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.

Funding emergency care : Australian style

The ongoing challenge for ED leaders is to remain abreast of system-wide changes that impact on the day-to-day management of their departments. Changes to the funding model creates another layer of complexity and this introductory paper serves as the beginning of a discussion about the way in which EDs are funded and how this can and will impact on business decisions, models of care and resource allocation within Australian EDs. Furthermore it is evident that any funding model today will mature and change with time, and moves are afoot to refine and contextualise ED funding over the medium term. This perspective seeks to provide a basis of understanding for our current and future funding arrangements in Australian EDs.

Country of Origin and Internet Publication: Applying the Berne Convention in the Digital Age

Historically, determining the country of origin of a published work presented few challenges, because works were generally published physically – whether in print or otherwise – in a distinct location or few locations. However, publishing opportunities presented by new technologies mean that we now live in a world of simultaneous publication – works that are first published online are published simultaneously to every country in world in which there is Internet connectivity. While this is certainly advantageous for the dissemination and impact of information and creative works, it creates potential complications under the Berne Convention for the Protection of Literary and Artistic Works (“Berne Convention”), an international intellectual property agreement to which most countries in the world now subscribe. Under the Berne Convention’s national treatment provisions, rights accorded to foreign copyright works may not be subject to any formality, such as registration requirements (although member countries are free to impose formalities in relation to domestic copyright works). In Kernel Records Oy v. Timothy Mosley p/k/a Timbaland, et al. however, the Florida Southern District Court of the United States ruled that first publication of a work on the Internet via an Australian website constituted “simultaneous publication all over the world,” and therefore rendered the work a “United States work” under the definition in section 101 of the U.S. Copyright Act, subjecting the work to registration formality under section 411. This ruling is in sharp contrast with an earlier decision delivered by the Delaware District Court in Håkan Moberg v. 33T LLC, et al. which arrived at an opposite conclusion. The conflicting rulings of the U.S. courts reveal the problems posed by new forms of publishing online and demonstrate a compelling need for further harmonization between the Berne Convention, domestic laws and the practical realities of digital publishing. In this chapter, we argue that even if a work first published online can be considered to be simultaneously published all over the world it does not follow that any country can assert itself as the “country of origin” of the work for the purpose of imposing domestic copyright formalities. More specifically, we argue that the meaning of “United States work” under the U.S. Copyright Act should be interpreted in line with the presumption against extraterritorial application of domestic law to limit its application to only those works with a real and substantial connection to the United States. There are gaps in the Berne Convention’s articulation of “country of origin” which provide scope for judicial interpretation, at a national level, of the most pragmatic way forward in reconciling the goals of the Berne Convention with the practical requirements of domestic law. We believe that the uncertainties arising under the Berne Convention created by new forms of online publishing can be resolved at a national level by the sensible application of principles of statutory interpretation by the courts. While at the international level we may need a clearer consensus on what amounts to “simultaneous publication” in the digital age, state practice may mean that we do not yet need to explore textual changes to the Berne Convention.

Symposium on World tuna fisheries: commemorating the 50th anniversary of the establishment of the Inter-American Tropical Tuna Commission

The Inter-American Tropical Tuna Commission (lA TTC) came into existence in 1950, after its convention, signed by representatives ofCosta Rica and the United States in 1949, was ratified. It was the first international tuna organization, and only the third international fisheries organization, whose staff has had the responsibility for performing scientific research, the others being the International Pacific Halibut Commission, established in 1923, and the International Pacific Salmon Fisheries Commission, established in 1937. The current members of the IATTC are Costa Rica, Ecuador, EI Salvador, France, Guatemala, Japan, Mexico, Nicaragua, Panama, the United States, Vanuatu, and Venezuela. The first Director ofthe IATTC was Dr. Milner B. Schaefer, who was in that position from 1950 to 1963. He was followed by Dr. John L. Kask (1963-1969), Dr. James Joseph (1969-1999), and Dr. Robin L. Allen (1999-present). The success ofthe IATIC showed that it was possible to carry out research and management on an international, high-seas fishery successfully. Since then other international organizations for tuna management, including the International Commission for the Conservation of Atlantic Tunas (1969), the Forum Fisheries Agency (1979), the Commission for the Conservation of Southern Bluefin Tuna (1994), and the Indian Ocean Tuna Commission (1996), were established. Appropriately, the 50th anniversary celebration was held in Costa Rica, one of the two charter members of the IATTC. Persons who have held important positions in international fishery management in various parts ofthe world spoke at the celebration. Their presentations, except for that describing the Indian Ocean Tuna Commission, are reproduced in this volume.

Estratégias terapêuticas no tratamento da dor crônica: uma genealogia da Clínica da Dor

O objetivo desse trabalho é analisar a singularidade das estratégias terapêuticas introduzidas pelo modelo das Clínicas da Dor, através de um estudo genealógico desse projeto terapêutico e sua contextualização no âmbito da racionalidade científica moderna. Mais especificamente, pretende-se analisar as transformações na racionalidade médica que permitiram, sucessivamente, a apreensão da dor pelo discurso médico, a concepção da dor como uma doença e a construção e a consolidação do modelo terapêutico das Clínicas da Dor. Para tal, inicialmente, analisamos o modelo terapêutico desenvolvido pelo médico anestesista John Bonica, idealizador do modelo das Clínicas da Dor, destacando as ferramentas conceituais que possibilitaram a compreensão da dor crônica como doença e como fenômeno biopsicossocial. Num segundo momento, realizamos uma descrição e análise dos principais eventos que permitiram a consolidação da medicina da dor como uma prática específica e multidisciplinar, dando destaque à inserção deste modelo no contexto do Sistema Único de Saúde Brasileiro. Finalmente, a partir de uma experiência clínico-institucional buscamos refletir sobre os limites e possibilidades da aplicação prática deste modelo, lançando luz sobre os impasses da clínica e tensões oriundas da problematização, do dualismo mente e corpo e das práticas terapêuticas interdisciplinares.

A comparison of four extraction methods for substance P, neurokinin A and calcitonin gene-related peptide from human dental pulp tissue

Measuring neuropeptides in biological tissues by radioimmunoassay requires efficient extraction that maintains their immunoreactivity. Many different methods for extraction have been described, but there is little information on optimal extraction methods for individual neuropeptides from human dental pulp tissue. The aim was therefore to identify an effective extraction procedure for three pulpal neuropeptides: substance P. neurokinin A and calcitonin gene-related peptide. Tissue was obtained from 20 pulps taken from teeth freshly extracted for orthodontic reasons. The pulp samples were divided into four equal groups and different extraction methods were used for each group. Boiling whole pulp in acetic acid gave the highest overall yield and, in addition, offered an easy and rapid means of pulp tissue processing. The use of protease inhibitors did not increase the recovery of the immunoreactive neuropeptides but did provide the best combination of maximal recoveries and minimal variability. These results should be useful for planning the extraction of these neuropeptides from human pulp tissue in future studies. (C) 1999 Elsevier Science Ltd. All rights reserved.

Almanach de Gotha : contenant diverses connaissances curieuses et utiles pour l'année ...

1881 (A118).

Sean O'Sullivan fonds

Sean O’Sullivan was born in Hamilton, Ontario, in 1952. At an early age, he demonstrated an interest in politics. A chance meeting with John Diefenbaker in 1963, when Sean was just 11 years old, marked the beginning of his involvement with the Progressive Conservative Party. Diefenbaker became a mentor to him, and the two exchanged correspondence for many years. Sean became an active member of the Party, and his political career took off quickly. In 1965, he was elected to the executive of the Hamilton Area Young Progressive Conservatives, in 1968 was elected President, and also served as Youth Director for Diefenbaker’s re-election campaign. In 1970 he was elected President of the Ontario Young Progressive Conservatives, and in 1971 became Youth Adviser to Premier William Davis. Later that year, Diefenbaker chose Sean to be his Executive Assistant. In addition to his political activities, Sean enrolled at Brock University in 1969 to study political science. In 1972, he resigned as Diefenbaker’s assistant in order to run as a candidate for Hamilton-Wentworth in the federal election that year. At just 20 years of age, Sean was the youngest MP elected to the House of Commons. While working as an MP, Sean continued his studies at Brock University part-time, graduating with distinction. After being re-elected in 1974, he rose to greater prominence when he succeeded in having a private member’s bill passed making the beaver one of Canada’s national symbols. In 1977, he resigned as MP in order to pursue religious studies and become a Catholic priest. After completing four years of studies at the Irish College of Rome’s Gregorian University, Sean was ordained a priest in Toronto in 1981. In July, 1982, he was appointed Director of Vocations (full-time recruiter) for the archdiocese of Toronto. In this capacity, he implemented a controversial and widely publicized campaign to recruit priests. The recruitment succeeded in generating interest in the priesthood, doubling the number of students in the archdiocese. He was one of the founding members of Serra House, a residence for students considering the priesthood. After his term as Vocations Director ended in 1985, O’Sullivan became publisher of The Catholic Register, a weekly church newspaper. That same year, he was awarded an honorary doctorate from Brock University. In January 1987, he was appointed a Member of the Order of Canada. Later that year, he submitted a report to the Attorney General of Ontario, titled You’ve got a Friend, after conducting an independent review of Advocacy for Vulnerable Adults in Ontario at the request of the government. In 1983, O’Sullivan was diagnosed with leukemia. The disease went into remission after treatment, but was incurable. In 1989, he had a bone marrow transplant at Princess Margaret Hospital in Toronto, but died shortly afterwards. He was 37 years old. A memorial fund was established in his name, and included contributions from prominent business, church and political leaders such as Prime Minister Brian Mulroney, Toronto Sun Chairman Doug Crieghton and His Eminence G. Emmett Carter. The O’Sullivan family requested that Brock University be the beneficiary of the proceeds of the campaign.