The Applicability of Video Self-Modeling for Adults With Developmental and Intellectual Disabilities

Video Self-Modeling (VSM) has shown to be an effective intervention in modifying maladaptive behaviors in children, particularly those with Intellectual and/or Developmental Disabilities (ID/DD). Although the effectiveness of VSM with children with ID/DD has been well established in the extant literature, considerably fewer studies have addressed the applicability of VSM with adults of the same population. Thus, the goal of the current study was to examine the utility of VSM with three adults with ID/DD, specifically targeting table manners as the behavior of interest for the intervention. Two aspects of table manners were measured utilizing a multiple baseline design: food spillage on the person and appropriate napkin use. Data were graphed and analyzed on the basis of level, trend, and variability. Results indicated that the intervention was successful with Participant 2 on the appropriate napkin use variable, but not on food spillage on the person. Participants 1 and 3 did not evidence significant changes in behavior following the introduction of the VSM intervention. Possible reasons for the limited success of this intervention include the complexity of the target behaviors, age of participants at age of intervention, and lack of changes in environment to reinforce learning gained from videos. Future research should examine possible limits of the VSM technique as well as ways of utilizing the VSM procedure to function most effectively with older adults

Survivors Of Pediatric Brain Tumors: Psychosocial Outcomes And Executive Function

Children treated with CNS-directed therapy for brain tumor (BT) are at significant risk for developing late effects secondary to both disease and treatment. Executive functions (EF) encompass those skills necessary for appropriate problem solving and other goal-directed behaviors. Although no homogenous neuropsychological profile exists in patients with brain tumors, the most affected cognitive domains include EF and related processes, with the magnitude of effect increasing over time. Deficits in EF have been implicated in the etiology of internalizing, externalizing, and social disorders suggesting that EF is a foundational cognitive process. With a growing population of pediatric BT survivors at risk for EF deficits, it is important to consider the relationship between EF and psychosocial outcomes. The aim of the current study was to determine the relationship between EF and psychosocial outcomes over time among pediatric BT survivors. This study examined divergent trajectories of psychosocial outcomes and the association of change in executive function with these trajectories. Survivors of pediatric embryonal tumors (n = 166) treated on an international, multi-site protocol for newly diagnosed brain tumors were included in the current study. Participants were approximately 9 years at enrollment (SD = 3.10), mostly male (61.45%), Caucasian (75.90%), and treated for average risk disease (75.30%). Multiple tumor types were represented; however, most were diagnosed with medulloblastoma (83.73%). Participants and their families completed measures of psychosocial and executive functioning at baseline and yearly thereafter for five years. Growth mixture modeling revealed the presence of three latent class trajectories for Internalizing, Externalizing, and Total Problems. Two latent class trajectories were observed for Social Competence. Most did not report clinically significant concerns related to psychosocial functioning; however, a small subset did. Impairment persisted across 5-year follow-up. Working memory, attention, behavior regulation, and metacognition abilities declined over time. Binary and multinomial logistic regression demonstrated that change in EF over time is predictive of psychosocial trajectory. Findings suggest that a subset of pediatric BT survivors experience psychosocial difficulties secondary to disease and treatment that persist without intervention. EF appears to be foundationally related to psychosocial difficulties and may be an appropriate target of intervention

The Rise and Fall, and the Rise (Again) of Feminist Research in Music: 'What Goes Around Comes Around'

This article reports from a two-phase study that involved an analysis of the extant literature followed by a three-part survey answered by seventy-one women composers. Through these theoretical and empirical data, the authors explore the relationship between gender and music’s symbolic and cultural capital. Bourdieu’s theory of the habitus is employed to understand the gendered experiences of the female composers who participated in the survey. The article suggests that these female composers have different investments in gender but that, overall, they reinforce the male habitus given that the female habitus occupies a subordinate position in relation to that of the male. The findings of the study also suggest a connection between contemporary feminism and the attitudes towards gender held by the participants. The article concludes that female composers classify themselves, and others, according to gendered norms and that these perpetuate the social order in music in which the male norm dominates

Lupus-related single nucleotide polymorphisms and risk of diffuse large B-cell lymphoma

Objective: Determinants of the increased risk of diffuse large B-cell lymphoma (DLBCL) in SLE are unclear. Using data from a recent lymphoma genome-wide association study (GWAS), we assessed whether certain lupus-related single nucleotide polymorphisms (SNPs) were also associated with DLBCL. Methods: GWAS data on European Caucasians from the International Lymphoma Epidemiology Consortium (InterLymph) provided a total of 3857 DLBCL cases and 7666 general-population controls. Data were pooled in a random-effects meta-analysis. Results: Among the 28 SLE-related SNPs investigated, the two most convincingly associated with risk of DLBCL included the CD40 SLE risk allele rs4810485 on chromosome 20q13 (OR per risk allele=1.09, 95% CI 1.02 to 1.16, p=0.0134), and the HLA SLE risk allele rs1270942 on chromosome 6p21.33 (OR per risk allele=1.17, 95% CI 1.01 to 1.36, p=0.0362). Of additional possible interest were rs2205960 and rs12537284. The rs2205960 SNP, related to a cytokine of the tumour necrosis factor superfamily TNFSF4, was associated with an OR per risk allele of 1.07, 95% CI 1.00 to 1.16, p=0.0549. The OR for the rs12537284 (chromosome 7q32, IRF5 gene) risk allele was 1.08, 95% CI 0.99 to 1.18, p=0.0765. Conclusions: These data suggest several plausible genetic links between DLBCL and SLE

Phenotypic spectrum and transcriptomic profile associated with germline variants in TRAF7

PURPOSE: Somatic variants in tumor necrosis factor receptor-associated factor 7 (TRAF7) cause meningioma, while germline variants have recently been identified in seven patients with developmental delay and cardiac, facial, and digital anomalies. We aimed to define the clinical and mutational spectrum associated with TRAF7 germline variants in a large series of patients, and to determine the molecular effects of the variants through transcriptomic analysis of patient fibroblasts. METHODS: We performed exome, targeted capture, and Sanger sequencing of patients with undiagnosed developmental disorders, in multiple independent diagnostic or research centers. Phenotypic and mutational comparisons were facilitated through data exchange platforms. Whole-transcriptome sequencing was performed on RNA from patient- and control-derived fibroblasts. RESULTS: We identified heterozygous missense variants in TRAF7 as the cause of a developmental delay-malformation syndrome in 45 patients. Major features include a recognizable facial gestalt (characterized in particular by blepharophimosis), short neck, pectus carinatum, digital deviations, and patent ductus arteriosus. Almost all variants occur in the WD40 repeats and most are recurrent. Several differentially expressed genes were identified in patient fibroblasts. CONCLUSION: We provide the first large-scale analysis of the clinical and mutational spectrum associated with the TRAF7 developmental syndrome, and we shed light on its molecular etiology through transcriptome studies

Genetically predicted longer telomere length is associated with increased risk of B-cell lymphoma subtypes

Evidence from a small number of studies suggests that longer telomere length measured in peripheral leukocytes is associated with an increased risk of non-Hodgkin lymphoma (NHL). However, these studies may be biased by reverse causation, confounded by unmeasured environmental exposures and might miss time points for which prospective telomere measurement would best reveal a relationship between telomere length and NHL risk. We performed an analysis of genetically inferred telomere length and NHL risk in a study of 10 102 NHL cases of the four most common B-cell histologic types and 9562 controls using a genetic risk score (GRS) comprising nine telomere length-associated single-nucleotide polymorphisms. This approach uses existing genotype data and estimates telomere length by weighing the number of telomere length-associated variant alleles an individual carries with the published change in kb of telomere length. The analysis of the telomere length GRS resulted in an association between longer telomere length and increased NHL risk [four B-cell histologic types combined; odds ratio (OR) = 1.49, 95% CI 1.22–1.82, P-value = 8.5 × 10−5]. Subtype-specific analyses indicated that chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) was the principal NHL subtype contributing to this association (OR = 2.60, 95% CI 1.93–3.51, P-value = 4.0 × 10−10). Significant interactions were observed across strata of sex for CLL/SLL and marginal zone lymphoma subtypes as well as age for the follicular lymphoma subtype. Our results indicate that a genetic background that favors longer telomere length may increase NHL risk, particularly risk of CLL/SLL, and are consistent with earlier studies relating longer telomere length with increased NHL risk

Case Reports1. A Late Presentation of Loeys-Dietz Syndrome: Beware of TGFβ Receptor Mutations in Benign Joint Hypermobility

Background: Thoracic aortic aneurysms (TAA) and dissections are not uncommon causes of sudden death in young adults. Loeys-Dietz syndrome (LDS) is a rare, recently described, autosomal dominant, connective tissue disease characterized by aggressive arterial aneurysms, resulting from mutations in the transforming growth factor beta (TGFβ) receptor genes TGFBR1 and TGFBR2. Mean age at death is 26.1 years, most often due to aortic dissection. We report an unusually late presentation of LDS, diagnosed following elective surgery in a female with a long history of joint hypermobility. Methods: A 51-year-old Caucasian lady complained of chest pain and headache following a dural leak from spinal anaesthesia for an elective ankle arthroscopy. CT scan and echocardiography demonstrated a dilated aortic root and significant aortic regurgitation. MRA demonstrated aortic tortuosity, an infrarenal aortic aneurysm and aneurysms in the left renal and right internal mammary arteries. She underwent aortic root repair and aortic valve replacement. She had a background of long-standing joint pains secondary to hypermobility, easy bruising, unusual fracture susceptibility and mild bronchiectasis. She had one healthy child age 32, after which she suffered a uterine prolapse. Examination revealed mild Marfanoid features. Uvula, skin and ophthalmological examination was normal. Results: Fibrillin-1 testing for Marfan syndrome (MFS) was negative. Detection of a c.1270G > C (p.Gly424Arg) TGFBR2 mutation confirmed the diagnosis of LDS. Losartan was started for vascular protection. Conclusions: LDS is a severe inherited vasculopathy that usually presents in childhood. It is characterized by aortic root dilatation and ascending aneurysms. There is a higher risk of aortic dissection compared with MFS. Clinical features overlap with MFS and Ehlers Danlos syndrome Type IV, but differentiating dysmorphogenic features include ocular hypertelorism, bifid uvula and cleft palate. Echocardiography and MRA or CT scanning from head to pelvis is recommended to establish the extent of vascular involvement. Management involves early surgical intervention, including early valve-sparing aortic root replacement, genetic counselling and close monitoring in pregnancy. Despite being caused by loss of function mutations in either TGFβ receptor, paradoxical activation of TGFβ signalling is seen, suggesting that TGFβ antagonism may confer disease modifying effects similar to those observed in MFS. TGFβ antagonism can be achieved with angiotensin antagonists, such as Losartan, which is able to delay aortic aneurysm development in preclinical models and in patients with MFS. Our case emphasizes the importance of timely recognition of vasculopathy syndromes in patients with hypermobility and the need for early surgical intervention. It also highlights their heterogeneity and the potential for late presentation. Disclosures: The authors have declared no conflicts of interes