Lifting the Veil of Dust from NGC 0959: The Importance of a Pixel-Based 2D Extinction Correction

We present the results of a study of the late-type spiral galaxy NGC 0959, before and after application of the pixel-based dust extinction correction described in Tamura et al. 2009 (Paper I). Galaxy Evolution Explorer (GALEX) far-UV (FUV) and near-UV (NUV), ground-based Vatican Advanced Technology Telescope (VATT) UBVR, and Spitzer/Infrared Array Camera (IRAC) 3.6, 4.5, 5.8, and 8.0 micron images are studied through pixel Color-Magnitude Diagrams (pCMDs) and pixel Color-Color Diagrams (pCCDs). We define groups of pixels based on their distribution in a pCCD of (B - 3.6 micron) versus (FUV - U) colors after extinction correction. In the same pCCD, we trace their locations before the extinction correction was applied. This shows that selecting pixel groups is not meaningful when using colors uncorrected for dust. We also trace the distribution of the pixel groups on a pixel coordinate map of the galaxy. We find that the pixel-based (two-dimensional) extinction correction is crucial to reveal the spatial variations in the dominant stellar population, averaged over each resolution element. Different types and mixtures of stellar populations, and galaxy structures such as a previously unrecognized bar, become readily discernible in the extinction-corrected pCCD and as coherent spatial structures in the pixel coordinate map.Comment: 10 pages, LaTeX2e requires 'emulateapj.cls', 'graphicx.sty', and 'natbib.sty' (included), 9 postscript figures, 1 table. Accepted for publication in AJ

Artificial Immune Systems can find arbitrarily good approximations for the NP-Hard partition problem

Typical Artificial Immune System (AIS) operators such as hypermutations with mutation potential and ageing allow to efficiently overcome local optima from which Evolutionary Algorithms (EAs) struggle to escape. Such behaviour has been shown for artificial example functions such as Jump, Cliff or Trap constructed especially to show difficulties that EAs may encounter during the optimisation process. However, no evidence is available indicating that similar effects may also occur in more realistic problems. In this paper we perform an analysis for the standard NP-Hard Partition problem from combinatorial optimisation and rigorously show that hypermutations and ageing allow AISs to efficiently escape from local optima where standard EAs require exponential time. As a result we prove that while EAs and Random Local Search may get trapped on 4/3 approximations, AISs find arbitrarily good approximate solutions of ratio ( 1+ϵ ) for any constant ϵ within a time that is polynomial in the problem size and exponential only in 1/ϵ

“There’s a Catch-22”. The complexities of pain management for people with advanced dementia nearing the end of life: a qualitative exploration of physicians’ perspectives

Background: Pain management is a cornerstone of palliative care. The clinical issues encountered by physicians when managing pain in patients dying with advanced dementia, and how these may impact on prescribing and treatment, are unknown. Aim: To explore physicians’ experiences of pain management for patients nearing the end of life, the impact of these on prescribing and treatment approaches, and the methods employed to overcome these challenges. Design: Qualitative, semi-structured interview study exploring: barriers to and facilitators of pain management, prescribing and treatment decisions, and training needs. Thematic analysis was used to elicit key themes. Settings/Participants: Twenty-three physicians, responsible for treating patients with advanced dementia approaching the end of life, were recruited from primary care (n=9), psychiatry (n=7) and hospice care (n=7). Results: Six themes emerged: diagnosing pain, complex prescribing and treatment approaches, side-effects and adverse events, route of administration, importance of sharing knowledge and training needs. Knowledge exchange was often practised through liaison with physicians from other specialties. Cross-specialty mentoring, and the creation of knowledge networks were believed to improve pain management in this patient population. Conclusions: Pain management in end-stage dementia is complex, requiring cross-population of knowledge between palliative care specialists and non-specialists, in addition to collateral information provided by other health professionals and patients’ families. Regular, cost- and time-effective mentoring and ongoing professional development are perceived to be essential in empowering physicians to meet clinical challenges in this area

Diagnoses and visit length in complementary and mainstream medicine

<p>Abstract</p> <p>Background</p> <p>The demand for complementary medicine (CM) is growing worldwide and so is the supply. So far, there is not much insight in the activities in Dutch CM practices nor in how these activities differ from mainstream general practice. Comparisons on diagnoses and visit length can offer an impression of how Dutch CM practices operate.</p> <p>Methods</p> <p>Three groups of regularly trained physicians specialized in CM participated in this study: 16 homeopathic physicians, 13 physician acupuncturists and 11 naturopathy physicians. Every CM physician was asked to include a maximum of 75 new patients within a period of six months. For each patient an inclusion registration form had to be completed and the activities during a maximum of five repeat visits were subsequently registered. Registrations included patient characteristics, diagnoses and visit length. These data could be compared with similar data from general practitioners (GPs) participating in the second Dutch national study in general practice (DNSGP-2). Differences between CM practices and between CM and mainstream GP data were tested using multilevel regression analysis.</p> <p>Results</p> <p>The CM physicians registered activities in a total of 5919 visits in 1839 patients. In all types of CM practices general problems (as coded in the ICPC) were diagnosed more often than in mainstream general practice, especially fatigue, allergic reactions and infections. Psychological problems and problems with the nervous system were also diagnosed more frequently. In addition, each type of CM physician encountered specific health problems: in acupuncture problems with the musculoskeletal system prevailed, in homeopathy skin problems and in naturopathy gastrointestinal problems. Comparisons in visit length revealed that CM physicians spent at least twice as much time with patients compared to mainstream GPs.</p> <p>Conclusions</p> <p>CM physicians differed from mainstream GPs in diagnoses, partly related to general and partly to specific diagnoses. Between CM practices differences were found on specific domains of complaints. Visit length was much longer in CM practices compared to mainstream GP visits, and such ample time may be one of the attractive features of CM for patients.</p

Genetic variants associated with longitudinal changes in brain structure across the lifespan

Human brain structure changes throughout the lifespan. Altered brain growth or rates of decline are implicated in a vast range of psychiatric, developmental and neurodegenerative diseases. In this study, we identified common genetic variants that affect rates of brain growth or atrophy in what is, to our knowledge, the first genome-wide association meta-analysis of changes in brain morphology across the lifespan. Longitudinal magnetic resonance imaging data from 15,640 individuals were used to compute rates of change for 15 brain structures. The most robustly identified genes GPR139, DACH1 and APOE are associated with metabolic processes. We demonstrate global genetic overlap with depression, schizophrenia, cognitive functioning, insomnia, height, body mass index and smoking. Gene set findings implicate both early brain development and neurodegenerative processes in the rates of brain changes. Identifying variants involved in structural brain changes may help to determine biological pathways underlying optimal and dysfunctional brain development and aging

Genetic effects influencing risk for major depressive disorder in China and Europe

Major depressive disorder (MDD) is a common, complex psychiatric disorder and a leading cause of disability worldwide. Despite twin studies indicating its modest heritability (similar to 30-40%), extensive heterogeneity and a complex genetic architecture have complicated efforts to detect associated genetic risk variants. We combined single-nucleotide polymorphism (SNP) summary statistics from the CONVERGE and PGC studies of MDD, representing 10 502 Chinese (5282 cases and 5220 controls) and 18 663 European (9447 cases and 9215 controls) subjects. We determined the fraction of SNPs displaying consistent directions of effect, assessed the significance of polygenic risk scores and estimated the genetic correlation of MDD across ancestries. Subsequent trans-ancestry meta-analyses combined SNP-level evidence of association. Sign tests and polygenic score profiling weakly support an overlap of SNP effects between East Asian and European populations. We estimated the trans-ancestry genetic correlation of lifetime MDD as 0.33; female-only and recurrent MDD yielded estimates of 0.40 and 0.41, respectively. Common variants downstream of GPHN achieved genome-wide significance by Bayesian trans-ancestry meta-analysis (rs9323497; log10 Bayes Factor = 8.08) but failed to replicate in an independent European sample (P= 0.911). Gene-set enrichment analyses indicate enrichment of genes involved in neuronal development and axonal trafficking. We successfully demonstrate a partially shared polygenic basis of MDD in East Asian and European populations. Taken together, these findings support a complex etiology for MDD and possible population differences in predisposing genetic factors, with important implications for future genetic studies

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson’s disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

The genetic architecture of the human cerebral cortex

INTRODUCTION The cerebral cortex underlies our complex cognitive capabilities. Variations in human cortical surface area and thickness are associated with neurological, psychological, and behavioral traits and can be measured in vivo by magnetic resonance imaging (MRI). Studies in model organisms have identified genes that influence cortical structure, but little is known about common genetic variants that affect human cortical structure. RATIONALE To identify genetic variants associated with human cortical structure at both global and regional levels, we conducted a genome-wide association meta-analysis of brain MRI data from 51,665 individuals across 60 cohorts. We analyzed the surface area and average thickness of the whole cortex and 34 cortical regions with known functional specializations. RESULTS We identified 306 nominally genome-wide significant loci (P < 5 × 10−8) associated with cortical structure in a discovery sample of 33,992 participants of European ancestry. Of the 299 loci for which replication data were available, 241 loci influencing surface area and 14 influencing thickness remained significant after replication, with 199 loci passing multiple testing correction (P < 8.3 × 10−10; 187 influencing surface area and 12 influencing thickness). Common genetic variants explained 34% (SE = 3%) of the variation in total surface area and 26% (SE = 2%) in average thickness; surface area and thickness showed a negative genetic correlation (rG = −0.32, SE = 0.05, P = 6.5 × 10−12), which suggests that genetic influences have opposing effects on surface area and thickness. Bioinformatic analyses showed that total surface area is influenced by genetic variants that alter gene regulatory activity in neural progenitor cells during fetal development. By contrast, average thickness is influenced by active regulatory elements in adult brain samples, which may reflect processes that occur after mid-fetal development, such as myelination, branching, or pruning. When considered together, these results support the radial unit hypothesis that different developmental mechanisms promote surface area expansion and increases in thickness. To identify specific genetic influences on individual cortical regions, we controlled for global measures (total surface area or average thickness) in the regional analyses. After multiple testing correction, we identified 175 loci that influence regional surface area and 10 that influence regional thickness. Loci that affect regional surface area cluster near genes involved in the Wnt signaling pathway, which is known to influence areal identity. We observed significant positive genetic correlations and evidence of bidirectional causation of total surface area with both general cognitive functioning and educational attainment. We found additional positive genetic correlations between total surface area and Parkinson’s disease but did not find evidence of causation. Negative genetic correlations were evident between total surface area and insomnia, attention deficit hyperactivity disorder, depressive symptoms, major depressive disorder, and neuroticism. CONCLUSION This large-scale collaborative work enhances our understanding of the genetic architecture of the human cerebral cortex and its regional patterning. The highly polygenic architecture of the cortex suggests that distinct genes are involved in the development of specific cortical areas. Moreover, we find evidence that brain structure is a key phenotype along the causal pathway that leads from genetic variation to differences in general cognitive function

Identification of common genetic risk variants for autism spectrum disorder

Autism spectrum disorder (ASD) is a highly heritable and heterogeneous group of neurodevelopmental phenotypes diagnosed in more than 1% of children. Common genetic variants contribute substantially to ASD susceptibility, but to date no individual variants have been robustly associated with ASD. With a marked sample-size increase from a unique Danish population resource, we report a genome-wide association meta-analysis of 18,381 individuals with ASD and 27,969 controls that identified five genome-wide-significant loci. Leveraging GWAS results from three phenotypes with significantly overlapping genetic architectures (schizophrenia, major depression, and educational attainment), we identified seven additional loci shared with other traits at equally strict significance levels. Dissecting the polygenic architecture, we found both quantitative and qualitative polygenic heterogeneity across ASD subtypes. These results highlight biological insights, particularly relating to neuronal function and corticogenesis, and establish that GWAS performed at scale will be much more productive in the near term in ASD.Peer reviewe