Empirical investigation of multi-tier ensembles for the detection of cardiac autonomic neuropathy using subsets of the Ewing Features

This article is devoted to an empirical investigation of per- formance of several new large multi-tier ensembles for the detection of cardiac autonomic neuropathy (CAN) in diabetes patients using subsets of the Ewing features. We used new data collected by the diabetes screening research initiative (DiScRi) project, which is more than ten times larger than the data set originally used by Ewing in the investigation of CAN. The results show that new multi-tier ensembles achieved better performance compared with the outcomes published in the literature previously. The best accuracy 97.74% of the detection of CAN has been achieved by the novel multi-tier combination of AdaBoost and Bagging, where AdaBoost is used at the top tier and Bagging is used at the middle tier, for the set consisting of the following four Ewing features: the deep breathing heart rate change, the Valsalva manoeuvre heart rate change, the hand grip blood pressure change and the lying to standing blood pressure change.

Myoepithelial molecular markers in human breast carcinoma PMC42-LA cells are induced by extracellular matrix and stromal cells

The microenvironment plays a key role in the cellular differentiation of the two main cell lineages of the human breast, luminal epithelial, and myoepithelial. It is not clear, however, how the components of the microenvironment control the development of these cell lineages. To investigate how lineage development is regulated by 3-D culture and microenvironment components, we used the PMC42-LA human breast carcinoma cell line, which possesses stem cell characteristics. When cultured on a two-dimensional glass substrate, PMC42-LA cells formed a monolayer and expressed predominantly luminal epithelial markers, including cytokeratins 8, 18, and 19; E-cadherin; and sialomucin. The key myoepithelial-specific proteins alpha-smooth muscle actin and cytokeratin 14 were not expressed. When cultured within Engelbreth-Holm- Swarm sarcoma-derived basement membrane matrix (EHS matrix), PMC42-LA cells formed organoids in which the expression of luminal markers was reduced and the expression of other myoepithelial-specific markers (cytokeratin 17 and P-cadherin) was promoted. The presence of primary human mammary gland fibroblasts within the EHS matrix induced expression of the key myoepithelial-specific markers, alpha-smooth muscle actin and cytokeratin 14. Immortalized human skin fibroblasts were less effective in inducing expression of these key myoepithelial-specific markers. Confocal dual-labeling showed that individual cells expressed luminal or myoepithelial proteins, but not both. Conditioned medium from the mammary fibroblasts was equally effective in inducing myoepithelial marker expression. The results indicate that the myoepithelial lineage is promoted by the extracellular matrix, in conjunction with products secreted by breast-specific fibroblasts. Our results demonstrate a key role for the breast microenvironment in the regulation of breast lineage development.

Preliminary investigation of the costs of incubation in the Australasian Gannet (Morus serrator) breeding in Port Phillip Bay, Victoria

To optimise lifetime reproductive success, individuals must balance current reproductive effort against future reproductive prospects. In birds, incubation and chick-rearing must involve costs, and manipulation of the length of incubation offers an insight into some costs affecting adults. An experiment was conducted at a colony of Australasian Gannets in Port Phillip Bay, Victoria, in which length of incubation was manipulated so that some adults experienced short (10–20 days duration), long (70–80 days) or normal (~45 days) incubation periods. Adults with a manipulated incubation period did not show significant differences in weight change (taken here to reflect cost) during incubation or chick-rearing compared with controls. Manipulation of length of incubation did not significantly affect the hatching success or the growth rate of chicks involved and is not, therefore considered to impose an increased reproductive cost. This suggests that the Australasian Gannet has the capacity to maintain body condition and successfully rear young despite modified duration of incubation.

Antitumor activity and underlying mechamisms of ganopoly, the refined polysaccharides extracted from ganodrema lucidum, in mice

Ganopoly is an aqueous polysaccharide fraction extracted from G. lucidum by patented biochemical technique and has been marketed as an over-the-counter product for chronic diseases including cancer and hepatopathy in many Asian countries. This study was undertaken to explore the anti-tumour effect and the underlying mechanisms of Ganopoly in mice and human tumor cell lines. The maximum tolerateddose (MTD) of Ganopoly in mice was estimated to be 100 mg/kg from a pilot study. Treatment of mice with oral Ganopoly for 10 days significantly reduced the tumour weight of sarcoma-180 in a dose-dependent manner, with inhibition rates of 32.3, 48.2 and 84.9% and growth delays of 1.5, 3.5, and 13.1 days at 20, 50, and 100 mg/kg, respectively. Incubation of Ganopoly at 0.05-1.0 mg/ml for 48 hours showed little or negligible cytotoxicity against human tumor CaSki, SiHa, Hep3B, HepG2, HCT116, HT29, and MCF7 cells in vitro. In contrast, 10 mg/ml of Ganopoly caused significant cytotoxicity in all tumour cells tested except MCF7, with marked apoptotic effects observed in CaSki, HepG2, and HCT116 cells, as indicated by nuclear staining and DNA fragmentation. In addition, Ganopoly enhanced concanavalin A-stimulated proliferation of murine splenocytes by 35.3% at 10 mg/ml, and stimulated the production of nitric oxide in thioglycollate-primed murine peritoneal macrophages in a concentration-dependent manner over 0.05-10 mg/ml. Addition of Ganopoly at 1 mg/ml to murine peritoneal macrophages also potentiated lipopolysaccharide-induced nitric oxide production by 64.2%. Treatment of healthy mice or mice bearing sarsoma-180 with oral Ganopoly over 20-100 mg/kg for 7 day significantly increased the expression of both TNF-α and IFN-γ (at both mRNA and protein levels) in splenocytes in a dose-dependent manner. Moreover, treatment of Ganopoly over 20-100 mg/kg significantly increased cytotoxic T lymphocyte cytotoxicity and NK activity in mice. The overall findings indicated that Ganopoly had antitumor activity with a broad spectrum of immuno-modulating activities and may represent a novel promising immunotherapeutic agent in cancer treatment.

Mothers and sons : using memory-work to explore the subjectivities and practices of profeminist men

In this chapter I will outline the application of memory-work to understanding the subjectivities and practices of profeminist men. Profeminism for men involves a sense of responsibility to our own and other men's sexism, and a commitment to work with women to end men's violence (Douglas, 1993). It acknowledges that men benefit from the oppression of women, drawing men's attention to the privileges we receive as men and the harmful effects these privileges have on women (Thome-Finch, 1992). The research was undertaken as my PhD thesis and it began with questions that have been a personal challenge in my search· to understand my place as a white, heterosexual man who is committed to a profeminist position 1. What does it mean to be a profeminist man? What is the experience of endeavoring to live out a profeminist commitment? What do these experiences tell us about reforming men's subjectivities and practices towards gender equality? I believe that men's subjectivity is crucial to the maintenance and reproduction of gender domination and hence to its change. The purpose of the research was thus to theorize men's subjectivities and practices to inform a profeminist men's practice and to enact strategies that will, in themselves, promote the process of change. So the research was driven by practical concerns as well as by the imperatives of intellectual inquiry.

The effects of the social structure of digital networks on viral marketing performance

Viral marketing is a form of peer-to-peer communication in which individuals are encouraged to pass on promotional messages within their social networks. Conventional wisdom holds that the viral marketing process is both random and unmanageable. In this paper, we deconstruct the process and investigate the formation of the activated digital network as distinct from the underlying social network. We then consider the impact of the social structure of digital networks (random, scale free, and small world) and of the transmission behavior of individuals on campaign performance. Specifically, we identify alternative social network models to understand the mediating effects of the social structures of these models on viral marketing campaigns. Next, we analyse an actual viral marketing campaign and use the empirical data to develop and validate a computer simulation model for viral marketing. Finally, we conduct a number of simulation experiments to predict the spread of a viral message within different types of social network structures under different assumptions and scenarios. Our findings confirm that the social structure of digital networks play a critical role in the spread of a viral message. Managers seeking to optimize campaign performance should give consideration to these findings before designing and implementing viral marketing campaigns. We also demonstrate how a simulation model is used to quantify the impact of campaign management inputs and how these learnings can support managerial decision making.

Practitioner prognostications on the future of online marketing

In arguably the most dynamic period in the history of marketing, and in particular the management of marketing communication, the challenges and opportunities presented by online marketing are both immense and unprecedented. In an effort to understand how these challenges are perceived at the ‘coal face’, this paper solicits and longitudinally compares senior marketing practitioners’ perceptions and perspectives, both recently (late 2008) and five years prior (2003). Due to the rapid evolution of online marketing and its impact on both consumer behaviour and marketing strategy, a longitudinal qualitative research design was employed to track changes in senior marketers’ perceptions. Findings are presented and discussed within the context of six recurring themes: interactivity, personalisation, integration, evaluation, agency structures, and capabilities. The paper concludes by examining the utility of integrated marketing communication as a marketing management framework for online marketing strategy.

Exploring the potential of knowledge brokering to enhance natural resource management : findings from the Catchment Knowledge Exchange project in Victoria

Despite significant efforts in natural resource management (NRM), the environmental condition of Victoria’s catchments is mostly ‘poor to moderate’, and continuing to decline in many places. NRM is a complex undertaking involving social, economic, and environmental objectives, across policy, research, and practice dimensions. It is therefore not easy to ensure that the knowledge required to underpin effective NRM is readily available to practitioners. Knowledge brokering is an emerging approach with the potential to improve knowledge sharing and exchange. While it has attracted attention in other areas of public interest (such as health and information technology), its potential in NRM has received relatively limited attention. This article reports on a Victorian knowledge brokering case study which was a major element in the Catchment Knowledge Exchange project. A key finding is that knowledge brokering is a role that is being undertaken informally, without proper acknowledgement or definition. This raises challenges for knowledge management in the context of NRM. We conclude that the ‘people’ component of knowledge brokering is the driving element, although organisational processes and information technologies are critical in enhancing the effectiveness of knowledge brokers. Demonstrating the benefits of knowledge brokering in terms of the ultimate measure of its contribution towards improving the condition of catchments remains a challenge.

Three phases of the Pacific Islands Project (1995–2010)

The Pacific Islands Project (PIP), funded by AusAid and managed by the Royal Australasian College of Surgeons (RACS), has progressed through three phases from 1995 to 2010. During this time, it has sent over 520 teams to 11 Pacific Island Countries, providing over 60 000 consultations and some 16 000 procedures. In addition to this delivery of specialist medical and surgical services that were not previously available in-country, the project has contributed as a partner in capacity building with the Fiji School of Medicine and Ministries of Health of the individual nations. By 2011, Fiji School of Medicine, which began postgraduate specialist training in 1998, had awarded 51 doctors a diploma in surgery (1 year), 20 of whom had completed their Masters in Medicine (4 years). PIP was independently evaluated on completion of every phase, including the bridging Phase III (2006–2010). The project delivered on its design, to deliver services, and also helped build capacity. The relationship established with the RACS throughout the project allowed Pacific Island graduates to access the Rowan Nicks scholarship, and the majority of MMed graduates received International Travel Grants to attend the Annual Scientific Meeting. PIP has been a highly successful partnership in delivering and building specialist medical services. Although AusAid contributed some $20 million over 16 years, the value added from pro bono contributions by Specialist Teams, Specialty Coordinators and the Project Directors amounted to an equivalent amount. With the emergence of Pacific Island-trained specialists, PIP is ready to move into a new phase where the agendas are set, monitored and managed within the Pacific, and RACS fulfils the role of a service provider. A critical mass of Pacific Island surgeons has been trained, so that sub-specialization will be an option for the general surgeons of the larger island nations.

Rapid detection of SMARCB1 sequence variation using high resolution melting

Background : Rhabdoid tumors are rare cancers of early childhood arising in the kidney, central nervous system and other organs. The majority are caused by somatic inactivating mutations or deletions affecting the tumor suppressor locus SMARCB1 [OMIM 601607]. Germ-line SMARCB1 inactivation has been reported in association with rhabdoid tumor, epitheloid sarcoma and familial schwannomatosis, underscoring the importance of accurate mutation screening to ascertain recurrence and transmission risks. We describe a rapid and sensitive diagnostic screening method, using high resolution melting (HRM), for detecting sequence variations in SMARCB1. Methods : Amplicons, encompassing the nine coding exons of SMARCB1, flanking splice site sequences and the 5' and 3' UTR, were screened by both HRM and direct DNA sequencing to establish the reliability of HRM as a primary mutation screening tool. Reaction conditions were optimized with commercially available HRM mixes. Results : The false negative rate for detecting sequence variants by HRM in our sample series was zero. Nine amplicons out of a total of 140 (6.4%) showed variant melt profiles that were subsequently shown to be false positive. Overall nine distinct pathogenic SMARCB1 mutations were identified in a total of 19 possible rhabdoid tumors. Two tumors had two distinct mutations and two harbored SMARCB1 deletion. Other mutations were nonsense or frame-shifts. The detection sensitivity of the HRM screening method was influenced by both sequence context and specific nucleotide change and varied from 1: 4 to 1:1000 (variant to wild-type DNA). A novel method involving digital HRM, followed by re-sequencing, was used to confirm mutations in tumor specimens containing associated normal tissue. Conclusions : This is the first report describing SMARCB1 mutation screening using HRM. HRM is a rapid, sensitive and inexpensive screening technology that is likely to be widely adopted in diagnostic laboratories to facilitate whole gene mutation screening.

Impact of HIV-associated conditions on mortality in people commencing anti-retroviral therapy in resource limited settings

Objectives: To identify associations between specific WHO stage 3 and 4 conditions diagnosed after ART initiation and all cause mortality for patients in resource-limited settings (RLS).

Design, Setting: Analysis of routine program data collected prospectively from 25 programs in eight countries between 2002 and 2010.

Subjects, Participants: 36,664 study participants with median ART follow-up of 1.26 years (IQR 0.55–2.27).

Outcome Measures: Using a proportional hazards model we identified factors associated with mortality, including the occurrence of specific WHO clinical stage 3 and 4 conditions during the 6-months following ART initiation.

Results: There were 2922 deaths during follow-up (8.0%). The crude mortality rate was 5.41 deaths per 100 person-years (95% CI: 5.21–5.61). The diagnosis of any WHO stage 3 or 4 condition during the first 6 months of ART was associated with
increased mortality (HR: 2.21; 95% CI: 1.97–2.47). After adjustment for age, sex, region and pre-ART CD4 count, a diagnosis of extrapulmonary cryptococcosis (aHR: 3.54; 95% CI: 2.74–4.56), HIV wasting syndrome (aHR: 2.92; 95%CI: 2.21 -3.85), nontuberculous mycobacterial infection (aHR: 2.43; 95% CI: 1.80–3.28) and Pneumocystis pneumonia (aHR: 2.17; 95% CI 1.80–3.28) were associated with the greatest increased mortality. Cerebral toxoplasmosis, pulmonary and extra-pulmonary
tuberculosis, Kaposi’s sarcoma and oral and oesophageal candidiasis were associated with increased mortality, though at lower rates.

Conclusions: A diagnosis of certain WHO stage 3 and 4 conditions is associated with an increased risk of mortality in those initiating ART in RLS. This information will assist initiatives to reduce excess mortality, including prioritization of resources for
diagnostics, therapeutic interventions and research.

The good news about television: attitudes aren't getting worse: tracking public attitudes toward TV advertising

Periodically tracking public sentiment toward television advertising (TVA) is an important barometer for the advertising industry and its myriad stakeholders. To date, however, most studies of consumers’ attitudes to TVA have been cross-sectional. This study, alternatively, provides a quasi-longitudinal examination of Australian attitudes toward TVA across four time points (2002, 2005, 2008, and 2010). Findings suggest that although attitudes toward TVA are generally negative, in fact they have not deteriorated over time. Considerable scope consequently exists for improving consumer attitudes toward TVA.