Novel mutations in ACVR1 result in atypical features in two fibrodysplasia ossificans progressiva patients

Fibrodysplasia Ossificans Progressiva (FOP) is a rare, heritable condition typified by progression of extensive ossification within skeletal muscle, ligament and tendon together with defects in skeletal development. The condition is easily diagnosed by the presence of shortened great toes and there is severe advancement of disability with age. FOP has been shown to result from a point mutation (c.617G>A) in the ACVR1 gene in almost all patients reported. Very recently two other mutations have been described in three FOP patients. We present here evidence for two further unique mutations (c.605G>T and c.983G>A) in this gene in two FOP patients with some atypical digit abnormalities and other clinical features. The observation of disparate missense mutations mapped to the GS and kinase domains of the protein supports the disease model of mild kinase activation and provides a potential rationale for phenotypic variation. © 2009 Petrie et al.

Combining transcriptome assemblies from multiple de novo assemblers in the allo-tetraploid plant Nicotiana benthamiana

Background Nicotiana benthamiana is an allo-tetraploid plant, which can be challenging for de novo transcriptome assemblies due to homeologous and duplicated gene copies. Transcripts generated from such genes can be distinct yet highly similar in sequence, with markedly differing expression levels. This can lead to unassembled, partially assembled or mis-assembled contigs. Due to the different properties of de novo assemblers, no one assembler with any one given parameter space can re-assemble all possible transcripts from a transcriptome. Results In an effort to maximise the diversity and completeness of de novo assembled transcripts, we utilised four de novo transcriptome assemblers, TransAbyss, Trinity, SOAPdenovo-Trans, and Oases, using a range of k-mer sizes and different input RNA-seq read counts. We complemented the parameter space biologically by using RNA from 10 plant tissues. We then combined the output of all assemblies into a large super-set of sequences. Using a method from the EvidentialGene pipeline, the combined assembly was reduced from 9.9 million de novo assembled transcripts to about 235,000 of which about 50,000 were classified as primary. Metrics such as average bit-scores, feature response curves and the ability to distinguish paralogous or homeologous transcripts, indicated that the EvidentialGene processed assembly was of high quality. Of 35 RNA silencing gene transcripts, 34 were identified as assembled to full length, whereas in a previous assembly using only one assembler, 9 of these were partially assembled. Conclusions To achieve a high quality transcriptome, it is advantageous to implement and combine the output from as many different de novo assemblers as possible. We have in essence taking the ‘best’ output from each assembler while minimising sequence redundancy. We have also shown that simultaneous assessment of a variety of metrics, not just focused on contig length, is necessary to gauge the quality of assemblies.

Medical free-text to concept mapping as an information retrieval problem

Concept mapping involves determining relevant concepts from a free-text input, where concepts are defined in an external reference ontology. This is an important process that underpins many applications for clinical information reporting, derivation of phenotypic descriptions, and a number of state-of-the-art medical information retrieval methods. Concept mapping can be cast into an information retrieval (IR) problem: free-text mentions are treated as queries and concepts from a reference ontology as the documents to be indexed and retrieved. This paper presents an empirical investigation applying general-purpose IR techniques for concept mapping in the medical domain. A dataset used for evaluating medical information extraction is adapted to measure the effectiveness of the considered IR approaches. Standard IR approaches used here are contrasted with the effectiveness of two established benchmark methods specifically developed for medical concept mapping. The empirical findings show that the IR approaches are comparable with one benchmark method but well below the best benchmark.

Social Media Audience Metrics as a New Form of TV Audience Measurement

Digital media have contributed to significant disruptions in the business of audience measurement. Television broadcasters have long relied on simple and authoritative measures of who is watching what. The demand for ratings data, as a common currency in transactions involving advertising and program content, will likely remain, but accompanying measurements of audience engagement with media content would also be of value. Today's media environment increasingly includes social media and second-screen use, providing a data trail that affords an opportunity to measure engagement. If the limitations of using social media to indicate audience engagement can be overcome, social media use may allow for quantitative and qualitative measures of engagement. Raw social media data must be contextualized, and it is suggested that tools used by sports analysts be incorporated to do so. Inspired by baseball's Sabremetrics, the authors propose Telemetrics in an attempt to separate actual performance from contextual factors. Telemetrics facilitates measuring audience activity in a manner controlling for factors such as time slot, network, and so forth. It potentially allows both descriptive and predictive measures of engagement.

From users to citizens: Some thoughts on designing for polity and civics

This paper presents an essay aimed at prompting broad discussion crucial in keeping the interaction design discourse fresh, critical, and in motion. We trace the changing role of people who have advanced from consumers to producers, from stationary office workers to mobile urban nomads, from passive members of the plebs to active instigators of change. Yet, interaction designers often still refer to them only as ‘users.’ We follow some of the historic developments from the information superhighway to the smart city in order to provide the backdrop in front of which we critically analyse three core areas. First, the issue of echo chambers and filter bubbles in social media results in a political polarisation that jeopardises the formation of a functioning public sphere. Second, pretty lights and colourful façades in media architecture are increasingly making way for situated installations and interventions fostering community engagement. And third, civic activism is often reduced to forms of slacktivism. We synthesise our discussion to propose ‘citizen-ability’ as an alternative goal for interaction designers to aspire to in order to create new polities and civics for a better quality of life.

Health-related quality of life of individuals with transfemoral amputation fitted with the Transcutaneous Bone Anchoring Prosthesis following the OGAAP

Background The benefits and safety transcutaneous bone anchored prosthesis relying on a screw fixation are well reported.[1-17] However, most of the studies on press-fit implants and joint replacement technology have focused on surgical techniques.[3, 18-23] One European centre using this technique has reported on health related quality of life (HRQOL) for a group of individuals with transfemoral amputation (TFA).[3] Data from other centres are needed to assess the effectiveness of the technique in different settings. Aim This study aimed at reporting HRQOL data at baseline and up to 2-year follow-up for a group of TFAs treated by Osseointegration Group of Australia who followed the Osseointegration Group of Australia Accelerated Protocol (OGAAP), in Sydney between 08/12/2011 and 09/04/2014. Method A total of 16 TFAs (7 females and 9 males, age 51 ± 12 y, height 1.73 ± 0.12 m, weight 83 ±18 kg) participated in this study. The cause of amputation was trauma or congenital limb deficiency for 11 (69%) and 5 (31%) participants, respectively. A total of 12 (75%) participants were prosthetic users while 4(25%) were wheelchair bound prior the surgery. The HRQOL were obtained from Questionnaire for Persons with Transfemoral Amputation (Q-TFA) using the four main scales (i.e., Prosthetic use, Mobility, Problem, Global) one year before and between 6.5 and 24 months after the Stage 1 of the surgeries for the baseline and follow-up, respectively. Results The lapse of time before and after Stage 1 was -6.19±3.54 and 10.83±3.58 months respectively. The raw score and percentage of improvement are presented in Figures 1 and 2, respectively. Discussion & Conclusion The average results demonstrated an improvement in each domain, particularly in the reduction of problems and an increase in global state. Furthermore, 56%, 75%, 94% and 69% of the participants reported an improvement in Prosthetic use, Mobility, Problem, Global scales, respectively. These results were comparable to previous studies relying of screwed fixation confirming that press-fit implantation is a viable alternative for bone-anchored prostheses.[1, 7, 8]

Aging and everyday technology

This paper presents a literature review and indicative findings that are part of ongoing research into aging and technology. The review finds that research on older technology users has contributed valuable information on the impact of age-related changes on technology use, as well as older adults’ acceptance and adoption of contemporary technologies. However, the majority of the research has been conducted from the perspective of age-related differences in use and performance, or it is medically-focused, examining the potential of technology to improve an individual’s quality of life (QoL), for example. Research on older people and technology does not adequately address the integration of technology into the everyday lives of older people. This paper identifies that there is substantial opportunity to examine older users’ everyday information and communication technology (ICT) use, and to inform technology design beyond measures of performance, usability and adoption.

Mosaic PPM1D mutations are associated with predisposition to breast and ovarian cancer

Improved sequencing technologies offer unprecedented opportunities for investigating the role of rare genetic variation in common disease. However, there are considerable challenges with respect to study design, data analysis and replication. Using pooled next-generation sequencing of 507 genes implicated in the repair of DNA in 1,150 samples, an analytical strategy focused on protein-truncating variants (PTVs) and a large-scale sequencing case-control replication experiment in 13,642 individuals, here we show that rare PTVs in the p53-inducible protein phosphatase PPM1D are associated with predisposition to breast cancer and ovarian cancer. PPM1D PTV mutations were present in 25 out of 7,781 cases versus 1 out of 5,861 controls (P = 1.12 × 10-5), including 18 mutations in 6,912 individuals with breast cancer (P = 2.42 × 10-4) and 12 mutations in 1,121 individuals with ovarian cancer (P = 3.10 × 10-9). Notably, all of the identified PPM1D PTVs were mosaic in lymphocyte DNA and clustered within a 370-base-pair region in the final exon of the gene, carboxy-terminal to the phosphatase catalytic domain. Functional studies demonstrate that the mutations result in enhanced suppression of p53 in response to ionizing radiation exposure, suggesting that the mutant alleles encode hyperactive PPM1D isoforms. Thus, although the mutations cause premature protein truncation, they do not result in the simple loss-of-function effect typically associated with this class of variant, but instead probably have a gain-of-function effect. Our results have implications for the detection and management of breast and ovarian cancer risk. More generally, these data provide new insights into the role of rare and of mosaic genetic variants in common conditions, and the use of sequencing in their identification.

BPMN process views construction

Process view technology is catching more attentions in modern business process management, as it enables the customisation of business process representation. This capability helps improve the privacy protection, authority control, flexible display, etc., in business process modelling. One of approaches to generate process views is to allow users to construct an aggregate on their underlying processes. However, most aggregation approaches stick to a strong assumption that business processes are always well-structured, which is over strict to BPMN. Aiming to build process views for non-well-structured BPMN processes, this paper investigates the characteristics of BPMN structures, tasks, events, gateways, etc., and proposes a formal process view aggregation approach to facilitate BPMN process view creation. A set of consistency rules and construction rules are defined to regulate the aggregation and guarantee the order preservation, structural and behaviour correctness and a novel aggregation technique, called EP-Fragment, is developed to tackle non-well-structured BPMN processes.

Scalable document hashing and retrieval

This thesis studies document signatures, which are small representations of documents and other objects that can be stored compactly and compared for similarity. This research finds that document signatures can be effectively and efficiently used to both search and understand relationships between documents in large collections, scalable enough to search a billion documents in a fraction of a second. Deliverables arising from the research include an investigation of the representational capacity of document signatures, the publication of an open-source signature search platform and an approach for scaling signature retrieval to operate efficiently on collections containing hundreds of millions of documents.

The effect of ginger (Zingiber officinale) on platelet aggregation: A systematic literature review

Background The potential effect of ginger on platelet aggregation is a widely-cited concern both within the published literature and to clinicians; however, there has been no systematic appraisal of the evidence to date. Methods Using the PRISMA guidelines, we systematically reviewed the results of clinical and observational trials regarding the effect of ginger on platelet aggregation in adults compared to either placebo or baseline data. Studies included in this review stipulated the independent variable was a ginger preparation or isolated ginger compound, and used measures of platelet aggregation as the primary outcome. Results Ten studies were included, comprising eight clinical trials and two observational studies. Of the eight clinical trials, four reported that ginger reduced platelet aggregation, while the remaining four reported no effect. The two observational studies also reported mixed findings. Discussion Many of the studies appraised for this review had moderate risks of bias. Methodology varied considerably between studies, notably the timeframe studied, dose of ginger used, and the characteristics of subjects recruited (e.g. healthy vs. patients with chronic diseases). Conclusion The evidence that ginger affects platelet aggregation and coagulation is equivocal and further study is needed to definitively address this question.

Josh lovegrove: Infinite

Research background: Infinite by Josh Lovegrove is an extended play album co-produced in collaboration with ARIA-nominated artist Mark Sholtez. The album consists of original songs written by Lovegrove, and songs co-written by Lovegrove, Carfoot and Sholtez. The scholarly context of the project is informed by studies of songwriting and ambiguity by Negus and Astor, new approaches to the study of record production associated with Zagorski-Thomas, and studies of creative labour by Hesmondhalgh and Baker. The project focused on the dynamics of musical performance and production in the recording studio, investigating the interface between the creative tasks of songwriting, production and performance in the recording of popular music. The project asked, in what ways do collaborative songwriting and production processes overlap, how has the nature of creative labour changed as a result of new forms of digital recording technology, and how can these aspects inform developments in the learning and teaching of popular music? Research contribution: The project has demonstrated the nuanced ways that the practices of record production have changed in the face of technological developments, and how this has impacted upon the specific forms and divisions of creative labour. Research significance: The project resulted in a well-reviewed album release that has further established Lovegrove’s reputation as a performer and songwriter. The creative work underpins ongoing research into the nature of popular music production, in particular how the nature of collaborative songwriting can inform innovation in the learning and teaching of popular music.

Compact features for birdcall retrieval from environmental acoustic recordings

Bioacoustic data can be used for monitoring animal species diversity. The deployment of acoustic sensors enables acoustic monitoring at large temporal and spatial scales. We describe a content-based birdcall retrieval algorithm for the exploration of large data bases of acoustic recordings. In the algorithm, an event-based searching scheme and compact features are developed. In detail, ridge events are detected from audio files using event detection on spectral ridges. Then event alignment is used to search through audio files to locate candidate instances. A similarity measure is then applied to dimension-reduced spectral ridge feature vectors. The event-based searching method processes a smaller list of instances for faster retrieval. The experimental results demonstrate that our features achieve better success rate than existing methods and the feature dimension is greatly reduced.

Twitter hashtags from ad hoc to calculated publics

As the use of Twitter has become more commonplace throughout many nations, its role in political discussion has also increased. This has been evident in contexts ranging from general political discussion through local, state, and national elections (such as in the 2010 Australian elections) to protests and other activist mobilisation (for example in the current uprisings in Tunisia, Egypt, and Yemen, as well as in the controversy around Wikileaks). Research into the use of Twitter in such political contexts has also developed rapidly, aided by substantial advancements in quantitative and qualitative methodologies for capturing, processing, analysing, and visualising Twitter updates by large groups of users. Recent work has especially highlighted the role of the Twitter hashtag – a short keyword, prefixed with the hash symbol ‘#’ – as a means of coordinating a distributed discussion between more or less large groups of users, who do not need to be connected through existing ‘follower’ networks. Twitter hashtags – such as ‘#ausvotes’ for the 2010 Australian elections, ‘#londonriots’ for the coordination of information and political debates around the recent unrest in London, or ‘#wikileaks’ for the controversy around Wikileaks thus aid the formation of ad hoc publics around specific themes and topics. They emerge from within the Twitter community – sometimes as a result of pre-planning or quickly reached consensus, sometimes through protracted debate about what the appropriate hashtag for an event or topic should be (which may also lead to the formation of competing publics using different hashtags). Drawing on innovative methodologies for the study of Twitter content, this paper examines the use of hashtags in political debate in the context of a number of major case studies.

Drink and drug driving in Australian young adult users and non-users of illicit stimulants

- Introduction There is limited understanding of how young adults’ driving behaviour varies according to long-term substance involvement. It is possible that regular users of amphetamine-type stimulants (i.e. ecstasy (MDMA) and methamphetamine) may have a greater predisposition to engage in drink/drug driving compared to non-users. We compare offence rates, and self-reported drink/drug driving rates, for stimulant users and non-users in Queensland, and examine contributing factors. - Methods The Natural History Study of Drug Use is a prospective longitudinal study using population screening to recruit a probabilistic sample of amphetamine-type stimulant users and non-users aged 19-23 years. At the 4 ½ year follow-up, consent was obtained to extract data from participants’ Queensland driver records (ATS users: n=217, non-users: n=135). Prediction models were developed of offence rates in stimulant users controlling for factors such as aggression and delinquency. - Results Stimulant users were more likely than non-users to have had a drink-driving offence (8.7% vs. 0.8%, p < 0.001). Further, about 26% of ATS users and 14% of non-users self-reported driving under the influence of alcohol during the last 12 months. Among stimulant users, drink-driving was independently associated with last month high-volume alcohol consumption (Incident Rate Ratio (IRR): 5.70, 95% CI: 2.24-14.52), depression (IRR: 1.28, 95% CI: 1.07-1.52), low income (IRR: 3.57, 95% CI: 1.12-11.38), and male gender (IRR: 5.40, 95% CI: 2.05-14.21). - Conclusions Amphetamine-type stimulant use is associated with increased long-term risk of drink-driving, due to a number of behavioural and social factors. Inter-sectoral approaches which target long-term behaviours may reduce offending rates.