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Mental disorders can have a major impact on brain development. Peripheral blood concentrations of brain-derived neurotrophic factor (BDNF) are lower in adult psychiatric disorders. Serum BDNF concentrations and BDNF genotype have been associated with cortical maturation in children and adolescents. In 2 large independent samples, this study tests associations between serum BDNF concentrations, brain structure, and psychopathology, and the effects of BDNF genotype on BDNF serum concentrations in late childhood and early adolescence.
Children and adolescents (7-14 years old) from 2 cities (n = 267 in Porto Alegre; n = 273 in São Paulo) were evaluated as part of the Brazilian high-risk cohort (HRC) study. Serum BDNF concentrations were quantified by sandwich ELISA. Genotyping was conducted from blood or saliva samples using the SNParray Infinium HumanCore Array BeadChip. Subcortical volumes and cortical thickness were quantified using FreeSurfer. The Development and Well-Being Behavior Assessment was used to identify the presence of a psychiatric disorder.
Serum BDNF concentrations were not associated with subcortical volumes or with cortical thickness. Serum BDNF concentration did not differ between participants with and without mental disorders, or between Val homozygotes and Met carriers.
No evidence was found to support serum BDNF concentrations as a useful marker of developmental differences in brain and behavior in early life. Negative findings were replicated in 2 of the largest independent samples investigated to date.
The consumption of nitrate-rich vegetables can acutely lower blood pressure and improve mediators shown to optimise vascular health. However, we do not yet understand the impact of long-term habitual dietary nitrate intake and its association with CVD. Therefore, the aim of this investigation was to examine the relationship between habitual dietary nitrate intakes and risk of CHD in women from the Nurses’ Health Study. We prospectively followed 62 535 women who were free from diabetes, CVD and cancer at baseline in 1986. Information on diet was updated every 4 years with validated FFQ. The main outcome was CHD defined by the occurrence of non-fatal myocardial infarction or fatal CHD. Cox proportional hazard regression models were used to estimate the relative risks (RR) and 95 % CI. During 26 years of follow-up, 2257 cases of CHD were identified. When comparing the highest quintile of nitrate intake with the lowest quintile, in aged-adjusted analysis there was a protective association for CHD (RR=0·77, 95 % CI 0·68, 0·97; P=0·0002) which dissipated after further adjustment for smoking, physical activity, BMI and race (RR=0·91; 95 % CI 0·80, 1·04; P=0·27). This magnitude of association was further attenuated once we adjusted for the Alternative Healthy Eating Index excluding vegetable and fruit consumption (RR=1·04, 95 % CI 0·91, 1·20; P=0·34). Dietary nitrate intake was not related to the risk of CHD after adjustment for other lifestyle and non-vegetable dietary factors in a large group of US women.
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.
OBJECTIVES/SPECIFIC AIMS: We sought to investigate the role of the host microbiome during severe, acute respiratory infection (ARI) to understand the drivers of both acute clinical pathogenesis. METHODS/STUDY POPULATION: Nasopharyngeal swabs comprised of mixed cell populations at the active site of infection were collected from 192 hospitalized pediatric patients with ARI. We combined comprehensive respiratory virus detection and virus genome sequencing with 16S rRNA gene sequencing to evaluate the microbial content of the airway during ARI. This data was coupled with 11 clinical parameters, which were compiled to create a clinical severity score. The microbiome profiles were assessed to determine if clinical severity of infection, and/or specific virus was associated with increased clinical severity. RESULTS/ANTICIPATED RESULTS: We identified 8 major microbiome profiles classified by dominant bacterial genus, Moraxella, Corynebacterium, Staphylococcus, Haemophilus, Streptococcus, Alloiococcus, Schlegelella, and Diverse. Increased clinical severity was significantly associated with microbiome profiles dominated by Haemophilus, Streptococcus, and Schlegelella, whereas Corynebacterium and Alloiococcus were more prevalent in children with less severe disease. Independent of the microbial community, more than 60% of patients with the highest clinical severity were infected with either respiratory syncytial virus or rhinovirus. DISCUSSION/SIGNIFICANCE OF IMPACT: Our results indicate that individually and in combination, both virus and microbial composition may drive clinical severity during acute respiratory viral infections. It is still unclear how the complex interplay between virus, bacterial community, and the host response influence long-term respiratory impacts, such as the development of asthma. Nonetheless, during ARIs therapeutic interventions such as antibiotics and probiotics may be warranted in a subset of patients that are identified to have both a virus and microbiome profile that is associated with increased pathogenesis to limit both acute and long-term phenotypes.
Little is known about the association of cortical Aβ with depression and anxiety among cognitively normal (CN) elderly persons.
We conducted a cross-sectional study derived from the population-based Mayo Clinic Study of Aging in Olmsted County, Minnesota; involving CN persons aged ≥ 60 years that underwent PiB-PET scans and completed Beck Depression Inventory-II (BDI-II) and Beck Anxiety Inventory (BAI). Cognitive diagnosis was made by an expert consensus panel. Participants were classified as having abnormal (≥1.4; PiB+) or normal PiB-PET (<1.4; PiB−) using a global cortical to cerebellar ratio. Multi-variable logistic regression analyses were performed to calculate odds ratios (OR) and 95% confidence intervals (95% CI) after adjusting for age and sex.
Of 1,038 CN participants (53.1% males), 379 were PiB+. Each one point symptom increase in the BDI (OR = 1.03; 1.00–1.06) and BAI (OR = 1.04; 1.01–1.08) was associated with increased odds of PiB-PET+. The number of participants with BDI > 13 (clinical depression) was greater in the PiB-PET+ than PiB-PET- group but the difference was not significant (OR = 1.42; 0.83–2.43). Similarly, the number of participants with BAI > 10 (clinical anxiety) was greater in the PiB-PET+ than PiB-PET− group but the difference was not significant (OR = 1.77; 0.97–3.22).
As expected, depression and anxiety levels were low in this community-dwelling sample, which likely reduced our statistical power. However, we observed an informative albeit weak association between increased BDI and BAI scores and elevated cortical amyloid deposition. This observation needs to be tested in a longitudinal cohort study.
Astrobiology seeks to understand the limits of life and to determine the physiology of organisms in order to better assess the habitability of other worlds. To successfully achieve these goals we require microorganisms from environments on Earth that approximate to extraterrestrial environments in terms of physical and/or chemical conditions. The most challenging of these environments with respect to sample collection, isolation and cultivation of microorganisms are anoxic environments. In this paper, an approach to this challenge was implemented within the European Union's MASE (Mars Analogues for Space Exploration) project. In this review paper, we aim to provide a set of methods for future field work and sampling campaigns. A number of anoxic environment based on characteristics that make them analogous to past and present locations on Mars were selected. They included anoxic sulphur-rich springs (Germany), the salt-rich Boulby Mine (UK), a lake in a basaltic context (Iceland), acidic sediments in the Rio Tinto (Spain), glacier samples (Austria) and permafrost samples (Russia and Canada). Samples were collected under strict anoxic conditions to be used for cultivation and genomic community analysis. Using the samples, a culturing approach was implemented to enrich anaerobic organisms using a defined medium that would allow for organisms to be grown under identical conditions in future physiological comparisons. Anaerobic microorganisms were isolated and deposited with the DSMZ (Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH) culture collection to make them available to other scientists. In MASE, the selected organisms are studied with respect to survival and growth under Mars relevant stresses. They are artificially fossilized and the resulting biosignatures studied and used to investigate the efficacy of life detection instrumentation for planetary missions. Some of the organisms belong to genera with medical and environmental importance such as Yersinia spp., illustrating how astrobiology field research can be used to increase the availability of microbial isolates for applied terrestrial purposes.
The glycaemic and insulin indices assess postprandial glycaemic and insulin response to foods, respectively, which may not reflect the long-term effects of diet on insulin response. We developed and evaluated the validity of four empirical indices to assess the insulinaemic potential of usual diets and lifestyles, using dietary, lifestyle and biomarker data from the Nurses’ Health Study (NHS, n 5812 for hyperinsulinaemia, n 3929 for insulin resistance). The four indices were as follows: the empirical dietary index for hyperinsulinaemia (EDIH) and the empirical lifestyle index for hyperinsulinaemia (ELIH); the empirical dietary index for insulin resistance (EDIR) and the empirical lifestyle index for insulin resistance (ELIR). We entered thirty-nine FFQ-derived food groups in stepwise linear regression models, and defined indices as patterns most predictive of fasting plasma C-peptide, for the hyperinsulinaemia pathway (EDIH and ELIH), and of theTAG:HDL-cholesterol ratio, for the insulin-resistance pathway (EDIR and ELIR). We evaluated the validity of indices in two independent samples from NHS-II and Health Professionals Follow-up Study (HPFS) using multivariable-adjusted linear regression analyses to calculate relative concentrations of biomarkers. The EDIH is comprised of eighteen food groups; thirteen were positively associated with C-peptide and five were inversely associated. The EDIR is comprised of eighteen food groups; ten were positively associated with TAG:HDL-cholesterol and eight were inversely associated. Lifestyle indices had fewer dietary components, and included BMI and physical activity as components. In the validation samples, all indices significantly predicted biomarker concentrations – for example, the relative concentrations of the corresponding biomarkers comparing extreme index quintiles in the HPFS were EDIH, 1·29 (95 % CI 1·22, 1·37); ELIH, 1·78 (95 % CI 1·68, 1·88); EDIR, 1·44 (95 % CI 1·34, 1·55); and ELIR, 2·03 (95 % CI 1·89, 2·19); all Ptrend<0·0001. The robust associations of these novel hypothesis-driven indices with insulin response biomarker concentrations suggest their usefulness in assessing the ability of whole diets and lifestyles to stimulate and/or sustain insulin secretion.
This study investigates the origins of discrete interpersonal emotions in team-member dyads using two independent samples from an education institute and a telecommunication services company in China. Results across both studies showed that the quality of team members’ dyadic relationships positively relates to interpersonal admiration, sympathy, and envy, and negatively relates to interpersonal contempt. Furthermore, teams’ cooperative goals moderate these dyad-level linkages. The association of relationship quality with interpersonal emotions is particularly pronounced in teams with less cooperative goals but buffered in teams with more cooperative goals. Finally, on the individual level of analysis, envy and contempt are inversely associated with team members’ work performance, objectively measured. These findings provide new insights about key antecedents and crucial moderators in the development of interpersonal emotions in Chinese work teams and reiterate the relevance of these emotions for tangible performance outcomes.
Large floods bringing significant sediments into the coastal oceans have not been observed in Antarctica. We report evidence of a large flood event depositing over 50 cm of sediment onto the nearshore benthic habitat at Salmon Bay, Antarctica, between 1990 and 2010. Besides direct observations of the sedimentation, the evidence involves a debris flow covering old tyre tracks from the early 1960s, as well as evidence of a considerable amount of sediment transported onto the Salmon Creek delta. We believe that the flood was sourced from the Salmon Glacier and possibly the smaller Blackwelder Glacier. Such floods will be more common in the future and it is important to better understand their ecological impacts with good monitoring programmes.
Obesity and anxiety are often linked but the direction of effects is not clear.
Using genetic instrumental variable (IV) analyses in 5911 female participants from the Nurses' Health Study (NHS, initiated 1976) and 3697 male participants from the Health Professional Follow-up Study (HPFS, initiated 1986), we aimed to determine whether obesity increases symptoms of phobic anxiety. As instrumental variables we used the fat mass and obesity-associated (FTO) gene, the melanocortin 4 receptor (MC4R) gene and a genetic risk score (GRS) based on 32 single nucleotide polymorphisms (SNPs) that significantly predict body mass index (BMI). ‘Functional’ GRSs corresponding with specific biological pathways that shape BMI (adipogenesis, appetite and cardiopulmonary) were considered. The main outcome was phobic anxiety measured by the Crown Crisp Index (CCI) in 2004 in the NHS and in 2000 in the HPFS.
In observational analysis, a 1-unit higher BMI was associated with higher phobic anxiety symptoms [women: β = 0.05, 95% confidence interval (CI) 0.030–0.068; men: β = 0.04, 95% CI 0.016–0.071). IV analyses showed that BMI was associated with higher phobic anxiety symptoms in the FTO-instrumented analysis (p = 0.005) but not in the GRS-instrumented analysis (p = 0.256). Functional GRSs showed heterogeneous, non-significant effects of BMI on phobic anxiety symptoms.
Our findings do not provide conclusive evidence in favor of the hypothesis that higher BMI leads to higher levels of phobic anxiety, but rather suggest that genes that influence obesity, in particular FTO, may have direct effects on phobic anxiety, and hence that obesity and phobic anxiety may share common genetic determinants.
We studied the effect of a cross-conjugated bridging group (χC) on charge-transfer in a push-pull chromophore system. The hyperpolarizability of such molecules was found to be comparable to that of a fully π-conjugated molecule (πC) with the same donor and acceptor. The cross-conjugated moiety was then applied as a pendant to a fully π-conjugated chromophore containing a tricyanopyrroline acceptor (TCP). The addition of a χC moiety did not alter the intrinsic hyperpolarizability and provides an avenue for extending and aiding πC systems. The molecules were examined by X-ray diffraction (XRD), hyper-Raleigh scattering (HRS) and UV-visible (UV-vis) spectroscopy. Experimental results were compared with the predictions of density functional theory (DFT). Cross-conjugated molecules have comparable β values, relative to πC molecules, due to reduced spatial overlap between the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO). Thus, the χC architecture could facilitate independent modification of donor and acceptor strengths while minimizing unfavorable effects on electronic transitions and dipole moments.
Two methods for the fabrication of flexible and stretchable photonic crystal slabs are demonstrated and compared. In both cases a periodically nanostructured polydimethylsiloxane (PDMS) membrane is used as substrate. The first method is based on oblique-angle vapor deposition of SiO as a high refractive index material onto the nanostructured membrane. The deposition is made at an angle of 45° to the surface. The grooves of the nanostructure are aligned such that shading effects cause an inhomogeneous layer thickness distribution on the surface. This supports controlled, periodic cracking of the high index layer upon stretching. In the second approach ZnO nanoparticles are spin-coated on the nanostructured PDMS membrane. Here, the membrane can be stretched and serves as a photonic crystal slab without the need of any further treatment. For both types of flexible photonic crystal slabs a shift of the guided mode resonances to longer wavelengths is observed upon stretching. For a 20% strain perpendicular to the grating grooves a resonance shift of more than 50 nm is obtained.
Monitoring the glacier mass balance of summer-accumulation-type Himalayan glaciers is critical to not only assess the impact of climate change on the volume of such glaciers but also predict the downstream water availability and the global sea-level change in future. To better understand the change in meteorological parameters related to glacier mass balance and runoff in a glacierized basin and to assess the highly heterogeneous glacier responses to climate change in the Nepal Himalaya and nearby ranges, the Cryosphere Monitoring Project (CMP) carries out meteorological observations in Langtang Valley and mass-balance measurements on Yala Glacier, a debris-free glacier in the same valley. A negative annual mass balance of –0.89m w.e. and the rising equilibrium-line altitude of Yala Glacier indicate a continuation of a secular trend toward more negative mass balances. Lower temperature lapse rate during the monsoon, the effect of convective precipitation associated with mesoscale thermal circulation in the local precipitation and the occurrence of distinct diurnal cycles of temperature and precipitation at different stations in the valley are other conclusions of this comprehensive scientific study initiated by CMP which aims to yield multi-year glaciological, hydrological and meteorological observations in the glacierized Langtang River basin.
It is well known that exposure to ultraviolet (UV) light can result in various physical and psychological diseases. Therefore, there is a strong demand for a reliable sensor to monitor UV exposure levels in the physiologically relevant intensity ranges of mW/cm2. Here, we demonstrate a UV sensor based on a silica whispering gallery mode microresonator. This UV sensor works over physiologically relevant intensity ranges with linear performance both in the forward and backward operating directions, with very high signal-to-noise ratio that can be utilized in monitoring the UV exposure for various applications.
The use of organic nonlinear optical (ONLO) materials in electro-optic (EO) modulators requires that the active molecular components (chromophores) be acentrically oriented. The fundamental molecular constituents are in a condensed, glassy phase. Molecular orientation in such systems is typically achieved by applying a DC poling field to the glassy material. We are developing efficient coarse-grained classical Monte Carlo (MC) methods to simulate the order of such systems. The most challenging aspects of these simulations are convergence to an experimentally relevant equilibrium ensemble and verification of simulation accuracy. We use a variety of molecular descriptions and a variety of MC methods to achieve proper order in the shortest number of computational cycles possible. Herein, we illustrate a few examples of the types of calculations and compare with experimental results with representative amorphous organic materials, including electro-optic chromophores.