High coexpression of both EGFR and IGF1R correlates with poor patient prognosis in resected non-small-cell lung cancer

Background Recent experimental and biomarker evidence indicates that the epidermal growth factor receptor (EGFR) and insulin-like growth factor receptor 1 (IGF1R) interact in the pathogenesis of malignant epithelial tumors, including lung cancer. This study examines the expression of both receptors and their prognostic significance in surgically resected non-small-cell lung cancer (NSCLC). Methods EGFR and IGF1R expression were evaluated in 184 patients with NSCLC (83 squamous cell carcinomas [SCCs], 83 adenocarcinomas [ADCs], and 18 other types) using immunohistochemical (IHC) analysis. Expression of both receptors was examined in matched fresh frozen normal and tumor tissues from 40 patients with NSCLC (20 SCCs and 20 ADCs) by Western blot analysis. Results High EGFR expression was detected in 51% of patients, and SCCs had higher EGFR expression than did non-SCCs (57.4% vs. 42.5%; P =.028). High IGF1R expression was observed in 53.8% of patients, with SCC having higher expression than non-SCC (62.6% vs. 37.3%; P =.0004). A significant association was shown between EGFR and IGF1R protein overexpression (P <.005). Patients with high expression of both receptors had a poorer overall survival (OS) (P =.04). Higher EGFR and IGF1R expression was detected in resected tumors relative to matched normal tissues (P =.0004 and P =.0009), with SCC having higher expression levels than ADC. Conclusion Our findings indicate a close interrelationship between EGFR and IGF1R. Coexpression of both receptors correlates with poor survival. This subset of patients may benefit from treatments cotargeting EGFR and IGF1R. © 2014 Elsevier Inc. All rights reserved.

Linking dynamic-capability portfolios and innovation outcomes

The objective of this paper is to explore the relationship between dynamic capabilities and different types of online innovations. Building on qualitative data from the publishing industry, our analysis revealed that companies that had relatively strong dynamic capabilities in all three areas (sensing, seizing and reconfiguration) seem to produce innovations that combine their existing capabilities on either the market or the technology dimension with new capabilities on the other dimension thus resulting in niche creation and revolutionary type innovations. Correspondingly, companies with a weaker or more one-sided set of dynamic capabilities seem to produce more radical innovations requiring both new market and technological capabilities. The study therefore provides an empirical contribution to the emerging work on dynamic capabilities through its in-depth investigation of the capabilities of the four case firms, and by mapping the patterns between the firm's portfolio of dynamic capabilities and innovation outcomes.

Exploring retinal markers of diabetic neuropathy

Purpose To investigate the application of retinal nerve fibre layer (RNFL) thickness as a marker for severity of diabetic peripheral neuropathy (DPN) in people with Type 2 diabetes. Methods This was a cross-sectional study whereby 61 participants (mean age 61 [41-75 years], mean duration of diabetes 14 [1-40 years], 70% male) with Type 2 diabetes and DPN underwent optical coherence tomography (OCT) scans. Global and 4 quadrant (TSNI) RNFL thicknesses were measured at 3.45mm around the optic nerve head of one eye. Neuropathy disability score (NDS) was used to assess the severity of DPN on a 0 to 10 scale. Participants were divided into three age-matched groups representing mild (NDS=3-5), moderate (NDS=6-8) and severe (NDS=9-10) neuropathy. Two regression models were fitted for statistical analysis: 1) NDS scores as co-variate for global and quadrant RNFL thicknesses, 2) NDS groups as a factor for global RNFL thickness only. Results Mean (SD) RNFL thickness (µm) was 103(9) for mild neuropathy (n=34), 101(10) for moderate neuropathy (n=16) and 95(13) in the group with severe neuropathy (n=11). Global RNFL thickness and NDS scores were statistically significantly related (b=-1.20, p=0.048). When neuropathy was assessed across groups, a trend of thinner mean RNFL thickness was observed with increasing severity of neuropathy; however, this result was not statistically significant (F=2.86, p=0.065). TSNI quadrant analysis showed that mean RNFL thickness reduction in the inferior quadrant was 2.55 µm per 1 unit increase in NDS score (p=0.005). However, the regression coefficients were not statistically significant for RNFL thickness in the superior (b=-1.0, p=0.271), temporal (b=-0.90, p=0.238) and nasal (b=-0.99, p=0.205) quadrants. Conclusions RNFL thickness was reduced with increasing severity of DPN and the effect was most evident in the inferior quadrant. Measuring RNFL thickness using OCT may prove to be a useful, non-invasive technique for identifying severity of DPN and may also provide additional insight into common mechanisms for peripheral neuropathy and RNFL damage.

Retinal nerve fibre layer thickness is associated with higher risk of foot ulceration in diabetic peripheral neuropathy

Purpose To evaluate the association between retinal nerve fibre layer (RNFL) thickness and diabetic peripheral neuropathy in people with type 2 diabetes, and specifically those at higher risk of foot ulceration. Methods RNFL thicknesses was measured globally and in four quadrants (temporal, superior, nasal and inferior) at 3.45 mm diameter around the optic nerve head using optical coherence tomography (OCT). Severity of neuropathy was assessed using the Neuropathy Disability Score (NDS). Eighty-two participants with type 2 diabetes were stratified according to NDS scores (0-10) as: none, mild, moderate, and severe neuropathy. A control group was additionally included (n=17). Individuals with NDS≥ 6 (moderate and severe neuropathy) have been shown to be at higher risk of foot ulceration. A linear regression model was used to determine the association between RNFL and severity of neuropathy. Age, disease duration and diabetic retinopathy levels were fitted in the models. Independent t-test was employed for comparison between controls and the group without neuropathy, as well as for comparison between groups with higher and lower risk of foot ulceration. Analysis of variance was used to compare across all NDS groups. Results RNFL thickness was significantly associated with NDS in the inferior quadrant (b= -1.46, p=0.03). RNFL thicknesses globally and in superior, temporal and nasal quadrants did not show significant associations with NDS (all p>0.51). These findings were independent of the effect of age, disease duration and retinopathy. RNFL was thinner for the group with NDS ≥ 6 in all quadrants but was significant only inferiorly (p<0.005). RNFL for control participants was not significantly different from the group with diabetes and no neuropathy (superior p=0.07, global and all other quadrants: p>0.23). Mean RNFL thickness was not significantly different between the four NDS groups globally and in all quadrants (p=0.08 for inferior, P>0.14 for all other comparisons). Conclusions Retinal nerve fibre layer thinning is associated with neuropathy in people with type 2 diabetes. This relationship is strongest in the inferior retina and in individuals at higher risk of foot ulceration.

Elucidating the host–pathogen interaction between human colorectal cells and invading Enterovirus 71 using transcriptomics profiling

Enterovirus 71 (EV71) is one of the main etiological agents for Hand, Foot and Mouth Disease (HFMD) and has been shown to be associated with severe clinical manifestation. Currently, there is no antiviral therapeutic for the treatment of HFMD patients owing to a lack of understanding of EV71 pathogenesis. This study seeks to elucidate the transcriptomic changes that result from EV71 infection. Human whole genome microarray was employed to monitor changes in genomic profiles between infected and uninfected cells. The results reveal altered expression of human genes involved in critical pathways including the immune response and the stress response. Together, data from this study provide valuable insights into the host–pathogen interaction between human colorectal cells and EV71.

Food security in Australia in an era of neoliberalism, productivism and climate change

For over 150 years Australia has exported bulk, undifferentiated, commodities such as wool, wheat, meat and sugar to the UK and more recently to Japan, Korea, and the Middle East. It is estimated that, each year, Australia's farming system feeds a domestic population of some 22 million people, while exporting enough food to feed another 40 million. With the Australian population expected to double in the next 40 years, and with the anticipated growth in the world's population to reach a level of some 9 billion (from its present level of 7 billion) in the same period, there are strong incentives for an expansion of food production in Australia. Neoliberal settings are encouraging this expansion at the same time as they are facilitating importation of foods, higher levels of foreign direct investment and the commoditisation of resources (such as water). Yet, expansion in food production – and in an era of climate change – will continue to compromise the environment. After discussing Australia's neoliberal framework and its relation to farming, this paper outlines how Australia is attempting to address the issue of food security. It argues that productivist farming approaches that are favoured by both industry and government are proving incapable of bringing about long-term production outcomes that will guarantee national food security.

Practical Advice to Entrepreneurs Series by ACE Adjunct Professor Dean Shepherd: Practical advice for prisoners on developing an entrepreneurial career

The author, Dean Shepherd, is of entrepreneurship—how entrepreneurs think, decide to act, and feel. He recently realized that while his publications in academic journals have implications for entrepreneurs, those implications have remained relatively hidden in the text of the articles and hidden in articles published in journals largely inaccessible to those involved in the entrepreneurial process. This series is designed to bring the practical implications of his research to the forefront.

Terrorism risk, resilience and volatility : a comparison of terrorism patterns in three Southeast Asian countries

Objective This article explores patterns of terrorist activity over the period from 2000 through 2010 across three target countries: Indonesia, the Philippines and Thailand. Methods We use self-exciting point process models to create interpretable and replicable metrics for three key terrorism concepts: risk, resilience and volatility, as defined in the context of terrorist activity. Results Analysis of the data shows significant and important differences in the risk, volatility and resilience metrics over time across the three countries. For the three countries analysed, we show that risk varied on a scale from 0.005 to 1.61 “expected terrorist attacks per day”, volatility ranged from 0.820 to 0.994 “additional attacks caused by each attack”, and resilience, as measured by the number of days until risk subsides to a pre-attack level, ranged from 19 to 39 days. We find that of the three countries, Indonesia had the lowest average risk and volatility, and the highest level of resilience, indicative of the relatively sporadic nature of terrorist activity in Indonesia. The high terrorism risk and low resilience in the Philippines was a function of the more intense, less clustered pattern of terrorism than what was evident in Indonesia. Conclusions Mathematical models hold great promise for creating replicable, reliable and interpretable “metrics” to key terrorism concepts such as risk, resilience and volatility.

Surface analysis of lipids by mass spectrometry : More than just imaging

Mass spectrometry is now an indispensable tool for lipid analysis and is arguably the driving force in the renaissance of lipid research. In its various forms, mass spectrometry is uniquely capable of resolving the extensive compositional and structural diversity of lipids in biological systems. Furthermore, it provides the ability to accurately quantify molecular-level changes in lipid populations associated with changes in metabolism and environment; bringing lipid science to the "omics" age. The recent explosion of mass spectrometry-based surface analysis techniques is fuelling further expansion of the lipidomics field. This is evidenced by the numerous papers published on the subject of mass spectrometric imaging of lipids in recent years. While imaging mass spectrometry provides new and exciting possibilities, it is but one of the many opportunities direct surface analysis offers the lipid researcher. In this review we describe the current state-of-the-art in the direct surface analysis of lipids with a focus on tissue sections, intact cells and thin-layer chromatography substrates. The suitability of these different approaches towards analysis of the major lipid classes along with their current and potential applications in the field of lipid analysis are evaluated. © 2013 Elsevier Ltd. All rights reserved.

Noise levels in a general intensive care unit : a descriptive study.

The aim of this small-scale study was to measure, analyse and compare levels of acoustic noise, in a nine-bedded general intensive care unit (ICU). Measurements were undertaken using the Norsonic 116 sound level meter recording noise levels in the internationally agreed ‘A’ weighted scale. Noise level data were obtained and recorded at 5 min over 3 consecutive days. Results of noise level analysis indicated that mean noise levels within this clinical area was 56·42 dB(A), with acute spikes reaching 80 dB(A). The quietest noise level attained was that of 50 dB(A) during sporadic intervals throughout the 24-h period. Parametric testing using analysis of variance found a positive relationship (p ≤ 0·001) between the nursing shifts and the day of the week. However, Scheffe multiple range testing showed significant differences between the morning shift, and the afternoon and night shifts combined (p ≤ 0·05). There was no statistical difference between the afternoon and night shifts (p ≥ 0·05). While the results of this study may seem self-evident in many respects, what it has highlighted is that the problem of excessive noise exposure within the ICU continues to go unabated. More concerning is that the prolonged effects of excessive noise exposure on patients and staff alike can have deleterious effect on the health and well-being of these individuals.

Understanding the abnormal brain activity in epilepsy as a potential predictor of the onset of an epileptic seizure

The Brain Research Institute (BRI) uses various types of indirect measurements, including EEG and fMRI, to understand and assess brain activity and function. As well as the recovery of generic information about brain function, research also focuses on the utilisation of such data and understanding to study the initiation, dynamics, spread and suppression of epileptic seizures. To assist with the future focussing of this aspect of their research, the BRI asked the MISG 2010 participants to examine how the available EEG and fMRI data and current knowledge about epilepsy should be analysed and interpreted to yield an enhanced understanding about brain activity occurring before, at commencement of, during, and after a seizure. Though the deliberations of the study group were wide ranging in terms of the related matters considered and discussed, considerable progress was made with the following three aspects. (1) The science behind brain activity investigations depends crucially on the quality of the analysis and interpretation of, as well as the recovery of information from, EEG and fMRI measurements. A number of specific methodologies were discussed and formalised, including independent component analysis, principal component analysis, profile monitoring and change point analysis (hidden Markov modelling, time series analysis, discontinuity identification). (2) Even though EEG measurements accurately and very sensitively record the onset of an epileptic event or seizure, they are, from the perspective of understanding the internal initiation and localisation, of limited utility. They only record neuronal activity in the cortical (surface layer) neurons of the brain, which is a direct reflection of the type of electrical activity they have been designed to record. 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Psychosocial factors associated with controlling feeding practices of Indian and Australian-Indian mothers

This cross-sectional study examined the association between psychosocial factors (mothers’ perception of own and child weight, maternal self-efficacy in feeding and involvement of the mother-in-law in child-feeding) and controlling feeding practices (monitoring, restriction, pressure to eat and passive feeding). Participants were 531 affluent-Indian mothers in Australia and Mumbai with children aged 1-5 years. The psychosocial variables and feeding practices were measured using a combination of previously validated scales and study-developed items/scales. Multivariable regression analyses were stratified by sample (Australia and Mumbai) to investigate psychosocial factors related to the feeding practices, adjusting for covariates. Self-efficacy in feeding was associated with each of the feeding practices in at least one of the samples (β values between 0.1-0.2, p= 0.04-0.005). The greater involvement of the mother-in-law in child-feeding was related to the higher use of restriction in both samples (β values ≥0.2, p=0.02). In contrast, maternal weight perceptions were not consistently associated with feeding practices in either sample. The findings highlighted that unique (self-efficacy in feeding) and culturally-specific (involvement of the mother-in-law) variables not extensively researched within the context of child-feeding were important factors associated with Indian mothers’ feeding practices. Greater consideration of these factors may be required when tailoring child-feeding interventions for Indian mothers.

Pore size distribution and accessible pore size distribution in bituminous coals

The porosity and pore size distribution of coals determine many of their properties, from gas release to their behavior on carbonization, and yet most methods of determining pore size distribution can only examine a restricted size range. Even then, only accessible pores can be investigated with these methods. Small-angle neutron scattering (SANS) and ultra small-angle neutron scattering (USANS) are increasingly used to characterize the size distribution of all of the pores non-destructively. Here we have used USANS/SANS to examine 24 well-characterized bituminous and subbituminous coals: three from the eastern US, two from Poland, one from New Zealand and the rest from the Sydney and Bowen Basins in Eastern Australia, and determined the relationships of the scattering intensity corresponding to different pore sizes with other coal properties. The range of pore radii examinable with these techniques is 2.5nm to 7μm. We confirm that there is a wide range of pore sizes in coal. The pore size distribution was found to be strongly affected by both rank and type (expressed as either hydrogen or vitrinite content) in the size range 250nm to 7μm and 5 to 10nm, but weakly in intermediate regions. The results suggest that different mechanisms control coal porosity on different scales. Contrast-matching USANS and SANS were also used to determine the size distribution of the fraction of the pores in these coals that are inaccessible to deuterated methane, CD4, at ambient temperature. In some coals most of the small (~10nm) pores were found to be inaccessible to CD4 on the time scale of the measurement (~30min–16h). This inaccessibility suggests that in these coals a considerable fraction of inherent methane may be trapped for extended periods of time, thus reducing the effectiveness of methane release from (or sorption by) these coals. Although the number of small pores was less in higher rank coals, the fraction of total pores that was inaccessible was not rank dependent. In the Australian coals, at the 10nm to 50nm size scales the pores in inertinites appeared to be completely accessible to CD4, whereas the pores in the vitrinite were about 75% inaccessible. Unlike the results for total porosity that showed no regional effects on relationships between porosity and coal properties, clear regional differences in the relationships between fraction of closed porosity and coal properties were found. The 10 to 50nm-sized pores of inertinites of the US and Polish coals examined appeared less accessible to methane than those of the inertinites of Australian coals. This difference in pore accessibility in inertinites may explain why empirical relationships between fluidity and coking properties developed using Carboniferous coals do not apply to Australian coals.

Structuring acyclic process models

This article studies the problem of transforming a process model with an arbitrary topology into an equivalent well-structured process model. While this problem has received significant attention, there is still no full characterization of the class of unstructured process models that can be transformed into well-structured ones, nor an automated method for structuring any process model that belongs to this class. This article fills this gap in the context of acyclic process models. The article defines a necessary and sufficient condition for an unstructured acyclic process model to have an equivalent well-structured process model under fully concurrent bisimulation, as well as a complete structuring method. The method has been implemented as a tool that takes process models captured in the BPMN and EPC notations as input. The article also reports on an empirical evaluation of the structuring method using a repository of process models from commercial practice.

Generalized aggregate Quality of Service computation for composite services

This article addresses the problem of estimating the Quality of Service (QoS) of a composite service given the QoS of the services participating in the composition. Previous solutions to this problem impose restrictions on the topology of the orchestration models, limiting their applicability to well-structured orchestration models for example. This article lifts these restrictions by proposing a method for aggregate QoS computation that deals with more general types of unstructured orchestration models. The applicability and scalability of the proposed method are validated using a collection of models from industrial practice.