Sampling constrained probability distributions using Spherical Augmentation

Statistical models with constrained probability distributions are abundant in machine learning. Some examples include regression models with norm constraints (e.g., Lasso), probit, many copula models, and latent Dirichlet allocation (LDA). Bayesian inference involving probability distributions confined to constrained domains could be quite challenging for commonly used sampling algorithms. In this paper, we propose a novel augmentation technique that handles a wide range of constraints by mapping the constrained domain to a sphere in the augmented space. By moving freely on the surface of this sphere, sampling algorithms handle constraints implicitly and generate proposals that remain within boundaries when mapped back to the original space. Our proposed method, called {Spherical Augmentation}, provides a mathematically natural and computationally efficient framework for sampling from constrained probability distributions. We show the advantages of our method over state-of-the-art sampling algorithms, such as exact Hamiltonian Monte Carlo, using several examples including truncated Gaussian distributions, Bayesian Lasso, Bayesian bridge regression, reconstruction of quantized stationary Gaussian process, and LDA for topic modeling.Comment: 41 pages, 13 figure

Safety and efficacy of fluticasone propionate in the topical treatment of skin diseases

Fluticasone propionate - the first carbothioate corticosteroid - has been classified as a potent anti-inflammatory drug for dermatological use. It is available as 0.05% cream and 0.005% ointment formulations for the acute and maintenance treatment of patients with dermatological disorders such as atopic dermatitis, psoriasis and vitiligo. This glucocorticoid is characterized by high lipophilicity, high glucocorticoid receptor binding and activation, and a rapid metabolic turnover in skin. Although skin blanching following fluticasone propionate exceeds that of corticosteroids of medium strength, several clinical trials demonstrate a low potential for cutaneous and systemic side-effects, even in difficult-to-treat areas like the face, the eyelids and intertriginous areas. Even among paediatric patients with atopic dermatitis, fluticasone propionate proved to be safe and effective. These pharmacological and clinical properties are reflected by the high therapeutic index of this glucocorticoid

Personality trait development in midlife: exploring the impact of psychological turning points

This study examined long-term personality trait development in midlife and explored the impact of psychological turning points on personality change. Selfdefined psychological turning points reflect major changes in the ways people think or feel about an important part of their life, such as work, family, and beliefs about themselves and about the world. This study used longitudinal data from the Midlife in the US survey to examine personality trait development in adults aged 40–60 years. The Big Five traits were assessed in 1995 and 2005 by means of self-descriptive adjectives. Seven types of self-identified psychological turning points were obtained in 1995. Results indicated relatively high stability with respect to rankorders and mean-levels of personality traits, and at the same time reliable individual differences in change. This implies that despite the relative stability of personality traits in the overall sample, some individuals show systematic deviations from the sample mean-levels. Psychological turning points in general showed very little influence on personality trait change, although some effects were found for specific types of turning points that warrant further research, such as discovering that a close friend or relative was a much better person than one thought they were

Environmental variables, habitat discontinuity and life history shaping the genetic structure of Pomatoschistus marmoratus

Coastal lagoons are semi-isolated ecosystems exposed to wide fluctuations of environmental conditions and showing habitat fragmentation. These features may play an important role in separating species into different populations, even at small spatial scales. In this study, we evaluate the concordance between mitochondrial (previous published data) and nuclear data analyzing the genetic variability of Pomatoschistus marmoratus in five localities, inside and outside the Mar Menor coastal lagoon (SE Spain) using eight microsatellites. High genetic diversity and similar levels of allele richness were observed across all loci and localities, although significant genic and genotypic differentiation was found between populations inside and outside the lagoon. In contrast to the FST values obtained from previous mitochondrial DNA analyses (control region), the microsatellite data exhibited significant differentiation among samples inside the Mar Menor and between lagoonal and marine samples. This pattern was corroborated using Cavalli-Sforza genetic distances. The habitat fragmentation inside the coastal lagoon and among lagoon and marine localities could be acting as a barrier to gene flow and contributing to the observed genetic structure. Our results from generalized additive models point a significant link between extreme lagoonal environmental conditions (mainly maximum salinity) and P. marmoratus genetic composition. Thereby, these environmental features could be also acting on genetic structure of coastal lagoon populations of P. marmoratus favoring their genetic divergence. The mating strategy of P. marmoratus could be also influencing our results obtained from mitochondrial and nuclear DNA. Therefore, a special consideration must be done in the selection of the DNA markers depending on the reproductive strategy of the species

Chromosomal-level assembly of the Asian Seabass genome using long sequence reads and multi-layered scaffolding

We report here the ~670 Mb genome assembly of the Asian seabass (Lates calcarifer), a tropical marine teleost. We used long-read sequencing augmented by transcriptomics, optical and genetic mapping along with shared synteny from closely related fish species to derive a chromosome-level assembly with a contig N50 size over 1 Mb and scaffold N50 size over 25 Mb that span ~90% of the genome. The population structure of L. calcarifer species complex was analyzed by re-sequencing 61 individuals representing various regions across the species' native range. SNP analyses identified high levels of genetic diversity and confirmed earlier indications of a population stratification comprising three clades with signs of admixture apparent in the South-East Asian population. The quality of the Asian seabass genome assembly far exceeds that of any other fish species, and will serve as a new standard for fish genomics

Revealing the last 13,500 years of environmental history from the multiproxy record of a mountain lake (Lago Enol, northern Iberian Peninsula)

This is the author's accepted manuscript. The final publication is available at Springer via http://dx.doi.org/10.1007/s10933-009-9387-7.We present the Holocene sequence from Lago Enol (43°16′N, 4°59′W, 1,070 m a.s.l.), Cantabrian Mountains, northern Spain. A multiproxy analysis provided comprehensive information about regional humidity and temperature changes. The analysis included sedimentological descriptions, physical properties, organic carbon and carbonate content, mineralogy and geochemical composition together with biological proxies including diatom and ostracod assemblages. A detailed pollen study enabled reconstruction of variations in vegetation cover, which were interpreted in the context of climate changes and human impact. Four distinct stages were recognized for the last 13,500 years: (1) a cold and dry episode that includes the Younger Dryas event (13,500–11,600 cal. year BP); (2) a humid and warmer period characterizing the onset of the Holocene (11,600–8,700 cal. year BP); (3) a tendency toward a drier climate during the middle Holocene (8,700–4,650 cal. year BP); and (4) a return to humid conditions following landscape modification by human activity (pastoral activities, deforestation) in the late Holocene (4,650–2,200 cal. year BP). Superimposed on relatively stable landscape conditions (e.g. maintenance of well established forests), the typical environmental variability of the southern European region is observed at this site.The Spanish Inter-Ministry Commission of Science and Technology (CICYT), the Spanish National Parks agency, the European Commission, the Spanish Ministry of Science, and the European Social Fund

Common Variants at 10 Genomic Loci Influence Hemoglobin A(1C) Levels via Glycemic and Nonglycemic Pathways

OBJECTIVE Glycated hemoglobin (HbA1c), used to monitor and diagnose diabetes, is influenced by average glycemia over a 2- to 3-month period. Genetic factors affecting expression, turnover, and abnormal glycation of hemoglobin could also be associated with increased levels of HbA1c. We aimed to identify such genetic factors and investigate the extent to which they influence diabetes classification based on HbA1c levels. RESEARCH DESIGN AND METHODS We studied associations with HbA1c in up to 46,368 nondiabetic adults of European descent from 23 genome-wide association studies (GWAS) and 8 cohorts with de novo genotyped single nucleotide polymorphisms (SNPs). We combined studies using inverse-variance meta-analysis and tested mediation by glycemia using conditional analyses. We estimated the global effect of HbA1c loci using a multilocus risk score, and used net reclassification to estimate genetic effects on diabetes screening. RESULTS Ten loci reached genome-wide significant association with HbA1c, including six new loci near FN3K (lead SNP/P value, rs1046896/P = 1.6 × 10−26), HFE (rs1800562/P = 2.6 × 10−20), TMPRSS6 (rs855791/P = 2.7 × 10−14), ANK1 (rs4737009/P = 6.1 × 10−12), SPTA1 (rs2779116/P = 2.8 × 10−9) and ATP11A/TUBGCP3 (rs7998202/P = 5.2 × 10−9), and four known HbA1c loci: HK1 (rs16926246/P = 3.1 × 10−54), MTNR1B (rs1387153/P = 4.0 × 10−11), GCK (rs1799884/P = 1.5 × 10−20) and G6PC2/ABCB11 (rs552976/P = 8.2 × 10−18). We show that associations with HbA1c are partly a function of hyperglycemia associated with 3 of the 10 loci (GCK, G6PC2 and MTNR1B). The seven nonglycemic loci accounted for a 0.19 (% HbA1c) difference between the extreme 10% tails of the risk score, and would reclassify ∼2% of a general white population screened for diabetes with HbA1c. CONCLUSIONS GWAS identified 10 genetic loci reproducibly associated with HbA1c. Six are novel and seven map to loci where rarer variants cause hereditary anemias and iron storage disorders. Common variants at these loci likely influence HbA1c levels via erythrocyte biology, and confer a small but detectable reclassification of diabetes diagnosis by HbA1c

Understanding the Dynamic Behaviour of a Tennis Racket under Play Conditions

The 'feel' of tennis rackets is of increasing importance to manufacturers seeking product differentiation in a context where further performance enhancements are prevented by a combination of mechanical limits and regulations imposed to protect the integrity of the sport. Vibrations excited during a shot contribute greatly to the perception of 'feel'. Previous studies have been reported but none has covered the full set of mode families or the frequency range in this study. In-plane vibrations associated with the routine use of topspin shots in modern tennis have not been documented so far in the literature. To consider modal behaviour, multiple measurements during play conditions are required but this is practically impossible. This paper proposes an alternative approach and successfully relates a comprehensive modal analysis on a freely suspended racket to vibration measurements under play conditions. This is achieved through an intermediate stage comprising a necessarily more limited modal analysis on a hand-gripped racket and use of the mass modification modal analysis tool. This stage confirmed the prevailing view that hand-gripping can be considered as a mass modification distributed along the handle of the freely suspended racket but the associated mass was much lower than that of an actual hand and the hand also increased the damping ratio of frame modes significantly. Furthermore, in frame vibration measurements during forehand groundstrokes, a greater reduction in bending mode frequencies was observed, consistent with a mass-loading of around 25 % of the actual hand as a consequence of the tighter grip. In these play tests, the first two bending modes, the first torsional mode, the first eight stringbed modes, the first three hoop modes and the third in-plane bending mode were identified, with the stringbed modes being particularly prominent. © 2013 Society for Experimental Mechanics