Influences on speech output in acquired apraxia of speech: a comparison of English and German

The nature of breakdown in apraxia of speech (AoS) continues to be a subject of debate. Determining which output variables influence production could assist in settling this debate. This study with 7 German and 7 English speakers with post-stroke output impairment showed significant independent effects of word frequency and phonotactic probability on repetition accuracy of (near) homophones in English and German. Only a moderate correlation existed between accuracy for the English and German subjects. Results are discussed in terms of the possible loci of breakdown in models of speech output and the implications for the assessment and treatment of AoS

Do phonological neighbourhood density and phonotactic probability influence speech output accuracy in acquired speech impairment?

Phonological neighbourhood density (ND) and phonotactic probability (PROB) have been shown as important variables in speech output accuracy. We examined whether PROB and ND have an effect on output accuracy in English speakers after stroke when other key variables in output are controlled. We also looked at the significance of ND/PROB regarding differential diagnosis. Fourteen speakers showed a positive effect of PROB on accuracy. Only two individuals displayed a positive ND effect. No double dissociations regarding the ND/PROB effect were noted for individuals or for the group. Results are discussed regarding speech models and assessment/treatment of acquired output impairment

Changes in complementarity-determining regions significantly alter IgG binding to the neonatal Fc receptor

A large body of data exists demonstrating the key role of FcRn in extending the half-life of therapeutic antibodies by rescuing them from lysosomal degradation. This led to the widely accepted hypothesis that FcRn binding of an IgG via the CH2-CH3 interface of Fc correlates with IgG half-life. Several studies have demonstrated that in vivo half-life can be modified by changing the binding affinity of IgG to FcRn. These modifications were generated by mutating the coding sequence for the Fc region that resulted in enhanced or reduced FcRn binding at endosomal pH without enhancing binding at neutral pH. In contrast to this, we have observed that the half-lifes of IgG molecules that had showed no target-mediated disposition or off-target binding varies widely, even when they share identical Fc domains. This led us to hypothesize that domains of IgG molecules other than Fc could contribute to the modulation of FcRn binding and affect in vivo half-life. This hypothesis was strengthened by recent publications by other groups showing a correlation between antibody charge and the FcRn affinity and/or in vivo half-life. In this study we explored the role of IgG domains other than the FcRn binding domain in altering the affinity between IgG and FcRn and its relation to the in vivo half-life. Here we describe a surface plasmon resonance (SPR) based assay developed to examine the steady-state binding affinity (KD) of IgG molecules to FcRn. We systematically dissected the contributions of IgG variable domain regions in modulating the affinity between FcRn and IgG. Through analysis of a broad collection of therapeutic antibodies containing more than 100 unique IgG molecules against more than 25 different therapeutic targets we have demonstrated that variable domains and in particular CDRs significantly alter binding affinity to FcRn, by 10 to 80-fold, whereas heavy and light chain isotypes do not. Because CDRs modulate the affinity between IgG and FcRn in our in vitro studies, it is important to understand the role they play in modulation of IgG half-life in vivo as this would have far-reaching implications in the half-life optimization efforts of IgG therapeutics

Examining the feasibility of an economic analysis of dyadic developmental psychotherapy for children with maltreatment associated psychiatric problems in the United Kingdom

Background: Children with maltreatment associated psychiatric problems are at increased risk of developing behavioural or mental health disorders. Dyadic Developmental Psychotherapy (DDP) was proposed as treatment for children with maltreatment histories in the USA, however, being new to the UK little is known of its effectiveness or cost-effectiveness. As part of an exploratory study, this paper explores the feasibility of undertaking economic analysis of DDP in the UK. Methods: Feasibility for economic analysis was determined by ensuring such analysis could meet key criteria for economic evaluation. Phone interviews were conducted with professionals (therapists trained and accredited or in the process of becoming accredited DDP practitioners). Three models were developed to represent alternative methods of DDP service delivery. Once appropriate comparators were determined, economic scenarios were constructed. Cost analyses were undertaken from a societal perspective. Finally, appropriate outcome measurement was explored through clinical opinion, literature and further discussions with clinical experts. Results: Three DDP models were constructed: DDP Full-Basic, DDP Home-Based and DDP Long-Term. Two potential comparator interventions were identified and defined as Consultation with Carers and Individual Psychotherapy. Costs of intervention completion per case were estimated to be: £6,700 (DDP Full-Basic), £7,100 (Consultations with Carers), £7,200 (DDP Home-Based), £11,400 (Individual Psychotherapy) and £14,500 (DDP Long-Term). None of the models of service delivery were found to currently measure effectiveness consistently. The Strengths and Difficulties Questionnaire (SDQ) was deemed an appropriate primary outcome measure, however, it does not cover all disorders DDP intends to treat and the SDQ is not a direct measure of health gain. Inclusion of quality of life measurement is required for comprehensive economic analysis. Conclusions: Economic analysis of DDP in the UK is feasible if vital next steps are taken to measure intervention outcomes consistently, ideally with a quality of life measurement. An economic analysis using the models constructed could determine the potential cost-effectiveness of DDP in the UK and identify the most efficient mode of service delivery

The feasibility of a randomised controlled trial of Dyadic Developmental Psychotherapy

Background: Maltreated children have significant and complex problems which clinicians find difficult to diagnose and treat. Previous US pilot work suggests that Dyadic Developmental Psychotherapy (DDP) may be effective; however, rigorous evidence from a randomised controlled trial (RCT) is lacking. The purpose of this study is to establish the feasibility of an RCT of DDP by exploring the ways that DDP is operating across different UK sites and the impacts of current practice on the potential set-up of an RCT. Methods: Qualitative methods (interviews, focus groups and teleconferences) were used to explore trial feasibility with therapists and service managers from teams implementing both DDP and possible control interventions. Data were analysed thematically and related to various aspects of trial design. Results: DDP was commonly regarded as having a particular congruence with the complexity of maltreatment-associated problems and a common operating model of DDP was evident across sites. A single control therapy was harder to establish, however, and it is likely to be a non-specific and context-dependent intervention/s offered within mainstream Child and Adolescent Mental Health Services (CAMHS). Because a ‘gold standard’ Treatment as Usual (TAU) does not currently exist, randomisation between DDP and TAU (CAMHS) therefore looks feasible and ethical. The nature of family change during DDP was regarded as multi-faceted, non-linear and relationship-based. Assessment tools need to be carefully considered in terms of their ability to capture change that covers both individual child and family-based functioning. Conclusions: An RCT of DDP is feasible and timely. This study has demonstrated widespread interest, support and engagement regarding an RCT and permissions have been gained from sites that have shown readiness to participate. As maltreated children are among the most vulnerable in society, and as there are currently no treatments with RCT evidence, such a trial would be a major advance in the field

Tuning Interparticle Hydrogen Bonding in Shear-Jamming Suspensions: Kinetic Effects and Consequences for Tribology and Rheology

The shear-jamming of dense suspensions can be strongly affected by molecular-scale interactions between particles, e.g. by chemically controlling their propensity for hydrogen bonding. However, hydrogen bonding not only enhances interparticle friction, a critical parameter for shear jamming, but also introduces (reversible) adhesion, whose interplay with friction in shear-jamming systems has so far remained unclear. Here, we present atomic force microscopy studies to assess interparticle adhesion, its relationship to friction, and how these attributes are influenced by urea, a molecule that interferes with hydrogen bonding. We characterize the kinetics of this process with nuclear magnetic resonance, relating it to the time dependence of the macroscopic flow behavior with rheological measurements. We find that time-dependent urea sorption reduces friction and adhesion, causing a shift in the shear-jamming onset. These results extend our mechanistic understanding of chemical effects on the nature of shear jamming, promising new avenues for fundamental studies and applications alike

Vermont Adolescent Perception of Barriers to Smoking and Cessation

Introduction: Despite a decline in youth smoking rates over the past decade, thirteen percent of Vermont high school students still smoke (Vermont Youth Risk Behavior Survey, YRBS, 2013). Smoking and nicotine exposure at an early age can have detrimental effects on brain development and lead to long term, sustained tobacco use (Arrazola et. al 2015). It was our goal to characterize the barriers to cessation for these adolescents. Some important factors suggested by the literature include living with someone who smokes (50% of VT teen smokers report a parent or guardian who smokes) and having a close friend who smokes (70% of VT teen smokers) (American Lung Association 2015). Nationally, while teen smoking rates continue to decline, the decrease is being offset by a significant increase in electronic vapor products (e-cigs) (12% increase from 2011-2014) (Arrazola et. al 2015). The 2013 Vermont YRBS data may therefore be misleading, and not capture this increase in tobacco and e-cig use. Therefore, we were particularly interested in further characterizing the link, if any, between e-cig use and smoking initiation or successful smoking cessation.https://scholarworks.uvm.edu/comphp_gallery/1222/thumbnail.jp

Does tailoring instructional style to a medical student\u27s self-perceived learning style improve performance when teaching intravenous catheter placement? A randomized controlled study.

BACKGROUND: Students may have different learning styles. It is unclear, however, whether tailoring instructional methods for a student\u27s preferred learning style improves educational outcomes when teaching procedures. The authors sought to examine whether teaching to a student\u27s self-perceived learning style improved the acquisition of intravenous (IV) catheter placement skills. The authors hypothesized that matching a medical student\u27s preferred learning style with the instructor\u27s teaching style would increase the success of placing an IV catheter. METHODS: Using the VARK model (i.e., visual [V], auditory [A], read/write [R] and kinesthetic [K]), third-year medical students reported their self-perceived learning style and were subsequently randomized to instructors who were trained to teach according to a specific learning format (i.e., visual, auditory). Success was gauged by: 1) the placement of an IV on the first attempt and 2) the number of attempts made until an IV line was successfully placed. RESULTS: The average number of attempts in the matched learning style group was 1.53, compared to 1.64 in the unmatched learning style group; however, results were not statistically significant. Both matched and unmatched groups achieved a similar success rate (57 and 58 %, respectively). Additionally, a comparison of success between the unmatched and matched students within each learning style modality yielded no statistical significance. CONCLUSIONS: Results suggest that providing procedural instruction that is congruent with a student\u27s self-perceived learning style does not appear to improve outcomes when instructing students on IV catheter placement

Sost and its paralog Sostdc1 coordinate digit number in a Gli3-dependent manner.

WNT signaling is critical in most aspects of skeletal development and homeostasis, and antagonists of WNT signaling are emerging as key regulatory proteins with great promise as therapeutic agents for bone disorders. Here we show that Sost and its paralog Sostdc1 emerged through ancestral genome duplication and their expression patterns have diverged to delineate non-overlapping domains in most organ systems including musculoskeletal, cardiovascular, nervous, digestive, reproductive and respiratory. In the developing limb, Sost and Sostdc1 display dynamic expression patterns with Sost being restricted to the distal ectoderm and Sostdc1 to the proximal ectoderm and the mesenchyme. While Sostdc1(-/-) mice lack any obvious limb or skeletal defects, Sost(-/-) mice recapitulate the hand defects described for Sclerosteosis patients. However, elevated WNT signaling in Sost(-/-); Sostdc1(-/-) mice causes misregulation of SHH signaling, ectopic activation of Sox9 in the digit 1 field and preaxial polydactyly in a Gli1- and Gli3-dependent manner. In addition, we show that the syndactyly documented in Sclerosteosis is present in both Sost(-/-) and Sost(-/-); Sostdc1(-/-) mice, and is driven by misregulation of Fgf8 in the AER, a region lacking Sost and Sostdc1 expression. This study highlights the complexity of WNT signaling in skeletal biology and disease and emphasizes how redundant mechanism and non-cell autonomous effects can synergize to unveil new intricate phenotypes caused by elevated WNT signaling