Methods for Handling Unobserved Covariates in a Bayesian Update of a Cost-effectiveness Model

Health economic decision models often involve a wide-ranging and complicated synthesis of evidence from a number of sources, making design and implementation of such models resource-heavy. When new data become available and reassessment of treatment recommendations is warranted, it may be more efficient to perform a Bayesian update of an existing model than to construct a new model. If the existing model depends on many, possibly correlated, covariates, then an update may produce biased estimates of model parameters if some of these covariates are completely absent from the new data. Motivated by the need to update a cost-effectiveness analysis comparing diagnostic strategies for coronary heart disease, this study develops methods to overcome this obstacle by either introducing additional data or using results from previous studies. We outline a framework to handle unobserved covariates, and use our motivating example to illustrate both the flexibility of the proposed methods and some potential difficulties in applying them

An Update on BRAF Inhibitors and Other New Molecular Targets for the Treatment of Malignant Melanoma of the Skin

Malignant melanoma of the skin originates from mutations in melanocytes and can be lethal if unrecognized or untreated in its earlier stages. Deaths from melanoma are increasing in the United States and around the world every year. The available treatments produce low rates of response with modest survival impact. Among potential molecular targets under investigation, which are mostly in the tyrosine kinase pathway, the BRAF (V-raf murine sarcoma viral oncogene homolog B1) gene is the best studied and most frequently reported mutation in melanoma. The molecular targets for melanoma treatment, promising drugs for future melanoma treatment as well as the new molecular entities that are approved are reviewed here. Approved by FDA in 2011, vemurafenib (Zelboraf) is the first personalized targeted therapy for treatment of metastatic melanoma that acts by selectively inhibiting BRAFV600E. This has opened a new avenue for the discovery of targeted drug therapies for melanoma based on the principles of pharmacogenomics

Cosmological model with non-minimally coupled fermionic field

A model for the Universe is proposed whose constituents are: (a) a dark energy field modeled by a fermionic field non-minimally coupled with the gravitational field, (b) a matter field which consists of pressureless baryonic and dark matter fields and (c) a field which represents the radiation and the neutrinos. The coupled system of Dirac's equations and Einstein field equations is solved numerically by considering a spatially flat homogeneous and isotropic Universe. It is shown that the proposed model can reproduce the expected red-shift behaviors of the deceleration parameter, of the density parameters of each constituent and of the luminosity distance. Furthermore, for small values of the red-shift the constant which couples the fermionic and gravitational fields has a remarkable influence on the density and deceleration parameters.Comment: Accepted for publication in Europhysics Letter

C(60)-Fullerenes: detection of intracellular photoluminescence and lack of cytotoxic effects

We have developed a new method of application of C(60 )to cultured cells that does not require water-solubilization techniques. Normal and malignant cells take-up C(60 )and the inherent photoluminescence of C(60 )is detected within multiple cell lines. Treatment of cells with up to 200 μg/ml (200 ppm) of C(60 )does not alter morphology, cytoskeletal organization, cell cycle dynamics nor does it inhibit cell proliferation. Our work shows that pristine C(60 )is non-toxic to the cells, and suggests that fullerene-based nanocarriers may be used for biomedical applications

Development of risk prediction models to predict urine culture growth for adults with suspected urinary tract infection in the emergency department: protocol for an electronic health record study from a single UK university hospital

Background: Urinary tract infection (UTI) is a leading cause of hospital admissions and is diagnosed based on urinary symptoms and microbiological cultures. Due to lags in the availability of culture results of up to 72 h, and the limitations of routine diagnostics, many patients with suspected UTI are started on antibiotic treatment unnecessarily. Predictive models based on routinely collected clinical information may help clinicians to rule out a diagnosis of bacterial UTI in low-risk patients shortly after hospital admission, providing additional evidence to guide antibiotic treatment decisions. / Methods: Using electronic hospital records from Queen Elizabeth Hospital Birmingham (QEHB) collected between 2011 and 2017, we aim to develop a series of models that estimate the probability of bacterial UTI at presentation in the emergency department (ED) among individuals with suspected UTI syndromes. Predictions will be made during ED attendance and at different time points after hospital admission to assess whether predictive performance may be improved over time as more information becomes available about patient status. All models will be externally validated for expected future performance using QEHB data from 2018/2019. / Discussion: Risk prediction models using electronic health records offer a new approach to improve antibiotic prescribing decisions, integrating clinical and demographic data with test results to stratify patients according to their probability of bacterial infection. Used in conjunction with expert opinion, they may help clinicians to identify patients that benefit the most from early antibiotic cessation

Dynamic Provenance for SPARQL Update

While the Semantic Web currently can exhibit provenance information by using the W3C PROV standards, there is a "missing link" in connecting PROV to storing and querying for dynamic changes to RDF graphs using SPARQL. Solving this problem would be required for such clear use-cases as the creation of version control systems for RDF. While some provenance models and annotation techniques for storing and querying provenance data originally developed with databases or workflows in mind transfer readily to RDF and SPARQL, these techniques do not readily adapt to describing changes in dynamic RDF datasets over time. In this paper we explore how to adapt the dynamic copy-paste provenance model of Buneman et al. [2] to RDF datasets that change over time in response to SPARQL updates, how to represent the resulting provenance records themselves as RDF in a manner compatible with W3C PROV, and how the provenance information can be defined by reinterpreting SPARQL updates. The primary contribution of this paper is a semantic framework that enables the semantics of SPARQL Update to be used as the basis for a 'cut-and-paste' provenance model in a principled manner.Comment: Pre-publication version of ISWC 2014 pape

Photoactivatable genetically encoded calcium indicators for targeted neuronal imaging.

Circuit mapping requires knowledge of both structural and functional connectivity between cells. Although optical tools have been made to assess either the morphology and projections of neurons or their activity and functional connections, few probes integrate this information. We have generated a family of photoactivatable genetically encoded Ca(2+) indicators that combines attributes of high-contrast photolabeling with high-sensitivity Ca(2+) detection in a single-color protein sensor. We demonstrated in cultured neurons and in fruit fly and zebrafish larvae how single cells could be selected out of dense populations for visualization of morphology and high signal-to-noise measurements of activity, synaptic transmission and connectivity. Our design strategy is transferrable to other sensors based on circularly permutated GFP (cpGFP)

A Curvature Principle for the interaction between universes

We propose a Curvature Principle to describe the dynamics of interacting universes in a multi-universe scenario and show, in the context of a simplified model, how interaction drives the cosmological constant of one of the universes toward a vanishingly small value. We also conjecture on how the proposed Curvature Principle suggests a solution for the entropy paradox of a universe where the cosmological constant vanishes.Comment: Essay selected for an honorable mention by the Gravity Research Foundation, 2007. Plain latex, 8 page

Optical Activity From Extra Dimension

Optical activity, like Faraday effect, is a rotation of the plane of polarization of propagating light in a medium and can be attributed to different sources with distinct signatures. In this note we discuss the effect of optical activity {\it{in vacuum}} due to Kaluza-Klein scalar field $\phi$, in the presence of an external electro-magnetic field. The astrophysical implication of this effect is indicated. We also point out the possibility of observing the same in laboratory conditions.Comment: Four Page