Levels of glycosaminoglycans in the cerebrospinal fluid of healthy young adults, surrogate-normal children, and Hunter syndrome patients with and without cognitive impairment.

In mucopolysaccharidoses (MPS), glycosaminoglycans (GAG) accumulate in tissues. In MPS II, approximately two-thirds of patients are cognitively impaired. We investigated levels of GAG in cerebrospinal fluid (CSF) in different populations from four clinical studies (including NCT00920647 and NCT01449240). Data indicate that MPS II patients with cognitive impairment have elevated levels of CSF GAG, whereas those with the attenuated phenotype typically have levels falling between those of the cognitively affected patients and healthy controls

The Burst Alert Telescope (BAT) on the Swift MIDEX Mission

The Burst Alert Telescope (BAT) is one of 3 instruments on the Swift MIDEX spacecraft to study gamma-ray bursts (GRBs). The BAT first detects the GRB and localizes the burst direction to an accuracy of 1-4 arcmin within 20 sec after the start of the event. The GRB trigger initiates an autonomous spacecraft slew to point the two narrow field-of-view (FOV) instruments at the burst location within 20-70 sec so to make follow-up x-ray and optical observations. The BAT is a wide-FOV, coded-aperture instrument with a CdZnTe detector plane. The detector plane is composed of 32,768 pieces of CdZnTe (4x4x2mm), and the coded-aperture mask is composed of approximately 52,000 pieces of lead (5x5x1mm) with a 1-m separation between mask and detector plane. The BAT operates over the 15-150 keV energy range with approximately 7 keV resolution, a sensitivity of approximately 10E-8 erg*cm^-2*s^-1, and a 1.4 sr (half-coded) FOV. We expect to detect >100 GRBs/yr for a 2-year mission. The BAT also performs an all-sky hard x-ray survey with a sensitivity of approximately 2 mCrab (systematic limit) and it serves as a hard x-ray transient monitor.Comment: 18 Pages, 12 Figures, To be published in Space Science Review

A phase I/II study of intrathecal idursulfase-IT in children with severe mucopolysaccharidosis II

Approximately two-thirds of patients with the lysosomal storage disease mucopolysaccharidosis II have progressive cognitive impairment. Intravenous (i.v.) enzyme replacement therapy does not affect cognitive impairment because recombinant iduronate-2-sulfatase (idursulfase) does not penetrate the blood-brain barrier at therapeutic concentrations. We examined the safety of idursulfase formulated for intrathecal administration (idursulfase-IT) via intrathecal drug delivery device (IDDD). A secondary endpoint was change in concentration of glycosaminoglycans in cerebrospinal fluid. Sixteen cognitively impaired males with mucopolysaccharidosis II who were previously treated with weekly i.v. idursulfase 0.5 mg/kg for ≥6 months were enrolled. Patients were randomized to no treatment or 10-mg, 30-mg, or 1-mg idursulfase-IT monthly for 6 months (four patients per group) while continuing i.v. idursulfase weekly. No serious adverse events related to idursulfase-IT were observed. Surgical revision/removal of the IDDD was required in 6 of 12 patients. Twelve total doses were administrated by lumbar puncture. Mean cerebrospinal fluid glycosaminoglycan concentration was reduced by approximately 90% in the 10-mg and 30-mg groups and approximately 80% in the 1-mg group after 6 months. These preliminary data support further development of investigational idursulfase-IT in MPS II patients with the severe phenotype who have progressed only to a mild-to-moderate level of cognitive impairment.Genet Med advance online publication 02 April 2015Genetics in Medicine (2015); doi:10.1038/gim.2015.36

Carbone des sols en Afrique

Les sols sont une ressource essentielle à préserver pour la production d’aliments, de fibres, de biomasse, pour la filtration de l’eau, la préservation de la biodiversité et le stockage du carbone. En tant que réservoirs de carbone, les sols sont par ailleurs appelés à jouer un rôle primordial dans la lutte contre l’augmentation de la concentration de gaz à effet de serre. Ils sont ainsi au centre des objectifs de développement durable (ODD) des Nations unies, notamment les ODD 2 « Faim zéro », 13 « Lutte contre le changement climatique », 15 « Vie terrestre », 12 « Consommation et production responsables » ou encore 1 « Pas de pauvreté ». Cet ouvrage présente un état des lieux des sols africains dans toute leur diversité, mais au-delà, il documente les capacités de stockage de carbone selon les types de sols et leurs usages en Afrique. Il propose également des recommandations autour de l’acquisition et de l’interprétation des données, ainsi que des options pour préserver, voire augmenter les stocks de carbone dans les sols. Tous les chercheurs et acteurs du développement impliqués dans les recherches sur le rôle du carbone des sols sont concernés par cette synthèse collective. Fruit d’une collaboration entre chercheurs africains et européens, ce livre insiste sur la nécessité de prendre en compte la grande variété des contextes agricoles et forestiers africains pour améliorer nos connaissances sur les capacités de stockage de carbone des sols et lutter contre le changement climatique

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

A Cerebrospinal Fluid Collection Study in Pediatric and Adult Patients With Hunter Syndrome

Hunter syndrome (mucopolysaccharidosis II [MPS II]) is characterized by lysosomal glycosaminoglycan (GAG) accumulation. Although a majority of patients with MPS II experience neurocognitive involvement, few data are available on cerebrospinal fluid (CSF) GAG levels in these patients. This study measured GAG levels in CSF collected from 9 patients with MPS II, including 4 adults (aged ≥18 years) with normal cognition, and 5 children, 3 of them with cognitive impairment. The CSF total GAG levels were generally higher in the 3 patients with cognitive impairment (range 842.9-2360.9 ng/mL) versus those with normal cognitive status (range 356.8-1181.1 ng/mL). Heparan sulfate levels, as measured by mass spectrometry, generally followed a similar pattern, with patients with the severe phenotype having the highest values. These data, limited by small sample size, suggest CSF GAG levels and heparan sulfate levels may be higher in patients with cognitive impairment versus patients with cognitively intact MPS II