Hexyl aminolevulinate, 5-aminolevulinic acid nanoemulsion, and methyl aminolevulinate in photodynamic therapy of non-aggressive basal cell carcinomas: A non-sponsored, randomized, prospective and double-blinded trial

Abstract Background In the photodynamic therapy (PDT) of non-aggressive basal cell carcinomas (BCCs), 5-aminolevulinic acid nanoemulsion (BF-200ALA) has shown non-inferior efficacy when compared with methyl aminolevulinate (MAL), a widely used photosensitizer. Hexyl aminolevulinate (HAL) is an interesting alternative photosensitizer. To our knowledge, this is the first study using HAL-PDT in the treatment of BCCs. Objectives To compare the histological clearance, tolerability (pain and post-treatment reaction), and cosmetic outcome of MAL, BF-200 ALA, and low-concentration HAL in the PDT of non-aggressive BCCs. Methods Ninety-eight histologically verified non-aggressive BCCs met the inclusion criteria, and 54 patients with 95 lesions completed the study. The lesions were randomized to receive LED-PDT in two repeated treatments with MAL, BF-200 ALA, or HAL. Efficacy was assessed both clinically and confirmed histologically at three months by blinded observers. Furthermore, cosmetic outcome, pain, post-treatment reactions fluorescence, and photobleaching were evaluated. Results According to intention-to-treat analyses, the histologically confirmed lesion clearance was 93.8% (95% confidence interval [CI] = 79.9?98.3) for MAL, 90.9% (95% CI = 76.4?96.9) for BF-200 ALA, and 87.9% (95% CI = 72.7?95.2) for HAL, with no differences between the arms (p=0.84). There were no differences between the arms as regards pain, post-treatment reactions, or cosmetic outcome. Conclusions PDT with low-concentration HAL and BF-200 ALA have a similar efficacy, tolerability, and cosmetic outcome compared to MAL. HAL is an interesting new option in dermatological PDT, since good efficacy is achieved with a low concentration.Peer reviewe

An exploratory study looking at the relationship marketing techniques used in the music festival industry

There are current issues and trends in the music festival market, which may affect the success of an event, and market saturation is at the forefront of these issues. Previous literature, maintaining the need for a marketing approach to festivals, identifi es the need for maintaining strong stakeholder relationships in order to succeed in a business environment; attention has been focused to the theory of relationship marketing (RM) because of the recognition that this practice is complementary to the marketing of festivals. The very nature of the music festival as an annual, usually, 4-day event means that effective marketing is needed to keep connections with the consumer throughout the year. This article focuses on the RM techniques utilised within the music festival industry from the viewpoint of the festival organiser in an attempt to establish how festival organisations value and monitor organisational relationships. This article explores the extent to which these relationships are valued and managed; furthermore, the variations between these intricate relationships are considered by focusing on those held with the organisation ’ s consumers and sponsors, the results of which have provided the ability to establish the importance and relevance of RM to the industry and further identify the marketing communication methods employed to establish and maintain such relationships. In-depth, convergent interviews have been conducted with a segment of music festival organisers from a range of events. The results have been integrated with the study of current literature to best exemplify these issues. It has been established that RM has a strong role in today ’ s commercial and independent music festival industry; technological advances are enabling the organiser to support online relationships further and increase consumer loyalty. There is a need to expand the research further because of the complexity of organisational relationships and the varying categories of festivals

Early DNA methylation changes in children developing beta cell autoimmunity at a young age

Aims/hypothesis Type 1 diabetes is a chronic autoimmune disease of complex aetiology, including a potential role for epigenetic regulation. Previous epigenomic studies focused mainly on clinically diagnosed individuals. The aim of the study was to assess early DNA methylation changes associated with type 1 diabetes already before the diagnosis or even before the appearance of autoantibodies. Methods Reduced representation bisulphite sequencing (RRBS) was applied to study DNA methylation in purified CD4(+) T cell, CD8(+) T cell and CD4(-)CD8(-) cell fractions of 226 peripheral blood mononuclear cell samples longitudinally collected from seven type 1 diabetes-specific autoantibody-positive individuals and control individuals matched for age, sex, HLA risk and place of birth. We also explored correlations between DNA methylation and gene expression using RNA sequencing data from the same samples. Technical validation of RRBS results was performed using pyrosequencing. Results We identified 79, 56 and 45 differentially methylated regions in CD4(+) T cells, CD8(+) T cells and CD4-CD8- cell fractions, respectively, between type 1 diabetes-specific autoantibody-positive individuals and control participants. The analysis of pre-seroconversion samples identified DNA methylation signatures at the very early stage of disease, including differential methylation at the promoter of IRF5 in CD4(+) T cells. Further, we validated RRBS results using pyrosequencing at the following CpG sites: chr19:18118304 in the promoter of ARRDC2; chr21:47307815 in the intron of PCBP3; and chr14:81128398 in the intergenic region near TRAF3 in CD4(+) T cells. Conclusions/interpretation These preliminary results provide novel insights into cell type-specific differential epigenetic regulation of genes, which may contribute to type 1 diabetes pathogenesis at the very early stage of disease development. Should these findings be validated, they may serve as a potential signature useful for disease prediction and management.Peer reviewe

Dovitinib dilactic acid reduces tumor growth and tumor-induced bone changes in an experimental breast cancer bone growth model

Advanced breast cancer has a high incidence of bone metastases. In bone, breast cancer cells induce osteolytic or mixed bone lesions by inducing an imbalance in bone formation and resorption. Activated fibroblast growth factor receptors (FGFRs) are important in regulation of tumor growth and bone remodeling. In this study we used FGFR1 and FGFR2 gene amplifications containing human MFM223 breast cancer cells in an experimental xenograft model of breast cancer bone growth using intratibial inoculation technique. This model mimics bone metastases in breast cancer patients. The effects of an FGFR inhibitor, dovitinib dilactic acid (TKI258) on tumor growth and tumor-induced bone changes were evaluated. Cancer-induced bone lesions were smaller in dovitinib-treated mice as evaluated by X-ray imaging. Peripheral quantitative computed tomography imaging showed higher total and cortical bone mineral content and cortical bone mineral density in dovitinib-treated mice, suggesting better preserved bone mass. CatWalk gait analysis indicated that dovitinib-treated mice experienced less cancer-induced bone pain in the tumor-bearing leg. A trend towards decreased tumor growth and metabolic activity was observed in dovitinib-treated mice quantified by positron emission tomography imaging with 2-[ 18 F]fluoro-2-deoxy-D-glucose at the endpoint. We conclude that dovitinib treatment decreased tumor burden, cancer-induced changes in bone, and bone pain. The results suggest that targeting FGFRs could be beneficial in breast cancer patients with bone metastases.</p

Co-creation of Value in IT Service Processes Using Semantic MediaWiki

Abstract: Enterprises are substituting their own IT-Systems by services provided by external providers. This provisioning of services may be done in an industrialized way, separating the service provider from the consumer. However, using industrialized services diminishes the capability to differentiate from competitors. To counter this, collaborative service processes based on the co-creation of value between service providers and prosumers are of huge importance. The approach presented shows how the co-creation of value in IT-service processes can profit from social software, using the example of the Semantic MediaWiki

The dangers of using intention as a surrogate for Retention in brand positioning decision support systems

The purpose of this paper is to explore the dangers of using intention as a surrogate for retention in a decision support system (DSS) for brand positioning. An empirical study is conducted, using structural equations modeling and both data from the internal transactional database and a survey. The study is aimed at evaluating whether the DSS recommends different product benefits for brand positioning when intention is used as opposed to retention as a criterion variable. The results show that different product benefits are recommended contingent upon the criterion variable (intention vs. retention). The findings also indicate that the strength of the structural relationships is inflated when intention is used. This study is limited in that it investigates only one industry; the newspaper industry. This study provides guidance for brand managers in selecting the most appropriate benefit for brand positioning and advices against the use of intention as opposed to retention in DSS. To the best of our knowledge this study is the first to challenge and refute the commonly held belief that intention is a valid surrogate for retention in a DSS for brand positioning

Quality of service in public transport based on customer satisfaction surveys: A review and assessment of methodological approaches

The growth of literature in the field of quality of service in the public transport (PT) sector shows increasing concern for a better understanding of the factors affecting service quality (SQ) in PT organizations and companies. A large variety of approaches to SQ has been developed in recent years owing to the complexity of the concept; the broad range of attributes required to evaluate SQ; and the imprecision, subjectivity and heterogeneous nature of the data used to analyse it. Most of these approaches are based on customer satisfaction surveys. This paper seeks to summarize the evolution of research and current thinking as it relates to the different methodological approaches for SQ evaluation in the PT sector over the years, and provides a discussion of future directions.This study is sponsored by the Conserjería de Innovación, Ciencia y Economía of the Junta de Andalucía (Spain) through the Excellence Research Project denominated “Q-METROBUS-Quality of service indicator for METROpolitan public BUS transport services”

Yard vegetation is associated with gut microbiota composition

Gut microbes play an essential role in the development and functioning of the human immune system. A disturbed gut microbiota composition is often associated with a number of health disorders including immune-mediated diseases. Differences in host characteristics such as ethnicity, living habit and diet have been used to explain differences in the gut microbiota composition in inter-continental comparison studies. As our previous studies imply that daily skin contact with organic gardening materials modify gut microflora, here we investigated the association between living environment and gut microbiota in a homogenous western population along an urban-rural gradient. We obtained stool samples from 48 native elderly Finns in province Hame in August and November 2015 and identified the bacterial phylotypes using 16S rRNA Illumina MiSeq sequencing. We assumed that yard vegetation and land cover classes surrounding homes explain the stool bacterial community in generalized linear mixed models. Diverse yard vegetation was associated with a reduced abundance of Clostridium sensu stricto and an increased abundance of Faecalibacterium and Prevotellaceae. The abundance of Bacteroides was positively and strongly associated with the built environment. Exclusion of animal owners did not alter the main associations. These results suggest that diverse vegetation around homes is associated with health-related changes in gut microbiota composition. Manipulation of the garden diversity, possibly jointly with urban planning, is a promising candidate for future intervention studies that aim to maintain gut homeostasis. (C) 2020 The Authors. Published by Elsevier B.V.Peer reviewe

Umbilical cord blood DNA methylation in children who later develop type 1 diabetes

Aims/hypothesis Distinct DNA methylation patterns have recently been observed to precede type 1 diabetes in whole blood collected from young children. Our aim was to determine whether perinatal DNA methylation is associated with later progression to type 1 diabetes. Methods Reduced representation bisulphite sequencing (RRBS) analysis was performed on umbilical cord blood samples collected within the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) Study. Children later diagnosed with type 1 diabetes and/or who tested positive for multiple islet autoantibodies (n = 43) were compared with control individuals (n = 79) who remained autoantibody-negative throughout the DIPP follow-up until 15 years of age. Potential confounding factors related to the pregnancy and the mother were included in the analysis. Results No differences in the umbilical cord blood methylation patterns were observed between the cases and controls at a false discovery rate Conclusions/interpretation Based on our results, differences between children who progress to type 1 diabetes and those who remain healthy throughout childhood are not yet present in the perinatal DNA methylome. However, we cannot exclude the possibility that such differences would be found in a larger dataset.Peer reviewe

The sport value framework - a new fundamental logic for analyses in sport management

Research question: Sports economic theory and management models have frequently been criticised for not sufficiently explaining phenomena in sport management. This article addresses this gap by proposing a conceptual framework that can be used to understand sport management problems and derive appropriate strategies. Research methods: The framework proposed in this conceptual article has been developed through a critical review of existing literature on sport management and theoretical considerations based on the service-dominant logic. Results and findings: The sport value framework (SVF) provides 10 foundational premises on value co-creation in sport management and suggests three levels for its analysis. The main contribution is a new and better theoretical basis for explaining phenomena in sport management compared with traditional sport economic thinking. Moreover, the SVF provides guidance in structuring research in sport management. Implications: The framework encourages researchers and practitioners to rethink their strategies by applying a different logic that captures the complexity of sport management. © 2014 © 2014 European Association for Sport Management