Adaptive Bayesian compound designs for dose finding studies

We consider the problem of how to efficiently and safely design dose finding studies. Both current and novel utility functions are explored using Bayesian adaptive design methodology for the estimation of a maximum tolerated dose (MTD). In particular, we explore widely adopted approaches such as the continual reassessment method and minimizing the variance of the estimate of an MTD. New utility functions are constructed in the Bayesian framework and are evaluated against current approaches. To reduce computing time, importance sampling is implemented to re-weight posterior samples thus avoiding the need to draw samples using Markov chain Monte Carlo techniques. Further, as such studies are generally first-in-man, the safety of patients is paramount. We therefore explore methods for the incorporation of safety considerations into utility functions to ensure that only safe and well-predicted doses are administered. The amalgamation of Bayesian methodology, adaptive design and compound utility functions is termed adaptive Bayesian compound design (ABCD). The performance of this amalgamation of methodology is investigated via the simulation of dose finding studies. The paper concludes with a discussion of results and extensions that could be included into our approach.

Beat phenomena in metal nanowires, and their implications for resonance-based elastic property measurements

The elastic properties of 1D nanostructures such as nanowires are often measured experimentally through actuation of the nanowire at its resonance frequency, and then relating the resonance frequency to the elastic stiffness using elementary beam theory. In the present work, we utilize large scale molecular dynamics simulations to report a novel beat phenomenon in [110]oriented Ag nanowires. The beat phenomenon is found to arise from the asymmetry of the lattice spacing in the orthogonal elementary directions of the [110] nanowire, i.e. the [-110] and [001] directions, which results in two different principal moments of inertia. Because of this, actuations imposed along any other direction are found to decompose into two orthogonal vibrational components based on the actuation angle relative to these two elementary directions, with this phenomenon being generalizable to <110> FCC nanowires of different materials (Cu, Au, Ni, Pd and Pt). The beat phenomenon is explained using a discrete moment of inertia model based on the hard sphere assumption, the model is utilized to show that surface effects enhance the beat phenomenon, while the effect is reduced with increasing nanowires cross-sectional size or aspect ratio. Most importantly, due to the existence of the beat phenomena, we demonstrate that in resonance experiments only a single frequency component is expected to be observed, particularly when the damping ratio is relatively large or very small. Furthermore, for a large range of actuation angles, the lower frequency is more likely to be detected than the higher one, which implies that experimental predictions of Young’s modulus obtained from resonance may in fact be under predictions. The present study therefore has significant implications for experimental interpretations of Young’s modulus as obtained via resonance testing.

General theory of stigmergy : modelling stigma semantics

Stigmergy is a biological term used when discussing a sub-set of insect swarm-behaviour describing the apparent organisation seen during their activities. Stigmergy describes a communication mechanism based on environment-mediated signals which trigger responses among the insects. This phenomenon is demonstrated in the behavior of ants and their food gathering process when following pheromone trails, where the pheromones are a form of environment-mediated communication. What is interesting with this phenomenon is that highly organized societies are achieved without an apparent management structure. Stigmergy is also observed in human environments, both natural and engineered. It is implicit in the Web where sites provide a virtual environment supporting coordinative contributions. Researchers in varying disciplines appreciate the power of this phenomenon and have studied how to exploit it. As stigmergy becomes more widely researched we see its definition mutate as papers citing original work become referenced themselves. Each paper interprets these works in ways very specific to the research being conducted. Our own research aims to better understand what improves the collaborative function of a Web site when exploiting the phenomenon. However when researching stigmergy to develop our understanding we discover a lack of a standardized and abstract model for the phenomenon. Papers frequently cited the same generic descriptions before becoming intimately focused on formal specifications of an algorithm, or esoteric discussions regarding sub-facets of the topic. None provide a holistic and macro-level view to model and standardize the nomenclature. This paper provides a content analysis of influential literature documenting the numerous theoretical and experimental papers that have focused on stigmergy. We establish that stigmergy is a phenomenon that transcends the insect world and is more than just a metaphor when applied to the human world. We present from our own research our general theory and abstract model of semantics of stigma in stigmergy. We hope our model will clarify the nuances of the phenomenon into a useful road-map, and standardise vocabulary that we witness becoming confused and divergent. Furthermore, this paper documents the analysis on which we base our next paper: Special Theory of Stigmergy: A Design Pattern for Web 2.0 Collaboration.

Part 1 MOO methods for multidisciplinary design using parallel evolutionary algorithms, game theory and hierarchical topology. (Part 1.) Theoretical aspects

Two lecture notes describe recent developments of evolutionary multi objective optimization (MO) techniques in detail and their advantages and drawbacks compared to traditional deterministic optimisers. The role of Game Strategies (GS), such as Pareto, Nash or Stackelberg games as companions or pre-conditioners of Multi objective Optimizers is presented and discussed on simple mathematical functions in Part I , as well as their implementations on simple aeronautical model optimisation problems on the computer using a friendly design framework in Part II. Real life (robust) design applications dealing with UAVs systems or Civil Aircraft and using the EAs and Game Strategies combined material of Part I & Part II are solved and discussed in Part III providing the designer new compromised solutions useful to digital aircraft design and manufacturing. Many details related to Lectures notes Part I, Part II and Part III can be found by the reader in [68].

Stabilization of parametric roll resonance with active u-tanks via Lyapunov control design

Parametric ship roll resonance is a phenomenon where a ship can rapidly develop high roll motion while sailing in longitudinal waves. This effect can be described mathematically by periodic changes of the parameters of the equations of motion, which lead to a bifurcation. In this paper, the control design of an active u-tank stabilizer is carried out using Lyapunov theory. A nonlinear backstepping controller is developed to provide global exponential stability of roll. An extension of commonly used u-tank models is presented to account for large roll angles, and the control design is tested via simulation on a high-fidelity model of a vessel under parametric roll resonance.

Can social resilience inform SA/SIA for adaptive planning for climate change in vulnerable regions?

This book represents a landmark effort to probe and analyze the theory and empirics of designing water disaster management policies. It consists of seven chapters that examine, in-depth and comprehensively, issues that are central to crafting effective policies for water disaster management. The authors use historical surveys, institutional analysis, econometric investigations, empirical case studies, and conceptual-theoretical discussions to clarify and illuminate the complex policy process. The specific topics studied in this book include a review and analysis of key policy areas and research priority areas associated with water disaster management, community participation in disaster risk reduction, the economics and politics of ‘green’ flood control, probabilistic flood forecasting for flood risk management, polycentric governance and flood risk management, drought management with the aid of dynamic inter-generational preferences, and how social resilience can inform SA/SIA for adaptive planning for climate change in vulnerable areas. A unique feature of this book is its analysis of the causes and consequences of water disasters and efforts to address them successfully through policy-rich, cross-disciplinary and transnational papers. This book is designed to help enrich the sparse discourse on water disaster management policies and galvanize water professionals to craft creative solutions to tackle water disasters efficiently, equitably, and sustainably. This book should also be of considerable use to disaster management professionals, in general, and natural resource policy analysts.

Diffusion indices on magnetic resonance imaging and neuropsychological performance in amnestic mild cognitive impairment

Background: Magnetic resonance diffusion tensor imaging (DTI) shows promise in the early detection of microstructural pathophysiological changes in the brain. Objectives: To measure microstructural differences in the brains of participants with amnestic mild cognitive impairment (MCI) compared with an age-matched control group using an optimised DTI technique with fully automated image analysis tools and to investigate the correlation between diffusivity measurements and neuropsychological performance scores across groups. Methods: 34 participants (17 participants with MCI, 17 healthy elderly adults) underwent magnetic resonance imaging (MRI)-based DTI. To control for the effects of anatomical variation, diffusion images of all participants were registered to standard anatomical space. Significant statistical differences in diffusivity measurements between the two groups were determined on a pixel-by-pixel basis using gaussian random field theory. Results: Significantly raised mean diffusivity measurements (p<0.001) were observed in the left and right entorhinal cortices (BA28), posterior occipital-parietal cortex (BA18 and BA19), right parietal supramarginal gyrus (BA40) and right frontal precentral gyri (BA4 and BA6) in participants with MCI. With respect to fractional anisotropy, participants with MCI had significantly reduced measurements (p<0.001) in the limbic parahippocampal subgyral white matter, right thalamus and left posterior cingulate. Pearson's correlation coefficients calculated across all participants showed significant correlations between neuropsychological assessment scores and regional measurements of mean diffusivity and fractional anisotropy. Conclusions: DTI-based diffusivity measures may offer a sensitive method of detecting subtle microstructural brain changes associated with preclinical Alzheimer's disease.

Electron spin resonance absorption in organic metal polyaniline and its blend with PMMA

The electron spin resonance absorption in the synthetic metal polyaniline (PANI) doped with PTSA and its blend with poly(methylmethacrylate) (PMMA) is investigated in the temperature range between 4.2 and 300 K. The observed line shape follows Dyson's theory for a thick metallic plate with slowly diffusing magnetic dipoles. At low temperatures the line shape become symmetric and Lorentzian when the sample dimensions are small in comparison with the skin depth. The temperature dependence of electron spin relaxation time is discussed. (C) 1999 Elsevier Science Ltd. All rights reserved.

Theory For The Anomalous Hall Constant Of Mixed-Valence Systems

We show that the large anomalous Hall constants of mixed-valence and Kondo-lattice systems can be understood in terms of a simple resonant-level Fermi-liquid model. Splitting of a narrow, orbitally unquenched, spin-orbit split, f resonance in a magnetic field leads to strong skew scattering of band electrons. We interpret both the anomalous signs and the strong temperature dependence of Hall mobilities in CeCu2Si2, SmB6, and CePd3 in terms of this theory.

A novel approach to 6-DOF adaptive trajectory tracking control of an AUV in the presence of parameter uncertainties

In this paper, the trajectory tracking control of an autonomous underwater vehicle (AUVs) in six-degrees-of-freedom (6-DOFs) is addressed. It is assumed that the system parameters are unknown and the vehicle is underactuated. An adaptive controller is proposed, based on Lyapunov׳s direct method and the back-stepping technique, which interestingly guarantees robustness against parameter uncertainties. The desired trajectory can be any sufficiently smooth bounded curve parameterized by time even if consist of straight line. In contrast with the majority of research in this field, the likelihood of actuators׳ saturation is considered and another adaptive controller is designed to overcome this problem, in which control signals are bounded using saturation functions. The nonlinear adaptive control scheme yields asymptotic convergence of the vehicle to the reference trajectory, in the presence of parametric uncertainties. The stability of the presented control laws is proved in the sense of Lyapunov theory and Barbalat׳s lemma. Efficiency of presented controller using saturation functions is verified through comparing numerical simulations of both controllers.

Evaluation of driving ability of the disabled persons in the context of the psychological activity theory

In the future the number of the disabled drivers requiring a special evaluation of their driving ability will increase due to the ageing population, as well as the progress of adaptive technology. This places pressure on the development of the driving evaluation system. Despite quite intensive research there is still no consensus concerning what is the factual situation in a driver evaluation (methodology), which measures should be included in an evaluation (methods), and how an evaluation has to be carried out (practise). In order to find answers to these questions we carried out empirical studies, and simultaneously elaborated upon a conceptual model for driving and a driving evaluation. The findings of empirical studies can be condensed into the following points: 1) A driving ability defined by the on-road driving test is associated with different laboratory measures depending on the study groups. Faults in the laboratory tests predicted faults in the on-road driving test in the novice group, whereas slowness in the laboratory predicted driving faults in the experienced drivers group. 2) The Parkinson study clearly showed that even an experienced clinician cannot reliably accomplish an evaluation of a disabled person’s driving ability without collaboration with other specialists. 3) The main finding of the stroke study was that the use of a multidisciplinary team as a source of information harmonises the specialists’ evaluations. 4) The patient studies demonstrated that the disabled persons themselves, as well as their spouses, are as a rule not reliable evaluators. 5) From the safety point of view, perceptible operations with the control devices are not crucial, but correct mental actions which the driver carries out with the help of the control devices are of greatest importance. 6) Personality factors including higher-order needs and motives, attitudes and a degree of self-awareness, particularly a sense of illness, are decisive when evaluating a disabled person’s driving ability. Personality is also the main source of resources concerning compensations for lower-order physical deficiencies and restrictions. From work with the conceptual model we drew the following methodological conclusions: First, the driver has to be considered as a holistic subject of the activity, as a multilevel hierarchically organised system of an organism, a temperament, an individuality, and a personality where the personality is the leading subsystem from the standpoint of safety. Second, driving as a human form of a sociopractical activity, is also a hierarchically organised dynamic system. Third, in an evaluation of driving ability it is a question of matching these two hierarchically organised structures: a subject of an activity and a proper activity. Fourth, an evaluation has to be person centred but not disease-, function- or method centred. On the basis of our study a multidisciplinary team (practitioner, driving school teacher, psychologist, occupational therapist) is recommended for use in demanding driver evaluations. Primary in a driver’s evaluations is a coherent conceptual model while concrete methods of evaluations may vary. However, the on-road test must always be performed if possible.

Nonequilibrium charge transport in an interacting open system: Two-particle resonance and current asymmetry

We use the Lippman-Schwinger scattering theory to study nonequilibrium electron transport through an interacting open quantum dot. The two-particle current is evaluated exactly while we use perturbation theory to calculate the current when the leads are Fermi liquids at different chemical potentials. We find an interesting two-particle resonance induced by the interaction and obtain criteria to observe it when a small bias is applied across the dot. Finally, for a system without spatial inversion symmetry, we find that the two-particle current is quite different depending on whether the electrons are incident from the left or the right lead.

Molecular Breeding for Complex Adaptive Traits: How Integrating Crop Ecophysiology and Modelling Can Enhance Efficiency

Progress in crop improvement is limited by the ability to identify favourable combinations of genotypes (G) and management practices (M) in relevant target environments (E) given the resources available to search among the myriad of possible combinations. To underpin yield advance we require prediction of phenotype based on genotype. In plant breeding, traditional phenotypic selection methods have involved measuring phenotypic performance of large segregating populations in multi-environment trials and applying rigorous statistical procedures based on quantitative genetic theory to identify superior individuals. Recent developments in the ability to inexpensively and densely map/sequence genomes have facilitated a shift from the level of the individual (genotype) to the level of the genomic region. Molecular breeding strategies using genome wide prediction and genomic selection approaches have developed rapidly. However, their applicability to complex traits remains constrained by gene-gene and gene-environment interactions, which restrict the predictive power of associations of genomic regions with phenotypic responses. Here it is argued that crop ecophysiology and functional whole plant modelling can provide an effective link between molecular and organism scales and enhance molecular breeding by adding value to genetic prediction approaches. A physiological framework that facilitates dissection and modelling of complex traits can inform phenotyping methods for marker/gene detection and underpin prediction of likely phenotypic consequences of trait and genetic variation in target environments. This approach holds considerable promise for more effectively linking genotype to phenotype for complex adaptive traits. Specific examples focused on drought adaptation are presented to highlight the concepts.

Phylogeography and Adaptive Divergence of Three-spined Stickleback Populations

Genetic studies on phylogeography and adaptive divergence in Northern Hemisphere fish species such as three-spined stickleback (Gasterosteus aculeatus) provide an excellent opportunity to investigate genetic mechanisms underlying population differentiation. According to the theory, the process of population differentiation results from a complex interplay between random and deterministic processes as well historical factors. The main scope in this thesis was to study how historical factors like the Pleistocene ice ages have shaped the patterns molecular diversity in three-spined stickleback populations in Europe and how this information could be utilized in the conservation genetic context. Furthermore, identifying footprints of natural selection at the DNA level might be used in identifying genes involved in evolutionary change. Overall, the results from phylogeographic studies indicate that the three-spined stickleback has colonized the Atlantic basin relatively recently but constitutes three major evolutionary lineages in Europe. In addition, the colonization of freshwater appears to result from multiple and independent invasions by the marine conspecifics. Molecular data together with morphology suggest that the most divergent freshwater populations are located in the Balkan Peninsula and these populations deserve a special conservation genetic status without warranting further taxonomical classification. In order to investigate the adaptive divergence in Fennoscandian three-spined stickleback populations several approaches were used. First, sequence variability in the Eda-gene, coding for the number of lateral plates, was concordant with the previously observed global pattern. Full plated allele is in high frequencies among marine populations whereas low plated allele dominates in the freshwater populations. Second, a microsatellite based genome scan identified both indications of balancing and directional selection in the three-spined stickleback genome, i.e. loci with unusually similar or unusually different allele frequencies over populations. The directionally selected loci were mainly associated with the adaptation to freshwater. A follow up study conducting a more detailed analysis in a chromosome region containing a putatively selected gene locus identified a fairly large genomic region affected by natural selection. However, this region contained several gene predictions, all of which might be the actual target of natural selection. All in all, the phylogeographic and adaptive divergence studies indicate that most of the genetic divergence has occurred in the freshwater populations whereas the marine populations have remained relatively uniform.

An optimal dynamic inversion-based neuro-adaptive approach for treatment of chronic myelogenous leukemia

Combining the advanced techniques of optimal dynamic inversion and model-following neuro-adaptive control design, an innovative technique is presented to design an automatic drug administration strategy for effective treatment of chronic myelogenous leukemia (CML). A recently developed nonlinear mathematical model for cell dynamics is used to design the controller (medication dosage). First, a nominal controller is designed based on the principle of optimal dynamic inversion. This controller can treat the nominal model patients (patients who can be described by the mathematical model used here with the nominal parameter values) effectively. However, since the system parameters for a realistic model patient can be different from that of the nominal model patients, simulation studies for such patients indicate that the nominal controller is either inefficient or, worse, ineffective; i.e. the trajectory of the number of cancer cells either shows non-satisfactory transient behavior or it grows in an unstable manner. Hence, to make the drug dosage history more realistic and patient-specific, a model-following neuro-adaptive controller is augmented to the nominal controller. In this adaptive approach, a neural network trained online facilitates a new adaptive controller. The training process of the neural network is based on Lyapunov stability theory, which guarantees both stability of the cancer cell dynamics as well as boundedness of the network weights. From simulation studies, this adaptive control design approach is found to be very effective to treat the CML disease for realistic patients. Sufficient generality is retained in the mathematical developments so that the technique can be applied to other similar nonlinear control design problems as well.