Vibrational dependence of the H\u3csub\u3e2\u3c/sub\u3e–H\u3csub\u3e2\u3c/sub\u3e \u3ci\u3eC\u3c/i\u3e\u3csub\u3e6\u3c/sub\u3e coefficients

We use the sum-over-states formalism to compute the imaginary-frequency dipole polarizabilities for H2, as a function of the H–H bond length, at the full configuration interaction level of theory using atom-centered d-aug-cc-pVQZ basis sets. From these polarizabilities, we obtain isotropic and anisotropic C6 dispersion coefficients for a pair of H2 molecules as functions of the two molecules’ bond lengths

The He-LiH potential energy surface revisited. I. An interpolated rigid rotor surface

We reconsider the potential energy surface of the He–LiH system recently examined by Gianturco and co-workers [F. A. Gianturco et al., Chem. Phys. 215, 227 (1997)]. We compute the He–LiH interaction energy at the CCSD(T) level using large correlation consistent atomic basis sets supplemented with bond functions. To capture the severe anisotropy of the He–LiH potential, we interpolate our ab initio points in the angular direction with cubic splines, then expand the splines in terms of Legendre polynomials. The resulting smooth potential surface differs substantially from that of Gianturco et al.; in particular, our attractive He–LiH well is more than twice as deep as that of Gianturco et al., with a He–LiH binding energy of De = 176.7 cm–1

Infrared-active vibron bands associated with substitutional impurities in solid parahydrogen

We present a model for the line shapes of infrared-active Q1(0) vibron bands observed in solid parahydrogen doped with low concentrations of spherical substitutional impurities. The line shapes are highly sensitive to the H2 vibrational dependence of the dopant–H2 interaction. When this vibrational dependence is strong, the dopant can trap the infrared-active vibron in its first solvation shell; in this case, the trapped vibron manifests itself in the absorption spectrum as a narrow feature to the red of the pure solid’s vibron band

A six-dimensional H\u3csub\u3e2\u3c/sub\u3e–H\u3csub\u3e2\u3c/sub\u3e potential energy surface for bound state spectroscopy

We present a six-dimensional potential energy surface for the (H2)2 dimer based on coupled-cluster electronic structure calculations employing large atom-centered Gaussian basis sets and a small set of midbond functions at the dimer’s center of mass. The surface is intended to describe accurately the bound and quasibound states of the dimers (H2)2, (D2)2, and H2–D2 that correlate with H2 or D2 monomers in the rovibrational levels (v, j) =(0,0), (0,2), (1,0), and (1,2). We employ a close-coupled approach to compute the energies of these bound and quasibound dimer states using our potential energy surface, and compare the computed energies for infrared and Raman transitions involving these states with experimentally measured transition energies. We use four of the experimentally measured dimer transition energies to make two empirical adjustments to the ab initio potential energy surface; the adjusted surface gives computed transition energies for 56 experimentally observed transitions that agree with experiment to within 0.036 cm−1. For 26 of the 56 transitions, the agreement between the computed and measured transition energies is within the quoted experimental uncertainty. Finally, we use our potential energy surface to predict the energies of another 34 not-yet-observed infrared and Raman transitions for the three dimers

Steering H-atom diffusion through impurity-doped solid parahydrogen: the role of differential solvation energies

Ultraviolet irradiation of solid parahydrogen (pH$_2$) matrices doped with suitable H-atom precursor molecules generates H atoms {\it in situ\/} through a series of photoinitiated chemical reactions; these H atoms move through the pH$_2$ matrix through a quantum diffusion process that involves the tunneling-mediated process H + H$_2$ $\rightarrow$ H$_2$ + H. The mobile H atoms may react chemically with other species that are also embedded in the pH$_2$ matrix; an investigation of the kinetics of these H-atom chemical reactions provides us with information about reaction dynamics in the pH$_2$ matrix environment. A recent study of the H + N$_2$O $\rightarrow$ HNNO reaction in solid pH$_2$ [Mutunga, Follett, and Anderson, J. Chem. Phys. {\bf 139}, 151104 (2013)] demonstrates that this reaction exhibits strongly non-Arrhenius behavior, proceeding at measurable rates only when the temperature of the system drops below $T \approx 2.4$ K. A molecular-level understanding of these findings requires information about how the solid pH$_2$ matrix environment affects the long-range entrance channel of the H + N$_2$O reaction. Here, we carry out quantum Monte Carlo simulations of a simple model system (Ar-doped solid pH$_2$) to investigate matrix-induced changes to long-range interactions between H atoms and other impurities embedded in solid pH$_2$ matrices. Our results suggest that the pH$_2$ matrix creates an effective long-range repulsion between the H atom and the Ar impurity, which we explain in terms of differential solvation energies of Ar and H atoms in solid pH$_2$.Ope

Interaction-induced dipole moment of the Ar–H\u3csub\u3e2\u3c/sub\u3e dimer: dependence on the H\u3csub\u3e2\u3c/sub\u3e bond length

We present ab initio calculations of the interaction-induced dipole moment of the Ar–H2 van der Waals dimer. The primary focus of our calculations is on the H2 bond length dependence of the dipole moment, which determines the intensities of both the collision-induced H2 = 1 ← 0 fundamental band in gaseous Ar–H2 mixtures and the dopant-induced H2 = 1 ← 0 absorption feature in Ar-doped solid H2 matrices. Our calculations employ large atom-centered basis sets, diffuse bond functions positioned between the two monomers, and a coupled cluster treatment of valence electron correlation; core-valence correlation effects appear to make negligible contributions to the interaction-induced dipole moment for the Ar–H2 configurations considered here

Population size bias in descendant-weighted diffusion quantum Monte Carlo simulations

We consider the influence of population size on the accuracy of diffusion quantum Monte Carlo simulations that employ descendant weighting or forward walking techniques to compute expectation values of observables that do not commute with the Hamiltonian. We show that for a simple model system, the d-dimensional isotropic harmonic oscillator, the population size must increase rapidly with d in order to ensure that the simulations produce accurate results. When the population size is too small, expectation values computed using descendant-weighted diffusion quantum Monte Carlo simulations exhibit significant systematic biases

A six-dimensional H2-H2 potential energy surface for bound state spectroscopy

We present a six-dimensional potential energy surface for the H2-H2 dimer based on ab initio electronic structure calculations. The surface is intended to describe accurately the bound and quasibound states of the dimers H2-H2, D2-D2, and H2-D2 that correlate with H2 or D2 monomers in the rovibrational levels (v, j) = (0, 0), (0, 2), (1, 0), and (1, 2). We use four experimentally measured transition energies for these dimers to make two empirical adjustments to the ab initio surface; the adjusted surface gives computed transition energies for 56 experimentally observed transitions that agree with experiment to within 0.036 cm^{-1}. For 29 of the 56 transitions, the agreement between the computed and measured transition energies is within the quoted experimental uncertainty. We use our potential energy surface to predict the energies of another 34 not-yet-observed infrared and Raman transitions for the three dimers.Comment: 44 pages, 17 tables, 6 figures; accepted by Journal of Chemical Physic

The assessment and appraisal of regenerative medicines and cell therapy products : an exploration of methods for review, economic evaluation and appraisal

BACKGROUND: The National Institute for Health and Care Excellence (NICE) commissioned a 'mock technology appraisal' to assess whether changes to its methods and processes are needed. This report presents the findings of independent research commissioned to inform this appraisal and the deliberations of a panel convened by NICE to evaluate the mock appraisal. METHODS: Our research included reviews to identify issues, analysis methods and conceptual differences and the relevance of alternative decision frameworks, alongside the development of an exemplar case study of chimeric antigen receptor (CAR) T-cell therapy for treating acute lymphoblastic leukaemia. RESULTS: An assessment of previous evaluations of regenerative medicines found that, although there were a number of evidential challenges, none was unique to regenerative medicines or was beyond the scope of existing methods used to conceptualise decision uncertainty. Regarding the clinical evidence for regenerative medicines, the issues were those associated with a limited evidence base but were not unique to regenerative medicines: small non-randomised studies, high variation in response and the intervention subject to continuing development. The relative treatment effects generated from single-arm trials are likely to be optimistic unless it is certain that the historical data have accurately estimated the efficacy of the control agent. Pivotal trials may use surrogate end points, which, on average, overestimate treatment effects. To reduce overall uncertainty, multivariate meta-analysis of all available data should be considered. Incorporating indirectly relevant but more reliable (more mature) data into the analysis can also be considered; such data may become available as a result of the evolving regulatory pathways being developed by the European Medicines Agency. For the exemplar case of CAR T-cell therapy, target product profiles (TPPs) were developed, which considered the 'curative' and 'bridging to stem-cell transplantation' treatment approaches separately. Within each TPP, three 'hypothetical' evidence sets (minimum, intermediate and mature) were generated to simulate the impact of alternative levels of precision and maturity in the clinical evidence. Subsequent assessments of cost-effectiveness were undertaken, employing the existing NICE reference case alongside additional analyses suggested within alternative frameworks. The additional exploratory analyses were undertaken to demonstrate how assessments of cost-effectiveness and uncertainty could be impacted by alternative managed entry agreements (MEAs), including price discounts, performance-related schemes and technology leasing. The panel deliberated on the range of TPPs, evidence sets and MEAs, commenting on the likely recommendations for each scenario. The panel discussed the challenges associated with the exemplar and regenerative medicines more broadly, focusing on the need for a robust quantification of the level of uncertainty in the cost-effective estimates and the potential value of MEAs in limiting the exposure of the NHS to high upfront costs and loss associated with a wrong decision. CONCLUSIONS: It is to be expected that there will be a significant level of uncertainty in determining the clinical effectiveness of regenerative medicines and their long-term costs and benefits, but the existing methods available to estimate the implications of this uncertainty are sufficient. The use of risk sharing and MEAs between the NHS and manufacturers of regenerative medicines should be investigated further. FUNDING: The National Institute for Health Research Health Technology Assessment programme

Semantic transfer and contradictory evidence in intuitionistic fuzzy sets

The relationship between object level intuitionistic fuzzy sets and predicate based intuitionistic fuzzy sets is explored. Mass assignment uses a process called semantic unification to evaluate the degree to which one set supports another, the inverse function is semantic separation. Intuitionistic fuzzy sets are mapped onto a mass assignment framework and the semantic unification operator is generalised to support both mass assignment and intuitionistic fuzzy sets, as is semantic separation. Transfer of inconsistent and contradictory evidence are also dealt with