ExprAlign - the identification of ESTs in non-model species by alignment of cDNA microarray expression profiles

<p>Abstract</p> <p>Background</p> <p>Sequence identification of ESTs from non-model species offers distinct challenges particularly when these species have duplicated genomes and when they are phylogenetically distant from sequenced model organisms. For the common carp, an environmental model of aquacultural interest, large numbers of ESTs remained unidentified using BLAST sequence alignment. We have used the expression profiles from large-scale microarray experiments to suggest gene identities.</p> <p>Results</p> <p>Expression profiles from ~700 cDNA microarrays describing responses of 7 major tissues to multiple environmental stressors were used to define a co-expression landscape. This was based on the Pearsons correlation coefficient relating each gene with all other genes, from which a network description provided clusters of highly correlated genes as 'mountains'. We show that these contain genes with known identities and genes with unknown identities, and that the correlation constitutes evidence of identity in the latter. This procedure has suggested identities to 522 of 2701 unknown carp ESTs sequences. We also discriminate several common carp genes and gene isoforms that were not discriminated by BLAST sequence alignment alone. Precision in identification was substantially improved by use of data from multiple tissues and treatments.</p> <p>Conclusion</p> <p>The detailed analysis of co-expression landscapes is a sensitive technique for suggesting an identity for the large number of BLAST unidentified cDNAs generated in EST projects. It is capable of detecting even subtle changes in expression profiles, and thereby of distinguishing genes with a common BLAST identity into different identities. It benefits from the use of multiple treatments or contrasts, and from the large-scale microarray data.</p

Measuring coping style following acquired brain injury: a modification of the Coping Inventory for Stressful Situations Using Rasch analysis.

OBJECTIVE: The importance of coping style factors in the process of emotional adjustment following acquired brain injury (ABI) has been gaining increased attention. To assess ways of coping with distress accurately, clear conceptual definitions and measurement precision is vital. The purpose of this study was to investigate the psychometric properties of a well-known measure of coping, the Coping Inventory for Stressful Situations (CISS), for people who have experienced an ABI; and to modify the CISS, where necessary, to create a more reliable and valid measurement tool for this clinical group. METHODS: Psychometric properties were investigated using Rasch analysis of responses from a sample of adults with ABI (n = 207). The internal consistency reliability and construct validity of the scale were examined. RESULTS: All originally proposed subscales were not valid or reliable and, as such, were incapable of interval-level measurement within this sample - Task: χ(2) (32, N = 207) = 105.1, p < .001; Emotion: χ(2) (32, N = 204) = 121.9, p < .001; Avoidance: χ(2) (32, N = 207) = 66.7, p < .001. Three valid and reliable subscales were derived measuring emotion-, task-, and avoidance-oriented coping styles by removing items that provided the most unreliable information and exploring fit to the Rasch model. CONCLUSIONS: The original version of the CISS may not be a valid and reliable measure of coping style following ABI. Modified subscales of the three distinct coping domains have been proposed that would help to improve measurement of coping style following ABI in future research and clinical practice. PRACTITIONER POINTS: How people cope with difficulties following an ABI has been shown to impact upon emotional outcomes and functional recovery. The original version of the CISS was found to be an imprecise measure of coping following ABI. A modified version of the CISS was found to be a valid and reliable measure of three styles of coping (task-focused, emotion-focused, and avoidance-focused) that conforms to the properties of interval-level measurement as represented by the Rasch model. This structure is in keeping with previous theoretical models of coping. We advise caution about including items (1, 6, 7, 22, 24, 28, 29, 33, 34, and 46) that were found to diverge from the expectations of the Rasch measurement model in total subscale scores for measuring change in coping style. A conversion table for the three modified subscales is included in this paper to convert total raw scores into Rasch transformed logit values. Identifying strengths and weaknesses in coping style could be a means of guiding psychological intervention to promote good recovery following ABI. The sample included mainly people who had experienced non-traumatic brain injuries (e.g., a stroke). This research could be extended to include broader sample of people with differing brain injury aetiologies and neurological disorders.This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1111/bjc.1207

Detecting mental health problems after paediatric acquired brain injury: A pilot Rasch analysis of the strengths and difficulties questionnaire

The parent-reported Strengths and Difficulties Questionnaire (SDQ-P) is commonly used to assess for mental health problems, but its psychometric properties have not been studied in the paediatric Acquired Brain Injury (ABI) population. This study investigated the properties of the SDQ-P and its subscales in this population using Rasch analysis. One hundred and forty-three SDQ-Ps and 123 Impact Supplements were analyzed. Sixty-nine percent of SDQ-Ps were completed by female carers, 59% of young people were male, and 58% had Traumatic Brain Injury (TBI). In this population the SDQ-P Total Difficulties Scale and the Conduct Problems subscale showed questionable construct validity. The individual subscales and Impact Supplement did not meet the criteria for reliability. Two items had disordered thresholds. The individual subscales showed mistargeting and 13–24% person misfit. Two items were significantly underdiscriminating. There was differential item functioning with age and time post-injury, and local dependence between subscale items. The Total Difficulties scale was multidimensional. The most easily endorsed items were in keeping with common symptoms of brain injury. These findings suggest the SDQ-P in its current form may not be a reliable and valid assessment measure for mental health difficulties in the paediatric ABI population and requires further investigation

Building Wellbeing in People With Chronic Conditions: A Qualitative Evaluation of an 8-Week Positive Psychotherapy Intervention for People Living With an Acquired Brain Injury

Research indicates that Acquired Brain Injury (ABI) is associated with significant and chronic impairment across multiple areas of functioning including physical, cognitive, emotional and behavioural domains. Whilst impairments associated with ABI can be ameliorated, cure is seldom possible. The emergence of positive psychology reflects a paradigm shift in health and wellbeing research, highlighting the role of character strengths, positive emotions, meaning, and resilience. Positive psychology interventions have been demonstrated to improve wellbeing in a variety of populations, although research investigating the impact of positive psychotherapy for people living with ABI are sparse. Here we characterize the experience of an 8-week positive psychotherapy intervention for 13 people living with ABI including four mentors and nine participants using thematic analysis of transcripts collected during mini-groups and one-to-one interviews. Six main themes were identified including empowerment, social opportunity, coping, cultivation of positive emotion, consolidation of skills and barriers. Results indicated that wellbeing can be promoted and improved in individuals with ABI. Recent theoretical developments in wellbeing science highlight scope to improve the intervention by connecting individuals to their communities and spending time in nature

Selection and visualisation of outcome measures for complex post-acute acquired brain injury rehabilitation interventions.

BACKGROUND: Outcome measurement challenges rehabilitation services to select tools that promote stakeholder engagement in measuring complex interventions. OBJECTIVES: To examine the suitability of outcome measures for complex post-acute acquired brain injury (ABI) rehabilitation interventions, report outcomes of a holistic, neuropsychological ABI rehabilitation program and propose a simple way of visualizing complex outcomes. METHODS: Patient/carer reported outcome measures (PROMS), experience measures (PREMS) and staff-rated measures were collected for consecutive admissions over 1 year to an 18-week holistic, neuropsychological rehabilitation programme at baseline, 18 weeks and 3- and 6-month follow-up. RESULTS: Engagement with outcome measurement was poorest for carers and at follow-up for all stakeholders. Dependence, abilities, adjustment, unmet needs, symptomatology including executive dysfunction, and self-reassurance showed improvements at 18 weeks. Adjustment, social participation, perceived health, symptomatology including dysexecutive difficulties, and anxiety were worse at baseline for those who did not complete rehabilitation, than those who did. A radar plot facilitated outcome visualization. CONCLUSIONS: Engagement with outcome measurement was best when time and support were provided. Supplementing patient- with staff-rated and attendance measures may explain missing data and help quantify healthcare needs. The MPAI4, EBIQ and DEX-R appeared suitable measures to evaluate outcomes and distinguish those completing and not completing neuropsychological rehabilitation.National Institute for Health Researc

A randomized controlled trial of assisted intention monitoring for the rehabilitation of executive impairments following acquired brain injury

Background. Acquired brain injury (ABI) can impair executive function, impeding planning and attainment of intentions. Research shows promise for some goal-management rehabilitation interventions. However, evidence that alerts assist monitoring and completion of day-to-day intentions is limited. Objective. To examine the efficacy of brief goal-directed rehabilitation paired with periodic SMS text messages designed to enhance executive monitoring of intentions (assisted intention monitoring [AIM]). Methods. A randomized, double-blind, controlled trial was conducted. Following a baseline phase, 74 people with ABI and executive problems were randomized to receive AIM or control (information and games) for 3 weeks (phase 1) before crossing over to either AIM or no intervention (phase 2). The primary outcome was change in composite score of proportion of daily intentions achieved. A total of 59 people (71% male; 46% traumatic brain injury) completed all study phases. Results. Per protocol crossover analysis found a significant benefit of AIM for all intentions [F(1, 56) = 4.28; P = .04; f = 0.28; 3.7% mean difference; 95% CI = 0.1%-7.4%] and all intentions excluding a proxy prospective memory task [F(1, 55) = 4.79; P = .033; f = 0.28, medium effect size; 3% mean difference; 95% CI = 0.3%-5.6%] in the absence of significant changes on tests of executive functioning. Intention-to-treat analyses, comparing AIM against control at the end of phase 1 revealed no statistically significant differences in the attainment of intentions. Conclusion. Combining brief executive rehabilitation with alerts may be effective for some in improving achievement of daily intentions, but further evaluation of clinical effectiveness and mechanisms is required

An in vitro-identified high-affinity nucleosome-positioning signal is capable of transiently positioning a nucleosome in vivo

<p>Abstract</p> <p>Background</p> <p>The physiological function of eukaryotic DNA occurs in the context of nucleosomal arrays that can expose or obscure defined segments of the genome. Certain DNA sequences are capable of strongly positioning a nucleosome <it>in vitro</it>, suggesting the possibility that favorable intrinsic signals might reproducibly structure chromatin segments. As high-throughput sequencing analyses of nucleosome coverage <it>in vitro </it>and <it>in vivo </it>have become possible, a vigorous debate has arisen over the degree to which intrinsic DNA:nucleosome affinities orchestrate the <it>in vivo </it>positions of nucleosomes, thereby controlling physical accessibility of specific sequences in DNA.</p> <p>Results</p> <p>We describe here the <it>in vivo </it>consequences of placing a synthetic high-affinity nucleosome-positioning signal, the 601 sequence, into a DNA plasmid vector in mice. Strikingly, the 601 sequence was sufficient to position nucleosomes during an early phase after introduction of the DNA into the mice (when the plasmid vector transgene was active). This positioning capability was transient, with a loss of strong positioning at a later time point when the transgenes had become silent.</p> <p>Conclusions</p> <p>These results demonstrate an ability of DNA sequences selected solely for nucleosome affinity to organize chromatin <it>in vivo</it>, and the ability of other mechanisms to overcome these interactions in a dynamic nuclear environment.</p

Psychometric Properties of the Revised Dysexecutive Questionnaire in a Non-clinical Population

Aims: The aim of this study was to assess the psychometric properties of the revised self-rated version of the Dysexecutive Questionnaire (DEX-R) within a non-clinical sample. Methods: The study was hosted online, with 140 participants completing the DEX-R, GAD-2 and PHQ-2. Sixty participants also completed the FrSBe, with 99 additionally completing the DEX-R again 3 weeks later. Correlations with demographic factors and symptoms of anxiety and depression were conducted. Rasch and factor analysis were also used to explore underlying subconstructs. Results: The DEX-R correlated highly with the FrSBe, indicating sound concurrent validity. Internal consistency, split-half reliability and test-retest reliability were excellent. Age and symptoms of depression and anxiety correlated with DEX-R scores, with older age associated with less dysexecutive problems. The Rasch analysis confirmed the multidimensionality of the rating scale, and a three-factor structure was found relating to activation-self-regulatory, cognitive and social-emotional processes. Frequencies of responses on DEX-R items varied, many were not fully endorsed indicating specific relevance of most but not all items to patients. Conclusion: Interpretations of DEX-R ratings of dysexecutive problems should consider mood and individual variation. Systematic comparison of DEX-R responses between healthy and clinical groups could help identify a suitable cut off for dysexecutive symptoms

Cycles of heat exposure elevate metabolic enzyme genes and alters digestion in mussels

The intertidal sea mussel Mytilus californianus inhabits the Pacific coastline of North America. As a sessile organism it must cope with daily fluctuations of the marine and terrestrial environments. Organisms in stressful environments are commonly faced with energetic trade-offs between somatic and reproductive growth and stress management. Although, this energetic theory is generally accepted for mussels as well, the spectrum of mechanisms underlying this framework have not been widely investigated. In the current study we hypothesized that mussels acclimated to a cyclical moderately warm aerial environment would display enhanced transcript abundance of genes related to metabolism and exhibit resilient digestive enzyme activity (energy acquisition). Following acclimation to simulated tidal regimes in the laboratory we observed higher gene-expression of citrate synthase (CS), citrate lyase (ACLY), and mammalian target of rapamycin (MTOR) in heat stressed mussels. The expression of CS and MTOR was not elevated under acute thermal stress, suggestive that repeated stress is required for robust expression of these genes given that all other environmental variables are constant. We also observed reduced activity of the digestive enzyme, amylase in heat-shocked acclimated mussels (a proxy for energy acquisition). Our results suggest that mussels that settle high on shore not only face the challenge of thermal stress repair and limited access to food but may also be compromised by reduced digestive performance. Mussels may have adapted to cyclical energetic stress by overexpressing particular energy-related genes that can mitigate the disturbance to energy balance once the abundant transcripts are translated into functional proteins