Meaning behind measurement : self-comparisons affect responses to health related quality of life questionnaires

Purpose The subjective nature of quality of life is particularly pertinent to the domain of health-related quality of life (HRQOL) research. The extent to which participants’ responses are affected by subjective information and personal reference frames is unknown. This study investigated how an elderly population living with a chronic metabolic bone disorder evaluated self-reported quality of life. Methods Participants (n = 1,331) in a multi-centre randomised controlled trial for the treatment of Paget’s disease completed annual HRQOL questionnaires, including the SF-36, EQ-5D and HAQ. Supplementary questions were added to reveal implicit reference frames used when making HRQOL evaluations. Twenty-one participants (11 male, 10 female, aged 59–91 years) were interviewed retrospectively about their responses to the supplementary questions, using cognitive interviewing techniques and semi-structured topic guides. Results The interviews revealed that participants used complex and interconnected reference frames to promote response shift when making quality of life evaluations. The choice of reference frame often reflected external factors unrelated to individual health. Many participants also stated that they were unclear whether to report general or disease-related HRQOL. Conclusions It is important, especially in clinical trials, to provide instructions clarifying whether ‘quality of life’ refers to disease-related HRQOL. Information on selfcomparison reference frames is necessary for the interpretation of responses to questions about HRQOL.The Chief Scientist Office of the Scottish Government Health Directorates, The PRISM funding bodies (the Arthritis Research Campaign, the National Association for the Relief of Paget’s disease and the Alliance for Better Bone Health)Peer reviewedAuthor final versio

Hypoxia enhances the expression of autocrine motility factor and the motility of human pancreatic cancer cells

The incidence of distant metastases is higher in the tumours with low oxygen pressure than in those with high oxygen pressure. It is well known that hypoxia induces the transcription of various genes involved in angiogenesis and anaerobic metabolism necessary for the growth of tumour cells in vivo, suggesting that hypoxia may also induce the transcription of metastasis-associated genes. We sought to identify the metastasis-associated genes differentially expressed in tumour cells under hypoxic conditions with the use of a DNA microarray system. We found that hypoxia enhanced the expression of autocrine motility factor mRNA in various cancer cells and also enhanced the random motility of pancreatic cancer cells. Autocrine motility factor inhibitors abrogated the increase of motility under hypoxic conditions. In order to explore the roles of hypoxia-inducible factor-1α, we established hypoxia-inducible factor-1α-transfectants and dominant negative hypoxia-inducible factor-1α-transfectants. Transfection with hypoxia-inducible factor-1α and dominant-negative hypoxia-inducible factor-1α enhanced and suppressed the expression of autocrine motility factor/phosphohexase isomerase/neuroleukin mRNA and the random motility, respectively. These results suggest that hypoxia may promote the metastatic potential of cancer cells through the enhanced autocrine motility factor/phosphohexase isomerase/neuroleukin mRNA expression and that the disruption of the hypoxia-inducible factor-1 pathway may be an effective treatment for metastasis

Is Our Universe Natural?

It goes without saying that we are stuck with the universe we have. Nevertheless, we would like to go beyond simply describing our observed universe, and try to understand why it is that way rather than some other way. Physicists and cosmologists have been exploring increasingly ambitious ideas that attempt to explain why certain features of our universe aren't as surprising as they might first appear.Comment: Invited review for Nature, 11 page

Goldstone Bosons in Effective Theories with Spontaneously Broken Flavour Symmetry

The Flavour Symmetry of the Standard Model (SM) gauge sector is broken by the fermion Yukawa couplings. Promoting the Yukawa matrices to scalar spurion fields, one can break the flavour symmetry spontaneously by giving appropriate vacuum expectation values (VEVs) to the spurion fields, and one encounters Goldstone modes for every broken flavour symmetry generator. In this paper, we point out various aspects related to the possible dynamical interpretation of the Goldstone bosons: (i) In an effective-theory framework with local flavour symmetry, the Goldstone fields represent the longitudinal modes for massive gauge bosons. The spectrum of the latter follows the sequence of flavour-symmetry breaking related to the hierarchies in Yukawa couplings and flavour mixing angles. (ii) Gauge anomalies can be consistently treated by adding higher-dimensional operators. (iii) Leaving the U(1) factors of the flavour symmetry group as global symmetries, the respective Goldstone modes behave as axions which can be used to resolve the strong CP problem by a modified Peccei-Quinn mechanism. (iv) The dynamical picture of flavour symmetry breaking implies new sources of flavour-changing neutral currents, which arise from integrating out heavy scalar spurion fields and heavy gauge bosons. The coefficients of the effective operators follow the minimal-flavour violation principle.Comment: 27 pages, abstract and introduction extended, more detailed discussion of heavy gauge boson spectrum and auxiliary heavy fermions, outline restructured. Matches version to be published in JHE

Patients' constructions of disability in metastatic spinal cord compression

Metastatic spinal cord compression (MSCC) is characterised by poor prognosis and serious physical disability. Patients have complex rehabilitation needs, but the evidence on rehabilitation is sparse. This study aimed to ascertain the constructions placed upon disability by patients with MSCC. A series of nine process-tracing, longitudinal case studies, involving 58 interviews with 9 patients, 6 carers, and 29 staff in one NHS region. A context-mechanism-outcome configuration was adopted as a conceptual basis for data collection, together with a constant comparative method of data analysis. Patients’ orientation to disability incorporated two apparently inconsistent attitudes. Patients acknowledged that their situation had changed, and that their future plans would need to accommodate altered circumstances. However, they also resisted the idea of themselves as disabled, wanting to retain an image of themselves as resourceful and resilient. Patients used a number of strategies to reconcile the tension between these two positions. The illusions incorporated into the ‘failure to acknowledge’ pole of this orientation are self-protective and, like other positive illusions, have psychological benefits. Providing effective and acceptable support to patients living with disability relies on professional responses that are able to sustain patients’ sense of their own competence

The Custodial Randall-Sundrum Model: From Precision Tests to Higgs Physics

We reexamine the Randall-Sundrum (RS) model with enlarged gauge symmetry SU(2)_L x SU(2)_R x U(1)_X x P_LR in the presence of a brane-localized Higgs sector. In contrast to the existing literature, we perform the Kaluza-Klein (KK) decomposition within the mass basis, which avoids the truncation of the KK towers. Expanding the low-energy spectrum as well as the gauge couplings in powers of the Higgs vacuum expectation value, we obtain analytic formulas which allow for a deep understanding of the model-specific protection mechanisms of the T parameter and the left-handed Z-boson couplings. In particular, in the latter case we explain which contributions escape protection and identify them with the irreducible sources of P_LR symmetry breaking. We furthermore show explicitly that no protection mechanism is present in the charged-current sector confirming existing model-independent findings. The main focus of the phenomenological part of our work is a detailed discussion of Higgs-boson couplings and their impact on physics at the CERN Large Hadron Collider. For the first time, a complete one-loop calculation of all relevant Higgs-boson production and decay channels is presented, incorporating the effects stemming from the extended electroweak gauge-boson and fermion sectors.Comment: 74 pages, 13 figures, 3 tables. v2: Matches version published in JHE

Challenges Associated with Estimating Utility in Wet Age-Related Macular Degeneration : A Novel Regression Analysis to Capture the Bilateral Nature of the Disease

INTRODUCTION: The estimation of utility values for the economic evaluation of therapies for wet age-related macular degeneration (AMD) is a particular challenge. Previous economic models in wet AMD have been criticized for failing to capture the bilateral nature of wet AMD by modelling visual acuity (VA) and utility values associated with the better-seeing eye only. METHODS: Here we present a de novo regression analysis using generalized estimating equations (GEE) applied to a previous dataset of time trade-off (TTO)-derived utility values from a sample of the UK population that wore contact lenses to simulate visual deterioration in wet AMD. This analysis allows utility values to be estimated as a function of VA in both the better-seeing eye (BSE) and worse-seeing eye (WSE). RESULTS: VAs in both the BSE and WSE were found to be statistically significant (p < 0.05) when regressed separately. When included without an interaction term, only the coefficient for VA in the BSE was significant (p = 0.04), but when an interaction term between VA in the BSE and WSE was included, only the constant term (mean TTO utility value) was significant, potentially a result of the collinearity between the VA of the two eyes. The lack of both formal model fit statistics from the GEE approach and theoretical knowledge to support the superiority of one model over another make it difficult to select the best model. CONCLUSION: Limitations of this analysis arise from the potential influence of collinearity between the VA of both eyes, and the use of contact lenses to reflect VA states to obtain the original dataset. Whilst further research is required to elicit more accurate utility values for wet AMD, this novel regression analysis provides a possible source of utility values to allow future economic models to capture the quality of life impact of changes in VA in both eyes. FUNDING: Novartis Pharmaceuticals UK Limited

The Interplay Between GUT and Flavour Symmetries in a Pati-Salam x S4 Model

Both Grand Unified symmetries and discrete flavour symmetries are appealing ways to describe apparent structures in the gauge and flavour sectors of the Standard Model. Both symmetries put constraints on the high energy behaviour of the theory. This can give rise to unexpected interplay when building models that possess both symmetries. We investigate on the possibility to combine a Pati-Salam model with the discrete flavour symmetry $S_4$ that gives rise to quark-lepton complementarity. Under appropriate assumptions at the GUT scale, the model reproduces fermion masses and mixings both in the quark and in the lepton sectors. We show that in particular the Higgs sector and the running Yukawa couplings are strongly affected by the combined constraints of the Grand Unified and family symmetries. This in turn reduces the phenomenologically viable parameter space, with high energy mass scales confined to a small region and some parameters in the neutrino sector slightly unnatural. In the allowed regions, we can reproduce the quark masses and the CKM matrix. In the lepton sector, we reproduce the charged lepton masses, including bottom-tau unification and the Georgi-Jarlskog relation as well as the two known angles of the PMNS matrix. The neutrino mass spectrum can present a normal or an inverse hierarchy, and only allowing the neutrino parameters to spread into a range of values between $\lambda^{-2}$ and $\lambda^2$, with $\lambda\simeq0.2$. Finally, our model suggests that the reactor mixing angle is close to its current experimental bound.Comment: 62 pages, 4 figures; references added, version accepted for publication in JHE

Raising the profile of pilot and feasibility studies in relation to the development, evaluation and implementation of patient-reported outcome measures.

This editorial introduces a new special series on the pilot and feasibility testing of patient-reported outcome measures (PROMs) in the on-line open access journal Pilot and Feasibility Studies. Pilot and feasibility studies are typically implemented to address issues of uncertainty before undertaking a larger definitive study such as a randomised controlled trial or large scale survey. This editorial considers the role that such pilot and feasibility testing plays in relation to the development, evaluation and implementation of PROMs. This is often an essential element of PROM research but is typically overlooked-especially within current methodological guidance, reporting space and also debate. This editorial aims to open up a dialogue about the role of pilot and feasibility testing in relation to PROMs. It highlights some of the areas in PROMs research where these types of studies have been carried out and discusses the ways in which the PROM community may be better supported and encouraged to integrate this element of the research process into their PROM-based work

Beauty in Disability: An Aesthetics for Dance and for Life

To what extent does dance contribute to an ideal of beauty that can enrich human quality of life? To what extent are standards of beauty predicated on an ideal human body that has no disability? In this chapter, we show how conceptions of proportionality, perfection, and ethereality from the Ancient Greeks through the 19th century can still be seen today in some kinds of dance, particularly in ballet. Disability studies and disability-inclusive dance companies, however, have started to change this. The disabled person can be beautiful, we will show, in dance and in life, under a disability aesthetics that follows Edmund Burke (1730-1797) and that suggests an alternative standard of beauty, which we call “beauty-in-experience,” where beauty is perceived in the qualitative experience of abled and disabled dancers moving together in dance.https://ecommons.udayton.edu/books/1023/thumbnail.jp