Lane Medical Library

Books by Subject

Biomedical Engineering

  • Digital
    Michael Zabala.
    Rupture of the anterior cruciate ligament (ACL) is one of the most common injuries to the knee. Unfortunately, individuals who experience this injury are likely to develop osteoarthritis of the knee much earlier than would be expected due to the normal ageing process, and this remains true even after surgical reconstruction of the ligament. Research has suggested that a major contributing factor to the development of premature osteoarthritis is altered knee mechanics which change the loading conditions of the cartilage in the joint. Furthermore, it has been shown that altered knee mechanics are present following rupture of the ACL and persist after reconstruction surgery. Despite initial reports, there still remains a need for a comprehensive understanding of both altered knee mechanics in both ACL deficient and ACL reconstructed knees as well as changes in cartilage morphology following ACL injury. Therefore, the goal of this dissertation is to address the question of the relationship between certain changes in knee mechanics and cartilage morphology as they relate to the development of osteoarthritis following both ACL injury and reconstruction. The first study presented involves an analysis of the knee mechanics in individuals with unilateral ACL deficiencies. This group was important in that they were free of knee pain and had no sign of osteoarthritis on MRI over a time frame that ranged up to three decades from injury. This provided a unique opportunity to explore the potential for a protective functional adaption. The results of this study suggest that alteration in knee mechanics may act as a protective mechanism against osteoarthritis development since when subjects were separated into "Short Term" and "Long Term", based upon the time from injury, only those in the "Long Term" group demonstrated a relationship between the external knee flexion moment, which is representative of the interaction between quadriceps and hamstrings muscle to control rotation and translation during walking. This is indicative of an adaptive control mechanism present in some subjects who were able to last many years after the injury without reconstruction surgery. These results suggest the potential for new methods for rehabilitation following ACL injury. The second study presented involves an analysis of the knee mechanics of individuals with unilateral ACL reconstructions during gait, stair ascent, and stair descent at two years from surgery. The results demonstrate a reduction in the external joint moments of ACL reconstructed knees and an increase in the joint moments of uninjured contralateral knees during each activity compared to healthy controls. This suggests two things: 1.) compensation for residual muscle weakness in the affected limb is needed by the contralateral knee during ambulation and 2.) a decrease in daily joint loading in ACL reconstructed knees and an increase in joint loading in contralateral knees. Decreased loading of the ACL reconstructed knee may seem counterintuitive to what was expected in patients who will likely develop premature osteoarthritis in this knee. However, this finding is consistent with the suggestion that changes in joint kinematics and even decreased joint loading following the injury may contribute to the initial cartilage breakdown. Note: Taken together the results of study 1 and 2 suggest that the interaction between muscle function and kinematics should be further considered in the development of knee OA in this population. The third and final study involves articular cartilage morphology analysis of individuals with unilateral ACL reconstructions at two and four years from surgery. The results illustrate differences between cartilage thickness of ACL reconstructed and healthy contralateral knees at both times of testing. The findings show significantly thinner cartilage in the lateral tibial compartment of ACL reconstructed knees at two years from surgery. These differences became more pronounced at four years from surgery and include the addition of a significantly thicker medial region of the tibia of ACL reconstructed knees compared to healthy contralateral knees. The results indicate that patterns of cartilage thickness change are detectable as early two years following ACL reconstruction, and these patterns become more pronounced at 4 years which suggests cartilage begins a degenerative pathway substantially in advance of clinically detectable OA. This finding is important since it provides a basis for assessing early interventions to reduce the risk of knee OA following ACL injury. This dissertation helps to further the understanding of altered knee mechanics following both ACL rupture and reconstruction. In addition, a possible pattern of OA initiation has been reported. Each of these studies will benefit future studies with the ultimate goal of a complete understanding of OA initiation and development in ACL ruptured and reconstructed knees.
  • Digital
    Thais Russomano, Gustavo Dalmarco, and Felipe Prehn Falcão.
  • Digital
    Edwina S. Lai.
    The development of atherosclerosis, a chronic inflammatory disease of the arteries, can usually be attributed to specific regions of the blood vessel. In the straight segments of an artery, endothelial cells (ECs) align with the unidirectional blood flow which commonly occurs in these simple geometries. The elongated and aligned ECs are generally found to have a healthy, athero-resistant phenotype. In contrast, branches or curved vessel geometries have regions of disturbed flow, characterized by low shear stress and high shear stress gradients. In these regions of complicated flow patterns, ECs are non-aligned and have a cobblestone cellular morphology. The non-aligned ECs elicit biological properties that promote atherosclerosis, as the location of atherosclerotic fatty plaque is often found at these bends, branches, or bifurcations. Therefore, this correlation highly suggests that the morphology and biological function are inextricably linked in ECs. The ability to regulate both EC morphology and motility, with the aim to influence EC biology, might be highly beneficial in the prevention or treatment of vascular disease. In this dissertation, anisotropic matrices of collagen nanofibrils were fabricated with a simple flow processing technique and used to investigate fundamental cell-matrix interactions with ECs. The aligned fibrils were able to regulate both the morphology and biology of ECs, thereby suggesting the nanofibrillar collagen can be a useful tool to maintain vascular homeostasis. The ECs elongated and organized their actin cytoskeleton along the direction of the aligned collagen fibrils, as demonstrated by organized actin, microtubule networks, and focal adhesions. The nanofibrillar collagen also promoted increased cellular migration along the direction of the nanofibrils. The quantification of monocyte adhesion and expression level of adhesion molecules, known testing indicators of atherosclerosis development, suggested the aligned nanofibrils also promoted an athero-resistant phenotype in the ECs. ECs are subject to biophysical cues in vivo, either in the form of surface topography (provided by the basement membrane of the ECM) or the hemodynamic effects of blood flow. The combination of these cues regulate the organization and immunogenicity of ECs and is representative of the in vivo environment. Therefore, we also investigated the endothelial behavior when both types of cues (topography and flow) were simultaneously present. At physiological levels of high shear stress (14-17 dynes/cm2), the matrix-aligned ECs were able to resist reorientation despite shear flow perpendicular to the matrix direction. The anisotropic collagen matrix could preserve the alignment and elongation of ECs as well as promote an athero-resistant phenotype after exposure to antagonistic perpendicular flow. The ability of the anisotropic nanofibrillar collagen to regulate cell morphology and especially EC immunogenicity highlights its potential in the treatment of vascular diseases. Therefore, an aligned conduit of collagen nanofibrils was fabricated to address the need for a small-diameter vascular graft capable of regulating cellular function. The vascular graft was designed to have a mechanical integrity comparable to that of native vessels and was able to regulate EC attachment, morphology, and phenotype. In addition, the aligned collagen grafts could support an anti-thrombogenic surface modification, providing short-term patency in the carotid artery model of Sprague-Dawley rats.
  • Digital
    Jonathan Joi-Mun Wong.
    The heart is an essential heterogeneous organ that depends on strong coupling between electrical, chemical, and mechanical dynamics to properly function as a pump that supplies blood to the rest of the body. Cardiac arrhythmias are common disorders characterized by irregular beating of the heart that lead to serious clinical conditions. It is estimated that approximately 2.2 million adults in the United States are affected by atrial fibrillation, a prevalent arrhythmia. Unfortunately, a clinician often does not have enough information to diagnose a patient's heart condition to determine the optimal treatment procedure. This is an area that computational mechanics can address. While development of mechanical and electrophysiological models of cardiac tissue primarily started in the 1950s, fully-coupled models have only more recently been developed due to factors regarding computational cost, difficulty in quantifying material properties, and difficulty in integrating complex models in a cohesive and efficient manner. Therefore, in order for simulation tools to have impact in the clinical or experimental setting, these tools must be efficient, fast, robust, and accessible. The focus of this thesis is to develop methods of addressing the aforementioned issues and then illustrate how efficient electromechanical finite element models can be developed for the heart such that their use in the clinical and experimental setting can be realized in several examples. In this thesis, a global-local variable splitting formulation borrowed from the field of plasticity is used to address the issues of complex model integration, and to maintain numerical stability at low costs. Through careful examination of classical phenomenological models and detailed biophysical ionic models of the electrophysiology of the heart, almost all models can be reformulated into this global-local splitting framework. The numerical properties of cost-expensive ionic models are briefly analyzed within the context of this framework. Use of implicit-time stepping in tandem with a simple iteration and error tolerance based adaptive time-stepping algorithm allows for reduction of computation time from hours to minutes. Flexibility and modularity of the framework are illustrated through the development of electrical, electro-chemical, electro-chemical-mechanical, and opto-electro-mechanical models of cardiac tissue. The heart is modeled efficiently using custom finite element ventricular cell models for physiological electrical simulations and large deformation excitation-contraction dry-pumping simulations of the heart. The results accurately model the physiological condition of the heart. The flexibility and multiscale nature of the framework is also leveraged in developing novel optical-induced cardiac cell excitation models of new genetically engineered Channelrhodpsin-2 (ChR2) cardiac myocytes. An ionic model was developed for these particular bio-engineered stem cells, calibrated with experimental data from collaborators, and was able to predict the electrical excitation behavior of the cells to a reasonable degree of accuracy. This model was then combined with ionic pacemaker cell models and also with ventricular cell models into respective finite elements to simulate experiments and predict future therapies using ChR2 genetically modified cardiac tissue. The thesis also addresses difficulties relating to identification and characterization of material parameter identification in inhomogeneous cardiac tissue. Metrics for determining smoothness in electrical conduction in tissue cultures were validated with stochastic finite element models of microelectrode array cell conduction experiments. The results indicate that these metrics are useful in characterizing different conduction patterns based on two metrics borrowed from texture analysis. Difficulties in obtaining structural fiber data from clinical images were addressed by developing an algorithmic method for designating approximate physiologically accurate fiber distributions for the heart using only geometrical information obtained from MRI scans of the surfaces of the heart. Poisson interpolation is used and results in a smooth continuous rotating fiber description that matches experimentally obtained fiber directions from MRI scans. The main benefits of this algorithm are its simplicity of implementation, physiologically accuracy, and generality in interpolating fiber distributions. Lastly, the thesis demonstrates possible benefits of GPU computing in order to achieve near-real-time electrical simulations of arrhythmias in the heart. The assembly and solver routines from the finite element code, FEAP from Berkeley, were ported to the GPU using CUDA. Even with a minimally optimized proof-of-concept, the GPU-only finite element code achieves performance comparable to twelve cores using only one GPU. To increase the overall efficiency of the method, current sparse matrix vector multiplication GPU algorithms are analyzed, and possible alternative algorithms are developed specifically with unstructured finite element meshes in mind. Altogether, the different methods developed in this thesis have been shown to be effective in addressing issues related to efficiency, numerical stability, modularity, and flexibility in real computational applications of the heart. Special consideration was taken in designing the different methods to be compatible with one another, such that a majority of the methods could be integrated and the benefits of each method could be leveraged with each other to gain maximum efficiency. While these developed methods can still be improved, the thesis work as a whole serves to demonstrate and highlight future uses for computational models within experimental and clinical settings.
  • Digital
    edited by Anish Khan, Mohammad Jawaid, Aftab Aslam Parwaz Khan, and Abdullah M. Asiri.
    Wiley2018
    "A comprehensive and up-to-date overview of the latest research trends in conductive polymers and polymer hybrids, summarizing recent achievements. The book begins by introducing conductive polymer materials and their classification, while subsequent chapters discuss the various syntheses, resulting properties and up-scaling as well as the important applications in biomedical and biotechnological fields, including biosensors and biodevices. The whole is rounded off by a look at future technological advances. The result is a well-structured, essential reference for beginners as well as experienced researchers."-- Provided by publisher.
  • Digital
    Hesaam Esfandyarpour.
    The Human Genome Project was accomplished by a reduction in the cost of DNA sequencing by three orders of magnitude. Further cost reductions are required for sequencing to become a standard tool in clinical medicine and to enable personalized medicine via individual genome sequencing. The current cost varies between $50k to $100k over a period of months; depend on the technology, accuracy and read-length. It is desired to reduce the cost to $1000 per genome to enable profiling of individuals genome. To achieve this goal, a highly integrated platform with simplified chemistry is required. In this dissertation, we introduce a novel method for DNA sequencing based on electrical detection of polymerization reaction, called "Thermo/pH sequencing". Our proposed method is based on the direct measurement of the heat release or the pH modulation (change of H+ ion concentration in the solution) during DNA extension. For high throughput DNA sequencing, DNA strands are immobilized to small micron-size beads in a microfluidic platform. The DNA-beads are in a reaction mixture in contact with an array of sensitive micro-machined heat or pH sensors, which detect the electrical signature from incorporation of a complementary base (dNTP) in the presence of appropriate reagents (DNA polymerase, and polymerase reaction buffer). This results to a label-free, long-read and fast chemistry; 10x reduction in reagent cost with 10x increase in throughput can potentially yield to significant improvement in the cost of genome sequencing to less than $1000. In addition, substituting optical detection set-up with microelectronic sensor reduces the capital cost of sequencing instruments from $500k to less than $50k. We demonstrate the proof of concept for this technology at large scale. Then we describe the development of an appropriate microfluidic platform and two micromachined electrical biosensors that employ electrical detection for heat or pH detection. Both versatile platforms can be multiplexed and have the potential of providing rapid and inexpensive measurements without any compromise in the sensitivity, making them good potential candidates for use in the clinical setting. We report a chip-based integrated differential microfluidic nanocalimeters with on-chip injection and multiplexing unit, capable of characterizing the heat of reaction with unprecedented 2-nW resolution in 1 Hz bandwidth for nanoliter scale samples. We successfully demonstrate DNA Thermosequencing with sequential injection of different nucleotides into the integrated microfluidic calorimeter device. In addition, the device can serve as a powerful tool to characterize a variety of the biomedical processes, such as metabolic activities of microorganisms, living cells and catalyzed reactions. We also present a microfabricated device in microfluidics for pH sequencing, called nanoneedle biosensor. The key element for this device is a 10nm wide gap on the end of the needle of total diameter about 100nm. Any change in the population of molecules in this gap results in a change of impedance across the gap; single molecule detection should be possible. In addition, DNA-beads can be allocated iv near the sensors to measure the pH change during DNA extension. The design, fabrication, testing, optimization and a modified structure of the device for higher signal to noise ratio are presented. Toward an integrated sequencer platform, automation and reduced labor cost, higher throughput, accuracy and efficiency for genomics and proteomics analysis; further integration and optimization of the presented systems are required. We envision the integration of our CMOS-compatible devices with a CMOS integrated circuitry into a high throughput gene sequencer or proteomics system. The proteomics system enables multiplex analysis using an array of micro-channels for probing clinically relevant samples such as the human serum for various protein and nucleic acid biomarkers for cancer detection, and also the detection of pathogenic bacteria in solution.
  • Digital
    John G. Webster, editor in chief.
  • Digital
    Monica Elise Ortiz.
    Evolution has selected for organisms that benefit from genetically encoded cell-cell communication. We observe cell-cell communication throughout every scale in nature, from simple single-celled bacteria to complex multicellular mammals. Engineers have begun to repurpose elements of natural communication systems to coordinate their own population-level behaviors, including oscillations and programmed pattern formation. Existing engineered systems, however, rely on small, system-specific biomolecules to send messages among cells. However, such molecules are capable of sending only a single message, typically "regulate transcription.'' Thus, the information transmission capacity of such biological communication systems is fundamentally limited. Through this thesis, I demonstrated the decoupling of messages from a common communication channel via the autonomous transmission of numerous arbitrary genetic messages. To do so, I engineered a cell-cell communication platform using bacteriophage M13 gene products to autonomously package and deliver heterologous DNA messages of varying lengths and encoded functions. Further, I increased the range of engineered DNA messaging across semisolid media by coupling message transmission or receipt to active cellular chemotaxis. Through this coupling, I demonstrated that our system is adaptable to different contexts by creating simple patterns. Finally, using recombinase-mediated logic gates developed within the Endy laboratory, I demonstrated the ability to program bacteria by transmitting logic gates to surrounding cells. Overall, this work significantly enhances the suite of cell-cell communication tools available to engineers. I have shown that a variety of DNA messages can be transmitted among cells and have moved the field of synthetic biology closer to designing synthetic ecologies with more complex communication schemes and varied behaviors.
  • Digital
    Sarah Jean Moore.
    Proteins and peptides are an incredibly versatile class of biological molecules, with a vast array of naturally occurring functions. In cancer, the natural roles of proteins become incorrectly regulated, and the presence of cancer-related proteins on tumor cells can be detected and targeted for diagnosis and treatment. This thesis decribes novel engineered peptides for molecular recognition of cell surface receptors expressed in cancers, and application of these engineered peptides as diagnostic agents to identify solid tumors in mouse models. For this work. three different cystine-knot peptides were used for development and engineering: Agatoxin (AgTx), Agouti-related protein (AgRP), and Ecballium elaterium trypsin inhibitor-II (EETI). In addition, two protein receptors were employed as model tumor targets relevant for molecular imaging of cancer: carbonic anhydrase IX (CA IX) and tumor associated integrin receptors. New methods were developed towards engineering AgTx and AgRP to bind CA IX, and work to produce these peptides for further study and their limitations are described. In a parallel line of research, to further understand the promise of using knottin peptides in cancer imaging, the influence of amino acid loops on tissue biodistribution was examined using engineered AgTx, AgRP, and EETI peptides that bind tumor target integrins in mouse xenograft models. Finally, an engineered EETI knottin peptide that binds tumor-associated integrins was shown to specifically target and illuminate brain tumors in mouse models of medulloblastoma. Importantly, the protein engineering methods and molecular imaging applications described here have promise for influencing the clinical outcome of cancer patients through image-guided surgical resection, disease staging and management, and monitoring the effectiveness of therapeutic treatments.
  • Digital/Print
    Luiz E. Bertassoni, Paulo G. Coelho, editors.
    Digital : Springer2015
    Print2015
    This book offers a comprehensive overview of current challenges and strategies to regenerate load-bearing and calcified human tissues, including bone, cartilage,tendon, ligaments and dental structures (dentin, enamel, cementum and periodontal ligament). Tissue engineering has long held great promises as an improved treatment option for conditions affecting mineralized and load-bearing structures in the body. Although significant progress has been achieved in recent years, a number of challenges still exist. Scaffold vascularization, new biofabrication methods (3D printing, lithography, microfabrication), peptide conjugation methods, interface engineering, scaffold mechanical properties, iPS cells, organs-on-a-chip, are some of the topics discussed in this book. More specially, in the first section readers will find an overview of emerging biofabrication methods. In section 2, applied strategies for regeneration of (2.1) bone, cartilage and ligament, as well as (2.2) dentin, cementum, enamel and periodontal ligament are discussed across 14 chapters. While other volumes have addressed the regeneration of individual tissues, or exclusively focused on different regenerative strategies, the focus of this work is to bring together researchers integrating backgrounds in materials sciences, engineering, biology, mechanics, fluidics, etc, to address specific challenges common to regeneration of several load-bearing and calcified tissues. Therefore, this book provides a unique platform to stimulate progress in the regeneration of functional tissue substitutes. We envision that this book will represent a valuable reference source for university and college faculties, post-doctoral research fellows, senior graduate students, and researchers from R&D laboratories in their endeavors to fabricate biomimetic load bearing tissues.
  • Digital
    Sheng Ding.
    Recombinant proteins have been used widely in both basic research and biomedical applications including protein therapeutics and biomaterials. Many efforts have been devoted to the investigation of novel synthetic strategies for producing recombinant proteins for various applications, which is the focus of this dissertation. In the first section, a biosynthetic strategy was developed to produce collagenous proteins with post-translational modifications in E. coli. Collagen is the most abundant protein in human, and plays a dominant role in maintaining the biological and structural integrity. Recombinant expression of collagens and fragments of collagens is often difficult as their stability requires appropriate proline hydroxylation. Prolyl 4-hydroxylases (P4H) are ascorbate-dependent oxygenases that play key roles in collagen folding by catalyzing the post-translational hydroxylation of specific proline residues on target proteins to form (2S, 4R)-4-hydroxyproline. Thus far, the study of these post-translational modifications has been limited by the lack of a prokaryotic recombinant expression system for producing hydroxylated proteins. Unlike eukaryotic cells such as yeast and insect cells, bacterial cytoplasm cannot activate P4H, which requires an ascorbate co-factor that bacteria do not produce. By introducing a biosynthetic shunt to produce ascorbate-like molecules in E. coli cells that heterologously express human P4H, we have created a strain of E. coli that produces collagenous proteins with (2S, 4R)-4-hydroxyproline. Different levels of proline hydroxylation can be obtained by tuning culture conditions. We have verified that hydroxylation of collagenous materials produced in the new system leads to an increase in thermostability. Using this new system, we have observed hydroxylation patterns indicative of a processive catalytic mode for P4H that is active even in the absence of ascorbate. Our results provide insights into P4H enzymology, and create a foundation for better understanding how post-translational hydroxylation affects proteins. Further, we applied the novel E. coli expression system to produce a collagenous protein, adiponectin, which has many beneficial effects on obesity-related metabolic and cardiovascular disorders, and reverses insulin insensitivity. By introducing key post-translational modification enzymes to E. coli, we have endowed the expression system with capabilities of making necessary modifications on adiponectin for its correct assembly, and thus obtained biomimetic adiponectins. High-molecular weight (HMW) multimers of adiponectin have been obtained, and their biological activities of suppressing endothelial cell apoptosis have been confirmed with in vitro cell assays. In section 2, modular protein polymers have been created through genetic engineering and enzymatically crosslinked into hydrogels with tunable properties. The many challenges currently faced in regenerative medicine research require the development of new, modular biomaterial systems that can serve as scaffolds for cellular maintenance, expansion and growth, and which can be tuned by the user to mimic any necessary aspects of natural ECM to an optimal degree. Toward this goal, we have created a family of block co-polypeptides comprising amino acid sequence elements that allow mild enzymatic crosslinking into gels. These new families of protein polymers were designed to be linear, random coil, and contain either lysine or glutamine, which have the recognition substrates for transglutaminase (TG) crosslinking, evenly spaced along the protein backbone. Crosslinking occurred within two minutes upon the addition of TG under physiological conditions, as determined by particle tracking microrheology. The material properties of the gel can be tuned with the hydrogel composition to mimic cellular microenvironment of different tissues. Furthermore, in order to introduce biofunctionalities into the hydrogels, a versatile expression vector has been engineered that allows the insertion of bioactive protein domains into these block co-polypeptide. For example, a cell adhesion signal based on the RGD sequence from human fibronectin was incorporated. The RGD-containing hydrogel was successful in enhancing cell adhesion, and were also proven to be compatible with the culture of mesenchymal stem cells. The specific nature of these protein polymer precursors of the modular hydrogel composition allows tailoring of mechanical and biochemical properties, rendering these gels valuable for various tissue engineering applications.
  • Digital
    edited by Rebecca A. Bader, David A. Putnam.
    Wiley2014
    Polymers have played a critical role in the rational design and application of drug delivery systems that increase the efficacy and reduce the toxicity of new and conventional therapeutics. Beginning with an introduction to the fundamentals of drug delivery, Engineering Polymer Systems for Improved Drug Delivery explores traditional drug delivery techniques as well as emerging advanced drug delivery techniques. By reviewing many types of polymeric drug delivery systems, and including key points, worked examples and homework problems, this book will serve as a guide to for specialists and non-
  • Digital/Print
    edited by Ngan F. Huang, Nicolas L'Heureux, Song Li.
    Digital : World Scientific2018
    Print2018
    Mesenchymal stem cells for tissue regeneration / Guang Yang, Song Li and Ngan F. Huang -- Delivery vehicles for deploying mesenchymal stem cells in tissue repair / Ben P. Hung, Michael S. Friedman and J. Kent Leach -- Stem cells for cardiac tissue engineering / Jennifer L. Young, Karen L. Christman and Adam J. Engler -- Engineered mechanical factors to mature pluripotent stem cell-derived cardiomyocytes / Alexandre J.S. Ribeiro, Robin E. Wilson and Beth L. Pruitt -- Cardiovascular system : stem cells in tissue-engineered blood vessels / Rajendra Sawh-Martinez [and 5 others] -- Stem cell-derived endothelial cells for cardiovascular regeneration / Luqia Hou and Ngan F. Huang -- Angiogenic cytokines in the treatment of ischemic heart disease / Michael J. Paulsen and Y. Joseph Woo -- Adipose tissue engineering and stem cells / D. Adam Young, Brian Mailey, Jennifer Baker, Anne M. Wallace and Karen L. Christman -- Engineering cartilage : from materials to small molecules / Jeannine M. Coburn and Jennifer H. Elisseeff -- Adult stem cells for articular cartilage tissue engineering / Sushmita Saha, Jennifer Kirkham, David Wood, Stephen Curran and Xuebin B. Yang -- Stem cells for disc repair / Ann Ouyang, Aliza A Allon, Zorica Buser, Sigurd Berven and Jeffrey C. Lotz -- Clinical applications of a stem cell-based therapy for oral bone reconstruction / Thomas Eshraghi and Bradley McAllister -- Skeletal tissue engineering : progress and prospects / Nicholas J. Panetta, Deepak M. Gupta and Michael T. Longaker -- Recent advances and future perspectives on cell reprogramming / Bilal Cakir, Kun-Yong Kim and In-Hyun Park -- High-throughput systems for stem cell engineering / David A. Brafman, Karl Willert and Shu Chien -- Novel methods for characterizing and sorting single stem cells from their tissue niches / Ju Li, Eric Jabart, Sachin Rangarajan and Irina Conboy -- Label-free microfluidic techniques to isolate and screen single stem cells / Eric Jabart, Karthik Balakrishnan and Lydia L. Sohn -- Microscale technologies for tissue engineering and stem cell differentiation / Jason W. Nichol [and 5 others] -- Designing protein-engineered biomaterials for stem cell therapy / Lei Cai and Sarah C. Heilshorn -- Quality control of autologous cell and tissue-based therapies / Nathalie Dusserre, Todd McAllister and Nicolas L'Heureux -- Regulatory challenges for cell-based therapeutics / Todd McAllister, Corey Iyican and Nicolas L'Heureux.
  • Digital
    edited by Kursad Turksen, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
    Springer Protocols2014
    Differentiation of Human Induced Pluripotent Stem Cells into a Keratinocyte Lineage / Igor Kogut, Dennis R. Roop, and Ganna Bilousova -- Differentiation of Epidermal Keratinocytes from Human Embryonic Stem Cells / Fahad K. Kidwai, Tong Cao, and Kai Lu -- Protocol for Serial Cultivation of Epithelial Cells Without Enzymes or Chemical Compounds / Dongxia Ye and Antonio Peramo -- Growth and Differentiation of HaCaT Keratinocytes / Van G. Wilson -- Transgene Delivery to Cultured Keratinocytes Via Replication-Deficient Adenovirus Vectors / Vincent P. Ramirez and Brian J. Aneskievich -- Analyzing the Global Chromatin Structure of Keratinocytes by MNase-Seq / Jason M. Rizzo and Satrajit Sinha -- Analysis and Meta-Analysis of Transcriptional Profiling in Human Epidermis / Claudia Mimoso, Ding-Dar Lee, Jiri Zavadil, Marjana Tomic-Canic, and Miroslav Blumenberg -- Compound Screening and Transcriptional Profiling in Human Primary Keratinocytes: A Brief Guideline / Raphaela Rid, Harald Hundsberger, and Kamil Önder -- Preparation of Primary Cultures of Mouse Epidermal Keratinocytes and the Measurement of Phospholipase D Activity / Lakiea J. Bailey, Vivek Choudhary, Purnima Merai, and Wendy B. Bollag -- Lipid Rafts and Detergent-Resistant Membranes in Epithelial Keratinocytes / Kathleen P. McGuinn and Mỹ G. Mahoney -- MMP-2, 9 and TIMP-1, 2 Assays in Keratinocyte Cultures / Takashi Kobayashi -- Reactive Oxygen Species (ROS) Protection Via Cysteine Oxidation in the Epidermal Cornified Cell Envelope / Wilbert P. Vermeij and Claude Backendorf -- Modified Methods for Growing 3-D Skin Equivalents: An Update / Rebecca Lamb and Carrie A. Ambler -- A Novel Three-Dimensional Cell Culture Method to Analyze Epidermal Cell Differentiation In Vitro / Yoji Okugawa and Yohei Hirai -- Reconstruction of Normal and Pathological Human Epidermis on Polycarbonate Filter / Evelyne De Vuyst, Céline Charlier, Séverine Giltaire, Valérie De Glas, Catherine Lambert de Rouvroit, and Yves Poumay -- Methods for the Preparation of an Autologous Serum-Free Cultured Epidermis and for Autografting Applications / John J. Wille, Jeremy J. Burdge, and Jong Y. Park -- Human Keratinocyte Cultures in the Investigation of Early Steps of Human Papillomavirus Infection / Laura M. Griffin, Louis Cicchini, Tao Xu, and Dohun Pyeon -- Preparation and Delivery of 4-Hydroxy-Tamoxifen for Clonal and Polyclonal Labeling of Cells of the Surface Ectoderm, Skin, and Hair Follicle / Christine Chevalier, Jean-François Nicolas, and Anne-Cécile Petit -- Microdissection and Visualization of Individual Hair Follicles for Lineage Tracing Studies / Inês Sequeira, Emilie Legué, Suzanne Capgras, and Jean-François Nicolas -- Isolation and Characterization of a Stem Cell Side-Population from Mouse Hair Follicles / Paula L. Miliani de Marval, Sun Hye Kim, and Marcelo L. Rodriguez Puebla -- Multi-Scale Mathematical Modeling and Simulation of Cellular Dynamical Process / Shinji Nakaoka -- Erratum.
  • Digital
    edited by Kursad Turksen.
    Springer Protocols2010
    Isolation of adult mouse stem keratinocytes using magnetic cell sorting (MACS) / Corina Lorz [and others] -- Functional investigations of keratinocyte stem cells and progenitors at a single-cell level using multiparallel clonal microcultures / Nicolas O. Furtunel [and others] -- Growth and stratification of epithelial cells in minimal culture conditions / Federica Riva [and others] -- Matched cultures of keratinocytes and fibroblasts derived from normal and NER-deficient mouse models / Alex Pines and Claude Backendorf -- Establishment of spontaneously immortalized keratinocyte lines from wild-type and mutant mice / Julia Reichelt and Ingo Haase -- Study of epidermal differentiation in human kertinocytes cultured in autocrine conditions / Frédéric Minner, Franc̦oise Herphelin, and Yves Poumay -- Directed differentiation of human embryonic stem cells to epidermal progenitors / Christian M. Metallo [and others] -- Expression and analysis of exogenous proteins in epidermal cells / Lina Dagnino, Ernest Ho, and Wing Y. Change -- Using siRNA knockdown in HaCaT cells to study transcriptional control of epidermal proliferation potential / Julie Wells and Xing Dai -- RNA interference in keratinocytes and an organotypic model of human epidermis / Cory L. Simpson, Shin-ichiro Kojima, and Spiro Getsios -- Scanning for transcription factor binding by a variant EMSA / Igor Gurevich, Carmen Zhang, and Brian J. Aneskievich -- Chromatin immunoprecipitation for identifying transcription factor targets in kertinocytes / Kori Ortt and Satrajit Sinha -- Gene expression profiling of mouse epidermal keratinocytes / Ramón García-Escudero and Jesús M. Paramio -- Analysis of tissue-specific gene expression using laser capture microdissection / Martin Ruetze [and others] --Comprehensive transcriptional profiling of human epidermis, reconstituted epidermal equivalents, and cultured keratinocytes using DNA microarray chips / Din-Dar Lee [and others] -- Molecular profiling of the epidermis : a proteomics approach / Jianjun Shen and Susan M. Fischer -- Detection of gene expression in embryonic tissues and stratified epidermis by in situ hybridization / Maria I. Morasso -- Embryonic mammary anlagen analysis using immunolabelling of whole mounts / Heena Panchal, Olivia Wansbury, and Beatrice A. Howard -- Whole-mount assays for gene induction and barrier formation in the developing epidermis / Carolyn Byrne [and others] -- Tetracycline-regulated gene expession in transgenic mouse epidermis / Rose-Anne Romano and Satrajit Sinha -- A versatile murine 3D organotypic model to evaluate aspects of wound healing and epidermal organization / Eve Kandyba, Malcolm Hodgins, and Patricia Martin -- Optical and biochemical dissection of connexin and disease-linked connexin mutants in 3D organotypic epidermis / Stéphanie Langlois, Jared M. Churko, and Dale W. Laird -- Cytokine release in tissue-engineered epidermal equivalents after prolonged mechanical loading / Lisette H. Cornelissen [and others] -- Three-dimensional human tissue models of wounded skin / Christophe Egles, Jonathan A. Garlick, and Yulia Shamis -- In vivo transplantation of genetically modified mouse embryonic epidermis / Ana Belén Martínez-Cruz [and others] -- A transplant model for human epidermal skin regeneration / Sophie Paquet-Fifield [and others] -- Identification of epithelial stem cells in vivo and in vitro using keratin 19 and brdU / Danielle Larouche [and others] -- Isolation and culture of hair follicle pluripotent stem (hfPS) cells and their use for nerve and spinal cord regeneration / Yasuyuki Amoh and Robert M. Hoffman -- Limiting dilution analysis of murine epidermal stem cells using an in vivo regeneration assay / Lauren R. Strachan and Ruby Ghadially.
  • Digital
    editors, Robert Lanza ... [et al.].
    ScienceDirect2009
    Introduction to stem cells -- Basic biology/mechanisms -- Tissue and organ development -- Methods -- Applications -- Regulation and ethics.
  • Digital
    Laura Astolfi and Fabio Babiloni.
  • Digital
    Monique Frize.
    Atypon2011
    Increasingly, biomedical scientists and engineers are involved in projects, design, or research and development that involve humans or animals. The book presents general concepts on professionalism and the regulation of the profession of engineering, including a discussion on what is ethics and moral conduct, ethical theories and the codes of ethics that are most relevant for engineers. An ethical decision-making process is suggested. Other issues such as conflicts of interest, plagiarism, intellectual property, confidentiality, privacy, fraud, and corruption are presented. General guidelines, the process for obtaining ethics approval from ethics Review Boards,and the importance of obtaining informed consent from volunteers recruited for studies are presented. A discussion on research with animals is included. Ethical dilemmas focus on reproductive technologies, stem cells, cloning, genetic testing, and designer babies. The book includes a discussion on ethics and the technologies of body enhancement and of regeneration. The importance of assessing the impact of technology on people, society, and on our planet is stressed. Particular attention is given to nanotechnologies, the environment, and issues that pertain to developing countries. Ideas on gender, culture, and ethics focus on how research and access to medical services have, at times, been discriminatory towards women. The cultural aspects focus on organ transplantation in Japan, and a case study of an Aboriginal child in Canada; both examples show the impact that culture can have on how care is provided or accepted. The final section of the book discusses data collection and analysis and offers a guideline for honest reporting of results, avoiding fraud, or unethical approaches. The appendix presents a few case studies where fraud and/or unethical research have occurred.
  • Digital
    Polina A. Segalova.
    Abdominal aortic aneurysms (AAA's) are characterized by a permanent and irreversible enlargement of the abdominal aorta to at least 150 percent its expected normal size. Endovascular treatment of AAA's with endografts has gained tremendous popularity in the last decade, largely due to decreased perioperative mortality and faster recovery times, when compared to open surgical repair. Although endografts are an appealing treatment option for many patients, some device design and safety issues have yet to be addressed. One of the biggest problems with endografts is their tendency to shift their position in the patient anatomy over time. The forces that cause this shift and their relation to endograft design are not well understood. In addition, the degree of blood damage due to the insertion of an endograft into the abdominal aorta has not been quantified. The following studies were completed in order to investigate the issues described above. 1. Calculation of endograft displacement force in patient-specific device models. This study used electron-beam computed tomography (CT) image data to generate patient-specific anatomical models using novel segmentation techniques. The patient models were then virtually modeled to represent three different endograft designs, based on aortic stent-graft devices already available in the U.S. or currently in clinical trials. Computational Fluid Dynamics (CFD) simulations were run to characterize the hemodynamic factors for each patient and a total displacement force was calculated for each model. Results show that the location of the device bifurcation impacts the overall displacement force, with proximal bifurcation endograft designs generating a lesser force than distal bifurcation designs. 2. Characterization of blood damage due to endograft placement. Patient-specific computational models were created to represent endograft features that partially obstruct blood flow to the renal arteries, which is sometimes necessary to attain complete exclusion of the aneurysm after deploying the device. Findings show that the insertion of an endograft causes a two-fold increase in blood damage. However, the magnitude of blood damage is within acceptable safety standards. 3. Benchtop testing of red blood cell damage. A benchtop experimental setup was created to measure the damage to red blood cells under various flow conditions and flow obstructions. Samples were characterized at different time points using light scatter methods to determine cell volume and hemoglobin concentration. Results indicate that significant damage to red blood cells occurs only after prolonged exposure (> 103 seconds) to high shear (> 4000 dynes/cm2) conditions. In addition, the presence of flow obstructions creates red blood cell fragments, instead of destroying the cells entirely. Future directions for this work include additional CFD modeling of devices in more patients treated with different aortic stent graft designs to derive statistical significance relative to various design and anatomical features and extend the analysis to the evaluation of devices used for the treatment of thoracic aortic aneurysms (TAA's). Follow-up studies on device migration studies can also be completed in the cohort of patients where the endograft displacement forces were calculated. Further, blood damage models that incorporate the fragmentation of red blood cells can be developed.
  • Digital
    Erica M. Cherry.
    Magnetic drug targeting (MDT) is a noninvasive medical technique that has been proposed for treating diseases that are localized in the body. Currently, drugs meant to treat such conditions are inefficient and often damage healthy tissue because they spread throughout the blood stream. MDT combats this problem by steering the majority of the medicine to the right location in the body. An ideal MDT treatment would involve chemically binding the drug to magnetic particles, injecting the particles into the bloodstream, magnetically steering them through the arterial network, and trapping them near the diseased area so the drug they carry has time to diffuse into the surrounding tissue. There is still much to learn about how to manufacture drug-coated magnetic particles, image these particles in vivo, and control them using magnetic fields. This thesis focuses on understanding the dynamics of magnetic particles moving through the blood stream. A preliminary simulation and experiment were performed to determine realistic ranges of particle, flow, and magnetic field parameters within which MDT could work. Based on the results, an expanded simulation was performed and used to predict optimal conditions for successful magnetic drug targeting. The preliminary simulation and experiment evaluated the feasibility of stopping magnetic particles in a straight tube flow with conditions similar to those in a large artery. It was found that unrealistically high magnetic field gradients were needed to control particles small enough to safely inject into the circulatory system because the fluid drag force on the particles was too large to overcome with magnetic force. Composite spheres, made of micron-sized magnetic particles embedded in agarose (which could potentially be broken up in vivo), were much easier to control magnetically in the same setup. In order to develop an understanding of the dynamics of a cluster of small magnetic particles moving through the circulatory system, an expanded simulation was developed to track the motion of such a cluster in an artery-like flow. The hope was that the presence of an extended cloud of particles would reduce the average drag force per particle and thus small particles would be easier to control magnetically. Three unclosed forces needed to be modeled for this simulation. First, the viscous force on the particles was computed by formulating a non-Newtonian model for blood. Extensive simulations showed that non-Newtonian arterial flows differed significantly from Newtonian ones even in large arteries. Second, the interparticle magnetic force was calculated by developing a numerical method that summed magnetic interactions between grid cells instead of individual particle pairs. This approach is much more efficient than summing the forces for all particle pairs and is accurate as long as the grid is well-resolved and the local gradients of magnetic particle concentration are nonzero. Finally, the dispersion coefficient of the particles caused by their interactions with blood cells was computed by performing a separate Monte Carlo simulation of particles moving through a field of red blood cells with variable shear rate, hematocrit, and particle terminal velocity. The results of the expanded simulation showed that it was possible, but not easy, to slow down a particle cluster moving through a straight artery and somewhat easier to steer a particle cluster down one branch of an arterial bifurcation. In both cases, diffusion prevented successful control of the particle cluster long-term.
  • Digital
    Timothy Ryan Julian.
    This dissertation examines the factors that influence fomite-mediated (e.g., indirect contact) transmission of viral gastrointestinal and respiratory illness. Specifically, the dissertation investigates virus transfer between surfaces and virus recovery from surfaces, models human-fomites interactions to estimate exposure and infection risk, and elucidates causal links between microbial contamination and illness in child care centers. Indirect contact transmission refers to person-to-person transmission of disease via an intermediate fomite (e.g., inanimate object acting as a carrier of infectious disease). The role of indirect contact in disease spread is poorly understood in part because the transmission route of viral pathogens is often difficult to determine. Transmission of respiratory and gastrointestinal viruses can occur through multiple routes (e.g., direct contact, indirect contact, airborne, and common vehicle), and the relative contribution of each route to total disease burden is unclear. The first study in this dissertation examines virus transfer between skin and surfaces, a necessary step in fomite-mediated transmission of viral disease. In the study, transfer of virus between fingerpads and fomites is explored in a laboratory setting. Bacteriophage (fr, MS2, and PHIX174) are used as proxies for pathogenic virus, and over 650 unique transfer events are collected from 20 different volunteers. The study concludes that approximately one quarter (23%) of recoverable virus is readily transferred from a contaminated surface (e.g., a fomite) to an uncontaminated surface (e.g., a finger) on contact. Using the large data set, the direction of transfer (from fingerpads-to-fomite or fomite-to-fingerpad) and virus species are demonstrated to both significantly influence the fraction of virus transferred by approximately 2-5%. To investigate the relative importance of factors contributing to fomite-mediated transmission, a child's risk of illness from exposure to a contaminated fomite is modeled. Specifically, the model estimates a child's exposure to rotavirus using a stochastic-mechanistic framework. Simulations of a child's contacts with the fomite include intermittent fomite-mouth, hand-mouth, and hand-fomite contacts based on activities of a typical child under six years of age. In addition to frequency of contact data, parameters estimated for use in the model include virus concentration on surface; virus inactivation rates on hands and the fomite; virus transfer between hands, fomite, and the child's mouth; and the surface area of objects and hands in contact. From the model, we conclude that a child's median ingested dose from interacting with a rotavirus-contaminated ball ranges from 2 to 1,000 virus over a period of one hour, with a median value of 42 virus. These results were heavily influenced by selected values of model parameters, most notably, the concentration of rotavirus on fomite, frequency of fomite-mouth contacts, frequency of hand-mouth contacts, and virus transferred from fomite to mouth. The model demonstrated that mouthing of fomite is the primary exposure route, with hand mouthing contributions accounting for less than one-fifth of the child's dose over the first 10 minutes of interaction. Based on the findings from the model that concentration of virus on a fomite influences a child's risk of illness, we investigate methods to recover virus from fomites. In a literature review and subsequent meta analysis, we demonstrate that the outcome currently used to describe virus contamination, positivity rate, is biased by the authors' selected sampling methods. We follow up, in the laboratory, with a comparison of the identified methods and demonstrate that polyester-tipped swabs prewetted in 1/4-strength Ringer's solution or saline solution is the most efficient sampling method for virus recovery tested. The recommended method is compatible with plaque assay and quantitative reverse-transcription polymerase chain reaction, two techniques used to quantify virus. The link between hand / fomite contamination and infection risk was explored in a field study at two child care centers over four months. Both respiratory and gastrointestinal disease incidence were tracked daily, while hand and environmental surface contamination were monitored weekly between February 2009 and June 2009. Microbial contamination was determined using quantitative densities of fecal indicator bacteria (e.g. Escherichia coli, enterococci, and fecal coliform) on hands and fomites as well as presence/absence of viral pathogens (e.g. enterovirus and norovirus). Health was monitored daily by childcare staff, who tracked absences, illness-related absences, and symptomatic respiratory and gastrointestinal illness. The resultant data suggests that increases in microbial contamination led to increases in symptomatic respiratory illness four to six days later, in agreement with typical incubation periods for respiratory illness. Similarly, respiratory illness led to increases in microbial contamination on hands during presentation of symptoms, and on fomites in the following three days.
  • Digital
    Thanh M. Cabral and Rangaraj M. Rangayyan.
    Atypon2012
    Fractal analysis is useful in digital image processing for the characterization of shape roughness and gray-scale texture or complexity. Breast masses present shape and gray-scale characteristics in mammograms that vary between benign masses and malignant tumors. This book demonstrates the use of fractal analysis to classify breast masses as benign masses or malignant tumors based on the irregularity exhibited in their contours and the gray-scale variability exhibited in their mammographic images. A few different approaches are described to estimate the fractal dimension (FD) of the contour of a mass, including the ruler method, box-counting method, and the power spectral analysis (PSA) method. Procedures are also described for the estimation of the FD of the gray-scale image of a mass using the blanket method and the PSA method.
  • Digital/Print
    Carlos Hernández ... [et al.], editors.
    Digital : Springer2011
    Print2011
    Introduction: From Brains to the Machines of the Future / Ricardo Sanz, Carlos Hernández and Jaime Gómez-Ramirez -- Emergent Feature Sensitivity in a Model of the Auditory Thalamocortical System / Martin Coath, Robert Mill, Susan L. Denham and Thomas Wennekers -- STDP Pattern Onset Learning Depends on Background Activity / James Humble, Steve Furber, Susan L. Denham and Thomas Wennekers -- Emergence of Small-World Structure in Networks of Spiking Neurons Through STDP Plasticity / Gleb Basalyga, Pablo M. Gleiser and Thomas Wennekers -- Coupling BCM and Neural Fields for the Emergence of Self-organization Consensus / Mathieu Lefort, Yann Boniface and Bernard Girau -- Alpha and Theta Rhythm Abnormality in Alzheimer's Disease: A Study Using a Computational Model / Basabdatta Sen Bhattacharya, Damien Coyle and Liam P. Maguire -- Oscillatory Neural Network for Image Segmentation with Biased Competition for Attention / Tapani Raiko and Harri Valpola -- Internal Simulation of Perceptions and Actions / Magnus Johnsson and David Gil -- Building Neurocognitive Networks with a Distributed Functional Architecture / Marmaduke Woodman, Dionysios Perdikis, Ajay S. Pillai, Silke Dodel and Raoul Huys, et al. -- Reverse Engineering for Biologically Inspired Cognitive Architectures: A Critical Analysis / Andreas Schierwagen -- Competition in High Dimensional Spaces Using a Sparse Approximation of Neural Fields / Jean-Charles Quinton, Bernard Girau and Mathieu Lefort -- Informational Theories of Consciousness: A Review and Extension / Igor Aleksander and David Gamez -- Hippocampal Categories: A Mathematical Foundation for Navigation and Memory / Jaime Gómez-Ramirez and Ricardo Sanz -- The Role of Feedback in a Hierarchical Model of Object Perception / Salvador Dura-Bernal, Thomas Wennekers and Susan L. Denham -- Machine Free Will: Is Free Will a Necessary Ingredient of Machine Consciousness? / Riccardo Manzotti -- Natural Evolution of Neural Support Vector Machines / Magnus Jändel -- Self-conscious Robotic System Design Process - From Analysis to Implementation / Antonio Chella, Massimo Cossentino and Valeria Seidita -- Simulating Visual Qualia in the CERA-CRANIUM Cognitive Architecture / Raúl Arrabales, Agapito Ledezma and Araceli Sanchis -- The Ouroboros Model, Selected Facets / Knud Thomsen.
  • Digital
    Natasha Maurits.
    Springer2012
    1. Introduction -- 2. Carpal Tunnel Syndrome, Electroneurography, Electromyography, and Statistics -- 3. Tremor, Polymyography, and Spectral Analysis -- 4. Epilepsia, Electroencephalography, Filtering, and Feature Extraction -- 5. Multiple Sclerosis, Evoked Potentials, and Enhancing Signal-to-Noise Ratio -- 6. Cortical Myoclonus, EEG-EMG, Back-Averaging, and Coherence Analysis -- 7. Psychogenic Movement Disorders, Bereitschaftspotential, and Event-Related Potentials -- 8. Brain Tumor, Preoperative Function Localization, and Source Localization -- 9. Neuromuscular Diseases, Ultrasound, and Image Analysis -- 10. Cerebrovascular Disease, Ultrasound, and Hemodynamical Flow Parameters -- 11. Spinal Dysfunction, Transcranial Magnetic Stimulation, and Motor Evoked Potentials.
  • Digital
    Gary Shambat.
    Photonic nanocavities are wavelength-scale dielectric structures that possess remarkable properties due to their intrinsic small sizes and high quality factors. Simply by modifying the device materials and optical properties, one can realize nanocavities for diverse applications ranging from lasers to quantum optics and even biosensing. In this dissertation work, two drastically different functions of nanocavities are presented, both of which make them more practical for real-world adoption. The first part of this dissertation will focus on engineered optical devices for interconnect applications in computing and communications. We have shown that heavily doped germanium on silicon can be used as a CMOS-compatible light source with peak emission at 1.5 microns. Microdisk resonators were fabricated and shown to sustain cavity resonances through both photoluminescence (PL) and electroluminescence (EL) measurements. To access these microresonators, we developed a coupling process using a tapered optical fiber and further showed the versatility of these fibers by using them to tune the cavity wavelength. High performance optical sources were then demonstrated in a gallium arsenide platform containing embedded quantum dots (QDs). We have developed a new platform for efficiently driving photonic crystal (PC) cavities using a lithographically defined, lateral p-i-n junction. With our lateral junction we have demonstrated a world record low threshold laser with a threshold power of only 208 nW at 50K. At room temperature we find that these same devices behave as ultra-fast light-emitting diodes which can be directly modulated at up to 10 GHz with operational energies below 1 fJ/bit. Additional active photonic devices incorporating a lateral junction such as electro-optic modulators and photodetectors were also created using this same platform. The second part of this dissertation describes the demonstration of a whole new class of tools geared towards biomedical photonics that marry PC cavities to the tips of optical fibers. The form factor of the optical fiber lends itself to operation of the tool in exotic environments never before accessible to a nanocavity. Fiber-cavity hybrid devices were constructed using a custom epoxy-based assembly procedure which successfully relocates the small semiconductor templates containing nanocavities. The completed device, called a fiberPC, was then used as a sensor to detect gold nanoparticles through optical readout. We have used our probes to interrogate single human prostate cells with internalized PC cavities showing, for the first time, resonant photonic modes inside biological cells. The beams can be loaded in cells and tracked for days at a time, with cells undergoing regular division and migration. Furthermore, we present in vitro label-free protein sensing with our probes as a path towards quantitative, real-time biomarker detection in single cells. The developed tool may find future applications in drug screening, cancer detection, and fundamental cell biology.
  • Digital
    Remy Durand.
    Functional brain imaging techniques such as functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) have emerged over the last several decades as powerful methods for understanding brain function and neuropsychiatric disorders. However, due to an inability to precisely and distinctly control the heterogeneous population of circuit elements in the brain, understanding the fundamental physiological mechanisms of these imaging modalities and realizing their potential for functional brain mapping has been limited. Optogenetics is a novel technique that allows for cell-type specific, reversible focal control within the mammalian brain with millisecond-timescale precision. In this thesis, I have utilized the unique cell-type specific neuromodulatory capacity of optogenetics to demonstrate and characterize, for the first time, the effect of direct stimulation of a subclass of excitatory neurons on the in vivo functional hemodynamic response of a rodent brain as measured with functional magnetic resonance imaging (fMRI). I have then used this technique, which we have called ofMRI, to perform large-scale functional mapping of distinct neural circuits that are specified by cell-type, cell-body location, and projection topology. To complement ofMRI studies, I have also developed the use of PET imaging and the radiotracer [18F]-fluorodeoxyglucose (FDG) to further characterize the metabolic and hemodynamic response resulting from activation of genetically-specified neurons in the mammalian brain. Additionally, I have constructed an automated, parallelized all-optical ex vivo system for modulation and recording of distinct neural circuits relevant to neuropsychiatric disorders using voltage sensitive dye imaging (VSDI). Combining the highly specific and rapid control of optogenetics with the biological process sensitivity of PET, the spatial and temporal resolution of BOLD fMRI, and the neural circuit analysis capabilities of optical imaging has the potential to vastly increase our understanding of the roles of neural circuits in both normal and diseased brain states.
  • Digital
    Rebecca Sheets.
    ScienceDirect2018
    Fundamentals of Biologicals Regulation: Vaccines and Biotechnology Medicines serves as an introduction to the international regulatory arena in which biologicals are developed and offers an overview of the processes and insight into the scientific concepts underpinning global regulations. This book will provide multiple levels of readership with guidance on basic concepts, a detailed look at regulatory challenges, and practical insight into how regulators consider regulatory science and regulatory process issues across various regions. With numerous case studies, learning activities, and real-world examples across several classes of biotechnological products, this book is a valuable and comprehensive resource for graduate students, professors, regulatory officials, and industry scientists working with biologicals.
  • Digital
    Gerald E. Miller.
    Atypon2010
    Transport processes represents important life sustaining elements in all humans. These include mass transfer processes, including gas exchange in the lungs, transport across capillaries and alveoli, transport across the kidneys, and transport across cell membranes. These mass transfer processes affect how oxygen and carbon dioxide are exchanged in your bloodstream, how metabolic waste products are removed from your blood, how nutrients are transported to tissues, and how all cells function throughout the body. A discussion of kidney dialysis and gas exchange mechanisms is included. Another element in biomedical transport processes is that of momentum transport and fluid flow. This describes how blood is propelled from the heart and throughout the cardiovascular system, how blood elements affect the body, including gas exchange, infection control, clotting of blood, and blood flow resistance, which affects cardiac work. A discussion of the measurement of the blood resistance to flow (viscosity), blood flow, and pressure is also included. A third element in transport processes in the human body is that of heat transfer, including heat transfer inside the body towards the periphery as well as heat transfer from the body to the environment. A discussion of temperature measurements and body protection in extreme heat conditions is also included.
  • Digital
    Ulrich Meyer, Thomas Meyer, Jörg Handschel, Hans Peter Wiesmann, (eds.).
    Springer2009
  • Digital
    György Marko-Varga, editor.
    Springer2014
    This book offers a valuable resource that allows students, researchers, educators and the general public to learn about proteomics and genomics. Chromosomes form the basis for our genetic heritage and are the code for protein synthesis. The Human Genome Map was presented in 2002, and the Proteome Sequence Map is currently being created by a global consortia initiative. Proteome and genome building blocks already form the basis of scientific research areas and shape major areas of the pharmaceutical and biomedical industries. The book provides background information on and our current understanding of these gene and protein areas, and explains in detail how cutting-edge science is using these resources to develop new medicines and new diagnostics for patient treatment and care. The book will benefit all students and researchers who need a good understanding of genomics and proteomics within the clinical field. Its content is also suitable for a broad readership, including those not specialized in this field. Dr. Marko-Varga is head of Div. Clinical Protein Science & Imaging at the Biomedical Center, Dept. of Measurement Technology and Industrial Electrical Engineering, Lund University. He's also Professor at the 1st Department of Surgery, Tokyo Medical University, Tokyo, Japan.
  • Digital
    Richard S. Gaster.
    Nanotechnology has the unique capability of manipulating and sensing matter at the molecular scale with unprecedented speed, sensitivity, and throughput. The medical application of nanotechnology, nanomedicine, has leveraged nanoscience tools for the advancement of medical diagnostics, therapy, and basic science research. In this work, arrays of magnetically responsive nanosensors, originally developed for use as read heads in computer hard disk drives, have been utilized to achieve in-depth proteomic studies for the advancement of medical diagnostics and therapy. In particular, this dissertation will focus on the following four topics of applying magnetic nanotechnology to science and medicine. First, the application of magnetic nanosensor arrays to early cancer diagnostics and monitoring response to chemotherapy. The utility of magnetic nanosensors as a molecular diagnostics tool capable of profiling a patient's disease state and leveraging a patient's unique molecular signature will be demonstrated. Second, this report will discuss a novel mathematical model expressly developed to describe the kinetic interactions of magnetically labeled biomolecules binding to capture agents immobilized on a surface. Third, a novel autoassembly immunoassay capable of screening for antibody cross-reactivity in a high-density, high-fidelity, and rapid manner will be described. Finally, this report will address the utility of the autoassembly immunoassay in conjunction with a miniaturized magnetic nanosensor platform for point-of-care diagnostics in a cost-effective and easy-to-use (e.g. wash-free) process that can make a significant contribution to global health.
  • Digital
    Drew Alexander Hall.
    Nanotechnology has had a transformative effect on medical diagnostics due to the influx of new sensing modalities and transducers. Magnetic nanotechnologies, in particular, have shown significant potential in several areas of nanomedicine such as imaging, therapeutics, and early disease detection. Giant magnetoresistive spin-valve (GMR SV) sensors, commonly used in hard disk drives, coupled with magnetic nanotags have shown great promise as biosensors. In this work, we present several custom designed circuit interface and readout systems tailored to specific application spaces and their unique needs. Taken together, we have demonstrated that innovative electronic circuits play an indispensable role in unlocking the tremendous potential of nanosensors in the biomedical arena. The first system was designed for ultrasensitive early cancer diagnostics and built using off-the-shelf components for an 8x8 array of GMR SV sensors. At the core of this design, we demonstrate a new circuit architecture based on a transimpedance amplifier (TIA) with a carrier suppression technique to reduce the dynamic range requirement and a multiplexing scheme to reduce the readout time. This system is capable of real-time, multiplex detection with a detection limit of 5 femtomolar (fM) and over 6 orders of linear dynamic range. The second system is a miniaturized, portable platform called the nanoLAB. Although there is a growing need for point-of-care (POC) testing for global health, the current options are bulky, slow, expensive, and often not sensitive. The nanoLAB addresses these needs and pushes the state of the art with sensitive 8-plex detection using a wash-free assay that can be run by anyone, anywhere. This platform was tested and validated using human immunodeficiency virus (HIV) biomarkers with detection down to 50 fM in as little as 15 minutes. We also show how a GMR SV biosensor can be integrated into a continuous time sigma delta modulator. This proof-of-concept hybrid sigma delta modulator has a peak SNR of 99.3 dB and a dynamic range of over 92 dB in a 1 kHz bandwidth using the sensor as part of the first integrator. The carrier suppression and multiplexing concepts were also incorporated into the hybrid sigma delta modulator. Lastly, we conclude by describing an integrated platform for a large 16x16 array of GMR SV sensors implemented in a 0.18 [mu]m CMOS technology. Arranged like an imager chip, each of the 16 column level readout channels contains an analog front-end and an analog-to-digital converter. Each readout channel occupies less than 0.2 mm^2 of chip area and consumes 3.4 mW of power. This system is designed as a replacement for optical protein microarrays while being fully quantitative and providing real-time readout.
  • Digital
    Fabrizio De Vico Fallani and Fabio Babiloni.
    Atypon2010
  • Digital
    Bernhard Hirt, Harun Seyhan, Michael Wagner, Rainer Zumhasch ; translator: Karen Leube.
    Thieme-Connect2017
    Anatomy and functional anatomy of the hand -- Surface anatomy of the forearm, wrist, and hand structures.
  • Digital
    [edited by] Sandro Carrara, EPFL, Lausanne, Switzerland, Krzysztof Iniewski, CMOS Emerging Technologies Research, Inc.
    Cambridge2015
  • Digital
    edited by Konstantina S. Nikita.
    Wiley2014
  • Digital
    edited by Anil K. Jain, Patrick Flynn, Arun A. Ross.
    Springer2008
  • Print
    by Kewal K. Jain.
    Status: Not Checked OutLane Catalog Record
  • Digital
    Kewal K. Jain.
    Springer2012
    Nanotechnologies -- Nanotechnologies for Basic Research Relevant to Medicine -- Nanomolecular Diagnostics -- Nanopharmaceuticals -- Role of Nanotechnology in Biological Therapies -- Nanodevices and Techniques for Clinical Applications -- Nanooncology -- Nanoneurology -- Nanocardiology -- Nanopulmonology -- Nanoorthopedics -- Nano-ophthalmology -- Nanomicrobiology -- Miscellaneous Healthcare Applications of Nanobiotechnology -- Nanobiotechnology and Personalized Medicine -- Nanotoxicology -- Ethical and Regulatory Aspects of Nanomedicine -- Research and Future of Nanomedicine.
  • Digital
    Monique Frize.
    Atypon2013
    The first chapter describes the health care delivery systems in Canada and in the U.S. This is followed by examples of various approaches used to measure physiological variables in humans, either for the purpose of diagnosis or monitoring potential disease conditions; a brief description of sensor technologies is included. The function and role of the clinical engineer in managing medical technologies in industrialized and in developing countries are presented. This is followed by a chapter on patient safety (mainly electrical safety and electromagnetic interference); it includes a section on how to minimize liability and how develop a quality assurance program for technology management. The next chapter discusses applications of telemedicine, including technical, social, and ethical issues. The last chapter presents a discussion on the impact of technology on health care and the technology assessment process.
  • Digital
    Monique Frize.
    Atypon2013
    Chapter 7 presents some statistics on the occurrence of medical errors and adverse events, and includes some technological solutions. A chapter on electronic medical records follows. The knowledge management process divided into four steps is described; this includes a discussion on data acquisition, storage, and retrieval. The next two chapters discuss the other three steps of the knowledge management process (knowledge discovery, knowledge translation, knowledge integration and sharing). The last chapter briefly discusses usability studies and clinical trials. The two parts consolidate material that supports courses on technology development and management issues in health care institutions. It can be useful for anyone involved in design, development, or research, whether in industry, hospitals, or government.
  • Digital
    Paul A. Iaizzo, Richard W. Bianco, Alexander J. Hill, James D. St. Louis, editors.
    Springer2013
    Anatomy, Physiology, Congenital Defects, and Disease -- The Anatomy and Function of the Atrioventricular Valves / Michael G. Bateman, Jason L. Quill, Alexander J. Hill, Paul A. Iaizzo -- The Anatomy and Function of the Semilunar Valves / Michael G. Bateman, Jason L. Quill, Alexander J. Hill, Paul A. Iaizzo -- Congenital Heart Defects That Include Cardiac Valve Abnormalities / Roosevelt Bryant III -- Acquired Valve Disease and Processes / Cindy M. Martin -- Valve Repair and Replacement -- History of Heart Valve Repair / Lauren B. Kwasny, Richard W. Bianco, Luis H. Toledo-Pereyra, -- Heart Valve Disease / Ranjit John, Kenneth Liao -- Advanced 3D Imaging and Transcatheter Valve Repair/Implantation / Paul Schoenhagen, Andrew C. Y. To -- Transcatheter Mitral Repair and Replacement / Jason L. Quill, Ana R. Menk, Gilbert H. L. Tang -- Percutaneous Pulmonary Valve Implantation: The First Transcatheter Valve / Silvia Schievano, Andrew M. Taylor, Philipp Bonhoeffer -- Transcatheter Aortic Valve Implantation / Nicolo Piazza, Darren Mylotte -- Tissue-Engineered Heart Valves / Jillian B. Schmidt, Robert T. Tranquillo -- Testing and Regulatory Issues -- In Vitro Testing of Heart Valve Substitutes / Timothy A. Kelley, Sal Marquez, Carl F. Popelar -- Numerical Methods for Design and Evaluation of Prosthetic Heart Valves / Michael J. Schendel, Carl F. Popelar -- Animal Models for Cardiac Valve Research / Sarah E. Ahlberg, Michael G. Bateman, Michael D. Eggen, Jason L. Quill -- The Use of Isolated Heart Models and Anatomic Specimens as Means to Enhance the Design and Testing of Cardiac Valve Therapies / Michael G. Bateman, Alexander J. Hill, Jason L. Quill, Michael D. Eggen -- Successful Development and Regulatory Approval of Replacement Cardiac Valves / Stephen A. Howard, Michael G. Bateman, Timothy G. Laske, Paul A. Iaizzo -- Clinical Trial Requirements for Cardiac Valves / Jenna C. Iaizzo, Anna T. F. Lovas.
  • Digital
    Ga-Young Suh.
    Hemodynamic conditions are hypothesized to affect the initiation, growth, and rupture of abdominal aortic aneurysms (AAAs), a vascular disease characterized by progressive wall degradation and enlargement of the abdominal aorta. We hypothesized that the progression of AAA may be slowed by altering the hemodynamics in the abdominal aorta through exercise. The aim of the first study in this thesis was to use magnetic resonance imaging (MRI) and computational fluid dynamics (CFD) to quantify flow stagnation and recirculation in AAAs by computing particle residence time (PRT). Specifically, we used gadolinium-enhanced MR angiography (MRA) to obtain images of the vessel lumens, which were used to generate subject-specific models. Phase-contrast MRI was used to measure blood flow at supraceliac and infrarenal locations to prescribe physiologic boundary conditions. CFD was used to simulate pulsatile flow, and PRT, particle residence index, and particle half-life of PRT in the aneurysms were computed. We observed significant regional differences of PRT in the aneurysms with localized patterns that differed depending on aneurysm geometry and infrarenal flow. A saccular aneurysm with the lowest mean infrarenal flow demonstrated the slowest particle clearance. In addition, improvements in particle clearance were observed with increase of mean infrarenal flow. This result motivated the next study to quantify the effect of augmentation of mean infrarenal flow during exercise on reducing chronic flow stasis that may promote increased mural thrombus burden, degradation of the vessel wall, and aneurysm growth. In the second study, we investigated three levels of activity, rest, mild and moderate intensities of lower-limb exercise to quantify the effect of exercise on hemodynamic conditions in AAA subjects. We measured the abdominal aortic blood flow at rest and during dynamic exercise, and quantified mean wall shear stress (MWSS), oscillatory shear index (OSI), and PRT. We observed that an increase in the level of activity correlated with an increase of MWSS and a decrease of OSI at three locations in the abdominal aorta, and these changes were most significant below the renal arteries. As the level of activity increased, PRT in the aneurysm was significantly decreased: 50% of particles were cleared out of AAAs within 1.36 ± 0.43, 0.34 ± 0.10, and 0.22 ± 0.06 s at rest, mild exercise and moderate exercise levels, respectively. Most of the reduction of PRT occurred from rest to the mild exercise level suggesting that mild exercise may be sufficient to reduce flow stasis in AAAs. The third study aimed to correlate hemodynamic characteristics of AAA with its progression, and quantify morphologic changes of aneurysm from study intake to 1.5-3.5-year follow-up of subjects randomized to usual activity or exercise training cohort. We acquired MRA of 16 subjects, and mid-aneurysm wall content data of 12 subjects at each intake and follow-up visit. 3D lumen models were built based on each intake and follow-up MRAs of six subjects. We observed morphologic changes of aneurysm lumen from intake to follow-up MRA of 11 subjects which exhibited local smoothing, shrinkage or expansion. We observed thickening of thrombus burden from follow-up wall content image of seven subjects whose aneurysm lumen was eventually narrowed. Based on 3D model comparison between intake and follow-up, and the correlation of morphologic changes with wall content changes and PRT contour plots computed in the previous study, we suggest that the region of narrowed lumen induced by thrombus buildup may be consistent with the region of long PRT. As a future work, we will extend our research in conjunction with CT data to quantify the changes of aneurysm wall, and increase the number of subjects to find more conclusive results.
  • Digital
    Anderson N. Nnewihe.
    Breast cancer is the second leading cause of female cancer death in the United States with an average lifetime risk of 1 in 8. Early detection of the disease and subsequent treatment increase the chance of survival. X-ray mammography is the standard imaging technique for breast cancer screening, but it is difficult to identify malignant lesions in women with dense breasts using x-ray mammography. Dynamic-contrast-enhanced (DCE) magnetic resonance imaging (MRI) has provided high sensitivity for breast cancer diagnosis due to its excellent soft tissue contrast, but there have been varied reports on its specificity. A recent study with a small surface coil has shown that high spatial and temporal resolution breast DCE MRI can improve sensitivity and specificity of ductal carcinoma in situ diagnosis by visualizing smaller scale features such as ductal and periductal enhancement. However, a small surface coil is not suitable for screening or bilateral staging exams where volumetric coverage of both breasts is necessary. Conversely, many commercially-available breast coils offer volumetric coverage of the breasts, but the large coil elements limit the signal-to- noise ratio (SNR) and thus the ability to increase spatial and temporal resolution with high parallel imaging acceleration factors. To address these concerns, we have designed and developed a custom-fitted 18-channel, bilateral breast radiofrequency (RF) coil array for providing high-resolution images in clinically-feasible scan times. The purpose of this work was three-fold: outline the construction process of a high- SNR custom-fitted array, benchmark its performance compared to a commercial design, and evaluate its utility for high-resolution clinical breast MRI. By placing a chain of overlapping small coil elements close to the tissue, we were able to obtain high SNR over the entire breast volume for medium-sized women. To reduce the overall exam time, we laid the coil elements in a geometry that facilitated bidirectional parallel imaging. Comparing the custom-fitted array to a commercially-available 8-channel breast array, the results show 3.6 times higher average SNR and superior parallel imaging quality for the custom-fitted array in volunteers. Using parallel imaging and taking advantage of the SNR benefits from the 18-channel coil array, we clinically demonstrated a 10-fold improvement in spatial resolution over the current Stanford Hospital protocol. We have conducted a clinical study comparing the diagnostic quality of high-resolution scans with the 18-channel array versus lower resolution scans in patients with suspicious lesions on mammography. The initial findings show that the improved resolution enables better depiction of overall lesion morphology and tissue interfaces. In summary, we have presented a method for constructing an 18-channel custom-fitted breast RF array and demonstrated its SNR and parallel imaging benefits. In a clinical setting, our initial findings show improved morphology characterization in high-resolution exams with the 18-channel array.
  • Digital
    Vassilis Cutsuridis, Bruce Graham, Stuart Cobb, Imre Vida, editors.
    Springer2010
  • Digital
    Dierck Hillmann ; with a foreword by Gereon Hüttmann.
    Springer2014
    Holoscopy is a new tomographic imaging modality that combines techniques of digital holography with Fourier-domain optical coherence tomography (FD-OCT). Dierck Hillmann gives a theoretical introduction to the mathematics and physics of holoscopy and develops an efficient numerical reconstruction procedure. Compared to FD-OCT, holoscopy provides unique advantages by enabling tomographic imaging without a limited depth of focus, but results in an increased numerical cost for reconstruction. In further chapters, the author introduces techniques for FD-OCT that are relevant to holoscopy as well. He demonstrates and compares numerical reconstruction methods for FD-OCT and shows how motion and dispersion artifacts in FD-OCT can be numerically compensated. Contents Theoretical Introduction to Optical Coherence Tomography and Digital Holography FD-OCT Signal Processing Using the Non-Equispaced Fast Fourier Transform Motion and Dispersion Correction in FD-OCT Holoscopy Target Groups Academics and practitioners in the fields of computer science, optical coherence tomography, digital holography, and medical imaging. The Author Dierck Hillmann received his doctoral degree in the group of Gereon Hüttmann at the Institute of Biomedical Optics in Lübeck and is currently working for a leading company in the fields of science and photonics. The Editor The series Aktuelle Forschung Medizintechnik is edited by Thorsten M. Buzug.
  • Digital
    Katerina Blazek.
    Obesity, a condition characterized by excess adipose tissue, is becoming an important public health problem. Not only has the prevalence rate in adults risen steadily since the 1980's, obesity is a strong risk factor for the development of knee osteoarthritis (OA) and general mobility disability. There are currently no disease-modifying treatments for OA, so it is important to develop preventive strategies. However, we must first understand the mechanism of increased risk in the obese population. Knee cartilage and other joint structures respond both to mechanical loads during activities of daily living and to the biological environment within the joint, so the pathway to OA in the obese population therefore likely involves changes in both. The primary goal of this dissertation was to test the hypothesis that aging and obesity are linked to changes in gait mechanics and changes in the relationship between cartilage morphology and joint loads, and that these changes are consistent with increased knee OA risk. We also analyzed whether these changes are also observed in individuals with early asymptomatic knee joint degeneration. Finally, we tested the hypothesis that stair climbing requires adaptive changes that reflect a reduction in muscle strength in the aging obese population and indicate increased mobility disability risk. The results indicate that in obese, but not normal-weight individuals, age was associated with an increased adduction moment, which reflects increased loads on the medial compartment of the knee. Furthermore, the positive relationship between cartilage thickness and ambulatory load in young subjects was significantly weaker in middle-aged obese individuals. The increased OA risk in older obese individuals is therefore likely due to both an increase in ambulatory loads and to a change in the relationship between those ambulatory loads and cartilage properties due to the elevated pro-inflammatory cytokine levels characteristic of obesity. During stair climbing, middle-aged obese individuals also had lower peak knee flexion moments, indicative of quadriceps weakness due to aging and relative to their weight. Finally, the gait and stair climbing mechanics of individuals with early OA were not different from their age- and BMI-matched healthy counterparts, indicating that the gait alterations seen in healthy middle-aged obese individuals are the same as those in obese individuals who have already developed the disease, and are likely risk factors or early functional markers of OA.
  • Digital
    edited by John R. Masters and Bernhard Ø. Palsson.
    Springer2009
    1. Neural progenitors / Dustin R. Wakeman ... [et al.] -- 2. Multipotent stromal cells (hMSCs) / Margaret Wolfe ... [et al.] -- 3. Endothelium / Sangmo Kwon, Takayuki Asahara -- 4. Lung / Rabindra Tirouvanziam, Megha Makam, Bruno Péault -- 5. Eye / Maria Notara ... [et al.] -- 6. Colon / F. Iovino ... [et al.] -- 7. Spermatogonia / Makoto C. Nagano, Jonathan R. Yeh, Khaled Zohni -- 8. Hair follicle pluripotent stem (hfPS) cells / Robert M. Hoffman -- 9. Pancreas / Fang-Xu Jiang, Grant Morahan -- 10. Prostate / C. Foley ... [et al.].
  • Digital
    Jan Schildmann...[et al.], editors.
    Springer2012
    Part 1. Historical and Socio-Cultural Contexts in Medical Research / British Responses to Nazi Medical War Crimes / Fiona McClenaghan -- History and its Relevance in the Development and Teaching of Research Ethics / Rael D. Strous -- Human Embryo Research and Islamic Bioethics: A View from Iran / Mansooreh Saniei -- From Farming to Pharming: Transcending of Bodily Existence as a Question of Medical Ethics in an Intercultural Context / Axel Siegemund -- Introduction / Jan Schildmann, Verena Sandow, Oliver Rauprich and Jochen Vollmann -- Part 2. Considerations on Ethical and Legal Regulations for Medical Research / Rethinking the Therapeutic Obligation in Clinical Research / Nunziata Comoretto -- Biomedical Research in Developing Countries and International Human Rights Law / Ilja R. Pavone -- Research Involving Human Subjects and Human Biological Material from a European Patent Law Perspective. Autonomy, Commodification, Patentability / Tomasz Zimny -- The Development and Validation of a Guide for Peruvian Research Ethics Committees to Assist in the Review of Ethical-Scientific Aspects of Clinical Trials / Susy Olave Quispe, Duilio Fuentes Delgado, Gabriela Minaya Martínez, Rosa Surco Ibarra and Martín Yagui Moscoso, et al. -- Part 3. Conflicts in Medical Research / Conflicts of Interest in Medical Research: What can Ethics Contribute? / Verena Sandow, Jan Schildmann and Jochen Vollmann -- Research Ethics in Genomics Research: Feedback of Individual Genetic Data to Research Participants / Annelien L. Bredenoord and Johannes J. M. van Delden -- Regulating "Higher Risk, No Direct Benefit" Studies with Children: Challenging the US Federal Regulations / Anna E. Westra, Jan M. Wit, Rám N. Sukhai and Inez D. de Beaufort -- Part 4. New Developments in Medical Research and Ethical Implications / A Paradigm Change in Research Ethics / Rieke van der Graaf and Johannes J. M. van Delden -- Translation of Cancer Molecular Biomarkers: Ethical and Epistemological Issues / Flavio D'Abramo and Cecilia Guastadisegni -- Rethinking the Ethics of Human Biomedical Non-Interventional Research / Kristi L{tilde}ouk.
  • Digital/Print
    John D. Lambris, Kristina N. Ekdahl, Daniel Ricklin, Bo Nilsson, editors.
    Digital : Springer2015
    Print2015
    1. Thromboinflammation in therapeutic medicine -- 2. Complement interactions with blood cells, endothelial cells and microvesicles in thrombotic and inflammatory conditions -- 3. Role of complement on broken surfaces after trauma -- 4. Complement involvement in periodontitis: molecular mechanisms and rational therapeutic approaches -- 5. The lectin pathway of complement and biocompatibility -- 6. Foreign body reaction to subcutaneous implants -- 7. Molecular characterization of macrophage-biomaterial interactions -- 8. Heparan sulfate proteoglycan metabolism and the fate of grafted tissues -- 9. Xenotransplantation of cells, tissues, organs and the Greman research foundation Transregio Collaborative Research Centre 127 -- 10. Macroencapsulated pig islets correct induced diabetes in primates up to 6 months -- 11. Regulation of instant blood mediated inflammatory reaction (IBMIR) in pancreatic islet xeno-transplantation: points for therapeutic interventions -- 12. Cell surface engineering for reguation of immune reactions in cell therapy -- 13. Complement interception across humoral incompatibility in solid organ transplantation: a clinical perspective -- Index.
  • Digital
    edited by Evgeny Katz.
    Wiley2014
  • Digital
    David Korpas.
    Springer2013
    History and development of pacing -- Basic principles of cardiac pacemaker technology -- Heart anatomy and physiology -- Pharmacological treatment of cardiac rhythm disorders -- Pacing modes -- Indications for implantable system treatment -- Leads -- Pacing systems -- Pacemaker timing -- Implantable cardioverter-defibrillators -- Cardiac resynchronization therapy -- Implantation, explantation, and replacement of devices and leads -- Patient follow-up -- Electromagnetic compatibility and technical requirements.
  • Digital
    Thomas Daniel O'Sullivan.
    Molecular imaging is an established technique used to visualize and quantify functional information about biological processes in living systems. In vivo fluorescence imaging, in particular, is a molecular imaging technique capable of quantitatively imaging one or more fluorophores at high spatial and temporal resolution with high sensitivity, either at microscopic or macroscopic (whole-body) scales. While current fluorescent imaging technologies have led to key advances in the understanding of biology and biochemistry, there are limitations. Modern in vivo fluorescence imagers are bulky, and typically take snapshots, and only sample discrete points of continuous, dynamic processes. In order to overcome these obstacles and enable long-term, continuous fluorescence imaging in live animals, we have miniaturized the components of the optical imaging system, allowing for direct implantation. Miniature fluorescence sensors have been fabricated to match a particular fluorescent probe utilizing semiconductor processing technology and appropriate materials. We present the design and fabrication of a monolithically integrated semiconductor (GaAs-based) sensor for far-red to near infrared (NIR) in vivo fluorescence sensing. The sensor incorporates three basic components of a fluorescence system, including: a 675nm vertical-cavity surface-emitting laser (VCSEL) excitation source, a GaAs PIN photodiode, and a fluorescence emission filter. We have packaged the sensors in several integrated configurations, and developed readout mechanisms that include a system that can be implanted in small rodents. We have utilized this device to demonstrate that in vivo fluorescence imaging is possible with miniaturized, un-cooled semiconductor devices, including a demonstration of sensing in a freely-moving rodent. Such miniaturized, implantable biomedical devices have the potential to accelerate pre-clinical research and revolutionize clinical care by providing an inexpensive means for diagnosis, monitoring disease progression, and evaluating long-term treatment efficacy. By integrating this implantable sensor with the appropriate read-out electronics and wireless telemetry, un-tethered operation can ultimately be achieved.
  • Digital
    Gauri Mankekar, editor.
    Springer2014
    Hearing loss can vary in type ranging from conductive, mixed to sensorineural, as well as in degree from mild, moderate, severe to profound. There could also be multiple permutations and combinations like moderate mixed hearing loss or severe conductive hearing loss. In addition, the hearing loss could be unilateral or bilateral. While cochlear implants were devised for bilateral profound sensorineural hearing loss, various other devices have been invented for other types of hearing losses. Research continues to design a suitable implant which would amplify sound for patients who cannot be candidates for cochlear implants.
  • Digital
    Michael Quay Chen.
    The limited ability of the human heart to regenerate has made myocardial infarction and heart failure debilitating conditions. Recently, an approach using pluri- or multi-potent stem cells to repair damaged heart tissue is being explored for its potential to regenerate tissue as a tailored, patient-specific treatment. However, the mechanisms of integration remain unclear, and many cardiac grafting procedures utilizing both embryonic and adult stem cells have been met with limited success. While current evidence suggests that grafts are likely viable in host myocardium, clinical studies have reported pro arrhythmic side-effects following transplantation, which arise from disrupted propagation patterns. These issues may be attributed to grafts lacking cardiac differentiation, or possessing conduction properties inconsistent with the host tissue. Consequently, understanding the role of the electrical environment throughout the engraftment process is necessary, but infeasible due to a lack of proper tools. Elucidating the electrical aspects of stem cell transplantation aims to ensure proper integration of the transplanted cells to prevent aberrant electrical pathways in the heart. In this work, a set of in vitro tools were developed to study the potential mechanisms underlying the risk of arrhythmia following stem cell transplantation. A planar microelectrode array was first used to investigate the possibility of conduction block if undifferentiated or non cardiomyocyte stem cells, such as mesenchymal stem cells, are used as grafts. Conduction in murine cardiomyocytes was purposely blocked by co-culture with non-conducting murine fibroblasts, and a novel mathematical transform known as a co occurrence matrix was developed to quantitatively analyze the uniformity of conduction. The observed sensitivity of cardiomyocyte conduction illustrated the risk of grafting non-cardiomyocyte cell types despite any potential of differentiating into muscle-like cells. Unlike non-conducting fibroblasts, stem cell grafts are expected to electrically conduct if proper cardiac differentiation takes place. However, possible differences in the conduction properties of these grafts may still lead to arrhythmia. To perform a controlled study of such conduction mismatch, an in vitro co-culture system coupled to microelectrode arrays was developed. Spatially separated cultures representing the host and the graft were allowed to gradually merge above the microelectrode array, allowing the measurement of conduction throughout the integration process. Modeled host and graft cell populations were evaluated by analyzing the co occurrence matrix and conduction velocity for the quality and speed of conduction over time. Co cultures between murine cardiomyocytes (host) and murine skeletal myoblasts (graft) exhibited significant differences in conduction despite synchronous electrical activity. In contrast, conduction was well matched when the same host cells were co cultured with murine embryonic stem cells (mESC). A model using murine cardiomyocytes (host) and differentiating human embryonic stem cells (graft) allowed the characterization of conduction properties relevant to current trans-species animal models, and demonstrate the co-culture device as a screening platform for candidate graft cells. The limited region of the graft that supported conduction exhibited differences in the co-occurrence matrix as well as conduction velocity when compared to the host region. In an effort to improve the effects of conduction mismatch, both host and graft cell populations were electrically paced over the length of time the cultures remained viable (4-5 days). Although a difference between conduction velocities between host and graft was still observed, the overall uniformity of conduction improved in paced co-cultures, implying increased cardiac differentiation. A preliminary study of genomic changes due to paced mESCs resulted in a significant upregulation of several important cardiac genes and a significant downregulation of many embryonic genes. Further efforts are currently underway to examine gene expression with paced hESCs to optimize integration in the host-graft model, and ultimately to understand how the electrical environment influences stem cell transplantation.
  • Digital
    Rihard Trebše, editor.
    Springer2012
    Part 1 -- Introduction / Rihard Trebše -- Joint Replacement: Historical Overview / Rihard Trebše, Anže Mihelič -- Biomaterials in Artificial Joint Replacements / Rihard Trebše -- The Definition of Prosthetic Joint Infections (PJI) / Rihard Trebše, Andrej Trampuž -- Classification of Prosthetic Joint Infections / Rihard Trebše, Anže Mihelič -- The Epidemiology of Total Joint Arthroplasty Infections / David J. Jaekel, Kevin L. Ong, Edmund C. Lau -- Septic Complications in Arthroplasty / Gerold Labek -- Perioperative Antibiotic Prophylaxis in Total Joint Arthroplasty / Nataša Faganeli -- Risk Factors for Prosthetic Joint Infections / René Mihalič, Matevž Topolovec -- Pathogenesis of Prosthetic Joint Infections / Rihard Trebše, Jurij Štalc -- Bacteria-Biomaterial Interactions / Antti Soininen, Emilia Kaivosoja, Jaime Esteban -- Biomaterial-Host Interactions in Aseptic and Septic Conditions / Jukka Pajarinen, Yuya Takakubo, Zygmunt Mackiewicz -- Influence of Wear Particles on Local and Systemic Immune System / Emmanuel Gibon, Stuart B. Goodman -- Diagnostic Evaluations / Rihard Trebše -- Synovial Fluid Cytology / René Mihalič, Dunja Terčič -- Histological Analysis of Periprosthetic Tissue for Detecting Prosthetic Joint Infection / Andrej Cör -- Microbiological Diagnosis of Prosthetic Joint Infection / Jaime Esteban, Concepción Pérez-Jorge, Ramón Pérez-Tanoira -- Microbiological Processing of Samples in the Investigation of Suspected Prosthetic Joint Infection / David G. Partridge, Rob Towsend -- Part 2 -- Molecular Diagnosis of Prosthetic Joint Infection / Jaime Esteban, Diana Molina-Manso, Gema del-Prado -- Current Treatment Strategies in Prosthetic Joint Infections / Rihard Trebše Total Ankle Replacement Infections / Michaela Maria Schneiderbauer -- Periprosthetic Infection Issues with Osseointegrated (OI) Implant Technology in Amputees / Catherine Loc-Carrillo, Alec C. Runyon, James Peter Beck -- The Algorithm for Diagnostic Evaluation and Treatment / Rihard Trebše, Andrej Trampuž -- Bone Grafts and Bone Graft Substitutes in Infected Arthroplasty / Martin Clauss, Thomas Ilchmann.
  • Digital
    Lauren Marie Aquino Shluzas.
    Through an inductive, multi-case analysis, this dissertation examines how design and development practices, involving physicians and medical device developers, influence the clinical and financial outcomes of early stage medical device companies. This research was motivated by an interest in understanding the role of physicians in the device development process, specifically in terms of how physician interaction influences the acceptance or rejection of new medical products. An analytic framework for case-based research was first developed based on exploratory interviews with leaders in the medical device field. Retrospective case studies were then conducted on eight entrepreneurial firms (four rival pairs) in the areas of pulse oximetry, robotic surgery, cardiac bypass surgery, and minimally invasive spine surgery. Primary data sources included interviews with engineers, physicians, and business executives from each company; product development data including device prototypes, regulatory clearance data, and intellectual property (IP); and clinical and financial outcomes data. Following the period of data collection, within-case and across-case analyses were performed. The interview data for each case was coded for design and development practices involving physician-developer interaction, using NVivo qualitative analysis software (QSR International, Version 8). Development practices were analyzed using logic models to examine causal relationships between practices, and product and company outcomes. Design and development practices were further examined and supported using a combination of qualitative and quantitative evidence. Based on the multi-case analysis, this dissertation provides an overview of physician-developer interaction characteristics throughout each phase of the medical device development process. This includes a description of the roles and responsibilities of physicians engaged in development efforts, and their corresponding team affiliations. The research also illustrates four key factors that contributed to medical device adoption for the cases studied. First, the data highlight that designing products under variable use conditions (i.e. with variable patient populations and physicians of varying skill levels), enabled firms to optimize products for widespread clinical use and to increase the predictability of product outcomes. Second, the study shows that product adoption relied on maximizing benefits for multiple product stakeholders, while minimizing required changes in physician behavior. The data further illustrate that total benefit to product stakeholders was influenced to the greatest degree by benefits afforded to hospitals and physicians, assuming patient benefit was greater than or equal to the standard of care. Third, the study highlights that managing perceptions toward product use through performance data positively influenced product adoption to a greater degree than did market demand or regulatory clearance. Fourth, rival explanations for outcomes, involving limited physician interaction, indicate that competitive advantages were achieved through maintaining dominant financial and intellectual property positions. From these findings, the Insight-Value-Perception (iVP) Model for user-centered medical device design was constructed. The model links design and development practices to outcomes, from a combination of consumer-oriented, technical, and financial perspectives. This research provides theoretical contributions to product development and user-centered design literature, and provides practical contributions for developers in the medical device field. A contribution to product development literature is made through documenting the combined benefits of maximizing product value for stakeholders while managing data-driven perceptions toward product use. For the field of user-centered design, this research captures the benefits of designing medical technology with and for a broad consortium of product end-users, as opposed to industry leaders alone. The research also documents the importance of identifying the often-conflicting needs of product stakeholders, and then optimizing devices to satisfy the needs of those with the greatest influence over product use and adoption. For medical device practitioners, this dissertation provides design, regulatory, and product-testing strategies shown to increase technology adoption across the eight cases studied. From this thesis, the author proposes future studies to inform policies and strategies for device manufacturers and the FDA, and to advance knowledge in the fields of user-centered design and product development.
  • Digital
    edited by Murugan Ramalingam [and others].
    Wiley2012
  • Digital
    Jonathan S. Daniels.
    Affinity biosensors are important tools for detecting DNA, proteins, cells, and other biomedical analytes. Although optical readout is prevalent, impedance readout is promising for many applications due to lower cost, reduced system size, and label-free operation. Impedance biosensors detect the binding of a target biomolecule to an immobilized probe by quantifying changes in the the electrode-electrolyte interface impedance. Impedance biosensors traditionally use bulky and expensive instruments to monitor the impedance of a single electrode. We describe miniaturized and inexpensive readout circuitry for an array of such sensors. By using a sensor array, multiple analytes can be simultaneously detected and limitations inherent to individual sensors can be mitigated. Reducing the size and cost of the measurement system enables new applications. We present a measurement system for a 6x6 array of impedance biosensors built from off-the-shelf components. Experimental results with DNA probe-target pairs confirm others' reports that changes in the interface impedance can signify binding. Other experiments with proteins demonstrate that changes in the nonlinearity of the I-V relationship can also indicate probe-target binding. We show that the impedance and the nonlinearity can be quantified simultaneously by superimposing a large-amplitude tone on the impedance-measurement tone and analyzing the resulting intermodulation tones. We conclude by describing an integrated array of measurement circuits implemented in 0.18 um CMOS. Each of the 36 measurement pixels contains an impedance-measuring circuit plus tone cancellation circuitry, which enables simultaneous nonlinearity measurement. To prevent the large-amplitude excitation from saturating the amplifier output, a per-pixel digital feedback loop injects an appropriate cancelling current at the amplifier input. Impedance changes of 0.2% can be detected using the integrated measurement circuit. Each pixel occupies 0.14 mm2 and consumes 1.9 mW.
  • Digital
    editors, C.J. Bettinger, J. Rogers, M. Irimia-Vladu, L. Torsi.
    Cambridge2012
    Progress towards Melanin Integration in Bio-Inspired Devices. -- Bio Organic-Based Gate Dielectric Materials for Thin Film Transistors.
  • Digital
    edited by Marcus Textor, H. Michelle Grandin.
    Wiley2012
    Frontmatter -- Color Plates -- Stimulus-Responsive Polymers as Intelligent Coatings for Biosensors: Architectures, Response Mechanisms, and Applications / Vinalia Tjong, Jianming Zhang, Ashutosh Chilkoti, Stefan Zauscher -- Smart Surfaces for Point-of-Care Diagnostics / Michael A Nash, Allison L Golden, John M Hoffman, James J Lai, Patrick S Stayton -- Design of Intelligent Surface Modifications and Optimal Liquid Handling for Nanoscale Bioanalytical Sensors / Laurent Feuz, Fredrik H̲̲k, Erik Reimhult -- Intelligent Surfaces for Field-Effect Transistor-Based Nanobiosensing / Akira Matsumoto, Yuji Miyahara, Kazunori Kataoka -- Supported Lipid Bilayers: Intelligent Surfaces for Ion Channel Recordings / Andreas Janshoff, Claudia Steinem -- Antimicrobial and Anti-Inflammatory Intelligent Surfaces / Hans J Griesser, Heike Hall, Toby A Jenkins, Stefani S Griesser, Krasimir Vasilev -- Intelligent Polymer Thin Films and Coatings for Drug Delivery / Alexander N Zelikin, Brigitte St̃dler -- Micro- and Nanopatterning of Active Biomolecules and Cells / Daniel Aydin, Vera C Hirschfeld-Warneken, Ilia Louban, Joachim P Spatz -- Responsive Polymer Coatings for Smart Applications in Chromatography, Drug Delivery Systems, and Cell Sheet Engineering / Roǧrio P Pirraco, Masayuki Yamato, Yoshikatsu Akiyama, Kenichi Nagase, Masamichi Nakayama, Alexandra P Marques, Rui L Reis, Teruo Okano -- Index.
  • Digital
    Der-Song Lin.
    Capacitive micromachined ultrasonic transducers (CMUTs), have been widely studied in academia and industry over the last decade. CMUTs provide many benefits over traditional piezoelectric transducers including improvement in performance through wide bandwidth, and ease of electronics integration, with the potential to batch fabricate very large 2D arrays with low-cost and high-yield. Though many aspects of CMUT technology have been studied over the years, packaging the CMUT into a fully practical system has not been thoroughly explored. Two important interfaces of packaging that this thesis explores are device encapsulation (the interface between CMUTs and patients) and full electronic integration of large scale 2D arrays (the interface between CMUTs and electronics). In the first part of the work, I investigate the requirements for the CMUT encapsulation. For medical usage, encapsulation is needed to electrically insulate the device, mechanically protect the device, and maintain transducer performance, especially the access of the ultrasound energy. While hermetic sealing can protect many other MEMS devices, CMUTs require mechanical interaction to a fluid, which makes fulfilling the previous criterion very challenging. The proposed solution is to use a viscoelastic material with the glass-transition-temperature lower than room temperature, such as Polydimethylsiloxane (PDMS), to preserve the CMUT static and dynamic performance. Experimental implementation of the encapsulated imaging CMUT arrays shows the device performance was maintained; 95 % of efficiency, 85% of the maximum output pressure, and 91% of the fractional bandwidth (FBW) can be preserved. A viscoelastic finite element model was also developed and shows the performance effects of the coating can be accurately predicted. Four designs, providing acoustic crosstalk suppression, flexible substrate, lens focusing, and blood flow monitoring using PDMS layer were also demonstrated. The second part of the work, presents contributions towards the electronic integration and packaging of large-area 2-D arrays. A very large 2D array is appealing for it can enable advanced novel imaging applications, such as a reconfigurable array, and a compression plate for breast cancer screening. With these goals in mind, I developed the first large-scale fully populated and integrated 2D CMUTs array with 32 by 192 elements. In this study, I demonstrate a flexible and reliable integration approach by successfully combining a simple UBM preparation technique and a CMUTs-interposer-ASICs sandwich design. The results show high shear strength of the UBM (26.5 g), 100% yield of the interconnections, and excellent CMUT resonance uniformity ([lowercase Sigma] = 0.02 MHz). As demonstrated, this allows for a large-scale assembly of a tile-able array by using an interposer. Interface engineering is crucial towards the development of CMUTs into a practical ultrasound system. With the advances in encapsulation technique with a viscoelastic polymer and the combination of the UBM technique to the TSV fabrication for electronics integration, a fully integrated CMUT system can be realized.
  • Digital
    Jules J. VanDersarl.
    Cells communicate through direct contact and soluble chemical signals. Mimicking an extracellular environment requires controlling these signals at micron length scales. Integrated circuits make electronic control at these scales trivial, but fluidic control at these length scales requires very different principles. Standard microfluidic devices can finely control flowing fluids, but fluid flow affects cells in a myriad of ways. Alternatively, diffusion based chemical delivery methods tend to be crude, ill defined systems that offer very limited control. This thesis describes three distinctive platforms that combine the active spatial and temporal control of microfluidic systems with a delivery system that relies purely on diffusion. First, we detail a silicon based array of nanoreservoirs underneath the cell culture surface which are used to store and release bioactive molecules. These reservoirs are opened and closed with electrochemical dissolution and deposition at a narrow reservoir opening. Next, we describe an adaptation of traditional, elastomer based microfluidics. In these devices the cell culture area is separated from a microfluidic channel located directly underneath the chamber by a nanoporous membrane. The desirable microfluidic properties, including temporal and spatial control, are preserved, while fluidic flow over the cells is eliminated. Finally, we demonstrate a novel "nanostraw" culture surface, which is combined with the previous device to offer fluidic access directly to the cell cytosol, creating a powerful tool with implications for cell delivery and sampling. Additional work on probing the assembly of protein structures is also detailed. Clathrin 2-dimensional lattice assembly on lipid monolayers, serving as cell membrane mimics, was monitored and studied through surface rheological techniques. Rheological measurements elucidated important network properties, and the formation process was compared to various models for clathrin network assembly.
  • Digital
    Amin Nikoozadeh.
    Atrial fibrillation, the most common type of cardiac arrhythmia, now affects more than 2.2 million adults in the United States alone. Currently, electrophysiological interventions are performed under fluoroscopic guidance, which does not provide adequate soft-tissue resolution and exposes the patient and the operator to harmful ionizing radiation. Intracardiac echocardiography (ICE) provides real-time anatomical information that has proven valuable in reducing the fluoroscopy time and enhancing procedural success. This dissertation describes the design and implementation of two types of multi-functional, forward-looking ICE catheters developed using capacitive micromachined ultrasonic transducer (CMUT) technology: MicroLinear (ML) and Ring catheters. The ML catheter enables real-time, forward-looking 2D imaging using a 24-element, fine-pitch 1D CMUT phased array. The Ring catheter uses a 64-element, ring-shaped 2D CMUT array that enables real-time, forward-looking, volumetric imaging. Both of these catheters are equipped with custom-designed, front-end electronic circuits that are integrated with each transducer array at the catheter tip. The close integration of custom electronic circuits with the ML and Ring CMUT arrays improves the signal-to-noise ratio (SNR) in each case by 18 dB and 20dB, respectively. The integration process of the CMUT arrays with the electronics dice in the tight space available for full catheter construction shows 100% yield. The characterization of the fully-integrated CMUT arrays demonstrates excellent pulse-echo response with over 100% fractional bandwidth as well as surface transmit pressure levels in excess of 1 MPa (peak-to-peak). The first fully-functional 9F ML CMUT ICE catheter shows remarkable in vivo imaging performance using porcine animal models. A similar in vivo imaging experiment with the first fully-functional 12F Ring CMUT ICE catheter proves very promising. The volumetric imaging capability of the Ring ICE catheter and the versatility offered by its inner lumen make it an attractive interventional device. This dissertation also introduces a novel CMUT structure, called PCMUT. The preliminary simulation and experimental verification of the PCMUT structure show that it is possible to fabricate CMUTs that exhibit non-flexural piston-like plate motion with a significantly improved volume displacement and fill-factor.
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    Aleš Prokop, editor.
    Springer2011
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    Ferenc A. Jolesz, editor.
    Springer2014
    Image-guided therapy (IGT) uses imaging to improve the localization and targeting of diseased tissue and to monitor and control treatments. During the past decade, image-guided surgeries and image-guided minimally invasive interventions have emerged as advances that can be used in place of traditional invasive approaches. Advanced imaging technologies such as magnetic resonance imaging (MRI), computed tomography (CT), and positron emission tomography (PET) entered into operating rooms and interventional suites to complement already-available routine imaging devices like X-ray and ultrasound. At the same time, navigational tools, computer-assisted surgery devices, and image-guided robots also became part of the revolution in interventional radiology suites and the operating room. Intraoperative Imaging and Image-Guided Therapy explores the fundamental, technical, and clinical aspects of state-of the-art image-guided therapies. It presents the basic concepts of image guidance, the technologies involved in therapy delivery, and the special requirements for the design and construction of image-guided operating rooms and interventional suites. It also covers future developments such as molecular imaging-guided surgeries and novel innovative therapies like MRI-guided focused ultrasound surgery. IGT is a multidisciplinary and multimodality field in which teams of physicians, nurses, and other professionals, such as physicists, engineers, and computer scientists, collaborate in performing these interventions, an approach that is reflected in the organization of the book. Contributing authors include members of the National Center of Image-Guided Therapy program at Brigham and Womens Hospital and international leaders in the field of IGT.
  • Digital
    Douglas A. Christensen.
  • Digital
    Kyriacos A. Athanasiou and Roman M. Natoli.
  • Digital
    edited by Dario Farina, Winnie Jensen, Metin Akay.
    Wiley2013
    pt. I. Injuries of the nervous system -- pt. II. Signal detection and conditioning -- pt. III. Function replacement (prostheses and orthosis) -- pt. IV. Function restoration -- pt. V. Rehabilitation through neuromodulation.
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    Ravi Birla.
    Wiley2014
    Introduction to Tissue Engineering -- Cells for Tissue Engineering -- Biomaterials for Tissue Engineering -- Tissue Fabrication Technology -- Vascularization of Artificial Tissue.
  • Digital
    Rodrigo Alvarez-Icaza Rivera.
    In this dissertation, I revisit Kawato's proposal, that the cerebellum predictively modulates descending motor commands, to achieve smooth and coordinated motion, by acquiring an inverse model of the biomechanical plant, and extend it by describing a novel and precise mapping between a cerebellar multizonal microcomplex and a joint's inverse model. This mapping renders two novel predictions: First, inferior olive's oscillations mirror the biomechanical joint's oscillations. Second, deep cerebellar neurons implement a gain factor, set by Purkinje cell inhibition, on inferior olive's signals to mirror the spinal cord's gain. I use biophysical modeling to show that oscillations within the inferior olive match the range of natural frequencies and damping ratios of biophysical joints, and that deep cerebellar neurons enable a multiplicative interaction between the Purkinje and the olivary pathways. Furthermore, I determine the effects of current injection into the inferior olive and the deep cerebellar nuclei and use these results within a control theory model to predict that experimentally disturbing the inferior olive will introduce motor output ringing, while disturbing the deep nuclei will also scale motor output. In both cases, manipulating the inverse model implemented by microzonal microcomplex will unmask the joint's natural dynamics as observed by motor ringing at the joint's natural frequency.
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    Widya Mulyasasmita.
    The repair of damaged tissues through cell and growth factor administration is a promising strategy in regenerative medicine. However, clinical success has been limited due to the lack of effective delivery methods. While deemed minimally invasive, the conventional approach of direct injection in saline compromises the efficacy of the biological payloads. Post-injection cell survival is often dismally low, owing to the combination of shear forces during injection and hostile environments at the injury site. Growth factors delivered by bolus injections face rapid clearance and distribution to off-target sites, leading to suboptimal concentrations at the sites of therapy and potential side effects in normal tissues. These are major therapeutic hurdles because symptomatic relief following cell therapy is often correlated with the number of surviving donor cells. In the case of growth factor therapy, spatiotemporal control over growth factor distribution is critical for normal recovery, as tissue regeneration is a tightly coordinated process. This thesis presents a biomaterials approach to overcome these hurdles by harnessing polymer and protein engineering strategies to design injectable hydrogel carries for optimal cell and drug delivery. A broad survey of protein-engineered biomaterials is first given in Chapter 1 to provide a foundation for the design principles, synthesis, and characterization methods employed in subsequent chapters. Chapter 2 describes a mechanistic investigation into the physical forces imposed on cells during injection, using alginate polysaccharides as model carriers. This study reveals extensional stresses to be the dominant cause of cell death, and that cell viability can be restored by pre-encapsulation in hydrogel carriers that exhibit thixotropy, or the ability to shear-thin and self-heal. Subsequent chapters describe the design and characterization of a thixotropic protein-engineered hydrogel system called MITCH, or Mixing-Induced Two-Component Hydrogels, and their applications as cell and drug delivery vehicles in regenerative medicine. The crosslinking of the MITCH network relies on the reversible binding between complementary peptide domains, enabling gelation and cell encapsulation by simple mixing at physiological conditions. The design rationale and demonstration of thixotropy, cyto-compatibility, and three-dimensional cell encapsulation are discussed in Chapter 3. In Chapter 4, the specificity and stoichiometric precision of the peptide-peptide crosslinking interactions are highlighted as a distinguishing feature of MITCH. Polymer physics considerations are combined with protein science methodologies to enable the predictable tuning of macroscopic-level gel mechanics through molecular-level variations of component concentration and stoichiometric ratio. The remainder of the thesis focuses on the utility of the MITCH material as a delivery carrier for cell and drug regenerative therapy. Cell protection is demonstrated in Chapter 5, where adipose-derived stem cells injected subcutaneously in mice exhibit improved retention when encapsulated and delivered in MITCH, relative to saline and control biomatrices. Moreover, histological analyses of explants show endogenous cell invasion and signs of native extracellular matrix remodeling at day 3. The simple mixing protocol allows the encapsulation and release of peptide drugs and growth factors in their bioactive state. Chapter 6 describes the engineering of an affinity- and avidity-based peptide drug delivery system, developed by using the molecular recognition domains in MITCH. Fusion of angiogenic peptides to MITCH-specific affinity tags enables drug immobilization, sustained release, and prolonged local drug availability. This controlled release strategy induces higher levels of endothelial cell migration and matrix invasion compared to delivery from saline alone. Chapter 7 presents a therapeutic angiogenesis strategy by dual delivery of human induced stem cell-derived endothelial cells (hiPSC-ECs) and vascular endothelial growth factor (VEGF). This chapter also introduces MITCH 2.0, a new class of protein polymer/synthetic polymer hybrid hydrogel system created to improve tunability and ease of synthesis. Similar to the original version, MITCH 2.0 protects cells during injection and delivers drugs with tunable kinetics. In a murine hindlimb ischemia model, hiPSC-ECs co-delivered with VEGF in MITCH show improved post-transplantation viability and restore blood perfusion to the ischemic limb. All in all, by improving the delivery of cells and biochemical factors, the biomaterials work completed here provides enabling tools to advance other biological research endeavors, to ultimately realize the clinical translation and success of regenerative medicine.
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    M. Soledad Cortina, Jose de la Cruz, editors.
    Springer2015
    This book covers the field of keratoprosthesis in detail and focuses specifically on the Boston type 1 keratoprosthesis (KPro), which is the device most widely used today. Extensive information is provided on all aspects of KPro surgery, from history and preoperative evaluation to surgical techniques and postoperative management of complications. Surgical videos are included that will aid both beginning and advanced corneal surgeons in mastering these procedures. In addition, essential basic science concepts relevant to keratoprosthesis surgery are explained, and other keratoprostheses in use around the world are considered. A brief overview of integrating artificial corneas is provided, and the future of keratoprosthesis is also discussed. The book is written by some of the most distinguished and renowned experts in the field.
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    Shantanu Banik, Rangaraj M. Rangayyan, Graham S. Boag.
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    edited by Catherine Picart, Frank Caruso, and Jean-Claude Voegel.
    Wiley2015
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    Yusuf Ozuysal.
    Neurons have a limited dynamic range. To more efficiently encode the large range of natural inputs, neural circuits adapt by dynamically changing their output range as a function of the input statistics. Variance adaptation provides an informative example of this process, whereby neurons change their response characteristics as a function of variance of their input. When their input distribution changes, sensory systems shift and scale their response curves to efficiently cover the new range of input values and they focus on different segments of the frequency spectrum, for example by choosing to average out the noise in a low signal-to-noise ratio environment by low-pass filtering their input and sacrificing resolution. In multiple sensory systems, adaptation to the variance of a sensory input changes the sensitivity, kinetics and average response over timescales ranging from < 100 ms to tens of seconds. Here we present a simple biophysically relevant model of retinal contrast adaptation that accurately captures both the membrane potential response and all adaptive properties. The adaptive component of this model is a first-order kinetic process of the type used to describe ion channel gating and synaptic transmission. We conclude that all adaptive dynamics can be accounted for by depletion of a signaling mechanism, and that contrast adaptation can be explained as adaptation to the mean of a thresholded signal. A diverse set of adaptive properties that implement theoretical principles of efficient coding can be generated by a single type of molecule or synapse with just a few microscopic states. The LNK model helps to highlight important aspects of adaptation by letting us focus on individual computational blocks separately. By using the LNK model, we investigate the source of the adaptive process in On-Off retinal ganglion cells, which show strong changes in their kinetics as a function of contrast. By analyzing properties of the LNK model, we conclude that most of the adaptive effect is due to differences in the threshold of the two pathways, with a smaller contribution from different adaptive kinetics. Adaptive temporal decorrelation in the retina arises due to differential thresholding in two parallel neural pathways.
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    Zuley Rivera Alvidrez.
    Any time we move, our brains solve the difficult problem of translating our motor intentions to muscle commands. Understanding how this computation takes place, and in particular, what role the motor cortex plays in movement generation, has been a central issue in systems neuroscience that remains unresolved. In this thesis, we took an unconventional approach to the analysis of cortical neural activity and its relationship to executed movements. We used dimensionality reduction to extract the salient patterns of neural population activity, and related those to the muscle activity patterns generated during arm reaches to a grid of targets. We found that salient neural activity patterns appeared to tightly reflect muscle activity patterns with a biologically-plausible lag. We also applied our analyses to movements that were planned before being executed, and found that a muscle-framework view of the cortical activity was consistent with previously-described predictions of movement kinematics based on the state of the cortical population activity. Overall, our results elucidate remarkable simplicity of the motor-cortical activity at the population level, despite the complexity and heterogeneity of individual cell's activities.
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    Henrique do Carmo Miranda.
    Neural recording systems are fundamental to the advancement of brain-machine interfaces that can significantly improve the quality of lives of patients with neurological diseases, such as spinal cord injuries or quadriplegia. This thesis presents two newly developed wireless neural recording systems that are able to provide a high degree of usability and neural decoding accuracy. They are capable of simultaneously transmitting 32 to 96 channels of neural signals detected by an implanted neural sensor array. This work was carried out within the framework of the Hermes project and its technical design challenges will be addressed. The Hermes project is aimed at primarily developing hardware and software tools that extract neural information from the motor cortex. Those tools can enable practical prosthetic devices used to significantly ameliorate the life of patients with neurological impairments that directly affect motor functions. The first developed system, HermesD, is a 32-channel broadband transmission system using an FSK modulated carrier at 24 Mbit/s in the 3.7-4.1 GHz band. The link range extends beyond 20 m and the total power consumption is 142 mW. The HermesD system uses only COTS components and can be easily replicated. HermesD is fully operational and is currently used to transmit broadband neural data for neuroscience research in the Neural Prosthetic Systems Laboratory (NPSL) at Stanford University. HermesD is also planned as the base platform for future human trials to take place in the same laboratory. The second system that represents the next Hermes generation, HermesE, uses a novel UWB transmitter architecture implemented in a custom IC in the 65-nm CMOS technology. The transmitted signal bandwidth covers the 3.6 to 7.5 GHz frequency range. The time domain waveform is digitally programmable, allowing a very flexible control of the output spectrum to avoid interference and to allow multi-band operation. The UWB transmitter chip is part of a 96-channel broadband recording system delivering 40 Mbit/s. Its power consumption is 230 uW for a communication range of about 5 m. The antenna subsystems for these wireless recording devices presented a design challenge given the requirements for small size, large bandwidth and high efficiency. While HermesD has an operating FBW of 10%, HermesE is much more demanding in this respect, with 70% FBW, requiring unconventional antenna structures. The design techniques and performance of the antennas required to meet the specifications of both systems are also addressed in this work.
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    Dokyoon Kim.
    This dissertation presents the basic principles of the magnetic protein chip immunoassay and applications of the magnetic protein chip for the detection of protein biomarkers. The magnetic protein chip is based on the giant magnetoresistive (GMR) spin-valve sensors, and electrical resistance changes of the sensors are measured as signals. Immunoassays were developed using the magnetic protein chips to quantitate protein biomarkers with high sensitivity. The magnetic protein chip immunoassay has several advantages over conventional non-magnetic techniques, such as multiplex capability, smaller sample volume requirement, enhanced signal-to-noise ratio, and facile integration with electronics. Ionizing radiation is high energy radiation that can remove electrons from atoms, and it causes various cellular damages some of which are lethal. Using an in vivo mouse radiation model, we developed protocols for measuring fms-related tyrosine kinase 3 ligand (Flt3lg) and serum amyloid A1 (Saa1) in small amounts of blood collected during the first week after X-ray exposures of sham, 0.1, 1, 2, 3, or 6 Gy. Flt3lg concentrations showed excellent dose discrimination at >= 1 Gy in the time window of 1 to 7 days after exposure except 1 Gy at day 7. Saa1 dose response was limited to the first two days after exposure. A discriminant analysis using both proteins could show improved dose classification accuracy. Our magnetic protein chip immunoassay demonstrated the dose and time responses and low-dose sensitivity that have important advantages in radiation triage biodosimetry. Necrotizing enterocolitis (NEC) is an inflammatory bowel disease often observed in pre-term babies and has high mortality rate. However, timely diagnosis of NEC has been hampered due to its unspecific symptoms and ineffective clinical tests currently available. We developed a magnetic protein chip immunoassay for the validation of NEC biomarkers. Three biomarkers, C-reactive protein (CRP), matrix metalloproteinase-7 (MMP7), and epithelial cell adhesion molecule (EpCAM) were quantitated using a small amount of blood samples. Receiver operating characteristic (ROC) curve analysis combined with bootstrapping technique showed excellent discrimination of NEC from healthy control and NEC from sepsis. Given the generality of the detection scheme used in the magnetic protein chip immunoassay, the magnetic protein chips are expected to hold great potential for medical diagnosis and clinical research.
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    Ernesto Staroswiecki.
    Osteoarthritis (OA) is a degenerative joint disease that affects over 80% of the population of the U.S. by age 65. However, there is currently no disease-modifying treatment for OA. In order to develop and evaluate potential treatments, it is necessary to assess cartilage health over the course of the disease. Here, an MRI method is presented to obtain sodium images of tissue that pushes the current state of the art of sodium MRI and can provide new information about cartilage. The method presented here enables sodium imaging at high resolution and with lower noise levels than previously reported. This technique uses custom-made radio-frequency (RF) coils and a 3D-cones k-space trajectory and is well suited to imaging at high field strengths like 3 T and 7 T. A second novel method is presented for generating high-resolution, 3D T2 and ADC maps of the human knee in vivo. The maps are derived from diagnostic-quality morphological MR images. This method is based on a new variation of the 3D double echo steady-state (DESS) sequence and solves many of the current challenges of traditional imaging techniques. Finally, a third method is presented allowing independent excitation of two or more volumes with a short RF pulse for MRI. This method enables different volumes to be excited with different RF pulse parameters, including flip angle, slice profile or thickness, phase modulation, etc., increasing the flexibility of the excitation. In summary, the techniques presented here generate measurements of sodium, T2, and ADC in cartilage, all biomarkers of interest for this tissue. These measurements are either less noisy or more efficiently obtained than with previous methods. The methods presented in this dissertation also improve the efficiency of diagnostic image acquisition for the knee.
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    Gaurav Krishnamurthy.
    The mitral valve (MV) is a bicuspid valve that allows the unidirectional flow of blood from the left atrium (LA) into the left ventricle (LV). MV disease afflicts millions each year worldwide and if sufficiently severe, surgical therapy is indicated. Surgical repair is currently preferred but valve replacement is often required. Current replacement therapy involves implantation of a mechanical valve, associated with anticoagulation/ thromboembolic complications, or a tissue valve, associated with less than ideal durability. To overcome these limitations, a currently important research goal is to create bioengineered autologous tissue valves. A key component of this thrust is to understand more completely the structure and function of native valves which reliably cycle 100,000 times per day, more than 3 billion times in an average lifetime. Toward this end, this thesis presents, for the first time, the material properties of the anterior mitral leaflet in the beating heart. The methodology used in this research is as follows: Surgical preparation and radiopaque marker data acquisition: 16 miniature radiopaque markers were sewn to the MV annulus, 16 to the anterior MV leaflet, and one on each papillary muscle tip in male sheep. 4-D coordinates were obtained from biplane videofluoroscopic marker images (60f/s) during three complete cardiac cycles. Data were acquired sequentially with repeat control runs between saddlehorn electrical pulse stimulation and intravenous administration of esmolol to study the effect of pharmacological agents on mitral leaflet contractility, and vagal nerve stimulation to assess the potential for central neural control. Inverse finite element analysis: A finite element model of the anterior MV leaflet was developed using marker coordinates at the end of isovolumic relaxation (IVR, when pressure difference across the valve is approximately zero), as the stress-free reference state. Leaflet displacements were simulated during IVR using measured left ventricular and atrial pressures. The elastic moduli in both the commisure-commisure (Ecirc) and radial (Erad) directions were optimized using the Method of Feasible Directions to minimize the difference between simulated and measured displacements. The derived material properties were found to be orders of magnitude greater than previously determined ex vivo material properties. Histologic studies have shown that the mitral leaflets, rather than being simple collagen flaps (as once thought), contain complex networks of contractile elements (smooth and striated muscle; valvular interstitial cells), blood vessels, and both afferent & efferent nerves. The finding of higher stiffness in vivo than ex vivo suggests a mechanistic role for these elements; to modulate the stiffness of the active mitral valve in vivo -- a property necessarily missing in excised, flaccid valves ex vivo. Using the derived material properties, a forward analysis was performed to determine the stress-strain behavior of the anterior leaflet at various trans-mitral pressure gradients during IVR. This analysis showed that the leaflet material behaved linearly over a physiologic range of pressures. It is also shown in this thesis that these leaflet material properties vary over the cardiac cycle; leaflet stiffness is higher during early systole (Isovolumic Contraction, IVC) most likely due to force development in cardiac muscle cells in the annular third of the anterior leaflet, and as this force development wanes during systole, the stiffness of the leaflet drops. Stimulation of the neutrally-rich annular saddlehorn region adjacent to the anterior leaflet was shown to almost double leaflet stiffness, whereas administration of a beta-blocker (Esmolol) eliminated the early systolic increase in anterior leaflet stiffness. The initial homogeneous finite element model of the anterior leaflet was further developed to incorporate regionally varying material properties. This heterogeneous finite element model confirmed that Esmolol selectively reduced leaflet stiffness in the annular region (which contains the slip of cardiac muscle) during IVC and did not affect edge stiffness (which is devoid of cardiac muscle). Saddlehorn stimulation caused an increase in leaflet stiffness values for all regions (edge, belly and annular regions) during both IVC and IVR. Loss of atrial contraction had a similar effect on the anterior leaflet as administration of Esmolol, i.e. without atrial depolarization the leaflet stiffness during IVC in the annular region dropped to baseline IVR values. Finally, the functional role of autonomic nerves in the anterior leaflet was investigated by remote stimulation of the vagus nerve. This study showed that vagal nerve stimulation can result in a decrease in anterior leaflet stiffness during both IVR and IVC. In summary, the findings of this thesis suggest a permanent paradigm shift from one viewing the mitral valve leaflets as passive flaps to one viewing the leaflets as active, potentially adaptive, neurally-controlled tissues whose complex function and dysfunction must be taken into account when considering not only therapeutic approaches to mitral valve disease, but even the definitions of mitral valve disease itself. The improved understanding of the structure-function relationships in these native, active valves could uncover new targets for pharmacologic intervention, as well as provide important insights to improve the future design and durability of tissue-engineered mitral valves.
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    [edited by] Jan de Boer, Clemens A. van Blitterswijk.
    Cambridge2013
    "This complete, yet concise, guide introduces you to the rapidly developing field of high throughput screening of biomaterials: materiomics. Bringing together the key concepts and methodologies used to determine biomaterial properties, you will understand the adaptation and application of materomics in areas such as rapid prototyping, lithography and combinatorial chemistry. Each chapter is written by internationally renowned experts, and includes tutorial paragraphs on topics such as biomaterial-banking, imaging, assay development, translational aspects, and informatics. Case studies of state-of-the-art experiments provide illustrative examples, whilst lists of key publications allow you to easily read up on the most relevant background material. Whether you are a professional scientist in industry, a student, or a researcher, this book is not to be missed if you are interested in the latest developments in biomaterials research"--Provided by publisher.
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    Adam Shar Wang.
    Computed tomography (CT) has become an essential tool in modern medicine since its introduction in the early 1970s. It generates cross-sectional images of the body's x-ray attenuation by measuring the transmission of x-rays in many directions. Because CT uses ionizing radiation, a governing principle is to use the least amount of radiation dose that still provides diagnostic-quality images. One approach to ensure that dose is appropriately used is to explore the information content of CT scans. This work examines efficient methods for encoding, storing, and extracting information from CT scans, especially as they pertain to spectral x-ray imaging. CT systems that can take advantage of the different attenuation properties of x-rays at different energies can provide additional diagnostic information, known as dual energy imaging. A new technique called Synthetic CT is introduced that enables images from CT protocols other than what was acquired to be retrospectively synthesized. With this tool, the information contained within a dual energy scan can be used to demonstrate the effect of protocol selection on image quality and dose distribution. In addition to experimentally validating the developed synthetic CT theory, further efforts have led to image-based synthetic CT, incorporation of electronic noise models for ultra low dose simulation, and a simple graphical user interface that demonstrates the flexibility of synthetic CT. We also explore an important spectral imaging technology -- photon counting detectors with energy discrimination capabilities. In principle, these detectors capture all the spectral information of transmitted x-rays by counting the number of photons at each energy. Optimal configurations of ideal photon counting detectors are first investigated, leading to the elegant discovery that two energy-dependent weighted counts can form a sufficient statistic for dual energy imaging. In practice, photon counting detectors have count rate limitations and imperfect spectral responses. The performance of realistic photon counting detectors is modeled and compared to conventional dual kV techniques. We find that both optimized photon counting and dual kV systems can significantly increase the dose efficiency of dual energy imaging.
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    Peter J. Fabri.
    Springer2016
    Introduction to Measurement and Analysis -- Data and Types of Data -- Software for Analytics -- Measurement and Uncertainty -- Mathematical and Statistical Concepts in Data Analysis -- Analysis by Modeling Data -- Principles of Supervised Learning -- Unsupervised Machine Learning -- Datasets Without Outcomes -- Survival Analysis -- Interpreting Outcomes: Cause and Effect and p-values -- Useful Tools.
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    Melinda Joy Cromie.
    This dissertation addressed two challenges in musculoskeletal biomechanics. The first challenge was to understand the function of total knee prostheses after implantation in patients. Motions of the knee following total knee replacement affect a patient's ability to perform daily activities, such as walking and rising from a chair, and affect the longevity of the prosthesis. The millimeter-scale translations of the joint are difficult to measure with noninvasive methods such as analysis of skin mounted markers. We addressed this challenge by measuring passive knee kinematics using a surgical navigation system. The specific goal was to isolate the effects of posterior cruciate ligament removal on knee motion after total knee arthroplasty. We measured knee kinematics intraoperatively while the surgeon passively flexed and extended the knee at four surgical time points: after initial exposure, after removing the anterior cruciate ligament, after removing the posterior cruciate ligament, and after implanting the prosthesis. We calculated anterior femoral translation and the flexion angle at which femoral rollback began. We found that removing the posterior cruciate ligament introduced abnormal anterior translation, doubling the anterior translation from the initial exposure (from 5.1 +/- 4.3 mm to 10.4 +/- 5.1 mm) and increasing the flexion angle at which femoral rollback began (from 31.2 +/- 9.6 degrees to 49.3 +/- 7.3 degrees). Implanting the prosthesis did not restore the motion measured at initial exposure. Relative to the cruciate-deficient case, prosthesis implantation increased the amount of anterior translation (to 16.1 +/- 4.4 mm) and did not change the flexion angle at which femoral rollback began. Abnormal anterior translation was observed in low and mid flexion (0-60 degrees) after removing the posterior cruciate ligament, and normal motion was not restored by the posterior stabilized prosthesis. These findings can be used to interpret further motion analysis during functional tasks and to guide improvements in prosthesis design. The second challenge was to understand how the motions of sarcomeres, the contractile units of muscle, affect the force-generating capacity of muscles in humans. Sarcomere length over a muscle's range of motion in the body is an important factor that affects muscle excursions and force-generating capacity. The relationship between sarcomere length and joint angle can be altered in disease, and measurement of this relationship is important for guiding treatments. Second-harmonic generation (SHG) microendoscopy has recently been developed in our laboratories to image sarcomeres and measure their lengths in humans. However, technical challenges such as motion artifacts and low signal have thus far prevented this novel technique from being used to quantify sarcomere lengths in humans. We discovered that an excitation wavelength of 960 nm maximized image signal; this enabled an image acquisition rate of 3 frames-per-second, which decreased motion artifact. We then used microendoscopy to directly image sarcomeres in the extensor carpi radialis brevis (ECRB) in seven healthy adults with the wrist in 45 degrees extension and 45 degrees flexion. We determined the average sarcomere lengths and the length variability of in-series sarcomeres from the SHG images. Sarcomere lengths in 45 degrees wrist extension were 2.93 +/- 0.29 microns (mean +/- standard deviation) and increased to 3.58 +/- 0.19 microns in 45 degrees flexion. Within local regions of the fibers the standard deviation of sarcomere lengths in series was 0.20 +/- 0.07 microns. These measurements agree with measurements in the same muscle using laser diffraction. The lengths of sarcomeres in series within a small region of an individual fiber can vary substantially. This study demonstrates the suitability of SHG microendoscopy for imaging muscle microstructure and illustrates the potential of this technology to address a new class of questions about muscle architecture and remodeling in humans. The ability to measure sarcomere operating lengths in humans without surgery enables us to diagnose the involvement of specific muscles in neuromuscular disorders, and to design surgeries that will optimize an individual patient's outcome. Measurement of sarcomere operating length will also enable a new class of research questions to be addressed about the adaptations of muscles over time in response to surgeries or pharmacologic treatments.
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    Cynthia Anne Chestek.
    Cortical brain-machine interfaces, or BMIs, is a relatively new field with the potential to provide many different clinical treatments, particularly for fully paralyzed patients. In these applications, multichannel electrode arrays are implanted into motor cortical areas in order to extract useful control signals. My research focuses on taking proof-of-concept academic BMI systems, and solving the engineering challenges that currently prevent them from being used in a clinical setting. These challenges include running a BMI for more than a few hours or a single day, and finding ways to minimize the size, cost, and operational complexity of the complete system. This dissertation includes an analysis of neuron stability over long timescales. I will show that the relationship between neurons in motor cortices and behavior remains stationary over time despite substantial noise, which could mitigate some concerns about long-term BMI performance. I will also discuss the development of HermesC, a wireless system for recording multichannel neural data from freely moving primates. This device dramatically reduces the size and cost of current recording technology for real-time neural prosthetic systems, and could be useful for human clinical trials. It may also enable neural prosthetic studies with animals in a less constrained setting. Combining traditional neural recordings with overnight wireless neural recordings, I will also show that there are substantial changes in neural waveforms from single neurons across days. However, the quality of neural decodes (the extraction of useful control signals) is only slightly improved by sorting individual units rather than using simple threshold crossings. This may enable long term BMI operation because multiunit neural "hash" on electrode arrays tends to persist for a long time, perhaps years, after single neuron signals have declined due to various tissue responses. In fact, other recent work from this project has demonstrated high performance neural decodes using only threshold crossings on arrays ~2.5 years after implantation.
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    editors: Shaun D. Gregory, Michael C. Stevens, John F. Fraser.
    ScienceDirect2017
    1. Descent into heart and lung failure -- 2. Heart and lung transplantation -- 3. First-generation ventricular assist devices -- 4. Second-generation ventricular assist devices -- 5. Third-generation ventricular assist devices -- 6. Biventricular assist devices -- 7. Total artificial hearts -- 8. Extracorporeal membrane oxygenation -- 9. Pediatric devices -- 10. Hydraulic design -- 11. Motor design and impeller suspension -- 12. Pulsatile vs. continuous flow -- 13. Preclinical evaluation -- 14. Optimizing the patient and timing of the introduction of mechanical circulatory and extracorporeal respiratory support -- 15. Surgical implantation -- 16. Complications of mechanical circulatory and respiratory support -- 17. Medical management of the supported patient -- 18. Cannula design -- 19. Blood-device interaction -- 20. Physiological control -- 21. Percutaneous and transcutaneous connections -- 22. Wearable systems -- 23. Route to market -- 24. Cost-effectiveness -- 25. The past, present, and future -- Index.
  • Digital
    Julia Chinghua Chen.
    Our bones constantly adapt to their mechanical environment through a biological response from the womb to the tomb. Mechanobiology, the biological response to mechanical loading, is important for determining various properties of bone such as size and shape. During embryonic development, rapid growth generates significant tension in the periosteum, and tension has previously been shown to lead to bone apposition. In adults, intracortical stresses dominate and increased loading leads to elevated rates in bone apposition. Periosteal tension and intracortical stresses, then, are both experienced by bones, but their influences on bone apposition rates vary over time. This dissertation analyzes how embryonic bone growth rates and adult bone adaptation rates in long bones are related to their respective mechanical environments. The hypothesis that bones grow and adapt at rates corresponding to changes in the mechanical environment is investigated. In the first study, I investigated the mechanical environment of the periosteum during embryonic growth and its relationship to bone growth rates. The specific growth rate, or percent growth per day, was calculated using microCT images taken over embryonic days 11-20. Bones grew faster in length than in circumference during this time. Finite element techniques were then used to analyze the opening dimensions of incisions through the periosteum. Longitudinal and circumferential residual strains decreased from 46.2% to 29.3%, and 10.6% to 3.9%, respectively, during embryonic days 14-20. Residual strains were positively correlated to specific growth rates (p< 0.05). Many studies have investigated bone adaptation in adult mice and rats by applying loads to the long bones, and measuring changes in periosteal cortical bone apposition rates. However, results are difficult to compare because the loading schemes are generally different. The second study presents a theoretical framework for evaluating the mechanical stimulus based on the bone daily strain stimulus, which is a function of loading cycles and bone strains. The daily strain stimulus may act as a single unifying parameter for directly comparing data from existing in vivo experiments. Two approaches were used to determine the periosteal daily strain stimulus necessary for bone maintenance (xi_peri_0) and the strain-cycle weighting exponent (m), which are required to calculate the daily strain stimulus. In the first approach, data from bone maintenance studies were used to calculate xi_peri_0 to be 2793 microstrain/day, and m to be 4.5. In the second approach, strain gage recordings were used to calculate xi_peri_0 to be 1496 microstrain/day, and human bone compressive fatigue properties were used to assign m to be 11.88. Bone apposition rates generally increased with increasing daily strain stimulus, which was consistent with previous theoretical models. The third study provides examples of how the daily strain stimulus may be used to examine the effects of specific loading parameters on bone apposition rates. The effects of inserting periods of rest and frequency were examined. Inserting periods of rest during loading appeared to increase bone apposition rates by approximately 64% compared to continuously loaded bones. Frequency has been previously suggested to be most osteogenic at 5-10 Hz. Using this analysis, an increase in bone apposition rate was also observed at 10 Hz. The results of these studies provide insight into the effects of periosteal tension during embryonic development and intracortical strains during adulthood on bone apposition rates. These findings illustrate how important the mechanical loads experienced by bones and their surrounding tissues are in determining the sizes and shapes of bones.
  • Digital
    Chelsey Savannah Simmons.
    The heart is a complex integrated system that leverages mechanoelectrical signals to synchronize cardiomyocyte contraction and push blood throughout the body. Due to the heart's limited regenerative capacity and the wide variety of cardiovascular pathologies, heart disease is often studied in vitro. However, it is difficult to accurately replicate the cardiac environment outside of the body. In this dissertation, I describe an integrated strain array for cell culture that mimics the mechanical movement of the heart and enables high-throughput mechanotransduction studies. Along with mechanical strain, substrate stiffness is an important mechanical stimulus. The heart and vasculature, along with other organs, remodel in both development and disease, changing their mechanical properties. I successfully implement a method that can simultaneously tune both substrate stiffness and mechanical strain in normal and pathological ranges. Polyacrylamide gels, attached to stretchable silicone platforms by interpenetrating networks, can be stretched up to 50% without delaminating. To fully harness the potential of studying heart disease in vitro, better techniques for studying heart cell contractions are required in addition to biomimetic dynamic culture. In this dissertation, I also describe two successful new approaches to quantifying cardiomyocyte contractility using simple phase contrast videos: one for single cells plated on soft gels and one for cell monolayers attached to glass or plastic. Together, these innovations provide a suite of tools to stimulate and assess cardiovascular cells and advance our collective knowledge of cardiovascular health and disease.
  • Digital
    Marnie M. Saunders, The University of Akron, Akron, Ohio.
    Atypon2015
    Mechanical testing is a useful tool in the field of biomechanics. Classic biomechanics employs mechanical testing for a variety of purposes. For instance, testing may be used to determine the mechanical properties of bone under a variety of loading modes and various conditions including age and disease state. In addition, testing may be used to assess fracture fixation procedures to justify clinical approaches. Mechanical testing may also be used to test implants and biomaterials to determine mechanical strength and appropriateness for clinical purposes. While the information from a mechanical test will vary, there are basics that need to be understood to properly conduct mechanical testing. This book will attempt to provide the reader not only with the basic theory of conducting mechanical testing, but will also focus on providing practical insights and examples.
  • Digital
    Manuel K. Rausch.
    The mitral valve is one of four heart valves that ensure unidirectional blood flow through the heart. Due to mitral valve failure approximately 44,000 people in the US alone undergo open heart surgery every year. Current treatment options include mitral valve replacement and mitral valve repair, neither of which have shown satisfying long-term success. A deepened understanding of mitral valve mechanics may help in improving current medical device designs and treatment options for mitral valve regurgitation. Here I provide an in depth analysis of the in vivo mechanics of the mitral valve using the theory of finite kinematics and based on this data develop non-linear in silico models of the mitral valve employing the finite element method. Using mechanical metrics such as strain and curvature I reveal the in vivo deformation of the mitral annulus and the mitral leaflet in the healthy, diseased, and repaired mitral valve. Furthermore, in silico I explore the effects of prestrain as well as growth and remodeling on the mechanics of the mitral valve. The results of my in vivo studies extend our current understanding of the healthy mitral valve, reveal new insight into disease characteristics and progressions, and evaluate the efficacy of current device designs. Furthermore, results from the in silico studies provide improved means to simulate mitral valve mechanics and predict long term adaptation for basic science research and medical device design. In conclusion, with the current work I take a large step toward a deepened understanding of mitral valve mechanics that may help to optimize medical device designs and treatment options.
  • Digital
    edited by Simon C. F. Rawlinson.
    Wiley2017
    Extracellular Matrix Structure and Stem Cell Mechanosensing / Nicholas D Evans, Camelia G Tusan -- Molecular Pathways of Mechanotransduction / Hamish T J Gilbert, Joe Swift -- Sugar-Coating the Cell / Stefania Marcotti, Gwendolen C Reilly -- The Role of the Primary Cilium in Cellular Mechanotransduction / Kian F Eichholz, David A Hoey -- Mechanosensory and Chemosensory Primary Cilia in Ciliopathy and Ciliotherapy / Surya M Nauli, Rinzhin T Sherpa, Caretta J Reese, Andromeda M Nauli -- Mechanobiology of Embryonic Skeletal Development / Andrea S Pollard, Andrew A Pitsillides -- Modulating Skeletal Responses to Mechanical Loading by Targeting Estrogen Receptor Signaling / Gabriel L Galea, Lee B Meakin -- Mechanical Responsiveness of Distinct Skeletal Elements / Simon C F Rawlinson -- Pulmonary Vascular Mechanics in Pulmonary Hypertension / Zhijie Wang, Lian Tian, Naomi C Chesler -- Mechanobiology and the Kidney Glomerulus / Franziska Lausecker, Christoph Ballestrem, Rachel Lennon -- Dynamic Remodeling of the Heart and Blood Vessels / Ken Takahashi, Hulin Piao, Keiji Naruse -- Aortic Valve Mechanobiology / K Jane Grande-Allen, Daniel Puperi, Prashanth Ravishankar, Kartik Balachandran -- Testing the Perimenopause Ageprint using Skin Visoelasticity under Progressive Suction / Gérald E Piérard, Claudine Piérard-Franchimont, Ulysse Gaspard, Philippe Humbert, Sébastien L Piérard -- Mechanobiology and Mechanotherapy for Skin Disorders / Chao-Kai Hsu, Rei Ogawa -- Mechanobiology and Mechanotherapy for Cutaneous Wound-Healing / Chenyu Huang, Yanan Du, Rei Ogawa -- Mechanobiology and Mechanotherapy for Cutaneous Scarring / Rei Ogawa, Chenyu Huang -- Mechanobiology and Mechanotherapy for the Nail / Hitomi Sano, Rei Ogawa -- Bioreactors / James R Henstock, Alicia J El Haj -- Cell Sensing of the Physical Properties of the Microenvironment at Multiple Scales / Julien E Gautrot -- Predictive Modeling in Musculoskeletal Mechanobiology / Hanifeh Khayyeri, Hanna Isaksson, Patrick J Prendergast -- Porous Bone Graft Substitutes / Charlie Campion, Karin A Hing -- Exploitation of Mechanobiology for Cardiovascular Therapy / Winston Elliott, Amir Keshmiri, Wei Tan.
  • Digital
    Craig J. Goergen.
    The aorta is the largest blood vessel in the body, responsible for carrying blood from the heart directly to most major organs and ending at the iliac arteries which feed the lower extremities. This elastic vessel provides much of the vascular system's compliance and is composed of a heterogeneous mixture of smooth muscle cells, collagen, and elastin. The general purpose of our work has been to use in vivo imaging to determine abdominal aortic dynamics in a variety of healthy and diseased cases. First, a cross-species analysis in mice, rats, rabbits, pigs and humans showed with M-mode ultrasound that infrarenal abdominal aortic motion was similar in animals and humans, regardless of aortic size. Greater anterior than posterior wall motion was observed and aortic wall displacement increased linearly with diameter. Next, cardiovascular abnormalities in a recently developed mouse model for Williams-Beuren Syndrome (WBS) were investigated. WBS is a rare genetic disorder caused by a heterozygous 1.5-megabase deletion, which typically includes the elastin gene. In this study, we showed that Wbs mice have hypertension, reduced in vivo cyclic strain, and fragmented medial elastin sheets - all characteristics similar to human WBS. These data provide insight into the genotype-phenotype relationship between elastin levels, aortic stiffness, and the cardiovascular abnormalities associated with WBS and other microdeletion syndromes. Finally, the biomechanical influences on murine models of abdominal aortic aneurysms (AAA), a pathological dilation of the abdominal aorta, were investigated using magnetic resonance imaging. From this work, we showed that the location of aneurysm development may be correlated with the location of maximum abdominal aortic curvature in angiotensin II-induced murine AAAs. This model consistently forms abdominal aneurysms with repeatable leftward vessel expansion above the renal arteries. Our work has shown that this leftward saccular shape is likely influenced by leftward suprarenal aortic curvature and motion. Histological analysis provided evidence for degradation of medial elastin at one focal location on the left side of the vessel, with a majority of animals also developing an adventitial hematoma at a similar circumferential location. Conversely, elastase-induced infrarenal murine AAAs do not form in a location of high vessel curvature and do not expand in one general direction. This work will help to further our understanding of the role mechanics may play in AAA formation, progression, and eventual rupture.
  • Digital/Print
    Digital : ANSI2003Click fulltext button, Click guest acess (upper right) and Search for standard number 13485
    Print2003
  • Digital/Print
    Digital : WHO2010
    Print2010
  • Digital
    Binseng Wang.
    Atypon2012
    In addition to being essential for safe and effective patient care, medical equipment also has significant impact on the income and, thus, vitality of healthcare organizations. For this reason, its maintenance and management requires careful supervision by healthcare administrators, many of whom may not have the technical background to understand all of the relevant factors. This book presents the basic elements of medical equipment maintenance and management required of healthcare leaders responsible for managing or overseeing this function. It will enable these individuals to understand their professional responsibilities, as well as what they should expect from their supervised staff and how to measure and benchmark staff performance against equivalent performance levels at similar organizations. The book opens with a foundational summary of the laws, regulations, codes, and standards that are applicable to the maintenance and management of medical equipment in healthcare organizations. Next, the core functions of the team responsible for maintenance and management are described in sufficient detail for managers and overseers. Then the methods and measures for determining the effectiveness and efficiency of equipment maintenance and management are presented to allow performance management and benchmarking comparisons. The challenges and opportunities of managing healthcare organizations of different sizes, acuity levels, and geographical locations are discussed. Extensive bibliographic sources and material for further study are provided to assist students and healthcare leaders interested in acquiring more detailed knowledge.
  • Print
    John G. Webster, editor ; contributing authors, John W. Clark, Jr. ... [et al.].
    Basic concepts of medical instrumentation / Walter H. Olson -- Basic sensors and principles / Robert A. Peura and John G. Webster -- Amplifiers and signal processing / John G. Webster -- The origin of biopotentials / John W. Clark, Jr. -- Biopotential electrodes / Michael R. Neuman -- Biopotential amplifiers / Michael R. Neuman -- Blood pressure and sound / Robert A. Peura -- Measurement of flow and volume of blood / John G. Webster -- Measurements of the respiratory system / Frank P. Primiano, Jr. -- Chemical biosensors / Robert A. Peura -- Clinical laboratory instrumentation / Lawrence A. Wheeler -- Medical imaging systems / Melvin P. Siedband -- Therapeutic and prosthetic devices / Michael R. Neuman -- Electrical safety / Walter H. Olson.
  • Print
    Desmond J. Sheridan.
    Status: Not Checked OutLane Catalog Record
  • Digital
    Angela Ruohao Wu.
    Protein--DNA interactions are responsible for numerous critical cellular events: for example, gene expression and silencing are mediated by transcription factor protein binding and histone protein modifications, and DNA replication and repair rely on site specific protein binding. Chromatin immunoprecipitation (ChIP) is the only molecular assay that directly determines, in a living cell, the binding association between a protein of interest and specific genomic loci. It is an indispensible tool in the biologists' toolbox, but the many limitations of this technique prevent broad adoption of ChIP in biological studies. The typical ChIP assay can take up to one week to complete, and the process is technically tricky, yet tedious. ChIP assay yields are also low, thus requiring on the order of millions to billions of cells as starting material, which makes the assay unfeasible for studies on rare or precious samples. Cancer stem cells (CSCs), for instance, are obtained from primary tumors, and FACS sorting of the dissociated tumor cells rarely yields more than ~100,000 CSCs per tumor. This thesis describes the microfluidics-based strategies for performing ChIP. The first design for a microfluidic ChIP design utilizes the automation and scalability aspects of microfluidics to reduce both total and hands-on assay time, and improve throughput. It can take chromatin prepared using any existing ChIP protocol as input, and generate ChIP-qPCR results in just 1 day. The device is shown to be comparable to existing ChIP protocols, and can detect cellular epigenetic changes induced by external cytokine stimulants. It was used to investigate transcription factor binding dynamics in an aging-related pathway, and was able to link transcription factor binding to local changes in histone modifications. The second design of the microfluidic ChIP platform focuses on addressing the cell number requirements of ChIP. In addition to reducing assay time through automation, this design incorporates microfluidic designs that allow whole fixed cells as input, and enables automated ChIP from as few as 2,000 cells. Finally, using this high-sensitivity ChIP device in conjunction with next-generation sequencing technology, a protocol for determining genome-wide epigenetic landscapes from as few as 2,000 cells is developed, with the ultimate goal of performing protein-DNA association studies on CSCs.
  • Digital
    Luisa Ciobanu.
    TandFonline2017
    "In the past two decades, significant advances in magnetic resonance microscopy (MRM) have been made possible by a combination of higher magnetic fields and more robust data acquisition technologies. This technical progress has enabled a shift in MRM applications from basic anatomical investigations to dynamic and functional studies, boosting the use of MRM in biological and life sciences. This book provides a simple introduction to MRM emphasizing practical aspects relevant to high magnetic fields. It focuses on biological applications and presents a number of selected examples of neuroscience applications. The text is mainly intended for those who are beginning research in the field of MRM or are planning to incorporate high-resolution MRI in their neuroscience studies."--Provided by publisher.

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