Effect of biomechanical footwear on knee pain in people with knee osteoarthritis : the BIOTOK randomized clinical trial

Importance: Individually calibrated biomechanical footwear therapy may improve pain and physical function in people with symptomatic knee osteoarthritis, but the benefits of this therapy are unclear. Objective: To assess the effect of a biomechanical footwear therapy vs control footwear over 24 weeks of follow-up. Design, Setting, and Participants: Randomized clinical trial conducted at a Swiss university hospital. Participants (N = 220) with symptomatic, radiologically confirmed knee osteoarthritis were recruited between April 20, 2015, and January 10, 2017. The last participant visit occurred on August 15, 2017. Interventions: Participants were randomized to biomechanical footwear involving shoes with individually adjustable external convex pods attached to the outsole (n = 111) or to control footwear (n = 109) that had visible outsole pods that were not adjustable and did not create a convex walking surface. Main Outcomes and Measures: The primary outcome was knee pain at 24 weeks of follow-up assessed with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscore standardized to range from 0 (no symptoms) to 10 (extreme symptoms). The secondary outcomes included WOMAC physical function and stiffness subscores and the WOMAC global score, all ranging from 0 (no symptoms) to 10 (extreme symptoms) at 24 weeks of follow-up, and serious adverse events. Results: Among the 220 randomized participants (mean age, 65.2 years [SD, 9.3 years]; 104 women [47.3%]), 219 received the allocated treatment and 213 (96.8%) completed follow-up. At 24 weeks of follow-up, the mean standardized WOMAC pain subscore improved from 4.3 to 1.3 in the biomechanical footwear group and from 4.0 to 2.6 in the control footwear group (between-group difference in scores at 24 weeks of follow-up, -1.3 [95% CI, -1.8 to -0.9]; P < .001). The results were consistent for WOMAC physical function subscore (between-group difference, -1.1 [95% CI, -1.5 to -0.7]), WOMAC stiffness subscore (between-group difference, -1.4 [95% CI, -1.9 to -0.9]), and WOMAC global score (between-group difference, -1.2 [95% CI, -1.6 to -0.8]) at 24 weeks of follow-up. Three serious adverse events occurred in the biomechanical footwear group compared with 9 in the control footwear group (2.7% vs 8.3%, respectively); none were related to treatment. Conclusions and Relevance: Among participants with knee pain from osteoarthritis, use of biomechanical footwear compared with control footwear resulted in an improvement in pain at 24 weeks of follow-up that was statistically significant but of uncertain clinical importance. Further research would be needed to assess long-term efficacy and safety, as well as replication, before reaching conclusions about the clinical value of this device

Schr\"odinger Deformations of AdS_3 x S^3

We study Schr\"odinger invariant deformations of the AdS_3 x S^3 x T^4 (or K3) solution of IIB supergravity and find a large class of solutions with integer and half-integer dynamical exponents. We analyze the supersymmetries preserved by our solutions and find an infinite number of solutions with four supersymmetries. We study the solutions holographically and find that the dual D1-D5 (or F1-NS5) CFT is deformed by irrelevant operators of spin one and two.Comment: 23 page

Holographic flows to IR Lifshitz spacetimes

Recently we studied `vanishing' horizon limits of `boosted' black D3-brane geometry \cite{hsnr}. The type IIB solutions obtained by taking these special double limits were found to describe nonrelativistic Lifshitz spacetimes at zero temperature. In the present work we study these limits for TsT black-hole solutions which include $B$-field. The new Galilean solutions describe a holographic RG flow from Schr\"odinger ($a=2$) spacetime in UV to a Lifshitz universe ($a=3$) in the IR.Comment: 10 pages; v2: A bad typo in eq.8 corrected; v3: Discussion and reference on Kaigorodov spaces included, correction in sec-3, to be published in JHE

The Hydration Structure at Yttria-Stabilized Cubic Zirconia (110)-Water Interface with Sub-Angstrom Resolution

The interfacial hydration structure of yttria-stabilized cubic zirconia (110) surface in contact with water was determined with ~0.5&amp;#8201;&amp;Aring; resolution by high-resolution X-ray reflectivity measurement. The terminal layer shows a reduced electron density compared to the following substrate lattice layers, which indicates there are additional defects generated by metal depletion as well as intrinsic oxygen vacancies, both of which are apparently filled by water species. Above this top surface layer, two additional adsorbed layers are observed forming a characteristic interfacial hydration structure. The first adsorbed layer shows abnormally high density as pure water and likely includes metal species, whereas the second layer consists of pure water. The observed interfacial hydration structure seems responsible for local equilibration of the defective surface in water and eventually regulating the long-term degradation processes. The multitude of water interactions with the zirconia surface results in the complex but highly ordered interfacial structure constituting the reaction front.ope

The a-theorem and conformal symmetry breaking in holographic RG flows

We study holographic models describing an RG flow between two fixed points driven by a relevant scalar operator. We show how to introduce a spurion field to restore Weyl invariance and compute the anomalous contribution to the generating functional in even dimensional theories. We find that the coefficient of the anomalous term is proportional to the difference of the conformal anomalies of the UV and IR fixed points, as expected from anomaly matching arguments in field theory. For any even dimensions the coefficient is positive as implied by the holographic a-theorem. For flows corresponding to spontaneous breaking of conformal invariance, we also compute the two-point functions of the energy-momentum tensor and the scalar operator and identify the dilaton mode. Surprisingly we find that in the simplest models with just one scalar field there is no dilaton pole in the two-point function of the scalar operator but a stronger singularity. We discuss the possible implications.Comment: 50 pages. v2: minor changes, added references, extended discussion. v3: we have clarified some of the calculations and assumptions, results unchanged. v4: published version in JHE

Constructing Lifshitz solutions from AdS

Under general assumptions, we show that a gravitational theory in d+1 dimensions admitting an AdS solution can be reduced to a d-dimensional theory containing a Lifshitz solution with dynamical exponent z=2. Working in a d=4, N=2 supergravity setup, we prove that if the AdS background is N=2 supersymmetric, then the Lifshitz geometry preserves 1/4 of the supercharges, and we construct the corresponding Killing spinors. We illustrate these results in examples from supersymmetric consistent truncations of type IIB supergravity, enhancing the class of known 4-dimensional Lifshitz solutions of string theory. As a byproduct, we find a new AdS4 x S1 x T(1,1) solution of type IIB.Comment: 29 pages, no figures; v2 minor corrections, a reference adde

Lifshitz black holes in string theory

We provide the first black hole solutions with Lifshitz asymptotics found in string theory. These are expected to be dual to models enjoying anisotropic scale invariance with dynamical exponent z=2 at finite temperature. We employ a consistent truncation of type IIB supergravity to four dimensions with an arbitrary 5-dimensional Einstein manifold times a circle as internal geometry. New interesting features are found that significantly differ from previous results in phenomenological models. In particular, small black holes are shown to be thermodynamically unstable, analogously to the usual AdS-Schwarzschild black holes, and extremality is never reached. This signals a possible Hawking-Page like phase transition at low temperatures.Comment: 19 pages, 7 figures. v2 references adde

Holography for chiral scale-invariant models

Deformation of any d-dimensional conformal field theory by a constant null source for a vector operator of dimension (d + z -1) is exactly marginal with respect to anisotropic scale invariance, of dynamical exponent z. The holographic duals to such deformations are AdS plane waves, with z=2 being the Schrodinger geometry. In this paper we explore holography for such chiral scale-invariant models. The special case of z=0 can be realized with gravity coupled to a scalar, and is of particular interest since it is related to a Lifshitz theory with dynamical exponent two upon dimensional reduction. We show however that the corresponding reduction of the dual field theory is along a null circle, and thus the Lifshitz theory arises upon discrete light cone quantization of an anisotropic scale invariant field theory.Comment: 62 pages; v2, published version, minor improvements and references adde

Quark Number Susceptibility with Finite Chemical Potential in Holographic QCD

We study the quark number susceptibility in holographic QCD with a finite chemical potential or under an external magnetic field at finite temperature. We first consider the quark number susceptibility with the chemical potential. We observe that approaching the critical temperature from high temperature regime, the quark number susceptibility divided by temperature square develops a peak as we increase the chemical potential, which confirms recent lattice QCD results. We discuss this behavior in connection with the existence of the critical end point in the QCD phase diagram. We also consider the quark number susceptibility under the external magnetic field. We predict that the quark number susceptibility exhibits a blow-up behavior at low temperature as we raise the value of the magnetic field. We finally spell out some limitations of our study.Comment: 25 pages, 3 figures, published versio

Cryptosporidium Priming Is More Effective than Vaccine for Protection against Cryptosporidiosis in a Murine Protein Malnutrition Model

Cryptosporidium is a major cause of severe diarrhea, especially in malnourished children. Using a murine model of C. parvum oocyst challenge that recapitulates clinical features of severe cryptosporidiosis during malnutrition, we interrogated the effect of protein malnutrition (PM) on primary and secondary responses to C. parvum challenge, and tested the differential ability of mucosal priming strategies to overcome the PM-induced susceptibility. We determined that while PM fundamentally alters systemic and mucosal primary immune responses to Cryptosporidium, priming with C. parvum (106 oocysts) provides robust protective immunity against re-challenge despite ongoing PM. C. parvum priming restores mucosal Th1-type effectors (CD3+CD8+CD103+ T-cells) and cytokines (IFNγ, and IL12p40) that otherwise decrease with ongoing PM. Vaccination strategies with Cryptosporidium antigens expressed in the S. Typhi vector 908htr, however, do not enhance Th1-type responses to C. parvum challenge during PM, even though vaccination strongly boosts immunity in challenged fully nourished hosts. Remote non-specific exposures to the attenuated S. Typhi vector alone or the TLR9 agonist CpG ODN-1668 can partially attenuate C. parvum severity during PM, but neither as effectively as viable C. parvum priming. We conclude that although PM interferes with basal and vaccine-boosted immune responses to C. parvum, sustained reductions in disease severity are possible through mucosal activators of host defenses, and specifically C. parvum priming can elicit impressively robust Th1-type protective immunity despite ongoing protein malnutrition. These findings add insight into potential correlates of Cryptosporidium immunity and future vaccine strategies in malnourished children