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See detailSupervised inference of biological networks with trees : Application to genetic interactions in yeast
Schrynemackers, Marie ULg

Doctoral thesis (2015)

Networks or graphs provide a natural representation of molecular biology knowledge, in particular to model relationships between biological entities such as genes, proteins, drugs, or diseases. Because of ... [more ▼]

Networks or graphs provide a natural representation of molecular biology knowledge, in particular to model relationships between biological entities such as genes, proteins, drugs, or diseases. Because of the effort, the cost, or the lack of the experiments necessary to the elucidation of these networks, computational approaches for network inference have been frequently investigated in the literature. In this thesis, we focus on supervised network inference methods. These methods exploit supervised machine learning algorithms to train a model for identifying new interacting pairs of nodes from a training sample of known interacting and possibly non-interacting pairs and additional measurement data about the network nodes. Our contributions in this area are divided into three parts. First, the thesis examines the problem of the assessment of supervised network inference methods. Indeed, their reliable validation (in silico) poses a number of new challenges with respect to standard classification problems, related to the fact that pairs of objects are to be classified and to the specificities of biological networks. We perform a critical review and assessment of protocols and measures proposed in the literature. Through theoretical considerations and in silico experiments, we analyze in depth how important factors influence the outcome of performance estimation. These factors include the amount of information available for the interacting entities, the sparsity and topology of biological networks, and the lack of experimentally verified non-interacting pairs. From this analysis, we derived specific guidelines so as to how best exploit and evaluate machine learning techniques for network inference. Second, we systematically investigate, theoretically and empirically, the exploitation of tree- based methods for network inference. We consider these methods in the context of the two main generic classification-based approaches for network inference: the local approach, which trains a separate model for each network node, and the global approach, which trains a single model over pairs of nodes. We present and formalize these two approaches, extending the former for the prediction of interactions between two unseen network nodes, and discuss their specializations to tree-based methods, highlighting their interpretability and drawing links with clustering techniques. Extensive experiments are carried out with these methods on various biological networks that clearly highlight that these methods are competitive with existing methods. The interpretability of the resulting method family is illustrated on a drug-protein interaction network. In the last part of the thesis, we built on the experience gained in the two previous parts to try to predict at best the genetic interaction network in yeast S.cerevisiae. For that purpose, we collected a large dataset, assembling 4 millions gene pairs that were experimentally tested in the context of 11 different studies and 23 sets of measurements to use as gene input features for the inference. Through several cross-validation experiments on the resulting dataset, we showed that predicting genetic interactions is indeed possible to some useful extent and that actually in some settings, the accuracy of computational methods is not very far from that of experimental techniques. [less ▲]

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See detailAnalyzing Access, Egress, and Main Transport Mode of Public Transit Journeys: Evidence from the Flemish National Household Travel Survey
Creemers, Lieve; Bellemans, Tom; Janssens, Davy et al

in Proceedings of the 94th Annual Meeting of the Transportation Research Board (2015)

The primary objective of this paper is to explore the influence of socio-demographic and contextual variables on the multimodal character of public transit journeys. Accounting for multimodality in public ... [more ▼]

The primary objective of this paper is to explore the influence of socio-demographic and contextual variables on the multimodal character of public transit journeys. Accounting for multimodality in public transit journeys is important from a demand modeling point of view, especially in the assessment of new projected public transit infrastructure. To meet the objective, data from the national household travel survey of Flanders (Belgium) is analyzed. Based on 2,202 public transit journeys, the main public transit mode choice (bus/tram/metro or train) and access/egress mode choice are simultaneously estimated using a multinomial logit model, and by explicitly making a distinction between unimodal and multimodal transit journeys. The results indicate that various socio-demographical (e.g. age, gender, level of education, household income) and contextual factors (e.g. journey distance, journey motive, urbanization degree, car availability) significantly influence the joint decision process. Total journey distance and car availability are identified as the most important explanatory variables. In terms of model performance, the model appears to yield satisfactory predictions, justifying the integration of the model in more general demand modeling frameworks. [less ▲]

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See detailTiO2 Macroscopic Fibers with Enhanced Photocatalytic Properties Obtained through a Scale-Up Semi-Industrial Process
Kinadjian, Natacha; Le Bechec, Mickael; Henrist, Catherine ULg et al

in Advanced Engineering Materials (2015), 17(1), 36-44

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See detailBayesian inference for transportation origin–destination matrices: the Poisson–inverse Gaussian and other Poisson mixtures
Perrakis, Konstantinos; Karlis, Dimitris; Cools, Mario ULg et al

in Journal of the Royal Statistical Society. Series A Statistics in Society (2015), 178(1), 271-296

Transportation origin–destination analysis is investigated through the use of Poisson mixtures by introducing covariate-based models which incorporate different transport modelling phases and also allow ... [more ▼]

Transportation origin–destination analysis is investigated through the use of Poisson mixtures by introducing covariate-based models which incorporate different transport modelling phases and also allow for direct probabilistic inference on link traffic based on Bayesian predictions. Emphasis is placed on the Poisson–inverse Gaussian model as an alternative to the commonly used Poisson–gamma and Poisson–log-normal models. We present a first full Bayesian formulation and demonstrate that the Poisson–inverse Gaussian model is particularly suited for origin–destination analysis because of its desirable marginal and hierarchical properties. In addition, the integrated nested Laplace approximation is considered as an alternative to Markov chain Monte Carlo sampling and the two methodologies are compared under specific modelling assumptions. The case-study is based on 2001 Belgian census data and focuses on a large, sparsely distributed origin–destination matrix containing trip information for 308 Flemish municipalities. [less ▲]

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See detailMerging multi-camera data to reduce motion analysis instrumental errors using Kalman filters
Schwartz, Cédric ULg; Denoël, Vincent ULg; Forthomme, Bénédicte ULg et al

in Computer Methods in Biomechanics and Biomedical Engineering (2015), 18(9), 952-960

In motion capture systems, markers are often seen by multiple cameras. All cameras do not measure the position of the markers with the same reliability because of environmental factors such as the ... [more ▼]

In motion capture systems, markers are often seen by multiple cameras. All cameras do not measure the position of the markers with the same reliability because of environmental factors such as the position of the marker in the field of view or the light intensity received by the cameras. Kalman filters offer a general framework to take the reliability of the various cameras into account and consequently improve the estimation of the marker position. The proposed process can be applied to both passive and active systems. Several reliability models of the cameras are compared for the Codamotion active system, which is considered as a specific illustration. The proposed method significantly reduces the noise in the signal, especially at long range distances. Therefore, it improves the confidence of the positions at the limits of the field of view. [less ▲]

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See detailPaleomagnetic and geochemical record from cores from the Sea of Marmara, Turkey: Age constraints and implications of sapropelic deposition on early diagenesis
Drab, Laureen; Carlut, Julie; Hubert, Aurelia ULg et al

in Marine Geology (2015), 360

We present results of a multi-proxy analysis of two sediment cores from the Marmara Sea. The cores were ana- lyzed using paleomagnetic and geochemical measurements. Two sapropels are documented in the ... [more ▼]

We present results of a multi-proxy analysis of two sediment cores from the Marmara Sea. The cores were ana- lyzed using paleomagnetic and geochemical measurements. Two sapropels are documented in the last 11 kyr and are recorded in several locations across the Marmara Sea. These two sapropels have contrasting magnetic prop- erties. The magnetic record is affected by intense early diagenesis; the most recent upper sapropelic layer has low remanence and susceptibility values. A record of paleomagnetic inclinations could still be isolated above the dia- genesis front and is compared with secular variation models. The lower sapropel is identified in the deep part of the oldest studied core (Klg07) and has distinct magnetic properties characterized by high remanence and sus- ceptibility values. Using the magnetic properties it is possible to constrain bottom water ventilation and recon- nection episodes between the Marmara Sea and the Black Sea following the sea level rise during the last glacial to inter-glacial transition. [less ▲]

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See detailLearning the Tactile Signatures of Prototypical Object Parts for Robust Part-based Grasping of Novel Objects
Hyttinen, Emil; Kragic, Danica; Detry, Renaud ULg

in IEEE International Conference on Robotics and Automation (2015)

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See detailCost-effectiveness of vitamin D and calcium supplementation in the treatment of elderly women and men with osteoporosis.
Hiligsmann, Mickaël ULg; Ben Sedrine, Wafa; Bruyère, Olivier ULg et al

in European journal of public health (2015), 25(1), 20-25

BACKGROUND: The supplementation with vitamin D and calcium has been recommended for elderly, specifically those with increased risk of fractures older than 65 years. This study aims to assess the cost ... [more ▼]

BACKGROUND: The supplementation with vitamin D and calcium has been recommended for elderly, specifically those with increased risk of fractures older than 65 years. This study aims to assess the cost-effectiveness of vitamin D and calcium supplementation in elderly women and men with osteoporosis and therefore to assess if this recommendation is justified in terms of cost-effectiveness. METHODS: A validated model for economic evaluations in osteoporosis was used to estimate the cost per quality-adjusted life-year (QALY) gained of vitamin D/calcium supplementation compared with no treatment. The model was populated with cost and epidemiological data from a Belgian health-care perspective. Analyses were conducted in women and men with a diagnosis of osteoporosis (i.e. bone mineral density T-score </=-2.5). A literature search was conducted to describe the efficacy of vitamin D and calcium in terms of fracture risk reduction. RESULTS: The cost per QALY gained of vitamin D/calcium supplementation was estimated at euro40 578 and euro23 477 in women and men aged 60 years, respectively. These values decreased to euro7912 and euro10 250 at the age of 70 years and vitamin D and calcium supplementation was cost-saving at the age of 80 years, meaning that treatment cost was less than the costs of treating osteoporotic fractures of the no-treatment group. CONCLUSION: This study suggests that vitamin D and calcium supplementation is cost-effective for women and men with osteoporosis aged over 60 years. From an economic perspective, vitamin D and calcium should therefore be administrated in these populations including those also taking other osteoporotic treatments. [less ▲]

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See detailLes difficultés d'apprentissage procédural chez les enfants dysphasiques
Desmottes, Lise ULg; Meulemans, Thierry ULg; Maillart, Christelle ULg

in ANAE : Approche Neuropsychologique des Apprentissages chez l'Enfant (2015)

Through a review of the literature, this paper shows that linguistic and non-linguistic disorders in children with specific language impairment might be linked to difficulties in procedural learning ... [more ▼]

Through a review of the literature, this paper shows that linguistic and non-linguistic disorders in children with specific language impairment might be linked to difficulties in procedural learning, especially regarding sequential abilities. Indeed, children with specific language impairment encounter difficulties to learn visuo-motor and linguistic sequences. These difficulties are not limited to initial learning but extend to the consolidation stage in long-term memory. Finally, recent studies show that it is possible to improve procedural learning abilities, suggesting new avenues for rehabilitation. [less ▲]

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See detailRestoring testosterone levels by adding dehydroepiandrosterone to a drospirenone containing combined oral contraceptive: II. Clinical effects.
Zimmerman, Y.; Foidart, Jean-Michel ULg; Pintiaux, Axelle ULg et al

in Contraception (2015), 91(2), 134-42

OBJECTIVES: Combined oral contraceptives (COCs) decrease androgen levels, including testosterone (T), which may be associated with sexual dysfunction and mood complaints in some women. We have shown that ... [more ▼]

OBJECTIVES: Combined oral contraceptives (COCs) decrease androgen levels, including testosterone (T), which may be associated with sexual dysfunction and mood complaints in some women. We have shown that 'co-administration' of dehydroepiandrosterone (DHEA) to a drospirenone (DRSP)-containing COC restored total T levels to baseline and free T levels by 47%. Here we describe the effects on sexual function, mood and quality of life of such an intervention. STUDY DESIGN: This was a randomized, double-blind, placebo-controlled study in 99 healthy COC starters. A COC containing 30mcg ethinylestradiol (EE) and 3mg DRSP was used for three cycles, followed by six cycles of the same COC combined with 50mg/day DHEA or placebo. Subjects completed the Moos Menstrual Distress Questionnaire (MDQ), the McCoy Female Sexuality Questionnaire and the short form of the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q). Safety and tolerability, including effects on skin, were evaluated. RESULTS: The addition of DHEA induced small but significant improvements compared to placebo in the MDQ score for autonomic reactions during the menstrual (-2.0 vs. 0.71; p=0.05) and the premenstrual phase (-3.1 vs. 2.9; p=0.01) and for behavior during the intermenstrual phase (-1.4 vs. 3.6; p=0.02). A significant difference was found in the MDQ score for arousal during the premenstrual phase in favor of placebo (-5.0 vs. 1.0; p=0.01). There were no statistically significant differences between groups for the MSFQ and Q-LES-Q scores. DHEA 'co-administration' resulted in an acceptable safety profile. DHEA negated the beneficial effect of the COC on acne according to the subjects' self-assessment. CONCLUSIONS: 'Co-administration' with DHEA did not result in consistent improvements in sexual function, mood and quality of life indicators in women taking EE/DRSP. Retrospectively, the 50 mg dose of DHEA may be too low for this COC. IMPLICATIONS: A well-balanced judgment of the clinical consequences of normalizing androgens during COC use may require complete normalization of free T. [less ▲]

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See detailChemical abundances of fast-rotating OB stars
Cazorla, Constantin ULg; Morel, Thierry ULg; Nazé, Yaël ULg et al

in Proceedings of the International Astronomical Union - New windows on massive stars: asteroseismology, interferometry, and spectropolarimetry (2015)

Fast rotation in massive stars is predicted to induce mixing in their interior, but a population of fast-rotating stars with normal nitrogen abundances at their surface has recently been revealed (Hunter ... [more ▼]

Fast rotation in massive stars is predicted to induce mixing in their interior, but a population of fast-rotating stars with normal nitrogen abundances at their surface has recently been revealed (Hunter et al. 2009; Brott et al. 2011, but see Maeder et al. 2014). However, as the binary fraction of these stars is unknown, no definitive statements about the ability of single-star evolutionary models including rotation to reproduce these observations can be made. Our work combines for the first time a detailed surface abundance analysis with a radial-velocity monitoring for a sample of bright, fast-rotating Galactic OB stars to put strong constraints on stellar evolutionary and interior models. [less ▲]

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See detailRestoring testosterone levels by adding dehydroepiandrosterone to a drospirenone containing combined oral contraceptive: I. Endocrine effects.
Zimmerman, Y.; Foidart, Jean-Michel ULg; Pintiaux, Axelle ULg et al

in Contraception (2015), 91(2), 127-33

OBJECTIVES: Combined oral contraceptives (COCs) decrease testosterone (T) levels. This study investigated restoration of T and other androgen concentrations during COC use by 'co-administration' of ... [more ▼]

OBJECTIVES: Combined oral contraceptives (COCs) decrease testosterone (T) levels. This study investigated restoration of T and other androgen concentrations during COC use by 'co-administration' of dehydroepiandrosterone (DHEA). STUDY DESIGN: In this randomized, double-blind, placebo-controlled study in 99 new COC starters (18-35 years old with body mass index range 18-34kg/m(2)), a COC containing 30mcg ethinylestradiol (EE) and 3mg drospirenone (DRSP) was used for 3cycles, followed by 6cycles of the same COC combined with either 50mg/day DHEA or placebo. Total T, albumin, sex hormone-binding globulin (SHBG), DHEA-sulfate (DHEA-S), Delta4-androstenedione (AD), 3alpha-androstanediol glucuronide (ADG) and estradiol (E2) were measured, whereas free T and the free T index (FTI) were calculated. Assessments took place at baseline (no COC use), after the run-in period (COC use alone) and during the treatment period (DHEA or placebo). RESULTS: During COC use alone, androgen levels decreased, especially total T by 62% and free T by 86%, and SHBG increased by 243%. Total T increased with DHEA compared to placebo (change from end of run-in period to end of treatment period - 1.3+/-1.2nmol/L vs. 0.0+/-0.4nmol/L; p<.0001) - and was restored to baseline levels. Free T and the FTI increased significantly (p<.0001), but the free T level was still 53% below baseline levels. DHEA-S, AD and ADG increased significantly to levels above baseline (p<.0001 for each). DHEA had no effect on SHBG, albumin and E2. CONCLUSIONS: An EE/DRSP containing COC strongly suppressed endogenous androgen concentrations in all users. The addition of 50mg DHEA to a COC regimen containing EE/DRSP restored total T to baseline levels, but free T levels were restored by only 47% as most of the T remains bound to SHBG. IMPLICATIONS: When using a COC that increases SHBG considerably, a daily dose of 50mg DHEA is insufficient to normalize free T levels completely. [less ▲]

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See detailRoot System Markup Language: toward an unified root architecture description language
Lobet, Guillaume ULg; Pound, Michael; Diener, Julien et al

in Plant Physiology (2015)

The number of image analysis tools supporting the extraction of architectural features of root systems has increased over the last years. These tools offer a handy set of complementary facilities, yet it ... [more ▼]

The number of image analysis tools supporting the extraction of architectural features of root systems has increased over the last years. These tools offer a handy set of complementary facilities, yet it is widely accepted that none of these software tool is able to extract in an efficient way growing array of static and dynamic features for different types of images and species. . We describe the Root System Markup Language (RSML) that has been designed to overcome two major challenges: (i) to enable portability of root architecture data between different software tools in an easy and interoperable manner allowing seamless collaborative work, and (ii) to provide a standard format upon which to base central repositories which will soon arise following the expanding worldwide root phenotyping effort. RSML follows the XML standard to store 2D or 3D image metadata, plant and root properties and geometries, continuous functions along individual root paths and a suite of annotations at the image, plant or root scales, at one or several time points. Plant ontologies are used to describe botanical entities that are relevant at the scale of root system architecture. An xml-schema describes the features and constraints of RSML and open-source packages have been developed in several languages (R, Excel, Java, Python, C#) to enable researchers to integrate RSML files into popular research workflow. [less ▲]

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See detailA generic anisotropic continuum damage model integration scheme adaptable to both ductile damage and biological damage-like situations
Mengoni, Marlène ULg; Ponthot, Jean-Philippe ULg

in International Journal of Plasticity (2015), 66

This paper aims at presenting a general versatile time integration scheme applicable to anisotropic damage coupled to elastoplasticity, considering any damage rate and isotropic hardening formulations ... [more ▼]

This paper aims at presenting a general versatile time integration scheme applicable to anisotropic damage coupled to elastoplasticity, considering any damage rate and isotropic hardening formulations. For this purpose a staggered time integration scheme in a finite strain framework is presented, together with an analytical consistent tangent operator. The only restrictive hypothesis is to work with an undamaged isotropic material, assumed here to follow a J2 plasticity model. The only anisotropy considered is thus a damage-induced anisotropy. The possibility to couple any damage rate law with the present algorithm is illustrated with a classical ductile damage model for aluminium, and a biological damage-like application. The later proposes an original bone remodelling law coupled to trabecular bone plasticity for the simulation of orthodontic tooth movements. All the developments have been considered in the framework of the implicit non-linear finite element code Metafor (developed at the LTAS/MN2L, University of Liège, Belgium - www.metafor.ltas.ulg.ac.be). [less ▲]

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See detailCan meandering flows in shallow rectangular reservoir be modelled with the 2D shallow water equations?
Peltier, Yann ULg; Erpicum, Sébastien ULg; Archambeau, Pierre ULg et al

in Journal of Hydraulic Engineering (2015)

In this article, the ability of the 2D shallow water equations to model meandering flows in shallow rectangular reservoirs is discussed. Four meandering flows, of various shallowness, were modelled using ... [more ▼]

In this article, the ability of the 2D shallow water equations to model meandering flows in shallow rectangular reservoirs is discussed. Four meandering flows, of various shallowness, were modelled using the academic flow model WOLF 2D, which includes a depth-averaged k- model accounting for the horizontal and vertical turbulent length-scales. The bottom friction was modelled with the Colebrook-White formula and different roughness heights were considered. A Proper Orthogonal Decomposition (POD) was applied to the simulation results to extract the behaviour of the main structures responsible for the meandering flow. The same POD analysis was also performed for the reference experimental flow fields, obtained by Large-Scale Particle Image Velocimetry. The first two POD modes obtained from the numerical simulations assuming a smooth bottom are in good agreement with the experimental modes in terms of energy, as well as temporal and spatial variations, whatever the shallowness. In contrast, the remaining simulated modes are not well rendered. The effect of an increased roughness height in the simulations is finally discussed. It leads to an improved reproduction of the first two modes and of the following modes, except when significant viscous effects govern in the flow. [less ▲]

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See detailPharmacodynamics, Efficacy and Safety of Sodium-Glucose Co-Transporter Type 2 (SGLT2) Inhibitors for the Treatment of Type 2 Diabetes Mellitus.
Scheen, André ULg

in Drugs (2015), 75(1), 33-59

Inhibitors of sodium-glucose co-transporter type 2 (SGLT2) are proposed as a novel approach for the management of type 2 diabetes mellitus (T2DM). Several compounds are already available in many countries ... [more ▼]

Inhibitors of sodium-glucose co-transporter type 2 (SGLT2) are proposed as a novel approach for the management of type 2 diabetes mellitus (T2DM). Several compounds are already available in many countries (dapagliflozin, canagliflozin, empagliflozin and ipragliflozin) and some others are in a late phase of development. The available SGLT2 inhibitors share similar pharmacokinetic characteristics, with a rapid oral absorption, a long elimination half-life allowing once-daily administration, an extensive hepatic metabolism mainly via glucuronidation to inactive metabolites, the absence of clinically relevant drug-drug interactions and a low renal elimination as parent drug. SGLT2 co-transporters are responsible for reabsorption of most (90 %) of the glucose filtered by the kidneys. The pharmacological inhibition of SGLT2 co-transporters reduces hyperglycaemia by decreasing renal glucose threshold and thereby increasing urinary glucose excretion. The amount of glucose excreted in the urine depends on both the level of hyperglycaemia and the glomerular filtration rate. Results of numerous placebo-controlled randomised clinical trials of 12-104 weeks duration have shown significant reductions in glycated haemoglobin (HbA1c), resulting in a significant increase in the proportion of patients reaching HbA1c targets, and a significant lowering of fasting plasma glucose when SGLT2 inhibitors were administered as monotherapy or in addition to other glucose-lowering therapies including insulin in patients with T2DM. In head-to-head trials of up to 2 years, SGLT2 inhibitors exerted similar glucose-lowering activity to metformin, sulphonylureas or sitagliptin. The durability of the glucose-lowering effect of SGLT2 inhibitors appears to be better; however, this remains to be more extensively investigated. The risk of hypoglycaemia was much lower with SGLT2 inhibitors than with sulphonylureas and was similarly low as that reported with metformin, pioglitazone or sitagliptin. Increased renal glucose elimination also assists weight loss and could help to reduce blood pressure. Both effects were very consistent across the trials and they represent some advantages for SGLT2 inhibitors when compared with other oral glucose-lowering agents. The pharmacodynamic response to SGLT2 inhibitors declines with increasing severity of renal impairment, and prescribing information for each SGLT2 inhibitor should be consulted regarding dosage adjustments or restrictions in moderate to severe renal dysfunction. Caution is also recommended in the elderly population because of a higher risk of renal impairment, orthostatic hypotension and dehydration, even if the absence of hypoglycaemia represents an obvious advantage in this population. The overall effect of SGLT2 inhibitors on the risk of cardiovascular disease is unknown and will be evaluated in several ongoing prospective placebo-controlled trials with cardiovascular outcomes. The impact of SGLT2 inhibitors on renal function and their potential to influence the course of diabetic nephropathy also deserve more attention. SGLT2 inhibitors are generally well-tolerated. The most frequently reported adverse events are female genital mycotic infections, while urinary tract infections are less commonly observed and generally benign. In conclusion, with their unique mechanism of action that is independent of insulin secretion and action, SGLT2 inhibitors are a useful addition to the therapeutic options available for the management of T2DM at any stage in the natural history of the disease. Although SGLT2 inhibitors have already been extensively investigated, further studies should even better delineate the best place of these new glucose-lowering agents in the already rich armamentarium for the management of T2DM. [less ▲]

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See detailL’agentivité engagée chez Charles Taylor. De l’interprétation à l’évaluation de soi
Gauvry, Charlotte ULg

in Boccaccini, Federico; Cormann, Grégory (Eds.) Le soi agent (2015)

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See detailDéveloppements récents de l'assurance construction en droit européen
Kohl, Benoît ULg

in Revue trimestrielle de droit immobilier (2015), 1

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