Protocol of the Australasian Malignant Pleural Effusion (AMPLE) trial: a multicentre randomised study comparing indwelling pleural catheter versus talc pleurodesis

INTRODUCTION: Malignant pleural effusion can complicate most cancers. It causes breathlessness and requires hospitalisation for invasive pleural drainages. Malignant effusions often herald advanced cancers and limited prognosis. Minimising time spent in hospital is of high priority to patients and their families. Various treatment strategies exist for the management of malignant effusions, though there is no consensus governing the best choice. Talc pleurodesis is the conventional management but requires hospitalisation (and substantial healthcare resources), can cause significant side effects, and has a suboptimal success rate. Indwelling pleural catheters (IPCs) allow ambulatory fluid drainage without hospitalisation, and are increasingly employed for management of malignant effusions. Previous studies have only investigated the length of hospital care immediately related to IPC insertion. Whether IPC management reduces time spent in hospital in the patients' remaining lifespan is unknown. A strategy of malignant effusion management that reduces hospital admission days will allow patients to spend more time outside hospital, reduce costs and save healthcare resources. METHODS AND ANALYSIS: The Australasian Malignant Pleural Effusion (AMPLE) trial is a multicentred, randomised trial designed to compare IPC with talc pleurodesis for the management of malignant pleural effusion. This study will randomise 146 adults with malignant pleural effusions (1:1) to IPC management or talc slurry pleurodesis. The primary end point is the total number of days spent in hospital (for any admissions) from treatment procedure to death or end of study follow-up. Secondary end points include hospital days specific to pleural effusion management, adverse events, self-reported symptom and quality-of-life scores. ETHICS AND DISSEMINATION: The Sir Charles Gairdner Group Human Research Ethics Committee has approved the study as have the ethics boards of all the participating hospitals. The trial results will be published in peer-reviewed journals and presented at scientific conferences. TRIAL REGISTRATION NUMBERS: Australia New Zealand Clinical Trials Registry-ACTRN12611000567921; National Institutes of Health-NCT02045121.published_or_final_versio

Prognostication of serial post-intensity-modulated radiation therapy undetectable plasma EBV DNA for nasopharyngeal carcinoma

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Development of molecular clamp stabilized hemagglutinin vaccines for Influenza A viruses

Influenza viruses cause a significant number of infections and deaths annually. In addition to seasonal infections, the risk of an influenza virus pandemic emerging is extremely high owing to the large reservoir of diverse influenza viruses found in animals and the co-circulation of many influenza subtypes which can reassort into novel strains. Development of a universal influenza vaccine has proven extremely challenging. In the absence of such a vaccine, rapid response technologies provide the best potential to counter a novel influenza outbreak. Here, we demonstrate that a modular trimerization domain known as the molecular clamp allows the efficient production and purification of conformationally stabilised prefusion hemagglutinin (HA) from a diverse range of influenza A subtypes. These clamp-stabilised HA proteins provided robust protection from homologous virus challenge in mouse and ferret models and some cross protection against heterologous virus challenge. This work provides a proof-of-concept for clamp-stabilised HA vaccines as a tool for rapid response vaccine development against future influenza A virus pandemics

A pentagonal cyanostar macrocycle with cyanostilbene CH donors binds anions and forms dialkylphosphate [3]rotaxanes

Since the discovery of crown ethers, macrocycles have been recognized as powerful platforms for supramolecular chemistry. Although their numbers and variations are now legion, macrocycles that are simple to make using high-yielding reactions in one pot and on the multigram scale are rare. Here we present such a discovery obtained during the creation of a C 5 -symmetric cyanostilbene \u27campestarene\u27 macrocycle, cyanostar, that employs Knoevenagel condensations in the preparation of its cyanostilbene repeat unit. In the solid state, cyanostars form π-stacked dimers constituted of chiral P and M enantiomers. The electropositive central cavity stabilizes anions with CH hydrogen-bonding units that are activated by electron-withdrawing cyano groups. In solution, the cyanostar shows high-affinity binding as 2:1 sandwich complexes, log β 2 ≈ 12 and ΔG ≈ -70 kJ mol -1, of large anions (BF 4 -, ClO 4 - and PF 6 -) usually considered weakly coordinating. The cyanostar\u27s size preference allowed formation of an unprecedented [3]rotaxane templated around a dialkylphosphate. © 2013 Macmillan Publishers Limited. All rights reserved