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Diagnostic criteria for major depressive disorder allow for heterogeneous symptom profiles but genetic analysis of major depressive symptoms has the potential to identify clinical and etiological subtypes. There are several challenges to integrating symptom data from genetically informative cohorts, such as sample size differences between clinical and community cohorts and various patterns of missing data.
Methods
We conducted genome-wide association studies of major depressive symptoms in three cohorts that were enriched for participants with a diagnosis of depression (Psychiatric Genomics Consortium, Australian Genetics of Depression Study, Generation Scotland) and three community cohorts who were not recruited on the basis of diagnosis (Avon Longitudinal Study of Parents and Children, Estonian Biobank, and UK Biobank). We fit a series of confirmatory factor models with factors that accounted for how symptom data was sampled and then compared alternative models with different symptom factors.
Results
The best fitting model had a distinct factor for Appetite/Weight symptoms and an additional measurement factor that accounted for the skip-structure in community cohorts (use of Depression and Anhedonia as gating symptoms).
Conclusion
The results show the importance of assessing the directionality of symptoms (such as hypersomnia versus insomnia) and of accounting for study and measurement design when meta-analyzing genetic association data.
Depression is the largest global contributor to non-fatal disease burden(1). A growing body of evidence suggests that dietary behaviours, such as higher fruit and vegetable intake, may be protective against the risk of depression(2). However, this evidence is primarily from high-income countries, despite over 80% of the burden of depression being experienced in low- and middle-income countries(1). There are also limited studies to date focusing on older adults. The aim of this study was to prospectively examine the associations between baseline fruit and vegetable intake and incidence of depression in adults aged 45-years and older from 10 cohorts across six continents, including four cohorts from low and middle-income countries. The association between baseline fruit and vegetable intake and incident depression over a 3–6-year follow-up period was examined using Cox proportional hazard regression after controlling for a range of potential confounders. Participants were 7771 community-based adults aged 45+ years from 10 diverse cohorts. All cohorts were members of the Cohort Studies of Memory in an International Consortium collaboration(3). Fruit intake (excluding juice) and vegetable intake was collected using either a comprehensive food frequency questionnaire, short food questionnaire or diet history. Depressive symptoms were assessed using validated depression measures, and depression was defined as a score greater than or equal to a validated cut-off. Prior to analysis all data were harmonised. Analysis was performed by cohort and then cohort results were combined using meta-analysis. Subgroup analysis was performed by sex, age (45 – 64 versus 65+ years) and income level of country (high income countries versus low- and middle-income countries). There were 1537 incident cases of depression over 32,420 person-years of follow-up. Mean daily intakes of fruit were 1.7 ± 1.5 serves and vegetables 1.9 ± 1.4. serves. We found no association between fruit and vegetable intakes and risk of incident depression in any of the analyses, and this was consistent across the subgroup analyses. The low intake of fruit and vegetables of participants, diverse measures used across the different cohorts, and modest sample size of our study compared with prior studies in the literature, may have prevented an association being detected. Further investigation using standardised measures in larger cohorts of older adults from low- to middle-income countries is needed. Future research should consider the potential relationship between different types of fruits and vegetables and depression.
As the scale of cosmological surveys increases, so does the complexity in the analyses. This complexity can often make it difficult to derive the underlying principles, necessitating statistically rigorous testing to ensure the results of an analysis are consistent and reasonable. This is particularly important in multi-probe cosmological analyses like those used in the Dark Energy Survey (DES) and the upcoming Legacy Survey of Space and Time, where accurate uncertainties are vital. In this paper, we present a statistically rigorous method to test the consistency of contours produced in these analyses and apply this method to the Pippin cosmological pipeline used for type Ia supernova cosmology with the DES. We make use of the Neyman construction, a frequentist methodology that leverages extensive simulations to calculate confidence intervals, to perform this consistency check. A true Neyman construction is too computationally expensive for supernova cosmology, so we develop a method for approximating a Neyman construction with far fewer simulations. We find that for a simulated dataset, the 68% contour reported by the Pippin pipeline and the 68% confidence region produced by our approximate Neyman construction differ by less than a percent near the input cosmology; however, they show more significant differences far from the input cosmology, with a maximal difference of 0.05 in $\Omega_{M}$ and 0.07 in w. This divergence is most impactful for analyses of cosmological tensions, but its impact is mitigated when combining supernovae with other cross-cutting cosmological probes, such as the cosmic microwave background.
The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
The discovery of the first electromagnetic counterpart to a gravitational wave signal has generated follow-up observations by over 50 facilities world-wide, ushering in the new era of multi-messenger astronomy. In this paper, we present follow-up observations of the gravitational wave event GW170817 and its electromagnetic counterpart SSS17a/DLT17ck (IAU label AT2017gfo) by 14 Australian telescopes and partner observatories as part of Australian-based and Australian-led research programs. We report early- to late-time multi-wavelength observations, including optical imaging and spectroscopy, mid-infrared imaging, radio imaging, and searches for fast radio bursts. Our optical spectra reveal that the transient source emission cooled from approximately 6 400 K to 2 100 K over a 7-d period and produced no significant optical emission lines. The spectral profiles, cooling rate, and photometric light curves are consistent with the expected outburst and subsequent processes of a binary neutron star merger. Star formation in the host galaxy probably ceased at least a Gyr ago, although there is evidence for a galaxy merger. Binary pulsars with short (100 Myr) decay times are therefore unlikely progenitors, but pulsars like PSR B1534+12 with its 2.7 Gyr coalescence time could produce such a merger. The displacement (~2.2 kpc) of the binary star system from the centre of the main galaxy is not unusual for stars in the host galaxy or stars originating in the merging galaxy, and therefore any constraints on the kick velocity imparted to the progenitor are poor.
The SkyMapper Transient survey (SMT) is exploring variability in the southern sky by performing (a) a rolling search to discover and study supernovæ, and (b) a Target of Opportunity programme that uses the robotic SkyMapper Telescope at Siding Spring Observatory. The supernova survey is obtaining a non-targeted sample of Type Ia supernovæ (SNe Ia) at low redshifts, z < 0.1, and studying other interesting transients found with the search strategy. We have a Target of Opportunity programme with an automatic response mechanism to search for optical counterparts to gravitational-wave and fast radio-burst events; it benefits from SkyMapper’s large field of view of 5.7 sq. deg. and a rapid data reduction pipeline.
We present first results of the SMT survey. The SMT pipeline can process and obtain potential candidates within 12 hours of observation. It disentangles real transients from processing artefacts using a machine-learning algorithm. To date, SMT has discovered over 60 spectroscopically confirmed supernovæ, several peculiar objects, and over 40 SNe Ia including one (SNIa 2016hhd) which was found within the first few days of explosion. We have also participated in searches for optical counterparts of gravitational waves, fast radio bursts and other transients, and have published observations of the optical counterpart of the gravitational-wave event GW170817. We also participate in coordinated observations with the Deeper Wider Faster programme, and the Kepler K2 cosmology project.
The SkyMapper 1.3 m telescope at Siding Spring Observatory has now begun regular operations. Alongside the Southern Sky Survey, a comprehensive digital survey of the entire southern sky, SkyMapper will carry out a search for supernovae and other transients. The search strategy, covering a total footprint area of ~2 000 deg2 with a cadence of ⩽5 d, is optimised for discovery and follow-up of low-redshift type Ia supernovae to constrain cosmic expansion and peculiar velocities. We describe the search operations and infrastructure, including a parallelised software pipeline to discover variable objects in difference imaging; simulations of the performance of the survey over its lifetime; public access to discovered transients; and some first results from the Science Verification data.
The toxicity of 1,1'-dimethyl-4,4'-bipyridinium ion (paraquat) in soil can be related to the degree of bonding strength to the soil aggregates. Tightly bound material is unavailable to plants, while loosely bound material can be potentially available to plants. On the basis of growth of corn (Zea mays L., var. Golden Cross Bantam) and beans (Phaseolus vulgaris L., var. Idaho 1-11) in sand, loamy sand, loam, and muck treated with paraquat, it is concluded that planned and careful application would not lead to accumulation of lethal dosages in medium to heavy soils.
The Dark Energy Survey is undertaking an observational programme imaging 1/4 of the southern hemisphere sky with unprecedented photometric accuracy. In the process of observing millions of faint stars and galaxies to constrain the parameters of the dark energy equation of state, the Dark Energy Survey will obtain pre-discovery images of the regions surrounding an estimated 100 gamma-ray bursts over 5 yr. Once gamma-ray bursts are detected by, e.g., the Swift satellite, the DES data will be extremely useful for follow-up observations by the transient astronomy community. We describe a recently-commissioned suite of software that listens continuously for automated notices of gamma-ray burst activity, collates information from archival DES data, and disseminates relevant data products back to the community in near-real-time. Of particular importance are the opportunities that non-public DES data provide for relative photometry of the optical counterparts of gamma-ray bursts, as well as for identifying key characteristics (e.g., photometric redshifts) of potential gamma-ray burst host galaxies. We provide the functional details of the DESAlert software, and its data products, and we show sample results from the application of DESAlert to numerous previously detected gamma-ray bursts, including the possible identification of several heretofore unknown gamma-ray burst hosts.
Bioimpedance spectroscopy (BIS) has been used to track changes in total body water (TBW). Accurate TBW estimations can be influenced by both methodological and biological factors. One methodological variation that contributes to BIS TBW errors is the electrode placement. The purpose of the present study was to compare the reproducibility and validity of fixed-distance electrode placements (5 cm) with the standard single-site electrode placements. Twenty-nine subjects (fifteen men and fourteen women) participated in the reproducibility study, while sixty-nine subjects (thirty-three men and thirty-six women) participated in the validity study. The reproducibility study included two measurements that were taken 24 h apart, while the validity study consisted of a 12-week exercise intervention with measurements taken at weeks 1 and 12. TBW was estimated using BIS and 2H techniques. Reproducibility results indicated that fixed-distance electrodes reduced the day-to-day standard error of the measurement in men (from 1·13 to 0·81 litres) but not in women (0·47 litres). sem values were lower for women than for men, suggesting that BIS TBW estimates are sex dependent. Validity results produced similar accurate findings (mean difference < 0·21 litres). However, fixed-distance electrodes improved delta TBW errors (mean difference improvements>0·04 litres in men, women, and men and women combined). When tracking changes in TBW, fixed-distance electrodes may reduce reproducibility errors and allow for smaller changes to be detected. However, the reduction of reproducibility errors may be greater for men than for women. Therefore, reproducibility calculations should be based on the sex of the sample population.
To evaluate the prevalence and risk factors of nasal Staphylococcus aureus (SA) in the community.
Design:
Cross-sectional study.
Setting:
Wake Forest University, Winston-Salem, North Carolina.
Participants:
Four hundred fifty students were screened for nasal SA carriage during the fall of 2000, 2001, and 2002.
Methods:
Students were screened by nose swabs. A self-administered questionnaire collected information on demographics and medical history. Antibiotic testing and PFGE were performed on isolates. Risk factors were determined by logistic regression analysis.
Results:
Of 450 volunteers, 131 (29%) were SA carriers. Antibiotic resistance was high for azithromycin (26%) and low for ciprofloxacin (1%), tetracycline (5%), mupirocin (1%), and methicillin (2%). PFGE patterns were not associated with carriage. Age, male gender, white race, medical student, allergen injection therapy, chronic sinusitis, rheumatoid arthritis, hospitalization for 6 months or less, and use of antibiotics were associated with carrier status by univariate analysis. Stepwise multivariate logistic regression led to a best fitting model with older age (OR, 1.04; CI95, 1.005-1.079), male gender (OR, 1.50; CI95, 0.982-2.296), and chronic sinusitis (OR, 2.71; CI95, 0.897-8.195) as risk factors. Antibiotic use (< 4 weeks) (OR, 0.41; CI95, 0.152-1.095) and allergen injection therapy (OR 0.41; CI95, 0.133-1.238) were protective. Analyses of carriers revealed candidate factors for persistent carriage to be nasal SA colonization rate and male gender. Factors for azithromycin resistance were non-medical students and antibiotic use in the past 6 months.
Conclusion:
Older male volunteers suffering from chronic sinusitis and not taking antibiotics were at higher risk for carrying SA.
To investigate whether rhinovirus infection leads to increased airborne dispersal of coagulase-negative staphylococci (CoNS).
Design:
Prospective nonrandomized intervention trial.
Setting:
Wake Forest University School of Medicine, Winston-Salem, North Carolina.
Participants:
Twelve nasal Staphylococcus aureus-CoNS carriers among 685 students screened for S. aureus nasal carriage.
Interventions:
Participants were studied for airborne dispersal of CoNS in a chamber under three conditions (street clothes, sterile gown with a mask, and sterile gown without a mask). After 2 days of pre-exposure measurements, volunteers were inoculated with a rhinovirus and observed for 14 days. Daily quantitative nasal and skin cultures for CoNS and nasal cultures for rhinovirus were performed. In addition, assessment of cold symptoms was performed daily, mucous samples were collected, and serum titers before and after rhinovirus inoculation were obtained. Sneezing, coughing, and talking events were recorded during chamber sessions.
Results:
All participants had at least one nasal wash positive for rhinovirus and 10 developed a symptomatic cold. Postexposure, there was a twofold increase in airborne CoNS (P = .0004), peaking at day 12. CoNS dispersal was reduced by wearing a gown (57% reduction, P < .0001), but not a mask (P = .7). Nasal and skin CoNS colonization increased after rhinovirus infection (P<.05).
Conclusions:
We believe this is the first demonstration that a viral pathogen in the upper airways can increase airborne dispersal of CoNS in nasal S. aureus carriers. Gowns, gloves, and caps had a protective effect, whereas wearing a mask did not further reduce airborne spread.
Chemical action between cyclodextrins (CDs) and TOPO-(CdSe)ZnS quantum dots (QDs) generates a water-soluble solution of CD-QDs. Hydrophobic TOPO molecules on surface of the QDs are compatible to thread through the pockets of CDs and make the hydroxyl group on end of CDs to approach the ZnS surface, and then cause the interaction between ZnS and the hydroxyls. In this paper, Photoluminescence of the γ-CD-QD solution appeared about 15 nm of red movement compared with that of the QDs in hexane; 58% replacement of the crystal coordinate bond of Zn-S with that of Zn-O in the ZnS shell was demonstrated by using first-principles density functional theory and the red shift of the photoluminescence of CD-QDs; and –0.11eV of the energy gain of the exchange model was calculated by using an effective mass (EM) model. CD-QDs will provide water-soluble QDs with conjugational group for biology and molecule-device applications.
Using site-specific plan-view transmission electron microscopy (TEM) and lightemission imaging (LEI), we have identified SFs formed during forward biasing of 4H-SiC PiN diodes. These SFs are bounded by Shockley partial dislocations and are formed by shear strain rather than by condensation of vacancies or interstitials. Detailed analysis using TEM diffraction contrast experiments reveal SFs with leading carbon-core Shockley partial dislocations as well as with the silicon-core partial dislocations observed in plastic deformation of 4H-SiC at elevated temperatures. The leading Shockley partials are seen to relieve both tensile and compressive strain during PiN diode operation, suggesting the presence of a complex and inhomogeneous strain field in the 4H-SiC layer.