Background
Active Support is a person‐centred practice that enables people with intellectual disabilities (IDs) to engage in meaningful activities and social interactions. The Active Support Measure ...(ASM) is an observational tool designed to measure the quality of support that people with IDs living in supported accommodation services receive from staff. The aim of the study was to explore the underlying constructs of the ASM.
Methods
Multilevel exploratory factor analysis was conducted on ASM data (n = 884 people with IDs across 236 accommodation services) collected during a longitudinal study of Active Support in Australian accommodation services.
Results
Multilevel exploratory factor analysis indicated that 12 of the ASM's 15 items loaded on two factors, named Supporting Engagement in Activities and Interacting with the Person.
Conclusions
The 12‐item ASM measures two dimensions of the quality of staff support. Both technical and interpersonal skills comprise good Active Support.
Parents of children with autism spectrum disorder and other disabilities report high levels of distress, but systematically evaluated interventions are few. This study aimed to evaluate the ...feasibility of a novel, manualized Acceptance and Commitment Therapy group intervention (
Navigator ACT
) in a sample of 94 parents of children with disabilities. Feasibility was measured by treatment completion, credibility, and satisfaction, and preliminary outcomes by using self-rating scales administered at the baseline, post-intervention, and follow-up. The results imply the intervention is feasible in the context of Swedish outpatient habilitation services. A preliminary analysis of the outcome measures suggests that parents experienced significant improvements in well-being. The results indicate that the treatment is feasible and should be evaluated in a randomized controlled trial.
Enhancer elements in the human genome control how genes are expressed in specific cell types and harbor thousands of genetic variants that influence risk for common diseases
. Yet, we still do not ...know how enhancers regulate specific genes, and we lack general rules to predict enhancer-gene connections across cell types
. We developed an experimental approach, CRISPRi-FlowFISH, to perturb enhancers in the genome, and we applied it to test >3,500 potential enhancer-gene connections for 30 genes. We found that a simple activity-by-contact model substantially outperformed previous methods at predicting the complex connections in our CRISPR dataset. This activity-by-contact model allows us to construct genome-wide maps of enhancer-gene connections in a given cell type, on the basis of chromatin state measurements. Together, CRISPRi-FlowFISH and the activity-by-contact model provide a systematic approach to map and predict which enhancers regulate which genes, and will help to interpret the functions of the thousands of disease risk variants in the noncoding genome.
Laminar, internal forced convection utilizing nanofluids is analyzed, incorporating experimentally-verified descriptions of the nanofluid’s specific heat, and accounting for the dual effects of (i) ...increased thermal conductivity and (ii) reduced specific heat of the nanofluid relative to its base liquid. Heat transfer enhancement is quantified, and a dimensionless effectiveness is introduced to gage the nanofluid’s performance relative to that of the pure, base liquid. It is shown that use of nanofluidic versions of pure liquids can either enhance or degrade thermal performance.
Protein structures are dynamic and can explore a large conformational landscape
. Only some of these structural substates are important for protein function (such as ligand binding, catalysis and ...regulation)
. How evolution shapes the structural ensemble to optimize a specific function is poorly understood
. One of the constraints on the evolution of proteins is the stability of the folded 'native' state. Despite this, 44% of the human proteome contains intrinsically disordered peptide segments greater than 30 residues in length
, the majority of which have no known function
. Here we show that the entropic force produced by an intrinsically disordered carboxy terminus (ID-tail) shifts the conformational ensemble of human UDP-α-D-glucose-6-dehydrogenase (UGDH) towards a substate with a high affinity for an allosteric inhibitor. The function of the ID-tail does not depend on its sequence or chemical composition. Instead, the affinity enhancement can be accurately predicted based on the length of the intrinsically disordered segment, and is consistent with the entropic force generated by an unstructured peptide attached to the protein surface
. Our data show that the unfolded state of the ID-tail rectifies the dynamics and structure of UGDH to favour inhibitor binding. Because this entropic rectifier does not have any sequence or structural constraints, it is an easily acquired adaptation. This model implies that evolution selects for disordered segments to tune the energy landscape of proteins, which may explain the persistence of intrinsic disorder in the proteome.
A thermal network model is developed and used to analyze heat transfer in a high temperature latent heat thermal energy storage unit for solar thermal electricity generation. Specifically, the ...benefits of inserting multiple heat pipes between a heat transfer fluid and a phase change material (PCM) are of interest. Two storage configurations are considered; one with PCM surrounding a tube that conveys the heat transfer fluid, and the second with the PCM contained within a tube over which the heat transfer fluid flows. Both melting and solidification are simulated. It is demonstrated that adding heat pipes enhances thermal performance, which is quantified in terms of dimensionless heat pipe effectiveness.
Background
The present study aimed to explore the applicability of the attribution model to social workers' attributions towards clients with dual diagnosis of intellectual disability and psychiatric ...illness. Specifically, the study examined the relations between social workers' attribution of responsibility, causality, stereotypes of dangerousness, their emotional reactions and behavioural reactions towards clients with dual diagnosis.
Method
Social workers (N = 279) completed questionnaires measuring attributions of responsibility, causation and dangerousness, and reported on their emotional and behavioural reactions to clients diagnosed with DD.
Results
Most social workers reported high levels of helping behaviours. The strongest predictor of discriminatory behaviours was the stereotype of dangerousness. Social workers who reported feeling less anger and more pity towards clients with DD tended to report higher levels of helping behaviour. But contrary to attribution theory, fear and anger did not predict discriminatory behaviours.
Conclusion
The results are discussed in relation to the core values of social work and to professional identity.
ABSTRACT We present optical integral field spectroscopy of the circum-nuclear gas of the Seyfert 2 galaxy NGC 1386. The data cover the central 7″ × 9″ (530 × 680 pc) at a spatial resolution of 0 9 ...(68 pc), and the spectral range 5700-7000 at a resolution of 66 km s−1. The line emission is dominated by a bright central component, with two lobes extending 3″ north and south of the nucleus. We identify three main kinematic components. The first has low velocity dispersion ( 90 km s−1), extends over the whole field of view, and has a velocity field consistent with gas rotating in the galaxy disk. We interpret the lobes as resulting from photoionization of disk gas in regions where the active galactic nucleus radiation cones intercept the disk. The second has higher velocity dispersion ( 200 km s−1) and is observed in the inner 150 pc around the continuum peak. This component is double peaked, with redshifted and blueshifted components separated by 500 km s−1. Together with previous Hubble Space Telescope imaging, these features suggest the presence of a bipolar outflow for which we estimate a mass outflow rate of 0.1 yr−1. The third component is revealed by velocity residuals associated with enhanced velocity dispersion and suggests that outflow and/or rotation is occurring approximately in the equatorial plane of the torus. A second system of velocity residuals may indicate the presence of streaming motions along dusty spirals in the disk.
Genome-wide association studies have associated thousands of genetic variants with complex traits and diseases, but pinpointing the causal variant(s) among those in tight linkage disequilibrium with ...each associated variant remains a major challenge. Here, we use seven experimental assays to characterize all common variants at the multiple disease-associated TNFAIP3 locus in five disease-relevant immune cell lines, based on a set of features related to regulatory potential. Trait/disease-associated variants are enriched among SNPs prioritized based on either: (1) residing within CRISPRi-sensitive regulatory regions, or (2) localizing in a chromatin accessible region while displaying allele-specific reporter activity. Of the 15 trait/disease-associated haplotypes at TNFAIP3, 9 have at least one variant meeting one or both of these criteria, 5 of which are further supported by genetic fine-mapping. Our work provides a comprehensive strategy to characterize genetic variation at important disease-associated loci, and aids in the effort to identify trait causal genetic variants.
Mass spectrometry (MS)–based protein footprinting, a valuable structural tool in mapping protein-ligand interaction, has been extensively applied to protein-protein complexes, showing success in ...mapping large interfaces. Here, we utilized an integrated footprinting strategy incorporating both hydrogen-deuterium exchange (HDX) and hydroxyl radical footprinting (i.e., fast photochemical oxidation of proteins (FPOP)) for molecular-level characterization of the interaction of human bromodomain-containing protein 4 (BRD4) with a hydrophobic benzodiazepine inhibitor. HDX does not provide strong evidence for the location of the binding interface, possibly because the shielding of solvent by the small molecule is not large. Instead, HDX suggests that BRD4 appears to be stabilized by showing a modest decrease in dynamics caused by binding. In contrast, FPOP points to a critical binding region in the hydrophobic cavity, also identified by crystallography, and, therefore, exhibits higher sensitivity than HDX in mapping the interaction of BRD4 with compound 1. In the absence or under low concentrations of the radical scavenger, FPOP modifications on Met residues show significant differences that reflect the minor change in protein conformation. This problem can be avoided by using a sufficient amount of proper scavenger, as suggested by the FPOP kinetics directed by a dosimeter of the hydroxyl radical.
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