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ALBI grade predicts suitability for further systemic therapy following sorafenib in patients with advanced hepatocellular carcinoma.
No full textBackground & Aims: Preserved performance status (PS) and liver function are required for systemic therapy in patients with advanced hepatocellular carcinoma (aHCC). We investigated the frequency of suitability for further systemic therapies following sorafenib in aHCC.Methods: Demographic, tumour, and therapy-related data were collected retrospectively for patients with aHCC who received sorafenib at a UK tertiary referral centre (training cohort), and an independent French centre (validation cohort). The primary end point was percentage of patients with Child-Pugh class A (CP-A) liver disease and PS 0-1 after sorafenib discontinuation.Results: Sorafenib was received by 182 patients. After sorafenib discontinuation, 93 patients (51%) were CP-A and 60 patients (33%) were PS 0-1; 43 patients (24%) were both CP-A and PS 0-1. On multivariable analysis, patients with Albumin-Bilirubin (ALBI) score of 1 at time of sorafenib commencement were more likely to be suitable for post-sorafenib therapy, (44% grade 1 vs 15% grade 2) (OR 3.76, 95%CI 1.72-8.25, p=0.0009). In the validation cohort of 216 patients baseline ALBI grade was also significantly associated with suitability for further systemic therapy (p=0.008). Conclusions: Most patients with aHCC are not suitable for further systemic therapy after sorafenib, but those with ALBI grade 1 have a greater likelihood of suitability.<br/
Comparison of multiple gene expression platforms for measuring a bladder cancer hypoxia signature
No full textTumour hypoxia status provides prognostic information and predicts response to hypoxia-modifying treatments. We previously derived a 24-gene signature to assess hypoxia in bladder cancer. The objectives here were to: compare platforms for generating signature scores, identify cut-off values for prospective studies, assess intra-tumour heterogeneity and confirm hypoxia relevance. RNA was extracted from prospectively-collected diagnostic biopsies of muscle invasive bladder cancer (51 patients) and gene expression measured using customised Taqman Low Density Array (TLDA) cards, NanoString and Clariom S arrays. Cross-platform transferability of the gene signature was assessed using regression and concordance analysis. Cut-off values were the cohort median expression values. Intra- and inter-tumour variability were determined in a retrospective patient cohort (n=51) with multiple blocks (2-18) from the same tumour. To demonstrate relevance, bladder cancer cell lines were exposed to hypoxia (0.1% oxygen, 24 h), and extracted RNA run on custom TLDA cards. Hypoxia scores showed good agreement between platforms: Clariom S vs TLDA (r=0.72, p<0.0001; concordance 73%); Clariom S vs NanoString (r=0.84, p<0.0001; 78%); TLDA vs NanoString (r=0.80, p<0.0001; 78%). Cut-off values were 0.047 (TLDA), 7.328 (NanoString) and 6.667 (Clariom S). Intra-tumour heterogeneity in gene expression and HS (coefficient of variation 3.9%) was less than inter-tumour (7.9%) variability. Hypoxia scores were higher in bladder cancer cells exposed to hypoxia vs normoxia (p<0.02). Application of the 24-gene bladder cancer hypoxia signature is platform agnostic, cut-off values determined prospectively can be used in a clinical trial, intra-tumour heterogeneity is low and the signature is sensitive to changes in oxygen levels in vitro
Efficient Approximation of Expected Hypervolume Improvement using Gauss-Hermite Quadrature
No full textMany methods for performing multi-objective optimisation of computationally expensive problems have been proposed recently. Typically, a probabilistic surrogate for each objective is constructed from an initial dataset. The surrogates can then be used to produce predictive densities in the objective space for any solution. Using the predictive densities, we can compute the expected hypervolume improvement (EHVI) due to a solution. Maximising the EHVI, we can locate the most promising solution that may be expensively evaluated next. There are closed-form expressions for computing the EHVI, integrating over the multivariate predictive densities. However, they require partitioning the objective space, which can be prohibitively expensive for more than three objectives. Furthermore, there are no closed-form expressions for a problem where the predictive densities are dependent, capturing the correlationsbetween objectives. Monte Carlo approximation is used instead in such cases, which is not cheap. Hence, the need to develop new accurate but cheaper approximation methods remains. Here we investigate an alternative approach toward approximating the EHVI using Gauss-Hermite quadrature.We show that it can be an accurate alternative to Monte Carlo for both independent and correlated predictive densities with statistically signicant rank correlations for a range of popular test problems
A Bibliometric Mapping Study of the Literature on Oral Health-related Quality of Life
No full textBackgroundOral health is an indispensable component of overall health, and oral health status significantly influences people’s physical, mental, and social well-being. Oral health-related quality of life (OHRQoL), an important and widely used dental patient-reported outcome (dPRO), is attracting more and more researchers’ attention and interest. This study aimed to analyze and map the existing scientific literature regarding OHRQoL through a bibliometric approach, including a summary of the characteristics of OHRQoL-related publications, the identification of prolific entities, high-frequency keywords analysis and research trend analysis via periodic high-impact keywords.MethodsA literature search was conducted in the Web of Science Core Collection to collect OHRQoL-related original research and review articles. After examination and deduplication, the following bibliometric information was extracted from each article: title, abstract, keywords, authors, affiliations, geographic origin (countries/regions), year of publication, journal name, and references. Various scientometric mapping tools including Microsoft Office spreadsheet, VOSviewer, Biblioshiny R-package software, and Scimago Graphica were used to analyze basic bibliometric parameters, leading producers, highimpact keywords, and research trends.ResultsA total of 3324 OHRQoL-related articles (3119 original research articles and 205 review papers) were collected, which received 65704 citations. A total of 9950 authors from 2429 organizations contributed to this body of research. Prolific authors from Europe, USA, Brazil, New Zealand, China, and Canada were identified, and they also centered collaboration clusters in the co-author network. Community Dentistry and Oral Epidemiology was the most prolific journal. Twenty-one keywords with more than 200 occurrences, and 23 keywords with more than 150 occurrences, were identified for publications of 1994-2021 and 2012-2021, respectively. Keyword analysis revealed hot topics such as instrument development and validation, studies targeting children and adolescents, as well as clinical studies in operative dentistry, implantology, orthodontics, and community dentistry. Oral Health Impact Profile is the most commonly used instrument in OHRQoL-related research.ConclusionsOHRQoL is an impactful topic in dental health care as it is not only useful in dental research and patient-centered clinical outcome measures but also provides valuable guidance in dental public health administration and policy making. OHRQoL-related research presents a dynamic landscape and is expected to continue presenting high productivity and broad application in the future
Augmenting a Nature Documentary with a Lifelike Hologram in Virtual Reality
No full textWhile augmented reality television (ARTV) is being investigated in research labs, the high cost of AR headsets makes it difficult foraudiences to benefit from the research. However, the relative affordability of virtual reality (VR) headsets provides ARTV researcherswith opportunities to test their prototypes in VR. Additionally, as VR becomes an acceptable medium for watching conventional TV,augmenting such viewing experiences in VR creates new opportunities. We prototype a nature documentary ARTV experience inVR and conduct a remote user study (𝑛 = 10) to investigate six points on the visual display design dimension of presenting a lifelikeprogramme-related hologram. We manipulated the starting point and the movement behaviour of the hologram to gain insight intoviewer preferences. Our findings highlight the importance of personal preferences and that of the perceived role of a hologram inrelation to the underlying TV content; suggesting there may not be a single way to augment a TV programme. Instead, creators mayneed to provide the audiences with capabilities to customise ARTV content
SPLITTING HAIRS WITH TRANSCENDENTAL ENTIRE FUNCTIONS
No full textIn recent years, there has been significant progress in the understanding of the dynamics of transcendental entire functions with bounded postsingular set. In particular, for certain classes of such functions, a complete description of their topological dynamics in terms of a simpler model has been given inspired by methods from polynomial dynamics. In this paper, and for the first time, we give analogous results in cases when the postsingular set is unbounded. More specifically, we show that if f is of finite order, has bounded criticality on its Julia set J(f), and its singular set consists of finitely many critical values that escape to infinity and satisfy a certain separation condition, then J(f) is a collection of dynamic rays or hairs, that split at critical points, together with their corresponding landing points. In fact, our result holds for a much larger class of functions with bounded singular set. Moreover, this result is a consequence of a significantly more general one: we provide a topological model for the action of f on its Julia set
Optimised cell growth and poly(3-hydroxybutyrate) synthesis from saponified spent coffee grounds oil
No full textSpent coffee grounds (SCG) oil is an ideal substrate for the biosynthesis of polyhydroxyalkanoates (PHAs) by Cupriavidus necator. The immiscibility of lipids with water limits their bioavailability, but this can be resolved by saponifying the oil with potassium hydroxide to form water-soluble fatty acid potassium salts and glycerol. Total saponification was achieved with 0.5 mol/L of KOH at 50 °C for 90 min. The relationship between the initial carbon substrate concentration (C0) and the specific growth rate (µ) of C. necator DSM 545 was evaluated in shake flask cultivations; crude and saponified SCG oils were supplied at matching initial carbon concentrations (C0 = 2.9-23.0 g/L). The Han-Levenspiel model provided the closest fit to the experimental data and accurately described complete growth inhibition at 32.9 g/L (C0 = 19.1 g/L) saponified SCG oil. Peak µ-values of 0.139 h−1 and 0.145 h−1 were obtained with 11.99 g/L crude and 17.40 g/L saponified SCG oil, respectively. Further improvement to biomass production was achieved by mixing the crude and saponified substrates together in a carbon ratio of 75:25% (w/w), respectively. In bioreactors, C. necator initially grew faster on the mixed substrates (µ = 0.35 h−1) than on the crude SCG oil (µ = 0.23 h−1). After harvesting, cells grown on crude SCG oil obtained a total biomass concentration of 7.8 g/L and contained 77.8 % (w/w) PHA. Whereas cells grown on the mixed substrates produced 8.5 g/L of total biomass and accumulated 84.4 % (w/w) of PHA
Investigation of the Electronic Structure and Luminescence Spectra of Uranium-(IV), -(V) and -(VI) Complexes Using Multi-configurational Methods
No full textInterpreting electronic spectra of uranium-containing compounds is an important component of fundamental chemistry as well as in the assessment of waste streams in the nuclear fuel cycle. Here we employ multiconfigurational calculations with CASSCF or DMRGSCF methods on exemplar uranium molecules [UVIO2Cl4]2-, [UV(TRENTIPS)(N)]- and [UIVCl5(THF)]-, featuring an array of geometries and oxidation states, to determine their effectiveness in predicting electronic spectra, compared to literature calculations and experimental data. For [UVIO2Cl4]2-, DMRGSCF alone shows poor agreement with experiment, which can be improved by adding corrections for dynamic correlation with MC-PDFT to give results of similar quality to TD-DFT. However, for [UV(TRENTIPS)(N)]- the addition of dynamical correlation via MC-PDFT or CASPT2 made no improvements over CASSCF, suggesting that perhaps other factors such as solvation effects could be more important in this case. Finally, for [UIVCl5(THF)]-, dynamical correlation included via MS-CASPT2 on top of CASSCF calculations is crucial to obtain a quantitatively correct spectrum; here, MC-PDFT fails to even qualitatively describe the spectrum, highlighting the shortcomings of single-state methods in cases of near-degeneracy