Programming EU External Action Post-Lisbon: New Opportunities or Business as Usual?

Over 90% of the external relations budget of the EU is processed through its external financial instruments. With the Lisbon Treaty and the creation of the new European External Action Service (EEAS), the institutional architecture of these instruments was significantly reformed. This contribution analyses strategic programming both pre- and post-Lisbon, identifies ‘winners’ and ‘losers’, and examines the potential of the new provisions to increase the coherence of EU external action. The examination shows that the instruments can be categorised into three groupings: ‘the big three’ comprising the bulk of funding characterised by joint programming and responsibilities; the ‘Commission-only’ instruments where all powers remain with the Commission; and the ‘EEAS-led rest’ in which the High Representative and the EEAS play a strong role but only have limited financial resources available. The new system calls for strong coordination of all involved actors in order to make it work. Findings of a case study on the Instrument for Stability reveal, however, that so far the establishment of the EEAS has not made a substantial impact on strategic programming in its first two years.

Mécanismes d'action des cellules stromales mésenchymateuses dans le traitement de la réaction du greffon contre l'hôte

La maladie du greffon contre l’hôte (GvHD) est un effet secondaire sérieux de la transplantation de cellules souches hématopoïétiques (HSCT). Cette maladie entraine une haute mortalité et ses symptômes sont dévastateurs. Les traitements actuels de la GvHD comportent plusieurs produits, tels les corticostéroïdes, mais ces derniers sont immunosuppresseurs et leurs effets secondaires sont aussi très dommageables pour les patients et leur guérison. Les cellules stromales mésenchymateuses (MSC) représentent une alternative ou une addition potentielle de traitement pour la GvHD et ces cellules ne semblent pas posséder les effets secondaires des traitements classiques. Un nombre important d’études cliniques faisant l’objet des MSC ont été enregistrées. Malgré cet engouement, le mécanisme de leur immunomodulation reste encore à élucider. Notre objectif est donc de mieux définir ce mécanisme. Nous avons utilisé un modèle simplifié pour simuler la GvHD in vitro. Ce modèle se base sur la stimulation de lymphocytes CD4+ par des cellules dendritiques allogéniques. La mesure de la prolifération de ces cellules stimulées sert d’indicateur de leur réactivité. Selon les résultats obtenus par la technologie CRISPR de génie génétique, les MSC exerceraient leur immunosuppression sur les cellules T CD4+ principalement par la sécrétion de l’enzyme IDO1. Les MSC seraient également capables d’induire certaines cellules CD4+ en cellules régulatrices, un processus indépendant de la sécrétion d’IDO1. Toutefois, ces cellules ne semblent pas correspondre aux cellules Treg conventionnelles.

EEAS 2.0: Recommendations for the amendment of Council Decision 2010/427/EU on the European External Action Service. CEPS Special Report No. 78, 13 November 2013

This Special Report offers recommendations for the amendment of the Council Decision 2010/427/EU establishing the organisation and functioning of the European External Action Service. Its purpose is to contribute, in practical legal terms, to the ongoing review of the Decision in 2013, as well as to the possible discussion on its revision that may take place in 2014. In particular, it sheds light on possible adjustments in the application of the Decision ‘à droit constant’, but also suggests potential alteration of its formulation.

Light and shadows in Europe’s new Action Plan for Capital Markets Union. ECMI Commentary No. 40/5 October 2015

The European Commission’s Action Plan consists, in a nutshell, of a short list of technical proposals and a longer one of (rather general) potential actions. Overall, the plan indeed proposes to achieve some short-term objectives, such as a reduction of listing costs for SMEs, but it lacks long-term vision. The plan bundles actions under rather generic objectives of long-term finance or cross-border investing. Improving the informational infrastructure (e.g. accounting standards, company data) and cross-border enforcement of rules is left to vaguely defined future actions, but these constitute the core of the capital markets infrastructure. Without a well-defined set of measurable objectives, the whole plan may lose political momentum and become an opportunity for interested parties to cherry pick their pet provisions. Building a single market, i.e. removing cross-border obstacles to capital circulation, is too challenging a task to simply appear as one of many items on a long list of general objectives, which incidentally do not include institutional reform. The ultimate risk is that the Commission may just miss a unique opportunity to revamp and improve the financial integration process in Europe after almost a decade of harmful financial retrenchment.

Treatment of dementia with neurotransmission modulation

The prevalence of dementia is growing in developed countries where elderly patients are increasing in numbers. Neurotransmission modulation is one approach to the treatment of dementia. Cholinergic precursors, anticholinesterases, nicotine receptor agonists and muscarinic M-2 receptor antagonists are agents that enhance cholinergic neurotransmission and that depend on having some intact cholinergic innervation to be effective in the treatment of dementia. The cholinergic precursor choline alfoscerate may be emerging as a potential useful drug in the treatment of dementia, with few adverse effects. Of the anticholinesterases, donepezil, in addition to having a similar efficacy to tacrine in mild-to-moderate Alzheimer's disease (AD), appears to have major advantages; its use is associated with lower drop-out rates in clinical trials, a lower incidence of cholinergic-like side effects and no liver toxicity. Rivastigmine is efficacious in the treatment in dementia with Lewy bodies, a condition in which the other anticholinesterases have not been tested extensively to date. Galantamine is an anticholinesterase and also acts as an allosteric potentiating modulator at nicotinic receptors to increase the release of acetylcholine. Pooled data from clinical trials of patients with mild-to-moderate AD suggest that the benefits and safety profile of galantamine are similar to those of the anticholinesterases. Selective nicotine receptor agonists are being developed that enhance cognitive performance without influencing autonomic and skeletal muscle function, but these have not yet entered clinical trial for dementia. Unlike the cholinergic enhancers, the M, receptor agonists do not depend upon intact cholinergic nerves but on intact M, receptors for their action, which are mainly preserved in AD and dementia with Lewy bodies. The M, receptor-selective agonists developed to date have shown limited efficacy in clinical trials and have a high incidence of side effects. A major recent advancement in the treatment of dementia is memantine, a non-competitive antagonist at NMDA receptors. Memantine is beneficial in the treatment of severe and moderate to-severe AD and may also be of some benefit in the treatment of mild-to-moderate vascular dementia. Drugs that modulate 5-HT, somatostatin and noradrenergic neurotransmission are also being considered for the treatment of dementia.

A potential role for isothermal calorimetry in studies of the effects of thermodynamic non-ideality in enzyme-catalyzed reactions

Attention is drawn to the feasibility of using isothermal calorimetry for the characterization of enzyme reactions under conditions bearing greater relevance to the crowded biological environment, where kinetic parameters are likely to differ significantly from those obtained by classical enzyme kinetic studies in dilute solution. An outline of the application of isothermal calorimetry to the determination of enzyme kinetic parameters is followed by considerations of the nature and consequences of crowding effects in enzyme catalysis. Some of those effects of thermodynamic non-ideality are then illustrated by means of experimental results from calorimetric studies of the effect of molecular crowding on the kinetics of catalysis by rabbit muscle pyruvate kinase. This review concludes with a discussion of the potential of isothermal calorimetry for the experimental determination of kinetic parameters for enzymes either in biological environments or at least in media that should provide reasonable approximations of the crowded conditions encountered in vivo. Copyright (C) 2004 John Wiley Sons, Ltd.

The use of simultaneous H-1 & P-31 magic angle spinning nuclear magnetic resonance measurements to characterize energy metabolism during the conversion of muscle to meat

In order to investigate the potential of magic angle spinning nuclear magnetic resonance (MAS NMR) in the elucidation of post-mortem metabolism in muscle biopsies, simultaneous H-1 and (31)p MAS NMR measurements were made continuously on postmortem (20 min to 24 h) muscle longissimus samples from rabbits. The animals had either been or not been given adrenaline (0.5 mg kg(-1) 4 h pre-slaughter) to deplete stores of muscle glycogen. The intracellular pH was calculated from H-1 spectra, and the post-mortem rate of formation of lactate was followed and quantified. Comparison of measurements made on muscle samples from rabbits treated with adrenaline with measurements made on muscle samples from untreated' rabbits revealed significant effects of adrenaline treatment on both pH (pH24 h = 6.42 vs. pH24 It = 5.60) and formation of lactate (16 mmol g(-1) vs. 65 mmol g(-1)). The P-31 NMR spectra were used to follow the rate of degradation of ATP and phosphocreatine. The present study clearly shows that MAS NMR has potential for the study of post-mortem energy metabolism.

Potassium channels and membrane potential in the modulation of intracellular calcium in vascular endothelial cells

K+ Channels and Membrane Potential in Endothelial Cells. The endothelium plays a vital role in the control of vascular functions, including modulation of tone; permeability and barrier properties; platelet adhesion and aggregation; and secretion of paracrine factors. Critical signaling events in many of these functions involve an increase in intracellular free Ca2+ concentration ([Ca2+](i)). This rise in [Ca2+](i) occurs via an interplay between several mechanisms, including release from intracellular stores, entry from the extracellular space through store depletion and second messenger-mediated processes, and the establishment of a favorable electrochemical gradient. The focus of this review centers on the role of potassium channels and membrane potential in the creation of a favorable electrochemical gradient for Ca2+ entry. In addition, evidence is examined for the existence of various classes of potassium channels and the possible influence of regional variation in expression and experimental conditions.

Effect of prolonged inactivity on skeletal motor nerve terminals during aestivation in the burrowing frog, Cyclorana alboguttata

This study examined the effect of prolonged inactivity, associated with aestivation, on neuromuscular transmission in the green-striped burrowing frog, Cyclorana alboguttata. We compared the structure and function of the neuromuscular junctions on the iliofibularis muscle from active C. alboguttata and from C. alboguttata that had been aestivating for 6 months. Despite the prolonged period of immobility, there was no significant difference in the shape of the terminals (primary, secondary or tertiary branches) or the length of primary terminal branches between aestivators and non-aestivators. Furthermore, there was no significant difference in the membrane potentials of muscle fibres or in miniature end plate potential (EPP) frequency and amplitude. However, there was a significant decrease in evoked transmitter release characterised by a 56% decrease in mean EPP amplitude, and a 29% increase in the failure rate of nerve terminal action potentials to evoke transmitter release. The impact of this suite of neuromuscular characteristics on the locomotor performance of emergent frogs is discussed.

The effect of hormone replacement therapy and/or exercise on skeletal muscle attenuation in postmenopausal women: a yearlong intervention

Hormone replacement therapy (HRT) has been reported to exert a positive effect on preserving muscle strength following the menopause, however, the mechanism of action remains unclear. We examined whether the mechanism involved preservation of muscle composition as determined by skeletal muscle attenuation. Eighty women aged 50-57 years were randomly assigned to either: HRT, exercise (Ex), HRT + exercise (ExHRT), and control (Co) for 1 year. The study was double-blinded with subjects receiving oestradiol and norethisterone acetate (Kliogest) or placebo. Exercise included progressive high-impact training for the lower limbs. Skeletal muscle attenuation in Hounsfield units (HU) was determined by computed tomography of the mid-thigh. Areas examined were the quadriceps compartment (includes intermuscular adipose tissue), quadriceps muscles, the posterior compartment and posterior muscles. Muscle performance was determined by knee extensor strength, vertical jump height, and running speed over 20 m. Fifty-one women completed the intervention. Vertical jump height and running speed improved in the HRT and ExHRT groups compared with Co (interaction, P < 0.01). For both the quadriceps compartment and quadriceps muscles, HU significantly increased (interaction, P <= 0.005) for HRT, Ex, and ExHRT compared with Co. For the posterior compartment, HU for the HRT and ExHRT were significantly increased compared with Co, while for posterior muscles, ExHRT was significantly greater than Co. Although the effects were modest, the results indicate that HRT, either alone or combined with exercise, may play a role in preserving/improving skeletal muscle attenuation in early postmenopausal women and thereby exert a positive effect on muscle performance.

Conservation action in the Galapagos: Feral pig (Sus scrofa) eradication from Santiago Island

Introduced mammals are major drivers of extinction and ecosystem change. As omnivores, feral pigs (Sus scrofa) are responsible for wholesale adverse effects on islands. Here, we report on the eradication of feral pigs from Santiago Island in the Galápagos Archipelago, Ecuador, which is the largest insular pig removal to date. Using a combination of ground hunting and poisoning, over 18,000 pigs were removed during this 30-year eradication campaign. A sustained effort, an effective poisoning campaign concurrent with the hunting program, access to animals by cutting more trails, and an intensive monitoring program all proved critical to the successful eradication. While low and fluctuating control efforts may help protect select native species, current eradication methods, limited conservation funds, and the potential negative non-target impacts of sustained control efforts all favor an intense eradication effort, rather than a sustained control program. The successful removal of pigs from Santiago Island sets a new precedent, nearly doubling the current size of a successful eradication, and is leading to more ambitious projects. However, now we must turn toward increasing eradication efficiency. Given limited conservation funds, we can no longer afford to spend decades removing introduced mammals from islands.

Bone loss in Crohn's disease: Exercise as a potential countermeasure

Crohn's disease (CD) is associated with a number of secondary conditions including osteoporosis, which increases the risk of bone fracture. The cause of metabolic bone disease in this Population is believed to be multifactorial and may include the disease itself and associated inflammation, high-close corticosteroid use, weight loss and malabsorption, a lack of exercise and physical activity, and all underlying genetic predisposition to bone loss. Reduced bone mineral density has been reported in between 5% to 80% of CD sufferers, although it is generally believed that approximately 40% of patients suffer from osteopenia and 15% from osteoporosis. Recent studies Suggest a small but significantly increased risk of fracture compared with healthy controls and, perhaps, sufferers of other gastrointestinal disorders Such as ulcerative colitis. The role of physical activity and exercise in the prevention and treatment of CD-related bone loss has received little attention, despite the benefits of specific exercises being well documented in healthy populations. This article reviews the prevalence of and risk factors for low bone mass in CD patients and examines various treatments for osteoporosis in these patients, with a particular focus on physical activity.

Muscle fiber and motor unit behavior in the longest human skeletal muscle

The sartorius muscle is the longest muscle in the human body. It is strap-like, up to 600 mm in length, and contains five to seven neurovascular compartments, each with a neuromuscular endplate zone. Some of its fibers terminate intrafascicularly, whereas others may run the full length of the muscle. To assess the location and timing of activation within motor units of this long muscle, we recorded electromyographic potentials from multiple intramuscular electrodes along sartorius muscle during steady voluntary contraction and analyzed their activity with spike-triggered averaging from a needle electrode inserted near the proximal end of the muscle. Approximately 30% of sartorius motor units included muscle fibers that ran the full length of the muscle, conducting action potentials at 3.9 +/- 0.1 m/s. Most motor units were innervated within a single muscle endplate zone that was not necessarily near the midpoint of the fiber. As a consequence, action potentials reached the distal end of a unit as late as 100 ms after initiation at an endplate zone. Thus, contractile activity is not synchronized along the length of single sartorius fibers. We postulate that lateral transmission of force from fiber to endomysium and a wide distribution of motor unit endplates along the muscle are critical for the efficient transmission of force from sarcomere to tendon and for the prevention of muscle injury caused by overextension of inactive regions of muscle fibers.

Measuring environmental education program impacts and learning in the field: Using an action research cycle to develop a tool for use with young students

Despite the increasing importance of, and interest in, documenting the impact of environmental education programs on students' learning for sustainability, few tools are currently available to measure young students' environmental learning across all the dimensions of knowledge, skills, attitudes and behaviours. This paper reports on the development of such a tool, using an iterative action research process with 134 students, aged six to eleven, attending programs at an Environmental Education Centre in Queensland. The resulting instrument, the Environmental Learning Outcomes Survey (ELOS) incorporates observations of students' engagement in learning processes as well as measuring learning outcomes, and allows both of these aspects to be linked to particular components of the environmental education program. Test data using the instrument are reported to illustrate its potential usefulness. It is envisaged that the refined instrument will enable researchers to measure student environmental learning in the field, investigate environmental education program impacts and identify aspects of programs that are most effective in facilitating student learning. [Author abstract]

An MRI investigation into the function of the transversus abdominis muscle during "drawing-in" of the abdominal wall

Study Design. An operator blinded dual modality trial of measurement of the abdominal muscles during drawing-in of the abdominal wall. Objectives. 1) To investigate, using magnetic resonance imaging (MRI), the function of the transversus abdominis muscle bilaterally during a drawing-in of the abdominal wall. 2) To validate the use of real-time ultrasound imaging as a measure of the deep abdominal muscle during a drawing-in of the abdominal wall. Summary of Background Data. Previous research has implicated the deep abdominal muscle, transversus abdominis, in the support and protection of the spine and provided evidence that training this muscle is important in the rehabilitation of low back pain. One of the most important actions of the transversus abdominis is to draw-in the abdominal wall, and this action has been shown to stiffen the sacroiliac joints. It is hypothesized that in response to a draw in, the transversus abdominis muscle forms a deep musculofascial corset and that MRI could be used to view this corset and verify its mechanism of action on the lumbopelvic region. Methods. Thirteen healthy asymptomatic male elite cricket players aged 21.3 +/- 2.1 years were imaged using MRI and ultrasound imaging as they drew in their abdominal walls. Measurements of the thickness of the transversus abdominis and internal oblique muscles and the slide of the anterior abdominal fascia were measured using both MRI and ultrasound. Measurement of the whole abdominal cross-sectional area (CSA) was conducted using MRI. Results. Results of the MRI demonstrated that, as a result of draw-in, there was a significant increase in thickness of the transversus abdominis (P < 0.001) and the internal oblique muscles (P < 0.001). There was a significant decrease in the CSA of the trunk (P < 0.001). The mean slide ( +/- SD) of the anterior abdominal fascia was 1.54 +/- 0.38 cm for the left side and 1.48 +/- 0.35 cm for the right side. Ultrasound measurements of muscle thickness of both transversus abdominis and the internal oblique, as well as fascial slide, correlated with measures obtained using MRI (interclass correlations from 0.78 to 0.95). Conclusions. The MRI results demonstrated that during a drawing-in action, the transversus abdominis contracts bilaterally to form a musculofascial band that appears to tighten (like a corset) and most likely improves the stabilization of the lumbopelvic region. Real-time ultrasound imaging can also be used to measure changes in the transversus abdominis during the draw-in maneuver.