Reliability of Early Fetal Echocardiography for Congenital Heart Disease Detection: A Preliminary Experience and Outcome Analysis of 102 Fetuses to Demonstrate the Value of a Clinical Flow-Chart Designed for At-Risk Pregnancy Management

Early fetal echocardiography (EFEC) is a fetal cardiac ultrasound analysis performed between the 12th and 16th week of pregnancy (compared with the usual 18-22 weeks). In the last 10 years, the introduction of “aneuploidy sonographic markers” in screening for cardiac defects has led to a shift from late second to end of the first trimester or beginning of the second trimester of pregnancy for specialist fetal echocardiography. In this prospective study, early obstetric screening was performed between January 2014 and October 2015, using “aneuploidy sonographic markers” following SIEOG Guidelines 2014. These parameters were then collected and strategically combined in an evaluation score to select the group of pregnancies for performing EFEC, in accordance with the American Society of Echocardiography guidelines for fetal Echocardiography. All second-level examinations were performed transabdominally using a 3D convex volumetric probe with frequency range of 4-8 MHz (Accuvix – Samsung). The outcome data included transabdominal fetal echocardiography from 18 weeks to term and after birth. Overall, 99 pregnant women in the first trimester underwent EFEC (95 singleton and 4 twin pregnancies). Specifically, 30 fetuses were evaluated for extra-cardiac anomalies evidenced by obstetric screening (30%), 25 for family history of congenital heart diseases (25%), 8 for family history of genetic-linked diseases (8%), 4 for heart diseases suspected by obstetric screening (4%) and 19 by normal screening (19%). Was detected 11 (10.7%) CHD, when EFEC detected CHD, were compared to those performed later in pregnancy (18 weeks GA-term), a high degree of diagnosis correspondence was evidenced. The higher sensitivity value of EFEC vs late-FE, in comparison with the post-natal value, coupled with the high EFEC specificity shown vs both the end points, enabled us to consider it as a really reliable diagnostic technology, at least in perienced hands. The introduction of a key combination of the more sensitive obstetric and cardiologic variables should facilitate the formulation of a possible flow-chart as a guide for CHD at-risk pregnancies

Designing cost-sharing methods for Bayesian games

We study the design of cost-sharing protocols for two fundamental resource allocation problems, the Set Cover and the Steiner Tree Problem, under environments of incomplete information (Bayesian model). Our objective is to design protocols where the worst-case Bayesian Nash equilibria, have low cost, i.e. the Bayesian Price of Anarchy (PoA) is minimized. Although budget balance is a very natural requirement, it puts considerable restrictions on the design space, resulting in high PoA. We propose an alternative, relaxed requirement called budget balance in the equilibrium (BBiE).We show an interesting connection between algorithms for Oblivious Stochastic optimization problems and cost-sharing design with low PoA. We exploit this connection for both problems and we enforce approximate solutions of the stochastic problem, as Bayesian Nash equilibria, with the same guarantees on the PoA. More interestingly, we show how to obtain the same bounds on the PoA, by using anonymous posted prices which are desirable because they are easy to implement and, as we show, induce dominant strategies for the players

Elevated hepatocyte growth factor levels in osteoarthritis osteoblasts contribute to their altered response to bone morphogenetic protein-2 and reduced mineralization capacity

PURPOSE: Clinical and in vitro studies suggest that subchondral bone sclerosis due to abnormal osteoblasts is involved in the progression of osteoarthritis (OA). Human osteoblasts isolated from sclerotic subchondral OA bone tissue show an altered phenotype, a decreased canonical Wnt/ß-catenin pathway, and a reduced mineralization in vitro as well as in vivo. These alterations were linked with an abnormal response to BMP-2. OA osteoblasts release factors such as the hepatocyte growth factor (HGF) that contribute to cartilage loss whereas chondrocytes do not express HGF. HGF can stimulate BMP-2 expression in human osteoblasts, however, the role of HGF and its effect in OA osteoblasts remains unknown. Here we investigated whether elevated endogenous HGF levels in OA osteoblasts are responsible for their altered response to BMP-2. METHODS: We prepared primary human subchondral osteoblasts using the sclerotic medial portion of the tibial plateaus of OA patients undergoing total knee arthroplasty, or from tibial plateaus of normal individuals obtained at autopsy. The expression of HGF was evaluated by qRT-PCR and the protein production by western blot analysis. HGF expression was reduced with siRNA technique whereas its activity was inhibited using the selective inhibitor PHA665752. Alkaline phosphatase activity (ALPase) and osteocalcin release were measured by substrate hydrolysis and EIA respectively. Canonical Wnt/β-catenin signaling (cWnt) was evaluated both by target gene expression using the TOPflash TCF/lef luciferase reporter assay and western blot analysis of β-catenin levels in response to Wnt3a stimulation. Mineralization in response to BMP-2 was evaluated by alizarin red staining. RESULTS: The expression of HGF was increased in OA osteoblasts compared to normal osteoblasts and was maintained during their in vitro differentiation. OA osteoblasts released more HGF than normal osteoblasts as assessed by western blot analysis. HGF stimulated the expression of TGF-β1. BMP-2 dose-dependently (1 to 100ng/ml) stimulated both ALPase and osteocalcin in normal osteoblasts whereas, it inhibited them in OA osteoblasts. HGF-siRNA treatments reversed this response in OA osteoblasts and restored the BMP-2 response. cWnt is reduced in OA osteoblasts compared to normal, and HGF-siRNA treatments increased cWnt in OA osteoblasts almost to normal. Smad1/5/8 phosphorylation in response to BMP-2, which is reduced in OA osteoblasts, was corrected when these cells were treated with PHA665752. The BMP-2-dependent mineralization of OA osteoblasts, which is also reduced compared to normal, was only partially restored by PHA665752 treatment whereas 28days treatment with HGF reduced the mineralization of normal osteoblasts. CONCLUSION: OA osteoblasts expressed more HGF than normal osteoblasts. Increased endogenous HGF production in OA osteoblasts stimulated the expression of TGF-β1 and reduced their response to BMP-2. Inhibiting HGF expression or HGF signaling restored the response to BMP-2 and Smad1/5/8 signaling. In addition, decreased HGF signaling partly corrects the abnormal mineralization of OA osteoblasts while increased HGF prevents the normal mineralization of normal osteoblasts. In summary, we hypothesize that sustained elevated HGF levels in OA osteoblasts drive their abnormal phenotype and is implicated in OA pathophysiology

Seismic risk in the city of Al Hoceima (north of Morocco) using the vulnerability index method, applied in Risk-UE project

The final publication is available at Springer via http://dx.doi.org/10.1007/s11069-016-2566-8Al Hoceima is one of the most seismic active regions in north of Morocco. It is demonstrated by the large seismic episodes reported in seismic catalogs and research studies. However, seismic risk is relatively high due to vulnerable buildings that are either old or don’t respect seismic standards. Our aim is to present a study about seismic risk and seismic scenarios for the city of Al Hoceima. The seismic vulnerability of the existing residential buildings was evaluated using the vulnerability index method (Risk-UE). It was chosen to be adapted and applied to the Moroccan constructions for its practicality and simple methodology. A visual inspection of 1102 buildings was carried out to assess the vulnerability factors. As for seismic hazard, it was evaluated in terms of macroseismic intensity for two scenarios (a deterministic and probabilistic scenario). The maps of seismic risk are represented by direct damage on buildings, damage to population and economic cost. According to the results, the main vulnerability index of the city is equal to 0.49 and the seismic risk is estimated as Slight (main damage grade equal to 0.9 for the deterministic scenario and 0.7 for the probabilistic scenario). However, Moderate to heavy damage is expected in areas located in the newer extensions, in both the east and west of the city. Important economic losses and damage to the population are expected in these areas as well. The maps elaborated can be a potential guide to the decision making in the field of seismic risk prevention and mitigation strategies in Al Hoceima.Peer ReviewedPostprint (author's final draft

A method for the reconstruction of unknown non-monotonic growth functions in the chemostat

We propose an adaptive control law that allows one to identify unstable steady states of the open-loop system in the single-species chemostat model without the knowledge of the growth function. We then show how one can use this control law to trace out (reconstruct) the whole graph of the growth function. The process of tracing out the graph can be performed either continuously or step-wise. We present and compare both approaches. Even in the case of two species in competition, which is not directly accessible with our approach due to lack of controllability, feedback control improves identifiability of the non-dominant growth rate.Comment: expansion of ideas from proceedings paper (17 pages, 8 figures), proceedings paper is version v

Women and Illegal Activities: Gender Differences and Women's Willingness to Comply Over Time

In recent years the topics of illegal activities such as corruption or tax evasion have attracted a great deal of attention. However, there is still a lack of substantial empirical evidence about the determinants of compliance. The aim of this paper is to investigate empirically whether women are more willing to be compliant than men and whether we observe (among women and in general) differences in attitudes among similar age groups in different time periods (cohort effect) or changing attitudes of the same cohorts over time (age effect) using data from eight Western European countries from the World Values Survey and the European Values Survey that span the period from 1981 to 1999. The results reveal higher willingness to comply among women and an age rather than a cohort effect. Working Paper 06-5

The Influence of Leadership Style and Organizational Citizenship Behaviour (OCB) on Organizational Performance: A Case of ICT Firm in Saudi Arabia

The purpose of this quantitative study was to examine the influence of leadership style and organizational citizenship behaviour (OCB) on organizational behaviour. This study arises from the need to know the factors that can increase the organizational performance in the MOBAILI telecommunication company which located in Saudi Arabia. It is argued in this thesis that very limited number of studies have been conducted on the relationship between leadership style and OCB in the perspective of developing countries in general, so this study aimed at investigating whether leadership style and OCB have a positive impact on organizational performance in one of telecommunication company called MOBAILI located in Saudi Arabia. To this end, 86 respondents working in MOBAILI telecommunication company located in Saudi Arabia were selected to participate in the study. Organizational performance was measured by the 10-item developed by Steele (1987). Leadership style was measured by the 20-items and OCB was measured by 12-items developed by Podsakoff and Mackenzie(as cited in Niehoff & Moorman, 1993). The instruments for in this study were measured by using the 5-item questionnaire. The findings revealed that leadership style and organizational citizenship behaviour (OCB) were statistically and significantly related to organizational performance. OCB was found to be the best predictor of organizational performance. The limitations of this study and the recommendations for future research are also discussed

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13

Vaccination of stage III/IV melanoma patients with long NY-ESO-1 peptide and CpG-B elicits robust CD8(+) and CD4(+) T-cell responses with multiple specificities including a novel DR7-restricted epitope.

Long synthetic peptides and CpG-containing oligodeoxynucleotides are promising components for cancer vaccines. In this phase I trial, 19 patients received a mean of 8 (range 1-12) monthly vaccines s.c. composed of the long synthetic NY-ESO-179-108 peptide and CpG-B (PF-3512676), emulsified in Montanide ISA-51. In 18/18 evaluable patients, vaccination induced antigen-specific CD8(+) and CD4(+) T-cell and antibody responses, starting early after initiation of immunotherapy and lasting at least one year. The T-cells responded antigen-specifically, with strong secretion of IFNγ and TNFα, irrespective of patients' HLAs. The most immunogenic regions of the vaccine peptide were NY-ESO-189-102 for CD8(+) and NY-ESO-183-99 for CD4(+) T-cells. We discovered a novel and highly immunogenic epitope (HLA-DR7/NY-ESO-187-99); 7/7 HLA-DR7(+) patients generated strong CD4(+) T-cell responses, as detected directly ex vivo with fluorescent multimers. Thus, vaccination with the long synthetic NY-ESO-179-108 peptide combined with the strong immune adjuvant CpG-B induced integrated, robust and functional CD8(+) and CD4(+) T-cell responses in melanoma patients, supporting the further development of this immunotherapeutic approach