Dimensionality reduction and unsupervised learning techniques applied to clinical psychiatric and neuroimaging phenotypes

Unsupervised learning and other multivariate analysis techniques are increasingly recognized in neuropsychiatric research. Here, finite mixture models and random forests were applied to clinical observations of patients with major depression to detect and validate treatment response subgroups. Further, independent component analysis and agglomerative hierarchical clustering were combined to build a brain parcellation solely on structural covariance information of magnetic resonance brain images. Übersetzte Kurzfassung: Unüberwachtes Lernen und andere multivariate Analyseverfahren werden zunehmend auf neuropsychiatrische Fragestellungen angewendet. Finite mixture Modelle wurden auf klinische Skalen von Patienten mit schwerer Depression appliziert, um Therapieantwortklassen zu bilden und mit Random Forests zu validieren. Unabhängigkeitsanalysen und agglomeratives hierarchisches Clustering wurden kombiniert, um die strukturelle Kovarianz von Magnetresonanz­tomographie-Bildern für eine Hirnparzellierung zu nutzen

Advanced Sensing and Image Processing Techniques for Healthcare Applications

This Special Issue aims to attract the latest research and findings in the design, development and experimentation of healthcare-related technologies. This includes, but is not limited to, using novel sensing, imaging, data processing, machine learning, and artificially intelligent devices and algorithms to assist/monitor the elderly, patients, and the disabled population

Performance Evaluation of Smart Decision Support Systems on Healthcare

Medical activity requires responsibility not only from clinical knowledge and skill but also on the management of an enormous amount of information related to patient care. It is through proper treatment of information that experts can consistently build a healthy wellness policy. The primary objective for the development of decision support systems (DSSs) is to provide information to specialists when and where they are needed. These systems provide information, models, and data manipulation tools to help experts make better decisions in a variety of situations. Most of the challenges that smart DSSs face come from the great difficulty of dealing with large volumes of information, which is continuously generated by the most diverse types of devices and equipment, requiring high computational resources. This situation makes this type of system susceptible to not recovering information quickly for the decision making. As a result of this adversity, the information quality and the provision of an infrastructure capable of promoting the integration and articulation among different health information systems (HIS) become promising research topics in the field of electronic health (e-health) and that, for this same reason, are addressed in this research. The work described in this thesis is motivated by the need to propose novel approaches to deal with problems inherent to the acquisition, cleaning, integration, and aggregation of data obtained from different sources in e-health environments, as well as their analysis. To ensure the success of data integration and analysis in e-health environments, it is essential that machine-learning (ML) algorithms ensure system reliability. However, in this type of environment, it is not possible to guarantee a reliable scenario. This scenario makes intelligent SAD susceptible to predictive failures, which severely compromise overall system performance. On the other hand, systems can have their performance compromised due to the overload of information they can support. To solve some of these problems, this thesis presents several proposals and studies on the impact of ML algorithms in the monitoring and management of hypertensive disorders related to pregnancy of risk. The primary goals of the proposals presented in this thesis are to improve the overall performance of health information systems. In particular, ML-based methods are exploited to improve the prediction accuracy and optimize the use of monitoring device resources. It was demonstrated that the use of this type of strategy and methodology contributes to a significant increase in the performance of smart DSSs, not only concerning precision but also in the computational cost reduction used in the classification process. The observed results seek to contribute to the advance of state of the art in methods and strategies based on AI that aim to surpass some challenges that emerge from the integration and performance of the smart DSSs. With the use of algorithms based on AI, it is possible to quickly and automatically analyze a larger volume of complex data and focus on more accurate results, providing high-value predictions for a better decision making in real time and without human intervention.A atividade médica requer responsabilidade não apenas com base no conhecimento e na habilidade clínica, mas também na gestão de uma enorme quantidade de informações relacionadas ao atendimento ao paciente. É através do tratamento adequado das informações que os especialistas podem consistentemente construir uma política saudável de bem-estar. O principal objetivo para o desenvolvimento de sistemas de apoio à decisão (SAD) é fornecer informações aos especialistas onde e quando são necessárias. Esses sistemas fornecem informações, modelos e ferramentas de manipulação de dados para ajudar os especialistas a tomar melhores decisões em diversas situações. A maioria dos desafios que os SAD inteligentes enfrentam advêm da grande dificuldade de lidar com grandes volumes de dados, que é gerada constantemente pelos mais diversos tipos de dispositivos e equipamentos, exigindo elevados recursos computacionais. Essa situação torna este tipo de sistemas suscetível a não recuperar a informação rapidamente para a tomada de decisão. Como resultado dessa adversidade, a qualidade da informação e a provisão de uma infraestrutura capaz de promover a integração e a articulação entre diferentes sistemas de informação em saúde (SIS) tornam-se promissores tópicos de pesquisa no campo da saúde eletrônica (e-saúde) e que, por essa mesma razão, são abordadas nesta investigação. O trabalho descrito nesta tese é motivado pela necessidade de propor novas abordagens para lidar com os problemas inerentes à aquisição, limpeza, integração e agregação de dados obtidos de diferentes fontes em ambientes de e-saúde, bem como sua análise. Para garantir o sucesso da integração e análise de dados em ambientes e-saúde é importante que os algoritmos baseados em aprendizagem de máquina (AM) garantam a confiabilidade do sistema. No entanto, neste tipo de ambiente, não é possível garantir um cenário totalmente confiável. Esse cenário torna os SAD inteligentes suscetíveis à presença de falhas de predição que comprometem seriamente o desempenho geral do sistema. Por outro lado, os sistemas podem ter seu desempenho comprometido devido à sobrecarga de informações que podem suportar. Para tentar resolver alguns destes problemas, esta tese apresenta várias propostas e estudos sobre o impacto de algoritmos de AM na monitoria e gestão de transtornos hipertensivos relacionados com a gravidez (gestação) de risco. O objetivo das propostas apresentadas nesta tese é melhorar o desempenho global de sistemas de informação em saúde. Em particular, os métodos baseados em AM são explorados para melhorar a precisão da predição e otimizar o uso dos recursos dos dispositivos de monitorização. Ficou demonstrado que o uso deste tipo de estratégia e metodologia contribui para um aumento significativo do desempenho dos SAD inteligentes, não só em termos de precisão, mas também na diminuição do custo computacional utilizado no processo de classificação. Os resultados observados buscam contribuir para o avanço do estado da arte em métodos e estratégias baseadas em inteligência artificial que visam ultrapassar alguns desafios que advêm da integração e desempenho dos SAD inteligentes. Como o uso de algoritmos baseados em inteligência artificial é possível analisar de forma rápida e automática um volume maior de dados complexos e focar em resultados mais precisos, fornecendo previsões de alto valor para uma melhor tomada de decisão em tempo real e sem intervenção humana

Environmental drivers of deer population dynamics and spatial selection in Southeast Alaska

Thesis (Ph.D.) University of Alaska Fairbanks, 2015The coastal temperate rainforest is one of the rarest ecosystems in the world, and a major portion of the global total is found in Southeast Alaska. In this ecosystem, Sitka black-tailed deer are the dominant large herbivore, influencing large carnivores that prey on deer such as wolves and bears, as well as plant species and communities through browsing. In addition, deer play an important economic and cultural role for humans in Southeast Alaska, making up the large majority of terrestrial subsistence protein harvested each year as well as providing the backbone of a thriving tourism industry built around sport hunting. Given the importance of deer in this system, there remain a surprisingly large number of key gaps in our knowledge of deer ecology in Southeast Alaska. These knowledge gaps are potentially troubling in light of ongoing industrial timber-harvest across the region, which greatly alters habitat characteristics and value to wildlife. This dissertation research project was undertaken with the aim of filling several connected needs for further understanding deer ecology, specifically 1) patterns of reproduction and fawn survival, 2) population dynamics in response to environmental variability, and the underlying drivers of spatial selection during 3) reproduction and 4) winter. To fill these knowledge gaps, I developed robust statistical tools for estimating rates of fawn survival, and found that fawns must be captured at birth, rather than within several days of birth, in order to produce unbiased estimates because highly vulnerable individuals died quickly and were thus absent from the latter sample. I then use this robust approach to estimate vital rates, including fawn survival in winter and summer, and developed a model of population dynamics for deer. I found that winter weather had the strongest influence on population dynamics, via reduced over-winter fawn survival, with mass at birth and gender ratio of fawns important secondary drivers. To better understand deer-habitat relationships, I examined both summer and winter habitat selection patterns by female deer. Using summer-only data, I asked how reproductive female deer balance wolf and bear predation risk against access to forage over time. Predation risks and forage were strong drivers of deer spatial selection during summer, but reproductive period and time within reproductive period determined deer reaction to these drivers. To ensure adequate reproductive habitat for deer, areas with low predation risk and high forage should be conserved. Focusing on winter, I evaluated deer spatial selection during winter as a response to snow depth, vegetation classes, forage, and landscape features. I allowed daily snow depth measures to interact with selection of other covariates, and found strong support for deer avoidance of deep snow, as well as changes in deer selection of old-growth and second-growth habitats and landscape features with increasing snow depth. Collectively, this dissertation greatly improves our understanding of deer ecology in Alaska, and suggests habitat management actions that will help ensure resilient deer populations in the future

An Investigation into the Neurobiology of Treatment Response in patients with Major Depression: The Placebo Effect.

Recent trends in clinical neuroscience have moved toward identifying neurobiological predictors of antidepressant treatment effects in order to improve overall treatment efficacy in Major Depression, a pervasive and debilitating disorder in which complete remission occurs for only one-third of treatment-seeking patients. However, predictors of placebo effects have largely been overlooked. This is not a small concern: substantial placebo response rates have been documented within antidepressant clinical trials. Hence, neuroimaging predictors of placebo responses may elucidate the neural pathways responsible for depression recovery. Moreover, these predictors may identify patients with a greater susceptibility to placebo effects; in turn, informing patient stratification in antidepressant clinical trials to better distinguish between drug-specific and placebo effects or augment prescribed treatments for patients in clinical settings. This dissertation takes a network-based resting-state functional connectivity (rsFC) approach to investigate predictors of placebo and antidepressant responses with particular focus on the default-mode, salience, and executive networks. This approach allows for consistency with the inherent network organization of the brain and the network-based characterization of depression. Through this investigation, enhanced rsFC of the rostral anterior cingulate (rACC) within the salience network has emerged as a strong predictor of responses to placebo with antidepressant expectations. Furthermore, heightened rACC rsFC within the salience network manifests as a neurobiological pattern differentiating healthy subjects from depressed patients. Finally, in light of evidence that genetic variability within placebo-related pathways modulate placebo treatment outcomes in depression as well as analgesia, where neural and molecular bases of placebo have been extensively mapped, the final chapter of this dissertation observed an effect of genetic polymorphisms within the prepronociceptin gene, an endogenous opioid precursor neuropeptide associated with nociception and depression, on analgesic placebo-induced µ-opioid activation within the rACC and other well-established, placebo-related regions. This effect further corresponded with placebo-associated stress responses and anxiety. These findings enlighten our understanding of the neurobiology behind depression recovery through placebo effects and illustrate the importance of the rACC within antidepressant responses and healthy functioning. Finally, they contribute to a growing database of potential clinical neuroimaging and genetic markers of placebo responses which may substantially benefit therapeutic care in depression.PhDNeuroscienceUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/116639/1/masikora_1.pd

Learning vector quantization for proximity data

Hofmann D. Learning vector quantization for proximity data. Bielefeld: Universität Bielefeld; 2016.Prototype-based classifiers such as learning vector quantization (LVQ) often display intuitive and flexible classification and learning rules. However, classical techniques are restricted to vectorial data only, and hence not suited for more complex data structures. Therefore, a few extensions of diverse LVQ variants to more general data which are characterized based on pairwise similarities or dissimilarities only have been proposed recently in the literature. In this contribution, we propose a novel extension of LVQ to similarity data which is based on the kernelization of an underlying probabilistic model: kernel robust soft LVQ (KRSLVQ). Relying on the notion of a pseudo-Euclidean embedding of proximity data, we put this specific approach as well as existing alternatives into a general framework which characterizes different fundamental possibilities how to extend LVQ towards proximity data: the main characteristics are given by the choice of the cost function, the interface to the data in terms of similarities or dissimilarities, and the way in which optimization takes place. In particular the latter strategy highlights the difference of popular kernel approaches versus so-called relational approaches. While KRSLVQ and alternatives lead to state of the art results, these extensions have two drawbacks as compared to their vectorial counterparts: (i) a quadratic training complexity is encountered due to the dependency of the methods on the full proximity matrix; (ii) prototypes are no longer given by vectors but they are represented in terms of an implicit linear combination of data, i.e. interpretability of the prototypes is lost. We investigate different techniques to deal with these challenges: We consider a speed-up of training by means of low rank approximations of the Gram matrix by its Nyström approximation. In benchmarks, this strategy is successful if the considered data are intrinsically low-dimensional. We propose a quick check to efficiently test this property prior to training. We extend KRSLVQ by sparse approximations of the prototypes: instead of the full coefficient vectors, few exemplars which represent the prototypes can be directly inspected by practitioners in the same way as data. We compare different paradigms based on which to infer a sparse approximation: sparsity priors while training, geometric approaches including orthogonal matching pursuit and core techniques, and heuristic approximations based on the coefficients or proximities. We demonstrate the performance of these LVQ techniques for benchmark data, reaching state of the art results. We discuss the behavior of the methods to enhance performance and interpretability as concerns quality, sparsity, and representativity, and we propose different measures how to quantitatively evaluate the performance of the approaches. We would like to point out that we had the possibility to present our findings in international publication organs including three journal articles [6, 9, 2], four conference papers [8, 5, 7, 1] and two workshop contributions [4, 3]. References [1] A. Gisbrecht, D. Hofmann, and B. Hammer. Discriminative dimensionality reduction mappings. Advances in Intelligent Data Analysis, 7619: 126–138, 2012. [2] B. Hammer, D. Hofmann, F.-M. Schleif, and X. Zhu. Learning vector quantization for (dis-)similarities. Neurocomputing, 131: 43–51, 2014. [3] D. Hofmann. Sparse approximations for kernel robust soft lvq. Mittweida Workshop on Computational Intelligence, 2013. [4] D. Hofmann, A. Gisbrecht, and B. Hammer. Discriminative probabilistic prototype based models in kernel space. New Challenges in Neural Computation, TR Machine Learning Reports, 2012. [5] D. Hofmann, A. Gisbrecht, and B. Hammer. Efficient approximations of kernel robust soft lvq. Workshop on Self-Organizing Maps, 198: 183–192, 2012. [6] D. Hofmann, A. Gisbrecht, and B. Hammer. Efficient approximations of robust soft learning vector quantization for non-vectorial data. Neurocomputing, 147: 96–106, 2015. [7] D. Hofmann and B. Hammer. Kernel robust soft learning vector quantization. Artificial Neural Networks in Pattern Recognition, 7477: 14–23, 2012. [8] D. Hofmann and B. Hammer. Sparse approximations for kernel learning vector quantization. European Symposium on Artificial Neural Networks, 549–554, 2013. [9] D. Hofmann, F.-M. Schleif, B. Paaßen, and B. Hammer. Learning interpretable kernelized prototype-based models. Neurocomputing, 141: 84–96, 2014

Computational Design of Synthetic Microbial Communities

In naturally occurring microbial systems, species rarely exist in isolation. There is strong ecological evidence for a positive relationship between species diversity and the functional output of communities. The pervasiveness of these communities in nature highlights that there may be advantages for engineered strains to exist in cocultures as well. Building synthetic microbial communities allows us to create distributed systems that mitigate issues often found in engineering a monoculture, especially when functional complexity is increasing. The establishment of synthetic microbial communities is a major challenge we must overcome in order to implement coordinated multicellular systems. Here I present computational tools that help us design engineering strategies for establishing synthetic microbial communities. Using these tools I identify promising candidates for several design scenarios. This work highlights the importance of parameter inference and model selection to build robust communities. The findings highlight important interaction motifs that provide stability, and identify requirements for selecting genetic parts and tuning the community composition. Additionally, I show that fundamental interactions in small synthetic communities can produce chaotic behaviour that is unforecastable. Together these findings have important ramifications for how we build synthetic communities in the lab, and the considerations of interactions in microbiomes we manipulate

Incorporating standardised drift-tube ion mobility to enhance non-targeted assessment of the wine metabolome (LC×IM-MS)

Liquid chromatography with drift-tube ion mobility spectrometry-mass spectrometry (LCxIM-MS) is emerging as a powerful addition to existing LC-MS workflows for addressing a diverse range of metabolomics-related questions [1,2]. Importantly, excellent precision under repeatability and reproducibility conditions of drift-tube IM separations [3] supports the development of non-targeted approaches for complex metabolome assessment such as wine characterisation [4]. In this work, fundamentals of this new analytical metabolomics approach are introduced and application to the analysis of 90 authentic red and white wine samples originating from Macedonia is presented. Following measurements, intersample alignment of metabolites using non-targeted extraction and three-dimensional alignment of molecular features (retention time, collision cross section, and high-resolution mass spectra) provides confidence for metabolite identity confirmation. Applying a fingerprinting metabolomics workflow allows statistical assessment of the influence of geographic region, variety, and age. This approach is a state-of-the-art tool to assess wine chemodiversity and is particularly beneficial for the discovery of wine biomarkers and establishing product authenticity based on development of fingerprint libraries