Practical and clinical utility of non-invasive vagus nerve stimulation (nVNS) for the acute treatment of migraine. A post hoc analysis of the randomized, sham-controlled, double-blind PRESTO trial

Background: The PRESTO study of non-invasive vagus nerve stimulation (nVNS; gammaCore®) featured key primary and secondary end points recommended by the International Headache Society to provide Class I evidence that for patients with an episodic migraine, nVNS significantly increases the probability of having mild pain or being pain-free 2 h post stimulation. Here, we examined additional data from PRESTO to provide further insights into the practical utility of nVNS by evaluating its ability to consistently deliver clinically meaningful improvements in pain intensity while reducing the need for rescue medication. Methods: Patients recorded pain intensity for treated migraine attacks on a 4-point scale. Data were examined to compare nVNS and sham with regard to the percentage of patients who benefited by at least 1 point in pain intensity. We also assessed the percentage of attacks that required rescue medication and pain-free rates stratified by pain intensity at treatment initiation. Results: A significantly higher percentage of patients who used acute nVNS treatment (n = 120) vs sham (n = 123) reported a ≥ 1-point decrease in pain intensity at 30 min (nVNS, 32.2%; sham, 18.5%; P = 0.020), 60 min (nVNS, 38.8%; sham, 24.0%; P = 0.017), and 120 min (nVNS, 46.8%; sham, 26.2%; P = 0.002) after the first attack. Similar significant results were seen when assessing the benefit in all attacks. The proportion of patients who did not require rescue medication was significantly higher with nVNS than with sham for the first attack (nVNS, 59.3%; sham, 41.9%; P = 0.013) and all attacks (nVNS, 52.3%; sham, 37.3%; P = 0.008). When initial pain intensity was mild, the percentage of patients with no pain after treatment was significantly higher with nVNS than with sham at 60 min (all attacks: nVNS, 37.0%; sham, 21.2%; P = 0.025) and 120 min (first attack: nVNS, 50.0%; sham, 25.0%; P = 0.018; all attacks: nVNS, 46.7%; sham, 30.1%; P = 0.037). Conclusions: This post hoc analysis demonstrated that acute nVNS treatment quickly and consistently reduced pain intensity while decreasing rescue medication use. These clinical benefits provide guidance in the optimal use of nVNS in everyday practice, which can potentially reduce use of acute pharmacologic medications and their associated adverse events. Trial registration: ClinicalTrials.gov identifier: NCT02686034

Conductive Graphitic Networks: From Atoms to Fuel Cells

Graphitic materials have attracted a great interest in the field of sustainable energy production and storage because of their excellent electrical, mechanical and chemical properties. This thesis modestly contributes to this global research by investigating new interconnected carbon nanostructures, here called Carbon Nano-Networks (CNNs). The work is divided into two parts. The first part deals with the synthesis of CNNs consisting of Chemical Vapor Deposition (CVD) of ethene over metal catalyst nanoparticles (NPs) synthesized in bicontinuous microemulsions (BMEs). Chapter 1 focuses on the characterization of dense microemulsions, both experimentally and computationally, using a coarse-grained molecular dynamics simulation tool. Bicontinuity of microemulsions is visualized. Chapter 2 describes the synthesis of NPs in BMEs. The effect of the precursors and of the microemulsion composition on the size, polidispersity and stability of the NPs is analyzed. Finally a mechanism of formation of NPs in BMEs is proposed. Chapter 3 investigates the synthesis of CNNs via CVD of ethene over metallic particles synthesized in BMEs. The effect of synthesis parameters on the final structure is studied. Properties of CNNs, such as porosity and conductivity are investigated. The second part deals with the use of CNNs as catalyst support in Polymer electrolyte membranes (PEM) Fuel Cells. Chapter 4 gives a brief overview of PEM Fuel Cells basics, materials and challenges. In Chapter 5, activity and durability of Pt deposited over CNNs is compared to Pt over carbon nano-tubes and to commercial catalyst. In Chapter 6, CNNs are used as support for non-noble metal catalyst. Performances are evaluated in-situ and ex-situ. Chapter 7 deals with an innovative manufacturing technique for an electrode: CNNs are grown directly over carbon paper. Resistance to corrosion as a function of synthesis parameters is evaluated. Pt is electrodeposited over the synthesized electrode support, and its activity and durability is evaluated and compared to commercial catalyst. The results presented in terms of cost, activity or durability are either superior to commercial catalyst or of the same order of magnitude of state-of-the-art catalyst. Nevertheless, the simplicity of CNNs synthesis procedure, the low price of catalyst precursor and the reduction of manufacturing steps make this novel electrode promising as material for fuel cells. In conclusion, the work described in this thesis certainly does not lead to immediate improvements in efficiency of fuel cells but it does provide for new and potentially more sustainable material solutions with which it may well be possible to attain these improvements in the near future.Chemical EngineeringApplied Science

Stimulated-healing of proton exchange membrane fuel cell catalyst

Platinum nanoparticles, which are used as catalysts in Proton Exchange Membrane Fuel Cells (PEMFC), tend to degrade after long-term operation. We discriminate the following mechanisms of the degradation: poisoning, migration and coalescence, dissolution, and electrochemical Ostwald ripening. There are two ways to tackle this problem. The first option involves formulation of durable catalyst, which can resist harsh fuel cell conditions, and this is the conventional route. The second option is reactivation by dissolution and then redeposition of the catalyst nanoparticles, which is an unprecedented method for platinum catalyst regeneration/stimulated-healing and the one we shall discuss. Dissolution of platinum can be achieved electrochemically, by potential cycling of the fuel cell electrode impregnated with platinum nanoparticles in oxygen enriched acidic electrolyte according to following reactions [1]: Pt + H2O?PtO + 2H+ + 2e- (1) PtO + 2H+?Pt2+ + H2O (2) During the potential cycling, platinum oxides are formed at each positive cycle and subsequently dissolved as platinum ions in the electrolyte on the negative cycle. These cycles are alternated continuously. The partial dissolution of platinum nanoparticles results in a decrease in particles size and oxidation of the poisonous species on the platinum surface. The process of dissolution is monitored in-situ via cyclic voltammetry technique. The concentration of dissolved platinum is measured with Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES). The next step of the regeneration procedure is redeposition of the dissolved platinum back onto the carbon support of the fuel cell electrode. This can be realized by means of electrodeposition. A negative potential is applied to an electrode from where the platinum was dissolved and this results in a reduction of the dissolved platinum ions. Regenerated nanoparticles are characterized by AFM, TEM and XRD. The activity of the catalyst will be checked via voltammetric techniques.ChemE/Chemical EngineeringApplied Science

Reversible Nanoparticle Formation As a Potential Strategy for PEMFC Catalyst Regeneration (abstract)

ChemE/Chemical EngineeringApplied Science

Bicontinuous microemulsions for high yield, wet synthesis of ultrafine nanoparticles: A general approach

The design of a synthesis strategy for metal nanoparticles by templating dense microemulsions is proposed. Particle size is controlled by surfactant size rather than by microemulsion composition. The strategy was demonstrated with various systems with different surfactant: cationic, anionic and non-ionic and of different sizes. Formulations were determined using the microemulsion phase diagrams. Synthesis was demonstrated for platinum nanoparticles with some examples for gold. The nanoparticles were subsequently extracted from the microemulsion by absorption onto a carbon support, after which the surfactant was recycled.Chenical EngineeringApplied Science

Networked Graphitic Structures Grown from Dense Microemulsions as High Performance Electrode Material (abstract)

ChemE/Chemical EngineeringApplied Science

Experimental and molecular dynamics characterization of dense microemulsion systems: Morphology, conductivity and SAXS

Microemulsions are exciting systems that are promising as tuneable self-assembling templating reaction vessels at the nanoscale. Determination of the nano-structure of microemulsions is, however, not trivial, and there are fundamental questions regarding their design. We were able to reproduce experimental data for an important microemulsion system, sodium-AOT–n-heptane–water, using coarse-grained simulations involving relatively limited computational costs. The simulation allows visualization and deeper investigation of controversial phenomena such as bicontinuity and ion mobility. Simulations were performed using the Martini coarse-grained force field. AOT bonded parameters were fine-tuned by matching the geometry obtained from atomistic simulations. We investigated several compositions with a constant ratio of surfactant to oil while the water content was varied from 10 to 60% in weight. From mean square displacement calculation of all species, it was possible to quantify caging effects and ion mobility. Average diffusion coefficients were calculated for all charged species and trends in the diffusion coefficients were used to rationalize experimental conductivity data. Especially, the diffusion coefficient of charged species qualitatively matched the variation in conductivity as a function of water content. The scattering function was calculated for the hydrophilic species and up to 40% water content quantitatively matched the experimental data obtained from small angle X-ray scattering measurements. For higher water contents, discrepancies were observed and attributed to a nearby phase separation. In particular, bicontinuity of water and oil was computationally visualized by plotting the coordinates of hydrophilic beads. Equilibrated coarse-grained simulations were reversed to atomistic models in order both to compare ion mobility and to catch finer simulation details. Especially, it was possible to capture the intimate ion pair interaction between the sodium ion and the surfactant head group.ChemE/Chemical EngineeringApplied Science

Covalently, Non-Covalently and Non Functionalized Networked Graphitic Structures as robust catalyst support in PEM electrodes (abstract)

ChemE/Chemical EngineeringApplied Science

Electrocatalytic Activity and Durability of Pt-Decorated Non-Covalently Functionalized Graphitic Structures

Carbon graphitic structures that differ in morphology, graphiticity and specific surface area were used as support for platinum for Oxygen Reduction Reaction (ORR) in low temperature fuel cells. Graphitic supports were first non-covalently functionalized with pyrene carboxylic acid (PCA) and, subsequently, platinum nanoparticles were nucleated on the surface following procedures found in previous studies. Non-covalent functionalization has been proven to be advantageous because it allows for a better control of particle size and monodispersity, it prevents particle agglomeration since particles are bonded to the surface, and it does not affect the chemical and physical resistance of the support. Synthesized electrocatalysts were characterized by electrochemical half-cell studies, in order to evaluate the Electrochemically Active Surface Area (ECSA), ORR activity, and durability to potential cycling and corrosion resistance.ChemE/Chemical EngineeringApplied Science