Temperature-referenced high-sensitivity point-probe optical fiber chem-sensors based on cladding etched fiber Bragg gratings

Point-probe optical fiber chem-sensors have been implemented using cladding etched fiber Bragg gratings. The sensors possess refractive index sensing capability that can be utilized to measure chemical concentrations. The Bragg wavelength shift reaches 8 nm when the index of surrounding medium changes from 1.33 to 1.44, giving maximum sensitivity more than 10 times higher than that of previously reported devices. More importantly, the dual-grating configuration of the point-probe sensors offers a temperature reference function, permitting accurate measurement of refractive index encoded chemical concentrations.

Temperature-referenced high-sensitivity point-probe optical fiber chem-sensors based on cladding etched fiber Bragg gratings

Point-probe optical fiber chem-sensors have been implemented using cladding etched fiber Bragg gratings. The sensors possess refractive index sensing capability that can be utilized to measure chemical concentrations. The Bragg wavelength shift reaches 8 nm when the index of surrounding medium changes from 1.33 to 1.44, giving maximum sensitivity more than 10 times higher than that of previously reported devices. More importantly, the dual-grating configuration of the point-probe sensors offers a temperature reference function, permitting accurate measurement of refractive index encoded chemical concentrations.

Quantitative methods in neuropathology

The last decade has seen a considerable increase in the application of quantitative methods in the study of histological sections of brain tissue and especially in the study of neurodegenerative disease. These disorders are characterised by the deposition and aggregation of abnormal or misfolded proteins in the form of extracellular protein deposits such as senile plaques (SP) and intracellular inclusions such as neurofibrillary tangles (NFT). Quantification of brain lesions and studying the relationships between lesions and normal anatomical features of the brain, including neurons, glial cells, and blood vessels, has become an important method of elucidating disease pathogenesis. This review describes methods for quantifying the abundance of a histological feature such as density, frequency, and 'load' and the sampling methods by which quantitative measures can be obtained including plot/quadrat sampling, transect sampling, and the point-quarter method. In addition, methods for determining the spatial pattern of a histological feature, i.e., whether the feature is distributed at random, regularly, or is aggregated into clusters, are described. These methods include the use of the Poisson and binomial distributions, pattern analysis by regression, Fourier analysis, and methods based on mapped point patterns. Finally, the statistical methods available for studying the degree of spatial correlation between pathological lesions and neurons, glial cells, and blood vessels are described.

Implications of high power losses in IR femtosecond laser inscribed fibre Bragg gratings

We report on high power issues related to the reliability of fibre Bragg gratings inscribed with an infrared femtosecond laser using the point-by-point writing method. Conventionally, fibre Bragg gratings have usually been written in fibres using ultraviolet light, either holographically or using a phase mask. Since the coating is highly absorbing in the UV, this process normally requires that the protective polymer coating is stripped prior to inscription, with the fibre then being recoated. This results in a time consuming fabrication process that, unless great care is taken, can lead to fibre strength degradation, due to the presence of surface damage. The recent development of FBG inscription using NIR femtosecond lasers has eliminated the requirement for the stripping of the coating. At the same time the ability to write gratings point-by-point offers the potential for great flexibility in the grating design. There is, however, a requirement for reliability testing of these gratings, particularly for use in telecommunications systems where high powers are increasingly being used in long-haul transmission systems making use of Raman amplification. We report on a study of such gratings which has revealed the presence of broad spectrum power losses. When high powers are used, even at wavelengths far removed from the Bragg condition, these losses produce an increase in the fibre temperature due to absorption in the coating. We have monitored this temperature rise using the wavelength shift in the grating itself. At power levels of a few watts, various temperature increases were experienced ranging from a few degrees up to the point where the buffer completely melts off the fibre at the grating site. Further investigations are currently under way to study the optical loss mechanisms in order to optimise the inscription mechanism and minimise such losses.

Self-adaptive probabilistic roadmap generation for intelligent virtual agents

Agents inhabiting large scale environments are faced with the problem of generating maps by which they can navigate. One solution to this problem is to use probabilistic roadmaps which rely on selecting and connecting a set of points that describe the interconnectivity of free space. However, the time required to generate these maps can be prohibitive, and agents do not typically know the environment in advance. In this paper we show that the optimal combination of different point selection methods used to create the map is dependent on the environment, no point selection method dominates. This motivates a novel self-adaptive approach for an agent to combine several point selection methods. The success rate of our approach is comparable to the state of the art and the generation cost is substantially reduced. Self-adaptation therefore enables a more efficient use of the agent's resources. Results are presented for both a set of archetypal scenarios and large scale virtual environments based in Second Life, representing real locations in London.

Large scale organisational intervention to improve patient safety in four UK hospitals:mixed method evaluation

Objectives: To conduct an independent evaluation of the first phase of the Health Foundation's Safer Patients Initiative (SPI), and to identify the net additional effect of SPI and any differences in changes in participating and non-participating NHS hospitals. Design: Mixed method evaluation involving five substudies, before and after design. Setting: NHS hospitals in United Kingdom. Participants: Four hospitals (one in each country in the UK) participating in the first phase of the SPI (SPI1); 18 control hospitals. Intervention: The SPI1 was a compound (multicomponent) organisational intervention delivered over 18 months that focused on improving the reliability of specific frontline care processes in designated clinical specialties and promoting organisational and cultural change. Results: Senior staff members were knowledgeable and enthusiastic about SPI1. There was a small (0.08 points on a 5 point scale) but significant (P<0.01) effect in favour of the SPI1 hospitals in one of 11 dimensions of the staff questionnaire (organisational climate). Qualitative evidence showed only modest penetration of SPI1 at medical ward level. Although SPI1 was designed to engage staff from the bottom up, it did not usually feel like this to those working on the wards, and questions about legitimacy of some aspects of SPI1 were raised. Of the five components to identify patients at risk of deterioration - monitoring of vital signs (14 items); routine tests (three items); evidence based standards specific to certain diseases (three items); prescribing errors (multiple items from the British National Formulary); and medical history taking (11 items) - there was little net difference between control and SPI1 hospitals, except in relation to quality of monitoring of acute medical patients, which improved on average over time across all hospitals. Recording of respiratory rate increased to a greater degree in SPI1 than in control hospitals; in the second six hours after admission recording increased from 40% (93) to 69% (165) in control hospitals and from 37% (141) to 78% (296) in SPI1 hospitals (odds ratio for "difference in difference" 2.1, 99% confidence interval 1.0 to 4.3; P=0.008). Use of a formal scoring system for patients with pneumonia also increased over time (from 2% (102) to 23% (111) in control hospitals and from 2% (170) to 9% (189) in SPI1 hospitals), which favoured controls and was not significant (0.3, 0.02 to 3.4; P=0.173). There were no improvements in the proportion of prescription errors and no effects that could be attributed to SPI1 in non-targeted generic areas (such as enhanced safety culture). On some measures, the lack of effect could be because compliance was already high at baseline (such as use of steroids in over 85% of cases where indicated), but even when there was more room for improvement (such as in quality of medical history taking), there was no significant additional net effect of SPI1. There were no changes over time or between control and SPI1 hospitals in errors or rates of adverse events in patients in medical wards. Mortality increased from 11% (27) to 16% (39) among controls and decreased from17%(63) to13%(49) among SPI1 hospitals, but the risk adjusted difference was not significant (0.5, 0.2 to 1.4; P=0.085). Poor care was a contributing factor in four of the 178 deaths identified by review of case notes. The survey of patients showed no significant differences apart from an increase in perception of cleanliness in favour of SPI1 hospitals. Conclusions The introduction of SPI1 was associated with improvements in one of the types of clinical process studied (monitoring of vital signs) and one measure of staff perceptions of organisational climate. There was no additional effect of SPI1 on other targeted issues nor on other measures of generic organisational strengthening.

Development and validation of an HPLC method for the rapid and simultaneous determination of 6-mercaptopurine and four of its metabolites in plasma and red blood cells

An HPLC method has been developed and validated for the rapid determination of mercaptopurine and four of its metabolites; thioguanine, thiouric acid, thioxanthine and methylmercaptopurine in plasma and red blood cells. The method involves a simple treatment procedure based on deproteinisation by perchloric acid followed by acid hydrolysis and heating for 45min at 100 degrees C. The developed method was linear over the concentration range studied with a correlation coefficient >0.994 for all compounds in both plasma and erythrocytes. The lower limits of quantification were 13, 14, 3, 2, 95pmol/8 x 10(8) RBCs and 2, 5, 2, 3, 20ng/ml plasma for thioguanine, thiouric acid, mercaptopurine, thioxanthine and methylmercaptopurine, respectively. The method described is selective and sensitive enough to analyse the different metabolites in a single run under isocratic conditions. Furthermore, it has been shown to be applicable for monitoring these metabolites in paediatric patients due to the low volume requirement (200microl of plasma or erythrocytes) and has been successfully applied for investigating population pharmacokinetics, pharmacogenetics and non-adherence to therapy in these patients.

Polynomial function intervals for floating-point software verification

The focus of our work is the verification of tight functional properties of numerical programs, such as showing that a floating-point implementation of Riemann integration computes a close approximation of the exact integral. Programmers and engineers writing such programs will benefit from verification tools that support an expressive specification language and that are highly automated. Our work provides a new method for verification of numerical software, supporting a substantially more expressive language for specifications than other publicly available automated tools. The additional expressivity in the specification language is provided by two constructs. First, the specification can feature inclusions between interval arithmetic expressions. Second, the integral operator from classical analysis can be used in the specifications, where the integration bounds can be arbitrary expressions over real variables. To support our claim of expressivity, we outline the verification of four example programs, including the integration example mentioned earlier. A key component of our method is an algorithm for proving numerical theorems. This algorithm is based on automatic polynomial approximation of non-linear real and real-interval functions defined by expressions. The PolyPaver tool is our implementation of the algorithm and its source code is publicly available. In this paper we report on experiments using PolyPaver that indicate that the additional expressivity does not come at a performance cost when comparing with other publicly available state-of-the-art provers. We also include a scalability study that explores the limits of PolyPaver in proving tight functional specifications of progressively larger randomly generated programs. © 2014 Springer International Publishing Switzerland.

A preliminary evaluation of a novel method to monitor a triple antioxidant combination (vitamins E, C and alpha-lipoic acid) in diabetic volunteers using in vitro methaemoglobin formation

Eight otherwise healthy diabetic volunteers took a daily antioxidant supplement consisting of vitamin E (200 IU), vitamin C (250 mg) and α-lipoic acid (90 mg) for a period of 6 weeks. Diabetic dapsone hydroxylamine-mediated methaemoglobin formation and resistance to erythrocytic thiol depletion was compared with age and sex-matched non-diabetic subjects. At time zero, methaemoglobin formation in the non-diabetic subjects was greater at all four time points compared with that of the diabetic subjects. Resistance to glutathione depletion was initially greater in non-diabetic compared with diabetic samples. Half-way through the study (3 weeks), there were no differences between the two groups in methaemoglobin formation and thiol depletion in the diabetic samples was now lower than the non-diabetic samples at 10 and 20 min. At 6 weeks, diabetic erythrocytic thiol levels remained greater than those of non-diabetics. HbA1c values were significantly reduced in the diabetic subjects at 6 weeks compared with time zero values. At 10 weeks, 4 weeks after the end of supplementation, the diabetic HbA1c values significantly increased to the point where they were not significantly different from the time zero values. Total antioxidant status measurement (TAS) indicated that diabetic plasma antioxidant capacity was significantly improved during antioxidant supplementation. Conversion of α-lipoic acid to dihydrolipoic acid (DHLA) in vivo led to potent interference in a standard fructosamine assay kit, negating its use in this study. This report suggests that triple antioxidant therapy in diabetic volunteers attenuates the in vitro experimental oxidative stress of methaemoglobin formation and reduces haemoglobin glycation in vivo. © 2003 Elsevier Science B.V. All rights reserved.