Dose-response relationship in phase 1 clinical trials: a European Drug Development Network (EDDN) Collaboration Study

Introduction: Because a dose–response relationship is characteristic of conventional chemotherapy, this concept is widely used for the development of novel cytotoxic (CTX) drugs. However, the need to reach the MTD to obtain optimal benefit with molecularly targeted agents (MTA) is controversial. In this study, we evaluated the relationship between dose and efficacy in a large cohort of phase I patients with solid tumors.

Experimental Design: We collected data on 1,182 consecutive patients treated in phase I trials in 14 European institutions in 2005–2007. Inclusion criteria were: (i) patients treated within completed single-agent studies in which a maximum-administered dose was defined and (ii) RECIST/survival data available.

Results: Seventy-two percent of patients were included in trials with MTA (N = 854) and 28% in trials with CTX (N = 328). The objective response (OR) rate was 3% and disease control at 6 months was 11%. OR for CTX was associated with higher doses (median 92% of MTD); this was not the case for MTA, where patients achieving OR received a median of 50% of MTD. For trials with MTA, patients treated at intermediate doses (40%–80%) had better survival compared with those receiving low or high doses (P = 0.038). On the contrary, there was a direct association between higher dose and better OS for CTX agents (P = 0.003).

Conclusion: Although these results support the development of novel CTX based on MTD, we found no direct relationship between higher doses and response with MTA in unselected patients. However, the longest OS was seen in patients treated with MTA at intermediate doses (40%–80% of MTD)

Control of wild rubber extraction in the forests of northeast India, 1850-1880

This paper uses the history of rubber extraction to explore competing attempts to control the forest environments of Assam and beyond in the second half of the nineteenth century. Forest communities faced rival efforts at environmental control from both European and Indian traders, as well as from various centres of authority within the Raj. Government attempts to regulate rubber collection were undermined by the weak authority of the Raj in these regions, leading to widespread smuggling. Partly in response to the disruptive influence of rubber traders on the frontier, the Raj began to restrict the presence of outsiders in tribal regions, which came to be understood as distinct areas outside British control. When rubber yields from the forests nearest the Brahmaputra fell in the wake of intensive exploitation, India's scientific foresters demanded and from 1870 obtained the ability to regulate the Assamese forests, blaming indigenous rubber tapping strategies for the declining yields and arguing that Indian rubber could be ‘equal [to] if not better' than Amazonian rubber if only tappers would change their practices. The knowledge of the scientific foresters was fundamentally flawed, however, and their efforts to establish a new type of tapping practice failed. By 1880, the government had largely abandoned attempts to regulate wild Indian rubber, though wild sources continued to dominate the supply of global rubber until after 1910.

Catalogue of articles on exhibition at the second annual fair of the South-Carolina Institute, at the Military hall, November, 1850

This document contains a catalogue of the articles on exhibition at the 1850 annual fair of the South Carolina Institute. It includes 337 items exhibited at the fair in Charleston at the Military Hall.

Speech of Mr. Calhoun, of South Carolina, on the slavery question. Delivered in the Senate of the United States, March 4, 1850

The speech addresses the question, how can the union be preserved? He goes on to explain the threats to the union and give suggestions for how the threats can be handled.

An address delivered before the South-Carolina institute, at its second annual fair, on the 19th November, 1850. By Jos. H. Lumpkin

This speech by Georgia Supreme Court judge Joseph Lumpkin aims to ignite a spirit of improvement and bring about its influence. This improvement is not necessarily in the interest of agriculture alone, but in the interest of the state as well.

A Câmara Corporativa e o Estado Novo em Portugal (1935-1974): competências, interesses e políticas públicas

Este capítulo pretende apresentar e discutir o papel da Câmara Corporativa no processo de definição das políticas públicas do Estado Novo em Portugal, tendo em atenção os interesses que representava e as competências que lhe eram atribuídas.1 Ainda que tenha constituído um órgão lateral na arquitetura do regime, a Câmara elaborou análises críticas que influenciaram a conceção das linhas mestras da governação e as políticas a adotar nas principais áreas de ação do Estado. Os pareceres técnicos e políticos emitidos pela Câmara Corporativa permitiram sustentar opções formuladas nos gabinetes ministeriais, avaliar consequências de certas medidas e propor correções, pontuais ou de fundo. Recorrendo a especialistas e a representantes dos interesses económicos, esta instituição forneceu aos processos de decisão uma componente técnica de elevado grau de especialização.

Sex, Time and Place: Queer Histories of London, c.1850 to the Present

Sex, Time and Place extensively widens the scope of what we might mean by 'queer London studies'. Incorporating multidisciplinary perspectives – including social history, cultural geography, visual culture, literary representation, ethnography and social studies – this collection asks new questions, widens debates and opens new subject terrain. Featuring essays from an international range of established scholars and emergent voices, the collection is a timely contribution to this growing field. Its essays cover topics such as activist and radical communities and groups, AIDS and the city, art and literature, digital archives and technology, drag and performativity, lesbian London, notions of bohemianism and deviancy, sex reform and research and queer Black history. Going further than the existing literature on Queer London which focuses principally on the experiences of white gay men in a limited time frame, Sex, Time and Place reflects the current state of this growing and important field of study. It will be of great value to scholars, students and general readers who have an interest in queer history, London studies, cultural geography, visual cultures and literary criticism.

Charles e Ray Eames, o casamento entre razão e emoção no design

O racionalismo surge como uma corrente filosófica, cuja operação mental e lógica é evidenciada. Sendo a principal característica do pensamento moderno o método, a bauhaus representa para o design a forma como a indústria se despiu dos ornamentos, buscando o ideal de forma e função. Numa corrente contemporânea, o design emocional retoma, além das funções que um objeto pode ter, estéticas, práticas e simbólicas, também as emocionais de identificação, fazendo rever os métodos. Este artigo faz uma relação deste contexto com a forma brilhante com que o casal Charles e Ray Eames, criou um método absolutamente emocional para a criação do design, iniciando, com a invenção do contraplacado, e depois com acesso a diversas tecnologias advindas do pós-guerra, um processo muito interessante de construção de design, aliando arte e técnica, produzindo assentos atemporais, encontrados facilmente no mundo contemporâneo.