Multi-membership gene regulation in pathway based microarray analysis

This article is available through the Brunel Open Access Publishing Fund. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Gene expression analysis has been intensively researched for more than a decade. Recently, there has been elevated interest in the integration of microarray data analysis with other types of biological knowledge in a holistic analytical approach. We propose a methodology that can be facilitated for pathway based microarray data analysis, based on the observation that a substantial proportion of genes present in biochemical pathway databases are members of a number of distinct pathways. Our methodology aims towards establishing the state of individual pathways, by identifying those truly affected by the experimental conditions based on the behaviour of such genes. For that purpose it considers all the pathways in which a gene participates and the general census of gene expression per pathway. Results: We utilise hill climbing, simulated annealing and a genetic algorithm to analyse the consistency of the produced results, through the application of fuzzy adjusted rand indexes and hamming distance. All algorithms produce highly consistent genes to pathways allocations, revealing the contribution of genes to pathway functionality, in agreement with current pathway state visualisation techniques, with the simulated annealing search proving slightly superior in terms of efficiency. Conclusions: We show that the expression values of genes, which are members of a number of biochemical pathways or modules, are the net effect of the contribution of each gene to these biochemical processes. We show that by manipulating the pathway and module contribution of such genes to follow underlying trends we can interpret microarray results centred on the behaviour of these genes.The work was sponsored by the studentship scheme of the School of Information Systems, Computing and Mathematics, Brunel Universit

Polysomnographic evaluation of obstructive sleep apnea syndrome in children, before and after adenotonsillectomy

Introduction: In the last years the Obstructive Sleep Apnea/Hypopnea Syndrome (OSAHS) has much interested because it has not been completed established. Many criteria defined for OSAS in adults and children are different. We know that patient's clinical story is not sufficient for the diagnosis of OSAHS. In childhood, the most common cause of OSAHS is adenotonsillar hypertrophy, clinically characterised by snoring, apnea episodes, restless sleep, mouth breathing and daytime somnolence. Aim: This study has the purpose of comprovating, by objective way, the OSAS improving in children who underwent adenotonsillectomy. Study design: Clinical prospective. Material and method: For that, 23 children, among 2 and 13 years old, with adenotonsillar hypertrophy, were analysed. After endoscopy and polysomnography, they were submitted to adenotonsillectomy. Results: The polysomnography was repeated 2 months after surgery. The polysomnographic findings were compared through statistic study. Conclusion: All the patients had an important improve after adenotonsillectomy. Only two children (8.69%) persisted with light OSAHS, but they had moderate and important OSAHS before. We concluded that OSAHS is a precise indication for adenotonsillectomy in children.Introdução: Nos últimos anos a Síndrome da Apnéia/Hipopnéia Obstrutiva do Sono (SAHOS) tem despertado muito interesse por tratar-se de uma condição não totalmente estabelecida. Muitos critérios usados para definir SAHOS em adultos e crianças são diferentes entre si. Em 1995 Sabe-se que a história clínica do paciente não era suficiente para estabelecer o diagnóstico de SAHOS. Na criança a causa mais comum de SAOS é a hipertrofia adenoamigdaliana, normalmente caracterizada clinicamente pela presença de roncos noturnos, episódios de apnéia, sono agitado, respiração bucal e hipersonolência diurna4. Objetivo: Este estudo tem o intuito de comprovar de forma objetiva a melhora da SAHOS em crianças submetidas a adenoamigdalectomia. Forma de estudo: Clínico prospectivo. Material e método: Para isso, foram avaliadas 23 crianças entre 2 e 13 anos (1999-2001), com hipertrofia adenoamigdaliana, que após nasofibroscopia e polissonografia foram submetidas a cirurgia de adenoamigdalectomia. A polissonografia foi repetida após 2 meses de pós-operatório. Foi então realizado estudo estatístico dos dados obtidos na polissonografia pré- e pós-operatória. Resultado: Observamos que todos os pacientes tiveram melhora importante após adenoamigdalectomia. Duas crianças (8,69%) persistiram com SAOS leve, que anteriormente eram de grau moderado e acentuado. Conclusão: Concluímos assim que SAOS é uma indicação precisa para cirurgia de adenoamigdalectomia em crianças.UNIFESP-EPM Disciplina de Otorrinolaringologia PediátricaUNIFESP, EPM, Disciplina de Otorrinolaringologia PediátricaSciEL

No evidence for association of ataxia-telangiectasia mutated gene T2119C and C3161G amino acid substitution variants with risk of breast cancer

BACKGROUND: There is evidence that certain mutations in the double-strand break repair pathway ataxia-telangiectasia mutated gene act in a dominant-negative manner to increase the risk of breast cancer. There are also some reports to suggest that the amino acid substitution variants T2119C Ser707Pro and C3161G Pro1054Arg may be associated with breast cancer risk. We investigate the breast cancer risk associated with these two nonconservative amino acid substitution variants using a large Australian population-based case–control study. METHODS: The polymorphisms were genotyped in more than 1300 cases and 600 controls using 5' exonuclease assays. Case–control analyses and genotype distributions were compared by logistic regression. RESULTS: The 2119C variant was rare, occurring at frequencies of 1.4 and 1.3% in cases and controls, respectively (P = 0.8). There was no difference in genotype distribution between cases and controls (P = 0.8), and the TC genotype was not associated with increased risk of breast cancer (adjusted odds ratio = 1.08, 95% confidence interval = 0.59–1.97, P = 0.8). Similarly, the 3161G variant was no more common in cases than in controls (2.9% versus 2.2%, P = 0.2), there was no difference in genotype distribution between cases and controls (P = 0.1), and the CG genotype was not associated with an increased risk of breast cancer (adjusted odds ratio = 1.30, 95% confidence interval = 0.85–1.98, P = 0.2). This lack of evidence for an association persisted within groups defined by the family history of breast cancer or by age. CONCLUSION: The 2119C and 3161G amino acid substitution variants are not associated with moderate or high risks of breast cancer in Australian women

The effects of symmetry on the dynamics of antigenic variation

In the studies of dynamics of pathogens and their interactions with a host immune system, an important role is played by the structure of antigenic variants associated with a pathogen. Using the example of a model of antigenic variation in malaria, we show how many of the observed dynamical regimes can be explained in terms of the symmetry of interactions between different antigenic variants. The results of this analysis are quite generic, and have wider implications for understanding the dynamics of immune escape of other parasites, as well as for the dynamics of multi-strain diseases.Comment: 21 pages, 4 figures; J. Math. Biol. (2012), Online Firs

Perspectives of ammunition users on the use of lead ammunition and its potential impacts on wildlife and humans

This is the final version. Available on open access from Wiley via the DOI in this recordData availability statement: All data supporting the results in this paper are available from Zenodo (digital repository): https://zenodo.org/record/2653514#.XMbMXKbsZD8 (Newth et al., 2019).1. Recent national and international policy initiatives have aimed to reduce the exposure of humans and wildlife to lead from ammunition. Despite restrictions, in the UK, lead ammunition remains the most widespread source of environmental lead contamination to which wildlife may be exposed. 2. The risks arising from the use of lead ammunition and the measures taken to mitigate these have prompted intense and sometimes acrimonious discussion between stakeholder groups, including those advancing the interests of shooting, wildlife conservation, public health and animal welfare. 3. However, relatively little is known of the perspectives of individual ammunition users, despite their role in adding lead to the environment and their pivotal place in any potential changes to practice. Using Q‐methodology, we identified the perspectives of ammunition users in the UK on lead ammunition in an effort to bring forward evidence from these key stakeholders. 4. Views were characterised by two statistically and qualitatively distinct perspectives: (a) Open to change—comprised ammunition users that refuted the view that lead ammunition is not a major source of poisoning in wild birds, believed that solutions to reduce the risks of poisoning are needed, were happy to use non‐lead alternatives and did not feel that the phasing out of lead shot would lead to the demise of shooting; and (b) Status quo—comprised ammunition users who did not regard lead poisoning as a major welfare problem for wild birds, were ambivalent about the need for solutions and felt that lead shot is better than steel at killing and not wounding an animal. They believed opposition to lead ammunition was driven more by a dislike of shooting than evidence of any harm. 5. Adherents to both perspectives agreed that lead is a toxic substance. There was consensus that involvement of stakeholders from all sides of the debate was desirable and that to be taken seriously by shooters, information about lead poisoning should come from the shooting community

Foot pain and foot health in an educated population of adults: results from the Glasgow Caledonian University Alumni Foot Health Survey

Abstract Background Foot pain is common amongst the general population and impacts negatively on physical function and quality of life. Associations between personal health characteristics, lifestyle/behaviour factors and foot pain have been studied; however, the role of wider determinants of health on foot pain have received relatively little attention. Objectives of this study are i) to describe foot pain and foot health characteristics in an educated population of adults; ii) to explore associations between moderate-to-severe foot pain and a variety of factors including gender, age, medical conditions/co-morbidity/multi-morbidity, key indicators of general health, foot pathologies, and social determinants of health; and iii) to evaluate associations between moderate-to-severe foot pain and foot function, foot health and health-related quality-of-life. Methods Between February and March 2018, Glasgow Caledonian University Alumni with a working email address were invited to participate in the cross-sectional electronic survey (anonymously) by email via the Glasgow Caledonian University Alumni Office. The survey was constructed using the REDCap secure web online survey application and sought information on presence/absence of moderate-to-severe foot pain, patient characteristics (age, body mass index, socioeconomic status, occupation class, comorbidities, and foot pathologies). Prevalence data were expressed as absolute frequencies and percentages. Multivariate logistic and linear regressions were undertaken to identify associations 1) between independent variables and moderate-to-severe foot pain, and 2) between moderate-to-severe foot pain and foot function, foot health and health-related quality of life. Results Of 50,228 invitations distributed, there were 7707 unique views and 593 valid completions (median age [inter-quartile range] 42 [31–52], 67.3% female) of the survey (7.7% response rate). The sample was comprised predominantly of white Scottish/British (89.4%) working age adults (95%), the majority of whom were overweight or obese (57.9%), and in either full-time or part-time employment (82.5%) as professionals (72.5%). Over two-thirds (68.5%) of the sample were classified in the highest 6 deciles (most affluent) of social deprivation. Moderate-to-severe foot pain affected 236/593 respondents (39.8%). High body mass index, presence of bunions, back pain, rheumatoid arthritis, hip pain and lower occupation class were included in the final multivariate model and all were significantly and independently associated with moderate-to-severe foot pain (p < 0.05), except for rheumatoid arthritis (p = 0.057). Moderate-to-severe foot pain was significantly and independently associated lower foot function, foot health and health-related quality of life scores following adjustment for age, gender and body mass index (p < 0.05). Conclusions Moderate-to-severe foot pain was highly prevalent in a university-educated population and was independently associated with female gender, high body mass index, bunions, back pain, hip pain and lower occupational class. Presence of moderate-to-severe foot pain was associated with worse scores for foot function, foot health and health-related quality-of-life. Education attainment does not appear to be protective against moderate-to-severe foot pain

Generating synthetic fjord bathymetry for coastal Greenland

Bed topography is a critical boundary for the numerical modelling of ice sheets and ice-ocean interactions. A persistent issue with existing topography products for the bed of the Greenland Ice Sheet and surrounding sea floor is the poor representation of coastal bathymetry, especially in regions of floating ice and near the grounding line. Sparse data coverage, and the resultant coarse resolution at the ice-ocean boundary, poses issues in our ability to model ice flow advance and retreat from the present position. In addition, as fjord bathymetry is known to exert strong control on ocean circulation and ice-ocean forcing, the lack of bed data leads to an inability to model these processes adequately. Since the release of the last complete Greenland bed topography-bathymetry product, new observational bathymetry data have become available. These data can be used to constrain bathymetry, but many fjords remain completely unsampled and therefore poorly resolved. Here, as part of the development of the next generation of Greenland bed topography products, we present a new method for constraining the bathymetry of fjord systems in regions where data coverage is sparse. For these cases, we generate synthetic fjord geometries using a method conditioned by surveys of terrestrial glacial valleys as well as existing sinuous feature interpolation schemes. Our approach enables the capture of the general bathymetry profile of a fjord in north-west Greenland close to Cape York, when compared to observational data. We validate our synthetic approach by demonstrating reduced overestimation of depths compared to past attempts to constrain fjord bathymetry. We also present an analysis of the spectral characteristics of fjord centrelines using recently acquired bathymetric observations, demonstrating how a stochastic model of fjord bathymetry could be parameterised and used to create different realisations.This study was supported by UK NERC grant NE/M000869/1

The positive and negative impact of an intergenerational digital technology education programme on younger people’s perceptions of older adults

In order to meet the technological needs of older adults, and ensure digital inclusion, it is important for digital technology designers to accurately assess and understand older adults’ needs and requirements, free from the influence of societal assumptions of their capabilities. This study evaluated the impact of an intergenerational digital technology education programme on younger adults’ stereotypes of older people. Using an experimental design, results show that compared to a control group, students taking part in the programme subsequently rated older adults as more friendly but less competent. Practical implications for developing intergenerational education programmes are discussed