J D Bernal: philosophy, politics and the science of science

This paper is an examination of the philosophical and political legacy of John Desmond Bernal. It addresses the evidence of an emerging consensus on Bernal based on the recent biography of Bernal by Andrew Brown and the reviews it has received. It takes issue with this view of Bernal, which tends to be admiring of his scientific contribution, bemused by his sexuality, condescending to his philosophy and hostile to his politics. This article is a critical defence of his philosophical and political position

J D Bernal: philosophy, politics and the science of science

This paper is an examination of the philosophical and political legacy of John Desmond Bernal. It addresses the evidence of an emerging consensus on Bernal based on the recent biography of Bernal by Andrew Brown and the reviews it has received. It takes issue with this view of Bernal, which tends to be admiring of his scientific contribution, bemused by his sexuality, condescending to his philosophy and hostile to his politics. This article is a critical defence of his philosophical and political position

Inhibition of thoughts and actions in obsessive-compulsive disorder: extending the endophenotype?

Original article can be found at: http://journals.cambridge.org/ Copyright © Cambridge University Press 2009 The online version of this article is published within an Open Access environment subject to the conditions of the Creative Commons Attribution-NonCommercial-ShareAlike licence <http://creativecommons.org/licenses/by-nc-sa/2.5/>.Background: Obsessive-compulsive disorder (OCD) has been associated with impairments in stop-signal inhibition, a measure of motor response suppression. The study used a novel paradigm to examine both thought suppression and response inhibition in OCD, where the modulatory effects of stimuli relevant to OCD could also be assessed. Additionally, the study compared inhibitory impairments in OCD patients with and without co-morbid depression, as depression is the major co-morbidity of OCD. Method: Volitional response suppression and unintentional thought suppression to emotive and neutral stimuli were examined using a novel thought stop-signal task. The thought stop-signal task was administered to non-depressed OCD patients, depressed OCD patients and healthy controls (n=20 per group). Results: Motor inhibition impairments were evident in OCD patients, while motor response performance did not differ between patients and controls. Switching to a new response but not motor inhibition was affected by stimulus relevance in OCD patients. Additionally, unintentional thought suppression as measured by repetition priming was intact. OCD patients with and without depression did not differ on any task performance measures, though there were significant differences in all self-reported measures. Conclusions: Results support motor inhibition deficits in OCD that remain stable regardless of stimulus meaning or co-morbid depression. Only switching to a new response was influenced by stimulus meaning. When response inhibition was successful in OCD patients, so was the unintentional suppression of the accompanying thought.Peer reviewe

The Birmingham Boron Neutron Capture Therapy (BNCT) project : developments towards selective internal particle therapy

This paper will review progress on two aspects of the Birmingham BNCT project. Firstly on evaluation of the effects of high and low LET radiations when delivered simultaneously, and secondly on attempts to optimise delivery of the boron carrier compound BPA through pharmacokinetic studies. Simultaneous or non-simultaneous irradiations of V79 cells with alpha-particle and X-ray irradiations were performed. Alpha doses of 2 and 2.5 Gy were chosen and the impact on survival when delivered separately or simultaneously with variable doses of X-rays was evaluated. The pharmacokinetics of the delivery of a new formulation of BPA (BPA-mannitol) are being investigated in brain tumour patients through a study with 2 × 2 design featuring intravenous and intracarotid artery infusion of BPA, with or without a mannitol bolus. On the combined effect of low and high LET radiations, a synergistic effect was observed when alpha and X-ray doses are delivered simultaneously. The effect is only present at the 2.5 Gy alpha dose and is a very substantial effect on both the shape of the survival curve and the level of cell killing. This indicates that the alpha component may have the effect of inhibiting the repair of damage from the low LET radiation dose delivered simultaneously. On the pharmacokinetics of BPA, data on the first three cohorts indicate that bioavailability of BPA in brain ECF is increased substantially through the addition of a mannitol bolus, as well as by the use of intracarotid artery route of infusion. In both cases, for some patients the levels after infusion approach those seen in blood, whereas the ECF levels for intravenous infusion without mannitol are typically less than 10% of the blood values

Non‐pharmacological interventions for challenging behaviours of adults with intellectual disabilities: A meta‐analysis

Background  Non-pharmacological interventions are recommended for the treatment of challenging behaviours in individuals with intellectual disabilities by clinical guidelines. However, evidence for their effectiveness is ambiguous. The aim of the current meta-analysis is to update the existing evidence, to investigate long-term outcome, and to examine whether intervention type, delivery mode, and study design were associated with differences in effectiveness. Method An electronic search was conducted using the databases Medline, Eric, PsychINFO and Cinahl. Studies with experimental or quasi-experimental designs were included. We performed an overall random-effect meta-analysis and subgroup analyses. Results We found a significant moderate overall effect of non-pharmacological interventions on challenging behaviours (d = 0.573, 95% CI [0.352-0.795]), and this effect appears to be longlasting. Interventions combining mindfulness and behavioural techniques showed to be more effective than other interventions. However, this result should be interpreted with care due to possible overestimation of the subgroup analysis. No differences in effectiveness were found across assessment times, delivery modes or study designs. Conclusions Non-pharmacological interventions appear to be moderately effective on the short and long term in reducing challenging behaviours in adults with intellectual disabilities

Health-related quality of life in patients with inoperable malignant bowel obstruction: secondary outcome from a double-blind, parallel, placebo-controlled randomised trial of octreotide.

BACKGROUND:This analysis aims to evaluate health-related quality of life (HrQoL) (primary outcome for this analysis), nausea and vomiting, and pain in patients with inoperable malignant bowel obstruction (IMBO) due to cancer or its treatments randomised to standardised therapies plus octreotide or placebo over a maximum of 72 h in a double-blind clinical trial. METHODS:Adults with IMBO and vomiting recruited through 12 services spanning inpatient, consultative and community settings in Australia were randomised to subcutaneous octreotide infusion or saline. HrQoL was measured at baseline and treatment cessation (EORTC QLQ-C15-PAL). Mean within-group paired differences between baseline and post-treatment scores were analysed using Wilcoxon Signed Rank test and between group differences estimated using linear mixed models, adjusted for baseline score, sex, age, time, and study arm. RESULTS:One hundred six of the 112 randomised participants were included in the analysis (n = 52 octreotide, n = 54 placebo); 6 participants were excluded due to major protocol violations. Mean baseline HrQoL scores were low (octreotide 22.1, 95% CI 14.3, 29.9; placebo 31.5, 95% CI 22.3, 40.7). There was no statistically significant within-group improvement in the mean HrQoL scores in the octreotide (p = 0.21) or placebo groups (p = 0.78), although both groups reported reductions in mean nausea and vomiting (octreotide p < 0.01; placebo p = 0.02) and pain scores (octreotide p < 0.01; placebo p = 0.03). Although no statistically significant difference in changes in HrQoL scores between octreotide and placebo were seen, an adequately powered study is required to fully assess any differences in HrQoL scores. CONCLUSION:The HrQoL of patients with IMBO and vomiting is poor. Further research to formally evaluate the effects of standard therapies for IMBO is therefore warranted. TRIAL REGISTRATION:Australian New Zealand Clinical Trials Registry ACTRN12608000211369 (date registered 18/04/2008)

Analysis of epigenetic changes in survivors of preterm birth reveals the effect of gestational age and evidence for a long term legacy

BACKGROUND: Preterm birth confers a high risk of adverse long term health outcomes for survivors, yet the underlying molecular mechanisms are unclear. We hypothesized that effects of preterm birth can be mediated through measurable epigenomic changes throughout development. We therefore used a longitudinal birth cohort to measure the epigenetic mark of DNA methylation at birth and 18 years comparing survivors of extremely preterm birth with infants born at term. METHODS: Using 12 extreme preterm birth cases and 12 matched, term controls, we extracted DNA from archived neonatal blood spots and blood collected in a similar way at 18 years of age. DNA methylation was measured at 347,789 autosomal locations throughout the genome using Infinium HM450 arrays. Representative methylation differences were confirmed by Sequenom MassArray EpiTYPER. RESULTS: At birth we found 1,555 sites with significant differences in methylation between term and preterm babies. At 18 years of age, these differences had largely resolved, suggesting that DNA methylation differences at birth are mainly driven by factors relating to gestational age, such as cell composition and/or maturity. Using matched longitudinal samples, we found evidence for an epigenetic legacy associated with preterm birth, identifying persistent methylation differences at ten genomic loci. Longitudinal comparisons of DNA methylation at birth and 18 years uncovered a significant overlap between sites that were differentially-methylated at birth and those that changed with age. However, we note that overlapping sites may either differ in the same (300/1,555) or opposite (431/1,555) direction during gestation and aging respectively. CONCLUSIONS: We present evidence for widespread methylation differences between extreme preterm and term infants at birth that are largely resolved by 18 years of age. These results are consistent with methylation changes associated with blood cell development, cellular composition, immune induction and age at these time points. Finally, we identified ten probes significantly associated with preterm individuals and with greater than 5% methylation discordance at birth and 18 years that may reflect a long term epigenetic legacy of preterm birth

Development of a High Fidelity Dynamic Module of the Advanced Resistive Exercise Device (ARED) Using Adams

NASA's Digital Astronaut Project (DAP) implements well-vetted computational models to predict and assess spaceflight health and performance risks, and enhance countermeasure development. DAP provides expertise and computation tools to its research customers for model development, integration, or analysis. DAP is currently supporting the NASA Exercise Physiology and Countermeasures (ExPC) project by integrating their biomechanical models of specific exercise movements with dynamic models of the devices on which the exercises were performed. This presentation focuses on the development of a high fidelity dynamic module of the Advanced Resistive Exercise Device (ARED) on board the ISS. The ARED module, illustrated in the figure below, was developed using the Adams (MSC Santa Ana, California) simulation package. The Adams package provides the capabilities to perform multi rigid body, flexible body, and mixed dynamic analyses of complex mechanisms. These capabilities were applied to accurately simulate: Inertial and mass properties of the device such as the vibration isolation system (VIS) effects and other ARED components, Non-linear joint friction effects, The gas law dynamics of the vacuum cylinders and VIS components using custom written differential state equations, The ARED flywheel dynamics, including torque limiting clutch. Design data from the JSC ARED Engineering team was utilized in developing the model. This included solid modeling geometry files, component/system specifications, engineering reports and available data sets. The Adams ARED module is importable into LifeMOD (Life Modeler, Inc., San Clemente, CA) for biomechanical analyses of different resistive exercises such as squat and dead-lift. Using motion capture data from ground test subjects, the ExPC developed biomechanical exercise models in LifeMOD. The Adams ARED device module was then integrated with the exercise subject model into one integrated dynamic model. This presentation will describe the development of the Adams ARED module including its capabilities, limitations, and assumptions. Preliminary results, validation activities, and a practical application of the module to inform the relative effect of the flywheels on exercise will be discussed

Impulsivity in disorders of food and drug misuse.

BACKGROUND: Evidence suggests some overlap between the pathological use of food and drugs, yet how impulsivity compares across these different clinical disorders remains unclear. Substance use disorders are commonly characterized by elevated impulsivity, and impulsivity subtypes may show commonalities and differences in various conditions. We hypothesized that obese subjects with binge-eating disorder (BED) and abstinent alcohol-dependent cohorts would have relatively more impulsive profiles compared to obese subjects without BED. We also predicted decision impulsivity impairment in obesity with and without BED. METHOD: Thirty obese subjects with BED, 30 without BED and 30 abstinent alcohol-dependent subjects and age- and gender-matched controls were tested on delay discounting (preference for a smaller immediate reward over a larger delayed reward), reflection impulsivity (rapid decision making prior to evidence accumulation) and motor response inhibition (action cancellation of a prepotent response). RESULTS: All three groups had greater delay discounting relative to healthy volunteers. Both obese subjects without BED and alcohol-dependent subjects had impaired motor response inhibition. Only obese subjects without BED had impaired integration of available information to optimize outcomes over later trials with a cost condition. CONCLUSIONS: Delay discounting appears to be a common core impairment across disorders of food and drug intake. Unexpectedly, obese subjects without BED showed greater impulsivity than obese subjects with BED. We highlight the dissociability and heterogeneity of impulsivity subtypes and add to the understanding of neurocognitive profiles across disorders involving food and drugs. Our results have therapeutic implications suggesting that disorder-specific patterns of impulsivity could be targeted.V.V. is a Wellcome Trust Intermediate Fellow in Clinical Neurosciences (Wellcome Trust grant no. WT093705MA). Y.W. is supported by the Fyssen Fondation. N.A.H. is a Wellcome Trust Intermediate Fellow in Clinical Neurosciences. The BCNI is supported by both the Wellcome Trust and Medical Research Council.This is the accepted manuscript. The final version is available from CUP at http://dx.doi.org/10.1017/S003329171400183