Synthetic Polymer and Microbubble Systems for Gene Delivery to the Brain

Thesis (Ph.D.)--University of Washington, 2016-08

Debriefing in simulation conducted in small and large groups : nursing students’ experiences

The debriefing phase in human patient simulation is considered to be crucial for learning. To ensure good learning conditions, the use of small groups is recommended, which poses a major challenge when the student count is high. The use of large groups may provide an alternative for typical lecture-style education and contribute to a more frequently and repeated training which is considered to be important for achieving simulation competency. The purpose of the present study was to describe nursing students’ experiences obtained during the debriefing conducted in small and large groups with the use of a qualitative descriptive approach. The informants had participated in a human patient simulation situation either in large or small groups. Data was collected through the use of five focus-group interviews and analysed by content analysis. The findings showed that independent of group-size the informants experienced the learning strategies to be unfamiliar and intrusive, and in the large groups to such an extent that learning was hampered. Debriefing was perceived as offering excellent opportunities for transferable learning, and activity, predictability and preparedness were deemed essential. Small groups provided the best learning conditions in that safety and security were ensured, but were perceived as providing limited challenges to accommodate professional requirements as a nurse. Simulation competency as a prerequisite for learning was shown not to be developed isolated in conjunction with simulation, but depends on a systematic effort to build a learning community in the programme in general. The faculty needs to support the students to be conscious and accustomed to learning as a heightened experience of learning out of their comfort zone.

Computer simulations of soft particles in flow

Understanding the dynamics of blood cells is a crucial element to discover biological mechanisms, to develop new efficient drugs, design sophisticated microfluidic devices, for diagnostics. In this work, we focus on the dynamics of red blood cells in microvascular flow. Microvascular blood flow resistance has a strong impact on cardiovascular function and tissue perfusion. The flow resistance in microcirculation is governed by flow behavior of blood through a complex network of vessels, where the distribution of red blood cells across vessel cross-sections may be significantly distorted at vessel bifurcations and junctions. We investigate the development of blood flow and its resistance starting from a dispersed configuration of red blood cells in simulations for different hematocrits, flow rates, vessel diameters, and aggregation interactions between red blood cells. Initially dispersed red blood cells migrate toward the vessel center leading to the formation of a cell-free layer near the wall and to a decrease of the flow resistance. The development of cell-free layer appears to be nearly universal when scaled with a characteristic shear rate of the flow, which allows an estimation of the length of a vessel required for full flow development, $l_c \approx 25D$, with vessel diameter $D$. Thus, the potential effect of red blood cell dispersion at vessel bifurcations and junctions on the flow resistance may be significant in vessels which are shorter or comparable to the length $l_c$. The presence of aggregation interactions between red blood cells lead in general to a reduction of blood flow resistance. The development of the cell-free layer thickness looks similar for both cases with and without aggregation interactions. Although, attractive interactions result in a larger cell-free layer plateau values. However, because the aggregation forces are short-ranged at high enough shear rates ($\bar{\dot{\gamma}} \gtrsim 50~\text{s}^{-1}$) aggregation of red blood cells does not bring a significant change to the blood flow properties. Also, we develop a simple theoretical model which is able to describe the converged cell-free-layer thickness with respect to flow rate assuming steady-state flow. The model is based on the balance between a lift force on red blood cells due to cell-wall hydrodynamic interactions and shear-induced effective pressure due to cell-cell interactions in flow. We expect that these results can also be used to better understand the flow behavior of other suspensions of deformable particles such as vesicles, capsules, and cells. Finally, we investigate segregation phenomena in blood as a two-component suspension under Poiseuille flow, consisting of red blood cells and target cells. The spatial distribution of particles in blood flow is very important. For example, in case of nanoparticle drug delivery, the particles need to come closer to microvessel walls, in order to adhere and bring the drug to a target position within the microvasculature. Here we consider that segregation can be described as a competition between shear-induced diffusion and the lift force that pushes every soft particle in a flow away from the wall. In order to investigate the segregation, on one hand, we have 2D DPD simulations of red blood cells and target cell of different sizes, on the other hand the Fokker-Planck equation for steady state. For the equation we measure force profile, particle distribution and diffusion constant across the channel. We compare simulation results with those from the Fokker-Planck equation and find a very good correspondence between the two approaches. Moreover, we investigate the diffusion behavior of target particles for different hematocrit values and shear rates. Our simulation results indicate that diffusion constant increases with increasing hematocrit and depends linearly on shear rate. The third part of the study describes development of a simulation model of complex vascular geometries. The development of the model is important to reproduce vascular systems of small pieces of tissues which might be gotten from MRI or microscope images. The simulation model of the complex vascular systems might be divided into three parts: modeling the geometry, developing in- and outflow boundary conditions, and simulation domain decomposition for an efficient computation. We have found that for the in- and outflow boundary conditions it is better to use the SDPD fluid than DPD one because of the density fluctuations along the channel of the latter. During the flow in a straight channel, it is difficult to control the density of the DPD fluid. However, the SDPD fluid has not that shortcoming even in more complex channels with many branches and in- and outflows because the force acting on particles is calculated also depending on the local density of the fluid.

Proposta de processo de enfermagem em unidade de internação obstétrica: históricos, diagnósticos e cuidados de enfermagem à luz de horta fundamentada em nanda

O presente estudo teve como objetivo geral elaborar uma proposta de processo de enfermagem contemplando históricos de enfermagem, diagnósticos de enfermagem, prescrição de cuidados de enfermagem para gestantes e puérperas em Unidade de Internação Obstétrica à luz de Horta, fundamentada em NANDA e, como objetivos específicos: identificar os dados clínico-obstétricos mais frequentes das gestantes em Unidade de Internação Obstétrica; identificar os dados clínico-obstétricos mais frequentes das puérperas em Unidade de Internação Obstétrica; identificar os diagnósticos de enfermagem a partir dos dados clínico-obstétricos mais frequentes das gestantes em Unidade de Internação Obstétrica; identificar os diagnósticos de enfermagem a partir dos dados clínico-obstétricos mais frequentes das puérperas em Unidade de Internação Obstétrica; elaborar modelos de histórico de enfermagem e de prescrição de cuidados de enfermagem para os diagnósticos de enfermagem identificados; e obter o consenso dos enfermeiros assistenciais da Unidade de Internação Obstétrica sobre a proposta construída. Trata-se de pesquisa qualitativa, descritiva e exploratória, realizada em uma Unidade de Internação Obstétrica de um hospital universitário do Sul do Brasil. Realizou-se uma consulta documental em 148 prontuários, com vistas à identificação dos diagnósticos e cuidados de enfermagem, baseados, respectivamente, na taxonomia II da North American Diagnosis Association 2009-2011 e da Nursing Intervention Classification. Desenvolveu-se um modelo de histórico de enfermagem para gestante/puérpera e outro para o recém-nascido. No total, identificaram-se 26 diagnósticos de enfermagem, assim distribuídos: nove direcionados às gestantes; nove, às puérperas; dois, ao binômio mãe/filho; seis, ao recém-nascido. A análise foi realizada por meio da apresentação da proposta construída e discussão com base em autores da área. Com isso, almeja-se contribuir para direcionar o cuidado de enfermagem às necessidades das gestantes, puérperas, binômios mãe/filho e recém-nascidos nesse microcenário, favorecendo a educação em saúde, a identificação precoce e a prevenção de complicações. Permanecem lacunas quanto às necessidades psicoespirituais, visto que elas não foram abordadas nos resultados. Assim, essa proposta de Processo de Enfermagem em Unidade Obstétrica contemplando históricos, diagnósticos e cuidados de enfermagem mantém em aberto o aperfeiçoamento do modelo, visando à inclusão de outros diagnósticos de enfermagem, de forma a aproximar-se de um cuidado mais holístico.

ISA Training: Hair and beauty trainees take advantage of technology

ISA Training based in south Wales is taking steps to upskill its staff and learners in digital literacies in order to make most effective use of technology in delivery and assessment of courses in hairdressing, beauty therapy and business management. To increase the flexibility and efficiency of its provision, the company has adopted the Learning Assistant e-portfolio system.

Responsiveness of the frontal EMG for monitoring the sedation state of critically ill patients.

Background. Excessive sedation is associated with adverse patient outcomes during critical illness, and a validated monitoring technology could improve care. We developed a novel method, the responsiveness index (RI) of the frontal EMG. We compared RI data with Ramsay clinical sedation assessments in general and cardiac intensive care unit (ICU) patients. Methods. We developed the algorithm by iterative analysis of detailed observational data in 30 medical–surgical ICU patients and described its performance in this cohort and 15 patients recovering from scheduled cardiac surgery. Continuous EMG data were collected via frontal electrodes and RI data compared with modified Ramsay sedation state assessments recorded regularly by a blinded trained observer. RI performance was compared with EntropyTM across Ramsay categories to assess validity. Results. RI correlated well with the Ramsay category, especially for the cardiac surgery cohort (general ICU patients r¼0.55; cardiac surgery patients r¼0.85, both P,0.0001). Discrimination across all Ramsay categories was reasonable in the general ICU patient cohort [PK¼0.74 (SEM 0.02)] and excellent in the cardiac surgery cohort [PK¼0.92 (0.02)]. Discrimination between ‘lighter’ vs ‘deeper’ (Ramsay 1–3 vs 4–6) was good for general ICU patients [PK¼0.80 (0.02)] and excellent for cardiac surgery patients [PK¼0.96 (0.02)]. Performance was significantly better than EntropyTM. Examination of individual cases suggested good face validity. Conclusions. RI of the frontal EMG has promise as a continuous sedation state monitor in critically ill patients. Further investigation to determine its utility in ICU decision-making is warranted.

Humanização do atendimento à criança na atenção básica: visão dos profissionais

Objetivou-se compreender a humanização do atendimento à criança na Atenção Básica na visão dos profissionais. Estudo qualitativo, realizado em uma Unidade de Saúde da Família de Natal-RN, Brasil. Dezesseis profissionais responderam a um formulário contendo questões referentes ao atendimento à criança, à humanização e às práticas realizadas para humanizar o atendimento. Os dados foram categorizados por temas e analisados a partir dos princípios da Política Nacional de Humanização. Para os profissionais, humanizar o atendimento envolve acolher, escutar, aconselhar sobre o que está sendo realizado com a criança, valorizar a família, e tornar o sujeito ativo no atendimento, mesmo que de forma incipiente. A maioria dos profissionais descreveu atendimento que valorizava parte dos princípios da política de humanização, mesmo com dificuldades para implementá-los na rotina. Requer, portanto, estímulos e atualização dos profissionais para uma postura autocrítica sobre o atendimento

Blood donor motivation and recruitment : a comparative study in West of Scotland and the Sudan

In modern society, blood donor motivation and recruitment is a fundamental part of health care delivery. Well defined and documented programmes exist throughout the world but new ideas are always welcome. The situation in the Sudan is different and much remains to be done by way of comparison with elsewhere. This thesis outlines the objectives of a study, how it was supported, sponsored and achieved. It describes briefly the geography of the Sudan, the source of Sudanese economy, climate, culture and historical backgrounds. The problems of existing services in the Sudan are reviewed and a brief account of the demographic characteristics of the Sudanese population is given. Two surveys done in West of Scotland and in the Sudan are described in detail. This work discloses and compares the positive motives that enhances giving of blood and the negative motives that hinders its donation. The comparison is between an Eastern Society with a voluntary motivation not fully activated because of lack of understanding and awareness of the need to give blood voluntarily for strangers and Western Society with a well established voluntary system of donation. An addition to this research was the investigation into the immunity to tetanus and hepatitis in the Sudanese population. An estimate of the percentage of individuals with detectable levels of hepatitis A and B antibodies and tetanus antibodies is included since there is a need to establish a plasmapheresis programme as part of a good Blood Transfusion Service for the procurement of specific immunoglobulin's. This work has revealed major differences between the West of Scotland and the Sudan and suggestions are made for their resolution. The main conclusion and comparison are summarised in Chapter 7. It is hoped that many of the suggestions in this thesis can be introduced in the Sudan at an early date.

Encapsulation of Local Anesthetic Bupivacaine in Biodegradable Poly(DL-lactide-co-glycolide) Nanospheres: Factorial Design, Characterization and Cytotoxicity Studies

Local anesthetic agents cause temporary blockade of nerve impulses productiong insensitivity to painful stimuli in the area supplied by that nerve. Bupivacaine (BVC) is an amide-type local anesthetic widely used in surgery and obstetrics for sustained peripheral and central nerve blockade. in this study, we prepared and characterized nanosphere formulations containing BVC. To achieve these goals, BVC loaded poly(DL-lactide-co-glycolide) (PLGA) nanospheres (NS) were prepared by nanopreciptation and characterized with regard to size distribution, drug loading and cytotoxicity assays. The 2(3-1) factorial experimental design was used to study the influence of three different independent variables on nanoparticle drug loading. BVC was assayed by HPLC, the particle size and zeta potential were determined by dynamic light scattering. BVC was determined using a combined ultrafiltration-centrifugation technique. The results of optimized formulations showed a narrow size distribution with a polydispersivity of 0.05%, an average diameter of 236.7 +/- 2.6 nm and the zeta potential -2.93 +/- 1,10 mV. In toxicity studies with fibroblast 3T3 cells, BVC loaded-PLGA-NS increased cell viability, in comparison with the effect produced by free BVC. In this way, BVC-loaded PLGA-NS decreased BVC toxicity. The development of BVC formulations in carriers such as nanospheres could offer the possibility of controlling drug delivery in biological systems, prolonging the anesthetic effect and reducing toxicity.

Conocimientos, actitudes y prácticas del personal médico y de enfermería de la sala de partos del Hospital José Carrasco Arteaga, en la aplicación de las normas de Bioseguridad en la atención del recién nacido, Cuenca 2015

Antecedentes. La ejecución de las Normas de Bioseguridad, es una responsabilidad de la institución donde se incluye a todos los funcionarios. En el servicio de partos existen elementos nocivos o potencialmente peligrosos, como los productos biológicos provenientes de los pacientes y los reactivos químicos de diferente naturaleza. Es necesario reconocer estos peligros para establecer y aplicar medidas de prevención y seguridad (1). Objetivo: Determinar los conocimientos, actitudes y prácticas del personal médico y de enfermería en la sala de partos del hospital José Carrasco Arteaga, en la aplicación de las normas de bioseguridad en la atención del recién nacido, Cuenca 2015. Material y métodos: Se realizó un estudio cuantitativo - descriptivo, la muestra estaba constituida por 50 profesionales de la sala de partos del Hospital José Carrasco Arteaga. Las técnicas de investigación fueron la encuesta, la observación y la revisión bibliográfica, los instrumentos utilizados fueron ficha de registro, y la encuesta. Los resultados fueron analizados en tablas simples y de contingencia mediante los programas de Word. Excel y SPSS versión 21. Resultados: el 98% del personal desecha correctamente el material corto punzantes, el 86% del personal siempre lava sus manos antes y después de atender a la madre. Conclusiones: Al finalizar podemos decir que el 98% de los profesionales conoce lo que es bioseguridad, pero el 80% de los profesionales no aplica estas normas en el servicio. Para mejorar esto se debe elaborar y mejorar estrategias de capacitación.

The dynamics of professions and development of new roles in public services organizations: the case of modern matrons in the English NHS

This study contributes to research examining how professional autonomy and hierarchy impacts upon the implementation of policy designed to improve the quality of public services delivery through the introduction of new managerial roles. It is based on an empirical examination of a new role for nurses – modern matrons – who are expected by policy-makers to drive organizational change aimed at tackling health care acquired infections (HCAI) in the National Health Service (NHS) within England. First, we show that the changing role of nurses associated with their ongoing professionalization limits the influence of modern matrons over their own ranks in tackling HCAI. Second, the influence of modern matrons over doctors is limited. Third, government policy itself appears inconsistent in its support for the role of modern matrons. The attempts of modern matrons to tackle HCAI appear more effective where infection control activity is situated in professional practice and where modern matrons integrate aspirations for improved infection control within mainstream audit mechanisms in a health care organization.

Conjugated polymer nanoparticles for biological labeling and delivery

Cancer remains one of the world’s most devastating diseases, with more than 10 million new cases every year. However, traditional treatments have proven insufficient for successful medical management of cancer due to the chemotherapeutics’ difficulty in achieving therapeutic concentrations at the target site, non-specific cytotoxicity to normal tissues, and limited systemic circulation lifetime. Although, a concerted effort has been placed in developing and successfully employing nanoparticle(NP)-based drug delivery vehicles successfully mitigate the physiochemical and pharmacological limitations of chemotherapeutics, work towards controlling the subcellular fate of the carrier, and ultimately its payload, has been limited. Because efficient therapeutic action requires drug delivery to specific organelles, the subcellular barrier remains critical obstacle to maximize the full potential of NP-based delivery vehicles. The aim of my dissertation work is to better understand how NP-delivery vehicles’ structural, chemical, and physical properties affect the internalization method and subcellular localization of the nanocarrier. ^ In this work we explored how side-chain and backbone modifications affect the conjugated polymer nanoparticle (CPN) toxicity and subcellular localization. We discovered how subtle chemical modifications had profound consequences on the polymer’s accumulation inside the cell and cellular retention. We also examined how complexation of CPN with polysaccharides affects uptake efficiency and subcellular localization. ^ This work also presents how changes to CPN backbone biodegradability can significantly affect the subcellular localization of the material. A series of triphenyl phosphonium-containing CPNs were synthesized and the effect of backbone modifications have on the cellular toxicity and intracellular fate of the material. A mitochondrial-specific polymer exhibiting time-dependent release is reported. Finally, we present a novel polymerization technique which allows for the controlled incorporation of electron-accepting benzothiadiazole units onto the polymer chain. This facilitates tuning CPN emission towards red emission. ^ The work presented here, specifically, the effect that side-chain and structure, polysaccharide formulation and CPN degradability have on material’s uptake behavior, can help maximize the full potential of NP-based delivery vehicles for improved chemotherapeutic drug delivery.^

Knowledge of HIV transmission risk behavior, and perceptions of risk among Haitian women living in Miami, Florida

This study was conducted to gain a more comprehensive understanding of HIV risk among Haitian women. The variables measured were: knowledge of HIV transmission, sexual risk behaviors, and perceptions of risk among Haitian women. The sociocultural aspect of the Haitian women's lives with regard to their risky behaviors was also examined. A total of 101 Haitian women (aged 25-53) who attended two comprehensive health clinics were interviewed. A combined questionnaire derived from both the ARM-Q and the RBA was used. In general, the women had good knowledge of the sexual transmission of HIV I AIDS and indicated that they were susceptible to HIV infection. However, knowledge and perceptions of risk were not translated into sexual risk-reduction behaviors with their partners. Multiplicity of partners and low incidence of condom use were the two major sexual risk factors isolated in this study. Results indicate Haitian women were more likely to use condoms if they possessed greater HIV knowledge and their sexual partners held more positive attitudes toward using condoms. Also, Haitian women may have failed to protect themselves because behavior changes could have involved threats to their social and economic survival, relationships and culturally sanctioned roles. This suggests the need to include male partners in HIV prevention interventions with Haitian women. Future research should focus on preventing high-risk behavior by improving knowledge, altering the male partners' attitudes toward condoms, and enhancing communication and negotiation skills. Nursing implications and recommendations for culturally sensitive and relevant AIDS prevention efforts are discussed.

What Are Effective Program Characteristics of Self-Management Interventions in Patients With Heart Failure? : An Individual Patient Data Meta-analysis

Background To identify those characteristics of self-management interventions in patients with heart failure (HF) that are effective in influencing health-related quality of life, mortality, and hospitalizations. Methods and Results Randomized trials on self-management interventions conducted between January 1985 and June 2013 were identified and individual patient data were requested for meta-analysis. Generalized mixed effects models and Cox proportional hazard models including frailty terms were used to assess the relation between characteristics of interventions and health-related outcomes. Twenty randomized trials (5624 patients) were included. Longer intervention duration reduced mortality risk (hazard ratio 0.99, 95% confidence interval [CI] 0.97–0.999 per month increase in duration), risk of HF-related hospitalization (hazard ratio 0.98, 95% CI 0.96–0.99), and HF-related hospitalization at 6 months (risk ratio 0.96, 95% CI 0.92–0.995). Although results were not consistent across outcomes, interventions comprising standardized training of interventionists, peer contact, log keeping, or goal-setting skills appeared less effective than interventions without these characteristics. Conclusion No specific program characteristics were consistently associated with better effects of self-management interventions, but longer duration seemed to improve the effect of self-management interventions on several outcomes. Future research using factorial trial designs and process evaluations is needed to understand the working mechanism of specific program characteristics of self-management interventions in HF patients.