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.

Can measures of limb loading and dynamic stability during the squat maneuver provide an index of early functional recovery following unilateral total hip arthroplasty?

Objective: To investigate limb loading and dynamic stability during squatting in the early functional recovery of total hip arthroplasty (THA) patients. Design: Cohort study Setting: Inpatient rehabilitation clinic. Participants: A random sample of 61 THA patients (34♂/27♀; 62±9 yrs, 77±14 kg, 174±9 cm) was assessed twice, 13.2±3.8 days (PRE) and 26.6±3.3 days post-surgery (POST), and compared with a healthy reference group (REF) (22♂/16♀; 47±12yrs; 78±20kg; 175±10cm). Interventions: THA patients received two weeks of standard in-patient rehabilitation. Main Outcome Measure(s): Inter-limb vertical force distribution and dynamic stability during the squat maneuver, as defined by the root mean square (RMS) of the center of pressure in antero-posterior and medio-lateral directions, of operated (OP) and non-operated (NON)limbs. Self-reported function was assessed via FFb-H-OA 2.0 questionnaire. Results: At PRE, unloading of the OP limb was 15.8% greater (P<.001, d=1.070) and antero-posterior and medio-lateral center of pressure RMS were 30-34% higher in THA than REF P<.05). Unloading was reduced by 12.8% towards a more equal distribution from PRE to POST (P<.001, d=0.874). Although medio-lateral stability improved between PRE and POST (OP: 14.8%, P=.024, d=0.397; NON: 13.1%, P=.015, d=0.321), antero-posterior stability was not significantly different. Self-reported physical function improved by 15.8% (P<.001, d=0.965). Conclusion(s): THA patients unload the OP limb and are dynamically more unstable during squatting in the early rehabilitation phase following total hip replacement than healthy adults. Although loading symmetry and medio-lateral stability improved to the level of healthy adults with rehabilitation, antero-posterior stability remained impaired. Measures of dynamic stability and load symmetry during squatting provide quantitative information that can be used to clinically monitor early functional recovery from THA.

2nd ESMO consensus conference on lung cancer : early-stage non-small-cell lung cancer consensus on diagnosis, treatment and follow-up

To complement the existing treatment guidelines for all tumour types, ESMO organises consensus conferences to focus on specific issues in each type of tumour. The 2nd ESMO Consensus Conference on Lung Cancer was held on 11-12 May 2013 in Lugano. A total of 35 experts met to address several questions on non-small-cell lung cancer (NSCLC) in each of four areas: pathology and molecular biomarkers, first-line/second and further lines in advanced disease, earlystage disease and locally advanced disease. For each question, recommendations were made including reference to the grade of recommendation and level of evidence. This consensus paper focuses on early-stage disease. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Critical linguistics in the early years : exploring functions of language through sophisticated picture books and process drama strategies

In this chapter we describe a critical fairytales unit taught to 4.5 to 5.5 year olds in a context of intensifying pressure to raise literacy achievement. The unit was infused with lessons on reinterpreted fairytales followed by process drama activities built around a sophisticated picture book, Beware of the Bears (MacDonald, 2004). The latter entailed a text analytic approach to critical literacy derived from systemic functional linguistics (Halliday, 1978; Halliday & Matthiessen, 2004). This approach provides a way of analysing how words and discourse are used to represent the world in a particular way and shape reader relations with the author in a particular field (Janks, 2010).

Improving treatment for obese women with early stage cancer of the uterus : rationale and design of the levonorgestrel intrauterine device ±Metformin ±weight loss in endometrial cancer (feMME) trial

Purpose Endometrial adenocarcinoma (EC) is the most common gynaecologic cancer. Up to 90% of EC patients are obese which poses a health threat to patients post-treatment. Standard treatment for EC includes hysterectomy, although this has significant side effects for obese women at high risk of surgical complications and for women of childbearing age. This trial investigates the effectiveness of non-surgical or conservative treatment options for obese women with early stage EC. The primary aim is to determine the efficacy of: levonorgestrel intrauterine device (LNG-IUD); with or without metformin (an antidiabetic drug); and with or without a weight loss intervention to achieve a pathological complete response (pCR) in EC at six months from study treatment initiation. The secondary aim is to enhance understanding of the molecular processes and to predict a treatment response by investigating EC biomarkers. Methods An open label, three-armed, randomised, phase-II, multi-centre trial of LNG-IUD ± metformin ± weight loss intervention. 165 participants from 28 centres are randomly assigned in a 3:3:5 ratio to the treatment arms. Clinical, quality of life and health behavioural data will be collected at baseline, six weeks, three and six months. EC biomarkers will be assessed at baseline, three and six months. Conclusions There is limited prospective evidence for conservative treatment for EC. Trial results could benefit patients and reduce health system costs through a reduction in hospitalisations and through lower incidence of adverse events currently observed with standard treatment.

Are we there yet? Early education responding to the challenges of climate disruption and sustainability

We are now in ‘The Critical Decade’ (Steffen & Hughes, 2013) when the world’s peoples must make strong choices if we are to avert the worst impacts of climate disruption. Yet, addressing climate disruption, challenging though this is, is not humanity’s biggest problem – rather, climate disruption is a symptom of unsustainable development models that depend on continuous economic growth that shape how we live.

The decision-making processes of early childhood teachers when working with children experiencing parental separation and divorce

In this study, the pedagogical decision-making processes of 21 Australian early childhood teachers working with children experiencing parental separation and divorce were examined. Transcripts from interviews and a focus group with teachers were analysed using grounded theory methodology. The findings showed that as teachers interacted with young children experiencing parental separation and divorce, they reported using strategic, reflexive pedagogical decision-making processes. These processes comprised five stages: (1) teachers constructing their knowledge; (2) teachers thinking about their knowledge; (3) teachers using decision-making schemas; (4) teachers taking action, and; (5) teachers monitoring action and evaluating. This understanding of teachers’ reflexive pedagogical decision-making is useful for identifying how teachers and educational leaders can support children experiencing parental separation and divorce or other life challenges.

FluMum : a prospective cohort study of mother-infant pairs assessing the effectiveness of maternal influenza vaccination in prevention of influenza in early infancy

INTRODUCTION Influenza vaccination in pregnancy is recommended for all women in Australia, particularly those who will be in their second or third trimester during the influenza season. However, there has been no systematic monitoring of influenza vaccine uptake among pregnant women in Australia. Evidence is emerging of benefit to the infant with respect to preventing influenza infection in the first 6 months of life. The FluMum study aims to systematically monitor influenza vaccine uptake during pregnancy in Australia and determine the effectiveness of maternal vaccination in preventing laboratory-confirmed influenza in their offspring up to 6 months of age. METHODS AND ANALYSIS A prospective cohort study of 10 106 mother-infant pairs recruited between 38 weeks gestation and 55 days postdelivery in six Australian capital cities. Detailed maternal and infant information is collected at enrolment, including influenza illness and vaccination history with a follow-up data collection time point at infant age 6 months. The primary outcome is laboratory-confirmed influenza in the infant. Case ascertainment occurs through searches of Australian notifiable diseases data sets once the infant turns 6 months of age (with parental consent). The primary analysis involves calculating vaccine effectiveness against laboratory-confirmed influenza by comparing the incidence of influenza in infants of vaccinated mothers to the incidence in infants of unvaccinated mothers. Secondary analyses include annual and pooled estimates of the proportion of mothers vaccinated during pregnancy, the effectiveness of maternal vaccination in preventing hospitalisation for acute respiratory illness and modelling to assess the determinants of vaccination. ETHICS AND DISSEMINATION The study was approved by all institutional Human Research Ethics Committees responsible for participating sites. Study findings will be published in peer review journals and presented at national and international conferences. TRIAL REGISTRATION NUMBER The study is registered with the Australia and New Zealand Clinical Trials Registry (ANZCTR) number: 12612000175875.

A prospective study of natural recovery from cannabis use in early psychosis

Background and Objectives: Cannabis use is common in early psychosis and has been linked to adverse outcomes. However, factors that influence and maintain change in cannabis use in this population are poorly understood. An existing prospective dataset was used to predict abstinence from cannabis use over the 6 months following inpatient admission for early psychosis. Methods: Participants were 67 inpatients with early psychosis who had used cannabis in the 6 weeks prior to admission. Current diagnoses of psychotic and substance use disorders were confirmed using a clinical checklist and structured diagnostic interview. Measures of clinical, substance use and social and occupational functioning were administered at baseline and at least fortnightly over the 6-month follow up. Results: No substance use or clinical variables were associated with 6-months’ of cannabis abstinence. Only Caucasian ethnicity, living in private accommodation and receiving an income before the admission were predictive. Only private accommodation and receiving an income were significant predictors of abstinence when these variables were entered into a multivariate analysis. Conclusions: While the observed relationships do not necessarily imply causation, they suggest that more optimal substance use outcomes could be achieved by addressing the accommodation and employment needs of patients.

Can skin cancer prevention and early detection be improved via mobile phone text messaging? a randomised, attention-control trial.

Objective. To test the impact of a theory-based, SMS (text message)-delivered behavioural intervention (Healthy Text) targeting sun protection or skin self-examination behaviours compared to attention-control. Method. Overall, 546 participants aged 18–42 years were randomised using a computer-generated number list to the skin self-examination (N = 176), sun protection (N = 187), or attention-control (N = 183) text messages group. Each group received 21 text messages about their assigned topic over 12 months (12 weekly messages for three months, then monthly messages for the next nine months). Data was collected via telephone survey at baseline, three-, and 12-months across Queensland from January 2012 to August 2013. Results. One year after baseline, the sun protection (mean change 0.12; P = 0.030) and skin self-examination groups (mean change 0.12; P = 0.035) had significantly greater improvement in their sun protection habits (SPH) index compared to the attention-control group (reference mean change 0.02). The increase in the proportion of participants who reported any skin self-examination from baseline to 12 months was significantly greater in the skin self-examination intervention group (103/163; 63%; P < 0.001) than the sun protection (83/173; 48%), or attention-control (65/165; 36%) groups. There was no significant effect of the intervention for participants who self-reported whole-body skin self-examination, sun tanning behaviour, or sunburn behaviours. Conclusion. The Healthy Text intervention was effective in inducing significant improvements in sun protection and any type of skin self-examination behaviours.

Comparison of ocular modulation transfer function determined by a ray-tracing aberrometer and a double-pass system in early cataract patients

BACKGROUND: The evaluation of retinal image quality in cataract eyes has gained importance and the clinical modulation transfer functions (MTF) can obtained by aberrometer and double pass (DP) system. This study aimed to compare MTF derived from a ray tracing aberrometer and a DP system in early cataractous and normal eyes. METHODS: There were 128 subjects with 61 control eyes and 67 eyes with early cataract defined according to the Lens Opacities Classification System III. A laser ray-tracing wavefront aberrometer (iTrace) and a double pass (DP) system (OQAS) assessed ocular MTF for 6.0 mm pupil diameters following dilation. Areas under the MTF (AUMTF) and their correlations were analyzed. Stepwise multiple regression analysis assessed factors affecting the differences between iTrace- and OQAS-derived AUMTF for the early cataract group. RESULTS: For both early cataract and control groups, iTrace-derived MTFs were higher than OQAS-derived MTFs across a range of spatial frequencies (P < 0.01). No significant difference between the two groups occurred for iTrace-derived AUMTF, but the early cataract group had significantly smaller OQAS-derived AUMTF than did the control group (P < 0.01). AUMTF determined from both the techniques demonstrated significant correlations with nuclear opacities, higher-order aberrations (HOAs), visual acuity, and contrast sensitivity functions, while the OQAS-derived AUMTF also demonstrated significant correlations with age and cortical opacity grade. The factors significantly affecting the difference between iTrace and OQAS AUMTF were root-mean-squared HOAs (standardized beta coefficient = -0.63, P < 0.01) and age (standardized beta coefficient = 0.26, P < 0.01). CONCLUSIONS: MTFs determined from a iTrace and a DP system (OQAS) differ significantly in early cataractous and normal subjects. Correlations with visual performance were higher for the DP system. OQAS-derived MTF may be useful as an indicator of visual performance in early cataract eyes.

Growing rod analysis for the fusionless correction of early onset scoliosis (EOS)

Managing spinal deformities in young children is challenging, particularly early onset scoliosis (EOS). Surgical intervention is often required if EOS has been unresponsive to conservative treatment particularly with rapidly progressive curves. An emerging treatment option for EOS is fusionless scoliosis surgery. Similar to bracing, this surgical option potentially harnesses growth, motion and function of the spine along with correcting spinal deformity. Dual growing rods are one such fusionless treatment, which aims to modulate growth of the vertebrae. The aim of this study was to ascertain the extent to which semi-constrained growing rods (Medtronic Sofamor Danek Memphis, TN, USA) with a telescopic sleeve component, reduce rotational constraint on the spine compared with standard rigid rods and hence potentially provide a more physiological mechanical environment for the growing spine. This study found that semi-constrained growing rods would be expected to allow growth via the telescopic rod components while maintaining the axial flexibility of the spine and the improved capacity for final correction.

Intercultural Dialogues in Early Childhood Education for Sustainability : Embedding Indigenous Perspectives

Embedding Indigenous perspectives in early childhood education for sustainability (ECEfS) upholds social and political action goals that support a holistic approach to promoting sustainability in educational contexts. Such goals should be responsive to particular contexts and their histories to ensure local issues are a focus of sustainability alongside global areas of concern. This chapter explores how intercultural dialogues and priorities foreground broader themes of sustainability that attend to local issues around culture and diversity, and equity in relations between groups of people. Attending to such themes in educational practice unsettles a standard environmental narrative and broadens the scope and potential for ECEfS in early years settings. Strengthening intercultural priorities in ECEfS requires a commitment to reflective practices that attend to the influence of one's cultural background on teaching and learning processes. Educators committed to reflective practices provide even greater capacity for children to act as change agents (Davis, 2008, 2010) around multiple dimensions of sustainability.

Reconciliation and Early Childhood Education for Sustainability : Broadening the Environmental Paradigm

The uptake of sustainability initiatives in early childhood education curricula continues to gain momentum in Australia and internationally. Growing awareness about the fragility of natural environments in local and global contexts, along with prioritising sustainability in educational policy, has resulted in more broad-scale responses to sustainability in early years settings. To address issues of sustainability, many childcare centres and schools focus on environmental initiatives such as garden projects, recycling and water conservation. While important, such initiatives respond to just one dimension of sustainability. With expanding focus on sustainability initiatives in early childhood education, it is timely to consider why the environmental dimension receives the most attention and what this means for social, political and economic areas of concern.