Uniformisation et automatisation du monitoring des tensions dans les suspentes et haubans de ponts

La détermination des tensions des haubans et suspentes de ponts par mesures accélérométriques est maitrisée et utilisée depuis longtemps au SPW (ServicePublic de Wallonie), mais la méthode utilisée ne permet pas un calcul correct pour les suspentes présentant des géométries complexes, et le contrôle est effectué de manière ponctuelle avec une périodicité variable. Le projet présenté, issu d’une collaboration avec l’Université de Liège et la société V2i, spécialisée dans l’acquisition et le traitement vibratoire, a permis de développer un système performant d’instrumentation basé sur cette technique et destiné à remplacer la méthodologie actuelle: (1) Les algorithmes d’acquisition et de traitement des données issues des accéléromètres sans fil permettent un calcul précis des tensions pour toute géométrie complexe des suspentes (raideur flexionnelle, encastrements partiels,...); (2) Les données, recueillies plusieurs fois par jour, sont traitées et transmises sur le cloud, permettent un suivi sécuritaire en continu via une gestion automatisée des alertes mises en place.Peer reviewe

De digitale transitie is mensenwerk. Onderzoek naar de noden op het vlak van (her)gebruik van digitale culturele content in de samenleving

Dit rapport is het resultaat van het onderzoeksproject ‘ECultuur’ dat door de UGent- onderzoeksgroepen MICT, GhentCDH en Cultuur & Educatie werd uitgevoerd voor het Departement Cultuur, Jeugd en Media. Het onderzoeksproject vertrekt vanuit de centrale vraag naar de voorwaarden die vervuld moeten worden om te kunnen spreken van een volwaardig digitaal ecosysteem voor de creatie, distributie, gebruik en hergebruik van digitale culturele content. Al te vaak wordt deze analyse hierbij verenigd tot de technische voorwaarden (van metadata- en andere standaarden tot repositories). Wij zien ook een aantal andere belangrijke voorwaarden die moeten gerealiseerd worden om voluit de vruchten te plukken van de mogelijkheden die de digitale omwenteling met zich meebrengt: kennis, vaardigheden en vooral ook een reeks attitudes die tot nu volgens ons onderontwikkeld zijn. Dit onderzoeksproject wenst inzicht te verwerven in de noden op het vlak van (1) enerzijds het aanbieden van digitale culturele content aan andere sectoren dan de cultuursector en (2) anderzijds het gebruik van digitale culturele content door organisaties uit die sectoren. De algemene onderzoeksvraag van het project luidt: “Aan welke voorwaarden moet de cultuursector voldoen zodat de behoeften van de hergebruikers van digitale culturele content vervuld kunnen worden?”

Functional Validation of the Putative Oncogenic Activity of PLAU

Plasminogen activator, urokinase (PLAU) is involved in cell migration, proliferation and tissue remodeling. PLAU upregulation is associated with an increase in aggressiveness, metastasis, and invasion of several cancer types, including breast cancer. In patients, this translates into decreased sensitivity to hormonal treatment, and poor prognosis. These clinical findings have led to the examination of PLAU as a biomarker for predicting breast cancer prognosis and therapy responses. In this study, we investigated the functional ability of PLAU to act as an oncogene in breast cancers by modulating its expression using CRISPR-deactivated Cas9 (CRISPR-dCas9) tools. Different effector domains (e.g., transcription modulators (VP64, KRAB)) alone or in combination with epigenetic writers (DNMT3A/3L, MSssI) were fused to dCas9 and targeted to the PLAU promoter. In MDA-MB-231 cells characterized by high PLAU expression downregulation of PLAU expression by CRISPR-dCas9-DNMT3A/3L-KRAB, resulted in decreased cell proliferation. Conversely, CRISPR-dCas9-VP64 induced PLAU upregulation in low PLAU expressing MCF-7 cells and significantly increased aggressiveness and invasion. In conclusion, modulation of PLAU expression affected metastatic related properties of breast cancer cells, thus further validating its oncogenic activity in breast cancer cells.</p

TP53 outperforms other androgen receptor biomarkers to predict abiraterone or enzalutamide outcome in metastatic castration-resistant prostate cancer

Purpose: To infer the prognostic value of simultaneous androgen receptor (AR) and TP53 profiling in liquid biopsies from patients with metastatic castration-resistant prostate cancer (mCRPC) starting a new line of AR signaling inhibitors (ARSi). Experimental Design: Between March 2014 and April 2017, we recruited patients with mCRPC (n = 168) prior to ARSi in a cohort study encompassing 10 European centers. Blood samples were collected for comprehensive profiling of Cell Search-enriched circulating tumor cells (CTC) and circulating tumor DNA (ctDNA). Targeted CTC RNA sequencing (RNA-seq) allowed the detection of eight AR splice variants (ARV). Low-pass whole-genome and targeted gene-body sequencing of AR and TP53 was applied to identify amplifications, loss of heterozygosity, mutations, and structural rearrangements in ctDNA. Clinical or radiologic progression-free survival (PFS) was estimated by Kaplan-Meier analysis, and independent associations were determined using multivariable Cox regression models. Results: Overall, no single AR perturbation remained associated with adverse prognosis after multivariable analysis. Instead, tumor burden estimates (CTC counts, ctDNA fraction, and visceral metastases) were significantly associated with PFS. TP53 inactivation harbored independent prognostic value [HR 1.88; 95% confidence interval (CI), 1.18-3.00; P = 0.008], and outperformed ARV expression and detection of genomic AR alterations. Using Cox coefficient analysis of clinical parameters and TP53 status, we identified three prognostic groups with differing PFS estimates (median, 14.7 vs. 7.51 vs. 2.62 months; P < 0.0001), which was validated in an independent mCRPC cohort (n = 202) starting first-line ARSi (median, 14.3 vs. 6.39 vs. 2.23 months; P < 0.0001). Conclusions: In an all-comer cohort, tumor burden estimates and TP53 outperform any AR perturbation to infer prognosis. See related commentary by Rebello et al., p. 169

A technical framework for costing health workforce retention schemes in remote and rural areas

<p>Abstract</p> <p>Background</p> <p>Increasing the availability of health workers in remote and rural areas through improved health workforce recruitment and retention is crucial to population health. However, information about the costs of such policy interventions often appears incomplete, fragmented or missing, despite its importance for the sound selection, planning, implementation and evaluation of these policies. This lack of a systematic approach to costing poses a serious challenge for strong health policy decisions.</p> <p>Methods</p> <p>This paper proposes a framework for carrying out a costing analysis of interventions to increase the availability of health workers in rural and remote areas with the aim to help policy decision makers. It also underlines the importance of identifying key sources of financing and of assessing financial sustainability.</p> <p>The paper reviews the evidence on costing interventions to improve health workforce recruitment and retention in remote and rural areas, provides guidance to undertake a costing evaluation of such interventions and investigates the role and importance of costing to inform the broader assessment of how to improve health workforce planning and management.</p> <p>Results</p> <p>We show that while the debate on the effectiveness of policies and strategies to improve health workforce retention is gaining impetus and attention, there is still a significant lack of knowledge and evidence about the associated costs. To address the concerns stemming from this situation, key elements of a framework to undertake a cost analysis are proposed and discussed.</p> <p>Conclusions</p> <p>These key elements should help policy makers gain insight into the costs of policy interventions, to clearly identify and understand their financing sources and mechanisms, and to ensure their sustainability.</p

Cell-free DNA profiling of metastatic prostate cancer reveals microsatellite instability, structural rearrangements and clonal hematopoiesis.

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.BACKGROUND: There are multiple existing and emerging therapeutic avenues for metastatic prostate cancer, with a common denominator, which is the need for predictive biomarkers. Circulating tumor DNA (ctDNA) has the potential to cost-efficiently accelerate precision medicine trials to improve clinical efficacy and diminish costs and toxicity. However, comprehensive ctDNA profiling in metastatic prostate cancer to date has been limited. METHODS: A combination of targeted and low-pass whole genome sequencing was performed on plasma cell-free DNA and matched white blood cell germline DNA in 364 blood samples from 217 metastatic prostate cancer patients. RESULTS: ctDNA was detected in 85.9% of baseline samples, correlated to line of therapy and was mirrored by circulating tumor cell enumeration of synchronous blood samples. Comprehensive profiling of the androgen receptor (AR) revealed a continuous increase in the fraction of patients with intra-AR structural variation, from 15.4% during first-line metastatic castration-resistant prostate cancer therapy to 45.2% in fourth line, indicating a continuous evolution of AR during the course of the disease. Patients displayed frequent alterations in DNA repair deficiency genes (18.0%). Additionally, the microsatellite instability phenotype was identified in 3.81% of eligible samples (≥ 0.1 ctDNA fraction). Sequencing of non-repetitive intronic and exonic regions of PTEN, RB1, and TP53 detected biallelic inactivation in 47.5%, 20.3%, and 44.1% of samples with ≥ 0.2 ctDNA fraction, respectively. Only one patient carried a clonal high-impact variant without a detectable second hit. Intronic high-impact structural variation was twice as common as exonic mutations in PTEN and RB1. Finally, 14.6% of patients presented false positive variants due to clonal hematopoiesis, commonly ignored in commercially available assays. CONCLUSIONS: ctDNA profiles appear to mirror the genomic landscape of metastatic prostate cancer tissue and may cost-efficiently provide somatic information in clinical trials designed to identify predictive biomarkers. However, intronic sequencing of the interrogated tumor suppressors challenges the ubiquitous focus on coding regions and is vital, together with profiling of synchronous white blood cells, to minimize erroneous assignments which in turn may confound results and impede true associations in clinical trials.The Belgian Foundation Against Cancer (grant number C/2014/227); Kom op tegen Kanker (Stand up to Cancer), the Flemish Cancer Society (grant number 00000000116000000206); Royal College of Surgeons/Cancer Research UK (C19198/A1533); The Cancer Research Funds of Radiumhemmet, through the PCM program at KI (grant number 163012); The Erling-Persson family foundation (grant number 4-2689-2016); the Swedish Research Council (grant number K2010-70X-20430-04-3), and the Swedish Cancer Foundation (grant number 09-0677)

Genetic and lifestyle risk factors for MRI-defined brain infarcts in a population-based setting.

OBJECTIVE: To explore genetic and lifestyle risk factors of MRI-defined brain infarcts (BI) in large population-based cohorts. METHODS: We performed meta-analyses of genome-wide association studies (GWAS) and examined associations of vascular risk factors and their genetic risk scores (GRS) with MRI-defined BI and a subset of BI, namely, small subcortical BI (SSBI), in 18 population-based cohorts (n = 20,949) from 5 ethnicities (3,726 with BI, 2,021 with SSBI). Top loci were followed up in 7 population-based cohorts (n = 6,862; 1,483 with BI, 630 with SBBI), and we tested associations with related phenotypes including ischemic stroke and pathologically defined BI. RESULTS: The mean prevalence was 17.7% for BI and 10.5% for SSBI, steeply rising after age 65. Two loci showed genome-wide significant association with BI: FBN2, p = 1.77 × 10-8; and LINC00539/ZDHHC20, p = 5.82 × 10-9. Both have been associated with blood pressure (BP)-related phenotypes, but did not replicate in the smaller follow-up sample or show associations with related phenotypes. Age- and sex-adjusted associations with BI and SSBI were observed for BP traits (p value for BI, p [BI] = 9.38 × 10-25; p [SSBI] = 5.23 × 10-14 for hypertension), smoking (p [BI] = 4.4 × 10-10; p [SSBI] = 1.2 × 10-4), diabetes (p [BI] = 1.7 × 10-8; p [SSBI] = 2.8 × 10-3), previous cardiovascular disease (p [BI] = 1.0 × 10-18; p [SSBI] = 2.3 × 10-7), stroke (p [BI] = 3.9 × 10-69; p [SSBI] = 3.2 × 10-24), and MRI-defined white matter hyperintensity burden (p [BI] = 1.43 × 10-157; p [SSBI] = 3.16 × 10-106), but not with body mass index or cholesterol. GRS of BP traits were associated with BI and SSBI (p ≤ 0.0022), without indication of directional pleiotropy. CONCLUSION: In this multiethnic GWAS meta-analysis, including over 20,000 population-based participants, we identified genetic risk loci for BI requiring validation once additional large datasets become available. High BP, including genetically determined, was the most significant modifiable, causal risk factor for BI

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries

Damage Detection of Mechanical Components Using Null Subspace Analysis

This paper presents two original applications of the Null Subspace Analysis (NSA) method for fault diagnosis in mechanical components. The method is first applied to the case-study of electro-mechanical devices at the end of the assembly line with the aim of assessing their overall quality. The advantages of the proposed method rely in its rapidity of use and its reliability. At first, a set of five good (i.e. healthy) devices and four damaged devices was considered. The components were instrumented with one triaxial accelerometer on the flank and one monoaxial accelerometer on the top. Based on the NSA method, a mapping of the space [ active components, system order ] up to a system order of 100, was realized in order to select the appropriate order and number of active components. Eventually, thanks to this mapping, the method was able to successfully detect all the faulty components using the signal from only one accelerometer in one direction. The second application is related to the quality assessment of welded joints between stripes in a steel processing plan. Six welded joints with nominal welding parameters and twenty-seven welded joints with out-of-range parameters were realized. Again, the NSA method was able to diagnose successfully the welded joints using a single signal from one accelerometer.Maintenance Intelligente (MINT

Fault Diagnosis in Industrial Systems Based on Blind Source Separation Techniques Using One Single Vibration Sensor

In the field of structural health monitoring or machine condition monitoring, most vibration based methods reported in the literature require to measure responses at several locations on the structure. In machine condition monitoring, the number of available vibration sensors is often small and it is not unusual that only one single sensor is used to monitor a machine. The aim of this paper is to propose an extension of fault detection techniques that may be used when a reduced set of sensors or even one single sensor is available. Fault detection techniques considered here are based on output-only methods coming from the Blind Source Separation (BSS) family, namely Principal Component Analysis (PCA) and Second Order Blind Identification (SOBI). The advantages of PCA or SOBI rely on their rapidity of use and their reliability. Based on these methods, subspace identification may be performed by using the concept of block Hankel matrices which make possible the use of only one single measurement signal. Thus, the problem of fault detection in mechanical systems can be solved by using subspaces built from active principal components or modal vectors. It consists in comparing subspace features between the reference (undamaged) state and a current state. The angular coherence between subspaces is a good indicator of a dynamic change in the system due to the occurrence of faults or damages. The robustness of the methods is illustrated on industrial examples