Digital Cognitive Behavioral Therapy for Insomnia in Women With Chronic Migraines

Objective/Background: Insomnia commonly co-occurs with chronic migraines (CM). Non-pharmacological treatments for insomnia in CM patients remain understudied. This is a proof-of-concept study, which aims to evaluate the feasibility, acceptability, and preliminary efficacy of a digital cognitive behavioral therapy for insomnia (dCBT-I) for individuals with CM and insomnia (CM-I) in the United States. Methods: We recruited 42 females with CM-I symptoms from a U.S.-based observational cohort and from the general population via advertisements. Within a multiple baseline design, participants were randomized to receive dCBT-I after 2, 4, or 6 weeks of completing baseline sleep diaries. DCBT-I was scrutinized against benchmarks for completion rates (≥90% to complete dCBT-I), acceptability (≥80% to find dCBT-I acceptable), and posttreatment changes in insomnia symptoms (≥50% indicating a clinically relevant improvement in their insomnia symptoms). As a secondary measure, we also reported percentage of individuals reverting to episodic migraines. Results: Out of 42 randomized, 35 (83.3%) completed dCBT-I within the 12 weeks provided. Of these completers, 33 (94.3%) reported being satisfied (n = 16) or very satisfied (n = 17) with treatment. Additionally, 65.7% of completers responded to treatment as per universally accepted criteria for insomnia. Lastly, 34% of completers reverted from CM to episodic migraine. Conclusion: This study provides evidence for the feasibility and acceptability of dCBT-I in patients with CM-I complaints. Effects of improving insomnia and migraines were suggested. These results indicate that a randomized controlled trial is needed to determine the efficacy of dCBT-I in CM patients

Emergence of Anti-Cancer Drug Resistance: Exploring the Importance of the Microenvironmental Niche via a Spatial Model

Practically, all chemotherapeutic agents lead to drug resistance. Clinically, it is a challenge to determine whether resistance arises prior to, or as a result of, cancer therapy. Further, a number of different intracellular and microenvironmental factors have been correlated with the emergence of drug resistance. With the goal of better understanding drug resistance and its connection with the tumor microenvironment, we have developed a hybrid discrete-continuous mathematical model. In this model, cancer cells described through a particle-spring approach respond to dynamically changing oxygen and DNA damaging drug concentrations described through partial differential equations. We thoroughly explored the behavior of our self-calibrated model under the following common conditions: a fixed layout of the vasculature, an identical initial configuration of cancer cells, the same mechanism of drug action, and one mechanism of cellular response to the drug. We considered one set of simulations in which drug resistance existed prior to the start of treatment, and another set in which drug resistance is acquired in response to treatment. This allows us to compare how both kinds of resistance influence the spatial and temporal dynamics of the developing tumor, and its clonal diversity. We show that both pre-existing and acquired resistance can give rise to three biologically distinct parameter regimes: successful tumor eradication, reduced effectiveness of drug during the course of treatment (resistance), and complete treatment failure

A novel system to map protein interactions reveals evolutionarily conserved immune evasion pathways on transmissible cancers

Around 40% of humans and Tasmanian devils (Sarcophilus harrisii) develop cancer in their lifetime, compared to less than 10% for most species. In addition, devils are affected by two of the three known transmissible cancers in mammals. Immune checkpoint immunotherapy has transformed human medicine, but a lack of species-specific reagents has limited checkpoint immunology in most species. We developed a cut-and-paste reagent development system and used the fluorescent fusion protein system to show that immune checkpoint interactions are conserved across 160,000,000 years of evolution, CD200 is highly expressed on transmissible tumor cells, and coexpression of CD200R1 can block CD200 surface expression. The system’s versatility across species was demonstrated by fusing a fluorescent reporter to a camelid-derived nanobody that binds human programmed death ligand 1. The evolutionarily conserved pathways suggest that naturally occurring cancers in devils and other species can be used to advance our understanding of cancer and immunological tolerance.</p

Next-to-next-to-leading order prediction for the photon-to-pion transition form factor

We evaluate the next-to-next-to-leading order corrections to the hard-scattering amplitude of the photon-to-pion transition form factor. Our approach is based on the predictive power of the conformal operator product expansion, which is valid for a vanishing $\beta$-function in the so-called conformal scheme. The Wilson--coefficients appearing in the non-forward kinematics are then entirely determined from those of the polarized deep-inelastic scattering known to next-to-next-to-leading accuracy. We propose different schemes to include explicitly also the conformal symmetry breaking term proportional to the $\beta$-function, and discuss numerical predictions calculated in different kinematical regions. It is demonstrated that the photon-to-pion transition form factor can provide a fundamental testing ground for our QCD understanding of exclusive reactions.Comment: 62 pages LaTeX, 2 figures, 9 tables; typos corrected, some references added, to appear in Phys. Rev.

Spin-Charge Separation in the t−Jt-J Model: Magnetic and Transport Anomalies

A real spin-charge separation scheme is found based on a saddle-point state of the $t-J$ model. In the one-dimensional (1D) case, such a saddle-point reproduces the correct asymptotic correlations at the strong-coupling fixed-point of the model. In the two-dimensional (2D) case, the transverse gauge field confining spinon and holon is shown to be gapped at {\em finite doping} so that a spin-charge deconfinement is obtained for its first time in 2D. The gap in the gauge fluctuation disappears at half-filling limit, where a long-range antiferromagnetic order is recovered at zero temperature and spinons become confined. The most interesting features of spin dynamics and transport are exhibited at finite doping where exotic {\em residual} couplings between spin and charge degrees of freedom lead to systematic anomalies with regard to a Fermi-liquid system. In spin dynamics, a commensurate antiferromagnetic fluctuation with a small, doping-dependent energy scale is found, which is characterized in momentum space by a Gaussian peak at ($\pi/a$, $\pi/a$) with a doping-dependent width ($\propto \sqrt{\delta}$, $\delta$ is the doping concentration). This commensurate magnetic fluctuation contributes a non-Korringa behavior for the NMR spin-lattice relaxation rate. There also exits a characteristic temperature scale below which a pseudogap behavior appears in the spin dynamics. Furthermore, an incommensurate magnetic fluctuation is also obtained at a {\em finite} energy regime. In transport, a strong short-range phase interference leads to an effective holon Lagrangian which can give rise to a series of interesting phenomena including linear-$T$ resistivity and $T^2$ Hall-angle. We discuss the striking similarities of these theoretical features with those found in the high-$T_c$ cuprates and give aComment: 70 pages, RevTex, hard copies of 7 figures available upon request; minor revisions in the text and references have been made; To be published in July 1 issue of Phys. Rev. B52, (1995

Anomalous Heat Conduction and Anomalous Diffusion in Low Dimensional Nanoscale Systems

Thermal transport is an important energy transfer process in nature. Phonon is the major energy carrier for heat in semiconductor and dielectric materials. In analogy to Ohm's law for electrical conductivity, Fourier's law is a fundamental rule of heat transfer in solids. It states that the thermal conductivity is independent of sample scale and geometry. Although Fourier's law has received great success in describing macroscopic thermal transport in the past two hundreds years, its validity in low dimensional systems is still an open question. Here we give a brief review of the recent developments in experimental, theoretical and numerical studies of heat transport in low dimensional systems, include lattice models, nanowires, nanotubes and graphenes. We will demonstrate that the phonon transports in low dimensional systems super-diffusively, which leads to a size dependent thermal conductivity. In other words, Fourier's law is breakdown in low dimensional structures

Engineering serendipity: high-throughput discovery of materials that resist bacterial attachment

Controlling the colonisation of materials by microorganisms is important in a wide range of industries and clinical settings. To date, the underlying mechanisms that govern the interactions of bacteria with material surfaces remain poorly understood, limiting the ab initio design and engineering of biomaterials to control bacterial attachment. Combinatorial approaches involving high-throughput screening have emerged as key tools for identifying materials to control bacterial attachment. The hundreds of different materials assessed using these methods can be carried out with the aid of computational modelling. This approach can develop an understanding of the rules used to predict bacterial attachment to surfaces of non-toxic synthetic materials. Here we outline our view on the state of this field and the challenges and opportunities in this area for the coming years

Two first-in-human studies of xentuzumab, a humanised insulin-like growth factor (IGF)-neutralising antibody, in patients with advanced solid tumours

BACKGROUND: Xentuzumab, an insulin-like growth factor (IGF)-1/IGF-2-neutralising antibody, binds IGF-1 and IGF-2, inhibiting their growth-promoting signalling. Two first-in-human trials assessed the maximum-tolerated/relevant biological dose (MTD/RBD), safety, pharmacokinetics, pharmacodynamics, and activity of xentuzumab in advanced/metastatic solid cancers. METHODS: These phase 1, open-label trials comprised dose-finding (part I; 3 + 3 design) and expansion cohorts (part II; selected tumours; RBD [weekly dosing]). Primary endpoints were MTD/RBD. RESULTS: Study 1280.1 involved 61 patients (part I: xentuzumab 10–1800 mg weekly, n = 48; part II: 1000 mg weekly, n = 13); study 1280.2, 64 patients (part I: 10–3600 mg three-weekly, n = 33; part II: 1000 mg weekly, n = 31). One dose-limiting toxicity occurred; the MTD was not reached for either schedule. Adverse events were generally grade 1/2, mostly gastrointestinal. Xentuzumab showed dose-proportional pharmacokinetics. Total plasma IGF-1 increased dose dependently, plateauing at ~1000 mg/week; at ≥450 mg/week, IGF bioactivity was almost undetectable. Two partial responses occurred (poorly differentiated nasopharyngeal carcinoma and peripheral primitive neuroectodermal tumour). Integration of biomarker and response data by Bayesian Logistic Regression Modeling (BLRM) confirmed the RBD. CONCLUSIONS: Xentuzumab was well tolerated; MTD was not reached. RBD was 1000 mg weekly, confirmed by BLRM. Xentuzumab showed preliminary anti-tumour activity