Structural concepts and experimental considerations for a versatile high-speed research airplane

Future aircraft may be hydrogen fueled and fly at hypersonic speeds. The resulting environments will require new structural concepts to satisfy performance goals. Large representative structures will have to be flight tested prior to commitment to a costly vehicle fleet. To perform flight tests, a versatile, economical, high-speed research airplane is defined. Results of this study including experimental considerations for a hypersonic research airplane are reported

White coat hypertension is associated with increased small vessel disease in the brain

Objective: Small vessel disease, as measured by white matter hyperintensity (WMH) in the brain, is known to be associated with increased stroke risk and cognitive impairment. This study explored the relationship between WMH on computerised tomography (CT) and white coat hypertension/effect (WCH/E) in patients with recent transient ischaemic attack (TIA) or lacunar stroke (LS). Design and method: Ninety-six patients recruited for the ASIST trial (Arterial Stiffness in Lacunar Stroke and TIA) underwent measurement of clinic blood pressure (BP) and ambulatory BP monitoring (APBM) within two weeks of TIA or LS. Twenty-three patients had normotension (clinic BP / = 140/90mmHg and day-time ABPM < 135/85mmHg). Arterial stiffness was measured using carotid-femoral pulse wave velocity (PWV) (Complior®, ALAM Medical) and carotid-ankle vascular index (CAVI) (VaSera VS-1500N®, Fukuda Denshi). CT images were scored for WMH using the four-point Fazekas visual rating scale. Patients were grouped into no-mild WMH (scores 0–1) or moderate-severe (scores 2–3) groups. The relationship between BP, vascular stiffness and WMH was explored with t-tests, chi-square and logistic regression accounting for known cardiovascular risk factors. Results: Forty-four percent of patients with WCH/E had moderate-severe WMH compared to 17% of normotensives (p = 0.047). The regression model with WMH as the dependent factor, and WCH/E and cardiovascular risk factors as independent factors showed WCH/E and either CAVI or PWV to be the only independent significant factor contributing to WMH (CAVI:p = 0.038, PWV:p = 0.043)

Long-term therapeutic effect of eslicarbazepine acetate in children: An open-label extension of a cognition study in children aged 6-16 years

OBJECTIVE: In Europe, eslicarbazepine acetate (ESL) is approved as adjunctive therapy for the treatment of focal seizures (FS) in children aged >6 years. In the US, ESL is approved as both monotherapy and adjunctive therapy for the treatment of FS in patients aged ≥4 years. In a phase II study of children aged 6-16 years with FS, ESL had no significant effects on attention or behavioral functioning and decreased seizure frequency during double-blind therapy and a 1-year open-label extension (OLE). This report presents data from an additional 2-year OLE of the phase II study. METHODS: Previous recipients of ESL or placebo were treated with open-label ESL (10-30 mg/kg/day, adjusted for clinical response and/or adverse events [AEs]). Safety was assessed by incidence of treatment-emergent AEs (TEAEs). Efficacy endpoints were treatment retention time and change from baseline in Clinical Global Impression-Severity (CGI-S) scale scores. RESULTS: Forty-two patients entered and 31 (73.8%) completed the 2-year OLE. Median treatment retention time was 735 (95% confidence interval 728-741) days. Seven patients (17% of total, 23% of completed) experienced ≥1 TEAE during the 2-year OLE, mostly of mild or moderate intensity. The incidence of serious TEAEs was low (n = 2; 5% of total, 6% of completed) and none were related to ESL. One child was withdrawn because of splenomegaly that was considered possibly related to ESL. The only change from baseline in CGI-S was a 0.5-point reduction in the severity of illness score. All findings were consistent across patient subgroups based on previous double-blind treatment (placebo or ESL) and patient age (6-11 or 12-16 years). CONCLUSIONS: The majority of patients remained on ESL during the 2-year OLE, and treatment efficacy was maintained. Adverse events were consistent with the known safety profile of ESL, and no new safety signals were identified

Interscalene brachial plexus block for surgical repair of clavicle fracture: a matched case-controlled study.

Innervation of the clavicle is complex and debated, with scarce data on the analgesic and clinical impact of regional anaesthesia after surgical repair of clavicle fracture. In order to assess the analgesic efficiency of an interscalene brachial plexus block (ISB) for surgical repair of clavicle fracture, 50 consecutive patients scheduled for surgical fixation of middle/lateral clavicle fracture under general anaesthesia with ISB were prospectively enrolled. This cohort was compared to a historical control of 76 retrospective patients without regional block. The primary outcome was total intravenous morphine equivalent consumption at 2 postoperative hours. To assess the ISB impact, both an overall cohort analysis and a case-matched analysis with each ISB-treated patient matched to a Non-ISB-treated patient was performed. Matching employed a 1-to-1, nearest-neighbour approach using the Mahalanobis metric. In the overall cohort, patients with ISB had significantly lower i.v. morphine equivalent consumption at 2 postoperative hours (0.7 mg (95% CI 0.1 to 1.2) versus controls 8.8 mg (95% CI 7.1 to 10.4); P &lt; 0.0001). These results persisted after case-matching the cohorts (mean difference for the primary outcome: 8.3 mg (95% CI 6.5 to 10.0); P &lt; 0.001). ISB provides effective analgesia after surgical fixation of middle and lateral clavicle fracture. These results should help physicians in establishing an analgesic strategy for this type of surgery. Further research is needed to identify the optimal regional technique for medial third clavicle fractures and the clinically relevant contributions of the cervical and brachial plexus. Clinicaltrials.gov - NCT02565342, October 1st 2015

Tissue engineering a fetal membrane

The aim of this study was to construct an artificial fetal membrane (FM) by combination of human amniotic epithelial stem cells (hAESCs) and a mechanically enhanced collagen scaffold containing encapsulated human amniotic stromal fibroblasts (hASFs). Such a tissue-engineered FM may have the potential to plug structural defects in the amniotic sac after antenatal interventions, or to prevent preterm premature rupture of the FM. The hAESCs and hASFs were isolated from human fetal amniotic membrane (AM). Magnetic cell sorting was used to enrich the hAESCs by positive ATP-binding cassette G2 selection. We investigated the use of a laminin/fibronectin (1:1)-coated compressed collagen gel as a novel scaffold to support the growth of hAESCs. A type I collagen gel was dehydrated to form a material mimicking the mechanical properties and ultra-structure of human AM. hAESCs successfully adhered to and formed a monolayer upon the biomimetic collagen scaffold. The resulting artificial membrane shared a high degree of similarity in cell morphology, protein expression profiles, and structure to normal fetal AM. This study provides the first line of evidence that a compacted collagen gel containing hASFs could adequately support hAESCs adhesion and differentiation to a degree that is comparable to the normal human fetal AM in terms of structure and maintenance of cell phenotype

Episodic, compression-driven fluid venting in layered sedimentary basins

Fluid venting phenomena are prevalent in sedimentary basins globally. Offshore, these localised fluid-expulsion events are archived in the geologic record via the resulting pockmarks at the sea-floor. Venting is widely interpreted to occur via hydraulic fracturing, which requires near-lithostatic pore pressures for initiation. One common driver for these extreme pressures is horizontal tectonic compression, which pressurises the entire sedimentary column over a wide region. Fluid expulsion leads to a sudden, local relief of this pressure, which then gradually recharges through continued compression, leading to episodic venting. Pressure recharge will also occur through pressure diffusion from neighboring regions that remain pressurised, but the combined role of compression and pressure diffusion in episodic venting has not previously been considered. Here, we develop a novel poroelastic model for episodic, compression-driven venting. We show that compression and pressure diffusion together set the resulting venting period. We derive a simple analytical expression for this venting period, demonstrating that pressure diffusion can significantly reduce the venting period associated with a given rate of compression and allowing this rate of compression to be inferred from observations of episodic venting. Our results indicate that pressure diffusion is a major contributor to episodic fluid venting in mudstone-dominated basins

Episodic fluid venting from sedimentary basins fuelled by pressurised mudstones

Subsurface sandstone reservoirs sealed by overlying, low-permeability layers provide capacity for long-term sequestration of anthropogenic waste. Leakage can occur if reservoir pressures rise sufficiently to fracture the seal. Such pressures can be generated within the reservoir by vigorous injection of waste or, over thousands of years, by natural processes. In either case, the precise role of intercalated mudstones in the long-term evolution of reservoir pressure remains unclear; these layers have variously been viewed as seals, as pressure sinks or as pressure sources. Here, we use the geological record of episodic fluid venting in the Levant Basin to provide striking evidence for the pressure-source hypothesis. We use a Bayesian framework to combine recently published venting data, which record critical subsurface pressures since $\sim$2 Ma, with a stochastic model of pressure evolution to infer a pressure-recharge rate of $\sim$30 MPa/Myr. To explain this large rate, we quantify and compare a range of candidate mechanisms. We find that poroelastic pressure diffusion from mudstones provides the most plausible explanation for these observations, amplifying the $\sim$1 MPa/Myr recharge caused by tectonic compression. Since pressurised mudstones are ubiquitous in sedimentary basins, pressure diffusion from mudstones is likely to promote seal failure globally