Prostate cancer: important steps and considerations in the design of therapeutic vaccines

Vaccine-based immunotherapy can increase the overall survival of patients with advanced prostate cancer. However, the efficacy of vaccine-elicited anticancer immune responses is heavily influenced by the physical, nutritional, and psychological status of the patient. Given their importance, these parameters should be carefully considered for the design of future clinical trials testing this immunotherapeutic paradigm in prostate cancer patients.

Sample size considerations in active-control non-inferiority trials with binary data based on the odds ratio

This paper presents an approximate closed form sample size formula for determining non-inferiority in active-control trials with binary data. We use the odds-ratio as the measure of the relative treatment effect, derive the sample size formula based on the score test and compare it with a second, well-known formula based on the Wald test. Both closed form formulae are compared with simulations based on the likelihood ratio test. Within the range of parameter values investigated, the score test closed form formula is reasonably accurate when non-inferiority margins are based on odds-ratios of about 0.5 or above and when the magnitude of the odds ratio under the alternative hypothesis lies between about 1 and 2.5. The accuracy generally decreases as the odds ratio under the alternative hypothesis moves upwards from 1. As the non-inferiority margin odds ratio decreases from 0.5, the score test closed form formula increasingly overestimates the sample size irrespective of the magnitude of the odds ratio under the alternative hypothesis. The Wald test closed form formula is also reasonably accurate in the cases where the score test closed form formula works well. Outside these scenarios, the Wald test closed form formula can either underestimate or overestimate the sample size, depending on the magnitude of the non-inferiority margin odds ratio and the odds ratio under the alternative hypothesis. Although neither approximation is accurate for all cases, both approaches lead to satisfactory sample size calculation for non-inferiority trials with binary data where the odds ratio is the parameter of interest.

Further considerations of cosmic ray modulation of infra-red radiation in the atmosphere

Understanding effects of ionisation in the lower atmosphere is a new interdisciplinary area, crossing the traditionally distinct scientific boundaries between astro-particle and atmospheric physics and also requiring understanding of both heliospheric and magnetospheric influences on cosmic rays. Following the paper of Erlykin et al. (2014) we develop further the interpretation of our observed changes in long-wave (LW) radiation, Aplin and Lockwood (2013) by taking account of both cosmic ray ionisation yields and atmospheric radiative transfer. To demonstrate this, we show that the thermal structure of the whole atmosphere needs to be considered along with the vertical profile of ionisation. Allowing for, in particular, ionisation by all components of a cosmic ray shower and not just by the muons, reveals that the effect we have detected is certainly not inconsistent with laboratory observations of the LW absorption cross section. The analysis presented here, although very different from that of Erlykin et al., does come to the same conclusion that the events detected by AL were not caused by individual cosmic ray primaries – not because it is impossible on energetic grounds, but because events of the required energy are too infrequent for the 12 h_1 rate at which they were seen by the AL experiment. The present paper numerically models the effect of three different scenario changes to the primary GCR spectrum which all reproduce the required magnitude of the effect observed by AL. However, they cannot solely explain the observed delay in the peak effect which, if confirmed, would appear to open up a whole new and interesting area in the study of water oligomers and their effects on LW radiation. We argue that a technical artefact in the AL experiment is highly unlikely and that our initial observations merit both a wide-ranging follow-up experiment and more rigorous, self-consistent, three-dimensional radiative transfer modelling

Considerations on the use of the p-nitrophenyl phosphomonoesterase assay in the study of the phosphorus nutrition of soil borne fungi

The p-nitrophenyl phosphomonoesterase assay (p NPPase) is commonly used to measure cell-wall-associated and extracellular phosphatase activity of soil fungi. p NPPases are usually assayed in the context of fungal nutrition, where inorganic P supply might be enhanced by the mineralisation of monoester organic P sources in the soil. The importance of the assay to the P nutrition of soil fungi is considered based on the evidence currently available including the consistency of methodological approach. The nature of organic P in the soil and the relevance of the assay to some specific soil substrates is discussed, particularly the chemistry and bioavailability of myo-inositol hexakisphosphate and the lower inositol phosphates. The evidence for the long-term stability of p NPPases in the soil is examined in the light of the persistence of p NPPase in soils. The role of persistent extracellular fungal p NPPases in the soil P cycle is discussed. Conclusions from p NPPase based studies must be based upon an appreciation of the constraints of the assay and the complex chemistry of organic P and p NPPase in the soil.