Development and Validation of the FSIQ-RMS: A New Patient-Reported Questionnaire to Assess Symptoms and Impacts of Fatigue in Relapsing Multiple Sclerosis

Objectives: A new patient-reported outcome (PRO) instrument to measure fatigue symptoms and impacts in relapsing multiple sclerosis (RMS) was developed in a qualitative stage, followed by psychometric validation and migration from paper to an electronic format. Methods: Adult patients with relapsing-remitting multiple sclerosis (RRMS) were interviewed to elicit fatigue-related symptoms and impacts. A draft questionnaire was debriefed in cognitive interviews with further RRMS patients, and revised. Content confirmation interviews were conducted with patients with progressive-relapsing multiple sclerosis (PRMS) and relapsing secondary-progressive multiple sclerosis (RSPMS). Psychometric analyses used data from adult patients with different RMS subtypes and matched non-RMS controls in a multicenter, observational study. After item reduction, the final instrument was migrated to a smartphone (eDiary) and usability was confirmed in interviews with additional adult RMS patients. Results: The qualitative stage included 37 RRMS, 5 PRMS, and 5 RSPMS patients. Saturation of concepts was reached during concept elicitation. Cognitive interviews confirmed that participants understood the instructions, items, and response options of the instrument—named FSIQ-RMS—as intended. Psychometric validation included 164 RMS and 74 control patients. Internal consistency and test–retest reliability were demonstrated. The symptoms domain discriminated along the RMS symptom-severity continuum and between patients and controls. Patients were able to attribute fatigue-related symptoms to RMS. Usability and conceptual equivalence of the eDiary were confirmed (n = 10 participants). Conclusions: With 7 symptom items and 13 impact items (in 3 impacts subdomains: physical, cognitive and emotional, and coping) after item reduction, the FSIQ-RMS is a comprehensive, valid, and reliable measure of fatigue-related symptoms and impacts in RMS patients

Order parameters in the Verwey phase transition

The Verwey phase transition in magnetite is analyzed on the basis of the Landau theory. The free energy functional is expanded in a series of components belonging to the primary and secondary order parameters. A low-temperature phase with the monoclinic P2/c symmetry is a result of condensation of two order parameters X_3 and \Delta_5 . The temperature dependence of the shear elastic constant C_44 is derived and the mechanism of its softening is discussed.Comment: 4 pages, 1 figur

Ocular attention-sensing interface system

The purpose of the research was to develop an innovative human-computer interface based on eye movement and voice control. By eliminating a manual interface (keyboard, joystick, etc.), OASIS provides a control mechanism that is natural, efficient, accurate, and low in workload

The structure of an LIM-only protein 4 (LMO4) and deformed epidermal autoregulatory factor-1 (DEAF1) complex reveals a common mode of binding to LMO4

LIM-domain only protein 4 (LMO4) is a widely expressed protein with important roles in embryonic development and breast cancer. It has been reported to bind many partners, including the transcription factor Deformed epidermal autoregulatory factor-1 (DEAF1), with which LMO4 shares many biological parallels. We used yeast two-hybrid assays to show that DEAF1 binds both LIM domains of LMO4 and that DEAF1 binds the same face on LMO4 as two other LMO4-binding partners, namely LIM domain binding protein 1 (LDB1) and C-terminal binding protein interacting protein (CtIP/RBBP8). Mutagenic screening analysed by the same method, indicates that the key residues in the interaction lie in LMO4LIM2 and the N-terminal half of the LMO4-binding domain in DEAF1. We generated a stable LMO4LIM2-DEAF1 complex and determined the solution structure of that complex. Although the LMO4-binding domain from DEAF1 is intrinsically disordered, it becomes structured on binding. The structure confirms that LDB1, CtIP and DEAF1 all bind to the same face on LMO4. LMO4 appears to form a hub in protein-protein interaction networks, linking numerous pathways within cells. Competitive binding for LMO4 therefore most likely provides a level of regulation between those different pathways.SJ was funded by an Australian Postgraduate Award (education.gov.au/australian-postgraduate-awards). JPM and JMM were awarded Senior Research Fellowships from the Australian National and Medical Research Council (www.nhmrc.gov.au). This project was funded by an Australian Research Council (www. arc.gov.au) Discovery Project Grant (DP110104332) to JMM and LC

Well structured program equivalence is highly undecidable

We show that strict deterministic propositional dynamic logic with intersection is highly undecidable, solving a problem in the Stanford Encyclopedia of Philosophy. In fact we show something quite a bit stronger. We introduce the construction of program equivalence, which returns the value $\mathsf{T}$ precisely when two given programs are equivalent on halting computations. We show that virtually any variant of propositional dynamic logic has $\Pi_1^1$-hard validity problem if it can express even just the equivalence of well-structured programs with the empty program \texttt{skip}. We also show, in these cases, that the set of propositional statements valid over finite models is not recursively enumerable, so there is not even an axiomatisation for finitely valid propositions.Comment: 8 page

An analysis of the transformations of leadership and direction-setting in place marketing: a UK contextual view and case.

The marketing of places has experienced challenges in recent years. Prolonged and severe financial constraints have led to a considerable reduction in the public sector funding of initiatives. This is presenting new leadership imperatives. This paper elaborates place marketing and its changing identity and considers the nature and increasing need for effective leadership in the marketing of places. The study adopts an inductive approach and employs semi-structured interviews with senior executives from a range of destination marketing organisations. The research is contextualised within the UK and it uses places in North-West England to provide its focal setting developing two case studies with which to complement the wider data. The study identifies that the complexity of place marketing intertwined with financial pressures, creates a particular dynamic and a need for leadership to clarify, decode and respond to the resulting situations. The evidence presented points to a compelling need for leaders in the sector to accept and embrace the new realities and to provide a clear vision for the future

Noncovariant gauge fixing in the quantum Dirac field theory of atoms and molecules

Starting from the Weyl gauge formulation of quantum electrodynamics (QED), the formalism of quantum-mechanical gauge fixing is extended using techniques from nonrelativistic QED. This involves expressing the redundant gauge degrees of freedom through an arbitrary functional of the gauge-invariant transverse degrees of freedom. Particular choices of functional can be made to yield the Coulomb gauge and Poincar\'{e} gauge representations. The Hamiltonian we derive therefore serves as a good starting point for the description of atoms and molecules by means of a relativistic Dirac field. We discuss important implications for the ontology of noncovariant canonical QED due to the gauge freedom that remains present in our formulation.Comment: 8 pages, 0 figure