Effect of Chronic Escitalopram versus Placebo on Personality Traits in Healthy First-Degree Relatives of Patients with Depression: A Randomized Trial

The serotonergic neurotransmitter system is closely linked to depression and personality traits. It is not known if selective serotonin reuptake inhibitors (SSRI) have an effect on neuroticism that is independent of their effect on depression. Healthy individuals with a genetic liability for depression represent a group of particular interest when investigating if intervention with SSRIs affects personality. The present trial is the first to test the hypothesis that escitalopram may reduce neuroticism in healthy first-degree relatives of patients with major depressive disorder (MD).The trial used a randomized, blinded, placebo-controlled parallel-group design. We examined the effect of four weeks escitalopram 10 mg daily versus matching placebo on personality in 80 people who had a biological parent or sibling with a history of MD. The outcome measure on personality traits was change in self-reported neuroticism scores on the Revised Neuroticism-Extroversion-Openness-Personality Inventory (NEO-PI-R) and the Eysenck Personality Inventory (EPQ) from entry until end of four weeks of intervention.When compared with placebo, escitalopram did not significantly affect self-reported NEO-PI-R and EPQ neuroticism and extroversion, EPQ psychoticism, NEO-PI-R openness, or NEO-PI-R conscientiousness (p all above 0.05). However, escitalopram increased NEO-PI-R agreeableness scores significantly compared with placebo (mean; SD) (2.38; 8.09) versus (-1.32; 7.94), p = 0.046), but not following correction for multiplicity. A trend was shown for increased conscientiousness (p = 0.07). There was no significant effect on subclinical depressive symptoms (p = 0.6).In healthy first-degree relatives of patients with MD, there is no effect of escitalopram on neuroticism, but it is possible that escitalopram may increase the personality traits of agreeableness and conscientiousness.Clinicaltrials.gov NCT00386841

Alignment, orientation, and Coulomb explosion of difluoroiodobenzene studied with the pixel imaging mass spectrometry (PImMS) camera

Citation: Amini, K., Boll, R., Lauer, A., Burt, M., Lee, J. W. L., Christensen, L., . . . Rolles, D. (2017). Alignment, orientation, and Coulomb explosion of difluoroiodobenzene studied with the pixel imaging mass spectrometry (PImMS) camera. Journal of Chemical Physics, 147(1). doi:10.1063/1.4982220Laser-induced adiabatic alignment and mixed-field orientation of 2,6-difluoroiodobenzene (C6H3F2I) molecules are probed by Coulomb explosion imaging following either near-infrared strong-field ionization or extreme-ultraviolet multi-photon inner-shell ionization using free-electron laser pulses. The resulting photoelectrons and fragment ions are captured by a double-sided velocity map imaging spectrometer and projected onto two position-sensitive detectors. The ion side of the spectrometer is equipped with a pixel imaging mass spectrometry camera, a time-stamping pixelated detector that can record the hit positions and arrival times of up to four ions per pixel per acquisition cycle. Thus, the time-of-flight trace and ion momentum distributions for all fragments can be recorded simultaneously. We show that we can obtain a high degree of one-and three-dimensional alignment and mixed-field orientation and compare the Coulomb explosion process induced at both wavelengths. © 2017 Author(s)

A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes

dentification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined T1D+T2D GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 subjects with diabetes (18,582 with DKD). Analysis of specific DKD phenotypes identified a novel signal near GABRR1 (rs9942471, P = 4.5 x 10(-8)) associated with microalbuminuria in European T2D case subjects. However, no replication of this signal was observed in Asian subjects with T2D or in the equivalent T1D analysis. There was only limited support, in this substantially enlarged analysis, for association at previously reported DKD signals, except for those at UMOD and PRKAG2, both associated with estimated glomerular filtration rate. We conclude that, despite challenges in addressing phenotypic heterogeneity, access to increased sample sizes will continue to provide more robust inference regarding risk variant discovery for DKD.Peer reviewe

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Planck intermediate results. XV. A study of anomalous microwave emission in Galactic clouds

Anomalous microwave emission (AME) is believed to be due to electric dipole radiation from small spinning dust grains. The aim of this paper is a statistical study of the basic properties of AME regions and the environment in which they emit. We used WMAP and Planck maps, combined with ancillary radio and IR data, to construct a sample of 98 candidate AME sources, assembling SEDs for each source using aperture photometry on 1°-smoothed maps from 0.408 GHz up to 3000 GHz. Each spectrum is fitted with a simple model of free-free, synchrotron (where necessary), cosmic microwave background (CMB), thermal dust, and spinning dust components. We find that 42 of the 98 sources have significant (>5σ) excess emission at frequencies between 20 and 60 GHz. An analysis of the potential contribution of optically thick free-free emission from ultra-compact H ii regions, using IR colour criteria, reduces the significant AME sample to 27 regions. The spectrum of the AME is consistent with model spectra of spinning dust. Peak frequencies are in the range 20−35 GHz except for the California nebula (NGC 1499), which appears to have a high spinning dust peak frequency of (50 ± 17) GHz. The AME regions tend to be more spatially extended than regions with little or no AME. The AME intensity is strongly correlated with the sub-millimetre/IR flux densities and comparable to previous AME detections in the literature. AME emissivity, defined as the ratio of AME to dust optical depth, varies by an order of magnitude for the AME regions. The AME regions tend to be associated with cooler dust in the range 14−20 K and an average emissivity index, βd, of +1.8, while the non-AME regions are typically warmer, at 20−27 K. In agreement with previous studies, the AME emissivity appears to decrease with increasing column density. This supports the idea of AME originating from small grains that are known to be depleted in dense regions, probably due to coagulation onto larger grains. We also find a correlation between the AME emissivity (and to a lesser degree the spinning dust peak frequency) and the intensity of the interstellar radiation field, G0. Modelling of this trend suggests that both radiative and collisional excitation are important for the spinning dust emission. The most significant AME regions tend to have relatively less ionized gas (free-free emission), although this could be a selection effect. The infrared excess, a measure of the heating of dust associated with H ii regions, is typically >4 for AME sources, indicating that the dust is not primarily heated by hot OB stars. The AME regions are associated with known dark nebulae and have higher 12 μm/25 μm ratios. The emerging picture is that the bulk of the AME is coming from the polycyclic aromatic hydrocarbons and small dust grains from the colder neutral interstellar medium phase. Reproduced with permission from Astronomy & Astrophysics, © ESO 201

Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns

Epigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. Here we examine the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs) in 4 independent cohorts (overall n = 2365). We use Akaike’s information criterion to test which factors best explain variability of methylation in the cohort-specific VMRs: several prenatal environmental factors (E), genotypes in cis (G), or their additive (G + E) or interaction (GxE) effects. Genetic and environmental factors in combination best explain DNAm at the majority of VMRs. The CpGs best explained by either G, G + E or GxE are functionally distinct. The enrichment of genetic variants from GxE models in GWAS for complex disorders supports their importance for disease risk