The challenge of vector development in gene therapy

Gene therapy is the treatment of diseases based on the transfer of genetic information. Agents that carry or deliver DNA to target cells are called vectors (Latin vector: carrier, deliverer). Ideally, a vector should accommodate an unlimited amount of inserted DNA, lack the ability of autonomous replication of its own DNA, be easily manufactured, and be available in concentrated form. Secondly, it should have the ability to target specific cell types or to limit its gene expression to specific cell types, and to achieve sustained gene expression in the long term or in a controlled fashion. Finally, it should not be toxic or immunogenic. Such a vector does not exist and none of the DNA delivery systems so far available for in vivo gene transfer is perfect with respect to any of these points. Gene therapy and the means to promote it depend heavily on the development and improvement of new gene vector systems.

Poly-DL-lactide-co-glycolide microspheres as a controlled release antigen delivery system

Successful vaccine application means maximum protection with minimal number of administrations. A rational development of vaccines involves studies of the nature of the antigen as well as of the adjuvant to be used to improve the immune responses. This has provided the impetus for studies to design the degradable devices and for different approaches to antigen delivery by different routes of administration. The development of controlled release systems based on polymeric devices that permit a sustained or pulsed release of encapsulated antigens has attracted much interest. Polymeric delivery systems consist of polymers that release their content continuously in a controlled manner over a period of time. The development of a biocompatible delivery system for parenteral administration offers several advantages in terms of immunoadjuvanticity over other compounds. It was found that, in contrast to other carriers, microspheres are more stable, thus permitting administration by the oral or parenteral route. In the present study, we describe the main characteristics and potentialities of this new immunoadjuvant for oral and parenteral administration.

Preparation and cytotoxicity of cisplatin-containing liposomes

We encapsulated cisplatin into stealth pH-sensitive liposomes and studied their stability, cytotoxicity and accumulation in a human small-cell lung carcinoma cell line (GLC4) and its resistant subline (GLC4/CDDP). Since reduced cellular drug accumulation has been shown to be the main mechanism responsible for resistance in the GLC4/CDDP subline, we evaluated the ability of this new delivery system to improve cellular uptake. The liposomes were composed of dioleoylphosphatidylethanolamine (DOPE), cholesteryl hemisuccinate (CHEMS), and distearoylphosphatidylethanolamine-polyethyleneglycol 2000 (DSPE-PEG2000) and were characterized by determining the encapsulation percentage as a function of lipid concentration. Among the different formulations, DOPE/CHEMS/DSPE-PEG liposomes (lipid concentration equal to 40 mM) encapsulated cisplatin more efficiently than other concentrations of liposomes (about 20.0%, mean diameter of 174 nm). These liposomes presented good stability in mouse plasma which was obtained using a 0.24-M EDTA solution (70% cisplatin was retained inside the liposomes after 30 min of incubation). Concerning cytotoxic effects, they are more effective (1.34-fold) than free cisplatin for growth inhibition of the human lung cancer cell line A549. The study of cytotoxicity to GLC4 and GLC4/CDDP cell lines showed similar IC50 values (approximately 1.4 µM), i.e., cisplatin-resistant cells were sensitive to this cisplatin formulation. Platinum accumulation in both sensitive and resistant cell lines followed the same pattern, i.e., approximately the same intracellular platinum concentration (4.0 x 10-17 mol/cell) yielded the same cytotoxic effect. These results indicate that long-circulating pH-sensitive liposomes, also termed as stealth pH-sensitive liposomes, may present a promising delivery system for cisplatin-based cancer treatment. This liposome system proved to be able to circumvent the cisplatin resistance, whereas it was not observed when using non-long-circulating liposomes composed of phosphatidylcholine, phosphatidylserine, and cholesterol.

Exploring the use of effective learning strategies to increase students' reading comprehension and test taking skills /

This study examined the effects of providing students with explicit instruction in how to use a repertoire of reading comprehension strategies and test taking skills when reading and responding to three types of questions (direct, inferential, critical). Specifically, the study examined whether providing students with a "model" of how to read and respond to the text and to the comprehension questions improved their reading comprehension relative to providing them with implicit instruction on reading comprehension strategies and test taking skills. Students' reading comprehension and test taking performance scores were compared as a function of instructional condition. Students from 2 grade 8 classes participated in this study. The reading component of the Canadian Achievement Tests, Third Edition (CAT/3) was used to identify students' level of reading comprehension prior to the formal instructional sessions. Students received either explicit instruction, which involved modelling, or implicit instruction, which consisted of review and discussion of the strategies to be used. Comprehension was measured through the administration of formative tests after each instructional session. The formative tests consisted of reading comprehension questions pertaining to a specific form of text (narrative, informational, graphic). In addition, students completed 3 summative tests and a delayed comprehension test which consisted of the alternative version of the CAT/3 standardized reading assessment. These data served as a posttest measure to determine whether students had shown an improvement in their reading comprehension skills as a result of the program delivery. There were significant differences in students' Canadian Achievement Test performance scores prior to the onset of the study. Students in the implicit group attained significantly higher comprehension scores than did students in the explicit group. The results from the program sessions indicated no significant differences in reading comprehension between the implicit and explicit conditions, with the exception of the 6th session involving the reading and interpreting of graphic text. Students in the explicit group performed significantly better when reading and interpreting graphic text than those in the implicit group. No significant differences were evident between the two study conditions across the three summative tests. Upon completion of the study, the results from the Canadian Achievement Test indicated no significant differences in performance between the two study conditions. The findings from this study reveal the effectiveness of providing students with explicit strategy instruction when reading and responding to various forms of text. Modelling the appropriate reading comprehension strategies and test taking skills enabled students to apply the same thought processes to their own independent work. This form of instruction enabled students in the explicit group to improve in their abilities to comprehend and respond to text and therefore should be incorporated as an effective form of classroom teaching.

Sustaining Health Care Practice Change: The Experience of Best Practice Spotlight Organizations Implementing and Sustaining RNAO Best Practice Guidelines

Sustainability of change for improvement initiatives has been widely reported as a global challenge both within and outside health care settings. The purpose of this study was to examine the extent to which factors related to staff training and involvement, staff behaviour, and clinical leaders’ and senior leaders’ engagement and support impact the long term sustainability of practice changes for BPSO health care organizations who have implemented Registered Nursing Association of Ontario’s (RNAO) Best Practice Guidelines. Semi structured interviews with eleven organizational leaders’ from ten health care organizations were conducted to explore the unique experiences, views and perspectives on factors related to staff, clinical leaders and senior leaders and their involvement and impact on the long term sustainability of clinical practice changes within organizations who had implemented Registered Nursing Association of Ontario’s (RNAO) Best Practice Guidelines (BPGs). The interviews were coded and analyzed using thematic content analysis. Further analysis identified patterns and themes in relation to: 1. The National Health Service (NHS) Sustainability Model which was used as the theoretical framework for this research; and 2. Organizations found to have sustained practice changes longer term verses organizations that did not. Six organizations were found to have sustained practice changes while the remaining four were found to have been unsuccessful in their efforts to sustain the changes. Five major findings in relation to sustainability emerged from this study. First is the importance of early and sustained engagement and frontline staff, managers, and clinical leaders in planning, implementation and ongoing development of BPGs through use of working groups and champions models. Second is the importance of ongoing provision of formal training, tools and resources to all key stakeholders during and after the implementation phase and efforts made to embed changes in current processes whenever possible to ensure sustainability. Third is to ensure staff and management are receptive to the proposed change(s) and/or have been given the necessary background information and rationale so they understand and can support the need for the change. Fourth is the need for early and sustained fiscal and human resources dedicated to supporting BPG implementation and the ongoing use of the BPGs already in place. Fifth is ensuring clinical leaders are trusted, influential, respected and seen as clinical resources by frontline staff. The significance of this study lies in a greater understanding of the influence and impact of factors related to staff on the long term sustainability of implemented practice changes within health care organizations. This study has implications for clinical practice, policy, education and research in relation to sustainability in health care.

La collaboration interprofessionnelle vers une transformation des pratiques au sein d’un GMF de deuxième vague

INTRODUCTION : Les soins de première ligne au Québec vivent depuis quelques années une réorganisation importante. Les GMF, les cliniques réseaux, les CSSS, les réseaux locaux de service, ne sont que quelques exemples des nouveaux modes d’organisation qui voient le jour actuellement. La collaboration interprofessionnelle se trouve au cœur de ces changements. MÉTHODOLOGIE : Il s’agit d’une étude de cas unique, effectuée dans un GMF de deuxième vague. Les données ont été recueillies par des entrevues semi-dirigées auprès du médecin responsable du GMF, des médecins et des infirmières du GMF, et du cadre responsable des infirmières au CSSS. Les entrevues se sont déroulées jusqu’à saturation empirique. Des documents concernant les outils cliniques et les outils de communication ont aussi été consultés. RÉSULTATS : À travers un processus itératif touchant les éléments interactionnels et organisationnels, par l’évolution vers une culture différente, des ajustements mutuels ont pu être réalisés et les pratiques cliniques se sont réellement modifiées au sein du GMF étudié. Les participants ont souligné une amélioration de leurs résultats cliniques. Ils constatent que les patients ont une meilleure accessibilité, mais l’effet sur la charge de travail et sur la capacité de suivre plus de patients est évaluée de façon variable. CONCLUSION : Le modèle conceptuel proposé permet d’observer empiriquement les dimensions qui font ressortir la valeur ajoutée du développement de la collaboration interprofessionnelle au sein des GMF, ainsi que son impact sur les pratiques professionnelles.

Development and characterization of polymeric nanoparticles(NPs) made from functionalized poly (D,L- lactide) (PLA)polymers

Les nanoparticules polymériques biodégradable (NPs) sont apparues ces dernières années comme des systèmes prometteurs pour le ciblage et la libération contrôlée de médicaments. La première partie de cette étude visait à développer des NPs biodégradables préparées à partir de copolymères fonctionnalisés de l’acide lactique (poly (D,L)lactide ou PLA). Les polymères ont été étudiés comme systèmes de libération de médicaments dans le but d'améliorer les performances des NPs de PLA conventionnelles. L'effet de la fonctionnalisation du PLA par insertion de groupements chimiques dans la chaîne du polymère sur les propriétés physico-chimiques des NPs a été étudié. En outre, l'effet de l'architecture du polymère (mode d'organisation des chaînes de polymère dans le copolymère obtenu) sur divers aspects de l’administration de médicament a également été étudié. Pour atteindre ces objectifs, divers copolymères à base de PLA ont été synthétisés. Plus précisément il s’agit de 1) copolymères du poly (éthylène glycol) (PEG) greffées sur la chaîne de PLA à 2.5% et 7% mol. / mol. de monomères d'acide lactique (PEG2.5%-g-PLA et PEG7%-g-PLA, respectivement), 2) des groupements d’acide palmitique greffés sur le squelette de PLA à une densité de greffage de 2,5% (palmitique acid2.5%-g-PLA), 3) de copolymère « multibloc » de PLA et de PEG, (PLA-PEG-PLA)n. Dans la deuxième partie, l'effet des différentes densités de greffage sur les propriétés des NPs de PEG-g-PLA (propriétés physico-chimiques et biologiques) a été étudié pour déterminer la densité optimale de greffage PEG nécessaire pour développer la furtivité (« long circulating NPs »). Enfin, les copolymères de PLA fonctionnalisé avec du PEG ayant montré les résultats les plus satisfaisants en regard des divers aspects d’administration de médicaments, (tels que taille et de distribution de taille, charge de surface, chargement de drogue, libération contrôlée de médicaments) ont été sélectionnés pour l'encapsulation de l'itraconazole (ITZ). Le but est dans ce cas d’améliorer sa solubilité dans l'eau, sa biodisponibilité et donc son activité antifongique. Les NPs ont d'abord été préparées à partir de copolymères fonctionnalisés de PLA, puis ensuite analysés pour leurs paramètres physico-chimiques majeurs tels que l'efficacité d'encapsulation, la taille et distribution de taille, la charge de surface, les propriétés thermiques, la chimie de surface, le pourcentage de poly (alcool vinylique) (PVA) adsorbé à la surface, et le profil de libération de médicament. L'analyse de la chimie de surface par la spectroscopie de photoélectrons rayon X (XPS) et la microscopie à force atomique (AFM) ont été utilisés pour étudier l'organisation des chaînes de copolymère dans la formulation des NPs. De manière générale, les copolymères de PLA fonctionnalisés avec le PEG ont montré une amélioration du comportement de libération de médicaments en termes de taille et distribution de taille étroite, d’amélioration de l'efficacité de chargement, de diminution de l'adsorption des protéines plasmatiques sur leurs surfaces, de diminution de l’internalisation par les cellules de type macrophages, et enfin une meilleure activité antifongique des NPs chargées avec ITZ. En ce qui concerne l'analyse de la chimie de surface, l'imagerie de phase en AFM et les résultats de l’XPS ont montré la possibilité de la présence de davantage de chaînes de PEG à la surface des NPs faites de PEG-g-PLA que de NPS faites à partie de (PLA-PEG-PLA)n. Nos résultats démontrent que les propriétés des NPs peuvent être modifiées à la fois par le choix approprié de la composition en polymère mais aussi par l'architecture de ceux-ci. Les résultats suggèrent également que les copolymères de PEG-g-PLA pourraient être utilisés efficacement pour préparer des transporteurs nanométriques améliorant les propriétés de certains médicaments,notamment la solubilité, la stabilité et la biodisponibilité.

The Nursing Intensity Critical Care Questionnaire (NICCQ) : Validation Study in Cardiac Surgery Patients

Nurse Managers need today more than ever instruments that can be used to justify the billions of dollars that are invested in the healthcare sector annually. The objective of the study was to establish the validity and reliability of the Nursing Intensity Critical Care Questionnaire (NICCQ) in a cardiac surgery intensive care unit (CSICU) of a tertiary hospital. An expert panel evaluated the questionnaire’s content validity while generalizability theory was used to estimate the G and D coefficients. Decision studies enabled the investigators to determine if the current ward functioning of having one nurse rate one patient is adequate. Also, exploratory factorial analyses (EFA) preceded by principal component analyses (PCA) looked at establishing the factorial structure for the NICCQ. Finally, the NICCQ was correlated with a severity of illness score known as the Acute Physiology And Chronic Health Evaluation II (APACHE II) to estimate the correlation between patient illness and nursing intensity of care. The NICCQ was used by nurses using a sample of patients who had undergone cardiac surgery and were hospitalized on a CSICU of a tertiary teaching hospital. A convenience sample of nurses and patients on the CSICU was used to reflect the procedures and usual functioning of the unit. Each item on the questionnaire measured nursing intensity of care using a three point ordinal scale (Light, Moderate, and Severe) for the first 11 items, and a five point ordinal scale for the global assessment item (including the intermediate categories light/moderate and moderate/severe). The questionnaire proved to be both valid and able to be generalized to all nurses working in the CSICU. Overall results showed that 94.4% of the item generalizability coefficients indicated acceptable to excellent reliability, with most (86.1%) being larger than .90. The EFA established a simple 4 factor structure that explained little of the variance (32%). A correlation coefficient of 0.36 indicated that patient’ severity of illness is somewhat correlated with nursing intensity of care. The study showed that the NICCQ is a valid questionnaire with a generalizability coefficient that is large enough to be used by nurses’ managers for administrative purposes. Further research using larger samples would be needed to further test the factor structure of the NICCQ.

Percepción de los trabajadores acerca del sistema de seguridad y salud en el trabajo en un hospital de III nivel, Bogotá-Colombia. 2014.

Objetivo: Evaluar la percepción que tienen los trabajadores acerca del sistema de seguridad y salud en el trabajo en la población asistencial y administrativa en un Hospital de III nivel de atención., Bogotá-Colombia. Materiales y métodos: Estudio de corte transversal en población de trabajadores asistenciales y administrativos. Se aplicó el “Cuestionario Nórdico Sobre Seguridad en el Trabajo NOSACQ 50 Spanish” validado. La muestra fue probabilística estratificada aleatoria, en 308 trabajadores (230 asistenciales y 78 administrativos). Resultados: El promedio de edad fue 39.5± 12 años, con mayor frecuencia de género femenino (74.68%), estado civil soltero (38.96%) y nivel educativo técnico (34.40%). La percepción que tienen los trabajadores acerca del sistema de seguridad y salud en el trabajo fue independiente de su tipo de actividad laboral administrativa y asistencial (p>0.05), la mayor percepción en ambos grupos fue la confianza de los trabajadores en la eficacia del sistema de seguridad (2.71 y 2.77), y las de menor percepción presentaron el empoderamiento de seguridad de gestión (2.35 y 2.46) y la seguridad como prioridad de los empleados y rechazo del riesgo (2.35 y 2.40). Conclusiones: Los trabajadores del Hospital tienen un nivel adecuado de buena percepción acerca de los aspectos de seguridad y salud en el trabajo donde se evidenció que la fortaleza es la confianza de los trabajadores en la eficacia del sistema y la debilidad del sistema se encuentra en la falta de empoderamiento y rechazo al riesgo.

Herramienta para la gestión de convenios de docencia-servicio en Instituciones Prestadoras de Servicios de Salud

Los procesos de formación de profesionales de salud idóneos en el mundo, complementan su conocimiento entre dos componentes fundamentales, un componente teórico y el otro componente práctico. La formación que recibe en las aulas y la realización de las prácticas académicas a las cuales pueda acceder, le permite al estudiante trasformar el conocimiento académico adquirido en conocimiento cercano a la realidad y con fundamento profesional, razón por la cual las Instituciones Educativas tienen la responsabilidad de formar profesionales que sean capaces de desempeñarse en componentes sociales, administrativos y prácticos. Dentro de las ventajas que aporta la realización de las prácticas en la formación de los profesionales en salud se reconocen: la posibilidad de tener una visión de la responsabilidad del trabajo a la cual se van a ver enfrentados, desarrollar habilidades de interrelaciones sociales, incrementar su nivel de madurez, desarrollar e implementar estrategias de supervisión y así lograr el reconocimiento personal del nivel de confianza en su desempeño. Sin embargo también se puede convertir en un aspecto negativo si la práctica no se desarrolla de manera adecuada y si no logra tener una integración exitosa con el conocimiento teórico. Para el caso de la formación de talento humano en salud, el espacio utilizado para la realización de estas prácticas son las Instituciones Prestadoras de Servicios de Salud, deben ser lugares que les faciliten a los estudiantes encontrar una relación integral entre la formación teórica y su aplicación a la práctica profesional, de esta manera el estudiante podrá incrementar su preparación específica. Las prácticas académicas tienen interés en la formación de profesionales y representan un período donde el estudiante se convierte en sujeto entre la Institución Educativa y la Institución Prestadora. Es un espacio de inducción que le permite al estudiante realizar una evaluación de sí mismo y a la vez puede evaluar el entorno donde se va a desarrollar en su colectivo profesional. El objetivo de esta investigación es desarrollar una herramienta técnica que le permita a la Dirección facilitar la supervisión, el monitoreo y la evaluación de convenios de Docencia-Servicio en las Instituciones Prestadoras de Servicios de Salud, garantizando el respeto a los derechos de los usuarios, la calidad de los servicios prestados, la seguridad del paciente y la humanización de la atención, aspectos que no pueden ser afectados negativamente por el desarrollo de las prácticas académicas. Todas las actividades asistenciales que sean desarrolladas por estudiantes en la realización de su práctica profesional, deben ser realizadas bajo una estricta supervisión de docentes y de personal especializado responsable de la prestación del servicio, dando cumplimiento con el Sistema de Garantía de la Calidad del Sistema de Seguridad en Salud en Colombia.

Reflexiones en salud pública

Desde una visión general y práctica este texto facilita la reflexión sobre tópicos de interés para la salud pública. Con un lenguaje sencillo, busca aproximarse al estudio de la salud desde una visión interdisciplinar, partiendo del reconocimiento del rol que le compete al individuo, la sociedad y el Estado. El objetivo general es promover en el lector el análisis crítico de problemáticas relacionadas con el ámbito de la salud pública, constituyéndose en una iniciativa para el posterior desarrollo de acciones en el área.

A cross-taxonomic index for quantifying the health of farmland biodiversity

P>1. The development of sustainable, multi-functional agricultural systems involves reconciling the needs of agricultural production with the objectives for environmental protection, including biodiversity conservation. However, the definition of sustainability remains ambiguous and it has proven difficult to identify suitable indicators for monitoring progress towards, and the successful achievement of, sustainability. 2. In this study, we show that a trait-based approach can be used to assess the detrimental impacts of agricultural change to a broad range of taxonomic groupings and derive a standardised index of farmland biodiversity health, built around an objective of achieving stable or increasing populations in all species associated with agricultural landscapes. 3. To demonstrate its application, we assess the health of UK farmland biodiversity relative to this goal. Our results suggest that the populations of two-thirds of 333 plant and animal species assessed are unsustainable under current UK agricultural practices. 4. We then explore the potential benefits of an agri-environment scheme, Entry Level Stewardship (ELS), to farmland biodiversity in the UK under differing levels of risk mitigation delivery. We show that ELS has the potential to make a significant contribution to progress towards sustainability targets but that this potential is severely restricted by current patterns of scheme deployment. 5.Synthesis and applications: We have developed a cross-taxonomic sustainability index which can be used to assess both the current health of farmland biodiversity and the impacts of future agricultural changes relative to quantitative biodiversity targets. Although biodiversity conservation is just one of a number of factors that must be considered when defining sustainability, we believe our cross-taxonomic index has the potential to be a valuable tool for guiding the development of sustainable agricultural systems.

Application of computer-aided facilities management (CAFM) for intelligent buildings operation

Purpose – The purpose of this paper is to investigate the concepts of intelligent buildings (IBs), and the opportunities offered by the application of computer-aided facilities management (CAFM) systems. Design/methodology/approach – In this paper definitions of IBs are investigated, particularly definitions that are embracing open standards for effective operational change, using a questionnaire survey. The survey further investigated the extension of CAFM to IBs concepts and the opportunities that such integrated systems will provide to facilities management (FM) professionals. Findings – The results showed variation in the understanding of the concept of IBs and the application of CAFM. The survey showed that 46 per cent of respondents use a CAFM system with a majority agreeing on the potential of CAFM in delivery of effective facilities. Research limitations/implications – The questionnaire survey results are limited to the views of the respondents within the context of FM in the UK. Practical implications – Following on the many definitions of an IB does not necessarily lead to technologies of equipment that conform to an open standard. This open standard and documentation of systems produced by vendors is the key to integrating CAFM with other building management systems (BMS) and further harnessing the application of CAFM for IBs. Originality/value – The paper gives experience-based suggestions for both demand and supply sides of the service procurement to gain the feasible benefits and avoid the currently hindering obstacles, as the paper provides insight to the current and future tools for the mobile aspects of FM. The findings are relevant for service providers and operators as well.

Achieving whole-life value: The challenges of service-led construction

Major construction clients are increasingly looking to procure built facilities on the basis of added value, rather than capital cost. Recent advances in the procurement of construction projects have emphasised a whole-life value approach to meeting the client’s objectives, with strategies put in place to encourage long-term commitment and through-life service provision. Construction firms are therefore increasingly required to take on responsibility for the operation and maintenance of the construction project on the client’s behalf - with the emphasis on value and service. This inevitably throws up a host of challenges, not the least of which is the need for construction firms to manage and accommodate the new emphasis on service. Indeed, these ‘service-led’ projects represent a new realm of construction projects where the rationale for the project is driven by client’s objectives with some aspect of service provision. This vision of downstream service delivery increases the number of stakeholders, adds to project complexity and challenges deeply-ingrained working practices. Ultimately it presents a major challenge for the construction sector. This paper sets out to unravel some of the many implications that this change brings with it. It draws upon ongoing research investigating how construction firms can adapt to a more service-orientated built environment and add value in project-based environments. The conclusions lay bare the challenges that firms face when trying to compete on the basis of added-value and service delivery. In particular, how it affects deeply-ingrained working practices and established relationships in the sector.

Using cursor measures to determine appropriate computer input assistance for motion-impaired users

People with motion-impairments can often have difficulty with accurate control of standard pointing devices for computer input. The nature of the difficulties may vary, so to be most effective, methods of assisting cursor control must be suited to each user's needs. The work presented here involves a study of cursor trajectories as a means of assessing the requirements of motion-impaired computer users. A new cursor characteristic is proposed that attempts to capture difficulties with moving the cursor in a smooth trajectory. A study was conducted to see if haptic tunnels could improve performance in "point and click" tasks. Results indicate that the tunnels reduced times to target for those users identified by the new characteristic as having the most difficulty moving in a smooth trajectory. This suggests that cursor characteristics have potential applications in performing assessments of a user's cursor control capabilities which can then be used to determine appropriate methods of assistance.