Phase Transitions and Symmetry Breaking in Genetic Algorithms with Crossover

In this paper, we consider the role of the crossover operator in genetic algorithms. Specifically, we study optimisation problems that exhibit many local optima and consider how crossover affects the rate at which the population breaks the symmetry of the problem. As an example of such a problem, we consider the subset sum problem. In so doing, we demonstrate a previously unobserved phenomenon, whereby the genetic algorithm with crossover exhibits a critical mutation rate, at which its performance sharply diverges from that of the genetic algorithm without crossover. At this critical mutation rate, the genetic algorithm with crossover exhibits a rapid increase in population diversity. We calculate the details of this phenomenon on a simple instance of the subset sum problem and show that it is a classic phase transition between ordered and disordered populations. Finally, we show that this critical mutation rate corresponds to the transition between the genetic algorithm accelerating or preventing symmetry breaking and that the critical mutation rate represents an optimum in terms of the balance of exploration and exploitation within the algorithm

The importance of integration of stakeholder views in core outcome set development: Otitis Media with Effusion in children with cleft palate

© 2015 Harman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background: Approximately 75% of children with cleft palate (CP) have Otitis Media with Effusion (OME) histories. Evidence for the effective management of OME in these children is lacking. The inconsistency in outcome measurement in previous studies has led to a call for the development of a Core Outcome Set (COS). Despite the increase in the number of published COS, involvement of patients in the COS development process, and methods to integrate the views of patients and health professionals, to date have been limited. Methods and Findings: A list of outcomes measured in previous research was identified through reviewing the literature. Opinion on the importance of each of these outcomes was then sought from key stakeholders: Ear, Nose and Throat (ENT) surgeons, audiologists, cleft surgeons, speech and language therapists, specialist cleft nurses, psychologists, parents and children. The opinion of health professionals was sought in a three round Delphi survey where participants were asked to score each outcome using a bespoke online system. Parents and children were also asked to score outcomes in a survey and provided an in-depth insight into having OME through semi-structured interviews. The results of the Delphi survey, interviews and parent/patient survey were brought together in a final consensus meeting with representation from all stakeholders. A final set of eleven outcomes reached the definition of "consensus in" to form the recommended COS: hearing; chronic otitis media (COM); OME; receptive language skills; speech development; psycho social development; acute otitis media (AOM); cholesteatoma; side effects of treatment; listening skills; otalgia. Conclusions: We have produced a recommendation about the outcomes that should be measured, as a minimum, in studies of the management of OME in children with CP. The development process included input from key stakeholders and used novel methodology to integrate the opinion of healthcare professionals, parents and children

Identifying active vascular microcalcification by (18)F-sodium fluoride positron emission tomography.

Vascular calcification is a complex biological process that is a hallmark of atherosclerosis. While macrocalcification confers plaque stability, microcalcification is a key feature of high-risk atheroma and is associated with increased morbidity and mortality. Positron emission tomography and X-ray computed tomography (PET/CT) imaging of atherosclerosis using (18)F-sodium fluoride ((18)F-NaF) has the potential to identify pathologically high-risk nascent microcalcification. However, the precise molecular mechanism of (18)F-NaF vascular uptake is still unknown. Here we use electron microscopy, autoradiography, histology and preclinical and clinical PET/CT to analyse (18)F-NaF binding. We show that (18)F-NaF adsorbs to calcified deposits within plaque with high affinity and is selective and specific. (18)F-NaF PET/CT imaging can distinguish between areas of macro- and microcalcification. This is the only currently available clinical imaging platform that can non-invasively detect microcalcification in active unstable atherosclerosis. The use of (18)F-NaF may foster new approaches to developing treatments for vascular calcification.AI Wellcome Trust PhD Programme in Metabolic and Cardiovascular Disease Grant Number 096823/Z/11/Z, Wellcome Trust (WT103782AIA), British Heart Foundation (RG/10/007/28300, CH/09/002/26360, PG/12/8/29371), NHS Research Scotland and NIHR Cambridge Biomedical Research Centre.This is the final version of the article. It first appeared from the Nature Publishing Group via http://dx.doi.org/10.1038/ncomms849

Temporal spatial and metabolic measures of walking in highly functional individuals with lower limb amputations

OBJECTIVE: The aim of this descriptive exploratory study is to record the temporal spatial parameters and metabolic energy expenditure during walking of individuals with amputation, walking with advanced prostheses and following completion of comprehensive rehabilitation, to able-bodied controls. DESIGN: Cross-sectional SETTING: Multi-disciplinary comprehensive rehabilitation centre PARTICIPANTS: Thirty severely injured United Kingdom military personnel with amputation and subsequent completion of their rehabilitation programme (10 unilateral trans-tibial, 10 unilateral trans-femoral, and 10 bilateral trans-femoral) were compared to (and of similar age, height and mass (p < 0.537) as) 10 able-bodied controls. INTERVENTIONS: Not applicable Main Outcomes and Measures: Temporal spatial and metabolic energy expenditure data were captured during walking on level ground at self-selected speed. RESULTS: The individuals with amputation were all male, with a mean age 29 years (SD = 4) and mean New Injury Severity Score of 31 (SD = 16). Walking speed, stride length, step length and cadence of individuals with a unilateral trans-tibial or trans-femoral amputation was comparable to controls, and only for individuals with a bilateral trans-femoral amputation was walking speed significantly slower (1·12m/s, p = 0.025) and cadence reduced (96 steps/min, p = 0.026). Oxygen cost for individuals with a unilateral trans-tibial amputation (0·15 ml/kg/m) was the same as for controls (0·15 ml/kg/m), and significantly increased by 20% (0·18ml/kg/m, p = 0.023) for unilateral trans-femoral and by 60% (0·24 ml/kg/m, p < 0.001) for bilateral trans-femoral individuals with amputation. CONCLUSION: The scientific literature reports a wide range of gait and metabolic energy expenditure across individuals with amputation. The results of this study indicate that the individuals with amputation have a gait pattern which is highly functional and efficient. This is comparable to a small number of studies reporting similar outcomes for individuals with a unilateral trans-tibial amputation, but the results from this study are better than those on individuals with trans-femoral amputations reported elsewhere, despite comparison with populations wearing similar prosthetic componentry. Those studies that do report similar outcomes have included individuals who have been provided with a comprehensive rehabilitation programme. This suggests that such a programme may be as important as, or even more important than, prosthetic component selection in improving metabolic energy expenditure. The data are made available as a benchmark for what is achievable in the rehabilitation of some individuals with amputations, but agreeably may not be possible for all amputees to achieve

Observation of a Reflected Shock in an Indirectly Driven Spherical Implosion at the National Ignition Facility

A 200  μm radius hot spot at more than 2 keV temperature, 1  g/cm[superscript 3] density has been achieved on the National Ignition Facility using a near vacuum hohlraum. The implosion exhibits ideal one-dimensional behavior and 99% laser-to-hohlraum coupling. The low opacity of the remaining shell at bang time allows for a measurement of the x-ray emission of the reflected central shock in a deuterium plasma. Comparison with 1D hydrodynamic simulations puts constraints on electron-ion collisions and heat conduction. Results are consistent with classical (Spitzer-Harm) heat flux.United States. Dept. of Energy (Contract DE-AC52-07NA27344)Brookhaven National Laboratory (Laboratory Directed Research and Development Grant 11-ERD-050

Ion Thermal Decoupling and Species Separation in Shock-Driven Implosions

Anomalous reduction of the fusion yields by 50% and anomalous scaling of the burn-averaged ion temperatures with the ion-species fraction has been observed for the first time in D[superscript 3]He-filled shock-driven inertial confinement fusion implosions. Two ion kinetic mechanisms are used to explain the anomalous observations: thermal decoupling of the D and [superscript 3]He populations and diffusive species separation. The observed insensitivity of ion temperature to a varying deuterium fraction is shown to be a signature of ion thermal decoupling in shock-heated plasmas. The burn-averaged deuterium fraction calculated from the experimental data demonstrates a reduction in the average core deuterium density, as predicted by simulations that use a diffusion model. Accounting for each of these effects in simulations reproduces the observed yield trends.United States. National Nuclear Security Administration (Grant DE-NA0001857)University of Rochester. Fusion Science Center (Grant 415023-G)National Laser User’s Facility (Grant DE-NA0002035)University of Rochester. Laboratory for Laser Energetics (Grant 415935-G)Lawrence Livermore National Laboratory (Grant B600100

Residual Complex I activity and amphidirectional Complex II operation support glutamate catabolism through mtSLP in anoxia

Anoxia halts oxidative phosphorylation (OXPHOS) causing an accumulation of reduced compounds in the mitochondrial matrix which impedes dehydrogenases. By simultaneously measuring oxygen concentration, NADH autofluorescence, mitochondrial membrane potential and ubiquinone reduction extent in isolated mitochondria in real-time, we demonstrate that Complex I utilized endogenous quinones to oxidize NADH under acute anoxia. 13C metabolic tracing or untargeted analysis of metabolites extracted during anoxia in the presence or absence of site-specific inhibitors of the electron transfer system showed that NAD+ regenerated by Complex I is reduced by the 2-oxoglutarate dehydrogenase Complex yielding succinyl-CoA supporting mitochondrial substrate-level phosphorylation (mtSLP), releasing succinate. Complex II operated amphidirectionally during the anoxic event, providing quinones to Complex I and reducing fumarate to succinate. Our results highlight the importance of quinone provision to Complex I oxidizing NADH maintaining glutamate catabolism and mtSLP in the absence of OXPHOS.</p

Observation of strong electromagnetic fields around laser-entrance holes of ignition-scale hohlraums in inertial-confinement fusion experiments at the National Ignition Facility

Energy spectra and spectrally resolved one-dimensional fluence images of self-emitted charged-fusion products (14.7 MeV D[superscript 3]He protons) are routinely measured from indirectly driven inertial-confinement fusion (ICF) experiments utilizing ignition-scaled hohlraums at the National Ignition Facility (NIF). A striking and consistent feature of these images is that the fluence of protons leaving the ICF target in the direction of the hohlraum's laser entrance holes (LEHs) is very nonuniform spatially, in contrast to the very uniform fluence of protons leaving through the hohlraum equator. In addition, the measured nonuniformities are unpredictable, and vary greatly from shot to shot. These observations were made separately at the times of shock flash and of compression burn, indicating that the asymmetry persists even at ~0.5–2.5 ns after the laser has turned off. These phenomena have also been observed in experiments on the OMEGA laser facility with energy-scaled hohlraums, suggesting that the underlying physics is similar. Comprehensive data sets provide compelling evidence that the nonuniformities result from proton deflections due to strong spontaneous electromagnetic fields around the hohlraum LEHs. Although it has not yet been possible to uniquely determine whether the fields are magnetic (B) or electric (E), preliminary analysis indicates that the strength is ~1 MG if B fields or ~10[superscript 9] V cm[superscript −1] if E fields. These measurements provide important physics insight into the ongoing ignition experiments at the NIF. Understanding the generation, evolution, interaction and dissipation of the self-generated fields may help to answer many physics questions, such as why the electron temperatures measured in the LEH region are anomalously large, and may help to validate hydrodynamic models of plasma dynamics prior to plasma stagnation in the center of the hohlraum.United States. Dept. of Energy (DE-FG52-07 NA280 59)United States. Dept. of Energy (DE-FG03-03SF22691)Lawrence Livermore National Laboratory (B543881)Lawrence Livermore National Laboratory (LD RD-08-ER-062)University of Rochester. Fusion Science Center (412761-G)General Atomics (DE-AC52-06NA 27279)Stewardship Science Graduate Fellowship (DE-FC52-08NA28752

Exploration of the Transition from the Hydrodynamiclike to the Strongly Kinetic Regime in Shock-Driven Implosions

Clear evidence of the transition from hydrodynamiclike to strongly kinetic shock-driven implosions is, for the first time, revealed and quantitatively assessed. Implosions with a range of initial equimolar D[superscript 3]He gas densities show that as the density is decreased, hydrodynamic simulations strongly diverge from and increasingly overpredict the observed nuclear yields, from a factor of ∼2 at 3.1  mg/cm[superscript 3] to a factor of 100 at 0.14  mg/cm[superscript 3]. (The corresponding Knudsen number, the ratio of ion mean-free path to minimum shell radius, varied from 0.3 to 9; similarly, the ratio of fusion burn duration to ion diffusion time, another figure of merit of kinetic effects, varied from 0.3 to 14.) This result is shown to be unrelated to the effects of hydrodynamic mix. As a first step to garner insight into this transition, a reduced ion kinetic (RIK) model that includes gradient-diffusion and loss-term approximations to several transport processes was implemented within the framework of a one-dimensional radiation-transport code. After empirical calibration, the RIK simulations reproduce the observed yield trends, largely as a result of ion diffusion and the depletion of the reacting tail ions.United States. Dept. of Energy (Grant DE-NA0001857)United States. Dept. of Energy (Grant DE-FC52-08NA28752)University of Rochester. Fusion Science Center (5-24431)National Laser User’s Facility (DE-NA0002035)University of Rochester. Laboratory for Laser Energetics (415935-G)Lawrence Livermore National Laboratory (B597367