Robust multi-fidelity design of a micro re-entry unmanned space vehicle

This article addresses the preliminary robust design of a small-scale re-entry unmanned space vehicle by means of a hybrid optimization technique. The approach, developed in this article, closely couples an evolutionary multi-objective algorithm with a direct transcription method for optimal control problems. The evolutionary part handles the shape parameters of the vehicle and the uncertain objective functions, while the direct transcription method generates an optimal control profile for the re-entry trajectory. Uncertainties on the aerodynamic forces and characteristics of the thermal protection material are incorporated into the vehicle model, and a Monte-Carlo sampling procedure is used to compute relevant statistical characteristics of the maximum heat flux and internal temperature. Then, the hybrid algorithm searches for geometries that minimize the mean value of the maximum heat flux, the mean value of the maximum internal temperature, and the weighted sum of their variance: the evolutionary part handles the shape parameters of the vehicle and the uncertain functions, while the direct transcription method generates the optimal control profile for the re-entry trajectory of each individual of the population. During the optimization process, artificial neural networks are utilized to approximate the aerodynamic forces required by the optimal control solver. The artificial neural networks are trained and updated by means of a multi-fidelity approach: initially a low-fidelity analytical model, fitted on a waverider type of vehicle, is used to train the neural networks, and through the evolution a mix of analytical and computational fluid dynamic, high-fidelity computations are used to update it. The data obtained by the high-fidelity model progressively become the main source of updates for the neural networks till, near the end of the optimization process, the influence of the data obtained by the analytical model is practically nullified. On the basis of preliminary results, the adopted technique is able to predict achievable performance of the small spacecraft and the requirements in terms of thermal protection materials

From risk-based health surveillance to health promotion: an evidence-based experience in a health care setting.

Health surveillance’s aim consists in different aspects: (i) to ensure worker’s health, (ii) to comply regulation, (iii) to detect health changes at their onset, (iv) to reduce cost, (v) to provide a fitness for job judgement, (vi) to provide a medical baseline and (vii) to be part of a preventive programme. Some of these aspects are perceived as benefits from the different stakeholders. Employers indicated as benefits worker’s satisfaction improvement, cost reduction, relationship improvement, early detection of health changes5. The study showed some other benefits: an improvement in worker’s satisfaction, an improvement in the relationship between stakeholders (even though based on qualitative data only), an early detection of health changes in few cases and a sickness absence reduction after influenza vaccination programme

Endoplasmic Reticulum Associated Aminopeptidase 2 (ERAP2) is released in the secretome of activated MDMs and reduces in vitro HIV-1 infection

Background: Haplotype-specific alternative splicing of the endoplasmic reticulum (ER) aminopeptidase type 2 (ERAP2) gene results in either full-length (FL, haplotype A) or alternatively spliced (AS, haplotype B) mRNA. HapA/HapA homozygous (HomoA) subjects show a reduced susceptibility to HIV-1 infection, probably secondary to the modulation of the antigen processing/presenting machinery. ERAP1 was recently shown to be secreted from the plasma membrane in response to activation; we investigated whether ERAP2 can be released as well and if the secreted form of this enzyme retains its antiviral function. Methods: Human monocyte derived macrophages (MDMs) were differentiated from peripheral blood mononuclear cells (PBMCs) isolated from 6 HomoA healthy controls and stimulated with IFN\u3b3 and LPS. ERAP2-FL secretion was evaluated by mass spectrometry. PBMCs (14 HomoA and 16 HomoB) and CD8-depleted PBMCs (CD8-PBMCs) (4 HomoA and 4 HomoB) were in vitro HIV-infected in the absence/presence of recombinant human ERAP2-FL (rhERAP2) protein; p24 viral antigen quantification was used to assess viral replication. IFN\u3b3 and CD69 mRNA expression, as well as the percentage of perforin-producing CD8+ T Lymphocytes, were analyzed 3 and 7-days post in vitro HIV-1-infection, respectively. The effect of rhERAP2 addition in cell cultures on T cell apoptosis, proliferation, activation, and maturation was evaluated as well on 24 h-stimulated PBMCs. Results: ERAP2 can be secreted from human MDMs in response to IFN\u3b3/LPS stimulation. Notably, the addition of rhERAP2 to PBMC and CD8-PBMC cultures resulted in the reduction of viral replication, though these differences were statistically significant only in PBMCs (p < 0.05 in both HomoA and HomoB). This protective effect was associated with an increase in IFN\u3b3 and CD69 mRNA expression and in the percentage of perforin-expressing CD107+CD8+ cells. RhERAP2 addition also resulted in an increase in CD8+ activated lymphocyte (CD25+HLA-DRII+) and Effector Memory/Terminally differentiated CD8+ T cells ratio. Conclusions: This is the first report providing evidence for the release of ERAP2 in the secretome of immunocompetent cells. Data herein also indicate that exogenous ERAP2-FL exerts its protective function against HIV-1 infection, even in HomoB subjects who do not genetically produce it. Presumably, this defensive extracellular feature is only partially dependent on immune system modulation

Analytical Benchmark Problems for Multifidelity Optimization Methods

The paper presents a collection of analytical benchmark problems specifically selected to provide a set of stress tests for the assessment of multifidelity optimization methods. In addition, the paper discusses a comprehensive ensemble of metrics and criteria recommended for the rigorous and meaningful assessment of the performance of multifidelity strategies and algorithms

Prevention of congenital malformations and other adverse pregnancy outcomes with 4.0 mg of folic acid : community-based randomized clinical trial in Italy and the Netherlands

Background: In 2010 a Cochrane review confirmed that folic acid (FA) supplementation prevents the first- and second-time occurrence of neural tube defects (NTDs). At present some evidence from observational studies supports the hypothesis that FA supplementation can reduce the risk of all congenital malformations (CMs) or the risk of a specific and selected group of them, namely cardiac defects and oral clefts. Furthermore, the effects on the prevention of prematurity, foetal growth retardation and pre-eclampsia are unclear.Although the most common recommendation is to take 0.4 mg/day, the problem of the most appropriate dose of FA is still open.The aim of this project is to assess the effect a higher dose of peri-conceptional FA supplementation on reducing the occurrence of all CMs. Other aims include the promotion of pre-conceptional counselling, comparing rates of selected CMs, miscarriage, pre-eclampsia, preterm birth, small for gestational age, abruptio placentae.Methods/Design: This project is a joint effort by research groups in Italy and the Netherlands. Women of childbearing age, who intend to become pregnant within 12 months are eligible for the studies. Women are randomly assigned to receive 4 mg of FA (treatment in study) or 0.4 mg of FA (referent treatment) daily. Information on pregnancy outcomes are derived from women-and-physician information.We foresee to analyze the data considering all the adverse outcomes of pregnancy taken together in a global end point (e.g.: CMs, miscarriage, pre-eclampsia, preterm birth, small for gestational age). A total of about 1,000 pregnancies need to be evaluated to detect an absolute reduction of the frequency of 8%. Since the sample size needed for studying outcomes separately is large, this project also promotes an international prospective meta-analysis.Discussion: The rationale of these randomized clinical trials (RCTs) is the hypothesis that a higher intake of FA is related to a higher risk reduction of NTDs, other CMs and other adverse pregnancy outcomes. Our hope is that these trials will act as catalysers, and lead to other large RCTs studying the effects of this supplementation on CMs and other infant and maternal outcomes.Trial registration: Italian trial: ClinicalTrials.gov Identifier: NCT01244347.Dutch trial: Dutch Trial Register ID: NTR3161