Customized care 2020: how medical sequencing and network biology will enable personalized medicine

Applications of next-generation nucleic acid sequencing technologies will lead to the development of precision diagnostics that will, in turn, be a major technology enabler of precision medicine. Terabyte-scale, multidimensional data sets derived using these technologies will be used to reverse engineer the specific disease networks that underlie individual patients’ conditions. Modeling and simulation of these networks in the presence of virtual drugs, and combinations of drugs, will identify the most efficacious therapy for precision medicine and customized care. In coming years the practice of medicine will routinely employ network biology analytics supported by high-performance supercomputing

Fluoride Release from Model Glass Ionomer Cements

Glass ionomer cements (GICs) are an important class of biomedical material used extensively for color matched mercury free, dental restorations. GICs can release clinically beneficial amounts of fluoride and have acceptable handling properties which make them suitable as dental restoratives. The fluoride release of model GICs produced from specially synthesized fluoro-alumino-silicate glasses was studied. Nine glasses of varying fluoride content based on 4.5SiO2-3Al2O3-1.5P2O5-(5-Z)CaO-ZCaF2 were synthesized, and cement disks were prepared from them. The glass transition temperature reduced with increasing fluorine content of the glass. Fluoride ion release was measured into distilled water as a function of time for up to 140 days using a fluoride ion selective electrode. The quantity of fluoride released was found to be proportional to the fluorine content of the glass at all intervals time. The cumulative fluoride release was proportional to square root time. Substituting strontium for calcium in the glass had little influence on the fluoride release behavior of the cements. © 2002 Kluwer Academic Publishers

Characterization of the Positivity of the Density Matrix in Terms of the Coherence Vector Representation

A parameterization of the density operator, a coherence vector representation, which uses a basis of orthogonal, traceless, Hermitian matrices is discussed. Using this parameterization we find the region of permissible vectors which represent a density operator. The inequalities which specify the region are shown to involve the Casimir invariants of the group. In particular cases, this allows the determination of degeneracies in the spectrum of the operator. The identification of the Casimir invariants also provides a method of constructing quantities which are invariant under {\it local} unitary operations. Several examples are given which illustrate the constraints provided by the positivity requirements and the utility of the coherence vector parameterization.Comment: significantly rewritten and submitted for publicatio

Photoionization of High Altitude Gas in a Supernova-Driven Turbulent Interstellar Medium

We investigate models for the photoionization of the widespread diffuse ionized gas in galaxies. In particular we address the long standing question of the penetration of Lyman continuum photons from sources close to the galactic midplane to large heights in the galactic halo. We find that recent hydrodynamical simulations of a supernova-driven interstellar medium have low density paths and voids that allow for ionizing photons from midplane OB stars to reach and ionize gas many kiloparsecs above the midplane. We find ionizing fluxes throughout our simulation grids are larger than predicted by one dimensional slab models, thus allowing for photoionization by O stars of low altitude neutral clouds in the Galaxy that are also detected in Halpha. In previous studies of such clouds the photoionization scenario had been rejected and the Halpha had been attributed to enhanced cosmic ray ionization or scattered light from midplane H II regions. We do find that the emission measure distributions in our simulations are wider than those derived from Halpha observations in the Milky Way. In addition, the horizontally averaged height dependence of the gas density in the hydrodynamical models is lower than inferred in the Galaxy. These discrepancies are likely due to the absence of magnetic fields in the hydrodynamic simulations and we discuss how magnetohydrodynamic effects may reconcile models and observations. Nevertheless, we anticipate that the inclusion of magnetic fields in the dynamical simulations will not alter our primary finding that midplane OB stars are capable of producing high altitude diffuse ionized gas in a realistic three-dimensional interstellar medium.Comment: ApJ accepted. 17 pages, 7 figure

The development of the adult deterioration detection system (ADDS) chart

The Adult Deterioration Detection System (ADDS) observation chart described in this short report was developed as part of a research project carried out at The University of Queensland for Queensland Health and the Australian Commission on Safety and Quality in Health Care (ACSQHC). The aim of the project was to investigate the design and use of observation charts in recognising and managing patient deterioration, including the design and evaluation of a new adult observation chart that incorporated human factors principles

Paper-based patient chart design information sheet

The purpose of this document is to help those involved in creating paper-based patient charts improve the human factors aspects of the design of their charts. It is based on the outcomes of a research project (“Human Factors Research Regarding Observation Charts”) carried out at the University of Queensland for the Australian Commission on Safety and Quality in Health Care, the Queensland Health Patient Safety and Quality Improvement Service and the Clinical Skills Development Service. Copies of the reports associated with this project are available online from the Commission’s website (www.safetyandquality.gov.au). As part of this project, we systematically reviewed 25 existing patient observation charts and developed a new chart (the “ADDS chart”) designed to identify patient deterioration, which was then evaluated in behavioural experiments. In this document, we will use some of the issues arising from this process to illustrate human factors design considerations for paper-based patient charts in general

Detecting abnormal vital signs on six observation charts: An experimental comparison

Paper-based observation charts are the principal means of monitoring changes to patients’ vital signs. There is considerable variation in the design of observation charts and a lack of empirical research on the performance of different designs. This report describes the results of a study carried out as part of a project funded by the Australian Commission for Safety and Quality in Health Care and Queensland Health to investigate the design and use of observation charts in recognising and managing patient deterioration, including the design and evaluation of a new adult observation chart that incorporated human factors principles. The first phase of this project involved using a procedure known as heuristic analysis to review 25 observation charts from Australia and New Zealand. 1,189 usability problems, which could lead to errors in recording data and identifying patient deterioration, were identified in the charts. The results from the heuristic analysis were used to design a new chart (the Adult Deterioration Detection System [ADDS] chart) based on human factors principles and current best practice. The study described in this report involved an empirical comparison of six charts (two versions of the ADDS chart, two existing charts rated as “well designed” in the heuristic analysis, one existing chart rated as being of “average design”, and one existing chart rated as “poorly designed”). Novices (individuals who were unfamiliar with using patient charts) and health professionals (doctors and nurses) were recruited as participants. Each chart design was shown to each participant four times displaying different physiological data with one abnormal vital sign (e.g. a high systolic blood pressure), and four times displaying different normal physiological data. After memorising the normal ranges for each vital sign, participants had to classify the physiological data on the charts as “normal” or “abnormal”. Error rates (the proportion of trials where participants made an incorrect normal/abnormal judgement) and response time (the time to read the chart and make the judgement) were measured. Results indicated that chart design had a statistically significant effect on both error rates and response time, with the charts identified as having better design tending to yield fewer errors and shorter decision times. Specifically, the two versions of the ADDS chart outperformed all the existing charts on both metrics, where the other charts yielded between 2.5 and 3.3 times as many errors as the ADDS chart. There was no significant difference between novices and health professionals in error rates for any chart, but the health professionals were significantly faster than novices at making their decisions for the charts rated as “average” and “poor”. There was no significant difference between doctors and nurses on either of the two performance measures for any of the charts. These data indicate that differences in the design of observation charts have a profound impact on chart users’ decisions regarding patients’ vital signs as well as the time it takes to make such decisions. Based on the current data, it appears that the ADDS chart is significantly better at signalling patient deterioration than other currently available charts

Incommensurate Transverse Anisotropy Induced by Disorder and Spin-Orbit-Vibron Coupling in Mn12-acetate

It has been shown within density-functional theory that in Mn$_{12}$-acetate there are effects due to disorder by solvent molecules and a coupling between vibrational and electronic degrees of freedom. We calculate the in-plane principal axes of the second-order anisotropy caused by the second effect and compare them with those of the fourth-order anisotropy due to the first effect. We find that the two types of the principal axes are not commensurate with each other, which results in a complete quenching of the tunnel-splitting oscillation as a function of an applied transverse field.Comment: Will be presented at MMM conference 200