Multifocal urothelial cancers with the mutator phenotype are of monoclonal origin and require panurothelial treatment for tumor clearance

Purpose: UC is a disease of the entire urothelium, characterized by multiplicity and multifocality. The clonal relationship among multiple UCs has implications regarding adjuvant chemotherapy. It has been investigated in studies of chromosomal alteration and single gene mutation. However, these genetic changes can occur in unrelated tumors under similar carcinogenic selection pressures. Tumors with high MSI have numerous DNA mutations, of which many provide no selection benefit. While these tumors represent an ideal model for studying UC clonality, their low frequency has prevented their previous investigation. Materials and Methods: We investigated 32 upper and lower urinary tract UCs with high MSI and 4 nonUC primary cancers in 9 patients. We used the high frequency and specificity of individual DNA mutations in these tumors (MSI at 17 loci) and the early timing of epigenetic events (methylation of 7 gene promoters) to investigate tumor clonality. Results: Molecular alterations varied among tumors from different primary organs but they appeared related in the UCs of all 9 patients. While 7 patients had a high degree of concordance among UCs, in 2 the UCs shared only a few similar alterations. Genetic and epigenetic abnormalities were frequently found in normal urothelial samples. Conclusions: Multiple UCs in each patient appeared to arise from a single clone. The molecular order of tumor development varied from the timing of clinical presentation and suggested that residual malignant cells persist in the urinary tract despite apparent curative surgery. These cells lead to subsequent tumor relapse and new methods are required to detect and eradicate them.

Withholding and withdrawal of ‘futile’ life-sustaining treatment : unilateral medical decision-making in Australia and New Zealand

This article examines the law in Australia and New Zealand that governs the withholding and withdrawal of ‘futile’ life-sustaining treatment. Although doctors have both civil and criminal law duties to treat patients, those general duties do not require the provision of treatment that is deemed to be futile. This is either because futile treatment is not in a patient’s best interests or because stopping such treatment does not breach the criminal law. This means, in the absence of a duty to treat, doctors may unilaterally withdraw or withhold treatment that is futile; consent is not required. The article then examines whether this general position has been altered by statute. It considers a range of suggested possible legislation but concludes it is likely that only Queensland’s adult guardianship legislation imposes a requirement to obtain consent to withhold or withdraw such treatment.

Numerical solution of an optimal control model of dendritic cell treatment of a growing tumour

A new optimal control model of the interactions between a growing tumour and the host immune system along with an immunotherapy treatment strategy is presented. The model is based on an ordinary differential equation model of interactions between the growing tu- mour and the natural killer, cytotoxic T lymphocyte and dendritic cells of the host immune system, extended through the addition of a control function representing the application of a dendritic cell treat- ment to the system. The numerical solution of this model, obtained from a multi species Runge–Kutta forward-backward sweep scheme, is described. We investigate the effects of varying the maximum al- lowed amount of dendritic cell vaccine administered to the system and find that control of the tumour cell population is best effected via a high initial vaccine level, followed by reduced treatment and finally cessation of treatment. We also found that increasing the strength of the dendritic cell vaccine causes an increase in the number of natural killer cells and lymphocytes, which in turn reduces the growth of the tumour.

Fixed failure rate ambiguity validation methods for GPS and compass

Ambiguity resolution plays a crucial role in real time kinematic GNSS positioning which gives centimetre precision positioning results if all the ambiguities in each epoch are correctly fixed to integers. However, the incorrectly fixed ambiguities can result in large positioning offset up to several meters without notice. Hence, ambiguity validation is essential to control the ambiguity resolution quality. Currently, the most popular ambiguity validation is ratio test. The criterion of ratio test is often empirically determined. Empirically determined criterion can be dangerous, because a fixed criterion cannot fit all scenarios and does not directly control the ambiguity resolution risk. In practice, depending on the underlying model strength, the ratio test criterion can be too conservative for some model and becomes too risky for others. A more rational test method is to determine the criterion according to the underlying model and user requirement. Miss-detected incorrect integers will lead to a hazardous result, which should be strictly controlled. In ambiguity resolution miss-detected rate is often known as failure rate. In this paper, a fixed failure rate ratio test method is presented and applied in analysis of GPS and Compass positioning scenarios. A fixed failure rate approach is derived from the integer aperture estimation theory, which is theoretically rigorous. The criteria table for ratio test is computed based on extensive data simulations in the approach. The real-time users can determine the ratio test criterion by looking up the criteria table. This method has been applied in medium distance GPS ambiguity resolution but multi-constellation and high dimensional scenarios haven't been discussed so far. In this paper, a general ambiguity validation model is derived based on hypothesis test theory, and fixed failure rate approach is introduced, especially the relationship between ratio test threshold and failure rate is examined. In the last, Factors that influence fixed failure rate approach ratio test threshold is discussed according to extensive data simulation. The result shows that fixed failure rate approach is a more reasonable ambiguity validation method with proper stochastic model.

A systematic review on quality of life among patients at 1 year after treatment for head and neck cancer

Introduction: Although advances in treatment modalities have improved the survival of head and neck (H&N) cancer patients over recent years, survivors’ quality of life (QoL) could be impaired for a number of reasons. The investigation of QoL determinants can inform the design of supportive interventions for this population. Objectives: To examine the QoL of H&N cancer survivors at 1 year after treatment and to identify potential determinants affecting their QoL. Methods: A systematic search of literature was done in December 2011 in five databases: Pubmed, Medline, Scopus, Sciencedirect and CINAHL, using combined search terms ‘head and neck cancer’, ‘quality of life’, ‘health-related quality of life’ and ‘systematic review’. The methodological qualities of selected studies were assessed by two reviewers using predefined criteria. The study characteristics and results were abstracted and summarized. Results: Thirty-seven studies met all inclusion criteria with methodological quality from moderate to high. The global QoL of H&N cancer survivors returned to baseline at 1 year after treatment. Significant improvement showed in emotional functioning while physical functioning, xerostomia, sticky/insufficient saliva, and fatigue were consistently worse at 12 months compared with baseline. Age, cancer sites and stages, social support, smoking, presence of feeding tube are significant QoL determinants at 12 months. Conclusions: Although the global QoL of H&N cancer survivors recover by 12 months after treatment, problems with physical functioning, fatigue, xerostomia and sticky saliva persist. Regular assessment should be carried out to monitor these problems. Further research is required to develop appropriate and effective interventions for this population.

Current treatment for Alzheimer's disease : an overview

Despite extensive research, no cure has been found for Alzheimer's disease as yet. A large number of medications have been investigated to determine their potential for altering the natural history of the disease and this work is ongoing. In an effort to shed light on current and future (awaiting approval) medications, the following is a summary of published material and experiences with some of the drugs.

Studies of the off-field behaviours of sportspeople : are sponsors' objectives at risk?

The research reported here addresses the problem of athlete off-field behaviours as they influence sports’ sponsors, particularly the achievement of sponsorship objectives. The question arises because of incidents of sponsorship contract cancellation following news-media reporting of athletes’ off-field behaviours. Two studies are used to investigate the research question; the first establishes the content of news-media reports, and the second tests the effects of news’ reports on athlete, team and sponsor evaluations using an experimental design. Key assumptions of the research are that sponsorship objectives are principally consumer-based and mediated. Models of sponsorship argue that sponsors aim to reach and influence consumers through sponsees. Assuming this pathway exists is central to sponsorship activities. A corollary is that other mediators, in this case the news-media, may also communicate (uncontrollable) messages such that a consumer audience may be told of negative news that may then be associated with the sponsor. When sponsors cancel contracts it is assumed that their goal is to control the links between their brand and a negative referent. Balance theory is used to discuss the potential effects of negative off-field behaviours of athletes on sponsor’s objectives. Heider’s balance theory (1958) explains that individuals prefer to evaluate linked individuals or entities consistently. In the sponsorship context this presents the possibility that a negative evaluation of the athlete’s behaviour will contribute to correspondingly negative evaluations of the athlete’s team and sponsors. A content analysis (Study 1) was used to survey the types of athlete off-field behaviours commonly reported in a newspaper. In order to provide a local context for the research, articles from the Courier Mail were sampled and teams in the National Rugby League (NRL) competition were the focus of the research. The study identified nearly 2000 articles referring to the NRL competition; 258 of those refer to off-field incidents involving athletes. The various types of behaviours reported include assault, sexual assault allegations, driving under the influence of alcohol, illicit drug use, breaches of club rules, and positive off-field activities (i.e., charitable activities). An experiment (Study 2) tested three news’ article stimuli developed from the behaviours identified in Study 1 in a between-subjects design. A measure of Identification with the Team was used as a covariate variable in the Multivariate Analysis of Covariance analysis. Social identity theory suggests that when an individual identifies with a group, their attitudes and behaviours towards both in- and out-group members are modified. Use of Identification with the Team as a covariate acknowledges that respondents will evaluate behaviours differently according to the attribution of those behaviours to an in- or out-group member. Findings of the research suggest that the news’ article stimuli have significant, large effects on evaluations of athlete off-field behaviour and athlete Likability. Consistent with pretest results, charitable fundraising is regarded as extremely positive; the athlete, correspondingly, is likable. Assault is evaluated as extremely negative, and the athlete as unlikable. DUI scores reveal that the athlete’s behaviour is very negative; however, the athlete’s likability was evaluated as neutral. Treatment group does not produce any significant effects on team or sponsor variables. This research also finds that Identification with the Team has significant, large effects on team variables (Attitude toward the Brand and Corporate Image). Identification also has a significant large effect on athlete Likability, but not on Attitude toward the Act. Identification with the Team does not produce any significant effects on sponsor variables. The results of this research suggest that sponsor’s consumer-based objectives are not threatened by newspaper reports linking athlete off-field behaviour with their brand. Evaluations of sponsor variables (Attitude toward the Sponsor’s Brand and Corporate Image) were consistently positive. Variance in that data, however, cannot be attributed to experimental stimuli or Identification with the Team. These results argue that respondents may regard sponsorships, in principle, as good. Although it is good news for sponsors that negative evaluations of athletes will not produce correspondingly negative evaluations of consumer-based sponsorship objectives, the results indicate problems for sponsorship managers. The failure of Identification with the Team to explain sponsor variable variance indicates that the sponsor has not been evaluated as a linked entity in a relationship with the sporting team and athlete in this research. This result argues that the sponsee-mediated affective communication path that sponsors aim use to communicate with desirable publics is not necessarily a path available to them.

A comprehensive dual-scale wood torrefaction model : application to the analysis of thermal run-away in industrial heat treatment processes

A dual-scale model of the torrefaction of wood was developed and used to study industrial configurations. At the local scale, the computational code solves the coupled heat and mass transfer and the thermal degradation mechanisms of the wood components. At the global scale, the two-way coupling between the boards and the stack channels is treated as an integral component of the process. This model is used to investigate the effect of the stack configuration on the heat treatment of the boards. The simulations highlight that the exothermic reactions occurring in each single board can be accumulated along the stack. This phenomenon may result in a dramatic eterogeneity of the process and poses a serious risk of thermal runaway, which is often observed in industrial plants. The model is used to explain how thermal runaway can be lowered by increasing the airflow velocity, the sticker thickness or by gas flow reversal.

P.I.C.U., H.D.U., A.O.A. What treatment do we provide?: Current descriptions of the function of intensive care for inpatient Psychiatric Health Care.

Purpose – This paper adds to growing research of psychiatric intensive care units (PICU) by recounting descriptions of psychiatric intensive care settings and discusses the perceptions held by nurses of the organisational interfaces, arrangements and provisions of care in these settings. Design/methodology/approach – Data gathered from focus groups held with nurses from two PICUs was used to establish terminology, defining attributes, related concepts, antecedents, values, processes and concepts related to current practices. A literature search was conducted to permit a review of the conceptual arrangements and contemporary understanding of intensive care for people experiencing acute psychiatric illness based on the perspectives held by the nurses from the focus groups. Findings – Dissonance between service needs and the needs and management of individual patients overshadow strategies to implement comprehensive recovery-oriented approaches. Three factors are reported in this paper that influence standards and procedural practice in PICU; organisational structures; physical structures; and subtype nomenclature. Practical implications – Acute inpatient care is an important part of a comprehensive approach to mental health services. Commonly intensive acute care is delivered in specialised wards or units co-located with acute mental health inpatient units mostly known as PICU. Evidence of the most effective treatment and approaches in intensive care settings that support comprehensive recovery for improved outcomes is nascent. Originality/value – Current descriptions from nurses substantiate wide variations in the provisions, design and classifications of psychiatric intensive care. Idiosyncratic and localised conceptions of psychiatric intensive care are not adequately entailing effective treatment and methods in support of recovery principles for improved and comprehensive outcomes. The authors suggest that more concrete descriptions, guidelines, training and policies for provision of intensive psychiatric health care encompassing the perspective of nursing professionals, would reinforce conceptual construction and thus optimum treatments within a comprehensive, recovery-oriented approach to mental health services.

Urban Indigenous AOD treatment programs : addressing the lack of evaluative research of culturally appropriate youth services

This presentation discusses the limited research of urban rehabilitation service evaluations and assesses the progress of Goori House Rehabilitation Service, identifying issues preventing a sustainable organisational future.

Deformation and failure of graphene sheet and graphene-polymer interface

With a monolayer honeycomb-lattice of sp2-hybridized carbon atoms, graphene has demonstrated exceptional electrical, mechanical and thermal properties. One of its promising applications is to create graphene-polymer nanocomposites with tailored mechanical and physical properties. In general, the mechanical properties of graphene nanofiller as well as graphene-polymer interface govern the overall mechanical performance of graphene-polymer nanocomposites. However, the strengthening and toughening mechanisms in these novel nanocomposites have not been well understood. In this work, the deformation and failure of graphene sheet and graphene-polymer interface were investigated using molecular dynamics (MD) simulations. The effect of structural defects on the mechanical properties of graphene and graphene-polymer interface was investigated as well. The results showed that structural defects in graphene (e.g. Stone-Wales defect and multi-vacancy defect) can significantly deteriorate the fracture strength of graphene but may still make full utilization of corresponding strength of graphene and keep the interfacial strength and the overall mechanical performance of graphene-polymer nanocomposites.

Surgical treatment approaches and reimbursement costs of surgical site infections post hip arthroplasty in Australia : a retrospective analysis

BACKGROUND: The treatment for deep surgical site infection (SSI) following primary total hip arthroplasty (THA) varies internationally and it is at present unclear which treatment approaches are used in Australia. The aim of this study is to identify current treatment approaches in Queensland, Australia, show success rates and quantify the costs of different treatments. METHODS: Data for patients undergoing primary THA and treatment for infection between January 2006 and December 2009 in Queensland hospitals were extracted from routinely used hospital databases. Records were linked with pathology information to confirm positive organisms. Diagnosis and treatment of infection was determined using ICD-10-AM and ACHI codes, respectively. Treatment costs were estimated based on AR-DRG cost accounting codes assigned to each patient hospital episode. RESULTS: A total of n=114 patients with deep surgical site infection were identified. The majority of patients (74%) were first treated with debridement, antibiotics and implant retention (DAIR), which was successful in eradicating the infection in 60.3% of patients with an average cost of $13,187. The remaining first treatments were 1-stage revision, successful in 89.7% with average costs of $27,006, and 2-stage revisions, successful in 92.9% of cases with average costs of $42,772. Multiple treatments following 'failed DAIR' cost on average $29,560, for failed 1-stage revision were $24,357, for failed 2-stage revision were $70,381 and were $23,805 for excision arthroplasty. CONCLUSIONS: As treatment costs in Australia are high primary prevention is important and the economics of competing treatment choices should be carefully considered. These currently vary greatly across international settings.

Not all systematic reviews are systematic : a meta-review of the quality of systematic reviews for non-invasive remote monitoring in heart failure

Remote monitoring for heart failure has been evaluated in numerous systematic reviews. The aim of this meta-review was to appraise their quality and synthesise results. We electronically searched online databases, performed a forward citation search and hand-searched bibliographies. Systematic reviews of remote monitoring interventions that were used for surveillance of heart failure patients were included. Seven (41%) systematic reviews pooled results for meta-analysis. Eight (47%) considered all non-invasive remote monitoring strategies. Five (29%) focused on telemonitoring. Four (24%) included both non-invasive and invasive technologies. According to AMSTAR criteria, ten (58%) systematic reviews were of poor methodological quality. In high quality reviews, the relative risk of mortality in patients who received remote monitoring ranged from 0.53 (95% CI=0.29-0.96) to 0.88 (95% CI=0.76-1.01). High quality reviews also reported that remote monitoring reduced the relative risk of all-cause (0.52; 95% CI=0.28-0.96 to 0.96; 95% CI=0.90–1.03) and heart failure-related hospitalizations (0.72; 95% CI=0.64–0.81 to RR 0.79; 95% CI=0.67-0.94) and, as a consequence, healthcare costs. As the high quality reviews reported that remote monitoring reduced hospitalizations, mortality and healthcare costs, research efforts should now be directed towards optimising these interventions in preparation for more widespread implementation.

Not all systematic reviews are systematic : a meta-review of the quality of current systematic reviews and meta-analyses for remote monitoring in heart failure

Background/aims: Remote monitoring for heart failure has not only been evaluated in a large number of randomised controlled trials, but also in many systematic reviews and meta-analyses. The aim of this meta-review was to identify, appraise and synthesise existing systematic reviews that have evaluated the effects of remote monitoring in heart failure. Methods: Using a Cochrane methodology, we electronically searched all relevant online databases and search engines, performed a forward citation search as well as hand-searched bibliographies. Only fully published systematic reviews of invasive and/or non-invasive remote monitoring interventions were included. Two reviewers independently extracted data. Results: Sixty-five publications from 3333 citations were identified. Seventeen fulfilled the inclusion and exclusion criteria. Quality varied with A Measurement Tool to Assess Systematic Reviews (AMSTAR scores) ranging from 2 to 11 (mean 5.88). Seven reviews (41%) pooled results from individual studies for meta-analysis. Eight (47%) considered all non-invasive remote monitoring strategies. Four (24%) focused specifically on telemonitoring. Four (24%) included studies investigating both non-invasive and invasive technologies. Population characteristics of the included studies were not reported consistently. Mortality and hospitalisations were the most frequently reported outcomes 12 (70%). Only five reviews (29%) reported healthcare costs and compliance. A high degree of heterogeneity was reported in many of the meta-analyses. Conclusions: These results should be considered in context of two negative RCTs of remote monitoring for heart failure that have been published since the meta-analyses (TIM-HF and Tele-HF). However, high quality reviews demonstrated improved mortality, quality of life, reduction in hospitalisations and healthcare costs.