EXPLAIN Fragile-X: an explorative, longitudinal study on the characterization, treatment pathways, and patient-related outcomes of Fragile X Syndrome

BACKGROUND: Fragile X syndrome (FXS), caused by a mutation of the FMR1 gene on the X chromosome, is the most common inherited form of intellectual disability and autism spectrum disorders. Comprehensive data are lacking, however, on the characteristics and management patients with FXS in Germany. METHODS/DESIGN: EXPLAIN is a prospective, observational, longitudinal registry with a non-probability sampling approach. It collects data on patient characteristics, therapeutic interventions, psychosocial parameters (including those of family members and caregivers), quality of life of caregiver and patient, caregiver burden, and health economic parameters, such as hospitalisation time. It is designed to include data from 300 patients in ambulatory care from about 50 centres that employ psychiatrists, paediatricians, neurologists, and other relevant specialists, in Germany. The study was initiated in March, 2013. Patients will be followed for at least two years. DISCUSSION: The registry is expected to provide much-needed data on the characteristics and management of patients with FXS in Germany. It will also allow comparisons with other countries, and will enable gap analyses based on current guidelines for management of these patients. TRIAL REGISTRATION: The ClinicalTrials.gov identifier is NCT01711606

Grouping or Grounding? Cultural District and Creative Cluster Management in Nantes, France

This study examines the genesis of a cultural and creative cluster (CCC) as a collection of small or very small companies. The authors use the results of a longitudinal case study of the trajectory of a CCC to reflect on the management mechanisms in CCCs based on an analysis of management tools and how they operate to encourage Grounding and/or Grouping dynamics. This six-year study of Quartier de la Creation in Nantes, France, confirms the prevailing view of a CCC as a dynamic organization. The CCC shows distinct stages, each with its own governance and managerial difficulties. It reveals challenges in shaping the role of the support organization and in identifying the competencies to be developed. The governance mechanisms and the cluster practices of some localized groupings of very small creative enterprises require a balancing of Grouping and Grounding approaches, as hybridizing is central to cluster dynamics

Geographic and Sociodemographic Disparities in Drive Times to Joint Commission–Certified Primary Stroke Centers in North Carolina, South Carolina, and Georgia

Introduction: Timely access to facilities that provide acute stroke care is necessary to reduce disabilities and death from stroke. We examined geographic and sociodemographic disparities in drive times to Joint Commission–certified primary stroke centers (JCPSCs) and other hospitals with stroke care quality improvement initiatives in North Carolina, South Carolina, and Georgia. Methods: We defined boundaries for 30- and 60-minute drive-time areas to JCPSCs and other hospitals by using geographic information systems (GIS) mapping technology and calculated the proportions of the population living in these drive-time areas by sociodemographic characteristics. Age-adjusted county-level stroke death rates were overlaid onto the drive-time areas. Results: Approximately 55% of the population lived within a 30-minute drive time to a JCPSC; 77% lived within a 60-minute drive time. Disparities in percentage of the population within 30-minute drive times were found by race/ethnicity, education, income, and urban/rural status; the disparity was largest between urban areas (70% lived within 30-minute drive time) and rural areas (26%). The rural coastal plains had the largest concentration of counties with high stroke death rates and the fewest JCPSCs. Conclusion: Many areas in this tri-state region lack timely access to JCPSCs. Alternative strategies are needed to expand provision of quality acute stroke care in this region. GIS modeling is valuable for examining and strategically planning the distribution of hospitals providing acute stroke care

Beta-Amyloid peptide variants in brains and cerebrospinal fluid from amyloid precursor protein (APP) transgenic mice: comparison with human Alzheimer amyloid

In this study, we report a detailed analysis of the different variants of amyloid-β (Aβ) peptides in the brains and the cerebrospinal fluid from APP23 transgenic mice, expressing amyloid precursor protein with the Swedish familial Alzheimer disease mutation, at different ages. Using one- and two-dimensional gel electrophoresis, immunoblotting, and mass spectrometry, we identified the Aβ peptides Aβ(1–40), -(1–42), -(1–39), -(1–38), -(1–37), -(2–40), and -(3–40) as well as minor amounts of pyroglutamate-modified Aβ (Aβ(N3pE)) and endogenous murine Aβ in brains from 24-month-old mice. Chemical modifications of the N-terminal amino group of Aβ were identified that had clearly been introduced during standard experimental procedures. To address this issue, we additionally applied amyloid extraction in ultrapure water. Clear differences between APP23 mice and Alzheimer disease (AD) brain samples were observed in terms of the relative abundance of specific variants of Aβ peptides, such as Aβ(N3pE), Aβ(1–42), and N-terminally truncated Aβ(2/3–42). These differences to human AD amyloid were also noticed in a related mouse line transgenic for human wild type amyloid precursor protein. Taken together, our findings suggest different underlying molecular mechanisms driving the amyloid deposition in transgenic mice and AD patients

La création de valeur : glas ou Graal ? Revue critique et modélisation du concept

Cet article propose une revue critique et une modélisation du concept de « création de valeur » à partir d’une analyse de la littérature relative au modèle d’affaires. Les définitions de la création de valeur sont étudiées à partir des 50 articles anglophones les plus cités dont les titres contiennent value et creation. L’analyse révèle cinq thèmes : nature de la valeur créée pour le client, architecture de la valeur par l’entreprise, valeur perçue par l’utilisateur, partage économique entre les parties prenantes, co-création de la valeur avec celles-ci. Notre discussion se construit autour d’enjeux épistémologiques dans une perspective pragmatiste.This article provides a critical review and modeling of the concept of "value creation" from a literature analysis of the business model. The definitions of value creation are studied from the 50 most cited English-language articles whose titles contain value and creation. The analysis reveals five themes: nature of the value created for the customer, value architecture by the company, value perceived by the user, economic sharing between the stakeholders, co-creation of the value with these stakeholders. Our discussion is built around epistemological issues in a pragmatist perspective.Este artículo propone una revisión crítica y una modelización del concepto de “creación de valor” a partir de un análisis de la literatura relativa a los modelos de negocio. Las definiciones de creación de valor son estudiadas a partir de los 50 artículos de habla inglesa más citados, cuyos títulos contienen las palabras “valor añadido” y “creación”. En el análisis se identifican cinco temas: tipo del valor creado para el cliente, estructura de la creación del valor en la empresa, valor percibido por el usuario, repartición económica entre las partes interesadas y la cocreación de valor. Nuestra discusión se construye en torno al análisis epistemológico desde una perspectiva pragmática