Alterations in dihydropyridine receptors in dystrophin-deficient cardiac muscle

The deficiency of dystrophin, a critical membrane stabilizing protein, in the mdx mouse causes an elevation in intracellular calcium in myocytes. One mechanism that could elicit increases in intracellular calcium is enhanced influx via the L-type calcium channels. This study investigated the effects of the dihydropyridines BAY K 8644 and nifedipine and alterations in dihydropyridine receptors in dystrophin-deficient mdx hearts. A lower force of contraction and a reduced potency of extracellular calcium (P < 0.05) were evident in mdx left atria. The dihydropyridine agonist BAY K 8644 and antagonist nifedipine had 2.7- and 1.9-fold lower potencies in contracting left atria (P < 0.05). This corresponded with a 2.0-fold reduction in dihydropyridine receptor affinity evident from radioligand binding studies of mdx ventricular homogenates (P < 0.05). Increased ventricular dihydropyridine receptor protein was evident from both radioligand binding studies and Western blot analysis and was accompanied by increased mRNA levels (P < 0.05). Patch-clamp studies in isolated ventricular myocytes showed no change in L-type calcium current density but revealed delayed channel inactivation (P < 0.05). This study indicates that a deficiency of dystrophin leads to changes in dihydropyridine receptors and L-type calcium channel properties that may contribute to enhanced calcium influx. Increased influx is a potential mechanism for the calcium overload observed in dystrophin-deficient cardiac muscle.

Audit committees in Scottish local authorities 1998-2005

During the last 15 years corporate governance has become increasingly prominent in the public sector. The Audit Commission's 1993 report on probity in local government recommended the establishment of audit committees. However, progress on this was slow, as demonstrated by a survey of Scottish local authorities by the authors in 1998. Recent major changes in government in Scotland at both a local and national level have prompted councils to improve the accountability, openness and integrity of their operations. One major aspect of this exercise was the formation of scrutiny committees to provide objective scrutiny of the process and audit committees were the most common vehicle for this. This article explores recent developments in Scottish local government and their impact on audit committees. The article also reports the results of a 2005 survey of Scottish local authorities and compares these with the 1998 survey. This indicates a significant growth in the number of audit committees in Scottish councils and although the level of their perceived effectiveness is patchy, they are a more important feature of local government than they were in 1998.

City branding:can goods and services branding models be used to brand cities?

A city's branding is investigated using generic product and services branding models. Two generic branding models and tourism segmentation models guide an investigation into city branding 'as it should be' and 'as it is' using Birmingham, England as a case study. The unique characteristics of city brands are identified and Keller's Brand Report Card provides a theoretical framework for building a picture of the brand-building activity taking place in the city. Four themes emerge and are discussed: 1) the impact of a network on brand models developed for organisations; 2) segmentation of brand elements; 3) corporate branding; and 4) the political dimension. A conclusion is that city branding would be more effective if the systems and structures of generic branding models were adopted.

Vaccine entrapment in liposomes

The use of liposomes as carriers of peptide, protein, and DNA vaccines requires simple, easy-to-scale-up technology capable of high-yield vaccine entrapment. Work from this laboratory has led to the development of techniques that can generate liposomes of various sizes, containing soluble antigens such as proteins and particulate antigens (e.g., killed or attenuated bacteria or viruses), as well as antigen-encoding DNA vaccines. Entrapment of vaccines is carried out by the dehydration-rehydration procedure which entails freeze-drying of a mixture of "empty" small unilamellar vesicles and free vaccines. On rehydration, the large multilamellar vesicles formed incorporate up to 90% or more of the vaccine used. When such liposomes are microfluidized in the presence of nonentrapped material, their size is reduced to about 100 nm in diameter, with much of the originally entrapped vaccine still associated with the vesicles. A similar technique applied for the entrapment of particulate antigens (e.g., Bacillus subtilis spores) consists of freeze-drying giant vesicles (4-5 microm in diameter) in the presence of spores. On rehydration and sucrose gradient fractionation of the suspension, up to 30% or more of the spores used are associated with generated giant liposomes of similar mean size.

Entrapment of plasmid DNA vaccines into liposomes by dehydration/rehydration

Intramuscular injection of naked plasmid DNA is known (1-3) to elicit humoral and cell-mediated immune responses against the encoded antigen. It is thought (2,3) that immunity follows DNA uptake by muscle cells, leading to the expression and extracellular release of the antigen which is then taken up by antigen presenting cells (APC). In addition, it is feasible that some of the injected DNA is taken up directly by APC. Disadvantages (1-3) of naked DNA vaccination include: uptake of DNA by only a minor fraction of muscle cells, exposure of DNA to deoxyribonuclease in the interstitial fluid thus necessitating the use of relatively large quantities of DNA, and, in some cases, injection into regenerating muscle in order to enhance immunity. We have recently proposed (1,4) that DNA immunization via liposomes (phospholipid vesicles) could circumvent the need of muscle involvement and instead facilitate (5) uptake of DNA by APC infiltrating the site of injection or in the lymphatics, at the same time protecting DNA from nuclease attack (6). Moreover, transfection of APC with liposomal DNA could be promoted by the judicial choice of vesicle surface charge, size and lipid composition, or by the co-entrapment, together with DNA, of plasmids expressing appropriate cytokines (e.g., interleukin 2), or immunostimulatory sequences.

Quasi-Likelihood Estimation for Ornstein-Uhlenbeck Diffusion Observed at Random Time Points

2000 Mathematics Subject Classification: 60J60, 62M99.

Prenatal environmental exposure and neurodevelopmentally important gene expression in malformed brain tissue from pediatric intractable epilepsy patients

The primary objective of this proposal was to determine whether mitochondrial oxidative stress and variation in a particular mtDNA lineage contribute to the risk of developing cortical dysplasia and are potential contributing factors in epileptogenesis in children. The occurrence of epilepsy in children is highly associated with malformations of cortical development (MCD). It appears that MCD might arise from developmental errors due to environmental exposures in combination with inherited variation in response to environmental exposures and mitochondrial function. Therefore, it is postulated that variation in a particular mtDNA lineage of children contributes to the effects of mitochondrial DNA damage on MCD phenotype. Quantitative PCR and dot blot were used to examine mitochondrial oxidative damage and single nucleotide polymorphism (SNP) in the mitochondrial genome in brain tissue from 48 pediatric intractable epilepsy patients from Miami Children’s Hospital and 11 control samples from NICHD Brain and Tissue Bank for Developmental Disorders. Epilepsy patients showed higher mtDNA copy number compared to normal health subjects (controls). Oxidative mtDNA damage was lower in non-neoplastic but higher in neoplastic epilepsy patients compared to controls. There was a trend of lower mtDNA oxidative damage in the non-neoplastic (MCD) patients compared to controls, yet, the reverse was observed in neoplastic (MCD and Non-MCD) epilepsy patients. The presence of mtDNA SNP and haplogroups did not show any statistically significant relationships with epilepsy phenotypes. However, SNPs G9804A and G9952A were found in higher frequencies in epilepsy samples. Logistic regression analysis showed no relationship between mtDNA oxidative stress, mtDNA copy number, mitochondrial haplogroups and SNP variations with epilepsy in pediatric patients. The levels of mtDNA copy number and oxidative mtDNA damage and the SNPs G9952A and T10010C predicted neoplastic epilepsy, however, this was not significant due to a small sample size of pediatric subjects. Findings of this study indicate that an increase in mtDNA content may be compensatory mechanisms for defective mitochondria in intractable epilepsy and brain tumor. Further validation of these findings related to mitochondrial genotypes and mitochondrial dysfunction in pediatric epilepsy and MCD may lay the ground for the development of new therapies and prevention strategies during embryogenesis.

Model of Service Quality: Customer Loyalty for Hotels

The authors investigate the relationship between loyalty and perceived service quality of hotel customers and discus managerial implications to develop strategies to enhance loyalty of hotel customers. A survey was conducted among customers in the San Francisco Bay Area. Results indicate that customer loyalty is dependent on perceived service quality which is observed in terms of timelines, facilities, and ambience.

Evidências de validade do Millon Behavioral Medicine Diagnostic: avaliação de indicadores de adesão ao tratamento em pacientes com hipertensão

Systemic Arterial Hypertension – SAH – is defined as the syndrome which its main feature is the presence of high tensional levels, associated with alterations of functional or structural levels in the organs that it strikes. Its specific causes are not very well bounded and have an asymptomatic character. Due to its chronicity it requires adherence to the treatment plan in a systematic and permanent manner, implicating in lifestyle changes, combined or not with the use of medication. The personality inventories have been largely used in the lineation of indicative traits of difficulties with the adherence to the treatment. In this sense, developed by Theodore Millon, the Millon Behavioural Medicine Diagnostic – MBMD is an instrument made from the consensus among healthcare professionals, aiming at identifying psychological factors that may compromise medical treatment so that they can be conducted in a way to enable a better adherence. Objective: evaluation of the evidence of validity of the Millon Behavioural Medicine Diagnostic – MBMD for a public of patients with hypertension, aiming at investigating the indicators implicated in the adherence or not to the anti-hypertensive treatment. Method: there was a group of 200 participants in a university hospital in the city of Natal/RN, males and females, ranging from 20 to 70 years old. An interview protocol was administered in order to obtain information about socio-demographic data, clinical history, healthcare habits and way of conducting treatment, and after, the administration of the MBMD followed. Results: by means of Factor Analysis it was verified that the organization proposed by the factors is favorable and it adjusts to the theory, allowing the visualization of other underlying constructs to the scales, with adequate adjustment indexes and satisfactory Cronbach’s alpha indicators. Besides, the MBMD revealed itself sensitive to the intragroup differences relative to the sex, age, schooling, marital status, profession, income, SAH history, diagnostic time, medication use, comorbidity presence, hyposodic diet, social support and adherence criteria variables. The utilization of such instrument in the evaluation of the adherence to the anti-hypertensive treatment show, therefore, indicators of validity.

Análise do uso do Portal de Periódicos da CAPES na perspectiva de mestres e doutores formados pelo Programa de Pós-graduação em Administração da UFRN

The Brazilian CAPES Journal Portal aims to provide Information in Science and Technology (IST) for academic users. Thus, it is considered a relevant instrument for post-graduation dynamics and the country´s Science and Technology (S&T) development. Despite its importance, there are still few studies that focus on the policy analysis and efficiency of these resources. This research aims to fill in this gap once it proposes an analysis of the use of the CAPES Journal Portal done on behalf of the master´s and doctoral alumni of the Post Graduate Program in Management (PPGA) at the Federal University of Rio Grande do Norte (UFRN). The operationalization of the research´s main objective was possible through the specific objectives: characterize graduate profile as CAPES Journal Portal users b) identify motivation for the use of CAPES Journal Portal c) detect graduate satisfaction degree in information seeking done at CAPES Journal Portal d) verify graduate satisfaction regarding the use of the CAPES Journal Portal e) verify the use of the information that is obtained by graduates in the development of their academic activities. The research is of descriptive nature employing a mixed methodological strategy in which quantitative approach predominates. Data collection was done through a web survey questionnaire. Quantitative data analysis was made possible through the use of a statistical method. As for qualitative analysis, there was use of the Brenda Dervin´s sense-making approach as well as content analysis in open ended questions. The research samples were composed by 90 graduate students who had defended their dissertation/thesis in the PPGA program at UFRN in the time span of 2010-2013. This represented by 88% of this population. As for user profile, the analysis has made evident that there are no quantitative differences related to gender. There is predominance of male graduates that were aged 26 to 30 years old. As for female graduates, the great majority were 31 o 35 years old. Most graduates had Master´s degree scholarship in order to support their study. It was also seen that the great majority claim to use the Portal during their post graduation studies. The main reasons responsible for non use was: preference for the use of other data bases and lack of knowledge regarding the Portal. It was observed that the most used information resources were theses and dissertations. Data also indicate preference for complete text. Those who have used the Portal also claimed to have used other electronic information fonts in order to fulfill their information needs. The information fonts that were researched outside in the Portal were monographs, dissertations and thesis. Scielo was the most used information font. Results reveal that access and use of the Portal has been done in a regular manner during post graduation studies. But on the other hand, graduates also make use of other electronic information fonts in order to meet their information needs. The study also confirmed the important mission performed by the Portal regarding Brazilian scientific communication production. This was seen even though users have reported the need for improvement in some aspects such as: periodic training in order to promote, encourage and teach more effective use of the portal; investment aiming the expansion of Social Sciences Collection in the Portal as well as the need to implement continuous evaluation process related to user satisfaction in regarding the services provided.

El arte camaleónico de Marcos Irizarry: entre el modernismo europeo y la abstracción americana, (1950-1970)

Marcos Irizarry (Mayagüez, Puerto Rico 1936-San Juan, Puerto Rico 1995) es uno de los artistas plásticos puertorriqueños más destacados e influyentes que creó una de las obras gráficas y pictóricas abstractas más significativas en Puerto Rico y España. La presente investigación tiene como objetivo el estudio y análisis de la obra de Marcos Irizarry. El estudio de la obra de Marcos Irizarry es importante, ya que los trabajos y escritos realizados tanto en Puerto Rico como en España son limitados, y mayormente se basan en el contexto puertorriqueño. El objetivo de esta investigación es contribuir a la historia del arte de Puerto Rico, de modo que se fomente el estudio, y se logre un mayor entendimiento de la abstracción y de la extensa obra gráfica del artista puertorriqueño Marcos Irizarry, sobre todo el que se dio durante las décadas sugeridas y mostrar su trascendencia, su gran legado, su amplio alcance y reafirmar su carácter universal. La hipótesis fundamental de este trabajo se basa en que la obra del artista puertorriqueño, Marcos Irizarry posee características, estéticas, conceptos y rasgos que pueden responder a las estipuladas tanto por el informalismo europeo-español o por la abstracción americana-puertorriqueña. Se concluyó que la obra gráfica realizada entre finales de los cincuenta hasta finales de los setenta, cobra carácter distinto si se ve como parte del proceso estético español de la posguerra o si se la sitúa en el ámbito del arte puertorriqueño...

Psychosocial morbidity in women with abnormal cervical cytology managed by cytological surveillance or initial colposcopy : longitudinal analysis from the TOMBOLA randomised trial

We are grateful for the co-operation and assistance that we received from NHS staff in the co-ordinating centres and clinical sites. We thank the women who participated in TOMBOLA. The TOMBOLA trial was supported by the Medical Research Council (G9700808) and the NHS in England and Scotland. The TOMBOLA Group comprises the following: Grant-holders: University of Aberdeen and NHS Grampian, Aberdeen, Scotland: Maggie Cruickshank, Graeme Murray, David Parkin, Louise Smart, Eric Walker, Norman Waugh (Principal Investigator 2004–2008) University of Nottingham and Nottingham NHS, Nottingham, England: Mark Avis, Claire Chilvers, Katherine Fielding, Rob Hammond, David Jenkins, Jane Johnson, Keith Neal, Ian Russell, Rashmi Seth, Dave Whynes University of Dundee and NHS Tayside, Dundee, Tayside: Ian Duncan, Alistair Robertson (deceased) University of Ottawa, Ottawa, Canada: Julian Little (Principal Investigator 1999–2004) National Cancer Registry, Cork, Ireland: Linda Sharp Bangor University, Bangor, Wales: Ian Russell University of Hull, Hull, England: Leslie G Walker Staff in clinical sites and co-ordinating centres Grampian Breda Anthony, Sarah Bell, Adrienne Bowie, Katrina Brown (deceased), Joe Brown, Kheng Chew, Claire Cochran, Seonaidh Cotton, Jeannie Dean, Kate Dunn, Jane Edwards, David Evans, Julie Fenty, Al Finlayson, Marie Gallagher, Nicola Gray, Maureen Heddle, Alison Innes, Debbie Jobson, Mandy Keillor, Jayne MacGregor, Sheona Mackenzie, Amanda Mackie, Gladys McPherson, Ike Okorocha, Morag Reilly, Joan Rodgers, Alison Thornton, Rachel Yeats Tayside Lindyanne Alexander, Lindsey Buchanan, Susan Henderson, Tine Iterbeke, Susanneke Lucas, Gillian Manderson, Sheila Nicol, Gael Reid, Carol Robinson, Trish Sandilands Nottingham Marg Adrian, Ahmed Al-Sahab, Elaine Bentley, Hazel Brook, Claire Bushby, Rita Cannon, Brenda Cooper, Ruth Dowell, Mark Dunderdale, Dr Gabrawi, Li Guo, Lisa Heideman, Steve Jones, Salli Lawson, Zoë Philips, Christopher Platt, Shakuntala Prabhakaran, John Rippin, Rose Thompson, Elizabeth Williams, Claire Woolley Statistical analysis Seonaidh Cotton, Kirsten Harrild, John Norrie, Linda Sharp External Trial Steering Committee Nicholas Day (chair, 1999–2004), Theresa Marteau (chair 2004-), Mahesh Parmar, Julietta Patnick and Ciaran Woodman.