Improving the measurement of QALYs in dementia: developing patient- and carer-reported health state classification systems using Rasch analysis

Objectives: Cost-utility analysis is increasingly used to inform resource allocation. This requires a means of valuing health states before and after intervention. Although generic measures are typically used to generate values, these do not perform well with people with dementia. We report the development of a health state classification system amenable to valuation for use in studies of dementia, derived from the DEMQOL system, a measure of health-related quality of life in dementia by patient self-report (DEMQOL) and carer proxy-report (DEMQOL-Proxy). Methods: Factor analysis was used to determine the dimensional structure of DEMQOL and DEMQOL-Proxy. Rasch analysis was subsequently used to investigate item performance across factors in terms of item-level ordering, functioning across subgroups, model fit and severity-range coverage. This enabled the selection of one item from each factor for the classification system. A sample of people with a diagnosis of mild/moderate dementia (n=644) and a sample of carers of those with mild/moderate dementia (n=683) were used. Results: Factor analysis found different 5-factor solutions for DEMQOL and DEMQOL-Proxy. Following item reduction and selection using Rasch analysis, a 5-dimension classification for DEMQOL and a 4-dimension classification for DEMQOL-Proxy were developed. Each item contained 4 health state levels. Conclusion: Combining Rasch and classical psychometric analysis is a valid method of selecting items for dementia health state classifications from both the patient and carer perspectives. The next stage is to obtain preference weights so that the measure can be used in the economic evaluation of treatment, care and support arrangements for dementia.quality adjusted life years; health related quality of life; Rasch analysis; preference-based measures of health; health states; dementia

Substrate-dependent activation of the Vibrio cholerae vexAB RND efflux system requires vexR

Vibrio cholerae encodes six resistance-nodulation-division (RND) efflux systems which function in antimicrobial resistance, virulence factor production, and intestinal colonization. Among the six RND efflux systems, VexAB exhibited broad substrate specificity and played a predominant role in intrinsic antimicrobial resistance. The VexAB system was encoded in an apparent three gene operon that included vexR; which encodes an uncharacterized TetR family regulator. In this work we examined the role of vexR in vexRAB expression. We found that VexR bound to the vexRAB promoter and vexR deletion resulted in decreased vexRAB expression and increased susceptibility to VexAB antimicrobial substrates. Sub-strate-dependent induction of vexRAB was dependent on vexR and episomal vexR expression provided a growth advantage in the presence of the VexAB substrate deoxycholate. The expression of vexRAB increased, in a vexR-dependent manner, in response to the loss of RND efflux activity. This suggested that VexAB may function to export intracellular metabolites. Support for this hypothesis was provided by data showing that vexRAB was upregulated in several metabolic mutants including tryptophan biosynthetic mutants that were predicted to accumulate indole. In addition, vexRAB was found to be upregulated in response to exogenous indole and to contribute to indole resistance. The collective results indicate that vexR is required for vexRAB expression in response to VexAB substrates and that the VexAB RND efflux system modulates the intracellular levels of metabolites that could otherwise accumulate to toxic levels

Fundamental limitations for quantum and nano thermodynamics

The relationship between thermodynamics and statistical physics is valid in the thermodynamic limit - when the number of particles becomes very large. Here, we study thermodynamics in the opposite regime - at both the nano scale, and when quantum effects become important. Applying results from quantum information theory we construct a theory of thermodynamics in these limits. We derive general criteria for thermodynamical state transformations, and as special cases, find two free energies: one that quantifies the deterministically extractable work from a small system in contact with a heat bath, and the other that quantifies the reverse process. We find that there are fundamental limitations on work extraction from nonequilibrium states, owing to finite size effects and quantum coherences. This implies that thermodynamical transitions are generically irreversible at this scale. As one application of these methods, we analyse the efficiency of small heat engines and find that they are irreversible during the adiabatic stages of the cycle.Comment: Final, published versio

In-pile loop irradiation studies of organic coolant materials : progress report, October 1, 1963 - December 31, 1964,

Statement of responsibility on title page reads: Report prepared by: E. A. Mason, Project Supervisor; Contributors: W.N. Bley, J.C. Kim, T.H. Timmins, J.F. Terrien, A.H. Swan"Issued: February 1, 1965.""AEC Research and Development Report"--Cover"MIT-334-12."Includes bibliographical references (leaves 21-22)Progress report; October 1, 1963 - December 31, 1964M.I.T. Project no. DSR 9819U.S. Atomic Energy Commission, Savannah River Operations Office contract no. AT(38-1)-33

Computer-Generated Ovaries to Assist Follicle Counting Experiments

Precise estimation of the number of follicles in ovaries is of key importance in the field of reproductive biology, both from a developmental point of view, where follicle numbers are determined at specific time points, as well as from a therapeutic perspective, determining the adverse effects of environmental toxins and cancer chemotherapeutics on the reproductive system. The two main factors affecting follicle number estimates are the sampling method and the variation in follicle numbers within animals of the same strain, due to biological variability. This study aims at assessing the effect of these two factors, when estimating ovarian follicle numbers of neonatal mice. We developed computer algorithms, which generate models of neonatal mouse ovaries (simulated ovaries), with characteristics derived from experimental measurements already available in the published literature. The simulated ovaries are used to reproduce in-silico counting experiments based on unbiased stereological techniques; the proposed approach provides the necessary number of ovaries and sampling frequency to be used in the experiments given a specific biological variability and a desirable degree of accuracy. The simulated ovary is a novel, versatile tool which can be used in the planning phase of experiments to estimate the expected number of animals and workload, ensuring appropriate statistical power of the resulting measurements. Moreover, the idea of the simulated ovary can be applied to other organs made up of large numbers of individual functional units

Testing Yukawa-unified SUSY during year 1 of LHC: the role of multiple b-jets, dileptons and missing E_T

We examine the prospects for testing SO(10) Yukawa-unified supersymmetric models during the first year of LHC running at \sqrt{s}= 7 TeV, assuming integrated luminosity values of 0.1 to 1 fb^-1. We consider two cases: the Higgs splitting (HS) and the D-term splitting (DR3) models. Each generically predicts light gluinos and heavy squarks, with an inverted scalar mass hierarchy. We hence expect large rates for gluino pair production followed by decays to final states with large b-jet multiplicity. For 0.2 fb^-1 of integrated luminosity, we find a 5 sigma discovery reach of m(gluino) ~ 400 GeV even if missing transverse energy, E_T^miss, is not a viable cut variable, by examining the multi-b-jet final state. A corroborating signal should stand out in the opposite-sign (OS) dimuon channel in the case of the HS model; the DR3 model will require higher integrated luminosity to yield a signal in the OS dimuon channel. This region may also be probed by the Tevatron with 5-10 fb^-1 of data, if a corresponding search in the multi-b+ E_T^miss channel is performed. With higher integrated luminosities of ~1 fb^-1, using E_T^miss plus a large multiplicity of b-jets, LHC should be able to discover Yukawa-unified SUSY with m(gluino) up to about 630 GeV. Thus, the year 1 LHC reach for Yukawa-unified SUSY should be enough to either claim a discovery of the gluino, or to very nearly rule out this class of models, since higher values of m(gluino) lead to rather poor Yukawa unification.Comment: 32 pages including 31 EPS figure

Functional diversity of mesograzers in an eelgrass-epiphyte system

Historically, small invertebrate grazers in marine plant communities have been considered to be a relatively homogeneous group in their impact on ecosystem processes. However, recent studies propose that species composition is an important agent in determining grazer effects. We used four mesocosm experiments to test the biomass-specific and density-dependent effects of common mesograzers in temperate regions (Littorina littorea, Rissoa membranacea, Idotea baltica and Gammarus oceanicus) on epiphyte and eelgrass biomass and productivity. Mesograzer species identity strongly influenced epiphyte accumulation and eelgrass growth, where Rissoa was the most efficient mesograzer (per biomass) and Gammarus had the weakest impact. Density-dependent effects varied considerably among species. Both gastropod species reduced epiphyte accumulation in direct proportion to their density, and Littorina had the strongest negative effect on epiphyte biomass. The impact of Idotea seemed to level off to a threshold value and Gammarus had no density-dependent effect on epiphyte accumulation at all. Rissoa and Idotea increased eelgrass productivity in accordance with their effect on epiphyte accumulation, whereas Littorina showed a less positive effect than could be expected by its strong impact on epiphyte biomass. Gammarus had no significant impact on eelgrass growth. Our results show that the different functional traits of superficially similar mesograzers can have important consequences for ecosystem processes in macrophyte systems

An Adaptive Approach for Processing Evoked Potentials From Human Auditory Cortex

Presents an adaptive approach for the processing of evoked potentials from the an auditory association cortex in humans. The approach can be conceptualized as a bank of least mean square adaptive signal enhancers. The recording data of each trial is then divided into several segments and each segment of data is input to corresponding adaptive signal enhancers. This approach allows the temporal variations of the evoked potential signal to be estimated across individual trials. This is a powerful tool for both clinical and research neurosciences. Two illustrative cases are shown.published_or_final_versio

Evolution of Th2 responses : Characterization of IL-4/13 in sea bass (Dicentrarchus labrax L.) and studies of expression and biological activity

Acknowledgements This research was funded by the European Commission under the 7th Framework Programme for Research and Technological Development (FP7) of the European Union (Grant Agreement 311993 TARGETFISH). T.W. received funding from the MASTS pooling initiative (The Marine Alliance for Science and Technology for Scotland). MASTS is funded by the Scottish Funding Council (grant reference number HR09011) and contributing institutions.Peer reviewedPublisher PD

Autonomous quantum machines and the finite sized Quasi-Ideal clock

Processes such as quantum computation, or the evolution of quantum cellular automata are typically described by a unitary operation implemented by an external observer. In particular, an interaction is generally turned on for a precise amount of time, using a classical clock. A fully quantum mechanical description of such a device would include a quantum description of the clock whose state is generally disturbed because of the back-reaction on it. Such a description is needed if we wish to consider finite sized autonomous quantum machines requiring no external control. The extent of the back-reaction has implications on how small the device can be, on the length of time the device can run, and is required if we want to understand what a fully quantum mechanical treatment of an observer would look like. Here, we consider the implementation of a unitary by a finite sized device which we call the "Quasi-Ideal clock", and show that the back-reaction on it can be made exponentially small in the device's dimension with only a linear increase in energy. As a result, an autonomous quantum machine need only be of modest size and or energy. We are also able to solve a long-standing open problem by using a finite sized quantum clock to approximate the continuous evolution of an Idealised clock. The result has implications on the equivalence of different paradigms of quantum thermodynamics, some which allow external control and some which only allow autonomous thermal machines.Comment: Main text: 9 + 53 pages. V4: Close to the published version, J. Annales Henri Poincar\'e (2018) [Communicated by David P\'erez-Garc\'ia