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Biomedical subjects

Ian Walker

Publications and source records attributed to Ian Walker.

12 recordsLinked to original sources
PubMed2006

Drivers overtaking bicyclists: objective data on the effects of riding position, helmet use, vehicle type and apparent gender.

A naturalistic experiment used an instrumented bicycle to gather proximity data from overtaking motorists. The relationship between rider position and overtaking proximity was the opposite to that generally believed, such that the further the rider was from the edge of the road, the closer vehicles passed. Additionally, wearing a bicycle helmet led to traffic getting significantly closer when overtaking. Professional drivers of large vehicles were particularly likely to leave narrow safety margins. Finally, when the (male) experimenter wore a long wig, so that he appeared female from behind, drivers left more space when passing. Overall, the results demonstrate that motorists exhibit behavioural sensitivity to aspects of a bicyclist's appearance during an encounter. In the light of previous research on drivers' attitudes to bicyclists, we suggest drivers approaching a bicyclist use physical appearance to judge the specific likelihood of the rider behaving predictably and alter their overtaking accordingly. However, the extent to which a bicyclist's moment-to-moment behaviour can be inferred from their appearance is questionable, and so the tendency for drivers to alter their passing proximity based on this appearance probably has implications for accident probability.

Accidents, Traffic↗
PubMed2006

Use of click chemistry to define the substrate specificity of Leishmania beta-1,2-mannosyltransferases.

Leishmania spp. are human pathogens that utilize a novel beta-1,2-mannan as their major carbohydrate reserve material. We describe a new approach that combines traditional substrate-modification methods and "click chemistry" to assemble a library of modified substrates that were used to qualitatively define the substrate tolerance of the Leishmania beta-1,2-mannosyltransferases responsible for beta-1,2-mannan biosynthesis. The library was assembled by using the highly selective copper(I)-catalysed cycloaddition reaction of azides and alkynes to couple an assortment of azide- and alkyne-functionalized small molecules with complementary alkyne- and azide-functionalized mannose derivatives. All mannose derivatives with alpha-orientated substituents on the anomeric carbon were found to act as substrates when incubated with a Leishmania mexicana particulate fraction containing GDP-mannose. In contrast, 6-substituted mannose derivatives were not substrates. Representative products formed from the library compounds were analysed by mass spectrometry, methylation linkage analysis and beta-mannosidase digestions and showed extension with up to four beta-1,2-linked mannosyl residues. This work provides insights into the substrate specificity of this new class of glycosyltransferases that can be applied to the development of highly specific tools and inhibitors for their study.

Alkynes↗
PubMed2005

Signals are informative but slow down responses when drivers meet bicyclists at road junctions.

Three experiments used a laboratory analogue to the task of driving to look at drivers' responses to encounters with a bicyclist at a T-junction. In particular, a comparison was made between the bicyclist indicating an upcoming turn with an arm signal, an informal signal of intent, or no signal. Overall, arm signals worked relatively well to inform drivers of the bicyclist's intentions and were easier to perceive than informal signals. It was also found that simple failures to react to the bicyclist in time were more common at shorter thinking times whereas incorrect positive responses were unaffected by thinking time. Most interestingly, these experiments showed that arm signals often slowed down the participants' decision-making processes, leading to a lower probability of their stopping in time when the bicyclist was at risk. Moreover, the same was true for informal signals in which there was eye-contact between the bicyclist and the participant. It is suggested that these effects come about because both arm signals and eye-contact are communicative acts and therefore invoke extra stages of involuntary cognitive processing in the drivers, thereby slowing their reactions.

Adult↗
PubMed2005

Exploring function estimators as an alternative to regression in psychology.

Most forms of regression analysis make assumptions about the relationships between the variables being modeled. As a consequence, it can be difficult to know which form of analysis is most appropriate for a given data set. In this article, we explore the idea that function estimators might provide a better alternative in many situations. Function estimators discover the best function to link dependent and independent variables, no matter what form this takes. Four studies demonstrate that one type of function estimator (a neural network) not only performs the same tasks as linear regression and nonlinear regression, but often performs these tasks better and with more flexibility. Moreover, neural networks allow a useful secondary analysis in which useful groups of people can be identified. We recommend that function estimators be used in preference to regression-based techniques for many analyses. The Matlab script used to write this article may be downloaded from www.psychonomic.org/archive/.

Adolescent↗
PubMed2004

A comparative analysis of phenothiazinium salts for the photosensitisation of murine fibrosarcoma (RIF-1) cells in vitro.

Photodynamic therapy (PDT) is a treatment combining a photosensitiser, molecular oxygen and visible light of characteristic wavelength to produce cytotoxic reactive oxygen species (ROS). Within our centre, a series of phenothiazinium salts were synthesised and initial characterisation studies performed to determine any potential use for PDT. All photosensitisers within the series were shown to have useful spectral properties for PDT, with absorbance lambdamax above 667 nm. The Log P values of the compounds were shown to range from -0.9 to > +2.0. Furthermore, Log P values were shown to be important in determining the site of subcellular localisation and as such the site of photooxidative damage. Derivatives with a Log P value of greater than +1.0 were shown to initially localise to the lysosomes then relocalise throughout the cytoplasm following illumination, whereas compounds with intermediate Log P values (-0.7 to +1.0) all remained lysosomal. Only methylene blue (Log P-0.9) was shown to redistribute to the nucleus upon illumination. Following treatment of RIF-1 cells with each phenothiazinium salt for 1 h and subsequent exposure to 665 nm laser light at a fluence rate of 10 mW cm(-2)(18 J cm(-2)), it was determined that the most potent photosensitiser was 260-fold more potent than methylene blue. Furthermore, the PDT efficacy of the photosensitisers was shown to be related to the level of mitochondrial damage induced directly following illumination.

Animals↗
PubMed2004

The present and future role of photodynamic therapy in cancer treatment.

It is more than 25 years since photodynamic therapy (PDT) was proposed as a useful tool in oncology, but the approach is only now being used more widely in the clinic. The understanding of the biology of PDT has advanced, and efficient, convenient, and inexpensive systems of light delivery are now available. Results from well-controlled, randomised phase III trials are also becoming available, especially for treatment of non-melanoma skin cancer and Barrett's oesophagus, and improved photosensitising drugs are in development. PDT has several potential advantages over surgery and radiotherapy: it is comparatively non-invasive, it can be targeted accurately, repeated doses can be given without the total-dose limitations associated with radiotherapy, and the healing process results in little or no scarring. PDT can usually be done in an outpatient or day-case setting, is convenient for the patient, and has no side-effects. Two photosensitising drugs, porfirmer sodium and temoporfin, have now been approved for systemic administration, and aminolevulinic acid and methyl aminolevulinate have been approved for topical use. Here, we review current use of PDT in oncology and look at its future potential as more selective photosensitising drugs become available.

Clinical Trials, Phase III as Topic↗
PubMed2004

Clinical outcome in a series of cases of obstetric cholestasis identified via a patient support group.

OBJECTIVE: To explore the clinical features of obstetric cholestasis pregnancies in UK white Caucasians. DESIGN: A questionnaire survey. SETTING: Study coordinated at Queen Charlotte's Hospital. POPULATION: Clinical features of 352 affected pregnancies in 227 Caucasian women identified via a patient support group. METHODS: Evaluation of the gestation at which prematurity and intrauterine death occur, and recording of additional clinical features in pregnancies complicated by obstetric cholestasis. MAIN OUTCOME MEASURES: The timing of pregnancies complicated by intrauterine death and prematurity. RESULTS: Among the affected pregnancies, 23 (7%) were complicated by intrauterine death (20 singletons and 3 twins) and 133 (38%) were delivered prematurely (56 spontaneous and 77 iatrogenic). Eighteen of the 20 singleton intrauterine deaths occurred after 37 weeks. All three intrauterine deaths in twin pregnancies occurred before 37 weeks. Pruritus started earlier in pregnancies complicated by spontaneous prematurity, but not in those complicated by intrauterine death. CONCLUSIONS: Intrauterine death in singleton pregnancies complicated by obstetric cholestasis death mainly occurs after 37 weeks. The gestation at which pruritus is first reported may help to predict spontaneous prematurity.

Cholestasis↗
PubMed2003

A connectionist implementation of the theory of planned behavior: association of beliefs with exercise intention.

The theory of planned behavior suggests attitudes are a product of salient beliefs. This study examined whether aggregating salient beliefs was plausible within a more biologically centered information-processing environment. A neural network was used to examine associations among beliefs relating to exercise intention. Data on intentions and behavioral, normative, and control beliefs from 114 respondents were used to train (by error backpropagation) a neural network to associate beliefs with intention. The R-sup-2 between the network's estimated and self-reported intention was.66. The network's representation comprised 6 belief profiles associated with high, moderate, or low behavioral intention. The neural network accommodated complex relationships among beliefs and belief-intention associations and indicated how high-level constructs such as attitudes may be viewed as the best fit (compromise state) between aroused beliefs.

Adult↗
PubMed2002

Development of variable-number tandem repeat typing of Mycobacterium bovis: comparison of results with those obtained by using existing exact tandem repeats and spoligotyping.

Various genetic markers have been exploited for fingerprinting the Mycobacterium tuberculosis complex (MTBC) in molecular epidemiological studies, mainly through identifying restriction fragment length polymorphisms (RFLP). In large-scale studies, RFLP typing has practical processing and analysis limitations; therefore, attempts have been made to move towards PCR-based typing techniques. Spoligotyping (spacer oligotyping) and, more recently, variable-number tandem repeat (VNTR) typing have provided PCR-derived typing techniques. This study describes the identification and characterization of novel VNTR loci, consisting of tandem repeats in the size range of 53 to 59 bp in the MTBC, and their assessment as typing tools in 47 Mycobacterium bovis field isolates and nine MTBC strains. Spoligotyping and the previously described set of exact tandem repeats (ETRs) (R. Frothingham and W. A. Meeker-O'Connell, Microbiology 144:1189-1196, 1998) were also applied to the same panel of isolates. The allelic diversity of the individual VNTR loci was calculated, and a comparison of the novel VNTRs was made against the results obtained by spoligotyping and the existing set of ETRs. Eleven unique spoligotypes were discriminated in the panel of 47 M. bovis isolates. Greater resolution was obtained through the combination of the most-discriminating VNTRs from both sets. Considerable discrimination was achieved, with the 47 M. bovis isolates resolved into 14 unique profiles, while all nine MTBC isolates were uniquely differentiated. The novel VNTR markers described increased the discrimination possible in strain typing of M. bovis, with the added benefit of an intuitive digital nomenclature, with the allele copy number of the individual VNTRs providing a profile. VNTR typing was shown to be a valuable technique with great potential for further development and application to epidemiological tracing of tuberculosis transmissions.

Alleles↗
PubMed2002

The differential effectiveness of psychosocial and biogenetic causal explanations in reducing negative attitudes toward "mental illness".

Given the apparent failure of the "mental illness is an illness like any other" approach to reducing negative stereotypes of people with mental health problems, the differential effects of biogenetic and psychosocial explanations of psychiatric symptoms were evaluated. Attitude measures were administered to young New Zealand adults before and after a video portraying a young man with psychotic symptoms followed by either biogenetic or psychosocial explanations. Consistent with previous studies, the "medical model" approach significantly increased perceptions of dangerousness and unpredictability. Following the psychosocial explanation there was a slight but statistically insignificant improvement in attitudes. Participants who knew users of psychiatric services, or who had used services themselves, had more positive attitudes than other participants. It is recommended that destigmatization programs minimize efforts to persuade the public that mental health problems are biogenetic illnesses, and focus instead on increasing exposure to users of mental health services. Further research is required to determine whether such exposure should include life histories, so as to highlight the psychosocial causes of mental health problems.

Adult↗