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Background People with cystic fibrosis (pwCF) are central in the development of patient-led assessment tools. Qualitative analysis of a frequently used CF-specific patient-reported outcome measure (PROM) sought patient recommendations for development of a new quality of life (QoL) tool. Methods We performed an inventory of PROMs, symptom-report and QoL tools used in clinical trials within the European Cystic Fibrosis Society Clinical Trial Network (ECFS-CTN) and in routine clinical practice among Cystic Fibrosis Europe and ECFS members. A qualitative study using cognitive interviews with pwCF and their caregivers reviewed the Cystic Fibrosis Questionnaire (CFQ), the French initial form of the Cystic Fibrosis Questionnaire-Revised (CFQ-R). Results Survey results from 33 countries revealed over 70 tools used in routine clinical practice, utilized by clinical specialists (n=124), pwCF/parents/carers (n=49) and other allied health professionals (n=60). The CFQ-R was the main PROM used in clinical trials. The qualitative study enrolled 99 pwCF, 6 to 11 years (n=31); 12 to 18 years (n=38); >18 years (n=30) and 26 parents. Inductive thematic analysis based on the CFQ, revealed 19 key themes. Themes common across all cohorts included burden of treatment, impact of disease on day-to-day life, relationships/family, stress/mood, and nutrition. Themes unique to individual groups included, treatment when not symptomatic for the paediatric group; education/studies and planning for the future for adolescents, impact of anxiety and depression on day-to-day life for adults, and for parents, questions addressing anxiety and their role as carers. Conclusions Patient-centeredness is paramount in development of an up-to-date PROM in the era of novel therapies.

Aperçu des deux événements de co-création réalisés en mars et octobre 2019 avec les hôpitaux Necker, Cochin et le Fonds FHF de la Fédération hospitalière de France. L'objectif était de rendre le soin ludique en co-créant des jeux avec des jeunes de 16-24 ans qui ont la mucoviscidose. Nous avons adopté une méthode de conception participative pour concevoir deux jeux numériques (dont un multijoueur) et un capteur transformant le souffle (pression, débit) en signal numérique., Vidéo : télécharger le fichier m4a ci-dessous ou aller sur https://youtu.be/ZHMKuNcmiQQ – Découvrir et contribuer au projet : https://www.breathinggames.net/fr/

Cystic fibrosis, a rare, hereditary and chronic disease, affects the psychic functioning of children and their families. Since it is incurable, constant adjustments are essential to make sense of the inevitable evolution of the disease. The psychologists support the families and the patients so that all live as well as possible with cystic fibrosis.

Poster presented at the General Meeting of the Global Alliance against Respiratory Diseases in Beijing. Background: Worldwide, 6 people out of 10 have no access to treatment, or are not encouraged to follow it. Air pollution alone kills 7 million people yearly, reduces our life expectancy by 20 months, and costs 6% the gross world product. Devices to assess lung capacity remain often unavailable in low / middle income countries. Actions: We co-create inclusive, open science knowledge: open source breath and air quality controllers, and libre / gratis education to reduce risks and make care fun. Learnings: Awareness: breath as a way to feel life, from childhood. Universal health: mutualizing resources to end poverty. Partnership: reducing barriers with remote participation. Also watch our 2018 and 2017 posters: Next-gen advocacy for respiratory health: fun, empowering, participatory, freely adaptable When populations care about their respiratory health: a scalable bottom-up model to foster self-care for all

Cystic fibrosis, a rare, hereditary and chronic disease, affects the psychic functioning of children and their families. Since it is incurable, constant adjustments are essential to make sense of the inevitable evolution of the disease. The psychologists support the families and the patients so that all live as well as possible with cystic fibrosis.

Developments in managing CF continue to drive dramatic improvements in survival. As newborn screening rolls-out across Europe, CF centres are increasingly caring for cohorts of patients who have minimal lung disease on diagnosis. With the introduction of mutation-specific therapies and the prospect of truly personalised medicine, patients have the potential to enjoy good quality of life in adulthood with ever-increasing life expectancy. The landmark Standards of Care published in 2005 set out what high quality CF care is and how it can be delivered throughout Europe. This underwent a fundamental re-write in 2014, resulting in three documents; center framework, quality management and best practice guidelines. This document is a revision of the latter, updating standards for best practice in key aspects of CF care, in the context of a fast-moving and dynamic field. In continuing to give a broad overview of the standards expected for newborn screening, diagnosis, preventative treatment of lung disease, nutrition, complications, transplant/end of life care and psychological support, this consensus on best practice is expected to prove useful to clinical teams both in countries where CF care is developing and those with established CF centres. The document is an ECFS product and endorsed by the CF Network in ERN LUNG and CF Europe.

Life expectancy is increasing in cystic fibrosis and new aspects of the disease have to be taken into account in cystic fibrosis care.Pain is encountered among 70% of adult and pediatric patients with cystic fibrosis. This symptom is underestimated by the multidisciplinary team. It has been reported as impacting quality of life and adherence to treatments. The location of pain is inconstant among the different studies but the major symptoms are headaches, gastrointestinal, and chest pain. Pain is different for each patient and requires careful evaluation using questionnaires some of which specifically developed for patients with cystic fibrosis. Medical and nonmedical treatment such as ostheopathy or sophrology may relieve pain symptoms but have to be adjusted in the frame of a global personalized care.Pain maybe an underestimated symptom among patients with cystic fibrosis and impacts negatively on quality of life. VIDEO ABSTRACT.

In France patients with cystic fibrosis benefit from a multidisciplinary follow-up in Cystic Fibrosis Centres. In this follow-up, despite the numerous therapeutic benefits of exercise in this disease, little emphasis is placed on the promotion of physical activity. The aim of this article is to improve this aspect of management, giving advice from a working group of experts, based on the medical literature and clinical experience. These proposals include quantification of physical activity, evaluation of exercise, training and rehabilitation programs and finally, modification of behaviour to include physical activity in the overall cystic fibrosis treatment strategy. It is intended to set up multicentre studies to evaluate the impact of these proposals.

L’infection SIV induit la perte d’expression des facteurs de transcription Stat5a et Stat5b dans les cellules CD34+ Les patients infectes par le virus d’immunodeficience humaine (VIH) manifestent, en dehors des lymphopenies, de multiples deficiences hematologiques associees au syndrome d’immuno-deficience acquise (Sida). Ces deficiences combinees refletent un dysfonctionnement des cellules souches hematopoietiques (CSH) elles-memes. Pourtant, bien que les fonctions de ces cellules souches soient alterees, aucune sequence virale n’a pu y etre detectee [1], posant la question du mode d’action du VIH dans ce contexte cellulaire. Les memes types de desordres hematologiques caracterisent des singes infectes par le virus apparente SIV (simian immunodeficiency virus) [2]. Afin de comprendre l’origine du dereglement de telles CSH, nous avons infecte des macaques par l’isolat viral SIVmac251 et purifie une population de cellules medullaires contenant les CSH et les progeniteurs hematopoietiques multipotents, sur la base de l’expression du marqueur CD34 [3]. Nous avons observe que la capacite caracteristique de ces cellules a former des clones de differentes cellules hematopoietiques se trouve diminuee d’environ 50 a 60 % par rapport a la meme population issue de singes non infectes. L’analyse comparee des niveaux d’expression de divers facteurs transcriptionnels actifs dans cette population cellulaire CD34+ a revele la perte selective d’expression des facteurs Stat5a et Stat5b dans les progeniteurs hematopoietiques des animaux infectes. Cette perte est decelable tres tot apres l’administration de virus aux animaux et se maintient tout au long de l’infection (Figure 1). La simple introduction dans les CSH des singes malades d’un vecteur permettant l’expression du transgene Stat5b, conduit au retablissement de leurs proprietes clonogeniques [3]. Ces facteurs Stat5a/b sont des molecules de signalisation ubiquitaires, frequemment activees par des cytokines et facteurs de croissance, qui peuvent directement convertir le message d’une cytokine/facteur de croissance en une regulation de l’expression de genes particuliers grâce a leur double propriete de circuler du cytoplasme au noyau et d’agir comme facteurs de transcription. L’absence de ces facteurs chez la souris knock-out avait deja revele le role de Stat5a/b dans le maintien de CSH fonctionnelles capables de reconstituer l’hematopoiese de souris irradiees [4, 5]. Le fait que la seule reintroduction Vers un nouveau role du recepteur PPAR-g dans le syndrome d’immunodeficience acquise et les hemopathies chez l’homme Stephane Prost1, 2, 3, 9, Mikael Le Dantec1, 9, Sylvie Auge4, 5, Roger Le Grand1, Sonia Derdouch1, Gwenaelle Auregan1, 6, Nicole Deglon6, Francis Relouzat2, 3, Anne-Marie Aubertin7, Bernard Maillere8, Isabelle Dusanter-Fourt4, 5, 10, Marek Kirszenbaum1, 10 Institut des Maladies Emergentes et des Therapies Innovantes, 1 Service d’Immuno-Virologie et 2 Service des Therapies Innovantes, CEA, Fontenay-aux-Roses, France. 3 UMR U733 Inserm-CEA-Paris XI, CEA, Fontenay-aux-Roses, France. 4 Institut Cochin, Universite Paris Descartes, CNRS (UMR8104), Paris, France. 5 Inserm, U567, Paris, France. 6 CEA, I2BM et programme MIRCen, Orsay, France. 7 Laboratoire de Virologie, Universite Louis Pasteur, Strasbourg, France. 8 CEA, Departement d’Ingenierie et d’Etude des Proteines, Saclay, France. 9, 10 Ces auteurs ont respectivement contribue de facon identique a ce travail stephane.prost@cea.fr DERNIERE HEURE

Person First Language has been around for thirty years yet remains confined to the borders of government agencies, special education classrooms, and professional psychology. Beginning here in Salem, Oregon as an offshoot of the People First Movement (Wehmeyer, Bersani, & Gagne, 2000), a self-advocacy group for persons with disabilities at Fairview Rehabilitation Center. It has since grown from an isolated appeal into an international movement and is the current accepted terminology in the APA and reflects in the language of all pertinent government acts (ADA, IDEA, etc.). Despite all these well intended improvements everyday use of PFL by non-laypersons has not increased, even when the disabled community asks for it. This paper reviews the existing literature and data on Person First Language to discover why and seeks to determine means of increasing Person First Language awareness and use. Since the literature and studies have been extremely limited on PFL and spanning a broad range of disciplines, they have been condensed and presented in this comprehensive review. A survey has also been developed and proposed to test the efficacy of PFL awareness training to perhaps fill this gap in our current understanding. PERSON FIRST PLANET iii Dedication / Acknowledgements I would like to thank first and foremost Tiffany Jones, for all her knowledgeable support in the drafting of this paper. I would like to thank Portland State Special Education Department for all their guidance and support. To all my friends and family who have encouraged me along the way, with a special thanks to Solomon for all his countless hours keeping me focused. I would also like to acknowledge you, the reader, for participating. A category such as a number (singular vs. plural) is an attempted interpretation of a large order of experience, virtually of the world or of nature; it attempts to say how experience is to be segmented, what experience is to be called “one” and what “several.” Benjamin Lee Whorf PERSON FIRST PLANET iv

Receptor tyrosine kinases (RTKs) mediate cellular responses to the extracellular signals involved in the regulation of cell differentiation and proliferation. Ligand binding initiates a cascade of events, such as receptor dimerization and tyrosine phosphorylation. The c-kit gene encodes an RTK for stem cell factor (SCF), (c-kit ligand, KL), both of which play a critical role in the differentiation and growth of haemopoietic stem cells (HSCs). We investigated the expression of the c-kit and SCF genes and the presence of the corresponding proteins in haemopoietic tissues during human embryogenesis. We have examined c-kit and SCF transcripts levels in human embryonic yolk sac, the AGM region, and liver at different stages of gestation (days 25 to 63), using RT-PCR amplification combined with PhosphorImager quantitative analysis and RNase Protection Assay (RPA). Weak levels of SCF gene expression were observed in the AGM region (days 25 to 34) and high levels were found in the early-stage liver (day 34). The expression of c-kit transcript was observed in all studied tissues, but at various levels. The restricted presence of SCF protein following mRNA expression was demonstrated in embryonic liver CD38+ haemopoietic cells by immunocytochemistry. These observations suggest that the biological function of the c-kit receptor plays an important role in the early stages of human haemopoiesis, and that c-kit/SCF signalling is particularly involved in early human definitive haemopoiesis.

HLA-G expression is restricted to human trophoblasts and HLA-G may play an important role in immune tolerance of mother-versus-fetus. HLAG, A HLA class I antigen, was classified as non-classical because of its low polymorphism and restricted expression. Comparison of the genomic HLA-G sequences from the LCL721.144 cell line (allele G*01011) (Geraghty et al., 1987), from the Ice 6.23 clone (allele G*0102) (Pook et al., 1991), and from the Japanese placenta clone 7.0E (allele not officially assigned) (Tamaki et al., 1993), as well as the cDNA sequence from the BeWo cell line (allele G*01012) (Ellis et al., 1990) and the ARS53 clone (allele G*01011) (Shukla et al., 1990) show only eight substitutions in the coding region, all of which are synonymous in exons 1, 2, 3. Moreover, 24 substitutions were observed in noncoding regions of the genomic sequences (introns) (Tamaki et al., 1993). Sequence analysis of substitutions within exons 2 and 3 from 59 homozygous typing cells (HTCs) permitted assignment of four HLA-G alleles: G* 01011, G*II, G*0103, and G*01013 (Morales et al., 1993). Only G*0103 allele presents a nonsynonymous (A“T), but conservative, (Thr“Ser) substitution at the codon 31. Van der Ven and Ober, (1994) have been the

HLA-G is a non-classical major histocompatibility complex class I molecule selectively expressed on extravillous trophoblast cells at the fetal-maternal interface. HLA-G may play an important role in maintaining maternal immune tolerance of the semi-allogenic fetus. In this study, we demonstrate for the first time the protective role of HLA-G during pregnancy. Indeed, cytotrophoblast cells of the fetus are resistant to lytic activity by maternal decidual natural killer cells. In order to precisely characterize the immunological functions of HLA-G products, we have investigated the protective role of the membrane-bound HLA-G1 and HLA-G2 isoforms against NK cell cytotoxicity. For this purpose, HLA-G1 and HLA-G2 cDNAs were transfected into the HLA-class I negative human K562 cell line. We demonstrate that both HLA-G1 and HLA-G2 transfectants inhibit NK cytolysis observed in peripheral blood from 25 donors (males and females). This led us to the conjecture that HLA-G is the public ligand for natural killer inhibitory receptors present in all individuals.

The HLA-G antigen is specifically expressed on trophoblasts at the maternal-fetal interface, while expression of classical class I HLA-A, -B, -C products is repressed in this tissue. The transcriptional level of the HLA-G gene is high in trophoblast cells and in JEG-3 choriocarcinoma cells, is markedly reduced in blood cells, and is shown here to be undetectable in the YT2C2 NK cell line. In an attempt to understand molecular mechanisms controlling cell-specific transcriptional regulation of the HLA-G gene in these cells, we focused our study on protein interaction with a 244-bp region located over 1.1 kb from exon 1, which has been shown to direct HLA-G expression in transgenic mouse trophoblast. Three specific complexes were detected, two of which are found exclusively in cells showing HLA-G transcriptional activity. The YT2C2 nuclear extracts contain restricted DNAbinding activity of an additional factor which could correlate with repression of HLA-G transcription in these cells.

The HLA-G nonclassic MHC class I gene expressed at the maternal-fetal interface may be involved in cell protection against NK cell lysis. HLA-G mRNA is observed in different adult or fetal human cells and exhibits four alternative forms: HLA-G1, HLA-G2, HLA-G3, and HLA-G4 lacking, respectively, exon 7; exons 7 and 3, exons 7, 3, and 4; exons 7 and 4. Because exon 5 encodes the transmembrane domain of the HLA-G antigen, none of these transcripts could give a soluble form as detected in supernatant of trophoblasts. In this report, we describe an additional alternatively spliced for of HLA-G transcript (HLA-G5) present in adult PBMCs and first-trimester trophoblasts that contains intron 4. Moreover, as with all other transcripts, HLA-G5, is devoid of exon 7. Its relative frequency is, respectively, ~ 1:8 and ~ 1:26 in adult PBMCs and first-trimester trophoblasts. The presence of intron 4 generates a stop codon that excludes transmembrane region (exon 5) of the HLA-G molecule and therefore might produce a soluble antigen. These results are discussed with regard to data on soluble forms of classic HLA antigens and the possible role of HLA-G.

The HLA-G monomorphic, nonclassical class I gene encodes the major histocompatibility complex (MHC) molecule, which is the only MHC antigen expressed on cytotrophoblast cells of placenta. In this work, we have investigated expression of the HLA-G gene in fetal tissues and adult peripheral blood cells by using a sensitive hot-start reverse transcriptase PCR technique. PCR amplification with HLA-G primers specific for exon 3 has enabled us to demonstrate an alternatively spliced form of HLA-G mRNA present in fetal first trimester trophoblasts and lacking exon 4 (HLA-G.3-5). This low abundance transcript (approximately 1:200) in comparison to full-length mRNA may encode the protein that excludes the alpha 3 domain and by conformational changes may present a different ability to bind to peptides. Moreover, expression of the HLA-G transcript was found in adult peripheral lymphocytes and equally in B- and T-cell populations. These results are discussed in the context of the fetal-maternal relationship presented by HLA-G gene products.

Resume Nous avons mis au point une technique de PCR in situ pour les genes CD 34 et c-Kit dans des cellules mononucleees du sang peripherique humain. Apres depot et fixation des cellules sur des lames, afin de faciliter la penetration des reactifs necessaire a la PCR, une permeabilisation des membranes est effectuee par traitement a la proteinase K. La PCR terminee, une hybridation in situ est realisee en presence d'un oligonucleotide specifique marque a la digoxigenine. Ce marqueur ainsi lie au produit d'amplification est detecte par un anticorps antidigoxigenine marque par la phosphatase alcaline. L'addition des substrats de cette enzyme (le nitro-bleu tetrazolium [NBT] et le 5-bromo-4-chloro-3-indolyl phosphate [BCIP]) permet une revelation coloree en bleu-noir des cellulles dans lesquelles la PCR a ete realisee. Nous avons egalement montre que meme dans le cas de cellules fixees sur lame, un controle de la reaction d'amplification juste apres la PCR a ete effectue. En effet, la permeabilisation des membranes cellulaires provoque une diffusion du produit d'amplification vers l'exterieur de la cellule. En prelevant apres la PCR in situ le liquide reactionnel au-dessus des cellules, il est possible de visualiser par electrophorese en presence de bromure d'ethidium le produit d'amplification.

In France patients with cystic fibrosis benefit from a multidisciplinary follow-up in Cystic Fibrosis Centres. In this follow-up, despite the numerous therapeutic benefits of exercise in this disease, little emphasis is placed on the promotion of physical activity. The aim of this article is to improve this aspect of management, giving advice from a working group of experts, based on the medical literature and clinical experience. These proposals include quantification of physical activity, evaluation of exercise, training and rehabilitation programs and finally, modification of behaviour to include physical activity in the overall cystic fibrosis treatment strategy. It is intended to set up multicentre studies to evaluate the impact of these proposals.

Flow cytometry is a potential method for the separation of X and Y bearing spermatozoa, on the basis of their relative DNA content evaluated by the fluorescence emission intensity due to specific fluorochrome DNA staining. However, spermatozoa DNA is highly condensed and nuclei exhibit flat non spherical shape, which can produce artefacts impeding accurate analysis. In order to avoid these limitations, decondensation of DNA performed by enzymatic treatment and a modification of the flow cytometer that orients the spermatozoa relative to the laser beam are generally used. In this work, we describe alternative methods and materials for selection of (1) decondensed and thus dead spermatozoa without orientation, sorted on the basis of only the 10% spermatozoa containing the least DNA (expected Y) and the 10% spermatozoa containing the more DNA (expected X), or (2) native spermatozoa homogeneously oriented using a simultaneous measurement of Axial light loss (extinction) and Forward angle light scatter. For testing enrichment of each selected fraction we have worked out a molecular hybridization procedure using X and Y specific DNA probes. We analyse and sort bull spermatozoa on these basis: the purity obtained for these fractions is 80% without orientation after enzymatic treatment, and 70% on live spermatozoa “optically” oriented.

L’auteur tient à remercier Estelle Bories et Philippe Rozin pour leurs conseils, leur relecture et plus généralement pour leur aide inestimable, Gaëlle Morel et Thierry Gervais pour avoir permis d'affiner le propos, et François Brunet pour ses relectures successives, rigoureuses et averties. Ses remerciements s’adressent également à Amy Rule, Leslie Calmes, Harold Jones et l'équipe du Center for Creative Photography à Tucson, Arizona, ainsi qu’à la famille Lunn pour avoir facilité l'accès aux...

InfectionofprimatesbyHIV-1�andSIVinducesmultiplehematologicalabnormalitiesofcentralhematopoi- eticorigin.�AlthoughthesedefectsgreatlycontributetothepathophysiologyofHIV-1�infection,�themolecular� basisforalteredBMfunctionremainsunknown.�Hereweshowthatwhencynomolgusmacaqueswereinfected� withSIV,�themultipotentpotentialoftheirhematopoieticprogenitorcellswaslost,�andthiscorrelatedwith� downregulationofSTAT5AandSTAT5Bexpression.�However,�forcedexpressionofSTAT5Bentirelyres- cuedthemultipotentpotentialofthehematopoieticprogenitorcells.�Inaddition,�anaccessoryviralprotein� requiredforefficientSIVandHIVreplicationandpathogenicity,�"Negativefactor"�(Nef),�wasessentialfor� SIV-mediatedimpairmentofthemultipotentpotentialofhematopoieticprogenitorsexvivo andinvivo.�This� newlyuncoveredpropertyofNefwasbothconservedbetweenHIV-1�andSIVstrainsandentirelydependent� uponthepresenceofPPARγ�intargetedcells.�Further,�PPARγ�agonistsmimickedNefactivitybyinhibiting� STAT5AandSTAT5Bexpressionandhamperingthefunctionalityofhematopoieticprogenitorsbothexvivo andinvivo.�ThesefindingshaveextendedtheroleofNefinthepathogenicityofHIV-1�andSIVandreveala� pivotalroleforthePPARγ/STAT5�pathwayintheregulationofearlyhematopoiesis.�Thisstudymayprovidea� basisforinvestigatingthepotentialtherapeuticbenefitsofPPARγ�antagonistsinbothpatientswithAIDSand� individualswithhematopoieticdisorders.

De 1950 à 1990, 565 "coloramas", diapositives géantes de 5,5 par 18 mètres, ont été présentés aux passants sur le balcon Est de la gare centrale de New York, Grand Central. La dé­marche à elle seule constituait un véritable tour de force technique, réalisé par Kodak afin de promouvoir les pellicules et les appareils photo de la marque. En effet, l'entreprise de Rochester basait sa campagne sur le postulat publicitaire idéaliste et démocratique suivant: «Tous ceux qui voient un colorama devrai...