Hamiltonian ABC

Approximate Bayesian computation (ABC) is a powerful and elegant framework for performing inference in simulation-based models. However, due to the difficulty in scaling likelihood estimates, ABC remains useful for relatively low-dimensional problems. We introduce Hamiltonian ABC (HABC), a set of likelihood-free algorithms that apply recent advances in scaling Bayesian learning using Hamiltonian Monte Carlo (HMC) and stochastic gradients. We find that a small number forward simulations can effectively approximate the ABC gradient, allowing Hamiltonian dynamics to efficiently traverse parameter spaces. We also describe a new simple yet general approach of incorporating random seeds into the state of the Markov chain, further reducing the random walk behavior of HABC. We demonstrate HABC on several typical ABC problems, and show that HABC samples comparably to regular Bayesian inference using true gradients on a high-dimensional problem from machine learning.Comment: Submission to UAI 201

Конкурентоспроможність персоналу: сутність та місце у забезпеченні конкурентоспроможності підприємства

Розглянути різноманітні точки зору щодо конкурентоспроможності робочої сили та поняття конкурентоспроможності персоналу підприємства. Визначені передумови виникнення поняття конкурентоспроможності персоналу підприємства. Обґрунтовано зв'язок конкурентоспроможності персоналу із конкурентоспроможністю підприємства.Рассмотрены различные точки зрения относительно конкурентоспособности рабочей силы и понятие конкурентоспособности предприятия. Определены предпосылки возникновения понятия конкурентоспособности персонала предприятия. Обоснована связь конкурентоспособности персонала с конкурентоспособностью предприятия.Different points of view are considered in relation to the competitiveness of labour force and concept of competitiveness of enterprise. Pre-conditions of origin of concept of competitiveness of personnel of enterprise are certain. Communication of competitiveness of personnel with the competitiveness of enterprise is grounded

Southeast of What? Reflections on SEALS\u27 Success

In epidemiologic studies, measurement error in dietary variables often attenuates association between dietary intake and disease occurrence. To adjust for the attenuation caused by error in dietary intake, regression calibration is commonly used. To apply regression calibration, unbiased reference measurements are required. Short-term reference measurements for foods that are not consumed daily contain excess zeroes that pose challenges in the calibration model. We adapted two-part regression calibration model, initially developed for multiple replicates of reference measurements per individual to a single-replicate setting. We showed how to handle excess zero reference measurements by two-step modeling approach, how to explore heteroscedasticity in the consumed amount with variance-mean graph, how to explore nonlinearity with the generalized additive modeling (GAM) and the empirical logit approaches, and how to select covariates in the calibration model. The performance of two-part calibration model was compared with the one-part counterpart. We used vegetable intake and mortality data from European Prospective Investigation on Cancer and Nutrition (EPIC) study. In the EPIC, reference measurements were taken with 24-hour recalls. For each of the three vegetable subgroups assessed separately, correcting for error with an appropriately specified two-part calibration model resulted in about three fold increase in the strength of association with all-cause mortality, as measured by the log hazard ratio. Further found is that the standard way of including covariates in the calibration model can lead to over fitting the two-part calibration model. Moreover, the extent of adjusting for error is influenced by the number and forms of covariates in the calibration model. For episodically consumed foods, we advise researchers to pay special attention to response distribution, nonlinearity, and covariate inclusion in specifying the calibration model

Pedi-IKDC or KOOS-child: Which questionnaire should be used in children with knee disorders?

Background: The Pedi International Knee Documentation Committee (IKDC) and Knee Injury and Osteoarthritis Outcome Score (KOOS) child are validated questionnaires for children with knee disorders. The aim of this study was to translate these questionnaires in Dutch and to recommend which questionnaires should - based on their psychometric properties - be used in clinical practice. Methods: The English Pedi-IKDC and KOOS-Child were translated by the forward-backward procedure. Subsequently, content validity of the Pedi-IKDC and KOOS-Child was evaluated by both patients (n = 18) and experts (n = 18). To evaluate construct validity and interpretability participants with knee disorders (n = 100) completed the Numeric Rating Scale Pain, Lysholm Knee Scoring Scale, EuroQol-5 Dimension, Pedi-IKDC and KOOS-Child at baseline. Participants completed the anchor question, Pedi-IKDC and KOOS-child two weeks (n = 54) and one year (n = 71) after baseline, for evaluating the test-retest reliability and responsiveness. Psychometric properties were interpreted following the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) criteria. Results: The Pedi-IKDC showed adequate test-retest reliability (intraclass correlation coefficient (ICC) 0.9; standard error of measurement (SEM) 8.6; smallest detectable change (SDC) 23.8), adequate content validity (> 75% relevant), adequate construct validity (75% confirmed hypotheses), low floor or ceiling effects (scores between 5 and 95) and adequate responsiveness (> 75% confirmed hypotheses). The KOOS-Child showed an adequate test-retest reliability (ICC 0.8-0.9; SEM 8.9-16.9; SDC 24.7-46.9), adequate content validity (> 75% relevant, except KOOS-Child subscale ADL), adequate construct validity (75% confirmed hypotheses), low floor and ceiling effects (scores between 5 and 95, except KOOS-Child subscale activities of daily living and Sport/play) and moderate responsiveness (40% confirmed hypotheses). Conclusions: The Pedi IKDC showed better psychometric properties than the KOOS-Child and should therefore be used in children with knee disorders

Evolution of costs of inflammatory bowel disease over two years of follow-up

Background: With the increasing use of anti-TNF therapy in inflammatory bowel disease (IBD), a shift of costs has been observed with medication costs replacing hospitalization and surgery as major cost driver. We aimed to explore the evolution of IBD-related costs over two years of follow-up. Methods and Findings: In total 1,307 Crohn's disease (CD) patients and 915 ulcerative colitis (UC) patients were prospectively followed for two years by three-monthly web-based questionnaires. Changes of healthcare costs, productivity costs and out-of-pocket costs over time were assessed using mixed model analysis. Multivariable logistic regression analysis was used to identify costs drivers. In total 737 CD patients and 566 UC were included. Total costs were stable over two years of follow-up, with annual total costs of € 7,835 in CD and € 3,600 in UC. However, within healthcare costs, the proportion of anti-TNF therapy-related costs increased from 64% to 72% in CD (p<0.01) and from 31% to 39% in UC (p < 0.01). In contrast, the proportion of hospitalization costs decreased from 19% to 13% in CD (p<0.01), and 22% to 15% in UC (p < 0.01). Penetrating disease course predicted an increase of healthcare costs (adjusted odds ratio (adj. OR) 1.95 (95% CI 1.02-3.37) in CD and age <40 years in UC (adj. OR 4.72 (95% CI 1.61-13.86)). Conclusions: BD-related costs remained stable over two years. However, the proportion of anti-TNFrelated healthcare costs increased, while hospitalization costs decreased. Factors associated with increased costs were penetrating disease course in CD and age <40 in UC

Dairy products, dietary calcium and the risk of inflammatory bowel disease: results from a European prospective cohort investigation

Background: Dairy products may be involved in the etiology of inflammatory bowel disease by modulating gut microbiota and immune responses, but data from epidemiological studies examining this relationship are limited. We investigated the association between prediagnostic intake of these foods and dietary calcium, and the subsequent development of Crohn's disease (CD) and ulcerative colitis (UC). Methods: In total, 401,326 participants were enrolled in the European Prospective Investigation into Cancer and Nutrition cohort. At recruitment, consumption of total and specific dairy products (milk, yogurt, and cheese) and dietary calcium was measured using validated food frequency questionnaires. Cases developing incident CD (n = 110) or UC (n = 244) during follow-up were matched with 4 controls. Conditional logistic regression analyses were used to calculate odds ratios (ORs) with 95% confidence intervals (CIs), adjusted for total energy intake and smoking. Results: Compared with the lowest quartile, the ORs for the highest quartile of total dairy products and dietary calcium intake were 0.61 (95% CI, 0.32-1.19, p trend = 0.19) and 0.63 (95% CI, 0.28-1.42, p trend = 0.23) for CD, and 0.80 (95% CI, 0.50-1.30, p trend = 0.40) and 0.81 (95% CI, 0.49-1.34, p trend = 0.60) for UC, respectively. Compared with nonconsumers, individuals consuming milk had significantly reduced odds of CD (OR 0.30, 95% CI, 0.13-0.65) and nonsignificantly reduced odds of UC (OR 0.85, 95% CI, 0.49-1.47). Conclusions: Milk consumption may be associated with a decreased risk of developing CD, although a clear dose-response relationship was not established. Further studies are warranted to confirm this possible protective effect

Photography-based taxonomy is inadequate, unnecessary, and potentially harmful for biological sciences

The question whether taxonomic descriptions naming new animal species without type specimen(s) deposited in collections should be accepted for publication by scientific journals and allowed by the Code has already been discussed in Zootaxa (Dubois & Nemésio 2007; Donegan 2008, 2009; Nemésio 2009a–b; Dubois 2009; Gentile & Snell 2009; Minelli 2009; Cianferoni & Bartolozzi 2016; Amorim et al. 2016). This question was again raised in a letter supported by 35 signatories published in the journal Nature (Pape et al. 2016) on 15 September 2016. On 25 September 2016, the following rebuttal (strictly limited to 300 words as per the editorial rules of Nature) was submitted to Nature, which on 18 October 2016 refused to publish it. As we think this problem is a very important one for zoological taxonomy, this text is published here exactly as submitted to Nature, followed by the list of the 493 taxonomists and collection-based researchers who signed it in the short time span from 20 September to 6 October 2016

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation