Paracetamol Toxicity: Influence Of Ageing, Frailty, Resveratrol And Sirt1

The objective of this thesis was to help improve the safety of paracetamol for patients of all ages by adding evidence to the body of knowledge on the changing risks of paracetamol toxicity in ageing, frailty and non-acute exposures, and the potential for lifespan and healthspan increasing interventions to provide novel mechanisms of paracetamol hepatotoxicity protection. Furthermore, this thesis aimed to investigate the potential of both paracetamol, and lifespan and healthspan interventions in delaying or preventing frailty. Overall the work presented in this thesis used a series of mouse models to contribute to three main findings with clinical significance. Firstly, they demonstrated that there is no increase in susceptibility to paracetamol toxicity in old age or frailty, with either acute, chronic or sub-acute paracetamol exposure. Secondly, they showed that the currently used paracetamol hepatotoxicity therapy, NAC, does not protect against toxicity induced by sub-acute paracetamol exposure. Further studies showed that the mechanism of SIRT1 activation does not provide an alternative protective mechanism. Finally, this thesis found that the lifespan and healthspan increasing interventions of resveratrol and calorie restriction, but not therapeutic paracetamol, were able to delay frailty in aged mice

Scheduling Of Dataflow Models Within The Reconfigurable Video Coding Framework

The upcoming Reconfigurable Video Coding (RVC) standard from MPEG (ISO/IEC SC29WG11) defines a library of coding tools to specify existing or new compressed video formats and decoders. The coding tool library has been written in a dataflow/actor-oriented language named CAL. Each coding tool can be represented with an extended finite state machine and the dependencies between the tools are described as dataflow graphs. This paper proposes an approach to derive a multiprocessor execution schedule for RVC systems that are comprised of CAL actors. In addition to proposing a scheduling approach for RVC, an extension to the well-known permutation flow shop scheduling problem that enables rapid run-time scheduling of RVC tasks is introduced

Of “sluts” and “arseholes”: Antagonistic desire and the production of sexual vigilance

This article examines a contemporary antagonism in gendered safety discourses—the imperative to be free in public space against the obligation to be safe and “properly” feminine. We argue that this produces (and is produced by) contemporary rape culture, which might be contested through recourse to an agonistic ethic. Using qualitative interview data, we examine how participants contest victim-blaming discourses, while limiting how far they will accept the female body’s right to occupy public space. This article has significant implications for approaching social justice, in particular justice for women and their right to occupy public space

Who talks to whom about what? How interdisciplinary communication and knowledge of expertise distribution improves in integrated R&D labs

Although several studies have examined the impact of open workspaces, there is still an on-going debate about its advantages and disadvantages. Our paper contributes to this debate by shedding light on three issues: the effect of open workspaces on (1) the flow of communication along and across hierarchical lines; (2) the content of communication; and (3) the specificities of open integrated laboratories. Our findings derive from a longitudinal case in a large pharmaceutical company that has relocated some R&D teams from enclosed to multi-space offices and labs. The relocation has resulted in (a) increased interdisciplinary communication, particularly at lower hierarchical levels, (b) a shift of the location of discussions and the content of conversations and (c) an improved knowledge about expertise distribution. Practitioner Summary Communication is essential in knowledge-driven organisations. This article examines the impact of a relocation of R&D employees from enclosed to multi-space offices and labs on communication patterns. We explain how the new environment fosters interdisciplinary communication, shifts the location of discussions and increases the knowledge of expertise distribution

Static and Dynamic Lung Volumes in Swimmers and Their Ventilatory Response to Maximal Exercise

Purpose While the static and dynamic lung volumes of active swimmers is often greater than the predicted volume of similarly active non-swimmers, little is known if their ventilatory response to exercise is also different. Methods Three groups of anthropometrically matched male adults were recruited, daily active swimmers (n = 15), daily active in fields sport (Rugby and Football) (n = 15), and recreationally active (n = 15). Forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and maximal voluntary ventilation (MVV) was measured before and after exercise to volitional exhaustion. Results Swimmers had significantly larger FVC (6.2 ± 0.6 l, 109 ± 9% pred) than the other groups (5.6 ± 0.5 l, 106 ± 13% pred, 5.5 ± 0.8, 99% pred, the sportsmen and recreational groups, respectively). FEV1 and MVV were not different. While at peak exercise, all groups reached their ventilatory reserve (around 20%), the swimmers had a greater minute ventilation rate than the recreational group (146 ± 19 vs 120 ± 87 l/min), delivering this volume by breathing deeper and slower. Conclusions The swimmers utilised their larger static volumes (FVC) differently during exercise by meeting their ventilation volume through long and deep breaths

Exploring the cultural dimensions of environmental victimization

It has become increasingly clear in recent years that our understanding of ‘victimisation’ is informed by a whole range of societal and political factors which extend well beyond whatever particular form of words appears in any given directive, code or legislative instrument concerning crime, crime victims or criminal justice systems. In this paper, I will seek for the first time to apply recent developments in our understanding of so-called 'cultural victimology' to the issue of environmental harm and its impact on human and non-human animals. McCGarry and Waklate (2015) characterise cultural victimology as broadly comprising of two key aspects. These are the wider sharing and reflection of individual and collective victimisation experiences on the one hand and, on the other, the mapping of those experiences through the criminal justice process. In this discussion I will examine how environmental victimisation is viewed by and presented to society at large and will argue that such representations often fail, as a form of testimony, to adequately convey the traumas involved. Nor is this achieved through the application of present models of criminal, civil or administrative justice regimes in many jurisdictions. This lack of cultural acknowledgement of the harms vested on environmental victims, it is argued, afford us a clearer understand of the continued reticence amongst lawmakers, politicians and legal practitioners to adequately address the impacts of such victimisation through effective justice or regulatory mechanisms. This is unfortunate given that the often collective nature of environmental victimisation makes this particularly suited to a more cultural analysis and understanding. It is argued that various forms of environmental mediation processes might hold the key to this cultural reticence to accept environmental harm as a 'real' and pressing problem as compared to other criminal and civil justice concerns

Drivers for international innovation activities in developed and emerging countries

This paper aims to shed light on firm specific drivers that lead firms to internationalise their innovation activities. The paper draws a comprehensive picture of driving forces by including firm capabilities, characteristics of the firm’s competitive environment and the influence of innovation obstacles in the home country. In particular, the role of the potential driving forces is tested on the probability to carry out different innovative activities abroad (R&D, design/conception of new products, manufacturing of innovative products and implementation of new processes). In a second step these driving forces are used to observe their impact on the decision to locate innovation activities in various countries and regions (China, Eastern Europe, Western Europe and North America) as well as in groups of countries with similar levels of knowledge (country clubs). The analysis is based on the Mannheim Innovation Panel survey which represents the German CIS (Community Innovation Survey) contribution. Two survey waves are combined and result in a sample of about 1400 firms. The results show that the decision to perform innovation activities abroad is mainly driven by organisational capabilities such as absorptive capacities, international experience and existing technological competences of the respective firm. Innovation barriers at the German home base such as lack of labour and high innovation costs foster the set up of later-stage innovation activities abroad while the lack of demand demonstrates a barrier to the internationalisation decision for the development and manufacturing of new products. Location decisions receive the strongest influencing effects from the international experience of the firm. Firms which innovate in developing countries seem to require a more extensive level of international experience by international R&D cooperation

Beyond crime statistics: the construction and application of a criminogenity monitor in Amsterdam

Criminologists have devoted a great deal of attention to risk factors - also called criminogenic factors - leading to criminal offending. This paper presents a criminogenity monitor which includes 19 risk factors that underlie crime. These factors do not themselves cause criminal behaviour; rather, they must be seen as signals that crimes may be committed. After discussing how the criminogenity monitor was constructed, we apply the risk factors we examined to the situation in Amsterdam, capital city of the Netherlands. The monitor is intended to function particularly as an instrument to rationalise policy-makers' work in targeting and preventing symptoms of crime at three geographical levels: the entire city, its boroughs and its neighbourhoods. © 2012 The Author(s)

Drivers and Effects of Internationalising Innovation by SMEs

This paper investigates the drivers and the effects of the internationalisation of innovation activities in SMEs based on a large data set of German firms covering the period 2002-2007. We look at different stages of the innovation process (R&D, design, production and sales of new products, and implementation of new processes) and explore the role of internal resources, home market competition and innovationrelated location advantages for an SME’s decision to engage in innovation activities abroad. By linking international innovation activities to firm growth in the home market we try to identify likely internationalisation effects at the firm level. The results show that export experience and experience in knowledge protection are highly important for international innovation activities of SMEs. Fierce home market competition turns out to be rather an obstacle than a driver. High innovation costs stimulate internationalisation of non-R&D innovation activities, and shortage of qualified labour expels production of new products. R&D activities abroad and exports of new products spur firm growth in the home market while there are no negative effects on home market growth from shifting production of new products abroad