Treatment of migraine attacks based on the interaction with the trigemino-cerebrovascular system

Primary headaches such as migraine are among the most prevalent neurological disorders, affecting up to one-fifth of the adult population. The scientific work in the last decade has unraveled much of the pathophysiological background of migraine, which is now considered to be a neurovascular disorder. It has been discovered that the trigemino-cerebrovascular system plays a key role in migraine headache pathophysiology by releasing the potent vasodilator calcitonin gene-related peptide (CGRP). This neuropeptide is released in parallel with the pain and its concentration correlates well with the intensity of the headache. The development of drugs of the triptan class has provided relief for the acute attacks but at the cost of, mainly cardiovascular, side effects. Thus, the intention to improve treatment led to the development of small CGRP receptor antagonists such as olcegepant (BIBN4096BS) and MK-0974 that alleviate the acute migraine attack without acute side events. The purpose of this review is to give a short overview of the pathological background of migraine headache and to illustrate the mechanisms behind the actions of triptans and the promising CGRP receptor blockers

The Influence of Meteorology on the Spread of Influenza: Survival Analysis of an Equine Influenza (A/H3N8) Outbreak

The influences of relative humidity and ambient temperature on the transmission of influenza A viruses have recently been established under controlled laboratory conditions. The interplay of meteorological factors during an actual influenza epidemic is less clear, and research into the contribution of wind to epidemic spread is scarce. By applying geostatistics and survival analysis to data from a large outbreak of equine influenza (A/H3N8), we quantified the association between hazard of infection and air temperature, relative humidity, rainfall, and wind velocity, whilst controlling for premises-level covariates. The pattern of disease spread in space and time was described using extraction mapping and instantaneous hazard curves. Meteorological conditions at each premises location were estimated by kriging daily meteorological data and analysed as time-lagged time-varying predictors using generalised Cox regression. Meteorological covariates time-lagged by three days were strongly associated with hazard of influenza infection, corresponding closely with the incubation period of equine influenza. Hazard of equine influenza infection was higher when relative humidity was <60% and lowest on days when daily maximum air temperature was 20–25°C. Wind speeds >30 km hour−1 from the direction of nearby infected premises were associated with increased hazard of infection. Through combining detailed influenza outbreak and meteorological data, we provide empirical evidence for the underlying environmental mechanisms that influenced the local spread of an outbreak of influenza A. Our analysis supports, and extends, the findings of studies into influenza A transmission conducted under laboratory conditions. The relationships described are of direct importance for managing disease risk during influenza outbreaks in horses, and more generally, advance our understanding of the transmission of influenza A viruses under field conditions

Emerging Technologies for the Detection of Rabies Virus: Challenges and Hopes in the 21st Century

The diagnosis of rabies is routinely based on clinical and epidemiological information, especially when exposures are reported in rabies-endemic countries. Diagnostic tests using conventional assays that appear to be negative, even when undertaken late in the disease and despite the clinical diagnosis, have a tendency, at times, to be unreliable. These tests are rarely optimal and entirely dependent on the nature and quality of the sample supplied. In the course of the past three decades, the application of molecular biology has aided in the development of tests that result in a more rapid detection of rabies virus. These tests enable viral strain identification from clinical specimens. Currently, there are a number of molecular tests that can be used to complement conventional tests in rabies diagnosis. Indeed the challenges in the 21st century for the development of rabies diagnostics are not of a technical nature; these tests are available now. The challenges in the 21st century for diagnostic test developers are two-fold: firstly, to achieve internationally accepted validation of a test that will then lead to its acceptance by organisations globally. Secondly, the areas of the world where such tests are needed are mainly in developing regions where financial and logistical barriers prevent their implementation. Although developing countries with a poor healthcare infrastructure recognise that molecular-based diagnostic assays will be unaffordable for routine use, the cost/benefit ratio should still be measured. Adoption of rapid and affordable rabies diagnostic tests for use in developing countries highlights the importance of sharing and transferring technology through laboratory twinning between the developed and the developing countries. Importantly for developing countries, the benefit of molecular methods as tools is the capability for a differential diagnosis of human diseases that present with similar clinical symptoms. Antemortem testing for human rabies is now possible using molecular techniques. These barriers are not insurmountable and it is our expectation that if such tests are accepted and implemented where they are most needed, they will provide substantial improvements for rabies diagnosis and surveillance. The advent of molecular biology and new technological initiatives that combine advances in biology with other disciplines will support the development of techniques capable of high throughput testing with a low turnaround time for rabies diagnosis

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion

An ultrasonically facilitated boron-doped diamond voltammetric sensor for analysis of the priority pollutant 4-chlorophenol

Electroanalysis of the 'priority pollutant', 4-chlorophenol, is largely unreported in the scientific literature, due mainly to the electrode passivation observed from oxidative by-products. Work is presented which details the combination of high-intensity ultrasound with a mechanically and chemically robust boron-doped diamond electrode allowing successful development of an aqueous 4-chlorophenol voltammetric sensor. The surface regeneration abilities of power ultrasound, through cavitational erosion of electrodeposited 4-chlorophenol by-products, facilitates a reproducible, insonated limiting-current oxidative signal in dilute acid conditions, with increased mass-transport offering enhanced sensitivity. A lower limit of detection of 1 μM and a linear range of 1-300 μM are reported; the technique being analytically useful over a concentration range where aquatic 4-chlorophenol pollution is known to occur. The use of power ultrasound during the electrooxidation of 4-chlorophenol at boron-doped diamond has also been shown to be advantageous in the electrochemical degradation of the substance, potentially offering further waste-water clean-up applications of this dual technology

Sono-cathodic stripping voltammetry of manganese at a polished boron-doped diamond electrode: application to the determination of manganese in instant tea.

Ultrasonically assisted cathodic stripping voltammetry at a boron-doped diamond electrode was developed for the detection of manganese. Differential-pulse voltammetry was used to give the analytical signal from a cathodic strip of electrodeposited MnO2; linearity was observed from 10(-11) M to at least 3 x 10(-7) M, with 10(-11) M being the detection limit for a 2 min deposition. The procedure involves both ultrasonic-anodic deposition of MnO2 and ultrasonic-cathodic stripping. This novel analytical tool is robust, reproducible, mercury free, oxygen insensitive and highly specific towards manganese. The differential-pulse sono-cathodic stripping voltammetric technique was used to determine successfully the manganese content of two instant tea samples, giving excellent agreement with independent AAS analyses

Surface studies of the interaction of Cl2 with InP(100)(4 × 2); an investigation of adsorption, thermal etching and ion beam assisted processes

The reactions of chlorine on the InP(100)(4 × 2) surface have been investigated using LEED, AES and TDS techniques. Chlorine forms a strongly bound chemisorbed monolayer on the semiconductor surface during low gas exposures. At high gas exposures, bulk corrosion sets in and an In-rich chloride film is formed at the interface which desorbs as InCl3. The degree of surface segregation which takes place is found to depend on the chlorine dosing pressures employed and the chemistry exhibited is also very sensitive to the state of the semiconductor surface; on In enriched interfaces corrosion takes place some 300 times more rapidly and InCl rather than InCl3 is the desorbing product. The surface transformations brought about by low energy ion beams are investigated. Ion beam irradiation sputters InCl and P4 from the chloride layer and converts the chloride rich corrosion scale into InCl. A mechanism for ion beam assisted etching is proposed and the results compared to previous studies. © 1990 Elsevier Science Publishers B.V. (North-Holland)

Self-propulsion of catalytic nanomotors synthesised by seeded growth of asymmetric platinum–gold nanoparticles

Asymmetric bimetallic nanomotors are synthesised by seeded growth in solution, providing a convenient and high-throughput alternative to the usual top-down lithographic fabrication of self-propelled catalytic nanoparticles. These synthetic nanomotors catalyse H2O2 decomposition and exhibit enhanced diffusion that depends on fuel concentration, consistent with their chemical propulsion