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We examined longitudinally the course and predictors of treatment resistance in a large cohort of first-episode psychosis (FEP) patients from initiation of antipsychotic treatment. We hypothesized that antipsychotic treatment resistance is: (a) present at illness onset; and (b) differentially associated with clinical and demographic factors.
The study sample comprised 323 FEP patients who were studied at first contact and at 10-year follow-up. We collated clinical information on severity of symptoms, antipsychotic medication and treatment adherence during the follow-up period to determine the presence, course and predictors of treatment resistance.
From the 23% of the patients, who were treatment resistant, 84% were treatment resistant from illness onset. Multivariable regression analysis revealed that diagnosis of schizophrenia, negative symptoms, younger age at onset, and longer duration of untreated psychosis predicted treatment resistance from illness onset.
The striking majority of treatment-resistant patients do not respond to first-line antipsychotic treatment even at time of FEP. Clinicians must be alert to this subgroup of patients and consider clozapine treatment as early as possible during the first presentation of psychosis.
In view of the considerable ground covered by the Commission at its Paris meetings and the fairly complete record of the activities of institutes and observatories, etc. published in the Minutes, it has not been deemed profitable by the president to call for further reports in advance of the Stockholm meeting. At the Paris meeting it was agreed that such reports be printed independently before each meeting of the Union and that reprints of or references to the published reports be sent to the president. It is hoped that all such reports if ready will be made available before the Stockholm meeting so that they may be summarized by the representatives in attendance or by the president and recorded in the Minutes. With reference to the pronouncement at the Paris meeting “that it is eminently desirable that more attention be given to the development of accurate general perturbations and mean elements on the basis of accurate osculating elements”, the president has visited the Planeten-Institut at Frankfurt and the Rechen-Institut at Berlin and has been in correspondence with the Leningrad Institute. From these sources particularly valuable material has been received.
From the combination of VLBI phase-referenced observations and Hipparcos satellite data, we have found evidence of a low-mass object orbiting the late-type star AB Doradus. The mass of the new object is near the hydrogen burning limit and will constitute a precise point for calibrating the low end of the main sequence. This represents the first detection of a low-mass stellar companion using the VLBI technique, which could become an important tool in future searches for planets and brown dwarfs orbiting other stars.
We answer a question of Masser by showing that for the Weierstrass zeta function ζ corresponding to a given lattice Λ, the density of algebraic points of absolute multiplicative height bounded by T and degree bounded by k lying on the graph of ζ, restricted to an appropriate domain, does not exceed c(log T)15 for an effective constant c > 0 depending on k and on Λ. Using different methods, we also give two bounds of the same form for the density of algebraic points of bounded height in a fixed number field lying on the graph of ζ restricted to an appropriate subset of (0, 1). In one case the constant c can be shown not to depend on the choice of lattice; in the other, the exponent can be improved to 12.
Suppose that f : (a, b) → R is an analytic function definable in an o-minimal expansion of the real field, and suppose that f is transcendental, that is that there is no nonzero polynomial P such that P(t, f(t)) vanishes identically. The Pila-Wilkie theorem applied to the graph of f says that for all ∊ > 0 there is a c > 0 such that for all H ≥ 1 there are at most
rationals q in (a, b) of height at most H such that f(q) is also a rational of height at most H. See one of Wilkie's contributions to this volume for a discussion of this result, and its proof. The analyticity isn't necessary, and certainly isn't true piecewise of definable functions in general (indeed, they needn't even be piecewise infinitely differentiable, see ). But all the functions we will meet later are (possibly piecewise) analytic, so we may as well assume it from the beginning.
It is reasonable to ask whether the cH∊ bound in this result can be improved, say to a bound of the form c(logH)n for some c, n > 0. In fact, this sort of improvement is not possible. Constructions due to Surroca [19, 20] and to Bombieri and Pila  show the following. Suppose that ∊ : [1, ∞) → R is strictly decreasing and tends to 0. Then there is a transcendental real analytic function f on [0, 1] (that is, f has an analytic extension to a neighbourhood of [0, 1]) and an increasing sequence H1,H2, . . . of positive integers such that for each positive integer i there are at least
rational points (q, f(q)) on the graph of f of height at most Hi.
In July 2013 an LMS-EPSRC Short Instructional Course on ‘O-minimality and diophantine geometry’ was held in the School of Mathematics at the University of Manchester. This volume consists of lecture notes from the courses together with several other surveys. The motivation behind the short course was to introduce participants to some of the ideas behind Pila's recent proof of the André-Oort conjecture for products of modular curves. The underlying ideas are similar to an earlier proof by Pila and Zannier of the Manin-Mumford conjecture (which has in fact long been a theorem, originally due to Raynaud) and combining the results of the various contributions here leads to a proof of this conjecture in certain cases. The basic strategy has three main ingredients: the Pila-Wilkie theorem, bounds on Galois orbits, and functional transcendence results. Each of the topics was the focus of a course. Wilkie discussed o-minimality and the Pila-Wilkie theorem without assuming any background in mathematical logic. (The argument given here is, in fact, slightly different from that given in the original paper, at least in the one-dimensional case.) Habegger's course focused on the Galois bounds and on the completion of the proof (of certain cases of Manin-Mumford) from the various ingredients. And Pila's lectures covered functional transcendence, also touching on various recent related work by Zilber.We have also included some further lecture notes by Wilkie containing a proof of the o-minimality of the expansion of the real field by restricted analytic functions, which is sufficient for the application of Pila-Wilkie to Manin-Mumford. At the short course there were also three guest lectures. Yafaev spoke on very recent breakthroughs on the functional transcendence side in the setting of general Shimura varieties. Masser spoke on some other results (‘relative Manin-Mumford’) that can be obtained by a similar strategy. Jones discussed improvements to the Pila-Wilkie theorem. Unfortunately, Yafaev was unable to contribute to this volume. During the week of the course, tutorials were given by Daw and Orr. For this volume, Orr has written a survey of abelian varieties which contains a proof of the functional transcendence result necessary for the application in Habegger's course.
This collection of articles, originating from a short course held at the University of Manchester, explores the ideas behind Pila's proof of the Andre–Oort conjecture for products of modular curves. The basic strategy has three main ingredients: the Pila–Wilkie theorem, bounds on Galois orbits, and functional transcendence results. All of these topics are covered in this volume, making it ideal for researchers wishing to keep up to date with the latest developments in the field. Original papers are combined with background articles in both the number theoretic and model theoretic aspects of the subject. These include Martin Orr's survey of abelian varieties, Christopher Daw's introduction to Shimura varieties, and Jacob Tsimerman's proof via o-minimality of Ax's theorem on the functional case of Schanuel's conjecture.
We analyze the dust emission features seen in Spitzer Space Telescope Infrared Spectrograph (IRS) spectra of red supergiant (RSG) and oxygen-rich asymptotic giant branch (AGB) stars in the Large Magellanic Cloud and Small Magellanic Cloud galaxies and in various Milky Way globular clusters. The spectra come from the Spitzer Legacy program SAGE-Spectroscopy (PI: F. Kemper), the Spitzer program SMC-Spec (PI: G. Sloan), and other archival Spitzer-IRS programs. The broad 10 and 20 micron emission features attributed to amorphous dust of silicate composition seen in the spectra show evidence for systematic differences in the centroid of both emission features between O-rich AGB and RSG populations. Radiative transfer modeling using the GRAMS grid of models of AGB and RSG stars suggests that the centroid differences are due to differences in dust properties. We investigate differences in dust composition, size, shape, etc that might be responsible for these spectral differences. We explore how these differences may arise from the different circumstellar environments around RSG and O-rich AGB stars and assess effects of varying metallicity (LMC versus SMC versus Milky Way globular cluster) and other properties (mass-loss rate, luminosity, etc.) on the dust originating from these stars. BAS acknowledges funding from NASA ADAP grant NNX13AD54G.
Strategies to dissect phenotypic and genetic heterogeneity of major depressive disorder (MDD) have mainly relied on subphenotypes, such as age at onset (AAO) and recurrence/episodicity. Yet, evidence on whether these subphenotypes are familial or heritable is scarce. The aims of this study are to investigate the familiality of AAO and episode frequency in MDD and to assess the proportion of their variance explained by common single nucleotide polymorphisms (SNP heritability).
For investigating familiality, we used 691 families with 2–5 full siblings with recurrent MDD from the DeNt study. We fitted (square root) AAO and episode count in a linear and a negative binomial mixed model, respectively, with family as random effect and adjusting for sex, age and center. The strength of familiality was assessed with intraclass correlation coefficients (ICC). For estimating SNP heritabilities, we used 3468 unrelated MDD cases from the RADIANT and GSK Munich studies. After similarly adjusting for covariates, derived residuals were used with the GREML method in GCTA (genome-wide complex trait analysis) software.
Significant familial clustering was found for both AAO (ICC = 0.28) and episodicity (ICC = 0.07). We calculated from respective ICC estimates the maximal additive heritability of AAO (0.56) and episodicity (0.15). SNP heritability of AAO was 0.17 (p = 0.04); analysis was underpowered for calculating SNP heritability of episodicity.
AAO and episodicity aggregate in families to a moderate and small degree, respectively. AAO is under stronger additive genetic control than episodicity. Larger samples are needed to calculate the SNP heritability of episodicity. The described statistical framework could be useful in future analyses.
Although usually thought of as external environmental stressors, a significant heritable component has been reported for measures of stressful life events (SLEs) in twin studies.
We examined the variance in SLEs captured by common genetic variants from a genome-wide association study (GWAS) of 2578 individuals. Genome-wide complex trait analysis (GCTA) was used to estimate the phenotypic variance tagged by single nucleotide polymorphisms (SNPs). We also performed a GWAS on the number of SLEs, and looked at correlations between siblings.
A significant proportion of variance in SLEs was captured by SNPs (30%, p = 0.04). When events were divided into those considered to be dependent or independent, an equal amount of variance was explained for both. This ‘heritability’ was in part confounded by personality measures of neuroticism and psychoticism. A GWAS for the total number of SLEs revealed one SNP that reached genome-wide significance (p = 4 × 10−8), although this association was not replicated in separate samples. Using available sibling data for 744 individuals, we also found a significant positive correlation of R2 = 0.08 in SLEs (p = 0.03).
These results provide independent validation from molecular data for the heritability of reporting environmental measures, and show that this heritability is in part due to both common variants and the confounding effect of personality.
Toxoplasma gondii and Bartonella spp. are zoonotic pathogens of cats. Feline immunodeficiency virus (FIV), and feline leukaemia virus (FeLV) are immunosuppressive viruses of cats that can affect T. gondii oocyst shedding. In this study, the prevalence of antibodies to T. gondii, Bartonella spp., FIV, as well as FeLV antigens were determined in sera from feral cats (Felis catus) from Addis Ababa, Ethiopia. Using the modified agglutination test, IgG antibodies to T. gondii were found in 41 (85·4%) of the 48 cats with titres of 1:25 in one, 1:50 in one, 1:200 in six, 1:400 in six, 1:800 in six, 1:1600 in eight, and 1:3200 in 13 cats. Toxoplasma gondii IgM antibodies were found in 11/46 cats tested by ELISA, suggesting recent infection. Antibodies to Bartonella spp. were found in five (11%) of 46 cats tested. Antibodies to FIV or FeLV antigen were not detected in any of the 41 cats tested. The results indicate a high prevalence of T. gondii and a low prevalence of Bartonella spp. infection in cats in Ethiopia.
The influence of the substrate on composition and CuPt-type spontaneous order of MOVPE lattice matched InGaP/GaAs layers was studied. The study was carried out by microRaman and microphotoluminescence. The order was determined by the band gap, while the Raman parameters were also contributed by the surface topography that was also related to the type of substrate. The spontaneous order increases with Si- doping of the substrates. Doping the layers with Zn randomises the alloy.
We report large magnetoresistance (in excess of 1000%) in ferromagnet / superconductor / ferromagnet structures made of La0.7Ca0.3MnO3 and YBa2Cu3O7 in the current in plane (CIP) geometry. This magnetoresistance has many of the ingredients of the giant magnetoresistance of metallic superlattices: it is independent on the angle between current and magnetic field, depends on the relative orientation of the magnetization in the ferromagnetic layers, and takes very large values. The origin is enhanced scattering at the F/S interface in the anti parallel configuration of the magnetizations. Furthermore, we examine the dependence of the magnetoresistance effect on the thickness of the superconducting layer, and show that the magnetoresistance dies out for thickness in excess of 30 nm, setting a length scale for the diffusion of spin polarized quasiparticles.
We have been developing a variety of nanomaterials for their use in power devices. An example of this is our use of both single wall carbon nanotubes and several varieties of semiconducting quantum dots (e.g., CuInS2, CdSe, InAs) for use in space solar cells. The ability of these materials to withstand the rigors of the space radiation environment will be essential for this intended application. In addition, we have also been developing both nanostructure III-V devices and radioluminescent quantum dots for use in radioisotope batteries. In this application these nanomaterials are subjected to an extremely high radiation level. Their degradation rate will be the key to determining the ultimate lifetime of these power supplies, which in principle can have an energy density that is orders of magnitude higher than any conventional battery chemistry. The nanomaterials included in this study were subjected to alpha particles fluences and the degradation in various properties were monitored using different analytical techniques. Specifically, the radioluminescence of the quantum dot intended for use in the radioisotope batteries was monitored as a function of fluence. In the case of the III-V quantum dots, their photoluminescent degradation as a function of fluence was measured in comparison to the bulk substrate on which the quantum dots were grown. Finally for the carbon nanotubes, relative intensities of the Raman peaks associated with their inherent vibrational modes was used to monitor the effects of the alpha radiation damage. Results on the radiation tolerance of these nanomaterials and its implication with regard to their ultimately utility in power devices are presented.
One method for the fabrication of the superconducting compound Nb3Sn involves interdiffusion of a surface coating of Sn alloyed with Cu on Nb containing Zr and O. In this study, the kinetics and microstructure associated with this reaction have been studied in detail. The results show that small Nb3Sn grains nucleate at the Nb3Sn/Nb interface, and that the Nb3Sn grains experience grain growth immediately after they are formed. ZrO2 precipitates are observed in the Nb3Sn at the Nb3Sn/Nb interface and throughout the Nb3Sn. The ZrO2 precipitates occur in the form of small partially-coherent spheres in the Nb3Sn. No ZrO2 precipitates are observed by TEM in the unreacted Nb. The grain boundaries in the Nb3Sn region are coated with a Sn-Nb-Cu alloy which would have been liquid at the diffusion/reaction temperature. The thickness of the Nb3Sn reaction layer formed during the isothermal diffusion anneal is proportional to time to the first power, indicating “reaction”-controlled rather than “diffusion”-controlled kinetics. The absence of diffusion-controlled kinetics can be explained by the presence of the liquid coating on the Nb3Sn grains. Diffusion of Sn in this liquid layer is apparently fast enough to not be the limiting kinetic step.