Deficits in attention to emotional stimuli distinguish youth with severe mood dysregulation from youth with bipolar disorder.

Studying attention in the context of emotional stimuli may aid in differentiating pediatric bipolar disorder (BD) from severe mood dysregulation (SMD). SMD is characterized by chronic irritability, arousal, and hyper-reactivity; SMD youth frequently receive a BD diagnosis although they do not meet DSM-IV criteria for BD because they lack manic episodes. We compared 57 BD (14.4 +/- 2.9 years old, 56% male), 41 SMD (12.6 +/- 2.6 years old, 66% male), and 33 control subjects (13.7 +/- 2.5 years old, 52% male) using the Emotional Interrupt task, which examines how attention is impacted by positive, negative, or neutral distracters. We compared reaction time (RT) and accuracy and calculated attention interference scores by subtracting performance on neutral trials from emotional trials. Between-group analyses indicated that SMD subjects had significantly reduced attention interference from emotional distracters relative to BD and control subjects. Thus, attention in SMD youth was not modulated by emotional stimuli. This blunted response in SMD youth may contribute to their affective and behavioral dysregulation

Beryllium and Alpha-Element Abundances in a Large Sample of Metal-Poor Stars

The light elements, Li, Be, and B, provide tracers for many aspects of astronomy including stellar structure, Galactic evolution, and cosmology. We have taken spectra of Be in 117 metal-poor stars ranging in metallicity from [Fe/H] = -0.5 to -3.5 with Keck I + HIRES at a resolution of 42,000 and signal-to-noise ratios of near 100. We have determined the stellar parameters spectroscopically from lines of Fe I, Fe II, Ti I and Ti II. The abundances of Be and O were derived by spectrum synthesis techniques, while abundances of Fe, Ti, and Mg were found from many spectral line measurements. There is a linear relationship between [Fe/H] and A(Be) with a slope of +0.88 +-0.03 over three orders of magnitude in [Fe/H]. We fit the relationship between A(Be) and [O/H] with both a single slope and with two slopes. The relationship between [Fe/H] and [O/H] seems robustly linear and we conclude that the slope change in Be vs. O is due to the Be abundance. Although Be is a by-product of CNO, we have used Ti and Mg abundances as alpha-element surrogates for O in part because O abundances are rather sensitive to both stellar temperature and surface gravity. We find that A(Be) tracks [Ti/H] very well with a slope of 1.00 +-0.04. It also tracks [Mg/H] very well with a slope of 0.88 +-0.03. We find that there are distinct differences in the relationships of A(Be) and [Fe/H] and of A(Be) and [O/H] for our dissipative stars and our accretive stars. We suggest that the Be in the dissipative stars was primarily formed by GCR spallation and Be in the accretive stars was formed in the vicinity of SN II.Comment: Accepted for Ap.J. Nov. 10, 2011, v. 741 70 pages, 27 figures, 5 table

Specificity of facial expression labeling deficits in childhood psychopathology

Background: We examined whether face-emotion labeling deficits are illness-specific or an epiphenomenon of generalized impairment in pediatric psychiatric disorders involving mood and behavioral dysregulation. Method: Two hundred fifty-two youths (7-18 years old) completed child and adult facial expression recognition subtests from the Diagnostic Analysis of Nonverbal Accuracy (DANVA) instrument. Forty-two participants had bipolar disorder (BD), 39 had severe mood dysregulation (SMD; i.e., chronic irritability, hyperarousal without manic episodes), 44 had anxiety and/or major depressive disorders (ANX/MDD), 35 had attention-deficit/hyperactivity and/or conduct disorder (ADHD/CD), and 92 were controls. Dependent measures were number of errors labeling happy, angry, sad, or fearful emotions. Results: BD patients made more errors than ANX/MDD, ADHD/CD, or controls when labeling all emotional expressions, whether those expressions were on the faces of children or adults. SMD also showed emotion-labeling deficits, in particular as compared to ANX/MDD patients and controls. Conclusions: Face-emotion labeling deficits differentiate BD and SMD patients from those with ANX/MDD or ADHD/CD and controls. The extent to which such deficits cause vs. result from emotional dysregulation requires further study

Neural circuitry engaged during unsuccessful motor inhibition in pediatric bipolar disorder

Objective: Deficits in motor inhibition may contribute to impulsivity and irritability in children with bipolar disorder (BPD). Therefore, studies of the neural circuitry engaged during failed motor inhibition in pediatric BPD may contribute to our understanding of the pathophysiology of the illness. We tested the hypothesis that children with BPD and controls would differ in ventral prefrontal cortex (vPFC), striatal, and anterior cingulate activation during unsuccessful motor inhibition. We also compared activation in medicated vs. unmedicated children with BPD, and in children with BPD and ADHD (BPD+ADHD) vs. those with BPD but without ADHD (BPD-ADHD). Method: Event-related fMRI study comparing neural activation in children with BPD and controls while they performed a motor inhibition task. The sample included 26 children with BPD (13 unmedicated, 15 with ADHD) and 17 age, gender, and IQ matched controls. Results: On failed inhibitory trials, controls showed greater bilateral striatal and right vPFC activation than did patients. While our findings were somewhat more prominent in unmedicated than medicated, patients, and in BPD+ADHD than BPD-ADHD, the findings did not differ significantly (?) among these subgroups of children with BPD. Conclusions: Compared to controls, children with BPD may have deficits in their ability to engage striatal structures and right vPFC during unsuccessful inhibition. (this reads confusingly to me—they’re deficient in their capacity to engage structures when they’re behaviorally unsuccessful? Perhaps reword?) Further research is needed to determine whether these deficits play a role in the emotional and behavioral dysregulation characteristic of BPD

Evaluating the successful implementation of evidence into practice using the PARiHS framework : theoretical and practical challenges

Background The PARiHS framework (Promoting Action on Research Implementation in Health Services) has proved to be a useful practical and conceptual heuristic for many researchers and practitioners in framing their research or knowledge translation endeavours. However, as a conceptual framework it still remains untested and therefore its contribution to the overall development and testing of theory in the field of implementation science is largely unquantified. Discussion This being the case, the paper provides an integrated summary of our conceptual and theoretical thinking so far and introduces a typology (derived from social policy analysis) used to distinguish between the terms conceptual framework, theory and model – important definitional and conceptual issues in trying to refine theoretical and methodological approaches to knowledge translation. Secondly, the paper describes the next phase of our work, in particular concentrating on the conceptual thinking and mapping that has led to the generation of the hypothesis that the PARiHS framework is best utilised as a two-stage process: as a preliminary (diagnostic and evaluative) measure of the elements and sub-elements of evidence (E) and context (C), and then using the aggregated data from these measures to determine the most appropriate facilitation method. The exact nature of the intervention is thus determined by the specific actors in the specific context at a specific time and place. In the process of refining this next phase of our work, we have had to consider the wider issues around the use of theories to inform and shape our research activity; the ongoing challenges of developing robust and sensitive measures; facilitation as an intervention for getting research into practice; and finally to note how the current debates around evidence into practice are adopting wider notions that fit innovations more generally. Summary The paper concludes by suggesting that the future direction of the work on the PARiHS framework is to develop a two-stage diagnostic and evaluative approach, where the intervention is shaped and moulded by the information gathered about the specific situation and from participating stakeholders. In order to expedite the generation of new evidence and testing of emerging theories, we suggest the formation of an international research implementation science collaborative that can systematically collect and analyse experiences of using and testing the PARiHS framework and similar conceptual and theoretical approaches. We also recommend further refinement of the definitions around conceptual framework, theory, and model, suggesting a wider discussion that embraces multiple epistemological and ontological perspectives

Radiosensitization of mammary carcinoma cells by telomere homolog oligonucleotide pretreatment

Introduction: Ionizing radiation (IR) is a widely used approach to cancer therapy, ranking second only to surgery in rate of utilization. Responses of cancer patients to radiotherapy depend in part on the intrinsic radiosensitivity of the tumor cells. Thus, promoting tumor cell sensitivity to IR could significantly enhance the treatment outcome and quality of life for patients. Methods: Mammary tumor cells were treated by a 16-base phosphodiester-linked oligonucleotide homologous to the telomere G-rich sequence TTAGGG (T-oligo: GGTTAGGTGTAGGTTT) or a control-oligo (the partial complement, TAACCCTAACCCTAAC) followed by IR. The inhibition of tumor cell growth in vitro was assessed by cell counting and clonogenic cell survival assay. The tumorigenesis of tumor cells after various treatments was measured by tumor growth in mice. The mechanism underlying the radiosensitization by T-oligo was explored by immunofluorescent determination of phosphorylated histone H2AX ($\gamma$H2AX) foci, $\beta$-galactosidase staining, comet and Terminal deoxynucleotidyl transferase dUTP Nick End Labeling (TUNEL) assays. The efficacy of the combined treatment was assessed in a spontaneous murine mammary tumor model. Results: Pretreatment of tumor cells with T-oligo for 24 hours in vitro enhanced both senescence and apoptosis of irradiated tumor cells and reduced clonogenic potential. Radiosensitization by T-oligo was associated with increased formation and/or delayed resolution of $\gamma$H2AX DNA damage foci and fragmented DNA. T-oligo also caused radiosensitization in two in vivo mammary tumor models. Indeed, combined T-oligo and IR-treatment in vivo led to a substantial reduction in tumor growth. Of further significance, treatment with T-oligo and IR led to synergistic inhibition of the growth of spontaneous mammary carcinomas. Despite these profound antitumor properties, T-oligo and IR caused no detectable side effects under our experimental conditions. Conclusions: Pretreatment with T-oligo sensitizes mammary tumor cells to radiation in both in vitro and in vivo settings with minimal or no normal tissue side effects

The PAndAS view of the Andromeda satellite system - II. Detailed properties of 23 M31 dwarf spheroidal galaxies

We present a comprehensive analysis of the structural properties and luminosities of the 23 dwarf spheroidal galaxies that fall within the footprint of the Pan-Andromeda Archaeological Survey (PAndAS). These dwarf galaxies represent the large majority of Andromeda's known satellite dwarf galaxies and cover a wide range in luminosity ($-11.6<M_V<-5.8$ or $10^{4.2}< L <10^{6.5} L_\odot$) and surface brightness ($25.1<\mu_0<29.3$ mag/arcsec$^2$). We confirm most previous measurements, but find And XIX to be significantly larger than before ($r_h=3065^{+1065}_{-935}$ pc, $M_V=-10.1^{+0.8}_{-0.4}$) and cannot derive parameters for And XXVII as it is likely not a bound stellar system. We also significantly revise downward the luminosities of And~XV and And~XVI, which are now $M_V\sim-7.5$ or $L\sim10^5 L_\odot$. Finally, we provide the first detailed analysis of Cas II/And XXX, a fairly faint system ($M_V=-8.0^{+0.4}_{-0.3}$) of typical size ($r_h=270\pm50$ pc), located in close proximity to the two bright elliptical dwarf galaxies NGC 147 & 185. Combined with the set of homogeneous distances published in an earlier contribution, our analysis dutifully tracks all relevant sources of uncertainty in the determination of the properties of the dwarf galaxies from the PAndAS photometric catalogue. We further publish the posterior probability distribution functions of all the parameters we fit for in the form of MCMC chains available online; these inputs should be used in any analysis that aims to remain truthful to the data and properly account for covariance between parameters.Comment: 30 pages, 39 figures. Accepted for publication in Ap

Gene-centric approach identifies new and known loci for FVIII activity and VWF antigen levels in European Americans and African Americans: Genetic associations for FVIII:C and VWF:ag

Coagulation factor VIII and von Willebrand factor (VWF) are key proteins in procoagulant activation. Higher FVIII coagulant activity (FVIII:C) and VWF antigen (VWF:Ag) are risk factors for cardiovascular disease and venous thromboembolism. Beyond associations with ABO blood group, genetic determinants of FVIII and VWF are not well understood, especially in non European-American populations. We performed a genetic association study of FVIII:C and VWF:Ag that assessed 50,000 gene-centric single nucleotide polymorphisms (SNPs) in 18,556 European Americans (EAs) and 5,047 African Americans (AAs) from five population-based cohorts. Previously unreported associations for FVIII:C were identified in both AAs and EAs with KNG1 (most significantly associated SNP rs710446, Ile581Thr, P=5.10 × 10−7 in EAs and P=3.88 × 10−3 in AAs) and VWF rs7962217 (Gly2705Arg, P=6.30 × 10−9 in EAs and P=2.98 × 10−2 in AAs). Significant associations for FVIII:C were also observed with F8/TMLHE region SNP rs12557310 in EAs (P=8.02 × 10−10), with VWF rs1800380 in AAs (P=5.62 × 10−11), and with MAT1A rs2236568 in AAs (P=1.69 × 10−6). We replicated previously reported associations of FVIII:C and VWF:Ag with the ABO blood group, VWF rs1063856 (Thr789Ala), rs216321 (Ala852Gln), and VWF rs2229446 (Arg2185Gln). Findings from this study expand our understanding of genetic influences for FVIII:C and VWF:Ag in both EAs and AAs

Genome-Wide Association Study of Coronary Heart Disease and Its Risk Factors in 8,090 African Americans: The NHLBI CARe Project

Coronary heart disease (CHD) is the leading cause of mortality in African Americans. To identify common genetic polymorphisms associated with CHD and its risk factors (LDL- and HDL-cholesterol (LDL-C and HDL-C), hypertension, smoking, and type-2 diabetes) in individuals of African ancestry, we performed a genome-wide association study (GWAS) in 8,090 African Americans from five population-based cohorts. We replicated 17 loci previously associated with CHD or its risk factors in Caucasians. For five of these regions (CHD: CDKN2A/CDKN2B; HDL-C: FADS1-3, PLTP, LPL, and ABCA1), we could leverage the distinct linkage disequilibrium (LD) patterns in African Americans to identify DNA polymorphisms more strongly associated with the phenotypes than the previously reported index SNPs found in Caucasian populations. We also developed a new approach for association testing in admixed populations that uses allelic and local ancestry variation. Using this method, we discovered several loci that would have been missed using the basic allelic and global ancestry information only. Our conclusions suggest that no major loci uniquely explain the high prevalence of CHD in African Americans. Our project has developed resources and methods that address both admixture- and SNP-association to maximize power for genetic discovery in even larger African-American consortia