Early identification of stimulant treatment responders, partial responders and non-responders using objective measures in children and adolescents with hyperkinetic disorder

Background: The aim of this study was to evaluate stimulant medication response following a single dose of methylphenidate (MPH) in children and young people with hyperkinetic disorder using infrared motion analysis combined with a continuous performance task (QbTest system) as objective measures. The hypothesis was put forward that a moderate testdose of stimulant medication could determine a robust treatment response, partial response and non-response in relation to activity, attention and impulse control measures. Methods: The study included 44 children and young people between the ages of 7-18 years with a diagnosis of hyperkinetic disorder (F90 & F90.1). A single dose-protocol incorporated the time course effects of both immediate release MPH and extended release MPH (Concerta XL, Equasym XL) to determine comparable peak efficacy periods post intake. Results: A robust treatment response with objective measures reverting to the population mean was found in 37 participants (84%). Three participants (7%) demonstrated a partial response to MPH and four participants (9%) were determined as non-responders due to deteriorating activity measures together with no improvements in attention and impulse control measures. Conclusion: Objective measures provide early into prescribing the opportunity to measure treatment response and monitor adverse reactions to stimulant medication. Most treatment responders demonstrated an effective response to MPH on a moderate testdose facilitating a swift and more optimal titration process.

Self-exclusion from health care in women at high risk for postpartum depression

Background A significant proportion of women who are vulnerable to postnatal depression refuse to engage in treatment programmes. Little is known about them, other than some general demographic characteristics. In particular, their access to health care and their own and their infants' health outcomes are uncharted. Methods We conducted a nested cohort case-control study, using data from computerized health systems, and general practitioner (GP) and maternity records, to identify the characteristics, health service contacts, and maternal and infant health outcomes for primiparous antenatal clinic attenders at high risk for postnatal depression who either refused (self-exclusion group) or else agreed (take-up group) to receive additional Health Visiting support in pregnancy and the first 2 months postpartum. Results Women excluding themselves from Health Visitor support were younger and less highly educated than women willing to take up the support. They were less likely to attend midwifery, GP and routine Health Visitor appointments, but were more likely to book in late and to attend accident and emergency department (A&E). Their infants had poorer outcome in terms of gestation, birthweight and breastfeeding. Differences between the groups still obtained when age and education were taken into account for midwifery contacts, A&E attendance and gestation;the difference in the initiation of breast feeding was attenuated, but not wholly explained, by age and education. Conclusion A subgroup of psychologically vulnerable childbearing women are at particular risk for poor access to health care and adverse infant outcome. Barriers to take-up of services need to be understood in order better to deliver care.

Growth of the lava dome and extrusion rates at Soufrière Hills Volcano, Montserrat, West Indies: 2005–2008

The third episode of lava dome growth at Soufrière Hills Volcano began 1 August 2005 and ended 20 April 2007. Volumes of the dome and talus produced were measured using a photo-based method with a calibrated camera for increased accuracy. The total dense rock equivalent (DRE) volume of extruded andesite magma (306 ± 51 Mm3) was similar within error to that produced in the earlier episodes but the average extrusion rate was 5.6 ± 0.9 m3s−1 (DRE), higher than the previous episodes. Extrusion rates varied in a pulsatory manner from <0.5 m3s−1 to ∼20 m3s−1. On 18 May 2006, the lava dome had reached a volume of 85 Mm3 DRE and it was removed in its entirety during a massive dome collapse on 20 May 2006. Extrusion began again almost immediately and built a dome of 170 Mm3 DRE with a summit height 1047 m above sea level by 4 April 2007. There were few moderate-sized dome collapses (1–10 Mm3) during this extrusive episode in contrast to the first episode of dome growth in 1995–8 when they were numerous. The first and third episodes of dome growth showed a similar pattern of low (<0.5 m3s−1) but increasing magma flux during the early stages, with steady high flux after extrusion of ∼25 Mm3

Archaeology on Egypt's edge: archaeological research in the Dakhleh Oasis, 1819-1977

This article provides the first substantial survey of early archaeological research in Egypt’s Dakhleh Oasis. In addition to providing a much-needed survey of research, this study embeds Dakhleh’s regional research history within a broader archaeological research framework. Moreover, it explores the impact of contemporaneous historical events in Egypt and Europe upon the development of archaeology in Dakhleh. This contextualised approach allows us to trace influences upon past research trends and their impacts upon current research and approaches, as well as suggest directions for future research.

The central European floods of August 2002: Part 2 - Synoptic causes and considerations with respect to climatic change

In the first part of this paper (Ulbrich et al. 2003), we gave a description of the August 2002 rainfall events and the resultant floods, in particular of the flood wave of the River Elbe. The extreme precipitation sums observed in the first half of the month were primarily associated with two rainfall episodes. The first episode occurred on 6/7 August 2002. The main rainfall area was situated over Lower Austria, the south-western part of the Czech Republic and south-eastern Germany. A severe flash flood was produced in the Lower Austrian Waldviertel (`forest quarter’ ). The second episode on 11± 13 August 2002 most severely affected the Erz Mountains and western parts of the Czech Republic. During this second episode 312mm of rain was recorded between 0600GMT on 12 August and 0600GMT on 13 August at the Zinnwald weather station in the ErzMountains, which is a new 24-hour record for Germany. The flash floods resulting from this rainfall episode and the subsequent Elbe flood produced the most expensive weatherrelated catastrophe in Europe in recent decades. In this part of the paper we discuss the meteorological conditions and physical mechanisms leading to the two main events. Similarities to the conditions that led to the recent summer floods of the River Oder in 1997 and the River Vistula in 2001 will be shown. This will lead us to a consideration of trends in extreme rainfall over Europe which are found in numerical simulations of anthropogenic climate change.

Typography papers, 9

This latest issue of the series of Typography papers opens with a beautifully illustrated article by the type designer Gerard Unger on ‘Romanesque’ letters. A further installment of Eric Kindel’s pathbreaking history of stencil letters is published in contributions by him, Fred Smeijers, and James Mosley. Maurice Göldner writes the first history of an early twentieth-century German typefounder, Brüder Butter. William Berkson and Peter Enneson recover the notion of ‘readability’ through a history of the collaboration between Matthew Luckiesh and the Linotype Company. Paul Luna discusses the role of pictures in dictionaries. Titus Nemeth describes a new form of Arabic type for metal composition. The whole gathering shows the remarkable variety and vitality of typography now.

The Italian academies 1525-1700: networks of culture, innovation and dissent

The intellectual societies known as Academies played a vital role in the development of culture, and scholarly debate throughout Italy between 1525-1700. They were fundamental in establishing the intellectual networks later defined as the ‘République des Lettres’, and in the dissemination of ideas in early modern Europe, through print, manuscript, oral debate and performance. This volume surveys the social and cultural role of Academies, challenging received ideas and incorporating recent archival findings on individuals, networks and texts. Ranging over Academies in both major and smaller or peripheral centres, these collected studies explore the interrelationships of Academies with other cultural forums. Individual essays examine the fluid nature of academies and their changing relationships to the political authorities; their role in the promotion of literature, the visual arts and theatre; and the diverse membership recorded for many academies, which included scientists, writers, printers, artists, political and religious thinkers, and, unusually, a number of talented women. Contributions by established international scholars together with studies by younger scholars active in this developing field of research map out new perspectives on the dynamic place of the Academies in early modern Italy. The publication results from the research collaboration ‘The Italian Academies 1525-1700: the first intellectual networks of early modern Europe’ funded by the Arts and Humanities Research Council and is edited by the senior investigators.

Field trial using bone meal amendments to remediate mine waste derived soil contaminated with zinc, lead and cadmium

Bone meal amendments are being considered as a remediation method for metal-contaminated wastes. In various forms (biogenic, geogenic or synthetic), apatite, the principal mineral constituent of bone, has shown promise as an amendment to remediate metal-contaminated soils via the formation of insoluble phosphates of Pb and possibly other metals. The efficacy of commercially available bovine bone meal in this role was investigated in a field trial at Nenthead, Cumbria with a mine waste derived soil contaminated with Zn, Pb and Cd. Two 5 m(2) plots were set up: the first as a control and the second, a treatment plot where the soil was thoroughly mixed with bone meal to a depth of 50 cm at a soil to amendment ratio of 25:1 by weight. An array of soil solution samplers (Rhizon SMS (TM)) were installed in both plots and the soil pore water was collected and analysed for Ca, Cd, Zn and Pb regularly over a period of 2 a. Concurrently with the field trial, a laboratory trial with 800 mm high and 100 mm wide leaching Columns Was conducted using identical samplers and with soil from the held site. A substantial release of Zn, Pb, Cd and Ca was observed associated with the bone meal treatment. This release was transient in the case of the leaching columns, and showed seasonal variation in the case of the field trial. It is proposed that this effect resulted from metal complexation with organic acids released during breakdown of the bone meal organic fraction and was facilitated by the relatively high soil pH of 7.6-8.0. Even after this transient release effect had subsided or when incinerated bone meal was substituted in order to eliminate the organic fraction, no detectable decrease in dissolved metals was observed and no P was detected in solution, in contrast with an earlier small column laboratory study. It is concluded that due to the relative insolubility of apatite at above-neutral pH, the rate of supply of phosphate to soil solution was insufficient to result in significant precipitation of metal phosphates and that this may limit the effectiveness of the method to more acidic soils. (c) 2008 Elsevier Ltd. All rights reserved.

Genome-wide association study of response to cognitive behavioural therapy in children with anxiety disorders

Background Anxiety disorders are common, and cognitive–behavioural therapy (CBT) is a first-line treatment. Candidate gene studies have suggested a genetic basis to treatment response, but findings have been inconsistent. Aims To perform the first genome-wide association study (GWAS) of psychological treatment response in children with anxiety disorders (n = 980). Method Presence and severity of anxiety was assessed using semi-structured interview at baseline, on completion of treatment (post-treatment), and 3 to 12 months after treatment completion (follow-up). DNA was genotyped using the Illumina Human Core Exome-12v1.0 array. Linear mixed models were used to test associations between genetic variants and response (change in symptom severity) immediately post-treatment and at 6-month follow-up. Results No variants passed a genome-wide significance threshold (P = 5×10−8) in either analysis. Four variants met criteria for suggestive significance (P<5×10−6) in association with response post-treatment, and three variants in the 6-month follow-up analysis. Conclusions This is the first genome-wide therapygenetic study. It suggests no common variants of very high effect underlie response to CBT. Future investigations should maximise power to detect single-variant and polygenic effects by using larger, more homogeneous cohorts.

A randomised controlled trial of positive memory training for the treatment of depression within schizophrenia

Abstract Background: Depression is highly prevalent within individuals diagnosed with schizophrenia, and is associated with an increased risk of suicide. There are no current evidence based treatments for low mood within this group. The specific targeting of co-morbid conditions within complex mental health problems lends itself to the development of short-term structured interventions which are relatively easy to disseminate within health services. A brief cognitive intervention based on a competitive memory theory of depression, is being evaluated in terms of its effectiveness in reducing depression within this group. Methods/Design: This is a single blind, intention-to-treat, multi-site, randomized controlled trial comparing Positive Memory Training plus Treatment as Usual with Treatment as Usual alone. Participants will be recruited from two NHS Trusts in Southern England. In order to be eligible, participants must have a DSM-V diagnosis of schizophrenia or schizo-affective disorder and exhibit at least a mild level of depression. Following baseline assessment eligible participants will be randomly allocated to either the Positive Memory Training plus Treatment as Usual group or the Treatment as Usual group. Outcome will be assessed at the end of treatment (3-months) and at 6-month and 9-month post randomization by assessors blind to group allocation. The primary outcome will be levels of depression and secondary outcomes will be severity of psychotic symptoms and cost-effectiveness. Semi-structured interviews will be conducted with all participants who are allocated to the treatment group so as to explore the acceptability of the intervention. Discussion: Cognitive behaviour therapy is recommended for individuals diagnosed with schizophrenia. However, the number of sessions and length of training required to deliver this intervention has caused a limit in availability. The current trial will evaluate a short-term structured protocol which targets a co-morbid condition often considered of primary importance by service users. If successful the intervention will be an important addition to current initiatives aimed at increasing access to psychological therapies for people diagnosed with severe mental health problems. Trial registration: Current Controlled Trials. ISRCTN99485756. Registered 13 March 2014.

Can we harness computerised cognitive bias modification to treat anxiety in schizophrenia? A first step highlighting the role of mental imagery

A new wave of computerised therapy is under development which, rather than simulating talking therapies, uses bias modification techniques to target the core psychological process underlying anxiety. Such interventions are aimed at anxiety disorders, and are yet to be adapted for co-morbid anxiety in psychosis. The cognitive bias modification (CBM) paradigm delivers repeated exposure to stimuli in order to train individuals to resolve ambiguous information in a positive, rather than anxiety provoking, manner. The current study is the first to report data from a modified form of CBM which targets co-morbid anxiety within individuals diagnosed with schizophrenia. Our version of CBM involved exposure to one hundred vignettes presented over headphones. Participants were instructed to actively simulate the described scenarios via visual imagery. Twenty-one participants completed both a single session of CBM and a single control condition session in counter-balanced order. Within the whole sample, there was no significant improvement on interpretation bias of CBM or state anxiety, relative to the control condition. However, in line with previous research, those participants who engage in higher levels of visual imagery exhibited larger changes in interpretation bias. We discuss the implications for harnessing computerised CBM therapy developments for co-morbid anxiety in schizophrenia.

Controlled trial of the short- and long-term effect of psychological treatment of post-partum depression 2. Impact on the mother-child relationship and child outcome

Background: Postnatal depression is associated with adverse child cognitive and socio-emotional outcome. It is not known whether psychological treatment affects the quality of the mother-child relationship and child outcome. Aims: To evaluate the effect of three psychological treatments on the mother-child relationship and child outcome. Method: Women with post-partum depression (n=193) were assigned randomly to routine primary care, non-directive counselling, cognitive-behavioural therapy or psychodynamic therapy The women and their children, were assessed at 43, [8 and 60 months post-partum. Results: Indications of a positive benefit were limited. All three treatments had a significant benefit on maternal reports of early difficulties in relationships with the infants, counselling gave better infant emotional and behaviour ratings at 18 months and more sensitive early mother-infant interactions. The treatments had no significant impact on maternal management of early infant behaviour problems, security of infant-mother attachment. Infant cognitive development or any child outcome at 5 years. Conclusions: Early intervention was of short-term benefit to the mother-child relationship and infant behaviour problems. More-prolonged intervention may be needed. Health visitors could deliver this.

Assessment of depression, anxiety and apathy in prodromal and early Huntington disease

The Functional Rating Scale Taskforce for pre-Huntington Disease (FuRST-pHD) is a multinational, multidisciplinary initiative with the goal of developing a data-driven, comprehensive, psychometrically sound, rating scale for assessing symptoms and functional ability in prodromal and early Huntington disease (HD) gene expansion carriers. The process involves input from numerous sources to identify relevant symptom domains, including HD individuals, caregivers, and experts from a variety of fields, as well as knowledge gained from the analysis of data from ongoing large-scale studies in HD using existing clinical scales. This is an iterative process in which an ongoing series of field tests in prodromal (prHD) and early HD individuals provides the team with data on which to make decisions regarding which questions should undergo further development or testing and which should be excluded. We report here the development and assessment of the first iteration of interview questions aimed to assess Depression, Anxiety and Apathy in prHD and early HD individuals.

Data-driven treatment selection for seamless phase II/III trials incorporating early-outcome data

Seamless phase II/III clinical trials are conducted in two stages with treatment selection at the first stage. In the first stage, patients are randomized to a control or one of k > 1 experimental treatments. At the end of this stage, interim data are analysed, and a decision is made concerning which experimental treatment should continue to the second stage. If the primary endpoint is observable only after some period of follow-up, at the interim analysis data may be available on some early outcome on a larger number of patients than those for whom the primary endpoint is available. These early endpoint data can thus be used for treatment selection. For two previously proposed approaches, the power has been shown to be greater for one or other method depending on the true treatment effects and correlations. We propose a new approach that builds on the previously proposed approaches and uses data available at the interim analysis to estimate these parameters and then, on the basis of these estimates, chooses the treatment selection method with the highest probability of correctly selecting the most effective treatment. This method is shown to perform well compared with the two previously described methods for a wide range of true parameter values. In most cases, the performance of the new method is either similar to or, in some cases, better than either of the two previously proposed methods.