Use of the Metropolis-Hastings Algorithm in the Calibration of a Patient Level Simulation of Prostate Cancer Screening

Designing cancer screening programmes requires an understanding of epidemiology, disease natural history and screening test characteristics. Many of these aspects of the decision problem are unobservable and data can only tell us about their joint uncertainty. A Metropolis-Hastings algorithm was used to calibrate a patient level simulation model of the natural history of prostate cancer to national cancer registry and international trial data. This method correctly represents the joint uncertainty amongst the model parameters by drawing efficiently from a high dimensional correlated parameter space. The calibration approach estimates the probability of developing prostate cancer, the rate of disease progression and sensitivity of the screening test. This is then used to estimate the impact of prostate cancer screening in the UK. This case study demonstrates that the Metropolis-Hastings approach to calibration can be used to appropriately characterise the uncertainty alongside computationally expensive simulation models

Further studies of the efficacy of military, commercial and novel skin decontaminants against the chemical warfare agents sulphur mustard, soman and VX

Background/Aims: Following an incident involving toxic chemicals, deployment of countermeasures before the arrival of specialised services at the scene may provide a “therapeutic” window in which to mitigate skin absorption. Methods: Five potential candidates (itaconic acid, N,N′-methylenebisacrylamide, 2-trifluoromethylacrylic acid, fuller's earth and Fast-Act®) previously found effective against a simulant (methyl salicylate) were evaluated against a 10 μL droplet of 14C-sulphur mustard (HD), soman (GD) or VX applied to the surface of porcine skin mounted on static skin diffusion cells. Results: All the decontaminants applied to the skin 5 min post exposure achieved a marked reduction in the amount of 14C contaminant remaining within the skin at 24 h. Itaconic acid significantly (p <.05) reduced the amount of 14C-HD, GD and VX remaining in the skin at 24 h. Additionally, 2-trifluoromethylacrylic acid significantly reduced the amount of 14C-HD, whilst fuller's earth significantly reduced the amounts of 14C-HD and VX recovered within the skin at 24 h. Conclusion: All of the products evaluated in this study performed well in reducing the dermal absorption of all the chemical warfare agents tested.Peer reviewe

Optimization of Nonambulant Mass Casualty Decontamination Protocols as Part of an Initial or Specialist Operational Response to Chemical Incidents

© 2018 The Author(s). Published with license by Taylor & Francis.© 2018 Robert P. Chilcott, Hannah Mitchell, Hazem Matar. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-ncnd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.Objective: The UK's Initial Operational Response (IOR) is a new process for improving the survival of multiple casualties following a chemical, biological, radiological or nuclear incident. Whilst the introduction of IOR represents a patient-focused response for ambulant casualties, there is currently no provision for disrobe and dry decontamination of nonambulant casualties. Moreover, the current specialist operational response (SOR) protocol for nonambulant casualty decontamination (also referred to as “clinical decontamination”) has not been subject to rigorous evaluation or development. Therefore, the aim of this study was to confirm the effectiveness of putatively optimized dry (IOR) and wet (SOR) protocols for nonambulant decontamination in human volunteers. Methods: Dry and wet decontamination protocols were objectively evaluated using human volunteers. Decontamination effectiveness was quantified by liquid chromatography–mass spectrometry analysis of the recovery of a chemical warfare agent simulant (methylsalicylate) from skin and hair of volunteers, with whole-body fluorescence imaging to quantify the skin distribution of residual simulant. Results: Both the dry and wet decontamination processes were rapid (3 and 4 min, respectively) and were effective in removing simulant from the hair and skin of volunteers, with no observable adverse effects related to skin surface spreading of contaminant. Conclusions: Further studies are required to assess the combined effectiveness of dry and wet decontamination under more realistic conditions and to develop appropriate operational procedures that ensure the safety of first responders.Peer reviewe

Simulation sample sizes for Monte Carlo partial EVPI calculations

Partial expected value of perfect information (EVPI) quantifies the value of removing uncertainty about unknown parameters in a decision model. EVPIs can be computed via Monte Carlo methods. An outer loop samples values of the parameters of interest, and an inner loop samples the remaining parameters from their conditional distribution. This nested Monte Carlo approach can result in biased estimates if small numbers of inner samples are used and can require a large number of model runs for accurate partial EVPI estimates. We present a simple algorithm to estimate the EVPI bias and confidence interval width for a specified number of inner and outer samples. The algorithm uses a relatively small number of model runs (we suggest approximately 600), is quick to compute, and can help determine how many outer and inner iterations are needed for a desired level of accuracy. We test our algorithm using three case studies. (C) 2010 Elsevier B.V. All rights reserved

Directly perceiving Kṛṣṇa: Accounting for perceptual experiences of deities within the framework of naturalism

Using descriptions found in Viśvanātha Cakravārtin\u27s Mādhurya Kādambinī (c.17th century) as a case study, the author argues in this article that research in the psychological sciences offers a plausible account within the framework of naturalism for the occurrence of private perceptual experiences that can serve as a basis for what Viśvanātha and other early Gauḍīya theologians describe and appraise as direct perceptual experiences (sākṣātkāra) of Kṛṣṇa. The purpose of this investigation is to bridge the methodological divide that often separates the humanities and sciences and facilitate a richer interpretation and explanation of historical claims than what is usually available through traditional humanistic approaches alone. The results of this research have implications for the study of private perceptual experiences of deities across cultures in both historical and contemporary contexts