The simulation of action disorganisation in complex activities of daily living

Action selection in everyday goal-directed tasks of moderate complexity is known to be subject to breakdown following extensive frontal brain injury. A model of action selection in such tasks is presented and used to explore three hypotheses concerning the origins of action disorganisation: that it is a consequence of reduced top-down excitation within a hierarchical action schema network coupled with increased bottom-up triggering of schemas from environmental sources, that it is a more general disturbance of schema activation modelled by excessive noise in the schema network, and that it results from a general disturbance of the triggering of schemas by object representations. Results suggest that the action disorganisation syndrome is best accounted for by a general disturbance to schema activation, while altering the balance between top-down and bottom-up activation provides an account of a related disorder - utilisation behaviour. It is further suggested that ideational apraxia (which may result from lesions to left temporoparietal areas and which has similar behavioural consequences to action disorganisation syndrome on tasks of moderate complexity) is a consequence of a generalised disturbance of the triggering of schemas by object representations. Several predictions regarding differences between action disorganisation syndrome and ideational apraxia that follow from this interpretation are detailed

Clinical narrative analytics challenges

Precision medicine or evidence based medicine is based on the extraction of knowledge from medical records to provide individuals with the appropriate treatment in the appropriate moment according to the patient features. Despite the efforts of using clinical narratives for clinical decision support, many challenges have to be faced still today such as multilinguarity, diversity of terms and formats in different services, acronyms, negation, to name but a few. The same problems exist when one wants to analyze narratives in literature whose analysis would provide physicians and researchers with highlights. In this talk we will analyze challenges, solutions and open problems and will analyze several frameworks and tools that are able to perform NLP over free text to extract medical entities by means of Named Entity Recognition process. We will also analyze a framework we have developed to extract and validate medical terms. In particular we present two uses cases: (i) medical entities extraction of a set of infectious diseases description texts provided by MedlinePlus and (ii) scales of stroke identification in clinical narratives written in Spanish

Autotaxin-lysophosphatidic acid receptor signalling regulates hepatitis C virus replication

Background & Aims Chronic hepatitis C is a global health problem with an estimated 170 million hepatitis C virus (HCV) infected individuals at risk of progressive liver disease and hepatocellular carcinoma (HCC). Autotaxin (ATX, gene name: ENPP2) is a phospholipase with diverse roles in the physiological and pathological processes including inflammation and oncogenesis. Clinical studies have reported increased ATX expression in chronic hepatitis C, however, the pathways regulating ATX and its role in the viral life cycle are not well understood. Methods In vitro hepatocyte and ex vivo liver culture systems along with chimeric humanized liver mice and HCC tissue enabled us to assess the interplay between ATX and the HCV life cycle. Results HCV infection increased hepatocellular ATX RNA and protein expression. HCV infection stabilizes hypoxia inducible factors (HIFs) and we investigated a role for these transcription factors to regulate ATX. In vitro studies show that low oxygen increases hepatocellular ATX expression and transcriptome analysis showed a positive correlation between ATX mRNA levels and hypoxia gene score in HCC tumour tissue associated with HCV and other aetiologies. Importantly, inhibiting ATX-lysophosphatidic acid (LPA) signalling reduced HCV replication, demonstrating a positive role for this phospholipase in the viral life cycle. LPA activates phosphoinositide-3-kinase that stabilizes HIF-1α and inhibiting the HIF signalling pathway abrogates the pro-viral activity of LPA. Conclusions Our data support a model where HCV infection increases ATX expression which supports viral replication and HCC progression. Lay summary Chronic hepatitis C is a global health problem with infected individuals at risk of developing liver disease that can progress to hepatocellular carcinoma. Autotaxin generates the biologically active lipid lysophosphatidic acid that has been reported to play a tumorigenic role in a wide number of cancers. In this study we show that hepatitis C virus infection increases autotaxin expression via hypoxia inducible transcription factor and provides an environment in the liver that promotes fibrosis and liver injury. Importantly, we show a new role for lysophosphatidic acid in positively regulating hepatitis C virus replication.Research in the McKeating laboratory was funded by the MRC, NIHR Birmingham Liver BRU, EU FP7 PathCO and H2020 grant Hep-CAR. Research in the Wakelam lab is supported by BBSRC and Hep-CAR. Stephanie Roessler was supported by Hep-CAR, DFG grant RO4673, the Olympia-Morata Programme, a Brigitte-Schieben-Lange Fellowship and a Heidelberg School of Oncology Fellowship

An Incomplete TCA Cycle Increases Survival of Salmonella Typhimurium during Infection of Resting and Activated Murine Macrophages

In comparison to the comprehensive analyses performed on virulence gene expression, regulation and action, the intracellular metabolism of Salmonella during infection is a relatively under-studied area. We investigated the role of the tricarboxylic acid (TCA) cycle in the intracellular replication of Salmonella Typhimurium in resting and activated macrophages, epithelial cells, and during infection of mice.We constructed deletion mutations of 5 TCA cycle genes in S. Typhimurium including gltA, mdh, sdhCDAB, sucAB, and sucCD. We found that the mutants exhibited increased net intracellular replication in resting and activated murine macrophages compared to the wild-type. In contrast, an epithelial cell infection model showed that the S. Typhimurium ΔsucCD and ΔgltA strains had reduced net intracellular replication compared to the wild-type. The glyoxylate shunt was not responsible for the net increased replication of the TCA cycle mutants within resting macrophages. We also confirmed that, in a murine infection model, the S. Typhimurium ΔsucAB and ΔsucCD strains are attenuated for virulence.Our results suggest that disruption of the TCA cycle increases the ability of S. Typhimurium to survive within resting and activated murine macrophages. In contrast, epithelial cells are non-phagocytic cells and unlike macrophages cannot mount an oxidative and nitrosative defence response against pathogens; our results show that in HeLa cells the S. Typhimurium TCA cycle mutant strains show reduced or no change in intracellular levels compared to the wild-type. The attenuation of the S. Typhimurium ΔsucAB and ΔsucCD mutants in mice, compared to their increased net intracellular replication in resting and activated macrophages suggest that Salmonella may encounter environments within the host where a complete TCA cycle is advantageous

The Inclusiveness and Emptiness of <i>Gong Qi</i>: A Non-Anglophone Perspective on Ethics from a Sino-Japanese Corporation

This article introduces a non-Anglophone concept of gong qi(communal vessel, 公器) as a metaphor for ‘corporation’. It contributes an endogenous perspective from a Sino-Japanese organizational context that enriches mainstream business ethics literature, otherwise heavily reliant on Western traditions. We translate the multi-layered meanings of gong qi based on analysis of its ideograms, its references into classical philosophies, and contemporary application in this Japanese multinational corporation in China. Gong qi contributes a perspective that sees a corporation as an inclusive and virtuous social entity, and also addresses the elusive, implicit, and forever evolving nature of organizational life that is rarely noticed. We propose gong qi can be applied in other organizations and wider cultural contexts to show a new way of seeing and understanding business ethics and organization. Rather than considering virtue as a list of definable individual qualities, we suggest that the metaphor of gong qi reveals how virtue can be experienced as indeterminate, yet immanently present, like the substance of emptiness. This, then allows us to see the virtue of immanence, the beauty of implicitness, and hence, the efficacy of gong qi

Bowel management for the treatment of pediatric fecal incontinence

Fecal incontinence is a devastating underestimated problem, affecting a large number of individuals all over the world. Most of the available literature relates to the management of adults. The treatments proposed are not uniformly successful and have little application in the pediatric population. This paper presents the experience of 30 years, implementing a bowel management program, for the treatment of fecal incontinence in over 700 pediatric patients, with a success rate of 95%. The main characteristics of the program include the identification of the characteristics of the colon of each patient; finding the specific type of enema that will clean that colon and the radiological monitoring of the process