time-scales and redshift of formation. More important, the typical M/L of massive early type galaxies is larger than that of less massive ones, suggesting that their stellar population formed at higher z. The final K20 galaxy sample spans a range of stellar masses from M*=10^9Msun to M*=10^12Msun, with massive galaxies ($M*>10^11Msun) detected up to z~2. We compute the Galaxy Stellar Mass Function at various z, of which we observe only a mild evolution (i.e. by 20-30%) up to z~1. At z>1, the evolution of the GSMF appears to be much faster: at z~2, about 35% of the present day stellar mass in objects with M*~10^11Msun appear to have assembled. We also detect a change in the physical nature of the most massive galaxies, since at z>1 a population of massive star--forming galaxies progressively appears. We finally analyze our results in the framework of Lambda-CDM hierarchical models. First, we show that the large number of massive galaxies detected at high z does not violate any fundamental Lambda-CDM constraint based on the number of massive DM halos. Then, we compare our results with the predictions of renditions of both semianalytic and hydro-dynamical models, that range from severe underestimates to slight overestimates of the observed mass density at z<~2. We discuss how the differences among these models are due to the different implementation of the main physical processes. (Abridged)Comment: Accepted for publication on Astronomy & Astrophysic

Clinical Consensus Conference: Survey on Gram-Positive Bloodstream Infections with a Focus on Staphylococcus aureus

The increased incidence over the past decade of bloodstream infections (BSIs) caused by gram-positive bacteria, particularly methicillin-resistant Staphylococcus aureus , highlights the critical need for a consistent approach to therapy. However, there is currently no international consensus on the diagnosis and management of gram-positive BSIs. The Clinical Consensus Conference on Gram-Positive Bloodstream Infections was convened as a session at the 9th International Symposium on Modern Concepts in Endocarditis and Cardiovascular Infections held in 2007. Participants discussed various aspects of the practical treatment of patients who present with gram-positive BSI, including therapeutic options for patients with BSIs of undefined origin, the selection of appropriate empirical therapy, and treatment of complicated and uncomplicated BSIs. The opinions of participants about these key issues are reflected in this articl

A Planetary Microlensing Event with an Unusually Red Source Star: MOA-2011-BLG-291

We present the analysis of planetary microlensing event MOA-2011-BLG-291, which has a mass ratio of $q=(3.8\pm0.7)\times10^{-4}$ and a source star that is redder (or brighter) than the bulge main sequence. This event is located at a low Galactic latitude in the survey area that is currently planned for NASA's WFIRST exoplanet microlensing survey. This unusual color for a microlensed source star implies that we cannot assume that the source star is in the Galactic bulge. The favored interpretation is that the source star is a lower main sequence star at a distance of $D_S=4.9\pm1.3\,$kpc in the Galactic disk. However, the source could also be a turn-off star on the far side of the bulge or a sub-giant in the far side of the Galactic disk if it experiences significantly more reddening than the bulge red clump stars. However, these possibilities have only a small effect on our mass estimates for the host star and planet. We find host star and planet masses of $M_{\rm host} =0.15^{+0.27}_{-0.10}M_\odot$ and $m_p=18^{+34}_{-12}M_\oplus$ from a Bayesian analysis with a standard Galactic model under the assumption that the planet hosting probability does not depend on the host mass or distance. However, if we attempt to measure the host and planet masses with host star brightness measurements from high angular resolution follow-up imaging, the implied masses will be sensitive to the host star distance. The WFIRST exoplanet microlensing survey is expected to use this method to determine the masses for many of the planetary systems that it discovers, so this issue has important design implications for the WFIRST exoplanet microlensing survey