Caregiver- and Child-Reported Anxiety Using an Autism-Specific Measure: Measurement Properties and Correlates of the Anxiety Scale for Children with Autism Spectrum Disorder (ASC-ASD) in Verbal Young People with ASD

Identifying and measuring anxiety in young people on the autism spectrum can be challenging. The present study investigated the use of the Anxiety Scale for Children with Autism Spectrum Disorder (ASC-ASD), a self- and caregiver-rated screening tool in a Singaporean sample of ninety-one verbal autistic youths and their caregivers. Internal consistency ranged from satisfactory to desirable (α?=?.74–.92). Convergent validity with medium-large effect size was established using a structured diagnostic interview, the Mini-International Neuropsychiatric Interview for Children and Adolescents (MINI-KID). ASC-ASD scores were positively associated with autistic symptoms and response patterns indicated strong endorsement of autism-specific items. The findings are discussed in relation to existing literature on assessment of anxiety in ASD and in light of the study’s strengths and limitations.

     

The association between HLA genes and radiological erosions in Malaysian patients with rheumatoid arthritis

Objective: To assess the relationship between the HLA-DRB1 genes with disease severity as assessed by radiological erosions in Malaysian patients with rheumatoid arthritis (RA).

Methods: In this cross-sectional study, we studied 61 RA patients who fulfilled the ACR criteria for the diagnosis of RA. HLA-DRB1 genotyping was performed by sequence specific primer (SSP)—PCR. Radiological grading and erosive score of the hands and wrists was calculated according to the Larsen–Dale method. Demographic data and treatment given to the patients were obtained from their case records.

Results: Fifty-six females and five males were studied from three ethnic groups. In 57 patients with erosions, rheumatoid factor was detected in 80%, HLA-DR4 in 40%, HLA-DRB1*0405 in 24% and shared epitope (SE) in 31%. The median delay in starting DMARDs was 24 months. The presence of rheumatoid factor, HLA-DR4 and HLA-DRB1*0405 were not significantly associated with a worse erosive score. Patients who possessed the SE had a higher erosive scores, compared to those who did not (p = 0.05). Concurrently, a delay in starting DMARD was associated with a high erosive score (p = 0.023, r = 0.348). However, after adjustment for the delay in starting DMARD, SE was no longer significantly associated with the erosive score.

Conclusions: In these patients, the delay in starting DMARDs had a greater influence on the erosive score than SE alone. Whilst we cannot discount the contribution of the SE presence, we would advocate early usage of DMARDs in every RA patient to reduce joint erosions and future disability.     

An analysis of the continuing professional development needs of radiographers and radiation therapists in Singapore

IntroductionContinuing Professional development (CPD) is deemed essential for the Radiographers (DR) and Radiation Therapists (RT) after Singapore commenced state registration. Diagnostic imaging and radiotherapy treatment services are constantly revolutionizing and those working in this field requires sufficient knowledge of the uptrends for training and development. The purpose of this survey is to identify the current training needs of the registered DR and RT in Singapore, and to understand their views about CPD activities.MethodsAn online questionnaire was disseminated by the Singapore Society of Radiographers (SSR) to all registered DR and RT in Singapore, and all practicing in restructured and private hospitals were included. Data collection took place from January 2018 to April 2018.Results102 responses were analysed, where 89 were DR and 13 were RT. CPD was provided in 72.5% (n = 74) of the participants’ institutions, and 69.6% (n = 71) of participants were aware of CPD. Interestingly, participants were significantly more likely to be unaware of CPD when working in an institution which do not offer CPD. Training programme objective was the most important factor for selecting a programme. 93.1% (n = 95) preferred SSR to support them for CPD. There were a few constraints to CPD engagements identified such as financial factors, lack of time, and institution availability.ConclusionThere was significant intrinsic motivation in a quality CPD activity. CPD activities should be current, accessible and relevant for the healthcare professionals to increase participation, which directly contributes to high standards of clinical care.Implications for practiceLocal healthcare institutions should be aware and address needs, gaps and aspirations of the local DR and RT community to ensure adequate preparation has been made upon initiation of mandatory CPD.     

Numerical study of unsteady stenosis flow: parametric evaluation of power-law model

Currently the best indicator for surgical treatment of arteriosclerosis is the degree of stenosis. Although X-ray angiography is currently the standard, cost and morbidity are distinct disadvantages. By modelling stenosis and studying its biofluid mechanics, one can apply its results in the field of arterial disease research. This formed the motivation for this work. A non-Newtonian (power law) incompressible Navier-Stokes (N- S) solver was developed using the method of operator splitting and artificial compressibility. The vehicle used is the computational fluid dynamics (CFD) numerical library FASTFLO. The power-law model developed is then used to do a parametric study of the effect of 'n' on blood flow mechanics where 'n' is the power index that determines the haematocrit of blood. A pulsatile pressure wave over a cardiac cycle of a second was used to simulate transient flow over a hypothetical twodimensional stenotic geometry. By comparing the different velocity pressure, wall shear stress and viscosity profiles, it has been found when 'n' increases, the vortex formation and peak wall shear stress decreases (magnitudes of < 1.5 Pa). Since the formation of vortices and lowoscillatory wall shear stress on the stenotic wall is detrimental to the well-being of the arterial tract, it can therefore be inferred that there might be a relationship between the diseased state of blood (power law) and early genesis of atherosclerosis. However, the conclusion of this paper marks the advent of new research directions in this field of study.     

Streamlined human antibody generation and optimization by exploiting designed immunoglobulin loci in a B cell line

Monoclonal antibodies (mAbs) are widely utilized as therapeutic drugs for various diseases, such as cancer, autoimmune diseases, and infectious diseases. Using the avian-derived B cell line DT40, we previously developed an antibody display technology, namely, the ADLib system, which rapidly generates antigen-specific mAbs. Here, we report the development of a human version of the ADLib system and showcase the streamlined generation and optimization of functional human mAbs. Tailored libraries were first constructed by replacing endogenous immunoglobulin genes with designed human counterparts. From these libraries, clones producing full-length human IgGs against distinct antigens can be isolated, as exemplified by the selection of antagonistic mAbs. Taking advantage of avian biology, effective affinity maturation was achieved in a straightforward manner by seamless diversification of the parental clones into secondary libraries followed by single-cell sorting, quickly affording mAbs with improved affinities and functionalities. Collectively, we demonstrate that the human ADLib system could serve as an integrative platform with unique diversity for rapid de novo generation and optimization of therapeutic or diagnostic antibody leads. Furthermore, our results suggest that libraries can be constructed by introducing exogenous genes into DT40 cells, indicating that the ADLib system has the potential to be applied for the rapid and effective directed evolution and optimization of proteins in various fields beyond biomedicine.     

Dysregulated TGF‐β signaling alters bone microstructure in a mouse model of Loeys‐Dietz syndrome

Loeys‐Dietz syndrome (LDS) is a connective tissue disorder characterized by vascular and skeletal abnormalities resembling Marfan syndrome, including a predisposition for pathologic fracture. LDS is caused by heterozygous mutations in the genes encoding transforming growth factor‐β (TGF‐β) type 1 and type 2 receptors. In this study, we characterized the skeletal phenotype of mice carrying a mutation in the TGF‐β type 2 receptor associated with severe LDS in humans. Cortical bone in LDS mice showed significantly reduced tissue area, bone area, and cortical thickness with increased eccentricity. However, no significant differences in trabecular bone volume were observed. Dynamic histomorphometry performed in calcein‐labeled mice showed decreased mineral apposition rates in cortical and trabecular bone with normal numbers of osteoblasts and osteoclasts. Mechanical testing of femurs by three‐point bending revealed reduced femoral strength and fracture resistance. In vitro, osteoblasts from LDS mice demonstrated increased mineralization with enhanced expression of osteoblast differentiation markers compared with control cells. These changes were associated with impaired TGF‐β1–induced Smad2 and Erk1/2 phosphorylation and upregulated TGF‐β1 ligand mRNA expression, compatible with G357W as a loss‐of‐function mutation in the TGF‐β type 2 receptor. Paradoxically, phosphorylated Smad2/3 in cortical osteocytes measured by immunohistochemistry was increased relative to controls, possibly suggesting the cross‐activation of TGF‐β–related receptors. The skeletal phenotype observed in the LDS mouse closely resembles the principal structural features of bone in humans with LDS and establishes this mouse as a valid in vivo model for further investigation of TGF‐β receptor signaling in bone. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1447–1454, 2015.