Growth of confined cancer spheroids : a combined experimental marker, critical modelling approach

A critical step in the dissemination of ovarian cancer is the formation of multicellular spheroids from cells shed from the primary tumour. The objectives of this study were to apply bioengineered three-dimensional (3D) microenvironments for culturing ovarian cancer spheroids in vitro and simultaneously to build on a mathematical model describing the growth of multicellular spheroids in these biomimetic matrices. Cancer cells derived from human epithelial ovarian carcinoma were embedded within biomimetic hydrogels of varying stiffness and grown for up to 4 weeks. Immunohistochemistry, imaging and growth analyses were used to quantify the dependence of cell proliferation and apoptosis on matrix stiffness, long-term culture and treatment with the anti-cancer drug paclitaxel. The mathematical model was formulated as a free boundary problem in which each spheroid was treated as an incompressible porous medium. The functional forms used to describe the rates of cell proliferation and apoptosis were motivated by the experimental work and predictions of the mathematical model compared with the experimental output. This work aimed to establish whether it is possible to simulate solid tumour growth on the basis of data on spheroid size, cell proliferation and cell death within these spheroids. The mathematical model predictions were in agreement with the experimental data set and simulated how the growth of cancer spheroids was influenced by mechanical and biochemical stimuli including matrix stiffness, culture duration and administration of a chemotherapeutic drug. Our computational model provides new perspectives on experimental results and has informed the design of new 3D studies of chemoresistance of multicellular cancer spheroids.

Morphology-based model for predicting osteocyte-like cell line (MLO-Y4) growth process

This work has led to the development of empirical mathematical models to quantitatively predicate the changes of morphology in osteocyte-like cell lines (MLO-Y4) in culture. MLO-Y4 cells were cultured at low density and the changes in morphology recorded over 11 hours. Cell area and three dimensional shape features including aspect ratio, circularity and solidity were then determined using widely accepted image analysis software (ImageJTM). Based on the data obtained from the imaging analysis, mathematical models were developed using the non-linear regression method. The developed mathematical models accurately predict the morphology of MLO-Y4 cells for different culture times and can, therefore, be used as a reference model for analyzing MLO-Y4 cell morphology changes within various biological/mechanical studies, as necessary.

Posttraumatic growth and posttraumatic depreciation as predictors of psychological adjustment

Informed by current trauma literature, this study explored the relationships between Posttraumatic Growth (PTG; Tedeschi & Calhoun, 1995), Posttraumatic Depreciation (PTD; Cann et al., 2010) and other post-trauma outcomes including well-being, psychological flourishing, and psychological distress. The predictive utility of PTG and PTD was also examined. The sample comprised 104 trauma survivors who completed the Posttraumatic Growth Inventory – 42 (Baker et al., 2008) and several outcome measures. As expected, PTD showed strong linear correlations with well-being, flourishing and distress, and emerged as a significant predictor of scores on such measures. However, PTG showed negligible correlations with well-being, flourishing and distress. This reaffirms that PTG and PTD measure conceptually distinct and independent dimensions of experience, which has implications for therapeutic practice.

Working with refugee survivors of torture and trauma : an opportunity for vicarious posttraumatic growth

Clinical work with people who have survived trauma carries a risk of vicarious traumatisation for the service provider, but also the potential for vicarious posttraumatic growth. Despite growing interest in this area, the effects of working with survivors of refugee-related trauma have remained relatively unexplored. The aim of the current study was to examine the lived experiences of people working on a daily basis with survivors of torture and trauma who had sought refuge in Australia. Seventeen clinical, administrative, and managerial staff from a not-for-profit organisation participated in a semi-structured interview that was later analysed using interpretive phenomenological analysis. Analysis of the data demonstrated that the entire sample reported symptoms of vicarious trauma (e.g., strong emotional reactions, intrusive images, shattering of existing beliefs) as well as vicarious posttraumatic growth (e.g., forming new relationships, increased self-understanding, greater appreciation of life). Moreover, effortful meaning making processes appeared to facilitate such positive changes. Reduction in the risks associated with this work, enhancement of clinician well-being, and improvement of therapeutic outcomes is a shared responsibility of the organisation and clinician. Without negating the distress of trauma work, clinicians are encouraged to more deeply consider the unique positive outcomes that supporting survivors can provide.

Mentoring as professional development: ‘growth for both’ mentor and mentee

Teachers need professional development to keep current with teaching practices, although costs for extensive professional development can be prohibitive across an education system. Mentoring provides one way for embedding cost-effective professional development. This mixed-method study includes surveying mentor teachers (n = 101) on a five-part Likert scale and interviews with experienced mentors (n = 10) to investigate professional development for mentors as a result of the mentoring process. Quantitative data were analysed through a pedagogical knowledge framework and qualitative data were collated into themes. Survey data showed that although mentoring of pedagogical knowledge was variable, mentoring pedagogical knowledge practices occurs with the majority of mentors, which requires mentors to evaluate and articulate teaching practices. Qualitative data showed that mentoring acted as professional development and led towards enhancing communication skills, developing leadership roles (problem-solving and building capacity) and advancing pedagogical knowledge. Providing professional development to teachers on mentoring can help to build capacity in two ways: quality mentoring of preservice teachers through explicit mentoring practices, and reflecting and deconstructing teaching practices for mentors’ own pedagogical advancements.

Surrender to the void : life after creative industries

An extended review of Terry Flew's The Creative Industries: Culture and Policy (Sage, London, 2012).

New Perspectives On Firm Growth

This insightful volume presents a collection of innovative works by two of the leading researchers of firm growth: Per Davidsson, Director, Australian Centre for Entrepreneurship Research and Professor of Entrepreneurship, Queensland University of Technology, Australia and Jönköping International Business School, Sweden and Johan Wiklund, Professor of Entrepreneurship, Syracuse University, US and Jönköping International Business School, Sweden. The studies extend previous research by providing stronger theoretical underpinnings and using longitudinal databases that can separate in time the firms’ growth from its presumed causes. They also break new ground by examining different modes of growth, such as sales growth vs. employment growth, and organic growth vs. acquisition-based expansion. Further, the studies investigate the drivers of firm growth and take a critical look at the effects, such as under what circumstances high growth is associated with high profitability. The issue of how firm growth is achieved and managed, and what consequences it has for different stakeholders is both theoretically interesting and practically important. The book will strongly appeal to academics of entrepreneurship, small business management and strategy.

Asset specificity and behavioral uncertainty as moderators of the sales growth-employment growth relationship in emerging ventures

New venture growth is a central topic in entrepreneurship research. Although sales growth is emerging as the most commonly used measure of growth for emerging ventures, employment growth has also been used frequently. However, empirical research demonstrates that there are only very low to moderately sized correlations between the two (Delmar et aL, 2003; Weinzimmer, et al., 1998). In addition) sales growth and employment growth respond differently to a wide variety of criteria (Baum et al., 2001; Delmar et al., 2003). In this study we use transaction cost economics (Williamson, 1996) as a theoretical base to examine transaction cost influences on the addition of new employees as emerging ventures experience sales growth. \\le theorize that transaction cost economics variables will moderate the relationship between sales growth and employment growth. W'e develop and test hypotheses related to asset specificity, behavioral uncertainty, and the influence of resource munificence on the strength of the sales growth/ employment growth relationship. Asset specificity is theorized to be a positive moderator of the relationship between sales growth and employment growth. When the behavioral uncertainty associated with adding new employees is greater than that of outsourcing or subcontracting, it is hypothesized to be a negative moderator of the sales growth/employment growth relationship. We also hypothesize that resource scarcity will strengthen those relationships.

Towards an integrative framework for future research on small firm growth

Our review has demonstrated that small firm growth is a complex phenomenon. The concept ‘growth’ denotes both a change in amount and the process by which that change is attained. Further, the growth can be achieved in different ways and with varying degrees of regularity, and it manifests itself along several different dimensions such as sales, employment, and accumulation of assets. This complexity has naturally led researchers to adopt different approaches to studying growth and to use different measures to assess it. Further, although our review shows that it can fruitfully be regarded as a growth issue, the research on small firms' internationalization has largely developed as a separate stream. Similarly, other relatively separate literatures have evolved, which effectively focus on different modes of growth although mostly without regarding the studies first and foremost as growth studies. This goes for topics such as mergers and acquisitions, diversification, and integration - research streams which have largely ignored the particularities of small firms and which in turn have been largely ignored among researchers focusing on small firm growth.

Organic and acquisitive growth : re-examining, testing and extending Penrose’s growth theory

The Theory of the Growth of The Firm by Edith Penrose, first published in 1959, is a seminal contribution to the field of management. Penrose's intention was to create a theory of firm growth which was logically consistent and empirically tractable (Buckley and Casson, 2007). Much attention, however, has been focused on her unintended contribution to the resource-based view (henceforth RBV) (e.g. Kor and Mahoney, 2004; Lockett and Thompson, 2004) rather than her firm growth theory. We feel that this is unfortunate because despite a rapidly growing body of empirical work, conceptual advancement in growth studies has been limited (Davidsson and Wiklund, 2000; Davidsson et ai., 2006; Delmar, 1997; Storey, 1994). The growth literature frequently references Penrose's work, but little explicit testing of her ideas has been undertaken. This is surprising given that Penrose's work remains the most comprehensive theory of growth to date. One explanation is that she did not formality present her arguments, favouring verbal exposition over formalized models (Lockett, 2005; Lockett and Thompson, 2004). However, the central propositions and conclusions of her theory can be operationalized and empirically tested.

Performance configurations over time: implications for growth-and profit-oriented strategies

Entrepreneurship research and practice places emphasis on company growth as a measure of entrepreneurial success. In many cases, there has been a tendency to give growth a very central role, with some researchers even seeing growth as the very essence of entrepreneurship (Cole, 1949; Sexton, 1997; Stevenson & Gumpert, 1991). A large number of empirical studies of the performance of young and/or small firms use growth as the dependent variable (see reviews by Ardishvili, Cardozo, Harmon, & Vadakath, 1998; Delmar, 1997; Wiklund, 1998). By contrast, the two most prominent views of strategic management – strategic positioning (Porter, 1980) and the resource-based view (Barney, 1991; Wernerfelt, 1984) – are both concerned with achieving competitive advantage and regard achieving economic rents and profitability relative to other competitors as the central measures of firm performance. Strategic entrepreneurship integrates these two perspectives and is simultaneously concerned with opportunity seeking and advantage seeking (Hitt, Ireland, Camp, & Sexton, 2002; Ireland, Hitt, & Sirmon, 2003). Consequently, both company growth and relative profitability are together relevant measures of firm performance in the domain of strategic entrepreneurship.

A potential role for lamellar insulin-like growth factor-1 receptor in the pathogenesis of hyperinsulinaemic laminitis

The reason why a sustained high concentration of insulin induces laminitis in horses remains unclear. Cell proliferation occurs in the lamellae during insulin-induced laminitis and in other species high concentrations of insulin can activate receptors for the powerful cell mitogen, insulin-like growth factor (IGF)-1. The first aim of this study was to determine if IGF-1 receptors (IGF-1R) are activated in the hoof during insulin-induced laminitis. Gene expression for IGF-1R and the insulin receptor (InsR) was measured using qRT-PCR, in lamellar tissue from control horses and from horses undergoing a prolonged euglycaemic, hyperinsulinaemic clamp (p-EHC), during the mid-developmental (24 h) and acute (46 h) phases of insulin-induced laminitis. Gene expression for both receptors was decreased 13–32-fold (P < 0.05) at both time-points in the insulin-treated horses. A second aim was to determine if the down-regulation of the receptor genes could be accounted for by an increase in circulating IGF-1. Serum IGF-1 was measured at 0, 10, 25 and 46 h post-treatment in horses given a p-EHC for approximately 46 h, and in matched controls administered a balanced, electrolyte solution. There was no increase in serum IGF-1 concentrations during the p-EHC, consistent with down-regulation of both receptors by insulin. Stimulation of the IGF-1R by insulin may lead to inappropriate lamellar epidermal cell proliferation and lamellar weakening, a potential mechanism for hyperinsulinaemic laminitis. Targeting this receptor may provide insights into the pathogenesis or identify a novel therapy for hyperinsulinaemic laminitis.

Insulin and the insulin-like growth factor system : a novel theory for hyperinsulinemic laminitis pathogenesis

Research into hyperinsulinemic laminitis has progressed significantly in recent years with the use of the prolonged-euglycemic, hyperinsulinemic clamp (p-EHC). Previous investigations of laminitis pathophysiology have focused on digital vascular dysfunction, inflammation, altered glucose metabolism within the lamellae, and lamellar basement membrane breakdown by metalloproteinases. The etiopathogenesis of laminitis occurring in association with hyperinsulinemia is yet to be fully characterized, but it may not involve these mechanisms. Insulin stimulates cellular proliferation and can also affect other body systems, such as the insulin-like growth factor (IGF) system. Insulin-like growth factor-1 (IGF-1) is structurally homologous to insulin and, like insulin, binds with strong affinity to a specific tyrosine kinase receptor on the cell surface to produce its effects, which include promoting cell proliferation. Receptors for IGF-1 (IGF-1R) are present in the lamellar epidermis. An alternative theory for the pathogenesis of hyperinsulinemic laminitis is that uncontrolled cell proliferation, mediated through both the insulin receptor (InsR) and IGF-1R, leads to lengthening, weakening, and failure of the lamellae. An analysis of the proliferative activity of lamellar epidermal cells during the developmental and acute phases of hyperinsulinemic laminitis, and lamellar gene expression of the InsR and IGF-1R was undertaken.

Layered silicates in Chondritic Porous Aggregate W7029*A : a case of primary growth

An important subset of extraterrestrial particles that reach the Earth's stratosphere include the so-called Chondritic Porous Aggregates (CPA's) [1-3]. In general, CPA's have a fluffy morphology and consist of numerous (>104)subparticles that are often <100A in size [4]. Mineral species in CPA's include Mg-rich pyroxene and olivine, Fe- and (Fe,Ni)-sulphides, taenite, Fe,Ni-carbides, magnetite, Ti-metal, a Bi-phase (metal or oxide), and variable amounts of carbonaceous material [1, 5-7]. Hydrated silicates are rare in CPA's and are limited to aggregates that have not been severely altered (thermo-metamorphosed) during atmospheric entry [8]. The presence of hydrated silicates in one cosmic dust particle was established by X-ray diffraction [2] and has been inferred in others by infra-red spectroscopy [8]. If CPA's are cometary, their mineralogy and morphology suggest that at least two episodes of aggregation occurred and that variations in porosity may be related to local differences in ice-to-dust ratio [3].

Incorporation of exogenous RGD peptide and inter-species blending as strategies for enhancing human corneal limbal epithelial cell growth on Bombyx mori silk fibroin membranes

While fibroin isolated from the cocoons of domesticated silkworm Bombyx mori supports growth of human corneal limbal epithelial (HLE) cells, the mechanism of cell attachment remains unclear. In the present study we sought to enhance the attachment of HLE cells to membranes of Bombyx mori silk fibroin (BMSF) through surface functionalization with an arginine-glycine-aspartic acid (RGD)-containing peptide. Moreover, we have examined the response of HLE cells to BMSF when blended with the fibroin produced by a wild silkworm, Antheraea pernyi, which is known to contain RGD sequences within its primary structure. A procedure to isolate A. pernyi silk fibroin (APSF) from the cocoons was established, and blends of the two fibroins were prepared at five different BMSF/APSF ratios. In another experiment, BMSF surface was modified by binding chemically the GRGDSPC peptide using a water-soluble carbodiimide. Primary HLE were grown in the absence of serum on membranes made of BMSF, APSF, and their blends, as well as on RGD-modified BMSF. There was no statistically significant enhancing effect on the cell attachment due to the RGD presence. This suggests that the adhesion through RGD ligands may have a complex mechanism, and the investigated strategies are of limited value unless the factors contributing to this mechanism become better known.