30,633 research outputs found

    Exploring the effects of spinal cord stimulation for freezing of gait in parkinsonian patients

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    Dopaminergic replacement therapies (e.g. levodopa) provide limited to no response for axial motor symptoms including gait dysfunction and freezing of gait (FOG) in Parkinson’s disease (PD) and Richardson’s syndrome progressive supranuclear palsy (PSP-RS) patients. Dopaminergic-resistant FOG may be a sensorimotor processing issue that does not involve basal ganglia (nigrostriatal) impairment. Recent studies suggest that spinal cord stimulation (SCS) has positive yet variable effects for dopaminergic-resistant gait and FOG in parkinsonian patients. Further studies investigating the mechanism of SCS, optimal stimulation parameters, and longevity of effects for alleviating FOG are warranted. The hypothesis of the research described in this thesis is that mid-thoracic, dorsal SCS effectively reduces FOG by modulating the sensory processing system in gait and may have a dopaminergic effect in individuals with FOG. The primary objective was to understand the relationship between FOG reduction, improvements in upper limb visual-motor performance, modulation of cortical activity and striatal dopaminergic innervation in 7 PD participants. FOG reduction was associated with changes in upper limb reaction time, speed and accuracy measured using robotic target reaching choice tasks. Modulation of resting-state, sensorimotor cortical activity, recorded using electroencephalography, was significantly associated with FOG reduction while participants were OFF-levodopa. Thus, SCS may alleviate FOG by modulating cortical activity associated with motor planning and sensory perception. Changes to striatal dopaminergic innervation, measured using a dopamine transporter marker, were associated with visual-motor performance improvements. Axial and appendicular motor features may be mediated by non-dopaminergic and dopaminergic pathways, respectively. The secondary objective was to demonstrate the short- and long-term effects of SCS for alleviating dopaminergic-resistant FOG and gait dysfunction in 5 PD and 3 PSP-RS participants without back/leg pain. SCS programming was individualized based on which setting best improved gait and/or FOG responses per participant using objective gait analysis. Significant improvements in stride velocity, step length and reduced FOG frequency were observed in all PD participants with up to 3-years of SCS. Similar gait and FOG improvements were observed in all PSP-RS participants up to 6-months. SCS is a promising therapeutic option for parkinsonian patients with FOG by possibly influencing cortical and subcortical structures involved in locomotion physiology

    Comparative study of classification algorithms for quality assessment of resistance spot welding joints from preand post-welding inputs

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    Resistance spot welding (RSW) is a widespread manufacturing process in the automotive industry. There are different approaches for assessing the quality level of RSW joints. Multi-input-single-output methods, which take as inputs either the intrinsic parameters of the welding process or ultrasonic nondestructive testing variables, are commonly used. This work demonstrates that the combined use of both types of inputs can significantly improve the already competitive approach based exclusively on ultrasonic analyses. The use of stacking of tree ensemble models as classifiers dominates the classification results in terms of accuracy, F-measure and area under the receiver operating characteristic curve metrics. Through variable importance analyses, the results show that although the welding process parameters are less relevant than the ultrasonic testing variables, some of the former provide marginal information not fully captured by the latter

    Machine learning based adaptive soft sensor for flash point inference in a refinery realtime process

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    In industrial control processes, certain characteristics are sometimes difficult to measure by a physical sensor due to technical and/or economic limitations. This fact is especially true in the petrochemical industry. Some of those quantities are especially crucial for operators and process safety. This is the case for the automotive diesel Flash Point Temperature (FT). Traditional methods for FT estimation are based on the study of the empirical inference between flammability properties and the denoted target magnitude. The necessary measures are taken indirectly by samples from the process and analyzing them in the laboratory, this process implies time (can take hours from collection to flash temperature measurement) and thus make it very difficult for real-time monitorization, which in fact results in security and economical losses. This study defines a procedure based on Machine Learning modules that demonstrate the power of real-time monitorization over real data from an important international refinery. As input, easily measured values provided in real-time, such as temperature, pressure, and hydraulic flow are used and a benchmark of different regressive algorithms for FT estimation is presented. The study highlights the importance of sequencing preprocessing techniques for the correct inference of values. The implementation of adaptive learning strategies achieves considerable economic benefits in the productization of this soft sensor. The validity of the method is tested in the reality of a refinery. In addition, real-world industrial data sets tend to be unstable and volatile, and the data is often affected by noise, outliers, irrelevant or unnecessary features, and missing data. This contribution demonstrates with the inclusion of a new concept, called an adaptive soft sensor, the importance of the dynamic adaptation of the conformed schemes based on Machine Learning through their combination with feature selection, dimensional reduction, and signal processing techniques. The economic benefits of applying this soft sensor in the refinery's production plant and presented as potential semi-annual savings.This work has received funding support from the SPRI-Basque Gov- ernment through the ELKARTEK program (OILTWIN project, ref. KK- 2020/00052)

    Unraveling the effect of sex on human genetic architecture

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    Sex is arguably the most important differentiating characteristic in most mammalian species, separating populations into different groups, with varying behaviors, morphologies, and physiologies based on their complement of sex chromosomes, amongst other factors. In humans, despite males and females sharing nearly identical genomes, there are differences between the sexes in complex traits and in the risk of a wide array of diseases. Sex provides the genome with a distinct hormonal milieu, differential gene expression, and environmental pressures arising from gender societal roles. This thus poses the possibility of observing gene by sex (GxS) interactions between the sexes that may contribute to some of the phenotypic differences observed. In recent years, there has been growing evidence of GxS, with common genetic variation presenting different effects on males and females. These studies have however been limited in regards to the number of traits studied and/or statistical power. Understanding sex differences in genetic architecture is of great importance as this could lead to improved understanding of potential differences in underlying biological pathways and disease etiology between the sexes and in turn help inform personalised treatments and precision medicine. In this thesis we provide insights into both the scope and mechanism of GxS across the genome of circa 450,000 individuals of European ancestry and 530 complex traits in the UK Biobank. We found small yet widespread differences in genetic architecture across traits through the calculation of sex-specific heritability, genetic correlations, and sex-stratified genome-wide association studies (GWAS). We further investigated whether sex-agnostic (non-stratified) efforts could potentially be missing information of interest, including sex-specific trait-relevant loci and increased phenotype prediction accuracies. Finally, we studied the potential functional role of sex differences in genetic architecture through sex biased expression quantitative trait loci (eQTL) and gene-level analyses. Overall, this study marks a broad examination of the genetics of sex differences. Our findings parallel previous reports, suggesting the presence of sexual genetic heterogeneity across complex traits of generally modest magnitude. Furthermore, our results suggest the need to consider sex-stratified analyses in future studies in order to shed light into possible sex-specific molecular mechanisms

    Structure and adsorption properties of gas-ionic liquid interfaces

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    Supported ionic liquids are a diverse class of materials that have been considered as a promising approach to design new surface properties within solids for gas adsorption and separation applications. In these materials, the surface morphology and composition of a porous solid are modified by depositing ionic liquid. The resulting materials exhibit a unique combination of structural and gas adsorption properties arising from both components, the support, and the liquid. Naturally, theoretical and experimental studies devoted to understanding the underlying principles of exhibited interfacial properties have been an intense area of research. However, a complete understanding of the interplay between interfacial gas-liquid and liquid-solid interactions as well as molecular details of these processes remains elusive. The proposed problem is challenging and in this thesis, it is approached from two different perspectives applying computational and experimental techniques. In particular, molecular dynamics simulations are used to model gas adsorption in films of ionic liquids on a molecular level. A detailed description of the modeled systems is possible if the interfacial and bulk properties of ionic liquid films are separated. In this study, we use a unique method that recognizes the interfacial and bulk structures of ionic liquids and distinguishes gas adsorption from gas solubility. By combining classical nitrogen sorption experiments with a mean-field theory, we study how liquid-solid interactions influence the adsorption of ionic liquids on the surface of the porous support. The developed approach was applied to a range of ionic liquids that feature different interaction behavior with gas and porous support. Using molecular simulations with interfacial analysis, it was discovered that gas adsorption capacity can be directly related to gas solubility data, allowing the development of a predictive model for the gas adsorption performance of ionic liquid films. Furthermore, it was found that this CO2 adsorption on the surface of ionic liquid films is determined by the specific arrangement of cations and anions on the surface. A particularly important result is that, for the first time, a quantitative relation between these structural and adsorption properties of different ionic liquid films has been established. This link between two types of properties determines design principles for supported ionic liquids. However, the proposed predictive model and design principles rely on the assumption that the ionic liquid is uniformly distributed on the surface of the porous support. To test how ionic liquids behave under confinement, nitrogen physisorption experiments were conducted for micro‐ and mesopore analysis of supported ionic liquid materials. In conjunction with mean-field density functional theory applied to the lattice gas and pore models, we revealed different scenarios for the pore-filling mechanism depending on the strength of the liquid-solid interactions. In this thesis, a combination of computational and experimental studies provides a framework for the characterization of complex interfacial gas-liquid and liquid-solid processes. It is shown that interfacial analysis is a powerful tool for studying molecular-level interactions between different phases. Finally, nitrogen sorption experiments were effectively used to obtain information on the structure of supported ionic liquids

    The applied psychology of addictive orientations : studies in a 12-step treatment context.

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    The clinical data for the studies was collected at The PROMIS Recovery Centre, a Minnesota Model treatmentc entre for addictions,w hich encouragesth e membership and use of the 12 step Anonymous Fellowships, and is abstinence based. The area of addiction is contextualised in a review chapter which focuses on research relating to the phenomenon of cross addiction. A study examining the concept of "addictive orientations" in male and female addicts is described, which develops a study conductedb y StephensonM, aggi, Lefever, & Morojele (1995). This presents study found a four factor solution which appeared to be subdivisions of the previously found Hedonism and Nurturance factors. Self orientated nurturance (both food dimensions, shopping and caffeine), Other orientated nurturance (both compulsive helping dimensions and work), Sensation seeking hedonism (Drugs, prescription drugs, nicotine and marginally alcohol), and Power related hedonism (Both relationship dimensions, sex and gambling. This concept of "addictive orientations" is further explored in a non-clinical population, where again a four factor solution was found, very similar to that in the clinical population. This was thought to indicate that in terms of addictive orientation a pattern already exists in this non-clinical population and that consideration should be given to why this is the case. These orientations are examined in terms of gender differences. It is suggested that the differences between genders reflect power-related role relationships between the sexes. In order to further elaborate the significance and meaning behind these orientations, the next two chapters look at the contribution of personality variables and how addictive orientations relate to psychiatric symptomatology. Personality variables were differentially, and to a considerable extent predictably involved with the four factors for both males and females.Conscientiousness as positively associated with "Other orientated Nurturance" and negatively associated with "Sensation seeking hedonism" (particularly for men). Neuroticism had a particularly strong association with the "Self orientated Nurturance" factor in the female population. More than twice the symptomatology variance was explained by the factor scores for females than it was for males. The most important factorial predictors for psychiatric symptomatology were the "Power related hedonism" factor for males, and "Self oriented nurturance" for females. The results are discussed from theoretical and treatment perspectives
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