miRNAs in head and neck cancer revisited

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cause of cancer mortality in the world and the 5th most commonly occurring cancer. Tobacco smoking, alcohol consumption and human papilloma virus (HPV) infections have been associated with the occurrence of HNSCC. Despite advances that have been made in HNSCC treatment, smoking-associated HNSCC patients still exhibit a poor 5 year survival rate (30-50 %) and a concomitant poor quality of life. The major clinical challenge to date lies in the early detection of dysplastic lesions,which can progress to malignancy. In addition, there are currently no tools available to monitor HNSCC patients for early stages of local recurrences or distant metastases. In the recent past, micro-RNAs (miRNA) have been assessed for their role in cancer initiation and progression, including HNSCC. It is now well-established that deregulation of these single stranded, small non-coding, 19-25 nt RNAs can e.g. enhance the expression of oncogenes or subdue the expression of tumor suppressor genes. The aims of this review are three-fold: first to retrieve from the literature miRNAs that have specifically been associated with HNSCC, second to group these miRNAs into those regulating tumor initiation, progression and metastasis, and third to discern miRNAs related to smoking-associated HNSCC versus HPV-associated HNSCC development. This review gives an overview on the miRNAs regulating the development of head and neck cancers. The ultimate establishment of miRNA expression profiles that are HNSCC specific, and miRNAs that orchestrate altered gene and protein expression levels in HNSCC, could pave the way for a better understanding of the mechanism underlying its pathogenesis and the development of novel, targeted therapies.

DNA methylation at the novel CpG sites in the promoter of MED15/PCQAP gene as a biomarker for head and neck cancers

Head and neck cancers (HNCs) represent a significant and ever-growing burden to the modern society, mainly due to the lack of early diagnostic methods. A significant number of HNCs is often associated with drinking, smoking, chewing beetle nut, and human papilloma virus (HPV) infections. We have analyzed DNA methylation patterns in tumor and normal tissue samples collected from head and neck squamous cell carcinoma (HNSCC) patients who were smokers. We have identified novel methylation sites in the promoter of the mediator complex subunit 15 (MED15/PCQAP) gene (encoing a co-factor important for regulation of transcription initiation for promoters of many genes), hypermethylated specifically in tumor cells. Two clusters of CpG dinucleotides methylated in tumors, but not in normal tissue from the same patients, were identified. These CpG methylation events in saliva samples were further validated in a separate cohort of HNSCC patients (who developed cancer due to smoking or HPV infections) and healthy controls using methylation-specific PCR (MSP). We used saliva as a biological medium because of its non-invasive nature, close proximity to the tumors, easiness and it is an economically viable option for large-scale screening studies. The methylation levels for the two identified CpG clusters were significantly different between the saliva samples collected from healthy controls and HNSCC individuals (Welch's t-test returning P, 0.05 and Mann-Whitney test P, 0.01 for both). The developed MSP assays also provided a good discriminative ability with AUC values of 0.70 (P, 0.01) and 0.63 (P, 0.05). The identified novel CpG methylation sites may serve as potential non-invasive biomarkers for detecting HNSCC. © the authors.

A novel saliva-based microRNA biomarker panel to detect head and neck cancers

Background MicroRNAs (miRNAs) are known to play an important role in cancer development by post-transcriptionally affecting the expression of critical genes. The aims of this study were two-fold: (i) to develop a robust method to isolate miRNAs from small volumes of saliva and (ii) to develop a panel of saliva-based diagnostic biomarkers for the detection of head and neck squamous cell carcinoma (HNSCC). Methods Five differentially expressed miRNAs were selected from miScript™ miRNA microarray data generated using saliva from five HNSCC patients and five healthy controls. Their differential expression was subsequently confirmed by RT-qPCR using saliva samples from healthy controls (n = 56) and HNSCC patients (n = 56). These samples were divided into two different cohorts, i.e., a first confirmatory cohort (n = 21) and a second independent validation cohort (n = 35), to narrow down the miRNA diagnostic panel to three miRNAs: miR-9, miR-134 and miR-191. This diagnostic panel was independently validated using HNSCC miRNA expression data from The Cancer Genome Atlas (TCGA), encompassing 334 tumours and 39 adjacent normal tissues. Receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic capacity of the panel. Results On average 60 ng/μL miRNA was isolated from 200 μL of saliva. Overall a good correlation was observed between the microarray data and the RT-qPCR data. We found that miR-9 (P <0.0001), miR-134 (P <0.0001) and miR-191 (P <0.001) were differentially expressed between saliva from HNSCC patients and healthy controls, and that these miRNAs provided a good discriminative capacity with area under the curve (AUC) values of 0.85 (P <0.0001), 0.74 (P < 0.001) and 0.98 (P < 0.0001), respectively. In addition, we found that the salivary miRNA data showed a good correlation with the TCGA miRNA data, thereby providing an independent validation. Conclusions We show that we have developed a reliable method to isolate miRNAs from small volumes of saliva, and that the saliva-derived miRNAs miR-9, miR-134 and miR-191 may serve as novel biomarkers to reliably detect HNSCC. © 2014 International Society for Cellular Oncology.

Analysis of resource efficiency : a production frontier approach

This article integrates the material/energy flow analysis into a production frontier framework to quantify resource efficiency (RE). The emergy content of natural resources instead of their mass content is used to construct aggregate inputs. Using the production frontier approach, aggregate inputs will be optimised relative to given output quantities to derive RE measures. This framework is superior to existing RE indicators currently used in the literature. Using the exergy/emergy content in constructing aggregate material or energy flows overcomes a criticism that mass content cannot be used to capture different quality of differing types of resources. Derived RE measures are both ‘qualitative’ and ‘quantitative’, whereas existing RE indicators are only qualitative. An empirical examination into the RE of 116 economies was undertaken to illustrate the practical applicability of the new framework. The results showed that economies, on average, could reduce the consumption of resources by more than 30% without any reduction in per capita gross domestic product (GDP). This calculation occurred after adjustments for differences in the purchasing power of national currencies. The existence of high variations in RE across economies was found to be positively correlated with participation of people in labour force, population density, urbanisation, and GDP growth over the past five years. The results also showed that economies of a higher income group achieved higher RE, and those economies that are more dependent on imports and primary industries would have lower RE performance.

Head-of-bed elevation improves end-expiratory lung volumes in mechanically ventilated subjects : a prospective observational study

BACKGROUND: Head-of-bed elevation (HOBE) has been shown to assist in reducing respiratory complications associated with mechanical ventilation; however, there is minimal research describing changes in end-expiratory lung volume. This study aims to investigate changes in end-expiratory lung volume in a supine position and 2 levels of HOBE. METHODS: Twenty postoperative cardiac surgery subjects were examined using electrical impedance tomography. End-expiratory lung impedance (EELI) was recorded as a surrogate measurement of end-expiratory lung volume in a supine position and at 20° and then 30°. RESULTS: Significant increases in end-expiratory lung volume were seen at both 20° and 30° HOBE in all lung regions, except the anterior, with the largest changes from baseline (supine) seen at 30°. From baseline to 30° HOBE, global EELI increased by 1,327 impedance units (95% CI 1,080–1,573, P < .001). EELI increased by 1,007 units (95% CI 880–1,134, P < .001) in the left lung region and by 320 impedance units (95% CI 188–451, P < .001) in the right lung. Posterior increases of 1,544 impedance units (95% CI 1,405–1,682, P < .001) were also seen. EELI decreased anteriorly, with the largest decreases occurring at 30° (−335 impedance units, 95% CI −486 to −183, P < .001). CONCLUSIONS: HOBE significantly increases global and regional end-expiratory lung volume; therefore, unless contraindicated, all mechanically ventilated patients should be positioned with HOBE.

Sensorineural hearing loss after treatment for head and neck cancer : a review of the literature

Background Definitive cisplatin-based is increasingly delivered as the treatment of choice for patients with head and neck cancer. Sensorineural hearing loss is a significant long term side effect of cisplatin-based chemoradiation and is associated with potential major quality of life issues for patients. Purpose The purpose of this manuscript was to review the mechanism behind sensorineural hearing loss in patients treated with cisplatin-based chemoradiation, including incidence, the contributions of radiotherapy and cisplatin to sensorineural hearing loss and the impact of the toxicity on patient quality of life. Methods Database searches were conducted through PubMed (National Centre for Biotechnology Information) and OvidSP Medline via the Queensland University of Technology Library website. General article searches were conducted through the online search engine Google Scholar. Articles were excluded if the full-text was unavailable, they were not in English or if they were published prior to 1990. Keywords included hearing loss, ototoxicity, cancer, quality of life, cisplatin and radiotherapy. Results/Discussion The total number of journal articles accessed was 290. Due to exclusion criteria, 129 articles were deemed appropriated for review. Findings indicated that sensorineural hearing loss is a significant, long term complication for patients treated with cisplatin-based chemoradiation. Current literature recognises the ototoxic effects of cisplatin and cranial irradiation as separate entities, however the impact of combined modality therapy on sensorineural hearing loss is seldom reported. Multiple risk factors for hearing loss are described, however there are contradictory opinions on incidence and severity and the exact radiation dose threshold responsible for inducing hearing loss in patients receiving combined modality therapy. Sensorineural hearing loss creates a subset of complexities for patients with head and neck cancer and that these patients face significant quality of life impairment. Conclusion The literature review identified that sensorineural hearing loss is a major quality of life issue for patients treated with cisplatin-based chemoradiation for head and neck cancer. Further investigation evaluating the contribution of cisplatin-based chemoradiation to sensorineural hearing loss and the subsequent effect on patient quality of life is warranted.

A mood stabiliser and antiepileptic for preventing head and neck cancers?

Cancer rates have been increasing over the past 26 years, but earlier detection and increasingly more treatment options also mean more and more people are surviving cancer.

Dance teaching and learning in context : activating the head, heart and hands

Traditionally, the art of teaching dance has largely been a skill transferred from teacher to student. This master-apprentice paradigm encourages the passing on of technical and artistic traditions associated with the various genres of dance. Whilst this approach supports the passing of the flame of the art form from generation to generation, it has, in part, limited the teaching pedagogy that informs dance as an art form. The future of dance teaching is reliant on teachers’ engagement with the further development of inquiry learning and reflective practice skills within the dance studio. This paper charts one component of a reflective pedagogy, Head, Heart, Hands (Pstalozzi as cited in Rud 2006), developed as a result of an action research project, within a suite of three units across a three-year undergraduate teacher-training course for school, community and studio dance teachers.

On the relevance of travel journalism : An introduction

Not many people will be instantly familiar with British woman Dale Sheppard-Floyd, but – at least symbolically – she represents a significant milestone in the development of travel and tourism. In fact, the milestone was so significant that the United Nations World Tourism Organization booked Madrid’s venerable Museo del Prado to announce to the world’s media her visit to Spain on 13 December 2012. For Ms Sheppard-Floyd’s arrival for a three-day trip meant that more than one billion times in that year, someone had crossed a border as a tourist. An astounding number, considering that, in 1950, there had been only 25 million tourist arrivals worldwide, and even only two decades previously – in 1990 – the number had been less than half at 435 million arrivals (World Tourism Organization, 2012a, 2012b). While people have traveled for pleasure for millennia (Towner, 1995), tourism really came into its own with the expansion of the middle classes in the 19th and 20th century, and today it is considered the world’s largest business sector, with unprecedented numbers of people venturing outside of their immediate environments to explore the world around them. In 2012, travel and tourism’s total contribution to the world economy amounted to a staggering $6.6 trillion, or 9 per cent of GDP (World Travel & Tourism Council, 2013). More than 260 million jobs were generated by it worldwide, which equates to one in every 11 jobs across the globe. While there were some hiccups during the Global Financial Crisis, growth in 2012 was stronger than in other industries, such as manufacturing, financial services and retail (World Travel & Tourism Council, 2013)...

Driver’s behavioural changes with new Intelligent Transport System interventions at railway level crossings: A driving simulator study

Improving safety at railway level crossings is an important issue for the Australian transport system. Governments, the rail industry and road organisations have tried a variety of countermeasures for many years to improve railway level crossing safety. New types of Intelligent Transport System (ITS) interventions are now emerging due to the availability and the affordability of technology. These interventions target both actively and passively protected railway level crossings and attempt to address drivers’ errors at railway crossings, which are mainly a failure to detect the crossing or the train and misjudgement of the train approach speed and distance. This study aims to assess the effectiveness of three emerging ITS that the rail industry considers implementing in Australia: a visual in-vehicle ITS, an audio in-vehicle ITS, as well as an on-road flashing beacons intervention. The evaluation was conducted on an advanced driving simulator with 20 participants per trialled technology, each participant driving once without any technology and once with one of the ITS interventions. Every participant drove through a range of active and passive crossings with and without trains approaching. Their speed approach of the crossing, head movements and stopping compliance were measured. Results showed that driver behaviour was changed with the three ITS interventions at passive crossings, while limited effects were found at active crossings, even with reduced visibility. The on-road intervention trialled was unsuccessful in improving driver behaviour; the audio and visual ITS improved driver behaviour when a train was approaching. A trend toward worsening driver behaviour with the visual ITS was observed when no trains were approaching. This trend was not observed for the audio ITS intervention, which appears to be the ITS intervention with the highest potential for improving safety at passive crossings.

Determinants of trade in recyclable wastes: Evidence from commodity-based trade of waste and scrap

This paper examines factors that affect the trade of recyclable waste in both exporting and importing countries. To this end, we employ two important elements: first, we adopt a gravity model in our empirical methodology; second, we select five waste and scrap commodities and undertake estimations using commodity-level trade data. We demonstrate that, the higher the wage/per capita GDP/population of an importing country, the more recyclable wastes it imports. This result suggests that the demand for final goods and, accordingly, the demand for materials including recycled material, have strong effects on the import volume of recyclable waste. Moreover, this implies that the imports of a developing country from developed countries increase with expanding industrial activity and economic growth. We find no evidence for a pollution haven for wastes and recycling.

Current trends and management in head and neck cancers

Book description: "Over 50,000 new cases of head and neck cancer are diagnosed each year in the United States. The majority of these are squamous cell carcinoma (HNSCC), associated with human papillomavirus infection and carcinogenic behaviors such as tobacco use and alcohol consumption. Although these are more common, there are several other causes that this book addresses. This book examines the epidemiology of head and neck cancer. It discusses the management of head neck cancer as well as treatment outcomes."--publisher website

Noise in my head: Voices from the ugly Australian underground

The Ugly Australian Underground documents the music, songwriting, aesthetics and struggles of fifty of Australia’s most innovative and significant bands and artists currently at the creative peak of their careers. The book provides a rare insight into the critically heralded cult music scene in Australia. The author, Jimi Kritzler, is both a journalist and a musician, and is personally connected to the musicians he interviews through his involvement in this music subculture. The interviews are extremely personal and reveal much more than any interview granted to street press or blogs. They deal with not only the music and songwriting processes of each band, but in some circumstances their struggles with drugs, involvement in crime and the death of band members.

Heritability of head motion during resting state functional MRI in 462 healthy twins

Head motion (HM) is a critical confounding factor in functional MRI. Here we investigate whether HM during resting state functional MRI (RS-fMRI) is influenced by genetic factors in a sample of 462 twins (65% fema≤ 101 MZ (monozygotic) and 130 DZ (dizygotic) twin pairs; mean age: 21 (SD=3.16), range 16-29). Heritability estimates for three HM components-mean translation (MT), maximum translation (MAXT) and mean rotation (MR)-ranged from 37 to 51%. We detected a significant common genetic influence on HM variability, with about two-thirds (genetic correlations range 0.76-1.00) of the variance shared between MR, MT and MAXT. A composite metric (HM-PC1), which aggregated these three, was also moderately heritable (h2=42%). Using a sub-sample (N=35) of the twins we confirmed that mean and maximum translational and rotational motions were consistent "traits" over repeated scans (r=0.53-0.59); reliability was even higher for the composite metric (r=0.66). In addition, phenotypic and cross-trait cross-twin correlations between HM and resting state functional connectivities (RS-FCs) with Brodmann areas (BA) 44 and 45, in which RS-FCs were found to be moderately heritable (BA44: h2-=0.23 (sd=0.041), BA45: h2-=0.26 (sd=0.061)), indicated that HM might not represent a major bias in genetic studies using FCs. Even so, the HM effect on FC was not completely eliminated after regression. HM may be a valuable endophenotype whose relationship with brain disorders remains to be elucidated.

A reproducible method for automated extraction of brain volumes from 3D human head MR images

An automated method for extracting brain volumes from three commonly acquired three-dimensional (3D) MR images (proton density, T1 weighted, and T2-weighted) of the human head is described. The procedure is divided into four levels: preprocessing, segmentation, scalp removal, and postprocessing. A user-provided reference point is the sole operator-dependent input required. The method's parameters were first optimized and then fixed and applied to 30 repeat data sets from 15 normal older adult subjects to investigate its reproducibility. Percent differences between total brain volumes (TBVs) for the subjects' repeated data sets ranged from .5% to 2.2%. We conclude that the method is both robust and reproducible and has the potential for wide application.