Frontoparietal function in young people with dysthymic disorder (DSM-5: Persistent depressive disorder) during spatial working memory

Background Dysthymic disorder (DD) is a depressive disorder characterised by persistent low and/or irritable mood and has been identified as a major risk factor for developing major depressive disorder (MDD). MDD and DD have been associated with executive function difficulties of working memory and attention. Little is known about how executive function networks in the brain are affected in children and adolescents with MDD and even less in DD. This study used fMRI and two spatial working memory paradigms to investigate associated brain function in young people with DD and an age-, gender- and IQ- matched typically developing group. Methods Nineteen male patients with DD (mean age 11.2±1.5 years) diagnosed according to DSM-IV criteria and 16 typically developing boys (mean age 10.5±1.1 years) performed a mental rotation and a delay-match to sample (DMTS) task while undergoing fMRI. All participants were medication-naïve at the time of testing. Results Compared to typically developing young people, the DD group showed less activation in left frontal regions including left ventro- and dorsolateral prefrontal cortices (PFC) during mental rotation. Medial frontal regions including dorsomedial PFC, anterior cingulate cortex and frontal pole also showed relatively reduced activation. During the DMTS task patients showed significantly more activation in the right precuneus and posterior cingulate cortex. Limitations This was a cross-sectional study with a small sample limiting the generalizability of the results. Conclusions The results complement previous findings in adults with MDD that have shown differential activation of left PFC regions during working memory tasks. Additionally, altered function of cortical midline structures in young patients with DD was identified. This supports findings in children, adolescents and adults with MDD suggesting that the pathophysiology of depressive disorders extends to DD as a risk factor for MDD and exhibits continuity over the lifespan

Active Galactic Nuclei in Groups and Clusters of Galaxies: Detection and Host Morphology

The incidence and properties of Active Galactic Nuclei (AGN) in the field, groups, and clusters can provide new information about how these objects are triggered and fueled, similar to how these environments have been employed to study galaxy evolution. We have obtained new XMM-Newton observations of seven X-ray selected groups and poor clusters with 0.02 < z < 0.06 for comparison with previous samples that mostly included rich clusters and optically-selected groups. Our final sample has ten groups and six clusters in this low-redshift range (split at a velocity dispersion of $\sigma = 500$ km/s). We find that the X-ray selected AGN fraction increases from $f_A(L_X>10^{41}; M_R<M_R^*+1) = 0.047^{+0.023}_{-0.016}$ in clusters to $0.091^{+0.049}_{-0.034}$ for the groups (85% significance), or a factor of two, for AGN above an 0.3-8keV X-ray luminosity of $10^{41}$ erg/s hosted by galaxies more luminous than $M_R^*+1$. The trend is similar, although less significant, for a lower-luminosity host threshold of $M_R = -20$ mag. For many of the groups in the sample we have also identified AGN via standard emission-line diagnostics and find that these AGN are nearly disjoint from the X-ray selected AGN. Because there are substantial differences in the morphological mix of galaxies between groups and clusters, we have also measured the AGN fraction for early-type galaxies alone to determine if the differences are directly due to environment, or indirectly due to the change in the morphological mix. We find that the AGN fraction in early-type galaxies is also lower in clusters $f_{A,n>2.5}(L_X>10^{41}; M_R<M_R^*+1) = 0.048^{+0.028}_{-0.019}$ compared to $0.119^{+0.064}_{-0.044}$ for the groups (92% significance), a result consistent with the hypothesis that the change in AGN fraction is directly connected to environment.Comment: 18 pages, 9 figures; accepted by The Astrophysical Journal; for higher-resolution versions of some figures, see http://u.arizona.edu/~tjarnold/Arnold09

Uncovering the neuroanatomical correlates of cognitive, affective and conative theory of mind in paediatric traumatic brain injury: a neural systems perspective

Deficits in theory of mind (ToM) are common after neurological insult acquired in the first and second decade of life, however the contribution of large-scale neural networks to ToM deficits in children with brain injury is unclear. Using paediatric traumatic brain injury (TBI) as a model, this study investigated the sub-acute effect of paediatric traumatic brain injury on grey-matter volume of three large-scale, domain-general brain networks (the Default Mode Network, DMN; the Central Executive Network, CEN; and the Salience Network, SN), as well as two domain-specific neural networks implicated in social-affective processes (the Cerebro-Cerebellar Mentalizing Network, CCMN and the Mirror Neuron/Empathy Network, MNEN). We also evaluated prospective structure&ndash;function relationships between these large-scale neural networks and cognitive, affective and conative ToM. 3D T1- weighted magnetic resonance imaging sequences were acquired sub-acutely in 137 children [TBI: n&thinsp;=&thinsp;103; typically developing (TD) children: n&thinsp;=&thinsp;34]. All children were assessed on measures of ToM at 24-months post-injury. Children with severe TBI showed sub-acute volumetric reductions in the CCMN, SN, MNEN, CEN and DMN, as well as reduced grey-matter volumes of several hub regions of these neural networks. Volumetric reductions in the CCMN and several of its hub regions, including the cerebellum, predicted poorer cognitive ToM. In contrast, poorer affective and conative ToM were predicted by volumetric reductions in the SN and MNEN, respectively. Overall, results suggest that cognitive, affective and conative ToM may be prospectively predicted by individual differences in structure of different neural systems&mdash;the CCMN, SN and MNEN, respectively. The prospective relationship between cerebellar volume and cognitive ToM outcomes is a novel finding in our paediatric brain injury sample and suggests that the cerebellum may play a role in the neural networks important for ToM. These findings are discussed in relation to neurocognitive models of ToM. We conclude that detection of sub-acute volumetric abnormalities of large-scale neural networks and their hub regions may aid in the early identification of children at risk for chronic social-cognitive impairment

Theory of mind mediates the prospective relationship between abnormal social brain network morphology and chronic behavior problems after pediatric traumatic brain injury

Childhood and adolescence coincide with rapid maturation and synaptic reorganization of distributed neural networks that underlie complex cognitive-affective behaviors. These regions, referred to collectively as the &lsquo;social brain network&rsquo; (SBN) are commonly vulnerable to disruption from pediatric traumatic brain injury (TBI); however, the mechanisms that link morphological changes in the SBN to behavior problems in this population remain unclear. In 98 children and adolescents with mild to severe TBI, we acquired 3D T1-weighted MRIs at 2&ndash;8 weeks post-injury. For comparison, 33 typically developing controls of similar age, sex and education were scanned. All participants were assessed on measures of Theory of Mind (ToM) at 6 months post-injury and parents provided ratings of behavior problems at 24-months post-injury. Severe TBI was associated with volumetric reductions in the overall SBN package, as well as regional gray matter structural change in multiple component regions of the SBN. When compared with TD controls and children with milder injuries, the severe TBI group had significantly poorer ToM, which was associated with more frequent behavior problems and abnormal SBN morphology. Mediation analysis indicated that impaired theory of mind mediated the prospective relationship between abnormal SBN morphology and more frequent chronic behavior problems. Our findings suggest that sub-acute alterations in SBN morphology indirectly contribute to long-term behavior problems via their influence on ToM. Volumetric change in the SBN and its putative hub regions may represent useful imaging biomarkers for prediction of post-acute social cognitive impairment, which may in turn elevate risk for chronic behavior problems

Developmental brain trajectories in children with ADHD and controls: a longitudinal neuroimaging study

BACKGROUND: The symptom profile and neuropsychological functioning of individuals with Attention Deficit/Hyperactivity Disorder (ADHD), change as they enter adolescence. It is unclear whether variation in brain structure and function parallels these changes, and also whether deviations from typical brain development trajectories are associated with differential outcomes. This paper describes the Neuroimaging of the Children\u27s Attention Project (NICAP), a comprehensive longitudinal multimodal neuroimaging study. Primary aims are to determine how brain structure and function change with age in ADHD, and whether different trajectories of brain development are associated with variations in outcomes including diagnostic persistence, and academic, cognitive, social and mental health outcomes. METHODS/DESIGN: NICAP is a multimodal neuroimaging study in a community-based cohort of children with and without ADHD. Approximately 100 children with ADHD and 100 typically developing controls will be scanned at a mean age of 10 years (range; 9-11years) and will be re-scanned at two 18-month intervals (ages 11.5 and 13 years respectively). Assessments include a structured diagnostic interview, parent and teacher questionnaires, direct child cognitive/executive functioning assessment and magnetic resonance imaging (MRI). MRI acquisition techniques, collected at a single site, have been selected to provide optimized information concerning structural and functional brain development. DISCUSSION: This study will allow us to address the primary aims by describing the neurobiological development of ADHD and elucidating brain features associated with differential clinical/behavioral outcomes. NICAP data will also be explored to assess the impact of sex, ADHD presentation, ADHD severity, comorbidities and medication use on brain development trajectories. Establishing which brain regions are associated with differential clinical outcomes, may allow us to improve predictions about the course of ADHD

Identification and immune assessment of T cell epitopes in five Plasmodium falciparum blood stage antigens to facilitate vaccine candidate selection and optimization

The hurdles to effective blood stage malaria vaccine design include immune evasion tactics used by the parasite such as redundant invasion pathways and antigen variation among circulating parasite strains. While blood stage malaria vaccine development primarily focuses on eliciting optimal humoral responses capable of blocking erythrocyte invasion, clinically-tested Plasmodium falciparum (Pf) vaccines have not elicited sterile protection, in part due to the dramatically high levels of antibody needed. Recent development efforts with non-redundant, conserved blood stage antigens suggest both high antibody titer and rapid antibody binding kinetics are important efficacy factors. Based on the central role of helper CD4 T cells in development of strong, protective immune responses, we systematically analyzed the class II epitope content in five leading Pf blood stage antigens (RH5, CyRPA, RIPR, AMA1 and EBA175) using in silico, in vitro, and ex vivo methodologies. We employed in silico T cell epitope analysis to enable identification of 67 HLA-restricted class II epitope clusters predicted to bind a panel of nine HLA-DRB1 alleles. We assessed a subset of these for HLA-DRB1 allele binding in vitro, to verify the in silico predictions. All clusters assessed (40 clusters represented by 46 peptides) bound at least two HLA-DR alleles in vitro. The overall epitope prediction to in vitro HLA-DRB1 allele binding accuracy was 71%. Utilizing the set of RH5 class II epitope clusters (10 clusters represented by 12 peptides), we assessed stimulation of T cells collected from HLA-matched RH5 vaccinees using an IFN-γ T cell recall assay. All clusters demonstrated positive recall responses, with the highest responses – by percentage of responders and response magnitude – associated with clusters located in the N-terminal region of RH5. Finally, a statistically significant correlation between in silico epitope predictions and ex vivo IFN-γ recall response was found when accounting for HLA-DR matches between the epitope predictions and donor HLA phenotypes. This is the first comprehensive analysis of class II epitope content in RH5, CyRPA, RIPR, AMA1 and EBA175 accompanied by in vitro HLA binding validation for all five proteins and ex vivo T cell response confirmation for RH5

Baryon Acoustic Oscillations in the Sloan Digital Sky Survey Data Release 7 Galaxy Sample

The spectroscopic Sloan Digital Sky Survey (SDSS) Data Release 7 (DR7) galaxy sample represents the final set of galaxies observed using the original SDSS target selection criteria. We analyse the clustering of galaxies within this sample, including both the Luminous Red Galaxy (LRG) and Main samples, and also include the 2-degree Field Galaxy Redshift Survey (2dFGRS) data. Baryon Acoustic Oscillations are observed in power spectra measured for different slices in redshift; this allows us to constrain the distance--redshift relation at multiple epochs. We achieve a distance measure at redshift z=0.275, of r_s(z_d)/D_V(0.275)=0.1390+/-0.0037 (2.7% accuracy), where r_s(z_d) is the comoving sound horizon at the baryon drag epoch, D_V(z)=[(1+z)^2D_A^2cz/H(z)]^(1/3), D_A(z) is the angular diameter distance and H(z) is the Hubble parameter. We find an almost independent constraint on the ratio of distances D_V(0.35)/D_V(0.2)=1.736+/-0.065, which is consistent at the 1.1sigma level with the best fit Lambda-CDM model obtained when combining our z=0.275 distance constraint with the WMAP 5-year data. The offset is similar to that found in previous analyses of the SDSS DR5 sample, but the discrepancy is now of lower significance, a change caused by a revised error analysis and a change in the methodology adopted, as well as the addition of more data. Using WMAP5 constraints on Omega_bh^2 and Omega_ch^2, and combining our BAO distance measurements with those from the Union Supernova sample, places a tight constraint on Omega_m=0.286+/-0.018 and H_0 = 68.2+/-2.2km/s/Mpc that is robust to allowing curvature and non-Lambda dark energy. This result is independent of the behaviour of dark energy at redshifts greater than those probed by the BAO and supernova measurements. (abridged)Comment: 22 pages, 16 figures, minor changes to match version published in MNRA

General practitioners' attitudes and preparedness towards Clinical Decision Support in e-Prescribing (CDS-eP) adoption in the West of Ireland: a cross sectional study

Background: Electronic clinical decision support (CDS) is increasingly establishing its role in evidence-based clinical practice. Considerable evidence supports its enhancement of efficiency in e-Prescribing, but some controversy remains. This study evaluated the practicality and identified the perceived benefits of, and barriers to, its future adoption in the West of Ireland. Methods: This cross sectional study was carried out by means of a 27-part questionnaire sent to 262 registered general practitioners in Counties Galway, Mayo and Roscommon. The survey domains encompassed general information of individual's practice, current use of CDS and the practitioner's attitudes towards adoption of CDS-eP. Descriptive and inferential analyses were performed to analyse the data collected. Results: The overall response rate was 37%. Nearly 92% of respondents employed electronic medical records in their practice. The majority acknowledged the value of electronic CDS in improving prescribing quality (71%) and reducing prescribing errors (84%). Despite a high degree of unfamiliarity (73%), the practitioners were open to the use of CDS-eP (94%) and willing to invest greater resources for its implementation (62%). Lack of a strategic implementation plan (78%) is the main perceived barrier to the incorporation of CDS-eP into clinical practice, followed by i) lack of financial incentives (70%), ii) lack of standardized product software (61%), iii) high sensitivity of drug-drug interaction or medication allergy markers (46%), iv) concern about overriding physicians' prescribing decisions(44%) and v) lack of convincing evidence on the systems' effectiveness (22%). Conclusions: Despite favourable attitudes towards the adoption of CDS-eP, multiple perceived barriers impede its incorporation into clinical practice. These merit further exploration, taking into consideration the structure of the Irish primary health care system, before CDS-eP can be recommended for routine clinical use in the West of Ireland.Healthcare Informatics Society of Ireland (HISI) research bursary 2007-2009Deposited by bulk impor