Synthesis and Characterization of Gold/Alanine Nanocomposites with Potential Properties for Medical Application as Radiation Sensors

Radiation dose assessment is essential for several medical treatments and diagnostic procedures. In this context, nanotechnology has been used in the development of improved radiation sensors, with higher sensitivity as well as smaller sizes and energy dependence. This paper deals with the synthesis and characterization of gold/alanine nanocomposites with varying mass percentage of gold, for application as radiation sensors. Alanine is an excellent stabilizing agent for gold nanoparticles because the size of the nanoparticles does not augment with increasing mass percentage of gold, as evidenced by UV-vis spectroscopy, dynamic light scattering, and transmission electron microscopy. X-ray diffraction patterns suggest that the alanine crystalline orientation undergoes alterations upon the addition of gold nanoparticles. Fourier transform infrared spectroscopy indicates that there is interaction between the gold nanoparticles and the amine group of the alanine molecules, which may be the reason for the enhanced stability of the nanocomposite. The application of the nanocomposites as radiation detectors was evaluated by the electron spin resonance technique. The sensitivity is improved almost 3 times in the case of the nanocomposite containing 3% (w/w) gold, so it can be easily tuned by changing the amount of gold nanoparticles in the nanocomposites, without the size of the nanoparticles influencing the radiation absorption. In conclusion, the featured properties, such as homogeneity, nanoparticle size stability, and enhanced sensitivity, make these nanocomposites potential candidates for the construction of small-sized radiation sensors with tunable sensitivity for application in several medical procedures.

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.

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.

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/.

Application of STOPP and START criteria: interrater reliability among pharmacists

BACKGROUND: Inappropriate prescribing is a well-documented problem in older people. The new screening tools, STOPP (Screening Tool of Older Peoples' Prescriptions) and START (Screening Tool to Alert doctors to Right Treatment) have been formulated to identify potentially inappropriate medications (PIMs) and potential errors of omissions (PEOs) in older patients. Consistent, reliable application of STOPP and START is essential for the screening tools to be used effectively by pharmacists. OBJECTIVE: To determine the interrater reliability among a group of clinical pharmacists in applying the STOPP and START criteria to elderly patients' records. METHODS: Ten pharmacists (5 hospital pharmacists, 5 community pharmacists) were given 20 patient profiles containing details including the patients' age and sex, current medications, current diagnoses, relevant medical histories, biochemical data, and estimated glomerular filtration rate. Each pharmacist applied the STOPP and START criteria to each patient record. The PIMs and PEOs identified by each pharmacist were compared with those of 2 academic pharmacists who were highly familiar with the application of STOPP and START. An interrater reliability analysis using the k statistic (chance corrected measure of agreement) was performed to determine consistency between pharmacists. RESULTS: The median ? coefficients for hospital pharmacists and community pharmacists compared with the academic pharmacists for STOPP were 0.89 and 0.88, respectively, while those for START were 0.91 and 0.90, respectively. CONCLUSIONS: Interrater reliability of STOPP and START tools between pharmacists working in different sectors is good. Pharmacists working in both hospitals and in the community can use STOPP and START reliably during their everyday practice to identify PIMs and PEOs in older patients.

Cellulose nanocomposites with nanofibres isolated from pineapple leaf fibers for medical applications

Nanocellulose is the crystalline domains obtained from renewable cellulosic sources, used to increase mechanical properties and biodegrability in polymer composites. This work has been to study how high pressure defibrillation and chemical purification affect the PALF fibre morphology from micro to nanoscale. Microscopy techniques and X-ray diffraction were used to study the structure and properties of the prepared nanofibers and composites. Microscopy studies showed that the used individualization processes lead to a unique morphology of interconnected web-like structure of PALF fibers. The produced nanofibers were bundles of cellulose fibers of widths ranging between 5 and 15 nm and estimated lengths of several micrometers. Percentage yield and aspect ratio of the nanofiber obtained by this technique is found to be very high in comparison with other conventional methods. The nanocomposites were prepared by means of compression moulding, by stacking the nanocellulose fibre mats between polyurethane films. The results showed that the nanofibrils reinforced the polyurethane efficiently. The addition of 5 wt% of cellulose nanofibrils to PU increased the strength nearly 300% and the stiffness by 2600%. The developed composites were utilized to fabricate various versatile medical implants. (C) 2011 Elsevier Ltd. All rights reserved.

O acesso aos exames de alta complexidade nos planos de saúde privados na perspectiva dos usuários

A dissertação trata do acesso aos serviços de alta complexidade, particularmente os exames diagnósticos e complementares, estudado entre usuários de planos de saúde privados que buscam atendimento e diagnóstico especializado. Desde a década de 80 o usuário do sistema público de saúde vem procurando a saúde suplementar. Contudo, afirmar que o acesso é garantido no domínio privado, através da contratação dos planos de saúde, é uma incerteza que rodeia a inspiração para esta pesquisa, que se justifica pela relevância de ações que possibilitem a melhora da qualidade regulatória dos planos de saúde, a partir do controle social de seus usuários. O objetivo geral é analisar as percepções do acesso aos exames de alta complexidade nos serviços de saúde privados entre usuários de planos de saúde. Os objetivos específicos são descrever as percepções dos usuários de planos de saúde acerca do acesso aos exames de alta complexidade; analisar as motivações dos usuários de planos de saúde privados para a realização de exames de alta complexidade através da rede privada de assistência; e analisar o nível de satisfação dos usuários de planos de saúde quanto ao acesso aos exames de alta complexidade. A metodologia é qualitativa-descritiva, onde a amostra foi de trinta usuários de planos de saúde, acima de 18 anos, selecionados no campo de estudo no ano de 2010. O cenário de estudo foi um laboratório privado de medicina diagnóstica no Rio de Janeiro. As técnicas de coleta de dados utilizadas foram formulário e entrevista individual estruturada. A análise do formulário foi realizada através de estatística descritiva, e as entrevistas através da análise de conteúdo temática-categorial. Os usuários de plano de saúde declararam que o acesso é garantido com facilidade para os exames de alta complexidade. Suas principais motivações para a realização desses exames na rede privada de assistência foram caracterizadas pela rapidez de atendimento, flexibilidade e facilidade de marcação pela internet, telefone ou pessoalmente no laboratório estudado, pronta entrega dos resultados, dificuldade e morosidade do atendimento do SUS, localização do prestador credenciado próxima de bairros residenciais ou do trabalho, resolutividade diagnóstica de imagem de excelência, possibilidade de escolha pelo usuário entre as modalidades aberta e fechada de ressonância magnética e tomografia computadorizada, além da densitometria óssea que foram facilmente acessíveis a todos os sujeitos da pesquisa. O nível de satisfação foi correspondido com a rapidez na realização dos exames em caráter eletivo e de urgência quase equiparados na escala de tempo de acordo com os usuários. Contudo, embora as notas de avaliação dos usuários quanto aos seus planos de saúde tenham sido altas, foram abordadas algumas dificuldades, tais como: prazos de validade dos pedidos médicos com datação prévia; solicitações de senhas de autorização pela operadora; burocracia nos procedimentos de agendamento; dificuldades de acesso para tratamentos como implantes, fisioterapia, RPG, pilates, home care, consultas de check up; negação de reembolsos; restrição de materiais cirúrgicos, em especial as próteses e órteses; e restrições específicas de grau para cirurgias de miopia. Conclui-se que o atendimento rápido dos exames de imagem de alto custo na amostra foi descrito como satisfatório, embora a percepção de rapidez possa variar em função do tipo de produto do plano de saúde privado contratado, com necessidade de melhoria regulatória em alguns aspectos pontuais da saúde suplementar.

Synteza i charakterystyka wybranych nanocząstek o potencjalnych zastosowaniach w medycynie

Zakład Biofizyki Molekularnej, Centrum NanoBioMedyczne UAM

ZAP-70 restoration in mice by in vivo thymic electroporation.

Viral and non-viral vectors have been developed for gene therapy, but their use is associated with unresolved problems of efficacy and safety. Efficient and safe methods of DNA delivery need to be found for medical application. Here we report a new monopolar system of non-viral electro-gene transfer into the thymus in vivo that consists of the local application of electrical pulses after the introduction of the DNA. We assessed the proof of concept of this approach by correcting ZAP-70 deficient severe combined immunodeficiency (SCID) in mice. The thymic electro-gene transfer of the pCMV-ZAP-70-IRES-EGFP vector in these mice resulted in rapid T cell differentiation in the thymus with mature lymphocytes detected by three weeks in secondary lymphoid organs. Moreover, this system resulted in the generation of long-term functional T lymphocytes. Peripheral reconstituted T cells displayed a diversified T cell receptor (TCR) repertoire, and were responsive to alloantigens in vivo. This process applied to the thymus could represent a simplified and effective alternative for gene therapy of T cell immunodeficiencies.

Regulatory or Regulating Publics? The European Union’s Regulation of Emerging Health Technologies and Citizen Participation

‘Citizen participation’ includes various participatory techniques and is frequently viewed as an unproblematic and important social good when used as part of the regulation of the innovation and implementation of science and technology. This is perhaps especially evident in debates around ‘anticipatory governance’ or ‘upstream engagement’. Here, we interrogate this thesis using the example of the European Union’s regulation of emerging health technologies (such as nanotechnology). In this case, citizen participation in regulatory debate is concerned with innovative objects for medical application that are considered to be emergent or not yet concrete. Through synthesising insights from law, regulatory studies, critical theory, and science and technology studies (STS), we seek to cast new light on the promises, paradoxes and pitfalls of citizen participation as a tool or technology of regulation in itself. As such we aim to generate a new vantage point from which to view the values and sociotechnical imaginaries that are both ‘designed-in’ and ‘designed-out’ of citizen participation. In so doing, we show not only how publics (do not) regulate technologies, but also how citizens themselves are regulated through the techniques of participation. © The Author [2012].

Characterization of polyhydroxyalkanoates accumulating vibrios from marine benthic environments and production studies of polyhydroxyalkanoates by Vibrio sp. BTKB33

The present work deals with the characterization of polyhydroxyalkanoates accumulating vibrios from marine benthic environments and production studies of polyhydroxyalkanoates by vibrio sp.BTKB33. Vibrios are a group of (iram negative, curved or straight motile rods that normally inhabit the aquatic environments.The present study therefore aimed at evaluating the occurrence of PHA accumulating vibrios inhabiting marine benthic environments; characterizing the potential PHA accumulators employing phenotypic and genotypic approaches and molecular characterization of the PHA synthase gene. The study also evaluated the PHA production in V:'hri0 sp. strain BTKB33, through submerged fennentation using statistical optimization and characterized the purified biopolymer. Screening for PHA producing vibrios from marine benthic environments. Characterization of PHA producers employing phenotypic and genotypic approaches.The incidence of PHA accumulation in Vibrio sp. isolated from marine sediments was observed to be high, indicating that the natural habitat of these bacteria are stressful. Considering their ubiquitous nature, the ecological role played by vibrios in maintaining the delicate balance of the benthic ecosystem besides returning potential strains, with the ability to elaborate a plethora of extracellular enzymes for industrial application, is significant. The elaboration of several hydrolytic enzymes by individuals also emphasize the crucial role of vibrios in the mineralization process in the marine environment. This study throws light on the extracellular hydrolytic enzyme profile exhibited by vibrios. It was concluded that apart from the PHA accumulation, presence of exoenzyme production and higher MAR index also aids in their survival in the highly challenging benthic enviromnents. The phylogenetic analysis of the strains and studies on intra species variation within PHA accumulating strains reveal their diversity. The isolate selected for production in this study was Vibrio sp. strain BTKB33, identified as V.azureus by 16S rDNA sequencing and phenotypic characterization. The bioprocess variables for PHA production utilising submerged fermentation was optimized employing one-factor-at-a-time-method, PB design and RSM studies. The statistical optimization of bioprocess variables revealed that NaCl concentration, temperature and incubation period are the major bioprocess variables influencing PHA production and PHA content. The presence of Class I PHA synthase genes in BTKB33 was also unveiled. The characterization of phaC genes by PCR and of the extracted polymer employing FTIR and NMR analysis revealed the presence of polyhydroxybutyrate, smallest known PI-IAs, having wider domestic, industrial and medical application. The strain BTKB33 bearing a significant exoenzyme profile, can thus be manipulatedin future for utilization of diverse substrates as C- source for PHA production. In addition to BTKB33, several fast growing Vibrio sp. having PHA accumulating ability were also isolated, revealing the prospects of this environment as a mine for novel PHA accumulating microbes. The findings of this study will provide a reference for further research in industrial production of PHAs from marine microorganisms .

Intrastriatal transplantation of adult human neural crest-derived stem cells improves functional outcome in parkinsonian rats

Parkinson's disease (PD) is considered the second most frequent and one of the most severe neurodegenerative diseases, with dysfunctions of the motor system and with nonmotor symptoms such as depression and dementia. Compensation for the progressive loss of dopaminergic (DA) neurons during PD using current pharmacological treatment strategies is limited and remains challenging. Pluripotent stem cell-based regenerative medicine may offer a promising therapeutic alternative, although the medical application of human embryonic tissue and pluripotent stem cells is still a matter of ethical and practical debate. Addressing these challenges, the present study investigated the potential of adult human neural crest-derived stem cells derived from the inferior turbinate (ITSCs) transplanted into a parkinsonian rat model. Emphasizing their capability to give rise to nervous tissue, ITSCs isolated from the adult human nose efficiently differentiated into functional mature neurons in vitro. Additional successful dopaminergic differentiation of ITSCs was subsequently followed by their transplantation into a unilaterally lesioned 6-hydroxydopamine rat PD model. Transplantation of predifferentiated or undifferentiated ITSCs led to robust restoration of rotational behavior, accompanied by significant recovery of DA neurons within the substantia nigra. ITSCs were further shown to migrate extensively in loose streams primarily toward the posterior direction as far as to the midbrain region, at which point they were able to differentiate into DA neurons within the locus ceruleus. We demonstrate, for the first time, that adult human ITSCs are capable of functionally recovering a PD rat model.

MRI study of radiation effect on Fricke gel solutions

The quality control optimization of medical processes that use ionizing radiation in the treatment of diseases like cancer is a key element for patient safety and success of treatment. The major medical application of radiation is radiotherapy, i.e. the delivery of dose levels to well-defined target tissues of a patient with the purpose of eliminating a disease. The need of an accurate tumour-edge definition with the purpose of preserving healthy surrounding tissue demands rigorous radiation treatment planning. Dosimetric methods are used for dose distribution mapping region of interest to assure that the prescribed dose and the irradiated region are correct. The Fricke gel (FXG) is the main dosimeter that supplies visualization of the three-dimensional (3D) dose distribution. In this work the dosimetric characteristics of the modified Fricke dosimeter produced at the Radiation Metrology Centre of the Institute of Energetic and Nuclear Research (IPEN) such as gel concentration dose response dependence, xylenol orange addition influence, dose response between 5 and 50Gy and signal stability were evaluated by magnetic resonance imaging (MRI). Using the same gel solution, breast simulators (phantoms) were shaped and absorbed dose distributions were imaged by MRI at the Nuclear Resonance Laboratory of the Physics Institute of Sao Paulo University. (C) 2007 Elsevier Ltd. All rights reserved.