Defining the Critical Hurdles in Cancer Immunotherapy

ABSTRACT: Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC), convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed in this report. Some of the identified hurdles impede all investigators, others hinder investigators only in certain regions or institutions or are more relevant to specific types of immunotherapy or first-in-humans studies. Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet be overcome to improve outcomes of patients with cancer

Waveform modelling for the laser interferometer space antenna

LISA, the Laser Interferometer Space Antenna, will usher in a new era in gravitational-wave astronomy. As the first anticipated space-based gravitational-wave detector, it will expand our view to the millihertz gravitational-wave sky, where a spectacular variety of interesting new sources abound: from millions of ultra-compact binaries in our Galaxy, to mergers of massive black holes at cosmological distances; from the early inspirals of stellar-mass black holes that will ultimately venture into the ground-based detectors’ view to the death spiral of compact objects into massive black holes, and many sources in between. Central to realising LISA’s discovery potential are waveform models, the theoretical and phenomenological predictions of the pattern of gravitational waves that these sources emit. This White Paper is presented on behalf of the Waveform Working Group for the LISA Consortium. It provides a review of the current state of waveform models for LISA sources, and describes the significant challenges that must yet be overcome

Intoxicação por monofluoroacetato em animais

O monofluoroacetato (MF) ou ácido monofluoroacético é utilizado na Austrália e Nova Zelândia no controle populacional de mamíferos nativos ou exóticos. O uso desse composto é proibido no Brasil, devido ao risco de intoxicação de seres humanos e de animais, uma vez que a substância permanece estável por décadas. No Brasil casos recentes de intoxicação criminosa ou acidental têm sido registrados. MF foi identificado em diversas plantas tóxicas, cuja ingestão determina "morte súbita"; de bovinos na África do Sul, Austrália e no Brasil. O modo de ação dessa substância baseia-se na formação do fluorocitrato, seu metabólito ativo, que bloqueia competitivamente a aconitase e o ciclo de Krebs, o que reduz produção de ATP. As espécies animais têm sido classificadas nas quatro Categorias em função do efeito provocado por MF: (I) no coração, (II) no sistema nervoso central (III) sobre o coração e sistema nervoso central ou (IV) com sintomatologia atípica. Neste trabalho, apresenta-se uma revisão crítica atualizada sobre essa substância. O diagnóstico da intoxicação por MF é realizado pelo histórico de ingestão do tóxico, pelos achados clínicos e confirmado por exame toxicológico. Uma forma peculiar de degeneração hidrópico-vacuolar das células epiteliais dos túbulos uriníferos contorcidos distais tem sido considerada como característica dessa intoxicação em algumas espécies. O tratamento da intoxicação por MF é um desafio, pois ainda não se conhece um agente capaz de reverte-la de maneira eficaz; o desfecho geralmente é fata