Activation During Observed Parent–Child Interactions with Anxious Youths: A Pilot Study

Parent–child interaction paradigms are often used to observe dysfunctional family processes; however, the influence of such tasks on a participant’s level of activation remain unclear. The aim of this pilot project is to explore the stimulus value of interaction paradigms that have been commonly used in child anxiety research. Twenty-nine parent–child dyads with clinically anxious (n = 16) and non-anxious (n = 13) youths engaged in a series of tasks (threat and non-threat) used in previous studies of parenting and youth anxiety. Heart rate (HR) data, as an indicator of physiological activation, were collected across tasks, and participants rated the perceived representativeness of their interactions in the laboratory to their usual behavior at home. Significant HR changes were observed for both parent and child. Change in child HR from baseline to non-threat task was smaller than change in HR from baseline to threat tasks. Change in parent HR from baseline to ambiguous situations tasks was smaller than changes from baseline to other threat tasks. Differences in HR change between anxious and non-anxious children were explored. Participants rated laboratory interactions as similar to those experienced in the home. Results suggest that presumably emotionally-charged discussion tasks may produce increased activation compared to tasks that were designed to be more neutral. Implications for future research and limitations are discussed

An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers

Introduction: Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. Methods: We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. Results: We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. Conclusions: This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects.Peer reviewe

Feedback in clinical practice: Enhancing the students’ experience through action research

Feedback to student nurses and midwives within clinical practice is known to be central to their learning and development. A study that focused on student experience of assessment identified that a high proportion of students reported that they had received insufficient feedback whilst on clinical placement. In response to this academics and members of the clinical education team set out to explore this with a view to improving the student experience using action research. Key findings indicated that responsibility for feedback on clinical placement lies with both students and mentors, distinct factors can enable effective feedback and that positive outcomes for mentors and students resulted through engaging with the project. The process, outcomes and actions taken to improve practice are the focus of this pape

Mutations in SRCAP, Encoding SNF2-Related CREBBP Activator Protein, Cause Floating-Harbor Syndrome

Floating-Harbor syndrome (FHS) is a rare condition characterized by short stature, delayed osseous maturation, expressive-language deficits, and a distinctive facial appearance. Occurrence is generally sporadic, although parent-to-child transmission has been reported on occasion. Employing whole-exome sequencing, we identified heterozygous truncating mutations in SRCAP in five unrelated individuals with sporadic MS. Sanger sequencing identified mutations in SRCAP in eight more affected persons. Mutations were de novo in all six instances in which parental DNA was available. SRCAP is an SNF2-related chromatin-remodeling factor that serves as a coactivator for CREB-binding protein (CREBBP, better known as CBP, the major cause of Rubinstein-Taybi syndrome [RTS]). Five SRCAP mutations, two of which are recurrent, were identified; all are tightly clustered within a small (111 codon) region of the final exon. These mutations are predicted to abolish three C-terminal AT-hook DNA-binding motifs while leaving the CBP-binding and ATPase domains intact. Our findings show that SRCAP mutations are the major cause of FHS and offer an explanation for the clinical overlap between FHS and RTS.government of Canada through Genome Canadagovernment of Canada through Genome CanadaCanadian Institutes of Health Research (CIHR)Canadian Institutes of Health Research (CIHR)Ontario Genomics Institute [OGI-049]Ontario Genomics InstituteGenome QuebecGenome QuebecGenome British ColumbiaGenome British ColumbiaCIHR Institute of GeneticsCIHR Institute of Genetic