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.

Invading edge vs. inner (edvin) patterns of vascularization : an interplay between angiogenic and vascular survival factors defines the clinical behaviour of non-small cell lung cancer

Neo-angiogenesis during neoplastic growth involves endothelial mitogenic and migration stimuli produced by cancer or tumour stromal cells. Although this active angiogenesis takes place in the tumour periphery, the process of vessel growth and survival in inner areas and its clinical role remain largely unexplored. The present study compared the microvessel score (MS) as well as the single endothelial cell score (ECS) in the invading edge and in inner areas of non-small cell lung carcinomas (NSCLCs). Three different patterns of vascular growth were distinguished: the edvin (edge vs. inner) type 1, where a low MS was observed in both peripheral and inner tumour areas; the edvin type 2, where a high MS was noted in the invading front but a low MS in inner areas; and the edvin type 3, where both peripheral and inner tumour areas had a high MS. The ECS was high in the invading edge in edvin type 2 and 3 cases and was sharply decreased in both types in inner areas, suggesting that endothelial cell migration is unlikely to contribute to the angiogenic process in areas away from the tumour front. Expression of the vascular endothelial growth factor (VEGF) and of thymidine phosphorylase (TP) was associated with a high MS in the invading edge. VEGF was associated with a high MS in inner areas (edvin 3), while TP expression was associated with edvin type 2, showing that VEGF (and not TP) contributes to the preservation of the inner vasculature. Both edvin type 2 and 3 cases showed an increased incidence of node metastasis, but edvin type 3 cases had a poorer prognosis, even in the N1-stage group. The present study suggests that tumour factors regulating angiogenesis and vascular survival are not identical. A possible method is reported to quantify these two parameters by comparing the MS in the invading edge and inner areas (edvin types). This observation may contribute to the evaluation of the effectiveness of different therapeutic approaches, namely vascular targeting vs. anti-angiogenesis. Copyright (C) 2000 John Wiley and Sons, Ltd.

Single-agent versus combination chemotherapy in patients with advanced non-small cell lung cancer and a performance status of 2 : prognostic factors and treatment selection based on two large randomized clinical trials

Purpose: Data from two randomized phase III trials were analyzed to evaluate prognostic factors and treatment selection in the first-line management of advanced non-small cell lung cancer patients with performance status (PS) 2. Patients and Methods: Patients randomized to combination chemotherapy (carboplatin and paclitaxel) in one trial and single-agent therapy (gemcitabine or vinorelbine) in the second were included in these analyses. Both studies had identical eligibility criteria and were conducted simultaneously. Comparison of efficacy and safety was performed between the two cohorts. A regression analysis identified prognostic factors and subgroups of patients that may benefit from combination or single-agent therapy. Results: Two hundred one patients were treated with combination and 190 with single-agent therapy. Objective responses were 37 and 15%, respectively. Median time to progression was 4.6 months in the combination arm and 3.5 months in the single-agent arm (p < 0.001). Median survival imes were 8.0 and 6.6 months, and 1-year survival rates were 31 and 26%, respectively. Albumin <3.5 g, extrathoracic metastases, lactate dehydrogenase ≥200 IU, and 2 comorbid conditions predicted outcome. Patients with 0-2 risk factors had similar outcomes independent of treatment, whereas patients with 3-4 factors had a nonsignificant improvement in median survival with combination chemotherapy. Conclusion: Our results show that PS2 non-small cell lung cancer patients are a heterogeneous group who have significantly different outcomes. Patients treated with first-line combination chemotherapy had a higher response and longer time to progression, whereas overall survival did not appear significantly different. A prognostic model may be helpful in selecting PS 2 patients for either treatment strategy. © 2009 by the International Association for the Study of Lung Cancer.

Clinico-pathological and biological prognostic factors in pleural malignant mesothelioma

In the UK mortality from malignant mesothelioma (MM) is likely to more than double over the next 20 years and despite advances in surgery, chemotherapy and radiation treatment the overall prognosis for patients remains poor. A number of scoring systems based on assessment of clinicopathological features of patients with the disease have been developed but the search continues for further prognostic indicators. Angiogenesis, tumour necrosis (TN), epidermal growth factor receptor (EGFR) expression, cyclooxygenase-2 (COX-2) and matrix metalloproteinases (MMPs) have been linked with poor prognosis in some types of solid tumour and their relevance as prognostic factors in malignant mesothelioma is examined in this paper. © 2004 Elsevier Ireland Ltd. All rights reserved.

Prognostic factors in patients with advanced non-small cell lung cancer : data from the phase III FLEX study

The FLEX study demonstrated that the addition of cetuximab to chemotherapy significantly improved overall survival in the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC). In the FLEX intention to treat (ITT) population, we investigated the prognostic significance of particular baseline characteristics. Individual patient data from the treatment arms of the ITT population of the FLEX study were combined. Univariable and multivariable Cox regression models were used to investigate variables with potential prognostic value. The ITT population comprised 1125 patients. In the univariable analysis, longer median survival times were apparent for females compared with males (12.7 vs 9.3 months); patients with an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 compared with 1 compared with 2 (13.5 vs 10.6 vs 5.9 months); never smokers compared with former smokers compared with current smokers (14.6 vs 11.1 vs 9.0); Asians compared with Caucasians (19.5 vs 9.6 months); patients with adenocarcinoma compared with squamous cell carcinoma (12.4 vs 9.3 months) and those with metastases to one site compared with two sites compared with three or more sites (12.4 months vs 9.8 months vs 6.4 months). Age (<65 vs ≥65 years), tumor stage (IIIB with pleural effusion vs IV) and percentage of tumor cells expressing EGFR (<40% vs ≥40%) were not identified as possible prognostic factors in relation to survival time. In multivariable analysis, a stepwise selection procedure identified age (<65 vs ≥65 years), gender, ECOG PS, smoking status, region, tumor histology, and number of organs involved as independent factors of prognostic value. In summary, in patients with advanced NSCLC enrolled in the FLEX study, and consistent with previous analyses, particular patient and disease characteristics at baseline were shown to be independent factors of prognostic value. The FLEX study is registered with ClinicalTrials.gov, number NCT00148798. © 2012 Elsevier Ireland Ltd.

Exploring the influences of country-level factors on mid-age women’s drink driving attitudes

Drink driving remains a major cause of serious and fatal car crashes in Australia and internationally. While this problem is more prevalent among male drivers, the rates of female intoxicated drivers have increased steadily over the past decades in many motorised countries. A combination of police enforcement, media awareness campaigns, and community initiatives has played a key role in reducing incidents of illegal drink driving by targeting public drink driving attitudes. However, important cultural differences in regards to the tolerance towards drink driving have been noted. While many countries, including Australia, have a legal Blood Alcohol Concentration (BAC) limit of .05 or higher, some countries have moved towards a zero –or low tolerance approach to drink driving; several European countries, including Sweden, Hungary, Slovakia, and Estonia currently enforce .00 or .02 BAC limits.

Modelling the salient factors influencing retired business professionals' participation in episodic skilled volunteering in rural settings

Retired business professionals represent an unexplored source of skill support for struggling rural communities. This research examined the feasibility of drawing on this valuable pool of knowledge and experience by engaging retirees in short term, project based volunteering roles in rural, not for profit agencies. Using the theory of planned behaviour and the functional approach to volunteering, the program of study generated a model comprising the key psychological and contextual factors determining the volunteers' decision to provide skill assistance in rural settings. The model provides a useful resource for creating suitable volunteering opportunities and for informing volunteer recruitment strategies.

Factors influencing health professionals' response to victims of domestic violence

This thesis examined factors influencing health professional's response to victims of domestic violence in Vietnam. As this is the first time that this type of research has been conducted in Vietnam, it was expected that the results would contribute significantly to local knowledge and should add to global perspectives. Since it is the first questionnaire about this topic to be developed in Vietnam, the psychometric property of the questionnaire was primarily established, resulting in the questionnaire being recommended to use for further study. By explaining the factors that affect the intentions to respond of health workers, this project provides key data for authorities to design intervention strategies to improve the responses of health professionals to victims of domestic violence in Vietnam.

A Century of American Economic Review : Insights on Critical Factors in Journal Publishing

By using information collected from numerous American Economic Review publications from the last 100 years, Torgler and Piatti examine the top publishing institutions to determine their most renowned AER papers based on citation success. Areas of interest include how often an individual can publish in the AER, how equally successful citations are distributed and who the top AER publishing authors are. The book explores what the level of cooperation is among authors and what drives systems such as the alphabetical name ordering. Torgler and Piatti critically examine the individual characteristics of AER authors, editors, editorial board members and referees and even tackle more intricate details such as the frequency of female publications in the AER. The authors observe and analyse the relationship between academic age and publication performance to see if there is any pattern on these factors and citation success. The book then goes on to analyse data concerning awards, and whether awards can increase the probability of publishing in the AER at a later stage

Coexpression of epidermal growth factor receptor with related factors is associated with a poor prognosis in non-small-cell lung cancer

The epidermal growth factor receptor (EGFR) is commonly expressed in non-small-cell lung cancer (NSCLC) and promotes a host of mechanisms involved in tumorigenesis. However, EGFR expression does not reliably predict prognosis or response to EGFR-targeted therapies. The data from two previous studies of a series of 181 consecutive surgically resected stage I-IIIA NSCLC patients who had survived in excess of 60 days were explored. Of these patients, tissue was available for evaluation of EGFR in 179 patients, carbonic anhydrase (CA) IX in 177 patients and matrix metalloproteinase-9 (MMP-9) in 169 patients. We have previously reported an association between EGFR expression and MMP-9 expression. We have also reported that MMP-9 (P=0.001) and perinuclear (p)CA IX (P=0.03) but not EGFR expression were associated with a poor prognosis. Perinuclear CA IX expression was also associated with EGFR expression (P<0.001). Multivariate analysis demonstrated that coexpression of MMP-9 with EGFR conferred a worse prognosis than the expression of MMP-9 alone (P<0.001) and coexpression of EGFR and pCA IX conferred a worse prognosis than pCA IX alone (P=0.05). A model was then developed where the study population was divided into three groups: group 1 had expression of EGFR without coexpression of MMP-9 or pCA IX (number=21); group 2 had no expression of EGFR (number=75); and group 3 had coexpression of EGFR with pCA IX or MMP-9 or both (number=70). Group 3 had a worse prognosis than either groups 1 or 2 (P=0.0003 and 0.027, respectively) and group 1 had a better prognosis than group 2 (P=0.036). These data identify two cohorts of EGFR-positive patients with diametrically opposite prognoses. The group expressing either EGFR and or both MMP-9 and pCA IX may identify a group of patients with activated EGFR, which is of clinical relevance with the advent of EGFR-targeted therapies. © 2004 Cancer Research UK.

Exploring influencing factors of short-lived buildings in China's urban renewal : evidence from Chongqing

With the fast development of urban sprawl and renewal in China, many buildings are “non-nature” short-lived, i.e. demolished after only a few years. For this concern, this research explores the influencing factors of short-lived buildings and provides the scientific foundation for sustainable urban management and planning. Cases for this research are 1734 buildings demolished in Jiangbei district, the middle region of Chongqing City. Internal and external factors for the short-lived buildings are identified by applying logistic analysis. The results indicate that nine factors have significant influence on short-lived buildings. This research also find that buildings with low density, utilization and compensation while high land development potential are more likely to become short-lived buildings.

Prevalence of risk factors for undiagnosed obstructive sleep apnoea is high in truck drivers on UK roads

Objectives To determine the prevalence of symptoms and risk factors of obstructive sleep apnoea (OSA) in truck drivers at a UK large truck stop. Methods Over a 5 day period, truck drivers completed a short questionnaire at a major UK ‘truck stop’. The questionnaire asked about OSA rist factors and symptoms, and included the Epworth Sleepiness Scale (ESS). Additionally, measurements of height, weight and collar size were taken. 148 truck drivers participated and within this random group the risk factors of OSA that were looked for were:men age over 40 y, obesity, parge neck circumference, smoking, high ESS and bed partner reporting snoring with witnessed apnoeas. Results Our sample were all men, with 82% aged over 40 y. 47% were obese (compared with 23% for UK men in general) and average neck circumference was 42 cm (compared with 38 cm for UK men in general – Martin et al 1997). 31% smoked (vs 21% for general population), and ESS averaged 2.1 points higher than expected for a healthy population (Johns et al 1997). Snoring was quite evident at 57% (compared wth 40% for men in general) and witnessed apnoeas were almost double (7%) compared with 3.8% given by Ohayon et al (1997) generally for men. Conclusion 8 key symptoms and risk factors of OSA have been found to be prevalent in a sample of truck drivers on UK roads, and to greater extent that for estimates in the general male population. Bed partners of truck drivers reporting witnessed apnoeas strongly suggests this group has a high potential for undiagnosed OSA. OSA sufferers are known to be at high risk of causing road traffi c accidents. This, together with the large size of trucks, then the potential for serious road crashes is great. Truck drivers, especially those who are obese, ought to be a high priority population for OSA screening.

Sensorimotor and postural control factors associated with driving safety in a community-dwelling older driver population

Background. To establish whether sensorimotor function and balance are associated with on-road driving performance in older adults. Methods. The performance of 270 community-living adults aged 70–88 years recruited via the electoral roll was measured on a battery of peripheral sensation, strength, flexibility, reaction time, and balance tests and on a standardized measure of on-road driving performance. Results. Forty-seven participants (17.4%) were classified as unsafe based on their driving assessment. Unsafe driving was associated with reduced peripheral sensation, lower limb weakness, reduced neck range of motion, slow reaction time, and poor balance in univariate analyses. Multivariate logistic regression analysis identified poor vibration sensitivity, reduced quadriceps strength, and increased sway on a foam surface with eyes closed as significant and independent risk factors for unsafe driving. These variables classified participants into safe and unsafe drivers with a sensitivity of 74% and specificity of 70%. Conclusions. A number of sensorimotor and balance measures were associated with driver safety and the multivariate model comprising measures of sensation, strength, and balance was highly predictive of unsafe driving in this sample. These findings highlight important determinants of driver safety and may assist in developing efficacious driver safety strategies for older drivers.

Is recovery driven by central or peripheral factors? A role for the brain in recovery following intermittent-sprint exercise

Prolonged intermittent-sprint exercise (i.e., team sports) induce disturbances in skeletal muscle structure and function that are associated with reduced contractile function, a cascade of inflammatory responses, perceptual soreness, and a delayed return to optimal physical performance. In this context, recovery from exercise-induced fatigue is traditionally treated from a peripheral viewpoint, with the regeneration of muscle physiology and other peripheral factors the target of recovery strategies. The direction of this research narrative on post-exercise recovery differs to the increasing emphasis on the complex interaction between both central and peripheral factors regulating exercise intensity during exercise performance. Given the role of the central nervous system (CNS) in motor-unit recruitment during exercise, it too may have an integral role in post-exercise recovery. Indeed, this hypothesis is indirectly supported by an apparent disconnect in time-course changes in physiological and biochemical markers resultant from exercise and the ensuing recovery of exercise performance. Equally, improvements in perceptual recovery, even withstanding the physiological state of recovery, may interact with both feed-forward/feed-back mechanisms to influence subsequent efforts. Considering the research interest afforded to recovery methodologies designed to hasten the return of homeostasis within the muscle, the limited focus on contributors to post-exercise recovery from CNS origins is somewhat surprising. Based on this context, the current review aims to outline the potential contributions of the brain to performance recovery after strenuous exercise.

Environmental factors associated with active living in retirement village residents : findings from an exploratory qualitative enquiry

This exploratory enquiry employs qualitative methods to advance knowledge and understanding of physical environmental attributes related to active living among residents of Australian retirement villages. Six focus groups (n = 51 residents) were held and participants described how their current, and subsequently ideal, retirement village and neighborhood supported active lifestyles. Thematic analysis revealed three key environmental factors associated with active living: a positive social environment within the village; services and facilities provided in the village and wider neighborhood; and the presence of suitable pedestrian infrastructure. The unique discovery that environmental factors of both the retirement village and the surrounding neighborhood were associated with residents’ active living raises many questions for study. Findings informed the development of a survey instrument, and further understanding in this area has the potential to contribute to the design and siting practices of senior housing complexes within neighborhoods.