The use of IASI data to identify systematic errors in the ECMWF forecasts of temperature in the upper stratosphere

Since data from the Infrared Atmospheric Sounding Interferometer (IASI) became available in 2007, a number of papers have appeared in the literature which have reported relatively large discrepancies between IASI spectra and forward calculations in the centre of the CO<sub>2</sub> Q-branch at 667 cm<sup>−1</sup>. In this paper we show that these discrepancies are primarily due to errors in the temperature profiles used in the forward calculations. In particular, we have used forecasts of temperature profiles from the European Centre for Medium-Range Weather Forecasts (ECMWF) to demonstrate that, for the case study considered in this paper, these profiles are affected by systematic errors of the order of ≈10 K at the level of the stratopause. To derive the magnitude and the spatial location of the systematic errors in the temperature profile, we have carried out forward/inverse calculations for a number of clear-sky, daytime, IASI tropical soundings over the sea. The forward calculations have been performed using atmospheric state vectors which have been obtained either from the direct inversion of the IASI radiances or from space-time co-located profiles derived from radiosonde observations and from the ECMWF model. To rule out any effect due to the accuracy of the forward model, we have performed the forward calculations using two independent models. The sensitivity of the temperature biases to the variability of the CO<sub>2</sub> profile and to spectroscopy errors has also been studied

Unraveling the enigma of new-onset refractory status epilepticus: a systematic review of aetiologies

Background and purpose: New-onset refractory status epilepticus (NORSE) is a clinical presentation, neither a specific diagnosis nor a clinical entity. It refers to a patient without active epilepsy or other pre-existing relevant neurological disorder, with a NORSE without a clear acute or active structural, toxic or metabolic cause. This study reviews the currently available evidence about the aetiology of patients presenting with NORSE and NORSE-related conditions. Methods: A systematic search was carried out for clinical trials, observational studies, case series and case reports including patients who presented with NORSE, febrile-infection-related epilepsy syndrome or the infantile hemiconvulsion-hemiplegia and epilepsy syndrome. Results: Four hundred and fifty records were initially identified, of which 197 were included in the review. The selected studies were retrospective case–control (n = 11), case series (n = 83) and case reports (n = 103) and overall described 1334 patients both of paediatric and adult age. Aetiology remains unexplained in about half of the cases, representing the so-called ‘cryptogenic NORSE’. Amongst adult patients without cryptogenic NORSE, the most often identified cause is autoimmune encephalitis, either non-paraneoplastic or paraneoplastic. Infections are the prevalent aetiology of paediatric non-cryptogenic NORSE. Genetic and congenital disorders can have a causative role in NORSE, and toxic, vascular and degenerative conditions have also been described. Conclusions: Far from being a unitary condition, NORSE is a heterogeneous and clinically challenging presentation. The development and dissemination of protocols and guidelines to standardize diagnostic work-up and guide therapeutic approaches should be implemented. Global cooperation and multicentre research represent priorities to improve the understanding of NORSE

Geomorphological and bioclimatic relationships in the occurrence of species of agro-extractivist interest in the Cerrado biome.

The distribution of species of agro-extractivist interest and their ecological relationship with the physical environment geomorphological and bioclimatic allow supporting strategies aimed at socioeconomic and environmental development. We evaluated the contribution of high spatial resolution topographic variables in ecological niche models and the relationship of the distribution of five tree species with the geomorphological units and bioclimatic variables. The variables related to temperature variation and water availability proved to be important in predicting the areas of occurrence of the target species, with increased suitability of occurrence in regions with higher isothermality, located in the plateau and table geomorphological units. The predictions showed a significant difference when high spatial resolution variables were used, generating a more conservative scenario in the indication of suitable regions for the occurrence of species, important for local scale studies. The geomorphological units of plateau and tableland showed high suitability of occurrence, while the fluvial plains and dissected depressions did not present suitability for the occurrence of the species. The results allow us to strategically define areas with the greatest productive potential and prioritize areas for conservation, management, ecological restoration of forests, and targeting areas for the implementation of community agro-industries, essential for territorial planning within traditional communities

Anti-seizure medications for Lennox-Gastaut syndrome

Background Lennox‐Gastaut syndrome (LGS) is an age‐specific epilepsy syndrome characterised by multiple seizure types. LGS has a characteristic electroencephalogram, an onset before age eight years, and drug resistance. This is an updated version of the Cochrane Review published in 2013. Objectives To assess the efficacy and tolerability of anti‐seizure medications (ASMs) for LGS. Search methods We searched the Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid, 1946 to 28 February 2020) on 2 March 2020. CRS Web includes randomised controlled trials (RCTs) or quasi‐RCTs from the Cochrane Central Register of Controlled Trials (CENTRAL); the Specialised Registers of Cochrane Review Groups, including Cochrane Epilepsy; PubMed; Embase; ClinicalTrials.gov; and the World Health Organization's International Clinical Trials Registry Platform (ICTRP). We imposed no language restrictions. We contacted pharmaceutical companies and colleagues in the field to seek any unpublished or ongoing studies. Selection criteria We considered RCTs, including cross‐over trials, of ASMs for LGS in children and adults. We included studies of ASMs used as either monotherapy or as add‐on (adjunctive) therapy. We excluded studies comparing different doses of the same ASM. Data collection and analysis We used standard Cochrane methodological procedures, including independent, dual assessment for risk of bias, and applying the GRADE approach to rate the evidence certainty for outcomes. Main results We found no trials of ASM monotherapy. The review included 11 trials (1277 participants; approximately 11 weeks to 112 weeks follow‐up after randomisation) using add‐on ASMs for LGS in children, adolescents, and adults. Two studies compared add‐on cannabidiol (two doses) with add‐on placebo in children, adolescents, and adults. Insufficient information was provided for calculation of different response rate proportions in all seizures. We found high‐certainty evidence that 82 more people per 1000 (confidence interval (CI) 19 more to 350 more) had adverse events (AE) leading to study discontinuation with add‐on cannabidiol, compared to add‐on placebo (two studies; 396 participants; risk ratio (RR) 6.62, 95% CI 1.56 to 28.15). One study compared add‐on cinromide with add‐on placebo in children and adolescents only. We found very low‐certainty evidence that 35 more people per 1000 (CI 123 fewer to 434 more) had 50% or greater average reduction of overall seizures with add‐on cinromide compared to add‐on placebo (one study; 56 participants; RR 1.15, 95% CI 0.47 to 2.86). This study did not report participants with AE leading to study discontinuation. One study compared add‐on clobazam (three doses) with add‐on placebo. This study did not report overall seizure cessation or reduction. We found high‐certainty evidence that 106 more people per 1000 (CI 0 more to 538 more) had AE leading to study discontinuation with add‐on clobazam compared to add‐on placebo (one study; 238 participants; RR 4.12, 95% CI 1.01 to 16.87). One study compared add‐on felbamate with add‐on placebo. No cases of seizure cessation occurred in either regimen during the treatment phase (one study; 73 participants; low‐certainty evidence). There was low‐certainty evidence that 53 more people per 1000 (CI 19 fewer to 716 more) with add‐on felbamate were seizure‐free during an EEG recording at the end of the treatment phase, compared to add‐on placebo (RR 2.92, 95% CI 0.32 to 26.77). The study did not report overall seizure reduction. We found low‐certainty evidence that one fewer person per 1000 (CI 26 fewer to 388 more) with add‐on felbamate had AE leading to study discontinuation compared to add‐on placebo (one study, 73 participants; RR 0.97, 95% CI 0.06 to 14.97). Two studies compared add‐on lamotrigine with add‐on placebo. Neither study reported overall seizure cessation. We found high‐certainty evidence that 176 more people per 1000 (CI 30 more to 434 more) had ≥ 50% average seizure reduction with add‐on lamotrigine compared to add‐on placebo (one study; 167 participants; RR 2.12, 95% CI 1.19 to 3.76). We found low‐certainty evidence that 40 fewer people per 1000 (CI 68 fewer to 64 more) had AE leading to study‐discontinuation with add‐on lamotrigine compared to add‐on placebo (one study; 169 participants; RR 0.49, 95% CI 0.13 to 1.82). Two studies compared add‐on rufinamide with add‐on placebo. Neither study reported seizure cessation. We found high‐certainty evidence that 202 more people per 1000 (CI 34 to 567 more) had ≥ 50% average seizure reduction (one study; 138 participants; RR 2.84, 95% CI 1.31 to 6.18). We found low‐certainty evidence that 105 more people per 1000 (CI 17 fewer to 967 more) had AE leading to study discontinuation with add‐on rufinamide compared to add‐on placebo (one study; 59 participants; RR 4.14, 95% CI 0.49 to 34.86). One study compared add‐on rufinamide with another add‐on ASM. This study did not report overall seizure cessation or reduction. We found low‐certainty evidence that three fewer people per 1000 (CI 75 fewer to 715 more) had AE leading to study discontinuation with add‐on rufinamide compared to another add‐on ASM (one study; 37 participants; RR 0.96, 95% CI 0.10 to 9.57). One study compared add‐on topiramate with add‐on placebo. This study did not report overall seizure cessation. We found low‐certainty evidence for ≥ 75% average seizure reduction with add‐on topiramate (one study; 98 participants; Peto odds ratio (Peto OR) 8.22, 99% CI 0.60 to 112.62) and little or no difference to AE leading to study discontinuation compared to add‐on placebo; no participants experienced AE leading to study discontinuation (one study; 98 participants; low‐certainty evidence). Authors' conclusions RCTs of monotherapy and head‐to‐head comparison of add‐on ASMs are currently lacking. However, we found high‐certainty evidence for overall seizure reduction with add‐on lamotrigine and rufinamide, with low‐certainty evidence for AE leading to study discontinuation compared with add‐on placebo or another add‐on ASM. The evidence for other add‐on ASMs for overall seizure cessation or reduction was low to very low with high‐ to low‐certainty evidence for AE leading to study discontinuation. Future research should consider outcome reporting of overall seizure reduction (applying automated seizure detection devices), impact on development, cognition and behaviour; future research should also investigate age‐specific efficacy of ASMs and target underlying aetiologies

Mimicking microbial 'education' of the immune system: a strategy to revert the epidemic trend of atopy and allergic asthma?

Deficient microbial stimulation of the immune system, caused by hygiene, may underly the atopy and allergic asthma epidemic we are currently experiencing. Consistent with this 'hygiene hypothesis', research on immunotherapy of allergic diseases also centres on bacteria-derived molecules (eg DNA immunostimulatory sequences) as adjuvants for allergen-specific type 1 immune responses. If we understood how certain microbes physiologically 'educate' our immune system to interact safely with environmental nonmicrobial antigens, we might be able to learn to mimic their beneficial actions. Programmed 'immunoeducation' would consist of safe administration, by the correct route, dose and timing, of those microbial stimuli that are necessary to 'train' the developing mucosal immune system and to maintain an appropriate homeostatic equilibrium between its components. Overall, this would result in a prevention of atopy that is not limited to certain specific allergens. Although such a strategy is far beyond our present potential, it may in principle revert the epidemic trend of atopy and allergic asthma without jeopardizing the fight against infectious diseases

Land-use in Amazonia and the cerrado of Brazil.

The total area and annual rate of native vegetation clearing is greatest in the Cerrado region followed by the Brazilian states of Para, Mato Grosso, Maranhao and Rondonia. Amazonian forest clearing proceeds most quickly where abundant natural resources (wood or land) are accessible by roads and close to markets. These regions are concentrated along the eastern and southern flanks of Amazonia, particularly in eastern Para, Cuiaba and Rondonia. There are still large discrepancies in estimates of annual deforestation; Landsat (Thematic Mapper-based) mapping of deforestation in the closed-canopy forests of Amazonia has not include non-Brazilian countries and is incomplete for the cerrado biome. Amazonian deforestation was last mapped 1994. Current estimates of Amazonian forest clearing do not include most of the forests that are affected by logging each year, which is an area (about 7,000 km2 yr-1)more than half the size of the area of annual deforestation. Logging changes forest structure and increases forest flammability. The intensity of logging ranges from 1-to 100-species harvest, and averages 20m3 of wood harvested per hectare. Logging may increase dramatically in the coming years. Fire affects large, but difficult to measure, areas of pastureland, logged forests, secondary forests and primary forests. Forest ground fires are particularly difficult to map fom satellite data. Fire is more frequent where forest clearing is taking place, and where seasonal drought is most severe. The destiny of Amazonian forest land cleared for crops and cattle pasture is complex, and highly variables regionally. Areal estimates are needed for managed pasture, degraded pasture, cropland and secondadry forests, for these ecosystems are functionally distinct. Most forest clearing is for pasture establishment, followed by shifting cultivation. Cattle pasture is the logical land-use for both small-scale and large-scale rural Amazonians because cattle are easily sold or traded, and they maintain their value during inflation. Cattle patures help secure land claims and increase land value. In the Cerrado, there has been a shift from extensive cattle grazing of natural savannas to pasture planted with African forage grasses; mechanized soy bean production is the second most extensive land-use. Pastures are the most important land-cover for the LBA (Large-Scale Biosphere - Atmosphere experiment in Amazonia) science campaign. Brazilian Amazonia experiences reduced rainfall during ENSO events. ENSO-related drought is most severe in eastern Amazonia. A basin-wide reduction in rainfall would have its greatest affect on vegetation near the border between savanna and closed-canopy forest in Rondonia, Mato Grosso, Para and Tocantins. The LBA campaign should be conducted in variety of rural landscapes to capture the multiplicity of human effects on native ecosystems, as well as the range of cliamatic and edaphic conditions under which these ecosystems have evolved. It should address the current (ENSO) and predicted variations in climate, and should be designed to recommend those land-uses that best reconcile the maintenance of ecosystem processes with socially equitable economic growth

Preparation of gellan-cholesterol nanohydrogels embedding baicalin and evaluation of their wound healing activity

[EN] In the present work, the preparation, characterization and therapeutic potential of baicalin-loaded nanohydrogels are reported. The nanohydrogels were prepared by sonicating (S nanohydrogel) or autoclaving (A nanohydrogel) a dispersion of cholesterol-derivatized gellan in phosphate buffer. The nanohydrogel obtained by autoclave treatment showed the most promising results: smaller particles ( similar to 362 nm vs. similar to 530 nm), higher homogeneity (polydispersity index = similar to 0.24 vs. similar to 0.47), and lower viscosity than those obtained by sonication. In vitro studies demonstrated the ability of the nanohydrogels to favour the deposition of baicalin in the epidermis. A high biocompatibility was found for baicalin-loaded nanohydrogels, along with a great ability to counteract the toxic effect induced by hydrogen peroxide in cells, as the nanohydrogels re-established the normal conditions (similar to 100% viability). Further, the potential of baicalin-loaded nanohydrogels in skin wound healing was demonstrated in vivo in mice by complete skin restoration and inhibition of specific inflammatory markers (i.e., myeloperoxidase, tumor necrosis factor-alpha, and oedema.Financial support from University "Sapienza" - Progetti di Ricerca: grant RP116154C2EF9AC8 and grant RM11715C1743EE89 are acknowledged.Manconi, M.; Manca, M.; Caddeo, C.; Cencetti, C.; Di Meo, C.; Zoratto, N.; Nácher Alonso, A.... (2018). Preparation of gellan-cholesterol nanohydrogels embedding baicalin and evaluation of their wound healing activity. European Journal of Pharmaceutics and Biopharmaceutics. 127:244-249. https://doi.org/10.1016/j.ejpb.2018.02.015S24424912

Effect of lifestyle factors on Staphylococcus aureus gut colonization in Swedish and Italian infants

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Efficacy and Safety of Fenfluramine in Epilepsy: A Systematic Review and Meta-analysis

Introduction: Fenfluramine (FFA) is an amphetamine derivative that promotes the release and blocks the neuronal reuptake of serotonin. Initially introduced as an appetite suppressant, FFA also showed antiseizure properties. This systematic review aimed to assess the efficacy and safety of FFA for the treatment of seizures in patients with epilepsy. Methods: We systematically searched (in week 3 of June 2022) MEDLINE, the Cochrane Central Register of Controlled Trials, and the US National Institutes of Health Clinical Trials Registry. Randomized, double- or single-blinded, placebo-controlled studies of FFA in patients with epilepsy and uncontrolled seizures were identified. Efficacy outcomes included the proportions of patients with ≥ 50% and 100% reductions in baseline seizure frequency during the treatment period. Tolerability outcomes included the proportions of patients who withdrew from treatment for any reason and suffered adverse events (AEs). The risk of bias in the included studies was assessed according to the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions. The risk ratio (RR) along with the 95% confidence interval (CI) were estimated for each outcome. Results: Three trials were identified and a total of 469 Dravet syndrome (DS) and Lennox–Gastaut syndrome (LGS) subjects were randomized. All three trials were judged to be at low risk of biases. In patients with DS, the RRs for ≥ 50% and 100% reductions in convulsive seizure frequency for the FFA group compared to placebo were 5.61 (95% CI 2.73–11.54) and 4.71 (95% CI 0.57–39.30), respectively. In patients with LGS, the corresponding RRs for ≥ 50% and 100% reductions in drop seizure frequency were 2.58 (95% CI 1.33–5.02) and 0.50 (95% CI 0.031–7.81), respectively. The drug was withdrawn for any reason in 10.1% and 5.8% of patients receiving FFA and placebo, respectively (RR 1.79, 95% CI 0.89–3.59). Treatment discontinuation due to AEs occurred in 5.4% and 1.2% of FFA- and placebo-treated patients, respectively (RR 3.63, 95% CI 0.93–14.16). Decreased appetite, diarrhoea, fatigue, and weight loss were AEs associated with FFA treatment. Conclusion: Fenfluramine reduces the frequency of seizures in patients with DS and LGS. Decreased appetite, diarrhoea, fatigue, and weight loss are non-cardiovascular AEs associated with FFA

Pharmacotherapy for Dravet Syndrome: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials

Background: Dravet syndrome (DS) is a severe developmental and epileptic encephalopathy characterized by drug-resistant, lifelong seizures. The management of seizures in DS has changed in recent years with the approval of new antiseizure medications (ASMs). Objective: The aim of this study was to estimate the comparative efficacy and tolerability of the ASMs for the treatment of seizures associated with DS using a network meta-analysis (NMA). Methods: Studies were identified by conducting a systematic search (week 4, January 2023) of the MEDLINE (accessed by PubMed), EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and US National Institutes of Health Clinical Trials Registry (http://www.clinicaltrials.gov) databases. Any randomized, controlled, double- or single-blinded, parallel-group study comparing at least one ASM therapy against placebo, another ASM, or a different dose of the same ASM in participants with a diagnosis of DS was identified. The efficacy outcomes were the proportions of participants with ≥ 50% (seizure response) and 100% reduction (seizure freedom) in baseline convulsive seizure frequency during the maintenance period. The tolerability outcomes included the proportions of patients who withdrew from treatment for any reason and who experienced at least one adverse event (AE). Effect sizes were estimated by network meta-analyses within a frequentist framework. Results: Eight placebo-controlled trials were included, and the active add-on treatments were stiripentol (n = 2), pharmaceutical-grade cannabidiol (n = 3), fenfluramine hydrochloride (n = 2), and soticlestat (n = 1). The studies recruited 680 participants, of whom 409 were randomized to active treatments (stiripentol = 33, pharmaceutical-grade cannabidiol = 228, fenfluramine hydrochloride = 122, and soticlestat = 26) and 271 to placebo. Pharmaceutical-grade cannabidiol was associated with a lower rate of seizure response than fenfluramine hydrochloride (odds ratio [OR] 0.20, 95% confidence interval [CI] 0.07–0.54), and stiripentol was associated with a higher seizure response rate than pharmaceutical-grade cannabidiol (OR 14.07, 95% CI 2.57–76.87). No statistically significant differences emerged across the different ASMs for the seizure freedom outcome. Stiripentol was associated with a lower probability of drug discontinuation for any reason than pharmaceutical-grade cannabidiol (OR 0.45, 95% CI 0.04–5.69), and pharmaceutical-grade cannabidiol was associated with a lower proportion of participants experiencing any AE than fenfluramine hydrochloride (OR 0.22, 95% CI 0.06–0.78). Stiripentol had a higher risk of AE occurrence than pharmaceutical-grade cannabidiol (OR 75.72, 95% CI 3.59–1598.58). The study found high-quality evidence of efficacy and tolerability of the four ASMs in the treatment of convulsive seizures in DS. Conclusions: There exists first-class evidence that documents the efficacy and tolerability of stiripentol, pharmaceutical-grade cannabidiol, fenfluramine hydrochloride, and soticlestat for the treatment of seizures associated with DS, and allows discussion about the expected outcomes regarding seizure frequency reduction and tolerability profiles