Epidemiology and genetic architecture of blood pressure: a family based study of Generation Scotland

Hypertension is a major risk factor for cardiovascular disease and mortality, and a growing global public health concern, with up to one-third of the world’s population affected. Despite the vast amount of evidence for the benefits of blood pressure (BP) lowering accumulated to date, elevated BP is still the leading risk factor for disease and disability worldwide. It is well established that hypertension and BP are common complex traits, where multiple genetic and environmental factors contribute to BP variation. Furthermore, family and twin studies confirmed the genetic component of BP, with a heritability estimate in the range of 30-50%. Contemporary genomic tools enabling the genotyping of millions of genetic variants across the human genome in an efficient, reliable, and cost-effective manner, has transformed hypertension genetics research. This is accompanied by the presence of international consortia that have offered unprecedentedly large sample sizes for genome-wide association studies (GWASs). While GWAS for hypertension and BP have identified more than 60 loci, variants in these loci are associated with modest effects on BP and in aggregate can explain less than 3% of the variance in BP. The aims of this thesis are to study the genetic and environmental factors that influence BP and hypertension traits in the Scottish population, by performing several genetic epidemiological analyses. In the first part of this thesis, it aims to study the burden of hypertension in the Scottish population, along with assessing the familial aggregation and heritialbity of BP and hypertension traits. In the second part, it aims to validate the association of common SNPs reported in the large GWAS and to estimate the variance explained by these variants. In this thesis, comprehensive genetic epidemiology analyses were performed on Generation Scotland: Scottish Family Health Study (GS:SFHS), one of the largest population-based family design studies. The availability of clinical, biological samples, self-reported information, and medical records for study participants has allowed several assessments to be performed to evaluate factors that influence BP variation in the Scottish population. Of the 20,753 subjects genotyped in the study, a total of 18,470 individuals (grouped into 7,025 extended families) passed the stringent quality control (QC) criteria and were available for all subsequent analysis. Based on the BP-lowering treatment exposure sources, subjects were further classified into two groups. First, subjects with both a self-reported medications (SRMs) history and electronic-prescription records (EPRs; n =12,347); second, all the subjects with at least one medication history source (n =18,470). In the first group, the analysis showed a good concordance between SRMs and EPRs (kappa =71%), indicating that SRMs can be used as a surrogate to assess the exposure to BP-lowering medication in GS:SFHS participants. Although both sources suffer from some limitations, SRMs can be considered the best available source to estimate the drug exposure history in those without EPRs. The prevalence of hypertension was 40.8% with higher prevalence in men (46.3%) compared to women (35.8%). The prevalence of awareness, treatment and controlled hypertension as defined by the study definition were 25.3%, 31.2%, and 54.3%, respectively. These findings are lower than similar reported studies in other populations, with the exception of controlled hypertension prevalence, which can be considered better than other populations. Odds of hypertension were higher in men, obese or overweight individuals, people with a parental history of hypertension, and those living in the most deprived area of Scotland. On the other hand, deprivation was associated with higher odds of treatment, awareness and controlled hypertension, suggesting that people living in the most deprived area may have been receiving better quality of care, or have higher comorbidity levels requiring greater engagement with doctors. These findings highlight the need for further work to improve hypertension management in Scotland. The family design of GS:SFHS has allowed family-based analysis to be performed to assess the familial aggregation and heritability of BP and hypertension traits. The familial correlation of BP traits ranged from 0.07 to 0.20, and from 0.18 to 0.34 for parent-offspring pairs and sibling pairs, respectively. A higher correlation of BP traits was observed among first-degree relatives than other types of relative pairs. A variance-component model that was adjusted for sex, body mass index (BMI), age, and age-squared was used to estimate heritability of BP traits, which ranged from 24% to 32% with pulse pressure (PP) having the lowest estimates. The genetic correlation between BP traits showed a high correlation between systolic (SBP), diastolic (DBP) and mean arterial pressure (MAP) (G: 81% to 94%), but lower correlations with PP (G: 22% to 78%). The sibling recurrence risk ratio (λS) for hypertension and treatment were calculated as 1.60 and 2.04 respectively. These findings confirm the genetic components of BP traits in GS:SFHS, and justify further work to investigate genetic determinants of BP. Genetic variants reported in the recent large GWAS of BP traits were selected for genotyping in GS:SFHS using a custom designed TaqMan® OpenArray®. The genotyping plate included 44 single nucleotide polymorphisms (SNPs) that have been previously reported to be associated with BP or hypertension at genome-wide significance level. A linear mixed model that is adjusted for age, age-squared, sex, and BMI was used to test for the association between the genetic variants and BP traits. Of the 43 variants that passed the QC, 11 variants showed statistically significant association with at least one BP trait. The phenotypic variance explained by these variant for the four BP traits were 1.4%, 1.5%, 1.6%, and 0.8% for SBP, DBP, MAP, and PP, respectively. The association of genetic risk score (GRS) that were constructed from selected variants has showed a positive association with BP level and hypertension prevalence, with an average effect of one mmHg increase with each 0.80 unit increases in the GRS across the different BP traits. The impact of BP-lowering medication on the genetic association study for BP traits has been established, with typical practice of adding a fixed value (i.e. 15/10 mmHg) to the measured BP values to adjust for BP treatment. Using the subset of participants with the two treatment exposure sources (i.e. SRMs and EPRs), the influence of using either source to justify the addition of fixed values in SNP association signal was analysed. BP phenotypes derived from EPRs were considered the true phenotypes, and those derived from SRMs were considered less accurate, with some phenotypic noise. Comparing SNPs association signals between the four BP traits in the two model derived from the different adjustments showed that MAP was the least impacted by the phenotypic noise. This was suggested by identifying the same overlapped significant SNPs for the two models in the case of MAP, while other BP traits had some discrepancy between the two sources

Diseño e implementación de un sistema de soporte de decisiones para el Centro de Documentación Regional “Juan Bautista Vázquez”

El volumen de datos en bibliotecas ha aumentado enormemente en los últimos años, así como también la complejidad de sus fuentes y formatos de información, dificultando su gestión y acceso, especialmente como apoyo en la toma de decisiones. Sabiendo que una buena gestión de bibliotecas involucra la integración de indicadores estratégicos, la implementación de un Data Warehouse (DW), que gestione adecuadamente tal cantidad de información, así como su compleja mezcla de fuentes de datos, se convierte en una alternativa interesante a considerar. El artículo describe el diseño e implementación de un sistema de soporte de decisiones (DSS) basado en técnicas de DW para la biblioteca de la Universidad de Cuenca. Para esto, el estudio utiliza una metodología holística, propuesto por Siguenza-Guzman et al. (2014) para la evaluación integral de bibliotecas. Dicha metodología evalúa la colección y los servicios, incorporando importantes elementos para la gestión de bibliotecas, tales como: el desempeño de los servicios, el control de calidad, el uso de la colección y la interacción con el usuario. A partir de este análisis, se propone una arquitectura de DW que integra, procesa y almacena los datos. Finalmente, estos datos almacenados son analizados y visualizados a través de herramientas de procesamiento analítico en línea (OLAP). Las pruebas iniciales de implementación confirman la viabilidad y eficacia del enfoque propuesto, al integrar con éxito múltiples y heterogéneas fuentes y formatos de datos, facilitando que los directores de bibliotecas generen informes personalizados, e incluso permitiendo madurar los procesos transaccionales que diariamente se llevan a cabo.

A gestão da qualidade no ensino superior: Percursos e recursos

Este artigo condensa um conjunto de reflexões baseadas em factos relacionados com a gestão da qualidade nas Instituições de Ensino Superior (IES). São identificados factores internos e externos favoráveis à melhoria da qualidade dos serviços prestados por estas organizações, bem como algumas das barreiras que se lhe opõem. Relativamente às abordagens da qualidade, nestas organizações são consideradas: de um lado as que resultam da Supervisão do Estado e do outro as que estão associadas a sistemas de natureza voluntária, designadas aqui por Abordagem Qualidade, em que sobressai a Certificação baseada na norma ISO 9001 e os sistemas de Gestão pela Qualidade Total (GQT) também designados de Excelência Organizacional. São identificadas algumas das insuficiências dos modelos assentes na Supervisão do Estado e defendida a importância de atender ao conjunto de “boas práticas” já existentes, ao invés de abordagens que tratam desta problemática numa perspectiva ab initio, sem contemplar o conhecimento acumulado neste domínio da gestão das organizações.

The quality of rapid HIV testing in South Africa: an assessment of testers’ compliance.

Background: The aim of this study was to assess the quality of rapid HIV testing in South Africa. Method: A two-stage sampling procedure was used to select HCT sites in eight provinces of South Africa. The study employed both semi-structured interviews with HIV testers and observation of testing sessions as a means of data collection. In total, 63 HCT sites (one HIV tester per site) were included in the survey assessing qualification, training, testing practices and attitudes towards rapid tests. Quantitative data was analysed using descriptive statistics and qualitative data was content analysed. Results: Of the 63 HIV testers, 20.6% had a nursing qualification, 14.3% were professional counsellors, 58.7% were lay HIV counsellors and testers and 6.4% were from other professions. Most HIV testers (87.3%) had had a formal training in testing, which ranged between 10-14 days, while 6 (9.5%) had none. Findings revealed sub-standard practices in relation to testing. These were mainly related to non-adherence to testing algorithms, poor external quality control practices, poor handling and communication of discordant results. Conclusion: Quality of HIV rapid testing may be highly compromised through poor adherence to guidelines as observed in our study.

A Ouvidoria Pública como instrumento de controle das ações da Secretaria de Saúde do Pará

The State and Public Administration have gone through several reforms in search of a quick operation and the provision of services with quality. With the democratization of the country and the issue of the Constitution in 1988, further reform of the State and Public Administration, joined the government agenda in 1995 and included among its objectives, the principles of participation and social control. In view of this, it raises the Public Ombudsman in order to be a channel for the participation of users in the management of public affairs, social control, transparency of administrative actions, improving the quality of service and meeting the needs of the community. The aim of this study is to assess whether the Ombudsman of the State Department of Public Health to contribute to the period 2006-2008, for the improvement of specialized consulting services. The research is characterized as descriptive, qualitative approach. The collection technique used was the interview, conducted with 37 service users and two servants of the Ombudsman. The analysis was developed based on the perception of users and servers in the opinion of the Ombudsman. The most relevant results of the research showed that 41% of users search the Ombudsman because they believed that solve the problem presented. However, even with this level of public acceptance, the Ombudsman reached average index of resolvability of 53% in the period. In his role has not developed mechanisms for quality control of services, which is mentioned by 67% of users. It turned out the same fact in relation to popular participation, which is confirmed by 84% of users. For 24% of users, the problems raised were resolved, and of these, 56% believe that the Ombudsman has contributed to the positive outcome. As a result of the search results, it appears that the Ombudsman's SESPA / PA, is not fulfilling its role to ensuring the democratization of articipation in management, social control and has limited contribution to solving the problems of users and to improve the quality of services

Análise da estabilidade genética de células-tronco mesenquimais humanas

Human multipotent mesenchymal stromal cells (MSCs), also known as mesenchymal stem cells, have become an important and attractive therapeutic tool since they are easily isolated and cultured, have in vitro expansion potential, substantial plasticity and secrete bioactive molecules that exert trophic effects. The human umbilical cord as a cell source for cell therapy will help to avoid several ethical, political, religious and technical issues. One of the main issues with SC lines from different sources, mainly those of embryonic origin, is the possibility of chromosomal alterations and genomic instability during in vitro expansion. Cells isolated from one umbilical cord exhibited a rare balanced paracentric inversion, likely a cytogenetic constitutional alteration, karyotype: 46,XY,inv(3)(p13p25~26). Important genes related to cancer predisposition and others involved in DNA repair are located in 3p25~26. Titanium is an excellent biomaterial for bone-implant integration; however, the use can result in the generation of particulate debris that can accumulate in the tissues adjacent to the prosthesis, in the local bone marrow, in the lymph nodes, liver and spleen. Subsequently may elicit important biological responses that aren´t well studied. In this work, we have studied the genetic stability of MSC isolated from the umbilical cord vein during in vitro expansion, after the cryopreservation, and under different concentrations and time of exposition to titanium microparticles. Cells were isolated, in vitro expanded, demonstrated capacity for osteogenic, adipogenic and chondrogenic differentiation and were evaluated using flow cytometry, so they met the minimum requirements for characterization as MSCs. The cells were expanded under different concentrations and time of exposition to titanium microparticles. The genetic stability of MSCs was assessed by cytogenetic analysis, fluorescence in situ hybridization (FISH) and analysis of micronucleus and other nuclear alterations (CBMN). The cells were able to internalize the titanium microparticles, but MSCs preserve their morphology, differentiation capacity and surface marker expression profiles. Furthermore, there was an increase in the genomic instability after long time of in vitro expansion, and this instability was greater when cells were exposed to high doses of titanium microparticles that induced oxidative stress. It is necessary always assess the risks/ benefits of using titanium in tissue therapy involving MSCs, considering the biosafety of the use of bone regeneration using titanium and MSCs. Even without using titanium, it is important that the therapeutic use of such cells is based on analyzes that ensure quality, security and cellular stability, with the standardization of quality control programs appropriate. In conclusion, it is suggested that cytogenetic analysis, FISH analysis and the micronucleus and other nuclear alterations are carried out in CTMH before implanting in a patient

In-vitro evaluation of the quality of Paracetamol and Co-trimoxazole tablets used in Malawi based on pharmacopoeial standards

Objectives This study was an in-vitro evaluation of different brands of paracetamol and cotrimoxazole tablets, used or found in Malawi, based on Pharmacopoeia standards, in order to ascertain the existence and extent of substandard medicines in Malawi and to give an overview of their distribution in the public and private sectors. Methodology A cross-sectional analytical study was conducted using 11 samples each of paracetamol and cotrimoxazole tablets. Stratified random sampling was used to collect samples. Samples were analyzed using HPLC and Spectrophometric methods as outlined in the BP-2007 and USP-32 at the National Drug Quality Control Laboratory (NDQCL)-Lilongwe (under Pharmacy Medicines and Poisons Board-PMPB) and Orient Pharma Co. Ltd of Taiwan. The results were analyzed using Epi Info. Results and discussion Fifty percent of samples (n=22) were not registered in the country by the PMPB as required by the PMP Act with the majority of those coming from public health facilities. All paracetamol and cotrimoxazole samples complied with identification tests using spectrophotometric and HPLC method. Overall, 27.3% of samples failed to meet the BP-2007 standards for Active Ingredient content, while 22.7% of the samples failed the Friability test. The results from Malawi are similar in magnitude to those within surrounding countries in Africa. Conclusion This pilot study provides objective evidence to show that substandard and unregistered paracetamol and cotrimoxazole are present and being used in Malawi, and thus posing a considerable hazard to public health in Malawi. PMPB, together with the Ministry of Health, must continue to develop a quality assurance system to ensure that medicines are randomly and routinely checked.

Continuous Quality Assurance and Optimisation in Cloud-Based Virtual Enterprises

Part 18: Optimization in Collaborative Networks

THE DEVELOPMENT EFFECTIVENESS OF INTERNATIONAL WATER AND SANITATION INFRASTRUCTURE PROJECTS: DEFINING “QUALITY AT ENTRY” OF WORLD BANK PROJECTS.

Over the past 15 years, the number of international development projects aimed at combating global poverty has increased significantly. Within the water and sanitation sector however, and despite heightened global attention and an increase in the number of infrastructure projects, over 800 million people remain without access to appropriate water and sanitation facilities. The majority of donor aid in the water supply and sanitation sector of developing countries is delivered through standalone projects. The quality of projects at the design and preparation stage is a critical determinant in meeting project objectives. The quality of projects at early stage of design, widely referred to as quality at entry (QAE), however remains unquantified and largely subjective. This research argues that water and sanitation infrastructure projects in the developing world tend to be designed in the absence of a specific set of actions that ensure high QAE, and consequently have relatively high rates of failure. This research analyzes 32 cases of water and sanitation infrastructure projects implemented with partial or full World Bank financing globally from 2000 – 2010. The research uses categorical data analysis, regression analysis and descriptive analysis to examine perceived linkages between project QAE and project development outcomes and determines which upstream project design factors are likely to impact the QAE of international development projects in water supply and sanitation. The research proposes a number of specific design stage actions that can be incorporated into the formal review process of water and sanitation projects financed by the World Bank or other international development partners.

Trust and Leadership in Higher Education in the Downturn

This Leadership Academy Workshop presentation focused on 'Trust and Leadership in the Downturn', with particular reference to the public sector and to education. The presentation discussed a range of definitions of trust, including the view of Mayer, Davis and Schoorman (1995) that trust can be described as 'the willingness of a person to be vulnerable to the actions of another, based on the expectation that the other will perform a particular action important to the trustor, irrespective of the ability to monitor or control that action'. The presentation then focused on the reasons why this relational psychological state is important,particularly in an economic recession when people were facing job cuts and economic uncertainty in a wider political and social environment characterised by cynicism and a downturn in trust. If trust is defined in part as a belief in the honesty, competence and benevolence of others, it tends to act like 'social glue', cushioning difficult situations and enabling actions to take place easily that otherwise would not be permissible. A worrying state of affairs has recently been developing across the world, however, in the economic downturn, as reported in the Edelman Trust Barometer for 2009, in which there was a marked diminuition of trust in corporations, businesses and government, as a result of the credit crunch. While the US and parts of Europe was showing recovery from a generalised loss of trust by mid-year 2009, the UK had not. It seems that social attitudes in Britain may be hardening - it seems that from being a nation of sceptics we may be becoming a nation of cynics: for example, 69% of the population surveyed by Edelman trust the government less than six months ago. In this situation, there is a need to promote positive measures to build trust, including the establishment of more transparent and honest business practices and practices to ensure that employees are treated well. Following the presentation, a workshop was held to discuss the nature of a possible loss of trust in the downturn in the UK and its implications for leadership practices and development.

Origin discrimination and quality evaluation of Gastrodiae rhizoma (Orchidaceae) by high-performance liquid chromatographic fingerprint

Purpose: To develop a high-performance liquid chromatography (HPLC) fingerprint method for the quality control and origin discrimination of Gastrodiae rhizoma . Methods: Twelve batches of G. rhizoma collected from Sichuan, Guizhou and Shanxi provinces in china were used to establish the fingerprint. The chromatographic peak (gastrodin) was taken as the reference peak, and all sample separation was performed on a Agilent C18 (250 mm×4.6 mmx5 μm) column with a column temperature of 25 °C. The mobile phase was acetonitrile/0.8 % phosphate water solution (in a gradient elution mode) and the flow rate of 1 mL/min. The detection wavelength was 270 nm. The method was validated as per the guidelines of Chinese Pharmacopoeia. Results: The chromatograms of the samples showed 11 common peaks, of which no. 4 was identified as that of Gastrodin. Data for the samples were analyzed statistically using similarity analysis and hierarchical cluster analysis (HCA). The similarity index between reference chromatogram and samples’ chromatograms were all > 0.80. The similarity index of G. rhizoma from Guizhou, Shanxi and Sichuan is evident as follows: 0.854 - 0.885, 0.915 - 0.930 and 0.820 - 0.848, respectively. The samples could be divided into three clusters at a rescaled distance of 7.5: S1 - S4 as cluster 1; S5 - S8 cluster 2, and others grouped into cluster 3. Conclusion: The findings indicate that HPLC fingerprinting technology is appropriate for quality control and origin discrimination of G. rhizoma.

Adaptive Software Fault Prediction Approach Using Object-Oriented Metrics

As users continually request additional functionality, software systems will continue to grow in their complexity, as well as in their susceptibility to failures. Particularly for sensitive systems requiring higher levels of reliability, faulty system modules may increase development and maintenance cost. Hence, identifying them early would support the development of reliable systems through improved scheduling and quality control. Research effort to predict software modules likely to contain faults, as a consequence, has been substantial. Although a wide range of fault prediction models have been proposed, we remain far from having reliable tools that can be widely applied to real industrial systems. For projects with known fault histories, numerous research studies show that statistical models can provide reasonable estimates at predicting faulty modules using software metrics. However, as context-specific metrics differ from project to project, the task of predicting across projects is difficult to achieve. Prediction models obtained from one project experience are ineffective in their ability to predict fault-prone modules when applied to other projects. Hence, taking full benefit of the existing work in software development community has been substantially limited. As a step towards solving this problem, in this dissertation we propose a fault prediction approach that exploits existing prediction models, adapting them to improve their ability to predict faulty system modules across different software projects.

Update in the management of critically ill burned patients

The management of critically ill burn patients is challenging. These patients have to be managed in specialized centers, where the expertise of physicians and nursing personnel guarantees the best treatment. Mortality of burn patients has improved over the past decades due to a better understanding of burn shock pathophysiology, optimal surgical management, infection control and nutritional support. Indeed, a more aggressive resuscitation, early excision and grafting, the judicious use of topical antibiotics, and the provision of an adequate calorie and protein intake are key to attain best survival results. General advances in critical care have also to be implemented, including protective ventilation, glycemic control, selective decontamination of the digestive tract, and implementation of sedation protocols.

The significant role of third-party logistics (3pl) operators as fosterers of organizational performance in colombian companies

La eliminación de barreras entre países es una consecuencia que llega con la globalización y con los acuerdos de TLC firmados en los últimos años. Esto implica un crecimiento significativo del comercio exterior, lo cual se ve reflejado en un aumento de la complejidad de la cadena de suministro de las empresas. Debido a lo anterior, se hace necesaria la búsqueda de alternativas para obtener altos niveles de productividad y competitividad dentro de las empresas en Colombia, ya que el entorno se ha vuelto cada vez más complejo, saturado de competencia no sólo nacional, sino también internacional. Para mantenerse en una posición competitiva favorable, las compañías deben enfocarse en las actividades que le agregan valor a su negocio, por lo cual una de las alternativas que se están adoptando hoy en día es la tercerización de funciones logísticas a empresas especializadas en el manejo de estos servicios. Tales empresas son los Proveedores de servicios logísticos (LSP), quienes actúan como agentes externos a la organización al gestionar, controlar y proporcionar actividades logísticas en nombre de un contratante. Las actividades realizadas pueden incluir todas o parte de las actividades logísticas, pero como mínimo la gestión y ejecución del transporte y almacenamiento deben estar incluidos (Berglund, 2000). El propósito del documento es analizar el papel de los Operadores Logísticos de Tercer nivel (3PL) como promotores del desempeño organizacional en las empresas colombianas, con el fin de informar a las MIPYMES acerca de los beneficios que se obtienen al trabajar con LSP como un medio para mejorar la posición competitiva del país.

Optimización del proceso de empaque de BANAFRUTS S.A.S. desde el punto de vista de la Teoría de Restricciones

Como resultado de la Misión Empresarial Caribe realizada por la Escuela de Administración de la Universidad del Rosario en abril de 2016, se realizó el presente documento donde se plantea una propuesta de mejora para el proceso de empaque de BanaFruts S.A.S. mediante el uso de teorías administrativas enfocadas a la gestión de calidad del producto como: Teoría de Restricciones, Kaizen y Cero defectos. La propuesta consiste en tener un proceso de control de calidad mucho menos repetitivo y más eficiente a lo largo del empaque del producto, donde solo los operarios de desmane se deberán encargar de definir cuáles bananos cumplen o no con las especificaciones de DOLE en esa etapa y además se aseguren de cumplir con nuevos límites de saturación de los frutos en las piscinas. Éstos se encontrarán en donde se alcanza el 90% de la capacidad de cada tanque. Para el de desmane estará a una altura de 0.54m; y para el de saneo estará a una altura de 0.49m. Así se actuará der manera preventiva y no reactiva como sucede actualmente, garantizando que los bananos no se lastimen y se reduzca el exceso de revisión a lo largo del proceso. Este cambio de gestión de calidad permitirá en primera instancia que los trabajadores en etapas diferentes a las de desmane se enfoquen en una sola tarea y no tengan que volver a verificar los aspectos de calidad del producto, seguido de un aumento de productividad en el procesamiento de los bananos por parte de éstos. Adicionalmente, se hace énfasis en la importancia de la mejora continua del proceso en general para asegurar un incremento gradual en la productividad. Para esto se propone un nuevo modelo de gestión de los recursos humanos donde los operarios serán más proactivos, tendrán una mayor participación en la identificación y solución de problemas y se encargarán de llevar a cabo sus labores de manera más eficiente. En este sentido, las acciones a tomar serán: seleccionar, organizar, limpiar y estandarizar. Finalmente, hay que estandarizar el proceso, es decir que debe existir una revisión continua para no permitir que los errores se repitan. Todas estas acciones estarán a cargo de un equipo líder llamado “Equipo BanaFruts”. Éste tendrá la responsabilidad de acompañar a los trabajadores en la realización de las actividades mencionadas y medir sus resultados.