A Dependable Autonomic Computing Environment for Self-Testing of Complex Heterogeneous Systems

AbstractThis paper is part of a R&D project aiming at the definition and implementation of an environment for dependable autonomic computing. The primary goal of the study is the increase of dependability of digital systems using self-healing techniques. Mobile agents implement self-testing policies for complex and heterogeneous systems. The aim of this paper is to present the general ideas of the project, describe the design decisions and a detailed view of the current architecture. The research includes design and development of a working prototype

Phenomenology of COPD: interpreting phenotypes with the ECLIPSE study

The Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE) study was a large 3-year observational multicentre international study aimed at defining COPD phenotypes and identifying biomarkers and/or genetic parameters that help to predict disease progression. The study has contributed to a better understanding of COPD heterogeneity, with the characterization of clinically important subtypes/phenotypes of patients, such as the frequent exacerbators or patient with persistent systemic inflammation, who may have different prognosis or treatment requirements. Because of the big amount of information that is starting to be produced from metabolomic, proteomic and genomic approaches, one of the biggest challenges is the integration of data in a biological prospective such as clinical prognosis and response to medicinal products. In this article we highlight some of the progress in phenotyping the heterogeneity of the disease that have been made thanks to the analyses of this longitudinal study

Tanner-Whitehouse skeletal ages in male youth soccer players : TW2 or TW3?

BACKGROUND: The Tanner-Whitehouse radius-ulna-short bone protocol (TW2 RUS) for the assessment of skeletal age (SA) is widely used to estimate the biological (skeletal) maturity status of children and adolescents. The scale for converting TW RUS ratings to an SA has been revised (TW3 RUS) and has implications for studies of youth athletes in age-group sports. OBJECTIVES: The aim of this study was to compare TW2 and TW3 RUS SAs in an international sample of male youth soccer players and to compare distributions of players by maturity status defined by each SA protocol. METHODS: SA assessments with the TW RUS method were collated for 1831 male soccer players aged 11-17 years from eight countries. RUS scores were converted to TW2 and TW3 SAs using the appropriate tables. SAs were related to chronological age (CA) in individual athletes and compared by CA groups. The difference of SA minus CA with TW2 SA and with TW3 SA was used to classify players as late, average, or early maturing with each method. Concordance of maturity classifications was evaluated with Cohen's Kappa coefficients. RESULTS: For the same RUS score, TW3 SAs were systematically and substantially reduced compared with TW2 SAs; mean differences by CA group ranged from - 0.97 to - 1.16 years. Kappa coefficients indicated at best fair concordance of TW2 and TW3 maturity classifications. Across the age range, 42% of players classified as average with TW2 SA were classified as late with TW3 SA, and 64% of players classified as early with TW2 SA were classified as average with TW3 SA. CONCLUSION: TW3 SAs were systematically lower than corresponding TW2 SAs in male youth soccer players. The differences between scales have major implications for the classification of players by maturity status, which is central to some talent development programs

Acetylcholine regulates ghrelin secretion in humans

Ghrelin secretion has been reportedly increased by fasting and energy restriction but decreased by food intake, glucose, insulin, and somatostatin. However, its regulation is still far from clarified. The cholinergic system mediates some ghrelin actions, e.g. stimulation of gastric contractility and acid secretion and its orexigenic activity. To clarify whether ghrelin secretion undergoes cholinergic control in humans, we studied the effects of pirenzepine [PZ, 100 mg per os (by mouth)], a muscarinic antagonist, or pyridostigmine (PD, 120 mg per os), an indirect cholinergic agonist, on ghrelin, GH, insulin, and glucose levels in six normal subjects. PD increased (P < 0.05) GH (change in area under curves, mean +/- SEM, 790.9 +/- 229.3 microg(*)min/liter) but did not modify insulin and glucose levels. PZ did not significantly modify GH, insulin, and glucose levels. Circulating ghrelin levels were increased by PD (11290.5 +/- 6688.7 pg(*)min/ml; P < 0.05) and reduced by PZ (-23205.0 +/- 8959.5 pg(*)min/ml; P < 0.01). The PD-induced ghrelin peak did not precede that of GH. In conclusion, circulating ghrelin levels in humans are increased and reduced by cholinergic agonists and antagonists, respectively. Thus, ghrelin secretion is under cholinergic, namely muscarinic, control in humans. The variations in circulating ghrelin levels induced by PD and PZ are unlikely to mediate the cholinergic influence on GH secretion

Copeptin adaptive response to SGLT2 inhibitors in patients with type 2 diabetes mellitus: The GliRACo study

IntroductionIn type 2 diabetes mellitus (T2DM), the antidiuretic system participates in the adaptation to osmotic diuresis further increasing urinary osmolality by reducing the electrolyte-free water clearance. Sodium glucose co-transporter type 2 inhibitors (SGLT2i) emphasize this mechanism, promoting persistent glycosuria and natriuresis, but also induce a greater reduction of interstitial fluids than traditional diuretics. The preservation of osmotic homeostasis is the main task of the antidiuretic system and, in turn, intracellular dehydration the main drive to vasopressin (AVP) secretion. Copeptin is a stable fragment of the AVP precursor co-secreted with AVP in an equimolar amount.AimTo investigate the copeptin adaptive response to SGLT2i, as well as the induced changes in body fluid distribution in T2DM patients.MethodsThe GliRACo study was a prospective, multicenter, observational research. Twenty-six consecutive adult patients with T2DM were recruited and randomly assigned to empagliflozin or dapagliflozin treatment. Copeptin, plasma renin activity, aldosterone and natriuretic peptides were evaluated at baseline (T0) and then 30 (T30) and 90 days (T90) after SGLT2i starting. Bioelectrical impedance vector analysis (BIVA) and ambulatory blood pressure monitoring were performed at T0 and T90.ResultsAmong endocrine biomarkers, only copeptin increased at T30, showing subsequent stability (7.5 pmol/L at T0, 9.8 pmol/L at T30, 9.5 pmol/L at T90; p = 0.001). BIVA recorded an overall tendency to dehydration at T90 with a stable proportion between extra- and intracellular fluid volumes. Twelve patients (46.1%) had a BIVA overhydration pattern at baseline and 7 of them (58.3%) resolved this condition at T90. Total body water content, extra and intracellular fluid changes were significantly affected by the underlying overhydration condition (p &lt; 0.001), while copeptin did not.ConclusionIn patients with T2DM, SGLT2i promote the release of AVP, thus compensating for persistent osmotic diuresis. This mainly occurs because of a proportional dehydration process between intra and extracellular fluid (i.e., intracellular dehydration rather than extracellular dehydration). The extent of fluid reduction, but not the copeptin response, is affected by the patient’s baseline volume conditions.Clinical trial registrationClinicaltrials.gov, identifier NCT03917758