Addition to "Nanostars carrying multifunctional neurotrophic dendrimers protect neurons in preclinical in vitro models of neurodegenerative disorders".

In the original version of this article (p. 47457), some acknowledgments were not included. In the revised Acknowledgments section provided below, we additionally provide The REC reference for the ethical approval of the human astrocyte isolation, an acknowledgment to Dr. Alize Proust at the Francis Crick Institute for establishing the triple coculture BBB model used in this study, and the reference and the grant number for the source of the human fetal material. This does not affect the results or conclusions of our work

Oral chondroitin sulfate and prebiotics for the treatment of canine Inflammatory Bowel Disease: a randomized, controlled clinical trial

BACKGROUND Canine inflammatory bowel disease (IBD) is a chronic enteropathy of unknown etiology, although microbiome dysbiosis, genetic susceptibility, and dietary and/or environmental factors are hypothesized to be involved in its pathogenesis. Since some of the current therapies are associated with severe side effects, novel therapeutic modalities are needed. A new oral supplement for long-term management of canine IBD containing chondroitin sulfate (CS) and prebiotics (resistant starch, β-glucans and mannaoligosaccharides) was developed to target intestinal inflammation and oxidative stress, and restore normobiosis, without exhibiting any side effects. This double-blinded, randomized, placebo-controlled trial in dogs with IBD aims to evaluate the effects of 180 days administration of this supplement together with a hydrolyzed diet on clinical signs, intestinal histology, gut microbiota, and serum biomarkers of inflammation and oxidative stress. RESULTS Twenty-seven client-owned biopsy-confirmed IBD dogs were included in the study, switched to the same hydrolyzed diet and classified into one of two groups: supplement and placebo. Initially, there were no significant differences between groups (p > 0.05) for any of the studied parameters. Final data analysis (supplement: n = 9; placebo: n = 10) showed a significant decrease in canine IBD activity index (CIBDAI) score in both groups after treatment (p < 0.001). After treatment, a significant decrease (1.53-fold; p < 0.01) in histologic score was seen only in the supplement group. When groups were compared, the supplement group showed significantly higher serum cholesterol (p < 0.05) and paraoxonase-1 (PON1) levels after 60 days of treatment (p < 0.01), and the placebo group showed significantly reduced serum total antioxidant capacity (TAC) levels after 120 days (p < 0.05). No significant differences were found between groups at any time point for CIBDAI, WSAVA histologic score and fecal microbiota evaluated by PCR-restriction fragment length polymorphism (PCR-RFLP). No side effects were reported in any group. CONCLUSIONS The combined administration of the supplement with hydrolyzed diet over 180 days was safe and induced improvements in selected serum biomarkers, possibly suggesting a reduction in disease activity. This study was likely underpowered, therefore larger studies are warranted in order to demonstrate a supplemental effect to dietary treatment of this supplement on intestinal histology and CIBDAI

Use of linear mixed models for genetic evaluation of gestation length and birth weight allowing for heavy-tailed residual effects

<p>Abstract</p> <p>Background</p> <p>The distribution of residual effects in linear mixed models in animal breeding applications is typically assumed normal, which makes inferences vulnerable to outlier observations. In order to mute the impact of outliers, one option is to fit models with residuals having a heavy-tailed distribution. Here, a Student's-<it>t </it>model was considered for the distribution of the residuals with the degrees of freedom treated as unknown. Bayesian inference was used to investigate a bivariate Student's-<it>t </it>(BS<it>t</it>) model using Markov chain Monte Carlo methods in a simulation study and analysing field data for gestation length and birth weight permitted to study the practical implications of fitting heavy-tailed distributions for residuals in linear mixed models.</p> <p>Methods</p> <p>In the simulation study, bivariate residuals were generated using Student's-<it>t </it>distribution with 4 or 12 degrees of freedom, or a normal distribution. Sire models with bivariate Student's-<it>t </it>or normal residuals were fitted to each simulated dataset using a hierarchical Bayesian approach. For the field data, consisting of gestation length and birth weight records on 7,883 Italian Piemontese cattle, a sire-maternal grandsire model including fixed effects of sex-age of dam and uncorrelated random herd-year-season effects were fitted using a hierarchical Bayesian approach. Residuals were defined to follow bivariate normal or Student's-<it>t </it>distributions with unknown degrees of freedom.</p> <p>Results</p> <p>Posterior mean estimates of degrees of freedom parameters seemed to be accurate and unbiased in the simulation study. Estimates of sire and herd variances were similar, if not identical, across fitted models. In the field data, there was strong support based on predictive log-likelihood values for the Student's-<it>t </it>error model. Most of the posterior density for degrees of freedom was below 4. Posterior means of direct and maternal heritabilities for birth weight were smaller in the Student's-<it>t </it>model than those in the normal model. Re-rankings of sires were observed between heavy-tailed and normal models.</p> <p>Conclusions</p> <p>Reliable estimates of degrees of freedom were obtained in all simulated heavy-tailed and normal datasets. The predictive log-likelihood was able to distinguish the correct model among the models fitted to heavy-tailed datasets. There was no disadvantage of fitting a heavy-tailed model when the true model was normal. Predictive log-likelihood values indicated that heavy-tailed models with low degrees of freedom values fitted gestation length and birth weight data better than a model with normally distributed residuals.</p> <p>Heavy-tailed and normal models resulted in different estimates of direct and maternal heritabilities, and different sire rankings. Heavy-tailed models may be more appropriate for reliable estimation of genetic parameters from field data.</p

Development of an open technology sensor suite for assisted living: a student-led research project.

Many countries have a rapidly ageing population, placing strain on health services and creating a growing market for assistive technology for older people. We have, through a student-led, 12-week project for 10 students from a variety of science and engineering backgrounds, developed an integrated sensor system to enable older people, or those at risk, to live independently in their own homes for longer, while providing reassurance for their family and carers. We provide details on the design procedure and performance of our sensor system and the management and execution of a short-term, student-led research project. Detailed information on the design and use of our devices, including a door sensor, power monitor, fall detector, general in-house sensor unit and easy-to-use location-aware communications device, is given, with our open designs being contrasted with closed proprietary systems. A case study is presented for the use of our devices in a real-world context, along with a comparison with commercially available systems. We discuss how the system could lead to improvements in the quality of life of older users and increase the effectiveness of their associated care network. We reflect on how recent developments in open source technology and rapid prototyping increase the scope and potential for the development of powerful sensor systems and, finally, conclude with a student perspective on this team effort and highlight learning outcomes, arguing that open technologies will revolutionize the way in which technology will be deployed in academic research in the future.This is the final version of the article. It first appeared from Royal Society Publishing via http://dx.doi.org/10.1098/rsfs.2016.001

From evolutionary computation to the evolution of things

Evolution has provided a source of inspiration for algorithm designers since the birth of computers. The resulting field, evolutionary computation, has been successful in solving engineering tasks ranging in outlook from the molecular to the astronomical. Today, the field is entering a new phase as evolutionary algorithms that take place in hardware are developed, opening up new avenues towards autonomous machines that can adapt to their environment. We discuss how evolutionary computation compares with natural evolution and what its benefits are relative to other computing approaches, and we introduce the emerging area of artificial evolution in physical systems

Próteses parciais fixas reforçadas por fibras: um estudo clínico retrospectivo preliminar

The aim of this study was to evaluate the clinical performance (retention rate) of fiber-reinforced composite fixed partial dentures (FPDs). Polyethylene fiber (Ribbond®) was used combined with restorative composite during FPDs fabrication. FPDs were placed in thirteen patients in a private clinic. Nineteen FPDs were evaluated. The prosthetic space was filled with only one pontic using extracted teeth (2 cases), acrylic resin teeth (11 cases), or with composite resin (6 cases), combined with Polyethylene fiber. The clinical criterion used was based on retention rate of FPDs. If FPDs were in function in the mouth at the time of examination without previous repair they were classified as Complete Survival (CS) restorations. A classification of Survival with Rebonding (SR) was assigned in the event of an adhesive failure, but after rebonding the FPD still remained under evaluation. Treatment was classified as a Failure (F) if the FPD restoration was lost. The time of evaluation was 41.15 months (±15.13). The FPDs evaluated were retained (CS=94.75%), and no failure was found except for in one situation which required rebonding (SR=5.25%). According to the survival estimation method of Kaplan-Meyer the mean survival time was 42.3 months. At the time of evaluation investigated, polyethylene-reinforced FPDs showed a favorable retention rate in preliminary data.O objetivo deste estudo foi avaliar a performance clínica (percentagem de retenção) de próteses parciais fixas reforçadas por fibras. Fibras de polietileno (Ribbond®) foram usadas em combinação com resina composta durante a confecção das próteses. Os tratamentos foram realizadas em 13 pacientes, em uma clínica privada., sendo que 19 próteses foram reavaliadas. O espaço protético era preenchido com um pôntico usando o próprio dente extraído (2 casos), dentes de acrílico (11 casos) ou confeccionados com resina composta (6 casos), em todas as situações eram empregadas fibras de polietileno. Os critérios clínicos usados foram baseados na percentagem de retenção das próteses parciais fixas. As próteses que estavam em função no momento da avaliação, sem nunca necessitar de qualquer reparo prévio, foram classificadas como sobrevivência completa (SC). A classificação de sobrevivência com nova colagem (SR) foi utilizada para os casos de falha adesiva, com posterior cimentação da peça, a qual permanecia em função. O tratamento era classificado como falha (F) quando a restauração era perdida. O tempo médio de avaliação foi de 41,15 meses (±15,13). Nenhum caso de falha foi detectado, em apenas um caso houve falha adesiva com posterior colagem da peça (SR=5,25%) e em 94.75% dos casos as próteses permaneciam em função.. De acordo com o método de sobrevida de Kaplan-Meyer o tempo médio de sobrevida foi de 42,3 meses. As próteses parciais fixas reforçadas por fibras mostraram uma percentagem de retenção favorável neste estudo preliminar

ITGB5 and AGFG1 variants are associated with severity of airway responsiveness

Background: Airway hyperresponsiveness (AHR), a primary characteristic of asthma, involves increased airway smooth muscle contractility in response to certain exposures. We sought to determine whether common genetic variants were associated with AHR severity. Methods: A genome-wide association study (GWAS) of AHR, quantified as the natural log of the dosage of methacholine causing a 20% drop in FEV1, was performed with 994 non-Hispanic white asthmatic subjects from three drug clinical trials: CAMP, CARE, and ACRN. Genotyping was performed on Affymetrix 6.0 arrays, and imputed data based on HapMap Phase 2, was used to measure the association of SNPs with AHR using a linear regression model. Replication of primary findings was attempted in 650 white subjects from DAG, and 3,354 white subjects from LHS. Evidence that the top SNPs were eQTL of their respective genes was sought using expression data available for 419 white CAMP subjects. Results: The top primary GWAS associations were in rs848788 (P-value 7.2E-07) and rs6731443 (P-value 2.5E-06), located within the ITGB5 and AGFG1 genes, respectively. The AGFG1 result replicated at a nominally significant level in one independent population (LHS P-value 0.012), and the SNP had a nominally significant unadjusted P-value (0.0067) for being an eQTL of AGFG1. Conclusions: Based on current knowledge of ITGB5 and AGFG1, our results suggest that variants within these genes may be involved in modulating AHR. Future functional studies are required to confirm that our associations represent true biologically significant findings