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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.

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.

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.

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.

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.

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 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.

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.

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

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.

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