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Secretoneurin is an endogenous calcium/calmodulin-dependent protein kinase II inhibitor that attenuates Ca2+-dependent arrhythmia
No full textBackground: Circulating SN (secretoneurin) concentrations are increased in patients with myocardial dysfunction and predict poor outcome. Because SN inhibits CaMKIIδ (Ca2+/calmodulin-dependent protein kinase IIδ) activity, we hypothesized that upregulation of SN in patients protects against cardiomyocyte mechanisms of arrhythmia. Methods: Circulating levels of SN and other biomarkers were assessed in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT; n=8) and in resuscitated patients after ventricular arrhythmia–induced cardiac arrest (n=155). In vivo effects of SN were investigated in CPVT mice (RyR2 [ryanodine receptor 2]-R2474S) using adeno-associated virus-9–induced overexpression. Interactions between SN and CaMKIIδ were mapped using pull-down experiments, mutagenesis, ELISA, and structural homology modeling. Ex vivo actions were tested in Langendorff hearts and effects on Ca2+ homeostasis examined by fluorescence (fluo-4) and patch-clamp recordings in isolated cardiomyocytes. Results: SN levels were elevated in patients with CPVT and following ventricular arrhythmia–induced cardiac arrest. In contrast to NT-proBNP (N-terminal pro-B-type natriuretic peptide) and hs-TnT (high-sensitivity troponin T), circulating SN levels declined after resuscitation, as the risk of a new arrhythmia waned. Myocardial pro-SN expression was also increased in CPVT mice, and further adeno-associated virus-9–induced overexpression of SN attenuated arrhythmic induction during stress testing with isoproterenol. Mechanistic studies mapped SN binding to the substrate binding site in the catalytic region of CaMKIIδ. Accordingly, SN attenuated isoproterenol induced autophosphorylation of Thr287-CaMKIIδ in Langendorff hearts and inhibited CaMKIIδ-dependent RyR phosphorylation. In line with CaMKIIδ and RyR inhibition, SN treatment decreased Ca2+ spark frequency and dimensions in cardiomyocytes during isoproterenol challenge, and reduced the incidence of Ca2+ waves, delayed afterdepolarizations, and spontaneous action potentials. SN treatment also lowered the incidence of early afterdepolarizations during isoproterenol; an effect paralleled by reduced magnitude of L-type Ca2+ current. Conclusions: SN production is upregulated in conditions with cardiomyocyte Ca2+ dysregulation and offers compensatory protection against cardiomyocyte mechanisms of arrhythmia, which may underlie its putative use as a biomarker in at-risk patients
Reconstructing terrestrial water storage variations from 1980 to 2015 in the Beishan area of China
No full textTerrestrial water storage (TWS) is a key element in the global and continental water cycle. Since 2002, the Gravity Recovery and Climate Experiment (GRACE) has provided a highly valuable dataset, which allows the study of TWS over larger river basins worldwide. However, the lifetime of GRACE is too short to demonstrate long-term variability in TWS. In the Beishan area of northwestern China, which is selected as the most prospective site for high-level radioactive waste (HLRW) disposal, the assessment of long-term TWS changes is crucial to understand disposal safety. Monthly and annual TWS changes during the past 35 years are reconstructed using GRACE data, other remote sensing products, and the water balance method. Hydrological flux outputs from multisource remote sensing products are analyzed and compared to select appropriate data sources. The results show that a decreasing trend is found for GRACE-filtered and Center for Space Research (CSR) mascon solutions from 2003 to 2015, with slopes of −2.30 ± 0.52 and −1.52 ± 0.24 mm/year, respectively. TWS variations independently computed from the water balance method also show a similar decreasing trend with the GRACE observations, with a slope of −0.94 mm/year over the same period. Overall, the TWS anomalies in the Beishan area change seasonally within 10 mm and have been decreasing since 1980, keeping a desirable dry condition as a HLRW disposal site
Customer perceived value in periodic hallmark events: conceptualisation and impacts on customer outcomes
No full textPeriodic hallmark events (PHEs) are fundamental in triggering the growth of communities and destinations by attracting tourists to the host destination. However, a lack of understanding exists regarding the various benefits that PHE tourism customers value from a PHE consumption experience. To address this gap, this study sought to conceptualise how customers who travel to such PHEs perceive and derive value within this leisure consumption context and determine how such assessments influence customer attitudinal and behavioural responses, including customer satisfaction, behavioural intentions, destination image and subjective well-being. Following a mixed-method process, this study collected data across two research phases. Phase 1 involved qualitative semi-structured interviews with 12 event experts and 16 PHE customers. Informed by the findings from Phase 1, a theoretical framework labelled Framework for Value Creation in Periodic Hallmark Events was formulated and tested in Phase 2 via a survey across three separate studies. In total, 1,218 completed surveys provided the basis for empirical analysis across each of the three studies via partial least squares structural equation modelling. The findings indicated that the EVENTVAL construct is formed by multiple constituent dimensions that reflect benefits that influence various customer attitudinal and behavioural outcomes. In addition, moderating effects were largely not detected in relation to event category involvement and event attachment. Managerially, this research provides PHE event managers with the foundations for enhanced PHE customer attitudinal and behavioural outcomes through due consideration being given to the effect of the EVENTVAL construct and its seven customer perceived value dimensions on participants. From a theoretical perspective, this study is the first to conceptualise and operationalise the multidimensional EVENTVAL construct in a PHE setting, and to examine its effect on the customer attitudinal and behavioural outcomes of the PHE tourist. This resulted in the advancement of the Framework for Value Creation in Periodic Hallmark Events. As a result, this research provides a platform for future research investigation in this important field
Nutrition education and assessment methods for children: an investigation of methods, current nutrition education practices and opportunities in Australian primary schools
No full textBackground: In Australia, approximately 1 in 4 children have overweight or obesity. Contributing factors to this are the consumption of large portion sizes, continuous access to convenient and inexpensive energy-dense, nutrient-poor foods which displaces nutrient dense foods including fruit and vegetables. Only about half of Australian children meet the recommended daily intake for macro- and micronutrients. As children with overweight are likely to become adults with overweight, the personal and economic burden of overweight is substantial. Overweight adults are more likely to suffer from comorbidities such as type 2 diabetes, coronary heart disease and certain type of cancers. While overweight children do not suffer from chronic disease as much as adults, the stigma and bias experienced is likely to be psychologically damaging. In order to prevent overweight in children, a holistic approach is recommended. Educating children on healthy eating habits has been found to be effective in changing some eating behaviours. Given most children spend a significant portion of their time at school, the school environment is an opportune place for standardised nutrition education. However, the extent and content of nutrition education in Australian primary schools is unknown. More in-depth information is required before a curriculum-based nutrition knowledge intervention could be implemented into Australian primary schools. AIM: The purpose of my thesis was to develop a curriculum based nutrition knowledge program that teachers could use for nutrition education. Therefore, the extent and limitations of nutrition education in Australian primary schools needed to be explored and the acceptability and feasibility of a potential program informed by teachers, parents and students needed to be investigated. Hence, the current nutrition literacy and gaps in children’s knowledge were mapped in order to tailor the program. Methods: An online survey was developed specifically to explore the opinions and attitudes of teachers in regard to nutrition education in school. Year 5 and 6 students (aged 9 to 12 years) and a parent were invited to the University for an interview, a standardised food sorting task and a nutrition knowledge questionnaire. This was used to identify gaps in children’s nutrition knowledge. As a nutrition knowledge questionnaire for Australian children did not exist, one was developed by adapting an existing and validated Belgian nutrition knowledge survey. The nutrition knowledge questionnaire developed for Australian children (the CNK-AU) was tested for validity and reliability among a sample of year 5 and 6 primary school students. Furthermore, the ability of children to estimate portion sizes using different portion size estimation aids (PSEAs) was investigated in a systematic literature review. Lastly, a serious game called VitaVillage was developed and pilot tested for its impact on nutrition knowledge and likeability among a sample of year 5 and 6 students. Results: The teachers were positive towards enhancing nutrition education in schools, but indicated having a lack of time in class for teaching non-core subjects. Furthermore, other barriers identified included lack of self-efficacy concerning nutrition and no access to useful resources. Children and their parents reported they valued healthy eating and nutrition education and believe standardised nutrition education in school is essential. Children would like the nutrition education to be interactive and fun. The CNK-AU identified three gaps in the children’s nutrition knowledge: 1) Australian Guide to Healthy Eating recommendations and serving sizes, 2) nutrition label literacy and 3) nutrient functions. The CNK-AU was found to be a reliable nutrition knowledge questionnaire. Using a serious game for nutrition education was proposed as a solution to the teacher’s barriers identified in the earlier studies. In addition, for many children, playing a game is enjoyable and interactive. As serious games have been found to be effective in increasing nutrition knowledge, a new game called ‘VitaVillage’ was developed. In this game, the player takes the role of a farmer that has to increase the town’s health by completing quests for the benefit of the villagers. They have to acquire the correct food product’s seeds in the town’s shop and are able to then grow them into fruits or vegetables by answering questions about the food or its related vitamin/mineral content. They can also receive bonus points by answering single questions from the villagers about balanced meals, the AGHE serves, nutrient labels, food safety, food groups and food sources. VitaVillage was found to significantly increase children’s nutrition knowledge. In addition, the participants rated VitaVillage 70 out of 100 for overall likeability. Conclusion: Using a serious game for curriculum-based nutrition education can overcome barriers identified by teachers. A serious game developed by nutrition experts is ready-to-go, high quality, can be integrated into other subjects, is engaging and easy to use for teachers and enjoyable for children. The gaps identified in Australian children’s nutrition knowledge through my thesis can make a valuable contribution to the knowledge base in this area. These gaps need to be addressed and the point of focus in VitaVillage and future nutrition knowledge interventions. VitaVillage was found to be enjoyable and effective. Further developments of VitaVillage could focus including additional cross-curricular content, incorporating features that make the game more enjoyable and adapting the game for varying ages and cultures. Furthermore, future studies could investigate VitaVillage’s potential in influencing children’s eating behaviour
Technology use to support employment-related outcomes for people with intellectual and developmental disability: an updated meta-analysis
No full textObjectives: The aim of this study is to update and extend an original meta-analysis which included papers published up to and including 2003 and investigated the impact of technology use on employment-related outcomes for people with intellectual and developmental disability. Methods: Following on from the original meta-analysis, this study is a meta-analysis of pertinent single-subject experimental design studies conducted from 2004 to 2016 and employs the same metric methods as the original contribution. Results: The results are generally consistent with those of the original meta-analysis, namely, applied cognitive technology effectively supports employment-related outcomes for people with intellectual and developmental disability. Nevertheless, significant differences in the intervention effects were found (a) between groups of individuals with varying levels of disability, and (b) between interventions utilizing technology with and without universal design features. Conclusions: In line with the original contribution, applied cognitive technology seems to support people with intellectual and developmental disabilities to better achieve employment-related outcomes. More research is needed though to explore the impact of different types of technology on employment-related outcomes
Small-gain stability theorems for positive Lur'e inclusions
No full textStability results are presented for a class of differential and difference inclusions, so-called positive Lur'e inclusions which arise, for example, as the feedback interconnection of a linear positive system with a positive set-valued static nonlinearity. We formulate sufficient conditions in terms of weighted one-norms, reminiscent of the small-gain condition, which ensure that the zero equilibrium enjoys various global stability properties, including asymptotic and exponential stability. We also consider input-to-state stability, familiar from nonlinear control theory, in the context of forced positive Lur'e inclusions. Typical for the study of positive systems, our analysis benefits from comparison arguments and linear Lyapunov functions. The theory is illustrated with examples
Clinicopathologic diagnostic criteria for vulvar lichen planus
No full textObjective: The aim of the study was to describe the clinical and histopathologic features required for a clinicopathologic diagnosis of vulvar lichen planus (LP), which is divided into 3 types: Erosive, classic, and hypertrophic. Materials and Methods: The International Society of the Study of Vulvovaginal Diseases tasked the Difficult Pathologic Diagnoses committee with development of a consensus document for the clinicopathologic diagnosis of vulvar LP, lichen sclerosus, and differentiated vulvar intraepithelial neoplasia. The LP subgroup reviewed the literature and formulated diagnostic criteria, then approved by the International Society of the Study of Vulvovaginal Diseases membership. Results: The clinicopathologic diagnosis of erosive LP incorporates 5 criteria: (a) a well-demarcated, glazed red macule or patch at labia minora, vestibule, and/or vagina, (b) disease affects hairless skin, mucocutaneous junction, and/or nonkeratinized squamous epithelium, (c) evidence of basal layer damage, categorized as degenerative or regenerative, (d) a closely applied band-like lymphocytic infiltrate, and (e) absent subepithelial sclerosis. The clinicopathologic diagnoses of classic and hypertrophic LP each require a characteristic clinical appearance accompanied by hyperkeratosis, hypergranulosis, acanthosis, basal layer degeneration, a closely applied lymphocytic infiltrate, and absent dermal sclerosis, with hypertrophic LP showing marked epithelial abnormality compared with classic LP. Conclusions: Clinicopathological correlation yields the most reliable diagnosis of vulvar LP. Disease appearance overlaps with other physiologic, dermatologic, infectious, and neoplastic entities; a low threshold for biopsy at all morphologically distinct areas is recommended. Use of the histopathologic criteria described in this document may reduce the nondiagnostic biopsy rate for clinically diagnosed LP
Making mental health help-seeking easier: a rural Australian perspective
No full textRural residents are less likely to seek help for mental distress than their urban counterparts. Research has identified a number of attitudinal help-seeking barriers that may make mental health help-seeking more difficult for people living in rural areas. There is limited understanding, however, as to how changes in mental health services might lower these barriers and facilitate help-seeking. This research explores the mental health help-seeking barriers experienced by people living in rural Australia and the help-provider characteristics and environmental factors they believe would make mental health help-seeking easier. It considers the impact of different measures of rurality on mental health help-seeking behaviour preferences and seeks to better understand why some people struggle to seek help. The research acknowledges the rarity of enduring mental health and the high likelihood of brief periods of poor mental health. It drew on a novel approach that allowed people who had not experienced mental health help-seeking to contribute to the research and express their opinion with respect to future help-seeking. To do so, a cross-sectional survey based on people's perceptions, rather than actual experiences, explored mental health help-seeking behaviour. The survey design was framed by open, inclusive definitions of ‘mental health’ and ‘help-seeking’. The research surveyed adults living in the town of Wee Waa, New South Wales, via a traditional paper survey and adults living in 348 other rural NSW towns via an online survey advertised through social media. The study found that people living in rural New South Wales believe that there are many ways in which rural mental health services can increase the likelihood of their seeking help when experiencing mental distress. They perceive the need for service improvement, recognise the current shortcomings of services, and are deeply impacted by previous help-seeking experiences. They value professionalism in help-providers and are influenced by the environment and timing of the help-seeking encounter. Perceived and actual commonality between help-seeker and provider encourages them to seek help, as does the likeability, trustworthiness, and empathy of the help-provider. The research recommends increasing and promoting ‘peer’ relationships between help-seeker and provider, introducing flexible help-seeking options and further research into the impact of previous help-seeking experience on help-seeking behaviour
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No full textTropical Pacific stalagmites are commonly affected by dating uncertainties because of their low U concentration and/or elevated initial 230Th content. This poses problems in establishing reliable trends and periodicities for droughts and pluvial episodes in a region vulnerable to climate change. Here we constrain the chronology of a Cook Islands stalagmite using synchrotron µXRF two-dimensional mapping of Sr concentrations coupled with growth laminae optical imaging constrained by in situ monitoring. Unidimensional LA-ICP-MS-generated Mg, Sr, Ba and Na variability series were anchored to the 2D Sr and optical maps. The annual hydrological significance of Mg, Sr, Ba and Na was tested by principal component analysis, which revealed that Mg and Na are related to dry-season, wind-transported marine aerosols, similar to the host-rock derived Sr and Ba signatures. Trace element annual banding was then used to generate a calendar-year master chronology with a dating uncertainty maximum of ± 15 years over 336 years. Our approach demonstrates that accurate chronologies and coupled hydroclimate proxies can be obtained from speleothems formed in tropical settings where low seasonality and problematic U–Th dating would discourage the use of high-resolution climate proxies datasets
Mercutio's dance: aspects of inversion in Luhrmann's film William Shakespeare's Romeo + Juliet
No full textThis paper derives from a shared interest in Baz Luhrmann’s film William Shakespeare’s Romeo + Juliet. Although we were both fascinated by the character of Mercutio in the film, and in particular his prominent role in the party scene during which the two lovers meet, we realised that our individual perspectives were leading us to formulate separate, and yet not incompatible, readings: on the one hand a postmodern critique focusing on Queer theory and dance culture, and on the other, an analysis informed by Sartrean Existentialism and intertextuality. The common denominator is Mercutio’s, and indeed the film’s, use of inversion. Just as the term inversion itself covers a multitude of genres and meanings, this paper will explore different possibilities and draw seemingly contradictory conclusions. That is the nature of inversion, Luhrmann’s film and Shakespeare’s play itself. As Barbara Babcock writes, “[…] symbolic inversions create Spielraum, a space in which to take chances with new roles and ideas” (Babcock, 1978: 25). Whether he be considered to be toying with Romeo’s affections and making sport with adolescents, or guiding lovers to a place where love may be all there is, Mercutio has a role to play as a gobetween (variously he bridges the gaps between childhood and adulthood, existence and essence, male and female). He creates a space in which adults can play