Do emotional difficulties and peer problems hew together from childhood to adolescence? The case of children with a history of developmental language disorder (DLD)

Children and adolescents with developmental language disorder (DLD) are, overall, vulnerable to difficulties in emotional adjustment and in peer relations. However, previous research has shown that different subgroups follow different trajectories in respect of quality of peer relations. Less is known of the trajectories of emotional development. We consider here the possibility that development in these two domains is interrelated: that is, the trajectories of emotional and peer problems will proceed in parallel. We conducted longitudinal joint trajectories analyses of emotional and peer relations in a sample of young people identified as having DLD at age 7 years and seen at intervals up to 16 years. Potential influences on joint trajectory group membership were examined. Findings revealed five distinct joint trajectories. Emotional and peer difficulties do hew together from childhood to adolescence for just over half of the sample, but not all. The variables most clearly associated with group membership were pragmatic language ability, prosociality and parental mental health. This is the first study to examine joint longitudinal trajectories of emotional and peer difficulties in individuals with DLD. We demonstrate that development in individuals with DLD is heterogeneous and identify three key variables associated with personal and social adjustment from childhood to adolescence. Theoretical and clinical implications of these findings are discussed

PhD fieldwork in developing countries – The issue of time

Educational field research in developing country contexts often exposes the fragility of mutual understanding and the tensions of diversity between researchers and those with whom they are researching. Postgraduate researchers face particular challenges arising from their lack of experience, and from the focused, individual nature of their enquiry. Logistical, emotional and ethical issues present themselves, even for researchers studying their cultures of origin. This paper seeks to learn some lessons from the experiences of a group of researchers doing fieldwork in developing countries for the first time, as part of their PhD. A review of the literature around fieldwork reveals substantially conflicting guidance for field researchers. Practical tips (Robson et al, 1991; Nash, 2000) contrast with the writings of anthropologists such as Geertz (1988), Rosaldo (1993) or Scheper-Hughes (1992), suggesting unavoidable complexities in terms of ethics, the building and maintenance of relationships, and the perceptions of both the researcher and those with whom he or she is researching. The experiences of a group of individual PhD field researchers form the central section of the paper, making use of a framework in which each sets out to explore examples of the relationships between the person of the researcher; the activities of the research, and a central but easily-overlooked feature of the field: the issue of time. These relationships are seen to impact on the nature of the main and often contentious object of academic research, data: its nature, its validity and reliability; or more broadly, on the development of a deeper understanding of individuals and institutions. Part of the power of these examples lies in the range of contexts and individuals represented. Activity theory is used as a basic framework through which to interrogate these experiences. Finally, the arguments of literature are challenged and developed in relation to these experiences, leading to some propositions but also exploring some critical questions, to form a useful basis for further discussion. The experiences of the authors might be of interest to other researchers doing fieldwork in the developing world

Depression and Anxiety Change from Adolescence to Adulthood in Individuals with and without Language Impairment

This prospective longitudinal study aims to determine patterns and predictors of change in depression and anxiety from adolescence to adulthood in individuals with language impairment (LI). Individuals with LI originally recruited at age 7 years and a comparison group of age-matched peers (AMPs) were followed from adolescence (16 years) to adulthood (24 years). We determine patterns of change in depression and anxiety using the Child Manifest Anxiety Scale-Revised (CMAS-R) and Short Moods and Feelings Questionnaire (SMFQ). In addition to examining associations with gender, verbal and nonverbal skills, we use a time-varying variable to investigate relationships between depression and anxiety symptoms and transitions in educational/employment circumstances. The results show that anxiety was higher in participants with LI than age matched peers and remained so from adolescence to adulthood. Individuals with LI had higher levels of depression symptoms than did AMPs at 16 years. Levels in those with LI decreased post-compulsory schooling but rose again by 24 years of age. Those who left compulsory school provision (regardless of school type) for more choice-driven college but who were not in full-time employment or study by 24 years of age were more likely to show this depression pathway. Verbal and nonverbal skills were not predictive of this pattern of depression over time. The typical female vulnerability for depression and anxiety was observed for AMPs but not for individuals with LI. These findings have implications for service provision, career/employment advice and support for individuals with a history of LI during different transitions from adolescence to adulthood

PhD fieldwork in developing countries – The issue of time.

13 p. -- Accepted ManuscriptEducational field research in developing country contexts often exposes the fragility of mutual understanding and the tensions of diversity between researchers and those with whom they are researching. Postgraduate researchers face particular challenges arising from their lack of experience, and from the focused, individual nature of their enquiry. Logistical, emotional and ethical issues present themselves, even for researchers studying their cultures of origin. This paper seeks to learn some lessons from the experiences of a group of researchers doing fieldwork in developing countries for the first time, as part of their PhD. A review of the literature around fieldwork reveals substantially conflicting guidance for field researchers. Practical tips (Robson et al, 1991; Nash, 2000) contrast with the writings of anthropologists such as Geertz (1988), Rosaldo (1993) or Scheper-Hughes (1992), suggesting unavoidable complexities in terms of ethics, the building and maintenance of relationships, and the perceptions of both the researcher and those with whom he or she is researching. The experiences of a group of individual PhD field researchers form the central section of the paper, making use of a framework in which each sets out to explore examples of the relationships between the person of the researcher; the activities of the research, and a central but easily-overlooked feature of the field: the issue of time. These relationships are seen to impact on the nature of the main and often contentious object of academic research, data: its nature, its validity and reliability; or more broadly, on the development of a deeper understanding of individuals and institutions. Part of the power of these examples lies in the range of contexts and individuals represented. Activity theory is used as a basic framework through which to interrogate these experiences. Finally, the arguments of literature are challenged and developed in relation to these experiences, leading to some propositions but also exploring some critical questions, to form a useful basis for further discussion. The experiences of the authors might be of interest to other researchers doing fieldwork in the developing world

Assessment of the incorporation of CNV surveillance into gene panel next-generation sequencing testing for inherited retinal diseases.

BACKGROUND: Diagnostic use of gene panel next-generation sequencing (NGS) techniques is commonplace for individuals with inherited retinal dystrophies (IRDs), a highly genetically heterogeneous group of disorders. However, these techniques have often failed to capture the complete spectrum of genomic variation causing IRD, including CNVs. This study assessed the applicability of introducing CNV surveillance into first-tier diagnostic gene panel NGS services for IRD. METHODS: Three read-depth algorithms were applied to gene panel NGS data sets for 550 referred individuals, and informatics strategies used for quality assurance and CNV filtering. CNV events were confirmed and reported to referring clinicians through an accredited diagnostic laboratory. RESULTS: We confirmed the presence of 33 deletions and 11 duplications, determining these findings to contribute to the confirmed or provisional molecular diagnosis of IRD for 25 individuals. We show that at least 7% of individuals referred for diagnostic testing for IRD have a CNV within genes relevant to their clinical diagnosis, and determined a positive predictive value of 79% for the employed CNV filtering techniques. CONCLUSION: Incorporation of CNV analysis increases diagnostic yield of gene panel NGS diagnostic tests for IRD, increases clarity in diagnostic reporting and expands the spectrum of known disease-causing mutations

EyeG2P: an automated variant filtering approach improves efficiency of diagnostic genomic testing for inherited ophthalmic disorders

BACKGROUND: Genomic variant prioritisation is one of the most significant bottlenecks to mainstream genomic testing in healthcare. Tools to improve precision while ensuring high recall are critical to successful mainstream clinical genomic testing, in particular for whole genome sequencing where millions of variants must be considered for each patient. METHODS: We developed EyeG2P, a publicly available database and web application using the Ensembl Variant Effect Predictor. EyeG2P is tailored for efficient variant prioritisation for individuals with inherited ophthalmic conditions. We assessed the sensitivity of EyeG2P in 1234 individuals with a broad range of eye conditions who had previously received a confirmed molecular diagnosis through routine genomic diagnostic approaches. For a prospective cohort of 83 individuals, we assessed the precision of EyeG2P in comparison with routine diagnostic approaches. For 10 additional individuals, we assessed the utility of EyeG2P for whole genome analysis. RESULTS: EyeG2P had 99.5% sensitivity for genomic variants previously identified as clinically relevant through routine diagnostic analysis (n=1234 individuals). Prospectively, EyeG2P enabled a significant increase in precision (35% on average) in comparison with routine testing strategies (p<0.001). We demonstrate that incorporation of EyeG2P into whole genome sequencing analysis strategies can reduce the number of variants for analysis to six variants, on average, while maintaining high diagnostic yield. CONCLUSION: Automated filtering of genomic variants through EyeG2P can increase the efficiency of diagnostic testing for individuals with a broad range of inherited ophthalmic disorders

Sandbox university: Estimating influence of institutional action

The approach presented in this article represents a generalizable and adaptable methodology for identifying complex interactions in educational systems and for investigating how manipulation of these systems may affect educational outcomes of interest. Multilayer Minimum Spanning Tree and Monte-Carlo methods are used. A virtual Sandbox University is created in order to facilitate effective identification of successful and stable initiatives within higher education, which can affect students' credits and student retention - something that has been lacking up until now. The results highlight the importance of teacher feedback and teacher-student rapport, which is congruent with current educational findings, illustrating the methodology's potential to provide a new basis for further empirical studies of issues in higher education from a complex systems perspective

Mitochondrial Uncoupling Protein-2 (UCP2) Mediates Leptin Protection Against MPP+ Toxicity in Neuronal Cells

Mitochondrial dysfunction is involved in the pathogenesis of neurodegenerative diseases, including Parkinson’s disease (PD). Uncoupling proteins (UCPs) delink ATP production from biofuel oxidation in mitochondria to reduce oxidative stress. UCP2 is expressed in brain, and has neuroprotective effects under various toxic insults. We observed induction of UCP2 expression by leptin in neuronal cultures, and hypothesize that leptin may preserve neuronal survival via UCP2. We showed that leptin preserved cell survival in neuronal SH-SY5Y cells against MPP+ toxicity (widely used in experimental Parkinsonian models) by maintaining ATP levels and mitochondrial membrane potential (MMP); these effects were accompanied by increased UCP2 expression. Leptin had no effect in modulating reactive oxygen species levels. Stable knockdown of UCP2 expression reduced ATP levels, and abolished leptin protection against MPP+-induced mitochondrial depolarization, ATP deficiency, and cell death, indicating that UCP2 is critical in mediating these neuroprotective effects of leptin against MPP+ toxicity. Interestingly, UCP2 knockdown increased UCP4 expression, but not of UCP5. Our findings show that leptin preserves cell survival by maintaining MMP and ATP levels mediated through UCP2 in MPP+-induced toxicity