Understanding the in vitro dissolution rate of glasses with respect to future clinical applications

Glass is a unique material with a long history. Several glass products are used daily in our everyday life, often unnoticed. Glass can be found not only in obvious applications such as tableware, windows, and light bulbs, but also in tennis rackets, windmill turbine blades, optical devices, and medical implants. The glasses used at present as implants are inorganic silica-based melt-derived compositions mainly for hard-tissue repair as bone graft substitute in dentistry and orthopedics. The degree of glass reactivity desired varies according to implantation situation and it is vital that the ion release from any glasses used in medical applications is controlled. Understanding the in vitro dissolution rate of glasses provides a first approximation of their behavior in vivo. Specific studies concerning dissolution properties of bioactive glasses have been relatively scarce and mostly concentrated to static condition studies. The motivation behind this work was to develop a simple and accurate method for quantifying the in vitro dissolution rate of highly different types of glass compositions with interest for future clinical applications. By combining information from various experimental conditions, a better knowledge of glass dissolution and the suitability of different glasses for different medical applications can be obtained. Thus, two traditional and one novel approach were utilized in this thesis to study glass dissolution. The chemical durability of silicate glasses was tested in water and TRIS-buffered solution at static and dynamic conditions. The traditional in vitro testing with a TRISbuffered solution under static conditions works well with bioactive or with readily dissolving glasses, and it is easy to follow the ion dissolution reactions. However, in the buffered solution no marked differences between the more durable glasses were observed. The hydrolytic resistance of the glasses was studied using the standard procedure ISO 719. The relative scale given by the standard failed to provide any relevant information when bioactive glasses were studied. However, the clear differences in the hydrolytic resistance values imply that the method could be used as a rapid test to get an overall idea of the biodegradability of glasses. The standard method combined with the ion concentration and pH measurements gives a better estimate of the hydrolytic resistance because of the high silicon amount released from a glass. A sensitive on-line analysis method utilizing inductively coupled plasma optical emission spectrometer and a flow-through micro-volume pH electrode was developed to study the initial dissolution of biocompatible glasses. This approach was found suitable for compositions within a large range of chemical durability. With this approach, the initial dissolution of all ions could be measured simultaneously and quantitatively, which gave a good overall idea of the initial dissolution rates for the individual ions and the dissolution mechanism. These types of results with glass dissolution were presented for the first time during the course of writing this thesis. Based on the initial dissolution patterns obtained with the novel approach using TRIS, the experimental glasses could be divided into four distinct categories. The initial dissolution patterns of glasses correlated well with the anticipated bioactivity. Moreover, the normalized surface-specific mass loss rates and the different in vivo models and the actual in vivo data correlated well. The results suggest that this type of approach can be used for prescreening the suitability of novel glass compositions for future clinical applications. Furthermore, the results shed light on the possible bioactivity of glasses. An additional goal in this thesis was to gain insight into the phase changes occurring during various heat treatments of glasses with three selected compositions. Engineering-type T-T-T curves for glasses 1-98 and 13-93 were stablished. The information gained is essential in manufacturing amorphous porous implants or for drawing of continuous fibers of the glasses. Although both glasses can be hot worked to amorphous products at carefully controlled conditions, 1-98 showed one magnitude greater nucleation and crystal growth rate than 13-93. Thus, 13-93 is better suited than 1-98 for working processes which require long residence times at high temperatures. It was also shown that amorphous and partially crystalline porous implants can be sintered from bioactive glass S53P4. Surface crystallization of S53P4, forming Na2O∙CaO∙2SiO2, was observed to start at 650°C. The secondary crystals of Na2Ca4(PO4)2SiO4, reported for the first time in this thesis, were detected at higher temperatures, from 850°C to 1000°C. The crystal phases formed affected the dissolution behavior of the implants in simulated body fluid. This study opens up new possibilities for using S53P4 to manufacture various structures, while tailoring their bioactivity by controlling the proportions of the different phases. The results obtained in this thesis give valuable additional information and tools to the state of the art for designing glasses with respect to future clinical applications. With the knowledge gained we can identify different dissolution patters and use this information to improve the tuning of glass compositions. In addition, the novel online analysis approach provides an excellent opportunity to further enhance our knowledge of glass behavior in simulated body conditions.

An introduction to medical imaging with coherent terahertz frequency radiation

Methods have recently been developed that make use of electromagnetic radiation at terahertz (THz) frequencies, the region of the spectrum between millimetre wavelengths and the infrared, for imaging purposes. Radiation at these wavelengths is non-ionizing and subject to far less Rayleigh scatter than visible or infrared wavelengths, making it suitable for medical applications. This paper introduces THz pulsed imaging and discusses its potential for in vivo medical applications in comparison with existing modalities.

Culture bag systems for clinical applications of adult human neural crest-derived stem cells

Introduction Facing the challenging treatment of neurodegenerative diseases as well as complex craniofacial injuries such as those common after cancer therapy, the field of regenerative medicine increasingly relies on stem cell transplantation strategies. Here, neural crest-derived stem cells (NCSCs) offer many promising applications, although scale up of clinical-grade processes prior to potential transplantations is currently limiting. In this study, we aimed to establish a clinical-grade, cost-reducing cultivation system for NCSCs isolated from the adult human nose using cGMP-grade Afc-FEP bags. Methods We cultivated human neural crest-derived stem cells from inferior turbinate (ITSCs) in a cell culture bag system using Afc-FEP bags in human blood plasma-supplemented medium. Investigations of viability, proliferation and expression profile of bag-cultured ITSCs were followed by DNA-content and telomerase activity determination. Cultivated ITSCs were introduced to directed in vitro differentiation assays to assess their potential for mesodermal and ectodermal differentiation. Mesodermal differentiation was determined using an enzyme activity assay (alkaline phosphatase, ALP), respective stainings (Alizarin Red S, Von Kossa and Oil Red O), and RT-PCR, while immunocytochemistry and synaptic vesicle recycling were applied to assay neuroectodermal differentiation of ITSCs. Results When cultivated within Afc-FEP bags, ITSCs grew three-dimensionally in a human blood plasma-derived matrix, thereby showing unchanged morphology, proliferation capability, viability and expression profile in comparison to three dimensionally-cultured ITSCs growing in standard cell culture plastics. Genetic stability of bag-cultured ITSCs was further accompanied by unchanged telomerase activity. Importantly, ITSCs retained their potential to differentiate into mesodermal cell types, particularly including ALP-active, Alizarin Red S-, and Von Kossa-positive osteogenic cell types, as well as adipocytes positive in Oil Red O assays. Bag culture further did not affect the potential of ITSCs to undergo differentiation into neuroectodermal cell types coexpressing β-III-tubulin and MAP2 and exhibiting the capability for synaptic vesicle recycling. Conclusions Here, we report for the first time the successful cultivation of human NCSCs within cGMP-grade Afc-FEP bags using a human blood plasma-supplemented medium. Our findings particularly demonstrate the unchanged differentiation capability and genetic stability of the cultivated NCSCs, suggesting the great potential of this culture system for future medical applications in the field of regenerative medicine.

JML- Based formal development of a Java card application for managing medical appointments

Although formal methods can dramatically increase the quality of software systems, they have not widely been adopted in software industry. Many software companies have the perception that formal methods are not cost-effective cause they are plenty of mathematical symbols that are difficult for non-experts to assimilate. The Java Modelling Language (short for JML) Section 3.3 is an academic initiative towards the development of a common formal specification language for Java programs, and the implementation of tools to check program correctness. This master thesis work shows how JML based formal methods can be used to formally develop a privacy sensitive Java application. This is a smart card application for managing medical appointments. The application is named HealthCard. We follow the software development strategy introduced by João Pestana, presented in Section 3.4. Our work influenced the development of this strategy by providing hands-on insight on challenges related to development of a privacy sensitive application in Java. Pestana’s strategy is based on a three-step evolution strategy of software specifications, from informal ones, through semiformal ones, to JML formal specifications. We further prove that this strategy can be automated by implementing a tool that generates JML formal specifications from a welldefined subset of informal software specifications. Hence, our work proves that JML-based formal methods techniques are cost-effective, and that they can be made popular in software industry. Although formal methods are not popular in many software development companies, we endeavour to integrate formal methods to general software practices. We hope our work can contribute to a better acceptance of mathematical based formalisms and tools used by software engineers. The structure of this document is as follows. In Section 2, we describe the preliminaries of this thesis work. We make an introduction to the application for managing medical applications we have implemented. We also describe the technologies used in the development of the application. This section further illustrates the Java Card Remote Method Invocation communication model used in the medical application for the client and server applications. Section 3 introduces software correctness, including the design by contract and the concept of contract in JML. Section 4 presents the design structure of the application. Section 5 shows the implementation of the HealthCard. Section 6 describes how the HealthCard is verified and validated using JML formal methods tools. Section 7 includes some metrics of the HealthCard implementation and specification. Section 8 presents a short example of how a client-side of a smart card application can be implemented while respecting formal specifications. Section 9 describes a prototype tools to generate JML formal specifications from informal specifications automatically. Section 10 describes some challenges and main ideas came acrorss during the development of the HealthCard. The full formal specification and implementation of the HealthCard smart card application presented in this document can be reached at https://sourceforge.net/projects/healthcard/.

Hancornia speciosa latex for biomedical applications: physical and chemical properties, biocompatibility assessment and angiogenic activity

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Set up of a procedure for correlation analysis between current discharge and dose delivery in a pulsed power plasma device for medical application

This thesis work aims to find a procedure for isolating specific features of the current signal from a plasma focus for medical applications. The structure of the current signal inside a plasma focus is exclusive of this class of machines and a specific analysis procedure has to be developed. The hope is to find one or more features that shows a correlation with the dose erogated. The study of the correlation between the current discharge signal and the dose delivered by a plasma focus could be of some importance not only for the practical application of dose prediction but also for expanding the knowledge anbout the plasma focus physics. Vatious classes of time-frequency analysis tecniques are implemented in order to solve the problem.

Particle Accelerators and Detectors for medical Diagnostics and Therapy

This Habilitationsschrift (Habilitation thesis) is focused on my research activities on medical applications of particle physics and was written in 2013 to obtain the Venia Docendi (Habilitation) in experimental physics at the University of Bern. It is based on selected publications, which represented at that time my major scientific contributions as an experimental physicist to the field of particle accelerators and detectors applied to medical diagnostics and therapy. The thesis is structured in two parts. In Part I, Chapter 1 presents an introduction to accelerators and detectors applied to medicine, with particular focus on cancer hadrontherapy and on the production of radioactive isotopes. In Chapter 2, my publications on medical particle accelerators are introduced and put into their perspective. In particular, high frequency linear accelerators for hadrontherapy are discussed together with the new Bern cyclotron laboratory. Chapter 3 is dedicated to particle detectors with particular emphasis on three instruments I contributed to propose and develop: segmented ionization chambers for hadrontherapy, a proton radiography apparatus with nuclear emulsion films, and a beam monitor detector for ion beams based on doped silica fibres. Selected research and review papers are contained in Part II. For copyright reasons, they are only listed and not reprinted in this on-line version. They are available on the websites of the journals.

Applications of XPS to the study of inorganic compounds

The surface behaviour of materials is crucial to our everyday lives. Studies of the corrosive, reactive, optical and electronic properties of surfaces are thus of great importance to a wide range of industries including the chemical and electronics sectors. The surface properties of polymers can also be tuned for use in packaging, non stick coatings or for use in medical applications. Methods to characterise surface composition and reactivity are thus critical to the development of next generation materials. This report will outline the basic principles of X-ray photoelectron spectroscopy and how it can be applied to analyse the surfaces of inorganic materials. The role of XPS in understanding the nature of the active site in heterogeneous catalysts will also be discussed.

Physical and biological properties of a novel siloxane adhesive for soft tissue applications

The aim of this study was to investigate the adhesive properties of an in-house amino-propyltrimethoxysilane-methylenebisacrylamide (APTMS-MBA) siloxane system and compare them with a commercially available adhesive, n-butyl cyanoacrylate (nBCA). The ability of the material to perform as a soft tissue adhesive was established by measuring the physical (bond strength, curing time) and biological (cytotoxicity) properties of the adhesives on cartilage. Complementary physical techniques, X-ray photoelectron spectroscopy, Raman and infrared imaging, enabled the mode of action of the adhesive to the cartilage surface to be determined. Adhesion strength to cartilage was measured using a simple butt joint test after storage in phosphate-buffered saline solution at 37°C for periods up to 1 month. The adhesives were also characterised using two in vitro biological techniques. A live/dead stain assay enabled a measure of the viability of chondrocytes attached to the two adhesives to be made. A water-soluble tetrazolium assay was carried out using two different cell types, human dermal fibroblasts and ovine meniscal chondrocytes, in order to measure material cytotoxicity as a function of both supernatant concentration and time. IR imaging of the surface of cartilage treated with APTMS-MBA siloxane adhesive indicated that the adhesive penetrated the tissue surface marginally compared to nBCA which showed a greater depth of penetration. The curing time and adhesion strength values for APTMS-MBA siloxane and nBCA adhesives were measured to be 60 s/0.23 MPa and 38 min/0.62 MPa, respectively. These materials were found to be significantly stronger than either commercially available fibrin (0.02 MPa) or gelatin resorcinol formaldehyde (GRF) adhesives (0.1 MPa) (P <0.01). Cell culture experiments revealed that APTMS-MBA siloxane adhesive induced 2% cell death compared to 95% for the nBCA adhesive, which extended to a depth of approximately 100-150 μm into the cartilage surface. The WST-1 assay demonstrated that APTMS-MBA siloxane was significantly less cytotoxic than nBCA adhesive as an undiluted conditioned supernatant (P <0.001). These results suggest that the APTMS-MBA siloxane may be a useful adhesive for medical applications. © VSP 2005.

Scheduling medical application workloads on virtualized computing systems

This dissertation presents and evaluates a methodology for scheduling medical application workloads in virtualized computing environments. Such environments are being widely adopted by providers of "cloud computing" services. In the context of provisioning resources for medical applications, such environments allow users to deploy applications on distributed computing resources while keeping their data secure. Furthermore, higher level services that further abstract the infrastructure-related issues can be built on top of such infrastructures. For example, a medical imaging service can allow medical professionals to process their data in the cloud, easing them from the burden of having to deploy and manage these resources themselves. In this work, we focus on issues related to scheduling scientific workloads on virtualized environments. We build upon the knowledge base of traditional parallel job scheduling to address the specific case of medical applications while harnessing the benefits afforded by virtualization technology. To this end, we provide the following contributions: (1) An in-depth analysis of the execution characteristics of the target applications when run in virtualized environments. (2) A performance prediction methodology applicable to the target environment. (3) A scheduling algorithm that harnesses application knowledge and virtualization-related benefits to provide strong scheduling performance and quality of service guarantees. In the process of addressing these pertinent issues for our target user base (i.e. medical professionals and researchers), we provide insight that benefits a large community of scientific application users in industry and academia. Our execution time prediction and scheduling methodologies are implemented and evaluated on a real system running popular scientific applications. We find that we are able to predict the execution time of a number of these applications with an average error of 15%. Our scheduling methodology, which is tested with medical image processing workloads, is compared to that of two baseline scheduling solutions and we find that it outperforms them in terms of both the number of jobs processed and resource utilization by 20–30%, without violating any deadlines. We conclude that our solution is a viable approach to supporting the computational needs of medical users, even if the cloud computing paradigm is not widely adopted in its current form.

Dose-dependent hepatic response to subchronic administration of nandrolone decanoate

Background: Androgenic anabolic steroids (AAS) are synthetic hormone derivatives of testosterone and are mainly used to enhance athletic performance and muscle mass, but medical applications also have been described. Short- and long-term side effects have been demonstrated in many organs, but the liver adverse effects are the most common and serious ones associated with AAS use. However, these effects have been supported by few clinical and experimental studies. Objective: To evaluate the hepatic function and structure after 5 wk of nandrolone decanoate administration at three different doses. Methods: Twenty-seven adult male Wistar rats were randomly assigned to the following groups: control, clinical, intermediate, and suprapharmacological doses of nandrolone decanoate during 5 wk. Results: The biochemical studies showed that nandrolone decanoate administration leads to a dose-dependent increase in serum levels of the aspartate aminotransferase (AST) (P < 0.05), alanine aminotransferase (ALT) (P < 0.01), and alkaline phosphatase (ALP) (P < 0.001), as well as a significant decrease in total proteins (P < 0.01), bilirubin (P < 0.05), total cholesterol and fractions (P < 0.05), and triglycerides (P < 0.05). Although a significant statistical difference was found for AST, ALT, and ALP when compared with the control group, their values remained within the normal range. The number of Kupffer cells was increased in the liver parenchyma (P < 0.05), and the content of collagen was increased in the central lobular vein wall, in the hepatic parenchyma, and in the portal space (P < 0.05). Conclusions: These results suggest that subchronic treatment with nandrolone decanoate, mainly administered at higher-than-clinical doses, are potentially deleterious to the liver, leading to incipient fibrosis.

Mechanical properties of stent-graft materials

An aneurysm is a localized blood-filled dilatation of an artery whose consequences can be deadly. One of its current treatments is endovascular aneurysm repair, a minimally invasive procedure in which an endoprosthesis, called a stent-graft, is placed transluminally to prevent wall rupture. Early stent-grafts were custom designed for the patient through the assembling of off-the-shelf components by the operating surgeon. However, nowadays, stent-grafts have become a commercial product. The existing endoprostheses differ in several aspects, such as shape design and materials, but they have in common a metallic scaffold with a polymeric covering membrane. This article aims to gather relevant information for those who wish to understand the principles of stent-grafts and even to develop new devices. Hence, a stent-graft classification based on different characteristics is presented and the desired features for an ideal device are pointed out. Additionally, the materials currently in use to fabricate this type of endoprosthesis are reviewed and new materials are suggested.

Cloud-assisted Wireless Body Area Networks

Wireless Body Area Networks (WBANs) have emerged as a promising technology for medical and non-medical applications. WBANs consist of a number of miniaturized, portable, and autonomous sensor nodes that are used for long-term health monitoring of patients. These sensor nodes continuously collect information of patients, which are used for ubiquitous health monitoring. In addition, WBANs may be used for managing catastrophic events and increasing the effectiveness and performance of rescue forces. The huge amount of data collected by WBAN nodes demands scalable, on-demand, powerful, and secure storage and processing infrastructure. Cloud computing is expected to play a significant role in achieving the aforementioned objectives. The cloud computing environment links different devices ranging from miniaturized sensor nodes to high-performance supercomputers for delivering people-centric and context-centric services to the individuals and industries. The possible integration of WBANs with cloud computing (WBAN-cloud) will introduce viable and hybrid platform that must be able to process the huge amount of data collected from multiple WBANs. This WBAN-cloud will enable users (including physicians and nurses) to globally access the processing and storage infrastructure at competitive costs. Because WBANs forward useful and life-critical information to the cloud – which may operate in distributed and hostile environments, novel security mechanisms are required to prevent malicious interactions to the storage infrastructure. Both the cloud providers and the users must take strong security measures to protect the storage infrastructure.

Sol-gel-based biosensing applied to medicinal science

Biosensors have opened new horizons in biomedical analysis, by ensuring increased assay speed and flexibility, and allowing point-of-care applications, multi-target analyses, automation and reduced costs of testing. This has been a result of many studies merging nanotechnology with biochemistry over the years, thereby enabling the creation of more suitable environments to biological receptors and their substitution by synthetic analogue materials. Sol-gel chemistry, among other materials, is deeply involved in this process. Sol-gel processing allows the immobilization of organic molecules, biomacromolecules and cells maintaining their properties and activities, permitting their integration into different transduction devices, of electrochemical or optical nature, for single or multiple analyses. Sol-gel also allows to the production of synthetic materials mimicking the activity of natural receptors, while bringing advantages, mostly in terms of cost and stability. Moreover, the biocompatibility of sol-gel materials structures of biological nature allowed the use of these materials in emerging in vivo applications. In this chapter, biosensors for biomedical applications based on sol-gel derived composites are presented, compared and described, along with current emerging applications in vivo, concerning drug delivery or biomaterials. Sol-gel materials are shown as a promising tool for current, emerging and future medical applications. - See more at: http://www.eurekaselect.com/127191/article#sthash.iPqqyhox.dpuf

Performance Analysis of IEEE 802.15.6 Contention-based MAC Protocol

IEEE International Conference on Communications (IEEE ICC 2015). 8 to 12, Jun, 2015, IEEE ICC 2015 - Communications QoS, Reliability and Modeling, London, United Kingdom.