A metastatic neuroendocrine anaplastic small cell tumor in a patient with multiple endocrine neoplasia type 1 syndrome : assessment of disease status and response to doxorubicin, cyclophosphamide, etoposide chemotherapy through scintigraphic imaging with 111In-pentetreotide

Extrapulmonary small cell and small cell neuroendocrine tumors of unknown primary site are, in general, aggressive neoplasms with a short median survival. Like small cell lung cancer (SCLC), they often are responsive to chemotherapy and radiotherapy. Small cell lung cancer and well differentiated neuroendocrine carcinomas of the gastrointestinal tract and pancreas tend to express somatostatin receptors. These tumors may be localized in patients by scintigraphic imaging using radiolabeled somatostatin analogues. A patient with an anaplastic neuroendocrine small cell tumor arising on a background of multiple endocrine neoplasia type 1 syndrome is reported. The patient had a known large pancreatic gastrinoma and previously treated parathyroid adenopathy. At presentation, there was small cell cancer throughout the liver and skeleton. Imaging with a radiolabeled somatostatin analogue, 111In- pentetreotide (Mallinckrodt Medical B. V., Petten, Holland), revealed all sites of disease detected by routine biochemical and radiologic methods. After six cycles of chemotherapy with doxorubicin, cyclophosphamide, and etoposide, there was almost complete clearance of the metastatic disease. 111In-pentetreotide scintigraphy revealed uptake consistent with small areas of residual disease in the liver, the abdomen (in mesenteric lymph nodes), and posterior thorax (in a rib). The primary gastrinoma present before the onset of the anaplastic small cell cancer showed no evidence of response to the treatment. The patient remained well for 1 year and then relapsed with brain, lung, liver, and skeletal metastases. Despite an initial response to salvage radiotherapy and chemotherapy with carboplatin and dacarbazine, the patient died 6 months later.

Real-time video event detection in crowded scenes using MPEG derived features : a multiple instance learning approach

This paper presents an investigation into event detection in crowded scenes, where the event of interest co-occurs with other activities and only binary labels at the clip level are available. The proposed approach incorporates a fast feature descriptor from the MPEG domain, and a novel multiple instance learning (MIL) algorithm using sparse approximation and random sensing. MPEG motion vectors are used to build particle trajectories that represent the motion of objects in uniform video clips, and the MPEG DCT coefficients are used to compute a foreground map to remove background particles. Trajectories are transformed into the Fourier domain, and the Fourier representations are quantized into visual words using the K-Means algorithm. The proposed MIL algorithm models the scene as a linear combination of independent events, where each event is a distribution of visual words. Experimental results show that the proposed approaches achieve promising results for event detection compared to the state-of-the-art.

Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX) : an open-label randomised phase III trial

Background: Use of cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor (EGFR), has the potential to increase survival in patients with advanced non-small-cell lung cancer. We therefore compared chemotherapy plus cetuximab with chemotherapy alone in patients with advanced EGFR-positive non-small-cell lung cancer. Methods: In a multinational, multicentre, open-label, phase III trial, chemotherapy-naive patients (≥18 years) with advanced EGFR-expressing histologically or cytologically proven stage wet IIIB or stage IV non-small-cell lung cancer were randomly assigned in a 1:1 ratio to chemotherapy plus cetuximab or just chemotherapy. Chemotherapy was cisplatin 80 mg/m 2 intravenous infusion on day 1, and vinorelbine 25 mg/m 2 intravenous infusion on days 1 and 8 of every 3-week cycle) for up to six cycles. Cetuximab-at a starting dose of 400 mg/m 2 intravenous infusion over 2 h on day 1, and from day 8 onwards at 250 mg/m 2 over 1 h per week-was continued after the end of chemotherapy until disease progression or unacceptable toxicity had occurred. The primary endpoint was overall survival. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00148798. Findings: Between October, 2004, and January, 2006, 1125 patients were randomly assigned to chemotherapy plus cetuximab (n=557) or chemotherapy alone (n=568). Patients given chemotherapy plus cetuximab survived longer than those in the chemotherapy-alone group (median 11·3 months vs 10·1 months; hazard ratio for death 0·871 [95% CI 0·762-0·996]; p=0·044). The main cetuximab-related adverse event was acne-like rash (57 [10%] of 548, grade 3). Interpretation: Addition of cetuximab to platinum-based chemotherapy represents a new treatment option for patients with advanced non-small-cell lung cancer. Funding: Merck KGaA. © 2009 Elsevier Ltd. All rights reserved.

Effective technologies for noninvasive remote monitoring in heart failure

Background Trials of new technologies to remotely monitor for signs and symptoms of worsening heart failure are continually emerging. The extent to which technological differences impact the effectiveness of non-invasive remote monitoring for heart failure management is unknown. Objective To examine the effect of specific technology used for non-invasive remote monitoring of people with heart failure on all-cause mortality and heart failure-related hospitalisations. Methods A sub-analysis of a large systematic review and meta-analysis was conducted. Studies were stratified according to the specific type of technology used and separate meta-analyses were performed. Four different types of non-invasive remote monitoring technologies were identified including structured telephone calls, videophone, interactive voice response devices and telemonitoring. Results Only structured telephone calls and telemonitoring were effective in reducing the risk of all-cause mortality (RR 0.87; 95% CI=0.75-1.01; p=0.06 and 0.62; 95% CI=0.50-0.77; p<0.0001) and heart failure-related hospitalisations (RR 0.77; 95% CI=0.68-0.87; p<0.001) and 0.75; 95% CI=0.63-0.91; p=0.003). More research data is required for videophone and interactive voice response technologies. Conclusions This sub-analysis identified that only two of the four specific technologies used for non-invasive remote monitoring in heart failure improved outcomes. When results of studies that involved these disparate technologies were combined in previous meta-analyses, significant improvements in outcomes were identified. As such, this study has highlighted implications for future meta-analyses of randomised controlled trials focused on evaluating the effectiveness of remote monitoring in heart failure.

Multiple types of data are required to identify the mechanisms influencing the spatial expansion of melanoma cell colonies

Background The expansion of cell colonies is driven by a delicate balance of several mechanisms including cell motility, cell-to-cell adhesion and cell proliferation. New approaches that can be used to independently identify and quantify the role of each mechanism will help us understand how each mechanism contributes to the expansion process. Standard mathematical modelling approaches to describe such cell colony expansion typically neglect cell-to-cell adhesion, despite the fact that cell-to-cell adhesion is thought to play an important role. Results We use a combined experimental and mathematical modelling approach to determine the cell diffusivity, D, cell-to-cell adhesion strength, q, and cell proliferation rate, ?, in an expanding colony of MM127 melanoma cells. Using a circular barrier assay, we extract several types of experimental data and use a mathematical model to independently estimate D, q and ?. In our first set of experiments, we suppress cell proliferation and analyse three different types of data to estimate D and q. We find that standard types of data, such as the area enclosed by the leading edge of the expanding colony and more detailed cell density profiles throughout the expanding colony, does not provide sufficient information to uniquely identify D and q. We find that additional data relating to the degree of cell-to-cell clustering is required to provide independent estimates of q, and in turn D. In our second set of experiments, where proliferation is not suppressed, we use data describing temporal changes in cell density to determine the cell proliferation rate. In summary, we find that our experiments are best described using the range D = 161 - 243 ?m2 hour-1, q = 0.3 - 0.5 (low to moderate strength) and ? = 0.0305 - 0.0398 hour-1, and with these parameters we can accurately predict the temporal variations in the spatial extent and cell density profile throughout the expanding melanoma cell colony. Conclusions Our systematic approach to identify the cell diffusivity, cell-to-cell adhesion strength and cell proliferation rate highlights the importance of integrating multiple types of data to accurately quantify the factors influencing the spatial expansion of melanoma cell colonies.

Design, implementation and multisite evaluation of a system suitability protocol for the quantitative assessment of instrument performance in liquid chromatography-multiple reaction monitoring-MS (LC-MRM-MS)

Multiple reaction monitoring (MRM) mass spectrometry coupled with stable isotope dilution (SID) and liquid chromatography (LC) is increasingly used in biological and clinical studies for precise and reproducible quantification of peptides and proteins in complex sample matrices. Robust LC-SID-MRM-MS-based assays that can be replicated across laboratories and ultimately in clinical laboratory settings require standardized protocols to demonstrate that the analysis platforms are performing adequately. We developed a system suitability protocol (SSP), which employs a predigested mixture of six proteins, to facilitate performance evaluation of LC-SID-MRM-MS instrument platforms, configured with nanoflow-LC systems interfaced to triple quadrupole mass spectrometers. The SSP was designed for use with low multiplex analyses as well as high multiplex approaches when software-driven scheduling of data acquisition is required. Performance was assessed by monitoring of a range of chromatographic and mass spectrometric metrics including peak width, chromatographic resolution, peak capacity, and the variability in peak area and analyte retention time (RT) stability. The SSP, which was evaluated in 11 laboratories on a total of 15 different instruments, enabled early diagnoses of LC and MS anomalies that indicated suboptimal LC-MRM-MS performance. The observed range in variation of each of the metrics scrutinized serves to define the criteria for optimized LC-SID-MRM-MS platforms for routine use, with pass/fail criteria for system suitability performance measures defined as peak area coefficient of variation <0.15, peak width coefficient of variation <0.15, standard deviation of RT <0.15 min (9 s), and the RT drift <0.5min (30 s). The deleterious effect of a marginally performing LC-SID-MRM-MS system on the limit of quantification (LOQ) in targeted quantitative assays illustrates the use and need for a SSP to establish robust and reliable system performance. Use of a SSP helps to ensure that analyte quantification measurements can be replicated with good precision within and across multiple laboratories and should facilitate more widespread use of MRM-MS technology by the basic biomedical and clinical laboratory research communities.

The detection of incipient faults in small multi-cylinder diesel engines using multiple acoustic emission sensors

This thesis investigates condition monitoring (CM) of diesel engines using acoustic emission (AE) techniques. The AE signals recorded from a small size diesel engine are mixtures of multiple sources from multiple cylinders. Thus, it is difficult to interpret the information conveyed in the signals for CM purposes. This thesis develops a series of practical signal processing techniques to overcome this problem. Various experimental studies conducted to assess the CM capabilities of AE analysis for diesel engines. A series of modified signal processing techniques were proposed. These techniques showed promising results of capability for CM of multiple cylinders diesel engine using multiple AE sensors.

Reversibility of liver failure secondary to metastatic breast cancer by vinorelbine and cisplatin chemotherapy

Purpose: The development of liver metastases from breast cancer is associated with a very poor prognosis, estimated at 4 months median survival. Since treatment with many chemotherapeutic agents is relatively contraindicated, we assessed the safety, tolerability and potential efficacy of combination chemotherapy with vinorelbine and cisplatin (ViP). Method: Pilot study in 11 patients with histologically confirmed breast carcinoma, radiological evidence of liver metastases and serum bilirubin greater than 1.5 times the upper limit of normal. Patients received up to six cycles of cisplatin (75 mg/m 2) every 21 days and vinorelbine (20 mg/m 2) on days 1 and 8 of every 21-day cycle. Measurement of liver lesions was performed on CT scan every 8 weeks into treatment. Results: The most frequently reported adverse event was myelosuppression. Other adverse effects included nausea, vomiting and mild neurotoxicity. Two patients died after one treatment with ViP, one of whom suffered an intracerebral haemorrhage that was possibly treatment-related. Improvement in liver function tests was observed in 10 patients, and mean time to normalization of bilirubin levels was 36 days. Partial responses were documented radiologically in 7 out of 11 patients treated. Median overall survival from trial entry was 6.5 months (range 11-364 days), with one patient alive 13 months from trial entry. Conclusion: Normalization of liver function is possible with ViP treatment of metastatic breast cancer, offering the potential to prolong survival. Phase II clinical trials of this regimen in this patient group should include measurement of quality of life in order to assess risk versus benefit.

Perceptions of organ donors and willingness to donate organs upon death : a test of the prototype/willingness model

Understanding people's organ donation decisions may narrow the gap between organ supply and demand. In two studies, participants who had not recorded their posthumous organ donation decision (Study 1, N = 210; Study 2, N = 307) completed items assessing prototype/willingness model (PWM; attitude, subjective norm, donor prototype favorability and similarity, willingness) constructs. Attitude, subjective norm, and prototype similarity predicted willingness to donate. Prototype favorability and a Prototype Favorability × Similarity interaction predicted willingness (Study 2). These findings provide support for the PWM in altruistic health contexts, highlighting the importance of people's perceptions about organ donors in their donation decisions.

Pitfalls in the use of kappa when interpreting agreement between multiple raters in reliability studies

OBJECTIVE To compare different reliability coefficients (exact agreement, and variations of the kappa (generalised, Cohen's and Prevalence Adjusted and Biased Adjusted (PABAK))) for four physiotherapists conducting visual assessments of scapulae. DESIGN Inter-therapist reliability study. SETTING Research laboratory. PARTICIPANTS 30 individuals with no history of neck or shoulder pain were recruited with no obvious significant postural abnormalities. MAIN OUTCOME MEASURES Ratings of scapular posture were recorded in multiple biomechanical planes under four test conditions (at rest, and while under three isometric conditions) by four physiotherapists. RESULTS The magnitude of discrepancy between the two therapist pairs was 0.04 to 0.76 for Cohen's kappa, and 0.00 to 0.86 for PABAK. In comparison, the generalised kappa provided a score between the two paired kappa coefficients. The difference between mean generalised kappa coefficients and mean Cohen's kappa (0.02) and between mean generalised kappa and PABAK (0.02) were negligible, but the magnitude of difference between the generalised kappa and paired kappa within each plane and condition was substantial; 0.02 to 0.57 for Cohen's kappa and 0.02 to 0.63 for PABAK, respectively. CONCLUSIONS Calculating coefficients for therapist pairs alone may result in inconsistent findings. In contrast, the generalised kappa provided a coefficient close to the mean of the paired kappa coefficients. These findings support an assertion that generalised kappa may lead to a better representation of reliability between three or more raters and that reliability studies only calculating agreement between two raters should be interpreted with caution. However, generalised kappa may mask more extreme cases of agreement (or disagreement) that paired comparisons may reveal.

The human cost of change : tales from the campus about personal change fatigue, resistance, and resilience

For the last decade, one question has haunted me: what helps people to cope with large-scale organisational change in their workplace? This study explores the construct of personal change resilience, and its potential for identifying solutions to the problems of change fatigue and change resistance. The thesis has emerged from the fields of change management, leadership, training, mentoring, evaluation, management and trust within the context of higher education in Australia at the beginning of the twenty-first century. In this thesis I present a theoretical model of the factors to consider in increasing peoples’ personal change resilience as they navigate large-scale organisational change at work, thereby closing a gap in the literature on the construct of change resilience. The model presented is based on both the literature in the realms of business and education, and on the findings of the research. In this thesis, an autoethnographic case study of two Australian university projects is presented as one narrative, resulting in a methodological step forward in the use of multiple research participants’ stories in the development of a single narrative. The findings describe the experiences of workers in higher education and emphasise the importance of considerate management in the achievement of positive experiences of organisational change. This research makes a significant contribution to new knowledge in three ways. First, it closes a gap in the literature in the realm of change management around personal change resilience as a solution to the problem of change fatigue by presenting models of both change failure and personal change resilience. Second, it is methodologically innovative in the use of personae to tell the stories of multiple participants in one coherent tale presented as a work of ethnographic fiction seen through an autoethnographic lens. By doing so, it develops a methodology for giving a voice to those to whom change is done in the workplace. Third, it provides a perspective on organisational change management from the view of the actual workers affected by change, thereby adding to the literature that currently exists, which is based on the views of those with responsibility for leading or managing change rather than those it affects. This thesis is intended as a practical starting point for conversations by actual change managers in higher education, and it is written in such a way as to help them see how theory can be applied in real life, and how empowering and enabling the actual working staff members, and engaging with them in a considerate way before, during and even after the change process, can help to make them resilient enough to cope with the change, rather than leaving them burned out or disengaged and no longer a well-functioning member of the institution. This thesis shows how considerately managed large-scale organisational change can result in positive outcomes for both the organisation and the individuals who work in it.

Odometry-driven inference to link multiple exemplars of a location

A major challenge for robot localization and mapping systems is maintaining reliable operation in a changing environment. Vision-based systems in particular are susceptible to changes in illumination and weather, and the same location at another time of day may appear radically different to a system using a feature-based visual localization system. One approach for mapping changing environments is to create and maintain maps that contain multiple representations of each physical location in a topological framework or manifold. However, this requires the system to be able to correctly link two or more appearance representations to the same spatial location, even though the representations may appear quite dissimilar. This paper proposes a method of linking visual representations from the same location without requiring a visual match, thereby allowing vision-based localization systems to create multiple appearance representations of physical locations. The most likely position on the robot path is determined using particle filter methods based on dead reckoning data and recent visual loop closures. In order to avoid erroneous loop closures, the odometry-based inferences are only accepted when the inferred path's end point is confirmed as correct by the visual matching system. Algorithm performance is demonstrated using an indoor robot dataset and a large outdoor camera dataset.

Teacher Evidence Matrix : an evaluation using multiple lines of evidence

Welcome to the Teacher evidence matrix. This matrix is designed for highly qualified discipline experts to evaluate their teaching in a systematic manner. The primary purpose of the Teacher evidence matrix is to provide a tool that an academic staff member at university can annually review their teaching. The annual review will result in you being ready for performance, planning and review; promotion; awards; or employment application. This tool is designed for individual use and will lead to an action plan for implementation.

Towards bio-inspired place recognition over multiple spatial scales

This paper presents a new multi-scale place recognition system inspired by the recent discovery of overlapping, multi-scale spatial maps stored in the rodent brain. By training a set of Support Vector Machines to recognize places at varying levels of spatial specificity, we are able to validate spatially specific place recognition hypotheses against broader place recognition hypotheses without sacrificing localization accuracy. We evaluate the system in a range of experiments using cameras mounted on a motorbike and a human in two different environments. At 100% precision, the multiscale approach results in a 56% average improvement in recall rate across both datasets. We analyse the results and then discuss future work that may lead to improvements in both robotic mapping and our understanding of sensory processing and encoding in the mammalian brain.

CPD : Using evidence based clinical practice guidelines in the management of anaemia in patients with chronic renal failure

Anaemia is a chronic problem in patients with renal insufficiency, especially chronic renal failure (CRF). In patients with CRF, anaemia is primarily due to a deficiency in erythropoietin (EPO), a glycoprotein growth factor that stimulates RBC production. The long-term effects and burden of anaemia for patients with CRF can be physical, emotional and financial. With efficient, systematic management of anaemia, clinicians have the potential to realise not only better clinical outcomes for CRF patients but also significant cost savings for them and the health system. During the last decade, significant advances have been made in clinicians’ understanding of how best to manage anaemia in this vulnerable population. One of the most important efforts to improve clinical practice has been the development of best practice guidelines.