Most nuclear systemic autoantigens are extremely disordered proteins: implications for the etiology of systemic autoimmunity

Patients with systemic autoimmune diseases usually produce high levels of antibodies to self-antigens (autoantigens). The repertoire of common autoantigens is remarkably limited, yet no readily understandable shared thread links these apparently diverse proteins. Using computer prediction algorithms, we have found that most nuclear systemic autoantigens are predicted to contain long regions of extreme structural disorder. Such disordered regions would generally make poor B cell epitopes and are predicted to be under-represented as potential T cell epitopes. Consideration of the potential role of protein disorder may give novel insights into the possible role of molecular mimicry in the pathogenesis of autoimmunity. The recognition of extreme autoantigen protein disorder has led us to an explicit model of epitope spreading that explains many of the paradoxical aspects of autoimmunity – in particular, the difficulty in identifying autoantigen-specific helper T cells that might collaborate with the B cells activated in systemic autoimmunity. The model also explains the experimentally observed breakdown of major histocompatibility complex (MHC) class specificity in peptides associated with the MHC II proteins of activated autoimmune B cells, and sheds light on the selection of particular T cell epitopes in autoimmunity. Finally, the model helps to rationalize the relative rarity of clinically significant autoimmunity despite the prevalence of low specificity/low avidity autoantibodies in normal individuals

The UK Ministry of Defence Project Orientated Environmental Management System (POEMS)

The Project Orientated Environmental Management System (POEMS) is the UK Ministry of Defence (MoD) bespoke environmental management system for the acquisition and use of equipment. The full implementation of a site-specific environmental management system is challenging for the MoD because there are many permanent MoD sites with transient populations, frequently changing site activities and diverse types of equipment. Nevertheless, MoD policy requires that all sites are covered by an environmental management system. POEMS is based on international standards ISO14001 and ISO14040, which focus on environmental management systems and life cycle assessment, respectively. The primary aim of POEMS is to identify and manage any environmental aspects (causes) and impacts (effects) by scrutinising MoD equipment and activities during acquisition, operation and disposal. This is achieved by drawing up a priority list of activities associated with the equipment based on anticipated environmental impact scores, resulting in an environmental management plan that spans the life cycle of the equipment and any corresponding activities. This article describes the POEMS procedure for both experts and non-experts, and demonstrates the implementation of POEMS using a 105-mm artillery round as a theoretical case study. The results anticipated at each stage of the POEMS procedure are discussed in detail, and the documentation necessary to verify the correct application of POEMS is demonstrated

Accuracy and Consistency of Radiographic Interpretation Among Clinical Instructors Using Two Viewing Systems

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153540/1/jddj002203372006702tb04071x.pd

Accuracy and Consistency of Radiographic Interpretation Among Clinical Instructors in Conjunction with a Training Program

There are inaccuracies and inconsistencies of radiographic interpretation among clinical instructors. The purpose of this investigation was to determine if a training program could improve the accuracy and consistency of instructors’ ratings of bone loss. A total of thirty-five clinical instructors consisting of periodontal faculty (periodontists and general dentists), dental hygiene faculty, and periodontal graduate students viewed projected digitized radiographic images and quantified bone loss for twenty-five teeth into four descriptive categories. Ratings of bone loss were made immediately before (pretest) and after (post-test 1) initiation of the training program and then again three months later (post-test 2). Ratings were compared to the correct choice categories as determined by direct measurement using the Schei ruler. Overall agreement with the correct choice improved over time (from 64.5 percent to 85.2 percent) with the greatest change from pretest (64.5 percent) to post-test 1 (76.5 percent). Mean and absolute differences improved in three of the four categories, but worsened in one from pretest to post-test 1. This category returned to its original high value at post-test 2. The greatest improvement in consistency among instructors’ ratings was seen in one of the four categories, which was “none” (no bone loss). Extension of the training program may further enhance the accuracy and consistency of instructors’ radiographic interpretation

Accuracy and Consistency of Radiographic Interpretation Among Clinical Instructors Using Two Viewing Systems

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153540/1/jddj002203372006702tb04071x.pd

Transcription Factor Map Alignment of Promoter Regions

We address the problem of comparing and characterizing the promoter regions of genes with similar expression patterns. This remains a challenging problem in sequence analysis, because often the promoter regions of co-expressed genes do not show discernible sequence conservation. In our approach, thus, we have not directly compared the nucleotide sequence of promoters. Instead, we have obtained predictions of transcription factor binding sites, annotated the predicted sites with the labels of the corresponding binding factors, and aligned the resulting sequences of labels—to which we refer here as transcription factor maps (TF-maps). To obtain the global pairwise alignment of two TF-maps, we have adapted an algorithm initially developed to align restriction enzyme maps. We have optimized the parameters of the algorithm in a small, but well-curated, collection of human–mouse orthologous gene pairs. Results in this dataset, as well as in an independent much larger dataset from the CISRED database, indicate that TF-map alignments are able to uncover conserved regulatory elements, which cannot be detected by the typical sequence alignments

Using positive behavioural support as a treatment for trauma symptoms with a man with intellectual disabilities

Background. There is robust evidence that psychological therapies are an effective treatment for trauma-related symptoms, including post-traumatic stress disorder. However, there are relatively few studies involving people with intellectual disabilities, and no studies drawing on positive behavioural support as the mechanism for the delivery of treatment. Method and materials. This study was a descriptive case report of a young man with intellectual disabilities who had a history of early trauma. His challenging behaviour was associated with demand avoidance. A positive behavioural support plan, incorporating psychological therapies and medication, was developed, implemented and is described. Results. Over time, challenging behaviours reduced and were eventually extinguished. This was associated with an increase in engagement in a variety of activities and a reduction in trauma-related symptoms. Discussion. Using positive behaviour support plans as the organisational framework for the adaptation and delivery of both psychological therapies and medication for complex cases is advantageous. Excellent team working is necessary to ensure that interventions are successful

Evaluation of small-scale combustion of an insensitive high explosive formulation containing 3-nitro-1,2,4-triazol-5-one (NTO), 2,4-dinitroanisole (DNAN), and 1,3,5-trinitroperhydro-1,3,5-triazine (RDX)

Energetic materials are often disposed by open-burning or open-detonation as it is a cost-effective and efficient means of destroying explosive material, and often minimizes the need to transport hazardous explosives to treatment facilities. This practice is often scrutinized for the negative environmental impact of the odorous and unsightly toxic gaseous emissions as well as the resulting deposition residues, which often contain unburned energetic materials. With the increasing use of Insensitive High Explosive compositions in munitions, it is essential that the potential environmental impact of their disposal is assessed before their extensive use to prevent the kind of contamination incidents experienced with legacy explosives. Therefore, the aim of this work was to develop a controlled laboratory experiment to identify the gaseous emissions and the energetic material residues that are generated through the combustion of the IHE components 3-nitro-1,2,4-triazol-5-one (NTO), 2,4-dinitroanisole (DNAN), and 1,3,5-trinitroperhydro-1,3,5-triazine (RDX). A sealed vial containing small (mg) quantities of energetic material was heated until the energetic material combusted. Gas chromatography/mass spectrometry (GCMS) was used to calculate the oxygen consumption and to identify the gases that were generated. The solid residues were analyzed by high-performance liquid chromatography (HPLC) to quantify unburned energetic material. Results showed that DNAN was the most resistant to burning, thus leaving significant quantities of unreacted starting material in the vial. An interesting observation for the IHE formulation was that DNAN also inhibited the combustion of NTO and RDX. The gases emitted during the open burning of IHE components and mixtures included CO, CO2, and N2O as expected, but the proportions differed when the components and mixture were compared, reflecting the influence of DNAN on the burning behavior. From our data, we concluded that open-burning DNAN-based formulations is an environmentally unfavorable waste-management practice for the disposal of IHEs mainly due to generation of solid residues as well as unburnt DNAN

Public attitudes to the management of invasive non-native species in Scotland

Invasive non-native species are one of the main threats to biodiversity. Consequently there is a need to control or eradicate those species that are causing problems in order to mitigate their impact. Such management programmes can be controversial and in some cases have been delayed or halted because of opposition from pressure groups. Public support can be critical to the success of such projects, and understanding the underlying attitudes of the public can help inform outreach education activities. To assess attitudes towards invasive species management and investigate socio-demographic factors influencing such attitudes, a questionnaire survey of 600 randomly selected members of the public in Scotland was conducted, and a total of 248 completed questionnaires returned. The level of support for control and eradication programmes was, in general, high and was higher amongst men, older people, and people who had previously heard of control and eradication projects. The species to be managed influenced levels of support, and projects to control birds were the least supported. Respondents with prior knowledge of control and eradication programmes and members of conservation organisations, in general, showed higher levels of support, indicating the important role that awareness and education has in terms of increasing public support for invasive non-native species management projects

Rates of Anti-Tuberculosis Drug Resistance in Kampala-Uganda Are Low and Not Associated with HIV Infection

Background: Drug resistance among tuberculosis patients in sub-Saharan Africa is increasing, possibly due to association with HIV infection. We studied drug resistance and HIV infection in a representative sample of 533 smear-positive tuberculosis patients diagnosed in Kampala, Uganda. Methods/Principal Findings: Among 473 new patients, multidrug resistance was found in 5 (1.1%, 95% CI 0.3-2.5) and resistance to any drug in 57 (12.1%, 9.3-15.3). Among 60 previously treated patients this was 7 (11.7%, 4.8-22.6) and 17 (28.3%; 17.5-41.4), respectively. Of 517 patients with HIV results, 165 (31.9%, 27.9-36.1) tested positive. Neither multidrug (adjusted odds ratio (ORadj) 0.7; 95% CI 0.19-2.6) nor any resistance (ORadj 0.7; 0.43-1.3) was associated with HIV status. Primary resistance to any drug was more common among patients who had worked in health care (ORadj 3.5; 1.0-12.0). Conclusion/Significance: Anti-tuberculosis drug resistance rates in Kampala are low and not associated with HIV infection, but may be associated with exposure during health car