The disruptive technologies that will shape business in the years ahead

Regardless of your industry, the marketplace is continually evolving. The reason, increasingly, is the evolution of disruptive technology. Disruptive technologies are enhanced or new technological innovations that essentially displace conventional and established technology, rendering it obsolete. They can create opportunities for new products, new markets, and new ways of conducting business. In 2016, business models will again change as businesses adapt. The enhancement of current technology and the development of new technological innovations will undeniably transform how new businesses are established, and how existing businesses compete. For small and medium-sized firms, technology will also enable significant leaps forward in terms of innovation, efficiency and competitiveness. Adapting quickly will be essential, so here’s the top six we think you should be prepared for.

Multi-species sequence comparison reveals conservation of ghrelin gene-derived splice variants encoding a truncated ghrelin peptide

The peptide hormone ghrelin is a potent orexigen produced predominantly in the stomach. It has a number of other biological actions, including roles in appetite stimulation, energy balance, the stimulation of growth hormone release and the regulation of cell proliferation. Recently, several ghrelin gene splice variants have been described. Here, we attempted to identify conserved alternative splicing of the ghrelin gene by cross-species sequence comparisons. We identified a novel human exon 2-deleted variant and provide preliminary evidence that this splice variant and in1-ghrelin encode a C-terminally truncated form of the ghrelin peptide, termed minighrelin. These variants are expressed in humans and mice, demonstrating conservation of alternative splicing spanning 90 million years. Minighrelin appears to have similar actions to full-length ghrelin, as treatment with exogenous minighrelin peptide stimulates appetite and feeding in mice. Forced expression of the exon 2-deleted preproghrelin variant mirrors the effect of the canonical preproghrelin, stimulating cell proliferation and migration in the PC3 prostate cancer cell line. This is the first study to characterise an exon 2-deleted preproghrelin variant and to demonstrate sequence conservation of ghrelin gene-derived splice variants that encode a truncated ghrelin peptide. This adds further impetus for studies into the alternative splicing of the ghrelin gene and the function of novel ghrelin peptides in vertebrates.

‘I really needed help’: What mothers say about their post-birth care in Queensland, Australia

Background Australian mothers consistently rate postnatal care as the poorest aspect of their maternity care, and researchers and policymakers have widely acknowledged the need for improvement in how postnatal care is provided. Aim To identify and analyse mothers’ comments about postnatal care in their free text responses to an open ended question in the Having a Baby in Queensland Survey, 2010, and reflect on their implications for midwifery practice and maternity service policies. Methods The survey assessed mothers’ experiences of maternity care four months after birth. We analysed free-text data from an open-ended question inviting respondents to write ‘anything else you would like to tell us’. Of the final survey sample (N = 7193), 60% (N = 4310) provided comments, 26% (N = 1100) of which pertained to postnatal care. Analysis included the coding and enumeration of issues to identify the most common problems commented on by mothers. Comments were categorised according to whether they related to in-hospital or post-discharge care, and whether they were reported by women birthing in public or private birthing facilities. Results The analysis revealed important differences in maternal experiences according to birthing sector: mothers birthing in public facilities were more likely to raise concerns about the quality and/or duration of their in-hospital stay than those in private facilities. Conversely, mothers who gave birth in private facilities were more likely to raise concerns about inadequate post-discharge care. Regardless of birthing sector, however, a substantial proportion of all mothers spontaneously raised concerns about their experiences of inadequate and/or inconsistent breastfeeding support. Conclusion Women who birth in private facilities were more likely to spontaneously report concerns about their level of post-discharge care than women from public facilities in Queensland, and publically provided community based care is not sufficient to meet women's needs. Inadequate or inconsistent professional breastfeeding support remains a major issue for early parenting women regardless of birthing sector.

The need for cost-effectiveness analyses of antimicrobial stewardship programmes: A structured review

The cost effectiveness of antimicrobial stewardship (AMS) programmes was reviewed in hospital settings of Organisation for Economic Co-operation and Development (OECD) countries, and limited to adult patient populations. In each of the 36 studies, the type of AMS strategy and the clinical and cost outcomes were evaluated. The main AMS strategy implemented was prospective audit with intervention and feedback (PAIF), followed by the use of rapid technology, including rapid polymerase chain reaction (PCR)-based methods and matrix-assisted laser desorption/ionisation time-of-flight (MALDI-TOF) technology, for the treatment of bloodstream infections. All but one of the 36 studies reported that AMS resulted in a reduction in pharmacy expenditure. Among 27 studies measuring changes to health outcomes, either no change was reported post-AMS, or the additional benefits achieved from these outcomes were not quantified. Only two studies performed a full economic evaluation: one on a PAIF-based AMS intervention; and the other on use of rapid technology for the selection of appropriate treatment for serious Staphylococcus aureus infections. Both studies found the interventions to be cost effective. AMS programmes achieved a reduction in pharmacy expenditure, but there was a lack of consistency in the reported cost outcomes making it difficult to compare between interventions. A failure to capture complete costs in terms of resource use makes it difficult to determine the true cost of these interventions. There is an urgent need for full economic evaluations that compare relative changes both in clinical and cost outcomes to enable identification of the most cost-effective AMS strategies in hospitals.

Pushing the boundaries' versus identifying the boundaries: An institutional perspective of NPM Principles

This paper considers the boundaries of new public management (NPM) principles in the context of the mandate for a commercial approach within in a New Zealand state-owned enterprise (SOE). Investigating a commercial approach to NPM through an institutional theory lens, the case study highlights complexities and potential conflict between structured NPM principles and the more complex reality. Analysis reveals blurred lines and boundaries have implications for public sector organisations such as SOEs, government and other stakeholders, where managers push the boundaries beyond the point where stakeholders are comfortable. Thus, a key challenge involves developing clearer institutional boundaries to balance freedoms with stakeholder acceptability.

The sublime, affective process + architectural production

A year before Kate Nesbitt’s Theorising a New Agenda For Architecture (1996), the author penned a chapter on the significance of the sublime and its contribution to post-modern architecture via the uncanny or disturbing through the theories of Vidler and Eisenman (Nesbit, 1995). Twenty years on, we see its ongoing presence within the contemporary works of artists Kapoor, Ellison and Viola. Eisenmann and Libeskind aside, explicit reference to the Sublime whether through architectural praxis or theory appears to have been trumped by ecological derivatives and associated transactions, as catalyst for new architecture and architectural thinking. For Edmund Burke (1757), the Sublime was seen as a leading, an overpowering of self to a state of intense self-presence, often leading to a state of otherness. To experience the sublime is to experience affect, physiologically overwhelming the mental faculties through intensities of astonishment, terror, obscurity, magnificence, and reverence. Key here is Burke’s articulation of the stages of the sublime encounter, particularly so, its implications for the process of production which architectural theorists appear to have overstepped in their valorisation of the sublime object. This paper seeks to resituate the sublime within the context of architectural production. Through concepts such as material thinking, bodies and making strange, the paper explores a shift in focus toward affective processes traced from Burke’s inquiry. Rather than proposing strategies solely for affect within the work itself, the focus lies upon the designing experience, where blockage and desirous forces are critical partners in the process of production, as revealed through recent studio programs entitled Strange Space.

Sleep and self-regulation from birth to 7 years: A retrospective study of children with and without ADHD at 8-9 years

Objective To examine mean level differences, and longitudinal and reciprocal relations among behavioral sleep problems, emotional dysregulation, and attentional regulation across early childhood for children with and without ADHD at 8-9 years. Method This study used data from Growing Up in Australia: The Longitudinal Study of Australian Children (LSAC) – Infant Cohort (n = 4109 analyzed). Children with and without ADHD were identified at age 8-9 years via parent-report of ADHD diagnosis and the 5-item Inattention-Hyperactivity subscale from the Strengths and Difficulties Questionnaire. Maternal report of child sleep problems and self-regulation was collected at 0-1, 2-3, 4-5 and 6-7 years of age. ANOVA was used to compare mean level differences in sleep problems, emotional and attentional regulation by ADHD group. Longitudinal structural equation modeling examined the relations among sleep and self-regulation across time in children with and without ADHD. Results Children with ADHD had persistently elevated levels of sleep problems (from infancy) and emotional and attentional dysregulation compared to controls (from 2-3 years of age). Sleep problems, emotional dysregulation, and attentional regulation were stable over time for both groups. Sleep problems were associated with greater emotional dysregulation two years later from 2-3 years of age for both groups, which in turn was associated with poorer attentional regulation. There was no direct relationship between sleep problems and later attentional regulation. Conclusion Sleep problems in children with and without ADHD are associated with emotional dysregulation, which in turn contributes to poorer attentional functioning. This study highlights the importance of assessing and managing sleep problems in young children.

Early childhood profiles of sleep problems and self-regulation predict later school adjustment

Background Children’s sleep problems and self-regulation problems have been independently associated with poorer adjustment to school, but there has been limited exploration of longitudinal early childhood profiles that include both indicators. Aims This study explores the normative developmental pathway for sleep problems and self-regulation across early childhood, and investigates whether departure from the normative pathway is associated with later social-emotional adjustment to school. Sample This study involved 2880 children participating in the Growing Up in Australia: The Longitudinal Study of Australian Children (LSAC) – Infant Cohort from Wave 1 (0-1 years) to Wave 4 (6-7 years). Method Mothers reported on children’s sleep problems, emotional, and attentional self-regulation at three time points from birth to 5 years. Teachers reported on children’s social-emotional adjustment to school at 6-7 years. Latent profile analysis was used to establish person-centred longitudinal profiles. Results Three profiles were found. The normative profile (69%) had consistently average or higher emotional and attentional regulation scores and sleep problems that steadily reduced from birth to 5. The remaining 31% of children were members of two non-normative self-regulation profiles, both characterised by escalating sleep problems across early childhood and below mean self-regulation. Non-normative group membership was associated with higher teacher-reported hyperactivity and emotional problems, and poorer classroom self-regulation and prosocial skills. Conclusion Early childhood profiles of self-regulation that include sleep problems offer a way to identify children at risk of poor school adjustment. Children with escalating early childhood sleep problems should be considered an important target group for school transition interventions.

The Feeding Practices and Structure Questionnaire (FPSQ-28): A parsimonious version validated for longitudinal use from 2-5 years

Prospective studies and intervention evaluations that examine change over time assume that measurement tools measure the same construct at each occasion. In the area of parent-child feeding practices, longitudinal measurement properties of the questionnaires used are rarely verified. To ascertain that measured change in feeding practices reflects true change rather than change in the assessment, structure, or conceptualisation of the constructs over time, this study examined longitudinal measurement invariance of the Feeding Practices and Structure Questionnaire (FPSQ) subscales (9 constructs; 40 items) across 3 time points. Mothers participating in the NOURISH trial reported their feeding practices when children were aged 2, 3.7, and 5 years (N = 404). Confirmatory Factor Analysis (CFA) within a structural equation modelling framework was used. Comparisons of initial cross-sectional models followed by longitudinal modelling of subscales, resulted in the removal of 12 items, including two redundant or poorly performing subscales. The resulting 28-item FPSQ-28 comprised 7 multi-item subscales: Reward for Behaviour, Reward for Eating, Persuasive Feeding, Overt Restriction, Covert Restriction, Structured Meal Setting and Structured Meal Timing. All subscales showed good fit over 3 time points and each displayed at least partial scalar (thresholds equal) longitudinal measurement invariance. We recommend the use of a separate single item indicator to assess the family meal setting. This is the first study to examine longitudinal measurement invariance in a feeding practices questionnaire. Invariance was established, indicating that the subscales of the shortened FPSQ-28 can be used with mothers to validly assess change in 7 feeding constructs in samples of children aged 2-5 years of age.

Preventing infections through cleaner hospitals (PITCH): An environmental cleaning bundle

Translating the numerous lengthy cleaning standards and guidelines into meaningful and sustained improvements in cleaning practice is challenging. This research hypothesized that an evidence based cleaning bundle would improve cleaning performance, knowledge and attitudes, and ultimately reduces healthcare associated infections (HAI) in a way that is value for money. A bundle is a small, straightforward set of evidence based practices, that when performed collectively and reliably, improves patient outcomes.

Key drivers of the economic burden of community-associated Methicillin-resistant Staphylococcus aureus in Australia

Estimates of the economic cost of community-associated Methicillin-resistant Staphylococcus aureus(CA-MRSA) in the United States (US) are substantial, ranging from $1.4-13.8 billion. In Australia, it has been shown that rates of CA-MRSA are increasing, and individual studies have looked at the morbidity and mortality associated with CA-MRSA, however, it is not clear what is driving the economic burden of CA-MRSA at a national level. This study presents preliminary findings about the key drivers of the economic cost of CA-MRSA infections in Australia

Mutations in known monogenic high bone mass loci only explain a small proportion of high bone mass cases

High bone mass (HBM) can be an incidental clinical finding; however, monogenic HBM disorders (eg, LRP5 or SOST mutations) are rare. We aimed to determine to what extent HBM is explained by mutations in known HBM genes. A total of 258 unrelated HBM cases were identified from a review of 335,115 DXA scans from 13 UK centers. Cases were assessed clinically and underwent sequencing of known anabolic HBM loci: LRP5 (exons 2, 3, 4), LRP4 (exons 25, 26), SOST (exons 1, 2, and the van Buchem's disease [VBD] 52-kb intronic deletion 3'). Family members were assessed for HBM segregation with identified variants. Three-dimensional protein models were constructed for identified variants. Two novel missense LRP5 HBM mutations ([c.518C>T; p.Thr173Met], [c.796C>T; p.Arg266Cys]) were identified, plus three previously reported missense LRP5 mutations ([c.593A>G; p.Asn198Ser], [c.724G>A; p.Ala242Thr], [c.266A>G; p.Gln89Arg]), associated with HBM in 11 adults from seven families. Individuals with LRP5 HBM ( approximately prevalence 5/100,000) displayed a variable phenotype of skeletal dysplasia with increased trabecular BMD and cortical thickness on HRpQCT, and gynoid fat mass accumulation on DXA, compared with both non-LRP5 HBM and controls. One mostly asymptomatic woman carried a novel heterozygous nonsense SOST mutation (c.530C>A; p.Ser177X) predicted to prematurely truncate sclerostin. Protein modeling suggests the severity of the LRP5-HBM phenotype corresponds to the degree of protein disruption and the consequent effect on SOST-LRP5 binding. We predict p.Asn198Ser and p.Ala242Thr directly disrupt SOST binding; both correspond to severe HBM phenotypes (BMD Z-scores +3.1 to +12.2, inability to float). Less disruptive structural alterations predicted from p.Arg266Cys, p.Thr173Met, and p.Gln89Arg were associated with less severe phenotypes (Z-scores +2.4 to +6.2, ability to float). In conclusion, although mutations in known HBM loci may be asymptomatic, they only account for a very small proportion ( approximately 3%) of HBM individuals, suggesting the great majority are explained by either unknown monogenic causes or polygenic inheritance.

Reproducibility of scratch assays is affected by the initial degree of confluence: Experiments, modelling and model selection

Scratch assays are difficult to reproduce. Here we identify a previously overlooked source of variability which could partially explain this difficulty. We analyse a suite of scratch assays in which we vary the initial degree of confluence (initial cell density). Our results indicate that the rate of re-colonisation is very sensitive to the initial density. To quantify the relative roles of cell migration and proliferation, we calibrate the solution of the Fisher–Kolmogorov model to cell density profiles to provide estimates of the cell diffusivity, D, and the cell proliferation rate, λ. This procedure indicates that the estimates of D and λ are very sensitive to the initial density. This dependence suggests that the Fisher–Kolmogorov model does not accurately represent the details of the collective cell spreading process, since this model assumes that D and λ are constants that ought to be independent of the initial density. Since higher initial cell density leads to enhanced spreading, we also calibrate the solution of the Porous–Fisher model to the data as this model assumes that the cell flux is an increasing function of the cell density. Estimates of D and λ associated with the Porous–Fisher model are less sensitive to the initial density, suggesting that the Porous–Fisher model provides a better description of the experiments.

Effect of deletion of Ghrelin-O-Acyltransferase on the pulsatile release of growth hormone in mice

Ghrelin, a gut hormone originating from the post-translational cleavage of preproghrelin, is the endogenous ligand of growth hormone secretagogue receptor 1a (GHS-R1a). Within the growth hormone (GH) axis, the biological activity of ghrelin requires octanoylation by ghrelin-O-acyltransferase (GOAT), conferring selective binding to the GHS-R1a receptor via acylated ghrelin. Complete loss of preproghrelin-derived signalling (through deletion of the Ghrl gene) contributes to a decline in peak GH release; however, the selective contribution of endogenous acyl-ghrelin to pulsatile GH release remains to be established. We assessed the pulsatile release of GH in ad lib. fed male germline goat−/− mice, extending measures to include mRNA for key hypothalamic regulators of GH release, and peripheral factors that are modulated relative to GH release. The amount of GH released was reduced in young goat−/− mice compared to age-matched wild-type mice, whereas pulse frequency and irregularity increased. Altered GH release did not coincide with alterations in hypothalamic Ghrh, Srif, Npy or Ghsr mRNA expression, or pituitary GH content, suggesting that loss of Goat does not compromise canonical mechanisms that contribute to pituitary GH production and release. Although loss of Goat resulted in an irregular pattern of GH release (characterised by an increase in the number of GH pulses observed during extended secretory events), this did not contribute to a change in the expression of sexually dimorphic GH-dependent liver genes. Of interest, circulating levels of insulin-like growth factor (IGF)-1 were elevated in goat−/− mice. This rise in circulating levels of IGF-1 was correlated with an increase in GH pulse frequency, suggesting that sustained or increased IGF-1 release in goat−/− mice may occur in response to altered GH release patterning. Our observations demonstrate that germline loss of Goat alters GH release and patterning. Although the biological relevance of altered GH secretory patterning remains unclear, we propose that this may contribute to sustained IGF-1 release and growth in goat−/− mice.