Covariate Adjustment in Bayesian Adaptive Clinical Trials

In conventional randomized controlled trials, adjustment for baseline values of covariates known to be at least moderately associated with the outcome increases the power of the trial. Recent work has shown particular benefit for more flexible frequentist designs, such as information adaptive and adaptive multi-arm designs. However, covariate adjustment has not been characterized within the more flexible Bayesian adaptive designs, despite their growing popularity. We focus on a subclass of these which allow for early stopping at an interim analysis given evidence of treatment superiority. We consider both collapsible and non-collapsible estimands, and show how to obtain posterior samples of marginal estimands from adjusted analyses. We describe several estimands for three common outcome types. We perform a simulation study to assess the impact of covariate adjustment using a variety of adjustment models in several different scenarios. This is followed by a real world application of the compared approaches to a COVID-19 trial with a binary endpoint. For all scenarios, it is shown that covariate adjustment increases power and the probability of stopping the trials early, and decreases the expected sample sizes as compared to unadjusted analyses.Comment: 17 pages, 5 tables, 4 figure

Supersolutions for a class of semilinear heat equations

A semilinear heat equation $u_{t}=\Delta u+f(u)$ with nonnegative initial data in a subset of $L^{1}(\Omega)$ is considered under the assumption that $f$ is nonnegative and nondecreasing and $\Omega\subseteq \R^{n}$. A simple technique for proving existence and regularity based on the existence of supersolutions is presented, then a method of construction of local and global supersolutions is proposed. This approach is applied to the model case $f(s)=s^{p}$, $\phi\in L^{q}(\Omega)$: new sufficient conditions for the existence of local and global classical solutions are derived in the critical and subcritical range of parameters. Some possible generalisations of the method to a broader class of equations are discussed.Comment: Expanded version of the previous submission arXiv:1111.0258v1. 14 page

Nutritive value and phytochemical composition of processed Solanum incanum (Bitter garden egg)

No Abstract

The impact of power clean ability and training age on adaptations to weightlifting-style training

The purpose of this investigation was to determine whether weightlifting actions are a viable method for improving athletic performance amongst weaker, inexperienced lifters when compared to individuals with a greater power clean result, and hence weightlifting ability and experience. Two groups of males with distinctly different power clean performances (higher performance (HP): N = 8; BM = 78.1±4.0 kg; 1RM PC = 1.08±0.09 kg.BM-1; lower performance (LP): N = 8; BM=82.6±14.0 kg; 1RM PC=0.78±0.1 kg⸱BM-1) and resistance training age (HP: resistance training experience=3.5±1.2 years; LP: resistance training experience=1.44±1.50 years) undertook 10 weeks of training involving weightlifting derivatives, in addition to supplemental ballistic and plyometric exercises. Testing of athletic performance (represented by measures derived from the countermovement jump) occurred at baseline, after five weeks of training, and after ten weeks of training. Both groups significantly improved across the majority of outcome variables following training (Hedges g=0.98–2.55, P≤0.01-0.05). Only the HP participants experienced significant changes at mid-test (g = 0.99–1.27, P ≤ 0.01-0.05), while no significant changes were revealed between mid- and post-test in this group. In contrast to this, the LP participants displayed a significant improvement in relative impulse (g=1.39, P<0.01) and rate of force development (g=1.91, P<0.01) during this final period (P<0.01). As weaker, inexperienced lifters underwent a significant and meaningful enhancement in maximal neuromuscular measures following weightlifting derivative focused training, practitioners should consider early implementation of such exercises. However, it is important for coaches to note that a delayed training effect might be present in weaker, less experienced lifters

Multiple communication mechanisms between sensor kinases are crucial for virulence in Pseudomonas aeruginosa

This is the author accepted manuscript. The final version is available as an open access article from the publisher via the DOI in this recordBacteria and many non-metazoan Eukaryotes respond to stresses and threats using two-component systems (TCSs) comprising sensor kinases (SKs) and response regulators (RRs). Multikinase networks, where multiple SKs work together, detect and integrate different signals to control important lifestyle decisions such as sporulation and virulence. Here, we study interactions between two SKs from Pseudomonas aeruginosa, GacS and RetS, which control the switch between acute and chronic virulence. We demonstrate three mechanisms by which RetS attenuates GacS signalling: RetS takes phosphoryl groups from GacS-P; RetS has transmitter phosphatase activity against the receiver domain of GacS-P; and RetS inhibits GacS autophosphorylation. These mechanisms play important roles in vivo and during infection, and exemplify an unprecedented degree of signal processing by SKs that may be exploited in other multikinase networks.This work was supported by the Medical Research Council (MRC) (grant number MR/ M020045/1), the Leverhulme Trust (grant number RPG-2014-228), the RoseTrees Trust (grant number M328) and a NERC PhD studentship (grant number 1076449)

Post-mortem culture of Balamuthia mandrillaris from the brain and cerebrospinal fluid of a case of granulomatous amoebic meningoencephalitis, using human brain microvascular endothelial cells.

The first isolation in the UK of Balamuthia mandrillaris amoebae from a fatal case of granulomatous amoebic meningoencephalitis is reported. Using primary cultures of human brain microvascular endothelial cells (HBMECs), amoebae were isolated from the brain and cerebrospinal fluid (CSF). The cultures showed a cytopathic effect at 20-28 days, but morphologically identifiable B. mandrillaris amoebae were seen in cleared plaques in subcultures at 45 days. The identification of the organism was later confirmed using PCR on Chelex-treated extracts. Serum taken while the patient was still alive reacted strongly with slide antigen prepared from cultures of the post-mortem isolate, and also with those from a baboon B. mandrillaris strain at 1:10,000 in indirect immunofluorescence, but with Acanthamoeba castellanii (Neff) at 1:160, supporting B. mandrillaris to be the causative agent. If the presence of amoebae in the post-mortem CSF reflects the condition in life, PCR studies on CSF and on biopsies of cutaneous lesions may also be a valuable tool. The role of HBMECs in understanding the interactions of B. mandrillaris with the blood-brain barrier is discussed

A randomised controlled trial of laser scanning and casting for the construction of ankle foot orthoses

Study Design: Randomised controlled trial with blinding of orthotists and patients to the construction technique used. Background: Three-dimensional laser scanning has been used for patient measurement for cranial helmets and spinal braces. Ankle foot orthoses are commonly prescribed for children with orthopaedic conditions. This trial sought to compare ankle foot orthoses produced by laser scanning or traditional plaster casting. Objectives: Assessment of the effectiveness and efficiency of using laser scanning to produce AFOs. Methods: A randomised double blind trial comparing fabrication of AFOs from casts or laser scans. Results: The time spent in the rectification and moulding of scanned AFOs was around 50% less than for cast AFOs. A non-significant increase of 9 days was seen in the time to delivery to the patient for LSCAD/CAM. There was a higher incidence of problems with the scan-based AFOs at delivery of the device, but no difference in how long the AFOs lasted. Costs associated with laser scanning were not significantly different from traditional methods of AFO manufacture. Conclusions: Compared with conventional casting techniques laser scan based AFO manufacture neither significantly improved the quality of the final product nor delivered a useful saving in time