Randomized controlled trial to assess the effectiveness of a videotape about radiotherapy

In a randomized controlled trial, the additional provision of information on videotape was no more effective than written information alone in reducing pre-treatment worry about radiotherapy. Images of surviving cancer patients, however, may provide further reassurance to patients once therapy is completed. © 2001 Cancer Research Campaign http://www.bjcancer.co

Immunomodulatory drugs in sepsis: a systematic review and meta-analysis

\ua9 2024 The Authors. Anaesthesia published by John Wiley & Sons Ltd on behalf of Association of Anaesthetists. Dysregulation of the host immune response has a central role in the pathophysiology of sepsis. There has been much interest in immunomodulatory drugs as potential therapeutic adjuncts in sepsis. We conducted a systematic review and meta-analysis of randomised controlled trials evaluating the safety and clinical effectiveness of immunomodulatory drugs as adjuncts to standard care in the treatment of adults with sepsis. Our primary outcomes were serious adverse events and all-cause mortality. Fifty-six unique, eligible randomised controlled trials were identified, assessing a range of interventions including cytokine inhibitors; anti-inflammatories; immune cell stimulators; platelet pathway inhibitors; and complement inhibitors. At 1-month follow-up, the use of cytokine inhibitors was associated with a decreased risk of serious adverse events, based on 11 studies involving 7138 patients (RR (95%CI) 0.95 (0.90–1.00), I2 = 0%). The only immunomodulatory drugs associated with an increased risk of serious adverse events were toll-like receptor 4 antagonists (RR (95%CI) 1.18 (1.04–1.34), I2 = 0% (two trials, 567 patients)). Based on 18 randomised controlled trials, involving 11,075 patients, cytokine inhibitors reduced 1-month mortality (RR (95%CI) 0.88 (0.78–0.98), I2 = 57%). Mortality reduction was also shown in the subgroup of 13 randomised controlled trials that evaluated anti-tumour necrosis factor α interventions (RR (95%CI) 0.93 (0.87–0.99), I2 = 0%). Anti-inflammatory drugs had the largest apparent effect on mortality at 2 months at any dose (two trials, 228 patients, RR (95%CI) 0.64 (0.51–0.80), I2 = 0%) and at 3 months at any dose (three trials involving 277 patients, RR (95%CI) 0.67 (0.55–0.81), I2 = 0%). These data indicate that, except for toll-like receptor 4 antagonists, there is no evidence of safety concerns for the use of immunomodulatory drugs in sepsis, and they may show some short-term mortality benefit for selected drugs

Vascular endothelial growth factor (VEGF) expression is a prognostic factor for radiotherapy outcome in advanced carcinoma of the cervix

The aim of the study was to evaluate VEGF expression in tumour biopsies as a prognostic factor for radiotherapy outcome in advanced carcinoma of the cervix. A retrospective study was carried out on 100 patients. Pre-treatment tumour VEGF expression was examined immunohistochemically in formalin-fixed, paraffin-embedded biopsies using a widely available commercial antibody. A semi-quantitative analysis was made using a scoring system of 0, 1, 2, and 3, for increasing intensity of staining. High VEGF expression was associated with a poor prognosis. A univariate log rank analysis found a significant relationship with overall survival (P = 0.0008) and metastasis-free survival (P = 0.0062), but not local control (P = 0.23). There was no correlation between VEGF expression and disease stage, tumour differentiation, patient age, or tumour radiosensitivity (SF2). In a Cox multivariate analysis of survival VEGF expression was the most significant independent prognostic factor (P = 0.001). After allowing for VEGF only SF2 was a significant prognostic factor (P = 0.003). In conclusion, immunohistochemical analysis of VEGF expression is a highly significant and independent prognostic indicator of overall and metastasis-free survival for patients treated with radiotherapy for advanced carcinoma of the cervix. It is also a rapid and easy method that could be used in the clinical setting, to identify patients at high risk of failure with conventional radiotherapy who may benefit from novel approaches or chemoradiotherapy. © 2000 Cancer Research Campaig

Inferring Core-Collapse Supernova Physics with Gravitational Waves

Stellar collapse and the subsequent development of a core-collapse supernova explosion emit bursts of gravitational waves (GWs) that might be detected by the advanced generation of laser interferometer gravitational-wave observatories such as Advanced LIGO, Advanced Virgo, and LCGT. GW bursts from core-collapse supernovae encode information on the intricate multi-dimensional dynamics at work at the core of a dying massive star and may provide direct evidence for the yet uncertain mechanism driving supernovae in massive stars. Recent multi-dimensional simulations of core-collapse supernovae exploding via the neutrino, magnetorotational, and acoustic explosion mechanisms have predicted GW signals which have distinct structure in both the time and frequency domains. Motivated by this, we describe a promising method for determining the most likely explosion mechanism underlying a hypothetical GW signal, based on Principal Component Analysis and Bayesian model selection. Using simulated Advanced LIGO noise and assuming a single detector and linear waveform polarization for simplicity, we demonstrate that our method can distinguish magnetorotational explosions throughout the Milky Way (D <~ 10kpc) and explosions driven by the neutrino and acoustic mechanisms to D <~ 2kpc. Furthermore, we show that we can differentiate between models for rotating accretion-induced collapse of massive white dwarfs and models of rotating iron core collapse with high reliability out to several kpc.Comment: 22 pages, 9 figure

Developing a framework for risk-based surveillance of tuberculosis in cattle: a case study of its application in Scotland

Due to its substantially lower prevalence of bovine tuberculosis (bTB) relative to other areas of Great Britain, Scotland was designated as an officially (bovine) TB-free region in 2009. This paper investigates resultant possibilities for reducing surveillance by developing risk-based alternatives to current 4-year testing of eligible herds. A model of freedom of infection was used to develop strategies that specifically tested herds that are at risk of infection but would probably not be identified by slaughterhouse meat inspection. The performance of current testing is mimicked by testing all herds that slaughter fewer than 25% of their total stock per year and regularly import animals from high-incidence areas of England and Wales or from Ireland. This system offers a cost reduction by requiring 25% fewer herd and animal tests and 25% fewer false positives

Simplifying asteroseismic analysis of solar-like oscillators: An application of principal component analysis for dimensionality reduction

The asteroseismic analysis of stellar power density spectra is often computationally expensive. The models used in the analysis may use several dozen parameters to accurately describe features in the spectra caused by oscillation modes and surface granulation. Many parameters are often highly correlated, making the parameter space difficult to quickly and accurately sample. They are, however, all dependent on a smaller set of parameters, namely the fundamental stellar properties. We aim to leverage this to simplify the process of sampling the model parameter space for the asteroseismic analysis of solar-like oscillators, with an emphasis on mode identification. Using a large set of previous observations, we applied principal component analysis to the sample covariance matrix to select a new basis on which to sample the model parameters. Selecting the subset of basis vectors that explains the majority of the sample variance, we redefine the model parameter prior probability density distributions in terms of a smaller set of latent parameters. We are able to reduce the dimensionality of the sampled parameter space by a factor of two to three. The number of latent parameters needed to accurately model the stellar oscillation spectra cannot be determined exactly but is likely only between four and six. Using two latent parameters, the method is able to describe the bulk features of the oscillation spectrum, while including more latent parameters allows for a frequency precision better than $\approx10\%$ of the small frequency separation for a given target. We find that sampling a lower-rank latent parameter space still allows for accurate mode identification and parameter estimation on solar-like oscillators over a wide range of evolutionary stages. This allows for the potential to increase the complexity of spectrum models without a corresponding increase in computational expense.Comment: Accepted for publication in Astronomy & Astrophysics. 11 pages. 10 figure

Pretreatment apoptosis in carcinoma of the cervix correlates with changes in tumour oxygenation during radiotherapy

A relationship between hypoxia and apoptosis has been identified in vitro and in experimental tumours. The aim of this study was to investigate the relationship between apoptosis, hypoxia and the change in oxygenation during radiotherapy in human squamous cell carcinoma of the cervix. Forty-two patients with locally advanced disease underwent pretreatment evaluation of tumour oxygenation using an Eppendorf computerized microneedle electrode. Twenty-two of these patients also had a second evaluation of tumour oxygenation after receiving 40–45 Gy external beam radiotherapy. Paraffin-embedded histological sections were obtained from random pretreatment biopsies for all 42 patients. Apoptotic index (AI) was quantified by morphology on TUNEL stained sections. No correlation was found between pretreatment measures of AI and either the median pO2(r = 0.12, P = 0.44) or percentage of values < 5 mmHg (r = –0.02, P = 0.89). A significant positive correlation was found between AI and the change in tumour oxygenation (ratio of pre:post-treatment % values < 5 mmHg) following radiotherapy (r = 0.61, P = 0.002). The lack of correlation between apoptosis and hypoxia may occur because the Eppendorf measures both acute and chronic hypoxia, and the relative ability of acute hypoxia to induce apoptosis is unknown. These results indicate that cell death via apoptosis may be a mechanism of tumour reoxygenation during radiotherapy. © 2000 Cancer Research Campaig

Bayesian Conditioning, the Reflection Principle, and Quantum Decoherence

The probabilities a Bayesian agent assigns to a set of events typically change with time, for instance when the agent updates them in the light of new data. In this paper we address the question of how an agent's probabilities at different times are constrained by Dutch-book coherence. We review and attempt to clarify the argument that, although an agent is not forced by coherence to use the usual Bayesian conditioning rule to update his probabilities, coherence does require the agent's probabilities to satisfy van Fraassen's [1984] reflection principle (which entails a related constraint pointed out by Goldstein [1983]). We then exhibit the specialized assumption needed to recover Bayesian conditioning from an analogous reflection-style consideration. Bringing the argument to the context of quantum measurement theory, we show that "quantum decoherence" can be understood in purely personalist terms---quantum decoherence (as supposed in a von Neumann chain) is not a physical process at all, but an application of the reflection principle. From this point of view, the decoherence theory of Zeh, Zurek, and others as a story of quantum measurement has the plot turned exactly backward.Comment: 14 pages, written in memory of Itamar Pitowsk