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Porous GaN distributed Bragg reflectors offer an opportunity to provide the high reflectance, lattice-matched components required for efficient GaN vertical cavity surface emitting lasers. The birefringence of these structures is, therefore, of key interest as it could be used to control the polarization of the emitted light. Here, we present a detailed analysis of the optical birefringence for both laterally etched, patterned structures and self-assembled radial porous structures. We correlate this with the 3D structure of the pores, which we measure through the use of FIB milling and serial block-face SEM imaging. This is a powerful method for imaging the internal nanostructure of the sample and allows the internal pore morphology to be viewed in a reconstruction of any 3D plane. We measure the birefringence of our porous GaN layers as Δ n = 0.14 with a lower refractive index parallel to the pores (∥) than perpendicular to them (⟂). Using finite element modeling, we accurately reproduce the experimentally observed birefringence trends and find that this can be done by modeling GaN as a perfect dielectric. This indicates that the birefringence arises from the limited width across the pores. This also shows that standard modeling approaches can be used to design porous GaN birefringent devices effectively.

In this work we report the surface morphology of amorphous germanium (a-Ge) thin films (140 nm thickness) following thermal outgassing of SiO2/Si substrates. The thermal outgassing was performed by annealing the samples in air at different temperatures from 400 to 900 °C. Annealing at 400 °C in slow (2 °C/min) and fast (10 °C/min) modes promotes the formation of bubbles on the surface. A cross sectional view by transmission electron microscope taken of the sample slow annealed at 400 °C reveals traces of gas species embedded in the a-Ge film, allowing us to propose a possible mechanism for the formation of the bubbles. The calculated internal pressure and number of gas molecules for this sample are 30 MPa and 38 × 108, respectively. Over an area of 22 × 10−3 cm2 the density of bubbles obtained at slow annealing (9 × 103 cm−2) is smaller than that at rapid annealing (6.4 × 104 cm−2), indicating that the amount of liberated gas in both cases is only a fraction of the total gas contained in the substrate. After increasing the annealing temperature in the slow mode, bubbles of different diameters (from tens of nanometers up to tens of micrometers) randomly distribute over the Ge film and they grow with temperature. Vertical diffusion of the outgas species through the film dominates the annealing temperature interval 400–600 °C, whereas coalescence of bubbles caused by lateral diffusion is detected after annealing at 700 °C. The bubbles explode after annealing the samples at 800 °C. Annealing at higher temperatures, such as 900 °C, leads to surface migration of the film to the exploded bubbles and eventually forming islands of polycrystalline GeO2.

Objective Deaths and serious injuries among young drivers are an important public health concern. Road safety researchers and policy makers tend to focus on strategies to restrict the driving activities of young people. Other social research suggests the disadvantages experienced by young people in socially deprived groups are exacerbated by not having a driving licence or owning a car. In this qualitative study, we consider the views of young people from less affluent backgrounds in the south-west of England who took part in a brief intervention to encourage them to delay gaining a driving licence and car ownership. Methods Between September 2011 and January 2012, a researcher observed four training sessions involving 173 young people. Postintervention, digitally recorded focus groups were conducted at three venues involving 23 randomly selected young people. Data from the focus group transcripts were sorted into charts in relation to key research questions and scrutinised using constant comparison. Results These young people believed the ability to drive, and car ownership, could increase their independence, improve access to further education, widen their employment opportunities, and enable them to contribute to family or household responsibilities. Conclusions We argue there is a potential conflict between some strategies seeking to promote young driver safety and the impact this may have on equity and social disadvantage. Interdisciplinary work is required between professionals and researchers in transport, road safety, public health and social equity. Government policies should include low-cost, safe, reliable and attractive transport alternatives for young people in more deprived communities.

In this work, we report the mechanical reorientationof thiolated ferromagnetic microspheres bridging a pairof gold electrodes under an external magnetic field. Whenan external magnetic field (7 kG) is applied during themeasurement of the current–voltage characteristics of a carboxylferromagnetic microsphere (4 μm diameter) attachedto two gold electrodes by self-assembled monolayers(SAMs) of octane dithiol (C8H18S2), the current signal isdistorted. Rather than due to magnetoresistance, this effectis caused by a mechanical reorientation of the ferromagneticsphere, which alters the number of SAMs between thesphere and the electrodes and therefore affects conduction.To study the physical reorientation of the ferromagneticparticles, we measure their hysteresis loops while suspendedin a liquid solution.Keywords Magnetic microparticles

A new technique for the preparation of site specific plan-view specimens using a focused ion beam system is presented. The technique consists of milling a wedge shaped piece of material which is free from the substrate, lifting this out using a micromanipulator and needle, and orientating it on the substrate with the original surface vertical. The plan-view specimen is then milled from this piece of material using an approach based on the “lift-out” technique for the preparation of a cross-section specimen. Advantages of this technique over current methods based on the “lift-out” and the “trench” techniques are that the plan-view specimens are site specific, the surrounding substrate is left intact, and numerous plan-view specimens can be prepared in close proximity to one another.

The use of focused ion beam systems is becoming routine for the preparation of site specific TEM cross-section specimens which are typically 50-100 nm. thick. Generally, the cross-sections are milled using a 30 keV ion beam, which unfortunately, can result in large amounts of damage to the sidewalls of the cross-sections. This damage layer limits the minimum thickness to which a crystalline cross-section can be prepared and affects the quality of the images using high resolution electron microscopy. We report a technique that uses low energy broad ion beam milling to further thin FIB-prepared cross-sections and to decrease the thickness of the damage layer at the sidewalls. Energy filtered transmission electron microscopy has been used to measure the thickness and the amount of preferential milling of the different layers of Spin-Tunnel Junction cross-sections, which consist of metal-insulator-metal layers prepared using this technique.

OBJECTIVES: There is little consensus regarding the burden of pain in the UK. The purpose of this review was to synthesise existing data on the prevalence of various chronic pain phenotypes in order to produce accurate and contemporary national estimates. DESIGN: Major electronic databases were searched for articles published after 1990, reporting population-based prevalence estimates of chronic pain (pain lasting >3 months), chronic widespread pain, fibromyalgia and chronic neuropathic pain. Pooled prevalence estimates were calculated for chronic pain and chronic widespread pain. RESULTS: Of the 1737 articles generated through our searches, 19 studies matched our inclusion criteria, presenting data from 139 933 adult residents of the UK. The prevalence of chronic pain, derived from 7 studies, ranged from 35.0% to 51.3% (pooled estimate 43.5%, 95% CIs 38.4% to 48.6%). The prevalence of moderate-severely disabling chronic pain (Von Korff grades III/IV), based on 4 studies, ranged from 10.4% to 14.3%. 12 studies stratified chronic pain prevalence by age group, demonstrating a trend towards increasing prevalence with increasing age from 14.3% in 18-25 years old, to 62% in the over 75 age group, although the prevalence of chronic pain in young people (18-39 years old) may be as high as 30%. Reported prevalence estimates were summarised for chronic widespread pain (pooled estimate 14.2%, 95% CI 12.3% to 16.1%; 5 studies), chronic neuropathic pain (8.2% to 8.9%; 2 studies) and fibromyalgia (5.4%; 1 study). Chronic pain was more common in female than male participants, across all measured phenotypes. CONCLUSIONS: Chronic pain affects between one-third and one-half of the population of the UK, corresponding to just under 28 million adults, based on data from the best available published studies. This figure is likely to increase further in line with an ageing population.

Central neuropathic pain (CNP) occurs in many multiple sclerosis (MS) patients. The provision of adequate pain relief to these patients can very difficult. Here we report the first phase III placebo-controlled study of the efficacy of the endocannabinoid system modulator delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) oromucosal spray (USAN name, nabiximols; Sativex, GW Pharmaceuticals, Salisbury, Wiltshire, UK), to alleviate CNP. Patients who had failed to gain adequate analgesia from existing medication were treated with THC/CBD spray or placebo as an add-on treatment, in a double-blind manner, for 14 weeks to investigate the efficacy of the medication in MS-induced neuropathic pain. This parallel-group phase of the study was then followed by an 18-week randomized-withdrawal study (14-week open-label treatment period plus a double-blind 4-week randomized-withdrawal phase) to investigate time to treatment failure and show maintenance of efficacy. A total of 339 patients were randomized to phase A (167 received THC/CBD spray and 172 received placebo). Of those who completed phase A, 58 entered the randomized-withdrawal phase. The primary endpoint of responder analysis at the 30 % level at week 14 of phase A of the study was not met, with 50 % of patients on THC/CBD spray classed as responders at the 30 % level compared to 45 % of patients on placebo (p = 0.234). However, an interim analysis at week 10 showed a statistically significant treatment difference in favor of THC/CBD spray at this time point (p = 0.046). During the randomized-withdrawal phase, the primary endpoint of time to treatment failure was statistically significant in favor of THC/CBD spray, with 57 % of patients receiving placebo failing treatment versus 24 % of patients from the THC/CBD spray group (p = 0.04). The mean change from baseline in Pain Numerical Rating Scale (NRS) (p = 0.028) and sleep quality NRS (p = 0.015) scores, both secondary endpoints in phase B, were also statistically significant compared to placebo, with estimated treatment differences of -0.79 and 0.99 points, respectively, in favor of THC/CBD spray treatment. The results of the current investigation were equivocal, with conflicting findings in the two phases of the study. While there were a large proportion of responders to THC/CBD spray treatment during the phase A double-blind period, the primary endpoint was not met due to a similarly large number of placebo responders. In contrast, there was a marked effect in phase B of the study, with an increased time to treatment failure in the THC/CBD spray group compared to placebo. These findings suggest that further studies are required to explore the full potential of THC/CBD spray in these patients.

Dual platform (FIB/SEM) systems can be used to deposit platinum by both ion and electron beam assisted deposition by the breakdown of a suitable inorganic metallic precursor. The resistivity of electron beam deposited Pt is typically 2-3 orders of magnitude higher than that of the ion beam deposited Pt. Experiments to determine the cause of the difference in the resistivity and to decrease the resistivity of electron beam deposited Pt are reported. Changing the dwell times and incident energy did not affect the resistivity of the deposited Pt. Both annealing at 500^oC in forming gas (H"2/N"2) and implanting electron beam deposited Pt with gallium reduced its resistivity by a factor of 10. From the microstructure and chemical analysis and transport measurements, it is concluded that the difference in resistivity is due to the differences in the nanostructure and chemical composition and due to the presence of gallium.

The magnetic field dependent transport behaviour of Co contacted multi-wall nanotubes is investigated. A sample with three Co electrodes has been measured by two-channel method with an in-plane magnetic field. When the in-plane magnetic field is perpendicular to the tube, high positive magnetoresistance up to 30% is obtained at low temperature from 3 K to 25 K and with field parallel to the tube, negative magnetoresistance up to 15% is observed only from the high resistance junction. The detailed positive and negative magnetoresistance behaviour also changes with temperature.

A focused ion beam (FIB) system has been used to implant and mill (100) Si with ion dosages ranging from 1013 to 1017 ions cm−2, which are relatively low exposures compared to typical FIB applications. The topography of the resulting structures has been characterized using atomic force microscopy, including an analysis of edge effects. Conditions are presented for the controllable preparation of structures either protruding from, or recessed into, the surface by as little as 1 nm. Given the 10 nm lateral resolution of modern commercial FIB microscopes, direct nanofabrication for all three spatial orientations is therefore achievable.

The preparation of transmission electron microscope (TEM) thin foil specimens from metal alloys containing cracks is usually thwarted by the difficulty in preventing preferential erosion of material along the flanks and at the tips of cracks. Recent developments in focused ion beam (FIB) micromachining methods have the potential to overcome this inherent problem. In this article we describe the development of new procedures, one using FIB alone and the other using a combination of FIB with more conventional ion milling to generate TEM specimens that largely retain the microstructural information at stress corrosion cracks in austentic alloys. Examples of corrosion product phase identification and interfacial segregation are included to verify that detailed information is not destroyed by ion bombardment during specimen preparation.

Focused ion beam systems are similar to scanning electron microscopes except that a beam of focused ions rather than electrons is rastered over the sample. Images are formed by either the secondary ions or electrons that are emitted as the ion beam interacts with the sample and the typical image resolution using the electrons is of the order of 10 nm. A system can be used to implant/sputter away material, deposit or preferentially etch metals and insulators in selected areas. Up to about 10 years ago, focused ion beam systems were mainly used in the semiconductor industry for circuit modifications; by the cutting and re-routing of interconnects. However, they are now being used for a range of novel micro and nanoengineering applications. In this paper, the application and potential use of focused ion beam systems to micro and nanoengineering is discussed. Examples of applications, such as the milling of two-dimensional and three-dimensional shapes, ion lithography, and the preparation of site spec...

Focused ion beam (FIB) systems are ideal tools for micromachining three-dimensional structures. To mill a shape correctly numerous factors, such as the shape of the ion beam and the re-deposition of the sputtered materials have to be accounted for during the ion milling. In order to alter the ion milling process to account for these and other factors, the shape of the milled structure and how it differs to the intended shape has to be determined. For a non-symmetrical structure with high depth-to-width aspect ratios a cross-section through its centre, prepared using the FIB system, will not be representative and atomic force microscopy cannot be used because of the geometry of the atomic force microscope's tip. Here, the use of three-dimensional reconstruction from a sequential set of FIB-prepared two-dimensional cross-sections milled through a structure to determine its shape is outlined.

The preparation of transmission electron microscopy cross-section specimens using focused ion beam milling is outlined. The “liftout” and “trench” techniques are both described in detail, and their relative advantages and disadvantages are discussed. Artifacts such as ion damage to the top surface and sidewalls of the cross-section specimens, and methods of reducing them, are addressed.

The diffusion of oxygen into SiO2 encapsulated polycrystalline CdSe films and the diffusion of indium into polycrystalline CdSe films have been investigated over the temperature range 350 C to 500 C using SIMS. The oxygen profiles in the SiO2 indicated that both isotopic oxygen exchange and the diffusion of molecular oxygen along short circuit paths were occurring with activation energies of 1.1 eV and 0.66 eV, respectively. The activation energies determined for the diffusion of the oxygen and indium in the grains (0.39 eV and 0.10 eV, respectively) were smaller than the values determined for the diffusion in the grain boundaries (0.70 eV and 0.78 eV, respectively), and was attributed to impurities and intrinsic defects accumulating at the grain boundaries.

A technique is presented which enables both sides of a transmission electron microscopy cross section specimen prepared using a focused ion beam system to be milled using a broad ion beam source. The cross section specimen is prepared using the “lift-out” technique and is placed onto a copper mesh grid with 10 μm sized holes. The upper face of the cross section specimen is first milled in a broad ion beam source, after which a micromanipulator and needle is used to turn it over so that the other side can be milled. The use of a broad ion beam source enables lower incident beam energies and angles of incidence to be used than is currently possible in a commercial focused ion beam system. The technique can be used to decrease the thickness of the damage layer at the sidewalls of a focused ion beam prepared cross section specimen and to reduce its thickness in a controlled way.

The effects of different copper doping concentrations on the properties of SiO2 encapsulated CdSe films have been investigated. Two methods were used to dope the films with copper: ion implantation and diffusion from a surface layer. The room temperature dark resistivity of films annealed in oxygen at 450°C was found to increase as the copper concentration was increased until a maximum resistivity of 108 ohm cm occurred at a copper concentration of 1020 atoms cm−3. The room temperature resistivity in the light was found to be independent of the copper concentration and whether the films were annealed in argon or oxygen. During annealing the grains grew from 0.03 µm to 0.3 µm and this growth was independent of the doping or the annealing ambient. The energy levels, carrier mobilities, and microstructure of the annealed films were dependent on the method of doping. The ion implanted films had an additional energy level at 0.33 eV and their mobility was a factor of 4 smaller than films doped by the surface diffusion method, whose mobilities were 20 to 35 cm2V−1 s−1. The addition of chlorine to copper doped films had no effect on either the resistivity or photosensitivity but slowed the response times of the photocurrent by a factor of 10. No energy levels were observed which could be associated with the copper nor was the copper found to affect the density of the observed intrinsic levels at 0.65 and 1.1 eV.

This paper presents a comprehensive study of the effects of annealing silicon dioxide encapsulated CdSe films in oxygen on the microstructure, resistivity, photosensitivity and energy levels. The energy levels were investigated by using the independent methods of thermally stimulated current, photocurrent spectral response, and Hall measurements. The film structure is wurtzite with grains of average size 0.35 µm, which extend through the thickness of the films. Annealing the films in oxygen at 450°C increases the resistivity from 10 ohm cm to 106 ohm cm. The electron mobility, which has an activation energy of 0.08 eV, remains constant at about 100 cm2 V−1 s−1 during the anneal steps. The change in the resistivity is due to a combination of thermal rearrangement and oxygen diffusing uniformly into the films. Various energy levels ranging from 0.11 eV to 1.3 eV were detected and the density of all these decreased on annealing.

Studies of the spin diffusion and magnetoresistance of multiwall carbon nanotubes contacted to by both cobalt and gold electrodes in magnetic fields of up to 4T are reported. The measured room temperature contact resistance of the Au and Co electrodes ranged from 10^3 to 10^[email protected] The magnetoresistance of tubes contacted to by Au electrodes and measured up to 4T at 4.2 and 2.2K was observed to be negative. The maximum negative magnetoresistance for the nanotubes contacted to by Co electrodes was 25%. As the temperature was increased the magnetoresistance decreased and disappeared above 25K. The spin diffusion length was calculated to be 650nm.

The effects of Ga+ ion implantation in SiO2/Ta(5 nm)/NiFe(3.5 nm)/CoFe(1.5 nm)/Cu(2.9 nm) /CoFe(2.5 nm)/IrMn(10 nm)/Ta(5 nm) spin valve stacks were investigated. As-deposited films show a giant magnetoresistance (GMR) of 7.3% and an exchange bias field ( H ex ) of 42 mT. After implantation with 30 keV Ga+ ions at doses ranging from 1012 to 1016 ions/cm2, we observe a dramatic decrease in GMR and exchange bias field together with an increase in film resistance. The effects of Ga+ ion implantation during FIB milling of small GMR elements was investigated by reducing 10 μm spin valve lines to line widths ranging from 7 to 0.5 μm. The GMR and exchange bias field were found to rapidly decrease with decrease in spin valve width. Magnetic field annealing after Ga+ ion implantation does not restore the spin valve properties.

The administration rate of general anaesthetic drugs is at present guided by clinical experience, and indirect indicators such as haemodynamic parameters. In the presence of muscle relaxants most of the clinical signs of inadequate anaesthesia are lost and accidental awareness may occur. A number of monitoring modalities, primarily based on analysis of the electroencephalogram (EEG), have been proposed for measurement of the anaesthetic depth. Moreover intraoperative cerebral monitoring may also provide the anaesthetist with early warning of cerebral ischaemia, or information on specific neurological pathways. To facilitate this, it is essential to combine analysis of the spontaneous EEG with recording of evoked potentials, to assess both cortical and subcortical activity/events. None of the reviewed methods, however promising, can alone meet all of the requirements for intraoperative monitoring of cerebral function. We suggest that the future direction should be to integrate several modalities in a single device, to provide valuable new information, upon which to base clinical management decisions.

To characterize in vitro the formation and robustness of a layer formed on dentin following treatment with a fluoridated toothpaste containing calcium sodium phosphosilicate (NovaMin) using modem imaging and analysis techniques.Calcium sodium phosphosilicate (CSPS)-containing toothpaste was brushed on to etched dentin specimens twice daily for up to five days. In between applications the samples were stored in artificial saliva. Additionally, certain samples underwent a chemical challenge in the form of a dietary acid, whereby samples were exposed to a cola or grapefruit juice beverage for five minutes on day 4 of the five-day study. The ability of the CSPS-containing formulation to occlude tubules was assessed visually by scanning electron microscope (SEM) imaging and compared to a water control. In a second experiment, the mechanical resistance of the layer was assessed using profilometry after controlled brushing for 200 brush strokes with a wet medium-bristled toothbrush. To visualize the layer and characterize the tubule occlusion, longitudinal cross-sections were prepared using a focused ion beam scanning electron microscope (FIB SEM), and analysis performed by energy dispersive x-ray spectroscopy (EDS) and electron diffraction. Owing to the complexity of the mixed material deposited after application of the toothpaste, material from inside a dentin tubule was selectively removed after five days of treatment, and the morphologically different materials imaged and analyzed by electron diffraction in the transmission electron microscope (TEM).SEM inspection showed significant coverage of the dentin samples after application of CSPS toothpaste for all five days, in contrast to the water control where the majority of tubules remained open after all five days. Exposure of the NovaMin-treated samples to common dietary acids did not lead to re-exposure of the tubules. Profilometry measurements demonstrated an intact layer covering the dentin surface after one and five days. EDS analysis and electron diffraction indicated the layer and the material plugging the tubule to be a calcium phosphate material with a crystallographic structure similar to hydroxyapatite.CSPS contained in toothpaste formulations adhered to exposed dentin surfaces. The layer formed was resistant to acid and mechanical challenges. Characterization of this layer indicated it was hydroxyapatite-like in nature.

The aim of this study was to characterize, in vitro, the mode of action of calcium sodium phosphosilicate (NovaMin) in occluding dentin tubules for the purpose of treating dentin hypersensitivity.Calcium sodium phosphosilicate (CSPS) was combined with artificial saliva on surfaces of prepared dentin discs. The layer formed was initially examined by a scanning electron microscope (SEM). Focused ion beam (FIB) milling was used to make bulk cross-sections and thin film lamellae. Low kV scanning transmission electron microscopy (STEM), energy dispersive x-ray spectroscopy (EDS), and selected area electron diffraction were then used to characterize, chemically and structurally, the layer formed and the material occluding the tubules. Experiments were also performed to assess the suitability of using an environmental scanning electron microscope (ESEM) in wet mode to follow the transition from CSPS to hydroxyapatite.SEM imaging showed that a layer was formed on the treated dentin samples, and that this layer occluded tubules. Chemical and structural analysis of this material showed that it was hydroxyapatite-like. The wet mode ESEM experiments demonstrated that this technique has the potential to follow the transition from CSPS to the crystalline hydroxyapatite material.The use of modern imaging and analysis techniques has demonstrated, in vitro, the reaction of CSPS from an amorphous material to a crystalline hydroxyapatite-like material. These experiments confirmed an occlusion mode of action for CSPS for the treatment of dentin hypersensitivity.

Background: Open-label studies are not ideal for providing robust evidence for long-term maintenance of efficacy of medicines, especially where medicines provide symptom relief and where long-term use of a placebo may be problematic and not ethical. Objective: To evaluate the maintenance of efficacy of Sativex in subjects who have gained long-term symptomatic relief of spasticity in multiple sclerosis (MS), and to assess the impact of sudden medicine withdrawal. Methods: An enriched enrolment randomized withdrawal study design was used. Eligible subjects with ongoing benefit from Sativex for at least 12 weeks entered this 5-week placebo-controlled, parallel-group, randomized withdrawal study. Each subjects’ previous effective and tolerated dose was continued. Results: A total of 18 subjects per group were enrolled. Demographics showed a mean duration of MS of 16.4 years, spasticity 12.7 years, mean duration of Sativex use of 3.6 years (median 3.4 years) and a mean daily dose of 8.25 sprays. Primary outcome of time to treatment failure was significantly in favour of Sativex ( p = 0.013). Secondary endpoints showed significant changes in the Carer and Subject’s Global Impression of Change scales in favour of Sativex. Conclusions: Maintenance of Sativex efficacy in long-term symptomatic improvement of spasticity to a group of subjects with MS has been confirmed using this study design.

Oxycodone's respiratory profile (particularly the extent of respiratory depression in comparison to morphine) remains to be fully characterised in the peri-operative period. We randomly assigned ASA 1-2 adults for elective surgery under general anaesthesia to receive saline, morphine 0.1 mg.kg⁻¹, or oxycodone 0.05 mg.kg⁻¹, 0.1 mg.kg⁻¹, or 0.2 mg.kg(-1) . Results were obtained from six patients in the saline group, 12 patients in the groups receiving morphine 0.1 mg.kg⁻¹, oxycodone 0.05 mg.kg⁻¹ and 0.1 mg.kg⁻¹, and from 10 patients who received oxycodone 0.2 mg.kg⁻¹. Patients were breathing spontaneously and minute ventilation monitored with a wet wedge spirometer for 30 min. All active groups demonstrated significant respiratory depression compared to saline (p0.0001 for all groups). The mean (SD) reduction in minute volume from baseline was 22.6% (10.4%) for the morphine 0.1 group and 53.3% (27.2%), 74.4% (12.9%) and 88.6% (13.5%) for the oxycodone 0.05, 0.1 and 0.2 groups, respectively, with significant dose dependent differences between oxycodone groups (p = 0.0007). The extent and speed of onset of oxycodone induced respiratory depression was dose dependent and greater than an equivalent dose of morphine.

The aim of this study was to evaluate in vitro the dentin tubule occluding effect of an 8% strontium acetate dentifrice (Sensodyne Rapid Relief) compared to patent dentin tubules using modern sample preparation, imaging, and analysis techniques.Etched dentin discs, either untreated or treated with the dentifrice, were analyzed by preparing cross-sections using focused ion beam scanning electron microscopy (FIB-SEM) milling, and the strontium presence mapped using energy dispersive X-ray spectroscopy (EDX).Surface imaging showed the dentifrice had coated the treated sample. Sub-surface information gained by preparing longitudinal cross-sections of the treated samples showed the tubule openings to be plugged, and EDX mapping of the cross-section confirmed enhanced strontium levels within the tubules several microns below the treatment surface.The combination of modern sample preparation, imaging, and analysis techniques employed in this study has shown that the 8% strontium acetate dentifrice occludes dentin tubules. EDX analysis has shown the presence of strontium within the dentin tubules, with elemental maps illustrating how the strontium has been incorporated into the dentin.

A focused-ion beam has been used to pattern magnetic antidot arrays containing different sized antidots and spacings in Ni80Fe20 films. Their magnetic domain structure has been studied using Lorentz transmission electron microscopy, which has shown that the edges of the antidots pin the domain walls during magnetization reversal. The remanent domain structure was found to depend strongly on the antidot size and spacing, from domains pinned between the corners of adjacent rows of antidots for large sizes to domains pinned between the edges of adjacent antidots for small sizes. The relevance of such structures for high density recording is discussed.

Nickel nanocontacts for studying ballistic magnetoresistance have been fabricated by sputtering through FIB prepared nanostencil masks and by using electron beam assisted deposition of SiO2 to reduce the size of FIB milled pores through silicon nitride membranes. These two methods are discussed in terms of the nanocontact sizes, fabrication, and yield. The smallest size of the nanocontacts prepared using the nanostencil method was 40 nm and by the filling method was 1-2 nm. The maximum magnetoresistance measured was 1% and no evidence of a large ballistic magnetoresistance was observed.

Extended abstract of a paper presented at Microscopy and Microanalysis 2013 in Indianapolis, Indiana, USA, August 4 – August 8, 2013.

Pulse oximetry probes placed peripherally may fail to give accurate values of blood oxygen saturation when the peripheral circulation is poor. Because central blood flow may be preferentially preserved, we investigated the oesophagus as an alternative monitoring site. A reflectance blood oxygen saturation probe was developed and evaluated in 49 patients undergoing cardiothoracic surgery. The oesophageal pulse oximeter results were in good agreement with oxygen saturation measurements obtained by a blood gas analyser, a CO-oximeter and a commercial finger pulse oximeter. The median (IQR [range]) difference between the oesophageal oxygen saturation results and those from blood gas analysis were 0.00 (-0.30 to 0.30 [-4.47 to 2.60]), and between the oesophageal oxygen saturation results and those from CO-oximetry were 0.75 (0.30 to 1.20 [-1.80 to 1.80]). Bland-Altman analysis showed that the bias and the limits of agreement between the oesophageal and finger pulse oximeters were -0.3% and -3.3 to 2.7%, respectively. In five (10.2%) patients, the finger pulse oximeter failed for at least 10 min, whereas the oesophageal readings remained reliable. The results suggest that the oesophagus may be used as an alternative monitoring site for pulse oximetry even in patients with compromised peripheral perfusion.

The preparation of transmission electron microscope (TEM) thin foil specimens from metal alloys containing cracks is usually thwarted by the difficulty in preventing preferential erosion of material along the flanks and at the tips of cracks. Recent developments in focused ion beam (FIB) micromachining methods have the potential to overcome this inherent problem. In this article we describe the development of new procedures, one using FIB alone and the other using a combination of FIB with more conventional ion milling to generate TEM specimens that largely retain the microstructural information at stress corrosion cracks in austentic alloys. Examples of corrosion product phase identification and interfacial segregation are included to verify that detailed information is not destroyed by ion bombardment during specimen preparation.

The need for a clinically applicable method of detecting splanchnic hypoxia has led to experimental animal studies which indicated the usefulness of intestinal pulse oximetry. Pulse oximetry relies on detection of photoplethysmographic signals. Before developing a pulse oximeter for the measurement of organ oxygen saturation peri-operatively, we designed a system based on a reflectance photoplethysmographic probe to investigate photoplethysmographic signals from human viscera (bowel, liver, and kidney). Recordings were obtained simultaneously from the abdominal viscera and the finger using identical probes. The probe was held sequentially for up to 2 min on the surface of viscera of 12 patients during routine laparotomy. Measurable splanchnic photoplethysmographic signals were recorded for the first time in humans. There were no statistically significant differences between photoplethysmographic amplitudes from viscera and those from the finger. Our results indicate the feasibility of pulse oximetry for the measurement of visceral oxygenation in humans.

The primary aim of the Improved Monitoring for Brain Dysfunction during Intensive Care and Surgery (IBIS) project was to create a unique and comprehensively annotated data library (DL) of multiple physiological, including neurophysiological, signals. Data collection was undertaken in Kuopio, Finland and London, UK, and comparable protocols were used at all the sites. In London, 43 patients were recruited at the Royal Brompton Hospital, followed by nine at St. Bartholomew's Hospital, all of whom underwent cardiac or combined cardiac and carotid artery surgery. Thirty-seven patients underwent a single operation, while 15 underwent two procedures. The protocols and equipment used, problems specific to the electrically hostile environment and preliminary results are described, including those of clinical interest. The DL is being used for the development of clinically applicable neurophysiological monitoring tools.

Tramadol's two enantiomers produce analgesia, in acute and chronic pain states, by combining synergistically, weak opioid and monoaminergically-mediated mechanisms. Tramadol is interesting, being free of some of the clinically significant side-effects seen with other opioids of comparable efficacy.

OBJECTIVES Patients undergoing abdominal surgery often suffer from morbidity associated with increased protein catabolism. Therapeutic recombinant human insulin-like growth factor (rhIGF)-I has been proposed as a means of reversing this process. As IGFBPs modulate the bioavailability of the IGFs, we have studied the changes in the circulating levels of these peptides during surgery. DESIGN Patients undergoing elective intestinal surgery were recruited prospectively. Blood samples were taken before, during and after surgery. Standard anaesthetic techniques were used. METHODS Twelve adults (aged 30–70 years; 9 female, 3 male) undergoing surgery were studied. Serum was taken before premedication (preop), end of surgery (end surg), 2 h, 6 h post surgery, on days 1–4, 7, 10 and 14, and on recovery at 6 weeks. MEASUREMENTS Serum IGF-I, IGF-II, IGFBP-1, IGFBP-2, IGFBP-3, insulin and C-peptide were measured by radioimmunoassay. IGFBP profiles were also assessed by Western ligand blot (WLB). Samples taken preop and at 2 days were separated by fast-phase liquid chromatography (FPLC) using a Superose 12 column under neutral conditions (pH 7.4), and the fractions were analysed subsequently by WLB and immunoblot using a specific IGFBP-3 antiserum. RESULTS IGF-I fell rapidly during surgery from 170 ± 21 (preop) to 133 ± 14 μg/ll (end surg) (P

Nickel nanocontacts have been fabricated by focused ion-beam (FIB) milling of e-beam patterned planar contacts, FIB milling of conical-shaped nanoperforations in a silicon nitride membrane, and nanoimprinting using an atomic force microscope. Their sizes ranged from 1 to 30 nm. Magnetoresistance of up to 3% is developed in a field of a few millitesla. This is interpreted in terms of ballistic magnetoresistance across a wide domain wall whose structure is determined by dipolar interactions at the contact.

A method for the controlled fabrication of a nickel perpendicular nanocontact with diameters less than 5 nm is reported. The method involves milling pores through the 100 nm thick silicon nitride membrane using a focused ion beam, and depositing thin Ni film on the both side of the silicon nitride membrane. The shape of the resulting pore and nanocontact size is determined by the initial hole size and redeposition of the sputtered material onto the sidewalls of the holes. A sub-5 nm Ni nanocontact was prepared and the I-V and R-H characteristics measured.

Several regions of a 30 nm thick Ni80Fe20 (permalloy) thin film have been implanted using a focused ion-beam system with varying doses of Ga ions. Changes to their magnetization reversal have been investigated by Lorentz microscopy. Implantation with a dose of 1015 Ga+ cm−2 and 1016 Ga+ cm−2 has increased coercivity of the implanted region while no difference has been observed with a dose of 1014 Ga+ cm−2. Domain wall pinning was shown to be a major mechanism for the increase in coercivity. Also changes to the lattice parameter, composition, thickness and grain size in relation to magnetic properties were investigated using various transmission electron microscopy techniques. The lattice parameter change within the implanted region indicates that the stress can be a major contributor to the increase in coercivity. Relative contributions of changes in other factors such as Ni/Fe ratio, thickness, and grain size within the implanted area have also been discussed.

A new method for the preparation of cross sections for transmission electron microscopy using a focused ion beam workstation is presented. The new technique consists of micromachining a freestanding cantilever into which a membrane for transmission electron microscopy is milled. An advantage of this approach over the trench and lift out focused ion beam procedures for the preparation of cross sections for transmission electron microscopy is that the resulting cross sections can be both tilted through large angles (+45°) without the electron path becoming obstructed and they can be returned to the focused ion beam system for further thinning.

Summary Following the injection of suitable media, the arterial tree of 22 post-mortem human stomachs was studied by angiography, or corrosion and micro-dissection. In stomachs infused exclusively by the right gastroepiploic artery, i.e. following ligation of all other gastric vessels on the stomach wall, both methods produced good fundal filling, while demonstrating consistently poor filling of a strip of stomach wall along the lesser curve. These findings do not support the assertion that in operations involving mobilization and transposition of the stomach the viability of the fundus is critically dependent upon an anastomotic circulation involving the extragastric portion of the left gastric vessels, but rather indicate that these vessels can, if required, be excised with impunity in most patients, provided that there is no extensive atherosclerosis. However, these findings indicate that such a procedure may impair the blood supply of the lesser curve, and they provide an anatomical explanation of the occasional occurrence of necrosis of the lesser curve following proximal gastric vagotomy.

BrMedJ 1989;299:902-5 Thermal injury accounts for 14 000 casualties a year in the United Kingdom. With improvements in managing cutaneous burns mortality has steadily reduced so that inhalational injury from smoke and hot, toxic gases is increasingly important in outcome.'1 When overlooked, smoke inhalation can lead to early or late deterioration in the patient's condition due to damage to the airways or lungs. In addition, poisoning may occur by inhalation of gases such as hydrogen cyanide or carbon monoxide. These problems were experienced in the fire at King's Cross in 1987, in which a fifth of the victims were found at postmortem examination to have high concentrations of carboxyhaemoglobin. Furthermore, despite controversy over the forensic method used there was evidence that cyanide poisoning may have had a contributory role in some of the deaths. In this unusual fire, however, the heat blast led rapidly to asphyxiation, thus reducing the duration of exposure to toxic inhalation. This disaster, supported by previous experience with inhalational burns in this unit, suggested the need for a protocol to guide clinicians in the early management of these patients. We have proposed an immediate care plan in the form of an algorithm. This aims to promote early recognition and treatment of the airway problems and the poisoning that result from