The language of pain ? better requirements for pain tools

We describe a co-design method for development of an assessment tool for chronic pain. Here, by taking a "research through design" approach, we visualized and shared various strands of our domain knowledge. From this, a common understanding of the relevant issues was seen to emerge, which in turn facilitated creativity among the group. Thereafter, a collective proposal for a pain assessment tool was formulated After outlining this proposal, we move on to argue that, based on our experience this method provides a useful platform for interdisciplinary collaboration in healthcare technology development

The Spectrum of the Dirac Operator on Coset Spaces with Homogeneous Gauge Fields

The spectrum and degeneracies of the Dirac operator are analysed on compact coset spaces when there is a non-zero homogeneous background gauge field which is compatible with the symmetries of the space, in particular when the gauge field is derived from the spin-connection. It is shown how the degeneracy of the lowest Landau level in the recently proposed higher dimensional quantum Hall effect is related to the Atiyah-Singer index theorem for the Dirac operator on a compact coset space.Comment: 25 pages, typeset in LaTeX, uses youngtab.st

Imprints of Short Distance Physics On Inflationary Cosmology

We analyze the impact of certain modifications to short distance physics on the inflationary perturbation spectrum. For the specific case of power-law inflation, we find distinctive -- and possibly observable -- effects on the spectrum of density perturbations.Comment: Revtex 4, 3 eps figs, 4 page

A generic estimate of trans-Planckian modifications to the primordial power spectrum in inflation

We derive a general expression for the power spectra of scalar and tensor fluctuations generated during inflation given an arbitrary choice of boundary condition for the mode function at a short distance. We assume that the boundary condition is specified at a short-distance cutoff at a scale $M$ which is independent of time. Using a particular prescription for the boundary condition at momentum $p = M$, we find that the modulation to the power spectra of density and gravitational wave fluctuations is of order $(H/M)$, where $H$ is the Hubble parameter during inflation, and we argue that this behavior is generic, although by no means inevitable. With fixed boundary condition, we find that the shape of the modulation to the power spectra is determined entirely by the deviation of the background spacetime from the de Sitter limit.Comment: 15 pages (RevTeX), 2 figure

Diagonalization of the XXZ Hamiltonian by Vertex Operators

We diagonalize the anti-ferroelectric XXZ-Hamiltonian directly in the thermodynamic limit, where the model becomes invariant under the action of affine U_q( sl(2) ). Our method is based on the representation theory of quantum affine algebras, the related vertex operators and KZ equation, and thereby bypasses the usual process of starting from a finite lattice, taking the thermodynamic limit and filling the Dirac sea. From recent results on the algebraic structure of the corner transfer matrix of the model, we obtain the vacuum vector of the Hamiltonian. The rest of the eigenvectors are obtained by applying the vertex operators, which act as particle creation operators in the space of eigenvectors. We check the agreement of our results with those obtained using the Bethe Ansatz in a number of cases, and with others obtained in the scaling limit --- the $su(2)$-invariant Thirring model.Comment: 65 page

Cosmological String Gas on Orbifolds

It has long been known that strings wound around incontractible cycles can play a vital role in cosmology. In particular, in a spacetime with toroidal spatial hypersurfaces, the dynamics of the winding modes may help yield three large spatial dimensions. However, toroidal compactifications are phenomenologically unrealistic. In this paper we therefore take a first step toward extending these cosmological considerations to $D$-dimensional toroidal orbifolds. We use numerical simulation to study the timescales over which "pseudo-wound" strings unwind on these orbifolds with trivial fundamental group. We show that pseudo-wound strings can persist for many ``Hubble times'' in some of these spaces, suggesting that they may affect the dynamics in the same way as genuinely wound strings. We also outline some possible extensions that include higher-dimensional wrapped branes.Comment: 14 pages, 8 eps fig

Impact of Continuous Flow Left Ventricular Assist Device Therapy on Chronic Kidney Disease: A Longitudinal Multicenter Study

Background: Many patients undergoing durable left ventricular assist device (LVAD) implantation suffer from chronic kidney disease (CKD). Therefore, we investigated the effect of LVAD support on CKD. Methods: A retrospective multicenter cohort study, including all patients undergoing LVAD (HeartMate II (n = 330), HeartMate 3 (n = 22) and HeartWare (n = 48) implantation. In total, 227 (56.8%) patients were implanted as bridge-to-transplantation; 154 (38.5%) as destination therapy; and 19 (4.7%) as bridge-to-decision. Serum creatinine measurements were collected over a 2-year follow-up period. Patients were stratified based on CKD stage. Results: Overall, 400 patients (mean age 53 ± 14 years, 75% male) were included: 186 (46.5%) patients had CKD stage 1 or 2; 93 (23.3%) had CKD stage 3a; 82 (20.5%) had CKD stage 3b; and 39 (9.8%) had CKD stage 4 or 5 prior to LVAD implantation. During a median follow-up of 179 days (IQR 28–627), 32,629 creatinine measurements were available. Improvement of kidney function was noticed in every preoperative CKD-stage group. Following this improvement, estimated glomerular filtration rates regressed to baseline values for all CKD stages. Patients showing early renal function improvement were younger and in worse preoperative condition. Moreover, survival rates were higher in patients showing early improvement (69% vs 56%, log-rank P = 0.013). Conclusions: Renal function following LVAD implantation is characterized by improvement, steady state and subsequent deterioration. Patients who showed early renal function improvement were in worse preoperative condition, however, and had higher survival rates at 2 years of follow-up

Targeting eosinophils in respiratory diseases: Biological axis, emerging therapeutics and treatment modalities

Eosinophils are bi-lobed, multi-functional innate immune cells with diverse cell surface receptors that regulate local immune and inflammatory responses. Several inflammatory and infectious diseases are triggered with their build up in the blood and tissues. The mobilization of eosinophils into the lungs is regulated by a cascade of processes guided by Th2 cytokine generating T-cells. Recruitment of eosinophils essentially leads to a characteristic immune response followed by airway hyperresponsiveness and remodeling, which are hallmarks of chronic respiratory diseases. By analysing the dynamic interactions of eosinophils with their extracellular environment, which also involve signaling molecules and tissues, various therapies have been invented and developed to target respiratory diseases. Having entered clinical testing, several eosinophil targeting therapeutic agents have shown much promise and have further bridged the gap between theory and practice. Moreover, researchers now have a clearer understanding of the roles and mechanisms of eosinophils. These factors have successfully assisted molecular biologists to block specific pathways in the growth, migration and activation of eosinophils. The primary purpose of this review is to provide an overview of the eosinophil biology with a special emphasis on potential pharmacotherapeutic targets. The review also summarizes promising eosinophil-targeting agents, along with their mechanisms and rationale for use, including those in developmental pipeline, in clinical trials, or approved for other respiratory disorders

Characterisation of lamina I anterolateral system neurons that express Cre in a Phox2a-Cre mouse line

A recently developed Phox2a::Cre mouse line has been shown to capture anterolateral system (ALS) projection neurons. Here, we used this line to test whether Phox2a-positive cells represent a distinct subpopulation among lamina I ALS neurons. We show that virtually all lamina I Phox2a cells can be retrogradely labelled from injections targeted on the lateral parabrachial area (LPb), and that most of those in the cervical cord also belong to the spinothalamic tract. Phox2a cells accounted for ~ 50–60% of the lamina I cells retrogradely labelled from LPb or thalamus. Phox2a was preferentially associated with smaller ALS neurons, and with those showing relatively weak neurokinin 1 receptor expression. The Phox2a cells were also less likely to project to the ipsilateral LPb. Although most Phox2a cells phosphorylated extracellular signal-regulated kinases following noxious heat stimulation, ~ 20% did not, and these were significantly smaller than the activated cells. This suggests that those ALS neurons that respond selectively to skin cooling, which have small cell bodies, may be included among the Phox2a population. Previous studies have defined neurochemical populations among the ALS cells, based on expression of Tac1 or Gpr83. However, we found that the proportions of Phox2a cells that expressed these genes were similar to the proportions reported for all lamina I ALS neurons, suggesting that Phox2a is not differentially expressed among cells belonging to these populations. Finally, we used a mouse line that resulted in membrane labelling of the Phox2a cells and showed that they all possess dendritic spines, although at a relatively low density. However, the distribution of the postsynaptic protein Homer revealed that dendritic spines accounted for a minority of the excitatory synapses on these cells. Our results confirm that Phox2a-positive cells in lamina I are ALS neurons, but show that the Phox2a::Cre line preferentially captures specific types of ALS cells