Is Use of Optional Attributes and Associations in Conceptual Modeling Always Problematic? Theory and Empirical Tests

Prior research has argued that use of optional properties in conceptual models results in loss of information about the semantics of the domains represented by the models. Empirical research undertaken to date supports this argument. Nevertheless, no systematic analysis has been done of whether use of optional properties is always problematic. Furthermore, prior empirical research might have deliberately or unwittingly employed models where use of optionality always causes problems. Accordingly, we examine analytically whether use of optional properties is always problematic. We employ our analytical results to inform the design of an experiment where we systematically examined the impact of optionality on users’ ability to understand domains represented by different types of conceptual models. We found evidence that use of optionality undermines users’ ability to understand the domain represented by a model but that this effect weakens when use of mandatory properties to replace optional properties leads to more-complex models.

Improving the Semantics of Conceptual-Modeling Grammars:A New Perspective on an Old Problem

A core activity in information systems development involves understanding the
conceptual model of the domain that the information system supports. Any conceptual model is ultimately created using a conceptual-modeling (CM) grammar. Accordingly, just as high quality conceptual models facilitate high quality systems development, high quality CM grammars facilitate high quality conceptual modeling. This paper seeks to provide a new perspective on improving the quality of CM grammar semantics. For the past twenty years, the leading approach to this topic has drawn on ontological theory. However, the ontological approach captures just half of the story. It needs to be coupled with a logical approach. We show how ontological quality and logical quality interrelate and we outline three contributions of a logical approach: the ability to see familiar conceptualmodeling problems in simpler ways, the illumination of new problems, and the ability to prove the benefit of modifying CM grammars.

Regulation of TGF-β1-Driven Differentiation of Human Lung Fibroblasts: Emerging Roles of Cathepsin B and Cystatin C

Lung matrix homeostasis partly depends on the fine regulation of proteolytic activities. We examined the expression of human cysteine cathepsins (Cats) and their relative contribution to TGF-β1-induced fibroblast differentiation into myofibroblasts. Assays were conducted using both primary fibroblasts obtained from patients with idiopathic pulmonary fibrosis (IPF) and human lung CCD-19Lu fibroblasts. Pharmacological inhibition and genetic silencing of Cat B diminished α-smooth muscle actin expression, delayed fibroblast differentiation and led to an accumulation of intracellular 50-kDa TGF-β1. Moreover addition of Cat B generated 25-kDa mature form of TGF-β1 in Cat B siRNA-pretreated lysates. Inhibition of Cat B decreased Smad 2/3 phosphorylation, but had no effect on p38 MAPK and JNK phosphorylation indicating that Cat B mostly disturbs TGF-β1-driven canonical Smad signaling pathway. While mRNA expression of cystatin C was stable, its secretion, which was inhibited by brefeldin A, increased during TGF-β1-induced differentiation of IPF and CCD-19Lu fibroblasts. In addition cystatin C participated in the control of extracellular Cats, since its gene silencing restored their proteolytic activities. These data support the notion that Cat B participates in lung myofibrogenesis as suggested for stellate cells during liver fibrosis. Moreover, we propose that TGF-β1 promotes fibrosis by driving the effective cystatin C-dependent inhibition of extracellular matrix-degrading Cats.

Getting In and Getting On? The Experiences of Young People with Visual Impairments and Hearing Impairments in Third-Level Education

Young disabled people continue to be under-represented throughout further and higher education settings. Drawing on Pierre Bourdieu’s social theory of habitus, capital and field, this paper explores the practices of domination and oppression that have made it difficult for young people with visual impairments and hearing impairments to participate in third-level education on the same basis as non-disabled people. Twenty young people with hearing impairments and visual impairments were interviewed about their educational experiences. In addition, 31 interviews were conducted with third-level education providers, policy-makers and non-governmental organisations. This article has two aims: firstly, to critically examine the experiences of young people with hearing impairments and visual impairments in accessing and engaging with support provisions in further and higher education settings; and secondly, to identify and explore the diversity of ways in which these young people have managed and responded to the practices they have encountered. This article emphasises the journey from ability to dis-ability that young people with hearing and visual impairments experience in their quest for educational achievement. The ambiguities of “inclusion”, “widening participation” and “support” are highlighted and critiqued for their extensive failure to challenge taken-for-granted discourses.

Prospective clinical audit of chloral hydrate administration practices in a neonatal unit

Aim: Chloral hydrate is generally considered a safe and effective single dosing procedural sedative for neonates in the clinical setting. However, its safety profile as a repetitive dosing maintenance sedative is largely unknown. This study aimed to document current administration practices of chloral hydrate in the Neonatal Unit, Royal Children's Hospital, Melbourne, Australia, over a 6-month period.

Methods: Patients who had been prescribed chloral hydrate during the specified audit period were recruited into the study and prospectively followed for a period of 28 days, or until they were discharged from the unit. Demographic data were collected on recruitment, and daily documentation of chloral hydrate administration was recorded.

Results: A total of 238 doses of chloral hydrate were administered to a cohort of 32 patients during the study period. The majority of the audited doses (84%) were ordered as repeating doses. Doses were more likely to be given at night than during the day, and the median dosage for repetitive dosing was found to be above the study site's recommended dosing range. Pre-dose and/or post-dose assessment of distress/agitation accompanied dosage approximately half of the time. The audit did not reveal any recognisable pattern of sedation maintenance or weaning process for patients who received multiple doses.

Conclusions: Health-care professionals caring for hospitalised infants should be made aware of the potential risks of chloral hydrate as a repetitive dosing sedative, and of the importance of systematically evaluating the appropriateness and effectiveness of utilising such pharmacological intervention for managing and treating distress.

Identification of the Flagellin Glycosylation System in Burkholderia cenocepacia and the Contribution of Glycosylated Flagellin to Evasion of Human Innate Immune Responses

Burkholderia cenocepacia is an opportunistic pathogen threatening patients with cystic fibrosis. Flagella are required for biofilm formation, as well as adhesion to and invasion of epithelial cells. Recognition of flagellin via the Toll-like receptor 5 (TLR5) contributes to exacerbate B. cenocepacia-induced lung epithelial inflammatory responses. In this study, we report that B. cenocepacia flagellin is glycosylated on at least 10 different sites with a single sugar, 4,6-dideoxy-4-(3-hydroxybutanoylamino)-d-glucose. We have identified key genes that are required for flagellin glycosylation, including a predicted glycosyltransferase gene that is linked to the flagellin biosynthesis cluster and a putative acetyltransferase gene located within the O-antigen lipopolysaccharide cluster. Another O-antigen cluster gene, rmlB, which is required for flagellin glycan and O-antigen biosynthesis, was essential for bacterial viability, uncovering a novel target against Burkholderia infections. Using glycosylated and nonglycosylated purified flagellin and a cell reporter system to assess TLR5-mediated responses, we also show that the presence of glycan in flagellin significantly impairs the inflammatory response of epithelial cells. We therefore suggest that flagellin glycosylation reduces recognition of flagellin by host TLR5, providing an evasive strategy to infecting bacteria.

Multi-centre research in Australia:analysis of a recent National Health and Medical Research Council-funded project

BACKGROUND AND OBJECTIVE: Human research ethics committees provide essential review of research projects to ensure the ethical conduct of human research. Several recent reports have highlighted a complex process for successful application for human research ethics committee approval, particularly for multi-centre studies. Limited resources are available for the execution of human clinical research in Australia and around the world.

METHODS: This report overviews the process of ethics approval for a National Health and Medical Research Council-funded multi-centre study in Australia, focussing on the time and resource implications of such applications in 2007 and 2008.

RESULTS: Applications were submitted to 16 hospital and two university human research ethics committees. The total time to gain final approval from each committee ranged between 13 and 77 days (median = 46 days); the entire process took 16 months to complete and the research officer's time was estimated to cost $A34 143.

CONCLUSIONS: Obstacles to timely human research ethics committee approval are reviewed, including recent, planned and potential initiatives that could improve the ethics approval of multi-centre research.

Small leucine rich proteoglycan family regulates multiple signalling pathways in neural development and maintenance

The small leucine-rich repeat proteoglycan (SLRPs) family of proteins currently consists of five classes, based on their structural composition and chromosomal location. As biologically active components of the extracellular matrix (ECM), SLRPs were known to bind to various collagens, having a role in regulating fibril assembly, organization and degradation. More recently, as a function of their diverse proteins cores and glycosaminoglycan side chains, SLRPs have been shown to be able to bind various cell surface receptors, growth factors, cytokines and other ECM components resulting in the ability to influence various cellular functions. Their involvement in several signaling pathways such as Wnt, transforming growth factor-β and epidermal growth factor receptor also highlights their role as matricellular proteins. SLRP family members are expressed during neural development and in adult neural tissues, including ocular tissues. This review focuses on describing SLRP family members involvement in neural development with a brief summary of their role in non-neural ocular tissues and in response to neural injury.

Factors influencing survival after kidney transplant failure

BACKGROUND: The failure of a kidney transplant is now a common reason for initiation of dialysis therapy. Kidney transplant recipients commencing dialysis have greater morbidity and mortality than transplant-naïve, incident dialysis patients. This study aimed to identify variables associated with survival after graft failure.

METHODS: All recipients of first, deceased donor kidney transplants performed in Northern Ireland between 1986 and 2005 who had a functioning graft at 12 months were included (n = 585). Clinical and blood-derived variables (age, gender, primary renal disease, diabetic status, smoking status, human leukocyte antigen (HLA) mismatch, acute rejection episodes, immunosuppression, cardiovascular disease, graft survival, haemoglobin, albumin, phosphate, C reactive protein, estimated glomerular filtration rate (eGFR), rate of eGFR decline, dialysis modality, and access) were collected prospectively and investigated for association with re-transplantation and survival. The association between re-transplantation and survival was explored by modelling re-transplantation as a time-dependent covariate.

RESULTS: Median follow-up time was 12.1 years. Recipients with a failing graft (158/585) demonstrated rapid loss of eGFR prior to graft failure, reducing the time available to plan for alternative renal replacement therapy. Median survival after graft failure was 3.0 years. In multivariate analysis, age and re-transplantation were associated with survival after graft failure. Re-transplantation was associated with an 88% reduction in mortality.

CONCLUSIONS: Optimal management of kidney transplant recipients with failing grafts requires early recognition of declining function and proactive preparation for re-transplantation given the substantial survival benefit this confers. The survival benefit associated with re-transplantation persists after prolonged exposure to immunosuppressive therapy.

European Cystic Fibrosis Society Standards of Care: Quality Management in cystic fibrosis

Since the earliest days of cystic fibrosis (CF) treatment, patient data have been recorded and reviewed in order to identify the factors that lead to more favourable outcomes. Large data repositories, such as the US Cystic Fibrosis Registry, which was established in the 1960s, enabled successful treatments and patient outcomes to be recognized and improvement programmes to be implemented in specialist CF centres. Over the past decades, the greater volumes of data becoming available through Centre databases and patient registries led to the possibility of making comparisons between different therapies, approaches to care and indeed data recording. The quality of care for individuals with CF has become a focus at several levels: patient, centre, regional, national and international. This paper reviews the quality management and improvement issues at each of these levels with particular reference to indicators of health, the role of CF Centres, regional networks, national health policy, and international data registration and comparisons. 

A novel experimental approach to investigate radiolysis processes in liquid samples using collimated radiation sources

Here is detailed a novel and low-cost experimental method for high-throughput automated fluid sample irradiation. The sample is delivered via syringe pump to a nozzle, where it is expressed in the form of a hanging droplet into the path of a beam of ionising radiation. The dose delivery is controlled by an upstream lead shutter, which allows the beam to reach the droplet for a user defined period of time. The droplet is then further expressed after irradiation until it falls into one well of a standard microplate. The entire system is automated and can be operated remotely using software designed in-house, allowing for use in environments deemed unsafe for the user (synchrotron beamlines, for example). Depending on the number of wells in the microplate, several droplets can be irradiated before any human interaction is necessary, and the user may choose up to 10 samples per microplate using an array of identical syringe pumps, the design of which is described here. The nozzles consistently produce droplets of 25.1 ± 0.5 μl.

Holocene vegetation change in relation to fire and volcanic events in Jilin, Northeastern China

Volatiles erupted from large-scale explosive volcanic activities have a significant impact on climate and environmental changes. As an important ecological factor, the occurrence of fire is affected by vegetation cover, and fire can feed back into both vegetation and climatic change. The causes of fire events are diverse; and can include volcanic eruptions. The amount of charcoal in sediment sequences is related to the frequency and intensity of fire, and hence under good preservation conditions fire history can be reconstructed from fossil charcoal abundance. Until now, little research on the role of fire has been carried out in northeastern China. In this study, through research on charcoal and tephra shards from Gushantun and Hanlongwan, Holocene vegetation change in relation to fire and volcanic events in Jilin, Northeastern China, was investigated. Where tephra shards are present in Gushantun it is associated with low level of both conifers and broadleaved trees, and is also associated with a pronounced charcoal peak. This suggests forest cover was greatly reduced from a fire caused by an eruption of the Tianchi volcano. We also detected one tephra layer in Hanlongwan, which also has the almost same depth with low level forest pollen values and one charcoal peak. This was caused probably by an eruption of the Jinlongdingzi volcano.

Phenotypic characterization of an international Pseudomonas aeruginosa reference panel: strains of cystic fibrosis (CF) origin show less in vivo virulence than non-CF strains

Pseudomonas aeruginosa causes chronic lung infections in people with cystic fibrosis (CF) and acute opportunistic infections in people without CF. Forty two P. aeruginosa strains from a range of clinical and environmental sources were collated into a single reference strain panel to harmonise research on this diverse opportunistic pathogen. To facilitate further harmonized and comparable research on P. aeruginosa, we characterised the panel strains for growth rates, motility, virulence in the Galleria mellonella infection model, pyocyanin and alginate production, mucoid phenotype, lipopolysaccharide (LPS) pattern, biofilm formation, urease activity, antimicrobial and phage susceptibilities. Phenotypic diversity across the P. aeruginosa panel was apparent for all phenotypes examined agreeing with the marked variability seen in this species. However, except for growth rate, the phenotypic diversity among strains from CF versus non-CF sources was comparable. CF strains were less virulent in the G. mellonella model than non-CF strains (p=0.037). Transmissible CF strains generally lacked O antigen, produced less pyocyanin, and had low virulence in G. mellonella. Further, in the three sets of sequential CF strains, virulence, O-antigen expression and pyocyanin production were higher in the earlier isolate compared to the isolate obtained later in infection. Overall, full phenotypic characterization of the defined panel of P. aeruginosa strains increases our understanding of the virulence and pathogenesis of P. aeruginosa and may provide a valuable resource for the testing of novel therapies against this problematic pathogen.

Platform Competition as Network Contestability

Recent research in industrial organisation has investigated the essential place that middlemen have in the networks that make up our global economy. In this paper we attempt to understand how such middlemen compete with each other through a game theoretic analysis using novel techniques from decision-making under ambiguity.
We model a purposely abstract and reduced model of one middleman who provides a two-sided platform, mediating surplus-creating interactions between two users. The middleman evaluates uncertain outcomes under positional ambiguity, taking into account the possibility of the emergence of an alternative middleman offering intermediary services to the two users.
Surprisingly, we find many situations in which the middleman will purposely extract maximal gains from her position. Only if there is relatively low probability of devastating loss of business under competition, the middleman will adopt a more competitive attitude and extract less from her position.