Overview of Polkadot and its Design Considerations

In this paper we describe the design components of the heterogenous multi-chain protocol Polkadot and explain how these components help Polkadot address some of the existing shortcomings of blockchain technologies. At present, a vast number of blockchain projects have been introduced and employed with various features that are not necessarily designed to work with each other. This makes it difficult for users to utilise a large number of applications on different blockchain projects. Moreover, with the increase in number of projects the security that each one is providing individually becomes weaker. Polkadot aims to provide a scalable and interoperable framework for multiple chains with pooled security that is achieved by the collection of components described in this paper

Determining the Importance of Physicochemical Properties in the Perceived Quality of Wines

Wine is a relevant part of the diet in many countries, showing significant nutritional properties, providing health benefits to consumers, and having a significant weight in economy. Also, wine plays an important role in many cultures as a part of their social relationships, feasts, or religion where some of them may become a sign of luxury and distinction. For those reasons, objective and subjective quality of wines is an important issue in their production and marketing. To improve wine excellence, some production methods try to relate its physicochemical properties to the quality as it is perceived by humans. Then, modern data prescriptive analysis can be applied to measure the importance (the influence) of each wine attribute. This paper examines and compare several metrics of the attribute importance and its application to the quality-aware design and production of wines. Moreover, for the cases where the perceived quality is characterized using a discrete value, a novel importance metric, based on the Jensen-Shannon Divergence (JSD) is introduced and compared to the existing ones. The results show that JSD clearly overperforms other metrics previously proposed in the literature. Also, it can be asserted that JSD properly reflects the importance of discrete multivalued functions. The results, using this metric in an importance performance analysis of a public wine dataset, show that the main physicochemical attributes of a red wine are citric acidity, alcohol, sulphates and fixed acidity. As for the white wine case, the main attributes are alcohol, free sulfure dioxide and pH

The CD38/NAD/SIRTUIN1/EZH2 Axis Mitigates Cytotoxic CD8 T Cell Function and Identifies Patients with SLE Prone to Infections

Summary: Patients with systemic lupus erythematosus (SLE) suffer frequent infections that account for significant morbidity and mortality. T cell cytotoxic responses are decreased in patients with SLE, yet the responsible molecular events are largely unknown. We find an expanded CD8CD38high T cell subset in a subgroup of patients with increased rates of infections. CD8CD38high T cells from healthy subjects and patients with SLE display decreased cytotoxic capacity, degranulation, and expression of granzymes A and B and perforin. The key cytotoxicity-related transcription factors T-bet, RUNX3, and EOMES are decreased in CD8CD38high T cells. CD38 leads to increased acetylated EZH2 through inhibition of the deacetylase Sirtuin1. Acetylated EZH2 represses RUNX3 expression, whereas inhibition of EZH2 restores CD8 T cell cytotoxic responses. We propose that high levels of CD38 lead to decreased CD8 T cell-mediated cytotoxicity and increased propensity to infections in patients with SLE, a process that can be reversed pharmacologically. : Katsuyama et al. find that an expanded CD8CD38high T cell population in SLE patients is linked to infections. CD8CD38high T cells display decreased cytotoxic capacity by suppressing the expression of related molecules through an NAD+/Sirtuin1/EZH2 pathway. EZH2 inhibitors increase cytotoxicity offering a means to mitigate infection rates in SLE. Keywords: systemic lupus erythematosus, patients, CD8 T cell, CD38, cytotoxicity, infection, nicotinamide adenine dinucleotide, Sirtuin1, EZH

Effect of aliskiren on post-discharge outcomes among diabetic and non-diabetic patients hospitalized for heart failure: insights from the ASTRONAUT trial

Aims The objective of the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT) was to determine whether aliskiren, a direct renin inhibitor, would improve post-discharge outcomes in patients with hospitalization for heart failure (HHF) with reduced ejection fraction. Pre-specified subgroup analyses suggested potential heterogeneity in post-discharge outcomes with aliskiren in patients with and without baseline diabetes mellitus (DM). Methods and results ASTRONAUT included 953 patients without DM (aliskiren 489; placebo 464) and 662 patients with DM (aliskiren 319; placebo 343) (as reported by study investigators). Study endpoints included the first occurrence of cardiovascular death or HHF within 6 and 12 months, all-cause death within 6 and 12 months, and change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) at 1, 6, and 12 months. Data regarding risk of hyperkalaemia, renal impairment, and hypotension, and changes in additional serum biomarkers were collected. The effect of aliskiren on cardiovascular death or HHF within 6 months (primary endpoint) did not significantly differ by baseline DM status (P = 0.08 for interaction), but reached statistical significance at 12 months (non-DM: HR: 0.80, 95% CI: 0.64-0.99; DM: HR: 1.16, 95% CI: 0.91-1.47; P = 0.03 for interaction). Risk of 12-month all-cause death with aliskiren significantly differed by the presence of baseline DM (non-DM: HR: 0.69, 95% CI: 0.50-0.94; DM: HR: 1.64, 95% CI: 1.15-2.33; P < 0.01 for interaction). Among non-diabetics, aliskiren significantly reduced NT-proBNP through 6 months and plasma troponin I and aldosterone through 12 months, as compared to placebo. Among diabetic patients, aliskiren reduced plasma troponin I and aldosterone relative to placebo through 1 month only. There was a trend towards differing risk of post-baseline potassium ≥6 mmol/L with aliskiren by underlying DM status (non-DM: HR: 1.17, 95% CI: 0.71-1.93; DM: HR: 2.39, 95% CI: 1.30-4.42; P = 0.07 for interaction). Conclusion This pre-specified subgroup analysis from the ASTRONAUT trial generates the hypothesis that the addition of aliskiren to standard HHF therapy in non-diabetic patients is generally well-tolerated and improves post-discharge outcomes and biomarker profiles. In contrast, diabetic patients receiving aliskiren appear to have worse post-discharge outcomes. Future prospective investigations are needed to confirm potential benefits of renin inhibition in a large cohort of HHF patients without D

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Overcoming normative and regulatory barriers hampering PV hosting capacity enhancement in European distribution grids

Since 2012 a consortium of 20 partners from 15 EU countries is collaborating in the framework of the European project PV GRID - “Reducing barriers hampering large-scale integration of PV electricity into the distribution GRID” having as its main objective to prepare the grounds for the large-scale integration of photovoltaic (PV) systems in distribution grids across Europe and bring forward concrete suggestions on how this can be achieved. The electrical power supply has started a fundamental transformation process. The fast transition towards an electrical system with high shares of decentralised energy generation requires appropriate technical solutions for ensuring distribution grids with sufficient hosting capacity and with the ability to manage the power fluctuation. In order to ensure the stability, reliability and security of the future distribution grids and of the electrical system, a key aspect is identifying and prioritising appropriate technical solutions for large-scale integration of distributed generation units. Initially, the project consortium has identified the most promising available technical solutions and assessed their effectiveness from the perspective of both the distribution system operators (DSO) and the PV system owners. Contextually, the applicability of such solutions from the regulatory point of view has also been assessed in four focus countries: Czech Republic, Germany, Italy and Spain. While the effectiveness evaluation allows for an immediate ranking of technical solutions available to solve the aforementioned hosting capacity issues at low voltage (LV) and medium voltage (MV) levels, the regulatory analysis allows determining whether the implementation of a certain solution requires a change of the current regulatory or normative framework. Taking these results as a starting point, the PV GRID consortium has initiated an ongoing accurate analysis of existing barriers at the national level of the 15 participating countries, involving in the discussion the national stakeholders (regulators, policymakers and DSOs). The outcome of these activities have been used as a basis for the development of a European advisory paper containing recommendations for the introduction of regulatory and normative solutions enabling large-scale integration of PV generation in the distribution grids across Europe. In January 2014 a consultation version of the advisory paper has been published together with a shorter version to retrieve feed-back on proposed recommendations and in order to publish a final version of the PV GRID European Advisory Paper until September 2014.JRC.F.3-Energy Security, Systems and Marke

Neonatal Lung Ultrasound and Surfactant Administration: A Pragmatic, Multicenter Study

Background: Previous research shows that a lung ultrasound score (LUS) can anticipate CPAP failure in neonatal respiratory distress syndrome. Research Question: Can LUS also predict the need for surfactant replacement? Study Design and Methods: Multicenter, pragmatic study of preterm neonates who underwent lung ultrasound at birth and those given surfactant by masked physicians, who also were scanned within 24 h from administration. Clinical data and respiratory support variables were recorded. Accuracy of LUS, oxygen saturation to FIO2 ratio, FIO2, and Silverman score for surfactant administration were evaluated using receiver operating characteristic curves. The simultaneous prognostic values of LUS and oxygen saturation to FIO2 ratio for surfactant administration, adjusting for gestational age (GA), were analyzed through a logistic regression model. Results: Two hundred forty infants were enrolled. One hundred eight received at least one dose of surfactant. LUS predicted the first surfactant administration with an area under the receiver operating characteristic curve (AUC) of 0.86 (95% CI, 0.81-0.91), cut off of 9, sensitivity of 0.79 (95% CI, 0.70-0.86), specificity of 0.83 (95% CI, 0.76-0.89), positive predictive value of 0.79 (95% CI, 0.71-0.87), negative predictive value of 0.82 (95% CI, 0.75-0.89), positive likelihood ratio of 4.65 (95% CI, 3.14-6.89), and negative likelihood ratio of 0.26 (95% CI, 0.18-0.37). No significant difference was shown among different GA groups: 25 to 27 weeks’ GA (AUC, 0.91; 95% CI, 0.84-0.99), 28 to 30 weeks’ GA (AUC, 0.81; 95% CI, 0.72-0.91), and 31 to 33 weeks’ GA (AUC, 0.88; 95% CI, 0.79-0.95), respectively. LUS declined significantly within 24 h in infants receiving one surfactant dose. When comparing FIO2, oxygen saturation to FIO2 ratio, LUS, and Silverman scores as criteria for surfactant administration, only the latter showed a significantly poorer performance. The combination of oxygen saturation to FIO2 ratio and LUS showed the highest predictive power, with an AUC of 0.93 (95% CI, 0.89-0.97), regardless of the GA interval. Interpretation: LUS is a reliable criterion to administer the first surfactant dose regardless of GA. Its association with oxygen saturation to FIO2 ratio significantly improves the prediction power for surfactant need

Lung ultrasound score progress in neonatal respiratory distress syndrome

BACKGROUND AND OBJECTIVES: The utility of a lung ultrasound score (LUS) has been described in the early phases of neonatal respiratory distress syndrome (RDS). We investigated lung ultrasound as a tool to monitor respiratory status in preterm neonates throughout the course of RDS. METHODS: Preterm neonates, stratified in 3 gestational age cohorts (25-27, 28-30, and 31-33 weeks), underwent lung ultrasound at weekly intervals from birth. Clinical data, respiratory support variables, and major complications (sepsis, patent ductus arteriosus, pneumothorax, and persistent pulmonary hypertension of the neonate) were also recorded. RESULTS: We enrolled 240 infants in total. The 3 gestational age intervals had significantly different LUS patterns. There was a significant correlation between LUS and the ratio of oxygen saturation to inspired oxygen throughout the admission, increasing with gestational age (b = 20.002 [P,.001] at 25-27 weeks; b = 20.006 [P,.001] at 28-30 weeks; b = 20.012 [P,.001] at 31-33 weeks). Infants with complications had a higher LUS already at birth (12 interquartile range 13-8 vs 8 interquartile range 12-4 control group; P =.001). In infants 25 to 30 weeks' gestation, the LUS at 7 days of life predicted bronchopulmonary dysplasia with an area under the curve of 0.82 (95% confidence interval 0.71 to 93). CONCLUSIONS: In preterm neonates affected by RDS, the LUS trajectory is gestational age dependent, significantly correlates with the oxygenation status, and predicts bronchopulmonary dysplasia. In this population, LUS is a useful, bedside, noninvasive tool to monitor the respiratory status