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Spinal muscular atrophy is a rare, autosomal recessive, neuromuscular disease caused by biallelic loss of the survival motor neuron 1 (SMN1) gene, resulting in motor neuron dysfunction. In this STR1VE-EU study, we aimed to evaluate the safety and efficacy of onasemnogene abeparvovec gene replacement therapy in infants with spinal muscular atrophy type 1, using broader eligibility criteria than those used in STR1VE-US. STR1VE-EU was a multicentre, single-arm, single-dose, open-label phase 3 trial done at nine sites (hospitals and universities) in Italy (n=4), the UK (n=2), Belgium (n=2), and France (n=1). We enrolled patients younger than 6 months (180 days) with spinal muscular atrophy type 1 and the common biallelic pathogenic SMN1 exon 7–8 deletion or point mutations, and one or two copies of SMN2. Patients received a one-time intravenous infusion of onasemnogene abeparvovec (1·1 × 1014 vector genomes [vg]/kg). The outpatient follow-up consisted of assessments once per week starting at day 7 post-infusion for 4 weeks and then once per month until the end of the study (at age 18 months or early termination). The primary outcome was independent sitting for at least 10 s, as defined by the WHO Multicentre Growth Reference Study, at any visit up to the 18 months of age study visit, measured in the intention-to-treat population. Efficacy was compared with the Pediatric Neuromuscular Clinical Research (PNCR) natural history cohort. This trial is registered with ClinicalTrials.gov, NCT03461289 (completed). From Aug 16, 2018, to Sept 11, 2020, 41 patients with spinal muscular atrophy were assessed for eligibility. The median age at onasemnogene abeparvovec dosing was 4·1 months (IQR 3·0–5·2). 32 (97%) of 33 patients completed the study and were included in the ITT population (one patient was excluded despite completing the study because of dosing at 181 days). 14 (44%, 97·5% CI 26–100) of 32 patients achieved the primary endpoint of functional independent sitting for at least 10 s at any visit up to the 18 months of age study visit (vs 0 of 23 untreated patients in the PNCR cohort; p<0·0001). 31 (97%, 95% CI 91–100) of 32 patients in the ITT population survived free from permanent ventilatory support at 14 months compared with six (26%, 8–44) of 23 patients in the PNCR natural history cohort (p<0·0001). 32 (97%) of 33 patients had at least one adverse event and six (18%) had adverse events that were considered serious and related to onasemnogene abeparvovec. The most common adverse events were pyrexia (22 [67%] of 33), upper respiratory infection (11 [33%]), and increased alanine aminotransferase (nine [27%]). One death, unrelated to the study drug, occurred from hypoxic-ischaemic brain damage because of a respiratory tract infection during the study. STR1VE-EU showed efficacy of onasemnogene abeparvovec in infants with symptomatic spinal muscular atrophy type 1. No new safety signals were identified, but further studies are needed to show long-term safety. The benefit–risk profile of onasemnogene abeparvovec seems favourable for this patient population, including those with severe disease at baseline. Novartis Gene Therapies.

Pharmacological interventions that increase myofiber size counter the functional decline of dystrophic muscles 1 , 2 . We show that deacetylase inhibitors increase the size of myofibers in dystrophin-deficient (MDX) and α-sarcoglycan (α-SG)–deficient mice by inducing the expression of the myostatin antagonist follistatin 3 in satellite cells. Deacetylase inhibitor treatment conferred on dystrophic muscles resistance to contraction-coupled degeneration and alleviated both morphological and functional consequences of the primary genetic defect. These results provide a rationale for using deacetylase inhibitors in the pharmacological therapy of muscular dystrophies.

This article reports the first occurrence of (Rudolphi, 1819) (Digenea: Rhytidodidae) in the olive-ridley turtle (Testudines: Chelonidae), in an individual found in the State of Sergipe, Brazil. Although has already been described in other species of sea turtles in the world, this is the first report of this parasite in . We also present a list of hosts and locations where this helminth has already been identified.

Objective: The aim of this study was to identify risk factors for early-onset group B Streptococcus (EOGBS) disease in neonates of mothers with negative antenatal screening. Study Design: We performed a retrospective cohort study of neonates born to mothers with negative antenatal GBS screening between 2002 and 2012. Our primary outcome was EOGBS infection. We used multivariable logistic regression to assess factors associated with EOGBS. Results: EOGBS was confirmed in 492 of the 179 818 neonates that met the study inclusion criteria. Risk factors for EOGBS included black race (reference: white, odds ratio (OR) =1.81 (95% confidence interval: 1.43, 2.31)), maternal age <18 years (reference: >35 years, OR=2.63 (1.54, 4.51)) and maternal age 18 to 35 years (reference: >35 years, OR=1.94 (1.30, 2.88)). Conclusion: Maternal age <18 years and black race were the strongest predictors of EOGBS. Further research investigating contributors to the discordance between screening results and neonatal outcomes in these populations is needed.

The analysis of the electronic properties of strained or lattice deformed graphene combines ideas from classical condensed matter physics, soft matter, and geometrical aspects of quantum field theory (QFT) in curved spaces. Recent theoretical and experimental work shows the influence of strains in many properties of graphene not considered before, such as electronic transport, spin-orbit coupling, the formation of Moiré patterns, optics, ... There is also significant evidence of anharmonic effects, which can modify the structural properties of graphene. These phenomena are not restricted to graphene, and they are being intensively studied in other two dimensional materials, such as the metallic dichalcogenides. We review here recent developments related to the role of strains in the structural and electronic properties of graphene and other two dimensional compounds.

We study the surface resistivity of a three-dimensional topological insulator when the boundaries exhibit a non trivial curvature. We obtain an analytical solution for a spherical topological insulator, and we show that a non trivial quantum spin connection emerges from the three dimensional band structure. We analyze the effect of the spin connection on the scattering by a bump on a flat surface. Quantum effects induced by the geometry lead to resonances when the electron wavelength is comparable to the size of the bump.

Five important magnesite mines and small occurrences in the state of Ceará form a sequence of lenses that extend, discontinuously, for over 140km. The magnesite rocks are hosted by metadolomites with lutecite, sulphate nodules pseudomorphosed by fiber-radiated quartz, scapolite and dissolution breccias. This metacarbonate sequence is more voluminous and more calcic in the southwestern extremity of the belt, but less voluminous and more magnesian towards the northeastern portion of the belt, the highest Mg contents being observed in the Alencar-Orós region. Magnesite deposits pass gradually into metadolomites and then to almost pure calcitic marbles westward the belt. This group is hosted in a greenschists to amphibolite-facies metavolcanic-sedimentary sequence crosscut by basic sills and granitic intrusions of variable size, form, composition and age (middle to late Proterozoic ∼550Ma).Two types of magnesite marble may be distinguished: (1) medium-grained (1 to 9mm) and (2) sparry-magnesite marble (1 to 15cm). The latter displays wide textural variation (porphyric, rosette, layered and palisadic types) and exhibits remnants of the original sedimentary features. The sparry crystals, in spite of their deformation, are hypidiomorphic and pinolitic. The colors vary from white to light or dark gray, or even red. The dark banded term presents traces of microfossils and stromatolites structures. The medium-grained magnesite marble, on the other hand, shows more homogeneous texture and color and anhedral crystals are more abundant.The sparry-magnesite marble is less enriched in SiO2, Fe2O3, Al2O3 and CaO and richer in MgO than the medium-grained ones. The magnesitic marbles display positive Ce, and negative Eu anomalies. This suggests a shallow marine platform environment with continental, reduced influence (lagunar). These magnesitic marbles also show positive Ce and Eu anomalies in relation to the present seawater, suggesting compositional differences, materialized mainly by an enrichement of these elements in the past seawater.Fluid inclusions in the medium-grained magnesites of the Riacho Fundo deposit are aqueous inclusions, while in the sparry magnesite deposits, particularly in Cabeça de Negro, aquo-carbonic inclusions dominate. Hydrocarbons, however, are found in both cases.The calcitic marble, deposited on open-marine environment, displays positive13C (+0.5 to 2.1 ‰ PDB), while dolomitic to dolostone marbles, deposited on less open marine environment, display negative shift (0.7 to −3.2‰ PDB). This13C fluctuation is within the range for carbonates deposited around 1.8Ga.The depositional environment of these carbonates is close to a paralic system, lagoon, with strong evaporitic conditions. The depressions were of variable depth and lengths and could be isolated, in particular by stromatolitic barriers, dried and flooded by seawater with continental inflows. The largest and deepest ones correspond to the sparry magnesite deposits. These magnesites are located in a lateral way to almost pure calcitic marbles, through dolomitic marbles. This points to a process of chemical differentiation within a paralic system, from open sea to landwards, more calcic in the first to more magnesian in the confined environment, in which lagoon waters are progressively purified from Ca through preferential precipitation of calcic carbonates and secondly of gypsum/anhydrite, which increases the Mg/Ca ratio, and lead carbonate deposits towards the magnesite pole. These metacarbonates also reveal a fractionation of the light REE, starting from the calcitic, through the dolomitic to magnesitic marbles. In the calcitic marbles, REE are in association with the clay fraction, while in magnesitic marbles, they seem to be in association with organic and/or soluble complexes. The magnesitic marbles are of sedimentary origin and underwent important diagenetic evolution before being metamorphosed during the Brasiliano orogenic cycle.

The aim of this study was to determine the effect of cottonseed hull (CH) in the diets of rams on intake, digestibility, nitrogen balance, ingestive behaviour, and blood metabolites. Twenty males, uncastrated with an average body weight of 29.08 ± 4.18 kg, were distributed in a completely randomized design with four treatment diets and five replicates. The diet contained a forage to concentrate ratio of 50 : 50 (ground corn, soybean meal, corn silage, and CH), and the experimental treatments were inclusion of 0, 10, 20, and 30% CH (dry matter basis). Inclusion of CH linearly increased water intake, effective intake of ethereal extract and non-fibrous carbohydrates, and crude protein digestibility. Dry matter (DM) and neutral detergent fiber (NDF) digestibility, nitrogen faecal losses, and nitrogen balance reduced linearly with CH inclusion in the diet. Inclusion of CH in rams’ diet reduces intake, nutrient digestibility, and intake and rumination efficiencies. Thus, it is not recommended to add this by-product to the diet of high-performance rams, but for nurture that does not aim at high performance, inclusion of up to 5% of this by-product is recommended.

This study aimed to investigate the impact of dietary inclusion of babassu oil (BO) associated with sunflower oil (SO) on feeding behavior, water intake, and physiological parameters of feedlot lambs. Thirty‐five castrated male lambs (16.6 kg ± 3.9 kg) were distributed in a randomized block design with 5 treatments (diets) and 7 replications. The tested diets were oil‐free diet (OF), 45 g/kg BO (BO), 30 g/kg BO with an additional 15 g/kg SO (1.5 SO), 22.5 g/kg BO with an additional 22.5 g/kg SO (2.25 SO), and 30 g/kg SO with an additional 15 g/kg BO (3.0 SO) on dry matter (DM) basis. The experimental period lasted 60 days. Animals that received BO diet and the combination of BO with SO had lower intakes of DM and neutral detergent fiber (NDF) compared to the control diet ( P < 0.05). Differences on the respiratory rate (RR) was observed between animals in the control diet and those in the diets containing SO ( P = 0.001), with a linear increase in RR as the levels of SO in the diets increased ( P = 0.004). All physiological parameters showed a time effect ( P < 0.05). Animals fed with the control diet had higher water intake via drinking fountain ( P = 0.030) and total water intake ( P = 0.029) compared to animals fed with diets containing SO. In relation to SO levels, water intake via drinking fountain ( P = 0.002), total water intake ( P = 0.002), and total water intake per kg of DM ingested ( P = 0.001) linearly increased with the levels increase in the composition of the diets. The tested diets did not alter the feeding behavior of the feedlot lambs. However, the combination of BO with different levels of SO reduced DM and water intake via drinking fountain and RR.

The aim of this work was to explore the potential risk of vector-borne Chagas disease in urban districts in northeastern Brazil, by analyzing the spatiotemporal distributions and natural infection rates with Trypanosoma cruzi of triatomine species captured in recent years. The main motivation of this work was an acute human case of Chagas disease reported in 2008 in the municipality of Sobral. We analyzed data from community-based entomological surveillance carried out from 2010 to 2014. Triatomine natural T. cruzi infection was assessed by examination of insect feces by optical microscopy. Sites of triatomine capture were georeferenced through Google Earth and analyzed with ArcGIS. A total of 191 triatomines were collected, consisting of 82.2% Triatoma pseudomaculata, 7.9% Rhodnius nasutus, 5.8% T. brasiliensis, 3.7% Panstrongylus lutzi, and 0.5% P. megistus, with an overall natural infection index of 17.8%. Most infestations were reported in the districts of Dom José (36.2%), Padre Palhano (24.7%), and Alto do Cristo (10.6%). The overwhelming majority of insects (185/96.9%) were captured inside houses, and most insects tended to be collected in intermittent peaks. Moreover, captured triatomines tended to constitute colonies. The acute case reported in 2008 was found to be situated within a T. pseudomaculata hotspot. The triatomine collection events carried out by dwellers were aggregated in time and space into distinct foci, suggesting that insects are intermittently and artificially introduced into the city, possibly via accidental migration from their natural reservoirs. The relatively high T. cruzi infection rate indicates considerable circulation of the parasite in these areas, increasing the risk of vector-borne Chagas disease infection. These data suggest a need to strengthen epidemiological surveillance and integrate appropriate control actions targeting triatomines, T. cruzi reservoirs, and human populations. Our data also identify Chagas disease transmission as a hazard in urban areas of Sobral.