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This study sought to conduct a comprehensive search for genetic risk of cognitive decline in the context of geriatric depression.
A genome-wide association study (GWAS) analysis in the Neurocognitive Outcomes of Depression in the Elderly (NCODE) study.
Longitudinal, naturalistic follow-up study.
Older depressed adults, both outpatients and inpatients, receiving care at an academic medical center.
The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) neuropsychological battery was administered to the study participants at baseline and a minimum of twice within a subsequent 3-year period in order to measure cognitive decline. A GWAS analysis was conducted to identify genetic variation that is associated with baseline and change in the CERAD Total Score (CERAD-TS) in NCODE.
The GWAS of baseline CERAD-TS revealed a significant association with an intergenic single-nucleotide polymorphism (SNP) on chromosome 6, rs17662598, that surpassed adjustment for multiple testing (p = 3.7 × 10−7; false discovery rate q = 0.0371). For each additional G allele, average baseline CERAD-TS decreased by 8.656 points. The most significant SNP that lies within a gene was rs11666579 in SLC27A1 (p = 1.1 × 10−5). Each additional copy of the G allele was associated with an average decrease of baseline CERAD-TS of 4.829 points. SLC27A1 is involved with processing docosahexaenoic acid (DHA), an endogenous neuroprotective compound in the brain. Decreased levels of DHA have been associated with the development of Alzheimer’s disease. The most significant SNP associated with CERAD-TS decline over time was rs73240021 in GRXCR1 (p = 1.1 × 10−6), a gene previously linked with deafness. However, none of the associations within genes survived adjustment for multiple testing.
Our GWAS of cognitive function and decline among individuals with late-life depression (LLD) has identified promising candidate genes that, upon replication in other cohorts of LLD, may be potential biomarkers for cognitive decline and suggests DHA supplementation as a possible therapy of interest.
Serum-antibodies against an organ specific CNS antigen as well as against serotonin and gangliosides (Gm 1) were analysed by ELISA in 34 patients with schizophrenia, ten patients with schizoaffective psychosis and 13 patients with major depressive disorder. Sixty-two patients with various rheumatic disorders and 32 blood donors were included in the study as controls. Sixty-two percent of the 13 patients with major depressive disorder had antibodies to serotonin and 69% to gangliosides, whereas antibody positive sera was only found in 38% of the 34 patients with schizophrenia. The same antibodies were found in only 6% (antibodies to serotonin) and 13% (antibodies to gangliosides) of the 32 blood donors and in a similar frequency in patients with schizoaffective psychosis. Organ specific antibodies to CNS-antigen could not be detected in the psychiatric patient group at any significant level. It is speculated that auto-immune reactions towards a serotonin receptor may be involved in the etiopathogenesis of major depressive disorder.
In a representative nationwide survey, the Psychiatry and Migration Working Group of the German Federal Conference of Psychiatric Hospital Directors (Bundesdirektorenkonferenz) examined the use of inpatient psychiatric and psychotherapeutic services in Germany by patients of immigrant origin. Questionnaires were sent to a total of 350 general hospital psychiatric clinics throughout Germany, and 131 clinics responded. As shown by the 2005 Microcensus , almost one-fifth (18.6%) of the German population is of immigrant origin. In our study, persons of immigrant origin comprised 17% of patients in the responding facilities. This indicates that the percentage of inpatient psychiatric services used by patients of immigrant origin is almost proportionate to these patients’ percentage of the general population. The largest group of immigrant patients in our study were those of Russian heritage, followed by patients of Turkish, Arabic, or other origin. Almost two-thirds of the immigrant patients were born in Germany, and a considerably larger percentage were German citizens (74%). Sixty-two per cent of all patients of immigrant origin spoke a language other than German (e.g. Russian, Turkish, Polish) at home. Patients of immigrant origin were significantly more likely to receive an ICD-10 F2 diagnosis, and it was precisely patients with this diagnosis who were observed to experience difficulties in communication with caregivers.
The plasma membranes of cells are thin viscous sheets in which some transmembrane proteins have two-dimensional mobility and some are immobilized. Previous studies have shown that immobile proteins retard the short-time diffusivity of mobile particles through hydrodynamic interactions and that steric effects of immobile proteins reduce the long-time diffusivity in a model that neglects hydrodynamic interactions. We present a rigorous derivation of the long-time diffusivity of a single mobile protein interacting hydrodynamically and thermodynamically with an array of immobile proteins subject to periodic boundary conditions. This method is based on a finite element method (FEM) solution of the probability density of the mobile protein diffusing with a position-dependent mobility determined through a multipole solution of Stokes equations. The simulated long-time diffusivity in square arrays decreases as the spacing in the array approaches the particle size in a manner consistent with a lubrication analysis. In random arrays, steric effects lead to a percolation threshold volume fraction above which long-time diffusion is arrested. The FEM/multipole approach is used to compute the long-time diffusivity far away from this threshold. An approximate analysis of mobile protein diffusion through a network of pores connected by bonds with resistances determined by the FEM/multipole calculations is then used to explore higher immobile area fractions and to evaluate the finite simulation cell size scaling behaviour of diffusion near the percolation threshold. Surprisingly, the ratio of the long-time diffusivity to the spatially averaged short-time diffusivity in these two-dimensional fixed arrays is higher in the presence of hydrodynamic interactions than in their absence. Finally, the implications of this work are discussed, including the possibility of using the methods developed here to investigate more complex diffusive phenomena observed in cell membranes.
Tail lesions caused by tail biting are a widespread welfare issue in pig husbandry. Determining their prevalence currently involves labour intensive, subjective scoring methods. Increased societal interest in tail lesions requires fast, reliable and cheap systems for assessing tail status. In the present study, we aimed to test the reliability of neural networks for assessing tail pictures from carcasses against trained human observers. Three trained observers scored tail lesions from automatically recorded pictures of 13 124 pigs. Nearly all pigs had been tail docked. Tail lesions were classified using a 4-point score (0=no lesion, to 3=severe lesion). In addition, total tail loss was recorded. Agreement between observers was tested prior and during the assessment in a total of seven inter-observer tests with 80 pictures each. We calculated agreement between observer pairs as exact agreement (%) and prevalence-adjusted bias-adjusted κ (PABAK; value 1=optimal agreement). Out of the 13 124 scored pictures, we used 80% for training and 20% for validating our neural networks. As the position of the tail in the pictures varied (high, low, left, right), we first trained a part detection network to find the tail in the picture and select a rectangular part of the picture which includes the tail. We then trained a classification network to categorise tail lesion severity using pictures scored by human observers whereby the classification network only analysed the selected picture parts. Median exact agreement between the three observers was 80% for tail lesions and 94% for tail loss. Median PABAK for tail lesions and loss were 0.75 and 0.87, respectively. The agreement between classification by the neural network and human observers was 74% for tail lesions and 95% for tail loss. In other words, the agreement between the networks and human observers were very similar to the agreement between human observers. The main reason for disagreement between observers and thereby higher variation in network training material were picture quality issues. Therefore, we expect even better results for neural network application to tail lesions if training is based on high quality pictures. Very reliable and repeatable tail lesion assessment from pictures would allow automated tail classification of all pigs slaughtered, which is something that some animal welfare labels would like to do.
The secondary instability in the wake of a two-dimensional blunt body with a chord to thickness ratio of 46.5 was experimentally investigated for Reynolds numbers of 3500, 5200 and 7000 based on the blunt trailing edge height
. Planar, stereoscopic and high-speed particle image velocimetry (PIV) measurements were performed to characterise the wake and upstream boundary layer. The same mode B secondary instability that is found in the cylinder wake was found to be present in the wake of the elongated body studied here. The most probable wavelength of the secondary instability, defined as the spanwise distance between adjacent streamwise vortex pairs in the wake, was found to range from
by applying a spatial autocorrelation to the spanwise–wall-normal instantaneous fields of the
-criterion. The temporal evolution of the secondary wake vortices was investigated using time-resolved stereoscopic PIV measurements and it was shown that the vortices maintain both their directions of rotation and spanwise positions during the primary vortex shedding cycles. In agreement with previous literature, the secondary instability did not greatly change as the upstream boundary layer transitioned from laminar to turbulent. Moreover, any upstream boundary layer structures were found to rapidly evolve into wake structures just past the blunt trailing edge. The wavelength of the secondary instability was shown to match the spanwise distance between adjacent low-speed zones of streamwise velocity in the wake. These undulating velocity patterns proved to be a viable method for determining the secondary instability wavelength; however, this type of analysis is highly sensitive to the energy content used for data reconstruction when proper orthogonal decomposition is applied beforehand.
Avian influenza virus (AIV) subtypes H5 and H7 can infect poultry causing low pathogenicity (LP) AI, but these LPAIVs may mutate to highly pathogenic AIV in chickens or turkeys causing high mortality, hence H5/H7 subtypes demand statutory intervention. Serological surveillance in the European Union provides evidence of H5/H7 AIV exposure in apparently healthy poultry. To identify the most sensitive screening method as the first step in an algorithm to provide evidence of H5/H7 AIV infection, the standard approach of H5/H7 antibody testing by haemagglutination inhibition (HI) was compared with an ELISA, which detects antibodies to all subtypes. Sera (n = 1055) from 74 commercial chicken flocks were tested by both methods. A Bayesian approach served to estimate diagnostic test sensitivities and specificities, without assuming any ‘gold standard’. Sensitivity and specificity of the ELISA was 97% and 99.8%, and for H5/H7 HI 43% and 99.8%, respectively, although H5/H7 HI sensitivity varied considerably between infected flocks. ELISA therefore provides superior sensitivity for the screening of chicken flocks as part of an algorithm, which subsequently utilises H5/H7 HI to identify infection by these two subtypes. With the calculated sensitivity and specificity, testing nine sera per flock is sufficient to detect a flock seroprevalence of 30% with 95% probability.
The Society of Precision Agriculture Australia Inc. (SPAA) is recognised as a leading, grower driven farming group in Australia. As an organisation it provides programs and services to its members and wider industry to promote the development and adoption of Precision Agriculture (PA) technologies as a means of enhancing the profitability and sustainability of agricultural production systems. This is achieved through publishing Australia’s only PA-dedicated magazine, delivering field days, seminars and conducting on-farm PA demonstrations and experiments. SPAA provides farmers with an independent source of advice on new concepts and equipment. The grains industry was the springboard for initial adoption, with winegrapes, horticulture and the sugar industry the focus sectors for further expansion. The purpose of this paper is to share the SPAA experience with a view to assisting the development of similar organisations in other countries
Ion angular current and energy distributions are important parameters for ion thrusters, which are typically measured at a few tens of centimetres to a few metres distance from the thruster exit. However, fully kinetic particle-in-cell (PIC) simulations are not able to simulate such domain sizes due to high computational costs. Therefore, a parallelisation strategy of the code is presented to reduce computational time. The calculated ion beam angular distributions in the plume region are quite sensitive to boundary conditions of the potential, possible additional source contributions (e.g. from secondary electron emission at vessel walls) and charge exchange collisions. Within this work a model for secondary electrons emitted from the vessel wall is included. In order to account for limits of the model due to its limited domain size, a correction of the simulated angular ion energy distribution by the potential boundary is presented to represent the conditions at the location of the experimental measurement in
distance. In addition, a post-processing procedure is suggested to include charge exchange collisions in the plume region not covered by the original PIC simulation domain for the simulation of ion angular distributions measured at
In studies using magnetic resonance imaging (MRI), some have reported specific brain structure–function relationships among first-episode psychosis (FEP) patients, but findings are inconsistent. We aimed to localize the brain regions where cortical thickness (CTh) and surface area (cortical area; CA) relate to neurocognition, by performing an MRI on participants and measuring their neurocognitive performance using the Cambridge Neuropsychological Test Automated Battery (CANTAB), in order to investigate any significant differences between FEP patients and control subjects (CS).
Exploration of potential correlations between specific cognitive functions and brain structure was performed using CANTAB computer-based neurocognitive testing and a vertex-by-vertex whole-brain MRI analysis of 63 FEP patients and 30 CS.
Significant correlations were found between cortical parameters in the frontal, temporal, cingular and occipital brain regions and performance in set-shifting, working memory manipulation, strategy usage and sustained attention tests. These correlations were significantly dissimilar between FEP patients and CS.
Significant correlations between CTh and CA with neurocognitive performance were localized in brain areas known to be involved in cognition. The results also suggested a disrupted structure–function relationship in FEP patients compared with CS.
The Perth Astronomy Research Group (PARG), consisting of members from Curtin University of Technology, Perth Observatory and the University of Western Australia, is in the process of developing an automated supernova search system, using the 61-cm Lowell-Perth reflector, a CCD camera and an 80386-based computer for image analysis. Computer control of the telescope and dome, a liquid-nitrogen-cooled CCD camera, and modified VISTA image analysis software will be completed in late 1990, allowing initial semi-automatic searching of external galaxies, together with CCD photometry of flare stars and newly discovered supernovae. Full-scale automation will be introduced subsequently, in collaboration with the Berkeley group. This paper describes the project, and reports on its current status.
We have used dedicated 0.7m telescopes in California and Israel to image the halos of ~ 200 galaxies in the Local Volume to 29 mag/sq arcsec, the sample mainly drawn from the 2MASS Large Galaxy Atlas (LGA). We supplement the LGA sample with dwarf galaxies and more distant giant ellipticals. Low surface brightness halos exceeding 50 kpc in diameter are found only in galaxies more luminous than L*, and classic interaction signatures are relatively infrequent. Halo diameter is correlated with total galaxy luminosity. Extended low surface brightness halos are present even in galaxies as faint as MV = - 18. Edge-on galaxies with boxy bulges tend to lack extended spheroidal halos, while those with large classical bulges exhibit extended round halos, supporting the notions that boxy or barlike bulges originate from disks. Most face-on spiral galaxies present features that appear to be irregular extensions of spiral arms, although rare cases show smooth boundaries with no sign of star formation. Although we serendipitously discovered a dwarf galaxy undergoing tidal disruption in the halo of NGC 4449, we found no comparable examples in our general survey. A search for similar examples in the Local Volume identified hcc087, a tidally disrupting dwarf galaxy in the Hercules Cluster, but we do not confirm an anomalously large half-light radius reported for the dwarf VCC 1661.
This study aimed to measure changes in disease-specific quality of life in children following tonsillectomy or adenotonsillectomy.
A multicentre prospective cohort study was performed involving seven ENT departments in England. A total of 276 children entered the study over a 2-month period: 107 underwent tonsillectomy and 128 adenotonsillectomy. Forty-one children referred with throat problems initially managed by watchful waiting were also recruited. The follow-up period was 12 months. Outcome measures were the T14, parental impressions of their child's quality of life and the number of days absent from school.
One-year follow-up data were obtained from 150 patients (52 per cent). The mean baseline T14 score in the non-surgical group was significantly lower (T14 = 23) than in the tonsillectomy group (T14 = 31) or the adenotonsillectomy group (T14 = 35; p < 0.001). There was a significant improvement in the T14 scores of responders in all groups at follow up. The effect size was 1.3 standard deviations (SD) for the non-surgical group, 2.1 SD for the tonsillectomy group and 1.9 SD for the adenotonsillectomy group. Between-group differences did not reach statistical significance. A third of children in the non-surgical group underwent surgery during the follow-up period.
Children who underwent surgical intervention achieved a significant improvement in disease-specific quality of life. Less severely affected children were managed conservatively and also improved over 12 months, but 1 in 3 crossed over to surgical intervention.
The purpose of this study was to use selected Cambridge Neuropsychological Test Automated Battery (CANTAB) tests to examine the dimensional structure of cognitive dysfunction in first episode of psychosis (FEP) patients compared with cognition in healthy subjects.
A total of 109 FEP patients and 96 healthy volunteers were administered eight CANTAB tests of cognitive function. Principal components analysis (PCA) was used to estimate dimensionality within the test results. The dimensions identified by the PCA were assumed to reflect underlying cognitive traits. The plausibility of latent factor models was estimated using confirmatory factor analysis (CFA). Multi-group CFA (MGCFA) was used to test for measurement invariance of factors between groups. The nature and severity of cognitive deficits amongst patients as opposed to controls were evaluated using a general linear model.
Amongst subjects PCA identified two underlying cognitive traits: (i) a broad cognitive domain; (ii) attention/memory and executive function domains. Corresponding CFA models were built that fitted data well for both FEP patients and healthy volunteers. As in MGCFA latent variables appeared differently defined in patient and control groups, differences had to be ascribed using subtest scores rather than their aggregates. At subtest score level the patients performed significantly worse than healthy subjects in all comparisons (p < 0.001).
Results of this study demonstrate that the structure of underlying cognitive abilities as measured by a selection of CANTAB tests is not the same for healthy individuals and FEP patients, with patients displaying widespread cognitive impairment.
We investigated electronic structure of one-dimensional biradical molecular chain which is constructed by exploiting the covalency between organic molecules of a diphenyl derivative of s-indacenodiphenalene (Ph2-IDPL). To control the crystallinity, we used gas deposition method. Ultraviolet photoelectron spectroscopy (UPS) revealed developed band structure with wide dispersion of the one-dimensional biradical molecular chain.
Intrauterine growth restriction (IUGR) from uteroplacental dysfunction causes impaired nephrogenesis and ultimately hypertension, but it is unknown whether IUGR caused by insufficient space for placental development seen in uterine anomalies and/or multifetal gestation exerts the same effects. Fetal renal development and metabolism were studied in an ovine space-restriction model by combining unilateral horn surgical ligation and/or multifetal gestation. Reduced placental attachment sites and placental weight per fetus defined space-restricted (USR) v. control nonrestricted (NSR) fetuses. Space-restricted fetuses exhibited evidence for decreased plasma volume, with higher hematocrit and plasma albumin at gestational day (GD) 120, followed by lower blood pO2, and higher osmolarity and creatinine at GD130, P < 0.05 for all. By combining treatments, fetal kidney weight relative to fetal weight was inversely related to both fetal weight and plasma creatinine levels, P < 0.05 for both. At GD130, space-restricted fetal kidney weights, cortical depths and glomerular generations were decreased, P < 0.05 for all. Space-restricted kidneys underwent an adaptive response by prolonging active nephrogenesis and increasing maculae densa number, P < 0.05 for both. The major renal adaptations in space-restricted IUGR fetuses included immaturity in both development and endocrine function, with evidence for impaired renal excretory function.