NASA Quiet Clean General Aviation Turbofan (QCGAT) program status

The suitability of large engine technology to reduce noise, emissions, and fuel consumption of small turbine engines and develop new technology where required is determined. The design, fabrication, assembly, test, and delivery of the experimental engines to NASA are discussed

Human fur gene encodes a yeast KEX2-like endoprotease that cleaves pro-beta-NGF in vivo.

Extracts from BSC-40 cells infected with vaccinia recombinants expressing either the yeast KEX2 prohormone endoprotease or a human structural homologue (fur gene product) contained an elevated level of a membrane-associated endoproteolytic activity that could cleave at pairs of basic amino acids (-LysArg- and -ArgArg-). The fur-directed activity (furin) shared many properties with Kex2p including activity at pH 7.3 and a requirement for calcium. By using antifurin antibodies, immunoblot analysis detected two furin translation products (90 and 96 kD), while immunofluorescence indicated localization to the Golgi apparatus. Coexpression of either Kex2p or furin with the mouse beta-nerve growth factor precursor (pro-beta-NGF) resulted in greatly enhanced conversion of the precursor to mature nerve growth factor. Thus, the sequence homology shared by furin and the yeast KEX2 prohormone processing enzyme is reflected by significant functional homology both in vitro and in vivo

Aerobic Exercise Attenuates Risk of Coronary Artery Disease and Improves Mobility in SCI

Please see the pdf version of the abstract

Lamotrigine add-on therapy for drug-resistant generalised tonic-clonic seizures

BACKGROUND: This is an update of the Cochrane Review first published in 2010; it includes one additional study. Primary generalised tonic‐clonic seizures are a type of generalised seizure. Other types of seizures include: absence, myoclonic, and atonic seizures. Effective control of tonic‐clonic seizures reduces the risk of injury and death, and improves quality of life. While most people achieve seizure control with one antiepileptic drug, around 30% do not, and require a combination of antiepileptic drugs. OBJECTIVES: To assess the effectiveness and tolerability of add‐on lamotrigine for drug‐resistant primary generalised tonic‐clonic seizures. SEARCH METHODS: For the latest update, we searched these databases on 19 March 2019: Cochrane Register of Studies (CRS) Web, MEDLINE Ovid, and the WHO International Clinical Trials Registry Platform (ICTRP). The CRS includes records from the Cochrane Epilepsy Group Specialized Register, CENTRAL, Embase, and ClinicalTrials.gov. We imposed no language restrictions. We also contacted GlaxoSmithKline, manufacturers of lamotrigine. SELECTION CRITERIA: Randomised controlled parallel or cross‐over trials of add‐on lamotrigine for people of any age with drug‐resistant primary generalised tonic‐clonic seizures. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology; two review authors independently assessed trials for inclusion, evaluated risk of bias, extracted relevant data, and GRADE‐assessed evidence. We investigated these outcomes: (1) 50% or greater reduction in primary generalised tonic‐clonic seizure frequency; (2) seizure freedom; (3) treatment withdrawal; (4) adverse effects; (5) cognitive effects; and (6) quality of life. We used an intention‐to‐treat (ITT) population for all analyses, and presented results as risk ratios (RRs) with 95% confidence intervals (CIs); for adverse effects, we used 99% CIs to compensate for multiple hypothesis testing. MAIN RESULTS: We included three studies (total 300 participants): two parallel‐group studies and one cross‐over study. We assessed varied risks of bias across studies; most limitations arose from the poor reporting of methodological details. We meta‐analysed data extracted from the two parallel‐group studies, and conducted a narrative synthesis for data from the cross‐over study. Both parallel‐group studies (270 participants) reported all dichotomous outcomes. Participants taking lamotrigine were almost twice as likely to attain a 50% or greater reduction in primary generalised tonic‐clonic seizure frequency than those taking a placebo (RR 1.88, 95% CI 1.43 to 2.45; low‐certainty evidence). The results between groups were inconclusive for the likelihood of seizure freedom (RR 1.55, 95% CI 0.89 to 2.72; very low‐certainty evidence); treatment withdrawal (RR 1.20, 95% CI 0.72 to 1.99; very low‐certainty evidence); and individual adverse effects: ataxia (RR 3.05, 99% CI 0.05 to 199.36); dizziness (RR 0.91, 99% CI 0.29 to 2.86; very low‐certainty evidence); fatigue (RR 1.02, 99% CI 0.13 to 8.14; very low‐certainty evidence); nausea (RR 1.60, 99% CI 0.48 to 5.32; very low‐certainty evidence); and somnolence (RR 3.73, 99% CI 0.36 to 38.90; low‐certainty evidence). The cross‐over trial (26 participants) reported that 7/14 participants with generalised tonic‐clonic seizures experienced a 50% or greater reduction in seizure frequency with add‐on lamotrigine compared to placebo. The authors reported four treatment withdrawals, but did not specify during which treatment allocation they occurred. Rash (seven lamotrigine participants; zero placebo participants) and fatigue (five lamotrigine participants; zero placebo participants) were the most frequently reported adverse effects. None of the included studies measured cognition. One parallel‐group study (N = 153) evaluated quality of life. They reported inconclusive results for the overall quality of life score between groups (P = 0.74). AUTHORS' CONCLUSIONS: This review provides insufficient information to inform clinical practice. Low‐certainty evidence suggests that lamotrigine reduces the rate of generalised tonic‐clonic seizures by 50% or more. Very low‐certainty evidence found inconclusive results between groups for all other outcomes. Therefore, we are uncertain to very uncertain that the results reported are accurate, and suggest that the true effect could be grossly different. More trials, recruiting larger populations, over longer periods, are necessary to determine lamotrigine's clinical use

Lamotrigine add-on therapy for drug-resistant focal epilepsy.

BACKGROUND:This is an updated version of the Cochrane Review previously published in 2016. Epilepsy is a common neurological disorder, affecting 0.5% to 1% of the population. For nearly 30% of these people, their epilepsy is resistant to currently available drugs. Pharmacological treatment remains the first choice to control epilepsy. Lamotrigine is one of the newer antiepileptic drugs. Lamotrigine, in combination with other antiepileptic drugs (add-on), can reduce seizures, but with some adverse effects. OBJECTIVES:To determine the effects of lamotrigine on (1) seizures, (2) adverse-effect profile, and (3) cognition and quality of life, compared to placebo, when used as an add-on treatment for people with drug-resistant focal epilepsy. SEARCH METHODS:For the latest update of the review, we searched the following databases on 9 March 2020: Cochrane Register of Studies (CRS Web), MEDLINE (Ovid, 1946 to March 06, 2020). CRS Web includes randomized or quasi-randomized, controlled trials from PubMed, EMBASE, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the Specialized Registers of Cochrane Review Groups including Epilepsy. No language restrictions were imposed. SELECTION CRITERIA:Randomised placebo-controlled trials of people with drug-resistant focal epilepsy of any age, in which an adequate method of concealment of randomisation was used. The studies were double-, single- or unblinded, placebo-controlled. For cross-over studies, the first treatment period was treated as a parallel trial. Eligible participants were adults or children with drug-resistant focal epilepsy. DATA COLLECTION AND ANALYSIS:For this update, two review authors independently assessed the trials for inclusion, and extracted data. Outcomes included 50% or greater reduction in seizure frequency, treatment withdrawal (any reason), adverse effects, effects on cognition and quality of life. Primary analyses were by intention-to-treat. Sensitivity best- and worse-case analyses were undertaken to account for missing outcome data. Pooled risk ratios (RRs) with 95% confidence intervals (95% Cls) were estimated for the primary outcomes of seizure frequency and treatment withdrawal. For adverse effects, we calculated pooled RRs and 99% Cls. MAIN RESULTS:We did not identify any new studies for this update, therefore, the results and conclusions are unchanged. In previous updates of this review, the authors found five parallel add-on studies, eight cross-over studies in adults or children with drug-resistant focal epilepsy, and one parallel add-on study with a responder-enriched design in infants. In total, these 14 studies included 1806 eligible participants (38 infants, 199 children, 1569 adults). Baseline phases ranged from four to 12 weeks; treatment phases from eight to 36 weeks. Overall, 11 studies (1243 participants) were rated as having low risk of bias, and three (697 participants) had unclear risk of bias due to lack of reported information around study design. Effective blinding of studies was reported in four studies (563 participants). The overall risk ratio (RR) for 50% or greater reduction in seizure frequency was 1.80 (95% CI 1.45 to 2.23; 12 trials, 1322 participants (adults and children); moderate-certainty evidence) indicating that lamotrigine was significantly more effective than placebo in reducing seizure frequency. The overall RR for treatment withdrawal (for any reason) was 1.11 (95% CI 0.91 to 1.37; 14 trials; 1806 participants; moderate-certainty evidence). The adverse events significantly associated with lamotrigine were: ataxia, dizziness, diplopia (double vision), and nausea. The RR of these adverse effects were as follows: ataxia 3.34 (99% Cl 2.01 to 5.55; 12 trials; 1525 participants; high-certainty evidence); dizziness 2.00 (99% Cl 1.52 to 2.64;13 trials; 1768 participants; moderate-certainty evidence); diplopia 3.79 (99% Cl 2.15 to 6.68; 3 trials, 944 participants; high-certainty evidence); nausea 1.81 (99% Cl 1.22 to 2.68; 12 studies,1486 participants; moderate-certainty evidence). The limited data available precluded any conclusions about effects on cognition and quality of life. No important heterogeneity between studies was found for any of the outcomes. Overall, we assessed the evidence as high to moderate certainty, due to incomplete data for some outcomes. AUTHORS' CONCLUSIONS:Lamotrigine as an add-on treatment for drug-resistant focal seizures appears to be effective in reducing seizure frequency, and seems to be fairly well-tolerated. However, the trials were of relatively short duration and provided no evidence for the long term. Further trials are needed to assess the long-term effects of lamotrigine, and to compare lamotrigine with other add-on drugs

Expanding Aquatic Observations through Recreation

Accurate observations of the Earth system are required to understand how our planet is changing and to help manage its resources. The aquatic environment—including lakes, rivers, wetlands, estuaries, coastal and open oceans—is a fundamental component of the Earth system controlling key physical, biological, and chemical processes that allow life to flourish. Yet, this environment is critically undersampled in both time and space. New and cost-effective sampling solutions are urgently needed. Here, we highlight the potential to improve aquatic sampling by tapping into recreation. We draw attention to the vast number of participants that engage in aquatic recreational activities and argue, based on current technological developments and recent research, that the time is right to employ recreational citizens to improve large-scale aquatic sampling efforts. We discuss the challenges that need to be addressed for this strategy to be successful (e.g., sensor integration, data quality, and citizen motivation), the steps needed to realize its potential, and additional societal benefits that arise when engaging citizens in scientific sampling

Expanding aquatic observations through recreation

This is the final version. Available on open access from Frontiers Media via the DOI in this recordAccurate observations of the Earth system are required to understand how our planet is changing and to help manage its resources. The aquatic environment-including lakes, rivers, wetlands, estuaries, coastal and open oceans-is a fundamental component of the Earth system controlling key physical, biological, and chemical processes that allow life to flourish. Yet, this environment is critically undersampled in both time and space. New and cost-effective sampling solutions are urgently needed. Here, we highlight the potential to improve aquatic sampling by tapping into recreation. We draw attention to the vast number of participants that engage in aquatic recreational activities and argue, based on current technological developments and recent research, that the time is right to employ recreational citizens to improve large-scale aquatic sampling efforts. We discuss the challenges that need to be addressed for this strategy to be successful (e.g., sensor integration, data quality, and citizen motivation), the steps needed to realize its potential, and additional societal benefits that arise when engaging citizens in scientific sampling.UK National Centre for Earth ObservationSmartfin/Lostbird FoundationDefr