The CONSTANCES Cohort Biobank: An Open Tool for Research in Epidemiology and Prevention of Diseases.

"General-purpose cohorts" in epidemiology and public health are designed to cover a broad scope of determinants and outcomes, in order to answer several research questions, including those not defined at study inception. In this context, the general objective of the CONSTANCES project is to set up a large population-based cohort that will contribute to the development of epidemiological research by hosting ancillary projects on a wide range of scientific domains, and to provide public health information. CONSTANCES was designed as a randomly selected sample of French adults aged 18-69 years at study inception; 202,045 subjects were included over an 8-year period. At inclusion, the selected participants are invited to attend one of the 24 participating Health Prevention Centers (HPCs) for a comprehensive health examination. The follow-up includes a yearly self-administered questionnaire, and a periodic visit to an HPC. Procedures have been developed to use the national healthcare databases to allow identification and validation of diseases over the follow-up. The biological collection (serum, lithium heparinized plasma, EDTA plasma, urine and buffy coat) began gradually in June 2018. At the end of the inclusions, specimens from 83,000 donors will have been collected. Specimens are collected according to a standardized protocol, identical in all recruitment centers. All operations relating to bio-banking have been entrusted by Inserm to the Integrated Biobank of Luxembourg (IBBL). A quality management system has been put in place. Particular attention has been paid to the traceability of all operations. The nature of the biological samples stored has been deliberately limited due to the economic and organizational constraints of the inclusion centers. Some research works may require specific collection conditions, and can be developed on request for a limited number of subjects and in specially trained centers. The biological specimens that are collected will allow for a large spectrum of biomarkers studies and genetic and epigenetic markers through candidate or agnostic approaches. By linking the extensive data on personal, lifestyle, environmental, occupational and social factors with the biomarker data, the CONSTANCES cohort offers the opportunity to study the interplays between these factors using an integrative approach and state-of-the-art methods.

Recommendations for Improving the Quality of Rare Disease Registries.

Rare diseases (RD) patient registries are powerful instruments that help develop clinical research, facilitate the planning of appropriate clinical trials, improve patient care, and support healthcare management. They constitute a key information system that supports the activities of European Reference Networks (ERNs) on rare diseases. A rapid proliferation of RD registries has occurred during the last years and there is a need to develop guidance for the minimum requirements, recommendations and standards necessary to maintain a high-quality registry. In response to these heterogeneities, in the framework of RD-Connect, a European platform connecting databases, registries, biobanks and clinical bioinformatics for rare disease research, we report on a list of recommendations, developed by a group of experts, including members of patient organizations, to be used as a framework for improving the quality of RD registries. This list includes aspects of governance, Findable, Accessible, Interoperable and Reusable (FAIR) data and information, infrastructure, documentation, training, and quality audit. The list is intended to be used by established as well as new RD registries. Further work includes the development of a toolkit to enable continuous assessment and improvement of their organizational and data quality.

Resonantly pumped eye-safe Er3+:YAG SPS-HIP ceramic laser.

We report for the first time laser action in resonantly-pumped transparent polycrystalline Er3+:YAG ceramic developed through a 2-step approach combining spark plasma sintering and HIP post treatment. Microstructural and spectroscopic properties, as well as the laser performance of large scale 0.5at.% Er:YAG transparent polycrystalline ceramic are discussed. A maximum slope efficiency of ∼31% and optical-optical efficiency of 20% was measured.

Cell Colonization Ability of a Commercialized Large Porous Alveolar Scaffold.

The use of filling biomaterials or tissue-engineered large bone implant-coupling biocompatible materials and human bone marrow mesenchymal stromal cells seems to be a promising approach to treat critical-sized bone defects. However, the cellular seeding onto and into large porous scaffolds still remains challenging since this process highly depends on the porous microstructure. Indeed, the cells may mainly colonize the periphery of the scaffold, leaving its volume almost free of cells. In this study, we carry out an in vitro study to analyze the ability of a commercialized scaffold to be in vivo colonized by cells. We investigate the influence of various physical parameters on the seeding efficiency of a perfusion seeding protocol using large manufactured bone substitutes. The present study shows that the velocity of the perfusion fluid and the initial cell density seem to impact the seeding results and to have a negative effect on the cellular viability, whereas the duration of the fluid perfusion and the nature of the flow (steady versus pulsed) did not show any influence on either the fraction of seeded cells or the cellular viability rate. However, the cellular repartition after seeding remains highly heterogeneous.

Synthesis engineering of iron oxide raspberry-shaped nanostructures.

Magnetic porous nanostructures consisting of oriented aggregates of iron oxide nanocrystals display very interesting properties such as a lower oxidation state of magnetite, and enhanced saturation magnetization in comparison with individual nanoparticles of similar sizes and porosity. However, the formation mechanism of these promising nanostructures is not well understood, which hampers the fine tuning of their magnetic properties, for instance by doping them with other elements. Therefore the formation mechanism of porous raspberry shaped nanostructures (RSNs) synthesized by a one-pot polyol solvothermal method has been investigated in detail from the early stages by using a wide panel of characterization techniques, and especially by performing original in situ HR-TEM studies in temperature. A time-resolved study showed the intermediate formation of an amorphous iron alkoxide phase with a plate-like lamellar structure (PLS). Then, the fine investigation of PLS transformation upon heating up to 500 °C confirmed that the synthesis of RSNs involves two iron precursors: the starting one (hydrated iron chlorides) and the in situ formed iron alkoxide precursor which decomposes with time and heating and contributes to the growth step of nanostructures. Such an understanding of the formation mechanism of RSNs is necessary to envision efficient and rational enhancement of their magnetic properties.

Hemisphere specialisation and inter-hemispheric cooperation during a phonological task: effect of lexicality as assessed by the divided visual field approach.

In the presented experiment we explored the effect of lexicality on hemisphere specialisation and cooperation during a phonological task. The divided visual field (DVF) method with bilateral presentation (BVF) of redundant (identical) stimuli is considered an appropriate approach to assess inter-hemispheric cooperation (IHC). IHC is supposed to increase the efficiency of cognitive processes. Specifically, it has been shown that, compared to unilateral hemifield presentation, word processing is significantly more efficient if stimuli were presented under bilateral redundancy conditions. The performance enhancement during bilateral vs. unilateral presentation is called bilateral redundant gain (BRG). In the present experiment a DVF was used and participants were required to perform a rhyme detection task in two blocks, one in words and another one in pseudowords. Each item was presented in two different modes, one unilateral (right or left hemi-visual field) and another one bilateral (simultaneous redundant presentation). Unilateral trials allow one to study hemispheric specialisation, while bilateral redundant trials allow one to study inter-hemispheric cooperation. We obtained left hemisphere specialisation for both types of items (word, pseudoword). Moreover, words were more efficiently processed than pseudowords. Additionally, words were processed more efficiently in BVF than in unilateral presentation, inducing BRG. No similar effect was obtained for pseudowords. These results are discussed in respect to findings reported by other studies suggesting that hemispheric specialisation depends on lexicality. Moreover, compared to lexical decision tasks used in previous studies, the phonological task used in the present study seems to modulate the inter-hemispheric cooperation less.

On the paradoxical determinations of the lacuno-canalicular permeability of bone.

The lacuno-canalicular permeability has been shown to play a key role in the behavior of bone tissue. The aim of this study is, by giving an overview of the determinations of this parameter, to question the paradoxical values provided by theoretical predictions and recent experimental measurements. We propose therefore a Kozeny-like law obtained by a numerical method which relates the permeability to the textural parameters of cortical bone microstructure. Moreover, we suggest possible explanations for this paradox considering the empirical difficulties and possible multiphysical effects.

Bone necrosis around dental implants: A patient treated with oral bisphosphonates, drug holiday and no risk according to serum CTX.

Osteonecrosis of the jaw (ONJ) may appear following certain oral surgery procedures in patients treated with oral bisphosphonates (OB). Guidelines for the treatment of these patients were set out in the American Association of Oral and Maxillofacial Surgeons (AAOMS) Position Paper on Bisphosphonate-Related Osteonecrosis of The Jaws (Position Paper) and Approved by the Board of Trustees in September 2006. For the AAOMS the placement of implants in these patients is not contraindicated. In addition, the serum C-terminal telopeptide bone suppressor marker (CTX) test is available to determine the risk of ONJ. A case is presented of ONJ in a patient with 6 months of OB discontinuation ("drug holiday") before dental implant placement (following the guidelines of the AAOMS) and with no risk of osteonecrosis according to the serum CTX value (340 pg/ml). The wound healed favorably with complete healing at 7 months. In this case, the serum CTX test must be questioned as to its predictive value of ONJ, and more reliable markers of this risk are needed. Key words:Bisphosphonates, dental implants, bone necrosis, serum CTX.