Ambulatory biopotential measurement

Biopotential signals measure the electrical activity of different parts of the body. Conventional bedside monitors only provide information about the body under restricted conditions. Observation and documentation of biopotential signal during daily activities and the relation to patient symptoms may be important factors for clinical decision-making. Ambulatory monitoring helps to monitor the biopotential signal of a patient in the natural environment. The effective ambulatory system can help a physician to diagnose the patient\u27s abnormality. In this project, a low cost and flexible ambulatory biopotential system, compared to the commercially available systems, was designed and tested. Concurrently a software program was developed for data acquisition and analysis with a Personal Data Assistant (PDA). The data was analyzed in real time using the Lab VIEW PDA. Pilot data was collected using the developed hardware during different normal activities to confirm the accuracy and reliability of the developed hardware and data was collected simultaneously from both a standard ECU machine and the developed system. It was shown that during some activities the system performed as designed, however under extreme conditions where there was more motion artifact, the number of missing R waves increased. The quality of raw ECU from the developed system was as good as the standard ECU during low motion artifact. It has been demonstrated that this newly developed biopotential system is less expensive, flexible, accurate, and more reliable than the commercially available systems and could be used in different clinical and research studies

WHAT DO COMMUNITY HEALTH WORKERS NEED TO PROVIDE COMPREHENSIVE CARE THAT INCORPORATES NON-COMMUNICABLE DISEASES?

Non-Communicable Diseases (NCDs) such as heart disease, stroke, cancer, chronic respiratory diseases and diabetes are the leading cause of premature death and disability worldwide, accounting for 60% of all deaths globally and 80% of NCD related mortality occurring in low and middle-income countries (LMICs). Health systems in LMICs have been oriented toward maternal and child health, and infectious illnesses as these were the main causes of morbidity and mortality until recently. Over the last decade, health systems in LMICs have recognized the need to address NCDs, and have restructured health services to include relevant prevention and control strategies. Health workforce is one of the key building blocks of health systems; however, most LMICs have a shortage of physicians. In addition, the available health care providers are unevenly distributed within countries with the majority concentrated in urban regions compared to rural regions where large proportions of the population reside. This poor distribution and shortage of physicians has led some countries to rely on task shifting, where tasks normally performed by qualified health professionals are transferred to other health providers with a lower level of education and professional training. In 1978, the Declaration of Alma-Ata included trained community health workers (CHWs) and traditional medical practitioners as part of the health team as a fundamental step towards comprehensive primary care. Since then, CHWs have been a cornerstone of health systems in several countries with over 26 different CHW programs identified in the literature across more than 24 LMICs. Traditionally, CHWs do not hold formal professional certification but receive job-related pre-service training. However, there is a lot of variation across countries where some countries require CHW certification before they can start performing their roles. CHWs reside in the community where they work, and are usually volunteers and sometimes receive financial compensation for receiving training and performance-based incentives for health related activities. CHWs can enable essential health care services to be provided in a cost-effective manner. They have been instrumental in reducing maternal and neonatal mortality rates through their presence for home births and making referrals for emergency obstetric care, and by promoting vaccination uptake, breastfeeding, and education about infectious disease. More recently, CHWs have been useful in HIV/AIDS prevention and control, educating communities and performing tasks such as screening, counselling and supplying antiretroviral drugs. With the increasing prevalence of NCDs and to meet changing community health needs, CHWs are sought to provide a similarly appropriate care for NCD risk factors control. While CHWs may not replace qualified health providers, they can play a considerable role in improving health outcomes by educating, screening, referring and following-up individuals at high risk of NCDs. CHWs have been trained in some settings to screen, educate and follow-up patients with NCDs or people at increased risk of NCDs. However, there is a need to better understand how to support CHW programs to be more effective and sustainable. There is knowledge gap in terms of the CHWs current capacity, working conditions, training provided for NCD prevention and control, remuneration, supervision and other upstream challenges facing CHWs and the health systems. The literature suggests that the there is a range of context-specific factors which can have an impact on the performance of CHWs and the quality of the care they provide. Some of these factors include the remuneration schemes employed, the workload, task complexity, lack of clarity in job description, and other essential factors such as interpersonal relationships between CHWs and other members of the primary health care team. CHW programs operate differently across and within countries. Evidence-based policy interventions are required to inform policy decision to ensure effective CHW program implementation. This thesis applies a mixed-methods approach to explore the capacity of the CHWs and the system support necessary to facilitate the CHW’s role in providing comprehensive, community-oriented, continuous primary health care which includes prevention and control strategies for NCDs. Part One provides an insight into the historical background of CHWs and how their role has evolved due to global health needs. With the expanding role of CHWs to incorporate NCDs, part two throws light on training of CHWs for NCDs in LMICs. Chapter two presents results of a systematic review about the effectiveness of training CHWs for cardiovascular disease prevention and management in LMICs. The chapter findings demonstrate the importance of having interactive and culturally adapted training sessions to make the training easier to follow and understand by the CHWs. The findings also highlight the need for evaluating the knowledge and skill-set of the CHWs to capture the training impact; and the necessity of scheduling refresher training at regular intervals to ensure knowledge retention. Chapter three demonstrates the importance of using an evaluation framework such as Kirkpatrick’s evaluation model to evaluate the effectiveness of training among CHWs. Using an evaluation framework, not only assesses the knowledge change but rather employs multiple measures to assess knowledge, skills and behaviour change of the CHWs. This allows for a more comprehensive interpretation of the training outcomes. The qualitative data involved in Chapter three provided insight on the low morale and discontent of the CHWs with their working conditions. In part three, I use a discrete choice experiment (DCE) to provide evidence of effective interventions that can keep the CHWs motivated and retain them in the workforce. Chapter Four explains the process of designing a DCE for Accredited Social Health Activists (ASHAs), who are CHWs in India. It also provides evidence of the feasibility of using Android computer tablets to display the DCE for the CHWs. In chapter five, I examine the relative importance of stated preferences of ASHAs to remain in service using a DCE survey. Career progression was found to be the main influencing factor for ASHAs in addition to fixed salary and other non-financial factors such as priority free family health-check and reduced workload. The findings demonstrated that the ASHAs sociodemographic characteristics such as their education level plays a key role in shaping their preference profile. These findings can inform future policy decisions of evidence-based recruitment and retention strategies that are applicable to the local context. CHWs have proven to be effective in providing a wide range of services including NCDs care. However to optimize the performance of CHW programs, we need to understand the system level support needed and the strategies necessary to be considered in the design and operation of CHWs’ programs. Part four, investigates the policy and implementation elements and system level support needed to enable the CHWs in rural India to provide comprehensive primary health care that incorporates NCDs. Chapter six uses policy review and qualitative research to understand the policy and implementation gaps, current capacity, working conditions and challenges faced by ASHAs in providing NCDs care to their community. It provides an overview of the perspectives of the key stakeholders of the ASHA program including ASHAs, ANMs, primary care doctors, community members, and district medical officers. Findings revealed that ASHAs are unrecognised as formal members of the NCDs delivery team, however they are overburdened with extensive NCDs tasks without receiving training or remuneration for these tasks. ASHAs remain to be volunteers that receive performance based remuneration and are not covered by any of the workers’ rights or laws. However, ASHAs remain enthusiastic about helping their communities and aspire to be recognised as formal employees of the health system with a potential career progression pathway. The concluding chapter summarises the key findings, discusses the main themes emerging from the thesis and outlines the future research directions and policy recommendations

Upstream Effects on Microbial Community Selection in Biological Activated Carbon Filters

Limited literature has explored the development of bacterial communities in biofilters used in advanced water reclamation for potable water reuse and their specific role in the biodegradation of contaminants of interest. The study of microbial ecology and the development of bacterial communities in biofilters based on upstream effects in the treatment systems and downstream effects on effluent quality and process stability is imperative. Investigation of the role of upstream effects such as seeding of microorganisms from the conventional water reclamation processes and effects of ozone oxidation on the community before and during biofiltration are the main foci of this research. In addition to microbial ecology assessment for biofiltration processes, this examined the applicability of ozonation - biofiltration as a treatment barrier in water reuse projects and identify future needs to consolidate it as the preferred option. This research collected pilot-scale and bench-scale data from experiments with reclaimed water to understand the biofilters microbiology and its capabilities and resilience based on different influent characteristics, either selecting and/or defining microorganisms to enhance biofilter performance and efficiency. Ozonation employed to disinfect pathogens and make trace organics more biodegradable followed by activated carbon-based biofiltration (biological activated carbon (BAC) filtration) were studied in combination with Coagulation/Flocculation/Clarification/Granular Media Filtration, Granular Activated Carbon Filtration, and Ultraviolet disinfection. This advanced treatment train combined physical, chemical, and biological processes to successfully produce a high-water quality with low to non-detectable contaminant of emerging concern reducing the risk to potential public health concerns. In summary, this research highlights how the structure, composition, development, and fate of microbial community in ozone/BAC and other processes such as CFCGMF and GAC/UV/CF in advanced water treatment for water reuse purposes can be a key player to assess and control the overall system performance and ensuring high quality and safe finished water

A new audio-visual analysis approach and tools for parsing colonoscopy videos

Colonoscopy is an important screening tool for colorectal cancer. During a colonoscopic procedure, a tiny video camera at the tip of the endoscope generates a video signal of the internal mucosa of the colon. The video data are displayed on a monitor for real-time analysis by the endoscopist. We call videos captured from colonoscopic procedures colonoscopy videos. Because these videos possess unique characteristics, new types of semantic units and parsing techniques are required. In this paper, we introduce a new analysis approach that includes (a) a new definition of semantic unit - scene (a segment of visual and audio data that correspond to an endoscopic segment of the colon); (b) a novel scene segmentation algorithm using audio and visual analysis to recognize scene boundaries. We design a prototype system to implement the proposed approach. This system also provides the tools for video/image browsing. The tools enable the users to quickly locate and browse scenes of interest. Experiments on real colonoscopy videos show the effectiveness of our algorithms. The proposed techniques and software are useful (1) for post-procedure reviews, (2) for developing an effective content-based retrieval system for colonoscopy videos to facilitate endoscopic research and education, and (3) for development of a systematic approach to assess endoscopists\u27 procedural skills

On the role of metaheuristic optimization in bioinformatics

Metaheuristic algorithms are employed to solve complex and large-scale optimization problems in many different fields, from transportation and smart cities to finance. This paper discusses how metaheuristic algorithms are being applied to solve different optimization problems in the area of bioinformatics. While the text provides references to many optimization problems in the area, it focuses on those that have attracted more interest from the optimization community. Among the problems analyzed, the paper discusses in more detail the molecular docking problem, the protein structure prediction, phylogenetic inference, and different string problems. In addition, references to other relevant optimization problems are also given, including those related to medical imaging or gene selection for classification. From the previous analysis, the paper generates insights on research opportunities for the Operations Research and Computer Science communities in the field of bioinformatics

Computational Studies of Compressed Diborane and Engineered Narrow-Gap Semiconductors

The research contained in this thesis is two-fold: understanding the behavior of diborane under pressure, and engineering wide-gap semiconductors in order to promote their optical eciency. Each of these themes are further explained below. Diborane (B2H6), is a prototypical electron-deficient molecule and has received a great deal of attention in recent years due to its unique and peculiar structure, as well as its potential applications as a hydrogen-storage material. At high pressures, vibrational spectroscopy analysis have revealed several changes in the spectral profile that suggest occurrence of polymorphic transformations; however, the new crystal structures at high pressures have not been identified due to experimental challenges. In this study, we employ electronic structure calculations to investigate and assign the pressure-induced polymorphic transformations of crystalline diborane observed by vibrational spectroscopy up to 88 GPa. In particular, our density-functional calculations predict that diborane will remain in molecular form up to near-megabar pressures, above which it should transform into a structure with covalently bonded chains of boron atoms and eventually become metallic around 138 GPa. Zinc oxide (ZnO) and zinc sulfide (ZnS) are abundant and nontoxic compound semiconductors, but their band gaps are too wide for potential use in light-harvesting applications. Integration of these thermally and chemically stable compounds into a bulk heterostructure presents an opportunity for the generation of novel materials with notably different properties from their bulk counterparts. Using screened hybrid density-functional methods, we show that the band gaps of ZnO and ZnS can be dramatically reduced by creating layered ZnO/ZnS bulk heterostructures in which m contiguous monolayers of ZnO alternate with n contiguous monolayers of ZnS. In particular, the band gap decreases by roughly 40% upon substitution of every tenth monolayer of ZnS with a monolayer of ZnO (and vice versa) and becomes as low as 1.5 eV for heterostructures with m = 3 to m = 9 contiguous monolayers of ZnO alternating with n = 10 - m monolayers of ZnS. The predicted band gaps of layered ZnO/ZnS heterostructures span much of the visible spectrum, which makes these materials suitable for photovoltaic device engineering

ICASE/LaRC Symposium on Visualizing Time-Varying Data

Time-varying datasets present difficult problems for both analysis and visualization. For example, the data may be terabytes in size, distributed across mass storage systems at several sites, with time scales ranging from femtoseconds to eons. In response to these challenges, ICASE and NASA Langley Research Center, in cooperation with ACM SIGGRAPH, organized the first symposium on visualizing time-varying data. The purpose was to bring the producers of time-varying data together with visualization specialists to assess open issues in the field, present new solutions, and encourage collaborative problem-solving. These proceedings contain the peer-reviewed papers which were presented at the symposium. They cover a broad range of topics, from methods for modeling and compressing data to systems for visualizing CFD simulations and World Wide Web traffic. Because the subject matter is inherently dynamic, a paper proceedings cannot adequately convey all aspects of the work. The accompanying video proceedings provide additional context for several of the papers

Digital Image Processing Applications

Digital image processing can refer to a wide variety of techniques, concepts, and applications of different types of processing for different purposes. This book provides examples of digital image processing applications and presents recent research on processing concepts and techniques. Chapters cover such topics as image processing in medical physics, binarization, video processing, and more

Studying the folding of peptide dendrimers using molecular simulation methods

Tese de mestrado, Bioquímica, Universidade de Lisboa, Faculdade de Ciências, 2009Dendrimers are a family of branched compounds that share a common layout where wedges emerge radially from a core by means of a regular branching pattern. Peptide dendrimers are a specific kind of dendrimers formed by alternating functional amino acids with branching diamino acids. There has been increasing interest in the synthesis of peptide-based dendritic architectures modelling specific aspects of biological function. Some results are already available, demonstrating these molecules ability to act as enzyme models and to mimic natural ligands. Unfortunately, most studies concerning peptide dendrimers lack structural information at the molecular level. The theoretical study published so far, reported peptide dendrimers presenting shapes close to spheres, though experimental studies on the same systems suggest the existence of more disordered states. Herein, we characterize five third-generation peptide dendrimers (B1, B1H, B1HH, B1HHH and C1) through multiple long molecular dynamics simulations (MD), and analyse their conformational details and folding preferences in solution. Special emphasis is placed on the analysis of conformational trends representative of the examined models. The conformational sampling results, obtained through MM/MD simulations, were scrutinized using several approaches. Namely, histogram analysis, phi-psi dihedral distributions, inter-residue distance matrices, shape analysis and principal coordinate analysis. The adequacy of each approach to discern the conformation space of peptide dendrimers is discussed. Using these analysis procedures we were able to observe two distinct types of behaviour (sphere-like and bowl-like structures), both asserting the enormous structural flexibility characterizing these molecules; and the myriad of conformational states available to them. Our conclusions can be interpreted together with the available experimental results, contributing to a synergistic understanding of the structure-function relation in peptide dendrimers, and casting the bases for novel knowledge-based applications.Os dendrímeros são uma família de compostos ramificados que partilham uma arquitectura comum, onde diferentes cadeias emergem radialmente de um mesmo núcleo (ou centro) através de um padrão de ramificação regular. Os dendrímeros peptídicos, são uma classe particular de dendrímeros, constituída por estruturas que incorporam de forma alternada e iterativa resíduos de amino-ácidos funcionais (resíduos de espaçamento) com resíduos de diamino-ácidos ramificados (resíduos de ramificação). Os resíduos de diamino-ácidos ramificados promovem a bifurcação das cadeias peptídicas e a aquisição da estrutura dendrítica. A possibilidade de sintetizar dendrímeros com composições que mimetizem as funções de moléculas biológicas, constitui o aliciante para a investigação neste campo cientifico. Em particular, a síntese planeada e controlada de estruturas dendríticas baseadas nos componentes apresentados pelas moléculas biológicas, como peptidos ou glícidos, constitui um desafio atractivo pelas potenciais aplicações que dai podem emergir. De facto, já foram reportados dendrímeros peptídicos que modelam aspectos específicos de funções biológicas, tais como: modelos enzimáticos para catálise dirigida (“enzimas artificiais”); mimetização de co-factores naturais (de que e exemplo a vitamina B12); transportadores de fármacos, pois quando acopladas aos ligandos adequados estas moléculas tem a capacidade de aderir à membrana celular. É também importante referir que várias destas moléculas têm sido estudadas enquanto modelos de folding das proteínas naturais, pois investigações experimentais indiciam que alguns dendrímeros peptídicos podem apresentar, em solução, uma estrutura compacta semelhante à das proteínas globulares. Contudo, a maioria dos estudos experimentais realizados até à data são omissos no que concerne a informação estrutural, e carecem do enquadramento adequado a nível molecular e atómico. O único estudo teórico publicado sobre dendrímeros peptídicos parece confirmar a ideia de que, em solução estas moléculas apresentam, de facto, formas semelhantes a esferas, isto apesar de existirem evidências experimentais que sugerem a existência de estados conformacionais mais desordenados, nesses mesmos sistemas. Considerando o grande interesse que estas moléculas tem vindo a despertar, a verdade é que pouco se sabe sobre o seu arranjo estrutural tridimensional, e sobre os processos que a ele conduzem (folding). Nesta tese tentamos preencher algumas destas lacunas. Para tal, procedemos à caracterização de cinco dendrímeros peptídicos de terceira geração (que designamos por B1, B1H, B1HH, B1HHH e C1) com diferentes constituintes peptídicos. Os sistemas que escolhemos como objecto de estudo, estão directamente relacionados com a coordenação da aquocobalamina (análogo da vitamina B12) a dendrímeros peptídicos, ainda que apenas três deles tenham sido sintetizados e caracterizados experimentalmente (B1, B1H e C1). Deste modo, pretendemos não só investigar as suas preferências conformacionais, mas também inferir possíveis relações entre a sua estrutura e a capacidade para desempenhar uma função análoga à das moléculas biológicas (transcobalamina). É importante salientar que de entre os dendrímeros que foram sintetizados experimentalmente, e que são também aqui estudados, os que apresentam maior capacidade de coordenação com a aquacobalamina, são os que possuem um menor número de resíduos com potencial de coordenação. Este aparente paradoxo é por si só interessante e pode estar interligada com aspectos mais estruturais. Como temos por objectivo compreender as alterações e a variabilidade subjacentes às estruturas tridimensionais dos diferentes dendrímeros, empregamos metodologias adequadas ao detalhe da escala que pretendemos investigar. Nomeadamente, métodos computacionais de simulação molecular (MM/MD). Optámos portanto por simular cada um destes cinco sistemas através de múltiplas e longas simulações de dinâmica molecular, utilizando a água enquanto solvente explícito. Com efeito, no trabalho que conduziu a esta tese, realizamos simulações que contabilizam aproximadamente 1 μs-1 para cada um dos dendrímeros em estudo. No que respeita a estes sistemas, isto é muito superior ao tempo simulado em estudos anteriores. Nas últimas décadas a investigacao científica tem beneficiado imenso do avanço das técnicas de simulação computacional, que providenciam resultados e formas de escrutinar sistemas, que são de outra forma normalmente inacessíveis. A dinâmica molecular, especificamente, permite “seguir” a evolução temporal dos átomos que constituem um sistema, através da integração das equações de Newton para o movimento de corpos. É inclusive um dos métodos computacionais de eleição para estudar fenómenos biomoleculares. Os resultados obtidos com esta técnica de amostragem conformacional permitiram-nos analisar e identificar de forma adequada, os detalhes estruturais de cada um dos dendrímeros peptídicos. Colocamos especial ênfase nos arranjos estruturais mais estáveis. As conformações tridimensionais obtidas a partir das trajectórias resultantes das simulações, foram agrupadas de forma a obtermos os ensembles conformacionais característicos de cada dendrímero. Sobre estes conjuntos de conformações realizamos várias análises. Começamos por investigar algumas das propriedades que caracterizam estes sistemas, como o raio de giração, o número total de ligações de hidrogénio, a distância máxima entre os dois átomos mais afastados de cada estrutura, a superfície acessível ao solvente, entre outros. O raio de giração revelou ser a propriedade que individualmente, melhor espelha as variações intrínsecas a estes sistemas. Adicionalmente, procedemos também a caracterização da distribuição dos valores de phi-psi característicos dos diedros de cada um dos dendrímeros. Complementamos esta análise com o estudo das matrizes que reflectem as distãncias mínimas entre os resíduos de todas as conformações. Posteriormente aplicamos metodologias de análise conformacional que envolvem a determinação da energia livre, associada a diferentes coordenadas reaccionais (ou de folding) para cada estrutura nos diferentes ensembles, obtendo assim as correspondentes superfícies energéticas (folding landscapes). Utilizamos esta abordagem por forma a obter folding landscapes bi- e tridimensionais. Em especifíco, utilizamos como coordenadas de folding os valores do raio de giração, do root mean square deviation (RMSD), dos componentes principais do tensor do raio de giração diagonalizado, e os valores para a posição relativa das diferentes conformações, num espaço concordante com a matriz de RMSD, utilizando para tal o método de análise das coordenadas principais (PCoorA). Utilizando o tensor do raio de giração, foi possível investigar a forma dos arranjos estruturais de cada dendrímero peptídico, tendo inclusive sido definido um espaço tridimensional baseado nos componentes principais do tensor diagonalizado (espaço de giração). A capacidade de cada uma destas abordagens para discriminar de forma adequada o espaço das conformações dos dendrímeros peptídicos é discutida ao longo da tese. Dos diversos procedimentos de análise conformacional empregues, resulta uma clara indicação de que, em solução, os dendrímeros peptídicos podem apresentar dois comportamentos preferenciais distintos: estruturas compactas que privilegiam as interacções entre os diferentes resíduos, semelhantes a esferas (sphere-like); e estruturas “abertas” com as diferentes ramificações espaçadas, em que as interacções entre resíduos não adjacentes são minimizadas, semelhantes a taças (bowl-like). Ambas estas configurações atómicas consubstanciam a enorme flexibilidade estrutural que parece caracterizar estas moléculas, dando provas da miríade de estados conformacionais que lhes estão acessíveis. Foi ainda possível verificar a existência de evidências que suportam a ideia de que estas moléculas possuem uma grande robustez estrutural. Isto é, pequenas alterações na composição dos resíduos de amino-ácidos que as constituem não parecem desencadear alterações conformacionais significativas nos arranjos estruturais preferenciais. Através da comparação entre o coeficiente de difusao experimental disponível para um dos dendrímeros, e o coeficiente de difusão calculado com base nas trajectórias obtidas por simulação, foi possível verificar que os modelos utilizados, reflectem de forma adequada os sistemas experimentais. Concluiu-se também que o campo de força (force field) GROMOS 53A6 possui a capacidade de transferabilidade apropriada para lidar com estas moléculas. Os pontos fortes e fracos dos nossos modelos são discutidos ao longo da tese. Durante este trabalho foi ainda desenvolvida e implementada uma metodologia que permite o cálculo eficiente do RMSD entre estruturas dendríticas. As conclusões apresentadas nesta tese podem ser interpretadas juntamente com os resultados experimentais disponíveis, de forma a contribuir para uma compreensão sinérgica da relação entre a estrutura e a função dos dendrímeros peptídicos, lançando as fundações para aplicações inovadoras