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Wu J.,Salk Institute for Biological Studies | Okamura D.,Salk Institute for Biological Studies | Okamura D.,Kinki University | Li M.,Salk Institute for Biological Studies | And 25 more authors.
Nature | Year: 2015

Pluripotency, the ability to generate any cell type of the body, is an evanescent attribute of embryonic cells. Transitory pluripotent cells can be captured at different time points during embryogenesis and maintained as embryonic stem cells or epiblast stem cells in culture. Since ontogenesis is a dynamic process in both space and time, it seems counterintuitive that these two temporal states represent the full spectrum of organismal pluripotency. Here we show that by modulating culture parameters, a stem-cell type with unique spatial characteristics and distinct molecular and functional features, designated as region-selective pluripotent stem cells (rsPSCs), can be efficiently obtained from mouse embryos and primate pluripotent stem cells, including humans. The ease of culturing and editing the genome of human rsPSCs offers advantages for regenerative medicine applications. The unique ability of human rsPSCs to generate post-implantation interspecies chimaeric embryos may facilitate our understanding of early human development and evolution.

Sampietro-Colom L.,Hospital Clinic of Barcelona | Morilla-Bachs I.,Fundacio Clinic per la Recerca Biomedica | Gutierrez-Moreno S.,Fundacio Clinic per la Recerca Biomedica | Gallo P.,University of Barcelona
International Journal of Technology Assessment in Health Care | Year: 2012

Objective: To develop and test a decision-support tool for prioritizing new competing Health Technologies (HTs) after their assessment using the mini-HTA approach. Methods: A two layer value/risk tool was developed based on the mini-HTA. The first layer included 12 mini-HTA variables classified in two dimensions, namely value (safety, clinical benefit, patient impact, cost-effectiveness, quality of the evidence, innovativeness) and risk (staff, space and process of care impacts, incremental costs, net cost, investment effort). Weights given to these variables were obtained from a survey among decision-makers (at National/Regional level and hospital settings). A second layer included results from mini-HTA (scored as higher, equal or lower), which compares the performance of the new HT (in terms of the abovementioned 12 variables) with the available comparator. An algorithm combining the first (weights) and second (scores) layers was developed to obtain an overall score for each HT, which was then plotted in a value/risk matrix. The tool was tested using results from the mini-HTAs for three new HTs (Surgical Robot, Platelet Rich Plasma, Deep Brain Stimulation). Results: No significant differences among decision-makers were observed as regards the weights given to the 12 variables, therefore, the median aggregate weights from decision-makers were introduced in the first layer. The dot plot resulting from the mini-HTA presented good power to visually discriminate between the assessed HTs. Conclusion: The decision-support tool developed here makes possible a robust and straightforward comparison of different competing HTs. This facilitates hospital decision-makers deliberations on the prioritization of competing investments under fixed budgets. © Copyright 2012 Cambridge University Press.

Cilloniz C.,University of Barcelona | Albert R.K.,Denver Health | Albert R.K.,Aurora University | Liapikou A.,Sotiria Chest Diseases Hospital | And 6 more authors.
American Journal of Respiratory and Critical Care Medicine | Year: 2015

Rationale: There are conflicting reports describing the effect of macrolide resistance on the presentation and outcomes of patients with Streptococcus pneumoniae pneumonia. Objectives: We aimed to determine the effect of macrolide resistance on the presentation and outcomes of patients with pneumococcal pneumonia. Methods: We conducted a retrospective, observational study in the Hospital Clinic of Barcelona of all adult patients hospitalized with pneumonia who had positive cultures for S. pneumoniae from January 1, 2000 to December 31, 2013. Outcomes examined included bacteremia, pulmonary complications, acute renal failure, shock, intensive care unit admission, need for mechanical ventilation, length of hospital stay, and 30-day mortality. Measurements and Main Results: Of 643 patients hospitalized for S. pneumoniae pneumonia, 139 (22%) were macrolide resistant. Patients with macrolide-resistant organisms were less likely to have bacteremia, pulmonary complications, and shock, and were less likely to require noninvasive mechanical ventilation. We found no increase in the incidence of acute renal failure, the frequency of intensive care unit admission, the need for invasive ventilatory support, the length of hospital stay, or the 30-day mortality in patients with (invasive or noninvasive) macrolide-resistant S. pneumoniae pneumonia, and no effect on outcomes as a function of whether treatment regimens did or did not comply with current guidelines. Conclusions: We found no evidence suggesting that patients hospitalized for macrolide-resistant S. pneumoniae pneumonia were more severely ill on presentation or had worse clinical outcomes if they were treated with guideline-compliant versus noncompliant regimens. Copyright © 2015 by the American Thoracic Society.

Alarcon I.,IDIBAPS Institute dInvestigacions Biomediques August Pi i Sunyer | Carrera C.,IDIBAPS Institute dInvestigacions Biomediques August Pi i Sunyer | Carrera C.,Research Center Biomedica En Red Of Enfermedades Raras Ciberer | Palou J.,Hospital Clinic of Barcelona | And 6 more authors.
British Journal of Dermatology | Year: 2014

Background The number needed to treat (NNT) ratio is an effective method for measuring accuracy in melanoma detection. Dermoscopy reduces the number of false positives and subsequently unnecessary excisions. In vivo reflectance confocal microscopy (RCM) is a noninvasive technique that allows examination of the skin with cellular resolution. Objectives To assess the impact of RCM analysis on the number of equivocal lesions, assumed to be melanocytic, excised for every melanoma. Methods Consecutive patients (n = 343) presenting with doubtful lesions were considered for enrolment. The lesions were analysed by dermoscopy and RCM, with histopathological assessment considered the reference standard. The main outcome was the NNT, calculated as the proportion of equivocal lesions excised for every melanoma. Results Dermoscopy alone obtained a hypothetical NNT of 3·73; the combination of dermoscopy and RCM identified 264 equivocal lesions that qualified for excision, 92 of which were confirmed to be a melanoma, resulting in an NNT of 2·87, whereas the analysis of RCM images classified 103 lesions as melanoma, with a consequent NNT of 1·12. The difference in the reduction of this ratio was statistically significant between the three groups (P < 0·0001). There was no significant improvement in sensitivity when comparing the combination of dermoscopy and RCM with RCM alone (94·6% vs. 97·8%; P = 0·043). However, the differences between specificities were statistically significant (P < 1 × 10-6), favouring RCM alone. Conclusion The addition of RCM analysis to dermoscopy reduces unnecessary excisions with a high diagnostic accuracy and could be a means for reducing the economic impact associated with the management of skin cancer. What's already known about this topic? Dermoscopy enhances the diagnostic accuracy for melanoma and dramatically decreases the number need to treat ratio when used by properly trained dermatologists. Reflectance confocal microscopy (RCM) is a novel technique that provides a significant improvement in melanoma detection. What does this study add? The addition of RCM to dermoscopy has a significant impact on the number of dermoscopically equivocal pigmented lesions excised for every melanoma, reducing the excision of benign lesions. © 2013 British Association of Dermatologists.

Puig O.,Research Center Biomedica En Red Of Salud Mental Cibersam | Penades R.,Unitat Esquizofrenia Clinic | Baeza I.,Hospital Clinic of Barcelona | De La Serna E.,Research Center Biomedica En Red Of Salud Mental Cibersam | And 3 more authors.
Journal of the American Academy of Child and Adolescent Psychiatry | Year: 2014

Objective Cognitive impairment is an enduring and functionally relevant feature of early-onset schizophrenia (EOS). Cognitive remediation therapy (CRT) improves cognition and functional outcome in adults with schizophrenia, although data in adolescents with EOS remain scarce. The purpose of this study is to examine the efficacy of CRT in improving cognition and functional outcomes in a sample of symptomatically stable but cognitively disabled adolescents with EOS. Method We performed a randomized, controlled trial of individually delivered CRT plus treatment-as-usual compared with treatment-as-usual (TAU). Fifty adolescents with EOS were randomly assigned to receive CRT (n = 25) or TAU (n = 25) and were included in an intention-to-treat analysis. Clinical symptoms and cognitive and functional performance were assessed before and after treatment in both groups and after 3 months in the CRT group. Cognitive domains were defined according to the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) consensus battery and averaged in a global cognitive composite score. Results After CRT, significant improvements were found in verbal memory and executive functions, with medium-to-large effect sizes (ES). The derived cognitive composite score showed an improvement after the treatment, with a large ES. This change was reliable in more than two-thirds of the treated patients. Medium-sized ES were found for improvements after CRT in daily living and adaptive functioning, whereas large ES were observed for improvements in family burden. With the exception of functional gains, these changes were maintained after 3 months. Conclusion CRT appears to be a useful intervention strategy for adolescents with EOS. Cognitive improvements can be achieved through CRT, although further research is warranted to determine the durability of functional gains. Clinical trial registration information - Cognitive Remediation Therapy (CRT) in Adolescents With EOS; www.clinicaltrials.gov; NCT01701609. © 2014 American Academy of Child and Adolescent Psychiatry.

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