Genetic, Phenotypic, and Interferon Biomarker Status in ADAR1-Related Neurological Disease

International audienceWe investigated the genetic, phenotypic, and interferon status of 46 patients from 37 families with neurological disease due to mutations in ADAR1. The clinicoradiological phenotype encompassed a spectrum of Aicardi–Goutières syndrome, isolated bilateral striatal necrosis, spastic paraparesis with normal neuroimaging, a progressive spastic dystonic motor disorder, and adult-onset psychological difficulties with intracranial calcification. Homozygous missense mutations were recorded in five families. We observed a p.Pro193Ala variant in the heterozygous state in 22 of 23 families with compound heterozygous mutations. We also ascertained 11 cases from nine families with a p.Gly1007Arg dominant-negative mutation, which occurred de novo in four patients, and was inherited in three families in association with marked phenotypic variability. In 50 of 52 samples from 34 patients, we identified a marked upregulation of type I interferon-stimulated gene transcripts in peripheral blood, with a median interferon score of 16.99 (interquartile range [IQR]: 10.64–25.71) compared with controls (median: 0.93, IQR: 0.57–1.30). Thus, mutations in ADAR1 are associated with a variety of clinically distinct neurological phenotypes presenting from early infancy to adulthood, inherited either as an autosomal recessive or dominant trait. Testing for an interferon signature in blood represents a useful biomarker in this context

Qualitative Analysis of Cloud Computing Risks and Framework for the Rationalization and Mitigation of Cloud Risks

Cloud computing is a popular subject across the IT industry, but risks associated with this new technology and delivery model are not yet well understood. This research investigates, in a qualitative fashion, the vectors that contribute to cloud computing risks in the areas of security, business, and compliance. The focus of this research is on the identification of risk vectors that affect cloud computing and the creation of a framework that can help IT managers in their cloud adoption process. Economic pressures on businesses are creating a demand for an alternative delivery model that can provide flexible payments, dramatic cuts in capital investment, and reductions in operational cost. Cloud computing is positioned to take advantage of these economic pressures with low cost IT services and a flexible payment model—but at what risk to the business? Security concerns about cloud computing are heightened and fueled by misconceptions related to security and compliance risks. Unfortunately these security concerns are seldom expressed quantifiably. To bring clarity to cloud computing security, compliance, and business risks, this research focuses on a qualitative analysis of risk vectors drawn from one-on-one interviews with top IT leaders. The qualitative aspect of this research separates facts from unfounded suspicions, and creates a Framework that can help align perceived risks of cloud computing with actual risks. The qualitative research, through interviews with experts, is complemented with a survey to measure risk perceptions about cloud computing using a Likert scale. The decision model and Framework created by this research help rationalize the risk vectors on cloud environments and recommend mitigation strategies to bring the IT industry one step closer to a clearer understanding of the risks-tradeoffs implications of cloud computing environments

Impact of self-doubts on leaders at a point of transition in the workplace

Inner self-critical voices are scrutinising, attacking, and discouraging. They are also a pervasive part of human nature, which seems to have become more dominant in current times. This qualitative research study examines the effects of self-doubts and self-criticism on individuals holding a leadership role at a point of transition in the workplace. Taking a systems-psychodynamic perspective, this study aims to explore the origins and consequences of self-doubts, looking at both the individual (intra-psychic) perspective as well as the systemic (psycho-social) aspect of self-doubts. Situated within the social-constructivist paradigm, case study was chosen as a research design strategy and Grounded Theory methodology was used for data analysis. Semi-structured interviews were conducted with a sample of eight participants in leadership positions who had experienced a role transition while working in commercial organisations. Key findings suggest that the impact of self-doubts might be linked to the individual’s self-worth, sense of belonging, and need for external validation. An elite group identity, created as a social-defence mechanism, is collectively and unconsciously developed by members of an organisation to deal with self-doubts anxiety. Looking beyond the individual’s intra-psychic experience, another significant finding in this study is linked to the specific characteristics of the wider organisational and societal contexts in which these leaders operate, and the impacts of these characteristics on these individuals. The overlap between the individual and the system seems to create a re-enforcing cycle of self-doubts anxiety, which might have detrimental consequences for individuals and organisations. On this basis, it is recommended to create space for self-reflection and interventions at individual, group, and organisational levels, using an integrative approach to deal with the impact of self-doubts

Towards a new way of doing strategy: how Spanish companies incorporate innovation in their strategies

The paper focuses on how Spanish companies incorporate innovation management in their strategies. Specifically it focuses on three important issues: the elements to define innovative strategies, the way to create the pre-requisites for an innovative company and the innovation management processes. Based on an analysis of the literature and our experience, the study makes a theoretical and empirical contribution to existing models for strategy and innovation management. The model will be tested using a two-phase empirical approach. For the first phase response to a questionnaire will be received from more than 300 Spanish companies testing their innovation capacity and the impact of innovation on strategy. The second phase consist of a selected number of in-depth interviews to executives from very innovative Spanish companies

Evaluación del uso recreativo y turístico del jardin botanico de Guayaquil

El presente proyecto de tesis se ha llevado a cabo con el fin de evaluar el uso Turístico del Jardín Botánico de Guayaquil para llegar a saber cuál es el estado actual, tanto de sus instalaciones, servicios que ofrece, número de personas que lo visitan diariamente y qué tipo de personas son las interesadas en visitarlo y porqué. Para lo anterior expuesto planteamos los siguientes objetivos específicos: 1. Conocer las actividades y calidad de instalaciones que tiene el Jardín Botánico de Guayaquil. 2. Levantar información relativa a su entorno. 3. Realizar una evaluación del aprovechamiento turístico por medio de encuestas. 4. Calcular el uso efectivo y los impactos que se dan en el Jardín Botánico. Este proyecto se ha realizado bajo la hipótesis de que el estado actual de las instalaciones del Jardín Botánico de Guayaquil se reflejaría en el número de visitas que recibe. El proyecto consta de tres capítulos donde en el primero se da información detallada de las características generales del Jardín Botánico tales como su reseña histórica, ubicación geográfica, entorno, inventario de sus especies, actividades que en él se desarrollan, elaboración de ficha para inventario de Atractivos Turísticos del MINTUR y se analizó la oferta turística del Jardín Botánico de Guayaquil, es decir el estado de sus instalaciones como los senderos, señalética, servicios sanitarios, bar, etc. Para la elaboración del segundo capítulo se empleó una encuesta de campo, cuyo resultado permitió analizar la demanda turística actual, obteniendo de tal manera fundamentos para determinar la calidad de los productos y servicios turísticos del lugar así como sus recomendaciones y sugerencias. Posteriormente se detallan los resultados obtenidos y el análisis propio de cada una de las preguntas formuladas en las encuestas, para conocer cuántas personas estarían dispuestas a visitar el Jardín Botánico. Finalmente en el tercer capítulo se ha realizado la evolución del uso turístico – recreativo mediante dos herramientas tales como La Matriz de Causa – Efecto y Capacidad de Carga

Validación de un instrumento de medida para la relación entre la orientación a la responsabilidad social corporativa y otras variables estratégicas de la empresa: Validation of a measurement scale for the relationship between the orientation to corporate social responsibility and other business strategic variables

The importance of social responsibility in the corporate world is enhanced by its linkage with other variables of a strategic nature in the firm's activity (the competitive success the company achieves, its performance, and the innovations it implements). The objective of this study was to define and validate a scale for the measurement of social responsibility that will then allow the degree of linkage of the aforementioned elements to be determined, under the assumption of causal relationships posited on the basis of the limited existing literature in this field. The result of the analysis was an original scale of 21 indicators validated against a sample of 777 firms in the Autonomous Community of Extremadura.La importancia de la responsabilidad social es mayor al relacionar esta variable empresarial con otras de naturaleza estratégica en la actividad de las empresas (éxito competitivo que la empresa alcanza, rendimiento o desempeño que desarrolla e innovaciones que acomete). El objetivo de este trabajo ha sido definir y validar una escala de medida de la orientación a la responsabilidad social que permita posteriormente determinar el grado de relación entre los elementos señalados según las relaciones causales que se plantean y se justifican con base en la escasa literatura previa en este campo. Como resultado del análisis, se concluye con una escala original de 21 indicadores validada con una muestra de 777 empresas pertenecientes a la Comunidad Autónoma de Extremadura

Changes in adhesion and the expression of adhesion molecules in PBMCs after aneurysmal subarachnoid hemorrhage: relation to cerebral vasospasm

Aneurysmal subarachnoid hemorrhage (aSAH) is a neurovascular disease produced by extravasation of blood to the subarachnoid space after rupture of the cerebral vessels. After bleeding, the immune response is activated. The role of peripheral blood mononuclear cells (PBMCs) in this response is a current subject of research. We have analysed the changes in PBMCs of patients with aSAH and their interaction with the endothelium, focusing on their adhesion and the expression of adhesion molecules. Using an in vitro adhesion assay, we observed that the adhesion of PBMCs of patients with aSAH is increased. Flow cytometry analysis shows that monocytes increased signifcantly in patients, especially in those who developed vasospasm (VSP). In aSAH patients, the expression of CD162, CD49d, CD62L and CD11a in T lymphocytes and of CD62L in monocytes increased. However, the expression of CD162, CD43, and CD11a decreased in monocytes. Furthermore, monocytes from patients who developed arteriographic VSP had lower expression of CD62L. In conclusion, our results confrm that after aSAH, monocyte count and adhesion of PBMCs increase, especially in patients with VSP, and that the expression of several adhesion molecules is altered. These observations can help predict VSP and to improve the treatment of this pathology