Intrathecal heparan-N-sulfatase in patients with Sanfilippo syndrome type A: A phase IIb randomized trial.

Abstract Background Sanfilippo syndrome type A (mucopolysaccharidosis type IIIA) is a lysosomal disorder wherein deficient heparan-N-sulfatase (HNS) activity results in the accumulation of heparan sulfate in the central nervous system and is associated with progressive neurodegeneration in early childhood. We report on the efficacy, pharmacokinetics, safety, and tolerability of intrathecal (IT) administration of recombinant human HNS (rhHNS) from a phase IIb randomized open-label trial. Methods Twenty-one patients, randomized 1:1:1 to rhHNS IT 45 mg administered every 2 weeks (Q2W), every 4 weeks (Q4W), or no treatment, were assessed for amelioration in neurocognitive decline as determined by the Bayley Scales of Infant and Toddler Development®, Third Edition. The primary efficacy goal was defined as ≤10-point decline (responder) in at least three patients in a dosing cohort after 48 weeks. Other efficacy assessments included adaptive behavioral function, assessments of cortical gray matter volume, and glycosaminoglycan (GAG) levels in urine. Results A clinical response to rhHNS IT was observed in three treated patients (two in the Q2W group, one in the Q4W group). Cerebrospinal fluid heparan sulfate and urine GAG levels were reduced in all treated patients. However, most secondary efficacy assessments were similar between treated patients (n = 14; age, 17.8–47.8 months) and untreated controls (n = 7; age, 12.6–45.0 months). Treatment-emergent adverse events that occurred with rhHNS IT were mostly mild, none led to study discontinuation, and there were no deaths. Conclusion rhHNS IT treatment reduced heparan sulfate and GAG levels in treated patients. Though the primary neurocognitive endpoint was not met, important lessons in the design and endpoints for evaluation of cognitive and behavioral diseases resulted. Trial registration ClinicalTrials.gov NCT02060526 ; EudraCT 2013-003450-24

SAXO+ upgrade : second stage AO system end-to-end numerical simulations

SAXO+ is a proposed upgrade to SAXO, the AO system of the SPHERE instrument on the ESO Very Large Telescope. It will improve the capabilities of the instrument for the detection and characterization of young giant planets. It includes a second stage adaptive optics system composed of a dedicated near-infrared wavefront sensor and a deformable mirror. This second stage will remove the residual wavefront errors left by the current primary AO loop (SAXO). This paper focuses on the numerical simulations of the second stage (SAXO+) and concludes on the impact of the main AO parameters used to build the design strategy. Using an end-to-end AO simulation tool (COMPASS), we investigate the impact of several parameters on the performance of the AO system. We measure the performance in minimizing the star residuals in the coronagraphic image. The parameters that we study are : the second stage frequency, the photon flux on each WFS, the first stage gain and the DM number of actuators of the second stage. We show that the performance is improved by a factor 10 with respect to the current AO system (SAXO). The optimal second stage frequency is between 1 and 2 kHz under good observing conditions. In a red star case, the best SAXO+ performance is achieved with a low first stage gain of 0.05, which reduces the first stage rejection.Comment: 10 pages, 8 figures. Submitted to AO4ELT7 conference proceeding

Modified Delphi procedure-based expert consensus on endpoints for an international disease registry for Metachromatic Leukodystrophy:The European Metachromatic Leukodystrophy initiative (MLDi)

BACKGROUND: Metachromatic Leukodystrophy (MLD) is a rare lysosomal disorder. Patients suffer from relentless neurological deterioration leading to premature death. Recently, new treatment modalities, including gene therapy and enzyme replacement therapy, have been developed. Those advances increase the need for high-quality research infrastructure to adequately compare treatments, execute post-marketing surveillance, and perform health technology assessments (HTA). To facilitate this, a group of MLD experts started the MLD initiative (MLDi) and initiated an academia-led European MLD registry: the MLDi. An expert-based consensus procedure, namely a modified Delphi procedure, was used to determine the data elements required to answer academic, regulatory, and HTA research questions. RESULTS: Three distinct sets of data elements were defined by the 13-member expert panel. The minimal set (n = 13) contained demographics and basic disease characteristics. The core set (n = 55) included functional status scores in terms of motor, manual, speech and eating abilities, and causal and supportive treatment characteristics. Health-related quality of life scores were included that were also deemed necessary for HTA. The optional set (n = 31) contained additional clinical aspects, such as findings at neurological examination, detailed motor function, presence of peripheral neuropathy, gall bladder involvement and micturition. CONCLUSION: Using a modified Delphi procedure with physicians from the main expert centers, consensus was reached on a core set of data that can be collected retrospectively and prospectively. With this consensus-based approach, an important step towards harmonization was made. This unique dataset will support knowledge about the disease and facilitate regulatory requirements related to the launch of new treatments. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13023-022-02189-w

Autosomal recessive cerebellar ataxia caused by mutations in the PEX2 gene

<p>Abstract</p> <p>Objective</p> <p>To expand the spectrum of genetic causes of autosomal recessive cerebellar ataxia (ARCA).</p> <p>Case report</p> <p>Two brothers are described who developed progressive cerebellar ataxia at 3 1/2 and 18 years, respectively. After ruling out known common genetic causes of ARCA, analysis of blood peroxisomal markers strongly suggested a peroxisomal biogenesis disorder. Sequencing of candidate <it>PEX </it>genes revealed a homozygous c.865_866insA mutation in the <it>PEX2 </it>gene leading to a frameshift 17 codons upstream of the stop codon. <it>PEX </it>gene mutations usually result in a severe neurological phenotype (Zellweger spectrum disorders).</p> <p>Conclusions</p> <p>Genetic screening of PEX2 and other PEX genes involved in peroxisomal biogenesis is warranted in children and adults with ARCA.</p

Filière « Territoires, espaces, sociétés »

Participants : Isabelle Backouche, Juan Carlos Garavaglia, Nancy L. Green, Alexandra Laclau, Christian Lamouroux, Michèle de La Pradelle, Susanna Magri, Marie-Claude Maurel, Alain Musset, Daniel Nordman, Marie-Vic Ozouf-Marignier, Jacques Poloni-Simard, Paul-André Rosental, Annie Sevin, Annick Tanter-Toubon, Christian Topalov, Caroline Varlet, Nicolas Verdier, Françoise Vergneault-Belmont, François Weil, Pierre-Paul Zalio L’enseignement de la filière s’inscrit dans le cadre du séminaire bimen..

Filière « Territoires, espaces, sociétés »

Participants : Isabelle Backouche, Juan Carlos Garavaglia, Nancy L. Green, Alexandra Laclau, Christian Lamouroux, Michèle de La Pradelle, Susanna Magri, Marie-Claude Maurel, Alain Musset, Daniel Nordman, Marie-Vic Ozouf-Marignier, Jacques Poloni-Simard, Paul-André Rosental, Annie Sevin, Annick Tanter-Toubon, Christian Topalov, Caroline Varlet, Nicolas Verdier, Françoise Vergneault-Belmont, François Weil, Pierre-Paul Zalio L’enseignement de la filière s’inscrit dans le cadre du séminaire bimen..

SNAPSHOT USA 2019 : a coordinated national camera trap survey of the United States

This article is protected by copyright. All rights reserved.With the accelerating pace of global change, it is imperative that we obtain rapid inventories of the status and distribution of wildlife for ecological inferences and conservation planning. To address this challenge, we launched the SNAPSHOT USA project, a collaborative survey of terrestrial wildlife populations using camera traps across the United States. For our first annual survey, we compiled data across all 50 states during a 14-week period (17 August - 24 November of 2019). We sampled wildlife at 1509 camera trap sites from 110 camera trap arrays covering 12 different ecoregions across four development zones. This effort resulted in 166,036 unique detections of 83 species of mammals and 17 species of birds. All images were processed through the Smithsonian's eMammal camera trap data repository and included an expert review phase to ensure taxonomic accuracy of data, resulting in each picture being reviewed at least twice. The results represent a timely and standardized camera trap survey of the USA. All of the 2019 survey data are made available herein. We are currently repeating surveys in fall 2020, opening up the opportunity to other institutions and cooperators to expand coverage of all the urban-wild gradients and ecophysiographic regions of the country. Future data will be available as the database is updated at eMammal.si.edu/snapshot-usa, as well as future data paper submissions. These data will be useful for local and macroecological research including the examination of community assembly, effects of environmental and anthropogenic landscape variables, effects of fragmentation and extinction debt dynamics, as well as species-specific population dynamics and conservation action plans. There are no copyright restrictions; please cite this paper when using the data for publication.Publisher PDFPeer reviewe

Mammal responses to global changes in human activity vary by trophic group and landscape

Wildlife must adapt to human presence to survive in the Anthropocene, so it is critical to understand species responses to humans in different contexts. We used camera trapping as a lens to view mammal responses to changes in human activity during the COVID-19 pandemic. Across 163 species sampled in 102 projects around the world, changes in the amount and timing of animal activity varied widely. Under higher human activity, mammals were less active in undeveloped areas but unexpectedly more active in developed areas while exhibiting greater nocturnality. Carnivores were most sensitive, showing the strongest decreases in activity and greatest increases in nocturnality. Wildlife managers must consider how habituation and uneven sensitivity across species may cause fundamental differences in human–wildlife interactions along gradients of human influence.Peer reviewe

Suivi 2011 des captures d'anguilles pour la DCF : analyse des otolithes

Ce rapport synthétise l'analyse des otolithes d'anguilles prélevés en 2011 dans le cadre du suivi des captures de cette espèce inscrite à la DCF (Data Collection Framework règlement CE n°199/2008 du conseil du 25 février 2008). 140 anguilles ont été prélevées entre fin juillet et fin octobre 2011 dans la Loire, la Dordogne et la Gironde. La relation entre la longueur totale (Lt) et le poids total (Wt) des anguilles prélevées en 2011 dans toute la France (Loire, Garonne et Dordogne) est du type Wt = 5.10-7.Lt3,21. Ainsi, les anguilles présentent une allométrie majorante (b=3.21) c’est-à-dire que le poids croit plus vite que la longueur. L'institut IFREMER à travers le pôle national de Sclérochronologie à Boulogne-sur-mer a préparé et interprété les otolithes, pièce calcifiée de l'oreille interne, permettant d'estimer l'âge de ces poissons. Pour chaque otolithe, une lame mince transversale polie a été réalisée pour permettre d'estimer l'âge de chaque individu à l'aide du logiciel TNPC (Traitement Numérique des Pièces Calcifiées, www.tnpc.fr). Parmi les 140 poissons échantillonnés, l'âge de 130 anguilles a pu être estimé. L'âge de 10 poissons n'a pas pu être réalisé car soit les otolithes étaient cassés donc inutilisables soit les coupes d'otolithes ne présentaient pas de structures interprétables. Les âges estimés étaient dans la Garonne et la Dordogne de 2 à 16 ans avec une moyenne de 7 ans et dans la Loire de 5 à 15 ans avec une moyenne de 11 ans. Parmi les classes d'âge observées de 2 à 16 ans, on observe que les intervalles de longueur pour les classes d'âge de 2 à 10 ans sont relativement faibles à l'inverse des groupes d'âge supérieurs à 10 ans (Fig. 8). Ainsi, pour les groupes d'âge supérieurs à 10 ans, les variations de croissance entre les individus sont très importantes et pour une taille donnée, il est très difficile d'estimer l'âge sans interpréter l'otolithe. Tous ces otolithes et données associées (taille, poids, date de capture, lieu...) sont stockés et gérés actuellement dans la base nationale d'archivage et de gestion des pièces calcifiées développée par l'IFREMER