Parents' perspectives on the value of assistance dogs for children with autism spectrum disorder: a cross-sectional study

Objective While there is an emerging literature on the usefulness of assistance dogs for children with autism spectrum disorder (ASD), there is a dearth of quantitative data on the value of assistance dog interventions for the family unit and family functioning. Using previously validated scales and scales developed specifically for this study, we measured parents’/guardians’ perceptions of how having an assistance dog affects: (1) child safety from environmental dangers, (2) public reception of ASD and (3) levels of caregiver strain and sense of competence. We also obtained open-ended response data from parents/guardians on benefits and constraints of having an assistance dog. Setting This study was based in the primary care setting, within the context of a specific accredited assistance dog centre in Ireland. Participants A total of 134 parents/guardians with an assistance dog, and 87 parents of children on the waiting list were surveyed. Primary and secondary outcome measures The primary outcome measures were scores on environmental hazards and public reception scales. The secondary outcome measures were scores on caregiver strain and competence scales. Results Parents/guardians of children who have ASD and an assistance dog rate their child as significantly safer from environmental dangers (p<0.001), perceive that the public act more respectfully and responsibly towards their child (p<0.001) and feel more competent about managing their child (p=0.023) compared with parents on the waiting list. There was a concentration of positive feeling towards assistance dog interventions with particular focus on safety and comfort for children, and a sense of freedom from family restrictions associated with ASD. The amount of dedication and commitment required to care for a dog were viewed as the primary constraints. Conclusions Our findings indicate that parents perceive that assistance dog interventions can be a valuable intervention for families with children who have ASD

A 1D microphysical cloud model for Earth, and Earth-like exoplanets. Liquid water and water ice clouds in the convective troposphere

One significant difference between the atmospheres of stars and exoplanets is the presence of condensed particles (clouds or hazes) in the atmosphere of the latter. The main goal of this paper is to develop a self-consistent microphysical cloud model for 1D atmospheric codes, which can reproduce some observed properties of Earth, such as the average albedo, surface temperature, and global energy budget. The cloud model is designed to be computationally efficient, simple to implement, and applicable for a wide range of atmospheric parameters for planets in the habitable zone. We use a 1D, cloud-free, radiative-convective, and photochemical equilibrium code originally developed by Kasting, Pavlov, Segura, and collaborators as basis for our cloudy atmosphere model. The cloud model is based on models used by the meteorology community for Earth's clouds. The free parameters of the model are the relative humidity and number density of condensation nuclei, and the precipitation efficiency. In a 1D model, the cloud coverage cannot be self-consistently determined, thus we treat it as a free parameter. We apply this model to Earth (aerosol number density 100 cm^-3, relative humidity 77 %, liquid cloud fraction 40 %, and ice cloud fraction 25 %) and find that a precipitation efficiency of 0.8 is needed to reproduce the albedo, average surface temperature and global energy budget of Earth. We perform simulations to determine how the albedo and the climate of a planet is influenced by the free parameters of the cloud model. We find that the planetary climate is most sensitive to changes in the liquid water cloud fraction and precipitation efficiency. The advantage of our cloud model is that the cloud height and the droplet sizes are self-consistently calculated, both of which influence the climate and albedo of exoplanets.Comment: To appear in Icaru

Automatic segmentation of skeletal muscles from MR images using modified U-Net and a novel data augmentation approach

Rapid and accurate muscle segmentation is essential for the diagnosis and monitoring of many musculoskeletal diseases. As gold standard, manual annotation suffers from intensive labor and high inter-operator reproducibility errors. In this study, deep learning (DL) based automatic muscle segmentation from MR scans is investigated for post-menopausal women, who normally experience a decline in muscle volume. The performance of four Deep Learning (DL) models was evaluated: U-Net and UNet++ and two modified U-Net networks, which combined feature fusion and attention mechanisms (Feature-Fusion-UNet, FFU, and Attention-Feature-Fusion-UNet, AFFU). The models were tested for automatic segmentation of 16-lower limb muscles from MRI scans of two cohorts of post-menopausal women (11 subjects in PMW-1, 8 subjects in PMW-2; from two different studies so considered independent datasets) and 10 obese post-menopausal women (PMW-OB). Furthermore, a novel data augmentation approach is proposed to enlarge the training dataset. The results were assessed and compared by using the Dice similarity coefficient (DSC), relative volume error (RVE), and Hausdorff distance (HD). The best performance among all four DL models was achieved by AFFU (PMW-1: DSC 0.828 ± 0.079, 1-RVE 0.859 ± 0.122, HD 29.9 mm ± 26.5 mm; PMW-2: DSC 0.833 ± 0.065, 1-RVE 0.873 ± 0.105, HD 25.9 mm ± 27.9 mm; PMW-OB: DSC 0.862 ± 0.048, 1-RVE 0.919 ± 0.076, HD 34.8 mm ± 46.8 mm). Furthermore, the augmentation of data significantly improved the DSC scores of U-Net and AFFU for all 16 tested muscles (between 0.23% and 2.17% (DSC), 1.6%–1.93% (1-RVE), and 9.6%–19.8% (HD) improvement). These findings highlight the feasibility of utilizing DL models for automatic segmentation of muscles in post-menopausal women and indicate that the proposed augmentation method can enhance the performance of models trained on small datasets

Physiotherapy and occupational therapy vs no therapy in mild to moderate Parkinson disease: a randomized clinical trial

IMPORTANCE It is unclear whether physiotherapy and occupational therapy are clinically effective and cost-effective in Parkinson disease (PD). OBJECTIVE To perform a large pragmatic randomized clinical trial to evaluate the clinical effectiveness of individualized physiotherapy and occupational therapy in PD. DESIGN, SETTING, AND PARTICIPANTS The PD REHAB Trial was a multicenter, open-label, parallel group, controlled efficacy trial. A total of 762 patients with mild to moderate PD were recruited from 38 sites across the United Kingdom. Recruitment took place between October 2009 and June 2012, with 15 months of follow-up. INTERVENTIONS Participants with limitations in activities of daily living (ADL) were randomized to physiotherapy and occupational therapy or no therapy. MAIN OUTCOMES AND MEASURES The primary outcome was the Nottingham Extended Activities of Daily Living (NEADL) Scale score at 3 months after randomization. Secondary outcomes were health-related quality of life (assessed by Parkinson Disease Questionnaire–39 and EuroQol-5D); adverse events; and caregiver quality of life. Outcomes were assessed before trial entry and then 3, 9, and 15 months after randomization. RESULTS Of the 762 patients included in the study (mean [SD] age, 70 [9.1] years), 381 received physiotherapy and occupational therapy and 381 received no therapy. At 3 months, there was no difference between groups in NEADL total score (difference, 0.5 points; 95%CI, −0.7 to 1.7; P = .41) or Parkinson Disease Questionnaire–39 summary index (0.007 points; 95%CI, −1.5 to 1.5; P = .99). The EuroQol-5D quotient was of borderline significance in favor of therapy (−0.03; 95%CI, −0.07 to −0.002; P = .04). The median therapist contact time was 4 visits of 58 minutes over 8 weeks. Repeated-measures analysis showed no difference in NEADL total score, but Parkinson Disease Questionnaire–39 summary index (diverging 1.6 points per annum; 95%CI, 0.47 to 2.62; P = .005) and EuroQol-5D score (0.02; 95%CI, 0.00007 to 0.03; P = .04) showed small differences in favor of therapy. There was no difference in adverse events. CONCLUSIONS AND RELEVANCE Physiotherapy and occupational therapy were not associated with immediate or medium-term clinically meaningful improvements in ADL or quality of life in mild to moderate PD. This evidence does not support the use of low-dose, patient-centered, goal-directed physiotherapy and occupational therapy in patients in the early stages of PD. Future research should explore the development and testing of more structured and intensive physical and occupational therapy programs in patients with all stages of PD

Differential induction of nuclear factor-like 2 signature genes with toll-like receptors stimulation

Inflammation is associated with production of reactive oxygen species (ROS) and results in the induction of thioredoxin (TXN) and peroxiredoxins (PRDXs) and activation of nuclear factor-like 2 (Nrf2). In this study we have used the mouse RAW 264.7 macrophage and the human THP-1 monocyte cell line to investigate the pattern of expression of three Nrf2 target genes, PRDX1, TXN reductase (TXNRD1) and heme oxygenase (HMOX1), by activation of different Toll-like receptors (TLR). We found that, while the TLR4 agonist lipopolysaccharide (LPS) induces all three genes, the pattern of induction with agonists for TLR1/2, TLR3, TLR2/6 and TLR7/8 differs depending on the gene and the cell line. In all cases, the extent of induction was HMOX1>TXNRD1>PRDX1. Since LPS was a good inducer of all genes in both cell lines, we studied the mechanisms mediating LPS induction of the three genes using mouse RAW 264.7 cells. To assess the role of ROS we used the antioxidant N-acetylcysteine (NAC). Only LPS induction of HMOX1 was inhibited by NAC while that of TXNRD1 and PRDX1 was unaffected. These three genes were also induced by phorbol myristate acetate (PMA), a ROS-inducer acting by activation of protein kinase C (PKC). The protein kinase inhibitor staurosporine inhibited the induction of all three genes by PMA but only that of HMOX1 by LPS. This indicates that activation of these genes by inflammatory agents is regulated by different mechanisms involving either ROS or protein kinases, or both

Investigation of salicylate hepatic responses in comparison with chemical analogues of the drug

AbstractAnti-hyperglycaemic effects of the hydroxybenzoic acid salicylate might stem from effects of the drug on mitochondrial uncoupling, activation of AMP-activated protein kinase, and inhibition of NF-κB signalling. Here, we have gauged the contribution of these effects to control of hepatocyte glucose production, comparing salicylate with inactive hydroxybenzoic acid analogues of the drug. In rat H4IIE hepatoma cells, salicylate was the only drug tested that activated AMPK. Salicylate also reduced mTOR signalling, but this property was observed widely among the analogues. In a sub-panel of analogues, salicylate alone reduced promoter activity of the key gluconeogenic enzyme glucose 6-phosphatase and suppressed basal glucose production in mouse primary hepatocytes. Both salicylate and 2,6 dihydroxybenzoic acid suppressed TNFα-induced IκB degradation, and in genetic knockout experiments, we found that the effect of salicylate on IκB degradation was AMPK-independent. Previous data also identified AMPK-independent regulation of glucose but we found that direct inhibition of neither NF-κB nor mTOR signalling suppressed glucose production, suggesting that other factors besides these cell signalling pathways may need to be considered to account for this response to salicylate. We found, for example, that H4IIE cells were exquisitely sensitive to uncoupling with modest doses of salicylate, which occurred on a similar time course to another anti-hyperglycaemic uncoupling agent 2,4-dinitrophenol, while there was no discernible effect at all of two salicylate analogues which are not anti-hyperglycaemic. This finding supports much earlier literature suggesting that salicylates exert anti-hyperglycaemic effects at least in part through uncoupling

Effect of genetically low 25-hydroxyvitamin D on mortality risk: Mendelian randomization analysis in 3 large European cohorts

Source at https://doi.org/10.3390/nu11010074.The aim of this study was to determine if increased mortality associated with low levels of serum 25-hydroxyvitamin D (25(OH)D) reflects a causal relationship by using a Mendelian randomisation (MR) approach with genetic variants in the vitamin D synthesis pathway. Individual participant data from three European cohorts were harmonized with standardization of 25(OH)D according to the Vitamin D Standardization Program. Most relevant single nucleotide polymorphisms of the genes CYP2R1 (rs12794714, rs10741657) and DHCR7/NADSYN1 (rs12785878, rs11234027), were combined in two allelic scores. Cox proportional hazards regression models were used with the ratio estimator and the delta method for calculating the hazards ratio (HR) and standard error of genetically determined 25(OH)D effect on all-cause mortality. We included 10,501 participants (50.1% females, 67.1±10.1 years) of whom 4003 died during a median follow-up of 10.4 years. The observed adjusted HR for all-cause mortality per decrease in 25(OH)D by 20 nmol/L was 1.20 (95% CI: 1.15–1.25). The HR per 20 nmol/L decrease in genetically determined 25(OH)D was 1.32 (95% CI: 0.80–2.24) and 1.35 (95% CI of 0.81 to 2.37) based on the two scores. In conclusion, the results of this MR study in a combined sample from three European cohort studies provide further support for a causal relationship between vitamin D deficiency and increased all-cause mortality. However, as the current study, even with ~10,000 participants, was underpowered for the study of the effect of the allele score on mortality, larger studies on genetics and mortality are needed to improve the precision

Vitamin D and mortality: Individual participant data meta-analysis of standardized 25-hydroxyvitamin D in 26916 individuals from a European consortium

Source at http://doi.org/10.1371/journal.pone.0170791Background:Vitamin D deficiency may be a risk factor for mortality but previous meta-analyses lacked standardization of laboratory methods for 25-hydroxyvitamin D (25[OH]D) concentrations and used aggregate data instead of individual participant data (IPD). We therefore performed an IPD meta-analysis on the association between standardized serum 25(OH)D and mortality.Methods:In a European consortium of eight prospective studies, including seven general population cohorts, we used the Vitamin D Standardization Program (VDSP) protocols to standardize 25(OH)D data. Meta-analyses using a one step procedure on IPD were performed to study associations of 25(OH)D with all-cause mortality as the primary outcome, and with cardiovascular and cancer mortality as secondary outcomes. This meta-analysis is registered at ClinicalTrials.gov, number NCT02438488.Findings:We analysed 26916 study participants (median age 61.6 years, 58% females) with a median 25(OH)D concentration of 53.8 nmol/L. During a median follow-up time of 10.5 years, 6802 persons died. Compared to participants with 25(OH)D concentrations of 75 to 99.99 nmol/L, the adjusted hazard ratios (with 95% confidence interval) for mortality in the 25(OH)D groups with 40 to 49.99, 30 to 39.99, and Interpretation:In the first IPD meta-analysis using standardized measurements of 25(OH)D we observed an association between low 25(OH)D and increased risk of all-cause mortality. It is of public health interest to evaluate whether treatment of vitamin D deficiency prevents premature deaths

Gene expression markers of tendon fibroblasts in normal and diseased tissue compared to monolayer and three dimensional culture systems

<p>Abstract</p> <p>Background</p> <p>There is a paucity of data regarding molecular markers that identify the phenotype of the tendon cell. This study aims to quantify gene expression markers that distinguish between tendon fibroblasts and other mesenchymal cells which may be used to investigate tenogenesis.</p> <p>Methods</p> <p>Expression levels for 12 genes representative of musculoskeletal tissues, including the proposed tendon progenitor marker scleraxis, relative to validated reference genes, were evaluated in matched samples of equine tendon (harvested from the superficial digital flexor tendon), cartilage and bone using quantitative PCR (qPCR). Expression levels of genes associated with tendon phenotype were then evaluated in healthy, including developmental, and diseased equine tendon tissue and in tendon fibroblasts maintained in both monolayer culture and in three dimensional (3D) collagen gels.</p> <p>Results</p> <p>Significantly increased expression of scleraxis was found in tendon compared with bone (P = 0.002) but not compared to cartilage. High levels of COL1A2 and scleraxis and low levels of tenascin-C were found to be most representative of adult tensional tendon phenotype. While, relative expression of scleraxis in developing mid-gestational tendon or in acute or chronically diseased tendon did not differ significantly from normal adult tendon, tenascin-C message was significantly upregulated in acutely injured equine tendon (P = 0.001). Relative scleraxis gene expression levels in tendon cell monolayer and 3D cultures were significantly lower than in normal adult tendon (P = 0.002, P = 0.02 respectively).</p> <p>Conclusion</p> <p>The findings of this study indicate that high expression of both COL1A2 and scleraxis, and low expression of tenascin-C is representative of a tensional tendon phenotype. The <it>in vitro </it>culture methods used in these experiments however, may not recapitulate the phenotype of normal tensional tendon fibroblasts in tissues as evidenced by gene expression.</p