Acquisition of estrogen independence and antiestrogen resistance in breast cancer : association with the invasive and metastatic phenotype

A significant percentage of human breast cancer (HBC) is dependent upon the ovarian hormone estrogen for its onset and progression. The presence or lack of estrogen receptors (ERs) in human breast cancer is an important determinant both of prognosis and of choice of treatment - a poorer prognosis being associated with ER–ve disease. Cell lines established from human breast cancer provide models for breast cancer in various stages of progression (Engel & Young 1978). When grown as tumors in athymic nude mice, these lines represent the major in vivo experimental model for HBC studies (Brünner et al 1987). The ease of both in vitro and in vivo maintenance, the human derivation of the tissue, and the similarities in plasma estrogen levels between ovariectomized nude mice and postmenopausal women (Seibert et al. 1983, Brünner et al. 1986), make the growth of human breast cancer cell lines in nude mice an attractive...

Electron tomography reveals the steps in filovirus budding

The filoviruses, Marburg and Ebola, are non-segmented negative-strand RNA viruses causing severe hemorrhagic fever with high mortality rates in humans and nonhuman primates. The sequence of events that leads to release of filovirus particles from cells is poorly understood. Two contrasting mechanisms have been proposed, one proceeding via a "submarine-like" budding with the helical nucleocapsid emerging parallel to the plasma membrane, and the other via perpendicular "rocketlike" protrusion. Here we have infected cells with Marburg virus under BSL-4 containment conditions, and reconstructed the sequence of steps in the budding process in three dimensions using electron tomography of plastic-embedded cells. We find that highly infectious filamentous particles are released at early stages in infection. Budding proceeds via lateral association of intracellular nucleocapsid along its whole length with the plasma membrane, followed by rapid envelopment initiated at one end of the nucleocapsid, leading to a protruding intermediate. Scission results in local membrane instability at the rear of the virus. After prolonged infection, increased vesiculation of the plasma membrane correlates with changes in shape and infectivity of released viruses. Our observations demonstrate a cellular determinant of virus shape. They reconcile the contrasting models of filovirus budding and allow us to describe the sequence of events taking place during budding and release of Marburg virus. We propose that this represents a general sequence of events also followed by other filamentous and rod-shaped viruses.

Banking sector contingent liabilities and sovereign risk

The global financial crisis has underscored the need to pay attention to contingent government liabilities that could arise from bank failures for sovereign risk management. This paper proposes a simple method to construct a contingent liability index (CLI) for a banking sector that takes into account the size and concentration of the banking system, market expectations of bank defaults, and perceptions of government support to each bank. This method allows us to track potential government liabilities related to bank failures for 32 advanced and emerging economies on a monthly basis from 2006 to 2013. Furthermore, we find that the CLI is a significant determinant of sovereign CDS spreads. Our results suggest that a 1 percentage point increase in the CLI is associated with an increase in sovereign CDS spreads by 24 basis points for advanced economies and 75 basis points for emerging markets on average.

Driven by distraction: Investigating the effects of anxiety on driving performance using the Attentional Control Theory

This study investigates the effects of trait anxiety on self-reported driving behaviours through its negative impacts on Central Executive functions. Following a self-report study that found trait anxiety to be significantly related to driving behaviours, the present study extended the predictions of Eysenck and Calvo’s Attentional Control Theory, proposing that anxiety affects driving behaviours, in particular driving lapses, through its impact across the Central Executive. Seventy-five Australian drivers participated in the study, completing the Parametric Go/No-Go and n-back tasks, as well as the State-Trait Anxiety Inventory and the Driving Behaviour Questionnaire. While both trait anxiety and processing efficiency of the Central Executive was found to significantly predict driving lapses, trait anxiety remained a strong predictor of driving lapses after processing efficiency was controlled for. It is concluded that while processing efficiency of the central Executive is a key determinant of driving lapses, another Central Executive function that is closer to the driving lapses in the trait anxiety – driving lapses relationship may be needed. Suggestions regarding how to improve future trait anxiety – driving behaviours research are discussed.

Airborne viable fungi in school environments in different climatic regions – A review

Elevated levels of fungi in indoor environments have been linked with mould/moisture damage in building structures. However, there is a lack of information about “normal” concentrations and flora as well as guidelines of viable fungi in the school environment in different climatic conditions. We have reviewed existing guidelines for indoor fungi and the current knowledge of the concentrations and flora of viable fungi in different climatic areas, the impact of the local factors on concentrations and flora of viable fungi in school environments. Meta-regression was performed to estimate the average behaviour for each analysis of interest, showing wide variation in the mean concentrations in outdoor and indoor school environments (range: 101-103 cfu/m3). These concentrations were significantly higher for both outdoors and indoors in the moderate than in the continental climatic area, showing that the climatic condition was a determinant for the concentrations of airborne viable fungi. The most common fungal species both in the moderate and continental area were Cladosporium spp. and Penicillium spp. The suggested few quantitative guidelines for indoor air viable fungi for school buildings are much lower than for residential areas. This review provides a synthesis, which can be used to guide the interpretation of the fungi measurements results and help to find indications of mould/moisture in school building structures.

Sources of productivity growth in health services : a case study of Queensland public hospitals

Improving the performance of health sector is one of the most popular issues in Australia. This paper contributes to this important policy debate by examining the efficiency of health facilities in Queensland using the Malmquist Productivity Index (MPI). This method is selected because it is suitable for the multi-input, multi-output, and not-for-profit natures of public health services. In addition, with the availability of panel data we can decompose productivity growth into useful components, including technical efficiency changes, technological changes and scale changes. The results revealed an average of 1.6 per cent of growth in total factor productivity (TFP) among Queensland public hospitals in the study period. The main component contributing to the modest improvement of TFP during the period was catching-up at an average of 1.0 per cent. SFA estimates suggest that the number of nurses is the most influential determinant of output.

What determines weight loss behaviour and body weight satisfaction in Australia? Evidence from the HILDA survey

This thesis undertakes an empirical investigation to identify factors that influence the decision to undertake weight loss behaviour using the nationally representative HILDA dataset. Although many factors influenced the decision, the findings suggested that body weight satisfaction was the greatest determinant of weight loss dieting. This thesis therefore conducted a further empirical study to analyse the determinants of body weight satisfaction. A rank-hypothesis was found to better predict variation in body weight satisfaction levels than the absolute value of the individual's Body Mass Index (BMI) or the relative-norm hypothesis, which are commonly reported in the literature.

Prospective ten-month exercise intervention in premenarcheal girls: Positive effects on bone and lean mass

Enhancement of bone mineral acquisition during growth may be a useful preventive strategy against osteoporosis. The aim of this study was to explore the lean mass, strength, and bone mineral response to a 10-month, high-impact, strength-building exercise program in 71 premenarcheal girls, aged 9–10 years. Lean body mass, total body (TB), lumbar spine (LS), proximal femur (PF), and femoral neck (FN) bone mineral were measured using the Hologic QDR 2000+ bone densitometer. Strength was assessed using a grip dynamometer and the Cybex isokinetic dynamometer (Cybex II). At baseline, no significant difference in body composition, pubertal development, calcium intake, physical activity, strength, or bone mineral existed between groups. At completion, there were again no differences in height, total body mass, pubertal development, calcium intake, or external physical activity. In contrast, the exercise group gained significantly more lean mass, less body fat content, greater shoulder, knee and grip strength, and greater TB, LS, PF, and FN BMD (exercise: TB 3.5%, LS 4.8%, PF 4.5%, and FN 12.0%) compared with the controls (controls: TB 1.2%, LS 1.2%, PF 1.3%, and FN 1.7%). TB bone mineral content (BMC), LS BMC, PF BMC, FN BMC, LS bone mineral apparent density (BMAD), and FN bone area also increased at a significantly greater rate in the exercise group compared with the controls. In multiple regression analysis, change in lean mass was the primary determinant of TB, FN, PF, and LS BMD accrual. Although a large proportion of bone mineral accrual in the premenarcheal skeleton was related to growth, an osteogenic effect was associated with exercise. These results suggest that high-impact, strength building exercise is beneficial for premenarcheal strength, lean mass gains, and bone mineral acquisition.

Changes in cervical spine bone mineral density in response to flight training

BACKGROUND High magnitude loads and unusual loading regimes are two important determinants for increasing bone mass. Past research demonstrated that positive Gz-induced loading, providing high loads in an unaccustomed manner, had an osteogenic effect on bone. Another determinant of bone mass is that the bone response to loading is site specific. This study sought to further investigate the site specific bone response to loading, examining the cervical spine response, the site suspected of experiencing the greatest loading, to high performance flight. METHODS Bone mineral density (BMD) and bone mineral content (BMC) was monitored in 9 RAAF trainee fighter pilots completing an 8-mo flight training course on a PC-9 and 10 age-height-weight-matched controls. RESULTS At completion of the course, the pilots had a significant increase in cervical spine BMD and total body BMC. No significant changes were found for the control group. CONCLUSIONS This study demonstrated that the physical environment associated with flight training may have contributed to a significant increase in cervical spine bone mass in the trainee PC-9 pilots. The increase in bone mass was possibly a response to the strain generated by the daily wearing of helmet and mask assembly under the influence of positive sustained accelerative forces.

Small firm training: Just meeting the day-to-day needs of the business

Purpose The purpose of this paper is to explore what the attitudes of small firm owner-managers are to developing the skills of their key resources and then examine how these and other factors affect owner-managers’ preferences for training these employees. Design/methodology/approach This study of training in small road transport firms in West Australia is cast in light of the literature on human resource management in small firms underpinned by insights drawn using the resource based view of the firm. Small firms (less than 20 people) dominate this industry, while the increasing freight task, and extreme distances between West Australian ports, towns and mines highlight this sectors’ importance. Survey results from 39 small road transport firms and interviews with nine owner-managers are analysed. Findings Legislative, regulatory and licensing requirements were shown to be a key determinant of skills development. Employers ensured that basic standards for employee certification and qualification were met, as the penalty for not doing so would be too high. Regulations drove the need for certain types of training – licenses, fatigue management, occupational health and safety, handling dangerous goods, the Maritime Security Identification Card card, forklift license, mine site inductions – while owner-managers knew where to get the training their staff needed. Although regulation appeared most visible in prescribing what happened in relation to training for drivers, the relevance of owner-managers’ attitudes could not be ignored, nor could conditions in the firms external environment as this shaped how these requirements were met. Research limitations/implications The RBV is useful in showing how skill development enabled similarity in skills across firms, while the attitudes owner-managers and economic and social conditions meant what happened in firms around skill development varied. The importance of small firm owner-managers’ attitudes are clearly highlighted and shown to influence organizational decisions and choices around training, but these were not independent of the regulatory framework and the economic and social conditions within which the firm operated. The small firms in this study did engage workers in formal training when necessary but it was put in the context of the idiosyncratic approach of the owner-manager and the day-to-day needs of the firm. “Training” was essentially about ensuring certain types of skills were held by employees and then passing on knowledge to ensure the behavior of employees was consistent with the owner-manager’s vision for the firm in its current environment. Originality/value Ways industry and government can encourage training activity that goes beyond the day-to-day firm needs are suggested.

Best individual template selection from deformation tensor minimization

We study the influence of the choice of template in tensor-based morphometry. Using 3D brain MR images from 10 monozygotic twin pairs, we defined a tensor-based distance in the log-Euclidean framework [1] between each image pair in the study. Relative to this metric, twin pairs were found to be closer to each other on average than random pairings, consistent with evidence that brain structure is under strong genetic control. We also computed the intraclass correlation and associated permutation p-value at each voxel for the determinant of the Jacobian matrix of the transformation. The cumulative distribution function (cdf) of the p-values was found at each voxel for each of the templates and compared to the null distribution. Surprisingly, there was very little difference between CDFs of statistics computed from analyses using different templates. As the brain with least log-Euclidean deformation cost, the mean template defined here avoids the blurring caused by creating a synthetic image from a population, and when selected from a large population, avoids bias by being geometrically centered, in a metric that is sensitive enough to anatomical similarity that it can even detect genetic affinity among anatomies.

Grassland productivity limited by multiple nutrients

Terrestrial ecosystem productivity is widely accepted to be nutrient limited1. Although nitrogen (N) is deemed a key determinant of aboveground net primary production (ANPP)2,3, the prevalence of co-limitation by N and phosphorus (P) is increasingly recognized4,​5,​6,​7,​8. However, the extent to which terrestrial productivity is co-limited by nutrients other than N and P has remained unclear. Here, we report results from a standardized factorial nutrient addition experiment, in which we added N, P and potassium (K) combined with a selection of micronutrients (K+μ), alone or in concert, to 42 grassland sites spanning five continents, and monitored ANPP. Nutrient availability limited productivity at 31 of the 42 grassland sites. And pairwise combinations of N, P, and K+μ co-limited ANPP at 29 of the sites. Nitrogen limitation peaked in cool, high latitude sites. Our findings highlight the importance of less studied nutrients, such as K and micronutrients, for grassland productivity, and point to significant variations in the type and degree of nutrient limitation. We suggest that multiple-nutrient constraints must be considered when assessing the ecosystem-scale consequences of nutrient enrichment.

Perceived quality of e‐health services: A conceptual scale development of e‐health service quality based on the C‐OAR‐SE approach

Purpose Health service quality is an important determinant for health service satisfaction and behavioral intentions. The purpose of this paper is to investigate requirements of e‐health services and to develop a measurement model to analyze the construct of “perceived e‐health service quality.” Design/methodology/approach The paper adapts the C‐OAR‐SE procedure for scale development by Rossiter. The focal aspect is the “physician‐patient relationship” which forms the core dyad in the healthcare service provision. Several in‐depth interviews were conducted in Switzerland; first with six patients (as raters), followed by two experts of the healthcare system (as judges). Based on the results and an extensive literature research, the classification of object and attributes is developed for this model. Findings The construct e‐health service quality can be described as an abstract formative object and is operationalized with 13 items: accessibility, competence, information, usability/user friendliness, security, system integration, trust, individualization, empathy, ethical conduct, degree of performance, reliability, and ability to respond. Research limitations/implications Limitations include the number of interviews with patients and experts as well as critical issues associated with C‐OAR‐SE. More empirical research is needed to confirm the quality indicators of e‐health services. Practical implications Health care providers can utilize the results for the evaluation of their service quality. Practitioners can use the hierarchical structure to measure service quality at different levels. The model provides a diagnostic tool to identify poor and/or excellent performance with regard to the e‐service delivery. Originality/value The paper contributes to knowledge with regard to the measurement of e‐health quality and improves the understanding of how customers evaluate the quality of e‐health services.

The impact of international potentials, entrepreneurial motivations and firm stages on new venture internationalisation

Past research on early internationalising firms often examined factors and motivations potentially influencing internationalisation activities separately. The purpose of this paper was to investigate a set of indicators and their interplay with each other. Firstly, the impact of (a) international potential in the form of the depth and diversity of international experience and network contacts was investigated. Secondly, it was examined to what extent (b) motivational factors and (c) firm stages affect the relationship between international potential and internationalisation activities. This paper used longitudinal data from the Comprehensive Australian Study of Entrepreneurial Emergence (CAUSEE). Results suggest that the international potential of a new venture as a whole is a significant determinant of subsequent internationalisation activities. However, having a diverse international experience from a variety of foreign countries appears to be more beneficial than a long-lasting experience from only a limited number of foreign countries. Furthermore, analyses showed that the interplay of high growth ambitions and the depth of international experience positively affect internationalisation activities. Opportunity or necessity driven entrepreneurship, however, neither exaggerate nor weaken the positive relationship between international potentials and internationalisation activities. Similarly, no moderation by firm stages was found.

WNT16 influences bone mineral density, cortical bone thickness, bone strength, and osteoporotic fracture risk

We aimed to identify genetic variants associated with cortical bone thickness (CBT) and bone mineral density (BMD) by performing two separate genome-wide association study (GWAS) meta-analyses for CBT in 3 cohorts comprising 5,878 European subjects and for BMD in 5 cohorts comprising 5,672 individuals. We then assessed selected single-nucleotide polymorphisms (SNPs) for osteoporotic fracture in 2,023 cases and 3,740 controls. Association with CBT and forearm BMD was tested for ~2.5 million SNPs in each cohort separately, and results were meta-analyzed using fixed effect meta-analysis. We identified a missense SNP (Thr>Ile; rs2707466) located in the WNT16 gene (7q31), associated with CBT (effect size of -0.11 standard deviations [SD] per C allele, P = 6.2×10-9). This SNP, as well as another nonsynonymous SNP rs2908004 (Gly>Arg), also had genome-wide significant association with forearm BMD (-0.14 SD per C allele, P = 2.3×10-12, and -0.16 SD per G allele, P = 1.2×10-15, respectively). Four genome-wide significant SNPs arising from BMD meta-analysis were tested for association with forearm fracture. SNP rs7776725 in FAM3C, a gene adjacent to WNT16, was associated with a genome-wide significant increased risk of forearm fracture (OR = 1.33, P = 7.3×10-9), with genome-wide suggestive signals from the two missense variants in WNT16 (rs2908004: OR = 1.22, P = 4.9×10-6 and rs2707466: OR = 1.22, P = 7.2×10-6). We next generated a homozygous mouse with targeted disruption of Wnt16. Female Wnt16-/- mice had 27% (P<0.001) thinner cortical bones at the femur midshaft, and bone strength measures were reduced between 43%-61% (6.5×10-13<P<5.9×10-4) at both femur and tibia, compared with their wild-type littermates. Natural variation in humans and targeted disruption in mice demonstrate that WNT16 is an important determinant of CBT, BMD, bone strength, and risk of fracture. © 2012 Zheng et al.