Epidermal growth factor-induced epithelio-mesenchymal transition in human breast carcinoma cells

PMC42-LA cells display an epithelial phenotype: the cells congregate into pavement epithelial sheets in which E-cadherin and β-catenin are localized at cell-cell borders. They abundantly express cytokeratins, although 5% to 10% of the cells also express the mesenchymal marker vimentin. Stimulation of PMC42-LA cells with epidermal growth factor (EGF) leads to epithelio-mesenchymal transition-like changes including up-regulation of vimentin and down-regulation of E-cadherin. Vimentin expression is seen in virtually all cells, and this increase is abrogated by treatment of cells with an EGF receptor antagonist. The expression of the mesenchyme-associated extracellular matrix molecules fibronectin and chondroitin sulfate proteoglycan also increase in the presence of EGF. PMC42-LA cells adhere rapidly to collagen I, collagen IV, and laminin-1 substrates and markedly more slowly to fibronectin and vitronectin. EGF increases the speed of cell adhesion to most of these extracellular matrix molecules without altering the order of adhesive preference. EGF also caused a time-dependent increase in the motility of PMC42-LA cells, commensurate with the degree of vimentin staining. The increase in motility was at least partly chemokinetic, because it was evident both with and without chemoattractive stimuli. Although E-cadherin staining at cell-cell junctions disappeared in response to EGF, β-catenin persisted at the cell periphery. Further analysis revealed that N-cadherin was present at the cell-cell junctions of untreated cells and that expression was increased after EGF treatment. N- and E-cadherin are not usually coexpressed in human carcinoma cell lines but can be coexpressed in embryonic tissues, and this may signify an epithelial cell population prone to epithelio-mesenchymal-like responses.

Integrating understandability in the evaluation of consumer health search engines

In this paper we propose a method that integrates the no- tion of understandability, as a factor of document relevance, into the evaluation of information retrieval systems for con- sumer health search. We consider the gain-discount evaluation framework (RBP, nDCG, ERR) and propose two understandability-based variants (uRBP) of rank biased precision, characterised by an estimation of understandability based on document readability and by different models of how readability influences user understanding of document content. The proposed uRBP measures are empirically contrasted to RBP by comparing system rankings obtained with each measure. The findings suggest that considering understandability along with topicality in the evaluation of in- formation retrieval systems lead to different claims about systems effectiveness than considering topicality alone.

Exploring the factor structure of a new self- and other-oriented alcohol expectancy scale relating to sexual coercion and vulnerability

Introduction and Aim: Sexual assaults commonly involve alcohol use by the perpetrator, victim, or both. Beliefs about alcohol’s effects may impact on people’s perceptions of and responses to men and women who have had such experiences while intoxicated from alcohol. This study aimed to develop an alcohol expectancy scale that captures young adults’ beliefs about alcohol’s role in sexual aggression and victimisation. Design and Methods: Based on pilot focus groups, an initial pool of 135 alcohol expectancy items was developed, checked for readability and face validity, and administered via a cross-sectional survey to 201 male and female university students (18-25 years). Items were specified in terms of three target drinkers: self, men, and women. In addition, a social desirability measure was included. Results: Principal Axis Factoring revealed a 4-factor solution for the targets men and women and a 5-factor solution for the target self with 72 items retained. Factors related to sexual coercion, sexual vulnerability, confidence, self-centredness, and negative cognitive and behavioural effects. Social desirability issues were evident for the target self, but not for the targets men and women. Discussion and Conclusions: Young adults link alcohol’s effects with sexual vulnerabilities via perceived risky cognitions and behaviours. Due to social desirability, these expectancies may be difficult to explicate for the self but may be accessible instead via other-oriented assessment. The Sexual Coercion and Vulnerability Alcohol Expectancy Scale has potential as a tool to elucidate the established tendency for observers to excuse intoxicated sexual perpetrators while blaming intoxicated victims.

Study Protocol - Alcohol Management Plans (AMPs) in remote indigenous communities in Queensland: their impacts on injury, violence, health and social indicators and their cost-effectiveness

Background In 2002/03 the Queensland Government responded to high rates of alcohol-related harm in discrete Indigenous communities by implementing alcohol management plans (AMPs), designed to include supply and harm reduction and treatment measures. Tighter alcohol supply and carriage restrictions followed in 2008 following indications of reductions in violence and injury. Despite the plans being in place for over a decade, no comprehensive independent review has assessed to what level the designed aims were achieved and what effect the plans have had on Indigenous community residents and service providers. This study will describe the long-term impacts on important health, economic and social outcomes of Queensland’s AMPs. Methods/Design The project has two main studies, 1) outcome evaluation using de-identified epidemiological data on injury, violence and other health and social indicators for across Queensland, including de-identified databases compiled from relevant routinely-available administrative data sets, and 2) a process evaluation to map the nature, timing and content of intervention components targeting alcohol. Process evaluation will also be used to assess the fidelity with which the designed intervention components have been implemented, their uptake and community responses to them and their perceived impacts on alcohol supply and consumption, injury, violence and community health. Interviews and focus groups with Indigenous residents and service providers will be used. The study will be conducted in all 24 of Queensland’s Indigenous communities affected by alcohol management plans. Discussion This evaluation will report on the impacts of the original aims for AMPs, what impact they have had on Indigenous residents and service providers. A central outcome will be the establishment of relevant databases describing the parameters of the changes seen. This will permit comprehensive and rigorous surveillance systems to be put in place and provided to communities empowering them with the best credible evidence to judge future policy and program requirements for themselves. The project will inform impending alcohol policy and program adjustments in Queensland and other Australian jurisdictions. The project has been approved by the James Cook University Human Research Ethics Committee (approval number H4967 & H5241).

Validation of a framework for measuring hospital disaster resilience using factor analysis

Hospital disaster resilience can be defined as “the ability of hospitals to resist, absorb, and respond to the shock of disasters while maintaining and surging essential health services, and then to recover to its original state or adapt to a new one.” This article aims to provide a framework which can be used to comprehensively measure hospital disaster resilience. An evaluation framework for assessing hospital resilience was initially proposed through a systematic literature review and Modified-Delphi consultation. Eight key domains were identified: hospital safety, command, communication and cooperation system, disaster plan, resource stockpile, staff capability, disaster training and drills, emergency services and surge capability, and recovery and adaptation. The data for this study were collected from 41 tertiary hospitals in Shandong Province in China, using a specially designed questionnaire. Factor analysis was conducted to determine the underpinning structure of the framework. It identified a four-factor structure of hospital resilience, namely, emergency medical response capability (F1), disaster management mechanisms (F2), hospital infrastructural safety (F3), and disaster resources (F4). These factors displayed good internal consistency. The overall level of hospital disaster resilience (F) was calculated using the scoring model: F = 0.615F1 + 0.202F2 + 0.103F3 + 0.080F4. This validated framework provides a new way to operationalise the concept of hospital resilience, and it is also a foundation for the further development of the measurement instrument in future studies.

Evaluation of public hospital performance in Khanh Hoa Province : Vietnam in connection with patient and staff satisfaction surveys

This research aimed to develop a framework for performance evaluation of public hospitals in Vietnam that is culturally, socially, and politically appropriate. The research included both qualitative and quantitative methods and identified and validated novel instruments to measure patient satisfaction and job satisfaction of hospital staff and to determine a set of hospital indicators that reflect the quality of hospital performance. New models for understanding the determinants of patient and staff satisfaction were developed along with a new performance indicator framework for hospital performance. These instruments will now be applied to the evaluation of hospital services in Khanh Hoa Province, permitting longer term evaluation of their effectiveness in changing system wide performance and satisfaction.

Controlled systemic release of interleukin-12 after gene electrotransfer to muscle for cancer gene therapy alone or in combination with ionizing radiation in murine sarcomas

Background: The present study aimed to evaluate the antitumor effectiveness of systemic interleukin (IL)-12 gene therapy in murine sarcoma models, and to evaluate its interaction with the irradiation of tumors and metastases. To avoid toxic side-effects of IL-12 gene therapy, the objective was to achieve the controlled release of IL-12 after intramuscular gene electrotransfer. Methods: Gene electrotransfer of the plasmid pORF-mIL12 was performed into the tibialis cranialis in A/J and C57BL/6 mice. Systemic release of the IL-12 was monitored in the serum of mice after carrying out two sets of intramuscular IL-12 gene electrotransfer of two different doses of plasmid DNA. The antitumor effectiveness of IL-12 gene electrotransfer alone or in combination with local tumor or lung irradiation with X-rays, was evaluated on subcutaneous SA-1 and LPB tumors, as well as on lung metastases. Results: A synergistic antitumor effect of intramuscular gene electrotransfer combined with local tumor irradiation was observed as a result of the systemic distribution of IL-12. The gene electrotransfer resulted in up to 28% of complete responses of tumors. In combination with local tumor irradiation, the curability was increased by up to 100%. The same effect was observed for lung metastases, where a potentiating factor of 1.3-fold was determined. The amount of circulating IL-12 was controlled by the number of repeats of gene electrotransfer and by the amount of the injected plasmid. Conclusions: The present study demonstrates the feasibility of treatment by IL-12 gene electrotransfer combined with local tumor or lung metastases irradiation on sarcoma tumors for translation into the clinical setting. Copyright © 2009 John Wiley & Sons, Ltd.

Confirmatory factor analysis of the baby eating behaviour questionnaire and associations with infant weight, gender and feeding mode in an Australian sample

The aim of this study was to evaluate the factor structure of the Baby Eating Behaviour Questionnaire (BEBQ) in an Australian community sample of mother-infant dyads. A secondary aim was to explore the relationship between the BEBQ subscales and infant gender, weight and current feeding mode. Confirmatory factor analysis (CFA) utilising structural equation modelling examined the hypothesised 4-factor model of the BEBQ. Only mothers (N=467) who completed all items on the BEBQ (infant age: M=17 weeks, SD=3 weeks) were included in the analysis. The original 4-factor model did not provide an acceptable fit to the data due to poor performance of the Satiety responsiveness factor. Removal of this factor (3 items) resulted in a well-fitting 3-factor model. Cronbach’s α was acceptable for the Enjoyment of food (α=0.73), Food responsiveness (α=0.78) and Slowness in eating (α=0.68) subscales but low for the Satiety responsiveness (α=0.56) subscale. Enjoyment of food was associated with higher infant weight whereas Slowness in eating and Satiety responsiveness were both associated with lower infant weight. Differences on all four subscales as a function of feeding mode were observed. This study is the first to use CFA to evaluate the hypothesised factor structure of the BEBQ. Findings support further development work on the Satiety responsiveness subscale in particular, but confirm the utility of the Enjoyment of food, Food responsiveness and Slowness in eating subscales.

On governance structures for the cloud computing services and assessing their effectiveness

This research suggests information technology (IT) governance structures to manage the cloud computing services. The interest in acquiring IT resources as a utility from the cloud computing environment is gaining momentum. The cloud computing services present organizations with opportunities to manage their IT expenditure on an ongoing basis, and access to modern IT resources to innovate and manage their continuity. However, the cloud computing services are no silver bullet. Organizations would need to have appropriate governance structures and policies in place to manage the cloud computing services. The subsequent decisions from these governance structures will ensure the effective management of the cloud computing services. This management will facilitate a better fit of the cloud computing services into organizations’ existing processes to achieve the business (process-level) and the financial (firm-level) objectives. Using a triangulation approach, we suggest four governance structures for managing the cloud computing services. These structures are a chief cloud officer, a cloud management committee, a cloud service facilitation centre, and a cloud relationship centre. We also propose that these governance structures would relate directly to organizations cloud computing services-related business objectives, and indirectly to cloud computing services-related financial objectives. Perceptive field survey data from actual and prospective cloud computing service adopters suggest that the suggested governance structures would contribute directly to cloud computing-related business objectives and indirectly to cloud computing-related financial objectives.

The cost-effectiveness of total laparoscopic hysterectomy compared to total abdominal hysterectomy for the treatment of early stage endometrial cancer

Objective To summarise how costs and health benefits will change with the adoption of total laparoscopic hysterectomy compared to total abdominal hysterectomy for the treatment of early stage endometrial cancer. Design Cost-effectiveness modelling using the information from a randomised controlled trial. Participants Two hypothetical modelled cohorts of 1000 individuals undergoing total laparoscopic hysterectomy and total abdominal hysterectomy. Outcome measures Surgery costs; hospital bed days used; total healthcare costs; quality-adjusted life years; and net monetary benefits. Results For 1000 individuals receiving total laparoscopic hysterectomy surgery, the costs were $509 575 higher, 3548 hospital fewer bed days were used and total health services costs were reduced by $3 746 221. There were 39.13 more quality-adjusted life years for a 5 year period following surgery. Conclusions The adoption of total laparoscopic hysterectomy is almost certainly a good decision for health services policy makers. There is 100% probability that it will be cost saving to health services, a 86.8% probability that it will increase health benefits and a 99.5% chance that it returns net monetary benefits greater than zero.

Exploring potential factors leading to effective training : an exclusive study on commercial banks in Cambodia

Purpose A previous study found that the quality of education in Cambodia is poor compared to other developing countries. However, the working performance of commercial banks in Cambodia is high. It was speculated that effective training was the main factor underlying this contradiction. Therefore, the main purpose of this article is to explore the elements of training conducted by commercial banks in Cambodia and to examine their relationship with training effectiveness. Design/methodology/approach The research focuses on six factors: training needs assessment; training program; flexibility of training; self-efficacy; social support; and transfer of knowledge. The data came in the form of questionnaires and desk research. A descriptive analytical approach is then used to describe these six factors. Findings The banking industry in Cambodia offers very effective training to its employees. It is also worth noting that more than 80 percent of employees are satisfied with the training, despite few attempts on the part of management to elicit opinions from employees on what training methods should be employed. Research limitations/implications As research studies involving Cambodia are relatively rare, it was difficult for to gather primary data. Because of this limitation and the purpose of this study, descriptive data interpretation was employed. Practical implications – Even though training can make up for poor education, it is only a short-term solution. In the long term, education needs to be enhanced to increase working performance. Originality/value This research provides a good framework for commercial banks in other developing countries to compare. A cross-cultural study is also proposed for future research.

The role of the yeast cleavage and polyadenylation factor subunit Ydh1p/Cft2p in pre-mRNA 3'-end formation

Cleavage and polyadenylation factor (CPF) is a multi‐protein complex that functions in pre‐mRNA 3′‐end formation and in the RNA polymerase II (RNAP II) transcription cycle. Ydh1p/Cft2p is an essential component of CPF but its precise role in 3′‐end processing remained unclear. We found that mutations in YDH1 inhibited both the cleavage and the polyadenylation steps of the 3′‐end formation reaction in vitro. Recently, we demonstrated that an important function of CPF lies in the recognition of poly(A) site sequences and RNA binding analyses suggesting that Ydh1p/Cft2p interacts with the poly(A) site region. Here we show that mutant ydh1 strains are deficient in the recognition of the ACT1 cleavage site in vivo. The C‐terminal domain (CTD) of RNAP II plays a major role in coupling 3′‐end processing and transcription. We provide evidence that Ydh1p/Cft2p interacts with the CTD of RNAP II, several other subunits of CPF and with Pcf11p, a component of CF IA. We propose that Ydh1p/Cft2p contributes to the formation of important interaction surfaces that mediate the dynamic association of CPF with RNAP II, the recognition of poly(A) site sequences and the assembly of the polyadenylation machinery on the RNA substrate.

Organisational factors that drive fundraising effectiveness in Australian health charities

This research sought to explore organisational factors that drive successful fundraising. Drawing on Strategic Management theory, this qualitative study examined the key intraorganisational factors that organisations develop to be effective at fundraising within the context of extraorganisational factors that can affect fundraising effectiveness. In this way, it helps build a fundraising effectiveness theory. The findings from this study afford leaders of nonprofits an opportunity to reflect on their reasons for pursuing fundraising as an income stream, their level of understanding of fundraising, the degree of investment they are willing to make and the critical leadership required by the CEO.

Differential subcellular and extracellular localisations of proteins required for insulin-like growth factor- and extracellular matrix-induced signalling events in breast cancer progression

Background: Cancer metastasis is the main contributor to breast cancer fatalities as women with the metastatic disease have poorer survival outcomes than women with localised breast cancers. There is an urgent need to develop appropriate prognostic methods to stratify patients based on the propensities of their cancers to metastasise. The insulin-like growth factor (IGF)-I:IGF binding protein (IGFBP):vitronectin complexes have been shown to stimulate changes in gene expression favouring increased breast cancer cell survival and a migratory phenotype. We therefore investigated the prognostic potential of these IGF- and extracellular matrix (ECM) interaction-induced proteins in the early identification of breast cancers with a propensity to metastasise using patient-derived tissue microarrays. Methods: Semiquantitative immunohistochemistry analyses were performed to compare the extracellular and subcellular distribution of IGF- and ECM-induced signalling proteins among matched normal, primary cancer and metastatic cancer formalin-fixed paraffin-embedded breast tissue samples. Results: The IGF- and ECM-induced signalling proteins were differentially expressed between subcellular and extracellular localisations. Vitronectin and IGFBP-5 immunoreactivity was lower while β1 integrin immunoreactivity was higher in the stroma surrounding metastatic cancer tissues, as compared to normal breast and primary cancer stromal tissues. Similarly, immunoreactive stratifin was found to be increased in the stroma of primary as well as metastatic breast tissues. Immunoreactive fibronectin and β1 integrin was found to be highly expressed at the leading edge of tumours. Based on the immunoreactivity it was apparent that the cell signalling proteins AKT1 and ERK1/2 shuffled from the nucleus to the cytoplasm with tumour progression. Conclusion: This is the first in-depth, compartmentalised analysis of the distribution of IGF- and ECM-induced signalling proteins in metastatic breast cancers. This study has provided insights into the changing pattern of cellular localisation and expression of IGF- and ECM-induced signalling proteins in different stages of breast cancer. The differential distribution of these biomarkers could provide important prognostic and predictive indicators that may assist the clinical management of breast disease, namely in the early identification of cancers with a propensity to metastasise, and/or recur following adjuvant therapy.

Calculation of the oxygen isotope discrimination factor for studying plant respiration

Measurement of discrimination against 18O during dark respiration in plants is currently accepted as the only reliable method of estimating the partitioning of electrons between the cytochrome and alternative pathways. In this paper, we review the theory of the technique and its application to a gas-phase system. We extend it to include sampling effects and show that the isotope discrimination factor, D, is calculated as –dln(1 + δ)/dlnO*, where δ is isotopic composition of the substrate oxygen and O*=[O2]/[N2] in a closed chamber containing tissue respiring in the dark. It is not necessary to integrate the expression but, if the integrated form is used, the resultant regression should not be constrained through the origin. This is important since any error in D will have significant effects on the estimation of the flux of electrons through the two pathways.