Using the gross motor function measure evolution ratio to compare different dosage of hyperbaric treatment with conventional therapies in children with cerebral palsy – could it end the controversy?

The Gross Motor Function Measure is used in most studies measuring gross motor function in children with cerebral palsy. In many studies, including those evaluating the effect of hyperbaric treatment, the Gross Motor Function Measure variations were potentially misinterpreted because of the lack of control groups. The Gross Motor Function Measure Evolution Ratio (GMFMER) uses historical data from the Gross Motor Function Classification System curves and allows to re-analyze previous published studies which used the Gross Motor Function Measure by considering the natural expected evolution of the Gross Motor Function Measure. As the GMFMER is defined by the ratio between the recorded Gross Motor Function Measure score increase and the expected increase attributed to natural evolution during the duration of the study (natural evolution yields a GMFMER of 1), it becomes easy to assess and compare the efficacy of different treatments.ObjectiveThe objective of this study is to revisit studies done with different dosage of hyperbaric treatment and to compare the GMFMER measured in these studies with those assessing the effects of various recommended treatments in children with cerebral palsy.MethodsPubMed Searches were conducted to included studies that used the Gross Motor Function Measure to evaluate the effect of physical therapy, selective dorsal rhizotomy, botulinum toxin injection, hippotherapy, stem cell, or hyperbaric treatment. The GMFMER were computed for each group of the included studies.ResultsForty-four studies were included, counting 4 studies evaluating the effects of various dosage of hyperbaric treatment in children with cerebral palsy. Since some studies had several arms, the GMFMER has been computed for 69 groups. The average GMFMER for the groups receiving less than 2 h/week of physical therapy was 2.5 ± 1.8 whereas in context of very intensive physical therapy it increased to 10.3 ± 6.1. The GMFMER of stem cell, selective dorsal rhizotomy, hippotherapy, and botulinum toxin treatment was, 6.0 ± 5.9, 6.5 ± 2.0, 13.3 ± 0.6, and 5.0 ± 2.9, respectively. The GMFMER of the groups of children receiving hyperbaric treatment were 28.1 ± 13.0 for hyperbaric oxygen therapy and 29.8 ± 6.8 for hyperbaric air.ConclusionThe analysis of the included studies with the GMFMER showed that hyperbaric treatment can result in progress of gross motor function more than other recognized treatments in children with cerebral palsy

Genomic analyses inform on migration events during the peopling of Eurasia.

High-coverage whole-genome sequence studies have so far focused on a limited number of geographically restricted populations, or been targeted at specific diseases, such as cancer. Nevertheless, the availability of high-resolution genomic data has led to the development of new methodologies for inferring population history and refuelled the debate on the mutation rate in humans. Here we present the Estonian Biocentre Human Genome Diversity Panel (EGDP), a dataset of 483 high-coverage human genomes from 148 populations worldwide, including 379 new genomes from 125 populations, which we group into diversity and selection sets. We analyse this dataset to refine estimates of continent-wide patterns of heterozygosity, long- and short-distance gene flow, archaic admixture, and changes in effective population size through time as well as for signals of positive or balancing selection. We find a genetic signature in present-day Papuans that suggests that at least 2% of their genome originates from an early and largely extinct expansion of anatomically modern humans (AMHs) out of Africa. Together with evidence from the western Asian fossil record, and admixture between AMHs and Neanderthals predating the main Eurasian expansion, our results contribute to the mounting evidence for the presence of AMHs out of Africa earlier than 75,000 years ago.Support was provided by: Estonian Research Infrastructure Roadmap grant no 3.2.0304.11-0312; Australian Research Council Discovery grants (DP110102635 and DP140101405) (D.M.L., M.W. and E.W.); Danish National Research Foundation; the Lundbeck Foundation and KU2016 (E.W.); ERC Starting Investigator grant (FP7 - 261213) (T.K.); Estonian Research Council grant PUT766 (G.C. and M.K.); EU European Regional Development Fund through the Centre of Excellence in Genomics to Estonian Biocentre (R.V.; M.Me. and A.Me.), and Centre of Excellence for Genomics and Translational Medicine Project No. 2014-2020.4.01.15-0012 to EGC of UT (A.Me.) and EBC (M.Me.); Estonian Institutional Research grant IUT24-1 (L.S., M.J., A.K., B.Y., K.T., C.B.M., Le.S., H.Sa., S.L., D.M.B., E.M., R.V., G.H., M.K., G.C., T.K. and M.Me.) and IUT20-60 (A.Me.); French Ministry of Foreign and European Affairs and French ANR grant number ANR-14-CE31-0013-01 (F.-X.R.); Gates Cambridge Trust Funding (E.J.); ICG SB RAS (No. VI.58.1.1) (D.V.L.); Leverhulme Programme grant no. RP2011-R-045 (A.B.M., P.G. and M.G.T.); Ministry of Education and Science of Russia; Project 6.656.2014/K (S.A.F.); NEFREX grant funded by the European Union (People Marie Curie Actions; International Research Staff Exchange Scheme; call FP7-PEOPLE-2012-IRSES-number 318979) (M.Me., G.H. and M.K.); NIH grants 5DP1ES022577 05, 1R01DK104339-01, and 1R01GM113657-01 (S.Tis.); Russian Foundation for Basic Research (grant N 14-06-00180a) (M.G.); Russian Foundation for Basic Research; grant 16-04-00890 (O.B. and E.B); Russian Science Foundation grant 14-14-00827 (O.B.); The Russian Foundation for Basic Research (14-04-00725-a), The Russian Humanitarian Scientific Foundation (13-11-02014) and the Program of the Basic Research of the RAS Presidium “Biological diversity” (E.K.K.); Wellcome Trust and Royal Society grant WT104125AIA & the Bristol Advanced Computing Research Centre (http://www.bris.ac.uk/acrc/) (D.J.L.); Wellcome Trust grant 098051 (Q.A.; C.T.-S. and Y.X.); Wellcome Trust Senior Research Fellowship grant 100719/Z/12/Z (M.G.T.); Young Explorers Grant from the National Geographic Society (8900-11) (C.A.E.); ERC Consolidator Grant 647787 ‘LocalAdaptatio’ (A.Ma.); Program of the RAS Presidium “Basic research for the development of the Russian Arctic” (B.M.); Russian Foundation for Basic Research grant 16-06-00303 (E.B.); a Rutherford Fellowship (RDF-10-MAU-001) from the Royal Society of New Zealand (M.P.C.)

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Édifice John-Munn, rue Dalhousie, Québec, 1984

Firme d'architectes: Gagnon, Guy & Letellier.; Date de construction: 1984.; Édifice logeant le Quartier général de la Réserve navale.; Hartill Art Associates. ACa-1608

Quand les jeunes patients vivant avec la maladie de Duchenne négocient les actes de soin avec les adultes : personnalisation et pratiques de résistance

Cet article est basé sur une étude socio-anthropologique menée auprès d’enfants et d’adolescents âgés de 6 à 15 ans vivant avec la dystrophie musculaire de Duchenne. La recherche ethnographique a été menée en France, entre 2019 et 2020, à partir d’observations de consultations pluridisciplinaires à l’hôpital et d’une série d’entretiens réalisés avec les jeunes patients, leurs parents et les soignants. L’étude a visé à examiner la négociation des actes de soin entre enfants et adultes lors des interactions sociales en consultations cliniques. Les résultats de la recherche mettent en évidence comment les jeunes patients s’opposent, résistent aux actes de soin et contribuent à façonner les manières dont les soignants agissent autour de leur corps. Malgré l’asymétrie des rapports d’âge et de santé avec les adultes, les enfants et les adolescents manifestent des compétences liées à la gestion de leur santé, leur bien-être, et à la participation au processus de décision.This article is based on a socio-anthropological study with children and adolescents aged 6 to 15 years old living with Duchenne muscular dystrophy. Conducted in France between 2019 and 2020, this ethnographic research was based on observations of multidisciplinary hospital consultations and a series of interviews with young patients, their parents and healthcare professionals. Our study examined the negotiation of care between children and adults during social interactions in clinical consultations. The research findings show how young patients oppose and resist acts of care and help shape the ways in which healthcare professionals act towards their bodies. Despite the asymmetry of age and health relationships with adults, children and adolescents demonstrate capabilities in the management of their health, well-being and bodies, and in their participation in the decision-making process

Quand les jeunes patients vivant avec la maladie de Duchenne négocient les actes de soin avec les adultes : personnalisation et pratiques de résistance

This article is based on a socio-anthropological study with children and adolescents aged 6 to 15 years old living with Duchenne muscular dystrophy. Conducted in France between 2019 and 2020, this ethnographic research was based on observations of multidisciplinary hospital consultations and a series of interviews with young patients, their parents and healthcare professionals. Our study examined the negotiation of care between children and adults during social interactions in clinical consultations. The research findings show how young patients oppose and resist acts of care and help shape the ways in which healthcare professionals act towards their bodies. Despite the asymmetry of age and health relationships with adults, children and adolescents demonstrate capabilities in the management of their health, well-being and bodies, and in their participation in the decision-making process

Lack of functional benefit with glutamine versus placebo in Duchenne muscular dystrophy: a randomized crossover trial.

Oral glutamine decreases whole body protein breakdown in Duchenne muscular dystrophy (DMD). We evaluated the functional benefit of 4 months oral glutamine in DMD.30 ambulant DMD boys were included in this double-blind, randomized crossover trial with 2 intervention periods: glutamine (0.5 g/kg/d) and placebo, 4 months each, separated by a 1-month wash-out, at 3 outpatient clinical investigation centers in France. Functional benefit was tested by comparing glutamine versus placebo on change in walking speed at 4 months. Secondary outcome measures were: 2-minute walk test, work, power, muscle mass (urinary creatinine), markers of myofibrillar protein breakdown (urinary 3-methyl-histidine/creatinine), serum creatine phospho-kinase, body composition (fat free mass, fat mass percentage), safety and oral nutrient intake. There was no improvement in the primary end point (walking speed) or in secondary measures of muscle function (2-minute walk test, work, power) in the glutamine group compared with placebo. However, subjects receiving glutamine or placebo showed no deterioration in functional measures over the course of the 9-month trial. No differences in muscle mass, markers of protein breakdown or serum creatine phosho-kinase were observed, except for a blunted increase in fat free mass in the glutamine group which led to a greater increase in fat mass percentage. Glutamine was safe and well-tolerated.This trial did not identify additional benefit of 4 months oral glutamine over placebo on muscle mass or function in ambulatory DMD boys. Although apparently safe, current data cannot support routine supplementation in this population as a whole, until further research proves otherwise.(ClinicalTrials.gov) NCT00296621