Pirfenidone in idiopathic pulmonary fibrosis:expert panel discussion on the management of drug-related adverse events

Pirfenidone is currently the only approved therapy for idiopathic pulmonary fibrosis, following studies demonstrating that treatment reduces the decline in lung function and improves progression-free survival. Although generally well tolerated, a minority of patients discontinue therapy due to gastrointestinal and skin-related adverse events (AEs). This review summarizes recommendations based on existing guidelines, research evidence, and consensus opinions of expert authors, with the aim of providing practicing physicians with the specific clinical information needed to educate the patient and better manage pirfenidone-related AEs with continued pirfenidone treatment. The main recommendations to help prevent and/or mitigate gastrointestinal and skin-related AEs include taking pirfenidone during (or after) a meal, avoiding sun exposure, wearing protective clothing, and applying a broad-spectrum sunscreen with high ultraviolet (UV) A and UVB protection. These measures can help optimize AE management, which is key to maintaining patients on an optimal treatment dose.Correction in: Advances in Therapy, Volume 31, Issue 5, pp 575-576 , doi: 10.1007/s12325-014-0118-8</p

Análisis de los datos obtenidos de la red social Twitter para la identificación precoz de la tendencia al suicidio de los usuarios

Although not everyone is aware of it, data available on the Internet are very useful and have a great potential to help our society. The digital platform Twitter is a social network where people sometimes express their feelings and emotions. And this paper arises from the idea of doing an analysis of these data through a Machine Learning tool, to find a psychiatric picture of depression, and if it is possible, the associated suicidal tendency. Twitter data extraction tool has been Tweepy, and with the profile data users, it has been made, an excel database that collects the information. Next, with the Machine Learning tool called UMAP, an unsupervised analysis of the database has been carried out, thanks to which it has been possible to differentiate three groups, with a very low inter cluster distance, which suggest that each observation looks a lot like its neighbors. From these three groups, we find one which behavior or use of the platform would be associated with a normal or standard way. The two other two group of meet part of the characteristics associated with depression.  Aunque no todo el mundo sea consciente todos los datos disponibles en la red son útiles y tienen un gran potencial de ayuda a nuestra sociedad. La plataforma digital Twitter es una red social donde en ocasiones las personas expresan sus sentimientos y emociones, y este proyecto surge de la idea de hacer un análisis de estos datos de que se pueda realizar a través de una herramienta de Machine Learning un perfil típico un cuadro psiquiátrico de depresión, y si es posible la tendencia al suicidio asociada. La herramienta para la extracción de datos de Twitter utilizada ha sido Tweepy, y con los usuarios obtenidos con ésta y las características definidas para ellos, se ha generado una base de datos en formato excel en la nube One Drive que recoge toda esta información. A continuación, con la herramienta de Machine Learning llamada UMAP, se ha realizado un análisis de forma no supervisada de la base de datos, gracias al cuál se han podido diferenciar tres grupos, con una distancia intercluster muy baja, lo que quiere decir que cada observación se parece mucho a sus vecinos. De estos tres grupos hay uno al que se asociaría una conducta o uso de esta plataforma de una forma normal o estándar, y otros dos de diferente dimensión que cumplen parte de las características asociadas al trastorno de depresión

Detection of Extensive Cross-Neutralization between Pandemic and Seasonal A/H1N1 Influenza Viruses Using a Pseudotype Neutralization Assay

BACKGROUND: Cross-immunity between seasonal and pandemic A/H1N1 influenza viruses remains uncertain. In particular, the extent that previous infection or vaccination by seasonal A/H1N1 viruses can elicit protective immunity against pandemic A/H1N1 is unclear. METHODOLOGY/PRINCIPAL FINDINGS: Neutralizing titers against seasonal A/H1N1 (A/Brisbane/59/2007) and against pandemic A/H1N1 (A/California/04/2009) were measured using an HIV-1-based pseudovirus neutralization assay. Using this highly sensitive assay, we found that a large fraction of subjects who had never been exposed to pandemic A/H1N1 express high levels of pandemic A/H1N1 neutralizing titers. A significant correlation was seen between neutralization of pandemic A/H1N1 and neutralization of a standard seasonal A/H1N1 strain. Significantly higher pandemic A/H1N1 neutralizing titers were measured in subjects who had received vaccination against seasonal influenza in 2008-2009. Higher pandemic neutralizing titers were also measured in subjects over 60 years of age. CONCLUSIONS/SIGNIFICANCE: Our findings reveal that the extent of protective cross-immunity between seasonal and pandemic A/H1N1 influenza viruses may be more important than previously estimated. This cross-immunity could provide a possible explanation of the relatively mild profile of the recent influenza pandemic

The impact of cluster connectedness on firm innovation: R&D effort and outcomes in the textile industry

This is an Author's Accepted Manuscript of an article published in "The impact of cluster connectedness on firm innovation: R&D effort and outcomes in the textile industry" version of the article as published in the Entrepreneurship and Regional Development, 2012 september,[copyright Taylor & Francis], available online at: http://www.tandfonline.com/10.1080/08985626.2012.710260"[EN] Recent research into the clustering effect on firms has moved away from a simplistic view to a more complex approach. More realistic and complex causal relationships are now considered when analysing these territorial networks. Specifically, this paper attempts to analyse how cluster connect- edness moderates the relationship of a firm's innovation effort and the results obtained from this effort. We want to question the commonly accepted direct and positive impact of R&D effort, and moreover, we suggest the existence of a saturation effect and that the level of cluster's inter-connectedness in the cluster moderates this effect. We have developed our empirical study focusing on the Spanish textile industrial cluster. This is a complex manufacturing industry that uses relatively low-technology manufacturing and R&D. Our findings suggest that the degree to which a firm is involved with, or connected to, other firms in the cluster can moderate the effect of the R&D effort on its innovation results. More generally, we aim to contribute to the discussion on the degree to which firms should be involved in the cluster network in order to operate efficiently and gain the maximum competitive advantages. Our findings have implications both in recent cluster and network literature as well for institutional policy.Molina Morales, FX.; Expósito Langa, M. (2012). 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EFHC1 variants in juvenile myoclonic epilepsy: reanalysis according to NHGRI and ACMG guidelines for assigning disease causality

Peer reviewe

Comparison of performance-based measures among native Japanese, Japanese-Americans in Hawaii and Caucasian women in the United States, ages 65 years and over: a cross-sectional study

BACKGROUND: Japanese (both in Japan and Hawaii) have a lower incidence of falls and of hip fracture than North American and European Caucasians, but the reasons for these differences are not clear. SUBJECTS AND METHODS: A cross-sectional study. We compared neuromuscular risk factors for falls using performance-based measures (chair stand time, usual and rapid walking speed, and grip strength) among 163 Japanese women in Japan, 681 Japanese-American women in Hawaii and 9403 Caucasian women in the United States aged 65 years and over. RESULTS: After adjusting for age, the Caucasian women required about 40% more time to complete 5 chair stands than either group of Japanese. Walking speed was about 10% slower among Caucasians than native Japanese, whereas Japanese-American women in Hawaii walked about 11% faster than native Japanese. Grip strength was greatest in Japan, which may reflect the rural farming district that this sample was drawn from. Additional adjustment for height, weight or body mass index increased the adjusted means of chair stand time and grip strength among Japanese, but the differences remained significant. CONCLUSIONS: Both native Japanese and Japanese-American women in Hawaii performed better than Caucasians on chair stand time and walking speed tests, and native Japanese had greater grip strength than Japanese in Hawaii and Caucasians. The biological implications of these differences in performance are uncertain, but may be useful in planning future comparisons between populations

INSPIRE (INvestigating Social and PractIcal suppoRts at the End of life): Pilot randomised trial of a community social and practical support intervention for adults with life-limiting illness

YesBACKGROUND: For most people, home is the preferred place of care and death. Despite the development of specialist palliative care and primary care models of community based service delivery, people who are dying, and their families/carers, can experience isolation, feel excluded from social circles and distanced from their communities. Loneliness and social isolation can have a detrimental impact on both health and quality of life. Internationally, models of social and practical support at the end of life are gaining momentum as a result of the Compassionate Communities movement. These models have not yet been subjected to rigorous evaluation. The aims of the study described in this protocol are: (1) to evaluate the feasibility, acceptability and potential effectiveness of The Good Neighbour Partnership (GNP), a new volunteer-led model of social and practical care/support for community dwelling adults in Ireland who are living with advanced life-limiting illness; and (2) to pilot the method for a Phase III Randomised Controlled Trial (RCT). DESIGN: The INSPIRE study will be conducted within the Medical Research Council (MRC) Framework for the Evaluation of Complex Interventions (Phases 0-2) and includes an exploratory two-arm delayed intervention randomised controlled trial. Eighty patients and/or their carers will be randomly allocated to one of two groups: (I) Intervention: GNP in addition to standard care or (II) Control: Standard Care. Recipients of the GNP will be asked for their views on participating in both the study and the intervention. Quantitative and qualitative data will be gathered from both groups over eight weeks through face-to-face interviews which will be conducted before, during and after the intervention. The primary outcome is the effect of the intervention on social and practical need. Secondary outcomes are quality of life, loneliness, social support, social capital, unscheduled health service utilisation, caregiver burden, adverse impacts, and satisfaction with intervention. Volunteers engaged in the GNP will also be assessed in terms of their death anxiety, death self efficacy, self-reported knowledge and confidence with eleven skills considered necessary to be effective GNP volunteers. DISCUSSION: The INSPIRE study addresses an important knowledge gap, providing evidence on the efficacy, utility and acceptability of a unique model of social and practical support for people living at home, with advanced life-limiting illness. The findings will be important in informing the development (and evaluation) of similar service models and policy elsewhere both nationally and internationally. TRIAL REGISTRATION: ISRCTN18400594 18(th) February 2015

The ups and downs of volcanic unrest: Insights from integrated geodesy and numerical modelling

Part of the Advances in Volcanology book seriesThis is the final version of the chapter. Available from the publisher via the DOI in this record.Volcanic eruptions are often preceded by small changes in the shape of the volcano. Such volcanic deformation may be measured using precise surveying techniques and analysed to better understand volcanic processes. Complicating the matter is the fact that deformation events (e.g., inflation or deflation) may result from magmatic, non-magmatic or mixed/hybrid sources. Using spatial and temporal patterns in volcanic deformation data and mathematical models it is possible to infer the location and strength of the subsurface driving mechanism. This can provide essential information to inform hazard assessment, risk mitigation and eruption forecasting. However, most generic models over-simplify their representation of the crustal conditions in which the deformation source resides. We present work from a selection of studies that employ advanced numerical models to interpret deformation and gravity data. These incorporate crustal heterogeneity, topography, viscoelastic rheology and the influence of temperature, to constrain unrest source parameters at Uturuncu (Bolivia), Cotopaxi (Ecuador), Soufrière Hills (Montserrat), and Teide (Tenerife) volcanoes. Such model complexities are justified by geophysical, geological, and petrological constraints. Results highlight how more realistic crustal mechanical conditions alter the way stress and strain are partitioned in the subsurface. This impacts inferred source locations and magmatic pressures, and demonstrates how generic models may produce misleading interpretations due to their simplified assumptions. Further model results are used to infer quantitative and qualitative estimates of magma supply rate and mechanism, respectively. The simultaneous inclusion of gravity data alongside deformation measurements may additionally allow the magmatic or non-magmatic nature of the source to be characterised. Together, these results highlight how models with more realistic, and geophysically consistent, components can improve our understanding of the mechanical processes affecting volcanic unrest and geodetic eruption precursors, to aid eruption forecasting, hazard assessment and risk mitigation.s Work presented herein has received funding by the European Commission (FP7; Theme: ENV.2011.1.3.3-1; Grant 282759: VUELCO)

Quantitative bone marrow lesion size in osteoarthritic knees correlates with cartilage damage and predicts longitudinal cartilage loss

<p>Abstract</p> <p>Background</p> <p>Bone marrow lesions (BMLs), common osteoarthritis-related magnetic resonance imaging findings, are associated with osteoarthritis progression and pain. However, there are no articles describing the use of 3-dimensional quantitative assessments to explore the longitudinal relationship between BMLs and hyaline cartilage loss. The purpose of this study was to assess the cross-sectional and longitudinal descriptive characteristics of BMLs with a simple measurement of approximate BML volume, and describe the cross-sectional and longitudinal relationships between BML size and the extent of hyaline cartilage damage.</p> <p>Methods</p> <p>107 participants with baseline and 24-month follow-up magnetic resonance images from a clinical trial were included with symptomatic knee osteoarthritis. An 'index' compartment was identified for each knee defined as the tibiofemoral compartment with greater disease severity. Subsequently, each knee was evaluated in four regions: index femur, index tibia, non-index femur, and non-index tibia. Approximate BML volume, the product of three linear measurements, was calculated for each BML within a region. Cartilage parameters in the index tibia and femur were measured based on manual segmentation.</p> <p>Results</p> <p>BML volume changes by region were: index femur (median [95% confidence interval of the median]) 0.1 cm³(-0.5 to 0.9 cm³), index tibia 0.5 cm³(-0.3 to 1.7 cm³), non-index femur 0.4 cm³(-0.2 to 1.6 cm³), and non-index tibia 0.2 cm³(-0.1 to 1.2 cm³). Among 44 knees with full thickness cartilage loss, baseline tibia BML volume correlated with baseline tibia full thickness cartilage lesion area (<it>r </it>= 0.63, <it>p</it>< 0.002) and baseline femur BML volume with longitudinal change in femoral full thickness cartilage lesion area (<it>r </it>= 0.48 <it>p</it>< 0.002).</p> <p>Conclusions</p> <p>Many regions had no or small longitudinal changes in approximate BML volume but some knees experienced large changes. Baseline BML size was associated to longitudinal changes in area of full thickness cartilage loss.</p