New approaches for achieving more perfect transition metal oxide thin films

This perspective considers the enormous promise of epitaxial functional transition metal oxide thin films for future applications in low power electronic and energy applications since they offer wide-ranging and highly tunable functionalities and multifunctionalities, unrivaled among other classes of materials. It also considers the great challenges that must be overcome for transition metal oxide thin films to meet what is needed in the application domain. These challenges arise from the presence of intrinsic defects and strain effects, which lead to extrinsic defects. Current conventional thin film deposition routes often cannot deliver the required perfection and performance. Since there is a strong link between the physical properties, defects and strain, routes to achieving more perfect materials need to be studied. Several emerging methods and modifications of current methods are presented and discussed. The reasons these methods better address the perfection challenge are considered and evaluated

Long-term effects of delayed-release dimethyl fumarate in multiple sclerosis: Interim analysis of ENDORSE, a randomized extension study

BACKGROUND: Delayed-release dimethyl fumarate (DMF) demonstrated strong efficacy and a favorable benefit-risk profile for patients with relapsing-remitting multiple sclerosis (RRMS) in phase 3 DEFINE/CONFIRM studies. ENDORSE is an ongoing long-term extension of DEFINE/CONFIRM. OBJECTIVE: We report efficacy and safety results of a 5-year interim analysis of ENDORSE (2 years DEFINE/CONFIRM; minimum 3 years ENDORSE). METHODS: In ENDORSE, patients randomized to DMF 240 mg twice (BID) or thrice daily (TID) in DEFINE/CONFIRM continued this dosage, and those initially randomized to placebo (PBO) or glatiramer acetate (GA) were re-randomized to DMF 240 mg BID or TID. RESULTS: For patients continuing DMF BID (BID/BID), annualized relapse rates were 0.202, 0.163, 0.139, 0.143, and 0.138 (years 1-5, respectively) and 63%, 73%, and 88% were free of new or enlarging T2 hyperintense lesions, new T1 hypointense lesions, and gadolinium-enhanced lesions, respectively, at year 5. Adverse events (AEs; serious adverse events (SAEs)) were reported in 91% (22%; BID/BID), 95% (24%; PBO/BID), and 88% (16%; GA/BID) of the patients. One case of progressive multifocal leukoencephalopathy was reported in the setting of severe, prolonged lymphopenia. CONCLUSION: Treatment with DMF was associated with continuously low clinical and magnetic resonance imaging (MRI) disease activity in patients with RRMS. These interim data demonstrate a sustained treatment benefit and an acceptable safety profile with DMF

Optimisation of unenhanced MRI for detection of lesions in multiple sclerosis: a comparison of five pulse sequences with variable slice thickness

We used five MRI sequences in six patients with multiple sclerosis (MS): conventional spin-echo (CSE) with 5-mm slices; 2D fast spin-echo (FSE) with 2-mm slices; multishot T2*-weighted echo-planar imaging (EPI) with 5-mm slices; fast fluid-attenuated inversion recovery (fFLAIR) with 2-mm slices; and 3D fast spin-echo with 1.5mm-thick slices. A total of 225 lesions were detected on CSE, 274 on 2D FSE, 137 on EPI, 385 on fFLAIR and 320 on 3D FSE. The EPI sequence was clearly the least sensitive and susceptibility artefact was a problem, particularly in the brain stem and temporal lobes. Fast FLAIR displayed a much higher number of supratentorial lesions (380) than 3D FSE (297), 2D FSE (264) or CSE (211). However, in the posterior cranial fossa 3D FSE was the most sensitive sequence (23 lesions), followed by CSE (14) and 2D FSE (10), while fFLAIR (5) was extremely insensitive

Trigeminal neuralgia in patients with multiple sclerosis: Lesion localization with magnetic resonance imaging

We performed conventional T2-weighted brain MRI examinations in six patients with multiple sclerosis (MS) and trigeminal neuralgia. In all patients brainstem lesions in positions expected to involve trigeminal fibers, particularly the entry zone of sensory fibers, were demonstrated. Compression of the trigeminal nerve by ectatic vessels, a recognized cause of idiopathic trigeminal neuralgia, was not observed. We conclude that in MS trigeminal neuralgia is usually caused by demyelinating lesions affecting pontine trigeminal pathways

Numerical and experimental investigations of diffusion-induced boundary layer separation on aero-engine nacelles

Aero-engine nacelles have to fulfill design requirements at both cruise and off-design conditions. Under engine windmilling conditions the ingested streamtube massflow is relatively low. A key off-design condition is take-off, which, in conjunction with an engine windmilling scenario, results in the stagnation point of the ingested streamtube being located significantly inside the intake. The combination of high angle of attack and low engine massflow rates leads to a strong flow acceleration and subsequent diffusion of the boundary layer on the upper quadrants of the external nacelle cowl, which can terminate with subsonic separation from the leading-edge. Under this condition, Reynolds number effects can play a dominant role on the separation onset and characteristics and 3D-annular wind tunnel tests cannot always achieve Reynolds’ number equivalent to full scale. A novel quasi-2D rig configuration representative of the aerodynamics of a full-size aero-engine nacelle under windmilling end of runway conditions examined in detail the characteristics of the boundary layer on the external cowl of a nacelle prior to diffusion-induced separation. Separation of the boundary layer was independently promoted through changes to represent different engine massflow rates and freestream Mach number on the rig to determine the limits of steady Reynolds Averaged Navier Stokes (RANS) methods to discern the onset of boundary layer separation. For the conditions and geometry investigated, the combined experimental and computational results showed that there was laminar to turbulent transition of the boundary layer ahead of the subsonic diffusion. The work showed that steady RANS can predict the onset of boundary layer separation with an uncertainty of approximately 10% on notional engine massflow rate and 0.05 on freestream Mach number relative to a nominal operating freestream Mach number of 0.25. This provides guidance for the industrial design and optimization of future windmilling-tolerant nacelles for large ultra-high bypass ratio turbofan engines