A Charter to Fundamentally Change the Role of Oral Corticosteroids in the Management of Asthma

Asthma affects 339 million people worldwide, with an estimated 5–10% experiencing severe asthma. In emergency settings, oral corticosteroids (OCS) can be lifesaving, but acute and long-term treatment can produce clinically important adverse outcomes and increase the risk of mortality. Therefore, global guidelines recommend limiting the use of OCS. Despite the risks, research indicates that 40–60% of people with severe asthma are receiving or have received long-term OCS treatment. Although often perceived as a low-cost option, long-term OCS use can result in significant health impairments and costs owing to adverse outcomes and increased utilization of healthcare resources. Alternative treatment methods, such as biologics, may produce cost-saving benefits with a better safety profile. A comprehensive and concerted effort is necessary to tackle the continued reliance on OCS. Accordingly, a threshold for OCS use should be established to help identify patients at risk of OCS-related adverse outcomes. Receiving a total dose of more than 500 mg per year should trigger a review and specialist referral. Changes to national and local policies, following examples from other chronic diseases, will be crucial to achieving this goal. Globally, multiple barriers to change still exist, but specific steps have been identified to help clinicians reduce reliance on OCS. Implementing these changes will result in positive health outcomes for patients and social and economic benefits for societies.</p

The Stretchy Strap: supporting encumbered interaction with guitars

Guitarists struggle to play their instruments while simultaneously using additional computing devices (i.e., encumbered interaction). We explored designs with guitarists through co-design and somaesthetic design workshops, learning that they (unsurprisingly) preferred to focus on playing their guitars and keeping their instruments’ material integrity intact. Subsequently, we devised an interactive guitar strap controller, which guitarists found promising for tackling encumbered interaction during instrumental transcription, learning and practice. Our design process highlights three strategies: considering postural interaction, applying somaesthetic design to interactive music technology development, and augmenting guitar accessories

Standard requirements for GCP-compliant data management in multinational clinical trials

<p>Abstract</p> <p>Background</p> <p>A recent survey has shown that data management in clinical trials performed by academic trial units still faces many difficulties (e.g. heterogeneity of software products, deficits in quality management, limited human and financial resources and the complexity of running a local computer centre). Unfortunately, no specific, practical and open standard for both GCP-compliant data management and the underlying IT-infrastructure is available to improve the situation. For that reason the "Working Group on Data Centres" of the European Clinical Research Infrastructures Network (ECRIN) has developed a standard specifying the requirements for high quality GCP-compliant data management in multinational clinical trials.</p> <p>Methods</p> <p>International, European and national regulations and guidelines relevant to GCP, data security and IT infrastructures, as well as ECRIN documents produced previously, were evaluated to provide a starting point for the development of standard requirements. The requirements were produced by expert consensus of the ECRIN Working group on Data Centres, using a structured and standardised process. The requirements were divided into two main parts: an IT part covering standards for the underlying IT infrastructure and computer systems in general, and a Data Management (DM) part covering requirements for data management applications in clinical trials.</p> <p>Results</p> <p>The standard developed includes 115 IT requirements, split into 15 separate sections, 107 DM requirements (in 12 sections) and 13 other requirements (2 sections). Sections IT01 to IT05 deal with the basic IT infrastructure while IT06 and IT07 cover validation and local software development. IT08 to IT015 concern the aspects of IT systems that directly support clinical trial management. Sections DM01 to DM03 cover the implementation of a specific clinical data management application, i.e. for a specific trial, whilst DM04 to DM12 address the data management of trials across the unit. Section IN01 is dedicated to international aspects and ST01 to the competence of a trials unit's staff.</p> <p>Conclusions</p> <p>The standard is intended to provide an open and widely used set of requirements for GCP-compliant data management, particularly in academic trial units. It is the intention that ECRIN will use these requirements as the basis for the certification of ECRIN data centres.</p

Plasma DNA methylation: a potential biomarker for stratification of liver fibrosis in non-alcoholic fatty liver disease

Objective: Liver biopsy is currently the most reliable way of evaluating liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD). Its inherent risks limit its widespread use. Differential liver DNA methylation of peroxisome proliferator-activated receptor gamma (PPARγ) gene promoter has recently been shown to stratify patients in terms of fibrosis severity but requires access to liver tissue. The aim of this study was to assess whether DNA methylation of circulating DNA could be detected in human plasma and potentially used to stratify liver fibrosis severity in patients with NAFLD.Design: Patients with biopsy-proven NAFLD and age-matched controls were recruited from the liver and gastroenterology clinics at the Newcastle upon Tyne Hospitals NHS Foundation Trust. Plasma cell-free circulating DNA methylation of PPARγ was quantitatively assessed by pyrosequencing. Liver DNA methylation was quantitatively assessed by pyrosequencing NAFLD explant tissue, subjected to laser capture microdissection (LCM). Patients with alcoholic liver disease (ALD) were also subjected to plasma DNA and LCM pyrosequencing.Results: 26 patients with biopsy-proven NAFLD were included. Quantitative plasma DNA methylation of PPARγ stratified patients into mild (Kleiner 1–2) and severe (Kleiner 3–4) fibrosis (CpG1: 63% vs 86%, p0.05). Hypermethylation at the PPARγ promoter of plasma DNA correlated with changes in hepatocellular rather than myofibroblast DNA methylation. Similar results were demonstrated in patients with ALD cirrhosis.Conclusions: Differential DNA methylation at the PPARγ promoter can be detected within the pool of cell-free DNA of human plasma. With further validation, plasma DNA methylation of PPARγ could potentially be used to non-invasively stratify liver fibrosis severity in patients with NAFLD. Plasma DNA methylation signatures reflect the molecular pathology associated with fibrotic liver disease

Association of a sequence variant in DAB2IP with coronary heart disease

Aims: A sequence variant, rs7025486[A], in DAB2IP on chromosome 9q33 has recently been associated with coronary heart disease (CHD). We sought to replicate this finding and to investigate associations with a panel of inflammatory and haemostatic biomarkers. We also sought to examine whether this variant, in combination with a chromosome 9p21 CHD variant (rs10757278) and the Framingham risk score (FRS), could improve the prediction of events compared with the FRS alone. Methods and results: rs7025486 was genotyped in 1386 CHD cases and 3532 controls and was associated with CHD [odds ratio (OR) of 1.16, 95% confidence interval (CI) 1.05-1.29, P = 0.003]. Meta-analysis, using data from the original report and from genome-wide association studies in both the Wellcome Trust Case Control Consortium and the Cardiovascular Health Study, comprising 9968 cases and 20 048 controls, confirmed the association (OR of 1.10, 95% CI 1.06-1.14, P = 3.2 x 10 -6). There was no association with a panel of CHD biomarkers, including any lipid, inflammation, or coagulation trait, nor with telomere length. Addition to the FRS of this variant plus rs10757278 on chromosome 9p21 improved the area under the receiver-operating characteristic curve (AROC) from 0.61 to 0.64 (P = 0.03) as well as improving the reclassification (net reclassification index = 11.1%, P = 0.007). Conclusion: This study replicates a previous association of a variant in DAB2IP with CHD. Addition of multiple variants improves the performance of predictive models based upon classical cardiovascular risk factors

Igbo-English intrasentential codeswitching and the Matrix Language Frame model

This paper uses data from Igbo-English intrasentential codeswitching involving mixed nominal expressions to test the Matrix Language Frame (MLF) model. The MLF model is one of the most highly influential frameworks used in the study of grammatical aspects of codeswitching. Three principles associated with it, the Matrix Language Principle, the Asymmetry Principle and the Uniform Structure Principle, were tested on data collected from informal conversations by educated adult Igbo-English bilinguals resident in Port Harcourt. The results of the analyses suggest general support for the three principles and for identifying Igbo-English as a “classic” case of codeswitching

FusionFinder: A Software Tool to Identify Expressed Gene Fusion Candidates from RNA-Seq Data

The hallmarks of many haematological malignancies and solid tumours are chromosomal translocations, which may lead to gene fusions. Recently, next-generation sequencing techniques at the transcriptome level (RNA-Seq) have been used to verify known and discover novel transcribed gene fusions. We present FusionFinder, a Perl-based software designed to automate the discovery of candidate gene fusion partners from single-end (SE) or paired-end (PE) RNA-Seq read data. FusionFinder was applied to data from a previously published analysis of the K562 chronic myeloid leukaemia (CML) cell line. Using FusionFinder we successfully replicated the findings of this study and detected additional previously unreported fusion genes in their dataset, which were confirmed experimentally. These included two isoforms of a fusion involving the genes BRK1 and VHL, whose co-deletion has previously been associated with the prevalence and severity of renal-cell carcinoma. FusionFinder is made freely available for non-commercial use and can be downloaded from the project website (http://bioinformatics.childhealthresearch.org.au/software/fusionfinder/)

Diversity in African languages: Selected papers from the 46th Annual Conference on African Linguistics

Diversity in African Languages contains a selection of revised papers from the 46th Annual Conference on African Linguistics, held at the University of Oregon. Most chapters focus on single languages, addressing diverse aspects of their phonology, morphology, semantics, syntax, information structure, or historical development. These chapters represent nine different genera: Mande, Gur, Kwa, Edoid, Bantu, Nilotic, Gumuzic, Cushitic, and Omotic. Other chapters investigate a mix of languages and families, moving from typological issues to sociolinguistic and inter-ethnic factors that affect language and accent switching. Some chapters are primarily descriptive, while others push forward the theoretical understanding of tone, semantic problems, discourse related structures, and other linguistic systems. The papers on Bantu languages reflect something of the internal richness and continued fascination of the family for linguists, as well as maturation of research on the family. The distribution of other papers highlights the need for intensified research into all the language families of Africa, including basic documentation, in order to comprehend linguistic diversities and convergences across the continent. In this regard, the chapter on Daats’íin (Gumuzic) stands out as the first-ever published article on this hitherto unknown and endangered language found in the Ethiopian-Sudanese border lands

Diversity in African languages: Selected papers from the 46th Annual Conference on African Linguistics

Diversity in African Languages contains a selection of revised papers from the 46th Annual Conference on African Linguistics, held at the University of Oregon. Most chapters focus on single languages, addressing diverse aspects of their phonology, morphology, semantics, syntax, information structure, or historical development. These chapters represent nine different genera: Mande, Gur, Kwa, Edoid, Bantu, Nilotic, Gumuzic, Cushitic, and Omotic. Other chapters investigate a mix of languages and families, moving from typological issues to sociolinguistic and inter-ethnic factors that affect language and accent switching. Some chapters are primarily descriptive, while others push forward the theoretical understanding of tone, semantic problems, discourse related structures, and other linguistic systems. The papers on Bantu languages reflect something of the internal richness and continued fascination of the family for linguists, as well as maturation of research on the family. The distribution of other papers highlights the need for intensified research into all the language families of Africa, including basic documentation, in order to comprehend linguistic diversities and convergences across the continent. In this regard, the chapter on Daats’íin (Gumuzic) stands out as the first-ever published article on this hitherto unknown and endangered language found in the Ethiopian-Sudanese border lands

Diversity in African languages: Selected papers from the 46th Annual Conference on African Linguistics

Diversity in African Languages contains a selection of revised papers from the 46th Annual Conference on African Linguistics, held at the University of Oregon. Most chapters focus on single languages, addressing diverse aspects of their phonology, morphology, semantics, syntax, information structure, or historical development. These chapters represent nine different genera: Mande, Gur, Kwa, Edoid, Bantu, Nilotic, Gumuzic, Cushitic, and Omotic. Other chapters investigate a mix of languages and families, moving from typological issues to sociolinguistic and inter-ethnic factors that affect language and accent switching. Some chapters are primarily descriptive, while others push forward the theoretical understanding of tone, semantic problems, discourse related structures, and other linguistic systems. The papers on Bantu languages reflect something of the internal richness and continued fascination of the family for linguists, as well as maturation of research on the family. The distribution of other papers highlights the need for intensified research into all the language families of Africa, including basic documentation, in order to comprehend linguistic diversities and convergences across the continent. In this regard, the chapter on Daats’íin (Gumuzic) stands out as the first-ever published article on this hitherto unknown and endangered language found in the Ethiopian-Sudanese border lands