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Showing papers by "Monash University published in 2010"


Journal ArticleDOI
TL;DR: The objective of the paper is to provide an exploratory factor analysis protocol, offering potential researchers with an empirically-supported systematic approach that simplifies the many guidelines and options associated with completing EFA.
Abstract: Factor analysis is a multivariate statistical approach commonly used in psychology, education, and more recently in the health-related professions. This paper will attempt to provide novice researchers with a simplified approach to undertaking exploratory factor analysis (EFA). As the paramedic body of knowledge continues to grow, indeed into scale and instrument psychometrics, it is timely that an uncomplicated article such as this be offered to the paramedic readership both nationally and internationally. Factor analysis is an important tool that can be used in the development, refinement, and evaluation of tests, scales, and measures that can be used in education and clinical contexts by paramedics. The objective of the paper is to provide an exploratory factor analysis protocol, offering potential researchers with an empirically-supported systematic approach that simplifies the many guidelines and options associated with completing EFA.

1,679 citations


Journal ArticleDOI
14 May 2010-Science
TL;DR: Global extinction projections were validated with local extinctions observed from 1975 to 2009 for regional biotas on four other continents, suggesting that lizards have already crossed a threshold for extinctions caused by climate change.
Abstract: It is predicted that climate change will cause species extinctions and distributional shifts in coming decades, but data to validate these predictions are relatively scarce Here, we compare recent and historical surveys for 48 Mexican lizard species at 200 sites Since 1975, 12% of local populations have gone extinct We verified physiological models of extinction risk with observed local extinctions and extended projections worldwide Since 1975, we estimate that 4% of local populations have gone extinct worldwide, but by 2080 local extinctions are projected to reach 39% worldwide, and species extinctions may reach 20% Global extinction projections were validated with local extinctions observed from 1975 to 2009 for regional biotas on four other continents, suggesting that lizards have already crossed a threshold for extinctions caused by climate change

1,483 citations


Journal ArticleDOI
TL;DR: There is substantial information on low back pain prevalence and estimates of the point prevalence range from 1.0% to 58.1% (mean: 18.1%; median: 15.0%), and 1 year prevalence from 0.8% to 82.5% ( mean: 38.1; median: 37.4%).
Abstract: Low back pain is an extremely common problem that most people experience at some point in their life. While substantial heterogeneity exists among low back pain epidemiological studies limiting the ability to compare and pool data, estimates of the 1 year incidence of a first-ever episode of low back pain range between 6.3% and 15.4%, while estimates of the 1 year incidence of any episode of low back pain range between 1.5% and 36%. In health facility- or clinic-based studies, episode remission at 1 year ranges from 54% to 90%; however, most studies do not indicate whether the episode was continuous between the baseline and follow-up time point(s). Most people who experience activity-limiting low back pain go on to have recurrent episodes. Estimates of recurrence at 1 year range from 24% to 80%. Given the variation in definitions of remission and recurrence, further population-based research is needed to assess the daily patterns of low back pain episodes over 1 year and longer. There is substantial information on low back pain prevalence and estimates of the point prevalence range from 1.0% to 58.1% (mean: 18.1%; median: 15.0%), and 1 year prevalence from 0.8% to 82.5% (mean: 38.1%; median: 37.4%). Due to the heterogeneity of the data, mean estimates need to be interpreted with caution. Many environmental and personal factors influence the onset and course of low back pain. Studies have found the incidence of low back pain is highest in the third decade, and overall prevalence increases with age until the 60-65 year age group and then gradually declines. Other commonly reported risk factors include low educational status, stress, anxiety, depression, job dissatisfaction, low levels of social support in the workplace and whole-body vibration. Low back pain has an enormous impact on individuals, families, communities, governments and businesses throughout the world. The Global Burden of Disease 2005 Study (GBD 2005) is currently making estimates of the global burden of low back pain in relation to impairment and activity limitation. Results will be available in 2011. Further research is needed to help us understand more about the broader outcomes and impacts from low back pain.

1,465 citations


Journal ArticleDOI
TL;DR: Breaks For Additive Seasonal and Trend (BFAST) as mentioned in this paper is a change detection approach for time series by detecting and characterizing Breaks for Additive seasonal and trend, which integrates the decomposition of time series into trend, seasonal and remainder components with methods for detecting change within time series.

1,303 citations


Journal ArticleDOI
TL;DR: Severe hypoglycemia was strongly associated with increased risks of a range of adverse clinical outcomes, including respiratory, digestive, and skin conditions, and no relationship was found between repeated episodes of severe hypglycemia and vascular outcomes or death.
Abstract: Background Severe hypoglycemia may increase the risk of a poor outcome in patients with type 2 diabetes assigned to an intensive glucose-lowering intervention. We analyzed data from a large study of intensive glucose lowering to explore the relationship between severe hypoglycemia and adverse clinical outcomes. Methods We examined the associations between severe hypoglycemia and the risks of macrovascular or microvascular events and death among 11,140 patients with type 2 diabetes, using Cox proportional-hazards models with adjustment for covariates measured at baseline and after randomization. Results During a median follow-up period of 5 years, 231 patients (2.1%) had at least one severe hypoglycemic episode; 150 had been assigned to intensive glucose control (2.7% of the 5571 patients in that group), and 81 had been assigned to standard glucose control (1.5% of the 5569 patients in that group). The median times from the onset of severe hypoglycemia to the first major macrovascular event, the first major microvascular event, and death were 1.56 years (interquartile range, 0.84 to 2.41), 0.99 years (interquartile range, 0.40 to 2.17), and 1.05 years (interquartile range, 0.34 to 2.41), respectively. During follow-up, severe hypoglycemia was associated with a significant increase in the adjusted risks of major macrovascular events (hazard ratio, 2.88; 95% confidence interval [CI], 2.01 to 4.12), major microvascular events (hazard ratio, 1.81; 95% CI, 1.19 to 2.74), death from a cardiovascular cause (hazard ratio, 2.68; 95% CI, 1.72 to 4.19), and death from any cause (hazard ratio, 2.69; 95% CI, 1.97 to 3.67) (P<0.001 for all comparisons). Similar associations were apparent for a range of nonvascular outcomes, including respiratory, digestive, and skin conditions (P<0.01 for all comparisons). No relationship was found between repeated episodes of severe hypoglycemia and vascular outcomes or death. Conclusions Severe hypoglycemia was strongly associated with increased risks of a range of adverse clinical outcomes. It is possible that severe hypoglycemia contributes to adverse outcomes, but these analyses indicate that hypoglycemia is just as likely to be a marker of vulnerability to such events. (Funded by Servier and the National Health and Medical Research Council of Australia; ClinicalTrials.gov number, NCT00145925.)

1,280 citations


Journal ArticleDOI
Jörg Ederle1, Joanna Dobson2, Joanna Dobson1, Roland L Featherstone1  +348 moreInstitutions (40)
TL;DR: Completion of long-term follow-up is needed to establish the efficacy of carotid artery stenting compared with endarterectomy, but in the meantime, carotin artery stent should remain the treatment of choice for patients suitable for surgery.

1,115 citations


Journal ArticleDOI
TL;DR: It is suggested that cell size and elemental stoichiometry are promising ecophysiological traits for modelling and tracking changes in phytoplankton community structure in response to climate change.
Abstract: Global increases in atmospheric CO2 and temperature are associated with changes in ocean chemistry and circulation, altering light and nutrient regimes. Resulting changes in phytoplankton community structure are expected to have a cascading effect on primary and export production, food web dynamics and the structure of the marine food web as well the biogeochemical cycling of carbon and bio-limiting elements in the sea. A review of current literature indicates cell size and elemental stoichiometry often respond predictably to abiotic conditions and follow biophysical rules that link environmental conditions to growth rates, and growth rates to food web interactions, and consequently to the biogeochemical cycling of elements. This suggests that cell size and elemental stoichiometry are promising ecophysiological traits for modelling and tracking changes in phytoplankton community structure in response to climate change. In turn, these changes are expected to have further impacts on phytoplankton community structure through as yet poorly understood secondary processes associated with trophic dynamics.

919 citations


Journal ArticleDOI
TL;DR: Medium and/or high fidelity simulation using manikins is an effective teaching and learning method when best practice guidelines are adhered to.
Abstract: cant r.p. & cooper s.j. (2010) Simulation-based learning in nurse education: systematic review. Journal of Advanced Nursing66(1), 3–15. Abstract Title. Simulation-based learning in nurse education: systematic review. Aim. This paper is a report of a review of the quantitative evidence for medium to high fidelity simulation using manikins in nursing, in comparison to other educational strategies. Background. Human simulation is an educational process that can replicate clinical practices in a safe environment. Although endorsed in nursing curricula, its effectiveness is largely unknown. Review methods. A systematic review of quantitative studies published between 1999 and January 2009 was undertaken using the following databases: CINAHL Plus, ERIC, Embase, Medline, SCOPUS, ProQuest and ProQuest Dissertation and Theses Database. The primary search terms were ‘simulation’ and ‘human simulation’. Reference lists from relevant papers and the websites of relevant nursing organizations were also searched. The quality of the included studies was appraised using the Critical Appraisal Skills Programme criteria. Results. Twelve studies were included in the review. These used experimental or quasi-experimental designs. All reported simulation as a valid teaching/learning strategy. Six of the studies showed additional gains in knowledge, critical thinking ability, satisfaction or confidence compared with a control group (range 7–11%). The validity and reliability of the studies varied due to differences in design and assessment methods. Conclusion. Medium and/or high fidelity simulation using manikins is an effective teaching and learning method when best practice guidelines are adhered to. Simulation may have some advantage over other teaching methods, depending on the context, topic and method. Further exploration is needed to determine the effect of team size on learning and to develop a universal method of outcome measurement.

863 citations


Journal ArticleDOI
TL;DR: It is now becoming clear that sequential point mutations in key global regulatory genes contribute to the hVISA and VISA phenotypes, which are associated predominately with cell wall thickening and restricted vancomycin access to its site of activity in the division septum.
Abstract: The emergence of vancomycin-intermediate Staphylococcus aureus (VISA) and heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) over the past decade has provided a challenge to diagnostic microbiologists to detect these strains, clinicians treating patients with infections due to these strains, and researchers attempting to understand the resistance mechanisms. Recent data show that these strains have been detected globally and in many cases are associated with glycopeptide treatment failure; however, more rigorous clinical studies are required to clearly define the contribution of hVISA to glycopeptide treatment outcomes. It is now becoming clear that sequential point mutations in key global regulatory genes contribute to the hVISA and VISA phenotypes, which are associated predominately with cell wall thickening and restricted vancomycin access to its site of activity in the division septum; however, the phenotypic features of these strains can vary because the mutations leading to resistance can vary. Interestingly, changes in the staphylococcal surface and expression of agr are likely to impact host-pathogen interactions in hVISA and VISA infections. Given the subtleties of vancomycin susceptibility testing against S. aureus, it is imperative that diagnostic laboratories use well-standardized methods and have a framework for detecting reduced vancomycin susceptibility in S. aureus.

862 citations


Journal ArticleDOI
TL;DR: This study provides the first evidence that oxytocin nasal spray improves emotion recognition in young people diagnosed with autism spectrum disorders.

860 citations


Journal ArticleDOI
TL;DR: In this paper, the authors discuss the technology and production platforms for development and creation of different valuable consumer products from microalgal biomass, including triglycerides which can be converted into biodiesel.
Abstract: Microalgae biotechnology has recently emerged into the lime light owing to numerous consumer products that can be harnessed from microalgae. Product portfolio stretches from straightforward biomass production for food and animal feed to valuable products extracted from microalgal biomass, including triglycerides which can be converted into biodiesel. For most of these applications, the production process is moderately economically viable and the market is developing. Considering the enormous biodiversity of microalgae and recent developments in genetic and metabolic engineering, this group of organisms represents one of the most promising sources for new products and applications. With the development of detailed culture and screening techniques, microalgal biotechnology can meet the high demands of food, energy and pharmaceutical industries. This review article discusses the technology and production platforms for development and creation of different valuable consumer products from microalgal biomass.

Journal ArticleDOI
TL;DR: Molecular mechanisms associated with features of cardiac hypertrophy, including protein synthesis, sarcomeric organization, fibrosis, cell death and energy metabolism are discussed and a summary of profiling studies that have examined genes, microRNAs and proteins that are differentially expressed in models of pathological and physiologicalhypertrophy is provided.

Journal ArticleDOI
20 May 2010-Nature
TL;DR: This work shows that radial tissue organization is highly conserved with a central vascular cylinder in which two water conducting cell types, protoxylem and metaxylem, are patterned centripetally through crosstalk between the vascular cylinder and the surrounding endodermis mediated by cell-to-cell movement of a transcription factor in one direction and microRNAs in the other.
Abstract: A key question in developmental biology is how cells exchange positional information for proper patterning during organ development. In plant roots the radial tissue organization is highly conserved with a central vascular cylinder in which two water conducting cell types, protoxylem and metaxylem, are patterned centripetally. We show that this patterning occurs through crosstalk between the vascular cylinder and the surrounding endodermis mediated by cell-to-cell movement of a transcription factor in one direction and microRNAs in the other. SHORT ROOT, produced in the vascular cylinder, moves into the endodermis to activate SCARECROW. Together these transcription factors activate MIR165a and MIR166b. Endodermally produced microRNA165/6 then acts to degrade its target mRNAs encoding class III homeodomain-leucine zipper transcription factors in the endodermis and stele periphery. The resulting differential distribution of target mRNA in the vascular cylinder determines xylem cell types in a dosage-dependent manner.

Journal ArticleDOI
TL;DR: In this paper, a review of the pertinent literature combined with the authors' works reveals that a relationship exists between corrosion rate and grain size and reveals an important fundamental relationship that can be exploited for material durability and design.

Journal ArticleDOI
John Dixon1
TL;DR: As health care researchers and providers the authors are likely to play a peripheral role in the prevention of obesity, but a central role in effectively treating those afflicted by the obesity pandemic.

Journal ArticleDOI
TL;DR: The authors investigate whether consumers pursue the consumption of authentic objects with specific personal goals in mind, and find that consumers are motivated to focus on those particular cues in objects that for them convey authenticity (what is genuine, real, and/or true).
Abstract: Drawing from image-elicited depth interviews, we investigate whether consumers pursue the consumption of authentic objects with specific personal goals in mind. We find that consumers are motivated to focus on those particular cues in objects that for them convey authenticity (what is genuine, real, and/or true) and that this decision-making process is driven by a desire to draw different identity benefits (control, connection, virtue) from authentic objects. Our interpretive analysis elaborates contributions to theorizing related to consumer agency in seeking authentic consumption experience. We provide cultural explanations for the desire to assert the authentic self in these particular ways.

Journal ArticleDOI
10 Jun 2010-Nature
TL;DR: It is demonstrated that mouse mammary stem cells (MaSCs) are highly responsive to steroid hormone signalling, despite lacking the oestrogen and progesterone receptors, and indicates that breast cancer chemoprevention may be achieved, in part, through suppression of MaSC function.
Abstract: The ovarian hormones oestrogen and progesterone profoundly influence breast cancer risk, underpinning the benefit of endocrine therapies in the treatment of breast cancer. Modulation of their effects through ovarian ablation or chemoprevention strategies also significantly decreases breast cancer incidence. Conversely, there is an increased risk of breast cancer associated with pregnancy in the short term. The cellular mechanisms underlying these observations, however, are poorly defined. Here we demonstrate that mouse mammary stem cells (MaSCs) are highly responsive to steroid hormone signalling, despite lacking the oestrogen and progesterone receptors. Ovariectomy markedly diminished MaSC number and outgrowth potential in vivo, whereas MaSC activity increased in mice treated with oestrogen plus progesterone. Notably, even three weeks of treatment with the aromatase inhibitor letrozole was sufficient to reduce the MaSC pool. In contrast, pregnancy led to a transient 11-fold increase in MaSC numbers, probably mediated through paracrine signalling from RANK ligand. The augmented MaSC pool indicates a cellular basis for the short-term increase in breast cancer incidence that accompanies pregnancy. These findings further indicate that breast cancer chemoprevention may be achieved, in part, through suppression of MaSC function.

Journal ArticleDOI
TL;DR: Clinical pathways are associated with reduced in-hospital complications and improved documentation without negatively impacting on length of stay and hospital costs.
Abstract: Background Clinical pathways are structured multidisciplinary care plans used by health services to detail essential steps in the care of patients with a specific clinical problem. They aim to link evidence to practice and optimise clinical outcomes whilst maximising clinical efficiency. Objectives To assess the effect of clinical pathways on professional practice, patient outcomes, length of stay and hospital costs. Search methods We searched the Database of Abstracts of Reviews of Effectiveness (DARE), the Effective Practice and Organisation of Care (EPOC) Register, the Cochrane Central Register of Controlled Trials (CENTRAL) and bibliographic databases including MEDLINE, EMBASE, CINAHL, NHS EED and Global Health. We also searched the reference lists of relevant articles and contacted relevant professional organisations. Selection criteria Randomised controlled trials, controlled clinical trials, controlled before and after studies and interrupted time series studies comparing stand alone clinical pathways with usual care as well as clinical pathways as part of a multifaceted intervention with usual care. Data collection and analysis Two review authors independently screened all titles to assess eligibility and methodological quality. Studies were grouped into those comparing clinical pathways with usual care and those comparing clinical pathways as part of a multifaceted intervention with usual care. Main results Twenty-seven studies involving 11,398 participants met the eligibility and study quality criteria for inclusion. Twenty studies compared stand alone clinical pathways with usual care. These studies indicated a reduction in in-hospital complications (odds ratio (OR) 0.58; 95% confidence interval (CI) 0.36 to 0.94) and improved documentation (OR 11.95: 95%CI 4.72 to 30.30). There was no evidence of differences in readmission to hospital or in-hospital mortality. Length of stay was the most commonly employed outcome measure with most studies reporting significant reductions. A decrease in hospital costs/ charges was also observed, ranging from WMD +261 US$ favouring usual care to WMD -4919 US$ favouring clinical pathways (in US$ dollar standardized to the year 2000). Considerable heterogeneity prevented meta-analysis of length of stay and hospital cost results. An assessment of whether lower hospital costs contributed to cost shifting to another health sector was not undertaken. Seven studies compared clinical pathways as part of a multifaceted intervention with usual care. No evidence of differences were found between intervention and control groups. Authors' conclusions Clinical pathways are associated with reduced in-hospital complications and improved documentation without negatively impacting on length of stay and hospital costs.

Journal ArticleDOI
TL;DR: In this paper, the authors used CloudSat data to assess the realism of global model precipitation and found that the observed and modeled precipitation are significantly different from the character of liquid precipitation produced by global weather and climate models.
Abstract: [1] New, definitive measures of precipitation frequency provided by CloudSat are used to assess the realism of global model precipitation. The character of liquid precipitation (defined as a combination of accumulation, frequency, and intensity) over the global oceans is significantly different from the character of liquid precipitation produced by global weather and climate models. Five different models are used in this comparison representing state-of-the-art weather prediction models, state-of-the-art climate models, and the emerging high-resolution global cloud “resolving” models. The differences between observed and modeled precipitation are larger than can be explained by observational retrieval errors or by the inherent sampling differences between observations and models. We show that the time integrated accumulations of precipitation produced by models closely match observations when globally composited. However, these models produce precipitation approximately twice as often as that observed and make rainfall far too lightly. This finding reinforces similar findings from other studies based on surface accumulated rainfall measurements. The implications of this dreary state of model depiction of the real world are discussed.

Journal ArticleDOI
TL;DR: The role of several cytokines and chemokines following focal and diffuse TBI, as well as the controversies around the use of therapeutic anti-inflammatory treatments versus genetic deletion of cytokine expression are addressed.

Journal ArticleDOI
TL;DR: BFAST as mentioned in this paper integrates the decomposition of time series into trend, seasonal, and remainder components with methods for detecting change within time series, showing that the phenological change detection is influenced by the signal-to-noise ratio of the time series.

Journal ArticleDOI
TL;DR: A scholarly review of the published literature on menopausal hormonal therapy (MHT), make scientifically valid assessments of the available data, and grade the level of evidence available for each clinically important endpoint to arrive at major conclusions.
Abstract: Objective: Our objective was to provide a scholarly review of the published literature on menopausal hormonal therapy (MHT), make scientifically valid assessments of the available data, and grade the level of evidence available for each clinically important endpoint. Participants in Development of Scientific Statement: The 12-member Scientific Statement Task Force of The Endocrine Society selected the leader of the statement development group (R.J.S.) and suggested experts with expertise in specific areas. In conjunction with the Task Force, lead authors (n = 25) and peer reviewers (n = 14) for each specific topic were selected. All discussions regarding content and grading of evidence occurred via teleconference or electronic and written correspondence. No funding was provided to any expert or peer reviewer, and all participants volunteered their time to prepare this Scientific Statement. Evidence: Each expert conducted extensive literature searches of case control, cohort, and randomized controlled tria...

Journal ArticleDOI
TL;DR: Most studies indicate a higher incidence of neck pain among women and an increased risk of developing neck pain until the 35-49-year age group, after which the risk begins to decline.
Abstract: Neck pain is becoming increasingly common throughout the world. It has a considerable impact on individuals and their families, communities, health-care systems, and businesses. There is substantial heterogeneity between neck pain epidemiological studies, which makes it difficult to compare or pool data from different studies. The estimated 1 year incidence of neck pain from available studies ranges between 10.4% and 21.3% with a higher incidence noted in office and computer workers. While some studies report that between 33% and 65% of people have recovered from an episode of neck pain at 1 year, most cases run an episodic course over a person's lifetime and, thus, relapses are common. The overall prevalence of neck pain in the general population ranges between 0.4% and 86.8% (mean: 23.1%); point prevalence ranges from 0.4% to 41.5% (mean: 14.4%); and 1 year prevalence ranges from 4.8% to 79.5% (mean: 25.8%). Prevalence is generally higher in women, higher in high-income countries compared with low- and middle-income countries and higher in urban areas compared with rural areas. Many environmental and personal factors influence the onset and course of neck pain. Most studies indicate a higher incidence of neck pain among women and an increased risk of developing neck pain until the 35-49-year age group, after which the risk begins to decline. The Global Burden of Disease 2005 Study is currently making estimates of the global burden of neck pain in relation to impairment and activity limitation, and results will be available in 2011.

Journal ArticleDOI
TL;DR: The variation in RR among studies was explored and it was found that the effect of heterogeneity was highly related with sample size, method of assessment of body mass index (BMI) and method of ascertainment of type 2 diabetes.

Journal ArticleDOI
TL;DR: In this paper, the 18R and 14H long-period stacking ordered structures formed in Mg-Y-Zn alloys were examined systematically using electron diffraction and high-angle annular dark-field scanning transmission electron microscopy.

Journal ArticleDOI
TL;DR: Reduction of short‐chain poorly absorbed carbohydrates (FODMAPs) in the diet reduces symptoms of irritable bowel syndrome, and symptoms produced in response to diets that differed only in FODMAP content are compared.
Abstract: Background and Aim: Reduction of short-chain poorly absorbed carbohydrates (FODMAPs) in the diet reduces symptoms of irritable bowel syndrome (IBS). In the present study, we aimed to compare the patterns of breath hydrogen and methane and symptoms produced in response to diets that differed only in FODMAP content. Methods: Fifteen healthy subjects and 15 with IBS (Rome III criteria) undertook a single-blind, crossover intervention trial involving consuming provided diets that were either low (9 g/day) or high (50 g/day) in FODMAPs for 2 days. Food and gastrointestinal symptom diaries were kept and breath samples collected hourly over 14 h on day 2 of each diet. Results: Higher levels of breath hydrogen were produced over the entire day with the high FODMAP diet for healthy volunteers (181 77 ppm.14 h vs 43 18; mean SD P < 0.0001) and patients with IBS (242 79 vs 62 23; P < 0.0001), who had higher levels during each dietary period than the controls (P < 0.05). Breath methane, produced by 10 subjects within each group, was reduced with the high FODMAP intake in healthy subjects (47 29 vs 109 77; P = 0.043), but was not different in patients with IBS (126 153 vs 86 72). Gastrointestinal symptoms and lethargy were significantly induced by the high FODMAP diet in patients with IBS, while only increased flatus production was reported by healthy volunteers. Conclusions: Dietary FODMAPs induce prolonged hydrogen production in the intestine that is greater in IBS, influence the amount of methane produced, and induce gastrointes- tinal and systemic symptoms experienced by patients with IBS. The results offer mecha- nisms underlying the efficacy of the low FODMAP diet in IBS.

Journal ArticleDOI
01 Mar 2010-Surgery
TL;DR: Surgeons are subject to many intra-operative stressors that can impair their performance, and current evidence is characterized by marked heterogeneity of research designs and variable study quality.

Journal ArticleDOI
TL;DR: It is demonstrated that a paracrine mechanism driven by DeltaEGFR is the primary means for recruiting wtEGFR-expressing cells into accelerated proliferation in vivo, and support the view that a minor tumor cell population can potently drive accelerated growth of the entire tumor mass, and thereby actively maintain tumor cell heterogeneity within a tumor mass.
Abstract: Human solid tumors frequently have pronounced heterogeneity of both neoplastic and normal cells on the histological, genetic, and gene expression levels. While current efforts are focused on understanding heterotypic interactions between tumor cells and surrounding normal cells, much less is known about the interactions between and among heterogeneous tumor cells within a neoplasm. In glioblastoma multiforme (GBM), epidermal growth factor receptor gene (EGFR) amplification and mutation (EGFRvIII/ΔEGFR) are signature pathogenetic events that are invariably expressed in a heterogeneous manner. Strikingly, despite its greater biological activity than wild-type EGFR (wtEGFR), individual GBM tumors expressing both amplified receptors typically express wtEGFR in far greater abundance than the ΔEGFR lesion. We hypothesized that the minor ΔEGFR-expressing subpopulation enhances tumorigenicity of the entire tumor cell population, and thereby maintains heterogeneity of expression of the two receptor forms in different cells. Using mixtures of glioma cells as well as immortalized murine astrocytes, we demonstrate that a paracrine mechanism driven by ΔEGFR is the primary means for recruiting wtEGFR-expressing cells into accelerated proliferation in vivo. We determined that human glioma tissues, glioma cell lines, glioma stem cells, and immortalized mouse Ink4a/Arf−/− astrocytes that express ΔEGFR each also express IL-6 and/or leukemia inhibitory factor (LIF) cytokines. These cytokines activate gp130, which in turn activates wtEGFR in neighboring cells, leading to enhanced rates of tumor growth. Ablating IL-6, LIF, or gp130 uncouples this cellular cross-talk, and potently attenuates tumor growth enhancement. These findings support the view that a minor tumor cell population can potently drive accelerated growth of the entire tumor mass, and thereby actively maintain tumor cell heterogeneity within a tumor mass. Such interactions between genetically dissimilar cancer cells could provide novel points of therapeutic intervention.

Journal ArticleDOI
TL;DR: A comprehensive survey of the VHD algorithms designed to satisfy the required Quality of Service (QoS) requirements of the forthcoming Fourth Generation (4G) heterogeneous wireless networks is presented.

Journal ArticleDOI
TL;DR: In this article, the authors investigated the association between accruals quality and the characteristics of accounting experts and mix of accounting and non-accounting (finance and supervisory) expertise on audit committees.
Abstract: Prior literature suggests a positive relationship between financial reporting quality and the presence of accounting experts on audit committees. This study investigates the association between accruals quality and the characteristics of accounting experts and mix of accounting and non-accounting (finance and supervisory) expertise on audit committees. Using post-SOX data, our results indicate a positive relationship between accruals quality and audit committee accounting experts who are independent, hold fewer multiple directorships, and have lower tenure in their firms. Furthermore, the results suggest that the most positive effect of accounting expertise on accruals quality is achieved when accounting expertise is combined with finance expertise in audit committees. Supervisory expertise, on the other hand, seems to have no incremental impact on the effectiveness of audit committees that include accounting and finance expertise. The findings highlight the contextual nature of accounting expertise in overseeing the quality of financial reporting.