Early diagnosis of Alzheimer's disease: update on combining genetic and brain-imaging measures.

Diagnosis of Alzheimer's disease is often missed or delayed in clinical practice; thus, methods to improve early detection would provide opportunities for early intervention, symptomatic treatment, and improved patient function. Emerging data suggest that the disease process begins years before clinical diagnostic confirmation. This paper reviews current research focusing on methods for more specific and sensitive early detection using measures of genetic risk for Alzheimer's disease and functional brain imaging. This approach aims to identify patients in a presymptomatic stage for early treatment to delay progressive cognitive decline and disease onset

A marketing study of certain mathematics-based undergraduate courses at Brunel University

This Report presents some results of a limited study of the marketing situation of certain mathematics-based undergraduate courses at Brunel University

Four Station Knee Simulator Wear Testing Comparing Titanium Niobium Nitride with Cobalt Chrome

A new non-destructive method was applied in order to assess bone integrity. The method is based on measurement of bHypersensitivity to an orthopaedic implant was first published in 1966 and since then, in sensitive patients, is known to cause serious problems in joint replacement surgery. Titanium niobium nitride (TiNbN) can act as a surface coat for knee arthroplasty to “hide” the cobalt chrome (CoCr) femoral component beneath, therefore affording an immunoprivileged state. The aim of this study is to determine the wear properties of titanium niobium nitride against Ultra High Molecular Weight Polyethylene (UHMWPE) compared to cobalt chrome and to examine the metallic alloy surface of knee prostheses after loading cycles using a knee simulator. Three TiNbN coated and one CoCr Vanguard total knee femoral components were articulated against standard UHMWPE grade tibial inserts in the Stanmore-Instron knee simulator. Surface roughness, UHMWPE mass, lowest point, surface profiles and volumetric change were measuredevery one million cycles up to five million cycles. After five million cycles the average roughness of the cobalt chromemedial and lateral femoral condyles was over three times that of the TiNbN coated femoral condyles. There was no obvious difference in weight loss, volume loss or progression of lowest points of the tibial inserts articulating with the TiNbN coated and the cobalt chrome femoral component. Despite a clear reduction in roughness progression over the course of this in vitro test, there was no demonstrable improvement in UHMWPE wear measured gravimetrically or by surface profiling. The TiNbN implant tested may still be of great benefit to patients who are metal sensitive, but the coat offers no benefit in UHMWPE wear

Patterns of alcohol consumption and related behaviour in Great Britain: a latent class analysis of the alcohol use disorder identification test (AUDIT)

Aims: Attempts have been made to develop typologies to classify different types of alcoholism. However, limited research has focused on classifications to describe general patterns of alcohol use in general population samples. Methods: Latent class analysis was used to create empirically derived behaviour clusters of alcohol consumption and related problems from the Alcohol Use Disorder Identification Test (AUDIT) based on data from a large stratified multi-stage random sample of the population of Great Britain. Multinomial logistic regression was performed to describe these resultant classes using both demographic variables and mental health outcomes. Results: Six classes best described responses in the sample data. Three were heavy consumption groups, one with multiple negative consequences, one experiencing alcohol-related injury and social pressures to cut down and an additional class with memory loss. There was one moderate class with few negative consequences, and finally two mild consumption groups, one with alcohol-related injury and social pressure to cut down and one with no associated problems. Conclusions: Alcohol use in Great Britain can be hypothesized as reflecting six distinct classes, four of which follow a continuum of increased consumption leading to increased dependence and related problems and two that do not. Differences between alcohol use classes are apparent with reduced risk of depressive episode in moderate classes and an increased risk of anxiety disorders for the highest consumers of alcohol

Potassium channel subunits encoded by the KCNE gene family: physiology and pathophysiology of the MinK-related peptides (MiRPs).

Voltage-gated potassium channels provide tightly Controlled, ion-specific pathways across membranes and are key to the normal function of nerves muscles. They arise from the assembly of four pore-forming proteins called alpha-subunits. To attain the properties of native currents, alpha-subunits interact with additional molecules such as the mink-related peptides (MiRPs), single-transmembrane subunits encoded by the KCNE genes. Significantly, mutations in KCNE 1, 2 and 3 have been linked either to life-threatening cardiac arrhythmia or a disorder of skeletal muscle, familial periodic paralysis. The capacity of MiRPs to partner with multiple alpha-subunits in experimental cells appears to reflect still undiscovered roles for the KCNE-encoded peptides in vivo. Here, we consider these unique peptides in health disease and discuss future research directions

A superfamily of small potassium channel subunits: form and function of the MinK-related peptides (MiRPs).

MinK and MinK-related peptide I (MiRPI) are integral membrane peptides with a single transmembrane span. These peptides are active only when co-assembled with pore-forming K+ channel subunits and yet their role in normal ion channel behaviour is obligatory. In the resultant complex the peptides establish key functional attributes: gating kinetics, single-channel conductance, ion selectivity, regulation and pharmacology. Co-assembly is required to reconstitute channel behaviours like those observed in native cells. Thus, MinK/KvLQT1 and MiRPI/HERG complexes reproduce the cardiac currents called I(Ks) and I(Kr), respectively. Inherited mutations in KCNEI (encoding MinK) and KCNE2(encoding MiRPI) are associated with lethal cardiac arrhythmias. How these mutations change ion channel behaviour has shed light on peptide structure and function. Recently, KCNE3 and KCNE4 were isolated. In this review, we consider what is known and what remains controversial about this emerging superfamily

Research on continuous and instantaneous heavy gas clouds

This report describes the contribution of Brunel University to the joint CEC project 'Research on Continuous and Instantaneous Heavy Gas Clouds' under the Major Technological Hazards programme (CEC Contract EV4T.0025.UK(H)). Brunel University's main task in this project was concerned with the analysis of experimental data provided by some of the other project collaborators. Liaison with these collaborators, and with others undertaking other aspects of data analysis, was obviously also important. The experimental data were obtained both from full-scale field trials (Tuv/Risφ) and from wind tunnel experiments (TNO, University of Hamburg, Warren Spring Laboratory). Some of the data sets are very large. The main effort of data analysis has been concentrated on the data from Tuv/Ris sφ and Warren Spring Laboratory. This was mainly because of the timely arrival of substantial quantities of data from these sources, and also to avoid direct duplication of work carried out by other collaborators. Nevertheless, some analyses were made of TNO and University of Hamburg data. The Tuv/Risφ data set had one extremely valuable property, namely that the concentrations were measured by several different methods. Analysis here confirmed the view - hitherto essentially a theoretical speculation with no substantial experimental support - that the instrumentation can itself have a significant effect on the measured concentration. One consequence of the results of Brunel's analysis of the Tuv/Risφ data set is therefore that caution must be exercised in validating practical models of hazard assessment. Interest also attaches to this data set in that, in some of the experiments, obstacles were removed while the experiment was running; some analysis of "before and after" effects has been undertaken. For example, comparisons were made of such effects on levels of concentration and concentration variability, and two different algorithms have been developed to illustrate these features and, indeed, to determine, simply from the time series, when the obstacles were removed. A major and most welcome feature of the Warren Spring Laboratory data set was that it recorded many repetitions of gas releases under identical experimental conditions. Because of this, it was possible to study the variations in the concentration data from one release to another and to build up an initial simple statistical understanding of the situation. In such circumstances, statistical measures such as mean and variance may be estimated as ensemble averages, rather than by considering them as time averages within a single release; this latter approach can be questionable, particularly if the data do not exhibit statistical stationarity. The results of Brunel's analysis of this data set, though not yet complete, amply justify the "repetitions" strategy. The report illustrates this conclusion by presenting typical results that could not otherwise have been obtained, and which have important implications for real-life. The TNO wind tunnel experiments were conducted both for the purpose of comparing results with those from other wind tunnels and to provide a simulation of one of the full-scale Tuv/Risø field trials. The resulting data set is potentially very valuable, but Brunei's analysis has identified a number of points for concern. Thus there are some doubts about the behaviour of the instrumentation, while some of the experimental results are atypical of those obtained by other collaborators and occasionally seem hard to reconcile with physical intuition. Concerning the University of Hamburg data set, Brunel was aware that extensive and detailed analyses had been carried out by the Health and Safety Executive. Brunel did not wish to essentially duplicate this effort. Brunei's work here was, therefore, largely confined to replicating some of the HSE analyses for the purpose of confirming results - an aim that was always achieved. The HSE analyses are discussed formally in HSE's report under this contract, and were presented informally to meetings of the collaborators during the summer. Unavoidable resource constraints have prevented much progress in moving forward from data analysis to the development of models. However, work of this nature is still in progress after the termination of the formal contract. Such work is justified by the quantity and quality of the data, and is expected to form an important input to research under the FLADIS contract

GPS monitoring of a steel box girder viaduct

Structural performance monitoring of bridges has increased as major infrastructure ages and is required to sustain loads that are significantly greater than those predicted during design. Structural stiffness and/or mass distribution can change over the lifespan of a bridge structure. Resulting changes in profile or resonant frequency provide key indicators of change, and may identify structural defects. Field tests using GPS for monitoring relatively small deformations were carried out on a steel box girder viaduct bridge in the UK. The configuration consisted of five GPS receivers located at key locations on the viaduct and two reference GPS receivers. GPS data was collected at either 10 Hz or 20 Hz and post-processed using proprietary software, along with appropriate filtering and spectral analysis. Three main frequencies were clearly detected by the GPS in the vertical component. A previously reported frequency of approximately 0.56 Hz was identified along with two other frequencies. The peak vertical deflections lie in the range of ± 50 mm, while lateral and longitudinal deflections of much smaller magnitude - in the order of a few mm - are also measured. The use of GPS leads to readily obtained and useful engineering data for continued monitoring of structures