HiC-ACT: improved detection of chromatin interactions from Hi-C data via aggregated Cauchy test

Genome-wide chromatin conformation capture technologies such as Hi-C are commonly employed to study chromatin spatial organization. In particular, to identify statistically significant long-range chromatin interactions from Hi-C data, most existing methods such as Fit-Hi-C/FitHiC2 and HiCCUPS assume that all chromatin interactions are statistically independent. Such an independence assumption is reasonable at low resolution (e.g., 40 kb bin) but is invalid at high resolution (e.g., 5 or 10 kb bins) because spatial dependency of neighboring chromatin interactions is non-negligible at high resolution. Our previous hidden Markov random field-based methods accommodate spatial dependency but are computationally intensive. It is urgent to develop approaches that can model spatial dependence in a computationally efficient and scalable manner. Here, we develop HiC-ACT, an aggregated Cauchy test (ACT)-based approach, to improve the detection of chromatin interactions by post-processing results from methods assuming independence. To benchmark the performance of HiC-ACT, we re-analyzed deeply sequenced Hi-C data from a human lymphoblastoid cell line, GM12878, and mouse embryonic stem cells (mESCs). Our results demonstrate advantages of HiC-ACT in improving sensitivity with controlled type I error. By leveraging information from neighboring chromatin interactions, HiC-ACT enhances the power to detect interactions with lower signal-to-noise ratio and similar (if not stronger) epigenetic signatures that suggest regulatory roles. We further demonstrate that HiC-ACT peaks show higher overlap with known enhancers than Fit-Hi-C/FitHiC2 peaks in both GM12878 and mESCs. HiC-ACT, effectively a summary statistics-based approach, is computationally efficient (∼6 min and ∼2 GB memory to process 25,000 pairwise interactions)

Pharmacology of enalapril in children: a review

Enalapril is an angiotensin-converting enzyme (ACE) inhibitor that is used for the treatment of (paediatric) hypertension, heart failure and chronic kidney diseases. Because its disposition, efficacy and safety differs across the paediatric continuum, data from adults cannot be automatically extrapolated to children. This review highlights paediatric enalapril pharmacokinetic data and demonstrates that these are inadequate to support with certainty an age-related effect on enalapril/enalaprilat pharmacokinetics. In addition, our review shows that evidence to support effective and safe prescribing of enalapril in children is limited, especially in young children and heart failure patients; studies in these groups are either absent or show conflicting results. We provide explanations for observed differences between age groups and indications, and describe areas for future research

Assessing the impact of Bacillus strains mixture probiotic on water quality, growth performance, blood profile and intestinal morphology of Nile tilapia, Oreochromis niloticus

The aim of this study was to assess the impact of a commercial probiotic, Sanolife PRO‐F, on water quality, growth performance, blood profiles and intestinal morphometry of monosex Nile tilapia. A field trial was conducted for 10 weeks in which tilapia fingerlings (20 ± 1.26 g) were randomly distributed into three replicate ponds which were subdivided into three treatment groups, receiving Sanolife PRO‐F at 0 (B0), 0.1 (B1) and 0.2 (B2) g/kg diet, respectively. The results showed a significant improvement in growth performance, feed conversion ratio and blood profiles in tilapia fed on treated diets. The whole intestinal lengths, anterior and terminal intestinal villi heights and anterior goblet cells count were greater in tilapia fed on treated diets. There were no noticeable differences in growth and intestinal morphology between tilapia fed on B1 and B2 diets. The ammonia concentration in water was lower with B1 diet while electric conductivity, salinity and total dissolved solids were higher with the B2 diet. The pH level of pond water was enhanced by both diets, B1 and B2. In conclusion, application of Sanolife PRO‐F at 0.1–0.2 g/kg diet might have beneficial effects on growth, immunity, stress responses and gut health and function as well as the water quality of farmed Nile tilapia

Rapid Diagnostic Algorithms as a Screening Tool for Tuberculosis: An Assessor Blinded Cross-Sectional Study

Background: A major obstacle to effectively treat and control tuberculosis is the absence of an accurate, rapid, and low-cost diagnostic tool. A new approach for the screening of patients for tuberculosis is the use of rapid diagnostic classification algorithms. Methods: We tested a previously published diagnostic algorithm based on four biomarkers as a screening tool for tuberculosis in a Central European patient population using an assessor-blinded cross-sectional study design. In addition, we developed an improved diagnostic classification algorithm based on a study population at a tertiary hospital in Vienna, Austria, by supervised computational statistics. Results: The diagnostic accuracy of the previously published diagnostic algorithm for our patient population consisting of 206 patients was 54% (CI: 47%–61%). An improved model was constructed using inflammation parameters and clinical information. A diagnostic accuracy of 86% (CI: 80%–90%) was demonstrated by 10-fold cross validation. An alternative model relying solely on clinical parameters exhibited a diagnostic accuracy of 85% (CI: 79%–89%). Conclusion: Here we show that a rapid diagnostic algorithm based on clinical parameters is only slightly improved by inclusion of inflammation markers in our cohort. Our results also emphasize the need for validation of new diagnostic algorithms in different settings and patient populations

Field test of available methods to measure remotely SOx and NOx emissions from ships

Methods for the determination of ship fuel sulphur content and NOx emission factors based on remote measurements have been compared in the harbour of Rotterdam and compared to direct stack emission measurements on the ferry Stena Hollandica. The methods were selected based on a review of the available literature on ship emission measurements. They were either optical (LIDAR, Differential Optical Absorption Spectroscopy (DOAS), UV camera), combined with model-based estimates of fuel consumption, or based on the so called "sniffer" principle, where SO2 or NOx emission factors are determined from simultaneous measurement of the increase of CO2 and SO2 or NOx concentrations in the plume of the ship compared to the background. The measurements were performed from stations at land, from a boat and from a helicopter. Mobile measurement platforms were found to have important advantages compared to the land-based ones because they allow optimizing the sampling conditions and sampling from ships on the open sea. Although optical methods can provide reliable results it was found that at the state of the art level, the "sniffer" approach is the most convenient technique for determining both SO2 and NOx emission factors remotely. The average random error on the determination of SO2 emission factors comparing two identical instrumental set-ups was 6 %. However, it was found that apparently minor differences in the instrumental characteristics, such as response time, could cause significant differences between the emission factors determined. Direct stack measurements showed that about 14% of the fuel sulphur content was not emitted as SO2. This was supported by the remote measurements and is in agreement with the results of other field studies. S, 1984, Notes on Heavy Fuel Oi

JRC – Ispra Atmosphere – Biosphere – Climate Integrated monitoring Station 2013 report

The Institute for Environment and Sustainability provides long-term observations of the atmosphere within international programs and research projects. These observations are performed from the research infrastructure named ABC-IS: Atmosphere – Biosphere – Climate Integrated monitoring Station. Most measurements are performed at the JRC-Ispra site, but observations are also carried out from two other platforms: the forest station in San Rossore, and a ship cruising in the Western Mediterranean sea. This document reports about the measurement programs, the equipment which is deployed, the data quality assessment, and the results obtained for each site. Our observations are presented, compared to each other, as well as to historical data obtained over more than 25 years at the Ispra site.JRC.H.2-Air and Climat

JRC – Ispra Atmosphere – Biosphere – Climate Integrated monitoring Station: 2014 Report

The Institute for Environment and Sustainability provides long-term observations of the atmosphere within international programs and research projects. These observations are performed from the research infrastructure named ABC-IS: Atmosphere – Biosphere – Climate Integrated monitoring Station. Most measurements are performed at the JRC-Ispra site, but observations are also carried out from two other platforms: the forest station in San Rossore, and a ship cruising in the Western Mediterranean sea. This document reports about the measurement programs, the equipment which is deployed, the data quality assessment, and the results obtained for each site. Our observations are presented, compared to each other, as well as to historical data obtained over close to 30 years at the Ispra site.JRC.H.2-Air and Climat

Current knowledge, challenges and innovations in developmental pharmacology: A combined conect4children Expert Group and European Society for Developmental, Perinatal and Paediatric Pharmacology White Paper

Developmental pharmacology describes the impact of maturation on drug disposition (pharmacokinetics, PK) and drug effects (pharmacodynamics, PD) throughout the paediatric age range. This paper, written by a multidisciplinary group of experts, summarizes current knowledge, and provides suggestions to pharmaceutical companies, regulatory agencies and academicians on how to incorporate the latest knowledge regarding developmental pharmacology and innovative techniques into neonatal and paediatric drug development. Biological aspects of drug absorption, distribution, metabolism and excretion (ADME) throughout development are summarized. Although this area made enormous progress during the last two decades, remaining knowledge gaps were identified. Minimal risk and burden designs allow for optimally informative but minimally invasive PK sampling, while concomitant profiling of drug metabolites may provide additional insight in the unique PK behavior in children. Furthermore, developmental PD needs to be considered during drug development, which is illustrated by disease- and/or target organ-specific examples. Identifying and testing PD targets and effects in special populations, and application of age- and/or population-specific assessment tools are discussed. Drug development plans also need to incorporate innovative techniques like preclinical models to study therapeutic strategies, and shift from sequential enrollment of subgroups, to more rational designs. To stimulate appropriate research plans, illustrations of specific PK/PD-related as well as drug safety-related challenges during drug development are provided. The suggestions made in this joint paper of the Innovative Medicines Initiative conect4children Expert group on Developmental Pharmacology and the European Society for Developmental, Perinatal and Paediatric Pharmacology, should facilitate all those involved in drug development