Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Assessment of long-term psychological well-being following intensive care

The aim of this research, which remains in progress, has been the examination of long-term psychological consequences for survivors of intensive care. Seventy-two patients were followed up for 1 year, after discharge from the Intensive Care Unit (ICU) at St James's University Hospital in Leeds. Major objectives of the study included assessment of patients' sense of well-being at specified intervals post-discharge, and identification of ICU-related variables which might influence psychological recovery. Psychometric assessments used were the General Health Questionnaire 28-item version, the Rosenberg Self-esteem Scale, and the Impact of Event scale. This paper describes findings from the research so far. An exploratory analysis of the data suggests that distinctions can be drawn among surviving patients with regard to psychological recovery, by way of variables such as type of illness, mode of admission and amount of recall. The work expands previous research into post-ICU psychology and quality of life, and should allow increased understanding of this patient group

Difficult-To-Treat Pediatric Obsessive-Compulsive Disorder: Feasibility and Preliminary Results of a Randomized Pilot Trial of D-Cycloserine-Augmented Behavior Therapy

Background: This study examined the feasibility and preliminary effectiveness of d-cycloserine (DCS)–augmented cognitive behavioral therapy (CBT) for children and adolescents with difficult-to-treat Obsessive Compulsive Disorder, in a double-blind randomized controlled pilot trial (RCT). Methods: Seventeen children and adolescents (aged 8–18 years) with a primary diagnosis of OCD, which was deemed difficult-to-treat, were randomly assigned to either nine sessions of CBT including five sessions of DCS-augmented exposure and response prevention (ERP) [ERP + DCS] or nine sessions of CBT including five sessions of placebo-augmented ERP [ERP + PBO]. Weight-dependent DCS or placebo doses (25 or 50 mg) were taken 1 hour before ERP sessions. Results: At posttreatment, both groups showed significant improvements with 94% of the entire sample classified as responders. However, a greater improvement in the ERP + DCS relative to the ERP + PBO condition was observed at 1-month follow-up on clinician-rated obsessional severity and diagnostic severity, and parent ratings of OCD severity. There were no changes across time or condition from 1- to 3-month follow-up. Conclusions: In this preliminary study, DCS-augmented ERP produced significant improvements in OCD severity from posttreatment to 1-month follow-up, relative to a placebo control condition, in severe and difficult-to-treat pediatric OCD. The significant effect on obsessional severity suggests that DCS augmentation might be associated with enhanced modification of obsessional thoughts during ERP, and warrants further investigation

D-Cycloserine-Augmented One-Session Treatment of Specific Phobias in Children and Adolescents

Background: D-Cycloserine has potential to enhance exposure therapy outcomes. The current study presents a preliminary randomized, placebo-controlled double-blind pilot trial of DCS-augmented one-session treatment (OST) for youth (7–14 years) with specific phobia. A secondary aim of this pilot study was to explore the effects of youth age and within-session fear reduction as potential moderators of DCS outcomes in order to generate hypotheses for a larger trial. It was hypothesized that DCS would be associated with greater improvements than placebo, that children (7–10 years) would have greater benefits than adolescents (11–14 years), and that DCS effects would be stronger for participants with the greater within-session fear reduction during the OST. Methods: Thirty-five children and adolescents were randomized to either OST combined with DCS (n = 17), or OST combined with placebo (PBO; n = 18) and assessed at 1 week, 1 month, and 3 month following treatment. Results: There were no significant pre- to post-treatment or follow-up benefits of DCS relative to placebo. Secondary analyses of age indicated that relative to PBO, DCS was associated with greater improvements for children (but not adolescents) on measures of severity at 1-month follow-up. Children in the DCS condition also showed significantly greater improvement to 1 month on global functioning relative to other groups. Conversely, adolescents had significant post-treatment benefits in the PBO condition on symptom severity measures relative to DCS, and adolescents in the DCS condition had significantly poorer functioning at 3 months relative to all other groups. Finally, there was a trend for within-session fear reduction to be associated with moderating effects of DCS, whereby greater reduction in fear was associated with greater functioning at one-month follow-up for children who received DCS, relative to PBO. Limitations: The study sample was small and therefore conclusions are tentative and require replication. Conclusion: Age and within-session fear reduction may be important moderators of DCS-augmented one-session exposure therapy, which requires testing in a fully powered randomized controlled trial

D-Cycloserine-Augmented One-Session Treatment of Specific Phobias in Children and Adolescents

Background: D-Cycloserine has potential to enhance exposure therapy outcomes. The current study presents a preliminary randomized, placebo-controlled double-blind pilot trial of DCS-augmented one-session treatment (OST) for youth (7–14 years) with specific phobia. A secondary aim of this pilot study was to explore the effects of youth age and within-session fear reduction as potential moderators of DCS outcomes in order to generate hypotheses for a larger trial. It was hypothesized that DCS would be associated with greater improvements than placebo, that children (7–10 years) would have greater benefits than adolescents (11–14 years), and that DCS effects would be stronger for participants with the greater within-session fear reduction during the OST. Methods: Thirty-five children and adolescents were randomized to either OST combined with DCS (n = 17), or OST combined with placebo (PBO; n = 18) and assessed at 1 week, 1 month, and 3 month following treatment. Results: There were no significant pre- to post-treatment or follow-up benefits of DCS relative to placebo. Secondary analyses of age indicated that relative to PBO, DCS was associated with greater improvements for children (but not adolescents) on measures of severity at 1-month follow-up. Children in the DCS condition also showed significantly greater improvement to 1 month on global functioning relative to other groups. Conversely, adolescents had significant post-treatment benefits in the PBO condition on symptom severity measures relative to DCS, and adolescents in the DCS condition had significantly poorer functioning at 3 months relative to all other groups. Finally, there was a trend for within-session fear reduction to be associated with moderating effects of DCS, whereby greater reduction in fear was associated with greater functioning at one-month follow-up for children who received DCS, relative to PBO. Limitations: The study sample was small and therefore conclusions are tentative and require replication. Conclusion: Age and within-session fear reduction may be important moderators of DCS-augmented one-session exposure therapy, which requires testing in a fully powered randomized controlled trial