Countermanding in rats as a practical model for investigation of adaptive control of behaviour, lifespan changes in behavioural control and neurotransmitter function

The countermanding paradigm was designed to investigate the ability to cancel a prepotent response when a stop signal is presented and allows estimation of the stop signal response time (SSRT), an otherwise unobservable behaviour. Humans exhibit adaptive control of behaviour in the countermanding task, proactively lengthening response time (RT) in expectation of stopping and reactively lengthening RT following stop trials or errors. Human performance changes throughout the lifespan, with longer RT, SSRT and greater emphasis on post-error slowing reported for older compared to younger adults. Inhibition in the task has generally been improved by drugs that increase extracellular norepinephrine. The current thesis examined a novel choice response countermanding task in rats to explore whether rodent countermanding performance is a suitable model for the study of adaptive control of behaviour, lifespan changes in behavioural control and the role of neurotransmitters in these behaviours. Rats reactively adjusted RT in the countermanding task, shortening RT after consecutive correct go trials and lengthening RT following non-cancelled, but not cancelled stop trials, in sessions with a 10 s, but not a 1 s post-error timeout interval. Rats proactively lengthened RT in countermanding task sessions compared to go trial-only sessions. Together, these findings suggest that rats strategically lengthened RT in the countermanding task to improve accuracy and avoid longer, unrewarded timeout intervals. Next, rats exhibited longer RT and relatively conserved post-error slowing, but no significant change in SSRT when tested at 12, compared to 7 months of age, suggesting that rats exhibit changes in countermanding task performance with aging similar to those observed in humans. Finally, acute administration of yohimbine (1.25, 2.5 mg/kg) and d-amphetamine (0.25, 0.5 mg/kg), which putatively increase extracellular norepinephrine and dopamine respectively, resulted in RT shortening, baseline-dependent effects on SSRT, and attenuated adaptive RT adjustments in rats in the case of d-amphetamine. These findings suggest that dopamine and norepinephrine encouraged motivated, reward-seeking behaviour and supported inhibitory control in an inverted-U-like fashion. Taken together, these observations validate the rat countermanding task for further study of the neural correlates and neurotransmitters mediating adaptive control of behaviour and lifespan changes in behavioural control.

Nonparametric Identication and Structural Estimation of Auction Models

Thesis (Ph.D.)--University of Washington, 2016-06

A genetic estimation algorithm for parameters of stochastic ordinary differential equations

A generic method for the estimation of parameters for Stochastic Ordinary Differential Equations (SODEs) is introduced and developed. This algorithm, called the GePERs method, utilises a genetic optimisation algorithm to minimise a stochastic objective function based on the Kolmogorov-Smirnov statistic. Numerical simulations are utilised to form the KS statistic. Further, the examination of some of the factors that improve the precision of the estimates is conducted. This method is used to estimate parameters of diffusion equations and jump-diffusion equations. It is also applied to the problem of model selection for the Queensland electricity market. (C) 2003 Elsevier B.V. All rights reserved.

Lameness, metabolic and digestive disorders, and technical efficiency in Danish dairy herds: a stochastic frontier production function approach

The relationship between reported treatments of lameness, metabolic disorders (milk fever, ketosis), digestive disorders, and technical efficiency (TE) was investigated using neutral and non-neutral stochastic frontier analysis (SFA). TE is estimated relative to the stochastic frontier production function for a sample of 574 Danish dairy herds collected in 1997. Contrary to most published results, but in line with the expected negative impact of disorders on the average cow milk production, herds reporting higher frequencies of milk fever are less technically efficient. Unexpectedly, however, the opposite results were observed for lameness, ketosis, and digestive disorders. The non-neutral stochastic frontier indicated that the opposite results are due to the relative. high productivities of inputs. The productivity of the cows is also reflected by the direction of impact of herd management variables. Whereas efficient farms replace cows more frequently, enroll heifers in production at an earlier age, and have shorter calving intervals, they also report higher frequency of disorder treatments. The average estimated energy corrected milk loss per cow is 1036, 451 and 242 kg for low, medium and high efficient farms. The study demonstrates the benefit of the stochastic frontier production function involving the estimation of individual technical efficiencies to evaluate farm performance and investigate the source of inefficiency. (C) 2004 Elsevier B.V. All rights reserved.

Bayesian estimation of g-and-k distributions using MCMC

In this paper we investigate a Bayesian procedure for the estimation of a flexible generalised distribution, notably the MacGillivray adaptation of the g-and-κ distribution. This distribution, described through its inverse cdf or quantile function, generalises the standard normal through extra parameters which together describe skewness and kurtosis. The standard quantile-based methods for estimating the parameters of generalised distributions are often arbitrary and do not rely on computation of the likelihood. MCMC, however, provides a simulation-based alternative for obtaining the maximum likelihood estimates of parameters of these distributions or for deriving posterior estimates of the parameters through a Bayesian framework. In this paper we adopt the latter approach, The proposed methodology is illustrated through an application in which the parameter of interest is slightly skewed.

Assumption-free estimation of heritability from genome-wide identity-by-descent sharing between full siblings

The study of continuously varying, quantitative traits is important in evolutionary biology, agriculture, and medicine. Variation in such traits is attributable to many, possibly interacting, genes whose expression may be sensitive to the environment, which makes their dissection into underlying causative factors difficult. An important population parameter for quantitative traits is heritability, the proportion of total variance that is due to genetic factors. Response to artificial and natural selection and the degree of resemblance between relatives are all a function of this parameter. Following the classic paper by R. A. Fisher in 1918, the estimation of additive and dominance genetic variance and heritability in populations is based upon the expected proportion of genes shared between different types of relatives, and explicit, often controversial and untestable models of genetic and non-genetic causes of family resemblance. With genome-wide coverage of genetic markers it is now possible to estimate such parameters solely within families using the actual degree of identity-by-descent sharing between relatives. Using genome scans on 4,401 quasi-independent sib pairs of which 3,375 pairs had phenotypes, we estimated the heritability of height from empirical genome-wide identity-by-descent sharing, which varied from 0.374 to 0.617 (mean 0.498, standard deviation 0.036). The variance in identity-by-descent sharing per chromosome and per genome was consistent with theory. The maximum likelihood estimate of the heritability for height was 0.80 with no evidence for non-genetic causes of sib resemblance, consistent with results from independent twin and family studies but using an entirely separate source of information. Our application shows that it is feasible to estimate genetic variance solely from within- family segregation and provides an independent validation of previously untestable assumptions. Given sufficient data, our new paradigm will allow the estimation of genetic variation for disease susceptibility and quantitative traits that is free from confounding with non-genetic factors and will allow partitioning of genetic variation into additive and non-additive components.

Cardiovascular risk estimation by professionally active cardiovascular nurses: Results from the Basel 2005 Nurses Cohort

Background Nurses play a key role in the prevention of cardiovascular disease (CVD) and one would, therefore, expect them to have a heightened awareness of the need for systematic screening and their own CVD risk profile. The aim of this study was to examine personal awareness of CVD risk among a cohort of cardiovascular nurses attending a European conference. Methods Of the 340 delegates attending the 5th annual Spring Meeting on Cardiovascular Nursing (Basel, Switzerland, 2005), 287 (83%) completed a self-report questionnaire to assess their own risk factors for CVD. Delegates were also asked to give an estimation of their absolute total risk of experiencing a fatal CVD event in the next 10 years. Level of agreement between self-reported CVD risk estimation and their actual risk according to the SCORE risk assessment system was compared by calculating weighted Kappa (κw). Results Overall, 109 responders (38%) self-reported having either pre-existing CVD (only 2%), one or more markedly raised CVD risk factors, a high total risk of fatal CVD (≥ 5% in 10 years) or a strong family history of CVD. About half of this cohort (53%) did not know their own total cholesterol level. Less than half (45%) reported having a 10-year risk of fatal CVD of < 1%, while 13% reported having a risk ≥ 5%. Based on the SCORE risk function, the estimated 10-year risk of a fatal CVD event was < 1% for 96% of responders: only 2% had a ≥ 5% risk of such an event. Overall, less than half (46%) of this cohort's self-reported CVD risk corresponded with that calculated using the SCORE risk function (κw = 0.27). Conclusion Most cardiovascular nurses attending a European conference in 2005 poorly understood their own CVD risk profile, and the agreement between their self-reported 10-year risk of a fatal CVD and their CVD risk using SCORE was only fair. Given the specialist nature of this conference, our findings clearly demonstrate a need to improve overall nursing awareness of the role and importance of systematic CVD risk assessment.

Estimation of concentration-dependent diffusion coefficient in drying process from the space-averaged concentration versus time with experimental data

The estimation of a concentration-dependent diffusion coefficient in a drying process is known as an inverse coefficient problem. The solution is sought wherein the space-average concentration is known as function of time (mass loss monitoring). The problem is stated as the minimization of a functional and gradient-based algorithms are used to solve it. Many numerical and experimental examples that demonstrate the effectiveness of the proposed approach are presented. Thin slab drying was carried out in an isothermal drying chamber built in our laboratory. The diffusion coefficients of fructose obtained with the present method are compared with existing literature results.

Modelling of non-stationary processes using radial basis function networks

This paper reports preliminary progress on a principled approach to modelling nonstationary phenomena using neural networks. We are concerned with both parameter and model order complexity estimation. The basic methodology assumes a Bayesian foundation. However to allow the construction of pragmatic models, successive approximations have to be made to permit computational tractibility. The lowest order corresponds to the (Extended) Kalman filter approach to parameter estimation which has already been applied to neural networks. We illustrate some of the deficiencies of the existing approaches and discuss our preliminary generalisations, by considering the application to nonstationary time series.

Testing term structure estimation methods:evidence from the UK STRIPs market

Prices and yields of UK government zero-coupon bonds are used to test alternative yield curve estimation models. Zero-coupon bonds permit a more pure comparison, as the models are providing only the interpolation service and also not making estimation feasible. It is found that better yield curves estimates are obtained by fitting to the yield curve directly rather than fitting first to the discount function. A simple procedure to set the smoothness of the fitted curves is developed, and a positive relationship between oversmoothness and the fitting error is identified. A cubic spline function fitted directly to the yield curve provides the best overall balance of fitting error and smoothness, both along the yield curve and within local maturity regions.

A basis function approach to Bayesian inference in diffusion processes

In this paper, we present a framework for Bayesian inference in continuous-time diffusion processes. The new method is directly related to the recently proposed variational Gaussian Process approximation (VGPA) approach to Bayesian smoothing of partially observed diffusions. By adopting a basis function expansion (BF-VGPA), both the time-dependent control parameters of the approximate GP process and its moment equations are projected onto a lower-dimensional subspace. This allows us both to reduce the computational complexity and to eliminate the time discretisation used in the previous algorithm. The new algorithm is tested on an Ornstein-Uhlenbeck process. Our preliminary results show that BF-VGPA algorithm provides a reasonably accurate state estimation using a small number of basis functions.

A three dimensional surface measurement and reconstruction system for respiratory function analysis

Respiration is a complex activity. If the relationship between all neurological and skeletomuscular interactions was perfectly understood, an accurate dynamic model of the respiratory system could be developed and the interaction between different inputs and outputs could be investigated in a straightforward fashion. Unfortunately, this is not the case and does not appear to be viable at this time. In addition, the provision of appropriate sensor signals for such a model would be a considerable invasive task. Useful quantitative information with respect to respiratory performance can be gained from non-invasive monitoring of chest and abdomen motion. Currently available devices are not well suited in application for spirometric measurement for ambulatory monitoring. A sensor matrix measurement technique is investigated to identify suitable sensing elements with which to base an upper body surface measurement device that monitors respiration. This thesis is divided into two main areas of investigation; model based and geometrical based surface plethysmography. In the first instance, chapter 2 deals with an array of tactile sensors that are used as progression of existing and previously investigated volumetric measurement schemes based on models of respiration. Chapter 3 details a non-model based geometrical approach to surface (and hence volumetric) profile measurement. Later sections of the thesis concentrate upon the development of a functioning prototype sensor array. To broaden the application area the study has been conducted as it would be fore a generically configured sensor array. In experimental form the system performance on group estimation compares favourably with existing system on volumetric performance. In addition provides continuous transient measurement of respiratory motion within an acceptable accuracy using approximately 20 sensing elements. Because of the potential size and complexity of the system it is possible to deploy it as a fully mobile ambulatory monitoring device, which may be used outside of the laboratory. It provides a means by which to isolate coupled physiological functions and thus allows individual contributions to be analysed separately. Thus facilitating greater understanding of respiratory physiology and diagnostic capabilities. The outcome of the study is the basis for a three-dimensional surface contour sensing system that is suitable for respiratory function monitoring and has the prospect with future development to be incorporated into a garment based clinical tool.

Simultaneous estimation of global background synaptic inhibition and excitation from membrane potential fluctuations in layer III neurons of the rat entorhinal cortex in vitro

It is becoming clear that the detection and integration of synaptic input and its conversion into an output signal in cortical neurons are strongly influenced by background synaptic activity or "noise." The majority of this noise results from the spontaneous release of synaptic transmitters, interacting with ligand-gated ion channels in the postsynaptic neuron [Berretta N, Jones RSG (1996); A comparison of spontaneous synaptic EPSCs in layer V and layer II neurones in the rat entorhinal cortex in vitro. J Neurophysiol 76:1089-1110; Jones RSG, Woodhall GL (2005) Background synaptic activity in rat entorhinal cortical neurons: differential control of transmitter release by presynaptic receptors. J Physiol 562:107-120; LoTurco JJ, Mody I, Kriegstein AR (1990) Differential activation of glutamate receptors by spontaneously released transmitter in slices of neocortex. Neurosci Lett 114:265-271; Otis TS, Staley KJ, Mody I (1991) Perpetual inhibitory activity in mammalian brain slices generated by spontaneous GABA release. Brain Res 545:142-150; Ropert N, Miles R, Korn H (1990) Characteristics of miniature inhibitory postsynaptic currents in CA1 pyramidal neurones of rat hippocampus. J Physiol 428:707-722; Salin PA, Prince DA (1996) Spontaneous GABAA receptor-mediated inhibitory currents in adult rat somatosensory cortex. J Neurophysiol 75:1573-1588; Staley KJ (1999) Quantal GABA release: noise or not? Nat Neurosci 2:494-495; Woodhall GL, Bailey SJ, Thompson SE, Evans DIP, Stacey AE, Jones RSG (2005) Fundamental differences in spontaneous synaptic inhibition between deep and superficial layers of the rat entorhinal cortex. Hippocampus 15:232-245]. The function of synaptic noise has been the subject of debate for some years, but there is increasing evidence that it modifies or controls neuronal excitability and, thus, the integrative properties of cortical neurons. In the present study we have investigated a novel approach [Rudolph M, Piwkowska Z, Badoual M, Bal T, Destexhe A (2004) A method to estimate synaptic conductances from membrane potential fluctuations. J Neurophysiol 91:2884-2896] to simultaneously quantify synaptic inhibitory and excitatory synaptic noise, together with postsynaptic excitability, in rat entorhinal cortical neurons in vitro. The results suggest that this is a viable and useful approach to the study of the function of synaptic noise in cortical networks. © 2007 IBRO.