Timed rise from floor as a predictor of disease progression in Duchenne muscular dystrophy: An observational study

The role of timed items, and more specifically, of the time to rise from the floor, has been reported as an early prognostic factor for disease progression and loss of ambulation. The aim of our study was to investigate the possible effect of the time to rise from the floor test on the changes observed on the 6MWT over 12 months in a cohort of ambulant Duchenne boys.A total of 487 12-month data points were collected from 215 ambulant Duchenne boys. The age ranged between 5.0 and 20.0 years (mean 8.48 ±2.48 DS).The results of the time to rise from the floor at baseline ranged from 1.2 to 29.4 seconds in the boys who could perform the test. 49 patients were unable to perform the test at baseline and 87 at 12 month The 6MWT values ranged from 82 to 567 meters at baseline. 3 patients lost the ability to perform the 6mwt at 12 months. The correlation between time to rise from the floor and 6MWT at baseline was high (r = 0.6, p<0.01).Both time to rise from the floor and baseline 6MWT were relevant for predicting 6MWT changes in the group above the age of 7 years, with no interaction between the two measures, as the impact of time to rise from the floor on 6MWT change was similar in the patients below and above 350 m. Our results suggest that, time to rise from the floor can be considered an additional important prognostic factor of 12 month changes on the 6MWT and, more generally, of disease progression

Mitogenomes from Egyptian Cattle Breeds: New Clues on the Origin of Haplogroup Q and the Early Spread of Bos taurus from the Near East

Background Genetic studies support the scenario that Bos taurus domestication occurred in the Near East during the Neolithic transition about 10 thousand years (ky) ago, with the likely exception of a minor secondary event in Italy. However, despite the proven effectiveness of whole mitochondrial genome data in providing valuable information concerning the origin of taurine cattle, until now no population surveys have been carried out at the level of mitogenomes in local breeds from the Near East or surrounding areas. Egypt is in close geographic and cultural proximity to the Near East, in particular the Nile Delta region, and was one of the first neighboring areas to adopt the Neolithic package. Thus, a survey of mitogenome variation of autochthonous taurine breeds from the Nile Delta region might provide new insights on the early spread of cattle rearing outside the Near East. Methodology Using Illumina high-throughput sequencing we characterized the mitogenomes from two cattle breeds, Menofi (N = 17) and Domiaty (N = 14), from the Nile Delta region. Phylogenetic and Bayesian analyses were subsequently performed. Conclusions Phylogenetic analyses of the 31 mitogenomes confirmed the prevalence of haplogroup T1, similar to most African cattle breeds, but showed also high frequencies for haplogroups T2, T3 and Q1, and an extremely high haplotype diversity, while Bayesian skyline plots pointed to a main episode of population growth ~12.5 ky ago. Comparisons of Nile Delta mitogenomes with those from other geographic areas revealed that (i) most Egyptian mtDNAs are probably direct local derivatives from the founder domestic herds which first arrived from the Near East and the extent of gene flow from and towards the Nile Delta region was limited after the initial founding event(s); (ii) haplogroup Q1 was among these founders, thus proving that it underwent domestication in the Near East together with the founders of the T clades

The Enigmatic Origin of Bovine mtDNA Haplogroup R: Sporadic Interbreeding or an Independent Event of Bos primigenius Domestication in Italy?

BACKGROUND: When domestic taurine cattle diffused from the Fertile Crescent, local wild aurochsen (Bos primigenius) were still numerous. Moreover, aurochsen and introduced cattle often coexisted for millennia, thus providing potential conditions not only for spontaneous interbreeding, but also for pastoralists to create secondary domestication centers involving local aurochs populations. Recent mitochondrial genomes analyses revealed that not all modern taurine mtDNAs belong to the shallow macro-haplogroup T of Near Eastern origin, as demonstrated by the detection of three branches (P, Q and R) radiating prior to the T node in the bovine phylogeny. These uncommon haplogroups represent excellent tools to evaluate if sporadic interbreeding or even additional events of cattle domestication occurred. METHODOLOGY: The survey of the mitochondrial DNA (mtDNA) control-region variation of 1,747 bovine samples (1,128 new and 619 from previous studies) belonging to 37 European breeds allowed the identification of 16 novel non-T mtDNAs, which after complete genome sequencing were confirmed as members of haplogroups Q and R. These mtDNAs were then integrated in a phylogenetic tree encompassing all available P, Q and R complete mtDNA sequences. CONCLUSIONS: Phylogenetic analyses of 28 mitochondrial genomes belonging to haplogroups P (N = 2), Q (N = 16) and R (N = 10) together with an extensive survey of all previously published mtDNA datasets revealed major similarities between haplogroups Q and T. Therefore, Q most likely represents an additional minor lineage domesticated in the Near East together with the founders of the T subhaplogroups. Whereas, haplogroup R is found, at least for the moment, only in Italy and nowhere else, either in modern or ancient samples, thus supporting an origin from European aurochsen. Haplogroup R could have been acquired through sporadic interbreeding of wild and domestic animals, but our data do not rule out the possibility of a local and secondary event of B. primigenius domestication in Italy

Reliability of the Performance of Upper Limb assessment in Duchenne muscular dystrophy

Abstract The Performance of Upper Limb was specifically designed to assess upper limb function in Duchenne muscular dystrophy. The aim of this study was to assess (1) a cohort of typically developing children from the age of 3 years onwards in order to identify the age when the activities assessed in the individual items are consistently achieved, and (2) a cohort of 322 Duchenne children and young adults to establish the range of findings at different ages. We collected normative data for the scale validation on 277 typically developing subjects from 3 to 25 years old. A full score was consistently achieved by the age of 5 years. In the Duchenne cohort there was early involvement of the proximal muscles and a proximal to distal progressive involvement. The scale was capable of measuring small distal movements, related to activities of daily living, even in the oldest and weakest patients. Our data suggest that the assessment can be reliably used in both ambulant and non ambulant Duchenne patients in a multicentric setting and could therefore be considered as an outcome measure for future trials

Le retour de la restitution (3): Géopolitiques du patrimoine, éthiques du transfert, économies du retour

Séance 3 : Que penser, que faire des objets rapatriés ? Modération : Odile COPPEY (Université de Limoges) et Anne DOQUET (IRD-Imaf) [00:00:00 à 03:54:07] Présentation par Odile COPPEY (Université de Limoges) [03:54:07 à 18:05:01] Brice Medard CHANHOUN (Migrantour Paris): « Visite d’adieu aux objets rapatriés » [18:05:01 à 32:18:20] Emmanuelle CADET (directrice d’Alter Natives) : « Jeunesses du Bénin, du Sénégal et des diasporas : comment partager l’histoire des objets ? » [32:18:20 à 45:18:04] Sara TASSI (Habiter, ULB) & Amandine YÉHOUÉTOMÈ (U. Paris 1): « Un Gou de Blanc ! Le Gou du Louvre au regard de ses initié.e.s Ainonvis » [45:18:04 à 01:00:42:02] Saskia COUSIN (Canthel, U. Paris Descartes) « Porto-Novo contre le retour, tout contre : le musée de l’amitié coloniale et la résistance des maquis » [01:00:42:02 à fin] DiscussionPrésentation du colloque : Repatriation strikes back. Sujet récurrent depuis une trentaine d’année, la question de la restitution des objets volés ou spoliés est de retour, dans un contexte politique a priori plus favorable. Si les préconisations du rapport Sarr-Savoy (2018) suscitent de vives confrontations au sein des mondes muséaux et marchands, cette journée d’études vise à dépayser le débat en donnant la parole aux acteurs, aux publics et aux pays concernés par le retour et l’accueil de ces objets. La restitution est-elle le fait du prince, ou l’aboutissement de décennies de réclamations successives? De quelle géopolitique est-elle le nom ? Quels sont les acteurs de cette histoire ? Quelles places donner aux diasporas longtemps ignorées par les musées européens ? Comment penser les transferts et les appropriations ici et là-bas ? Quels statuts ces objets sacrés et royaux devenus « fétiches de musées » vont-ils prendre lors de leur retour ? Quels seront leurs publics ? Comment considérer et expliquer les oppositions locales au retour ? Mêlant acteurs et chercheurs, organisée autour de questions vives et actuelles, mais aussi immémoriales, cette journée ambitionne de lancer le débat plutôt que de le clore. Programme Contacts : [email protected] / [email protected]

Immunoglobulin gene analysis in chronic lymphocytic leukemia in the era of next generation sequencing

Twenty years after landmark publications, there is a consensus that the somatic hypermutation (SHM) status of the clonotypic immunoglobulin heavy variable (IGHV) gene is an important cornerstone for accurate risk stratification and therapeutic decision-making in patients with chronic lymphocytic leukemia (CLL). The IGHV SHM status has traditionally been determined by conventional Sanger sequencing. However, NGS has heralded a new era in medical diagnostics and immunogenetic analysis is following this trend. There is indeed a growing demand for shifting practice and using NGS for IGHV gene SHM assessment, although it is debatable whether it is always justifiable, at least taking into account financial considerations for laboratories with limited resources. Nevertheless, as this analysis impacts on treatment decisions, standardization of both technical aspects, and data interpretation becomes essential. Also, the need for establishing new recommendations and providing dedicated education and training on NGS-based immunogenetics is greater than ever before. Here we address potential and challenges of NGS-based immunogenetics in CLL. We are convinced that this perspective helps the hematological community to better understand the pros and cons of this new technological development for CLL patient management

Origin and Spread of Bos taurus: New Clues from Mitochondrial Genomes Belonging to Haplogroup T1

Background Most genetic studies on modern cattle have established a common origin for all taurine breeds in the Near East, during the Neolithic transition about 10 thousand years (ka) ago. Yet, the possibility of independent and/or secondary domestication events is still debated and is fostered by the finding of rare mitochondrial DNA (mtDNA) haplogroups like P, Q and R. Haplogroup T1, because of its geographic distribution, has been the subject of several investigations pointing to a possible independent domestication event in Africa and suggesting a genetic contribution of African cattle to the formation of Iberian and Creole cattle. Whole mitochondrial genome sequence analysis, with its proven effectiveness in improving the resolution of phylogeographic studies, is the most appropriate tool to investigate the origin and structure of haplogroup T1. Methodology A survey of >2200 bovine mtDNA control regions representing 28 breeds (15 European, 10 African, 3 American) identified 281 subjects belonging to haplogroup T1. Fifty-four were selected for whole mtDNA genome sequencing, and combined with ten T1 complete sequences from previous studies into the most detailed T1 phylogenetic tree available to date. Conclusions Phylogenetic analysis of the 64 T1 mitochondrial complete genomes revealed six distinct sub-haplogroups (T1a\u2013T1f). Our data support the overall scenario of a Near Eastern origin of the T1 sub-haplogroups from as much as eight founding T1 haplotypes. However, the possibility that one sub-haplogroup (T1d) arose in North Africa, in domesticated stocks, shortly after their arrival from the Near East, can not be ruled out. Finally, the previously identified \u201cAfrican-derived American" (AA) haplotype turned out to be a sub-clade of T1c (T1c1a1). This haplotype was found here for the first time in Africa (Egypt), indicating that it probably originated in North Africa, reached the Iberian Peninsula and sailed to America, with the first European settlers

Internal and external electron transport barriers in the RFX-mod reversed field pinch

An interesting result of magnetic chaos reduction in RFX-mod high current discharges is the development of strong electron transport barriers. An internal heat and particle transport barrier is formed when a bifurcation process changes the magnetic configuration into a helical equilibrium and chaos reduction follows, together with the formation of a null in the q shear. Strong temperature gradients develop, corresponding to a decreased thermal and particle transport. Turbulence analysis shows that the large electron temperature gradients are limited by the onset of micro-tearing modes, in addition to residual magnetic chaos. A new type of electron transport barrier with strong temperature gradients develops more externally (r/a = 0.8) accompanied by a 30% improvement of the global confinement time. The mechanism responsible for the formation of such a barrier is still unknown but it is likely associated with a local reduction of magnetic chaos. These external barriers develop primarily in situations of well-conditioned walls so that they might be regarded as attempts towards an L-H transition. Both types of barriers occur in high-current low-collisionality regimes. Analogies with tokamak and stellarators are discussed

Efficacy of Ertapenem for Treatment of Bloodstream Infections Caused by Extended-Spectrum-β-Lactamase-Producing Enterobacteriaceae

Ertapenem is active against extended-spectrum-β-lactamase (ESBL)-producing Enterobacteriaceae organisms but inactive against Pseudomonas aeruginosa and Acinetobacter baumannii. Due to a lack of therapeutic data for ertapenem in the treatment of ESBL bloodstream infections (BSIs), group 2 carbapenems (e.g., imipenem or meropenem) are often preferred for treatment of ESBL-producing Enterobacteriaceae, although their antipseudomonal activity is unnecessary. From 2005 to 2010, 261 patients with ESBL BSIs were analyzed. Outcomes were equivalent between patients treated with ertapenem and those treated with group 2 carbapenems (mortality rates of 6% and 18%, respectively; P = 0.18)

Helical equilibria and magnetic structures in the reversed field pinch and analogies to the tokamak and stellarator

The reversed field pinch configuration is characterized by the presence of magnetic structures both in the core and at the edge: in the core, at high plasma current the spontaneous development of a helical structure is accompanied by the appearance of internal electron transport barriers; at the edge strong pressure gradients, identifying an edge transport barrier, are observed too, related to the position of the field reversal surface. The aim of this paper is the experimental characterization of both the internal and edge transport barriers in relation to the magnetic topology, discussing possible analogies and differences with other confinement schemes