Genetic variants underlying risk of endometriosis: Insights from meta-analysis of eight genome-wide association and replication datasets

BACKGROUND Endometriosis is a heritable common gynaecological condition influenced by multiple genetic and environmental factors. Genome-wide association studies (GWASs) have proved successful in identifying common genetic variants of moderate effects for various complex diseases. To date, eight GWAS and replication studies from multiple populations have been published on endometriosis. In this review, we investigate the consistency and heterogeneity of the results across all the studies and their implications for an improved understanding of the aetiology of the condition. METHODS Meta-analyses were conducted on four GWASs and four replication studies including a total of 11 506 cases and 32 678 controls, and on the subset of studies that investigated associations for revised American Fertility Society (rAFS) Stage III/IV including 2859 cases. The datasets included 9039 cases and 27 343 controls of European (Australia, Belgium, Italy, UK, USA) and 2467 cases and 5335 controls of Japanese ancestry. Fixed and Han and Elkin random-effects models, and heterogeneity statistics (Cochran's Q test), were used to investigate the evidence of the nine reported genome-wide significant loci across datasets and populations. RESULTS Meta-analysis showed that seven out of nine loci had consistent directions of effect across studies and populations, and six out of nine remained genome-wide significant (P < 5 × 10(-8)), including rs12700667 on 7p15.2 (P = 1.6 × 10(-9)), rs7521902 near WNT4 (P = 1.8 × 10(-15)), rs10859871 near VEZT (P = 4.7 × 10(-15)), rs1537377 near CDKN2B-AS1 (P = 1.5 × 10(-8)), rs7739264 near ID4 (P = 6.2 × 10(-10)) and rs13394619 in GREB1 (P = 4.5 × 10(-8)). In addition to the six loci, two showed borderline genome-wide significant associations with Stage III/IV endometriosis, including rs1250248 in FN1 (P = 8 × 10(-8)) and rs4141819 on 2p14 (P = 9.2 × 10(-8)). Two independent inter-genic loci, rs4141819 and rs6734792 on chromosome 2, showed significant evidence of heterogeneity across datasets (P < 0.005). Eight of the nine loci had stronger effect sizes among Stage III/IV cases, implying that they are likely to be implicated in the development of moderate to severe, or ovarian, disease. While three out of nine loci were inter-genic, the remaining were in or near genes with known functions of biological relevance to endometriosis, varying from roles in developmental pathways to cellular growth/carcinogenesis. CONCLUSIONS Our meta-analysis shows remarkable consistency in endometriosis GWAS results across studies, with little evidence of population-based heterogeneity. They also show that the phenotypic classifications used in GWAS to date have been limited. Stronger associations with Stage III/IV disease observed for most loci emphasize the importance for future studies to include detailed sub-phenotype information. Functional studies in relevant tissues are needed to understand the effect of the variants on downstream biological pathways.

What are the barriers of quality survivorship care for haematology cancer patients? Qualitative insights from cancer nurses

Purpose: Many haematological cancer survivors report long-term physiological and psychosocial effects beyond treatment completion. These survivors continue to experience impaired quality of life (QoL) as a result of their disease and aggressive treatment. As key members of the multidisciplinary team, the purpose of this study is to examine the insights of cancer nurses to inform future developments in survivorship care provision. Methods: Open text qualitative responses from two prospective Australian cross-sectional surveys of nurses (n=136) caring for patients with haematological cancer. Data were analysed thematically, using an inductive approach to identify themes. Results: This study has identified a number of issues that nurses perceive as barriers to quality survivorship care provision. Two main themes were identified; the first relating to the challenges nurses face in providing care (‘care challenges’), and the second relating to the challenges of providing survivorship care within contemporary health care systems (‘system challenges’). Conclusions: Cancer nurses perceive the nature of haematological cancer and its treatment, and of the health care system itself, as barriers to the provision of quality survivorship care. Care challenges such as the lack of a standard treatment path and the relapsing or remitting nature of haematological cancers may be somewhat intractable, but system challenges relating to clearly defining and delineating professional responsibilities and exchanging information with other clinicians are not. Implications for Cancer Survivors: Addressing the issues identified will facilitate cancer nurses’ provision of survivorship care, and help address haematological survivors’ needs with regard to the physical and psychosocial consequences of their cancer and treatment.

New insights into the molecular structure of kaolinite–methanol intercalation complexes

A series of kaolinite–methanol complexes with different basal spacings were synthesized using guest displacement reactions of the intercalation precursors kaolinite–N-methyformamide (Kaol–NMF), kaolinite–urea (Kaol–U), or kaolinite–dimethylsulfoxide (Kaol–DMSO), with methanol (Me). The interaction of methanol with kaolinite was examined using X-ray diffraction (XRD), infrared spectroscopy (IR), and nuclear magnetic resonance (NMR). Kaolinite (Kaol) initially intercalated with N-methyformamide (NMF), urea (U), or dimethylsulfoxide (DMSO) before subsequent reaction with Me formed final kaolinite–methanol (Kaol–Me) complexes characterized by basal spacing ranging between 8.6 Å and 9.6 Å, depending on the pre-intercalated reagent. Based on a comparative analysis of the three Kaol–Me displacement intercalation complexes, three types of Me intercalation products were suggested to have been present in the interlayer space of Kaol: (1) molecules grafted onto a kaolinite octahedral sheet in the form of a methoxy group (Al-O-C bond); (2) mobile Me and/or water molecules kept in the interlayer space via hydrogen bonds that could be partially removed during drying; and (3) a mixture of types 1 and 2, with the methoxy group (Al-O-C bond) grafted onto the Kaol sheet and mobile Me and/or water molecules coexisted in the system after the displacement reaction by Me. Various structural models that reflected four possible complexes of Kaol–Me were constructed for use in a complimentary computational study. Results from the calculation of the methanol kaolinite interaction indicate that the hydroxyl oxygen atom of methanol plays the dominant role in the stabilization and localization of the molecule intercalated in the interlayer space, and that water existing in the intercalated Kaol layer is inevitable.

Criteria for interpreting kimberlite as coherent: Insights from the Muskox and Jericho kimberlites (Nunavut, Canada)

The Jurassic Muskox and Jericho kimberlites (Northern Slave Province, Nunavut, Canada) contain a variety of facies exhibiting different geometries, contact relationships, internal organisation, country rock abundance and olivine shapes, although many have similar matrix/groundmass mineralogies and textures. Five facies are examined that either have characteristics consistent with coherent rocks in general (i.e. intrusive and extrusive non-fragmental rocks) or are mineralogically and texturally similar to kimberlite described as coherent (or apparent coherent). Three facies are interpreted as coherent on the basis of: (1) geological setting, (2) apparent-porphyritic texture, (3) sharp contacts with fragmental kimberlite, (4) relative abundance of elongate and unbroken olivine crystals and (5) paucity of country rock xenoliths, while the remaining two facies are interpreted as fragmental on the basis of: (1) the gradational contacts with demonstrably fragmental kimberlite, (2) relative abundance and range of sizes of country rock lithic clasts and (3) numerous broken olivine crystals. Comparisons are made with coherent and apparent-coherent kimberlite from the literature. Our three coherent facies are similar to literature reported coherent kimberlite dykes hosted in country rock (CKd) in terms of internal organisation, low abundance of country rock xenoliths, and apparent-porphyritic texture. Conversely, our two fragmental facies share attributes with previously described pipe-filling coherent and apparent-coherent kimberlite (CKpf) in terms of geometry, internal organisation and abundance of country rock xenoliths. We conclude that CKd and most CKpf, although similar in matrix/groundmass mineralogy and texture, can be distinguished on the basis of internal organisation, country rock lithic clast abundance, texture (e.g. apparent-porphyritic texture) and possibly olivine crystal shapes and suggest that fragmental kimberlite is more common than reported.

The role of design in the future of digital channels: Conceptual insights and future research directions

Purpose In the past channel literature has looked to other disciplines in developing and refining their theories, models and methods in order to evolve the field. This paper traces such history and highlights the substantial changes caused by the digital age. In light of this, the inclusion of design theory into future channel management is presented to overcome existing concerns. Design/methodology/approach A comprehensive review of literature on the history of channels, the emotional experience (people), limitations of digital innovation (technology) and the role of design (business) has been conducted to create a new approach, built upon the theory of the techno-economic innovation model. Findings The findings of this study propose design-led channel management as a new research area, providing novel research questions and future research directions. The inclusion of design and emotion theories indicates that the future of digital channel design requires a deeper understanding of customers and needs to go beyond technological advances. Theoretical implications The findings provide an opportunity to explore dynamic theories and methodologies within the field of design that will broaden the horizons and challenge existing notions in channel literature. Originality/value This paper is the first paper that introduces the theory of Emotionate, as the next evolution of channel literature. The value of Emotionate lies in providing a new design-led process of integrating emotion to provide advice to practitioners as well as identifies research areas for academia, thereby extending the reach and richness of this emerging research field.

Becoming bilingual: Children’s insights about making friends in bilingual settings

The majority of the world speaks more than one language yet the impact of learning a second language has rarely been studied from a child’s perspective. This paper describes monolingual children’s insights into becoming bilingual at four time points: two months before moving to another country (while living in Australia), as well as one, six, and twelve months after moving to Germany. The participants were two monolingual English-speaking siblings (a male aged 7- to 8-years and a female aged 9- to 10-years) who subsequently learned to speak German. At each of the four time points, interviews were undertaken with each child using child-friendly drawing and questionnaire techniques. Three themes were identified: (1) the children’s awareness of language competence; (2) inclusion factors, and; (3) exclusion factors that influenced friendship formation. The impact of language ability on making friends was a dominant theme that arose across the four time points and was triangulated across data collection methods. The children made friends with others who had similar language competence in German, even though they were younger, and did not share the same first language. Age-matched peers who were more competent in German were less likely to be described as friends. Across all three themes, the playground was highlighted by both children as the key site where becoming bilingual most strongly impacted initiation and negotiation of friendships. Becoming bilingual impacted the children’s friendship formation and socialization opportunities with more competent language users.

New insights from IODP Expedition 340 offshore Montserrat: First drilling of large volcanic island landslides

Montserrat now provides one of the most complete datasets for understanding the character and tempo of hazardous events at volcanic islands. Much of the erupted material ends up offshore, and this offshore record may be easier to date due to intervening hemiplegic sediments between event beds. The offshore dataset includes the first scientific drilling of volcanic island landslides during IODP Expedition 340, together with an unusually comprehensive set of shallow sediment cores and 2-D and 3-D seismic surveys. Most recently in 2013, Remotely Operated Vehicle (ROV) dives mapped and sampled the surface of the main landslide deposits. This contribution aims to provide an overview of key insights from ongoing work on IODP Expedition 340 Sites offshore Montserrat.Key objectives are to understand the composition (and hence source), emplacement mechanism (and hence tsunami generation) of major landslides, together with their frequency and timing relative to volcanic eruption cycles. The most recent major collapse event is Deposit 1, which involved ~1.8 km cubed of material and produced a blocky deposit at ~12-14ka. Deposit 1 appears to have involved not only the volcanic edifice, but also a substantial component of a fringing bioclastic shelf, and material locally incorporated from the underlying seafloor. This information allows us to test how first-order landslide morphology (e.g. blocky or elongate lobes) is related to first-order landslide composition. Preliminary analysis suggests that Deposit 1 occurred shortly before a second major landslide on the SW of the island (Deposit 5). It may have initiated English's Crater, but was not associated with a major change in magma composition. An associated turbidite-stack suggests it was emplaced in multiple stages, separated by at least a few hours and thus reducing the tsunami magnitude. The ROV dives show that mega-blocks in detail comprise smaller-scale breccias, which can travel significant distances without complete disintegration. Landslide Deposit 2 was emplaced at ~130ka, and is more voluminous (~8.4km cubed). It had a much more profound influence on the magmatic system, as it was linked to a major explosive mafic eruption and formation of a new volcanic centre (South Soufriere Hills) on the island. Site U1395 confirms a hypothesis based on the site survey seismic data that Deposit 2 includes a substantial component of pre-existing seafloor sediment. However, surprisingly, this pre-existing seafloor sediment in the lower part of Deposit 2 at Site U1395 is completely undeformed and flat lying, suggesting that Site U1395 penetrated a flat lying block. Work to date material from the upper part of U1396, U1395 and U1394 will also be summarised. This work is establishing a chronostratigraphy of major events over the last 1 Ma, with particularly detailed constraints during the last ~250ka. This is helping us to understand whether major landslides are related to cycles of volcanic eruptions.

Super DNAging - New insights into DNA integrity, genome stability and telomeres in the oldest old

Reductions in DNA integrity, genome stability, and telomere length are strongly associated with the aging process, age-related diseases as well as the age-related loss of muscle mass. However, in people reaching an age far beyond their statistical life expectancy the prevalence of diseases, such as cancer, cardiovascular disease, diabetes or dementia, is much lower compared to “averagely” aged humans. These inverse observations in nonagenarians (90–99 years), centenarians (100–109 years) and super-centenarians (110 years and older) require a closer look into dynamics underlying DNA damage within the oldest old of our society. Available data indicate improved DNA repair and antioxidant defense mechanisms in “super old” humans, which are comparable with much younger cohorts. Partly as a result of these enhanced endogenous repair and protective mechanisms, the oldest old humans appear to cope better with risk factors for DNA damage over their lifetime compared to subjects whose lifespan coincides with the statistical life expectancy. This model is supported by study results demonstrating superior chromosomal stability, telomere dynamics and DNA integrity in “successful agers”. There is also compelling evidence suggesting that life-style related factors including regular physical activity, a well-balanced diet and minimized psycho-social stress can reduce DNA damage and improve chromosomal stability. The most conclusive picture that emerges from reviewing the literature is that reaching “super old” age appears to be primarily determined by hereditary/genetic factors, while a healthy lifestyle additionally contributes to achieving the individual maximum lifespan in humans. More research is required in this rapidly growing population of super old people. In particular, there is need for more comprehensive investigations including short- and long-term lifestyle interventions as well as investigations focusing on the mechanisms causing DNA damage, mutations, and telomere shortening.

Investigating how customer insights inform strategy leading to brand differentiation in the retail sector

Using qualitative research with case studies of firms in the Australian retail sector, this thesis explores the link between brand differentiation, customer insights, and strategy development to deliver a unique customer experience. The research focus is how brand expression is driven by customer insights. Findings indicate that customer experience is made tangible by the strategic design and alignment of the brand's expression and is crucial to retail success. A significant practical outcome is the development of the Brand Differentiated Model. Created as a tool to potentially assist retailers develop brands from the 'inside out' and confront future disruptions.

Molecular and pathological insights into Chlamydia pecorum-associated sporadic bovine encephalomyelitis (SBE) in Western Australia

Background Despite its global recognition as a ruminant pathogen, cases of Chlamydia pecorum infection in Australian livestock are poorly documented. In this report, a C. pecorum specific Multi Locus Sequence Analysis scheme was used to characterise the C. pecorum strains implicated in two cases of sporadic bovine encephalomyelitis confirmed by necropsy, histopathology and immunohistochemistry. This report provides the first molecular evidence for the presence of mixed infections of C. pecorum strains in Australian cattle. Case presentation Affected animals were two markedly depressed, dehydrated and blind calves, 12 and 16 weeks old. The calves were euthanized and necropsied. In one calf, a severe fibrinous polyserositis was noted with excess joint fluid in all joints whereas in the other, no significant lesions were seen. No gross abnormalities were noted in the brain of either calf. Histopathological lesions seen in both calves included: multifocal, severe, subacute meningoencephalitis with vasculitis, fibrinocellular thrombosis and malacia; diffuse, mild, acute interstitial pneumonia; and diffuse, subacute epicarditis, severe in the calf with gross serositis. Immunohistochemical labelling of chlamydial antigen in brain, spleen and lung from the two affected calves and brain from two archived cases, localised the antigen to the cytoplasm of endothelium, mesothelium and macrophages. C. pecorum specific qPCR, showed dissemination of the pathogen to multiple organs. Phylogenetic comparisons with other C. pecorum bovine strains from Australia, Europe and the USA revealed the presence of two genetically distinct sequence types (ST). The predominant ST detected in the brain, heart, lung and liver of both calves was identical to the C. pecorum ST previously described in cases of SBE. A second ST detected in an ileal tissue sample from one of the calves, clustered with previously typed faecal bovine isolates. Conclusion This report provides the first data to suggest that identical C. pecorum STs may be associated with SBE in geographically separated countries and that these may be distinct from those found in the gastrointestinal tract. This report provides a platform for further investigations into SBE and for understanding the genetic relationships that exist between C. pecorum strains detected in association with other infectious diseases in livestock.

Empirical insights into the development of a service-oriented enterprise architecture

Organisations use Enterprise Architecture (EA) to reduce organisational complexity, improve communication, align business and information technology (IT), and drive organisational change. Due to the dynamic nature of environmental and organisational factors, EA descriptions need to change over time to keep providing value for its stakeholders. Emerging business and IT trends, such as Service-Oriented Architecture (SOA), may impact EA frameworks, methodologies, governance and tools. However, the phenomenon of EA evolution is still poorly understood. Using Archer's morphogenetic theory as a foundation, this research conceptualises three analytical phases of EA evolution in organisations, namely conditioning, interaction and elaboration. Based on a case study with a government agency, this paper provides new empirically and theoretically grounded insights into EA evolution, in particular in relation to the introduction of SOA, and describes relevant generative mechanisms affecting EA evolution. By doing so, it builds a foundation to further examine the impact of other IT trends such as mobile or cloud-based solutions on EA evolution. At a practical level, the research delivers a model that can be used to guide professionals to manage EA and continually evolve it.

Genetic insights into common pathways and complex relationships among iImmune-mediated diseases

Shared aetiopathogenic factors among immune-mediated diseases have long been suggested by their co-familiality and co-occurrence, and molecular support has been provided by analysis of human leukocyte antigen (HLA) haplotypes and genome-wide association studies. The interrelationships can now be better appreciated following the genotyping of large immune disease sample sets on a shared SNP array: the 'Immunochip'. Here, we systematically analyse loci shared among major immune-mediated diseases. This reveals that several diseases share multiple susceptibility loci, but there are many nuances. The most associated variant at a given locus frequently differs and, even when shared, the same allele often has opposite associations. Interestingly, risk alleles conferring the largest effect sizes are usually disease-specific. These factors help to explain why early evidence of extensive 'sharing' is not always reflected in epidemiological overlap. © 2013 Macmillan Publishers Limited. All rights reserved.

Stakeholder analysis of a retirement village development in Australia : Insights from an interdisciplinary workshop

In Australia, the retirement village is regarded as a viable accommodation option for the fast-growing population of older people. Given that diverse stakeholders are involved in the village development process, a comprehensive stakeholder analysis, especially understanding stakeholders' concerns and expectations, is of critical importance to project success. This paper describes a stakeholder analysis based on a typical retirement village. The main methods utilized in this research were case study and an interdisciplinary workshop comprising intensive work sessions and cross-functional review. The participants of this 2014 Brisbane workshop included four village managers from an Australian retirement village developer and eight academics from diverse disciplines from a large university. Through this workshop, 24 village stakeholders and their specific concerns and expectations were identified. Results suggest that both concerns and expectations of these stakeholders are multidimensional and vary considerably, and the concerns and expectations of different stakeholders have complex relationships. Implications for a retirement village development are also proposed. The findings of the study serve as a valuable reference for developers' understanding of stakeholder concerns and expectations, and for taking corresponding actions in the final stages of the retirement village development.