A Community-Driven Validation Service for Standard Medical Imaging Objects

Digital medical imaging laboratories contain many distinct types of equipment provided by different manufacturers. Interoperability is a critical issue and the DICOM protocol is a de facto standard in those environments. However, manufacturers' implementation of the standard may have non-conformities at several levels, which will hinder systems' integration. Moreover, medical staff may be responsible for data inconsistencies when entering data. Those situations severely affect the quality of healthcare services since they can disrupt system operations. The existence of software able to confirm data quality and compliance with the DICOM standard is important for programmers, IT staff and healthcare technicians. Although there are a few solutions that try to accomplish this goal, they are unable to deal with certain situations that require user input. Furthermore, these cases usually require the setup of a working environment, which makes the sharing of validation information more difficult. This article proposes and describes the development of a Web DICOM validation service for the community. This solution requires no configuration by the user, promotes validation results share-ability in the community and preserves patient data privacy since files are de-identified on the client side.Comment: Computer Standards & Interfaces, 201

Recuperação de informação multimodal em repositórios de imagem médica

The proliferation of digital medical imaging modalities in hospitals and other diagnostic facilities has created huge repositories of valuable data, often not fully explored. Moreover, the past few years show a growing trend of data production. As such, studying new ways to index, process and retrieve medical images becomes an important subject to be addressed by the wider community of radiologists, scientists and engineers. Content-based image retrieval, which encompasses various methods, can exploit the visual information of a medical imaging archive, and is known to be beneficial to practitioners and researchers. However, the integration of the latest systems for medical image retrieval into clinical workflows is still rare, and their effectiveness still show room for improvement. This thesis proposes solutions and methods for multimodal information retrieval, in the context of medical imaging repositories. The major contributions are a search engine for medical imaging studies supporting multimodal queries in an extensible archive; a framework for automated labeling of medical images for content discovery; and an assessment and proposal of feature learning techniques for concept detection from medical images, exhibiting greater potential than feature extraction algorithms that were pertinently used in similar tasks. These contributions, each in their own dimension, seek to narrow the scientific and technical gap towards the development and adoption of novel multimodal medical image retrieval systems, to ultimately become part of the workflows of medical practitioners, teachers, and researchers in healthcare.A proliferação de modalidades de imagem médica digital, em hospitais, clínicas e outros centros de diagnóstico, levou à criação de enormes repositórios de dados, frequentemente não explorados na sua totalidade. Além disso, os últimos anos revelam, claramente, uma tendência para o crescimento da produção de dados. Portanto, torna-se importante estudar novas maneiras de indexar, processar e recuperar imagens médicas, por parte da comunidade alargada de radiologistas, cientistas e engenheiros. A recuperação de imagens baseada em conteúdo, que envolve uma grande variedade de métodos, permite a exploração da informação visual num arquivo de imagem médica, o que traz benefícios para os médicos e investigadores. Contudo, a integração destas soluções nos fluxos de trabalho é ainda rara e a eficácia dos mais recentes sistemas de recuperação de imagem médica pode ser melhorada. A presente tese propõe soluções e métodos para recuperação de informação multimodal, no contexto de repositórios de imagem médica. As contribuições principais são as seguintes: um motor de pesquisa para estudos de imagem médica com suporte a pesquisas multimodais num arquivo extensível; uma estrutura para a anotação automática de imagens; e uma avaliação e proposta de técnicas de representation learning para deteção automática de conceitos em imagens médicas, exibindo maior potencial do que as técnicas de extração de features visuais outrora pertinentes em tarefas semelhantes. Estas contribuições procuram reduzir as dificuldades técnicas e científicas para o desenvolvimento e adoção de sistemas modernos de recuperação de imagem médica multimodal, de modo a que estes façam finalmente parte das ferramentas típicas dos profissionais, professores e investigadores da área da saúde.Programa Doutoral em Informátic

Project Retrosight. Understanding the returns from cardiovascular and stroke research: Case Studies

Copyright @ 2011 RAND Europe. All rights reserved. The full text article is available via the link below.This project explores the impacts arising from cardiovascular and stroke research funded 15-20 years ago and attempts to draw out aspects of the research, researcher or environment that are associated with high or low impact. The project is a case study-based review of 29 cardiovascular and stroke research grants, funded in Australia, Canada and UK between 1989 and 1993. The case studies focused on the individual grants but considered the development of the investigators and ideas involved in the research projects from initiation to the present day. Grants were selected through a stratified random selection approach that aimed to include both high- and low-impact grants. The key messages are as follows: 1) The cases reveal that a large and diverse range of impacts arose from the 29 grants studied. 2) There are variations between the impacts derived from basic biomedical and clinical research. 3) There is no correlation between knowledge production and wider impacts 4) The majority of economic impacts identified come from a minority of projects. 5) We identified factors that appear to be associated with high and low impact. This report presents the key observations of the study and an overview of the methods involved. It has been written for funders of biomedical and health research and health services, health researchers, and policy makers in those fields. It will also be of interest to those involved in research and impact evaluation.This study was initiated with internal funding from RAND Europe and HERG, with continuing funding from the UK National Institute for Health Research, the Canadian Institutes of Health Research, the Heart and Stroke Foundation of Canada and the National Heart Foundation of Australia. The UK Stroke Association and the British Heart Foundation provided support in kind through access to their archives

Glioma on Chips Analysis of glioma cell guidance and interaction in microfluidic-controlled microenvironment enabled by machine learning

In biosystems, chemical and physical fields established by gradients guide cell migration, which is a fundamental phenomenon underlying physiological and pathophysiological processes such as development, morphogenesis, wound healing, and cancer metastasis. Cells in the supportive tissue of the brain, glia, are electrically stimulated by the local field potentials from neuronal activities. How the electric field may influence glial cells is yet fully understood. Furthermore, the cancer of glia, glioma, is not only the most common type of brain cancer, but the high-grade form of it (glioblastoma) is particularly aggressive with cells migrating into the surrounding tissues (infiltration) and contribute to poor prognosis. In this thesis, I investigate how electric fields in the microenvironment can affect the migration of glioblastoma cells using a versatile microsystem I have developed. I employ a hybrid microfluidic design to combine poly(methylmethacrylate) (PMMA) and poly(dimethylsiloxane) (PDMS), two of the most common materials for microfluidic fabrication. The advantages of the two materials can be complemented while disadvantages can be mitigated. The hybrid microfluidics have advantages such as versatile 3D layouts in PMMA, high dimensional accuracy in PDMS, and rapid prototype turnaround by facile bonding between PMMA and PDMS using a dual-energy double sided tape. To accurately analyze label-free cell migration, a machine learning software, Usiigaci, is developed to automatically segment, track, and analyze single cell movement and morphological changes under phase contrast microscopy. The hybrid microfluidic chip is then used to study the migration of glioblastoma cell models, T98G and U-251MG, in electric field (electrotaxis). The influence of extracellular matrix and chemical ligands on glioblastoma electrotaxis are investigated. I further test if voltage-gated calcium channels are involved in glioblastoma electrotaxis. The electrotaxes of glioblastoma cells are found to require optimal laminin extracellular matrices and depend on different types of voltage-gated calcium channels, voltage-gated potassium channels, and sodium transporters. A reversiblysealed hybrid microfluidic chip is developed to study how electric field and laminar shear can condition confluent endothelial cells and if the biomimetic conditions affect glioma cell adhesion to them. It is found that glioma/endothelial adhesion is mediated by the Ang1/Tie2 signaling axis and adhesion of glioma is slightly increased to endothelial cells conditioned with shear flow and moderate electric field. In conclusion, robust and versatile hybrid microsystems are employed for studying glioma biology with emphasis on cell migration. The hybrid microfluidic tools can enable us to elucidate fundamental mechanisms in the field of the tumor biology and regenerative medicine.Okinawa Institute of Science and Technology Graduate Universit

An architecture for secure data management in medical research and aided diagnosis

Programa Oficial de Doutoramento en Tecnoloxías da Información e as Comunicacións. 5032V01[Resumo] O Regulamento Xeral de Proteccion de Datos (GDPR) implantouse o 25 de maio de 2018 e considerase o desenvolvemento mais importante na regulacion da privacidade de datos dos ultimos 20 anos. As multas fortes definense por violar esas regras e non e algo que os centros sanitarios poidan permitirse ignorar. O obxectivo principal desta tese e estudar e proponer unha capa segura/integracion para os curadores de datos sanitarios, onde: a conectividade entre sistemas illados (localizacions), a unificacion de rexistros nunha vision centrada no paciente e a comparticion de datos coa aprobacion do consentimento sexan as pedras angulares de a arquitectura controlar a sua identidade, os perfis de privacidade e as subvencions de acceso. Ten como obxectivo minimizar o medo a responsabilidade legal ao compartir os rexistros medicos mediante o uso da anonimizacion e facendo que os pacientes sexan responsables de protexer os seus propios rexistros medicos, pero preservando a calidade do tratamento do paciente. A nosa hipotese principal e: os conceptos Distributed Ledger e Self-Sovereign Identity son unha simbiose natural para resolver os retos do GDPR no contexto da saude? Requirense solucions para que os medicos e investigadores poidan manter os seus fluxos de traballo de colaboracion sen comprometer as regulacions. A arquitectura proposta logra eses obxectivos nun ambiente descentralizado adoptando perfis de privacidade de datos illados.[Resumen] El Reglamento General de Proteccion de Datos (GDPR) se implemento el 25 de mayo de 2018 y se considera el desarrollo mas importante en la regulacion de privacidad de datos en los ultimos 20 anos. Las fuertes multas estan definidas por violar esas reglas y no es algo que los centros de salud puedan darse el lujo de ignorar. El objetivo principal de esta tesis es estudiar y proponer una capa segura/de integración para curadores de datos de atencion medica, donde: la conectividad entre sistemas aislados (ubicaciones), la unificacion de registros en una vista centrada en el paciente y el intercambio de datos con la aprobacion del consentimiento son los pilares de la arquitectura propuesta. Esta propuesta otorga al titular de los datos un rol central, que le permite controlar su identidad, perfiles de privacidad y permisos de acceso. Su objetivo es minimizar el temor a la responsabilidad legal al compartir registros medicos utilizando el anonimato y haciendo que los pacientes sean responsables de proteger sus propios registros medicos, preservando al mismo tiempo la calidad del tratamiento del paciente. Nuestra hipotesis principal es: .son los conceptos de libro mayor distribuido e identidad autosuficiente una simbiosis natural para resolver los desafios del RGPD en el contexto de la atencion medica? Se requieren soluciones para que los medicos y los investigadores puedan mantener sus flujos de trabajo de colaboracion sin comprometer las regulaciones. La arquitectura propuesta logra esos objetivos en un entorno descentralizado mediante la adopcion de perfiles de privacidad de datos aislados.[Abstract] The General Data Protection Regulation (GDPR) was implemented on 25 May 2018 and is considered the most important development in data privacy regulation in the last 20 years. Heavy fines are defined for violating those rules and is not something that healthcare centers can afford to ignore. The main goal of this thesis is to study and propose a secure/integration layer for healthcare data curators, where: connectivity between isolated systems (locations), unification of records in a patientcentric view and data sharing with consent approval are the cornerstones of the proposed architecture. This proposal empowers the data subject with a central role, which allows to control their identity, privacy profiles and access grants. It aims to minimize the fear of legal liability when sharing medical records by using anonymisation and making patients responsible for securing their own medical records, yet preserving the patient’s quality of treatment. Our main hypothesis is: are the Distributed Ledger and Self-Sovereign Identity concepts a natural symbiosis to solve the GDPR challenges in the context of healthcare? Solutions are required so that clinicians and researchers can maintain their collaboration workflows without compromising regulations. The proposed architecture accomplishes those objectives in a decentralized environment by adopting isolated data privacy profiles

Chemical imaging analysis of the brain with X-ray methods

Cells employ various metal and metalloid ions to augment the structure and the function of proteins and to assist with vital biological processes. In the brain they mediate biochemical processes, and disrupted metabolism of metals may be a contributing factor in neurodegenerative disorders. In this tutorial review we will discuss the particular role of X-ray methods for elemental imaging analysis of accumulated metal species and metal-containing compounds in biological materials, in the context of post-mortem brain tissue. X-rays have the advantage that they have a short wavelength and can penetrate through a thick biological sample. Many of the X-ray microscopy techniques that provide the greatest sensitivity and specificity for trace metal concentrations in biological materials are emerging at synchrotron X-ray facilities. Here, the extremely high flux available across a wide range of soft and hard X-rays, combined with state-of-the-art focusing techniques and ultra-sensitive detectors, makes it viable to undertake direct imaging of a number of elements in brain tissue. The different methods for synchrotron imaging of metals in brain tissues at regional, cellular, and sub-cellular spatial resolution are discussed. Methods covered include X-ray fluorescence for elemental imaging, X-ray absorption spectrometry for speciation imaging, X-ray diffraction for structural imaging, phase contrast for enhanced contrast imaging and scanning transmission X-ray microscopy for spectromicroscopy. Two- and three-dimensional (confocal and tomographic) imaging methods are considered as well as the correlation of X-ray microscopy with other imaging tools

Vitamin D in the Prevention and Treatment of Multiple Sclerosis

Background: Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS); it is the most common cause of neurological disability in young adults. The cause of MS is unknown but it is believed to be precipitated by both genetic and environmental risk factors. An association between vitamin D deficiency and increased risk of MS has been detected in several epidemiological and case-control studies and is further supported by immunological and genetic studies. It is still unclear whether there is any special age at which exposure to vitamin D deficiency increases the MS risk e.g. is in utero vitamin D deficiency particularly detrimental. Serum levels of vitamin D are associated with both clinical and magnetic resonance imaging (MRI)-assessed disease activity but there have been very few randomized placebo-controlled trials (RCTs) investigating the benefits of vitamin D supplementation in established MS patients. Aims of the study: This study initially investigated the association between vitamin D status during early pregnancy and the risk of MS in the offspring in the Finnish Maternity Cohort. Secondly, we performed the first RCT with vitamin D in MS, evaluating the safety and efficacy of 500 ug weekly dose of vitamin D supplementation or placebo in 68 MS patients receiving interferon beta-therapy. We also studied the mechanism of action of vitamin D supplementation in our study participants. Finally, we updated the MS prevalence and studied the fracture risk and the role of vitamin D in the risk of fractures in MS patients in Southwest Finland. Results: Maternal vitamin D deficiency during early pregnancy was associated with a nearly 2-fold increased risk of MS in their children in comparison with children born to mothers who were non-deficient for vitamin D. In the vitamin D supplementation study there was a statistically significant decrease in the total number of T1 Gadolinium (Gd) enhancing lesions in patients treated with vitamin D in comparison with placebo treated patients. Serum levels of transforming growth factor beta (TGF-β), an immunoregulating cytokine, indirectly measured by a latency-associated peptide (LAP) immunoassay, increased significantly in the vitamin D treated group but not in the placebo group. The prevalence of MS in southwest Finland was 212/105. The relative risk was 1.3 for all types of fractures and 1.5 for osteoporotic fractures in patients with MS compared with matched controls. Conclusions: Correcting vitamin D deficiency during pregnancy may exert a beneficial effect on the risk of the offspring developing MS. Vitamin D supplementation at 500 ug/week influenced the MRI-assessed activity in patients with MS. The immunoregulatory effects of TGF-β may play a role in the improved MRI outcomes observed in our vitamin D treated MS patients. At a mean serum level of 110 nmol/l of 25-hydroxyvitamin D (25(OH)D), its immunological effects can already be detected. We observed a statistically significantly elevated risk of osteoporotic fractures in patients with MS. Several conclusions emerge from our results. First, we recommend correcting vitamin D deficiency during pregnancy at the population level but especially in MS patients planning to become pregnant. Second, we recommend that vitamin D levels should be analyzed in all MS patients after the diagnosis of MS and vitamin D supplementation should be initiated at a dose of 50 to 100 ug/day, targeting serum levels above 100 nmol/l.D-vitamiini MS-taudin ehkäisyssä ja hoidossa Tausta: Multippeliskleroosi eli MS-tauti on keskushermoston krooninen autoimmuunisairaus ja yleisin liikunta- ja toimintakykyyn vaikuttava neurologinen sairaus nuorilla aikuisilla. MS-taudin aiheuttajaa ei tiedetä, mutta sen uskotaan syntyvän perintötekijöiden ja ympäristöriskitekijöiden yhteisvaikutuksesta. D-vitamiinin puute on noussut tärkeäksi MS-taudin ympäristöriskitekijäksi useissa epidemiologisissa ja tapaus-verrokkitutkimuksissa sekä immunologisissa ja geneettisissä tutkimuksissa. Vielä on epäselvää, missä iässä koettu D-vitamiinin puute lisää MS-taudin riskiä ja vaikuttaako esimerkiksi äidin raskaudenaikainen D-vitamiinin puute lapsen riskiin sairastua MS-tautiin. Seerumin D-vitamiinitasojen on todettu olevan yhteydessä MS-taudin kliiniseen ja magneettikuvauksella (MRI) todettavaan aktiivisuuteen, mutta D-vitamiinilisän tehoa jo puhjenneessa MS-taudissa on tutkittu vasta vähän satunnaistetussa lumekontrolloidussa asetelmassa. Tavoitteet: Tämän tutkimuksen tavoitteena oli tutkia äidin raskaudenaikaisen D-vitamiinitason yhteyttä lapsen MS-tautiriskiin Äitiysneuvolakohorttiin kuuluvilla naisilla. Tavoitteenamme oli myös tutkia 500 ug viikossa annosteltavan D-vitamiinilisän tai lumevalmisteen vaikutusta aivojen magneettikuvauksella todettavaan ja kliiniseen tautiaktiviteettiin MS-potilailla, jotka käyttävät interferoni beetaa, sekä selvittää D-vitamiinin immunologisen vaikutuksen mekanismeja näillä potilailla. Tavoitteenamme oli myös päivittää MS-taudin esiintyvyysluvut ja murtumariski MS-potilailla Varsinais-Suomen sairaanhoitopiirin alueella ja tutkia D-vitamiinin yhteyttä MS-potilaiden murtumariskiin. Tulokset: Äidin raskaudenaikainen D-vitamiinin puute oli yhteydessä lapsen lähes kaksinkertaiseen riskiin sairastua MS-tautiin verrattuna niihin lapsiin, joiden äidillä ei ollut D-vitamiinin puutetta. D-vitamiinilisän vaikutuksia selvittäneessä tutkimuksessa D-vitamiinilisää saaneilla potilailla aivojen MRI:ssä nähtävät T1-painotteiset gadoliniumilla (Gd) tehostuvat muutokset vähenivät tilastollisesti merkitsevästi verrattuna lumevalmistetta saaneisiin potilaisiin. Immunologisessa osatutkimuksessa todettiin immuunivastetta vaimentavan sytokiinin, transformoiva kasvutekijä beetan (TGF-β), pitoisuutta mittaavan latency-associated peptide LAP:n pitoisuuden nousevan tilastollisesti merkitsevästi enemmän D-vitamiini- kuin lumeryhmässä. MS-taudin esiintyvyys Varsinais-Suomessa oli 212/105 vuonna 2012. Murtumariski MS-potilailla oli 1.3-kertainen ja osteoporoottisten murtumien riski 1.5-kertainen verrokkeihin nähden. Johtopäätökset: Äidin raskaudenaikaisen D-vitamiinin puutoksen korjaamisesta saattaa olla hyötyä lasten MS-taudin ehkäisyssä. D-vitamiinilisä 500 ug viikossa vähensi aivojen magneettikuvauksella todettavaa MS-taudin aktiivisuutta. TGF-β:n immuunivastetta säätelevillä vaikutuksilla saattaa olla osuus MRI-tuloksiin, jotka havaittiin D-vitamiiniryhmässä. Immunologisia vaikutuksia voitiin todeta keskimäärin D-vitamiinitasolla 110 nmol/l. MS-potilaiden riski saada osteoporoottinen murtuma on merkitsevästi kohonnut. Tulostemme pohjalta suosittelemme D-vitamiinin puutoksen korjaamista raskausaikana sekä väestötasolla että erityisesti MS-potilailla, jotka suunnittelevat raskautta. Suosittelemme D-vitamiinitason määrittämistä kaikilta MS-potilailta ja D-vitamiinilisän aloittamista annoksella 50-100 ug päivässä tavoitteena seerumin D-vitamiinitaso yli 100 nmol/l

Functionalization, growth and applications of single wall carbon nanotubes

Because of their remarkable structural, mechanical and electrical properties, carbon nanotubes, and especially single wall carbon nanotubes (SWNTs), represent one of the most widely investigated materials today in the emerging field of nanotechnology. The development of oriented growth of SWNTs critical for applications, novel approaches for the creation of functional SWNTs, and applications of both as-prepared and chemically functionalized SWNTs for electrochemically-induced hydrogen storage, in-situ formation of new polymer and ceramic nanocomposites with SWNTs, and the fabrication and study for the first time, to the best of our knowledge, of a SWNT-based biofuel cell and self-powered biosensor, are the thrusts of the research discussed in this thesis. Introduction to the science and the potential applications of carbon nanotubes are presented in Chapters 1 to 2 of the thesis, and an overview of the methods used in this work is discussed in Chapter 3. Chapters 4 to 6 discuss the results of the work performed. Spin-coating deposition of a polymer-chelated catalyst precursor on conductive silicon wafers developed for the oriented growth of SWNTs, is discussed in Chapter 4. Oriented growth of SWNTs was obtained using chemical vapor deposition with alcohol as the carbon source. For application in biofuel cells and biosensors (discussed in the final segment), the oriented SWNTs on silicon were functionalized with selected redox enzymes to form the fuel cell and sensor electrodes. In initial tests, a substantial open circuit cell voltage of 200 mV, and analyte-sensitive direct electron transfer, were observed from the fabricated biofuel cell and biosensor devices, respectively. Environmentally friendly, rapid and efficient microwave-induced chemical functionalization of SWNTs was achieved for the first time in the course of this work and is described in Chapter 5 of the thesis. The microwave radiation assisted technique has brought down the functionalization time from days using typical chemical methods, such as refluxing, to the order of minutes. Chemical functionalizations by the microwave method achieved include amidation, 1 ,3-dipolar cycloaddition and nitration, with the latter providing SWNTs that are very soluble in water and alcohol. Both microwave-induced and supercritical carbon dioxide approaches were also used to prepare and study the formation of ceramic (silicon carbide, SiC) and polymer (polymethyl methacrylate, PMMA) nanocomposites with SWNTs, respectively. Electrochemically-induced functionalization of SWNTs by nitro groups and enzymes has been studied in some detail, whereas electrochemical hydrogen storage for fuel cell operation using pristine and functionalized SWNTs as the storage medium has also been studied in this work and discussed in Chapter 6 of this thesis. Strong evidence for electrochemically-induced hydrogen uptake approaching 3 wt % based on thermogravimetric measurements has been obtained on SWNT nanopaper membranes on which the nitrogen-containing conducting polymer, polyaniline, was deposited. A summary of the work performed and suggestions for future work are provided in Chapter 7. The schematic molecular structures of the more complex molecules, polymers and enzymes used in this work (except those shown in the tables) are shown schematically in Appendix A

A critical review of the current state of forensic science knowledge and its integration in legal systems

Forensic science has a significant historical and contemporary relationship with the criminal justice system. It is a relationship between two disciplines whose origins stem from different backgrounds. It is trite that effective communication assist in resolving underlying problems in any given context. However, a lack of communication continues to characterise the intersection between law and science. As recently as 2019, a six-part symposium on the use of forensic science in the criminal justice system again posed the question on how the justice system could ensure the reliability of forensic science evidence presented during trials. As the law demands finality, science is always evolving and can never be considered finite or final. Legal systems do not always adapt to the nature of scientific knowledge, and are not willing to abandon finality when that scientific knowledge shifts. Advocacy plays an important role in the promotion of forensic science, particularly advocacy to the broader scientific community for financial support, much needed research and more testing. However, despite its important function, advocacy should not be conflated with science. The foundation of advocacy is a cause; whereas the foundation of science is fact. The objective of this research was to conduct a qualitative literature review of the field of forensic science; to identify gaps in the knowledge of forensic science and its integration in the criminal justice system. The literature review will provide researchers within the field of forensic science with suggested research topics requiring further examination and research. To achieve its objective, the study critically analysed the historical development of, and evaluated the use of forensic science evidence in legal systems generally, including its role regarding the admissibility or inadmissibility of the evidence in the courtroom. In conclusion, it was determined that the breadth of forensic scientific knowledge is comprehensive but scattered. The foundational underpinning of the four disciplines, discussed in this dissertation, has been put to the legal test on countless occasions. Some gaps still remain that require further research in order to strengthen the foundation of the disciplines. Human influence will always be present in examinations and interpretations and will lean towards subjective decision making.JurisprudenceD. Phil

Decoding Neural Circuits Modulating Behavioral Responses to Aversive Social Cues

Understanding how the human brain functions on a molecular and cellular level is nearly impossible with current technology and ethical considerations. Utilizing the small nematode, Caenorhabditis elegans, and its innate behavioral responses to olfactory social cues, we can begin to unravel the mechanisms underlying social behavior. This is made possible given that innate behaviors are crucial for survival, and therefore hardwired into the genome of organisms. This allows for genetic-level analysis of neural circuitries driving behavior. Studying the neuronal mechanisms underlying C. elegans’ behavioral responses to social cues will not only assist in our overall understanding of how the brain perceives stimuli to enact a behavioral response at the cellular and molecular level, but also our understanding as to how the nervous system properly integrates information to enact social behavioral responses: mis-integration and social abnormalities are commonalities seen in many neuropsychiatric disorders, and these studies will provide fruitful insights into the defects observed in these disorders. Lastly, by comparing the perception of several different types of social chemicals, we can further our understanding of neural coding strategies for the various behaviors crucial for survival. Chapter One of this thesis orients the reader to social, innate behavior, and the usefulness of C. elegans as a tool for understanding behavioral coding. Chapter Two explores and establishes the required components of a socially aversive pheromone, providing insight into signaling evolution and co-option of biological machineries. Chapter Three examines how multiple, competing stimuli are integrated to modulate behavioral output, furthering our understanding of molecular and cellular integration and decision making within the nervous system. Chapter Four highlights the importance of predator pressure, and provides insights into circuit strategies of redundant and promiscuous networks of threat detection. Lastly, Chapter Five considers the implications of these findings as a whole, in the perspective of evolutionary strategies leading to neuronal coding of different behavioral outputs. Taken together, this dissertation aimed to fill the void in our understanding of social behavior neural circuitries, and how integration governed at the molecular and cellular level of the nervous system affects those behaviors