Lipase inhibition attenuates the acute inhibitory effects of oral fat on food intake in healthy subjects

The lipase inhibitor, orlistat, is used in the treatment of obesity and reduces fat absorption by about 30%. However, the mean weight loss induced by orlistat is less than expected for the degree of fat malabsorption. It was hypothesised that lipase inhibition with orlistat attenuates the suppressive effects of oral fat on subsequent energy intake in normal-weight subjects. Fourteen healthy, lean subjects (nine males, five females; aged 25 +/- 1.3 years) were studied twice, in a double-blind fashion. The subjects received a high-fat yoghurt 'preload' (males 400 g (2562 kJ); females 300 g (1923 kJ)), containing orlistat (120 mg) on one study day (and no orlistat on the other 'control' day), 30 min before ad libitum access to food and drinks; energy intake was assessed during the following 8 h. Blood samples were taken at regular intervals for the measurement of plasma cholecystokinin (CCK). Each subject performed a 3 d faecal fat collection following each study. Energy intake during the day was greater following orlistat (10,220 (SEM 928) kJ) v. control (9405 (SEM 824) kJ) (P=0.02). On both days plasma CCK increased (P<0.05) after the preload. Plasma CCK 20 min following ingestion of the preload was less after orlistat (4.1 (SEM 0.9) pmol/l) v. control (5.3 (SEM 0.9) pmol/l (P=0.028); however there was no difference in the area under the curve 0-510 min between the two study days. Fat excretion was greater following orlistat (1017 (SEM 168) kJ) v. control (484 (SEM 90) kJ) (P=0.004). In conclusion, in healthy, lean subjects the acute inhibitory effect of fat on subsequent energy intake is attenuated by orlistat and the increase in energy intake approximates the energy lost due to fat malabsorption.Deirdre O’Donovan, Christine Feinle-Bisset, Judith Wishart and Michael Horowit

Workshop: Lassoing unicorns: how to map capabilities for better interdisciplinary research

Sometimes doing interdisciplinary work feels like trying to lasso unicorns. Working with big players from foreign disciplines and interdepartmental drifters. Negotiating over language and frameworks. Agreeing common research questions. All the while trying to gather data and do good work. Building on methods developed in ESRC and Horizon 2020 funded projects on interdisciplinary research, this workshop will: a) introduce the concept interdisciplinary capabilities - the disciplinary skills and informal aptitudes needed for people like environmental engineers, ecological economists and machine learning developers to work well together. b) present a mixed-method approach to mapping capabilities using bibliometric analysis and interviews. c) offer hands-on reflexive exercises on personal ‘capability mapping’, tailored to workshop participants The session will help scholars of all levels recognise power and knowledge in research and identify opportunities to steer that research together

Public Trust, Deliberative Engagement and Health Data Projects: Beyond Legal Provisions

In England, a new scheme for collating and sharing General Practitioners’ data has faced resistance from various quarters and has been deferred twice. While insufficient communication and ambiguous safeguards explain the widespread dissatisfaction expressed by the public and experts, we argue how dwindling public trust can be the most damaging variable in this picture - with implications not only for this scheme, but for any future project that aims to mobilise health data for medical research and innovation. We also highlight the indispensability of deliberative public engagement on the values being prioritised in health data initiatives, the significance of securing social license in addition to legal assurances, and the lessons in it of global pertinence

c-axis Josephson Tunnelling in Twinned and Untwinned YBCO-Pb Junctions

Within a microscopic two band model of planes and chains with a pairing potential in the planes and off diagonal pairing between planes and chains we find that the chains make the largest contribution to the Josephson tunnelling current and that through them the d-wave part of the gap contributes to the current. This is contrary to the usual assumption that for a d-wave tetragonal superconductor the c-axis Josephson current for incoherent tunnelling into an s-wave superconductor is zero while that of a d-wave orthorhombic superconductor with a small s-wave component to its gap it is small but non-zero. Nevertheless it has been argued that the effect of twins in YBCO would lead to cancellation between pairs of twins and so the observation of a current in c-axis YBCO-Pb experiments is evidence against a d-wave type order parameter. We argue that both theory and experiment give evidence that the two twin orientations are not necessarily equally abundant and that the ratio of tunnelling currents in twinned and untwinned materials should be related to the relative abundance of the two twin orientations.Comment: 6 pages, RevTeX 3.0, 15 PostScript figur

Two Hands on the Wheel: Steering Robotics Innovation in Useful Directions

Practices of innovation are not autonomous. Research in STS and innovation studies has shown both the speed of knowledge production, and crucially its direction, may be susceptible to change. Indeed, interventions to the rate and direction of innovation are crucial if we are to address address the transformations needed in the economy and wider society that might for example avoid the extremes of climate change and meet the sustainable development goals. Yet interventions in these regards remain inexact. Innovation policy is one way in which government seeks to drive the production of policy towards or away from specific ends. Recent initiatives such as efforts to include "co-creation" have sought to open up innovation practices to a wider range of actors, broadening participation. But what arrangements of objects, sites, publics, and concepts do these instruments create? And how might these arrangements contribute to the laudable if lofty goals of steering innovation in useful directions? The paper follows two innovation instruments designed to influence innovation in the domain of robotics; the establishment of a "certified testbed" and a "co-creation facility". The paper asks how do co-creation instruments in the field of robotics steer innovation towards social progress or otherwise? Using a situated analysis method, this paper traces the two instruments in and around a single robotics innovation facility in the United Kingdom

How much dystrophin is enough: the physiological consequences of different levels of dystrophin in the mdx mouse

Splice modulation therapy has shown great clinical promise in Duchenne muscular dystrophy, resulting in the production of dystrophin protein. Despite this, the relationship between restoring dystrophin to established dystrophic muscle and its ability to induce clinically relevant changes in muscle function is poorly understood. In order to robustly evaluate functional improvement, we used in situ protocols in the mdx mouse to measure muscle strength and resistance to eccentric contraction-induced damage. Here, we modelled the treatment of muscle with pre-existing dystrophic pathology using antisense oligonucleotides conjugated to a cell-penetrating peptide. We reveal that 15% homogeneous dystrophin expression is sufficient to protect against eccentric contraction-induced injury. In addition, we demonstrate a >40% increase in specific isometric force following repeated administrations. Strikingly, we show that changes in muscle strength are proportional to dystrophin expression levels. These data define the dystrophin restoration levels required to slow down or prevent disease progression and improve overall muscle function once a dystrophic environment has been established in the mdx mouse model

Cmah-dystrophin deficient mdx mice display an accelerated cardiac phenotype that is improved following peptide-PMO exon skipping treatment

Duchenne muscular dystrophy (DMD) is caused by loss of dystrophin protein, leading to progressive muscle weakness and premature death due to respiratory and/or cardiac complications. Cardiac involvement is characterized by progressive dilated cardiomyopathy, decreased fractional shortening and metabolic dysfunction involving reduced metabolism of fatty acids—the major cardiac metabolic substrate. Several mouse models have been developed to study molecular and pathological consequences of dystrophin deficiency, but do not recapitulate all aspects of human disease pathology and exhibit a mild cardiac phenotype. Here we demonstrate that Cmah (cytidine monophosphate-sialic acid hydroxylase)-deficient mdx mice (Cmah−/−;mdx) have an accelerated cardiac phenotype compared to the established mdx model. Cmah−/−;mdx mice display earlier functional deterioration, specifically a reduction in right ventricle (RV) ejection fraction and stroke volume (SV) at 12 weeks of age and decreased left ventricle diastolic volume with subsequent reduced SV compared to mdx mice by 24 weeks. They further show earlier elevation of cardiac damage markers for fibrosis (Ctgf), oxidative damage (Nox4) and haemodynamic load (Nppa). Cardiac metabolic substrate requirement was assessed using hyperpolarized magnetic resonance spectroscopy indicating increased in vivo glycolytic flux in Cmah−/−;mdx mice. Early upregulation of mitochondrial genes (Ucp3 and Cpt1) and downregulation of key glycolytic genes (Pdk1, Pdk4, Ppara), also denote disturbed cardiac metabolism and shift towards glucose utilization in Cmah−/−;mdx mice. Moreover, we show long-term treatment with peptide-conjugated exon skipping antisense oligonucleotides (20-week regimen), resulted in 20% cardiac dystrophin protein restoration and significantly improved RV cardiac function. Therefore, Cmah−/−;mdx mice represent an appropriate model for evaluating cardiac benefit of novel DMD therapeutics

Strategies and challenges to facilitate situated learning in virtual worlds post-Second Life

Virtual worlds can establish a stimulating environment to support a situated learning approach in which students simulate a task within a safe environment. While in previous years Second Life played a major role in providing such a virtual environment, there are now more and more alternative—often OpenSim-based—solutions deployed within the educational community. By drawing parallels to social networks, we discuss two aspects: how to link individually hosted virtual worlds together in order to implement context for immersion and how to identify and avoid “fake” avatars so people behind these avatars can be held accountable for their actions

Putting a social-constructivist assessment process model into practice: building the feedback loop into the assessment process through peer review

This paper reports the latest stage of a research project focused on developing students' understanding of assessment criteria, the assessment process and assessment standards. It explains the theory of a social-constructivist assessment process model and details one particular module where the authors have tried to put it into practice. In particular, it focuses on attempts to actively engage the students with feedback on their work, and the feedback process, and considers the evidence of whether it has been effective