Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment : the M77001 study group

Purpose: This randomized, multicenter trial compared first-line trastuzumab plus docetaxel versus docetaxel alone in patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). Patients and Methods: Patients were randomly assigned to six cycles of docetaxel 100 mg/m 2 every 3 weeks, with or without trastuzumab 4 mg/kg loading dose followed by 2 mg/kg weekly until disease progression. Results: A total of 186 patients received at least one dose of the study drug. Trastuzumab plus docetaxel was significantly superior to docetaxel alone in terms of overall response rate (61% v 34%; P = .0002), overall survival (median, 31.2 v 22.7 months; P = .0325), time to disease progression (median, 11.7 v 6.1 months; P = .0001), time to treatment failure (median, 9.8 v 5.3 months; P = .0001), and duration of response (median, 11.7 v 5.7 months; P = .009). There was little difference in the number and severity of adverse events between the arms. Grade 3 to 4 neutropenia was seen more commonly with the combination (32%) than with docetaxel alone (22%), and there was a slightly higher incidence of febrile neutropenia in the combination arm (23% v 17%). One patient in the combination arm experienced symptomatic heart failure (1%). Another patient experienced symptomatic heart failure 5 months after discontinuation of trastuzumab because of disease progression, while being treated with an investigational anthracycline for 4 months. Conclusion: Trastuzumab combined with docetaxel is superior to docetaxel alone as first-line treatment of patients with HER2-positive MBC in terms of overall survival, response rate, response duration, time to progression, and time to treatment failure, with little additional toxicity. © 2005 by American Society of Clinical Oncology.

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.

The continuing decline of science and mathematics enrolments in Australian high schools

Is there a crisis in Australian science and mathematics education? Declining enrolments in upper secondary Science and Mathematics courses have gained much attention from the media, politicians and high-profile scientists over the last few years, yet there is no consensus amongst stakeholders about either the nature or the magnitude of the changes. We have collected raw enrolment data from the education departments of each of the Australian states and territories from 1992 to 2012 and analysed the trends for Biology, Chemistry, Physics, two composite subject groups (Earth Sciences and Multidisciplinary Sciences), as well as entry, intermediate and advanced Mathematics. The results of these analyses are discussed in terms of participation rates, raw enrolments and gender balance. We have found that the total number of students in Year 12 increased by around 16% from 1992 to 2012 while the participation rates for most Science and Mathematics subjects, as a proportion of the total Year 12 cohort, fell (Biology (-10%), Chemistry (-5%), Physics (-7%), Multidisciplinary Science (-5%), intermediate Mathematics (-11%), advanced Mathematics (-7%) in the same period. There were increased participation rates in Earth Sciences (+0.3%) and entry Mathematics (+11%). In each case the greatest rates of change occurred prior to 2001 and have been slower and steadier since. We propose that the broadening of curriculum offerings, further driven by students' self-perception of ability and perceptions of subject difficulty and usefulness, are the most likely cause of the changes in participation. While these continuing declines may not amount to a crisis, there is undoubtedly serious cause for concern.

John Frazer

John Frazer, Professor, trained at the Architectural Association, taught first at Cambridge University and then the AA in the 1970s and again in the '90s. He was Head of School of Design Research History and Criticism at the University of Ulster in the 1980s, he also ran a systems and design consultancy with his wife Julia (including projects for Cedric Price and Walter Segal) and was founder and chairman of Autographics software. He is currently Swire Chair Professor and Head of School of Design in Hong Kong.----- This is a very personal perspective on a concept of universal and future significance. It is personal, both is the sense that it is an unashamedly biased view of both the significance of the project, and the nature of that significance and because the author was personally involved as one of the consultants on GENERATOR and subsequently involved Cedric Price in its educational application at the Architectural Association. GENERATOR is still very much alive and was still developing whilst this chapter was being written.

Concerning the house museum and the picturesque landscape in the work of Sir John Soane : with raw hints for post-heritage museum space

The picturesque aesthetic in the work of Sir John Soane, architect and collector, resonates in the major work of his very personal practice – the development of his house museum, now the Soane Museum in Lincoln’s Inn Fields in London. Soane was actively involved with the debates, practices and proponents of picturesque and classical practices in architecture and landscape and his lectures reveal these influences in the making of The Soane, which was built to contain and present diverse collections of classical and contemporary art and architecture alongside scavenged curiosities. The Soane Museum has been described as a picturesque landscape, where a pictorial style, together with a carefully defined itinerary, has resulted in the ‘apotheosis of the Picturesque interior’. Soane also experimented with making mock ruinscapes within gardens, which led him to construct faux architectures alluding to archaeological practices based upon the ruin and the fragment. These ideas framed the making of interior landscapes expressed through spatial juxtapositions of room and corridor furnished with the collected object that characterise The Soane Museum. This paper is a personal journey through the Museum which describes and then reviews aspects of Soane’s work in the context of contemporary theories on ‘new’ museology. It describes the underpinning picturesque practices that Soane employed to exceed the boundaries between interior and exterior landscapes and the collection. It then applies particular picturesque principles drawn from visiting The Soane to a speculative project for a house/landscape museum for the Oratunga historic property in outback South Australia, where the often, normalising effects of conservation practices are reviewed using minimal architectural intervention through a celebration of ruinous states.

Decision Matrix Compared with Partnering Principles

The ideas for this CRC research project are based directly on Sidwell, Kennedy and Chan (2002). That research examined a number of case studies to identify the characteristics of successful projects. The findings were used to construct a matrix of best practice project delivery strategies. The purpose of this literature review is to test the decision matrix against established theory and best practice in the subject of construction project management.

Art, popular culture and cultural policy: variations on a theme of John Carey

The article presents a criticism of the accounts of John Carey in his book entitled "The Intellectuals and the Masses." The author focuses on Carey's argument that the art is not an eternal category but an invention of the late eighteenth century and it no longer has any intellectual legitimacy other than that of provoking feelings which are no more and no less valuable than those provoked by any other form of entertainment or physical activity

Sir Neville Howse (VC), Private John Simpson Kirkpatrick and Private Martin O’Meara (VC) and their contributions to Australian military medicine

Medical personnel serving with the Defence Forces have contributed to the evolution of trauma treatment and the advancement of prehospital care within the military environment. This paper investigates the stories of an Australian Medical Officer, Sir Neville Howse, and two stretcher bearers, Private John Simpson (Kirkpatrick) and Private Martin O’Meara, In particular it describes the gruelling conditions under which they performed their roles, and reflects on the legacy that they have left behind in Australian society. While it is widely acknowledged that conflicts such as World War One should never have happened, as civilian and defence force paramedics, we should never forget the service and sacrifice of defence force medical personnel and their contribution to the body of knowledge on the treatment of trauma. These men and women bravely provided emergency care in the most harrowing conditions possible. However, men like Martin O’Meara may not have been given the same status in society today as Sir Neville Howse or Simpson and his donkey, due to the public’s lack of awareness and acceptance of war neurosis and conditions such as post traumatic stress disorder, reactive psychosis and somatoform disorders which were suffered by many soldiers during their wartime service and on their return home after fighting in war.

A quite unreasonable state of affairs : corporate social responsibility and the John Lewis Partnership

On the surface the subjects of Corporate Social Responsibility (CSR) and Critical Management Studies (CMS) seem to be closely related. Both are concerned with reflecting on the impact of management and organisation on employees, the wider community and the environment. Both suggest that there may be a need for organisations to take responsibility for and account of people other than shareholders and both have used the concept of accountability to suggest that organisations may need to do more than just comply with the legal framework.

Kava and St. John's wort : current evidence for use in mood and anxiety disorders

Background: Mood and anxiety disorders pose significant health burdens on the community. Kava and St John’s wort (SJW) are the most commonly used herbal medicines in the treatment of anxiety and depressive disorders, respectively. Objectives: To conduct a comprehensive review of kava and SJW, to review any evidence of efficacy, mode of action, pharmacokinetics, safety and use in Major Depressive Disorder (MDD), Bipolar Disorder (BP), Seasonal Affective Disorder (SAD), Generalized Anxiety Disorder (GAD), Social Phobia (SP), Panic Disorder (PD), Obsessive-Compulsive Disorder (OCD), and Post Traumatic Stress Disorder (PTSD). Methods: A systematic review was conducted using the electronic databases MEDLINE, CINAHL, and The Cochrane Library during late 2008. The search criteria involved mood and anxiety disorder search terms in combination with kava, Piper methysticum, kavalactones, St John’s wort, Hypericum perforatum, hypericin and hyperforin. Additional search criteria for safety, pharmacodynamics , and pharmacokinetics was employed. A subsequent forward search was conducted of the papers using Web of Science cited reference search. Results: Current evidence supports the use of SJW in treating mild-moderate depression, and for kava in treatment of generalized anxiety. In respect to the other disorders, only weak preliminary evidence exists for use of SJW in SAD. Currently there is no published human trial on use of kava in affective disorders, or in OCD, PTSD, PD or SP. These disorders constitute potential applications that warrant exploration. Conclusions: Current evidence for herbal medicines in the treatment of depression and anxiety only supports the use of Hypericum perforatum for depression, and Piper methysticum for generalized anxiety.