A 5-year profile of the incidence of total joint replacement in South Africa (1985 - 1989)

This survey was conducted to determine the number of total joint replacements (TJRs) carried out annually in South Africa from 1985 to 1989 and the nwnber of surgeons performing these procedures. During this period there was a 28% increase in the number of TJRs performed annually with an average increase of 20% in total hip replacements and 40% in total knee replacements. The number of surgeons involved in joint replacement during the survey period decreased by 7% in state-subsidised institutions but increased by 57% in the private sector. This is reflected in the number of TJRs performed each year, which has remained static in the state institutions but exhibits a threefold increase in the private sector. This probably reflects a shift in emphasis in state health care policy

Integrative transcriptomic analysis in human and mouse model of anaphylaxis identifies gene signatures associated with cell movement, migration and neuroinflammatory signalling

Background: Anaphylaxis is an acute life-threatening allergic reaction and a concern at a global level; therefore, further progress in understanding the underlying mechanisms and more effective strategies for diagnosis, prevention and management are needed. Objective: We sought to identify the global architecture of blood transcriptomic features of anaphylaxis by integrating expression data from human patients and mouse model of anaphylaxis. Methods: Bulk RNA-sequencings of peripheral whole blood were performed in: i) 14 emergency department (ED) patients with acute anaphylaxis, predominantly to Hymenoptera venom, ii) 11 patients with peanut allergy undergoing double-blind, placebo-controlled food challenge (DBPCFC) to peanut, iii) murine model of IgE-mediated anaphylaxis. Integrative characterisation of differential gene expression, immune cell-type-specific gene expression profiles, and functional and pathway analysis was undertaken. Results: 1023 genes were commonly and significantly dysregulated during anaphylaxis in ED and DBPCFC patients; of those genes, 29 were also dysregulated in the mouse model. Cell-type-specific gene expression profiles showed a rapid downregulation of blood basophil and upregulation of neutrophil signature in ED and DBPCFC patients and the mouse model, but no consistent and/or significant differences were found for other blood cells. Functional and pathway analysis demonstrated that human and mouse blood transcriptomic signatures of anaphylaxis follow trajectories of upregulation of cell movement, migration and neuroinflammatory signalling, and downregulation of lipid activating nuclear receptors signalling. Conclusion: Our study highlights the matched and extensive blood transcriptomic changes and suggests the involvement of discrete cellular components and upregulation of migration and neuroinflammatory pathways during anaphylaxis

Integrative transcriptomic analysis in human and mouse model of anaphylaxis identifies gene signatures associated with cell movement, migration and neuroinflammatory signalling

BackgroundAnaphylaxis is an acute life-threatening allergic reaction and a concern at a global level; therefore, further progress in understanding the underlying mechanisms and more effective strategies for diagnosis, prevention and management are needed.ObjectiveWe sought to identify the global architecture of blood transcriptomic features of anaphylaxis by integrating expression data from human patients and mouse model of anaphylaxis.MethodsBulk RNA-sequencings of peripheral whole blood were performed in: i) 14 emergency department (ED) patients with acute anaphylaxis, predominantly to Hymenoptera venom, ii) 11 patients with peanut allergy undergoing double-blind, placebo-controlled food challenge (DBPCFC) to peanut, iii) murine model of IgE-mediated anaphylaxis. Integrative characterisation of differential gene expression, immune cell-type-specific gene expression profiles, and functional and pathway analysis was undertaken.Results1023 genes were commonly and significantly dysregulated during anaphylaxis in ED and DBPCFC patients; of those genes, 29 were also dysregulated in the mouse model. Cell-type-specific gene expression profiles showed a rapid downregulation of blood basophil and upregulation of neutrophil signature in ED and DBPCFC patients and the mouse model, but no consistent and/or significant differences were found for other blood cells. Functional and pathway analysis demonstrated that human and mouse blood transcriptomic signatures of anaphylaxis follow trajectories of upregulation of cell movement, migration and neuroinflammatory signalling, and downregulation of lipid activating nuclear receptors signalling.ConclusionOur study highlights the matched and extensive blood transcriptomic changes and suggests the involvement of discrete cellular components and upregulation of migration and neuroinflammatory pathways during anaphylaxis

Just a wind-up? Ethnicity, religion and prejudice in Scottish football-related comedy

This article probes how media representations of football in Scotland sustain the hegemonic ideologies associated with ethnicity and religion. The paper probes the football-related comedy output of one radio programme; radio output and football comedy are both neglected cultural material in studies of sport in Scotland. It argues that ambiguity and allusive language in comedy construct multiple interpretative possibilities that can demean the social and cultural identity of particular groups in society. The discussion analyses specific sketches from the Scottish radio comedy show Watson's Wind Up. It is concluded that although humorous, these sketches reveal how ideas, myths and stereotypes that coalesce round Celtic FC and the Irish-descended and Catholic communities in Scotland reinforce and sustain anti-Irish and anti-Catholic bigotry

Inherited variants in CHD3 show variable expressivity in Snijders Blok-Campeau syndrome

Purpose Common diagnostic next-generation sequencing strategies are not optimized to identify inherited variants in genes associated with dominant neurodevelopmental disorders as causal when the transmitting parent is clinically unaffected, leaving a significant number of cases with neurodevelopmental disorders undiagnosed. Methods We characterized 21 families with inherited heterozygous missense or protein-truncating variants in CHD3, a gene in which de novo variants cause Snijders Blok-Campeau syndrome. Results Computational facial and Human Phenotype Ontology–based comparisons showed that the phenotype of probands with inherited CHD3 variants overlaps with the phenotype previously associated with de novo CHD3 variants, whereas heterozygote parents are mildly or not affected, suggesting variable expressivity. In addition, similarly reduced expression levels of CHD3 protein in cells of an affected proband and of healthy family members with a CHD3 protein-truncating variant suggested that compensation of expression from the wild-type allele is unlikely to be an underlying mechanism. Notably, most inherited CHD3 variants were maternally transmitted. Conclusion Our results point to a significant role of inherited variation in Snijders Blok-Campeau syndrome, a finding that is critical for correct variant interpretation and genetic counseling and warrants further investigation toward understanding the broader contributions of such variation to the landscape of human disease

Mixed accents: Scottish children with English parents

We discuss accent mixture and the creation of idiosyncratic phonological systems in acquisition, with a focus on Scottish English. Such mixing is in addition to the relatively stable sociolinguistic systems of variation expected within a speech community, and arises when parents have radically different accents from each other or from the child's peers or other adult models. In terms of traditional geographic dialectology, there are a number of isoglosses around the Scotland/England border, but modern social mobility means that in some Scottish cities there are large numbers of families with at least one non-Scottish adult accent acting as a model for acquisition, which may feed into phonological change. Of particular interest is the influence of Southern British English accents. We exemplify the issues with two short case studies. The first concerns a child with mixed Scottish/English input in the home. His speech patterns do indeed indicate the acquisition of a mixed system. The second focuses on inter-sibling variation, looking at two sibling pairs who exemplify a different mix of accent features from each other. We examine two main diagnostics: monophthongal vs. diphthongal productions of the vowels in FACE and GOAT; and rhoticity. We also describe a parental demographic and accent attitude questionnaire as part of Case Study 2. The results support the need for speaker-by-speaker study of how incompatibility between two target systems is handled. We conclude that descriptions of mixed accents should be more common in the literature and approached on a feature-by-feature basis to help develop models of accent interference.caslpub3959pu

An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge

There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. RESULTS: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. CONCLUSIONS: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups

Damaged hardmen: organised crime and the half-life of deindustrialisation

Despite frequent associations, deindustrialization features rarely in studies of organized crime, and organized crime is at best a spectral presence in studies of deindustrialization. By developing an original application of Linkon's concept of the “half‐life,” we present an empirical case for the symbiotic relationship between former sites of industry and the emergence of criminal markets. Based on a detailed case‐study in the west of Scotland, an area long associated with both industry and crime, the paper interrogates the environmental, social, and cultural after‐effects of deindustrialization at a community level. Drawing on 55 interviews with residents and service‐providers in Tunbrooke, an urban community where an enduring criminal market grew in the ruins of industry, the paper elaborates the complex landscapes of identity, vulnerability, and harm that are embedded in the symbiosis of crime and deindustrialization. Building on recent scholarship, the paper argues that organized crime in Tunbrooke is best understood as an instance of “residual culture” grafted onto a fragmented, volatile criminal marketplace where the stable props of territorial identity are unsettled. The analysis allows for an extension of both the study of deindustrialization and organized crime, appreciating the “enduring legacies” of closure on young people, communal identity, and social relations in the twenty‐first century

Integration of Cost Planning in the Architectural Design of Housing

Cost estimation in the initial phases of a project is of great interest to the construction industry. This paper proposes a new way of the integration of an architectural project and its cost estimate so as to optimise the design solutions, according to technical and economic criteria. This work explores the capacity of an elemental cost estimation method for residential buildings, when integrated with Computer Aided Design systems, to increase cost estimate precision during the early stages of design. A Cost Planning and CAD model (CP/CAD) is developed by the integration of a database and a CAD system which provides for the automatic exchange of information relative to the geometric layout of the building, the construction element build-up and the construction costs of the same. Finally the CP/CAD model is tested through the estimation of costs for some theoretical cases and also for a group of one-family houses with similar architectural characteristics. The results show the increased precision and the advantages of the model for cost estimation in the early design stages.