Automatic quantification of lobular inflammation and hepatocyte ballooning in NAFLD liver biopsies

Automatic quantification of cardinal histologic features of nonalcoholic fatty liver disease (NAFLD) may reduce human variability and allow continuous rather than semiquantitative assessment of injury. We recently developed an automated classifier that can detect and quantify macrosteatosis with greater than or equal to 95% precision and recall (sensitivity). Here, we report our early results on the classifier's performance in detecting lobular inflammation and hepatocellular ballooning. Automatic quantification of lobular inflammation and ballooning was performed on digital images of hematoxylin and eosin–stained slides of liver biopsy samples from 59 individuals with normal liver histology and varying severity of NAFLD. Two expert hepatopathologists scored liver biopsies according the nonalcoholic steatohepatitis clinical research network scoring system and provided annotations of lobular inflammation and hepatocyte ballooning on the digital images. The classifier had precision and recall of 70% and 49% for lobular inflammation, and 91% and 54% for hepatocyte ballooning. In addition, the classifier had an area under the curve of 95% for lobular inflammation and 98% for hepatocyte ballooning. The Spearman rank correlation coefficient for comparison with pathologist grades was 45.2% for lobular inflammation and 46% for hepatocyte ballooning. Our novel observations demonstrate that automatic quantification of cardinal NAFLD histologic lesions is feasible and offer promise for further development of automatic quantification as a potential aid to pathologists evaluating NAFLD biopsies in clinical practice and clinical trials

Fractal Structures and Scaling Laws in the Universe: Statistical Mechanics of the Self-Gravitating Gas

Fractal structures are observed in the universe in two very different ways. Firstly, in the gas forming the cold interstellar medium in scales from 10^{-4} pc till 100 pc. Secondly, the galaxy distribution has been observed to be fractal in scales up to hundreds of Mpc. We give here a short review of the statistical mechanical (and field theoretical) approach developed by us. We consider a non-relativistic self-gravitating gas in thermal equilibrium at temperature T inside a volume V. The statistical mechanics of such system has special features and, as is known, the thermodynamical limit does not exist in its customary form. Moreover, the treatments through microcanonical, canonical and grand canonical ensembles yield different results.We present here for the first time the equation of state for the self-gravitating gas in the canonical ensemble. We find that it has the form p = [N T/ V] f(eta), where p is the pressure, N is the number of particles and \eta \equiv {G m^2 N \over V^{1/3} T}. The N \to\infty and V \to\infty limit exists keeping \eta fixed. We compute the function f(\eta) using Monte Carlo simulations and for small eta analytically. We compute the thermodynamic quantities of the system as free energy, entropy, chemical potential, specific heat, compressibility and speed of sound. We reproduce the well-known gravitational phase transition associated to the Jeans' instability. Namely, a gaseous phase for eta < eta_c and a condensed phase for eta > eta_c. Moreover, we derive the precise behaviour of the physical quantities near the transition. In particular, the pressure vanishes as p \sim(eta_c-eta)^B with B \sim 0.2 and eta_c \sim 1.6 and the energy fluctuations diverge as \sim(eta_c-eta)^{B-1}. The speed of sound decreases monotonically and approaches the value sqrt{T/6} at the transition.Comment: Invited paper to the special issue of the `Journal of Chaos, Solitons and Fractals': `Superstrings, M, F, S...theory', M. S El Naschie and C. Castro, Editors. Latex file, 16 pages plus three .ps figure

On three-manifolds dominated by circle bundles

We determine which three-manifolds are dominated by products. The result is that a closed, oriented, connected three-manifold is dominated by a product if and only if it is finitely covered either by a product or by a connected sum of copies of the product of the two-sphere and the circle. This characterization can also be formulated in terms of Thurston geometries, or in terms of purely algebraic properties of the fundamental group. We also determine which three-manifolds are dominated by non-trivial circle bundles, and which three-manifold groups are presentable by products.Comment: 12 pages; to appear in Math. Zeitschrift; ISSN 1103-467

Sanctioning Memory; Changing Identity: Using 3D laser scanning to identify two ‘new’ portraits of the emperor Nero in English antiquarian collections

Using 3D laser scanning, two badly damaged and heavily restored Roman portraits from English country house collections are here identified as originally being representations of the Emperor Nero. The first portrait, from Petworth House, is of Nero at the time of his formal adoption as heir by the Emperor Claudius in AD51, while the second, from Wilton House, represents a new intermediate portrait type of the fifth emperor, marking his transition from traditional Julio-Claudian prince to more flamboyant princeps, made between AD54 and 59. Given that few replicas of Nero exist in anything like their complete state, following the memory sanctions that followed his death in AD68, any 'new' discovery represents a significant find, to be analysed and cross-compared with established portraits. This article further assesses the importance of recording head dislocation and mutilation in images of Nero while the dangers of over restoration in classical portraiture, in which original identity can be obscured, are also considered

Automatic classification of white regions in liver biopsies by supervised machine learning

Automated assessment of histological features of non-alcoholic fatty liver disease (NAFLD) may reduce human variability and provide continuous rather than semiquantitative measurement of these features. As part of a larger effort, we perform automatic classification of steatosis, the cardinal feature of NAFLD, and other regions that manifest as white in images of hematoxylin and eosin-stained liver biopsy sections. These regions include macrosteatosis, central veins, portal veins, portal arteries, sinusoids and bile ducts. Digital images of hematoxylin and eosin-stained slides of 47 liver biopsies from patients with normal liver histology (n = 20) and NAFLD (n = 27) were obtained at 20× magnification. The images were analyzed using supervised machine learning classifiers created from annotations provided by two expert pathologists. The classification algorithm performs with 89% overall accuracy. It identified macrosteatosis, bile ducts, portal veins and sinusoids with high precision and recall (≥ 82%). Identification of central veins and portal arteries was less robust but still good. The accuracy of the classifier in identifying macrosteatosis is the best reported. The accurate automated identification of macrosteatosis achieved with this algorithm has useful clinical and research-related applications. The accurate detection of liver microscopic anatomical landmarks may facilitate important subsequent tasks, such as localization of other histological lesions according to liver microscopic anatomy

Local electrical imaging of tetragonal domains and field-induced ferroelectric twin walls in conducting SrTiO3

This work is supported by the National University of Singapore (NUS) Academic Research Fund (AcRF Tier 1 Grants No. R-144-000-346-112 and No. R-144-000-364-112) and the Singapore National Research Foundation (NRF) under the Competitive Research Programs (CRP Awards No. NRF-CRP 8-2011-06 and No. NRF-CRP10-2012-02) by the Institutional Strategy of the University of Tübingen (Deutsche Forschungsgemeinschaft, Grant No. ZUK 63), and by the EU-FP6-COST Grant No. MP1308.We demonstrate electrical mapping of tetragonal domains and electric field-induced twin walls in SrTiO3 as a function of temperature and gate bias utilizing the conducting LaAlO3/SrTiO3 interface and low-temperature scanning electron microscopy. Conducting twin walls appear below 105 K, and new twin patterns are observed after thermal cycling through the transition or on electric field gating. The nature of the twin walls is confirmed by calculating their intersection angles for different substrate orientations. Numerous walls formed when a large side- or back-gate voltage is applied are identified as field-induced ferroelectric twin walls in the paraelectric tetragonal matrix. The walls persist after switching off the electric field and on thermal cycling below 105 K. These observations point to a new type of ferroelectric functionality in SrTiO3, which could be exploited together with magnetism and superconductivity in a multifunctional context.Publisher PDFPeer reviewe

The Ricci flow on noncommutative two-tori

In this paper we construct a version of Ricci flow for noncommutative 2-tori, based on a spectral formulation in terms of the eigenvalues and eigenfunction of the Laplacian and recent results on the Gauss-Bonnet theorem for noncommutative tori.Comment: 18 pages, LaTe

The sources of management innovation: when firms introduce new management practices

Management innovation is the introduction of management practices new to the firm and intended to enhance firm performance. Building on the organizational reference group literature, this article shows that management innovation is a consequence of a firm's internal context and of the external search for new knowledge. Furthermore the article demonstrates a trade-off between context and search, in that there is a negative effect on management innovation associated with their joint occurrence. Finally the article shows that management innovation is positively associated with firm performance in the form of subsequent productivity growth

Challenges facing sustainable protein production: Opportunities for cereals

Rising demands for protein across the world are likely to increase livestock production, as meat provides ∼40% of dietary protein. This will come at significant environmental expense; therefore, a shift towards plant-based protein sources would provide major benefits. While legumes provide substantial plant-based proteins, cereals are the major constituents of global foods with wheat alone accounting for 15–20% of the required protein intake. Improving protein content in wheat is limited by phenotyping challenges, lack of genetic potential of modern germplasms, negative yield trade-off, and the environmental cost of nitrogen fertilisers. Presenting wheat as a case study, we discuss how increasing protein content in cereals through a revised breeding strategy combined with robust phenotyping can ensure a sustainable protein supply while minimising the environmental impact of nitrogen fertiliser

Vocal Tract Images Reveal Neural Representations of Sensorimotor Transformation During Speech Imitation

Imitating speech necessitates the transformation from sensory targets to vocal tract motor output, yet little is known about the representational basis of this process in the human brain. Here, we address this question by using real-time MR imaging (rtMRI) of the vocal tract and functional MRI (fMRI) of the brain in a speech imitation paradigm. Participants trained on imitating a native vowel and a similar nonnative vowel that required lip rounding. Later, participants imitated these vowels and an untrained vowel pair during separate fMRI and rtMRI runs. Univariate fMRI analyses revealed that regions including left inferior frontal gyrus were more active during sensorimotor transformation (ST) and production of nonnative vowels, compared with native vowels; further, ST for nonnative vowels activated somatomotor cortex bilaterally, compared with ST of native vowels. Using test representational similarity analysis (RSA) models constructed from participants' vocal tract images and from stimulus formant distances, we found that RSA searchlight analyses of fMRI data showed either type of model could be represented in somatomotor, temporal, cerebellar, and hippocampal neural activation patterns during ST. We thus provide the first evidence of widespread and robust cortical and subcortical neural representation of vocal tract and/or formant parameters, during prearticulatory ST