Intravenous ketamine for subacute treatment of refractory chronic migraine: a case series.

BACKGROUND: Refractory migraine is a challenging condition with great impact on health related quality of life. Intravenous (IV) ketamine has been previously used to treat various refractory pain conditions. We present a series of patients with refractory migraine treated with intravenous ketamine in the hospital setting. METHODS: Based on retrospective chart review, we identified six patients with refractory migraine admitted from 2010 through 2014 for treatment with intravenous ketamine. Ketamine was administered using a standard protocol starting with a dose of 0.1 mg/kg/hr and increased by 0.1 mg/kg/hr every 3 to 4 h as tolerated until the target pain score of 3/10 was achieved and maintained for at least 8 h. Visual Analogue Scale (VAS) scores at time of hospital admission were obtained as well as average baseline VAS scores prior to ketamine infusion. A phone interview was conducted for follow-up of migraine response in the 3 to 6 months following ketamine infusion. RESULTS: The study sample had a median age of 36.5 years (range 29-54) and 83% were women. Pre-treatment pain scores ranged from 9 to 10. All patients achieved a target pain level of 3 or less for 8 h; the average ketamine infusion rate at target was 0.34 mg/kg/hour (range 0.12-0.42 mg/kg/hr). One patient reported a transient out-of-body hallucination following an increase in the infusion rate, which resolved after decreasing the rate. There were no other significant side effects. CONCLUSION: IV ketamine was safely administered in the hospital setting to patients with refractory chronic migraine. Treatment was associated with short term improvement in pain severity in 6 of 6 patients with refractory chronic migraine. Prospective placebo-controlled trials are needed to assess short term and long-term efficacy of IV ketamine in refractory chronic migraine

Mathematical modelling of the pathogenesis of multiple myeloma-induced bone disease

Multiple myeloma (MM) is the second most common haematological malignancy and results in destructive bone lesions. The interaction between MM cells and the bone microenvironment plays an important role in the development of the tumour cells and MM-induced bone disease and forms a 'vicious cycle' of tumour development and bone destruction, intensified by suppression of osteoblast activity and promotion of osteoclast activity. In this paper, a mathematical model is proposed to simulate how the interaction between MM cells and the bone microenvironment facilitates the development of the tumour cells and the resultant bone destruction. It includes both the roles of inhibited osteoblast activity and stimulated osteoclast activity. The model is able to mimic the temporal variation of bone cell concentrations and resultant bone volume after the invasion and then removal of the tumour cells and explains why MM-induced bone lesions rarely heal even after the complete removal of MM cells. The behaviour of the model compares well with published experimental data. The model serves as a first step to understand the development of MM-induced bone disease and could be applied further to evaluate the current therapies against MM-induced bone disease and even suggests new potential therapeutic targets

Logic Programming in Tabular Allegories

We develop a compilation scheme and categorical abstract machine for execution of logic programs based on allegories, the categorical version of the calculus of relations. Operational and denotational semantics are developed using the same formalism, and query execution is performed using algebraic reasoning. Our work serves two purposes: achieving a formal model of a logic programming compiler and efficient runtime; building the base for incorporating features typical of functional programming in a declarative way, while maintaining 100% compatibility with existing Prolog programs

DFN-02, Sumatriptan 10 mg Nasal Spray with Permeation Enhancer, for the Acute Treatment of Migraine: A Randomized, Double-Blind, Placebo-Controlled Study Assessing Functional Disability and Subject Satisfaction with Treatment.

BackgroundThe commercial formulation of sumatriptan nasal spray is an effective option for migraine patients requiring or preferring a non-oral route of drug administration, but its utility is limited by poor absorption and tolerability issues. DFN-02, a new formulation of sumatriptan 10 mg nasal spray, is co-formulated with a permeation enhancer that gives it pharmacokinetics comparable to subcutaneous sumatriptan. As reported previously, DFN-02 was significantly better than placebo on multiple efficacy endpoints at 2 h postdose, including pain freedom, absence of the most bothersome symptom, and pain relief, and its safety and tolerability profiles were excellent.ObjectiveThe objective of this study was to assess the efficacy of acute treatment of migraine with DFN-02, including its effect on migraine-related functional disability and patient satisfaction with treatment.MethodsThis was a multicenter, randomized, double-blind, placebo-controlled efficacy and safety study of DFN-02 in adults with episodic migraine. Functional disability and subject satisfaction with treatment were prespecified endpoints, assessed in real-time by subjects, using an electronic diary.ResultsIn total, 107 subjects were randomized. DFN-02 was significantly superior to placebo for the reduction in functional disability score from predose level at 2 h after treatment (- 1.2 vs. - 0.6, p < 0.001). Subjects treated with DFN-02 were also more likely to be satisfied or very satisfied than subjects treated with placebo at 2 h postdose (70.0% vs. 44.2%, p = 0.027). Using the Patient Perception of Migraine Questionnaire-Revised at 24 h postdose, DFN-02 mean scores were significantly superior to placebo for the subscales of efficacy (65.2 vs. 42.5, p = 0.016) and function (68.9 vs. 42.1, p = 0.001), and for total score (71.0 vs. 56.6, p = 0.016); global medication effectiveness (p = 0.027); and overall satisfaction (p = 0.019). Placebo was significantly better than DFN-02 on the tolerability subscale (94.8 vs. 88.5, p = 0.026). At 24 h postdose, subjects reported significantly higher satisfaction with DFN-02 compared with satisfaction reported pre-randomization regarding their usual migraine medication (p = 0.012).ConclusionDFN-02 was superior to placebo for the relief of migraine-related functional disability, and provided greater satisfaction than placebo or subjects' usual acute treatment.Trial registrationClinicalTrials.gov identifier: NCT02856802

Precautionary Measures for Credit Risk Management in Jump Models

Sustaining efficiency and stability by properly controlling the equity to asset ratio is one of the most important and difficult challenges in bank management. Due to unexpected and abrupt decline of asset values, a bank must closely monitor its net worth as well as market conditions, and one of its important concerns is when to raise more capital so as not to violate capital adequacy requirements. In this paper, we model the tradeoff between avoiding costs of delay and premature capital raising, and solve the corresponding optimal stopping problem. In order to model defaults in a bank's loan/credit business portfolios, we represent its net worth by Levy processes, and solve explicitly for the double exponential jump diffusion process and for a general spectrally negative Levy process.Comment: 31 pages, 4 figure

Tunable Double Negative Band Structure from Non-Magnetic Coated Rods

A system of periodic poly-disperse coated nano-rods is considered. Both the coated nano-rods and host material are non-magnetic. The exterior nano-coating has a frequency dependent dielectric constant and the rod has a high dielectric constant. A negative effective magnetic permeability is generated near the Mie resonances of the rods while the coating generates a negative permittivity through a field resonance controlled by the plasma frequency of the coating and the geometry of the crystal. The explicit band structure for the system is calculated in the sub-wavelength limit. Tunable pass bands exhibiting negative group velocity are generated and correspond to simultaneously negative effective dielectric permittivity and magnetic permeability. These can be explicitly controlled by adjusting the distance between rods, the coating thickness, and rod diameters

On a whale shark caught at Vizhinjam, Kerala

On 20th June 2005, a female whale shark Rhincodon typus entangled in a ozhukuvala net at about 1000 hrs from 45 meter depth was dragged to the Vizhinjam landing centre

Bond-Propagation Algorithm for Thermodynamic Functions in General 2D Ising Models

Recently, we developed and implemented the bond propagation algorithm for calculating the partition function and correlation functions of random bond Ising models in two dimensions. The algorithm is the fastest available for calculating these quantities near the percolation threshold. In this paper, we show how to extend the bond propagation algorithm to directly calculate thermodynamic functions by applying the algorithm to derivatives of the partition function, and we derive explicit expressions for this transformation. We also discuss variations of the original bond propagation procedure within the larger context of Y-Delta-Y-reducibility and discuss the relation of this class of algorithm to other algorithms developed for Ising systems. We conclude with a discussion on the outlook for applying similar algorithms to other models.Comment: 12 pages, 10 figures; submitte

Nuclear-spin relaxation of 207^{207}Pb in ferroelectric powders

Motivated by a recent proposal by O. P. Sushkov and co-workers to search for a P,T-violating Schiff moment of the $^{207}$Pb nucleus in a ferroelectric solid, we have carried out a high-field nuclear magnetic resonance study of the longitudinal and transverse spin relaxation of the lead nuclei from room temperature down to 10 K for powder samples of lead titanate (PT), lead zirconium titanate (PZT), and a PT monocrystal. For all powder samples and independently of temperature, transverse relaxation times were found to be $T_2\approx 1.5$ms, while the longitudinal relaxation times exhibited a temperature dependence, with $T_1$ of over an hour at the lowest temperatures, decreasing to $T_1\approx 7$s at room temperature. At high temperatures, the observed behavior is consistent with a two-phonon Raman process, while in the low temperature limit, the relaxation appears to be dominated by a single-phonon (direct) process involving magnetic impurities. This is the first study of temperature-dependent nuclear-spin relaxation in PT and PZT ferroelectrics at such low temperatures. We discuss the implications of the results for the Schiff-moment search.Comment: 6 pages, 4 figure

The Cop Number of the One-Cop-Moves Game on Planar Graphs

Cops and robbers is a vertex-pursuit game played on graphs. In the classical cops-and-robbers game, a set of cops and a robber occupy the vertices of the graph and move alternately along the graph's edges with perfect information about each other's positions. If a cop eventually occupies the same vertex as the robber, then the cops win; the robber wins if she can indefinitely evade capture. Aigner and Frommer established that in every connected planar graph, three cops are sufficient to capture a single robber. In this paper, we consider a recently studied variant of the cops-and-robbers game, alternately called the one-active-cop game, one-cop-moves game or the lazy-cops-and-robbers game, where at most one cop can move during any round. We show that Aigner and Frommer's result does not generalise to this game variant by constructing a connected planar graph on which a robber can indefinitely evade three cops in the one-cop-moves game. This answers a question recently raised by Sullivan, Townsend and Werzanski.Comment: 32 page