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Biomedical subjects

R J Williams

Publications and source records attributed to R J Williams.

At least 19 recordsLinked to original sources

Impacts of climate change on the fate and behaviour of pesticides in surface and groundwater--A UK perspective.

Over the last two decades significant effort has been dedicated to understanding the fate and transport of pesticides in surface water and groundwater and to use this understanding in the development of environmental policy and regulation. However, there have been few studies that have investigated the relationships between pesticides and climate change, and where this work has been undertaken it has principally been in relation to the impacts of climate change on agricultural production rather than in the context of environmental protection. This study addresses that gap by reviewing how climate change may impact the fate and transport of pesticides in surface and groundwaters as a pre-cursor to quantitative studies. In order to structure the review, we have adopted a source-pathway-receptor approach where climate sensitivities of pesticide source terms, environmental pathways and receptors are reviewed. The main climate drivers for changing pesticide fate and behaviour are thought to be changes in rainfall seasonality and intensity and increased temperatures, but the effect of climate change on pesticide fate and transport is likely to be very variable and difficult to predict. In the long-term, indirect impacts, such as land-use change driven by changes in climate, may have a more significant effect on pesticides in surface and groundwaters than the direct impacts of climate change on pesticide fate and transport. The review focuses on climate change scenarios and case studies from the UK; however, the general conclusions can be applied more widely.

Agriculture↗

A practical demonstration in modelling diclofenac and propranolol river water concentrations using a GIS hydrology model in a rural UK catchment.

An existing GIS hydrology water quality model, LF2000-WQX, was applied to predict the concentrations of the pharmaceuticals diclofenac and propranalol in catchments. As a practical exercise the predominantly rural Tamar (UK) catchment was chosen. Consumption, excretion, and fate data were used to estimate the pharmaceutical input load for the model. The predicted concentrations throughout most of the catchment were 1 ng/L or less under low flow (90th percentile) conditions. However, at a few locations, downstream of small sewage treatment plants, concentrations above 25 ng/L were predicted. This exercise shows that it is relatively straightforward to predict the concentrations of new and emerging organic microcontaminants in real catchments using existing GIS hydrology water quality models. Further testing will be required to establish their accuracy.

Computer Simulation↗

Cyclin-dependent kinase 5, Munc18a and Munc18-interacting protein 1/X11alpha protein up-regulation in Alzheimer's disease.

Besides formation of neurofibrillary tangles and neuron loss, the Alzheimer's disease brain is characterized by neuritic plaques consisting of beta-amyloid peptide deposits and impaired neurotransmission. The proteins Munc18a, Munc18-interacting protein 1 and Munc18-interacting protein 2 mediate exocytosis and decrease beta-amyloid peptide formation. Cyclin-dependent kinase 5 and its activator p35 disrupt Munc18a-syntaxin 1 binding, thereby promoting synaptic vesicle fusion during exocytosis. We investigated protein levels of the signaling pathway: p35, cyclin-dependent kinase 5, Munc18a, syntaxin 1A and 1B, Munc18-interacting protein 1 and Munc18-interacting protein 2 in Alzheimer's disease cortex and found that this pathway was up-regulated in the Alzheimer's disease parietal and occipital cortex. In the cortex of transgenic Tg2576 mice over-expressing human beta-amyloid precursor protein with the Swedish mutation known to lead to familial Alzheimer's disease, which have substantial levels of beta-amyloid peptide but lack neurofibrillary tangles and neuron loss, no alterations of protein levels were detected. These data suggest that the pathway is enhanced in dying or surviving neurons and might serve a protective role by compensating for decreased neurotransmission and decreasing beta-amyloid peptide levels early during the progression of Alzheimer's disease.

Adaptor Proteins, Signal Transducing↗

Use of CAD/CAM technology to fabricate a removable partial denture framework.

This article reports on the first patient-fitted chromium cobalt removable partial denture framework produced by computer-assisted design, computer-assisted manufacture and rapid prototype technologies. Once the dental cast was scanned, virtual surveying and design of the framework on a 3-dimensional computer model was accomplished. A rapid prototype machine was used for direct fabrication of the alloy framework. Traditional finishing techniques were applied, the framework was assessed by a clinician in a conventional manner, fitted to the patient, and judged to be satisfactory by both the patient and clinician.

Aged↗

Trial fitting of a removable partial denture framework made using computer-aided design and rapid prototyping techniques.

Previous studies of CAD/CAM-produced sacrificial patterns for removable partial denture frameworks have been documented but to date, no such restorations have been test-fitted to a patient. This paper provides details of the first trial fitting to a patient of an RPD framework, the sacrificial pattern of which was produced by CAD/CAM and RP technologies. A cast of the patient was scanned and the normal procedures of dental surveying and pattern build were undertaken with reference to the scanned model using computer-aided design. A sacrificial pattern of the design was produced by rapid prototyping technology. After spruing the pattern, investment-casting and finishing techniques were carried out according to conventional principles. The framework was successfully trial-fitted to the patient and clinically judged to be acceptable for the next stage of denture fabrication, that of adding acrylic bases and artificial teeth.

Computer-Aided Design↗

Evaporative tunnel cooling of dairy cows in the southeast. I: effect on body temperature and respiration rate.

The techniques used to mitigate the effects of heat stress on lactating dairy cows are often overwhelmed in the southeastern United States, where elevated heat and humidity often persist for extended periods. A model free-stall barn located at the North Mississippi Branch Experiment Station in Holly Springs was used to evaluate the potential of tunnel ventilation with evaporative cooling to alleviate heat stress in lactating dairy cows. Two studies were conducted using 2 groups of 10 lactating Holsteins housed in the tunnel barn (inside) and 2 groups of matched herdmates housed in an adjacent covered free-stall barn (outside), which was cooled by fans and sprinklers during 2001 or by shade and fans alone in 2003. Peak daytime temperatures inside were 5.2 +/- 0.18 degrees C below that outside in 2001 and 3.1 +/- 0.20 degrees C lower in 2003. Although evaporative cooling increased humidity by 22%, cows housed in the tunnel barn received 84% less exposure to moderate heat stress (temperature-humidity index > 80) in both years. Cooling cows with evaporative tunnel ventilation reduced respiration rates by 15.5 +/- 0.56 breaths/min and rectal temperatures by 0.6 +/- 0.02 degrees C compared with shade and fans alone in 2003. Cooling cows with evaporative tunnel ventilation reduced respiration rates by 13.1 +/- 0.78 breaths/min and rectal temperatures by 0.4 +/- 0.03 degrees C compared with fans and sprinklers in 2001. Thus, tunnel ventilation cooling dramatically reduced the exposure to heat stress and improved the comfort of lactating dairy cows when compared with traditional cooling technologies under the conditions present in the southeastern United States.

Air Conditioning↗

Evaporative tunnel cooling of dairy cows in the southeast. II: impact on lactation performance.

Heat stress has a dramatic impact on the dairy industry, reducing production and profitability throughout the southeastern United States. In many regions, management techniques can be used to mitigate the effects of heat stress, but available cooling technologies are often overwhelmed by the conditions of chronic heat stress present in southeastern United States. Although combining tunnel ventilation and evaporative cooling (evaporative tunnel cooling) seems to provide superior cooling for dairy cows, there is a dearth of reports on the impact of this technology on milk production. A model evaporative tunnel cooling facility in northern Mississippi was studied using 2 groups of 10 lactating Holstein cows housed in the tunnel barn and 2 groups of 10 matched herdmates housed in an adjacent naturally ventilated free-stall barn. Two 10-wk trials were performed in 2 yr beginning June 25, 2001, and May 26, 2003, in which cows housed outside were cooled by traditional fans and shade alone (2003) or with sprinklers (2001). In both years, the use of evaporative tunnel cooling decreased exposure to conditions of moderate heat stress by 84%. Cows cooled by evaporative tunnel ventilation increased feed intake by 12 and 11% over cows housed outside in 2001 and 2003, respectively. Evaporative tunnel cooling had no effect on milk composition, but increased milk yield over the 10-wk trial by 2.6 +/- 0.27 and 2.8 +/- 0.19 kg/cow per day in 2001 and 2003, respectively. In addition, somatic cell count was decreased 27 to 49% by evaporative tunnel cooling. Thus, under the range of environmental conditions present, evaporative tunnel cooling reliably reduced exposure to conditions of heat stress and improved milk production of lactating dairy cows during the summer season.

Air Conditioning↗

Analysis of the QUESTOR water quality model using a Fourier amplitude sensitivity test (FAST) for two UK rivers.

This paper presents the sensitivity analysis of a well-known in-stream water quality model, QUESTOR (QUality Evaluation and Simulation TOol for River systems) as applied to two rivers of contrasting land-use in the northeast of England: the 'rural' Ouse and the 'urban' Aire. The analysis employed a version of the Fourier Amplitude Sensitivity Test (FAST) that quantifies the contribution of changes in individual parameters and combination of parameters to the variance of the model output (here the Nash-Sutcliffe) in an efficient way. The quantification of the sensitivity of the model output to the parameters led to the identification of the most influential parameters. Differences between the Aire and the Ouse were found, reflecting their different water quality regime. Results highlighted the importance of interactions between two, or more, parameters on the model output. It led to question the one-at-a-time calibration method currently applied with QUESTOR and underlined the importance of including interactions between parameters in sensitivity analyses. Comparison of the relative influence of parameters versus input data showed contrasting results. In the urban system, the inputs from discharges (sewage treatment works and industrial effluents) were highly influential on model outputs and generally more important than the model parameters. For the rural river, the tributary discharges were most influential, but only at a similar or a lower level than the model parameters.

Chlorides↗

The potential steroid hormone contribution of farm animals to freshwaters, the United Kingdom as a case study.

The combined farm animal population is considerably larger than the human one in the United Kingdom, implying a possibly important contribution to the environmental load of steroid hormones entering water. To make comparisons on the amount of steroid hormones produced by the different livestock, information was gathered on the structure of the UK farm animal populations and the amount of hormones excreted by animals at each of their life stages. An individual normalised dairy cow excretes two orders of magnitude more, and a normalised pig excretes more than one order of magnitude more steroid oestrogens than a normalised human. In terms of excretion, the combined farm animal population (including sheep and poultry) probably generates around four times more oestrogens than the human population in the UK. The biggest contributor on the animal side is the relatively small dairy cow population. If steroid oestrogens behave like herbicides, in which a worst case loss to surface waters is around 1%, then it could be argued that farm animals are responsible for 15% of all the oestrogens in UK waters. When simulations were made with the MACRO pesticide leaching model, predicted concentrations for field drains failed to exceed 1 ng/L. The rapid biodegradation rates, and high sorption rates taken from the literature and used in the model suggested less than 0.001% of oestrogens would reach the field drains. This survey suggests that direct excretion of steroid hormones by animals into water courses, or discharges from farmyard drains, are likely to be more important sources of contamination rather than via normal agricultural scenarios.

Animals↗

Design and performance of a planar-array MIT system with normal sensor alignment.

In this study the performance of a planar array for magnetic induction tomography (MIT) was investigated and the results of measurements to determine the precision and sensitivity of the sensor were undertaken. A planar-array MIT system utilizing flux-linkage minimization for the primary field has been constructed and evaluated. The system comprises 4 printed excitation coils of 4 turns which were shielded, 8 surface-mount inductors of inductance 10 microH as sensor, mounted such that in principle no primary-field flux threads them, and a calibration coil to produce a strong primary field. The excitation current was multiplexed via relays to drive the excitation and reference coils. The noise values were similar in real and imaginary components in the lower frequencies and the factor to which the primary field could be reduced was greatest in the nearest coil. Methods for determining the true real and imaginary components and for flux-linkage minimization for the primary field for variations in channel sensitivities are described and the results of measurements of the system's noise and drift are given. A SNR of 47 dB was observed at 4 MHz when a 0.3 Sm-1 saline filled tank of dimensions 20 cmx20 cmx10 cm was placed centrally over the array. Finally, images were reconstructed from measurements of saline samples in a free space background, with the samples moved past the array in 21 1 cm steps to emulate mechanical scanning of the array. The image reconstruction characteristics of the planar array in conjunction with the reconstruction technique employed are discussed.

Animals↗

A comparison of sensors for minimizing the primary signal in planar-array magnetic induction tomography.

In magnetic induction tomography reducing the influence of the primary excitation field on the sensors can provide a significant improvement in SNR and/or allow the operating frequency to be reduced. For the purposes of imaging, it would be valuable if all, or a useful subset, of the detection coils could be rendered insensitive to the primary field for any excitation coil activated. Suitable schemes which have been previously suggested include the use of axial gradiometers and coil-orientation methods (Bx sensors). This paper examines the relative performance of each method through computer simulation of the sensitivity profiles produced by a single sensor, and comparison of reconstructed images produced by sensor arrays. A finite-difference model was used to determine the sensitivity profiles obtained with each type of sensor arrangement. The modelled volume was a cuboid of dimensions 50 cmx50 cmx12 cm with a uniform conductivity of 1 S m-1. The excitation coils were of 5 cm diameter and the detection coils of 5 mm diameter. The Bx sensors provided greater sensitivity than the axial gradiometers at all depths, other than on the surface layer of the volume. Images produced using a single-planar array were found to contain distortion which was reduced by the addition of a second array.

Animals↗

Measurement of the skin microcirculation through intact bandages using laser Doppler flowmetry.

The microcirculation under compression bandages has been assessed by numerous methods; however, the measurement techniques can disrupt the bandage-skin interface, affecting the measurement. In this study, a non-invasive method for measuring cutaneous blood flow using laser Doppler flowmetry (LDF) is presented. Ten volunteers had their microcirculation assessed by a laser Doppler probe being placed on their upper forearm with and without a light-transmissive gel and with a compression bandage plus light-transmissive gel. A circulatory challenge to the bandaged forearm in two of the volunteers was also undertaken. The median (95% confidence interval) perfusion (p.u.) for the skin surface was 24 (15-33) perfusion units (p.u.), and the skin plus light-transmissive gel demonstrated a higher perfusion: 66 (50-82) p.u., (p < 0.012). The addition of the compression bandage, with additional gel allowed to permeate through to the underlying skin, decreased the perfusion to 27 (20-34) p.u. (p < 0.007). In both volunteers, the microcirculatory flow responded to the vascular challenge, resulting in flow changes related to the cuff pressure (45-27 and 14-8 p.u.). This method demonstrated that it may be possible to assess the microcirculation through intact bandages, without the need to place any sensors at the skin-bandage interface.

Adult↗

A technique for fabricating patterns for removable partial denture frameworks using digitized casts and electronic surveying.

Although computer-aided design and manufacture techniques have shown some promising applications in the fabrication of crowns, inlays, and maxillofacial and oral surgery, the field of removable prosthodontics has not embraced these technologies so far. This article describes the development and investigation of computer-aided techniques that may eventually enable prosthodontic procedures such as surveying and the production of sacrificial patterns to be performed digitally. A 3-dimensional computer model of a conventional cast from a patient was obtained using an optical surface capture device (a scanner). The shape of a number of components of a removable partial denture framework was modeled on the 3-dimensional scan electronically, using computer-aided design software. A physical plastic shape of the components was produced using a Rapid Prototyping machine and used as a sacrificial pattern. Techniques to allow digital cast surveying before the production of sacrificial patterns were also developed. The results show that digital dental surveying and machine-produced sacrificial patterns can be accomplished. This article forms a basis for further developments leading to a fully integrated approach to the computer-aided design and fabrication of removable partial denture frameworks.

Computer Simulation↗

A primary field compensation scheme for planar array magnetic induction tomography.

In biomedical magnetic induction tomography (MIT), measurement precision may be improved by incorporating some form of primary field compensation/cancellation scheme. Schemes which have been described previously include gradiometric approaches and the use of 'back-off' coils. In each of these methods, however, the primary field cancellation was achieved only for a single transmitter/receiver combination. For the purpose of imaging, it would be desirable for a fully electronically scanned MIT system to provide a complete set of measurements, all with the primary field cancelled. A single channel suitable for incorporation into an MIT system with planar-array geometry is described. The transmitter is a 6-turn coil of wire 5 cm in diameter. The receiver is a surface mount inductor, of inductance 10 microH, mounted such that, in principle, no net primary field flux threads it. The results of measurements carried out with the single channel system suggest that the signal due to the primary excitation field can be reduced on average by a factor of 298 by the sensor geometry over the operating frequency range 1-10 MHz. The standard deviation and drift of the signal with the system adjusted for maximum primary field cancellation, expressed as a percentage of the signal when the receiver coil was rotated until its axis of sensitivity lay along the primary field, were 0.0009% and 0.009%, respectively. The filter time constant used was 30 ms.

Artifacts↗

Magnetic induction tomography: phase versus vector-voltmeter measurement techniques.

In magnetic induction tomography (MIT) the in-quadrature component, and hence the phase, of the received signal contains information about the conductivity of the tissue. The quality of imaging will depend on the precision with which phase can be measured. Preliminary studies suggest that a precision of 10 m degrees may be required for a practical biomedical MIT system operating at 10 MHz. This paper describes the results of measurements carried out with a 16-channel, downconverting, 10 MHz, MIT system utilizing two types of data extraction techniques: direct-phase measurement and measurement of the in-phase and in-quadrature components of the signal with a vector voltmeter. The basic precision provided by each technique was 50 m degrees, with thermal drift representing the major limiting factor. Preliminary measurements of average conductivity and permittivity for a human thigh in vivo are given.

Artifacts↗

Measuring in-stream productivity: the potential of continuous chlorophyll and dissolved oxygen monitoring for assessing the ecological status of surface waters.

Continuous (hourly) measurements of dissolved oxygen and chlorophyll (determined by fluorimetry) were made for an inter-linked lowland river and canal system. The dissolved oxygen data were used to estimate daily rates of re-aeration, photosynthesis and respiration, using a process-based analytical technique (the Delta method). In-situ fluorimeter measurements of chlorophyll were ground-truthed on a fortnightly basis using laboratory methanol extraction of chlorophyll and spectrophotometric analysis. Water samples were also analysed for algal species on a fortnightly basis. The river and canal exhibited very similar rates of photosynthesis and respiration during the summer of 2001, despite much higher chlorophyll concentrations and total algal counts, indicating that benthic algae and/or aquatic macrophytes may be making an important contribution to photosynthesis rates in the river. Suspended algal populations in the canal are dominated by planktonic species, whereas the river has a higher proportion of species which are predominantly benthic in habitat. The river exhibited higher rates of respiration, reflecting a higher organic loading from external (e.g. sewage effluent) sources.

Chlorophyll↗

Staphylococcus aureus fibronectin binding proteins A and B possess a second fibronectin binding region that may have biological relevance to bone tissues.

Staphylococcus aureus is a major human pathogen that has a propensity for targeting to bone tissues and thereby causing bone disease. A plausible hypothesis is that S. aureus targets to bone using the MSCRAMM family of surface proteins possessed by this organism. Two such proteins that have recently been shown to be important in bone infections are the S. aureus fibronectin binding proteins (FnBP) A and B. To identify fibronectin-binding domains from S. aureus that have biological relevance to bone, a phage display library of S. aureus genomic DNA was constructed and panned sequentially against immobilized fibronectin and cultured osteoblasts. Using this system, phage displaying a second fibronectin-binding region within the N-terminal part of FnBPA and FnBPB, which is distinct from the primary fibronectin-binding domain located within the D repeat region of these proteins, was isolated. Phage displaying this second region bound to both immobilized fibronectin and to osteoblasts and/or the extracellular matrix synthesized by these cells, thereby suggesting a biological relevance for these regions in S. aureus binding to bone tissues. Analysis of these binding regions for their ability to bind to other extracellular matrix proteins revealed a preference for fibronectin, with slight binding to fibrinogen and no binding to collagen or laminin.

Adhesins, Bacterial↗

Expression of the S. aureus hysA gene in S. carnosus from a modified E. coli-staphylococcal shuttle vector.

We have modified an E. coli-staphylococcal shuttle vector for use in the general cloning and expression of genes from pathogenic staphylococci in Staphylococcus carnosus. As S. carnosus is non-pathogenic, this expression system will facilitate the study of the roles of individual gene products in the disease process. To evaluate the use of this expression system, a DNA fragment containing the Staphylococcus aureus hyaluronate lyase (hysA) gene was cloned into the modified vector, pNW21, and introduced into S. carnosus. Hyaluronate lyase was both produced and secreted by S. carnosus. In addition, the secreted HysA protein was enzymatically active, as determined using a zymographic assay.

Base Sequence↗