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To identify genetic risk loci for major depressive disorder (MDD), two broad study design approaches have been applied: (1) to maximize sample size by combining data from different phenotype assessment modalities (e.g. clinical interview, self-report questionnaires) and (2) to reduce phenotypic heterogeneity through selecting more homogenous MDD subtypes. The value of these strategies has been debated. In this review, we summarize the most recent findings of large genomic studies that applied these approaches, and we highlight the merits and pitfalls of both approaches with particular attention to methodological and psychometric issues. We also discuss the results of analyses that investigated the heterogeneity of MDD. We conclude that both study designs are essential for further research. So far, increasing sample size has led to the identification of a relatively high number of genomic loci linked to depression. However, part of the identified variants may be related to a phenotype common to internalizing disorders and related traits. As such, samples containing detailed clinical information are needed to dissect depression heterogeneity and enable the potential identification of variants specific to a more restricted MDD phenotype. A balanced portfolio reconciling both study design approaches is the optimal approach to progress further in unraveling the genetic architecture of depression.
Epoch of Reionisation (EoR) data analysis requires unprecedented levels of accuracy in radio interferometer pipelines. We have developed an imaging power spectrum analysis to meet these requirements and generate robust 21 cm EoR measurements. In this work, we build a signal path framework to mathematically describe each step in the analysis, from data reduction in the Fast Holographic Deconvolution (FHD) package to power spectrum generation in the εppsilon package. In particular, we focus on the distinguishing characteristics of FHD/εppsilon: highly accurate spectral calibration, extensive data verification products, and end-to-end error propagation. We present our key data analysis products in detail to facilitate understanding of the prominent systematics in image-based power spectrum analyses. As a verification to our analysis, we also highlight a full-pipeline analysis simulation to demonstrate signal preservation and lack of signal loss. This careful treatment ensures that the FHD/εppsilon power spectrum pipeline can reduce radio interferometric data to produce credible 21 cm EoR measurements.
Thin film metallization is used on integrated circuit chips and ceramic and/or organic substrates for a number of different purposes, On chips the metallization forms Ohmic and Schottky Barrier Diode contact to the semiconductor and the electrical properties of these contacts are strongly influenced by the metals used. Interaction of the metal and semiconductor during processing can result in major variations in the electrical properties of the contacts, Chip metallization is also employed to provide electrical interconnection between devices on a chip. The interconnections can all be made in a single layer, or for more complex chips, a number of layers might be employed using dielectric layers to separate metal layers and via holes through the dielectric for layer-to-layer interconnection. Chip metallization is also used to form the interconnections between the chips and the substrate carrier.
Most studies underline the contribution of heritable factors for psychiatric disorders. However, heritability estimates depend on the population under study, diagnostic instruments, and study designs that each has its inherent assumptions, strengths, and biases. We aim to test the homogeneity in heritability estimates between two powerful, and state of the art study designs for eight psychiatric disorders.
We assessed heritability based on data of Swedish siblings (N = 4 408 646 full and maternal half-siblings), and based on summary data of eight samples with measured genotypes (N = 125 533 cases and 208 215 controls). All data were based on standard diagnostic criteria. Eight psychiatric disorders were studied: (1) alcohol dependence (AD), (2) anorexia nervosa, (3) attention deficit/hyperactivity disorder (ADHD), (4) autism spectrum disorder, (5) bipolar disorder, (6) major depressive disorder, (7) obsessive-compulsive disorder (OCD), and (8) schizophrenia.
Heritability estimates from sibling data varied from 0.30 for Major Depression to 0.80 for ADHD. The estimates based on the measured genotypes were lower, ranging from 0.10 for AD to 0.28 for OCD, but were significant, and correlated positively (0.19) with national sibling-based estimates. When removing OCD from the data the correlation increased to 0.50.
Given the unique character of each study design, the convergent findings for these eight psychiatric conditions suggest that heritability estimates are robust across different methods. The findings also highlight large differences in genetic and environmental influences between psychiatric disorders, providing future directions for etiological psychiatric research.
Race, psychiatric history, and adverse life events have all been independently associated with postpartum depression (PPD). However, the role these play together in Black and Latina women remains inadequately studied. Therefore, we performed a case–control study of PPD, including comprehensive assessments of symptoms and biomarkers, while examining the effects of genetic ancestry.
We recruited our sample (549 cases, 968 controls) at 6 weeks postpartum from obstetrical clinics in North Carolina. PPD status was determined using the MINI-plus. Psychiatric history was extracted from medical records. Participants were administered self-report instruments to assess depression (Edinburgh Postnatal Depression Scale) and adverse life events. Levels of estradiol, progesterone, brain-derived neurotrophic factor, oxytocin, and allopregnanalone were assayed. Principal components from genotype data were used to estimate genetic ancestry and logistic regression was used to identify predictors of PPD.
This population was racially diverse (68% Black, 13% Latina, 18% European). Genetic ancestry was not a predictor of PPD. Case status was predicted by a history of major depression (p = 4.01E-14), lifetime anxiety disorder diagnosis (p = 1.25E-34), and adverse life events (p = 6.06E-06). There were no significant differences between groups in any hormones or neurosteroids.
Psychiatric history and multiple exposures to adverse life events were significant predictors of PPD in a population of minority and low-income women. Genetic ancestry and hormone levels were not predictive of case status. Increased genetic vulnerability in conjunction with risk factors may predict the onset of PPD, whereas genetic ancestry does not appear predictive.
Family history is a long-standing and readily obtainable risk factor for schizophrenia (SCZ). Low-cost genotyping technologies have enabled large genetic studies of SCZ, and the results suggest the utility of genetic risk scores (GRS, direct assessments of inherited common variant risk). Few studies have evaluated family history and GRS simultaneously to ask whether one can explain away the other.
We studied 5959 SCZ cases and 8717 controls from four Nordic countries. All subjects had family history data from national registers and genome-wide genotypes that were processed through the quality control procedures used by the Psychiatric Genomics Consortium. Using external training data, GRS were estimated for SCZ, bipolar disorder (BIP), major depression, autism, educational attainment, and body mass index. Multivariable modeling was used to estimate effect sizes.
Using harmonized genomic and national register data from Denmark, Estonia, Norway, and Sweden, we confirmed that family history of SCZ and GRS for SCZ and BIP were risk factors for SCZ. In a joint model, the effects of GRS for SCZ and BIP were essentially unchanged, and the effect of family history was attenuated but remained significant. The predictive capacity of a model including GRS and family history neared the minimum for clinical utility.
Combining national register data with measured genetic risk factors represents an important investigative approach for psychotic disorders. Our findings suggest the potential clinical utility of combining GRS and family history for early prediction and diagnostic improvements.
We present techniques developed to calibrate and correct Murchison Widefield Array low-frequency (72–300 MHz) radio observations for polarimetry. The extremely wide field-of-view, excellent instantaneous (u, v)-coverage and sensitivity to degree-scale structure that the Murchison Widefield Array provides enable instrumental calibration, removal of instrumental artefacts, and correction for ionospheric Faraday rotation through imaging techniques. With the demonstrated polarimetric capabilities of the Murchison Widefield Array, we discuss future directions for polarimetric science at low frequencies to answer outstanding questions relating to polarised source counts, source depolarisation, pulsar science, low-mass stars, exoplanets, the nature of the interstellar and intergalactic media, and the solar environment.
Universal screening for postpartum depression is recommended in many countries. Knowledge of whether the disclosure of depressive symptoms in the postpartum period differs across cultures could improve detection and provide new insights into the pathogenesis. Moreover, it is a necessary step to evaluate the universal use of screening instruments in research and clinical practice. In the current study we sought to assess whether the Edinburgh Postnatal Depression Scale (EPDS), the most widely used screening tool for postpartum depression, measures the same underlying construct across cultural groups in a large international dataset.
Ordinal regression and measurement invariance were used to explore the association between culture, operationalized as education, ethnicity/race and continent, and endorsement of depressive symptoms using the EPDS on 8209 new mothers from Europe and the USA.
Education, but not ethnicity/race, influenced the reporting of postpartum depression [difference between robust comparative fit indexes (∆*CFI) < 0.01]. The structure of EPDS responses significantly differed between Europe and the USA (∆*CFI > 0.01), but not between European countries (∆*CFI < 0.01).
Investigators and clinicians should be aware of the potential differences in expression of phenotype of postpartum depression that women of different educational backgrounds may manifest. The increasing cultural heterogeneity of societies together with the tendency towards globalization requires a culturally sensitive approach to patients, research and policies, that takes into account, beyond rhetoric, the context of a person's experiences and the context in which the research is conducted.
Data were pooled from three Australian sentinel general practice influenza surveillance networks to estimate Australia-wide influenza vaccine coverage and effectiveness against community presentations for laboratory-confirmed influenza for the 2012, 2013 and 2014 seasons. Patients presenting with influenza-like illness at participating GP practices were swabbed and tested for influenza. The vaccination odds of patients testing positive were compared with patients testing negative to estimate influenza vaccine effectiveness (VE) by logistic regression, adjusting for age group, week of presentation and network. Pooling of data across Australia increased the sample size for estimation from a minimum of 684 to 3,683 in 2012, from 314 to 2,042 in 2013 and from 497 to 3,074 in 2014. Overall VE was 38% [95% confidence interval (CI) 24–49] in 2012, 60% (95% CI 45–70) in 2013 and 44% (95% CI 31–55) in 2014. For A(H1N1)pdm09 VE was 54% (95% CI–28 to 83) in 2012, 59% (95% CI 33–74) in 2013 and 55% (95% CI 39–67) in 2014. For A(H3N2), VE was 30% (95% CI 14–44) in 2012, 67% (95% CI 39–82) in 2013 and 26% (95% CI 1–45) in 2014. For influenza B, VE was stable across years at 56% (95% CI 37–70) in 2012, 57% (95% CI 30–73) in 2013 and 54% (95% CI 21–73) in 2014. Overall VE against influenza was low in 2012 and 2014 when A(H3N2) was the dominant strain and the vaccine was poorly matched. In contrast, overall VE was higher in 2013 when A(H1N1)pdm09 dominated and the vaccine was a better match. Pooling data can increase the sample available and enable more precise subtype- and age group-specific estimates, but limitations remain.
A major astrophysical problem is related to the fact that rotation curves (RCs)) of galaxies are flat. The presence of a dark halo is most often invoked to explain that. Some controversies exist concerning the existence of a dark halo for galaxies in very hostile environments like in center of clusters. Using a scanning Fabry-Perot interferometer, we have observed Hα velocity fields of a sample of 38 galaxies located in 7 different clusters of galaxies. From this sample, our conclusion is that spirals located in the central part of clusters do not have decreasing RCs within the optical radius.
The red variables whose amplitude is larger than 1.3 mag in the MOA database are studied for the LMC. Among 3 196 such stars, 532 stars are likely to be Miras or red semiregular variables. The period–colour relation of these stars is shown.
A large database of CCD photometry for 1.4 million stars towards both the LMC and the SMC, which has been established by the MOA project, is a useful resource to study variable stars. In our preliminary study, variables identified as β Lyrae type stars and Herbig Ae/Be stars have been found amongst blue stars.
The variability of CD-24 7599 (V=11.48 mag) was discovered by JCC during observing run XCOV7 of the Whole Earth Telescope (WET, Nather et al. 1990) network in February, 1992. The star was observed as an additional target and 117 hours of high-quality temporal spectroscopic observations were obtained.
Our analysis of these data revealed the presence of 7 independent pulsation modes between 27.0 and 38.1 cycles per day (313 – 441 μHz) with semiamplitudes of 2.1 – 10.2 milli-modulation amplitudes (mma). We showed that peaks at linear combination frequencies detected in the power spectra were not due to eigenmodes excited to visible amplitude by resonant mode coupling.
A review of the MOA (Microlensing Observations in Astrophysics) project is presented. MOA is a collaboration of approximately 30 astronomers from New Zealand and Japan established with the aim of finding and detecting microlensing events towards the Magellanic Clouds and the Galactic bulge, which may be indicative of either dark matter or of planetary companions. The observing program commenced in 1995, using very wide band blue and red filters and a nine-chip mosaic CCD camera.
As a by-product of these observations a large database of CCD photometry for 1.4 million stars towards both LMC and SMC has been established. In one preliminary analysis 576 bright variable stars were confirmed, nearly half of them being Cepheids. Another analysis has identified large numbers of blue variables, and 205 eclipsing binaries are included in this sample. In addition 351 red variables (AGB stars) have been found. Light curves have been obtained for all these stars. The observations are carried out on a 61-cm f/6.25 telescope at Mt John University Observatory where a new larger CCD camera was installed in 1998 July. From this latitude (44° S) the Magellanic Clouds can be monitored throughout the year.
Childhood emotional maltreatment (CEM) increases the likelihood of developing an anxiety disorder in adulthood, but the neural processes underlying conferment of this risk have not been established. Here, we test the potential for neuroimaging the adult brain to inform understanding of the mechanism linking CEM to adult anxiety symptoms.
One hundred eighty-two adults (148 females, 34 males) with a normal-to-clinical range of anxiety symptoms underwent structural and functional magnetic resonance imaging while completing an emotion-processing paradigm with facial expressions of fear, anger, and happiness. Participants completed self-report measures of CEM and current anxiety symptoms. Voxelwise mediation analyses on gray-matter volumes and activation to each emotion condition were used to identify candidate brain mechanisms relating CEM to anxiety in adulthood.
During processing of fear and anger faces, greater amygdala and less right dorsolateral prefrontal (dlPFC) activation partially mediated the positive relationship between CEM and anxiety symptoms. Greater right posterior insula activation to fear also partially mediated this relationship, as did greater ventral anterior cingulate (ACC) and less dorsal ACC activation to anger. Responses to happy faces in these regions did not mediate the CEM-anxiety relationship. Smaller right dlPFC gray-matter volumes also partially mediated the CEM-anxiety relationship.
Activation patterns of the adult brain demonstrate the potential to inform mechanistic accounts of the CEM conferment of anxiety symptoms. Results support the hypothesis that exaggerated limbic activation to negative valence facial emotions links CEM to anxiety symptoms, which may be consequent to a breakdown of cortical regulatory processes.
The Murchison Widefield Array is a new low-frequency interferometric radio telescope built in Western Australia at one of the locations of the future Square Kilometre Array. We describe the automated radio-frequency interference detection strategy implemented for the Murchison Widefield Array, which is based on the aoflagger platform, and present 72–231 MHz radio-frequency interference statistics from 10 observing nights. Radio-frequency interference detection removes 1.1% of the data. Radio-frequency interference from digital TV is observed 3% of the time due to occasional ionospheric or atmospheric propagation. After radio-frequency interference detection and excision, almost all data can be calibrated and imaged without further radio-frequency interference mitigation efforts, including observations within the FM and digital TV bands. The results are compared to a previously published Low-Frequency Array radio-frequency interference survey. The remote location of the Murchison Widefield Array results in a substantially cleaner radio-frequency interference environment compared to Low-Frequency Array’s radio environment, but adequate detection of radio-frequency interference is still required before data can be analysed. We include specific recommendations designed to make the Square Kilometre Array more robust to radio-frequency interference, including: the availability of sufficient computing power for radio-frequency interference detection; accounting for radio-frequency interference in the receiver design; a smooth band-pass response; and the capability of radio-frequency interference detection at high time and frequency resolution (second and kHz-scale respectively).
Although evidence exists for abnormal brain function across various
anxiety disorders, direct comparison of neural function across diagnoses
is needed to elicit abnormalities common across disorders and those
distinct to a particular diagnosis.
To delineate common and distinct abnormalities within generalised anxiety
(GAD), panic and social anxiety disorder (SAD) during affective
Fifty-nine adults (15 with GAD, 15 with panic disorder, 14 with SAD, and
15 healthy controls) underwent functional magnetic resonance imaging
while completing a facial emotion matching task with fearful, angry and
Greater differential right amygdala activation to matching fearful
v. happy facial expressions related to greater
negative affectivity (i.e. trait anxiety) and was heightened across all
anxiety disorder groups compared with controls. Collapsing across
emotional face types, participants with panic disorder uniquely displayed
greater posterior insula activation.
These preliminary results highlight a common neural basis for clinical
anxiety in these diagnoses and also suggest the presence of