Using Rasch analysis to form plausible health states amenable to valuation: the development of CORE-6D from CORE-OM in order to elicit preferences for common mental health problems

Purpose: To describe a new approach for deriving a preference-based index from a condition specific measure that uses Rasch analysis to develop health states. Methods: CORE-OM is a 34-item instrument monitoring clinical outcomes of people with common mental health problems. CORE-OM is characterised by high correlation across its domains. Rasch analysis was used to reduce the number of items and response levels in order to produce a set of unidimensionally-behaving items, and to generate a credible set of health states corresponding to different levels of symptom severity using the Rasch item threshold map. Results: The proposed methodology resulted in the development of CORE-6D, a 2-dimensional health state description system consisting of a unidimensionally-behaving 5-item emotional component and a physical symptom item. Inspection of the Rasch item threshold map of the emotional component helped identify a set of 11 plausible health states, which, combined with the physical symptom item levels, will be used for the valuation of the instrument, resulting in the development of a preference-based index. Conclusions: This is a useful new approach to develop preference-based measures where the domains of a measure are characterised by high correlation. The CORE-6D preference-based index will enable calculation of quality adjusted life years in people with common mental health problems.Rasch analysis; health-related quality of life; condition-specific measure; preference-based health; health states; CORE-6D; CORE-OM; mental health; quality-adjusted life years

Ageing makes us dyslexic

Background: The effects of typical ageing on spoken language are well known: word production is disproportionately affected while syntactic processing is relatively well preserved. Little is known, however, about how ageing affects reading.Aims: What effect does ageing have on written language processing? In particular, how does it affect our ability to read words? How does it affect phonological awareness (our ability to manipulate the sounds of our language)?Methods & Procedures: We tested 14 people with Parkinson's disease (PD), 14 typically ageing adults (TAA), and 14 healthy younger adults on a range of background neuropsychological tests and tests of phonological awareness. We then carried out an oral naming experiment where we manipulated consistency, and a nonword repetition task where we manipulated the word-likeness of the nonwords.Outcomes & Results: We find that normal ageing causes individuals to become mildly phonologically dyslexic in that people have difficulty pronouncing nonwords. People with Parkinson's disease perform particularly poorly on language tasks involving oral naming and metalinguistic processing. We also find that ageing causes difficulty in repeating nonwords. We show that these problems are associated with a more general difficulty in processing phonological information, supporting the idea that language difficulties, including poorer reading in older age, can result from a general phonological deficit.Conclusions: We suggest that neurally this age-induced dyslexia is associated with frontal deterioration (and perhaps deterioration in other regions) and cognitively to the loss of executive processes that enable us to manipulate spoken and written language. We discuss implications for therapy and treatment

Influence of 100% and 40% oxygen on penumbral blood flow, oxygen level, and T2*-weighted MRI in a rat stroke model

Accurate imaging of the ischemic penumbra is a prerequisite for acute clinical stroke research. T2* magnetic resonance imaging (MRI) combined with an oxygen challenge (OC) is being developed to detect penumbra based on changes in blood deoxyhemoglobin. However, inducing OC with 100% O2 induces sinus artefacts on human scans and influences cerebral blood flow (CBF), which can affect T2* signal. Therefore, we investigated replacing 100% O2 OC with 40% O2 OC (5 minutes 40% O2 versus 100% O2) and determined the effects on blood pressure (BP), CBF, tissue pO2, and T2* signal change in presumed penumbra in a rat stroke model. Probes implanted into penumbra and contralateral cortex simultaneously recorded pO2 and CBF during 40% O2 (n=6) or 100% O2 (n=8) OC. In a separate MRI study, T2* signal change to 40% O2 (n=6) and 100% O2 (n=5) OC was compared. Oxygen challenge (40% and 100% O2) increased BP by 8.2% and 18.1%, penumbra CBF by 5% and 15%, and penumbra pO2 levels by 80% and 144%, respectively. T2* signal significantly increased by 4.56%±1.61% and 8.65%±3.66% in penumbra compared with 2.98%±1.56% and 2.79%±0.66% in contralateral cortex and 1.09%±0.82% and −0.32%±0.67% in ischemic core, respectively. For diagnostic imaging, 40% O2 OC could provide sufficient T2* signal change to detect penumbra with limited influence in BP and CBF

On the improvement of the low energy neutrino factory

The low energy neutrino factory has been proposed as a very sensitive setup for future searches for CP violation and matter effects. Here we study how its performance is affected when the experimental specifications of the setup are varied. Most notably, we have considered the addition of the 'platinum' nu_{mu} -> nu_{e} channel. We find that, whilst theoretically the extra channel provides very useful complementary information and helps to lift degeneracies, its practical usefulness is lost when considering realistic background levels. Conversely, an increase in statistics in the 'golden' nu_{e} -> nu_{mu} channel and, to some extent, an improvement in the energy resolution, lead to an important increase in the performance of the facility, given the rich energy dependence of the 'golden' channel at these energies. We show that a low energy neutrino factory with a baseline of 1300 km, muon energy of 4.5 GeV, and either a 20 kton totally active scintillating detector or 100 kton liquid argon detector, can have outstanding sensitivity to the neutrino oscillation parameters theta13, delta and the mass hierarchy. For our estimated exposure of 2.8 x 10^{23} kton x decays per muon polarity, the low energy neutrino factory has sensitivity to theta13 and delta for sin^{2}(2theta13) > 10^{-4} and to the mass hierarchy for sin^{2}(2theta13) > 10^{-3}.Comment: 13 pages, 8 eps figures. Version published in PRD - experimental section with preliminary results removed, abstract and conclusions re-written accordingly, title changed, author list amended

Using new and innovative technologies to assess clinical stage in early intervention youth mental health services: Evaluation study

Background: Globally there is increasing recognition that new strategies are required to reduce disability due to common mental health problems. As 75% of mental health and substance use disorders emerge during the teenage or early adulthood years, these strategies need to be readily accessible to young people. When considering how to provide such services at scale, new and innovative technologies show promise in augmenting traditional clinic-based services. Objective: The aim of this study was to test new and innovative technologies to assess clinical stage in early intervention youth mental health services using a prototypic online system known as the Mental Health eClinic (MHeC). Methods: The online assessment within the MHeC was compared directly against traditional clinician assessment within 2 Sydney-based youth-specific mental health services (headspace Camperdown and headspace Campbelltown). A total of 204 young people were recruited to the study. Eligible participants completed both face-to-face and online assessments, which were randomly allocated and counterbalanced at a 1-to-3 ratio. These assessments were (1) a traditional 45- to 60-minute headspace face-to-face assessment performed by a Youth Access Clinician and (2) an approximate 60-minute online assessment (including a self-report Web-based survey, immediate dashboard of results, and a video visit with a clinician). All assessments were completed within a 2-week timeframe from initial presentation. Results: Of the 72 participants who completed the study, 71% (51/72) were female and the mean age was 20.4 years (aged 16 to 25 years); 68% (49/72) of participants were recruited from headspace Camperdown and the remaining 32% (23/72) from headspace Campbelltown. Interrater agreement of participants’ stage, as determined after face-to-face assessment or online assessment, demonstrated fair agreement (kappa=.39, P\u3c.001) with concordance in 68% of cases (49/72). Among the discordant cases, those who were allocated to a higher stage by online raters were more likely to report a past history of mental health disorders (P=.001), previous suicide planning (P=.002), and current cannabis misuse (P=.03) compared to those allocated to a lower stage. Conclusions: The MHeC presents a new and innovative method for determining key clinical service parameters. It has the potential to be adapted to varied settings in which young people are connected with traditional clinical services and assist in providing the right care at the right tim

Optimal classical-communication-assisted local model of n-qubit Greenberger-Horne-Zeilinger correlations

We present a model, motivated by the criterion of reality put forward by Einstein, Podolsky, and Rosen and supplemented by classical communication, which correctly reproduces the quantum-mechanical predictions for measurements of all products of Pauli operators on an n-qubit GHZ state (or ``cat state''). The n-2 bits employed by our model are shown to be optimal for the allowed set of measurements, demonstrating that the required communication overhead scales linearly with n. We formulate a connection between the generation of the local values utilized by our model and the stabilizer formalism, which leads us to conjecture that a generalization of this method will shed light on the content of the Gottesman-Knill theorem.Comment: New version - expanded and revised to address referee comment

The zebrafish eye—a paradigm for investigating human ocular genetics

Although human epidemiological and genetic studies are essential to elucidate the aetiology of normal and aberrant ocular development, animal models have provided us with an understanding of the pathogenesis of multiple developmental ocular malformations. Zebrafish eye development displays in depth molecular complexity and stringent spatiotemporal regulation that incorporates developmental contributions of the surface ectoderm, neuroectoderm and head mesenchyme, similar to that seen in humans. For this reason, and due to its genetic tractability, external fertilisation, and early optical clarity, the zebrafish has become an invaluable vertebrate system to investigate human ocular development and disease. Recently, zebrafish have been at the leading edge of preclinical therapy development, with their amenability to genetic manipulation facilitating the generation of robust ocular disease models required for large-scale genetic and drug screening programmes. This review presents an overview of human and zebrafish ocular development, genetic methodologies employed for zebrafish mutagenesis, relevant models of ocular disease, and finally therapeutic approaches, which may have translational leads in the future.Eye advance online publication, 9 September 2016; doi:10.1038/eye.2016.198

Cost Minimization Analysis of Same-Day Long-Acting Reversible Contraception for Adolescents

Importance: Long-acting reversible contraception (LARC) is considered first-line contraception for adolescents but often requires multiple clinic visits to obtain. Objective: To analyze Indiana Medicaid's cost savings associated with providing adolescents with same-day access to LARC. Design, Setting, and Participants: An economic evaluation of cost minimization from the payer's (Medicaid) perspective was performed from August 2017 through August 2018. The cost model examined the anticipated outcome of providing LARC at the first visit compared with requiring a second visit for placement. The costs and probabilities of clinic visits, devices, device insertions and removals, unintended pregnancy, and births, according to previously published sources, were incorporated into the model. The participants were payers (Medicaid). Main Outcomes and Measures: The outcomes were the cost of same-day LARC placement vs LARC placement at a subsequent visit in US dollars, and rates of unintended pregnancy and abortion. One-way sensitivity analysis was done. Results: Same-day LARC placement was associated with lower overall costs ($2016 per patient over 1 year) compared with LARC placement at a subsequent visit ($4133 per patient over 1 year). Compared with the return-visit strategy, same-day LARC was associated with an unintended pregnancy rate of 14% vs 48% and an abortion rate of 4% vs 14%. Conclusions and Relevance: Providing same-day LARC could save costs for Medicaid, largely by preventing unintended pregnancy. Expected cost savings could be used to implement policies that make this strategy feasible in all clinical settings