Showing papers by "Newcastle University published in 1991"
TL;DR: The integration of multi-criteria evaluation techniques with GIS is forwarded as providing the user with the means to evaluate various alternatives on the basis of multiple and conflicting criteria and objectives.
Abstract: Geographical information systems (GIS) provide the decision-maker with a powerful set of tools for the manipulation and analysis of spatial information. The functionality of GIS is, however, limited to certain deterministic analyses in key application areas such as spatial search. The integration of multi-criteria evaluation (MCE) techniques with GIS is forwarded as providing the user with the means to evaluate various alternatives on the basis of multiple and conflicting criteria and objectives. An example application based on the search for suitable sites for the disposal of radioactive waste in the UK using the Arc/Info GIS is included. The potential use of a combined GIS-MCE approach in the development of spatial decision support systems is considered.
1,023 citations
TL;DR: The main intention of the paper is to describe and illustrate a new technique for the identification of small clusters of disease, and discuss some common pitfalls in the application of tests of clustering to epidemiological data.
Abstract: SUMMARY Tests for clustering of rare diseases investigate whether an observed pattern of cases in one or more geographical regions could reasonably have arisen by chance alone, bearing in mind the variation in background population density. In contrast, tests for the detection of clusters are concerned with screening a large region for evidence of individual 'hot spots' of disease but without any preconception about their likely locations; the results of such tests may form the basis for subsequent small area investigations, statistical or non-statistical, but will rarely be an end in themselves. The main intention of the paper is to describe and illustrate a new technique for the identification of small clusters of disease. A secondary purpose is to discuss some common pitfalls in the application of tests of clustering to epidemiological data.
629 citations
TL;DR: In this article, a simple algorithm to solve the GLS problem subject to inequality constraints is presented and its convergence is proven and expressions are derived for the variances and covariances of the fitted values both without active constraints.
Abstract: The Generalised Least Squares (GLS) approach to the estimation of Origin-Destination (OD) matrices permits the combination of survey and traffic count data in a way that allows for the relative accuracy of the two data sources. However, the procedure may result in estimates that infringe non-negativity or other constraints on the fitted values. A simple algorithm to solve the GLS problem subject to inequality constraints is presented and its convergence is proven. Expressions are derived for the variances and covariances of the fitted values both without active constraints. It is demonstrated that the imposition of inequality constraints can improve the accuracy of those fitted values directly and indirectly affected them, by reducing their sensitivity to error in the inputs.
314 citations
TL;DR: It is shown that nm23 expression in human breast cancer was associated with good prognosis and a lack of lymph node metastasis and suggests that the nm23 gene product may play an important role in suppressing the metastatic phenotype.
Abstract: The nm23 gene was identified in murine melanoma cells, in which its expression is associated with the cells' metastatic potential. Expression of nm23 has been detected in human breast tumors by means of hybridization and immunocytochemistry. We measured nm23 mRNA in 71 patients with primary breast cancer and found variable levels of nm23 expression. The nm23 gene was expressed at higher levels in well-differentiated tumors (P less than .02). There was a significant inverse relationship between nm23 expression and nodal status (P less than .02). Expression of nm23 was positively associated with longer disease-free survival and overall survival, and the relationships were significant (P less than .002 and P less than .003, respectively). This study showed that nm23 expression in human breast cancer was associated with good prognosis and a lack of lymph node metastasis and suggests that the nm23 gene product may play an important role in suppressing the metastatic phenotype.
295 citations
TL;DR: The present findings could be particularly significant in view of recent suggestions that pheomelanin, rather than protecting the skin against UV radiation, may actually contribute to UV-induced skin damage.
284 citations
TL;DR: The background to the concept of the term “molten globule” as a description of intermediates observed in the folding of globular proteins is discussed, highlighting the temporal relationship between general collapse of the polypeptide chain and the formation of secondary structure.
Abstract: The background to the concept of the term “molten globule” as a description of intermediates observed in the folding of globular proteins is discussed. These compact intermediates are characterised by certain properties including the presence of secondary structure and considerable conformational mobility compared to the native, functional state. Those intermediates that are thermodynamically stable under mild denaturing conditions have many features in common with the transient intermediates that accumulate significantly during the process of folding. Attention is drawn to cases where the two types are however distinguished on grounds of their Stokes radius, in which cases there is currently no direct evidence for the involvement of the stable intermediates on the folding pathway. Experimental evidence relating to the early stages in folding is reviewed and compared, highlighting the temporal relationship between general collapse of the polypeptide chain and the formation of secondary structure. The continued use of the term “molten globule” is recommended where the minimum essential structural criteria for this state are met.
270 citations
TL;DR: Patients with a relapsing encephalopathy in association with Hashimoto's disease and high titers of anti-thyroid antibodies should be recognized as a definite neurologic entity and added to the list of CNS complications of thyroid disease.
Abstract: We describe 5 patients with a relapsing encephalopathy in association with Hashimoto's disease and high titers of anti-thyroid antibodies. The presentation is usually with a subacute onset of confusion, alteration in conscious level, and focal or generalized seizures. The relapsing course, association with myoclonus or tremulousness, and episodes of stroke-like deterioration are characteristic features. The long-term prognosis is favorable with steroid therapy, though additional immunosuppressive therapy may be required. Neurologic investigation typically shows a diffusely abnormal EEG, high CSF protein level without pleocytosis, and normal brain CT and cerebral angiogram. Isotope brain scan may show patchy abnormal uptake. Hashimoto's encephalopathy should be recognized as a definite neurologic entity and added to the list of CNS complications of thyroid disease.
267 citations
261 citations
TL;DR: In this article, the mitochondrial respiratory chain function in skeletal muscle from patients with Parkinson's disease was studied and the results showed low activity in all complexes studied (I, II and IV).
226 citations
TL;DR: In this paper, the authors present a rigorous defence of paradigm incommensurability as con ceptualized by Burrell and Morgan, arguing that it is a necessary defence against scientistic authoritarianism.
Abstract: This paper presents a rigorous defence of paradigm incommensurability as con ceptualized by Burrell and Morgan, arguing that it is a necessary defence against scientistic authoritarianism. Two recent attacks on paradigm incommensurability are examined which, although emerging from different intellectual traditions, are both seen to imply the restoration of the authority of scientism characteristic of the postmodernism of reaction. Both critiques base their attack on the work of Kuhn but this basis is rejected on the grounds, inter alia, of a clear absence of isomorphism between the paradigmatic model of Kuhn and that of Burrell and Morgan. Finally, the paper considers the relevance of paradigm incommensur ability in the context of non-reactive postmodernism.
215 citations
TL;DR: The objective is to assess their capacity to analyse the detail of agency relationships in the negotiation of development projects, while at the same time offering ways of generalizing about the significance of actors and events in the development process under different conditions.
Abstract: Summary This paper reviews models of the development process. The objective is to assess their capacity to analyse the detail of agency relationships in the negotiation of development projects, while at the same time offering ways of generalizing about the significance of actors and events in the development process under different conditions. The models reviewed are grouped into four types: equilibrium models, event sequence models, agency models and structural models. Each makes a contribution to the objective set out, but none fully addresses the range of possible forms and dynamics which the development process may make. An alternative model is developed in a subsequent paper.
Book•
29 Mar 1991TL;DR: In this article, the surface Vorticity Boundary Integral Method of Fluid Flow Analysis (SVBILIM) is used for surface singularity modeling and vortex cloud analysis.
Abstract: Part I. The Surface Vorticity Boundary Integral Method of Fluid Flow Analysis: 1. The basis of surface singularity modelling 2. Lifting bodies, two-dimensional aerofoils and cascades 3. Mixed-flow and radial cascades 4. Bodies of revolution, ducts and annuli 5. Ducted propellers and fans 6. Three-dimensional and meridional flows in turbo-machines 7. Free vorticity shear layers and inverse methods Part II. Vortex Dynamics and Vortex Cloud Analysis: 8. Vortex dynamics in inviscid flows 9. Simulation of viscous diffusion in discrete vortex modelling 10. Vortex cloud modelling by the boundary integral method 11. Further development and applications of vortex cloud modelling to lifting bodies and cascades 12. Use of grid systems in vortex dynamics and meridional flows Appendix.
28 Sep 1991
TL;DR: In this paper, a comprehensive approach to the control of synchronous reluctance machines (SYNCRELs) based on the machine's ideal model is presented. But the effects of saturation and iron losses are briefly considered.
Abstract: This work develops a comprehensive approach to the control of inverter-fed synchronous reluctance machines (SYNCREL), based on the machine's ideal model. From the theory a control simulation is designed. Simulation and experimental results are presented. The effects of saturation and iron losses are briefly considered. >
TL;DR: Direct viable counts and culturable counts decreased at a similar rate in seawater and in freshwater in visible light and the presence of humic acids significantly reduced loss of culturability but only in low salinity conditions.
Abstract: Escherichia coli and some salmonellas were exposed in seawater and freshwater to natural sunlight, visible light of comparable intensity, and light containing a similar proportion of u.v. as natural sunlight but of a much lower intensity. Direct viable bacterial counts and culturable counts on selective and non-selective media were made at intervals. The rate of decrease in numbers of culturable bacteria was significantly faster in seawater than in freshwater when exposed to natural sunlight. No significant difference was found between the rates of decrease in numbers of culturable bacteria in seawater and those in freshwater when bacteria were exposed to light with a small u.v. component of similar intensity. The effect of salinity no loss of culturability is, therefore, more significant in the presence of u.v. radiation. Direct counts by the acridine orange direct viable count method decreased much more slowly than the culturable counts in seawater but comparably with culturable counts in freshwater in natural sunlight. Direct viable counts and culturable counts decreased at a similar rate in seawater and in freshwater in visible light. This may signify the evolution of enteric bacteria towards a viable but non-culturable form in seawater when exposed to natural sunlight. The presence of humic acids significantly reduced loss of culturability but only in low salinity conditions. Salinity appears to be an important factor influencing culturability in bacteria exposed to sunlight.
TL;DR: The Global Positioning System has been used to measure the relative displacements of fifteen monuments in a hundred-year-old triangulation network spanning part of the Aegean extensional basin this article.
Abstract: The Global Positioning System has been used to measure the relative displacements of fifteen monuments in a hundred-year-old triangulation network spanning part of the Aegean extensional basin. These displacements reflect the tectonic deformation of the region over the past century, showing more than one metre of north-south extension across the network. The crust in this region appears to contain a few slowly deforming blocks separated by more rapidly deforming zones.
TL;DR: Although a remarkable lack of correlation between patient, stimulator and outcome variables was found to exist, the analysis revealed much information of importance: 47% of patients found TENS reduced their pain by more than half; TENS analgesia was rapid both in onset and offset.
Abstract: This in-depth study examines the relationships between patient, stimulator and outcome variables in a large number of chronic pain patients utilising TENS on a long-term basis. 179 patients completed a TENS questionnaire designed to record age, sex, cause and site of pain and TENS treatment regime. Of these 179 patients, 107 attended our research unit for assessment of the electrical characteristics of TENS during self-administered treatment. Although a remarkable lack of correlation between patient, stimulator and outcome variables was found to exist, the analysis revealed much information of importance: 47% of patients found TENS reduced their pain by more than half; TENS analgesia was rapid both in onset (less than 0.5 h in 75% patients) and in offset (less than 0.5 h in 51% patients); one-third of patients utilised TENS for over 61 h/week; pulse frequencies between 1 and 70 Hz were utilised by 75% of patients; 44% of patients benefitted from burst mode stimulation. The clinical implications of these findings are discussed.
TL;DR: It is concluded that attention to plaque control and the removal of local irritants is of some benefit for the gingival health of cyclosporin-treated adult renal transplant patients, but these measures alone did not preventGingival overgrowth.
Abstract: The efficacy of plaque control as a means of preventing cyclosporin-induced gingival overgrowth was assessed in 27 adult renal transplant patients. After baseline examination, patients were randomly allocated to receive intensive oral hygiene instructions, scaling and root planing (OH group) or no treatment (no treatment group). Gingival condition was assessed 6 months after baseline and changes in gingival form were related to various periodontal and pharmacokinetic measures. In both treatment groups, there was a significant increase (P less than 0.05) in gingival hyperplasia scores at 6 months. In the OH group, plaque scores were significantly lower (P less than 0.05) at 6 months, whereas in the no treatment group, a significant increase in plaque scores, gingival inflammation and probing depths was observed at 6 months. Dosages of cyclosporin, whole blood concentrations of cyclosporin, baseline gingival index, hyperplasia scores, and 6-month plaque index were not important determinants for the increase in gingival over-growth in both treatment groups. It is concluded that attention to plaque control and the removal of local irritants is of some benefit for the gingival health of cyclosporin-treated adult renal transplant patients, but these measures alone did not prevent gingival overgrowth. Pharmacokinetic variables of cyclosporin and various periodontal measures were not good predictors of cyclosporin-induced gingival changes.
TL;DR: The data suggest p53 protein expression may be a marker of more aggressive carcinomas but that the prognostic power of expression is likely to be weak and unlikely, therefore, to be of clinical value.
Abstract: In a study of 90 breast cancer patients, tumour p53 protein expression was determined by immunohistochemistry using the monoclonal antibody PAb1801. Patient lymph node status and Bloom's grade were determined, and both oestrogen and progesterone status assessed, also by immunohistochemistry. Lymph node status, tumour grade, and progesterone receptor status all had a significant influence on survival. Patients with p53-positive tumours showed poorer survival but this did not achieve significance. p53 protein expression showed a significant relationship to high tumour grade and a weak correlation with negative oestrogen receptor status. The data suggest taht p53 protein expression may be a marker of more aggressive carcinomas but that the prognostic power of expression is likely to be weak and unlikely, therefore, to be of clinical value. The results do not resolve whether detectable p53 protein expression represents a random product of dedifferentiation, or an important feature of the malignant phenotype, playing a key role in tumour behaviour. The number of patients in our study is small, however, and investigation of a larger series is clearly indicated.
TL;DR: In this paper, the authors consider the manner in which people's altruistic concern for other people's safety should be incorporated in willingness-to-pay based values of statistical life and safety.
Abstract: This article considers the manner in which people's altruistic concern for other people's safety should be incorporated in willingness-to-pay based values of statistical life and safety. It is shown that, within a utilitarian framework, the traditional prescription that such values should take full account of people's willingness to pay for others' safety is validif andonly if altruism is exclusivelysafety-focused, in the sense that whilei is concerned forj's safety, he is quite indifferent to other determinants ofj's utility.
TL;DR: The cumulative birth incidence of Becker muscular dystrophy was about one third that of Duchenne muscular dystrophin immunolabelling, suggesting that the disorder is more common than previously thought.
TL;DR: Simulation results for data containing geometrically distributed travel times suggests that fitting the correctly specified model produces better estimates of the turning proportions than does the conventional approach where travel times are restricted to a fixed number of time intervals.
Abstract: A number of procedures for the estimation in real time of origin-destination flows in junctions or small networks are reviewed. These are based on the assumption that the time taken by vehicles to traverse the junction or network is either small in relation to the chosen time interval or equal to some fixed number of time intervals. In reality, there will be a distribution of travel times that may span a number of time intervals. This paper proposes two ways to allow for this in the estimation of origin-destination flows. The first, appropriate if travel times are approximately geometrically distributed, makes use of the recurrence model of platoon dispersion. The second makes no assumption about the form of the distribution of travel times, but in general requires the estimation of substantially more parameters. Simulation results for data containing geometrically distributed travel times suggests that fitting the correctly specified model produces better estimates of the turning proportions than does the conventional approach where travel times are restricted to a fixed number of time intervals.
TL;DR: More work is needed to improve pre-pregnancy assessment criteria, to understand the mechanisms of gestational renal dysfunction and proteinuria, to assess the side effects and implications of immunosuppression in pregnancy, and to elucidate the remote effects of pregnancy on both renal prognosis and the offspring.
TL;DR: Quantitative data suggest that although extrapyramidal symptoms relate to striatal levels of dopamine, cognitive impairment is most closely associated with cholinergic (but not monoaminergic) deficits in temporal and archicortical areas.
Abstract: Cholinergic and monoaminergic (dopaminergic and serotonergic) activities have been examined in postmortem brain tissue in senile dementia of Lewy body type, Parkinson's disease, and Alzheimer's disease. Quantitative data suggest that although extrapyramidal symptoms relate to striatal levels of dopamine, cognitive impairment is most closely associated with cholinergic (but not monoaminergic) deficits in temporal and archicortical areas. Hallucinations, which are most frequent in Lewy body dementia, appear to be related to an extensive cholinergic deficit in temporal neocortex and the resulting imbalance between decreased cholinergic and relatively preserved serotonergic activities. Topographic analyses such as these including consideration of quantitative "threshold" effects, may be relevant to the future anatomic focus of neurochemical investigations in dementia and to the development of appropriate experimental models.
Journal Article•
TL;DR: There was a significant correlation of intracellular dUTP levels with the level of DNA strand breaks, which strongly suggests that growth inhibition following thymidylate synthase inhibition is mediated through an increase in intrACEllular d UTP, leading to uracil misincorporation into DNA, its subsequent excision, and resultant strand breakage.
Abstract: The thymidylate synthase inhibitor N 10-propargyl-5,8-dideazafolic acid (CB3717) inhibits the growth of human lung carcinoma A549 cells. The cytotoxicity of CB3717 is potentiated by the nucleoside transport inhibitor dipyridamole (DP), which not only inhibits the uptake and therefore salvage of thymidine but also inhibits the efflux of deoxyuridine, thereby enhancing the intracellular accumulation of deoxyuridine nucleotides. Measurement of intracellular deoxyuridine triphosphate (dUTP) pools, by sensitive radioimmunoassay, demonstrated a large increase in response to CB3717, in a dose- and time-related manner, and this accumulation was enhanced by coincubation with DP. In untreated cells and those treated with DP alone, dUTP was close to or below the limit of detection of the assay. In cells treated for 24 h with 3 µm CB3717 (concentration producing 50% growth inhibition) the intracellular dUTP was 46.1 ± 9.6 (SEM) pmol/106 cells and after 24 h exposure to 30 µm CB3717, 337.5 ± 37.9 pmol dUTP/106 cells was detected. There was significant enhancement by DP of the accumulation of dUTP in cells treated with CB3717; coincubation of cells with 1 µm DP + 3 µm CB3717 for 24 h resulted in intracellular dUTP levels of 174.7 ± 57.7 pmol/106 cells. Accumulation of DNA strand breaks, measured by alkaline elution, also increased in response to CB3717 concentration and exposure period. Newly synthesized (nascent) DNA was more sensitive to damage by CB3717 than was mature DNA. As with the accumulation of dUTP, coincubation with DP also enhanced the accumulation of strand breaks, whereas DP alone had little or no effect on DNA fragmentation.
When data for cells treated with CB3717 alone and CB3717 in combination with DP were combined, there was a significant correlation of intracellular dUTP levels with the level of DNA strand breaks. This strongly suggests that growth inhibition following thymidylate synthase inhibition is mediated through an increase in intracellular dUTP, leading to uracil misincorporation into DNA, its subsequent excision, and resultant strand breakage.
TL;DR: Compared ADH2, ADH3 and ALDH2 allele frequencies in patients with alcohol‐related cirrhosis and chronic pancreatitis are compared with 79 local healthy control subjects to study genetically determined differences in ethanol metabolism.
TL;DR: C‐peptide and insulin secretion rates after a 75‐gm oral glucose load and during a 10 mmol/L hyperglycemic clamp are derived and cirrhotic patients were confirmed as insulin‐insensitive during a euglycemic clamp.
TL;DR: It was found that the sensitivity of the pure cultures was similar to that of the methanogens in the sludge, and the numbers of methanogenic bacteria were affected by the presence of propionate even at concentrations as low as 20 or 30 mM.
Abstract: The effect of propionate toxicity at different pH values (6.5, 7.0, and 8.0) on methanogen-enriched sludge. Methanobrevibacter smithii, and Methanospirillum hungatii was studied. Organisms were grown in Balch medium 3 in Hungate tubes, and toxicity was characterized by a decrease in production of methane and in bacterial numbers. Propionate inhibited bacterial growth and cumulative methane production at concentrations as low as 20 mM. In the absence of propionate, the methanogen-enriched sludge and M. smithii showed better cumulative methane production at pH 6.5 and 7.0 than at pH 8.0. However, in the presence of propionate, these organisms showed better cumulative methane production at pH 8.0. M. hungatii differed in its behavior; the best values of cumulative methane production for this organism occurred at pH 7.0. Bacterial numbers reflected the microbial response to the presence of propionate. The highest counts of methanogenic bacteria were observed at pH 6.5 and 8.0. The numbers of methanogens were affected by the presence of propionate even at concentrations as low as 20 or 30 mM; at propionate concentrations above 80 mM, the methanogen count was affected by at least 2 orders of magnitude. Upon comparison of the responses of the pure cultures and the methanogen-enriched sludge to increasing propionate concentrations, it was found that the sensitivity of the pure cultures was similar to that of the methanogens in the sludge.
TL;DR: In this article, the authors present a different representation of the geometry of the gravitational field, one in which the paths of test bodies play a crucial role, and give a new version of the construction of a bundle and connection from holonomy data.
Abstract: This article is about a different representation of the geometry of the gravitational field, one in which the paths of test bodies play a crucial role. The primary concept is the geometry of the motion of a test body, and the relation between different such possible motions. Space-time as a Lorentzian manifold is regarded as a secondary construct, and it is shown how to construct it from the primary data. Some technical problems remain. Yang-Mills fields are defined by their holonomy in an analogous construction. I detail the development of this idea in the literature, and give a new version of the construction of a bundle and connection from holonomy data. The field equations of general relativity are discussed briefly in this context.
TL;DR: The data support previous studies which demonstrate increased serum concentrations of TBARS in subjects with macrovascular disease but suggest that levels are similarly elevated in diabetic and non‐diabetic subjects.
Abstract: Lipid peroxides are thought to be formed by free radicals and may play an important role in the development of atheromatous vascular disease. We have investigated the relationship between lipids, lipoproteins, coagulation factors, and lipid peroxides (measured as thiobarbituric acid reacting species (TBARS)) in Type 2 diabetic patients with macrovascular disease. Eighteen diabetic and 20 non-diabetic subjects with clinical evidence of ischaemic heart disease and/or peripheral vascular disease were investigated, together with 28 healthy subjects without evidence of vascular disease. TBARS concentrations in non-diabetic (mean 5.0 (95% CI 4.5–5.7) μmol I−1) and diabetic groups (5.6 (5.1–6.0) μmol I−1) with macrovascular disease were not significantly different although values were higher in both groups of patients with vascular disease by comparison with control subjects (2.7 (2.4–3.1) (μmol I−1, p < 0.001). Significant univariate correlations between TBARS concentrations and measures of blood glucose control (fructosamine, blood glucose and HbA,) were found for all 66 subjects (r = 0.35–0.42, p < 0.01–p < 0.001), although no independent association between these parameters and TBARS was demonstrated in multiple regression analysis. In addition, TBARS levels were significantly correlated in univariate analysis with the apolipoprotein (apo) Al:apoB ratio (r = −0.56, p< 0.001), total cholesterol:high density lipoprotein cholesterol ratio (r = 0.52, p < 0.001), apoB (r = 0.51, p < 0.001), low density lipoprotein cholesterol (r = 0.40, p < 0.001), serum total triglyceride (r = 0.46, p < 0.001), apoAl (r = −0.35, p < 0.01) and serum total cholesterol (r = 0.39, p < 0.001). Multiple regression analysis of continuous variables showed that apoB (p < 0.001), age (p < 0.001), and apoAl (p = 0.008) were independently associated with serum TBARS although these associations disappeared if macrovascular disease was added to the regression equation as a categorical variable. Our data support previous studies which demonstrate increased serum concentrations of TBARS in subjects with macrovascular disease but suggest that levels are similarly elevated in diabetic and non-diabetic subjects.
Journal Article•
TL;DR: ADRP is an extremely heterogeneous disorder which can result from a range of defects in rhodopsin and which can have a locus or loci elsewhere in the genome.
Abstract: Autosomal dominant retinitis pigmentosa (ADRP) has recently been linked to locus D3S47 (probe C17), with no recombination, in a single large Irish family. Other ADRP pedigrees have shown linkage at zero recombination, linkage with recombination, and no linkage, demonstrating genetic heterogeneity. The gene encoding rhodopsin, the rod photoreceptor pigment, is closely linked to locus D3S47 on chromosome 3q. A point mutation changing a conserved proline to histidine in the 23d codon of the gene has been demonstrated in affected members of one ADRP family and in 17 of 148 unrelated ADRP patients. We have sequenced the rhodopsin gene in a C17-linked ADRP family and have identified in the 4th exon and in-frame 3-bp deletion which deletes one of the two isoleucine monomers at codons 255 and 256. This mutation was not found in 30 other unrelated ADRP families. The deletion has arisen in the sequence TCATCATCAT, deleting one of a run of three x 3-bp repeats. The mechanism by which this occurred may be similar to that which creates length variation in so-called mini- and microsatellites. Thus ADRP is an extremely heterogeneous disorder which can result from a range of defects in rhodopsin and which can have a locus or loci elsewhere in the genome.