Overexpression of the mammalian target of rapamycin (mTOR) and angioinvasion are poor prognostic factors in early stage NSCLC: A verification study

Background: A recent study by Dhillon et al. [12], identified both angioinvasion and mTOR as prognostic biomarkers for poor survival in early stage NSCLC. The aim of this study was to verify the above study by examining the angioinvasion and mTOR expression profile in a cohort of early stage NSCLC patients and correlate the results to patient clinico-pathological data and survival. Methods: Angioinvasion was routinely recorded by the pathologist at the initial assessment of the tumor following resection. mTOR was evaluated in 141 early stage (IA-IIB) NSCLC patients (67 - squamous; 60 - adenocarcinoma; 14 - others) using immunohistochemistry (IHC) analysis with an immunohistochemical score (IHS) calculated (% positive cells × staining intensity). Intensity was scored as follows: 0 (negative); 1+ (weak); 2+ (moderate); 3+ (strong). The range of scores was 0-300. Based on the previous study a cut-off score of 30 was used to define positive versus negative patients. The impact of angioinvasion and mTOR expression on prognosis was then evaluated. Results: 101 of the 141 tumors studied expressed mTOR. There was no difference in mTOR expression between squamous cell carcinoma and adenocarcinoma. Angioinvasion (p= 0.024) and mTOR staining (p= 0.048) were significant univariate predictors of poor survival. Both remained significant after multivariate analysis (p= 0.037 and p= 0.020, respectively). Conclusions: Our findings verify angioinvasion and mTOR expression as new biomarkers for poor outcome in patients with early stage NSCLC. mTOR expressing patients may benefit from novel therapies targeting the mTOR survival pathway. © 2011 Elsevier Ireland Ltd.

Design, construction, and analysis of cell line arrays and tissue microarrays for gene expression analysis

Cell line array (CMA) and tissue microarray (TMA) technologies are high-throughput methods for analysing both the abundance and distribution of gene expression in a panel of cell lines or multiple tissue specimens in an efficient and cost-effective manner. The process is based on Kononen's method of extracting a cylindrical core of paraffin-embedded donor tissue and inserting it into a recipient paraffin block. Donor tissue from surgically resected paraffin-embedded tissue blocks, frozen needle biopsies or cell line pellets can all be arrayed in the recipient block. The representative area of interest is identified and circled on a haematoxylin and eosin (H&E)-stained section of the donor block. Using a predesigned map showing a precise spacing pattern, a high density array of up to 1,000 cores of cell pellets and/or donor tissue can be embedded into the recipient block using a tissue arrayer from Beecher Instruments. Depending on the depth of the cell line/tissue removed from the donor block 100-300 consecutive sections can be cut from each CMA/TMA block. Sections can be stained for in situ detection of protein, DNA or RNA targets using immunohistochemistry (IHC), fluorescent in situ hybridisation (FISH) or mRNA in situ hybridisation (RNA-ISH), respectively. This chapter provides detailed methods for CMA/TMA design, construction and analysis with in-depth notes on all technical aspects including tips to deal with common pitfalls the user may encounter. © Springer Science+Business Media, LLC 2011.

Waterfalls, science and aesthetics

Waterfalls and rapids are a subject of study by scientists and scholars from a variety of academic and professional backgrounds. Unlike cave research, known as speleology, which also involves many different disciplines, the study of waterfalls is not generally regarded as a distinct branch of knowledge. Long neglected as subjects of research, waterfalls have received considerable attention since the 1980s. This paper traces the study of waterfalls from the late eighteenth century, a period when both a scientific and an aesthetic interest in landscape developed in Europe, to the present. The work of geographers, geologists and others who studied landforms and landscapes is examined, with particular attention to those who expressed a special interest in waterfalls, notably Alexander von Humboldt. The study argues that the scientific and aesthetic approaches to landscape research are not incompatible and supports the view that both are necessary for a full understanding and appreciation of the environment in which we live.

Cardiac safety concerns for ondansetron, an antiemetic commonly used for nausea linked to cancer treatment and following anaesthesia

Introduction: Ondansetron is a 5-HT3 receptor antagonist commonly used as an anti-emetic to prevent the nausea and vomiting associated with anti-cancer drugs, cancer radiotherapy, or postoperatively. Recently, the US Food and Drug Administration (FDA) issued a warning for ondansetron due to a potential for prolongation of the QT interval of the electrocardiogram (ECG), a phenomenon that is associated with an increased risk of the potentially fatal arrhythmia torsade de pointes. Areas covered: We undertook a review of the cardiac safety of ondansetron. Our primary sources of information were PubMed (with downloading of full articles), and the internet. Expert opinion: The dose of ondansetron that the FDA has concerns about is 32 mg iv (or several doses that are equivalent to this), which is only used in preventing nausea and vomiting associated with cancer chemotherapy. This suggests that ondansetron may be safe in the lower doses used to prevent the nausea and vomiting in radiation treatment or postoperatively. However, as there is a report that a lower dose of ondansetron prolonged the QT interval in healthy volunteers, this needs to be clarified by the FDA. More research needs to be undertaken of the relationship between QT prolongation and torsades in order that the FDA can produce clear-cut evidence of pro-arrhythmic risk when introducing warnings for this.

Hypoxia-inducible factor-1α in non small cell lung cancer: Relation to growth factor, protease and apoptosis pathways

Hypoxia-inducible factor (HIF)-1α is the regulatory subunit of HIF-1 that is stabilized under hypoxic conditions. Under different circumstances, HIF-1α may promote both tumorigenesis and apoptosis. There is conflicting data on the importance of HIF-1α as a prognostic factor. This study evaluated HIF-1α expression in 172 consecutive patients with stage I-IIIA non small cell lung cancer (NSCLC) using standard immunohistochemical techniques. The extent of HIF-1α nuclear immunostaining was determined using light microscopy and the results were analyzed using the median (5%) as a low cut-point and 60% as a high positive cut-point. Using the low cut-point, positive associations were found with epidermal growth factor receptor (EGFR; p = 0.01), matrix metalloproteinase (MMP)-9 (p = 0.003), membranous (p < 0.001) and perinuclear (p = 0.004) carbonic anhydrase (CA) IX, pS3 (p = 0.008), T-stage (p = 0.042), tumor necrosis (TN; p < 0.001) and squamous histology (p < 0.001). No significant association was found with Bcl-2 or either N- or overall TMN stage or prognosis. When the high positive cut-point was used, HIF-1α was associated with a poor prognosis (p = 0.034). In conclusion, the associations with EGFR, MMP-9, p53 and CA IX suggest that these factors may either regulate or be regulated by HIF-1α. The association with TN and squamous-type histology, which is relatively more necrotic than other NSCLC types, reflects the role of hypoxia in the regulation of HIF-1α. The prognostic data may reflect a change in the behavior of HIF-1α in increasingly hypoxic environments. © 2004 Wiley-Liss, Inc.

Accuracy of weight status perception in contemporary Australian children and adolescents

Aim: To explore weight status perception and its relation to actual weight status in a contemporary cohort of 5- to 17-year-old children and adolescents. Methods: Body mass index (BMI), derived from height and weight measurements, and perception of weight status (‘too thin’, ‘about right’ and ‘too fat’) were evaluated in 3043 participants from the Healthy Kids Queensland Survey. In children less than 12 years of age, weight status perception was obtained from the parents, whereas the adolescents self-reported their perceived weight status. Results: Compared with measured weight status by established BMI cut-offs, just over 20% of parents underestimated their child's weight status and only 1% overestimated. Adolescent boys were more likely to underestimate their weight status compared with girls (26.4% vs. 10.2%, P < 0.05) whereas adolescent girls were more likely to overestimate than underestimate (11.8% vs. 3.4%, P < 0.05). Underestimation was greater by parents of overweight children compared with those of obese children, but still less than 50% of parents identified their obese child as ‘too fat’. There was greater recognition of overweight status in the adolescents, with 83% of those who were obese reporting they were ‘too fat’. Conclusion: Whilst there was a high degree of accuracy of weight status perception in those of healthy weight, there was considerable underestimation of weight status, particularly by parents of children who were overweight or obese. Strategies are required that enable parents to identify what a healthy weight looks like and help them understand when intervention is needed to prevent further weight gain as the child gets older.

A rapid and simple method of assaying plants transformed with hygromycin or PPT resistance genes

A very simple leaf assay is described that rapidly and reliably identifies transgenic plants expressing the hygromycin resistance gene, hph or the phosphinothricin resistance gene, bar. Leaf tips were cut from plants propagated either in the glasshouse or in tissue culture and the cut surface embedded in solid medium containing the appropriate selective agent. Non-transgenic barley or rice leaf tips had noticeable symptoms of either bleaching or necrosis after three days on the medium and were completely bleached or necrotic after one week. Transgenic leaf tips remained green and healthy over this period. This gave unambiguous discrimination between transgenic and non-transgenic plants. The leaf assay was also effective for dicot plants tested (tobacco and peas).

Image segmentation and pose estimation of humans in video

This thesis introduces improved techniques towards automatically estimating the pose of humans from video. It examines a complete workflow to estimating pose, from the segmentation of the raw video stream to extract silhouettes, to using the silhouettes in order to determine the relative orientation of parts of the human body. The proposed segmentation algorithms have improved performance and reduced complexity, while the pose estimation shows superior accuracy during difficult cases of self occlusion.

Maternal exposure to heatwave and preterm birth in Brisbane, Australia

Objective To quantify the short-term effects of maternal exposure to heatwave on preterm birth. Design An ecological study. Setting: A population-based study in Brisbane, Australia. Population All pregnant women who had a spontaneous singleton live birth in Brisbane between November and March in 2000–2010 were studied. Methods Daily data on pregnancy outcomes, meteorological factors, and ambient air pollutants were obtained. The Cox proportional hazards regression model with time-dependent variables was used to examine the short-term impact of heatwave on preterm birth. A series of cut-off temperatures and durations were used to define heatwave. Multivariable analyses were also performed to adjust for socio-economic factors, demographic factors, meteorological factors, and ambient air pollutants. Main outcome measure Spontaneous preterm births. Results The adjusted hazard ratios (HRs) ranged from 1.13 (95% CI 1.03–1.24) to 2.00 (95% CI 1.37–2.91) by using different heatwave definitions, after controlling for demographic, socio-economic, and meteorological factors, and air pollutants. Conclusions Heatwave was significantly associated with preterm birth: the associations were robust to the definitions of heatwave. The threshold temperatures, instead of duration, could be more likely to influence the evaluation of birth-related heatwaves. The findings of this study may have significant public health implications as climate change progresses.

How neoliberalism and ecological modernization shaped environmental policy in Australia

‘Sustainability’ provides the dominant frame within which environmental policy debate occurs, notwithstanding its divergent meanings. However, how different discourses combine to shape understanding of the environment, the causes of environmental issues, and the responses required, is less clear cut. Drawing primarily on the approach to critical discourse analysis (CDA) developed by Fairclough, this paper explores the way in which neoliberal and ecologically modern discourses combine to shape environmental policy. Environmental scholars have made relatively little use of this approach to CDA to date, despite the significant interest in the discursive aspects of environmental issues, and its wide use in other areas of policy interest. Using the case of environmental policy-making in Victoria, Australia, this paper illustrates how neoliberalism and weak ecological modernization represented sustainability in ways that seriously limited the importance of environmental issues.

Corneal confocal microscopy detects early nerve regeneration in diabetic neuropathy after simultaneous pancreas and kidney transplantation

Diabetic neuropathy is associated with increased morbidity and mortality. To date, limited data in subjects with impaired glucose tolerance and diabetes demonstrate nerve fiber repair after intervention. This may reflect a lack of efficacy of the interventions but may also reflect difficulty of the tests currently deployed to adequately assess nerve fiber repair, particularly in short-term studies. Corneal confocal microscopy (CCM) represents a novel noninvasive means to quantify nerve fiber damage and repair. Fifteen type 1 diabetic patients undergoing simultaneous pancreas-kidney transplantation (SPK) underwent detailed assessment of neurologic deficits, quantitative sensory testing (QST), electrophysiology, skin biopsy, corneal sensitivity, and CCM at baseline and at 6 and 12 months after successful SPK. At baseline, diabetic patients had a significant neuropathy compared with control subjects. After successful SPK there was no significant change in neurologic impairment, neurophysiology, QST, corneal sensitivity, and intraepidermal nerve fiber density (IENFD). However, CCM demonstrated significant improvements in corneal nerve fiber density, branch density, and length at 12 months. Normalization of glycemia after SPK shows no significant improvement in neuropathy assessed by the neurologic deficits, QST, electrophysiology, and IENFD. However, CCM shows a significant improvement in nerve morphology, providing a novel noninvasive means to establish early nerve repair that is missed by currently advocated assessment techniques.

Martha and her sisters : women in films about journalism

HBO's Hemingway and Gellhorn (Philip Kaufman, 2012), broadcast in May on US television and starring Nicole Kidman as the pioneering female foreign correspondent, hasn't been well reviewed by the majority of critics. Variety described the biopic (with Clive Owen as Hemingway) as “swollen and heavy-handed”, while the Huffington Post declared it an “expensive misfire … a gigantic missed opportunity, a jaw-droppingly trying waste of time”. Regardless of whether such criticisms are fair—as this essay went to press I had been unable to see the film, so I cannot judge one way or the other—Hemingway and Gellhorn should be viewed as a significant addition to the filmography of journalism, retrieving from history as it does the achievements of one of the most significant of the early female practitioners. Gellhorn was a pioneer in a patriarchal press universe, a foreign and war correspondent at a time when this branch of the profession was seen very much as man's work. She covered the Spanish Civil War and the Second World War, and with just as much viscerality as any man.

Nutrition screening and assessment in Parkinson's disease : a comparison of methods

Background & Aims Nutrition screening and assessment enable early identification of malnourished people and those at risk of malnutrition. Appropriate assessment tools assist with informing and monitoring nutrition interventions. Tool choice needs to be appropriate to the population and setting. Methods Community-dwelling people with Parkinson’s disease (>18 years) were recruited. Body mass index (BMI) was calculated from weight and height. Participants were classified as underweight according to World Health Organisation (WHO) (≤18.5kg/m2) and age specific (<65 years,≤18.5kg/m2; ≥65 years,≤23.5kg/m2) cut-offs. The Mini-Nutritional Assessment (MNA) screening (MNA-SF) and total assessment scores were calculated. The Patient-Generated Subjective Global Assessment (PG-SGA), including the Subjective Global Assessment (SGA), was performed. Sensitivity, specificity, positive predictive value, negative predictive value and weighted kappa statistic of each of the above compared to SGA were determined. Results Median age of the 125 participants was 70.0(35-92) years. Age-specific BMI (Sn 68.4%, Sp 84.0%) performed better than WHO (Sn 15.8%, Sp 99.1%) categories. MNA-SF performed better (Sn 94.7%, Sp 78.3%) than both BMI categorisations for screening purposes. MNA had higher specificity but lower sensitivity than PG-SGA (MNA Sn 84.2%, Sp 87.7%; PG-SGA Sn 100.0%, Sp 69.8%). Conclusions BMI lacks sensitivity to identify malnourished people with Parkinson’s disease and should be used with caution. The MNA-SF may be a better screening tool in people with Parkinson’s disease. The PG-SGA performed well and may assist with informing and monitoring nutrition interventions. Further research should be conducted to validate screening and assessment tools in Parkinson’s disease.  

Observability analysis of electric networks considering branch impedance

This paper presents an analytical method to analyze the effect of X to R ratio as well as impedance value of branches on observability of a network based on un-decoupled formulation of state estimation (SE) and null space of matrices. The results showed that the X to R ratio of branches had no effect on the observability of networks. In addition, it was shown that observability of some networks was affected by impedance values while some others were not affected. In addition, for branch observability analysis of radial network, a simple and quick method is developed. Illustrative examples of the network under transmission and distribution voltages demonstrate the effectiveness of the proposed methods.

Violence in and around entertainment districts : a longitudinal analysis of the impact of late-night lockout legislation

Violence in entertainment districts is a major problem across urban landscapes throughout the world. Research shows that licensed premises are the third most common location for homicides and serious assaults, accounting for one in ten fatal and nonfatal assaults. One class of interventions that aims to reduce violence in entertainment districts involves the use of civil remedies: a group of strategies that use civil or regulatory measures as legal “levers” to reduce problem behavior. One specific civil remedy used to reduce problematic behavior in entertainment districts involves manipulation of licensed premise trading hours. This article uses generalized linear models to analyze the impact of lockout legislation on recorded violent offences in two entertainment districts in the Australian state of Queensland. Our research shows that 3 a.m. lockout legislation led to a direct and significant reduction in the number of violent incidents inside licensed premises. Indeed, the lockouts cut the level of violent crime inside licensed premises by half. Despite these impressive results for the control of violence inside licensed premises, we found no evidence that the lockout had any impact on violence on streets and footpaths outside licensed premises that were the site for more than 80 percent of entertainment district violence. Overall, however, our analysis suggests that lockouts are an important mechanism that helps to control the level of violence inside licensed premises but that finely grained contextual responses to alcohol-related problems are needed rather than one-size-fits-all solutions.