Practical Bayesian optimization in the presence of outliers

Inference in the presence of outliers is an important field of research as outliers are ubiquitous and may arise across a variety of problems and domains. Bayesian optimization is method that heavily relies on probabilistic inference. This allows outstanding sample efficiency because the probabilistic machinery provides a memory of the whole optimization process. However, that virtue becomes a disadvantage when the memory is populated with outliers, inducing bias in the estimation. In this paper, we present an empirical evaluation of Bayesian optimization methods in the presence of outliers. The empirical evidence shows that Bayesian optimization with robust regression often produces suboptimal results. We then propose a new algorithm which combines robust regression (a Gaussian process with Student-t likelihood) with outlier diagnostics to classify data points as outliers or inliers. By using an scheduler for the classification of outliers, our method is more efficient and has better convergence over the standard robust regression. Furthermore, we show that even in controlled situations with no expected outliers, our method is able to produce better results.Comment: 10 pages (2 of references), 6 figures, 1 algorith

An evaluation of the fast-mixed spectrum reactor

"February 1980."Also issued as an M.S. thesis written by the first author and supervised by the second and third authors, MIT Dept. of Nuclear Engineering, 1980Includes bibliographical references (pages 145-147)An independent evaluation of the neutronic characteristics of a gas-cooled fast-mixed spectrum reactor (FMSR) core design has been performed. A benchmark core configuration for an early FMSR design was provided by Brookhaven National Laboratory, the originators of the concept. The results of the evaluation were compared with those of BNL. Points of comparison included system reactivity and breeding ratio, and region-wise power densities and isotopic compositions as a function of burnup. The results are in sufficiently good agreement to conclude that the neutronic feasibility of the FMSR concept has been independently validated. Significant differences, primarily in higher plutonium isotope concentrations, occur only in regions of low neutronic importance, and plausible reasons for the differences are advanced based on sensitivity studies and comparison of spectral indices. While both M.I.T. and BNL calculations tend to predict that the benchmark design is slightly subcritical, at the beginning of equilibrium cycle, the margin to k = 1.0 is close enough (Ak < 0.03) that the situation can be remedied. Establishment of a consensus fission product cross section set was identified as an objective of merit, since non-negligible differences were found in results computed using various extant sets (BNL, LIB-IV, Japanese). Non-fission heating by gamma and neutron interactions was evaluated for the reference core design using a coupled neutron/gamma cross section set and SN calculations. In the unfueled regions of the core, moderator elements in particular, the non-fission heating rate was found to be significant (averaging about 6 kw/liter), but posed no obvious problems. In fueled regions the common assumption of local deposition of all energy at the point of fission was verified to be a good approximation for most engineering purposes.Engineering and Advanced Reactor Safety Division of the U.S. Department of Energy at Brookhaven National Laboratory contract 472241-

GPS comparison of training activities and game demands of professional rugby union

Closely matching training session exertions with actual match-play intensities ensures players are physically prepared for competition. The movement patterns of four typical rugby union training activities (traditional endurance, high-intensity interval, game-based and skills training) were compared with match-play using global positioning systems. The degree of difference from match-play was determined by calculating Cohen’s effect size statistic. Training activities for players in different positions (tight forward, loose forward, scrumhalf, inside back and outside back) were similarly assessed. Movement patterns were measured as relative distance, distance walking (0–2 m.s1 ), jogging (2–4 m.s1 ), striding (4–6 m.s1 ) and sprinting (>6 m.s1 ) and sprint and acceleration (>2.75 m.s2 ) frequency. Overall, high-intensity interval training was the most similar to match-play, and could be adopted as a primary training activity. Game-based training failed to meet match intensity in all positions (Effect size ¼ medium to large). If game-based training is used as the primary training activity, supplementary training is required to ensure players are adequately prepared for match demands

A TSC signaling node at the peroxisome regulates mTORC1 and autophagy in response to ROS

Subcellular localization is emerging as an important mechanism for mTORC1 regulation. We report that the tuberous sclerosis complex (TSC) signaling node, TSC1, TSC2 and Rheb, localizes to peroxisomes, where it regulates mTORC1 in response to reactive oxygen species (ROS). TSC1 and TSC2 were bound by PEX19 and PEX5, respectively, and peroxisome-localized TSC functioned as a Rheb GAP to suppress mTORC1 and induce autophagy. Naturally occurring pathogenic mutations in TSC2 decreased PEX5 binding, abrogated peroxisome localization, Rheb GAP activity, and suppression of mTORC1 by ROS. Cells lacking peroxisomes were deficient in mTORC1 repression by ROS and peroxisome-localization deficient TSC2 mutants caused polarity defects and formation of multiple axons in neurons. These data identify a role for TSC in responding to ROS at the peroxisome, and identify the peroxisome as a signaling organelle involved in regulation of mTORC1

Editorial: HIV-1 genetic diversity, volume II

EditorialS

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

The effectiveness of schemes that refine referrals between primary and secondary care - the UK experience with glaucoma referrals: the Health Innovation & Education Cluster (HIEC) Glaucoma Pathways Project

Objectives: A comparison of glaucoma referral refinement schemes (GRRS) in the UK during a time period of considerable change in national policy and guidance. Design: Retrospective multisite review. Setting: The outcomes of clinical examinations by optometrists with a specialist interest in glaucoma (OSIs) were compared with optometrists with no specialist interest in glaucoma (non-OSIs). Data from Huntingdon and Nottingham assessed non-OSI findings, while Manchester and Gloucestershire reviewed OSI findings. Participants: 1086 patients. 434 patients were from Huntingdon, 179 from Manchester, 204 from Gloucestershire and 269 from Nottingham. Results: The first-visit discharge rate (FVDR) for all time periods for OSIs was 14.1% compared with 36.1% from non-OSIs (difference 22%, CI 16.9% to 26.7%; p<0.001). The FVDR increased after the April 2009 National Institute for Health and Clinical Excellence (NICE) glaucoma guidelines compared with pre-NICE, which was particularly evident when pre-NICE was compared with the current practice time period (OSIs 6.2–17.2%, difference 11%, CI −24.7% to 4.3%; p=0.18, non-OSIs 29.2–43.9%, difference 14.7%, CI −27.8% to −0.30%; p=0.03). Elevated intraocular pressure (IOP) was the commonest reason for referral for OSIs and non-OSIs, 28.7% and 36.1%, respectively, of total referrals. The proportion of referrals for elevated IOP increased from 10.9% pre-NICE to 28.0% post-NICE for OSIs, and from 19% to 45.1% for non-OSIs. Conclusions: In terms of ‘demand management’, OSIs can reduce FVDR of patients reviewed in secondary care; however, in terms of ‘patient safety’ this study also shows that overemphasis on IOP as a criterion for referral is having an adverse effect on both the non-OSIs and indeed the OSIs ability to detect glaucomatous optic nerve features. It is recommended that referral letters from non-OSIs be stratified for risk, directing high-risk patients straight to secondary care, and low-risk patients to OSIs