Economics of tandem mass spectrometry screening of neonatal inherited disorders

Objectives: The aim of this study was to evaluate the cost-effectiveness of neonatal screening for phenylketonuria (PKU) and medium-chain acyl-coA dehydrogenase (MCAD) deficiency using tandem mass spectrometry (tandem MS). Methods: A systematic review of clinical efficacy evidence and cost-effectiveness modeling of screening in newborn infants within a UK National Health Service perspective was performed. Marginal costs, life-years gained, and cost-effectiveness acceptability curves are presented. Results: Substituting the use of tandem MS for existing technologies for the screening of PKU increases costs with no increase in health outcomes. However, the addition of screening for MCAD deficiency as part of a neonatal screening program for PKU using tandem MS, with an operational range of 50,000 to 60,000 specimens per system per year, would result in a mean incremental cost of −£17,298 (−£129,174, £66,434) for each cohort of 100,000 neonates screened. This cost saving is associated with a mean incremental gain of 57.3 (28.0, 91.4) life-years. Conclusions: Cost-effectiveness analysis using economic modeling indicates that substituting the use of tandem MS for existing technologies for the screening of PKU alone is not economically justified. However, the addition of screening for MCAD deficiency as part of a neonatal screening program for PKU using tandem MS would be economically attractive

Conical diffraction and the dispersion surface of hyperbolic metamaterials

Hyperbolic metamaterials are materials in which at least one principal dielectric constant is negative. We describe the refractive index surface, and the resulting refraction effects, for a biaxial hyperbolic metamaterial, with principal dielectric constants $\epsilon_1<0$, $0<\epsilon_2\neq\epsilon_3$. In this general case the two sheets of the index surface intersect forming conical singularities. We derive the ray description of conical refraction in these materials, and show that it is topologically and quantitatively distinct from conical refraction in a conventional biaxial material. We also develop a wave optics description, which allows us to obtain the diffraction patterns formed from arbitrary beams incident close to the optic axis. The resulting patterns lack circular symmetry, and hence are qualitatively different from those obtained in conventional, positive index materials.Comment: 10 pages, 7 figure

The new physics of non-equilibrium condensates: insights from classical dynamics

We discuss the dynamics of classical Dicke-type models, aiming to clarify the mechanisms by which coherent states could develop in potentially non-equilibrium systems such as semiconductor microcavities. We present simulations of an undamped model which show spontaneous coherent states with persistent oscillations in the magnitude of the order parameter. These states are generalisations of superradiant ringing to the case of inhomogeneous broadening. They correspond to the persistent gap oscillations proposed in fermionic atomic condensates, and arise from a variety of initial conditions. We show that introducing randomness into the couplings can suppress the oscillations, leading to a limiting dynamics with a time-independent order parameter. This demonstrates that non-equilibrium generalisations of polariton condensates can be created even without dissipation. We explain the dynamical origins of the coherence in terms of instabilities of the normal state, and consider how it can additionally develop through scattering and dissipation.Comment: 10 pages, 4 figures, submitted for a special issue of J. Phys.: Condensed Matter on "Optical coherence and collective phenomena in nanostructures". v2: added discussion of links to exact solution

Newborn screening using tandem mass spectrometry: A systematic review

Objectives: To evaluate the evidence for the clinical effectiveness of neonatal screening for phenylketonuria (PKU) and medium-chain acyl-coA dehydrogenase (MCAD) deficiency using tandem mass spectrometry (tandem MS). Study design: Systematic review of published research. Data sources: Studies were identified by searching 12 electronic bibliographic databases; conference proceedings and experts consulted. Results: Six studies were selected for inclusion in the review. The evidence of neonatal screening for PKU and MCAD deficiency using tandem MS was primarily from observational data of large-scale prospective newborn screening programmes and systematic screening studies from Australia, Germany and the USA. Tandem MS based newborn screening of dried blood spots for PKU and/or MCAD deficiency was shown to be highly sensitive (>93.220%) and highly specific (>99.971%). The false positive rate for PKU screening was less than 0.046% and for MCAD deficiency the false positive rate was less than 0.023%. The positive predictive values ranged from 20 to 32% and 19 to 100%, respectively. Conclusions: This review suggests that neonatal screening of dried blood spots using a single analytical technique (tandem MS) is highly sensitive and specific for detecting cases of PKU and MCAD deficiency, and provides a basis for modelling of the clinical benefits and potential costeffectiveness

Isospectral Mathieu-Hill Operators

In this paper we prove that the spectrum of the Mathieu-Hill Operators with potentials ae^{-i2{\pi}x}+be^{i2{\pi}x} and ce^{-i2{\pi}x}+de^{i2{\pi}x} are the same if and only if ab=cd, where a,b,c and d are complex numbers. This result implies some corollaries about the extension of Harrell-Avron-Simon formula. Moreover, we find explicit formulas for the eigenvalues and eigenfunctions of the t-periodic boundary value problem for the Hill operator with Gasymov's potential

Finite momentum condensation in a pumped microcavity

We calculate the absorption spectra of a semiconductor microcavity into which a non-equilibrium exciton population has been pumped. We predict strong peaks in the spectrum corresponding to collective modes analogous to the Cooper modes in superconductors and fermionic atomic gases. These modes can become unstable, leading to the formation of off-equilibrium quantum condensates. We calculate a phase diagram for condensation, and show that the dominant instabilities can be at a finite momentum. Thus we predict the formation of inhomogeneous condensates, similar to Fulde-Ferrel-Larkin-Ovchinnikov states.Comment: 7 pages, 4 figures, updated to accepted versio

Quantum condensation from a tailored exciton population in a microcavity

An experiment is proposed, on the coherent quantum dynamics of a semiconductor microcavity containing quantum dots. Modeling the experiment using a generalized Dicke model, we show that a tailored excitation pulse can create an energy-dependent population of excitons, which subsequently evolves to a quantum condensate of excitons and photons. The population is created by a generalization of adiabatic rapid passage, and then condenses due to a dynamical analog of the BCS instability.Comment: 5 pages, 3 figures. Version 2 is extensively rewritten, and incorporates some new results in further support of our claim

Mechanism for the failure of the Edwards hypothesis in the SK spin glass

The dynamics of the SK model at T=0 starting from random spin configurations is considered. The metastable states reached by such dynamics are atypical of such states as a whole, in that the probability density of site energies, $p(\lambda)$, is small at $\lambda=0$. Since virtually all metastable states have a much larger $p(0)$, this behavior demonstrates a qualitative failure of the Edwards hypothesis. We look for its origins by modelling the changes in the site energies during the dynamics as a Markov process. We show how the small $p(0)$ arises from features of the Markov process that have a clear physical basis in the spin-glass, and hence explain the failure of the Edwards hypothesis.Comment: 5 pages, new title, modified text, additional reference