Ergodic properties of quasi-Markovian generalized Langevin equations with configuration dependent noise and non-conservative force

We discuss the ergodic properties of quasi-Markovian stochastic differential equations, providing general conditions that ensure existence and uniqueness of a smooth invariant distribution and exponential convergence of the evolution operator in suitably weighted $L^{\infty}$ spaces, which implies the validity of central limit theorem for the respective solution processes. The main new result is an ergodicity condition for the generalized Langevin equation with configuration-dependent noise and (non-)conservative force

Distinct Behaviour of the Homeodomain Derived Cell Penetrating Peptide Penetratin in Interaction with Different Phospholipids

Penetratin is a protein transduction domain derived from the homeoprotein Antennapedia. Thereby it is currently used as a cell penetrating peptide to introduce diverse molecules into eukaryotic cells, and it could also be involved in the cellular export of transcription factors. Moreover, it has been shown that it is able to act as an antimicrobial agent. The mechanisms involved in all these processes are quite controversial.In this article, we report spectroscopic, calorimetric and biochemical data on the penetratin interaction with three different phospholipids: phosphatidylcholine (PC) and phosphatidylethanolamine (PE) to mimic respectively the outer and the inner leaflets of the eukaryotic plasma membrane and phosphatidylglycerol (PG) to mimic the bacterial membrane. We demonstrate that with PC, penetratin is able to form vesicle aggregates with no major change in membrane fluidity and presents no well defined secondary structure organization. With PE, penetratin aggregates vesicles, increases membrane rigidity and acquires an α-helical structure. With PG membranes, penetratin does not aggregate vesicles but decreases membrane fluidity and acquires a structure with both α-helical and β–sheet contributions.These data from membrane models suggest that the different penetratin actions in eukaryotic cells (membrane translocation during export and import) and on prokaryotes may result from different peptide and lipid structural arrangements. The data suggest that, for eukaryotic cell penetration, penetratin does not acquire classical secondary structure but requires a different conformation compared to that in solution

Assessing the ‘active couch potato’ phenomenon in cardiac rehabilitation: rationale and study protocol

BACKGROUND: There is little evidence of whether or not those who have attended cardiac rehabilitation (CR) are meeting the physical activity guidelines recommended for secondary prevention of cardiovascular disease. In healthy individuals, there is evidence, that even if individuals are meeting the physical activity guidelines, the harmfulness of too much sedentary behaviour remains (active couch potato (ACP) phenomenon). Currently, there appears to be no evidence of the ACP phenomenon in those attending CR. The aims of the study are to examine the level of physical activity and sedentary behaviour in those with coronary heart disease (CHD) who have attended CR, and to investigate the potential independent associations between these behaviours and cardio-metabolic health, health-related quality of life, exercise capacity, anxiety and depression. METHODS: A prospective cohort study will be conducted in Australia over 12-months. Baseline data from this study will contribute to an international, multi-centre cross-sectional study (Australia, New Zealand, United States of America, South Africa, Spain, and Portugal). Adults currently enrolled in a 6-week phase II cardiac rehabilitation program with stable CHD and receiving optimal medical treatment +/− revascularisation will be recruited. Outcome measures will be taken at baseline (commence CR), 6 weeks (complete CR), 6 and 12-months. Physical activity and sedentary behaviour will be measured using accelerometry and two questionnaires (Active Australia Survey, Past-Day Adults’ Sedentary Time questionnaire). Health outcomes will include body mass index, waist-to-hip ratio, lipid profile, blood glucose level, quality-of-life (MacNew), exercise capacity (6-min walk test), anxiety and depression (Hospital Anxiety and Depression Scale). DISCUSSION: There has been limited investigation of the physical activity levels and sedentary behaviour of individuals with CHD attending CR. There are no studies assessing the relationship of these behaviours with health outcomes over the short and medium-term. As in healthy individuals, physical activity and sedentary behaviour may have independent effects on cardiovascular risk factors in people with CHD, which may contribute to recurrent cardiovascular events. If this is so, reducing sedentary behaviour may be a feasible first-line, additional and more achievable strategy to improve the health of those with CHD, alongside traditional recommendations to increase the time spent in moderate-to-vigorous intensity physical activity. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN1261500099557

Using perturbed underdamped langevin dynamics to efficiently sample from probability distributions

In this paper we introduce and analyse Langevin samplers that consist of perturbations of the standard underdamped Langevin dynamics. The perturbed dynamics is such that its invariant measure is the same as that of the unperturbed dynamics. We show that appropriate choices of the perturbations can lead to samplers that have improved properties, at least in terms of reducing the asymptotic variance. We present a detailed analysis of the new Langevin sampler for Gaussian target distributions. Our theoretical results are supported by numerical experiments with non-Gaussian target measures

Effects of early, combined endurance and resistance training in mechanically ventilated, critically ill patients: a study protocol for a randomised controlled trial

BACKGROUND Prolonged need for intensive care is associated with neuromuscular weakness, termed Intensive Care Unit Acquired Weakness. Those affected suffer from severe functional impairment that can persist for years. First studies suggest a positive effect of physiotherapy and early mobilisation. However, the ideal intervention for a preferential functional outcome is not known. So far no randomised controlled trial has been conducted to specifically evaluate an early endurance and resistance training in the mechanically ventilated, critically ill patient. METHODS/DESIGN A randomised controlled trial with blinded assessors and 6-month follow-up will be conducted in a tertiary, interdisciplinary intensive care unit in Switzerland. Participants (n = 115; expected dropouts: n = 15) will be randomised to a control group receiving standard physiotherapy and to an experimental group that undergoes early mobilisation combined with endurance and resistance training. The inclusion criteria are being aged 18 years or older, expected mechanical ventilation for more than 72 h and qualitative independence before the illness. Primary endpoints are functional capacity (6-Minute Walk Test) and the ability to perform activities of daily living (Functional Independence Measure) measured at hospital discharge. Secondary endpoints include muscle strength (Medical Research Council sum score, handgrip strength and handheld dynamometry for quadriceps muscle), joint contractures (range of motion), exercise capacity (Timed 'Up & Go' Test) and health-related quality of life (Short Form 36). Safety will be monitored during interventions by indirect calorimetry and continuous intensive care standard monitoring. All previously defined adverse events will be noted. The statistical analysis will be by intention-to-treat with the level of significance set at p < 0.05. DISCUSSION This prospective, single-centre, allocation-concealed and assessor-blinded randomised controlled trial will evaluate participant's function after an early endurance and resistance training compared to standard care. Limitations of this study are the heterogeneity of the critically ill and the discontinuity of the protocol after relocation to the ward. The strengths lie in the pragmatic design and the clinical significance of the chosen outcome measures. TRIAL REGISTRATION German Clinical Trials Register (DRKS): DRKS00004347 , registered on 10 September 2012