Computerised cognitive-behavioural therapy for depression in adolescents : feasibility results and 4-month outcomes of a UK randomised controlled trial

OBJECTIVES: Computer-administered cognitive-behavioural therapy (CCBT) may be a promising treatment for adolescents with depression, particularly due to its increased availability and accessibility. The feasibility of delivering a randomised controlled trial (RCT) comparing a CCBT program (Stressbusters) with an attention control (self-help websites) for adolescent depression was evaluated. DESIGN: Single centre RCT feasibility study. SETTING: The trial was run within community and clinical settings in York, UK. PARTICIPANTS: Adolescents (aged 12-18) with low mood/depression were assessed for eligibility, 91 of whom met the inclusion criteria and were consented and randomised to Stressbusters (n=45) or websites (n=46) using remote computerised single allocation. Those with comorbid physical illness were included but those with psychosis, active suicidality or postnatal depression were not. INTERVENTIONS: An eight-session CCBT program (Stressbusters) designed for use with adolescents with low mood/depression was compared with an attention control (accessing low mood self-help websites). PRIMARY AND SECONDARY OUTCOME MEASURES: Participants completed mood and quality of life measures and a service Use Questionnaire throughout completion of the trial and 4 months post intervention. Measures included the Beck Depression Inventory (BDI) (primary outcome measure), Mood and Feelings Questionnaire (MFQ), Spence Children's Anxiety Scale (SCAS), the EuroQol five dimensions questionnaire (youth) (EQ-5D-Y) and Health Utility Index Mark 2 (HUI-2). Changes in self-reported measures and completion rates were assessed by treatment group. RESULTS: From baseline to 4 months post intervention, BDI scores and MFQ scores decreased for the Stressbusters group but increased in the website group. Quality of life, as measured by the EQ-5D-Y, increased for both groups while costs at 4 months were similar to baseline. Good feasibility outcomes were found, suggesting the trial process to be feasible and acceptable for adolescents with depression. CONCLUSIONS: With modifications, a fully powered RCT is achievable to investigate a promising treatment for adolescent depression in a climate where child mental health service resources are limited. TRIAL REGISTRATION NUMBER: ISRCTN31219579

A doubly-refined enumeration of alternating sign matrices and descending plane partitions

It was shown recently by the authors that, for any n, there is equality between the distributions of certain triplets of statistics on nxn alternating sign matrices (ASMs) and descending plane partitions (DPPs) with each part at most n. The statistics for an ASM A are the number of generalized inversions in A, the number of -1's in A and the number of 0's to the left of the 1 in the first row of A, and the respective statistics for a DPP D are the number of nonspecial parts in D, the number of special parts in D and the number of n's in D. Here, the result is generalized to include a fourth statistic for each type of object, where this is the number of 0's to the right of the 1 in the last row of an ASM, and the number of (n-1)'s plus the number of rows of length n-1 in a DPP. This generalization is proved using the known equality of the three-statistic generating functions, together with relations which express each four-statistic generating function in terms of its three-statistic counterpart. These relations are obtained by applying the Desnanot-Jacobi identity to determinantal expressions for the generating functions, where the determinants arise from standard methods involving the six-vertex model with domain-wall boundary conditions for ASMs, and nonintersecting lattice paths for DPPs.Comment: 28 pages; v2: published versio

Growth charts for children with Ellis–van Creveld syndrome

Ellis–van Creveld (EvC) syndrome is a congenital malformation syndrome with marked growth retardation. In this study, specific growth charts for EvC patients were derived to allow better follow-up of growth and earlier detection of growth patterns unusual for EvC. With the use of 235 observations of 101 EvC patients (49 males, 52 females), growth charts for males and females from 0 to 20 years of age were derived. Longitudinal and cross-sectional data were collected from an earlier review of growth data in EvC, a database of EvC patients, and from recent literature. To model the growth charts, the GAMLSS package for the R statistical program was used. Height of EvC patients was compared to healthy children using Dutch growth charts. Data are presented both on a scale for age and on a scale for the square root of age. Compared to healthy Dutch children, mean height standard deviation score values for male and female EvC patients were −3.1 and −3.0, respectively. The present growth charts should be useful in the follow-up of EvC patients. Most importantly, early detection of growth hormone deficiency, known to occur in EvC, will be facilitated

Online social networking and psychological experiences:the perceptions of young people with mental health difficulties

Objectives This study explores the interaction between online social networking experiences and wellbeing in 12 young people accessing mental health services. Methods Data from semi-structured interviews was analysed using Grounded Theory methodology. Results “Threats and judgement” and “connection and support” were experienced by adolescents, facilitated by having continuous access to a vast social network. These experiences influenced adolescents' psychological wellbeing, mediated by their responses to threat and judgement and maintaining “safe sharing” with their network. Social network use was conceived as a gamble of balancing its potentially positive and negative impact in a culture in which social network use appears to be unavoidable. Conclusions The findings indicate the importance of routine assessment and formulation of social networking use in understanding adolescents' psychological distress. Furthermore, a range of opportunities exist for clinicians to utilise the anonymity and peer support that social networks offer to broaden the range of mental health services offered to young people

Neural Processing of Short-Term Recurrence in Songbird Vocal Communication

BACKGROUND: Many situations involving animal communication are dominated by recurring, stereotyped signals. How do receivers optimally distinguish between frequently recurring signals and novel ones? Cortical auditory systems are known to be pre-attentively sensitive to short-term delivery statistics of artificial stimuli, but it is unknown if this phenomenon extends to the level of behaviorally relevant delivery patterns, such as those used during communication. METHODOLOGY/PRINCIPAL FINDINGS: We recorded and analyzed complete auditory scenes of spontaneously communicating zebra finch (Taeniopygia guttata) pairs over a week-long period, and show that they can produce tens of thousands of short-range contact calls per day. Individual calls recur at time scales (median interval 1.5 s) matching those at which mammalian sensory systems are sensitive to recent stimulus history. Next, we presented to anesthetized birds sequences of frequently recurring calls interspersed with rare ones, and recorded, in parallel, action and local field potential responses in the medio-caudal auditory forebrain at 32 unique sites. Variation in call recurrence rate over natural ranges leads to widespread and significant modulation in strength of neural responses. Such modulation is highly call-specific in secondary auditory areas, but not in the main thalamo-recipient, primary auditory area. CONCLUSIONS/SIGNIFICANCE: Our results support the hypothesis that pre-attentive neural sensitivity to short-term stimulus recurrence is involved in the analysis of auditory scenes at the level of delivery patterns of meaningful sounds. This may enable birds to efficiently and automatically distinguish frequently recurring vocalizations from other events in their auditory scene

A Model of Late Long-Term Potentiation Simulates Aspects of Memory Maintenance

Late long-term potentiation (L-LTP) appears essential for the formation of long-term memory, with memories at least partly encoded by patterns of strengthened synapses. How memories are preserved for months or years, despite molecular turnover, is not well understood. Ongoing recurrent neuronal activity, during memory recall or during sleep, has been hypothesized to preferentially potentiate strong synapses, preserving memories. This hypothesis has not been evaluated in the context of a mathematical model representing biochemical pathways important for L-LTP. I incorporated ongoing activity into two such models: a reduced model that represents some of the essential biochemical processes, and a more detailed published model. The reduced model represents synaptic tagging and gene induction intuitively, and the detailed model adds activation of essential kinases by Ca. Ongoing activity was modeled as continual brief elevations of [Ca]. In each model, two stable states of synaptic weight resulted. Positive feedback between synaptic weight and the amplitude of ongoing Ca transients underlies this bistability. A tetanic or theta-burst stimulus switches a model synapse from a low weight to a high weight stabilized by ongoing activity. Bistability was robust to parameter variations. Simulations illustrated that prolonged decreased activity reset synapses to low weights, suggesting a plausible forgetting mechanism. However, episodic activity with shorter inactive intervals maintained strong synapses. Both models support experimental predictions. Tests of these predictions are expected to further understanding of how neuronal activity is coupled to maintenance of synaptic strength.Comment: Accepted to PLoS One. 8 figures at en

Genomic analysis and relatedness of P2-like phages of the Burkholderia cepacia complex

<p>Abstract</p> <p>Background</p> <p>The <it>Burkholderia cepacia </it>complex (BCC) is comprised of at least seventeen Gram-negative species that cause infections in cystic fibrosis patients. Because BCC bacteria are broadly antibiotic resistant, phage therapy is currently being investigated as a possible alternative treatment for these infections. The purpose of our study was to sequence and characterize three novel BCC-specific phages: KS5 (vB_BceM-KS5 or vB_BmuZ-ATCC 17616), KS14 (vB_BceM-KS14) and KL3 (vB_BamM-KL3 or vB_BceZ-CEP511).</p> <p>Results</p> <p>KS5, KS14 and KL3 are myoviruses with the A1 morphotype. The genomes of these phages are between 32317 and 40555 base pairs in length and are predicted to encode between 44 and 52 proteins. These phages have over 50% of their proteins in common with enterobacteria phage P2 and so can be classified as members of the <it>Peduovirinae </it>subfamily and the "P2-like viruses" genus. The BCC phage proteins similar to those encoded by P2 are predominantly structural components involved in virion morphogenesis. As prophages, KS5 and KL3 integrate into an AMP nucleosidase gene and a threonine tRNA gene, respectively. Unlike other P2-like viruses, the KS14 prophage is maintained as a plasmid. The P2 <it>E+E' </it>translational frameshift site is conserved among these three phages and so they are predicted to use frameshifting for expression of two of their tail proteins. The <it>lysBC </it>genes of KS14 and KL3 are similar to those of P2, but in KS5 the organization of these genes suggests that they may have been acquired via horizontal transfer from a phage similar to λ. KS5 contains two sequence elements that are unique among these three phages: an IS<it>Bmu</it>2-like insertion sequence and a reverse transcriptase gene. KL3 encodes an EcoRII-C endonuclease/methylase pair and Vsr endonuclease that are predicted to function during the lytic cycle to cleave non-self DNA, protect the phage genome and repair methylation-induced mutations.</p> <p>Conclusions</p> <p>KS5, KS14 and KL3 are the first BCC-specific phages to be identified as P2-like. As KS14 has previously been shown to be active against <it>Burkholderia cenocepacia in vivo</it>, genomic characterization of these phages is a crucial first step in the development of these and similar phages for clinical use against the BCC.</p

H2S biosynthesis and catabolism: new insights from molecular studies

Hydrogen sulfide (H2S) has profound biological effects within living organisms and is now increasingly being considered alongside other gaseous signalling molecules, such as nitric oxide (NO) and carbon monoxide (CO). Conventional use of pharmacological and molecular approaches has spawned a rapidly growing research field that has identified H2S as playing a functional role in cell-signalling and post-translational modifications. Recently, a number of laboratories have reported the use of siRNA methodologies and genetic mouse models to mimic the loss of function of genes involved in the biosynthesis and degradation of H2S within tissues. Studies utilising these systems are revealing new insights into the biology of H2S within the cardiovascular system, inflammatory disease, and in cell signalling. In light of this work, the current review will describe recent advances in H2S research made possible by the use of molecular approaches and genetic mouse models with perturbed capacities to generate or detoxify physiological levels of H2S gas within tissue

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference