Miossec P.,University of Lyon |
Verweij C.L.,VU University Amsterdam |
Klareskog L.,Karolinska Institutet |
Pitzalis C.,Experimental Medicine and Rheumatology |
And 17 more authors.
Annals of the Rheumatic Diseases | Year: 2011
Rheumatoid arthritis (RA) is one of the most appropriate conditions for the application of personalised medicine as a high degree of heterogeneity has been recognised, which remains to be explained. Such heterogeneity is also reflected in the large number of treatment targets and options. A growing number of biologics as well as small molecules are already in use and there are promising new drugs in development. In order to make the best use of treatment options, both targeted and nontargeted biomarkers have to be identified and validated. To this aim, new rules are needed for the interaction between academia and industry under regulatory control. Setting up multi-centre biosample collections with clear definition of access, organising early, possibly noncommitting discussions with regulatory authorities, and defining a clear route for the validation, qualification and registration of the biomarker-drug combination are some of the more critical areas where effective collaboration between the drug industry, academia and regulators is needed.
Reginster J.-Y.,University of Liege |
Reginster J.-Y.,Center ville |
Neuprez A.,University of Liege
Expert Opinion on Pharmacotherapy | Year: 2010
Importance of the field: Osteoporosis is now considered a major health problem in all developed and in most developing (non-African) countries. Areas covered in this review: In this review, we provide an extensive literature survey (MEDLINE, PubMed, Cochrane Controlled Register), for articles dealing with osteoporosis management and/or strontium ranelate, from 1920 to 2010. What the reader will gain : The objective is to provide an extensive, unbiased assessment of the available data allowing strontium ranelate to be placed in perspective with other anti-osteoporosis treatments. Take home message : Owing to a positive benefit-to-risk ratio, strontium ranelate may now be considered a first-line treatment in the management of osteoporosis. © 2010 Informa UK, Ltd.
Sharma R.,University of Quebec at Montreal |
Naresh K.,University of Quebec at Montreal |
Chabre Y.M.,University of Quebec at Montreal |
Rej R.,University of Quebec at Montreal |
And 2 more authors.
Polymer Chemistry | Year: 2014
We report herein a novel "onion peel strategy" for the divergent construction of glycodendrimers using different building blocks at each layer of the dendritic growth. A combination of successive highly efficient, versatile, and robust chemical reactions, namely thiol-ene or thiol-yne, esterification, and azide-alkyne click chemistry, generated dendrimers having chemically heterogeneous layers, some of which having UV-visible functions. The dendrimers prepared using this strategy are fundamentally different to conventional dendritic systems that are usually built from repetitive building nanosynthons with limited surface groups. The applicability of this novel approach towards the construction of biologically active glycodendrimers having dense surface sugar residues within low dendrimer generations was fully demonstrated using Erythrina cristagalli, a leguminous lectin known to bind natural killer cells through its galactoside recognition ability. The dendrimer's surface was decorated with an azido derivative of N-acetyllactosamine using click chemistry which led to new glycodendrimers having high affinities as compared to the corresponding monovalent analog. The ongoing quest for better parameterization of critical carbohydrate-protein recognition factors necessitates structures with tailored biophysical properties, sizes, and shapes together with optimized tri-dimensional architectures. The proposed methodology, for which entirely orthogonal building blocks can be applied, represents an additional contribution to the wide arsenal of existing strategies which can create higher structural diversity among dendritic structures of biological interest. © 2014 the Partner Organisations.
Reginster J.Y.,University of Liege |
Reginster J.Y.,Center ville |
Neuprez A.,Service de Medecine de LAppareil Locomoteur |
Lecart M.P.,Service de Medecine de LAppareil Locomoteur |
And 4 more authors.
Revue Medicale de Liege | Year: 2015
Osteoporosis is at the very early stages of the implementation of personalized medicine. However, the development of FRAX®, an algorithm offering the opportunity to calculate, in an individual patient, his/her 10-year fracture risk improves the decision process on the appropriateness to initiate a pharmacological treatment. This algorithm helps the physician to select drugs which are active on non-vertebral fractures only in high risk patients. Taking into consideration patients' preferences, when selecting a therapeutic option, will improve long term adherence and subsequently efficacy and efficiency of the treatments. Attempts to define the natural course of osteoporosis or the response to therapy in individual patients by assessing their genetic profile remains, so far, inconclusive.
Eric M.,University of Orleans |
Khadija N.,Mohammed V University |
Yannick B.,University of Orleans |
Claire R.,University of Orleans |
And 4 more authors.
Journal of African Earth Sciences | Year: 2015
Gold have been recently recognized in the Tighza (formerly Jebel Aouam) district, in the Hercynian belt of central Morocco. This district has long been known for its W mineralization, as well as major Pb-Ag-Zn, and minor Sb-Ba deposits, all geographically associated with late-Hercynian calc-alkaline magmatism. Gold mineralization in the district is mainly hosted by thick W-Au quartz veins located around the "Mine granite" small granitic plug. Within the veins, gold grade is highest (up to 70g/t) close to the granite but rapidly decreases going outward from the granite, defining a perigranitic zoning. Anomalous gold grades have also been measured in hydrothermal skarn layers close to two other granitic plugs (Kaolin granite and Mispickel granite), associated with disseminated As-Fe sulfides. The paragenetic sequence for the W-Au quartz veins shows three stages: (1) an early oxidized stage with wolframite-scheelite associated with early quartz (Q1), (2) an intermediate Bi-As-Te-Mo-Au sulfide stage with loellingite, bismuth minerals and native gold with a later quartz (Q2), restricted to a narrow distance from the granite, and (3) a late lower temperature As-Cu-Zn-(Pb) stage with abundant massive pyrrhotite, arsenopyrite and sphalerite, locally forming independent veins ("pyrrhotite vein"). Both Q1 hyaline and Q2 saccharoidal gold-bearing quartz display aqua-carbonic fluids with minor H2S and Cu and an homogeneous composition (81mole% H2O, 18mole% CO2 and about 1mole% NaCl). The trapping pressure is estimated to 1.5-2kbar with temperature ranging from 300 to 350°C. Q1 inclusions have exploded indicating an uplift of the Tighza block, that lead to saccharoidal Q2 quartz deposition with multiphase NaCl-saturated fluid inclusions. 40Ar/39Ar dating demonstrates that the "Mine granite", tungsten skarnoid, scheelite-molybdenite veins, and very likely gold-bearing veins are coeval, emplaced at 286±1Ma. Multiple and widespread metal sources are indicated by radiogenic isotope studies. Nd and Sr isotope compositions of scheelite and granites suggest the participation of a juvenile component while lead isotopes demonstrate a major participation of the basement.Both gold mineralization and zoning suggest that the system developed at the end of the magmatic activity, accompanying a major transition in magmatic fluid composition. The morphology of the gold-bearing mineralization is dependent of the permeability and the reactivity of host-rocks: focus circulation of fluids through pre-existing tectonic corridors, reactivated by late-Hercynian intrusions favor the formation of large W-type gold veins, while infiltration of fluid within reactive stratigraphic layers gives rise to skarn mineralization. A 40Ar/39Ar date (W1 north vein: 291.8±0.3Ma) indicates that hydrothermal circulation predates gold and tungsten deposition in open fractures as well as Mine granite emplacement.The W-Au mineralization preceded the onset of a large convective hydrothermal cell around the intrusion that led to the formation of the Pb-Ag-Zn mined veins. The Tighza polymetallic district displays numerous similarities with the R-IRG model that was defined in the American Cordillera, such as thermal and zonation patterns, carbonic hydrothermal fluids and chronology of intrusion and related deposits, but also provides new insight to the R-IRG model such as wide Au-quartz veins instead of sheeted Au-veins, oxidation state of the magma, and Sr-Nd isotopic data. These results establish a major magmatic contribution and discard a direct genetic relationship between gold mineralization and major neighboring Pb-Ag-Zn veins. A large number of classic Pb-Zn district of the Western Hercynides belong to the same clan. © 2015 Elsevier Ltd.