Intracoronary infusion of mononuclear cells after PCI-treated myocardial infarction and arrhythmogenesis: is it safe?

To reduce long-term morbidity after revascularised acute myocardial infarction, different therapeutic strategies have been investigated. Cell therapy with mononuclear cells from bone marrow (BMMC) or peripheral blood (PBMC) has been proposed to attenuate the adverse processes of remodelling and subsequent heart failure. Previous trials have suggested that cell therapy may facilitate arrhythmogenesis. In the present substudy of the HEBE cell therapy trial, we investigated whether intracoronary cell therapy alters the prevalence of ventricular arrhythmias after 1 month or the rate of severe arrhythmogenic events (SAE) in the first year. In 164 patients of the trial we measured function and infarct size with cardiovascular magnetic resonance (CMR) imaging. Holter registration was performed after 1 month from which the number of triplets (3 successive PVCs) and ventricular tachycardias (VT, ≥4 successive PVCs) was assessed. Thirty-three patients (20%) showed triplets and/or VTs, with similar distribution amongst the groups (triplets: control n = 8 vs. BMMC n = 9, p = 1.00; vs. PBMC n = 10, p = 0.67. VT: control n = 9 vs. BMMC n = 9, p = 0.80; vs. PBMC n = 11, p = 0.69). SAE occurred in 2 patients in the PBMC group and 1 patient in the control group. In conclusion, intracoronary cell therapy is not associated with an increase in ventricular arrhythmias or SAE

Nitrogen Excretion and Ammonia Emissions from Pigs Fed Modified Diets

Two swine feeding trials were conducted (initial body weight = 47 ± 2 and 41 ± 3 kg for Trials 1 and 2, respectively) to evaluate reduced crude protein (CP) and yucca (Yucca schidigera Roezl ex Ortgies) extract–supplemented diets on NH3 emissions. In Trial 1, nine pigs were offered a corn–soybean meal diet (C, 174 g kg−1 CP), a Lys-supplemented diet (L, 170 g kg−1 CP), or a 145 g kg−1 CP diet supplemented with Lys, Met, Thr, and Trp (LMTT). In Trial 2, nine pigs were fed diet L supplemented with 0, 62.5, or 125 mg of yucca extract per kg diet. Each feeding period consisted of a 4-d dietary adjustment followed by 72 h of continuous NH3 measurement. Urine and fecal samples were collected each period. Feeding the LMTT diet reduced (P \u3c 0.05) average daily gain (ADG) and feed efficiency (G:F) compared to diet L. Fecal N concentration decreased with a reduction in dietary CP, but urinary ammonium increased from pigs fed diet LMTT (2.0 g kg−1, wet basis) compared to those fed diet C (1.1 g kg−1) or L (1.0 g kg−1). When pigs were fed reduced CP diets NH3emission rates decreased (2.46, 2.16, and 1.05 mg min−1 for diets C, L, and LMTT). Yucca had no effect on feed intake, ADG, or G:F. Ammonium and N concentrations of manure and NH3 emission rates did not differ with yucca content. Caution must be executed to maintain animal performance when strategies are implemented to reduce NH3 emissions

Genome-wide association analysis of eosinophilic esophagitis provides insight into the tissue specificity of this allergic disease

Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder associated with allergic hypersensitivity to food. We interrogated >1.5 million genetic variants in European EoE cases and subsequently in a multi-site cohort with local and out-of-study control subjects. In addition to replication of the 5q22 locus (meta-analysis p = 1.9×10−16), we identified association at 2p23 (encoding CAPN14, p = 2.5×10−10). CAPN14 was specifically expressed in the esophagus, dynamically upregulated as a function of disease activity and genetic haplotype and after exposure of epithelial cells to IL-13, and located in an epigenetic hotspot modified by IL-13. There was enriched esophageal expression for the genes neighboring the top 208 EoE sequence variants. Multiple allergic sensitization loci were associated with EoE susceptibility (4.8×10−2 < p < 5.1×10−11). We propose a model that elucidates the tissue specific nature of EoE that involves the interplay of allergic sensitization with an EoE-specific, IL-13–inducible esophageal response involving CAPN14

Lightweight reflection for middleware-based database replication

Middleware-based database replication approaches have emerged in the last few years as an alternative to traditional database replication implemented within the database kernel. A middleware approach enables third party vendors to provide high availability solutions, a growing practice nowadays in the software industry. However, middleware solutions often lack scalability and exhibit a number of consistency and performance issues. The reason is that in most cases the middleware has to handle the database as a black box, and hence, cannot take advantage of the many optimizations implemented in the database kernel. Thus, middleware solutions often reimplement key functionality but cannot achieve the same efficiency as a kernel implementation. Reflection has been proposed during the last decade as a fruitful paradigm to separate non-functional aspects from functional ones, simplifying software development and maintenance whilst fostering reuse. However, fully reflective databases are not feasible due to the high cost of reflection. Our claim is that by exposing some minimal database functionality through a lightweight reflective interface, efficient and scalable middleware database replication can be attained. In this paper we explore a wide variety of such lightweight reflective interfaces and discuss what kind of replication algorithms they enable. We also discuss implementation alternatives for some of these interfaces and evaluate their performance

Adaptive middleware for data replication

Abstract. Dynamically adaptive systems sense their environment and adjust themselves to accommodate to changes in order to maximize performance. Depending on the type of change (e.g., modifications of the load, the type of workload, the available resources, the client distribution, etc.), different adjustments have to be made. Coordinating them is already difficult in a centralized system. Doing so in the currently prevalent component-based distributed systems is even more challenging. In this paper, we present an adaptive distributed middleware for data replication that is able to adjust to changes in the amount of load submitted to the different replicas and to the type of workload submitted. Its novelty lies in combining load-balancing techniques with feedback driven adjustments of multiprogramming levels (number of transactions that are allowed to execute concurrently). An extensive performance analysis shows that the proposed adaptive replication solution can provide high throughput, good scalability, and low response times for changing loads and workloads with little overhead.