Discovery of candidate serum proteomic and metabolomic biomarkers in ankylosing spondylitis

Ankylosing Spondylitis (AS) is a common inflammatory rheumatic disease with a predilection for the axial skeleton, affecting 0.2% of the population. Current diagnostic criteria rely on a composite of clinical and radiological changes, with a mean time to diagnosis of 5 to 10 years. In this study we employed nano liquid-chromatography mass spectrometry analysis to detect and quantify proteins and small compounds including endogenous peptides and metabolites in serum from 18 AS patients and nine healthy individuals. We identified a total of 316 proteins in serum, of which 22 showed significant up- or down-regulation (p < 0.05) in AS patients. Receiver operating characteristic analysis of combined levels of serum amyloid P component and inter-α-trypsin inhibitor heavy chain 1 revealed high diagnostic value for Ankylosing Spondylitis (area under the curve = 0.98). We also depleted individual sera of proteins to analyze endogenous peptides and metabolic compounds. We detected more than 7000 molecular features in patients and healthy individuals. Quantitative MS analysis revealed compound profiles that correlate with the clinical assessment of disease activity. One molecular feature identified as a Vitamin D3 metabolite-(23S,25R)-25-hydroxyvitamin D3 26,23-peroxylactone-was down-regulated in AS. The ratio of this vitamin D metabolite versus vitamin D binding protein serum levels was also altered in AS as compared with controls. These changes may contribute to pathological skeletal changes in AS. Our study is the first example of an integration of proteomic and metabolomic techniques to find new biomarker candidates for the diagnosis of Ankylosing Spondylitis

A road safety strategy for Norfolk Island, an Australian external territory

Norfolk Island is an Australian external territory in Oceania. The significant road safety reforms in Australia from the 1970s onward bypassed the island, and most road safety ‘silver bullets’ adopted in other Australian jurisdictions were not introduced. While legislative amendments in 2010 introduced mandatory seat belt wearing for vehicle occupants on Norfolk Island, other critical issues face the community including drink driving by residents and visitors, occupant protection for vehicle passengers, and the provision of a more protective road environment. The release of the first Norfolk Island road safety strategy 2014-2016 proposed, inter alia: • a lower BAC of 0.05 and the introduction of compulsory driver alcohol and drug testing by police; • targeted enforcement of occupant protection for vehicle passengers, particularly for passengers riding on vehicle tray backs; • education interventions to challenge values held by some members of the community that support unsafe road use; • ensuring that driver information, training and testing is adequate for all drivers; • identification and rectification of hazardous roadside infrastructure, particularly barrier protection at “high drop locations” within the road network; and • developing a specification for vehicle standards for vehicles imported into Norfolk Island. Norfolk Island is engaging in a process of integration with the Australian community, and wider issues relating to funding and resources have impacted on the implementation of the road safety strategy. The response to the strategy will be discussed, particularly in terms of current attempts to address drink driving and the provision of a safer road environment.

A critical appraisal of the relational management paradigm in an international setting: A future research agenda

Purpose In the mainstream relationship management literature, critical appraisal of the relationship paradigm in an international setting is virtually non-existent. The extant literature reveals a gap in terms of linking relationship management theories with international management. Furthermore, little research attention has been paid to synthesise the existing theories in a cohesive manner towards developing a theoretical paradigm in the interface of the importer-supplier relationship dyad. Thus, the purpose of this paper is to strengthen the theoretical grounds of relationship marketing in an international setting in an importer-exporter relationship context. Design/methodology/approach The paper follows a comprehensive review approach and applies the fundamental theory of trust and commitment to identify the relational factors. More precisely, the paper identifies and applies other relevant theories such as internationalisation process theory, resource-based theory of the firm, dependence theory and transaction cost theory in developing an innovative theoretical paradigm. Findings Based on the integration of extant theories, this paper proposes a new direction in the theoretical realm of the trust and commitment building process within an importer and supplier relationship management paradigm. The research concludes that trust and commitment are the focal factors within the international relational paradigm. Research limitations/implications The proposed research direction suggests an emerging framework integrating mainstream theoretical variables of trust and commitment in importer and foreign-supplier context. This novel framework has the potential for use in further research. Originality/value This paper advances a grounded theoretical exploration within an international management domain in the context of importers and foreign-suppliers.

Pathophysiology team teaching: Bioscientist contribution to knowledge integration in a nursing subject

Bioscience content within undergraduate nursing degrees provides foundational knowledge of pathophysiology, anatomy, physiology, microbiology and pharmacology. However, nursing students often find studying the bioscience components of undergraduate nursing program daunting (Friedel & Treagust 2005, Craft et al. 2013). This is related to factors such as the volume of content, degree of difficulty and insufficient linkage between bioscience concepts and nurses' clinical practice. Students who are unable to conceptualise the relevance of bioscience with nursing subjects and subsequent nursing practice may not appreciate the broader importance of bioscience, and hence may adopt a surface approach to learning (Craft et al. 2013). The aim of this study was to develop a model within Nursing Practice in the Context theory subject, to include a bioscientist lecturing to complement the nursing lecturer, in order to explicitly demonstrate links between physiology, pathophysiology and nursing practice.

Advancing practice in critical care: A model of knowledge integration

It could be argued that advancing practice in critical care has been superseded by the advanced practice agenda. Some would suggest that advancing practice is focused on the core attributes of an individuals practice progressing onto advanced practice status. However, advancing practice is more of a process than identifiable skills and as such is often negated when viewing the development of practitioners to the advanced practice level. For example practice development initiatives can be seen as advancing practice for the masses which ensures that practitioners are following the same level of practice. The question here is; are they developing individually.

Interaction Between Two Residues in the Inter-Domain Interface of Escherichia coli Peptidase N Modulates Catalytic Activity

The role of interaction between Asn259 (catalytic domain) with Gln821 (C-terminal domain) in PeptidaseN was investigated. The k(cat) of PeptidaseN containing Asn259Asp or Gln821Glu is enhanced whereas it is suppressed in Asn259AspGln821Glu. Structural analysis shows this interaction to change the relative disposition of active site residues, which modulates catalytic activity.

Intra and Inter-Molecular Communications Through Protein Structure Network

Communication within and across proteins is crucial for the biological functioning of proteins. Experiments such as mutational studies on proteins provide important information on the amino acids, which are crucial for their function. However, the protein structures are complex and it is unlikely that the entire responsibility of the function rests on only a few amino acids. A large fraction of the protein is expected to participate in its function at some level or other. Thus, it is relevant to consider the protein structures as a completely connected network and then deduce the properties, which are related to the global network features. In this direction, our laboratory has been engaged in representing the protein structure as a network of non-covalent connections and we have investigated a variety of problems in structural biology, such as the identification of functional and folding clusters, determinants of quaternary association and characterization of the network properties of protein structures. We have also addressed a few important issues related to protein dynamics, such as the process of oligomerization in multimers, mechanism on protein folding, and ligand induced communications (allosteric effect). In this review we highlight some of the investigations which we have carried out in the recent past. A review on protein structure graphs was presented earlier, in which the focus was on the graphs and graph spectral properties and their implementation in the study of protein structure graphs/networks (PSN). In this article, we briefly summarize the relevant parts of the methodology and the focus is on the advancement brought out in the understanding of protein structure-function relationships through structure networks. The investigations of structural/biological problems are divided into two parts, in which the first part deals with the analysis of PSNs based on static structures obtained from x-ray crystallography. The second part highlights the changes in the network, associated with biological functions, which are deduced from the network analysis on the structures obtained from molecular dynamics simulations.

The introduction of an Inter-professional learning unit: staff and student perspectives

Background The School of Clinical Sciences comprises a number of health disciplines including podiatry, paramedic science, pharmacy, medical imaging and radiation therapy. A new inter-professional unit was introduced in 2014, which covered key introductory learnings applicable for future health practitioners. This study examined teaching staff and student perspectives about their experience with the new unit for first year students. Methods Qualitative interviews with teaching staff (n=9) and focus group interviews with students (5 groups which ranged in size from 4-30) were conducted. Extensive notes were taken during the interviews Issues emerging from the interviews were identified and organised according to themes and subthemes. Results Four major themes were identified namely: Something new; To be or not to be that is the question; Advantages of the new unit; and Areas for improvement. Previous staff experience with inter-professional learning (IPL) had been ad-hoc, whereas the new unit brought together several disciplines in a planned and deliberate way. There was strong philosophical agreement about the value of IPL but some debate about the extent to which the unit provided IPL experience. The unit was seen as assisting students’ social and academic adjustment to university and provided opportunity for professional socialisation, exposure to macro and micro aspects of the Australian health care system and various types of communication. For podiatry students it was their first opportunity to formally meet and work with other podiatry students and moved their identity from ‘university student’ to ‘podiatry student’. Other positives included providing the opportunity for staff and students to interact at an early stage with the perceived benefit of reducing attrition. Areas for unit improvement included institutional arrangements, unit administration aspects and assessment. Conclusion The unit was seen as beneficial by staff and students however, students were more polarised in their views than staff. There was a tension between feeling apart of and learning about one's own profession and feeling apart of and learning about the roles of other health professionals in relation to patient care and the health care system.

Comment on path integration of a quadratic action with a generalized memory

Using the promeasure technique, we give an alternative evaluation of a path integral corresponding to a quadratic action with a generalized memory.

Effect of inter-edge Coulomb interactions on transport through a point contact in nu=5/2 quantum Hall state

We study transport across a point contact separating two line junctions in a nu = 5/2 quantum Hall system. We analyze the effect of inter-edge Coulomb interactions between the chiral bosonic edge modes of the half-filled Landau level (assuming a Pfaffian wave function for the half-filled state) and of the two fully filled Landau levels. In the presence of inter-edge Coulomb interactions between all the six edges participating in the line junction, we show that the stable fixed point corresponds to a point contact that is neither fully opaque nor fully transparent. Remarkably, this fixed point represents a situation where the half-filled level is fully transmitting, while the two filled levels are completely backscattered; hence the fixed point Hall conductance is given by G(H) = 1/2e(2)/h. We predict the non-universal temperature power laws by which the system approaches the stable fixed point from the two unstable fixed points corresponding to the fully connected case (G(H) = 5/2e(2)/h) and the fully disconnected case (G(H) = 0).

Advancing practice in critical care : A model of knowledge integration: A Singaporean context

It could be argued that advancing practice in critical care has been superseded by the advanced practice agenda. Some would suggest that advancing practice is focused on the core attributes of an individuals practice progressing onto advanced practice status. However, advancing practice is more of a process than identifiable skills and as such is often negated when viewing the development of practitioners to the advanced practice level. For example practice development initiatives can be seen as advancing practice for the masses which ensures that practitioners are following the same level of practice. The question here is; are they developing individually. To discuss the potential development of a conceptual model of knowledge integration pertinent to critical care nursing practice. In an attempt to explore the development of leading edge critical care thinking and practice, a new model for advancing practice in critical care is proposed. This paper suggests that reflection may not be the best model for advancing practice unless the individual practitioner has a sound knowledge base both theoretically and experientially. Drawing on the contemporary literature and recent doctoral research, the knowledge integration model presented here uses multiple learning strategies that are focused in practise to develop practice, for example the use of work-based learning and clinical supervision. Ongoing knowledge acquisition and its relationship with previously held theory and experience will enable individual practitioners to advance their own practice as well as being a resource for others.

Advancing practice in critical care: A model of knowledge integration

Explore and describe a conceptual model of knowledge integration pertinent to the development of individual practitioners in critical care. Discussion of how multiple learning strategies that are embedded in practice can be beneficial in developing knowledge.

Inter-lamellar shear resistance confers compressive stiffness in the intervertebral disc: An image-based modelling study on the bovine caudal disc

The intervertebral disc withstands large compressive loads (up to nine times bodyweight in humans) while providing flexibility to the spinal column. At a microstructural level, the outer sheath of the disc (the annulus fibrosus) comprises 12–20 annular layers of alternately crisscrossed collagen fibres embedded in a soft ground matrix. The centre of the disc (the nucleus pulposus) consists of a hydrated gel rich in proteoglycans. The disc is the largest avascular structure in the body and is of much interest biomechanically due to the high societal burden of disc degeneration and back pain. Although the disc has been well characterized at the whole joint scale, it is not clear how the disc tissue microstructure confers its overall mechanical properties. In particular, there have been conflicting reports regarding the level of attachment between adjacent lamellae in the annulus, and the importance of these interfaces to the overall integrity of the disc is unknown. We used a polarized light micrograph of the bovine tail disc in transverse cross-section to develop an image-based finite element model incorporating sliding and separation between layers of the annulus, and subjected the model to axial compressive loading. Validation experiments were also performed on four bovine caudal discs. Interlamellar shear resistance had a strong effect on disc compressive stiffness, with a 40% drop in stiffness when the interface shear resistance was changed from fully bonded to freely sliding. By contrast, interlamellar cohesion had no appreciable effect on overall disc mechanics. We conclude that shear resistance between lamellae confers disc mechanical resistance to compression, and degradation of the interlamellar interface structure may be a precursor to macroscopic disc degeneration.

The development and inter-relationship of metacognitive components among primary school children

Much interest has been expressed in the construct metacognition, the individual's knowledge and control of his own cognitive processes. Recent educational proposals have suggested the training of general metacognitive principles in schools. The exact nature of the construct has, however, remained vague. The aim of the present study was to provide some clarity. In a study of the metacognitive responses of 144 primary school children (aged 7‐11 years) four measures commonly used to assess metacognitive function were examined. First, the content of each measure was examined. Secondly, in an attempt to identify a metacognitive factor, commonality among the measures, both of developmental patterns and statistical relationship, was sought. Whilst a common pattern of development in the children's responses to the four measures was identified, factor analysis failed to provide evidence for a common metacognitive factor and unified construct.

The impact of inter-fraction set-up errors on the probability of pulmonary and cardiac complication in left-sided breast cancer patients

Purpose This study evaluated the impact of patient set-up errors on the probability of pulmonary and cardiac complications in the irradiation of left-sided breast cancer. Methods and Materials Using the CMS XiO Version 4.6 (CMS Inc., St Louis, MO) radiotherapy planning system's NTCP algorithm and the Lyman -Kutcher-Burman (LKB) model, we calculated the DVH indices for the ipsilateral lung and heart and the resultant normal tissue complication probabilities (NTCP) for radiation-induced pneumonitis and excess cardiac mortality in 12 left-sided breast cancer patients. Results Isocenter shifts in the posterior direction had the greatest effect on the lung V20, heart V25, mean and maximum doses to the lung and the heart. Dose volume histograms (DVH) results show that the ipsilateral lung V20 tolerance was exceeded in 58% of the patients after 1cm posterior shifts. Similarly, the heart V25 tolerance was exceeded after 1cm antero-posterior and left-right isocentric shifts in 70% of the patients. The baseline NTCPs for radiation-induced pneumonitis ranged from 0.73% - 3.4% with a mean value of 1.7%. The maximum reported NTCP for radiation-induced pneumonitis was 5.8% (mean 2.6%) after 1cm posterior isocentric shift. The NTCP for excess cardiac mortality were 0 % in 100% of the patients (n=12) before and after setup error simulations. Conclusions Set-up errors in left sided breast cancer patients have a statistically significant impact on the Lung NTCPs and DVH indices. However, with a central lung distance of 3cm or less (CLD <3cm), and a maximum heart distance of 1.5cm or less (MHD<1.5cm), the treatment plans could tolerate set-up errors of up to 1cm without any change in the NTCP to the heart.