A phase I dose-escalating study of DaunoXome, liposomal daunorubicin, in metastatic breast cancer

The aims of this phase I study were to establish the maximum tolerated dose, safety profile and activity of liposomal daunorubicin, DaunoXome (NeXstar Pharmaceuticals), in the treatment of metastatic breast cancer. DaunoXome was administered intravenously over 2 h in 21 day cycles and doses were increased from 80 to 100, 120 and 150 mg m 2. Sixteen patients were enrolled. A total of 70 cycles of DaunoXome were administered. The maximum tolerated dose was 120 mg m 2, the dose-limiting toxicity being prolonged grade 4 neutropenia or neutropenic pyrexia necessitating dose reductions at 120 and 150 mg m 2. Asymptomatic cardiotoxicity was observed in three patients: grade 1 in one treated with a cumulative dose of 800 mg m 2 and grade 2 in two, one who received a cumulative dose of 960 mg m 2 and the other a cumulative dose of 600 mg m 2 with a previous neoadjuvant doxorubicin chemotherapy of 300 mg m 2. Tumour response was evaluable in 15 patients, of whom two had objective responses, six had stable disease and seven had progressive disease. In conclusion, DaunoXome is associated with mild, manageable toxicities and has anti-tumour activity in metastatic breast cancer. The findings support further phase II evaluation of DaunoXome alone and in combination with other standard non-anthracycline cytotoxic or novel targeted agents. Although the dose-limiting toxicity for DaunoXome was febrile neutropenia at 120 mg m 2, we would recommend this dose for further evaluation, as the febrile neutropenia occurred after four or more cycles in three of the four episodes seen, was short lived and uncomplicated. © 2002 Cancer Research UK.

Long-term outcomes following neoadjuvant chemoradiotherapy for esophageal cancer

OBJECTIVE: We present and analyze long-term outcomes following multimodal therapy for esophageal cancer, in particular the relative impact of histomorphologic tumor regression and nodal status. PATIENTS AND METHODS: A total of 243 patients [(adenocarcinoma (n = 170) and squamous cell carcinoma (n = 73)] treated with neoadjuvant chemoradiotherapy in the period 1990 to 2004 were followed prospectively with a median follow-up of 60 months. Pathologic stage and tumor regression grade (TRG) were documented, the site of first failure was recorded, and Kaplan-Meier survival curves were plotted. RESULTS: Thirty patients (12%) did not undergo surgery due to disease progression or deteriorated performance status. Forty-one patients (19%) had a complete pathologic response (pCR), and there were 31(15%) stage I, 69 (32%) stage II, and 72 (34%) stage III cases. The overall median survival was 18 months, and the 5-year survival was 27%. The 5-year survival of patients achieving a pCR was 50% compared with 37% in non-pCR patients who were node-negative (P = 0.86). Histomorphologic tumor regression was not associated with pre-CRT cTN stage but was significantly (P < 0.05) associated with ypN stage. By multivariate analysis, ypN status (P = 0.002) was more predictive of overall survival than TRG (P = 0.06) or ypT stage (P = 0.39). CONCLUSION: Achieving a node-negative status is the major determinant of outcome following neoadjuvant chemoradiotherapy. Histomorphologic tumor regression is less predictive of outcome than pathologic nodal status (ypN), and the need to include a primary site regression score in a new staging classification is unclear. © 2007 Lippincott Williams & Wilkins, Inc.

Developing an evidence-based clinical pathway for the assessment, diagnosis and management of acute Charcot Neuro-Arthropathy : a systematic review

Background: Charcot Neuro-Arthropathy (CN) is one of the more devastating complications of diabetes. To the best of the authors' knowledge, it appears that no clinical tools based on a systematic review of existing literature have been developed to manage acute CN. Thus, the aim of this paper was to systematically review existing literature and develop an evidence-based clinical pathway for the assessment, diagnosis and management of acute CN in patients with diabetes. Methods: Electronic databases (Medline, PubMed, CINAHL, Embase and Cochrane Library), reference lists, and relevant key websites were systematically searched for literature discussing the assessment, diagnosis and/or management of acute CN published between 2002-2012. At least two independent investigators then quality rated and graded the evidence of each included paper. Consistent recommendations emanating from the included papers were then fashioned in a clinical pathway. Results: The systematic search identified 267 manuscripts, of which 117 (44%) met the inclusion criteria for this study. Most manuscripts discussing the assessment, diagnosis and/or management of acute CN constituted level IV (case series) or EO (expert opinion) evidence. The included literature was used to develop an evidence-based clinical pathway for the assessment, investigations, diagnosis and management of acute CN. Conclusions: This research has assisted in developing a comprehensive, evidence-based clinical pathway to promote consistent and optimal practice in the assessment, diagnosis and management of acute CN. The pathway aims to support health professionals in making early diagnosis and providing appropriate immediate management of acute CN, ultimately reducing its associated complications such as amputations and hospitalisations.

Festival of Dangerous Ideas: ‘Are some Aboriginals more Aboriginal than others?’

"White Australia has always had a view on what makes a 'real' Aboriginal person. Andrew Bolt is the merely the latest in a long line of commentators who have put forward their views about 'black' and 'white' Aboriginals. Spread across a continent after 200 years of colonisation, Aboriginal people are diverse in a way that is at odds with media stereotypes of 'traditional' Aboriginal people living in troubled remote communities. At a crucial time for recognition and reconciliation, does 'white' or 'black' matter? Who speaks for Aboriginal people and defines who they are?"--Festivals, Talks & Ideas website

More than just HD

Television’s 50th anniversary marks half a century of extraordinary technological development. This begs the question: is the best we can expect for the next 50 years just Higher Definition pictures of the same old crap?

Taxonomy and redescription of the Fawn Antechinus, Antechinus bellus (Thomas) (Marsupialia: Dasyuridae)

We provide a taxonomic redescription of the Fawn Antechinus, Antechinus bellus (Thomas). A. bellus is the only member of its genus to occur in Australia’s Northern Territory, where it can be found in savannah woodlands of the Top End. It is perhaps the most distinctive antechinus, and clearly distinguishable from the other 10 extant species of antechinus found in Australia: externally, A. bellus has pale body fur, white feet and large ears; A. bellus skulls have large auditory bullae and narrow interorbital width, while broadening abruptly at the molar row; mitochondrial and nuclear genes clearly dis-tinguish A. bellus from all congeners, phylogenetically positioning the Fawn Antechinus as sister to Queensland’s A. leo Van Dyck, 1980, with which it shares a curled supratragus of the external ear and a similar tropical latitudinal range.

Screening for risk of later mental health problems : a longitudinal study

Purpose: This is one of the first studies to report that the Achenbach internalising scales were much more effective at identifying those with current comorbid depression and anxiety, rather than individual mood disorder. Introduction: The Achenbach behaviour checklists (YSR,YASR) are widely used, low cost screening tools used to assess problem behaviour. Several studies report good association between the checklists and psychiatric diagnoses; although with varying degrees of agreement. Most are cross-sectional studies involving adolescents referred to mental health services; few are in large community-based studies. This study examined the usefulness of the Achenbach internalising scales in the primary screening (both predictive and concurrent)for depression and anxiety. Methods: The sample was 2400 young adults from an Australian population-based prospective birth cohort study. The association between the empirical anxiety and depression scales were individually assessed against DSM-IV depression and anxiety diagnoses. Odds ratios and diagnostic efficiency tests report the findings. Results: Adolescents with internalising symptoms were twice (OR 2.3, 95%CI 1.7 to 3.1) as likely to be diagnosed with later DSM-IV depression. YASR internalising scale predicted DSM-IV mood disorders (depression OR = 6.9, 95% CI 5.0–9.5; anxiety OR = 5.1, 95% CI 3.8–6.7) in the previous 12 months. The internalising scales were much more effective at identifying those with comorbid depression and anxiety. Conclusions: Adolescence and early adulthood are key risk periods for the onset of anxiety and depression. This study found that young people with internalising behaviour problems were more likely to have comorbid depression and anxiety DSM-IV disorder.

Taxonomy and redescription of the Atherton Antechinus, Antechinus godmani (Thomas) (Marsupialia: Dasyuridae)

We provide a taxonomic redescription of the dasyurid marsupial Atherton Antechinus, Antechinus godmani (Thomas). A. godmani is only rarely encountered and limited to wet tropical rainforests of north-east Queensland, Australia, between the towns of Cardwell and Cairns (a distribution spanning 135 kilometres from north to south). The distinctive species occurs at altitudes of over 600 meters asl, in all major rainforest types, and can be found with both the northern subspecies of the Yellow-footed Antechinus, A. flavipes rubeculus Van Dyck and the Rusty Antechinus, A. adustus (Thomas). A. god-mani is clearly separated from all congeners on the basis of both morphometrics and genetics. A. godmani can be distin-guished from all extant congeners based on external morphology by a combination of large size, naked-looking tail and reddish fur on the face and head. A. godmani skulls are characteristically large, with a suite of long features: basicranium, palate, upper premolar tooth row, inter-palatal vacuity distance and dentary. Phylogenies generated from mt- and nDNA data position Antechinus godmani as monophyletic with respect to other members of the genus; A. godmani is strongly supported as the sister-group to a clade containing all other antechinus, but excluding the south-east Australian Dusky An-techinus, A. swainsonii (Waterhouse) and Swamp Antechinus, A. minimus (Geoffroy). Antechinus godmani are genetically very divergent compared to all congeners (mtDNA: range 12.9–16.3%).

Honesty about adverse events - more honoured in the breach than in the observance

The medical board of Australia Code of conduct reminds doctors that" "When adverse events occur, you have a responsibility to be open and honest in your communication with your patient, to review what has occurred and to report appropriately." More honoured in the breach rather than the observence may or may not be correct. Faced with the English concerns and the Netherlands research, an evidence based assessment of compliance with the ethical duty to disclose adverse events is warranted.

Predicting fault-prone software modules with rank sum classification

The detection and correction of defects remains among the most time consuming and expensive aspects of software development. Extensive automated testing and code inspections may mitigate their effect, but some code fragments are necessarily more likely to be faulty than others, and automated identification of fault prone modules helps to focus testing and inspections, thus limiting wasted effort and potentially improving detection rates. However, software metrics data is often extremely noisy, with enormous imbalances in the size of the positive and negative classes. In this work, we present a new approach to predictive modelling of fault proneness in software modules, introducing a new feature representation to overcome some of these issues. This rank sum representation offers improved or at worst comparable performance to earlier approaches for standard data sets, and readily allows the user to choose an appropriate trade-off between precision and recall to optimise inspection effort to suit different testing environments. The method is evaluated using the NASA Metrics Data Program (MDP) data sets, and performance is compared with existing studies based on the Support Vector Machine (SVM) and Naïve Bayes (NB) Classifiers, and with our own comprehensive evaluation of these methods.

Assessment of freestanding membranes prepared from Antheraea pernyi silk fibroin as a potential vehicle for corneal epithelial cell transplantation

Freestanding membranes created from Bombyx mori silk fibroin (BMSF) offer a potential vehicle for corneal cell transplantation since they are transparent and support the growth of human corneal epithelial cells (HCE). Fibroin derived from the wild silkworm Antheraea pernyi (APSF) might provide a superior material by virtue of containing putative cell- attachment sites that are absent from BMSF. Thus we have investigated the feasibility of producing transparent, freestanding membranes from APSF and have analysed the behaviour of HCE cells on this material. No significant differences in cell numbers or phenotype were observed in short term HCE cell cultures established on either fibroin. Production of transparent freestanding APSF membranes, however, proved to be problematic as cast solutions of APSF were more prone to becoming opaque, displayed significantly lower permeability and were more brittle than BMSF-membranes. Cultures of HCE cells established on either membrane developed a normal stratified morphology with cytokeratin pair 3/12 being immuno-localized to the superficial layers. We conclude that while it is feasible to produce transparent freestanding membranes from APSF, the technical difficulties associated with this biomaterial, along with an absence of enhanced cell growth, currently favours the continued development of BMSF as a preferred vehicle for corneal cell transplantation. Nevertheless, it remains possible that refinement of techniques for processing APSF might yet lead to improvements in the handling properties and performance of this material.

Australian baby boomers switched to more environment friendly modes of transport during the global financial crisis

The global financial crisis (GFC) in 2008 rocked local, regional, and state economies throughout the world. Several intermediate outcomes of the GFC have been well documented in the literature including loss of jobs and reduced income. Relatively little research has, however, examined the impacts of the GFC on individual level travel behaviour change. To address this shortcoming, HABITAT panel data were employed to estimate a multinomial logit model to examine mode switching behaviour between 2007 (pre-GFC) and 2009 (post-GFC) of a baby boomers cohort in Brisbane, Australia—a city within a developed country that has been on many metrics the least affected by the GFC. In addition, a Poisson regression model was estimated to model the number of trips made by individuals in 2007, 2008, and 2009. The South East Queensland Travel Survey datasets were used to develop this model. Four linear regression models were estimated to assess the effects of the GFC on time allocated to travel during a day: one for each of the three travel modes including public transport, active transport, less environmentally friendly transport; and an overall travel time model irrespective of mode. The results reveal that individuals were more likely to switch to public transport who lost their job or whose income reduced between 2007 and 2009. Individuals also made significantly fewer trips in 2008 and 2009 compared to 2007. Individuals spent significantly less time using less environmentally friendly transport but more time using public transport in 2009. Baby boomers switched to more environmentally friendly travel modes during the GFC.

Mandatory sentencing : a criminological perspective

This paper will give a ‘criminological perspective’ on mandatory sentencing. It will however largely avoid the issues of the effect of mandatory sentencing provisions on the judicial process and judicial independence, as this has already been covered by Sir Anthony Mason. It will also avoid the legal issues concerning the constitutional, human rights and international law aspects of mandatory sentencing which will be covered by later speakers. The aim will be to give a brief overview of research which evaluates the effects of mandatory sentencing provisions in terms of the available evidence of whether they meet their stated aims of deterrence, selective incapacitation and the reduction of crime rates. This will be done in two parts, first in relation to the more extensive experiment in mandatory sentencing in the USA which has provided some of the impetus and metaphors ("three strikes") for recent Australian developments; and second the recent mandatory sentencing provisions in Western Australia (WA) and the Northern Territory (NT). Evidence from both the US and WA (NT is hard to assess because of the lack of proper monitoring and criminal statistics) indicates that mandatory sentencing does not produce the effects of deterrence, selective incapacitation and crime reduction which are its stated justifications and does produce a range of damaging side effects in terms of distortion of the judicial process, wildly disproportionate sentencing, additional financial and social cost and deepening social exclusion of individuals and particular communities. So what is left are the less acknowledged underpinnings of mandatory sentencing in the form of the symbolic politics of law and order, the politics of social exclusion and a displacement of racial anxieties and hostilities onto the terrain of the legal. In fashioning this necessarily brief overview a number of sources have been heavily drawn upon, in particular the excellent work by Neil Morgan from UWA (Morgan, 1995;1999; 2000); Dianne Johnson and George Zdenkowski in their detailed report to the Senate Inquiry (2000); and a number of articles appearing in 1999 in an excellent special issue of the UNSW Law Journal, all of which are highly recommended for further reading.

Admission as a lawyer : the fearful spectre of academic misconduct

Notwithstanding a cultural critique of the concepts that underpin the values of academic integrity, both the university, as a community of scholarship, and the legal profession, as a vocation self-defined by integrity, retain traditional values. Despite the lack of direct relevance of plagiarism to legal practice, courts now demonstrate little tolerance for applicants for admission against whom findings of academic misconduct have been made. Yet this lack of tolerance is neither fatal nor absolute, with the most egregious forms of academic misconduct, coupled with less than complete candour, resulting in no more than a deferral of an application for admission for six months. Where allegations are of a less serious nature, law schools deal with allegations in a less formal or punitive fashion, regarding it as an educative function of the university, assisting students to understand the cultural practices of scholarship. For law students seeking admission to practice, applicants are under an obligation of complete candour in disclosing any matters that bear on their suitability, including any finding of academic misconduct. Individual legal academics, naturally adhering to standards of academic integrity, often have only a general understanding of the admissions process. Applying appropriate standards of academic integrity, legal academics can create difficulties for students seeking admission by not recognising a pastoral obligation to ensure that students have a clear understanding of the impact adverse findings will have on admission. Failure to fulfil this obligation deprives students of the opportunity to take prompt remedial action as well as presenting practical problems for the practitioner who moves their admission.

Continuity, Rupture, or just more of the 'Volatile and Contradictory': Glimpses of New South Wales' Penal Practice behind and through the Discursive

Throughout much of the western world more and more people are being sent to prison, one of a number of changes inspired by a 'new punitiveness' in penal and political affairs. This book seeks to understand these developments, bringing together leading authorities in the field to provide a wide-ranging analysis of new penal trends, compare the development of differing patterns of punishment across different types of societies, and to provide a range of theoretical analyses and commentaries to help understand their significance. As well as increases in imprisonment this book is also concerned to address a number of other aspects of 'the new punitiveness': firstly, the return of a number of forms of punishment previously thought extinct or inappropriate, such as the return of shaming punishments and chain gangs (in parts of the USA); and secondly, the increasing public involvement in penal affairs and penal development, for example in relation to length of sentences and the California Three Strikes Law, and a growing accreditation of the rights of victims. The book will be essential reading for students seeking to understand trends and theories of punishment on law, criminology, penology and other courses.