Experimental measurement of preferences in health care using best-worst scaling (BWS): theoretical and statistical issues.

For optimal solutions in health care, decision makers inevitably must evaluate trade-offs, which call for multi-attribute valuation methods. Researchers have proposed using best-worst scaling (BWS) methods which seek to extract information from respondents by asking them to identify the best and worst items in each choice set. While a companion paper describes the different types of BWS, application and their advantages and downsides, this contribution expounds their relationships with microeconomic theory, which also have implications for statistical inference. This article devotes to the microeconomic foundations of preference measurement, also addressing issues such as scale invariance and scale heterogeneity. Furthermore the paper discusses the basics of preference measurement using rating, ranking and stated choice data in the light of the findings of the preceding section. Moreover the paper gives an introduction to the use of stated choice data and juxtaposes BWS with the microeconomic foundations.

Impact of coverage-dependent marginal costs on optimal HPV vaccination strategies.

The effectiveness of vaccinating males against the human papillomavirus (HPV) remains a controversial subject. Many existing studies conclude that increasing female coverage is more effective than diverting resources into male vaccination. Recently, several empirical studies on HPV immunization have been published, providing evidence of the fact that marginal vaccination costs increase with coverage. In this study, we use a stochastic agent-based modeling framework to revisit the male vaccination debate in light of these new findings. Within this framework, we assess the impact of coverage-dependent marginal costs of vaccine distribution on optimal immunization strategies against HPV. Focusing on the two scenarios of ongoing and new vaccination programs, we analyze different resource allocation policies and their effects on overall disease burden. Our results suggest that if the costs associated with vaccinating males are relatively close to those associated with vaccinating females, then coverage-dependent, increasing marginal costs may favor vaccination strategies that entail immunization of both genders. In particular, this study emphasizes the necessity for further empirical research on the nature of coverage-dependent vaccination costs.

Scaling limits of a model for selection at two scales

The dynamics of a population undergoing selection is a central topic in evolutionary biology. This question is particularly intriguing in the case where selective forces act in opposing directions at two population scales. For example, a fast-replicating virus strain outcompetes slower-replicating strains at the within-host scale. However, if the fast-replicating strain causes host morbidity and is less frequently transmitted, it can be outcompeted by slower-replicating strains at the between-host scale. Here we consider a stochastic ball-and-urn process which models this type of phenomenon. We prove the weak convergence of this process under two natural scalings. The first scaling leads to a deterministic nonlinear integro-partial differential equation on the interval $[0,1]$ with dependence on a single parameter, $\lambda$. We show that the fixed points of this differential equation are Beta distributions and that their stability depends on $\lambda$ and the behavior of the initial data around $1$. The second scaling leads to a measure-valued Fleming-Viot process, an infinite dimensional stochastic process that is frequently associated with a population genetics.

The upstream enhancer elements of the G6PC promoter are critical for optimal G6PC expression in murine glycogen storage disease type Ia.

Glycogen storage disease type-Ia (GSD-Ia) patients deficient in glucose-6-phosphatase-α (G6Pase-α or G6PC) manifest impaired glucose homeostasis characterized by fasting hypoglycemia, growth retardation, hepatomegaly, nephromegaly, hyperlipidemia, hyperuricemia, and lactic acidemia. Two efficacious recombinant adeno-associated virus pseudotype 2/8 (rAAV8) vectors expressing human G6Pase-α have been independently developed. One is a single-stranded vector containing a 2864-bp of the G6PC promoter/enhancer (rAAV8-GPE) and the other is a double-stranded vector containing a shorter 382-bp minimal G6PC promoter/enhancer (rAAV8-miGPE). To identify the best construct, a direct comparison of the rAAV8-GPE and the rAAV8-miGPE vectors was initiated to determine the best vector to take forward into clinical trials. We show that the rAAV8-GPE vector directed significantly higher levels of hepatic G6Pase-α expression, achieved greater reduction in hepatic glycogen accumulation, and led to a better toleration of fasting in GSD-Ia mice than the rAAV8-miGPE vector. Our results indicated that additional control elements in the rAAV8-GPE vector outweigh the gains from the double-stranded rAAV8-miGPE transduction efficiency, and that the rAAV8-GPE vector is the current choice for clinical translation in human GSD-Ia.

Accurate localized resolution of identity approach for linear-scaling hybrid density functionals and for many-body perturbation theory

© 2015 IOP Publishing Ltd and Deutsche Physikalische Gesellschaft.A key component in calculations of exchange and correlation energies is the Coulomb operator, which requires the evaluation of two-electron integrals. For localized basis sets, these four-center integrals are most efficiently evaluated with the resolution of identity (RI) technique, which expands basis-function products in an auxiliary basis. In this work we show the practical applicability of a localized RI-variant ('RI-LVL'), which expands products of basis functions only in the subset of those auxiliary basis functions which are located at the same atoms as the basis functions. We demonstrate the accuracy of RI-LVL for Hartree-Fock calculations, for the PBE0 hybrid density functional, as well as for RPA and MP2 perturbation theory. Molecular test sets used include the S22 set of weakly interacting molecules, the G3 test set, as well as the G2-1 and BH76 test sets, and heavy elements including titanium dioxide, copper and gold clusters. Our RI-LVL implementation paves the way for linear-scaling RI-based hybrid functional calculations for large systems and for all-electron many-body perturbation theory with significantly reduced computational and memory cost.