Assessment of depression, anxiety and apathy in prodromal and early Huntington disease

The Functional Rating Scale Taskforce for pre-Huntington Disease (FuRST-pHD) is a multinational, multidisciplinary initiative with the goal of developing a data-driven, comprehensive, psychometrically sound, rating scale for assessing symptoms and functional ability in prodromal and early Huntington disease (HD) gene expansion carriers. The process involves input from numerous sources to identify relevant symptom domains, including HD individuals, caregivers, and experts from a variety of fields, as well as knowledge gained from the analysis of data from ongoing large-scale studies in HD using existing clinical scales. This is an iterative process in which an ongoing series of field tests in prodromal (prHD) and early HD individuals provides the team with data on which to make decisions regarding which questions should undergo further development or testing and which should be excluded. We report here the development and assessment of the first iteration of interview questions aimed to assess Depression, Anxiety and Apathy in prHD and early HD individuals.

Assessment of motor symptoms and functional impact in prodromal and early Huntington disease.

The Functional Rating Scale Taskforce for pre-Huntington Disease (FuRST-pHD) is a multinational, multidisciplinary initiative with the goal of developing a data-driven, comprehensive, psychometrically sound, rating scale for assessing symptoms and functional ability in prodromal and early Huntington disease (HD) gene expansion carriers. The process involves input from numerous sources to identify relevant symptom domains, including HD individuals, caregivers, and experts from a variety of fields, as well as knowledge gained from the analysis of data from ongoing large-scale studies in HD using existing clinical scales. This is an iterative process in which an ongoing series of field tests in prodromal (prHD) and early HD individuals provides the team with data on which to make decisions regarding which questions should undergo further development or testing and which should be excluded. We report here the development and assessment of the first iteration of interview questions aimed to assess functional impact of motor manifestations in prHD and early HD individuals.

British pharmacy professionals' beliefs and participation in continuing professional development: a review of the literature

Objectives:  Continuing professional development (CPD) has potential to be useful in pharmacy revalidation but past uptake and attitudes to CPD in Great Britain (GB) need to be mapped. This review examines published literature to chart the participation and beliefs of pharmacy professionals towards CPD in GB in a decade that had seen a formal transition from continuing education to CPD. Methods:  A comprehensive review of the published literature was conducted to identify studies of the uptake of, or attitudes towards, CPD cross different sectors of pharmacy in GB from 2000 to 2010. Key findings:  Twenty-two studies were included and analysed, including 13 research papers, six conference papers, two news items reporting survey outcomes and one commissioned study. Eight barriers to CPD were identified as: time, financial costs and resource issues, understanding of CPD, facilitation and support for CPD, motivation and interest in CPD, attitudes towards compulsory CPD, system constraints, and technical problems. Pharmacy professionals on the whole agreed with the principle of engaging with CPD but there was little evidence to suggest widespread and wholehearted acceptance and uptake of CPD, essential for revalidation. Conclusions:  If CPD is to succeed, people's beliefs and attitudes must be addressed by recognising and modifying perceived barriers through a combination of regulatory, professional, work-related and personal channels. A number of recommendations are made. Direct experience of effective CPD in the absence of perceived barriers could impact on personal development, career development and patient benefit thus strengthening personal beliefs in the value of CPD in an iterative manner.

Wave trapping in a two-dimensional sound-soft or sound-hard acoustic waveguide of slowly-varying width

In this paper we derive novel approximations to trapped waves in a two-dimensional acoustic waveguide whose walls vary slowly along the guide, and at which either Dirichlet (sound-soft) or Neumann (sound-hard) conditions are imposed. The guide contains a single smoothly bulging region of arbitrary amplitude, but is otherwise straight, and the modes are trapped within this localised increase in width. Using a similar approach to that in Rienstra (2003), a WKBJ-type expansion yields an approximate expression for the modes which can be present, which display either propagating or evanescent behaviour; matched asymptotic expansions are then used to derive connection formulae which bridge the gap across the cut-off between propagating and evanescent solutions in a tapering waveguide. A uniform expansion is then determined, and it is shown that appropriate zeros of this expansion correspond to trapped mode wavenumbers; the trapped modes themselves are then approximated by the uniform expansion. Numerical results determined via a standard iterative method are then compared to results of the full linear problem calculated using a spectral method, and the two are shown to be in excellent agreement, even when $\epsilon$, the parameter characterising the slow variations of the guide’s walls, is relatively large.

Background-noise reduction

Interference by siren background-noise with speech transmitted from radio equipment (3) of an emergency-service vehicle, is reduced by apparatus (1) that subtracts (43) an estimate nk of the correlated siren-noise component from the contaminated signal yk supplied by the cab-microphone (2). The estimate nk is computed by FIR (finite impulse response) filtering of a siren-reference signal xk supplied by a unit (4) from one or more microphones located on or near the siren, or from the electric waveform driving the siren. The filter-coefficients wk are adjusted according to an LMS (least mean square) adaptive algorithm that is applied to the correlated-noise component ek of the fed-back noise-reduced signal, so as to bring about iterative cancellation with close frequency-tracking, of the siren noise.

NANA: Novel assessment of nutrition and ageing

Purpose NANA is a 3-year project using sensitively-designed technology to improve data collection and integrate information on nutrition, physical and cognitive function and mental health to identify individuals at risk of under-nourishment and improve targeting of interventions. This research will also improve our understanding of the interactions between these factors, in order to better medical treatment and social provision. The toolkit has potential for commercial development for additional segments of the population. Method This is a multi-disciplinary program involving psychology, nutrition, engineering and software engineering. The first phase is a user needs analysis and will involve consulting with a broad cross-section of older people, caregivers, and health professionals, to establish what technical approaches would be useful and acceptable. The second phase focuses on the development of an integrated measurement toolkit. There are three inter-related subsections: (i) an iterative program to develop the assessment technology, (ii) techniques for dietary assessment in older people, and (iii) a parallel investigation of measures of cognition and mental health in older people. It includes a full validation of the assessment toolkit and will comprise a comparison of the new, integrated assessment with traditional 'pen and paper' methods with volunteers having the equipment installed in their homes.

A simple analysis of thermodynamic properties for classical plasmas: I. theory

By eliminating the short range negative divergence of the Debye–Hückel pair distribution function, but retaining the exponential charge screening known to operate at large interparticle separation, the thermodynamic properties of one-component plasmas of point ions or charged hard spheres can be well represented even in the strong coupling regime. Predicted electrostatic free energies agree within 5% of simulation data for typical Coulomb interactions up to a factor of 10 times the average kinetic energy. Here, this idea is extended to the general case of a uniform ionic mixture, comprising an arbitrary number of components, embedded in a rigid neutralizing background. The new theory is implemented in two ways: (i) by an unambiguous iterative algorithm that requires numerical methods and breaks the symmetry of cross correlation functions; and (ii) by invoking generalized matrix inverses that maintain symmetry and yield completely analytic solutions, but which are not uniquely determined. The extreme computational simplicity of the theory is attractive when considering applications to complex inhomogeneous fluids of charged particles.

Vocabulary is important for some, but not all reading skills

Although there is evidence for a close link between the development of oral vocabulary and reading comprehension, less clear is whether oral vocabulary skills relate to the development of word-level reading skills. This study investigated vocabulary and literacy in 81 children aged 8 to 10 years. In regression analyses, vocabulary accounted for unique variance in exception word reading and reading comprehension, but not text reading accuracy, decoding, or regular word reading. Consistent with these data, children with poor reading comprehension exhibited oral vocabulary weaknesses and read fewer exception words correctly. These findings demonstrate that oral vocabulary is associated with some, but not all, reading skills. Results are discussed in terms of current models of reading development.

Investigating orthographic and semantic aspects of word learning in poor comprehenders

This study compared orthographic and semantic aspects of word learning in children who differed in reading comprehension skill. Poor comprehenders and controls matched for age (9-10 years), nonverbal ability and decoding skill were trained to pronounce 20 visually presented nonwords, 10 in a consistent way and 10 in an inconsistent way. They then had an opportunity to infer the meanings of the new words from story context. Orthographic learning was measured in three ways: the number of trials taken to learn to pronounce nonwords correctly, orthographic choice and spelling. Across all measures, consistent items were easier than inconsistent items and poor comprehenders did not differ from control children. Semantic learning was assessed on three occasions, using a nonword-picture matching task. While poor comprehenders showed equivalent semantic learning to controls immediately after exposure to nonword meaning, this knowledge was not well retained over time. Results are discussed in terms of the language and reading skills of poor comprehenders and in relation to current models of reading development.

The role of self-teaching in learning orthographic and semantic aspects of new words

This study explores how children learn the meaning (semantics) and spelling patterns (orthography) of novel words encountered in story context. English-speaking children (N = 88) aged 7 to 8 years read 8 stories and each story contained 1 novel word repeated 4 times. Semantic cues were provided by the story context such that children could infer the meaning of the word (specific context) or the category that the word belonged to (general context). Following story reading, posttests indicated that children showed reliable semantic and orthographic learning. Decoding was the strongest predictor of orthographic learning, indicating that self-teaching via phonological recoding was important for this aspect of word learning. In contrast, oral vocabulary emerged as the strongest predictor of semantic learning.

Optimal linearization trajectories for tangent linear models

We examine differential equations where nonlinearity is a result of the advection part of the total derivative or the use of quadratic algebraic constraints between state variables (such as the ideal gas law). We show that these types of nonlinearity can be accounted for in the tangent linear model by a suitable choice of the linearization trajectory. Using this optimal linearization trajectory, we show that the tangent linear model can be used to reproduce the exact nonlinear error growth of perturbations for more than 200 days in a quasi-geostrophic model and more than (the equivalent of) 150 days in the Lorenz 96 model. We introduce an iterative method, purely based on tangent linear integrations, that converges to this optimal linearization trajectory. The main conclusion from this article is that this iterative method can be used to account for nonlinearity in estimation problems without using the nonlinear model. We demonstrate this by performing forecast sensitivity experiments in the Lorenz 96 model and show that we are able to estimate analysis increments that improve the two-day forecast using only four backward integrations with the tangent linear model. Copyright © 2011 Royal Meteorological Society

Beyond the computer: changing medium from digital to physical

How can organizations use digital infrastructure to realise physical outcomes? The design and construction of London Heathrow Terminal 5 is analysed to build new theoretical understanding of visualization and materialization practices in the transition from digital design to physical realisation. In the project studied, an integrated software solution is introduced as an infrastructure for delivery. The analyses articulate the work done to maintain this digital infrastructure and also to move designs beyond the closed world of the computer to a physical reality. In changing medium, engineers use heterogeneous trials to interrogate and address the limitations of an integrated digital model. The paper explains why such trials, which involve the reconciliation of digital and physical data through parallel and iterative forms of work, provide a robust practice for realizing goals that have physical outcomes. It argues that this practice is temporally different from, and at times in conflict with, building a comprehensive dataset within the digital medium. The paper concludes by discussing the implications for organizations that use digital infrastructures in seeking to accomplish goals in digital and physical media.

Some numerical experiments on the effect of the variation of static stability in two-layer quasi-geostrophic models

A method to solve a quasi-geostrophic two-layer model including the variation of static stability is presented. The divergent part of the wind is incorporated by means of an iterative procedure. The procedure is rather fast and the time of computation is only 60–70% longer than for the usual two-layer model. The method of solution is justified by the conservation of the difference between the gross static stability and the kinetic energy. To eliminate the side-boundary conditions the experiments have been performed on a zonal channel model. The investigation falls mainly into three parts: The first part (section 5) contains a discussion of the significance of some physically inconsistent approximations. It is shown that physical inconsistencies are rather serious and for these inconsistent models which were studied the total kinetic energy increased faster than the gross static stability. In the next part (section 6) we are studying the effect of a Jacobian difference operator which conserves the total kinetic energy. The use of this operator in two-layer models will give a slight improvement but probably does not have any practical use in short periodic forecasts. It is also shown that the energy-conservative operator will change the wave-speed in an erroneous way if the wave-number or the grid-length is large in the meridional direction. In the final part (section 7) we investigate the behaviour of baroclinic waves for some different initial states and for two energy-consistent models, one with constant and one with variable static stability. According to the linear theory the waves adjust rather rapidly in such a way that the temperature wave will lag behind the pressure wave independent of the initial configuration. Thus, both models give rise to a baroclinic development even if the initial state is quasi-barotropic. The effect of the variation of static stability is very small, qualitative differences in the development are only observed during the first 12 hours. For an amplifying wave we will get a stabilization over the troughs and an instabilization over the ridges.

Realistic mean field forward predictions for the integration of co-registered EEG/fMRI

Brain activity can be measured non-invasively with functional imaging techniques. Each pixel in such an image represents a neural mass of about 105 to 107 neurons. Mean field models (MFMs) approximate their activity by averaging out neural variability while retaining salient underlying features, like neurotransmitter kinetics. However, MFMs incorporating the regional variability, realistic geometry and connectivity of cortex have so far appeared intractable. This lack of biological realism has led to a focus on gross temporal features of the EEG. We address these impediments and showcase a "proof of principle" forward prediction of co-registered EEG/fMRI for a full-size human cortex in a realistic head model with anatomical connectivity, see figure 1. MFMs usually assume homogeneous neural masses, isotropic long-range connectivity and simplistic signal expression to allow rapid computation with partial differential equations. But these approximations are insufficient in particular for the high spatial resolution obtained with fMRI, since different cortical areas vary in their architectonic and dynamical properties, have complex connectivity, and can contribute non-trivially to the measured signal. Our code instead supports the local variation of model parameters and freely chosen connectivity for many thousand triangulation nodes spanning a cortical surface extracted from structural MRI. This allows the introduction of realistic anatomical and physiological parameters for cortical areas and their connectivity, including both intra- and inter-area connections. Proper cortical folding and conduction through a realistic head model is then added to obtain accurate signal expression for a comparison to experimental data. To showcase the synergy of these computational developments, we predict simultaneously EEG and fMRI BOLD responses by adding an established model for neurovascular coupling and convolving "Balloon-Windkessel" hemodynamics. We also incorporate regional connectivity extracted from the CoCoMac database [1]. Importantly, these extensions can be easily adapted according to future insights and data. Furthermore, while our own simulation is based on one specific MFM [2], the computational framework is general and can be applied to models favored by the user. Finally, we provide a brief outlook on improving the integration of multi-modal imaging data through iterative fits of a single underlying MFM in this realistic simulation framework.

A fast two-grid and finite section method for a class of integral equations on the real line with application to an acoustic scattering problem in the half-plane

We consider the numerical treatment of second kind integral equations on the real line of the form ∅(s) = ∫_(-∞)^(+∞)▒〖κ(s-t)z(t)ϕ(t)dt,s=R〗 (abbreviated ϕ= ψ+K_z ϕ) in which K ϵ L_1 (R), z ϵ L_∞ (R) and ψ ϵ BC(R), the space of bounded continuous functions on R, are assumed known and ϕ ϵ BC(R) is to be determined. We first derive sharp error estimates for the finite section approximation (reducing the range of integration to [-A, A]) via bounds on (1-K_z )^(-1)as an operator on spaces of weighted continuous functions. Numerical solution by a simple discrete collocation method on a uniform grid on R is then analysed: in the case when z is compactly supported this leads to a coefficient matrix which allows a rapid matrix-vector multiply via the FFT. To utilise this possibility we propose a modified two-grid iteration, a feature of which is that the coarse grid matrix is approximated by a banded matrix, and analyse convergence and computational cost. In cases where z is not compactly supported a combined finite section and two-grid algorithm can be applied and we extend the analysis to this case. As an application we consider acoustic scattering in the half-plane with a Robin or impedance boundary condition which we formulate as a boundary integral equation of the class studied. Our final result is that if z (related to the boundary impedance in the application) takes values in an appropriate compact subset Q of the complex plane, then the difference between ϕ(s)and its finite section approximation computed numerically using the iterative scheme proposed is ≤C_1 [kh log⁡〖(1⁄kh)+(1-Θ)^((-1)⁄2) (kA)^((-1)⁄2) 〗 ] in the interval [-ΘA,ΘA](Θ<1) for kh sufficiently small, where k is the wavenumber and h the grid spacing. Moreover this numerical approximation can be computed in ≤C_2 N log⁡N operations, where N = 2A/h is the number of degrees of freedom. The values of the constants C1 and C2 depend only on the set Q and not on the wavenumber k or the support of z.