Promoting the 3Rs to enhance the OECD fish toxicity testing framework.

Fish toxicity testing has been conducted since the 1860's in order to help define safe levels of chemical contaminants in lakes, rivers and coastal waters. The historical emphasis on acute lethality testing of chemicals has more recently focussed on long term sublethal effects of chemicals on fish and their prey species. Fish toxicity testing is now embedded in much environment legislation on chemical safety while it is recognized that animal use should be Replaced, Reduced and Refined (the 3Rs) where possible. The OECD Fish Toxicity Testing Framework provides a useful structure with which to address the needs of environmental safety assessment whilst implementing the 3Rs. This commentary aims to promote the implementation of the recommendations of the OECD Fish Toxicity Testing Framework

Kaluza-Klein dimensional reduction and Gauss-Codazzi-Ricci equations

In this paper we imitate the traditional method which is used customarily in the General Relativity and some mathematical literatures to derive the Gauss-Codazzi-Ricci equations for dimensional reduction. It would be more distinct concerning geometric meaning than the vielbein method. Especially, if the lower dimensional metric is independent of reduced dimensions the counterpart of the symmetric extrinsic curvature is proportional to the antisymmetric Kaluza-Klein gauge field strength. For isometry group of internal space, the SO(n) symmetry and SU(n) symmetry are discussed. And the Kaluza-Klein instanton is also enquired.Comment: 15 page

Curie-Weiss model of the quantum measurement process

A hamiltonian model is solved, which satisfies all requirements for a realistic ideal quantum measurement. The system S is a spin-\half, whose $z$-component is measured through coupling with an apparatus A=M+B, consisting of a magnet \RM formed by a set of $N\gg 1$ spins with quartic infinite-range Ising interactions, and a phonon bath \RB at temperature $T$. Initially A is in a metastable paramagnetic phase. The process involves several time-scales. Without being much affected, A first acts on S, whose state collapses in a very brief time. The mechanism differs from the usual decoherence. Soon after its irreversibility is achieved. Finally the field induced by S on M, which may take two opposite values with probabilities given by Born's rule, drives A into its up or down ferromagnetic phase. The overall final state involves the expected correlations between the result registered in M and the state of S. The measurement is thus accounted for by standard quantum statistical mechanics and its specific features arise from the macroscopic size of the apparatus.Comment: 5 pages Revte

Gravitation with superposed Gauss--Bonnet terms in higher dimensions: Black hole metrics and maximal extensions

Our starting point is an iterative construction suited to combinatorics in arbitarary dimensions d, of totally anisymmetrised p-Riemann 2p-forms (2p\le d) generalising the (1-)Riemann curvature 2-forms. Superposition of p-Ricci scalars obtained from the p-Riemann forms defines the maximally Gauss--Bonnet extended gravitational Lagrangian. Metrics, spherically symmetric in the (d-1) space dimensions are constructed for the general case. The problem is directly reduced to solving polynomial equations. For some black hole type metrics the horizons are obtained by solving polynomial equations. Corresponding Kruskal type maximal extensions are obtained explicitly in complete generality, as is also the periodicity of time for Euclidean signature. We show how to include a cosmological constant and a point charge. Possible further developments and applications are indicated.Comment: 13 pages, REVTEX. References and Note Adde

Multidimensional Supernova Simulations with Approximative Neutrino Transport I. Neutron Star Kicks and the Anisotropy of Neutrino-Driven Explosions in Two Spatial Dimensions

By means of two-dimensional (2D) simulations we study hydrodynamic instabilities during the first seconds of neutrino-driven supernova explosions, using a PPM hydrodynamics code, supplemented with a gray, non-equilibrium approximation of radial neutrino transport. We consider three 15 solar mass progenitors with different structures and one rotating model, in which we replace the dense core of the newly formed neutron star (NS) by a contracting inner grid boundary, and trigger neutrino-driven explosions by systematically varying the neutrino fluxes emitted at this boundary. Confirming more idealized studies as well as supernova simulations with spectral transport, we find that random seed perturbations can grow by hydrodynamic instabilities to a globally asymmetric mass distribution, leading to a dominance of dipole (l=1) and quadrupole (l=2) modes in the explosion ejecta. Anisotropic gravitational and hydrodynamic forces are found to accelerate the NS on a timescale of 2-3 seconds. Since the explosion anisotropies develop chaotically, the magnitude of the corresponding kick varies stochastically in response to small differences in the fluid flow. Our more than 70 models separate into two groups, one with high and the other with low NS velocities and accelerations after 1s of post-bounce evolution, depending on whether the l=1 mode is dominant in the ejecta or not. This leads to a bimodality of the distribution when the NS velocities are extrapolated to their terminal values. The fast group has an average velocity of about 500 km/s and peak values in excess of 1000 km/s. Establishing a link to the measured distribution of pulsar velocities, however, requires a much larger set of calculations and ultimately 3D modeling. (abridged)Comment: 40 pages, 28 figures; significantly shortened and revised version according to referee's comments; accepted by Astronomy & Astrophysic

Development of an IS change reason - IS change type combination matrix

Firms change their information systems (IS) for various reasons, ranging from compliance with government regulations to the development of new capabilities. When making these changes a firm can choose between four different IS change types: IS introduction, IS extension, IS replacement, and IS merger. This paper proposes that change reasons and change types are interrelated, and that certain reason-type combinations are more likely than others to result in a successful IS change. To identify these combinations, an IS change reason–IS change type matrix is developed. While the matrix is created from prior IS research, we conducted a focus group study of IS professionals to further explore and refine the matrix. The findings from the focus group study reveal that some IS change reason–IS change type combinations are more appropriate than others to carry out the IS change project successfully. We also present three examples of IS change projects to illustrate the use and value of the matrix in practice

Identifying critically important cardiovascular outcomes for trials in hemodialysis: an international survey with patients, caregivers and health professionals

BACKGROUND: Cardiovascular disease (CVD) is a major contributor to morbidity and mortality in people on hemodialysis (HD). Cardiovascular outcomes are reported infrequently and inconsistently across trials in HD. This study aimed to identify the priorities of patients/caregivers and health professionals (HPs) for CVD outcomes to be incorporated into a core outcome set reported in all HD trials. METHODS: In an international online survey, participants rated the absolute importance of 10 cardiovascular outcomes (derived from a systematic review) on a 9-point Likert scale, with 7-9 being critically important. The relative importance was determined using a best-worst scale. Likert means, medians and proportions and best-worst preference scores were calculated for each outcome. Comments were thematically analyzed. RESULTS: Participants included 127 (19%) patients/caregivers and 549 (81%) HPs from 53 countries, of whom 530 (78%) completed the survey in English and 146 (22%) in Chinese. All but one cardiovascular outcome ('valve replacement') was rated as critically important (Likert 7-9) by all participants; 'sudden cardiac death', 'heart attack', 'stroke' and 'heart failure' were all rated at the top by patients/caregivers (median Likert score 9). Patients/caregivers ranked the same four outcomes as the most important outcomes with mean preference scores of 6.2 (95% confidence interval 4.8-7.5), 5.9 (4.6-7.2), 5.3 (4.0-6.6) and 4.9 (3.6-6.3), respectively. The same four outcomes were ranked most highly by HPs. We identified five themes underpinning the prioritization of outcomes: 'clinical equipoise and potential for intervention', 'specific or attributable to HD', 'severity or impact on the quality of life', 'strengthen knowledge and education', and 'inextricably linked burden and risk'. CONCLUSIONS: Patients and HPs believe that all cardiovascular outcomes are of critical importance but consistently identify sudden cardiac death, myocardial infarction, stroke and heart failure as the most important outcomes to be measured in all HD trials

PICS-Ord: unlimited coding of ambiguous regions by pairwise identity and cost scores ordination

<p>Abstract</p> <p>Background</p> <p>We present a novel method to encode ambiguously aligned regions in fixed multiple sequence alignments by 'Pairwise Identity and Cost Scores Ordination' (PICS-Ord). The method works via ordination of sequence identity or cost scores matrices by means of Principal Coordinates Analysis (PCoA). After identification of ambiguous regions, the method computes pairwise distances as sequence identities or cost scores, ordinates the resulting distance matrix by means of PCoA, and encodes the principal coordinates as ordered integers. Three biological and 100 simulated datasets were used to assess the performance of the new method.</p> <p>Results</p> <p>Including ambiguous regions coded by means of PICS-Ord increased topological accuracy, resolution, and bootstrap support in real biological and simulated datasets compared to the alternative of excluding such regions from the analysis a priori. In terms of accuracy, PICS-Ord performs equal to or better than previously available methods of ambiguous region coding (e.g., INAASE), with the advantage of a practically unlimited alignment size and increased analytical speed and the possibility of PICS-Ord scores to be analyzed together with DNA data in a partitioned maximum likelihood model.</p> <p>Conclusions</p> <p>Advantages of PICS-Ord over step matrix-based ambiguous region coding with INAASE include a practically unlimited number of OTUs and seamless integration of PICS-Ord codes into phylogenetic datasets, as well as the increased speed of phylogenetic analysis. Contrary to word- and frequency-based methods, PICS-Ord maintains the advantage of pairwise sequence alignment to derive distances, and the method is flexible with respect to the calculation of distance scores. In addition to distance and maximum parsimony, PICS-Ord codes can be analyzed in a Bayesian or maximum likelihood framework. RAxML (version 7.2.6 or higher that was developed for this study) allows up to 32-state ordered or unordered characters. A GTR, MK, or ORDERED model can be applied to analyse the PICS-Ord codes partition, with GTR performing slightly better than MK and ORDERED.</p> <p>Availability</p> <p>An implementation of the PICS-Ord algorithm is available from <url>http://scit.us/projects/ngila/wiki/PICS-Ord</url>. It requires both the statistical software, R <url>http://www.r-project.org</url> and the alignment software Ngila <url>http://scit.us/projects/ngila</url>.</p

The PrEscription of intraDialytic exercise to improve quAlity of Life in patients with chronic kidney disease trial: study design and baseline data for a multicentre randomized controlled trial.

BACKGROUND: Exercise interventions designed to improve physical function and reduce sedentary behaviour in haemodialysis (HD) patients might improve exercise capacity, reduce fatigue and lead to improved quality of life (QOL). The PrEscription of intraDialytic exercise to improve quAlity of Life study aimed to evaluate the effectiveness of a 6-month intradialytic exercise programme on QOL and physical function, compared with usual care for patients on HD in the UK. METHODS: We conducted a prospective, pragmatic multicentre randomized controlled trial in 335 HD patients and randomly (1:1) assigned them to either (i) intradialytic exercise training plus usual care maintenance HD or (ii) usual care maintenance HD. The primary outcome of the study was the change in Kidney Disease Quality of Life Short Form (KDQOL-SF 1.3) Physical Component Score between baseline and 6 months. Additional secondary outcomes included changes in peak aerobic capacity, physical fitness, habitual physical activity levels and falls (International Physical Activity Questionnaire, Duke’s Activity Status Index and Tinetti Falls Efficacy Scale), QOL and symptom burden assessments (EQ5D), arterial stiffness (pulse wave velocity), anthropometric measures, resting blood pressure, clinical chemistry, safety and harms associated with the intervention, hospitalizations and cost-effectiveness. A nested qualitative study investigated the experience and acceptability of the intervention for both participants and members of the renal health care team. RESULTS: At baseline assessment, 62.4% of the randomized cohort were male, the median age was 59.3 years and 50.4% were white. Prior cerebrovascular events and myocardial infarction were present in 8 and 12% of the cohort, respectively, 77.9% of patients had hypertension and 39.4% had diabetes. Baseline clinical characteristics and laboratory data for the randomized cohort were generally concordant with data from the UK Renal Registry. CONCLUSIONS: The results from this study will address a significant knowledge gap in the prescription of exercise interventions for patients receiving maintenance HD therapy and inform the development of intradialytic exercise programmes both nationally and internationally. TRIAL REGISTRATION: ISRCTN N83508514; registered on 17 December 2014