Volume 9 - 2016 | https://doi.org/10.3389/fnmol.2016.00128 Growing evidence suggests that increased levels of α-synuclein might contribute to the pathogenesis of Parkinson’s disease (PD) and therefore it is crucial to understand the mechanisms underlying α-synuclein expression microRNAs (miRNAs) have emerged as key regulators of gene expression involved in several diseases such as PD and other neurodegenerative disorders A systematic literature search was performed here to identify microRNAs that directly or indirectly impact in α-synuclein expression/accumulation and describe its mechanism of action A total of 27 studies were incorporated in the review article showing evidences that six microRNAs directly bind and regulate α-synuclein expression while several miRNAs impact on α-synuclein expression indirectly by targeting other genes α-synuclein overexpression also impacts miRNAs expression indicating the complex network between miRNAs and α-synuclein From the current knowledge on the central role of α-synuclein in PD pathogenesis/progression miRNAs are likely to play a crucial role at different stages of PD and might potentially be considered as new PD therapeutic approaches Mechanisms of action of microRNAs (miRNAs) that directly bind and regulate α-synuclein expression Biogenesis of miRNAs required a multi-step process that takes place in the nucleus and the cytoplasm of the cells miRNAs are transcribed in the nucleus by the RNA polymerase II as long primary miRNAs (pri-miRNAs) a RNAse III enzyme called Drosha converts pri-miRNAs into 60 base-pair (bp) stem-loop structures (pre-miRNAs) Pre-miRNAs are subsequently exported to the cytoplasm by the Exportin 5 where a second RNase II enzyme called Dicer will process pre-miRNAs into a ~22nt miRNA-miRNA complex The RNA-duplex binds to an Argonaute (AGO) protein and one of the strands is removed resulting in the mature RNA-induced silencing complex (RISC) RISC binds to complementary mRNA sequence (seed matches) and represses its expression by: (i) translational repression; (ii) mRNA decapping and decay; or (iii) direct cleavage of mRNAs target by RISC six miRNAs have been described to directly bind the 3′-untranslational region (UTR) of the α-synuclein mRNA transcript and repress its expression Considering the importance of modulating α-synuclein levels in PD and other related disorders the objective of this study is to review miRNAs that impact directly or indirectly in α-synuclein expression and describe their mechanisms of action Following PRISMA recommendations (Liberati et al., 2009; PRISMA Checklist available in Supplementary Materials) the systematic review was registered in The Joanna Bridge Institute (JBI) website with date 27th July 2016 Registration details are described in Supplementary Table 1 All the studies selected for the review satisfied the PICOS selection criteria detailed in Supplementary Methods No language or publication date restrictions were imposed Three different database were used in this review article: PubMed, Scopus and Web of Science. The last search was run on 25th May 2016. No supplementary approaches were used to identify additional studies. Duplicated records were removed. The full electronic search strategy for each database is described in Table 1 Full electronic search strategy for each database used in the review article an over-inclusive screening by titles and abstracts was done to identify potential relevant studies Full-text articles from the candidate studies were read and a second screening was done accordingly to the exclusion criteria detailed in Supplementary Methods All the included studies were divided into two groups: (i) overexpressing studies: studies using α-synuclein overexpressing models (OEM); and (ii) standard studies Relevant information from all included studies was extracted using two different extraction datasheets depending on the category of the article (overexpressing vs See Supplementary Methods for detailed data extraction Flow diagram of the selection process by which the studies were included in the review article Summary of studies included in the review article The results derived from all included studies demonstrated that a total of six miRNAs (miR-7, miR-153, miR-34b, miR-34c, miR-214 and miR-1643) directly bind to the 3′-untranslated region (UTR) of the α-synuclein mRNA transcript and negatively regulate its expression (Figure 1) These bindings sites were verified by cotransfecting SH-SY5Y cells with a plasmid construct expressing α-synuclein 3′-UTR with miR-34b or miR-34c the introduction of a polymorphic variation (rs10024743) which lies within the target site 1 of miR-34b significantly decreased the impact of miR-34b in the luciferase activity As a consequence of the direct binding between miR-34b/miR-34c and α-synuclein overexpression of miR-34b or miR-34c in SH-SY5Y cells resulted in significant reduction in α-synuclein mRNA and protein levels miR-34b and miR-34c did not repress β-synuclein but rather increased its expression by up to 2.3-fold inhibition of miR-34b and miR-34c increased α-synuclein mRNA and protein level as well as the formation of α-synuclein-containing aggregates in DA neurons This work also investigated whether the regulation of α-synuclein by miR-214 was the mechanism underlying the neuroprotective effect of Resveratrol they showed that Resveratrol could ameliorate MPP+/MPTP-induced cell death both in vitro and in vivo miR-214 inhibitors reversed the neuroprotective effect of resveratrol treatment in MPP+/MPTP models One study found that miR-1643 is a direct regulator of α-synuclein expression (Lim and Song, 2014) Luciferase assay in 293TF cells confirmed the direct binding of miR-1643 to α-synuclein 3′-UTR sequence miRNAs that impact on α-synuclein expression by modulating proteolytic degradation pathways α-Synuclein can be degraded by several proteolytic pathways including chaperone-mediated autophagy (CMA) and autophagy-lysosomal pathway (ALP) the KFREQ-like sequence of the α-synuclein protein is recognized by a chaperone complex which includes the Heat shock protein 70 (Hsc70) This complex is guided to the lysosomes and recognized by the Lysosome-associated membrane protein 2 (Lamp2A) which in turn translocate the α-synuclein into the lysosome where it is finally degraded by hydrolytic enzymes nine microRNAs have been described to modulate the CMA pathway and impact on α-synuclein degradation by directly binding and repressing the expression of Hsc70 (miR-301b α-synuclein is firstly enclosed into an autophagosome Then the autophagosome is guided and fused with a lysosome where α-synuclein is finally degraded miRNA-128 activates transcription factor EB (TFEB) which has been demonstrated to promote the transcription of genes involved in ALP pathway Lamp2a or TFEB result in alterations in the α-synuclein degradation and its consequent accumulation miR-133 and miR-433 indirectly influence α-synuclein by targeting Ras homolog gene family member A (RhoA) and fibroblast growth factor 20 (FGF20) respectively miR-133 targets and regulates RhoA expression which has been previously reported to regulate α-synuclein expression RhoA first activates megakaryoblastic leukemia 1 (MKL-1) factor which in turn activates serum response element (SRF) transcription factor MKL-1 and SRF activation promote the transcription of early immediate (EI) genes Finally SRF forms a multiprotein complex with GATA-2 factor which regulates α-synuclein expression via occupancy at the intron-1 which has been suggested to directly regulate α-synuclein expression through the FGF-receptor 1 (FGFR1) hsa-miR-21*; hsa-miR-224; hsa-miR-373*; and hsa-miR-379) and Heat shock protein 70 (Hsc70 hsa-miR-26b: hsa-miR-106a*; and hsa-miR-301b) In addition to the expected reduction in Lamp2a and Hsc70 gene expression transfection with the seven candidate miRNAs significantly increased α-synuclein protein levels only two of them (miR-106a* and miR-301b) caused a significant decrease in α-synuclein mRNA levels miR-106a* was predicted to target the 3′-UTR of α-synuclein although the direct binding has not yet been confirmed Another proteolytic pathway related with α-synuclein induced-toxicity is the autophagy-lysosomal pathway (ALP). The impact of ALP-associated miRNAs in α-synuclein expression was studied by Decressac et al. (2013) using rat midbrain overexpressing human wild-type α-synuclein they demonstrated that α-synuclein toxicity is linked to impairment of the transcription factor EB (TFEB) a master regulator of the ALP controlled by mTOR signaling AAV-mediated overexpression of miR-128 (which directly targeted TFEB) increased the formation of α-synuclein oligomers and the number of α-synuclein-positive axonal swellings which resulted in α-synuclein-induced toxicity as revealed by a significant loss of nigral DA neurons as well as development of motor deficits at 8 weeks after vector injection Summary of the impacts on the miRNAs profile after α-synuclein-overexpression in multiple in vivo models Overexpression of α-synuclein induces alterations of several miRNAs in mice Considering the growing evidence that neuroinflammation plays a key role in the pathogenesis and progression of PD, Thome et al. (2016) investigated the impact of miR-155 expression one of the key microRNA modulators of neuroinflammation in the α-synuclein transgenic mice adenovirus-mediated overexpression of α-synuclein (AAV2-Syn) enhanced the expression of miR-155 in the SN of α-synuclein-overexpressing mice compared to control (30% increment 2 weeks after transduction) and induced a 29.7 ± 6.6% loss of TH positive neurons in the SN 6 months after transduction Reactive microgliosis markers Major Histocompatibility Complex Class II (MHCII) and CD68 were also increased in the AAV2-Syn transgenic mice genetic deletion of miR-155 prevented the increments of MHCII and CD68 and markedly attenuated the TH positive neuronal loss in the SN of AAV2-syn transgenic mice These results were confirmed in vitro using primary microglial murine cells The authors first showed that microglial cells treated with fibrils of human wild-type α-synuclein exhibited increased levels of MHCII and inducible nitric oxide synthase (iNOS) while monomeric α-synuclein did not activate the inflammatory response α-synuclein fibrils did not activate the inflammatory process in microglial cells derived from miR-155−/− mice miR-155 mimic treatment restored the inflammatory activity in miR-155−/− microglial cells miRNAs both regulate and are regulated by α-synuclein expression Similar to other neurodegenerative diseases there is still no treatment available that stops or halts the progression of PD; and symptomatic treatments are the only option for PD patients a large proportion of therapeutic approaches under development are aimed to reduce α-synuclein expression levels Targeting miRNAs seems to be a potential therapeutic opportunity for PD multiple α-synuclein-targeting miRNAs (miR-7 miR-214 and miR-133b) have displayed protective effects against the PD-like-induced toxins MPP+/MPTP their effects are normally attributed to α-synuclein-independent mechanisms; for example miR-7 may exert its protective effect by activating RelA each miRNAs is unique and displays its own protective/deleterious effect: overexpression of miR-7 or miR-155 induced a protective effect in MPP+/MPTP models and α-synuclein-induced toxicity while overexpression of miR-128 targeting TFEB exacerbated α-synuclein-induced toxicity in mice when considering miRNAs as therapeutic opportunities one have to keep in mind that each miRNA can target various mRNA transcripts rendering difficult to target a specific molecular way This review article highlights that miRNAs regulate and are subject to regulation by α-synuclein Considering the central role of α-synuclein in PD pathogenesis/progression miRNAs are likely to play a crucial role at different stages of PD and might potentially be used in the future in new PD therapeutic approaches AR: conception and design of the work; acquisition analysis and interpretation of data for the work; drafting final approval of the version to be published and agreement to be accountable for all aspects of the work CP: substantial contributions to the design of the work; drafting the work revising it critically for important intellectual content; final approval of the version to be published and agreement to be accountable for all aspects of the work CMS: substantial contributions to the conception of the work; revising it critically for important intellectual content; final approval of the version to be published and agreement to be accountable for all aspects of the work This study was supported by the Sydney Medical School Foundation (University of Sydney) The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest Garcia Cardenas (University Technology of Sydney) for her technical assistance The Supplementary Material for this article can be found online at: http://journal.frontiersin.org/article/10.3389/fnmol.2016.00128/full#supplementary-material (2008).α-synuclein gene 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The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration Identification of novel regulatory genes in development of the avian reproductive tracts Altered microRNA expression following traumatic spinal cord injury Advances with microRNAs in Parkinson’s disease research The roles of non-coding RNAs in Parkinson’s disease Collaborative analysis of α-synuclein gene promoter variability and Parkinson disease Identification of blood microRNAs associated to Parkinsonis disease α-synuclein interacton and GWAS in Parkinson’s disease Activation of β-glucocerebrosidase reduces pathological α-synuclein and restores lysosomal function in Parkinson’s patient Midbrain neurons Mechanisms of gene silencing by double-stranded RNA Miñones-Moyano Upregulation of a small vault RNA (svtRNA2–1a) is an early event in parkinson disease and induces neuronal dysfunction Methodological challenges in utilizing miRNAs as circulating biomarkers Synucleins are developmentally expressed and α-synuclein regulates the size of the presynaptic vesicular pool in primary hippocampal neurons LRRK2 mutant iPSC-derived DA neurons demonstrate increased susceptibility to oxidative stress MiR-133b ameliorates axon degeneration induced by MPP+ via targeting RhoA Preferential neurotrophic activity of fibroblast growth factor-20 for dopaminergic neurons through fibroblast growth factor receptor-1c Preclinical evaluation of miR-15/107 family members as multifactorial drug targets for Alzheimer’s disease α-synuclein expression in the substantia nigra of MPTP-lesioned non-human primates Regulation of α-synuclein by bFGF in cultured ventral midbrain dopaminergic neurons Genomic investigation of α-synuclein multiplication and parkinsonism Non-coding RNAs with essential roles in neurodegenerative disorders Sánchez-Danés Disease-specific phenotypes in dopamine neurons from human iPS-based models of genetic and sporadic 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role of microRNAs in biological processes Tüfekci Widespread microRNA dysregulation in multiple system atrophy–disease-related alteration in miR-96 Fibroblast growth factor 20 polymorphisms and haplotypes strongly influence risk of Parkinson disease Bax ablation prevents dopaminergic neurodegeneration in the 1-methyl- 4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson’s disease Alpha-synuclein up-regulation in substantia nigra dopaminergic neurons following administration of the parkinsonian toxin MPTP Variation in the miRNA-433 binding site of FGF20 confers risk for Parkinson disease by overexpression of α-synuclein MicroRNA-214 participates in the neuroprotective effect of Resveratrol via inhibiting α-synuclein expression in MPTP-induced Parkinson’s disease mouse microRNAs: emerging targets regulating oxidative stress in the models of Parkinson’s disease MiR-133b promotes neural plasticity and functional recovery after treatment of stroke with multipotent mesenchymal stromal cells in rats via transfer of exosome-enriched extracellular particles MicroRNA miR-133b is essential for functional recovery after spinal cord injury in adult zebrafish miR-16–1 promotes the aberrant α-synuclein accumulation in parkinson disease via targeting heat shock protein 70 Rho GTPase regulation of α-synuclein and VMAT2: implications for pathogenesis of Parkinson’s disease MicroRNA-7 targets Nod-like receptor protein 3 inflammasome to modulate neuroinflammation in the pathogenesis of Parkinson’s disease Perier C and Sue CM (2016) Role of microRNAs in the Regulation of α-Synuclein Expression: A Systematic Review Received: 10 October 2016; Accepted: 07 November 2016; Published: 21 November 2016 Copyright © 2016 Recasens, Perier and Sue. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) distribution and reproduction in other forums is permitted provided the original author(s) or licensor are credited and that the original publication in this journal is cited in accordance with accepted academic practice distribution or reproduction is permitted which does not comply with these terms *Correspondence: Carolyn M. Sue, Y2Fyb2x5bi5zdWVAc3lkbmV5LmVkdS5hdQ== Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher 94% of researchers rate our articles as excellent or goodLearn more about the work of our research integrity team to safeguard the quality of each article we publish “You’re going on tour with Ella Fitzgerald and Dizzy Gillespie for the paper.” Jean-Marie Périer couldn’t believe it He was 17 and his boss had just given him a Leica and instructions to pick up the American artists at the airport in Nice he took the musician to the sea and photographed him in his swimming trunks on the beach at Juan-les-Pins blowing bubbles with his trumpet in the blue Mediterranean water “That’s how I made the cover of Jazz Magazine for the first time!” the young Fred Astaire fan who became a photographer “by chance and luck” was on the cusp of a career that would take him from the palace hotels of Paris to the dusty roads of the American West These adventures revealed his sensitive creative style as well as an astonishing ability to tell the story of the world and its leading figures – without ever envying them and fans all had long hair and dressed like Mick [ Jagger] I was trying to play it more like Cecil Beaton the Queen of England’s incredible photographer.” Three father figures are partly why this astonishing journey first began The photographer’s biological father is none other than jazz star and beloved French crooner Henri Salvador Jean-Marie Périer only learned who he was in his teenage years He provided the young man with affection and culture before a third “father,” Daniel Filipacchi an eccentric press magnate with a passion for jazz Filipacchi made him his assistant and then the top photographer for his best-selling publications A journalist at The Wall Street Journal had written a mocking piece on Johnny Hallyday describing the French singer as a pale imitation of Elvis Presley who “couldn’t fill a phone booth in Pacific Palisades,” a chic neighborhood in Los Angeles The country was entering the modern era and French teenagers – nicknamed yéyés – were part of the avant-garde using electric guitar chords to expand and deconstruct representations of the old world The French rock star exemplified this perfectly Jean-Marie Périer had a unique knack for winning the trust of this “youth idol” and his acolytes – France Gall his one-time partner – by making them look their best and they knew I had good intentions,” says the photographer Johnny Hallyday has a special place in this pantheon Jean-Marie Périer photographed him at the wheel of a Ferrari California which the star crashed just a few hours after buying We both believed that the only unreasonable thing in life was being reasonable.” His images tell the story of a France unchained emerging from the dark ages of the post-war period to jump feet-first into the Swinging Sixties They also depict English and American bands bursting onto the French scene Jean- Marie Périer invited Brigitte Bardot to join the Beatles in their hotel suite leaving them speechless in front of “the sexiest woman in the world.” This was when he took one of his most famous shots: the “Fab Four,” lighting their cigarettes together in the dark The French photographer had earned his pass into the exclusive counterculture club He was soon rubbing shoulders with the hottest bands of the moment From an early age, Jean-Marie Périer also photographed the American jazz stars performing at Saint-Germain-des-Prés and the Antibes Jazz Festival “the jazz band godfather,” Duke Ellington seated at his piano He then developed a passion for rock icons whom he discovered after returning from military service in Algeria “the father of rock ‘n’ roll,” with whom he traveled across the American South in a Ford Thunderbird in 1965 The French photographer went from strength to strength he was filled with a deep sense of loneliness You’re on your own.” Separated from his loved ones by the nine-hour time difference and fed up with “the obsession with success at any cost,” he left the United States and returned to his first profession “I’m really glad I decided to live the rest of my life in France As Patrick Modiano wrote: ‘There comes a time when your heart’s no longer in it!’” and Jean Paul Gaultier were now the stars of the day He photographed their creations and models as well as the “next generation of actresses,” such as Laetitia Casta This latter celebrity and future director walked into his studio “wrapped in a dress the editors had picked for her She hated the look; it didn’t suit her at all She was like a deer frozen in front of a hunter!” and directed a public health campaign for which he invented the slogan: La drogue Jean-Marie Périer is now working on his “definitive” book “I’m probably the best-known photographer in France having previously been convinced that he would die before the age of 30 “People only know me through one period of my life when I shot the French pop and rock idols of the 1960s-1970s But I’ve had four or five other lives and have long since given up photography!” Mes nuits blanches by Jean-Marie Périer, Calmann-Lévy Article published in the March 2024 of France-Amérique Discover the best of France-Amérique every week in our newsletter. Your Ads Privacy ChoicesIMDb Globecast announces the appointment of Jean-Christophe Perier as Chief Marketing Officer Perier leads both marketing communications and product marketing for Globecast and is responsible for steering the marketing and external communications strategy worldwide Perier is focussed on continuing to deploy innovative services that satisfy an ever-evolving marketplace not least across IP and moves to the cloud This is alongside the strengthening of external communications to support the company’s global strategic initiatives announced last year Perier brings extensive experience across broadcast Etisalat and Orange during his time at Technicolor and SoftAtHome “I am thrilled to be taking up this new role with Globecast especially at such an exciting time in the industry as we see migration to the cloud and IP really taking shape I am looking forward to identifying more growth opportunities launching strong partnerships with industry leaders and developing innovative services to support Globecast’s continued success in the marketplace.” Globecast’s previous head of Marketing departs after 22 years with the company having held several managerial positions in pre-sales “I would like to thank Denis for his commitment and his involvement with Globecast; he will be missed We are delighted to welcome Jean-Christophe to the team and believe his expertise and leadership will be instrumental in driving Globecast’s growth and increasing our visibility and awareness in the markets that we serve.” © 2025 Sports Video Group. All rights reserved. Site by Brightgreen Design/Arturan/Sfera Interactive InvestingMoleskine Owner D’Ieteren’s Holding Family Rejigs Stake in GroupBy Sarah JacobPublished: September 10, 2024 at 10:16AM EDT (Bloomberg) -- Shares of Belgian holding company D’Ieteren Group slumped after a member of its controlling family began selling its stake and the company said it would pay almost €4 billion ($4.4 billion) in a special dividend to shareholders using mostly borrowed money. The stock sank as much as 9.7%, the most in two and a half years, and was trading 7.1% lower at €210.00 at 4:15 p.m. in Brussels. D’Ieteren, which began as a carriage maker in the Belgian capital in 1805, now distributes Volkswagen cars in Belgium, owns the Moleskine notebook business and runs Belron, a company that repairs car windshields under brand names including Carglass. The transactions announced late Monday will solidify the control of Chairman Nicolas D’Ieteren. His investment vehicle will buy an almost 17% stake from a firm tied to one of his relatives, Deputy Chairman Olivier Perier, at €223.75 a share, increasing Nicolas D’Ieteren’s holding to 50%. Perier’s ownership will drop to less than 11%, with the remaining shares to be sold over the next five years, the company said. D’Ieteren will pay a special dividend of €74 a share, financed largely by Belron, which will take on additional debt of about €3.8 billion, according to the statement. The parent company also will raise €1 billion of bank loans. The transactions are “one of the more aggressive pieces of capital management I’ve seen, especially from bicentennial family-controlled company,” Andrew Brown manager of East 72 Dynasty Trust, said in a post on X. The fund, which invests in companies with controlling shareholders, counts D’Ieteren among its top five holdings, he said. D’Ieteren said “the once-in-a generation” reorganization will ensure long-term stability of the family shareholding. Belron, which is 50% owned by D’Ieteren, will pay a €4.3 billion dividend to its shareholders, which also include buyout firms Clayton, Dubilier & Rice LLC and Hellman & Friedman, Singapore sovereign wealth fund GIC Pte and investment firm BlackRock Inc. Belron will have net debt of €8.9 billion after the borrowing, D’Ieteren said, which can be paid down rapidly over the next few years given its cash generation. “Some investors might not like the leverage at Belron, certainly not given the economic uncertainty the world is facing,” Kris Kippers, an analyst at Degroof Petercam, said in a note to clients. The reorganization was “very surprising” but offered clear shareholding along with a dividend representing a third of D’Ieteren’s market value, he said. The news also probably means it’s unlikely that D’Ieteren will conduct an initial public offering for Belron for at least a year, said David Vagman, an analyst at ING. Twitter feed ©2025 BellMedia All Rights Reserved Tissue Engineering and Regenerative Medicine Volume 10 - 2022 | https://doi.org/10.3389/fbioe.2022.980727 The treatment of large bone defects is a clinical challenge 3D printed scaffolds are a promising treatment option for such critical-size defects the design of scaffolds to treat such defects is challenging due to the large number of variables impacting bone regeneration; material stiffness architecture or equivalent scaffold stiffness—due it specific architecture—have all been demonstrated to impact cell behavior and regeneration outcome Computer design optimization is a powerful tool to find optimal design solutions within a large parameter space for given anatomical constraints scaffold structures have been optimized to avoid mechanical failure while providing beneficial mechanical stimulation for bone formation within the scaffold pores immediately after implantation due to the dynamics of the bone regeneration process the mechanical conditions do change from immediately after surgery throughout healing we propose a computer framework to optimize scaffold designs that allows to promote the final bone regeneration outcome The framework combines a previously developed and validated mechanobiological bone regeneration computer model a surrogate model for bone healing outcome and an optimization algorithm to optimize scaffold design based on the level of regenerated bone volume The capability of the framework is verified by optimization of a cylindrical scaffold for the treatment of a critical-size tibia defect using a clinically relevant large animal model The combined framework allowed to predict the long-term healing outcome Such novel approach opens up new opportunities for sustainable strategies in scaffold designs of bone regeneration their translation to the clinic has been limited so far partly due to the large number of scaffold design variables influencing the regeneration process which limits the predictability of the clinical outcome; hence bone scaffold design is often the result of a trial-and-error process also this model did not account for any other tissue type but bone nor for the needed initial cell infiltration into the defect we propose a novel in silico framework to optimize scaffold design based on the level of regenerated bone volume aimed at the end of the regeneration process Such prediction has to consider the activity of individual cells and the potential for different tissue types to be formed during the healing process a computer framework combining a multiscale mechanobiological bone regeneration model a surrogate model for bone healing outcome and an optimization algorithm was developed This framework was applied to optimize scaffolds for a large defect in a sheep tibia To realize an optimization taking into account the regeneration outcome this study focuses on the design optimization of a cylindrical scaffold to be implanted in a large bone defect in the sheep tibia as an example The in silico framework to optimize scaffolds was realized by using a finite element model that was coupled to an agent-based model to simulate bone regeneration within such scaffolds This computer model was first used to simulate bone regeneration in a relatively large set of scaffold designs to generate the interpolation data necessary for a surrogate model Based on the results of the bone regeneration model a simplified relationship between the scaffold design parameters and the predicted regenerated bone outcome was computed (i.e. this relationship was used in an optimization framework to find the optimal scaffold design parameters to maximize the amount of regenerated bone was modelled in and around the defect by rotating a circle arc of maximum width 10 mm at mid-height and overlapping the intact bone extremities by 10 mm (A) Finite element model set-up: longitudinal cut through the defect configuration showing the intact bone extremities the implanted scaffold and the fixation plate; the dashed line represents the symmetry plane used in the analysis (B–D) Cylindrical scaffold description and parametrization: (B) longitudinal view of the full scaffold geometry; (C) radial view of the scaffold defining the vertical pore size parameter x3; (D) longitudinal view of the half scaffold (taking advantage of the symmetry) defining the horizontal pore size parameters x1 and x2 while the upper bound was chosen to avoid that neighboring pores overlap This model was implemented in the finite element (FE) software Abaqus v.6.18 (Simulia, Rhode Island) to perform mechanical analyses. Because of the symmetry of the geometry, only one half of the model was simulated, following the dashed line along the horizontal plane at mid-height (Figure 1A) The different geometrical parts were meshed with second-order elements as follows: hexahedral elements of average size 2.5 mm for the intact cortical bone the bone marrow and the plate; beam elements of size 1 mm for the screws; and tetrahedral elements of average sizes 1.2 mm for the callus and scaffold—this size was adapted depending on the size of the meshed geometry The following constraints were defined between the different geometrical parts: the intact bone extremities (cortical bone and bone marrow) were tied to the callus; the screws were tied to the intact bone; the screw heads were constrained by multi-point constraints of type beam with the plate holes; the callus was constrained such that it was tied to the scaffold The biological parts (cortical bone and bone marrow) were modelled as poroelastic materials with properties summarized in Table 1. The callus space was assumed to be initially filled with granulation tissue (poroelastic material, Table 1) regenerating tissue material properties were updated according to the predicted tissue formation of the bone regeneration model (Section 2.2) TABLE 1. Material properties (Perier-Metz et al., 2020) A compression load of 1372 N and a bending moment of 17.125 Nm were applied on the proximal end of the bone, corresponding to two body weights (BW) proximal-distal compression and an anterior-posterior moment of 0.025 BWm at the fixed end of a 20-cm intact bone, respectively (Duda et al., 1997; Perier-Metz et al., 2020) A symmetry boundary condition was defined on the xy symmetry plane (“ZSYMM”) pore pressure was constrained to be zero on the outer surfaces of the poroelastic parts (callus Two different scaffold optimization studies were performed, assuming different scaffold Young’s moduli (Table 1): defined as a linear elastic material with Young’s modulus 104 GPa defined as a linear elastic material with Young’s modulus 0.2 MPa (similar to the Young’s modulus of granulation tissue) A previously described mechanobiological bone regeneration (MBBR) model, which was able to explain bone regeneration within scaffolds in different experimental setups, was used to predict tissue formation during the healing process (Perier-Metz et al., 2020, 2022) It consisted in a 3D agent-based computer model implemented in C++ and coupled with the afore-mentioned FE model (Section 2.1) could represent one cell of one of the following phenotypes: progenitor cell chondrocyte and immature or mature osteoblast with the associated extracellular matrix: granulation tissue Progenitor cells were allowed to migrate randomly with an average speed of 30 μm/h (Appeddu and Shur, 1994). The origin of these cells was mimicked by initially seeding them randomly in the bone marrow cavity and along the periosteum with a 30% occupancy rate (Perier-Metz et al., 2020) The rest of the tissue volume was considered cell-free at the initial time point The FE analysis and agent-based simulations were run iteratively to predict the full regeneration process the input values and the corresponding output (as simulated with the MBBR model) were added to the dataset to compute a new surrogate model and a new optimum was determined based on this improved surrogate model The second loop consisted in building the surrogate model with the given dataset and computing an optimum based on this surrogate model until an optimum was reached that was better than all previously stored values (to avoid local optima) The output was simulated again with the MBBR model to ensure a good confidence in the result this new data point was added to the dataset to build the surrogate model and improve it further (A) Flow chart of the scaffold design optimization computational framework for enhanced bone regeneration (B) Locations of the initial samples (in the space defined by the three parameters x1 x3) for which the MBBR model is run to compute the surrogate model The initial dataset used to build the surrogate model was determined using the Latin Hypercube Sampling technique (Simon et al., 2002). Based on preliminary studies, 20 times the number of variables was found to be sufficient to obtain an accurate enough surrogate model, i.e, 60 samples in this set-up. The locations of the samples are given in Figure 2B The surrogate model was built using the predicted regenerated bone volume using the Matlab kriging toolbox DACE (Lophaven et al., 2002). An exponential auto-correlation was assumed as it gave the best results in a preliminary study. To perform the optimization, the Matlab Global optimization toolbox was used where different optimization algorithms were tested: direct search, genetic algorithm and particle swarm optimization (The MathWorks, Inc. 2020) x2 and x3 has to be defined to initialize the optimization process: the values 2.05 the default settings were used to perform the optimization In summary, the surrogate optimization framework includes the following steps (Figure 2A): 1) Run the MBBR model for a set of input parameters obtained by Latin Hypercube Sampling technique (LHS) 2) Build a kriging surrogate model based on the initial data using the Matlab kriging toolbox DACE 3) Perform optimization based on the surrogate model predictions using the Matlab Global optimization toolbox (The MathWorks, Inc. 2020): direct search 4) Run the MBBR model for the optimum scaffold parameters found in step 3 and compare the MBBR model output to the surrogate prediction (loop 1) or current optimal value (loop 2) 5) Repeat steps two to four to ensure model accuracy (loop 1 allowing max 5% discrepancy between the surrogate prediction and the MBBR model output) and optimality of the outcome (loop 2) To automate the creation of the FE models for each scaffold design, a Python script was developed for Abaqus, which allowed to define the pore corner positions based on the pore size. MATLAB R2018b (The MathWorks, Inc. 2020) was used to run the actual optimization framework including launching Abaqus CAE for the geometry update and the C++-Abaqus MBBR model Pore size values (input) and corresponding output (bone volume in the scaffold pores) were stored in a text file for further analysis The main outcome of the MBBR simulations was the predicted regenerated bone volume fraction in the scaffold pores after 24 weeks Regenerated bone volume fraction was computed as the total amount of agents within the scaffold pores occupied by osteoblasts divided by the total number of agent positions within the scaffold pores The porosity of the resulting scaffold was computed as the scaffold pore volume divided by the hollow cylinder volume (outer radius 10 mm and inner radius 5 mm) The regenerated bone volume fraction could then be related to the scaffold macroscopic porosity In addition, histology-like images of bone regeneration predictions were computed in the mid-sagittal plane of the defect using histology-like colors, similar to the experimental Safranin Orange/von Kossa staining: bone in black, fibrous tissue in light red and cartilage in dark red (Pobloth et al., 2018; Perier-Metz et al., 2020) This representation allowed a comparison between different designs and study cases Predicted regenerated bone volume fraction (bone volume/total pore volume) within the scaffold pores for scaffold designs with different porosities for 60 initial scaffold designs: (A) made of titanium; (B) made of a soft material (Young’s modulus 0.2 MPa) some areas of bone resorption appeared around some scaffold walls Optimization results for both scaffold compositions using various algorithms initial absolute principal strain distribution in the mid-sagittal plane and 24-week histology predictions in the mid-sagittal plane for different scaffold designs: (A) optimal titanium scaffold design; (B) a good titanium graded design (X1=1.84mm X2=3.45mm X3=2.26mm); (C) scaffold design optimized for titanium but now made of soft material; (D) optimal soft material scaffold design The optimal titanium scaffold design was predicted to perform very badly when assuming that it would be made of the very soft material with Young’s modulus 0.2 MPa: large amounts of fibrous tissue and cartilage were predicted to grow. As a consequence, only 27% of bone was present in the scaffold pores after 24 weeks compared to 96% when the scaffold was made of titanium (Figure 4C) The much softer material yielded high strain values in the defect thus leading to a mechanoregulation stimulus favoring more fibrocartilage formation The optimization processes presented in Sections 3.1 and 3.2 took ca including 10 days for the simulation of the bone regeneration process in the 60 initial scaffold geometries used to build the surrogate model and 2–7 days for each tested optimization algorithm (5–20 additional MBBR simulations) on a standard desktop PC when using the PSO algorithm—the algorithm that performed best in both cases—for the optimization step 4 days) of computation were needed for the titanium scaffold optimization and 26 h for the soft material scaffold in addition to the initial 10 days for the initial dataset simulations a standard optimization approach would have required thousands of simulation runs lasting 6 h each the computing performance was improved by a factor of at least 100 We propose here a computational framework for time-dependent mechanobiological optimization of 3D-printed scaffolds towards enhanced bone regeneration Our method is based on the bone regeneration outcome to optimize scaffold design instead of only the post-surgery mechanical stimulus or scaffold mechanical properties The framework uses surrogate modelling and design of experiments methods that allow for a set-up that can be run in a reasonable amount of time on standard computing machines the framework was used to optimize a scaffold for the treatment of a large bone defect in sheep where scaffolds of two different material properties were considered: titanium and a very soft material (with a Young’s modulus similar to that of granulation tissue) Even though the optimization was performed on a relatively simple scaffold geometry with square-section pores the computed optimum proved capable of performing as good as a more complex experimental design This first result is therefore very promising as the optimum of a simple parameterized geometry is already predicted to yield very good bone regeneration capabilities Further studies should test the potential of the optimization approach in other which could have a larger number of design parameters and therefore yield even better results the lower loading conditions decreased more strongly the regenerated bone volume fraction within the scaffold pores (79% compared to 96%) future studies could perform a polymer-ceramic composite scaffold optimization for large bone defect regeneration including the degradable behavior of these materials This would add a further dynamic aspect in the optimization process due to the degradation of the scaffold material it would have been possible to include the material stiffness in the optimization process but this might be less realistic (only some stiffness values are possible) and would distort the optimization results as the variation of material stiffness values can be of orders of magnitude compared to the pore size values despite the implementation of a surrogate modelling approach the computation time (a few weeks for one scaffold design optimization set-up) is still too long for a clinical routine usage where an optimal design should be designed in a few days for a patient-specific case Future studies should take advantage of high-performance computing technologies by using dedicated hardware and parallelized algorithms to further reduce the computing time we propose here a technological platform that allows to optimize hierarchically-structured bone scaffold designs not only against mechanical failure and initial in-growth of bone but for a sustainable long-term optimized regenerative process With improved computational efficiency and providing that the healing potential of an individual is known this method could be employed for the development of personalized 3D-printed bone scaffolds to ensure an optimal regeneration outcome to a given patient The raw data supporting the conclusion of this article will be made available by the authors All authors contributed to the conception and design of the study CP-M and SC developed the in silico models CP-M wrote the first draft of the manuscript SC provided technical guidance on the project All authors revised and edited the manuscript and approved its content This work was part of Camille Perier-Metz’ PhD project funded by MINES Paris—PSL Research University The authors acknowledge funding from the German Federal Ministry of Education and Research (BMBF) (grant number: 01ZX 1910) All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher The Supplementary Material for this article can be 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Available at: https://de.mathworks.com/help/gads/(Accessed February 18 Google Scholar Topological shape optimization of multifunctional tissue engineering scaffolds with level set method CrossRef Full Text | Google Scholar Numerical optimization of open-porous bone scaffold structures to match the elastic properties of human cortical bone PubMed Abstract | CrossRef Full Text | Google Scholar A time-dependent mechanobiology-based topology optimization to enhance bone growth in tissue scaffolds PubMed Abstract | CrossRef Full Text | Google Scholar Topology optimization of microstructure and selective laser melting fabrication for metallic biomaterial scaffolds CrossRef Full Text | Google Scholar Duda GN and Checa S (2022) A mechanobiological computer optimization framework to design scaffolds to enhance bone regeneration Received: 28 June 2022; Accepted: 16 August 2022;Published: 07 September 2022 Copyright © 2022 Perier-Metz, Duda and Checa. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use distribution or reproduction in other forums is permitted provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited *Correspondence: Sara Checa, c2FyYS5jaGVjYUBiaWgtY2hhcml0ZS5kZQ== Broadband TV News May 31, 2023 08.30 Europe/London By Chris Dziadul Globecast has appointed Jean-Christophe Perier as its CMO Perier will lead both marketing communications and product marketing for Globecast and be responsible for steering the marketing and external communications strategy worldwide Perier will be focussed on continuing to deploy innovative services that satisfy an ever-evolving marketplace Perier said: “I am thrilled to be taking up this new role with Globecast launching strong partnerships with industry leaders and developing innovative services to support Globecast’s continued success in the marketplace” Globecast’s previous head of marketing departs after 22 years with the company said: “I would like to thank Denis for his commitment and his involvement with Globecast; he will be missed We are delighted to welcome Jean-Christophe to the team and believe his expertise and leadership will be instrumental in driving Globecast’s growth and increasing our visibility and awareness in the markets that we serve” Filed Under: Newsline, People Tagged With: Globecast, Jean-Christophe Perier Edited: 31 May 2023 09:32 Today, consumers are increasingly using bandwidth-intensive and latency-sensitive workloads, such as 4K and 8K streaming, online gaming, and AR/VR applications. 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leaderboard maintained their dominance in Event 1 at the CrossFit Games Thirty-year-old Ole Kristian Antonsen and 25-year-old Séraphin Périer finished first and second in Event 1 Antonsen completed his 6,000 meters on the SkiErg in 23:08.00 and took the event win with Périer following just a short 23 seconds behind Antonsen continued his dominance in Event 2 finishing in 4:07.57 and averaging well under a minute per round took second in the event at 5:59.00 and was the only other athlete to finish under the time cap Antonsen and Périer went into Day 1 seeded in first and second and finished the day maintaining their positions Antonsen’s dominating performance in Events 1 and 2 coupled with a third-place finish in Event 3 earned him the top spot on the leaderboard at the end of Day 1 with Périer in second overall just 50 points back New York competitor Beth Tannatt and 27-year-old Valerie Cohen made it to the Games after clinching fourth and fifth And the two competitors brought their A games to their first day in Madison as well She was the only woman to complete the event and finished with a time of 3:26.03 Cohen rounded out Day 1 with her third event win followed closely by 38-year-old Natalie Bieule Casey Acree came into the CrossFit Games having taken first place in his division in the 2021 Open Acree’s momentum continued on Day 1 in Madison All competitors finished under the 6-minute time cap in Event 2 Acree shared that he trains rope climbs frequently Logan Aldridge made quick work of his rope climbs and finished second in the event After tasting second place in Event 1 and third place in Event 2 Maldonado decided it was time for an event win max deadlift and took his first event win of the competition Here’s what Dave Castro had to say about Aldridge’s lift: A post shared by @thedavecastro Elizabeth Bride was both the oldest and most dominant competitor to step onto the competition field for the Women’s Upper Extremity Event 1 The 44-year-old finished over two minutes ahead of the next-closest athlete Event 2 was a repeat neck-and-neck race between Bride and Lopez This time it was Lopez who came out on top and won the event with a time of 4:57.09 Lopez rounded out Day 1 with her second event win she is sitting on top of the leaderboard heading into Day 2 32-year-old Eileen Quinn was in her element deadlift earned her a second-place finish in the event Event 1 was a tight race between 25-year-old Brett Horchar and 33-year-old Mijail Pedrini Horchar was able to hold off Pedrini and finish the three-mile run in 24:23.14 Pedrini finished second with a time of 25:49.51 Horchar was the only competitor in his field to finish under the time cap he finished just over halfway to the time cap with a time of 3:16.57 just shy of crossing the finish line before time expired Thirty-five-year-old Sylvania Harrod broke Horchar’s winning streak in Event 3 clean to earn his first event win of the competition The race was on between 33-year-old Alisha Davis and 45-year-old Rebecca Shingledecker in Event 1 Davis did just enough to edge out Shingledecker and finish first in the three-mile run event with a time of 21:12.95 Thirty-year-old Shannon Ogar took her first event win in Event 2 She finished under the time cap at 5:13.59 Ogar and Shingledecker were the only two competitors in their field to finish under the cap The battle for second was between 41-year-old Ebby Isbill and Ogar but Isbill edged out Ogar for second place in the event by 10 lb Ogar finished third in the event with a 150-lb lift Learn more about Ogar’s story in “The Other Ogar,” by Brittney Saline Never miss an update from the CrossFit Games Legendary snapper Jean-Marie Perier on 60s icons family truths and Saint Laurent’s goodbye Even in a crowd he seemed lonely and sad.” The ‘guy’ in the photo is Yves Saint Laurent; remembering him is the man behind the camera: Jean-Marie Perier From our morning news briefing to a weekly Good News Newsletter get the best of The Week delivered directly to your inbox “I couldn’t imagine not loving the man she loved,” Perier says and because of this I put down my camera and made films with him.” Hardy and Dutronc are still very close friends of Perier who lives a quiet existence in the pretty medieval town of Villeneuve Perier was a talented musician and dreamt of becoming a jazz star but a family secret changed the course of his life I found out my father [actor Francois Perier] was not my biological father my biological father was a famous musician [singer Henri Salvador] so I didn’t play music again.” arranging for Jean-Marie to meet future publishing mogul Daniel Filipacchi then a young snapper at Paris Match who also had a radio show dedicated to jazz Filipacchi hired Perier on the spot as his assistant He worked at Paris Match for a year before being drafted into the French army to serve in Algeria They joined forces on what was to become one of the biggest success stories in French publishing history we started with 100.000 copies,” says Perier we were producing more than a million magazines a month.” suited and booted James Brown stepping off his jet in Long Island in 1967 ‘Just take pictures that parents will hate!’ It was much easier back then no one asked to see a picture before I printed it?” After a relatively short career as a film director Perier moved to LA to make commercials for brands such as Coca-Cola and Ford the beginning of the trend for European directors over there It was amazing working with people like Ridley Scott I stayed another 10 years and made more than 600 ads Then I changed directions again in 1990.” was editor of French Elle at the time and suggested he move back to Paris to photograph fashion “She has a good sense of humour and thought it would be interesting for me to create the same mise-en-scène I did in the 1960s it was very funny for me to make pictures of designers Saint Laurent had made many smoking [tuxedos] for Francoise [Hardy] Karl Lagerfeld or Jean Paul Gaultier back then No one had their imagination and craziness.” When Perier took this shot (above) in 1995 he wanted to challengethe (albeit accurate) perception of Saint Laurent as painfully shy and reclusive The Elle spread was to be one of the very last photoshoots of the great couturier Perier had a chance meeting with Saint Laurent at a restaurant in Paris just before his death “He told me he loved the picture and asked if he could have a print so of course I made sure I sent it to his apartment the next day but he’d already arranged to send me flowers and a card thanking me for the gift Perier is preparing for his next adventures: an exhibition at London’s Little Black Gallery and the publication of a series of short stories inspired by old age ‘Being old is wonderful.’ Why do they think it’s so great What’s important is to never sit back Designers by Jean-Marie Perier is at The Little Black Gallery A free daily email with the biggest news stories of the day – and the 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of the Gard département where the site is located gave the company formal notice to "immediately suspend" the operation of one of its seven water extraction points in Vergèze which had been "contaminated from March 10 and over several days by germs indicative of contamination of fecal origin (coliforms but also by germs of the species Pseudomonas aeruginosa." 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You have 81.25% of this article left to read Lecture du Monde en cours sur un autre appareil Vous pouvez lire Le Monde sur un seul appareil à la fois Ce message s’affichera sur l’autre appareil Parce qu’une autre personne (ou vous) est en train de lire Le Monde avec ce compte sur un autre appareil Vous ne pouvez lire Le Monde que sur un seul appareil à la fois (ordinateur En cliquant sur « Continuer à lire ici » et en vous assurant que vous êtes la seule personne à consulter Le Monde avec ce compte Que se passera-t-il si vous continuez à lire ici Ce dernier restera connecté avec ce compte Vous pouvez vous connecter avec votre compte sur autant d’appareils que vous le souhaitez mais en les utilisant à des moments différents Nous vous conseillons de modifier votre mot de passe Votre abonnement n’autorise pas la lecture de cet article merci de contacter notre service commercial In advance of the 2024 IBC Show who will be exhibiting at Stand 5.C75 in the show's Content Everywhere Zone TV Tech: Why did you choose to exhibit in the Content Everywhere Zone this year Jean-Christophe Perier: We felt that the Content Everywhere Zone was more in line with our initiatives for media integration and orchestration hybrid cloud solutions and content monetization than the other areas of the Show We also find value in the speaking and stage opportunities on the Content Everywhere stages on the show floor TVT: What will you be highlighting at your exhibit JCP: We will be highlighting the latest in advanced transmission and connectivity capabilities and end-to-end hybrid cloud solutions as well as OTT and media management updates Globecast has significantly broadened its acquisition TVT: Which trends do you expect will be most important at the show this year?JCP: We expect to see advances in media integration and managed services and the implementation of AI for streamlining of workflows We are excited to hear about the sustainability initiatives that are being undertaken in the industry and learn how we can benefit from implementing and discussing these initiatives with our colleagues TVT: What brings you back to IBC every year?JCP: IBC is must-attend event for our category of services to customers we can interact with attendees from all over the world and we believe IBC is the gold standard for technology events The partnerships and connections we have made during IBC over the years have enabled us to continue to grow learn and stay ahead of the most current advances in the broadcast industry are the relationships fostered and the comradery we enjoy during the Show For more information, visit https://show.ibc.org/content-everywhere The professional video industry's #1 source for news, trends and product and tech information. 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Volume 10 - 2022 | https://doi.org/10.3389/fchem.2022.888285 is the most common radiation modality used for medical device and biopharmaceutical products sterilization Although X-ray and electron-beam (e-beam) sterilization technologies are mature and have been in use for decades impediments remain to switching to these sterilization modalities because of lack of data on the resulting radiation effects for the associated polymers as well as a lack of education for manufacturers and regulators on the viability of these sterilization alternatives the compatibility of ethylene vinyl acetate (EVA) multilayer films with different ionizing radiation sterilization (X-ray and gamma irradiation) is determined by measuring chemical and physical film properties using high performance liquid chromatography Fourier-Transform InfraRed spectroscopy (FTIR) The results indicate that the three irradiation modalities induce no differences in thermal properties in the investigated dose range Gamma and X-Ray irradiations generate the same level of reactive species in the EVA multilayer film whereas e-beam generates a reduced quantity of reactive species and they found no change in the shelf life The generation of reactive species such as peroxides and peracids were probed by the methionine oxidation (mimicking the oxidation of proteins) monitored by high performance liquid chromatography (HPLC) Long-lived radicals were tracked by electron spin resonance (ESR) The single-use plastic bags studied were made from an EVA-based multilayer film composed of one layer of EVOH (5 µm) sandwiched between two layers of EVA, with a total thickness of about 360 µm (Figure 1) Polyethylene (PE) was present as a tie layer (5 µm) between the EVA and EVOH Structure of the EVA/EVOH/EVA multilayer film EVA bags (series #1) and pre-cut EVA films (series #2) were packed and wrapped in multilayer packaging (polyethylene/polyamide/polyethylene) of thickness 100 ± 20 µm and irradiated at room temperature with a cobalt-60 gamma source at Ionisos Irradiation was performed under environmental atmosphere the average target dose was 59 ± 3 kGy for the methionine oxidation evaluation 54.3 ± 2.7 kGy for the thermal property evaluation and 48.2 ± 2.1 kGy for the surface energy evaluation the average measured gamma doses for samples used in methionine oxidations thermal property and surface energy evaluation were 30.0 ± 1.9 kGy The dose rate provided was of 1–2 kGy/h Alanine dosimeters were used on the cardboard box containing the samples to assess the radiation delivered to the single use bag samples (±5%) it was necessary to perform several sterilization cycles including a waiting time not controlled between each cycle All the boxes have been exposed to a double-sided irradiation EVA bags (series #1) were individually wrapped in multilayer packaging (polyethylene/polyamide/polyethylene) and placed side-by-side in a thin cardboard box (8 cm) to have only one thickness of plastic material Bags (series #1) were irradiated with a 10 MeV Rhodotron (Ionisos France) at a dose rate of 18,000 kGy/h with a power source at 28 kW Alanine dosimeters were used on cardboard boxes containing the samples to assess the radiation delivered to single use bag samples (±5%) The range in delivered surface dosage was 51 ± 1 kGy using double-sided irradiation These samples were used for thermal property Pre-cut films (series #2) were processed using two 10 MeV, 20 kW e-beam Mevex accelerators at Steri-Tek (steri-tek.com) in Fremont United States B3 dosimeters were used on cardboard boxes containing the samples to assess the radiation delivered to film samples used in thermal property and spectroscopic evaluation to be delivered at 31 ± 2 EVA bags (series #1) were individually wrapped in multilayer packaging (polyethylene/polyamide/polyethylene) They were irradiated with a 7 MeV Rhodotron (Steris Däniken Switzerland) with an average dose rate of 50 ± 30 kGy/h with a maximum power source of 560 kW The range in delivered surface dosage was 68 ± 0.6 kGy for the methionine oxidation evaluation using double-sided irradiation EVA bags (series #1) used in other tests were irradiated with a 7 MeV Rhodotron (Aerial The range in delivered surface dosage was 50.6 ± 4.0 kGy for the thermal property measurements and 54.7 ± 2.5 for the surface energy evaluation using double-sided irradiation EVA film samples (series #2) were wrapped in multilayer packaging (polyethylene/polyamide/polyethylene) They were irradiated with a 7 MeV Rhodotron (Aerial Strasbourg France) with an average dose rate of 15 kGy/h The delivered surface dosages were 33.2 ± 0.4 kGy and 59.8 ± 1.1 kGy using double-sided irradiation An EVA bag irradiated up to 98.9 ± 0.7 kGy was also included in series #2 Series #2 samples were used in thermal property The pre-cut films (series #2) were tested on a TA Instruments (Waters LLC The melting temperatures were determined in the second heating cycle from −140 to 200°C at 10°C/min after a 10°C/min cooling step from 200°C to −140°C Three replicates of films (series #2) were tested at each irradiation condition Unirradiated specimens in series #1 and #2 were measured on corresponding DSC instruments to calibrate systematic differences The samples were analyzed within 10 days following irradiation ESR measurements were carried out on a Bruker EMX X-band spectrometer operating at 9.5 GHz and equipped with a highly sensitive rectangular microwave cavity The spectroscopic parameters were modulation amplitude 2 G Four scans were performed to record each ESR signal Surface energy measurements were performed on EVA bags (series #1) using a GBX goniometer at controlled temperature and humidity (23°C/50% RH) Measurements were performed with ethylene glycol and diiodomethane with respective capillary volume (2.097 µL; 2.72 µL; 1.24 µL) Ten droplets were deposited on each sample The surface tension energies were calculated using the “Owens-Wendt-2 equation” from the average of the contact angle measurements for each liquid The surface energies were also measured on pre-cut films (series #2) using a Krüss Mobile Surface Analyzer (MSA) equipped with ADVANCE software and diiodomethane (Thermo Scientific; >99% purity) and distilled water syringes Measurements were performed in quintuplicate using the double sessile drop program and an unmodified version of the automation program provided with the ADVANCE software Droplet size (2 μL target) was calibrated every 10 measurements Contact angles were measured using the automatic baseline function and the ellipse (tangent−1) fitting method Erroneous contact angle measurements were corrected by the manual baseline method The surface free energy was calculated using the Owens and Kaelbe (OWRK) method with a correlation coefficient of 1.00 Additional parameters accounting for microscale surface roughness were not used in this work The surfaces of sample films (series #2) were characterized using a Bruker Alpha II OPUS Touch FTIR spectrometer with an attenuated total reflection (ATR) attachment The specimens were conditioned following ASTM D618 Procedure A at 23 ± 2°C and 50 ± 10% relative humidity for at least 40 h the spectra for each specimen were recorded from 4,000 to 700 cm−1 64 scans were collected at a resolution at 4 cm−1 for each specimen and each specimen was measured at four locations near four edges Peak absorbance intensities corresponding to the methylene group (maximum absorbance between 2,846 and 2,850 cm−1, CH2 symmetric stretch) and carbonyl group (1715 cm−1, C=O stretch) were used to calculate the carbonyl index. The carbonyl index (CI) is given in Eq. 1 where AC=O and AC−H are the absorbance peak values found in the ranges of 1,650–1830 cm−1 and 1,400–1,510 cm−1 Samples were stored in boxes in the dark following irradiation in an air-conditioned room at 20 ± 2°C Data are displayed as the difference between the irradiated and unirradiated sample values to directly compare data measured by the partner organizations Measurements of the melting points of EVA and EVOH layers showed close results between samples exposed to X-ray FIGURE 2. Change in melting temperatures of (A) EVA, (B) PE, and (C) EVOH components with respect to non-sterile films. Triangles: series #1. Circles: series #2. Triangles pointing up and down represent data obtained for samples from two different manufacturing batches. Representative DSC responses of EVA/EVOH/EVA films (series 2) are shown in Supplementary Figure S1 A statistical evaluation was achieved with an “equivalency test” using the software Minitab® The Null hypotheses HO for the mean values difference was either µGamma—µXray ≤ −5°C or µGamma—µXray ≥ 5°C The alternative hypotheses H1 was either −5°C<µGamma—µXray <0°C or 0°C<µGamma—µXray < 5°C The equivalency criterion used to check was whether the measurement results of gamma and e-beam irradiated samples fell within the equivalence interval The statistical evaluation was an initial tool to check the clustering of data The understanding of the polymer behavior remains the predominant parameter to finally evaluate the potential impact difference between all ionizing radiation modalities While the effect of irradiation on the measured surface energy of the films was small (Figure 3) surface energy was observed to increase slightly with dose except for the 45 kGy X-ray and 48 kGy gamma scenarios No trend in difference was observed between the results of the modalities Surface free energy of the (A) exterior and (B) interior side of the bag Effects of dose and modality on carbonyl index showed a slight decrease with exposure as seen in Figure 4 although the values for exposed and unexposed samples were almost equivalent within the uncertainty of the measurements the ratio of FTIR absorbance peak intensities for C=O and C=H bonds tends to increase with oxidation for polyolefins The slight decrease with exposure observed here indicates a lack of significant oxidation of the surface of the EVA multilayer films with irradiation up to 60 kGy At the higher dose of 45 and 60 kGy the carbonyl index values of the gamma irradiated samples are slightly larger than those for the other two modalities FIGURE 4. Carbonyl index of series #2 multilayer films. Representative FTIR response of EVA/EVOH/EVA films (series 2) are shown in Supplementary Figure S2 potentially explaining the lower methionine sulfoxide quantities detected in e-beam irradiated samples Methionine sulfoxide concentration (µM) in stored solution for 10 days in series #1 bags and analyzed by HPLC Irradiation doses were 59 kGy for gamma irradiation 51 kGy for e-beam and 68 kGy for X-rays The solid line indicates the Limit of Quantification (LOQ) and the dashed line indicates the Limit of Detection (LOD) ** means that the difference is statistically significant EVA/EVOH-based multilayer films were irradiated with 7 MeV X-rays and cobalt-60 gamma at doses between 50 and 70 kGy Potential polymer changes under these three irradiation modalities were investigated by assessing the general multilayer structural attributes for use in biopharmaceutical applications or in interaction with biopharmaceutical solutions it was shown that the different irradiation modalities did not significantly affect the thermal properties of the multilayer film constituents the irradiation modalities did significantly change the quantity of reactive oxygen species generated under irradiation (lower amount of methionine sulfoxide generated by e-beam irradiation than by X-ray or gamma) This first evaluation of effects of ionizing radiations with this multilayer film reveals that the interaction with EVA/EVOH materials seems to be identical for the high energy photons such as gamma-rays and X-rays In order to confirm and complete this trend further studies bracketing and exceeding the established worse case irradiation dose (i.e. ∼59 kGy with gamma-rays) and overlapping the common routine irradiation dose range (i.e. approximately 25–45 kGy) will be undertaken The original contributions presented in the study are included in the article/Supplementary Material further inquiries can be directed to the corresponding authors All authors listed have made a substantial and intellectual contribution to the work and approved it for publication We acknowledge Sartorius Stedim FMT S.A.S for partial financial support of this work TAMU and Steri-Tek participation in this work for the irradiation and the additional analysis which was supported by the U.S Department of Energy National Nuclear Security Administration Office of Radiological Security The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest The authors declare that this study received funding from Sartorius The funder had the following involvement in the study: study design These funders had the following involvement in the study: irradiation and additional analysis (which was supported by the U.S Department of Energy National Nuclear Security Administration Office of Radiological Security) MC-B and SRAM are thankful to AMU and CNRS for support The Pacific Northwest National Laboratory is operated by Battelle for the United States Department of Energy under Contract DE-AC05-76RL01830 The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fchem.2022.888285/full#supplementary-material The Effect of Gamma Irradiation on Mechanical and thermal Properties of Recycling Polyethylene Terephthalate and Low Density Polyethylene (R-PET/LDPE) Blend Compatibilized by Ethylene Vinyl Acetate (EVA) CrossRef Full Text | Google Scholar Adliéné Dose Measurements and Radiation protection,” in Applications of Ionizing Radiation in Materials Processing (Warszawa: Institute of Nuclear Chemistry and Technology) Google Scholar Adliéné “Radiation Interaction with Condensed Matter,” in Applications of Ionizing Radiation in Materials Processing (Warszawa: Institute of Nuclear Chemistry and Technology) Google Scholar Degradation of γ-irradiated Polyethylene-Ethylene Vinyl Alcohol-Polyethylene Multilayer Films: An ESR Study CrossRef Full Text 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Full Text | Google Scholar Electron Beam and X-Ray Irradiation Effects on Single-Use Blood Collection Devices with Plastic Components CrossRef Full Text | Google Scholar Effect of Electron-Beam and Gamma-Irradiation on Physicochemical and Mechanical Properties of Polypropylene Syringes as a Function of Irradiation Dose: Study under Vacuum CrossRef Full Text | Google Scholar FTIR Study of Ageing of γ-irradiated Biopharmaceutical EVA Based Film CrossRef Full Text | Google Scholar Ageing and Their Interactions on Multilayer Films Followed by AComDim PubMed Abstract | CrossRef Full Text | Google Scholar Monitoring of the Discoloration on γ-irradiated PE and EVA Films to Evaluate Antioxidant Stability CrossRef Full Text | Google Scholar GIPA and IIA (2017) X-ray and Ethylene Oxide Technologies for the Industrial Sterilization of Medical Devices and Healthcare Products Google Scholar Electron Beam and Gamma Irradiation on PE/EVOH/PE Multilayer Film Properties CrossRef Full Text | Google 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Volume 8 - 2020 | https://doi.org/10.3389/fbioe.2020.585799 Large segmental bone defects represent a clinical challenge for which current treatment procedures have many drawbacks 3D-printed scaffolds may help to support healing but their design process relies mainly on trial and error due to a lack of understanding of which scaffold features support bone regeneration The aim of this study was to investigate whether existing mechano-biological rules of bone regeneration can also explain scaffold-supported bone defect healing we examined the distinct roles of bone grafting and scaffold structure on the regeneration process scaffold-surface guided migration and tissue deposition as well as bone graft stimulatory effects were included in an in silico model and predictions were compared to in vivo data We found graft osteoconductive properties and scaffold-surface guided extracellular matrix deposition to be essential features driving bone defect filling in a 3D-printed honeycomb titanium structure This knowledge paves the way for the design of more effective 3D scaffold structures and their pre-clinical optimization prior to their application in scaffold-based bone defect regeneration current scaffold design processes are mainly based on trial and error approaches An in-depth understanding of how structural design parameters impact each other and the biology of bone defect healing appears mandatory to allow predictive healing to occur a 3D-printed bone scaffold should not aim to replace the missing bone identically but rather to provide a suitable environment for bone to regrow Computer modeling (benchmarked against in vivo data) could help unraveling the principles of bone defect regeneration and allow a pre-operative planning of a patient own scaffolding strategy and thus the optimization of a 3D-printed customized scaffold enabling bone defect healing their predictive capability has never been tested against experimental data most of these models have ignored or highly simplified any mechanical or biological interaction between the scaffold and the regeneration process the relative role of scaffold guidance for bone regeneration remains largely unclear how these properties contribute to the overall healing process remains poorly understood a systematic analysis of these bone graft stimulatory features is lacking as well as the understanding of which of the 3D-printed scaffold features are essential in bone defect regeneration A previously described in vivo study (Pobloth et al., 2018) was used to compare in silico predictions to in vivo observations of large bone defect tissue patterning Details of the experimental study design are only briefly described here A large tibial bone defect in sheep was used to study bone defect healing To investigate the role of scaffold overall stiffness on bone regeneration 12 sheep underwent a 4 cm osteotomy in the right tibia that was filled with a relatively soft or stiff customized 3D printed titanium scaffold identical topology but different strut thicknesses (1.2 or 1.6 mm) leading to overall soft (0.84 GPa) or stiff (2.88 GPa) scaffolds The osteotomy was held in place using a steel locking compression plate autografts taken from the iliac crest were crushed and filled into the scaffold pores before implantation Radiographs were performed every 4 weeks to evaluate progress in bone defect regeneration The animals were sacrificed 24 weeks post-surgery tibia was harvested and histomorphometrical analysis was performed on a mid-sagittal cut to visualize bone and cartilage formation within the defect the soft scaffold was used to investigate the influence of scaffold guidance and bone graft stimulation on scaffold-supported bone regeneration all parameter analyses were done for the soft scaffold configuration Only the model with best prediction capabilities was then tested in the stiff scaffold configuration A previously described and experimentally validated bone regeneration computer model was used (Checa et al., 2011). The computer model couples agent-based and finite element (FE) models to simulate bone growth within the healing region as depicted in Figure 1 This framework will be referred to as “baseline model” in the following and described in sections “Agent-Based Model” and “Finite Element model.” Bone regeneration computer model flowchart An agent-based model accounting for cellular activities (proliferation and differentiation) was implemented in C++ The callus space was discretized into a 3D grid (spacing 100 μm) in which each point was occupied by maximum one of the following cell phenotypes: progenitor cell Since the distance between agents was larger than the expected cell size a single agent would actually contain several cells as well as the corresponding extracellular matrix cells and tissues were identified in the model Cells and corresponding tissues being identified the simulated differentiation included the matrix deposition process Mechano-regulation algorithms for progenitor cell differentiation All cell phenotypes were allowed to proliferate providing that their surrounding mechanical microenvironment was appropriate (depending on the mechano-regulation thresholds) or would undergo apoptosis otherwise, with proliferation and apoptosis rates given in Table 2 Table 2. Cell activity rates (adapted from Checa et al. (2011) (A) Finite element model of the 4 cm osteotomy with a zoom within scaffold pores The color code given on the left shows the different materials defined at the initial time point (after implantation) All biological tissues were modeled as poroelastic materials with properties given in Table 3 Titanium and steel were considered linear elastic materials with Young’s modulus 104 and 210 GPa Table 3. Tissue material properties (adapted from Checa et al., 2011) Mechanical loading conditions aimed to simulate the peak load under normal walking conditions: a proximal-distal axial load (compression) of 1,372 N [corresponding to 2 body weights (BW)] and an anterior-posterior moment (bending) of 17.125 Nm (corresponding to 0.025 BWm at the fixed end of an intact bone) (Duda et al., 1997) were applied on the bone proximal extremity the distal being constrained in rotation and translation (encastre) Pore pressure was constrained to be zero on the poroelastic materials’ outer surface (callus The screws were fixed to the plate using multi-point constraints of type beam Tie constraints were defined between callus and intact bone extremities The model was meshed using second-order elements of the following types: hexahedral elements of average size 2.5 mm for the cortical bone the bone marrow and the plate; beam elements of size 1 mm for the screws; and tetrahedral elements of average size 0.7 mm for the callus and the scaffold The FE model was next run in ABAQUS/Standard v.6.12 (Simulia Rhode Island) to compute the corresponding mechano-regulation stimulus The baseline bone healing algorithm was modified to account for three potential biological stimulatory effects of the bone graft present in the scaffold pores (Figures 2C, 3A,B and Table 4): Pseudo-code for the newly implemented features (A) Graft stimulatory effect on progenitor cell migration (B) Graft stimulatory effect on progenitor cell proliferation (D) Surface-guided extracellular matrix deposition Summary of the bone healing simulations and their characteristics 1. Osteoconductive effects (guiding new bone ingrowth) (Finkemeier, 2002) were modeled by limiting progenitor cell migration and/or proliferation after a latency period (15 days) to the regions containing graft This latency period was defined to account for the fact that progenitor cells would stop being biologically active after a few days without a biological stimulus 2. Osteoinductive effects (enhancing bone deposition) (Finkemeier, 2002) were modeled by increasing the rate of progenitor cell differentiation toward osteoblasts from 0.3 to 0.5 in the regions containing graft progenitor cell migration and proliferation were limited to the latency period defined above 3. Bone graft-contained progenitor cells (Finkemeier, 2002) were modeled by the initial seeding of progenitor cells in 0.1% of the available graft volume A 15-days latency period was also implemented in this case Those effects were investigated both independently and in the following combinations: osteoconductive and osteoinductive effects without and with bone graft-contained progenitor cells a hypothetical case corresponding to the absence of any stimulatory effect of the graft was simulated by implementing a latency period in the baseline simulation after which both progenitor cell migration and proliferation would stop This “non-stimulated bone regeneration model” served as a new baseline to investigate further effects Two features were implemented to investigate the role of scaffold-surface guidance (Sengers et al., 2007; Cipitria et al., 2012; Werner et al., 2018) on bone regeneration (Figures 2B, 3C,D and Table 4): Surface-guided migration: a progenitor cell was allowed to migrate to a randomly picked new position only if at least one of the new position’s neighboring points was occupied by tissue (bone This assumes that a progenitor cell can only migrate along an existing tissue or scaffold-surface and not within the granulation tissue Surface-guided extracellular matrix (ECM) deposition: a progenitor cell was allowed to differentiate into a new phenotype and thus deposit the corresponding tissue only if at least one of its neighboring positions was occupied by tissue or scaffold This assumes that new tissue deposition cannot happen within granulation tissue but needs a substrate (pre-existing tissue These two features were compared to the non-stimulated bone regeneration model (as explained in section “Simulation of the Bone Graft Stimulatory Effects”) and in combination with graft osteoconductive effects (section “Simulation of the Bone Graft Stimulatory Effects”). Since in vivo tissue formation was not observed along the plate (Pobloth et al., 2018) the plate was not simulated to provide any guidance in any of the cases Computer model predictions were compared to X-ray and histological data algorithms were developed to extract similar images as computer model output quantification of the regenerated bone was compared to histological measures To compare the time evolution of the bone healing process within the scaffolds X-ray-like images were computationally generated at the same time points than experimentally: 0 Neglecting the surrounding soft tissues and their X-ray scattering the images were obtained using the Beer-Lambert law: with I the observed intensity, I0 the initial intensity (an arbitrary value 1 was chosen for normalization), k the material attenuation coefficient and x the material thickness (Bushberg, 2012). Taking the grid spacing (100 μm) of the agent-based model for x and the attenuation coefficients defined by the NIST,1 the attenuation over all crossed grid points in the X-ray beam direction was summed thereby revealing the corresponding radiograph The contrast was then adapted to be as close as possible to the experimental images Histology-like images were extracted from the computer model predictions to compare with the experimental histology images obtained at 24 weeks post-surgery using Safranin Orange/von Kossa staining the predicted tissue distribution in the mid-sagittal plane was represented with 100 μm-sided pixels in colors similar to the staining: black for bone dark red for cartilage and light red for fibrous tissue scaffold and fixation plate were depicted in gray nuances To allow comparison between different in silico predictions the images were generated at the same time points as the X-ray pictures: 4–24 weeks Bone area quantification in the mid-sagittal plane (B) Percentage quantification in the experiment (the error bar shows the minimal and maximal values among the six animals) and in various simulation cases referred to in the legend on the bottom The output obtained for the baseline model and the non-stimulated bone regeneration model were compared to the experimental data (section “Baseline Simulation”). Then, the results of the addition of bone graft stimulatory effects and scaffold-surface guidance features were investigated individually and in combination to compare them between each other and to the experimental data (as summarized in Table 4) tissue formation was characterized by fibrocartilage patterning or endochondral ossification along the scaffold struts that was hardly predicted by the bone healing algorithm in silico the bone healing algorithm predicted a dynamic filling process with bridging of the defect after roughly 18 weeks whereas experimentally bridging occurred on average after 12 weeks the computer model algorithm predicted significant bone remodeling that was not observed in vivo Figure 5. Bone healing dynamics over time: (A) in vivo, X-ray images (anteroposterior); (B) in silico, simulated X-ray images (anteroposterior) using the baseline bone healing algorithm (Checa et al., 2011); (C) in vivo Safranin Orange/von Kossa staining; (D) in silico simulated histology pictures (mid-sagittal) with baseline simulation; (E) in silico simulated histology pictures (mid-sagittal) in the non-stimulated bone regeneration model The color code for the simulated histology pictures is given on the right If the stimulatory effects were taken out in the baseline bone healing algorithm (non-stimulated bone regeneration model: progenitor cell migration and proliferation stopped after a 15-days latency period; Figure 5E) resulting in non-union and capping of the bone marrow cavities Making graft presence a prerequisite for progenitor cell migration or proliferation (bone graft osteoconductive effects: Figures 6A,B) resulted in bone growth patterning confined within the scaffold pores. However, it did not reproduce the experimentally observed differences in bone regeneration between medial (under the plate) and lateral sides (Figure 4B) The dynamics of the simulated osteoconductive effects was slightly slower than the baseline simulation (bridging achieved after ca and consequently slower than in vivo (average bridging after 12 weeks) Bone graft stimulatory effects on scaffold-supported bone regeneration: (A) graft stimulatory effect on cell migration (osteoconductivity); (B) graft stimulatory effect on cell proliferation (osteoconductivity); (C) graft stimulatory effect on cell differentiation; (D) combined graft osteoconductive and osteoinductive effects; (E) bone graft-contained progenitor cells; (F) combined bone graft-contained progenitor cells with osteoconductive and osteoinductive effects Enhancing progenitor cell differentiation into osteoblasts in regions containing graft (bone graft osteoinductive effects: Figure 6C) did not have much impact when compared to the non-stimulated bone regeneration model leading to similar patterning and very slow regeneration process When combining bone graft osteoconductive and osteoinductive effects (Figure 6D), the patterning resulting from isolated osteoconductive effects was further enhanced, eventually confining bone deposition within the scaffold pores and achieving bridging in ca. 20 weeks. In particular, the central ROI quantification fitted well the experimental data: 41 vs. 35% (Figure 4B) not only did the final patterning not reproduce the medial-lateral difference observed in vivo but it also led to a marrow cavity capping by regenerated bone consistently not seen in vivo The central ROI prediction of 55% was within the range of the experimental measures (maximal value of 58%) the healing process was very homogeneous through the entire defect instead of starting from the bone osteotomy cuts Surface guidance features further slowed down the impaired regeneration predicted in the non-stimulated bone regeneration model, confining bone growth mostly to the scaffold pores (Figures 7A,B) and marrow cavity capping was observed due to osteoblast proliferation and consequent bone deposition Surface guidance features: (A) surface-guided migration with non-stimulated bone regeneration; (B) surface ECM deposition with non-stimulated bone regeneration; (C) surface-guided migration with bone graft osteoconductive effects; (D) surface ECM deposition with bone graft osteoconductive effects what did not match the in vivo observations and 36% were predicted by the model in the lateral while experimentally they were in average of 44 Stiff scaffold (strut width 1.6 mm)—surface ECM deposition with bone graft osteoconductive effects 3D printed scaffolds appear as a promising alternative for the treatment of large bone defects; however until now there is little understanding of the mechano-biological rules driving scaffold-supported bone regeneration we analyzed whether a previously validated bone healing algorithm could predict scaffold-supported bone defect healing to identify specific mechano-biological factors which might differ between these modes of bone regeneration The new bone defect healing algorithm introduced in the present work revealed specific mechanisms behind scaffold-supported bone healing Our findings illustrate the relevance of (1) scaffold surfaces as a guide for bone defect regeneration and (2) the stimulatory role of autologous bone grafting as filling for such scaffolds Both features taken together allowed to mimic the experimentally observed bone tissue patterning in a large bone defect supported by a titanium scaffold and autologous bone grafting Our results show that mechano-biological models of uneventful bone regeneration are not able to explain scaffold-supported bone regeneration For the specific experimental setup investigated in this study our simulations showed an overestimation of the bone formation with different dynamics and patterning from those observed experimentally our results suggest that bone graft osteoconductive effects play a major role for the regeneration of the bone while graft-contained progenitor cells do not seem major actors in this healing process They developed a computer model to predict soft and mineralized tissue formation within a PCL 3D-printed scaffold as guided by scaffold surface curvature They showed that curvature could account for the collagen and mineralized bone tissue patterning observed ex vivo the model only investigated non-healing sample groups using a computer model of bone regeneration we investigated the mechanisms behind scaffold-supported bone healing Further work is required to investigate which of those mechanisms can explain the in vivo differences what could partially contribute to observed healing patterns Future studies should further investigate the relative effect of angiogenesis on scaffold-supported healing a strong remodeling was predicted in silico in the baseline model due to the high sensitivity of the model to slight strain changes around the mature bone formation to resorption limit This is however not likely to happen in vivo Future in silico models should investigate the mechanical regulation of bone remodeling during healing here we presented new model features for a coupled multiscale mechano-biological model for bone regeneration to predict scaffold-supported bone regeneration including bone graft stimulatory effects (osteoconduction source of progenitor cells) and scaffold-surface guidance features We showed that a combination of bone graft osteoconductive effects and scaffold-surface guided ECM deposition could explain the patterning and healing dynamics observed in an in vivo scaffold-supported large bone defect regeneration study Validated in silico models of scaffold-supported bone regeneration are a powerful tool for the prediction of the healing outcome of a given large bone defect with a specific scaffold Rather than mimicking intact bone mechanical properties and internal structure scaffold design should make use of such in silico modeling approaches allowing for a yet missing a priori evaluation of scaffold performance in enhancing the natural bone regeneration process The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation, to any qualified researcher. The computer model source files were made available on the following repository: https://github.com/camille-PM/mechanobio_bone CP-M developed in silico models and collected the data CP-M and SC interpreted the data and drafted the manuscript All authors read and revised the manuscript and approved its content This work was supported by MINES ParisTech – PSL Research University (France) We acknowledge support from the German Research Foundation (DFG) and the Open Access Publication Fund of Charité – Universitätsmedizin Berlin The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fbioe.2020.585799/full#supplementary-material Google Scholar Molecular analysis of cell surface beta-1,4-galactosyltransferase function during cell migration Effects of scaffold architecture on cranial bone healing CrossRef Full Text | Google Scholar Multiscale in Silico Model to Investigate Compromised Bone Healing Conditions CrossRef Full Text | Google 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bioactive glass on osseointegration: an experimental study in dogs Bioactive polymeric scaffolds for tissue engineering Effects of titanium nanotubes on the osseointegration mineralisation and antibacterial properties of orthopaedic implant surfaces doi: 10.1302/0301-620X.100B1.BJJ-2017-0551.R1 Modeling vascularized bone regeneration within a porous biodegradable CaP scaffold loaded with growth factors The spatio-temporal arrangement of different tissues during bone healing as a result of simple mechanobiological rules Long-bone critical-size defects treated with tissue-engineered grafts: a study on sheep Von Offenberg Sweeney Cyclic strain-mediated regulation of vascular endothelial cell migration and tube formation Mesoscale substrate curvature overrules nanoscale contact guidance to direct bone marrow stromal cell migration Duda GN and Checa S (2020) Mechano-Biological Computer Model of Scaffold-Supported Bone Regeneration: Effect of Bone Graft and Scaffold Structure on Large Bone Defect Tissue Patterning Copyright © 2020 Perier-Metz, Duda and Checa. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) *Correspondence: Sara Checa, c2FyYS5jaGVjYUBjaGFyaXRlLmRl Day 3 of the 2021 NOBULL CrossFit Games was one for the history books The adaptive athletes demonstrated resilience and drive across three days of fierce competition in their bid to become the Fittest on Earth Ole Kristian Antonsen was in the lead going into the third and final day of competition 50 points ahead of 25-year-old Séraphin Périer in second and collected on his double-unders in Event 7 and walked away with his fourth event win thereby extending his lead over Périer to 75 points Learn more about Antonsen’s story in “Forged by Fire.” Event 9 was the first event for the adaptive competitors inside the Coliseum Rugby player and physiotherapist Elliot Young jumped out to an early lead making short work of his handstand push-ups and holding on for his second event win Young was in fourth place going into the final event 40 points behind 28-year-old Felipe Maturana Infante The event win awarded him enough points to shift the leaderboard in his favor Day 3 Men’s Lower Extremity Final Standings While none of the competitors were able to finish under the time cap Valerie Cohen picked up her fifth event win and extended her overall lead Cohen had first place clinched with a 160-point lead over second place But that didn’t stop her from leaving it all out on the Coliseum floor She won Event 9 and finished the competition with six event wins But Cohen wasn’t the only competitor to rile the crowd in Event 9; the grit and determination of Amy Bream set the stadium ablaze with positive energy Bream is new to the sport of CrossFit and only started training in January of 2021 The push presses in Event 9 were a challenging weight for Bream the rookie approached her bar with a look of determination on her face and finished one more rep before the final buzzer sounded The tearful embrace between Bream and fellow competitor Beth Tannatt after the close of the event displayed the true heart of CrossFit competition Day 3 Women’s Lower Extremity Final Standings Mono-ropes made an appearance in Event 7 as the athletes tackled 324 double-unders continued his dominating performance and picked up his fifth event win Acree and 22-year-old Josue Maldonado had mathematically clinched first and second place But that didn’t stop Acree from taking his sixth event win with a time of 3:19.68 Day 3 Men’s Upper Extremity Final Standings Anne Laure Coutenceau went two for two with event wins on Day 3 The 31-year-old French competitor performed her first CrossFit workout in 2016 and has been hooked ever since Coutenceau won Event 7 and finished Event 9 over a minute ahead of Sabrina Daniela Lopez Day 3 Women’s Upper Extremity Final Standings 25-year-old Brett Horchar was diagnosed with multiple sclerosis (MS) he not only competed in his first-ever CrossFit Games — he established one of the largest point spreads in CrossFit Games history Horchar went into Day 3 sitting at the top of the leaderboard with four event wins and a 220-point lead over second place He was the only competitor to complete Event 7 He closed out the final day of competition with a sixth event win in Event 9 the athletes on the women’s side of the Neuromuscular division were locking horns in the tightest race out of all the adaptive divisions and 45 separated third from Rebecca Shingledecker and Ebby Isbill Shannon Ogar found her double-unders in Event 7 and took the event win which moved her to the top of the leaderboard 40 points ahead of 23-year-old Letchen Du Plessis Du Plessis needed an event win and one competitor to finish ahead of Ogar to regain the lead Du Plessis did her part and took the event win But Ogar delivered as well and finished second in the event Ogar finished at the top of the leaderboard Day 3 Women’s Neuromuscular Final Standings Cover photo and podium shots by flsportsguy photography The World's Best Bar and The Best Bar in Europe 2023 We have added a new feature - video hosting Please click here to upload videos and insert them in your post By logging in to LiveJournal using a third-party service you accept LiveJournal's User agreement Françoise Hardy and Jacques Dutronc by Jean-Marie Périer, 1967 has been named supervisor of public art in the redesigned Riverfront Park the Spokane Park Board and Spokane Arts jointly announced last week Yoon, the first woman to head the Department of Architecture at the Massachusetts Institute of Technology, is most famous for designing a display honoring Sean Collier, the MIT police officer slain by the Boston Marathon bombers, and “White Noise/White Light,” a fiber optic art display featured at the 2004 Olympic Games in Athens said Yoon was selected from a field of 83 nationwide applicants for her experience working with communities to deliver public artwork with local flair an artist that would engage with the public,” Becker said 2-acre island splitting the upper Spokane Falls will have another name an as-yet-undecided moniker that will be selected by the Spokane Tribe of Indians which is expected to occur in the coming months “We were happy to be caretakers of the island for that period of time,” Hill said last week “We’re equally honored to participate in a ceremony that gave it back to a First Nations people.” which City Councilwoman Candace Mumm said likely would be in the Salish language the tribe will be responsible for making decisions about artwork on the island as part of the massive renovation of Riverfront Park over the next five years to see what they want,” said Fianna Dickson spokeswoman for the Spokane Parks Department confirmed leaders were discussing possible names for the island The renaming was announced at a ceremony involving Spokane park officials Hill and the tribe during the Gathering at the Falls Pow Wow in August was an important fishing ground for area tribes it was the farthest that migrating salmon could swim up the Spokane River The site of the city’s first water pumping facility the island was purchased by the city in August 1972 from Crystal Laundry which was the sole occupant of the island for 68 years The island had been known as Crystal Island for the laundry business headquartered there for decades banker and second mayor Anthony McCue Cannon designer of the city’s first upriver dam and the man who historically has borne much of the blame for the city’s catastrophic 1889 fire Some news accounts of the time reported Jones and those left at the pumping station didn’t know how to produce the water necessary to fight the quickly spreading flames that would level much of the city Rolla’s daughter told The Spokesman-Review in 1974 that her father had left someone else in charge that day Canada’s government initially was hesitant to participate in the 1974 World’s Fair in Spokane due to a lagging economy Canadian officials eventually decided on a modest presentation at the fair: an amphitheater and playground made from recycled wood and other materials The island’s ties both to Canada and to native tribes dates back to Expo ’74 and beyond was hand-carved during the exposition by Joe David a member of the Clayoquot tribe in British Columbia one of the founders of Crystal Laundry and an early Spokane businessman A resolution signed in March 1974 renamed the island Canada Island and a subsequent resolution by the City Council in August of that year requires that the American and Canadian flags fly above the island “in perpetuity,” which they continue to do today said the city is still discussing with the tribe whether the flags will remain and possibly be joined by other flags Hill said the decision should be left to local stakeholders “It’s certainly not an expectation” that the Canadian flag would remain Canada Island became a popular spot for weddings and an annual Halloween scarefest sometimes being rebranded as “Haunted Island” for the month of October A 15-foot-tall slide that resembled a crow was moved from the island after Expo ’74 and wound up in the driveway of Frank W in 1978 as a “gag” gift by some friends for his 40th birthday you’re more likely to see parkgoers looking down at their smartphones near the totem poles and amphitheater The island became a popular spot for players of the mobile game “Pokemon Go” this summer The City Council expects to receive a name suggestion from the tribe in the coming weeks when they would rescind the resolution naming the island for Canada and pass a resolution to adopt the tribe’s name Canada Island’s name change follows a resolution from the City Council renaming Columbus Day to Indigenous Peoples’ Day last month and the naming of the plaza next to City Hall in 2014 as “The Gathering Place,” honoring the historic trading location of the Spokane Tribe Hill applauded Spokane’s efforts honoring the native history of the region saying they aligned with the government of Canada under new Prime Minister Justin Trudeau to revisiting some decisions that made sense at the time but they don’t necessarily make sense now,” Hill said Give directly to The Spokesman-Review's Northwest Passages community forums series -- which helps to offset the costs of several reporter and editor positions at the newspaper -- by using the easy options below Gifts processed in this system are tax deductible Get breaking news delivered to your inbox as it happens TDS Telecommunications continues expanding its high-speed all-fiber internet network into more Spokane-area neighborhoods © Copyright 2025, The Spokesman-Review | Community Guidelines | Terms of Service | Privacy Policy | Copyright Policy \nAs we drive forty kilometres out of Thakkek District in Khammuane Province on red earth road we arrive at Laphathong School in Nassad District of Khammuane Province Children were getting ready to be vaccinated for Japanese Encephalitis (JE) the children were left with relatives and neighbours and asked to remain in the village while some of their parents left to work in the field \nCommunication is vital to a successful campaign when mobilizing and engaging the community made it a point to remain in the village at the time when the health workers visited This has ensured that all children aged 9 months to 14 years received the vaccine they need to protect them against JE You don't have permission to access the page you requested What is this page?The website you are visiting is protected.For security reasons this page cannot be displayed Philip Calvert: I have everybody breathing down my neck: the Admiralty Grubby little men with gabardine raincoats and dandruff Philip Calvert: Well I don't have dandruff Uncle Arthur: Yes, I don't think you need demonstrate your questionable attitude to authority *quite* so early. Lapee is a new industrial standard female toilet for festivals and outdoor events designed for quick and safe use Developed by Gina Périer and Alexander Egebjerg the pink plastic structure has three urinals arranged in a spiral with curving back rests that provide privacy while allowing the user to remain aware of their surroundings Lapee can be linked to an existing sewage system if it's available but it also has its own 1,100 litre tank so it can stand alone and collect liquid waste for processing which means it can be hosed down for cleaning and withstand the knocks of an outdoor event "We had observed that there had been some tests for women's urinals before but they were always installations or something put together on site - nothing fully industrialised The designers studied the form of male urinals to create a solution for people who need to sit down to urinate - a position that leaves people more vulnerable "Guys have to be covered only from the front and the female has to be covered from front and back," Périer told Dezeen "Because it's a urinal to be intimate enough for people to pee have a raised seat and walls that are low enough that users can see over without people being able to look in "You're way more safe than if you're behind a door which is locked and no one can see," she explained "You're also 60 centimetres above the ground We did that so we don't have the vulnerable feeling of squatting down - your eye level is at the same height as someone standing." Périer and Egebjerg hope this design could also be used in disaster recovery situations or refugee camps « go back It’s been an eventful start to the year in Germany, writes Katja Scholz, as the country goes to the polls. Volume 5 - 2014 | https://doi.org/10.3389/fpsyg.2014.00416 This article is part of the Research TopicMultisensory and sensorimotor interactions in speech perceptionView all 25 articles Speech perception for both hearing and deaf people involves an integrative process between auditory and lip-reading information. In order to disambiguate information from lips, manual cues from Cued Speech may be added. Cued Speech (CS) is a system of manual aids developed to help deaf people to clearly and completely understand speech visually (Cornett, 1967) have to combine both types of information in order to get one coherent percept we examined how audio-visual (AV) integration is affected by the presence of manual cues and on which form of information (auditory labial or manual) the CS receptors primarily rely we designed a unique experiment that implemented the use of AV McGurk stimuli (audio /pa/ and lip-reading /ka/) which were produced with or without manual cues The manual cue was congruent with either auditory information Participants were asked to repeat the perceived syllable aloud Their responses were then classified into four categories: audio (when the response was /pa/) fusion (when the response was /ta/) and other (when the response was something other than /pa/ Data were collected from hearing impaired individuals who were experts in CS (all of which had either cochlear implants or binaural hearing aids; N = 8) hearing-individuals who were experts in CS (N = 14) and hearing-individuals who were completely naïve of CS (N = 15) deaf people can merge auditory and lip-reading information into a single unified percept McGurk stimuli induced the same percentage of fusion responses in both groups Results also suggest that manual cues can modify the AV integration and that their impact differs between hearing and deaf people In face-to-face communication, speech perception is a multi-modal process involving mainly auditory and visual (lip-reading) modalities (Sumby and Pollack, 1954; Grant and Seitz, 2000). Hearing-people merge auditory and visual information into a unified percept, a mechanism called audio-visual integration (AV integration). This merging of information has been demonstrated through the McGurk effect (McGurk and MacDonald, 1976) in which integration occurs even when auditory and visual modalities provide incongruent information the simultaneous presentation of the visual velar /ka/ and auditory bilabial /pa/ normally leads hearing-individuals to perceive the illusory fusion alveo-dental /ta/ The McGurk effect suggests that visual articulatory cues about place of articulation are integrated into the auditory percept which is then modified The AV integration is thus an adaptive process in which the respective weights of each modality depend on the level of uncertainty in auditory and visual signals Figure 1. Cues in French Cued Speech: hand-shapes for consonants and hand placements for vowels. Adapted from http://sourdsressources.wordpress.com These results reverse the classic way of considering the CS system: manual cues could be the primary source of phonological information for deaf CS-users Despite the fact that manual cues are artificial they might constitute the main source of phonological information and labial information would then be used to disambiguate this manual information Alegria and Lechat (2005) studied the integration of articulatory movements in CS perception they investigated the relative influence of labial and manual information on speech perception with normal intelligence and schooling) were split into two groups depending on their age of exposure to CS (early or late) They were asked to identify CV syllables uttered without manual cues (lip-reading alone) or with manual cues (Cued Speech) lip movements and manual cues were either congruent (e.g. lip-reading /ka/ and hand-shape n°2 lip-reading /ka/ and hand-shape n°1 Identification scores were better in the congruent and lip-reading alone condition than when syllables were presented with incongruent manual cues participants reported syllables coded with the same manual cues as the actual syllables Between the different syllables coded by a matching manual cue deaf participants selected the one that had less visible lip movements; that is the one that was less inconsistent with lip information presented in the syllable stimuli the lip movements /ka/ with hand-shape n°1 (coding /d Ʒ/) was perceived as /da/ which is less visible on the lips than /pa/ and /Ʒa/ This suggests an integrative process between lip and manual cue information deaf children who were exposed to CS early (prior to 2 years) integrated manual cue and lip-read information better than deaf children who were exposed to CS later (after 2 years) when lip-read information and manual cues diverge participants choose a compromise that is compatible with manual information and not incompatible with the lip-read one The goal of the present research was to examine how manual cue information is integrated in AV speech perception by deaf and hearing participants We wondered whether (1) CS receptors combine auditory lips and manual information to produce a unitary percept; (2) on which information (auditory labial or manual) they primarily rely; and (3) how this integration is modulated by auditory status To address these issues we designed the first experiment using audio-visual McGurk stimuli produced with manual cues The manual cue was either congruent with auditory information lip information or with the expected fusion We examined whether or not these experimental conditions would impact the pattern of responses differently for deaf and hearing subjects hereafter referred to as the CS-hearing group Two of them had close relatives that were deaf; the rest were students in speech therapy and had participated in CS training sessions The third group consisted of 15 hearing-individuals who had never been exposed to CS (mean age: 23 years) hereafter referred to as the control hearing group All participants were native French speakers with normal or corrected-to-normal vision and did not have any language or cognitive disorder. In order to assess CS knowledge level, a French CS reception test was administered to all participants (TERMO). Scores groups and participants are indicated in Appendix, Table A1 The experimental protocol was approved by the ethical committee of the Faculty of Psychological Science and Education (Université Libre de Bruxelles) All participants provided informed consent indicating their agreement to participate in study They were informed they had the option to withdraw from the study at any time A female French speaker was videotaped while uttering CV syllables consisting of one of the /p, k, t/ consonants articulated with /a/ (Figure 2) Video frame of lip-reading with congruent cue condition (A) Two uni-modal and four multi-signal congruent conditions were created (see Table 2) Each stimulus from the congruent conditions was presented 6 times Stimulus composition of congruent control conditions Stimuli were also presented in incongruent conditions. Incongruent AV syllables were created by carefully combining audio files /pa/ with non-corresponding video files /ka/ and matching their onset. Four incongruent conditions were created which consisted of McGurk stimuli (audio/pa/ and lip-reading /ka/) presented with or without manual cues (see Table 3) Each stimulus from the incongruent condition was presented 6 times The composition of McGurk stimuli in incongruent conditions The experiment took place in a quiet room. Videos were displayed on a 17.3 inch monitor on a black background at eye level and at 70 cm from the participant's head. The audio track was presented at 65 dB SPL (deaf participants used their hearing-aids during the experiment). On each trial, participants saw a speaker's video (duration 1000 ms; see Figure 2) They were then asked to repeat aloud the perceived syllable Their answers were transcribed by the experimenter The experiment consisted of 120 items (16 × 6 congruent stimuli and 4 × 6 incongruent stimuli) presented in two blocks of 60 items participants were shown five training items The total duration of the experiment was approximately 30 min we wanted to compare participants according to two criteria: auditory status (hearing vs Mann-Whitney tests were used to compare hearing (CS and non-CS together) with deaf groups and to compare CS users (deaf and hearing together) with the control group participant 2 had a low level of auditory recovery When data were re-analyzed without this atypical participant the outcome remained unchanged: Deaf and hearing-individuals had the same percentage of correct responses for the stimulus /pa/ (U = 91; p = 0.373) the CS-deaf group had more difficulty than the two hearing groups in identifying stimuli /ta/ (U = 29; p < 0.005) and /ka/ (U = 43.50; p < 0.005) the addition of cues improved the percentages of correct answers for the CS-deaf group nonetheless the hearing groups still had more correct responses for /pa/ (U = 73.5; p < 0.05) /ta/ (U = 31.5; p < 0.001) and /ka/ (U = 87; p < 0.01) Mean percentages of correct responses for all groups in Audio-Only and Audio + CS cue conditions Mean percentages of correct responses for all groups in Lip-reading-Only and Lip-reading + CS cue conditions Mean percentages of correct responses for all groups in Audio + Lip-reading (LR) and Audio + LR + CS cue conditions participants had the same percentage of correct responses for /pa/ Participant responses were classified into four categories: audio (when the response was /pa/) fusion (when the response was /ta/) and other we used Mann-Whitney tests to compare hearing (CS and non-CS together) with deaf groups the Wilcoxon test was used to compare response patterns between baseline and other experimental conditions As illustrated in Table 7 deaf and hearing-individuals had the same percentages of fusion (p = 0.39) and auditory (p = 0.18) responses Mean percentages of each kind of response (audio fusion and other) for all groups in incongruent conditions Response patterns for each group in the McGurk-audio condition are shown in Table 7 Ʒ/ cue reduced the percentage of fusion responses in the CS-deaf group (p = 0.03) in favor of other responses congruent with cue information (60% of other responses: 38% of /da/ and 19% of /Ʒa/) the addition of cue n°1 reduced the percentage of fusion responses (p = 0.001) and increased auditory responses from 17% to 60% (p = 0.003) the addition of the cue had no effect on the response pattern reduced the percentage of fusion responses (p = 0.02) and increased the percentage of lip-reading responses (p = 0.03) some participants responded with the alternative the addition of cue n°2 also decreased fusion responses (p = 0.002) and increased lip-reading responses (p = 0.003) the addition of cue had no effect on the response pattern In all groups, the addition of the cue coding /m, t, f/ had no effect on response patterns (see Table 7) There was no increase of fusion responses when compared to the baseline condition The goal of the present study was to examine how manual cue information is integrated in AV speech perception We examined whether CS receivers can combine auditory lip and manual information to produce a unitary percept We expected that CS would modulate the respective weights of lip-read and auditory information differently the addition of cues decreased performance for the control group It seems as though the CS cue served as a distractor for this group causing a disruption in responses Their attention could have been drawn to the hand gesture resulting in less focus on lip-read information Compared to the Lip-reading-Only condition the addition of cues decreased their percentages of correct responses the presence of hand information possibly unbound audio and visual information Being more attracted to irrelevant hand information than by lip information participants tended to not integrate AV information resulting in fewer fusion responses and favoring auditory responses deaf individuals did not tend to report more responses based on visual information than hearing-participants One explanation might be that deaf and hearing-individuals both exhibited comparable levels of performance in uni-modal conditions: percentages for identification of the auditory syllable /pa/ and the lip-reading syllable /ka/ did not differ between neither deaf nor hearing groups Whereas manual cues decreased fusion responses in both hearing- and deaf-CS users their effect on other responses depended on auditory status the addition of manual cues congruent with auditory information (but not with lip-read information) increased only audio responses for /pa/ in the CS-hearing group but not in the CS-deaf group fusion responses decreased in favor of other responses despite their good performance in the Audio-Only condition (85%) CS-deaf users seemed more confident with visual information (such as lip-read or manual cues) They were unable ignore lip-read information and relied more heavily on such information than on auditory The addition of manual cues congruent with lip-read information increased lip-reading responses in both groups These results suggest that deaf- and hearing-CS users are capable of ignoring auditory information when such information is contradicted by lip-reading or manual cues As the CS system is not necessarily used with auditory information ignoring auditory information could be easier deaf-CS receptors first integrate manual and lip information before taking auditory information into account deaf-CS users cannot ignore manual information the deaf-CS user group was too small of a sample to be split into two groups according to the participants' auditory recuperation We were therefore not able to examine the effect of auditory recuperation on the nature of integration processes Auditory status and auditory abilities were thus confounded (A) Sequential model with late integration of manual cue; (B) Sequential model with early integration of manual cue; (C) Simultaneous model with early integration of manual cue and fusion responses to McGurk audio-visual stimuli are relative to CI proficiency CI children who are AO− seemed to rely more on vision and CI children who are AO+ seemed to rely more on auditory information Although these studies analyzed AV perception without cues they reinforce our proposition that we should distinguish AO+ and AO− profiles in future studies of speech perception in participants with CI and CS Auditory and visual features are assessed and compared to prototypes stored in memory Comparison is based on a continued value scale and is independent in each modality Values of each feature are integrated in order to determine the degree of global adequacy of sensory input with each prototype in memory The prototype that is the most consistent with the features extracted during the uni-modal assessment will be the percept heard One important issue in this model is the fact that the influence of each source of information depends on its ambiguity all individuals integrate AV information optimally all differences in the percept have to be explained by differences within the initial They tested the robustness of bias toward the visual modality in McGurk stimuli perception in CI users they designed an experiment in which the performances were compared in a “visual clear” condition and a “visual reduction” condition in which the visual speech cues were degraded Results showed that “visual reduction” had increased the number of auditory-based responses to McGurk stimuli in normally-hearing as well as CI children (whose perception is generally dominated by vision) The authors used both FMLP and WFLMP to determine whether the differences in response patterns between “visual reduction” and “visual clear” conditions occurred at the uni-modal processing stage or at the integration stage The FLMP model better fits the data in the “visual reduction” condition when an additional weight is applied to the auditory modality The degradation of visual information seems to have an impact on speech perception not only at the uni-modal stage of processing but at the integrative processing level WFLMP seems to be a relevant model to explain AV speech perception in CI-users our studies have not allowed us to choose between these three hypotheses It is clear that manual cue could impact AV integration our behavioral data are not sufficient to determine whether this impact occurs early (as in the first hypothesis) or later (as in the second hypothesis) we have learned that deaf participants are capable of ignoring auditory cues whereas they cannot ignore labial or manual information we aim to analyze more precisely the effect of auditory efficiency on speech perception In natural speech (without CS), humans speak and spontaneously produce gestures to support what they are saying. Analysis of speech and symbolic gesture production in adults suggest that both “are coded as a unique signal by a unique communication system” (Bernadis and Gentilucci, 2006). In addition, gestures play a crucial role in language development and a co-development of speech and signs exists (for a review see Capone and McGregor, 2004) Thus gesturing seems to be a genuine component of multi-modal communication CS cues are created specifically for communication Due to this privileged link between gestures and language it is probable that these cues are naturally integrated into multi-modal communication it is difficult to ignore information provided by a cue Speech perception is a multimodal process in which different kinds of information are likely to be merged: naturally and relevant information (provided by lip-reading and audition) naturally but irrelevant information (like in audio-aerotactile integration) or non-natural but relevant information (such as CS cues) Findings from our work also suggest that the integration of different types of information (e.g. manual cues) related to a common source (i.e. the production of a speech signal) is a flexible process that depends on the informational content from the different sources of information as well as on the auditory status and hearing proficiency of the participants We thank Marie Devautour for her help in collecting data Carol LaSasso and Jeromy Hrabovecky for their comments suggestions and corrections of previous versions of this manuscript This work was financially supported by grant 2.4539.11 from the Fonds National de la Recherche Scientifique (FRS-FNRS Belgium) to Jacqueline Leybaert and Cécile Colin Clémence Bayard is funded by a Mini Arc award (ULB) for her PhD Thesis Reconnaissance de la Langue Française Parlée Complétée (LPC): Décodage Phonétique des Gestes Main-Lèvre Institut National Polytechnique de Grenoble Phonological processing in deaf children: when Lip-reading and Cues are incongruent Pubmed Abstract | Pubmed Full Text | CrossRef Full Text La Langue Française Parlée Complétée: Production et Perception A pilot study of temporal organization in Cued Speech production of French syllables: rules for a Cued Speech synthetizer CrossRef Full Text Development of audiovisual comprehension skills in prelingually deaf children with cochlear implants Pubmed Abstract | Pubmed Full Text | CrossRef Full Text Speech and gesture share the same communication system Pubmed Abstract | Pubmed Full Text Gesture development: a review for clinical and research practices Pubmed Abstract | Pubmed Full Text | CrossRef Full Text The rhyming skills of deaf children educated with phonetically augmented speechreading Pubmed Abstract | Pubmed Full Text | CrossRef Full Text Relation between deaf children's phonological skills in kindergarten and word recognition performance in first grade Pubmed Abstract | Pubmed Full Text | CrossRef Full Text Auditory-visual speech perception in normal-hearing and cochlear-implant listeners Pubmed Abstract | Pubmed Full Text | CrossRef Full Text A 12-consonant confusion study on a multiple-channel cochlear implant patient Pubmed Abstract | Pubmed Full Text visual and auditory visual recognition of consonants by children with normal and impaired hearing Pubmed Abstract | Pubmed Full Text Language skills of children with early cochlear implantation Pubmed Abstract | Pubmed Full Text | CrossRef Full Text The use of visible speech cues for improving auditory detection of spoken sentences Pubmed Abstract | Pubmed Full Text | CrossRef Full Text visual and auditory-visual perception of vowels by hearing impaired children Pubmed Abstract | Pubmed Full Text Degradation of labial information modifies audiovisual speech perception in cochlear-implanted children Pubmed Abstract | Pubmed Full Text | CrossRef Full Text Comparison of speech recognition with different speech coding strategies (SPEAK and ACE) and their relationship to telemetric measures of compound action potentials in the nucleus CI 24M cochlear implant system Pubmed Abstract | Pubmed Full Text | CrossRef Full Text Use of audiovisual information in speech perception by prelingually deaf children with cochlear implants: a first report Pubmed Abstract | Pubmed Full Text | CrossRef Full Text Audiovisual segregation in cochlear implant users Pubmed Abstract | Pubmed Full Text | CrossRef Full Text Rhyme generation in deaf students: the effect of exposure to Cued Speech Pubmed Abstract | Pubmed Full Text | CrossRef Full Text Phonology acquired through the eyes and spelling in deaf children Pubmed Abstract | Pubmed Full Text | CrossRef Full Text Le rôle des informations visuelles dans le développement du langage de l'enfant sourd muni d'un implant cochléaire CrossRef Full Text Speech Perception by Ear and Eye: A Paradigm for Psychological Inquiry Pubmed Abstract | Pubmed Full Text | CrossRef Full Text Cued speech and the reception of spoken language Pubmed Abstract | Pubmed Full Text Périer Evaluation of the effect of prolonged Cued Speech practice upon the reception of spoken language McGurk effects in cochlear-implanted deaf subjects Pubmed Abstract | Pubmed Full Text | CrossRef Full Text Auditory-visual fusion in speech perception in children with cochlear implants Pubmed Abstract | Pubmed Full Text | CrossRef Full Text A reanalysis of McGurk data suggest that audiovisual fusion on speech perception is subject-dependant Pubmed Abstract | Pubmed Full Text | CrossRef Full Text Identification of speech by cochlear implant recipients with the Multipeak (MPEAK) and Spectral Peak (SPEAK) speech coding strategies II Pubmed Abstract | Pubmed Full Text | CrossRef Full Text Visual contribution to speech intelligibility in noise CrossRef Full Text De la Perception Audiovisuelle des Flux Oro-Faciaux en Parole à la Perception des Flux Manuo-Faciaux en Langue Française Parlée Complétée A Perceptual Desynchronization Study of Manual and Facial Information in French Cued Speech Performance over time of adult patients using the Ineraid or nucleus cochlear implant Pubmed Abstract | Pubmed Full Text TERMO scores by group and participant for Audio-Only and Visual with CS (V + CS) cue conditions Colin C and Leybaert J (2014) How is the McGurk effect modulated by Cued Speech in deaf and hearing adults Received: 31 January 2014; Accepted: 21 April 2014; Published online: 19 May 2014 Copyright © 2014 Bayard, Colin and Leybaert. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) *Correspondence: Clémence Bayard, Laboratoire Cognition Langage et Développement, Center for Research in Cognition and Neurosciences, Université Libre de Bruxelles, 50 Avenue Franklin Roosevelt – CP191, 1050 Brussels, Belgium e-mail:Y2xlbWVuY2UuYmF5YXJkQHVsYi5hYy5iZQ== February 13, 2017 08.37 Europe/London By Broadband TV News Correspondent “Go OTT or go home” — for the TV industry OTT hasn’t merely joined the mainstream; it’s driving global broadcast strategies You’ll see how in Ooyala’s new State of the Broadcast Industry 2017 Report the ideas and the numbers that will drive video in the coming year 41% of US pay TV customers say they plan to shave or cut the cord in the next year consumers are getting video on their time and their terms Download the report by completing the form below Your details may be shared with our partner Ooyala Submitting this form signifies your permission to do so Filed Under: White Papers Edited: 13 February 2017 08:40 July 12, 2011 09.32 Europe/London By Julian Clover GlobeCast has named Philippe Rouxel as its new chief marketing officer with a brief to develop the company’s global product strategy across all business units in France He will lead the implementation of a strategy focused on value-added products in the broadcast market Rouxel has spent the last four years as vice president of international distribution for France 24 he held business development positions with channels belonging to Lagardère Rouxel graduated from EDHEC and CELSA Paris-Sorbonne Filed Under: Newsline, People Edited: 12 July 2011 09:32 Julian Clover is a Media and Technology journalist based in Cambridge, UK. He works in online and printed media. Julian is also a voice on local radio. You can talk to Julian on X @julianclover, or by email at jclover@broadbandtvnews.com