Structural neural networks subserving oculomotor function in first-episode schizophrenia

BACKGROUND: Smooth pursuit and antisaccade abnormalities are well documented in schizophrenia, but their neuropathological correlates remain unclear. METHODS: In this study, we used statistical parametric mapping to investigate the relationship between oculomotor abnormalities and brain structure in a sample of first-episode schizophrenia patients (n = 27). In addition to conventional volumetric magnetic resonance imaging, we also used magnetization transfer ratio, a technique that allows more precise tissue characterization. RESULTS: We found that smooth pursuit abnormalities were associated with reduced magnetization transfer ratio in several regions, predominantly in the right prefrontal cortex. Antisaccade errors correlated with gray matter volume in the right medial superior frontal cortex as measured by conventional magnetic resonance imaging but not with magnetization transfer ratio. CONCLUSIONS: These preliminary results demonstrate that specific structural abnormalities are associated with abnormal eye movements in schizophrenia

Cognitive behavioural therapy for clozapine-resistant schizophrenia: the FOCUS RCT

Background: Clozapine (clozaril, Mylan Products Ltd) is a first-choice treatment for people with schizophrenia who have a poor response to standard antipsychotic medication. However, a significant number of patients who trial clozapine have an inadequate response and experience persistent symptoms, called clozapine-resistant schizophrenia (CRS). There is little evidence regarding the clinical effectiveness of pharmacological or psychological interventions for this population. Objectives: To evaluate the clinical effectiveness and cost-effectiveness of cognitive–behavioural therapy (CBT) for people with CRS and to identify factors predicting outcome. Design: The Focusing on Clozapine Unresponsive Symptoms (FOCUS) trial was a parallel-group, randomised, outcome-blinded evaluation trial. Randomisation was undertaken using permuted blocks of random size via a web-based platform. Data were analysed on an intention-to-treat (ITT) basis, using random-effects regression adjusted for site, age, sex and baseline symptoms. Cost-effectiveness analyses were carried out to determine whether or not CBT was associated with a greater number of quality-adjusted life-years (QALYs) and higher costs than treatment as usual (TAU). Setting: Secondary care mental health services in five cities in the UK. Participants: People with CRS aged up to 16 years, with an International Classification of Diseases, Tenth Revision (ICD-10) schizophrenia spectrum diagnoses and who are experiencing psychotic symptoms. Interventions: Individual CBT included up to 30 hours of therapy delivered over 9 months. The comparator was TAU, which included care co-ordination from secondary care mental health services. Main outcome measures: The primary outcome was the Positive and Negative Syndrome Scale (PANSS) total score at 21 months and the primary secondary outcome was PANSS total score at the end of treatment (9 months post randomisation). The health benefit measure for the economic evaluation was the QALY, estimated from the EuroQol-5 Dimensions, five-level version (EQ-5D-5L), health status measure. Service use was measured to estimate costs. Results: Participants were allocated to CBT (n = 242) or TAU (n = 245). There was no significant difference between groups on the prespecified primary outcome [PANSS total score at 21 months was 0.89 points lower in the CBT arm than in the TAU arm, 95% confidence interval (CI) –3.32 to 1.55 points; p = 0.475], although PANSS total score at the end of treatment (9 months) was significantly lower in the CBT arm (–2.40 points, 95% CI –4.79 to –0.02 points; p = 0.049). CBT was associated with a net cost of £5378 (95% CI –£13,010 to £23,766) and a net QALY gain of 0.052 (95% CI 0.003 to 0.103 QALYs) compared with TAU. The cost-effectiveness acceptability analysis indicated a low likelihood that CBT was cost-effective, in the primary and sensitivity analyses (probability < 50%). In the CBT arm, 107 participants reported at least one adverse event (AE), whereas 104 participants in the TAU arm reported at least one AE (odds ratio 1.09, 95% CI 0.81 to 1.46; p = 0.58). Conclusions: Cognitive–behavioural therapy for CRS was not superior to TAU on the primary outcome of total PANSS symptoms at 21 months, but was superior on total PANSS symptoms at 9 months (end of treatment). CBT was not found to be cost-effective in comparison with TAU. There was no suggestion that the addition of CBT to TAU caused adverse effects. Future work could investigate whether or not specific therapeutic techniques of CBT have value for some CRS individuals, how to identify those who may benefit and how to ensure that effects on symptoms can be sustained. Trial registration: Current Controlled Trials ISRCTN99672552

Simulating Evolution’s First Steps

Abstract. We demonstrate a simple artificial chemistry environment in which two small evolutionary transitions from the simplest self-replicators to larger ones are observed. The replicators adapt to increasingly harsh environments, where they must synthesise the components they need for replication. The evolution of a biosynthetic pathway of increasing length is thus achieved, through the use of simple chemical rules for catalytic action.

Romano-British Re-Use of Prehistoric Ritual Sites

AbstractMuch interest has been taken recently in the reuse of prehistoric ceremonial sites during later prehistory and early history, but only limited attention has been paid to this phenomenon during the Romano-British period. This article seeks to build on existing work by making a detailed study of such activity in three specific cases: the limestone caves of the Bristol Channel region, the Neolithic chambered tombs of the Cotswold-Severn area and the Peak District, and the three most spectacular prehistoric monuments of the Wessex chalklands: Stonehenge, the Avebury complex and the Uffington White Horse.</jats:p

Morfología Fluvial.- Ephemeral Channel Modelling at Historic timescales in Semi-arid Environments

ABSTRACT There is an increasing need to understand how ephemeral channels mediate the movement of water through catchment systems, both to identify the quantity of groundwater and reservoir recharge and to inform flash flood prediction. At historic timescales (101-102 years) it is recognised that this requires an understanding of the interactions between flow, sediment and vegetation which feedback to control morphological change and future flood wave propagation. Reduced-complexity models provide a means to develop such understanding. This paper presents a coupled 1D-2D numerical model that can be applied at the catchment scale to account for transmission losses and floodwave propagation (1D model), but which also simulates local-scale flow patterns that may be applied to simulate geomorphic response to flood inundation (2D model). The initial model evaluation, conducted at the Walnut Gulch Experimental Watershed, Arizona is presented