The implausibility of ‘usual care’ in an open system: sedation and weaning practices in Paediatric Intensive Care Units (PICUs) in the United Kingdom (UK).

Background
The power of the randomised controlled trial depends upon its capacity to operate in a closed system whereby the intervention is the only causal force acting upon the experimental group and absent in the control group, permitting a valid assessment of intervention efficacy. Conversely, clinical arenas are open systems where factors relating to context, resources, interpretation and actions of individuals will affect implementation and effectiveness of interventions. Consequently, the comparator (usual care) can be difficult to define and variable in multi-centre trials. Hence outcomes cannot be understood without considering usual care and factors that may affect implementation and impact on the intervention.

Methods
Using a fieldwork approach, we describe PICU context, ‘usual’ practice in sedation and weaning from mechanical ventilation, and factors affecting implementation prior to designing a trial involving a sedation and ventilation weaning intervention. We collected data from 23 UK PICUs between June and November 2014 using observation, individual and multi-disciplinary group interviews with staff.

Results
Pain and sedation practices were broadly similar in terms of drug usage and assessment tools. Sedation protocols linking assessment to appropriate titration of sedatives and sedation holds were rarely used (9 % and 4 % of PICUs respectively). Ventilator weaning was primarily a medical-led process with 39 % of PICUs engaging senior nurses in the process: weaning protocols were rarely used (9 % of PICUs). Weaning methods were variably based on clinician preference. No formal criteria or use of spontaneous breathing trials were used to test weaning readiness. Seventeen PICUs (74 %) had prior engagement in multi-centre trials, but limited research nurse availability. Barriers to previous trial implementation were intervention complexity, lack of belief in the evidence and inadequate training. Facilitating factors were senior staff buy-in and dedicated research nurse provision.

Conclusions
We examined and identified contextual and organisational factors that may impact on the implementation of our intervention. We found usual practice relating to sedation, analgesia and ventilator weaning broadly similar, yet distinctively different from our proposed intervention, providing assurance in our ability to evaluate intervention effects. The data will enable us to develop an implementation plan; considering these factors we can more fully understand their impact on study outcomes.

High-resolution genetic analysis reveals extensive gene flow within the jellyfish Pelagia noctiluca (Scyphozoa) in the North Atlantic and Mediterranean Sea

Despite the importance of gelatinous zooplankton as components of marine ecosystems, both ecologically and socio-economically, relatively little is known about population persistence or connectivity in jellyfish. In the present study, we employed a combination of nuclear microsatellite markers and sequence data from the mitochondrial cytochrome oxidase I (COI) gene to determine levels and patterns of population genetic structuring in the holoplanktonic jellyfish Pelagia noctiluca across the northeast Atlantic Ocean and Mediterranean Sea. Our results indicate a high degree of connectivity in P. noctiluca, with little evidence of geographical structuring of genetic variation. A small but significant differentiation of Atlantic Ocean and Mediterranean stocks was detected based on the microsatellite data, but no evidence of differentiation was observed with the mtDNA, probably due to the higher power of the microsatellites to detect low levels of genetic structuring. Two clearly distinct groups of genotypes were observed within the mtDNA COI, which probably diverged in the early Pleistocene, but with no evidence of geographical structuring. Palaeodistribution modelling of P. noctiluca at the Last Glacial Maximum (LGM; ca. 21 KYA) indicated large areas of suitable habitat south of the species’ current-day distribution, with little reduction in area. The congruent evidence for minimal genetic differentiation from the nuclear microsatellites and the mtDNA, coupled with the results of the palaeodistribution modelling, supports the idea of long-term population stability and connectivity, thus providing key insights into the population dynamics and demography of this important species

Foreign Direct Investment and Country Risk::Is There Evidence of 'Malign Investment in the Former Soviet States'

This paper examines the relationship between concepts of MNE bargaining power and broader concepts of political power. It notes that the analysis of MNE bargaining power presents a number of puzzles from the perspective of political theory. These puzzles arise, in part, from the fact that the overlap between traditional concepts of MNE bargaining power and broader concepts of political power is only a partial one. Despite these problems, it is suggested that political- theory-based approaches can add realism to our understanding of bargaining power.

Government as Institutional Entrepreneur: Extending Working Life in the UK and Japan

Through the lens of Institutional Entrepreneurship, this paper discusses how governments use the levers of power afforded through business and welfare systems to affect change in the organisational management of older workers. It does so using national stakeholder interviews in two contrasting economies: the United Kingdom and Japan. Both governments have taken a ‘light-touch’ approach to work and retirement. However, the highly institutionalised Japanese system affords the government greater leverage than that of the liberal UK system in changing employer practices at the workplace level.

The Casimir effect in the presence of compactified universal extra dimensions

The Casimir force in a system consisting of two parallel conducting plates in the presence of compactified universal extra dimensions (UXD) is analyzed. The Casimir force with UXDs differs from the force obtained without extra dimensions. A new power law for the Casimir force is derived. By comparison to experimental data the size R of the universal extra dimensions can be restricted to R⩽10 nm for one extra dimension.

Economic Stability and Economic Governance in the Euro Area:What the European Crisis Can Teach on the Limits of Economic Integration

The recent European economic crisis has dramatically exposed the failures of
the various institutional mechanisms in place to maintain economic stability
in Europe, and has unveiled the difficulty in achieving international coordination
on fiscal and financial stability policies. Drawing on the European
experience, this article analyzes the concept of economic stability in international
law and highlights the peculiar problems connected to its maintenance
or promotion. First, we demonstrate that policies that safeguard and
protect economic stability are largely regulated and managed at the national
level, due to their inextricable relationship with the exercise of national political
power. Until recently, more limited levels of pan-European integration
did not make the coordination of economic stability policies seem necessary.
However, a much deeper level of economic integration makes it very difficult
to tackle an international economic crisis through national responses. If EU
Member states wish to maintain and deepen economic integration, they
must accept an erosion of sovereignty over their economic stability policies.
This will not only deprive states of a fundamental anchor of political power,
but also create a challenge for the maintenance of democratic control over
economic policies. Second, this article argues that soft law approaches are
likely ineffective in enforcing the regulatory disciplines required to ensure
economic stability.

The dust environment of comet 67P/Churyumov-Gerasimenko from Rosetta OSIRIS and VLT observations in the 4.5 to 2.9 au heliocentric distance range inbound

Context. The ESA Rosetta spacecraft, currently orbiting around comet 67P/Churyumov-Gerasimenko, has already provided in situ measurements of the dust grain properties from several instruments,particularly OSIRIS and GIADA. We propose adding value to those measurements by combining them with ground-based observations of the dust tail to monitor the overall, time-dependent dust-production rate and size distribution.
Aims. To constrain the dust grain properties, we take Rosetta OSIRIS and GIADA results into account, and combine OSIRIS data during the approach phase (from late April to early June 2014) with a large data set of ground-based images that were acquired with the ESO Very Large Telescope (VLT) from February to November 2014.
Methods. A Monte Carlo dust tail code, which has already been used to characterise the dust environments of several comets and active asteroids, has been applied to retrieve the dust parameters. Key properties of the grains (density, velocity, and size distribution) were obtained from Rosetta observations: these parameters were used as input of the code to considerably reduce the number of free parameters. In this way, the overall dust mass-loss rate and its dependence on the heliocentric distance could be obtained accurately.
Results. The dust parameters derived from the inner coma measurements by OSIRIS and GIADA and from distant imaging using VLT data are consistent, except for the power index of the size-distribution function, which is α = −3, instead of α = −2, for grains smaller than 1 mm. This is possibly linked to the presence of fluffy aggregates in the coma. The onset of cometary activity occurs at approximately 4.3 AU, with a dust production rate of 0.5 kg/s, increasing up to 15 kg/s at 2.9 AU. This implies a dust-to-gas mass ratio varying between 3.8 and 6.5 for the best-fit model when combined with water-production rates from the MIRO experiment.

Philosophy and Political Engagement: Reflection in the Public Sphere

Do philosophers have a responsibility to their society that is distinct from their responsibility to it as citizens? This edited volume explores both what type of contribution philosophy can make and what type of reasoning is appropriate when addressing public matters now. These questions are posed by leading international scholars working in the fields of moral and political philosophy. Each contribution also investigates the central issue of how to combine critical, rational analysis with a commitment to politically relevant public engagement. The contributions to this volume analyse issues raised in practical ethics, including abortion, embryology, and assisted suicide. They consider the role of ethical commitment in the philosophical analysis of contemporary political issues, and engage with matters of public policy such as poverty, the arts, meaningful work, as well as the evidence base for policy. They also examine the normative legitimacy of power, including the use of violence.

Off-Duty Resilience: Re-orienting Tourism, Leisure and Recreation in the US Army BOSS program

Understanding how US imperial strategy is sustained by tourism and militarism requires an account of how American soldiers learn to understand themselves in relation to a variety of marginalized others. This paper explores how the US Army’s ‘Ready and Resilient’ (R2) campaign constructs soldier / other relations by mobilizing off-duty time through the ‘Better Opportunities for Single Soldiers’ (BOSS) program. BOSS’s first two platforms of ‘Well-Being’ and ‘Community Service’ feed into the R2 agenda by producing highly-skilled leaders (who govern a disengaged rank and file) and benevolent humanitarians (who provide charity for abject civilians). When these dispositions are transposed into BOSS’s third platform of ‘Recreation and Leisure’, soldiers turn away from the goals of leadership and humanitarianism to reveal the privileged narcissism underscoring the R2 agenda. This self-focus is intensified by familiar power relations in the tourism industry as soldiers pursue self-improvement by commodifying, distancing and effacing local tourist workers. Using the BOSS program as a case study, this paper critically interrogates how the US Army is assimilating off-duty practices of tourism, leisure and recreation into the wider program of resilience training.

The Adaptiveness in Stock Markets: Testing the Stylized Facts in the DAX 30

By testing a simple asset pricing model of heterogeneous agents to characterize the power-law behavior of the DAX 30 from 1975 to 2007, we provide supporting evidence on empirical findings that investors and fund managers use combinations of fixed and switching strategies based on fundamental and technical analysis when making investment decisions. By conducting econometric analysis via Monte Carlo simulations, we show that the autocorrelation patterns, the estimates of the power-law decay indices, (FI)GARCH parameters, and tail index of the model match closely the corresponding estimates for the DAX 30. A mechanism analysis based on the calibrated model provides further insights into the explanatory power of heterogeneous agent models.

Effect assessment of nanoparticles toxicity in the terrestrial compartment

Over 11 million tons of nanomaterials (NMs) have been produced in 2012 and predictions point the increase in production. Despite predictions and extended usage via consumer products and industry, the understanding of the potential impact of these materials on the environment is virtually absent. The main aim of this thesis is to understand how a selected group of nanomaterials (metal based particles) may impact soil invertebrates, with special focus on the mechanisms of response. Since a case-by-case Environmental Risk Assessment (ERA) of all the emerging contaminants (particularly NMs) is impossible, among others due to time and cost reasons, to gain understanding on the mechanism of action and response is very important to reach a common paradigm. Understanding the modes of action provides predictive characters in cross particle extrapolation. Besides, it also provides insight for the production of new and sustainable materials. Overall, the effects of the selected NMs (Copper and Silver, Titanium and Zirconium oxides) and the respective salt forms, were investigated at the gene expression (using high-throughput tools, microarray and qPCR technology), biochemical (using enzymatic assays for analysis of oxidative stress markers) and organism (survival and reproduction as in OECD test guidelines) levels, this using standard soil species (Enchytraeus albidus, Enchytraeus crypticus, Eisenia fetida). Gene expression analysis provided valuable information on the mechanisms affected by each of the NMs. The gene expression profile highlighted a (nano)material signature and the effect of the duration of exposure. The functional analyses integrated with the biochemical and organism data, revealed a good understanding power. The biochemical parameters (oxidative stress related) were distinct across the materials and also influenced by duration of exposure and concentration. The standardized organismal responses differed the least between the various materials. The overall outcome is that, in this context of NMs effect assessment, gene expression and enzymatic assays introduced a very important knowledge gap, which could not had been achieved by the standard organismal effects alone. A reoccurring issue with some metal based NMs is the possible dissolution and subsequent release of ions that then causes toxicity e.g. Cu-NPs or Ag-NPs release Cu2+ or Ag+. The oxidation state of the particles was investigated, although this was not the focus of the thesis. The study of fate, e.g. dissolution of NPs, is also only in its beginning and the appropriate techniques are currently being developed. The results showed a specific nanoparticle effect. The UV exposure with titanium dioxide nanoparticles increased its effect.

Integer-valued APARCH processes in the analysis of time series of counts

The Asymmetric Power Arch representation for the volatility was introduced by Ding et al.(1993) in order to account for asymmetric responses in the volatility in the analysis of continuous-valued financial time series like, for instance, the log-return series of foreign exchange rates, stock indices or share prices. As reported by Brannas and Quoreshi (2010), asymmetric responses in volatility are also observed in time series of counts such as the number of intra-day transactions in stocks. In this work, an asymmetric power autoregressive conditional Poisson model is introduced for the analysis of time series of counts exhibiting asymmetric overdispersion. Basic probabilistic and statistical properties are summarized and parameter estimation is discussed. A simulation study is presented to illustrate the proposed model. Finally, an empirical application to a set of data concerning the daily number of stock transactions is also presented to attest for its practical applicability in data analysis.

The discursive construction of Portuguese national identity in the media thirty years after the 1974 revolution

Tese dout., Philosophy, Lancaster University, 2010

Co-localization of GnRH ligands and their receptors in the European sea bass, Dicentrarchus labrax

The migration of the hypophysiotropic GnRH (GnRH-I) neurons during early development is a crucial step in establishing a normally functioning reproductive system in all vertebrates. These neurons derive from progenitor cells in the olfactory placode and subsequently migrate to their final position in the ventral forebrain, where they mediate hypophysiotropic control over Lh. We use zebrafish as a model to investigate the path and the factors that mediate the migration of the GnRH-I neurons during early development. A transgenic line of zebrafish, in which GnRH- I neurons specifically express a reporter gene (GFP) has been developed in our lab. This was achieved by integrating a GnRH-I promoter/GFP reporter transgene into the zebrafish genome. The resulting transgenic line allows us to track the route of the GnRH-I neuronal migration in real time and in vivo. We have used this line to conduct time lapse imaging to ascertain the exact migrational path and the final position in the ventral forebrain of the GnRH-I neurons.