Marine heatwaves and the collapse of marginal North Atlantic kelp forests.

Extreme climatic events including marine heatwaves (MHWs) are becoming more frequent and severe in the Anthropocene. However, our understanding of how these events affect population dynamics of ecologically important species is limited, in part because extreme events are rare and difficult to predict. Here, we quantified the occurrence and severity of MHWs over 60 years in warm range edge kelp forests on both sides of the North Atlantic. The cumulative annual intensity of MHWs increased two- to four-fold during this period, coinciding with the disappearance of kelps. We experimentally demonstrated a relationship between strong and severe 2018 heatwaves and high kelp mortality in both regions. Patterns of kelp mortality were strongly linked to maximum temperature anomalies, which crossed lethal thresholds in both regions. Translocation and tagging experiments revealed similar kelp mortality rates on reefs dominated by healthy kelp forests and degraded sediment-laden algal 'turfs', indicating equal vulnerability to extreme events. These results suggest a mechanistic link between MHWs and broad-scale kelp loss, and highlight how warming can make ecosystem boundaries unstable, forcing shifts to undesirable ecosystem states under episodically extreme climatic conditions.

Nicotinic acetylcholine receptor alpha4 subunit gene polymorphism and attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) is a highly heritable, common psychiatric disorder that presents in childhood and that probably involves several genes. There are several lines of evidence suggesting that the nicotinic system may be functionally significant in ADHD: (a) nicotine promotes the release of dopamine and has been shown to improve attention in adults with ADHD, smokers and non-smokers; (b) ADHD is a significant risk factor for early initiation of cigarette smoking in children; (c) maternal cigarette smoking appears to be a risk factor for ADHD; (d) animal studies in rats and monkeys also suggest that nicotine may be involved in attentional systems and locomotor activity; and (e) a central nicotinic agonist, ABT-418, improves attention in both monkeys and ADHD adults. The current study examined the alpha 4 receptor, one of the sites of action of ABT-418. A known Cfol polymorphism within the nicotinic acetylcholine alpha 4 receptor gene, CHRNA4, was studied in 70 ADHD parent-proband trios from an ongoing sample collection of children aged 6-12 with ADHD, according to DSM-IV criteria. Children with known major medical or psychiatric conditions or mental retardation (IQ < 70) were excluded from the study. The Transmission Disequilibrium Test demonstrated no evidence that variation at the nicotinic acetylcholine alpha 4 receptor Cfol polymorphism influences susceptibility to ADHD (P > 0.35). The continuing sample collection will enable further study of other potential nicotinic system polymorphisms in ADHD in more powerful samples.

Autistic symptoms in children with attention deficit-hyperactivity disorder.

Children with the syndrome of disorders of attention, motor control and perception (DAMP) invariably fill diagnostic criteria for attention deficit hyperactivity disorder (ADHD) and commonly have symptoms of autistic spectrum disorders. This study estimates the rate of autistic symptoms in a sample of children with ADHD by using the parent-rated Autism Criteria Checklist. A high proportion of parents (between 65-80%) reported significant difficulties in social interaction (particularly in empathy and peer relationships), and communication (particularly in imaginative ability, nonverbal communication and maintaining conversation). The nature and relationship between ADHD and pervasive developmental disorders is considered, as well as implications for assessment, diagnosis and treatment.

Two-year outcome of children treated for depression.

Fifty-four children and adolescents (age 8-17) were assessed two years after a clinical intervention trial of cognitive-behavioural vs. non-focused treatment for depression. Eleven (20.4%) subjects fulfilled criteria for depression, while 21 (38.9%) reported significant depressive symptoms during the previous year. Seventeen young people (31.5%) had a psychiatric disorder (including depression). Overall, the sample maintained the improvement since the termination of treatment, without detecting specific treatment effects. Presence of depression at two-year follow-up was best predicted by self-esteem ratings before and after treatment, and co-morbidity at post-treatment. Depression in young life carries a high risk of recurrence, despite initial remission. Continuation or preventative treatment for young people at risk of relapse needs development and evaluation.

Detection of major and minor depression in children and adolescents: evaluation of the Mood and Feelings Questionnaire.

The detection of major and minor depression in children and adolescents was evaluated in an outpatient sample of 113 children employing the Mood and Feelings Questionnaire (both child and parent versions) and the K-SADS interview. Differences between depressed and nondepressed groups, those with major or minor depression, and depressed children compared with those comorbid for anxiety, were examined. Our findings support the validity of the MFQ as a screening instrument for major and minor depression in a population with a high proportion of depressed cases. High agreement between parent and child ratings was found, with cognitive items being the best predictors of depression.

A randomised controlled out-patient trial of cognitive-behavioural treatment for children and adolescents with depression: 9-month follow-up.

Nine-month outcome data of a randomized controlled out-patient trial of cognitive-behavioural treatment (CBT) for children and adolescents with depression are presented. CBT was compared with a non-focussed intervention (NFI) in 56 subjects. At 9 months after thr termination of the trial, 21 children (37.5%) fulfilled criteria for a psychiatric disorder (DSM-III-R), out of whom 15 (26.8%) had a depressive illness. However, 25 subjects (45%) reported depressive symptoms of significant severity to suggest a depressive episode during the previous 9-month period. Both treatment groups maintained a significant improvement on all psychosocial measures since the post-treatment assessment. No significant treatment effect was established. Low self-esteem at the time of referral, predicted presence of psychiatric disorder, and child-reported scores of depressive symptoms and low self-esteem at follow-up. The research and clinical implications for the treatment of depressive disorders in young life are discussed.

Neutrophil rolling altered by inhibition of L-selectin shedding in vitro.

The L-selectin adhesion molecule is involved in guiding leukocytes to sites of inflammation. L-selectin is cleaved by an unusual proteolytic activity at a membrane-proximal site resulting in rapid shedding from the cell surface. Although it has been demonstrated that L-selectin mediates, in part, the early event of leukocyte rolling under hydrodynamic flow, the contribution of shedding to L-selectin function has remained unknown. Here we show that hydroxamic acid-based metalloprotease inhibitors block L-selectin downregulation from the cell surface of stimulated neutrophils, without affecting Mac-1 mobilization or general neutrophil activation, and inhibit cleavage of L-selectin in a cell-free system. Unexpectedly, the hydroxamic acid-based inhibitors reduced neutrophil rolling velocity under hydrodynamic flow, resulting in increased neutrophil accumulation. These results suggest that L-selectin is cleaved in seconds--much faster than previously suspected--during the process of rolling under hydrodynamic flow, and that shedding of L-selectin may contribute significantly to the velocity of leukocyte rolling. L-selectin shedding during rolling interactions may be physiologically important for limiting leukocyte aggregation and accumulation at sites of inflammation.

Shedding of the lymphocyte L-selectin adhesion molecule is inhibited by a hydroxamic acid-based protease inhibitor. Identification with an L-selectin-alkaline phosphatase reporter.

Expression of the L-selectin adhesion molecule can be rapidly down-modulated by regulated proteolysis at a membrane-proximal site. The L-selectin secretase has remained undefined, and the secretase activity is resistant to a broad panel of common protease inhibitors. We have developed an L-selectin-alkaline phosphatase reporter, consisting of the ectodomain of human placental alkaline phosphatase fused to the membrane-proximal cleavage, transmembrane, and cytoplasmic domains of L-selectin, to aid in the screening for L-selectin secretase inhibitors. A hydroxamic acid-based metalloprotease inhibitor, KD-IX-73-4, inhibited release of the L-selectin-alkaline phosphatase reporter in a dose-dependent manner. The hydroxamic acid-based peptide was also found to inhibit wild type L-selectin down-regulation from the surfaces of phorbol myristate acetate-activated peripheral blood lymphocytes and phytohemagglutinin-stimulated lymphoblasts. Analysis of the proteolytic cleavage fragments of L-selectin confirmed that KD-IX-73-4 inhibited L-selectin proteolysis. Lymphocyte L-selectin was not down-regulated when co-cultured with formylmethionylleucylphenylalanine-stimulated neutrophils, suggesting that the putative secretase acts in cis with the membrane-bound L-selectin. These results suggest that the L-selectin secretase activity may involve a cell surface, zinc-dependent metalloprotease, although L-selectin shedding is not affected by EDTA and may be related to the recently described activity involved in processing of membrane-bound TNF-alpha.

Child sexual abuse: helping children and their families.

The reality of child sexual abuse has only recently been accepted by professionals. Previously, treatment strategies were aimed at adult survivors rather than at children. Treatment programmes for children have a short history and their long-term effects cannot be validated yet, although some attempts have been made (Bentovim et al, 1987).

Method for detection of picornavirus capsid binders with soluble intercellular adhesion molecule 1.

A method utilizing immobilized major group rhinoviruses and biotinylated soluble intercellular adhesion molecule 1 has been developed for the detection of capsid binders. Binding measurements indicate a loss in relative affinity of biotinylated soluble intercellular adhesion molecule 1 for rhinoviruses by capsid binders. This method and a new class of capsid binders are discussed.