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The susceptibility to develop coeliac disease (CD) has a strong genetic component, which is not entirely explained by HLA associations. Two previous genome wide linkage studies have been performed to identify additional loci outside this region. These studies both used a sib-pair design and produced conflicting results. Our aim is to identify non-MHC genetic loci contributing to coeliac disease using a family based linkage study. We performed a genome wide search in 16 highly informative multiply affected pedigrees using 400 microsatellite markers with an average spacing of 10 cM. Linkage analysis was performed using lod score and model free methods. We identified two new potential susceptibility loci with lod scores of 1.9, at 10q23.1, and 16q23.3. Significant, but lower lod scores were found for 6q14 (1.2), 11p11 (1.5), and 19q13.4 (0.9), areas implicated in a previous genome wide study. Lod scores of 0.9 were obtained for both D78507, which lies 1 cM from the gammaT-cell receptor gene, and for D2S364, which lies 12 cM from the CTLA4 gene.

This paper describes Shell U.K. Exploration and Production's (Shell Expro) approach to managing safety critical activities when bringing onshore underbalanced drilling techniques into an offshore North Sea environment. Prior to 1996 underbalanced drilling (UBD), including low or reduced head had never been carried out, offshore, in the North Sea. However, sound economic justification provided the impetus to introduce this technique and associated technology. There were many significant safety challenges that had to be addressed to demonstrate that the risks were within the limits of tolerability and as low as is reasonably practical (ALARP). The primary HS&E concerns related to: loss of containment (continuous pressure at surface), competence of personnel (UBD differs from conventional drilling operations) and safely designing, installing and operating the new technology required for offshore UBD activities. While UBD had been successfully carried out in many onshore environments it was recognised that this experience did not readily translate to an offshore North Sea environment. Consequently, much of the technique and technology had to be revisited to provide the project team with the necessary level of assurance required to confidently proceed with underbalanced operations. Since 1996, the Shell Expro UBD Project Team has successfully implemented underbalanced drilling; this paper illustrates some of the main HSE issues that need to be managed for UBD operations.

Breaking the Cycle of Educational Alienation: A Multi-Professional Approach. By Richard Williams and Colin Pritchard. Pp. 217. Maidenhead: Open University Press. 2006. £18.99 (pbk), £55.00 (hbk). ISBN 0 335 21917 9 (pbk), 0 335 21918 7 (hbk).

Segregation studies have shown that Gilles de la Tourette Syndrome (GTS) is probably transmitted as an autosomal dominant gene disorder and can therefore be studied by classical linkage analysis to identify susceptibility loci. Many neurotransmitter systems have been implicated in the etiology of GTS. Most recently the alpha-1 subunit of the glycine receptor etiologically responsible for hyperekplexia has been hypothesized as the cause of the susceptibility to GTS. Because of this and the high concentration of other neuroreceptor genes at 5q33-35, it was decided to study this region and the associated gene cluster on chromosome 4p12-16 in a large British kindred multiply affected with GTS and chronic motor tics. The genotypes of the microsatellite markers at these loci were determined by polymerase chain reaction. The allele data were analyzed using both parametric and nonparametric methods. Approximate multipoint maps were constructed across the regions of interest using FASTLINK. All of the lod scores produced were negative, showing no evidence of linkage to GTS in the family studied. The multipoint maps showed good exclusion across these regions. The glycine receptor gene responsible for hyperekplexia and the other neuroreceptor genes examined in this paper are not involved in the etiology of GTS in this large pedigree.

Gilles de la Tourette syndrome (GTS) and related disorders such as chronic multiple ties and obsessive compulsive behaviour are likely to be genetically transmitted with a Mendelian autosomal dominant mode of transmission. Following our discovery of a patient with GTS who also carried a balanced translocation 46 XY, t(3:8) (p21.3 q24.1), a linkage study of several families was performed covering the areas on chromosomes 3 and 8 implicated by the cytogenetic abnormality in this unique GTS patient. A positive multipoint lod score of 2.9 was obtained on chromosome 3 with markers at the loci RAF1, THRB, and D3S11. Subsequently, the genetic map of this region was improved and new polymorphic markers close to our original three markers mere identified. With the new map the maximum two-point lod with any marker was reduced to 1.77 at RAF1, and the FASTMAP approximate multipoint lod excluded the likely region of the breakpoint. After constructing a somatic cell hybrid, the original three markers were mapped relative to the break point of the translocation and to other new markers. It was confirmed that the original markers were at least 20 cM away from the position of the break point. In addition, we traced further family members of our translocation GTS proband, and identified affected individuals who did not possess the translocation. We concluded that the translocation was not responsible for the GTS symptoms in our affected proband.

Segregation analyses have shown that Gilles de la Tourette Syndrome (GTS) is transmitted as an autosomal dominant gene disorder indicating that classical linkage analysis should be able to identify susceptibility loci. Previous studies of GTS have included investigations of neuroreceptor function, neurotransmitters, and their metabolites as well as neurotransmitter-related enzymes in an attempt to determine the pathophysiology of GTS. The neurotransmitter systems most often thought to be involved in GTS include those involving adrenaline, noradrenaline, and dopamine. We have carried out research to test the hypothesis that genes encoding proteins in the catecholamine pathways may contribute to the genetic etiology of GTS. Polymorphic markers at or near the D1, D2, D3, D4, D5 neuroreceptor gene loci as well as at the genes encoding dopamine beta hydroxylase (DBH), tyrosinase (TY) and tyrosine hydroxylase (TH) were studied in one large multiple affected pedigree. The linkage results of this investigation exclude a major role of these candidate genes in the etiology of GTS in the pedigree.

Objectives. Cochlea implantation involves drilling a cochleostomy through which the electrode array can be inserted. This is a freehand procedure requiring great accuracy. On breaking through the medial bony cochlea wall the drill penetrates through the endosteal membrane traumatizing the basilar membrane and scala tympani and contaminates them with bone dust. This probably causes a destruction of any residual hearing. Our objective was to produce an autonomous surgical drilling robot capable of drilling a cochleostomy but stopping prior to disrupting the endosteal membrane. Method. The autonomous surgical robot senses the force and torque at the tool point and uses this information to predict the start of breaking through the medial bony cochlea wall. Drilling is stopped prior to penetrating the endosteal membrane. The autonomous robot was used to drill a cochleostomy in 5-porcine cochlea's. Results. In all 5 procedures the autonomous surgical drilling robot stopped at the point of breakthrough. The endosteal membrane was not perforated in any of the specimens. The intact membrane was visible at the base of the cochleostomy. Conclusions. The autonomous surgical robot can drill a cochleostomy that minimizes damage to the membranous cochlea. The effect of this increased accuracy on residual hearing and post-operative infection is under further investigation.

An embedded signal processing system that uses a low number of sensors and cascaded neural networks to provide tactile feedback for a novel flexible digit for clinical applications is described. The design has been implemented as an FPGA-based application-specific digital signal processing circuit that computes real-time tactile feedback with clinically significant accuracy.

Key parameters for any bistable device are operating voltage and temperature range. The development of liquid crystal mixtures for use with grating aligned Zenithal Bistable Displays (ZBD™) is described for the first time. Latching at voltages less than 5V, with 20V addressing faster than 80μs per line and operation over a temperature range from −20°C to 80°C are all demonstrated in the same 4μm device.

The osteogenic and osseointegrative potential of a small molecule was examined to assess its usefulness in regenerative procedures. Purmorphamine was used to stimulate bone growth and repair in an in vitro cell-based assay and an in vivo chick embryo CAM-assay with and without the presence of an implant. Purmorphamine adhered to precipitated hydroxyapatite coating, could activate the sonic hedgehog pathway and thereby stimulated osteodifferentiation. Porous calcium phosphate beads were used to deliver this small molecule in vivo and showed that purmorphamine increased the trabecular bone to bone area significantly. The assay showed purmorphamine failed to induce any significant difference in osseointegration on titanium coated PTFE implants. This suggests that, while a small molecule can enhance osteogenesis and might be useful in regenerative procedures, it failed to enhance the osseointegration of a Ti coated implant, suggesting that this sort of stimulation might be useful for enhancing bone regeneration where bone loss due to disease exists, but not for enhancing early stability of an implant.

Preprint of: P.T.B. Brett and R. Guida. Bright line detection in COSMO-SkyMed SAR images of urban areas. In Joint Urban Remote Sensing Event 2011 (JURSE 2011), pages 253-256, 11-13 April 2011. Published version: doi:10.1109/JURSE.2011.5764767.

A long-standing curriculum controversy erupted in Pakistan in 2009 between two relatively polarised interpretive communities – represented by individuals drawing upon theocratic and liberal-democratic influences respectively. Following the announcement of a new National Education Policy, civil society groups and influential commentators vigorously debated features of the policy in opinions and editorial sections of national newspapers.

Objectives: The aim of this study was to assess the systemic effects of treating severe widespread periodontitis in a population of otherwise healthy individuals by examining treatment associated changes in markers of inflammation that are also implicated in cardiovascular atherosclerotic diseases. The potential impact of specific polymorphisms in cytokine genes known to influence both periodontitis and cardiovascular diseases was also examined.Materials and Methods: A convenience sample of patients affected with severe generalised periodontitis was enrolled into a prospective single blind longitudinal intervention trial with a 6 months follow-up. Serum C-reactive protein (CRP) and interleukin-6 (IL-6) levels were assessed by high-sensitivity assays. Serological and clinical periodontal parameters were evaluated at baseline, 2 and 6 months after completion of non-surgical periodontal therapy.Results: In the 94 subjects that completed this pilot trial improvements in all clinical periodontal parameters were achieved. These were accompanied with significant reductions in serum IL-6 and CRP concentrations. In a multivariate model, serum CRP levels were significantly associated with the outcome of periodontal treatment after correcting for potential covariates (age, body mass index, gender, smoking) and polymorphisms in the IL-6 (-174 C/G) and IL-1A (-889) genes. A median decrease in serum CRP of 0.5 mg/l (95% CI 0.4-0.7 mg/l) was observed 6 months after completion of periodontal therapy in this population. Subjects with above average response to periodontal therapy (

The focus question grounding this paper is "How can teachers use a visit to Port Arthur to promote historical and critical thinking and develop the capacity of upper primary children to make meaning from their affective experience at a site of human suffering?" The interpretational qualitative data drawn upon for the paper comes from second year pre-service primary teachers writing about past visits to Port Arthur as part of a unit introducing them to the aims and purposes of humanities and social sciences education, including History. The paper makes use of the education students’ assignments to analyse the potential of Port Arthur to engage the emotions in developing a critical and empathetic approach to the past. The paper advocates for teachers to implement a sophisticated place-based pedagogy that foregrounds affective history and emotional responses to a site of punishment.

A poster presented at the "IET Seminar on Earth Observation Satellites: applications and maximisation of commercial opportunities" on Monday, 29 November 2010.

Recent reports of cytogenetic abnormalities linked to psychiatric illness and the localisations of the genes for the dopamine (D2) receptor and tyrosinase on the long arm of chromosome 11 have suggested that susceptibility loci for schizophrenia and manic depression might be situated in this region. We could find no evidence for linkage in five Icelandic pedigrees between manic depression and markers in this region, and we have excluded candidate genes coding for the D2 receptor and tyrosinase. We conclude that mutations at loci in this region are not a common cause of manic depression in the population studied.

Preprint of: P.T.B. Brett and R. Guida. Geometry-based SAR curvilinear feature selection for damage detection. In 9th European Conference on Synthetic Aperture Radar - Invited Papers (EUSAR 2012 - Invited Papers), pages 62-65, 23-26 April 2011. No DOI for the published version unfortunately. Please also see the errata.

Growing evidence suggests that individual genetic susceptibility may influence the host's response to infections. Previously, we showed that a common variation in the interleukin (IL)-6 gene was associated with increased odds of detection of common periodontal pathogens from individuals with aggressive periodontitis. The aim of this study was to investigate the association between IL-6 polymorphisms and periodontopathogenic bacteria in a larger, ethnically mixed population of subjects with periodontitis.Genomic DNA was extracted from 107 subjects diagnosed with severe forms of periodontitis to study a cluster of polymorphisms in inflammatory genes, including IL-6. The presence of Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans), Porphyromonas gingivalis, and Tannerella forsythia (previously T. forsythensis) in their subgingival biofilm was determined by polymerase chain reaction analysis. Serum IL-6 and C-reactive protein (CRP) concentrations were analyzed by enzyme-linked immunosorbent assay.Multiple logistic regression analysis revealed that the IL-6 -6106 polymorphism was associated with the detection of A. actinomycetemcomitans (P = 0.009; odds ratio [OR] = 3.5; 95% confidence interval [CI]: 1.38 to 9.16) and the concomitant detection of A. actinomycetemcomitans and P. gingivalis (P = 0.015; OR = 3.6; 95% CI: 1.28 to 10.04). The IL-6 -174 polymorphism was associated with increased odds of the concomitant detection of A. actinomycetemcomitans and P. gingivalis (P = 0.042; OR = 2.8; 95% CI: 1.04 to 7.75). Haplotype analysis of all five IL-6 polymorphisms confirmed an association with the detection of A. actinomycetemcomitans (P = 0.046). The IL-6 -6106 polymorphism was also associated with CRP serum levels at multivariate analysis (P = 0.024).These findings confirm the hypothesis that complex interactions between the microbiota and host genome are at the basis of susceptibility to periodontitis. Periodontal disease may represent a useful model to study the pathways and mechanisms of host-pathogen interactions in inflammatory diseases.

The proposal of an entrenched Bill of Rights in Canada has been the subject of a great deal of interest. In this article Professor Brett concludes that the present Bill of Rights has been ineffectual. He further disagrees with the concept of entrenchment because it could not catalogue all rights nor ensure that encroachment of basic liberties would not take place. His solution would leave the matter in the political rather than the legal arena, subject to the wilt of a liberty-conscious electorate.