THEORY OF DIFFUSION OF HEAVY IMPURITIES IN ALKALI-METALS

Interatomic potentials have been developed for heavy atom impurities in alkali metal hosts, and they have been used to calculate characteristic energies for the diffusion of gold in sodium and of silver in lithium. The calculations show that, whilst most impurity atoms should be present substitutionally, the diffusion is dominated by interstitial motion for both Li-Ag and Na-Au. The large difference in observed behaviour stems from the different forms of the interatomic potentials but cannot be described simply in terms of atomic radii or electronegativity arguments. The activation energies predicted are in good quantitative agreement with experiment

Growth and optical characterisation of multilayers of InGaN quantum dots

We report on the growth (using metal-organic vapour phase epitaxy) and optical characterization of single and multiple layers of InGaN quantum dots (QDs), which were formed by annealing InGaN epilayers at the growth temperature in nitrogen. The size and density of the nanostructures have been found to be fairly similar for uncapped single and three layer QD samples if the GaN barriers between the dot layers are grown at the same temperature as the InGaN epilayer. The distribution of nanostructure heights of the final QD layer of three is wider and is centred around a larger size if the GaN barriers are grown at two temperatures (first a thin layer at the dot growth temperature, then a thicker layer at a higher temperature). Micro-photoluminescence studies at 4.2 K of capped samples have confirmed the QD nature of the capped nanostructures by the observation of sharp emission peaks with full width at half maximum limited by the resolution of the spectrometer. We have also observed much more QD emission per unit area in a sample with three QD layers, than in a sample with a single QD layer, as expected

The TLR2/6 ligand PAM2CSK4 is a Th2 polarizing adjuvant in Leishmania major and Brugia malayi murine vaccine models.

Toll-like receptors (TLRs) play an important role in the innate and adaptive immune responses to pathogens, and are the target of new vaccine adjuvants. TLR2 plays a role in parasite recognition and activation of immune responses during cutaneous leishmaniasis infection, suggesting that TLR2 could be targeted by adjuvants for use in Leishmania vaccines. We therefore explored using Pam2CSK4 (Pam2) and Pam3CSK4 (Pam3) lipopeptide adjuvants, which activate TLR2/6 and TLR2/1 heterodimers respectively, in vaccine models for parasitic infections.The use of lipopeptide adjuvants was explored using two vaccine models. For cutaneous leishmaniasis, the lipopeptide adjuvants Pam2 and Pam3 were compared to that of the Th1-driving double-stranded DNA TLR9 agonist CpG for their ability to improve the efficacy of the autoclaved Leishmania major (ALM) vaccine to protect against L. major infection. The ability of Pam2 to enhance the efficacy of a soluble Brugia malayi microfilariae extract (BmMfE) vaccine to protect against filarial infection was also assessed in a peritoneal infection model of B. malayi filariasis. Parasite antigen-specific cellular and humoral immune responses were assessed post-challenge.The use of lipopeptides in ALM-containing vaccines did not provide any protection upon infection with L. major, and Pam2 exacerbated the disease severity in vaccinated mice post-challenge. Pam2, and to a lesser extent Pam3, were able to elevate antigen-specific immune responses post-challenge in this model, but these responses displayed a skewed Th2 phenotype as characterised by elevated levels of IgG1. In the B. malayi vaccine model, the use of Pam2 as an adjuvant with BmMfE induced significant protective immunity to the same level as inclusion of an Alum adjuvant. Here, both Pam2 and Alum were found to enhance antigen-specific antibody production post-challenge, and Pam2 significantly elevated levels of antigen-specific IL-4, IL-5 and IL-13 produced by splenocytes.These data indicate that TLR2/6-targeting ligands could be considered as adjuvants for vaccines that require robust Th2 and/or antibody-dependent immunity

Predictors of pain relief following spinal cord stimulation in chronic back and leg pain and failed back surgery syndrome: a systematic review and meta-regression analysis

This is the final version of the article. Available from the publisher via the DOI in this record.We sought to assess the extent to which pain relief in chronic back and leg pain (CBLP) following spinal cord stimulation (SCS) is influenced by patient-related factors, including pain location, and technology factors. A number of electronic databases were searched with citation searching of included papers and recent systematic reviews. All study designs were included. The primary outcome was pain relief following SCS, we also sought pain score (pre- and post-SCS). Multiple predictive factors were examined: location of pain, history of back surgery, initial level of pain, litigation/worker's compensation, age, gender, duration of pain, duration of follow-up, publication year, continent of data collection, study design, quality score, method of SCS lead implant, and type of SCS lead. Between-study association in predictive factors and pain relief were assessed by meta-regression. Seventy-four studies (N = 3,025 patients with CBLP) met the inclusion criteria; 63 reported data to allow inclusion in a quantitative analysis. Evidence of substantial statistical heterogeneity (P < 0.0001) in level of pain relief following SCS was noted. The mean level of pain relief across studies was 58% (95% CI: 53% to 64%, random effects) at an average follow-up of 24 months. Multivariable meta-regression analysis showed no predictive patient or technology factors. SCS was effective in reducing pain irrespective of the location of CBLP. This review supports SCS as an effective pain relieving treatment for CBLP with predominant leg pain with or without a prior history of back surgery. Randomized controlled trials need to confirm the effectiveness and cost-effectiveness of SCS in the CLBP population with predominant low back pain.This study was sponsored by Medtronic, Inc

The effect of intervertebral cartilage on neutral posture and range of motion in the necks of sauropod dinosaurs

The necks of sauropod dinosaurs were a key factor in their evolution. The habitual posture and range of motion of these necks has been controversial, and computer-aided studies have argued for an obligatory sub-horizontal pose. However, such studies are compromised by their failure to take into account the important role of intervertebral cartilage. This cartilage takes very different forms in different animals. Mammals and crocodilians have intervertebral discs, while birds have synovial joints in their necks. The form and thickness of cartilage varies significantly even among closely related taxa. We cannot yet tell whether the neck joints of sauropods more closely resembled those of birds or mammals. Inspection of CT scans showed cartilage:bone ratios of 4.5% for Sauroposeidon and about 20% and 15% for two juvenile Apatosaurus individuals. In extant animals, this ratio varied from 2.59% for the rhea to 24% for a juvenile giraffe. It is not yet possible to disentangle ontogenetic and taxonomic signals, but mammal cartilage is generally three times as thick as that of birds. Our most detailed work, on a turkey, yielded a cartilage:bone ratio of 4.56%. Articular cartilage also added 11% to the length of the turkey's zygapophyseal facets. Simple image manipulation suggests that incorporating 4.56% of neck cartilage into an intervertebral joint of a turkey raises neutral posture by 15°. If this were also true of sauropods, the true neutral pose of the neck would be much higher than has been depicted. An additional 11% of zygapophyseal facet length translates to 11% more range of motion at each joint. More precise quantitative results must await detailed modelling. In summary, including cartilage in our models of sauropod necks shows that they were longer, more elevated and more flexible than previously recognised

Knowledge representation for missing persons investigations

Purpose: The application of situation calculus for knowledge representation in missing persons investigations. Design/methodology/approach: The development of a knowledge representation model for the missing persons investigation process based upon situation calculus, with a demonstration of the use of the model for a missing persons example case. Findings: Situation calculus is valuable for knowledge representation for missing persons investigations, since such investigations have state changes over time, and due to the complexity of the differing investigation activities applicable to different situations, can be difficult to represent using simpler approaches such as tables or flowcharts. Research limitations/implications: Situation calculus modelling for missing persons investigations adds formalism to the process beyond that which can be afforded by the current use of text, tables or flowcharts. The additional formalism is useful in dealing with the uncertainty present in such investigations. Practical implications: A simplification of the application of the current police guidelines, and thoroughness in the application of such guidelines for missing persons investigations via situation calculus modelling. Social implications: Supporting the management of missing person investigations, by utilizing the most critical variables in a missing persons investigation to determine relevant investigation and search activities applicable to the circumstances of a given case. Originality/value: The novelty of the knowledge representation approach is the application of situation calculus via state and action vectors and a matrix of fluents to the process of missing persons investigations

Long reaction times are associated with delayed brain activity in Lewy body dementia

A significant symptom of Lewy body dementia (LBD) is slow cognitive processing or bradyphrenia. In a previous fMRI task-based study, we found slower responses in LBD, accompanied by greater deactivation in the default mode network. In this study, we investigated the timing and magnitude of the activations and deactivations with respect to reaction time to determine whether the slower responses in LBD were associated with delayed neuronal activity. Using fMRI, we examined the magnitude and latency of activations and deactivations during an event-related attention task in 32 patients with LBD and 23 healthy controls using predefined regions of interest. Default mode network deactivations did not significantly differ in their timing between groups or task conditions, while the task-related activations in the parietal, occipital, frontal, and motor cortex were all significantly later in the LBD group. Repeating the analysis with reaction time as a parametric modulator of activation magnitude produced similar findings, with the reaction time modulator being significant in a number of regions including the default mode network, suggesting that the increased deactivation in LBD is partly explained by slower task completion. Our data suggest that the default mode network deactivation is initiated at the start of the task, and remains deactivated until its end, with the increased magnitude of deactivation in LBD reflecting the more prolonged cognitive processing in these patients. These data add substantially to our understanding of the neural origins of bradyphrenia, which will be essential for determining optimum therapeutic strategies for cognitive impairment in LBD.Funded by: National Institute for Health Research, Newcastle Biomedical Research Unit based at Newcastle Hospitals NHS Foundation Trust, Newcastle University, Wellcome Trust. Grant Number: WT088441M

Disease prevention versus data privacy : using landcover maps to inform spatial epidemic models

The availability of epidemiological data in the early stages of an outbreak of an infectious disease is vital for modelers to make accurate predictions regarding the likely spread of disease and preferred intervention strategies. However, in some countries, the necessary demographic data are only available at an aggregate scale. We investigated the ability of models of livestock infectious diseases to predict epidemic spread and obtain optimal control policies in the event of imperfect, aggregated data. Taking a geographic information approach, we used land cover data to predict UK farm locations and investigated the influence of using these synthetic location data sets upon epidemiological predictions in the event of an outbreak of foot-and-mouth disease. When broadly classified land cover data were used to create synthetic farm locations, model predictions deviated significantly from those simulated on true data. However, when more resolved subclass land use data were used, moderate to highly accurate predictions of epidemic size, duration and optimal vaccination and ring culling strategies were obtained. This suggests that a geographic information approach may be useful where individual farm-level data are not available, to allow predictive analyses to be carried out regarding the likely spread of disease. This method can also be used for contingency planning in collaboration with policy makers to determine preferred control strategies in the event of a future outbreak of infectious disease in livestock