Development of sampling methods for Raman analysis of solid dosage forms of therapeutic and illicit drugs

The results of a study aimed at determining the most important experimental parameters for automated, quantitative analysis of solid dosage form pharmaceuticals (seized and model 'ecstasy' tablets) are reported. Data obtained with a macro-Raman spectrometer were complemented by micro-Raman measurements, which gave information on particle size and provided excellent data for developing statistical models of the sampling errors associated with collecting data as a series of grid points on the tablets' surface. Spectra recorded at single points on the surface of seized MDMA-caffeine-lactose tablets with a Raman microscope (lambda(ex) = 785 nm, 3 mum diameter spot) were typically dominated by one or other of the three components, consistent with Raman mapping data which showed the drug and caffeine microcrystals were ca 40 mum in diameter. Spectra collected with a microscope from eight points on a 200 mum grid were combined and in the resultant spectra the average value of the Raman band intensity ratio used to quantify the MDMA: caffeine ratio, mu(r), was 1.19 with an unacceptably high standard deviation, sigma(r), of 1.20. In contrast, with a conventional macro-Raman system (150 mum spot diameter), combined eight grid point data gave mu(r) = 1.47 with sigma(r) = 0.16. A simple statistical model which could be used to predict sigma(r) under the various conditions used was developed. The model showed that the decrease in sigma(r) on moving to a 150 mum spot was too large to be due entirely to the increased spot diameter but was consistent with the increased sampling volume that arose from a combination of the larger spot size and depth of focus in the macroscopic system. With the macro-Raman system, combining 64 grid points (0.5 mm spacing and 1-2 s accumulation per point) to give a single averaged spectrum for a tablet was found to be a practical balance between minimizing sampling errors and keeping overhead times at an acceptable level. The effectiveness of this sampling strategy was also tested by quantitative analysis of a set of model ecstasy tablets prepared from MDEA-sorbitol (0-30% by mass MDEA). A simple univariate calibration model of averaged 64 point data had R-2 = 0.998 and an r.m.s. standard error of prediction of 1.1% whereas data obtained by sampling just four points on the same tablet showed deviations from the calibration of up to 5%.

Increasing the accuracy of Nitrogen Dioxide (NO2) pollution mapping using geographically weighted regression (GWR) and geostatistics.

Nitrogen Dioxide (NO2) is known to act as an environmental trigger for many respiratory illnesses. As a pollutant it is difficult to map accurately, as concentrations can vary greatly over small distances. In this study three geostatistical techniques were compared, producing maps of NO2 concentrations in the United Kingdom (UK). The primary data source for each technique was NO2 point data, generated from background automatic monitoring and background diffusion tubes, which are analysed by different laboratories on behalf of local councils and authorities in the UK. The techniques used were simple kriging (SK), ordinary kriging (OK) and simple kriging with a locally varying mean (SKlm). SK and OK make use of the primary variable only. SKlm differs in that it utilises additional data to inform prediction, and hence potentially reduces uncertainty. The secondary data source was Oxides of Nitrogen (NOx) derived from dispersion modelling outputs, at 1km x 1km resolution for the UK. These data were used to define the locally varying mean in SKlm, using two regression approaches: (i) global regression (GR) and (ii) geographically weighted regression (GWR). Based upon summary statistics and cross-validation prediction errors, SKlm using GWR derived local means produced the most accurate predictions. Therefore, using GWR to inform SKlm was beneficial in this study.

Integrating Multiple Point Statistics with Aerial Geophysical Data to assist Groundwater Flow Models

The process of accounting for heterogeneity has made significant advances in statistical research, primarily in the framework of stochastic analysis and the development of multiple-point statistics (MPS). Among MPS techniques, the direct sampling (DS) method is tested to determine its ability to delineate heterogeneity from aerial magnetics data in a regional sandstone aquifer intruded by low-permeability volcanic dykes in Northern Ireland, UK. The use of two two-dimensional bivariate training images aids in creating spatial probability distributions of heterogeneities of hydrogeological interest, despite relatively ‘noisy’ magnetics data (i.e. including hydrogeologically irrelevant urban noise and regional geologic effects). These distributions are incorporated into a hierarchy system where previously published density function and upscaling methods are applied to derive regional distributions of equivalent hydraulic conductivity tensor K. Several K models, as determined by several stochastic realisations of MPS dyke locations, are computed within groundwater flow models and evaluated by comparing modelled heads with field observations. Results show a significant improvement in model calibration when compared to a simplistic homogeneous and isotropic aquifer model that does not account for the dyke occurrence evidenced by airborne magnetic data. The best model is obtained when normal and reverse polarity dykes are computed separately within MPS simulations and when a probability threshold of 0.7 is applied. The presented stochastic approach also provides improvement when compared to a previously published deterministic anisotropic model based on the unprocessed (i.e. noisy) airborne magnetics. This demonstrates the potential of coupling MPS to airborne geophysical data for regional groundwater modelling.

A photospheric bright point model

Aims. A magneto-hydrostatic model is constructed with spectropolarimetric properties close to those of solar photospheric magnetic bright points.
Methods. Results of solar radiative magneto-convection simulations are used to produce the spatial structure of the vertical component of the magnetic field. The horizontal component of magnetic field is reconstructed using the self-similarity condition, while the magneto-hydrostatic equilibrium condition is applied to the standard photospheric model with the magnetic field embedded. Partial ionisation processes are found to be necessary for reconstructing the correct temperature structure of the model.
Results. The structures obtained are in good agreement with observational data. By combining the realistic structure of the magnetic field with the temperature structure of the quiet solar photosphere, the continuum formation level above the equipartition layer can be found. Preliminary results are shown of wave propagation through this magnetic structure. The observational consequences of the oscillations are examined in continuum intensity and in the Fe I 6302 angstrom magnetically sensitive line.

Somatic point mutations in mtDNA control region are influenced by genetic background and associated with healthy aging: a GEHA stud

Tissue specific somatic mutations occurring in the mtDNA control region have been proposed to provide a survival advantage. Data on twins and on relatives of long-lived subjects suggested that the occurrence/accumulation of these mutations may be genetically influenced. To further investigate control region somatic heteroplasmy in the elderly, we analyzed the segment surrounding the nt 150 position (previously reported as specific of Leukocytes) in various types of leukocytes obtained from 195 ultra-nonagenarians sib-pairs of Italian or Finnish origin collected in the frame of the GEHA Project. We found a significant correlation of the mtDNA control region heteroplasmy between sibs, confirming a genetic influence on this phenomenon. Furthermore, many subjects showed heteroplasmy due to mutations different from the C150T transition. In these cases heteroplasmy was correlated within sibpairs in Finnish and northern Italian samples, but not in southern Italians. This suggested that the genetic contribution to control region mutations may be population specific. Finally, we observed a possible correlation between heteroplasmy and Hand Grip strength, one of the best markers of physical performance and of mortality risk in the elderly. Our study provides new evidence on the relevance of mtDNA somatic mutations in aging and longevity and confirms that the occurrence of specific point mutations in the mtDNA control region may represent a strategy for the age-related remodelling of organismal functions.

Limitations of instantaneous water quality sampling in surface-water catchments: Comparison with near-continuous phosphorus time-series data.

The validity of load estimates from intermittent, instantaneous grab sampling is dependent on adequate spatial coverage by monitoring networks and a sampling frequency that re?ects the variability in the system under study. Catchments with a ?ashy hydrology due to surface runoff pose a particular challenge as intense short duration rainfall events may account for a signi?cant portion of the total diffuse transfer of pollution from soil to water in any hydrological year. This can also be exacerbated by the presence of strong background pollution signals from point sources during low flows. In this paper, a range of sampling methodologies and load estimation techniques are applied to phosphorus data from such a surface water dominated river system, instrumented at three sub-catchments (ranging from 3 to 5 km2 in area) with near-continuous monitoring stations. Systematic and Monte Carlo approaches were applied to simulate grab sampling using multiple strategies and to calculate an estimated load, Le based on established load estimation methods. Comparison with the actual load, Lt, revealed signi?cant average underestimation, of up to 60%, and high variability for all feasible sampling approaches. Further analysis of the time series provides an insight into these observations; revealing peak frequencies and power-law scaling in the distributions of P concentration, discharge and load associated with surface runoff and background transfers. Results indicate that only near-continuous monitoring that re?ects the rapid temporal changes in these river systems is adequate for comparative monitoring and evaluation purposes. While the implications of this analysis may be more tenable to small scale ?ashy systems, this represents an appropriate scale in terms of evaluating catchment mitigation strategies such as agri-environmental policies for managing diffuse P transfers in complex landscapes.

Antimicrobial prescribing in Nursing Homes in Northern Ireland: Results of Two Point-Prevalence Surveys

BACKGROUND: In 2005, the European Commission recommended that all member states should establish or strengthen surveillance systems for monitoring the use of antimicrobial agents. There is no evidence in the literature of any surveillance studies having been specifically conducted in nursing homes (NHs) in Northern Ireland (NI).

OBJECTIVE: The aim of this study was to determine the prevalence of antimicrobial prescribing and its relationship with certain factors (e.g. indwelling urinary catheterization, urinary incontinence, disorientation, etc.) in NH residents in NI.

METHODS: This project was carried out in NI as part of a wider European study under the protocols of the European Surveillance of Antimicrobial Consumption group. Two point-prevalence surveys (PPSs) were conducted in 30 NHs in April and November 2009. Data were obtained from nursing notes, medication administration records and staff in relation to antimicrobial prescribing, facility and resident characteristics and were analysed descriptively.

RESULTS: The point prevalence of antimicrobial prescribing was 13.2% in April 2009 and 10.7% in November 2009, with a 10-fold difference existing between the NHs with the highest and lowest antimicrobial prescribing prevalence during both PPSs. The same NH had the highest rate of antimicrobial prescribing during both April (30.6%) and November (26.0%). The group of antimicrobials most commonly prescribed was the penicillins (April 28.6%, November 27.5%) whilst the most prevalent individual antimicrobial prescribed was trimethoprim (April 21.3%, November 24.3%). The majority of antimicrobials were prescribed for the purpose of preventing urinary tract infections (UTIs) in both April (37.8%) and in November (46.7%), with 5% of all participating residents being prescribed an antimicrobial for this reason. Some (20%) antimicrobials were prescribed at inappropriate doses, particularly those which were used for the purpose of preventing UTIs. Indwelling urinary catheterization and wounds were significant risk factors for antimicrobial use in April [odds ratio {OR} (95% CI) 2.0 (1.1, 3.5) and 1.8 (1.1, 3.0), respectively] but not in November 2009 [OR (95% CI) 1.6 (0.8, 3.2) and 1.2 (0.7, 2.2), respectively]. Other resident factors, e.g. disorientation, immobility and incontinence, were not associated with antimicrobial use. Furthermore, none of the NH characteristics investigated (e.g. number of beds, hospitalization episodes, number of general practitioners, etc.) were found to be associated with antimicrobial use in either April or November 2009.

CONCLUSIONS: This study has identified a high overall rate of antimicrobial use in NHs in NI, with variability evident both within and between homes. More research is needed to understand which factors influence antimicrobial use and to determine the appropriateness of antimicrobial prescribing in this population in general and more specifically in the management of recurrent UTIs.

Protection Assessment using Reduced Power System Fault Data

Wavelet transforms provide basis functions for time-frequency analysis and have properties that are particularly useful for the compression of analogue point on wave transient and disturbance power system signals. This paper evaluates the compression properties of the discrete wavelet transform using actual power system data. The results presented in the paper indicate that reduction ratios up to 10:1 with acceptable distortion are achievable. The paper discusses the application of the reduction method for expedient fault analysis and protection assessment.

POINT-AGAPE pixel lensing survey of M31 - Evidence for a MACHO contribution to galactic halos

The POINT-AGAPE collaboration is carrying out a search for gravitational microlensing toward M31 to reveal galactic dark matter in the form of MACHOs (Massive Astrophysical Compact Halo Objects) in the halos of the Milky Way and M31. A high-threshold analysis of 3 years of data yields 6 bright, short- duration microlensing events, which are confronted to a simulation of the observations and the analysis. The observed signal is much larger than expected from self lensing alone and we conclude, at the 95% confidence level, that at least 20% of the halo mass in the direction of M31 must be in the form of MACHOs if their average mass lies in the range 0.5-1 M-circle dot. This lower bound drops to 8% for MACHOs with masses similar to 0.01 M-circle dot. In addition, we discuss a likely binary microlensing candidate with caustic crossing. Its location, some 32' away from the centre of M31, supports our conclusion that we are detecting a MACHO signal in the direction of M31.

Classical novae from the POINT-AGAPE microlensing survey of M31 - I. The nova catalogue

The POINT-AGAPE (Pixel-lensing Observations with the Isaac Newton Telescope-Andromeda Galaxy Amplified Pixels Experiment) survey is an optical search for gravitational microlensing events towards the Andromeda galaxy (M31). As well as microlensing, the survey is sensitive to many different classes of variable stars and transients. Here we describe the automated detection and selection pipeline used to identify M31 classical novae (CNe) and we present the resulting catalogue of 20 CN candidates observed over three seasons. CNe are observed both in the bulge region as well as over a wide area of the M31 disc. Nine of the CNe are caught during the final rise phase and all are well sampled in at least two colours. The excellent light-curve coverage has allowed us to detect and classify CNe over a wide range of speed class, from very fast to very slow. Among the light curves is a moderately fast CN exhibiting entry into a deep transition minimum, followed by its final decline. We have also observed in detail a very slow CN which faded by only 0.01 mag d(-1) over a 150-d period. We detect other interesting variable objects, including one of the longest period and most luminous Mira variables. The CN catalogue constitutes a uniquely well-sampled and objectively-selected data set with which to study the statistical properties of CNe in M31, such as the global nova rate, the reliability of novae as standard-candle distance indicators and the dependence of the nova population on stellar environment. The findings of this statistical study will be reported in a follow-up paper.

The POINT-AGAPE survey - I. The variable stars in M31

For the purposes of identifying microlensing events, the POINT-AGAPE collaboration has been monitoring the Andromeda galaxy (M31) for three seasons (1999-2001) with the Wide Field Camera on the Isaac Newton Telescope. In each season, data are taken for one hour per night for roughly 60 nights during the six months that M31 is visible. The two 33 x 33 arcmin(2) fields of view straddle the central bulge, northwards and southwards. We have calculated the locations, periods and brightness of 35 414 variable stars in M31 as a by-product of the microlensing search. The variables are classified according to their period and brightness. Rough correspondences with classical types of variable star (such as Population I and II Cepheids, Miras and semiregular long-period variables) are established. The spatial distribution of Population I Cepheids is clearly associated with the spiral arms, while the central concentration of the Miras and long-period variables varies noticeably, the brighter and the shorter period Miras being much more centrally concentrated.

CHARACTERIZATION OF A LASER-PRODUCED PLASMA USING THE TECHNIQUE OF POINT-PROJECTION ABSORPTION-SPECTROSCOPY

The technique of point-projection spectroscopy has been shown to be applicable to the study of expanding aluminum plasmas generated by approximately 80 ps laser pulses incident on massive, aluminum stripe targets of approximately 125-mu-m width. Targets were irradiated at an intensity of 2.5 +/- 0.5 x 10(13) W/cm2 in a line focus geometry and under conditions similar to those of interest in x-ray laser schemes. Hydrogenic and heliumlike aluminum resonance lines were observed in absorption using a quasicontinuous uranium back-lighter plasma. Using a pentaerythrital Bragg crystal as the dispersive element, a resolving power of approximately 3500 was achieved with spatial resolution at the 5-mu-m level in frame times of the order of 100 ps. Reduction of the data for times up to 150 ps after the peak of the incident laser pulse produced estimates of the temperature and ion densities present, as a function of space and time. The one-dimensional Lagrangian hydrodynamic code MEDUSA coupled to the atomic physics non-local-thermodynamic-equilibrium ionized material package was used to simulate the experiment in planar geometry and has been shown to be consistent with the measurements.

64-point Fourier transform chip for digital television applications

A 64-point Fourier transform chip is described that performs a forward or inverse, 64-point Fourier transform on complex two's complement data supplied at a rate of 13.5MHz and can operate at clock rates of up to 40MHz, under worst-case conditions. It uses a 0.6µm double-level metal CMOS technology, contains 535k transistors and uses an internal 3.3V power supply. It has an area of 7.8×8mm, dissipates 0.9W, has 48 pins and is housed in a 84 pin PLCC plastic package. The chip is based on a FFT architecture developed from first principles through a detailed investigation of the structure of the relevant DFT matrix and through mapping repetitive blocks within this matrix onto a regular silicon structure.

The Forgiving Graph: a distributed data structure for low stretch under adversarial attack

We consider the problem of self-healing in peer-to-peer networks that are under repeated attack by an omniscient adversary. We assume that, over a sequence of rounds, an adversary either inserts a node with arbitrary connections or deletes an arbitrary node from the network. The network responds to each such change by quick “repairs,” which consist of adding or deleting a small number of edges. These repairs essentially preserve closeness of nodes after adversarial deletions, without increasing node degrees by too much, in the following sense. At any point in the algorithm, nodes v and w whose distance would have been l in the graph formed by considering only the adversarial insertions (not the adversarial deletions), will be at distance at most l log n in the actual graph, where n is the total number of vertices seen so far. Similarly, at any point, a node v whose degree would have been d in the graph with adversarial insertions only, will have degree at most 3d in the actual graph. Our distributed data structure, which we call the Forgiving Graph, has low latency and bandwidth requirements. The Forgiving Graph improves on the Forgiving Tree distributed data structure from Hayes et al. (2008) in the following ways: 1) it ensures low stretch over all pairs of nodes, while the Forgiving Tree only ensures low diameter increase; 2) it handles both node insertions and deletions, while the Forgiving Tree only handles deletions; 3) it requires only a very simple and minimal initialization phase, while the Forgiving Tree initially requires construction of a spanning tree of the network.