The cost-effectiveness of nivolumab monotherapy for the treatment of advanced melanoma patients in England

Background: Nivolumab was the first programmed death receptor 1 (PD-1) immune checkpoint inhibitor to demonstrate long-term survival benefit in a clinical trial setting for advanced melanoma patients. Objective: To evaluate the cost effectiveness of nivolumab monotherapy for the treatment of advanced melanoma patients in England. Methods: A Markov state-transition model was developed to estimate the lifetime costs and benefits of nivolumab versus ipilimumab and dacarbazine for BRAF mutation-negative patients and versus ipilimumab, dabrafenib, and vemurafenib for BRAF mutation-positive patients. Covariate-adjusted parametric curves for time to progression, pre-progression survival, and post-progression survival were fitted based on patient-level data from two trials and long-term ipilimumab survival data. Indirect treatment comparisons between nivolumab, ipilimumab, and dacarbazine were informed by these covariate-adjusted parametric curves, controlling for differences in patient characteristics. Kaplan–Meier data from the literature were digitised and used to fit progression-free and overall survival curves for dabrafenib and vemurafenib. Patient utilities and resource use data were based on trial data or the literature. Patients are assumed to receive nivolumab until there is no further clinical benefit, assumed to be the first of progressive disease, unacceptable toxicity, or 2 years of treatment. Results: Nivolumab is the most cost-effective treatment option in BRAF mutation-negative and mutation-positive patients, with incremental cost-effectiveness ratios of £24,483 and £17,362 per quality-adjusted life year, respectively. The model results are most sensitive to assumptions regarding treatment duration for nivolumab and the parameters of the fitted parametric survival curves. Conclusions: Nivolumab is a cost-effective treatment for advanced melanoma patients in England

CO2Vec: Embeddings of co-ordered networks based on mutual reinforcement

National Research Foundation (NRF) Singapore under International Research Centres in Singapore Funding Initiativ

A Descriptive Analysis of Political Campaign Advertising of the 1972 Presidential Campaign

The purpose of this research was to determine the aural and visual issues present in televised political campaign advertising of the 1972 Presidential election year. Content analysis was the method employed to determine these issues. The campaign commercials of George McGovern and Richard Nixon were the subject of the analysis. The issues coded were Social Welfare, Natural Resources, Labor, Management, Civil Rights, Economy, Foreign Affairs, Vietnam, Government, Public Order, Defense, Republicans, and Democrats. The results show that the campaigns used issues appearing in network news coverage, the percentage of time each campaign spent on the issues, and that the aural content was supported by the visual images in the commercials

Selecting stimuli parameters for video quality studies based on perceptual similarity distances

This work presents a methodology to optimize the selection of multiple parameter levels of an image acquisition, degradation, or post-processing process applied to stimuli intended to be used in a subjective image or video quality assessment (QA) study. It is known that processing parameters (e.g. compression bit-rate) or technical quality measures (e.g. peak signal-to-noise ratio, PSNR) are often non-linearly related to human quality judgment, and the model of either relationship may not be known in advance. Using these approaches to select parameter levels may lead to an inaccurate estimate of the relationship between the parameter and subjective quality judgments – the system’s quality model. To overcome this, we propose a method for modeling the relationship between parameter levels and perceived quality distances using a paired comparison parameter selection procedure in which subjects judge the perceived similarity in quality. Our goal is to enable the selection of evenly sampled parameter levels within the considered quality range for use in a subjective QA study. This approach is tested on two applications: (1) selection of compression levels for laparoscopic surgery video QA study, and (2) selection of dose levels for an interventional X-ray QA study. Subjective scores, obtained from the follow-up single stimulus QA experiments conducted with expert subjects who evaluated the selected bit-rates and dose levels, were roughly equidistant in the perceptual quality space - as intended. These results suggest that a similarity judgment task can help select parameter values corresponding to desired subjective quality levels

Processing punctuation and word changes in different editions of prose fiction

The digital era has brought with it a shift in the field of literary editing in terms of the amount and kind of textual variation that can reasonably be annotated by editors. However, questions remain about how far readers engage with textual variants, especially minor ones such as small-scale changes to punctuation. In this study we present an eye-tracking experiment investigating reader sensitivity to variations in surface textual features of prose fiction. We monitored eye movements while participants read textual variants from Dickens and James, hypothesising that readers may pay more attention to lexical rather than punctuation changes. We found longer reading times for both types, but only lexical changes also increased reading times for the rest of the sentence. In addition, eye movement behaviour and conscious ability to report changes were highly correlated. We discuss the implications for how such methods might be applied to questions of “literary” significance and textual processing

Xenobiotic metabolism: the effect of acute kidney injury on non-renal drug clearance and hepatic drug metabolism.

Acute kidney injury (AKI) is a common complication of critical illness, and evidence is emerging that suggests AKI disrupts the function of other organs. It is a recognized phenomenon that patients with chronic kidney disease (CKD) have reduced hepatic metabolism of drugs, via the cytochrome P450 (CYP) enzyme group, and drug dosing guidelines in AKI are often extrapolated from data obtained from patients with CKD. This approach, however, is flawed because several confounding factors exist in AKI. The data from animal studies investigating the effects of AKI on CYP activity are conflicting, although the results of the majority do suggest that AKI impairs hepatic CYP activity. More recently, human study data have also demonstrated decreased CYP activity associated with AKI, in particular the CYP3A subtypes. Furthermore, preliminary data suggest that patients expressing the functional allele variant CYP3A5*1 may be protected from the deleterious effects of AKI when compared with patients homozygous for the variant CYP3A5*3, which codes for a non-functional protein. In conclusion, there is a need to individualize drug prescribing, particularly for the more sick and vulnerable patients, but this needs to be explored in greater depth

RecipeGPT: Generative pre-training based cooking recipe generation and evaluation system

National Research Foundation (NRF) Singapore under International Research Centres in Singapore Funding Initiativ

Quasi-One-Dimensional Spin Dynamics in dd-Electron Heavy-Fermion Metal Y1−x_{1-x}Scx_xMn2_2

Slow spin fluctuations ($\nu < 10^{12}$ s$^-1$) observed by the muon spin relaxation technique in Y$_{1-x}$Sc$_x$Mn$_2$ exhibits a power law dependence on temperature ($\nu \propto T^\alpha$), where the power converges asymptotically to unity ($\alpha\rightarrow 1$) as the system moves away from spin-glass instability with increasing Sc content $x$. This linear $T$ dependence, which is common to that observed in LiV$_2$O$_4$, is in line with the prediction of the "intersecting Hubbard chains" model for a metallic pyrochlore lattice, suggesting that the geometrical constraints to t2g bands specific to the pyrochlore structure serve as a basis of the $d$-electron heavy-fermion state.Comment: 5 pages, 4 figures, to appear in J. Phys. Soc. Jp

Fructose transport-deficient Staphylococcus aureus reveals important role of epithelial glucose transporters in limiting sugar-driven bacterial growth in airway surface liquid.

Hyperglycaemia as a result of diabetes mellitus or acute illness is associated with increased susceptibility to respiratory infection with Staphylococcus aureus. Hyperglycaemia increases the concentration of glucose in airway surface liquid (ASL) and promotes the growth of S. aureus in vitro and in vivo. Whether elevation of other sugars in the blood, such as fructose, also results in increased concentrations in ASL is unknown and whether sugars in ASL are directly utilised by S. aureus for growth has not been investigated. We obtained mutant S. aureus JE2 strains with transposon disrupted sugar transport genes. NE768(fruA) exhibited restricted growth in 10 mM fructose. In H441 airway epithelial-bacterial co-culture, elevation of basolateral sugar concentration (5-20 mM) increased the apical growth of JE2. However, sugar-induced growth of NE768(fruA) was significantly less when basolateral fructose rather than glucose was elevated. This is the first experimental evidence to show that S. aureus directly utilises sugars present in the ASL for growth. Interestingly, JE2 growth was promoted less by glucose than fructose. Net transepithelial flux of D-glucose was lower than D-fructose. However, uptake of D-glucose was higher than D-fructose across both apical and basolateral membranes consistent with the presence of GLUT1/10 in the airway epithelium. Therefore, we propose that the preferential uptake of glucose (compared to fructose) limits its accumulation in ASL. Pre-treatment with metformin increased transepithelial resistance and reduced the sugar-dependent growth of S. aureus. Thus, epithelial paracellular permeability and glucose transport mechanisms are vital to maintain low glucose concentration in ASL and limit bacterial nutrient sources as a defence against infection