Influence of chylomicron remnants on human monocyte activation in vitro

Background and aims Atherosclerosis is known to be an inflammatory disease and there is increasing evidence that chylomicron remnants (CMR), the lipoproteins which carry dietary fats in the blood, cause macrophage foam cell formation and inflammation. In early atherosclerosis the frequency of activated monocytes in the peripheral circulation is increased, and clearance of CMR from blood may be delayed, however, whether CMR contribute directly to monocyte activation and subsequent egress into the arterial wall has not been established. Here, the contribution of CMR to activation of monocyte pro-inflammatory pathways was assessed using an in vitro model. Methods and results Primary human monocytes and CMR-like particles (CRLP) were used to measure several endpoints of monocyte activation. Treatment with CRLP caused rapid and prolonged generation of reactive oxygen species by monocytes. The pro-inflammatory chemokines MCP-1 and IL-8 were secreted in nanogram quantities by the cells in the absence of CRLP. IL-8 secretion was transiently increased after CRLP treatment, and CRLP maintained secretion in the presence of pharmacological inhibitors of IL-8 production. In contrast, exposure to CRLP significantly reduced MCP-1 secretion. Chemotaxis towards MCP-1 was increased in monocytes pre-exposed to CRLP and was reversed by addition of exogenous MCP-1. Conclusion Our findings indicate that CRLP activate human monocytes and augment their migration in vitro by reducing cellular MCP-1 expression. Our data support the current hypothesis that CMR contribute to the inflammatory milieu of the arterial wall in early atherosclerosis, and suggest that this may reflect direct interaction with circulating blood monocytes.

Prevalence, Predictors & Prevention of Motion Sickness in Zero-G Parabolic Flights

INTRODUCTION Zero-G parabolic flight reproduces the weightlessness of space for short periods of time. However motion sickness may affect some fliers. The aim was to assess the extent of this problem and to find possible predictors and modifying factors. METHODS Airbus Zero-G flights consist of 31 parabolas performed in blocks. Each parabola consisted of 20s 0g sandwiched by 20s hypergravity of 1.5-1.8g. The survey covered n=246 person-flights (193 Males 53 Females), aged (M+/-SD) 36.0+/-11.3 years. An anonymous questionnaire included motion sickness rating (1=OK to 6=Vomiting), Motion Sickness Susceptibility Questionnaire (MSSQ), anti-motion sickness medication, prior Zero-G experience, anxiety level, and other characteristics. RESULTS Participants had lower MSSQ percentile scores 27.4+/-28.0 than the population norm of 50. Motion sickness was experienced by 33% and 12% vomited. Less motion sickness was predicted by older age, greater prior Zero-G flight experience, medication with scopolamine, lower MSSQ scores, but not gender nor anxiety. Sickness ratings in fliers pre-treated with scopolamine (1.81+/-1.58) were lower than for non-medicated fliers (2.93+/-2.16), and incidence of vomiting in fliers using scopolamine treatment was reduced by half to a third. Possible confounding factors including age, sex, flight experience, MSSQ, could not account for this. CONCLUSION Motion sickness affected one third of Zero-G fliers, despite being intrinsically less motion sickness susceptible compared to the general population. Susceptible individuals probably try to avoid such a provocative environment. Risk factors for motion sickness included younger age and higher MSSQ scores. Protective factors included prior Zero-G flight experience (habituation) and anti-motion sickness medication.

Dynamic cost indexing

This paper describes the development of a generic tool for dynamic cost indexing (DCI), which encompasses the ability to manage flight delay costs on a dynamic basis, trading accelerated fuel burn against ‘cost of time’. Many airlines have significant barriers to identifying which costs should be included in ‘cost of time’ calculations and how to quantify them. The need is highlighted to integrate historical passenger delay and policy data with real-time passenger connections data. The absence of industry standards for defining and interfacing necessary tools is recognised. Delay recovery decision windows and ATC cooperation are key constraints. DCI tools could also be used in the pre-departure phase, and may offer environmental decision support functionality: which could be used as a differentiating technology required for access to designated, future ‘green’ airspace. Short-term opportunities for saving fuel and/or reducing emissions are also identified.

Dynamic cost indexing: cost estimations and building the prototype

The design of a decision-support prototype tool for managing flight delay costs in the pre-departure and airborne phases of a flight is described. The tool trades accelerated fuel burn and emissions charges against 'cost of time'. Costs for all major 'cost of time' components, by three cost scenarios, twelve aircraft types and by magnitude of delay are derived. Short-term opportunities for saving fuel and/or reducing environmental impacts are identified. A shift in ATM from managing delay minutes to delay cost is also supported.

The challenge of managing airline delay costs

Estimates of airline delay costs as a function of delay magnitude are combined with fuel and (future) emissions charges to make cost-benefit trade-offs in the pre-departure and airborne phases. Hypothetical scenarios for the distribution of flow management slots are explored in terms of their cost and target-setting implications. The general superiority of passenger-centric metrics is of significance for delay measurement, although flight delays are still the only commonly-reported type of metric in both the US and Europe. There is a particular need for further research into reactionary (network) effects, especially with regard to passenger metrics and flow management delay.

EU Criminal Law and Enlargement

Since creation of the European Communities the number of Member States has gradually increased from the original six to current twenty-eight. Enlargement has become an EU’s flagship external policy, demonstrating the EU’s ability to shape its neighbourhood and to serve as a catalyst of deep and multilayered reforms. The consecutive seven enlargement rounds went in parallel with widespread internal developments, culminating with the creation of the European Union and, most recently, entry into force of the Treaty of Lisbon. As this volume demonstrates, EU criminal law has evolved considerably from its early days under the legal framework laid down by the Treaty of Maastricht to its current post-Lisbon shape. On 1 December 2014, that is with expiry of a five year transitional regime for the jurisdiction of the Court of Justice, Police and Judicial Co-operation in Criminal Matters became a fully fledged EU policy, governed largely by the same modus operandi as other areas of EU competence and with compulsory jurisdiction of the Court of Justice. As EU criminal law developed internally, so did its external dimension, including the role it plays in the enlargement policy. In case of the latter the expiry of the same transitional period has brought to an end a rather anomalous situation whereby the European Union had more enforcement tools before and after accession vis-à-vis its future/new Member States than it could employ against the old ones. This bifurcation, quite rightly, triggered a lot of discussions about double standards used by the European Union in its pre-accession policy. This is exacerbated by the fact that some of those standards are neither defined in EU law, nor pursued vis-à-vis the existing EU’s Member States. The aim of this chapter is to demonstrate that evolution with particular emphasis on the role of EU Criminal Law in the policy currently employed by the European Union vis-à-vis candidate and potential candidate countries of the Western Balkans and to Turkey. Arguably, together with political conditionality, it has become one of the pillars of the enlargement process and, as the examples of accession negotiations with Montenegro and Serbia prove, its role is likely to increase as rapprochement of other candidates and potential candidates progresses to the next stages.