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Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Agitation is common across neuropsychiatric disorders and contributes to disability, institutionalization, and diminished quality of life for patients and their caregivers. There is no consensus definition of agitation and no widespread agreement on what elements should be included in the syndrome. The International Psychogeriatric Association formed an Agitation Definition Work Group (ADWG) to develop a provisional consensus definition of agitation in patients with cognitive disorders that can be applied in epidemiologic, non-interventional clinical, pharmacologic, non-pharmacologic interventional, and neurobiological studies. A consensus definition will facilitate communication and cross-study comparison and may have regulatory applications in drug development programs.
The ADWG developed a transparent process using a combination of electronic, face-to-face, and survey-based strategies to develop a consensus based on agreement of a majority of participants. Nine-hundred twenty-eight respondents participated in the different phases of the process.
Agitation was defined broadly as: (1) occurring in patients with a cognitive impairment or dementia syndrome; (2) exhibiting behavior consistent with emotional distress; (3) manifesting excessive motor activity, verbal aggression, or physical aggression; and (4) evidencing behaviors that cause excess disability and are not solely attributable to another disorder (psychiatric, medical, or substance-related). A majority of the respondents rated all surveyed elements of the definition as “strongly agree” or “somewhat agree” (68–88% across elements). A majority of the respondents agreed that the definition is appropriate for clinical and research applications.
A provisional consensus definition of agitation has been developed. This definition can be used to advance interventional and non-interventional research of agitation in patients with cognitive impairment.
We have observed 79 supernova remnants (SNRs) with the Urumqi 25 m telescope at λ6 cm during the Sino-German λ6 cm polarization survey of the Galactic plane. We measured flux densities of SNRs at λ6 cm, some of which are the first ever measured or the measurements at the highest frequency, so that we can determine or improve spectra of SNRs. Our observations have ruled out spectral breaks or spectral flattening that were suggested for a few SNRs, and confirmed the spectral break of S147. By combining our λ6 cm maps with λ11 cm and λ21 cm maps from the Effelsberg 100 m telescope, we calculated the spectral index maps of several large SNRs. For many remnants we obtained for the first time polarization images, which show the intrinsic magnetic field structures at λ6 cm. We disapproved three objects as being SNRs, OA184, G192.8−1.1 and G16.8−1.1, which show a thermal spectrum and no polarization. We have discovered two large supernova remnants, G178.2−4.2 and G25.1−2.3., in the survey maps.
The Sino-German λ6 cm polarization survey has mapped in total intensity and polarization intensity over an area of approximately 2200 square degrees in the Galactic disk. This survey provides an opportunity to search for Galactic supernova remnants (SNRs) that were previously unknown. We discovered the new SNRs G178.2−4.2 and G25.1−2.3 which have non-thermal spectra, using the λ6 cm data together with the observations with the Effelsberg telescope at λ11 cm and λ21 cm. Both G178.2−4.2 and G25.1−2.3 are faint and have an apparent diameter greater than 1°. G178.2−4.2 shows a polarized shell. HI data suggest that G25.1−2.3 might have a distance of about 3 kpc. The λ6 cm survey data were also very important to identify two other new SNRs, G152.4−2.1 and G190.9−2.2.
After Prof. R. Wielebinski visited China in 1999, we started to plan the Sino-German λ6 cm polarization survey of the Galactic plane, using the Urumqi 25-m radio telescope of Xinjiang (formerly Urumqi) Astronomical Observatory, Chinese Academy of Sciences. It is a high-frequency complement of previous Effelsberg 21-cm and 11-cm surveys, using the same observing and processing methods. The telescope is located at an altitude of 2029 m above sea level at geographic longitude of 87°E and latitude 43°N. The dual-channel λ6 cm receiver with a polarimeter and a bandwidth of 600 MHz was designed by O. Lochner and constructed at the MPIfR in Germany with involvements by the Urumqi engineers M.Z. Chen and J. Ma. In August 2004, the receiver was installed at the secondary focus of the Urumqi 25-m telescope.
Methods for the analysis of the joint transmission of two phenotypes are described and used to determine the extent to which lipoprotein concentrations share a common genetic and/or environmental background. Analysis of data on 160 Caucasian nuclear families revealed that the observed phenotypic association between high-density cholesterol (HDL) and low-density cholesterol (LDL) could be accounted for in terms of common family environmental effects alone (estimated genetic correlation, ρG = −0·132±0·136; estimated residual environmental correlation, ρR = 0·065±0·230). The association between HDL and very-low-density cholesterol (VLDL) could not be accounted for in terms of family environmental effects alone. For HDL and VLDL the residual environmental correlation was significant while the genetic correlation was not (ρG = −0·111±0·214, ρR = −0·421±0·172). The correlation between LDL and VLDL also could not be accounted for in terms of common family environmental effects alone, although here a genetic relationship appears to be the important factor (ρG = 0·330±0·192, ρR = 0·010±0·217).
Obesity and osteoporosis affect millions of Americans. While phenotypically, obesity is negatively correlated with fracture risk, research on a genetic basis for this relationship is lacking. We used males and females from 16 LGXSM recombinant inbred (RI) mouse strains to investigate the genetically mediated relationship between obesity and osteoporosis-related traits. First, heritabilities were estimated for (1) bone morphology properties determined by microCT (femoral and radial diaphyseal bone cross-sectional area and moments of inertia, as well as proximal tibial trabecular bone volume, connectivity density, structure model index, trabecular number, trabecular thickness and trabecular separation), (2) mechanical properties determined by bending tests (femoral and radial rigidity, yield moment, ultimate moment, fracture displacement and post-yield displacement), and (3) effective material properties (femoral and radial modulus of elasticity and ultimate tensile strength). All femoral (H2=43–74%) and tibial traits (H2=31–56%) were heritable; as were 8 of 10 radial traits (H2=21–33%). Eighteen significant genetic correlations were discovered between obesity- and osteoporosis-related phenotypes. Genetic correlations indicate that gene effects associated with increased fat mass and leptin levels are also associated with larger, stronger femora. Gene effects associated with larger, stronger radii and with denser tibiae were also associated with increased fat mass but not with leptin levels. Furthermore, quantitative trait loci (QTLs) previously reported for obesity and leptin levels also had effects on bone morphology, mechanical and material properties. Our results support the use of the LG/J-by-SM/J mouse intercross populations as models for normal, complex genetic variation in obesity, bone properties and their interrelationship.
As part of the Canadian Galactic Plane Survey (CGPS) we have imaged the polarized emission from the plane of the Milky Way at 1420 MHz, covering 1200 square degrees with arc-minute resolution. Structure on all scales is represented by combining aperture-synthesis data with single-antenna data. The survey depicts the Magneto-Ionic Medium at a resolution that matches images of other components of the Interstellar Medium within the CGPS database (http://www4.cadc.hia.nrc.gc.ca).
The Global Magneto-Ionic Medium Survey (GMIMS) is a project to map the diffuse polarized emission over the entire sky, Northern and Southern hemispheres, from 300 MHz to 1.8 GHz. With an angular resolution of 30–60 arcmin and a frequency resolution of 1 MHz or better, GMIMS will provide the first spectro-polarimetric data set of the large-scale polarized emission over the entire sky, observed with single-dish telescopes. GMIMS will provide an invaluable resource for studies of the magneto-ionic medium of the Galaxy in the local disk, halo, and its transition.
Commensurate BaTiO3/SrTiO3 superlattices were grown by reactive molecular-beam epitaxy on four different substrates: TiO2-terminated (001) SrTiO3, (101) DyScO3, (101) GdScO3, and (101) SmScO3. With the aid of reflection high-energy electron diffraction (RHEED), precise single-monolayer doses of BaO, SrO, and TiO2 were deposited sequentially to create commensurate BaTiO3/SrTiO3 superlattices with a variety of periodicities. X-ray diffraction (XRD) measurements exhibit clear superlattice peaks at the expected positions. The rocking curve full width half-maximum of the superlattices was as narrow as 7 arc s (0.002°). High-resolution transmission electron microscopy reveals nearly atomically abrupt interfaces. Temperature-dependent ultraviolet Raman and XRD were used to reveal the paraelectric-to-ferroelectric transition temperature (TC). Our results demonstrate the importance of finite size and strain effects on the TC of BaTiO3/SrTiO3 superlattices. In addition to probing finite size and strain effects, these heterostructures may be relevant for novel phonon devices, including mirrors, filters, and cavities for coherent phonon generation and control.
The large surface to volume ratio in nanometer sized wire structures cause a strong dependence of the optical Raman mode on the thermal conductivity of a surrounding medium. On the basis of optical measurements on silicon nanowires as a function of excitation laser power we explain the very large red-shifted Raman spectra observed already for moderate laser powers. This thermal effect is enhanced by a silicon oxide sheath, rendering a reduced thermal contact of the wires to the substrate. The intrinsic redshift due to spatial confinement in silicon nanowires is found to be smaller than 2 cm−1.
Background. Genetic influences have been shown to play a major role in determining the risk of attention-deficit hyperactivity disorder (ADHD). In addition, prenatal exposure to nicotine and/or alcohol has also been suggested to increase risk of the disorder. Little attention, however, has been directed to investigating the roles of genetic transmission and prenatal exposure simultaneously.
Method. Diagnostic telephone interview data from parents of Missouri adolescent female twin pairs born during 1975–1985 were analyzed. Logistic regression models were fitted to interview data from a total of 1936 twin pairs (1091 MZ and 845 DZ pairs) to determine the relative contributions of parental smoking and drinking behavior (both during and outside of pregnancy) as risk factors for DSM-IV ADHD. Structural equation models were fitted to determine the extent of residual genetic and environmental influences on ADHD risk while controlling for effects of prenatal and parental predictors on risk.
Results. ADHD was more likely to be diagnosed in girls whose mothers or fathers were alcohol dependent, whose mothers reported heavy alcohol use during pregnancy, and in those with low birth weight. Controlling for other risk factors, risk was not significantly increased in those whose mothers smoked during pregnancy. After allowing for effects of prenatal and childhood predictors, 86% of the residual variance in ADHD risk was attributable to genetic effects and 14% to non-shared environmental influences.
Conclusions. Prenatal and parental risk factors may not be important mediators of influences on risk with much of the association between these variables and ADHD appearing to be indirect.
In this article, we provide an overview of the different statistical procedures that have been developed for linkage mapping of quantitative trait loci. We outline the model assumptions, the data requirements and the underlying tests for linkage for the different methods.
The selective interaction of metal clusters with various polymers constitutes the basis for the self-assembly approach to the synthesis of organic-inorganic hybrid materials, that leads to the control of particle size, geometry and dispersion gradient. Metal particles were synthesized by the thermal decomposition of an organometallic precursor, in this case, iron pentacarbonyl, in the presence of a polymer matrix. Under the conditions utilized for these reactions, the aggregation of the metallic clusters competed with the interactions between the growing metal fragments and the polymer matrix. The dominance of one reaction route as compared to the other, ultimately determined the equilibrium particle shape, size and distribution for each metal-polymer system. In this work, we attempted to analyze the formation of iron oxide nanoclusters in several structurally-distinct polymers, and developed a general mechanistic view to explain the characteristics of the polymer-metal oxide hybrid materials that were obtained.
One of the features of ultra high intensity (UHI) short
pulse laser–matter interactions is the prospect of
creating a cheap, compact source of hard X rays
with femtosecond pulse duration. The properties of such
Kα sources are studied using analytical and
numerical models of hot electron generation and subsequent
transport in a range of materials (Reich et al., 2000).
First, we find that there is an optimum laser intensity for
Kα generation from bulk targets, which scales as
Z4.4. Second, we show that efficient hard
X-ray pulses with durations below 100 fs can be generated at
intensities of ∼1016 W/cm2.