Magnetic resonance spectroscopy and neurocognitive dysfunction in obstructive sleep apnea before and after CPAP treatment

STUDY OBJECTIVES: To determine whether cerebral metabolite changes may underlie abnormalities of neurocognitive function and respiratory control in OSA. DESIGN: Observational, before and after CPAP treatment. SETTING: Two tertiary hospital research institutes. PARTICIPANTS: 30 untreated severe OSA patients, and 25 age-matched healthy controls, all males free of comorbidities, and all having had detailed structural brain analysis using voxel-based morphometry (VBM). MEASUREMENTS AND RESULTS: Single voxel bilateral hippocampal and brainstem, and multivoxel frontal metabolite concentrations were measured using magnetic resonance spectroscopy (MRS) in a high resolution (3T) scanner. Subjects also completed a battery of neurocognitive tests. Patients had repeat testing after 6 months of CPAP. There were significant differences at baseline in frontal N-acetylaspartate/choline (NAA/Cho) ratios (patients [mean (SD)] 4.56 [0.41], controls 4.92 [0.44], P = 0.001), and in hippocampal choline/creatine (Cho/Cr) ratios (0.38 [0.04] vs 0.41 [0.04], P = 0.006), (both ANCOVA, with age and premorbid IQ as covariates). No longitudinal changes were seen with treatment (n = 27, paired t tests), however the hippocampal differences were no longer significant at 6 months, and frontal NAA/Cr ratios were now also significantly different (patients 1.55 [0.13] vs control 1.65 [0.18] P = 0.01). No significant correlations were found between spectroscopy results and neurocognitive test results, but significant negative correlations were seen between arousal index and frontal NAA/Cho (r = -0.39, corrected P = 0.033) and between % total sleep time at SpO(2) < 90% and hippocampal Cho/Cr (r = -0.40, corrected P = 0.01). CONCLUSIONS: OSA patients have brain metabolite changes detected by MRS, suggestive of decreased frontal lobe neuronal viability and integrity, and decreased hippocampal membrane turnover. These regions have previously been shown to have no gross structural lesions using VBM. Little change was seen with treatment with CPAP for 6 months. No correlation of metabolite concentrations was seen with results on neurocognitive tests, but there were significant negative correlations with OSA severity as measured by severity of nocturnal hypoxemia. CITATION: O'Donoghue FJ; Wellard RM; Rochford PD; Dawson A; Barnes M; Ruehland WR; Jackson ML; Howard ME; Pierce RJ; Jackson GD. Magnetic resonance spectroscopy and neurocognitive dysfunction in obstructive sleep apnea before and after CPAP treatment.

Perceptions of visitor relationship marketing opportunities by destination marketers : an importance-performance analysis

Customer relationship marketing (CRM) initiatives are increasingly being adopted by businesses in the attempt to enhance brand loyalty and stimulate repeat purchases. The purpose of this study was to examine the extent to which destination marketing organisations (DMOs) around the world have developed a visitor relationship marketing (VRM) orientation. The proposition underpinning the study is that maintaining meaningful dialogue with previous visitors in some markets would represent a more efficient use of resources than above the line advertising to attract new visitors. Importance-performance analysis was utilised to measure destination marketers’ perceptions of the efficacy of CRM initiatives, and then rate their own organisation’s performance across the same range of initiatives. A key finding was that mean importance was higher than perceived performance for every item. While the small sample limits generalisability, in general there are appears to be a lack of strategic intent by DMOs to invest in VRM.

When There's Love

This work is an installation featuring three video projections, music and mirror balls. The three projections fill the walls with scrolling text borrowed from love song lyrics. Headphones in the gallery space allow you to hear a male voice sing the same words to an impromptu tune. Mirror balls send fragments of light spinning around the room while The Righteous Brothers’ Unchained Melody plays on repeat. This work emphasizes fragmentary, repetitious and spatio-temporal experiences of language in order to question the symbolic conventions of romance. By exaggerating and mixing hackneyed symbolic elements, this work extends on some of Nicolas Bourriaud’s theoretical insights into the creative and critical strategies of ‘postproduction’. In particular, it toys with the intersections between popular culture and inter-subjective experiences.

Flightless, secreted through a late endosome/lysosome pathway, binds LPS and dampens cytokine secretion.

Flightless (Flii) is upregulated in response to wounding and has been shown to function in wound closure and scarring. In macrophages intracellular Flii negatively modulates TLR signalling and dampens cytokine production. We now show that Flii is constitutively secreted from macrophages and fibroblasts and is present in human plasma. Secretion from fibroblasts is upregulated in response to scratch wounding and LPS-activated macrophages also temporally upregulate their secretion of Flii. Using siRNA, wild-type and mutant proteins we show that Flii is secreted via a late endosomal/lysosomal pathway that is regulated by Rab7 and Stx11. Flii contains 11 leucine rich repeat (LRR) domains in its N-terminus that have nearly 50% similarity to those in the extracellular pathogen binding portion of Toll-like receptor 4 (TLR4). We show secreted Flii can also bind LPS and has the ability to alter macrophage activation. LPS activation of macrophages in Flii depleted conditioned media leads to enhanced macrophage activation and increased TNF secretion compared to cells activated in the presence of Flii. These results show secreted Flii binds to LPS and in doing so alters macrophage activation and cytokine secretion, suggesting that like the intracellular pool of Flii, secreted Flii also has the ability to alter inflammation.

The role of organisational culture, trust and mechanisms in inter-project knowledge sharing

Knowledge has been recognised as a powerful yet intangible asset, which is difficult to manage. This is especially true in a project environment where there is the potential to repeat mistakes, rather than learn from previous experiences. The literature in the project management field has recognised the importance of knowledge sharing (KS) within and between projects. However, studies in that field focus primarily on KS mechanisms including lessons learned (LL) and post project reviews as the source of knowledge for future projects, and only some preliminary research has been carried out on the aspects of project management offices (PMOs) and organisational culture (OC) in KS. This study undertook to investigate KS behaviours in an inter-project context, with a particular emphasis on the role of trust, OC and a range of knowledge sharing mechanisms (KSM) in achieving successful inter-project knowledge sharing (I-PKS). An extensive literature search resulted in the development of an I-PKS Framework, which defined the scope of the research and shaped its initial design. The literature review indicated that existing research relating to the three factors of OC, trust and KSM remains inadequate in its ability to fully explain the role of these contextual factors. In particular, the literature review identified these areas of interest: (1) the conflicting answers to some of the major questions related to KSM, (2) the limited empirical research on the role of different trust dimensions, (3) limited empirical evidence of the role of OC in KS, and (4) the insufficient research on KS in an inter-project context. The resulting Framework comprised the three main factors including: OC, trust and KSM, demonstrating a more integrated view of KS in the inter-project context. Accordingly, the aim of this research was to examine the relationships between these three factors and KS by investigating behaviours related to KS from the project managers‘ (PMs‘) perspective. In order to achieve the aim, this research sought to answer the following research questions: 1. How does organisational culture influence inter-project knowledge sharing? 2. How does the existence of three forms of trust — (i) ability, (ii) benevolence and (iii) integrity — influence inter-project knowledge sharing? 3. How can different knowledge sharing mechanisms (relational, project management tools and process, and technology) improve inter-project knowledge sharing behaviours? 4. How do the relationships between these three factors of organisational culture, trust and knowledge sharing mechanisms improve inter-project knowledge sharing? a. What are the relationships between the factors? b. What is the best fit for given cases to ensure more effective inter-project knowledge sharing? Using multiple case studies, this research was designed to build propositions emerging from cross-case data analysis. The four cases were chosen on the basis of theoretical sampling. All cases were large project-based organisations (PBOs), with a strong matrix-type structure, as per the typology proposed by the Project Management Body of Knowledge (PMBoK) (2008). Data were collected from project management departments of the respective organisations. A range of analytical techniques were used to deal with the data including pattern matching logic and explanation building analysis, complemented by the use of NVivo for data coding and management. Propositions generated at the end of the analyses were further compared with the extant literature, and practical implications based on the data and literature were suggested in order to improve I-PKS. Findings from this research conclude that OC, trust, and KSM contribute to inter-project knowledge sharing, and suggest the existence of relationships between these factors. In view of that, this research identified the relationships between different trust dimensions, suggesting that integrity trust reinforces the relationship between ability trust and knowledge sharing. Furthermore, this research demonstrated that characteristics of culture and trust interact to reinforce preferences for mechanisms of knowledge sharing. This means that cultures that facilitate characteristics of Clan type are more likely to result in trusting relationships, hence are more likely to use organic sources of knowledge for both tacit and explicit knowledge exchange. In contrast, cultures that are empirically driven, based on control, efficiency, and measures (characteristics of Hierarchy and Market types) display tendency to develop trust primarily in ability of non-organic sources, and therefore use these sources to share mainly explicit knowledge. This thesis contributes to the project management literature by providing a more integrative view of I-PKS, bringing the factors of OC, trust and KSM into the picture. A further contribution is related to the use of collaborative tools as a substitute for static LL databases and as a facilitator for tacit KS between geographically dispersed projects. This research adds to the literature on OC by providing rich empirical evidence of the relationships between OC and the willingness to share knowledge, and by providing empirical evidence that OC has an effect on trust; in doing so this research extends the theoretical propositions outlined by previous research. This study also extends the research on trust by identifying the relationships between different trust dimensions, suggesting that integrity trust reinforces the relationship between ability trust and KS. Finally, this research provides some directions for future studies.

A mitochondrial genome phylogeny of termites (Blattodea: Termitoidae) : robust support for interfamilial relationships and molecular synapomorphies define major clades

Despite their ecological significance as decomposers and their evolutionary significance as the most speciose eusocial insect group outside the Hymenoptera, termite (Blattodea: Termitoidae or Isoptera) evolutionary relationships have yet to be well resolved. Previous morphological and molecular analyses strongly conflict at the family level and are marked by poor support for backbone nodes. A mitochondrial (mt) genome phylogeny of termites was produced to test relationships between the recognised termite families, improve nodal support and test the phylogenetic utility of rare genomic changes found in the termite mt genome. Complete mt genomes were sequenced for 7 of the 9 extant termite families with additional representatives of each of the two most speciose families Rhinotermitidae (3 of 7 subfamilies) and Termitidae (3 of 8 subfamilies). The mt genome of the well supported sister group of termites, the subsocial cockroach Cryptocercus, was also sequenced. A highly supported tree of termite relationships was produced by all analytical methods and data treatment approaches, however the relationship of the termites + Cryptocercus clade to other cockroach lineages was highly affected by the strong nucleotide compositional bias found in termites relative to other dictyopterans. The phylogeny supports previously proposed suprafamilial termite lineages, the Euisoptera and Neoisoptera, a later derived Kalotermitidae as sister group of the Neoisoptera and a monophyletic clade of dampwood (Stolotermitidae, Archotermopsidae) and harvester termites (Hodotermitidae). In contrast to previous termite phylogenetic studies, nodal supports were very high for family-level relationships within termites. Two rare genomic changes in the mt genome control region were found to be molecular synapomorphies for major clades. An elongated stem-loop structure defined the clade Polyphagidae + (Cryptocercus + termites), and a further series of compensatory base changes in this stem loop is synapomorphic for the Neoisoptera. The complicated repeat structures first identified in Reticulitermes, composed of short (A-type) and long (B-type repeats) defines the clade Heterotermitinae + Termitidae, while the secondary loss of A-type repeats is synapomorphic for the non-macrotermitine Termitidae.

Effect of caffeine on adenosine-induced reversible perfusion defects assessed by automated analysis

Objectives This prospective study investigated the effects of caffeine ingestion on the extent of adenosine-induced perfusion abnormalities during myocardial perfusion imaging (MPI). Methods Thirty patients with inducible perfusion abnormalities on standard (caffeine-abstinent) adenosine MPI underwent repeat testing with supplementary coffee intake. Baseline and test MPIs were assessed for stress percent defect, rest percent defect, and percent defect reversibility. Plasma levels of caffeine and metabolites were assessed on both occasions and correlated with MPI findings. Results Despite significant increases in caffeine [mean difference 3,106 μg/L (95% CI 2,460 to 3,752 μg/L; P < .001)] and metabolite concentrations over a wide range, there was no statistically significant change in stress percent defect and percent defect reversibility between the baseline and test scans. The increase in caffeine concentration between the baseline and the test phases did not affect percent defect reversibility (average change −0.003 for every 100 μg/L increase; 95% CI −0.17 to 0.16; P = .97). Conclusion There was no significant relationship between the extent of adenosine-induced coronary flow heterogeneity and the serum concentration of caffeine or its principal metabolites. Hence, the stringent requirements for prolonged abstinence from caffeine before adenosine MPI—based on limited studies—appear ill-founded.

Relationship between the nature of the search task types and query reformulation behaviour

Success of query reformulation and relevant information retrieval depends on many factors, such as users’ prior knowledge, age, gender, and cognitive styles. One of the important factors that affect a user’s query reformulation behaviour is that of the nature of the search tasks. Limited studies have examined the impact of the search task types on query reformulation behaviour while performing Web searches. This paper examines how the nature of the search tasks affects users’ query reformulation behaviour during information searching. The paper reports empirical results from a user study in which 50 participants performed a set of three Web search tasks – exploratory, factorial and abstract. Users’ interactions with search engines were logged by using a monitoring program. 872 unique search queries were classified into five query types – New, Add, Remove, Replace and Repeat. Users submitted fewer queries for the factual task, which accounted for 26%. They completed a higher number of queries (40% of the total queries) while carrying out the exploratory task. A one-way MANOVA test indicated a significant effect of search task types on users’ query reformulation behaviour. In particular, the search task types influenced the manner in which users reformulated the New and Repeat queries.

Analysis of genome survey sequences and SSR marker development for Siamese Mud Carp, Henicorhynchus siamensis, using 454 Pyrosequencing

Siamese mud carp (Henichorynchus siamensis) is a freshwater teleost of high economic importance in the Mekong River Basin. However, genetic data relevant for delineating wild stocks for management purposes currently are limited for this species. Here, we used 454 pyrosequencing to generate a partial genome survey sequence (GSS) dataset to develop simple sequence repeat (SSR) markers from H. siamensis genomic DNA. Data generated included a total of 65,954 sequence reads with average length of 264 nucleotides, of which 2.79% contain SSR motifs. Based on GSS-BLASTx results, 10.5% of contigs and 8.1% singletons possessed significant similarity (E value < 10–5) with the majority matching well to reported fish sequences. KEGG analysis identified several metabolic pathways that provide insights into specific potential roles and functions of sequences involved in molecular processes in H. siamensis. Top protein domains detected included reverse transcriptase and the top putative functional transcript identified was an ORF2-encoded protein. One thousand eight hundred and thirty seven sequences containing SSR motifs were identified, of which 422 qualified for primer design and eight polymorphic loci have been tested with average observed and expected heterozygosity estimated at 0.75 and 0.83, respectively. Regardless of their relative levels of polymorphism and heterozygosity, microsatellite loci developed here are suitable for further population genetic studies in H. siamensis and may also be applicable to other related taxa.

Sustainable urban development : an integrated framework for urban planning and development

Sustainable development has long been promoted as the best answer to the world’s environmental problems. This term has generated mass appeal as it implies that both the development of the built environment and its associated resource consumption can be achieved without jeopardising the natural environment. In the urban context, sustainability issues have been reflected in the promotion of sustainable urban development, which emphasises the sensible exploitation of scarce natural resources for urbanisation in a manner that allows future generations to repeat the process. This chapter highlights attempts to promote sustainable urban development through an integration of three important considerations: planning, development and the ecosystem. It highlights the fact that spatial planning processes were traditionally driven by economic and social objectives, and rarely involved promoting the sustainability agenda to achieve a sustainable urban future. As a result, rapid urbanisation has created a variety of pressures on the ecosystem upon which we rely. It is believed that the integration of the urban planning and development processes within the limitations of the ecosystem, monitored by a sustainability assessment mechanism, would offer a better approach to maintaining sustainable resource use without compromising urban development.

Identification of long intergenic region sequences involved in maize streak virus replication

The main cis-acting control regions for replication of the single-stranded DNA genome of maize streak virus (MSV) are believed to reside within an approximately 310 nt long intergenic region (LIR). However, neither the minimum LIR sequence required nor the sequence determinants of replication specificity have been determined experimentally. There are iterated sequences, or iterons, both within the conserved inverted-repeat sequences with the potential to form a stem-loop structure at the origin of virion-strand replication, and upstream of the rep gene TATA box (the rep-proximal iteron or RPI). Based on experimental analyses of similar iterons in viruses from other geminivirus genera and their proximity to known Rep-binding sites in the distantly related mastrevirus wheat dwarf virus, it has been hypothesized that the iterons may be Rep-binding and/or -recognition sequences. Here, a series of LIR deletion mutants was used to define the upper bounds of the LIR sequence required for replication. After identifying MSV strains and distinct mastreviruses with incompatible replication-specificity determinants (RSDs), LIR chimaeras were used to map the primary MSV RSD to a 67 nt sequence containing the RPI. Although the results generally support the prevailing hypothesis that MSV iterons are functional analogues of those found in other geminivirus genera, it is demonstrated that neither the inverted-repeat nor RPI sequences are absolute determinants of replication specificity. Moreover, widely divergent mastreviruses can trans-replicate one another. These results also suggest that sequences in the 67 nt region surrounding the RPI interact in a sequence-specific manner with those of the inverted repeat.

A rep-based hairpin inhibits replication of diverse maize streak virus isolates in a transient assay

Centre for High-Performance Computing, Rosebank, Cape Town, South Africa Maize streak disease, caused by the A strain of the African endemic geminivirus, maize streak mastrevirus (MSV-A), threatens the food security and livelihoods of subsistence farmers throughout sub-Saharan Africa. Using a well-established transient expression assay, this study investigated the potential of a spliceable-intron hairpin RNA (hpRNA) approach to interfere with MSV replication. Two strategies were explored: (i) an inverted repeat of a 662 bp region of the MSV replication-associated protein gene (rep), which is essential for virus replication and is therefore a good target for post-transcriptional gene silencing; and (ii) an inverted repeat of the viral long intergenic region (LIR), considered for its potential to trigger transcriptional silencing of the viral promoter region. After co-bombardment of cultured maize cells with each construct and an infectious partial dimer of the cognate virus genome (MSV-Kom), followed by viral replicativeform-specific PCR, it was clear that, whilst the hairpin rep construct (pHPrepDI662) completely inhibited MSV replication, the LIR hairpin construct was ineffective in this regard. In addition, pHPrepDI662 inhibited or reduced replication of six MSV-A genotypes representing the entire breadth of known MSV-A diversity. Further investigation by real-time PCR revealed that the pHPrepDI662 inverted repeat was 22-fold more effective at reducing virus replication than a construct containing the sense copy, whilst the antisense copy had no effect on replication when compared with the wild type. This is the first indication that an hpRNA strategy targeting MSV rep has the potential to protect transgenic. © 2011 SGM.

Akin Collection : curation of a collaboration between Indigenous artists and fashion designers to create a retail-ready luxury fashion label

The Akin collection is the outcome of a project to lead, guide and curate a luxury, retail-ready fashion collection from a collaboration between five emerging fashion designers and five established Indigenous artists. Research background There is a history of Indigenous artists in Australia being treated unethically; by misappropriation and misrepresentation of their work, inequity of payment for their creativity and little acknowledgement of their cultural contribution to collaborative fashion product sold globally. This has created an atmosphere of bad press for fashion, as well as a fear for emerging designers to include/collaborate with Indigenous artists for textile prints. This fear has been so intense that many emerging Australian designers are now seeking collaboration with other countries’ Indigenous communities, thus missing out on a rich cultural and diverse aesthetic that could brand a truly unique Australian label in the international marketplace. The fashion brands that have collaborated with Indigenous Australian artists have traditionally been a ONE designer label incorporating Indigenous prints, for collections that have little acknowledgement of the artist’s contribution and strong branding for the label and/or fashion designer. This collection seeks to create an equitable and profitable fashion collection under one brand where all artists and designers receive equal payment, equal promotion/credibility, as well as equal royalties for any garments ordered by retailers. Research question Is it possible to curate an ethical, luxury, retail-ready, international fashion brand with a collaboration of five (5) emerging designers and five (5) Indigenous artists? Research contribution In the fashion industry, existing collaborations for Australian Indigenous artists have been with ONE fashion designer or one existing fashion label. This is the first fashion collection created under one brand name with equal credibility and profits for both artists and designers. The process involved presenting workshops ranging from understanding the logistics and timing of the fashion supply chain, costing of garments, the process of ‘ranging’ fashion product for a collection and creating repeat prints from a specific artwork, ready for digital printing. A workshop was also facilitated so both designer and artist could work together to create (and co-own) unique t shirt prints. Lawyers were consulted and ethical contracts were drawn up to cover all participants in this innovative collaboration. While the collaboration of artist and designer was important, the collection required curation of all elements so that the final collection came together as a professional and cohesive, quality, retail- ready product. This could only be created by experienced practitioners. Research significance The Akin Collection is the first Australian fashion brand to be created as a collaboration between five equally recognised Indigenous artists and five emerging fashion designers. It has familiarized the Indigenous artists to the logistics and culture of the fashion industry and the emerging fashion designers have been familiarized to the logistics and culture of how to collaborate with the unique Indigenous artwork that exists in Australia. After only three months, this culminated in a fashion parade showcasing the Akin collection to over 400 members of the public, government, media and retail. Feedback has been strong from the media and the industry, and a lookbook and photoshoot has been organised to promote and sell the collection both nationally and internationally. These concepts plus the curation outlined, has created a successful, luxury, quality collection ready for the international runways. This project has devised an ethical template for other Indigenous artists and emerging designers to create fashion collections that offer a unique aesthetic that could position and brand Australian fashion in the international marketplace. Key Words Indigenous artists, emerging fashion designers, Australian fashion design, ethical fashion, luxury Australian brand

Factors affecting two- and five-year re-offence rates in Queensland drink drivers

Risk factors for repeat drink driving, an important road safety issue, are well known, but estimates of Australian recidivism rates by risk factors, apart from a recent NSW study, are not. Driving records of a cohort of Queensland drink drivers matched by age, region, BAC level and prior offence to participants in a drink driving rehabilitation program were used to estimate sex-specific two- and five-year re-offence rates overall and by these factors. Estimates of the proportion of Queensland drink drivers with a prior DD offence in 2004 were used to standardise rates to the Queensland drink driving population. Rates were higher in remote areas, as were rates in males, young drivers, drivers with high BAC levels and in drivers with one and especially with at least two prior DD convictions. Five-year rates for Queensland were estimated as 21.8% in males and 16.4% in females, appreciably higher than in NSW.

Long terminal repeats act as androgen-responsive enhancers for the PSA-Kallikrein locus

The androgen receptor (AR) signaling pathway is a common therapeutic target for prostate cancer, because it is critical for the survival of both hormone-responsive and castrate-resistant tumor cells. Most of the detailed understanding that we have of AR transcriptional activation has been gained by studying classical target genes. For more than two decades, Kallikrein 3 (KLK3) (prostate-specific antigen) has been used as a prototypical AR target gene, because it is highly androgen responsive in prostate cancer cells. Three regions upstream of the KLK3 gene, including the distal enhancer, are known to contain consensus androgen-responsive elements required for AR-mediated transcriptional activation. Here, we show that KLK3 is one of a specific cluster of androgen-regulated genes at the centromeric end of the kallikrein locus with enhancers that evolved from the long terminal repeat (LTR) (LTR40a) of an endogenous retrovirus. Ligand-dependent recruitment of the AR to individual LTR-derived enhancers results in concurrent up-regulation of endogenous KLK2, KLK3, and KLKP1 expression in LNCaP prostate cancer cells. At the molecular level, a kallikrein-specific duplication within the LTR is required for maximal androgen responsiveness. Therefore, KLK3 represents a subset of target genes regulated by repetitive elements but is not typical of the whole spectrum of androgen-responsive transcripts. These data provide a novel and more detailed understanding of AR transcriptional activation and emphasize the importance of repetitive elements as functional regulatory units