Intelligent technologies for the aging brain: opportunities and challenges

Intelligent computing is rapidly reshaping healthcare. In light of the global burden of population aging and neurological disorders, dementia and elderly care are among the healthcare sectors that are most likely to benefit from this technological revolution. Trends in artificial intelligence, robotics, ubiquitous computing, neurotechnology and other branches of biomedical engineering are progressively enabling novel opportunities for technology-enhanced care. These Intelligent Assistive Technologies (IATs) open the prospects of supporting older adults with neurocognitive disabilities, maintain their independence, reduce the burden on caregivers and delay the need for long-term care (1, 2). While technology develops fast, yet little knowledge is available to patients and health professionals about the current availability, applicability, and capability of existing IATs. This thesis proposes a state-of-the-art analysis of IATs in dementia and elderly care. Our findings indicate that advances in intelligent technology are resulting in a rapidly expanding number and variety of assistive solutions for older adults and people with neurocognitive disabilities. However, our analysis identifies a number of challenges that negatively affect the optimal deployment and uptake of IATs among target users and care institutions. These include design issues, sub-optimal approaches to product development, translational barriers between lab and clinics, lack of adequate validation and implementation, as well as data security and cyber-risk weaknesses. Additionally, in virtue of their technological novelty, intelligent technologies raise a number of Ethical, Legal and Social Implications (ELSI). Therefore, a significant portion of this thesis is devoted to providing an early ethical Technology Assessment (eTA) of intelligent technology, hence contributing to preparing the terrain for its safe and ethically responsible adoption. This assessment is primarily focused on intelligent technologies at the human-machine interface, as these applications enable an unprecedented exposure of the intimate dimension of individuals to the digital infosphere. Issues of privacy, integrity, equality, and dual-use were addressed at the level of stakeholder analysis, normative ethics and human-rights law. Finally, this thesis is aimed at providing evidence-based recommendations for guiding participatory and responsible development in intelligent technology, and delineating governance strategies that maximize the clinical benefits of IATs for the aging world, while minimizing unintended risks

Assessment of ambient assisted living systems for patients with mild cognitive impairment

According to the World Health Organization, about 50 million people worldwide suffer from dementia. Ten million new cases added every year. Mild Cognitive Impairment (MCI) affects more than 15% of the population aged 65. Technological solutions, such as smart home technology with ubiquitous computing devices, 24/7 telemedical observation and support can alleviate the growing problem and lower pressure on the healthcare system. This approach is also preferable for homecare patients in distant and rural areas. MCI patients are mostly home-based. Ambient Assisted Living (AAL) systems provide tools for automatic registration of vital signs and other medically and socially important information. AAL system for MCI patients is a logical answer to the problem. At the same time, many of the proposed AAL systems are proprietary, technically complicated and have a high price tag for implementation and service. Also, some proposed technical solutions not entirely reflect the opinion of healthcare stakeholders. The current study was proposed as a way to bridge the possible differences in the positions. An online anonymous questionnaire for healthcare professionals was created to prove or disprove the number of interconnected hypotheses about the necessity and feasibility of AAL system for MCI patients. The main focus was made on the hypotheses: "There is necessity of AAL systems for the healthcare" and "AAL systems are capable of providing assistance for patients with Mild Cognitive Impairment". The questionnaire was presented to more than three hundred potential respondents. Around a hundred and twenty agreed to fill it, and sixty completed the whole questionnaire. Results were analyzed to produce some directions guideline for future technical applications of AAL systems for MCI patients and future research. Descriptive statistics show support for the implementation of general AAL and variants for MCI patients. Comparative analysis of ordinal data for specific groups of respondents is done with help of non-parametric tests. Mann–Whitney–Wilcoxon test and Kruskal-Wallis test are applied. Table questions results are analyzed with chisquare for frequency tables. Group analysis demonstrated relative positive uniformity in of responses in the support of AAL of MCI patients.Segundo a Organização Mundial da Saúde, cerca de 50 milhões de pessoas em todo o mundo sofrem de demência. Dez milhões de novos casos adicionados a cada ano. O comprometimento cognitivo leve (MCI) afeta mais de 15% da população com 65 anos. Soluções tecnológicas, como tecnologia de casa inteligente com dispositivos de computação onipresentes, observação e suporte telemédico 24 horas por dia, 7 dias por semana, podem aliviar o problema crescente e diminuir a pressão sobre o sistema de saúde. Essa abordagem também é preferível para pacientes de cuidados domiciliares em áreas distantes e rurais. Os pacientes com CCL são, em sua maioria, domiciliares. Os sistemas Ambient Assisted Living (AAL) fornecem ferramentas para registro automático de sinais vitais e outras informações médicas e socialmente importantes. O sistema AAL para pacientes com MCI é uma resposta lógica para o problema. Ao mesmo tempo, muitos dos sistemas AAL propostos são proprietários, tecnicamente complicados e têm um alto preço para implementação e serviço. Além disso, algumas soluções técnicas propostas não refletem inteiramente a opinião das partes interessadas na área da saúde. O presente estudo foi proposto como forma de colmatar as possíveis diferenças nas posições. Um questionário anônimo online para profissionais de saúde foi criado para comprovar ou refutar o número de hipóteses interligadas sobre a necessidade e viabilidade do sistema AAL para pacientes com CCL. O foco principal foi feito nas hipóteses: "Há necessidade de sistemas de AAL para a saúde" e "Os sistemas de AAL são capazes de prestar assistência a pacientes com Comprometimento Cognitivo Leve". O questionário foi apresentado a mais de trezentos respondentes potenciais. Cerca de cento e vinte concordaram em preenchê-lo e sessenta preencheram todo o questionário. Os resultados foram analisados para produzir algumas diretrizes para futuras aplicações técnicas de sistemas AAL para pacientes com MCI e pesquisas futuras. Estatísticas descritivas mostram suporte para a implementação de AAL geral e variantes para pacientes com CCL. A análise comparativa de dados ordinais para grupos específicos de respondentes é feita com a ajuda de testes não paramétricos. Aplicam-se os testes de Mann-Whitney-Wilcoxon e Kruskal-Wallis. Os resultados das questões da tabela são analisados com qui-quadrado para tabelas de frequência. A análise do grupo demonstrou relativa uniformidade positiva nas respostas no suporte de AAL de pacientes com CCL.Selon l'Organisation mondiale de la santé, environ 50 millions de personnes dans le monde souffrent de démence. Dix millions de nouveaux cas ajoutés chaque année. Les troubles cognitifs légers (MCI) touchent plus de 15 % de la population âgée de 65 ans. Les solutions technologiques, telles que la technologie de la maison intelligente avec des appareils informatiques omniprésents, l'observation et le soutien télémédicaux 24 heures sur 24, 7 jours sur 7, peuvent atténuer le problème croissant et réduire la pression sur le système de santé. Cette approche est également préférable pour les patients en soins à domicile dans les régions éloignées et rurales. Les patients MCI sont pour la plupart à domicile. Les systèmes Ambient Assisted Living (AAL) fournissent des outils pour l'enregistrement automatique des signes vitaux et d'autres informations importantes sur le plan médical et social. Le système AAL pour les patients MCI est une réponse logique au problème. Dans le même temps, bon nombre des systèmes AAL proposés sont propriétaires, techniquement compliqués et ont un prix élevé pour la mise en oeuvre et le service. De plus, certaines solutions techniques proposées ne reflètent pas entièrement l'opinion des acteurs de santé. L'étude actuelle a été proposée comme un moyen de combler les différences possible dans les positions. Un questionnaire anonyme en ligne destiné aux professionnels de la santé a été créé pour prouver ou réfuter le nombre d'hypothèses interconnectées sur la nécessité et la faisabilité du système AAL pour les patients MCI. L'accent a été mis principalement sur les hypothèses: "Il existe une nécessité de systèmes AAL pour les soins de santé" et "Les systèmes AAL sont capables de fournir une assistance aux patients atteints de troubles cognitifs légers". Le questionnaire a été présenté à plus de trois cents répondants potentiels. Environ cent vingt ont accepté de le remplir, et soixante ont rempli tout le questionnaire. Les résultats ont été analysés pour produire des lignes directrices pour les futures applications techniques des systèmes AAL pour les patients MCI et l'avenir de la recherche. Les statistiques descriptives montrent un soutien à la mise en oeuvre de l'AAL général et des variantes pour les patients MCI. L'analyse comparative des données ordinales pour des groupes spécifiques de répondants est effectuée à l'aide de tests non paramétriques. Le test de Mann-Whitney-Wilcoxon et le test de Kruskal-Wallis sont appliqués. Les résultats des questions de tableau sont analysés avec le chi carré pour les tableaux de fréquence. L'analyse de groupe a démontré une uniformité positive relative dans les réponses à l'appui de l'AAL des patients MCI

Investigations in acute and chronic allodynia : using human psychophysics, sensory analysis, glial modulation & functional proteomics in the dorsal horn of the spinal cord

In many chronic pain pathologies, stimuli that are normally non-painful to healthy humans, such as light touch or small decrements in temperature, can cause painful responses – a phenomenon called allodynia. The majority of research on tactile allodynia has focused on myelinated low threshold A mechanoreceptors (A-LTMR) that are otherwise known to mediate innocuous mechano-sensation (1, 2). Recently, there is a growing recognition of the contribution of more than one class of low threshold fibres to pain processing, i.e. unmyelinated low threshold C mechanoreceptors (C-LTMRs), which are believed to be responsible for affective touch processing. (3-6). The first evidence of the contribution of C tactile fibres (CTs), the human counterpart of C-LTMRs, to cutaneous allodynia was shown in human models of rapid-onset skin and muscle pain as well as delayed-onset muscle soreness (3-9). In addition, recent studies in transgenic mice, in both acute and chronic pain models, have provided molecular mechanisms at the spinal level, which functionally correspond to the tactile and cold allodynia perceived in human subjects (10-13). In the last few years, both animal and human studies have argued for a convergence of low threshold C fibre input to nociceptive fibre signalling at the dorsal horn level (3, 4, 7, 10, 14-17). On the basis of the behavioural observations of bilateral cold and tactile allodynia post unilateral median nerve injury (from Paper I) in this thesis, it is hypothesised that central interactions of fibres conducting noxious (i.e. nociceptors) as well as non-noxious stimuli (i.e.non-nociceptors) at the dorsal horn level are responsible in driving these sensations. In addition, the actions of spinal immune cells in the dorsal horn such as microglia and astrocytes to influence nociceptive processing have been firmly established (18-22). Akin to the canonical perspective of attributing allodynia to A-LTMRs, the role of spinal glial cells in injury induced hypersensitivity has always been looked at in the context of these ALTMRs in addition to the unmyelinated high threshold C nociceptors (20, 23, 24). From previous observations of such neuro-glial modulation mentioned above, it is hypothesized that the glial cells can modulate bilateral noxious signalling and the percept of allodynia evoked by otherwise innocuous stimuli, i.e. normally non-painful touch and cooling in this model of bilateral allodynia due to a unilateral nerve injury. Incidentally, rapid cooling and non-painful gentle touch are hallmark of CTs in humans (5, 6) and in mice (10, 12, 13) and hence, cannot be ignored as one of the likely substrates of this phenomena in this rat model. In the dorsal horn, lamina II, which is the main termination site of CT inputs, has been postulated to act as a 'gate' for processing noxious as well as innocuous information by converging and processing inputs from superficial as well as deep dorsal horn (25). This work supports the view, also discussed in Abraira, Kuehn (26), that of low and high threshold inputs from the periphery, it is the dorsal horn (lamina I-III), that acts as the primary convergence centre to 'gate' or 'gain' painful and non-painful information before it is passed over to higher order neurons. Furthermore, by studying the neuronal and nonneuronal interactions in the dorsal horn at the peak time point of the bilateral allodynia seen in our model, it is possible to understand the biochemical changes responsible for this behaviour. These changes help us understand key mechanisms of protein signalling at the cellular dorsal horn that has been often overlooked in other experiments involving proteomics due to experimental bias. Hence, the animal studies in this thesis provide a greater understanding of mechanisms of allodynia and its modulation using pharmacological tools in animals. In rats, following a unilateral median nerve injury, bilateral allodynia was ameliorated using minocycline, a glial inhibitor, by modulation of the dorsal horn interactions between glia and primary afferent fibres that respond to non-painful stimuli. These interactions (Paper I & II) were studied using immuno-staining and proteomic profiling of the dorsal horn – prior to and following nerve injury and its modulation by minocycline. The key result from the animal work, presented in this thesis, is the presentation of modulatory proteins responsible for the sensory behaviour at the contralateral, uninjured side as opposed to the primarily studied injured side of the dorsal horn. To understand the ‘gating’ and ‘gaining’ mechanism of the dorsal horn discussed previously in rodent models, it is important to ask what dissimilates the perception of painfulness from non-painfulness or pleasure in humans with acute pain. Therefore, in healthy humans (Paper III), pain modulation was tested in the context of acute background muscle pain with concurrent ‘affective’ tactile stimulation. Furthermore, the resulting percept and its peripheral substrates was determined using a preferential block of myelinated fibres. In this study, we demonstrated that activation of CTs can produce a stimulus-locked, bi-directional (excitatory/inhibitory) affective modulation of pain that is consistent with previously documented CT function in the rodent dorsal horn. From this human study, it is hypothesised that CT dependent context driven affective stimulus can determine the direction of the perception, in this case, pleasurable or painful. This study also presents with the idea that long term changes in the dorsal horn circuitry may not be necessary to initiate this type of context-dependent bi-directional stimulation and can be achieved in an acute setting. Hence, the animal and human studies combine the animal sensory behaviour and human perception of allodynia (and its modulation) to explore the link between the activation of low threshold sensory fibres such as CTs (by innocuous stimuli) and nociceptive processing in acute and pathological pain states. This thesis comprises of an introduction section and 3 manuscripts. The introduction provides a short review of the peripheral and central mechanisms of allodynia with the aim of interlacing it with the work presented in the 3 manuscripts (referred to in the text by their Roman numerals)

12 Chapters on Nuclear Medicine

The development of nuclear medicine as a medical specialty has resulted in the large-scale application of its effective imaging methods in everyday practice as a primary method of diagnosis. The introduction of positron-emitting tracers (PET) has represented another fundamental leap forward in the ability of nuclear medicine to exert a profound impact on patient management, while the ability to produce radioisotopes of different elements initiated a variety of tracer studies in biology and medicine, facilitating enhanced interactions of nuclear medicine specialists and specialists in other disciplines. At present, nuclear medicine is an essential part of diagnosis of many diseases, particularly in cardiologic, nephrologic and oncologic applications and it is well-established in its therapeutic approaches, notably in the treatment of thyroid cancers. Data from official sources of different countries confirm that more than 10-15 percent of expenditures on clinical imaging studies are spent on nuclear medicine procedures

Mass spectrometry-based studies of synthetic and natural macromolecules

Originally established as an analytical technique in the fields of physics and chemistry, mass spectrometry has recently become an essential tool in biological research. Advances in ionisation methods and novel types of instrumentation have led to the development of mass spectrometry for the analysis of a wide variety of biological samples. The work presented here describes the use of mass spectrometry to characterise a variety of synthetic and natural macromolecules. Transmissible spongiform encephalopathies (TSEs), also known as prion diseases, are a class of fatal, infectious neurodegenerative diseases that affect both humans and animals. Prion proteins are unprecedented infectious pathogens that cause a group of invariably fatal neurodegenerative diseases by means of an entirely novel mechanism. Ion mobility mass spectrometry (IM-MS) was used to probe the conformation of a variety of different prion proteins in the gas-phase. It was shown that IM-MS could distinguish between two recombinant structures representative of normal cellular prion protein, PrPC and the pathogenic scrapie form (PrPSc). The structure of the full-length prion protein was probed by means of IM-MS. A comparison of the estimated cross-sections of truncated prion protein constructs and full-length constructs suggested that the N-terminal flexible tail was associated with the core structure. Metal binding to two different prion protein constructs was investigated. It was observed that copper coordination to the N-terminal fragment could induce conformational changes in the octarepeat fragment. These changes were relatively small and could not be measured in the full-length prion protein. The data suggested that minor structural changes in the N-terminal could stimulate endocytosis via a minor, undetected, conformational change in the C-terminal domain. IM-MS was used as a high resolution separation technique to distinguish between mixtures of isobaric synthetic polymers. It was observed that the resolving power of IM-MS/MS was insufficient to resolve the higher molecular weight oligomers. In comparison, gel permeation chromatography (GPC)-nuclear magnetic resonance (NMR) spectroscopy (GPC-NMR) analysis of the same isobaric mixture could not separate the two components. It was observed that IM-MS was better than GPCNMR at separating isobaric poly(ethylene glycol) mixtures, especially when taking speed and sensitivity into account

2019 Oklahoma Research Day Full Program

Oklahoma Research Day 2019 - SWOSU Celebrating 20 years of Undergraduate Research Successes

KEER2022

Avanttítol: KEER2022. DiversitiesDescripció del recurs: 25 juliol 202