The Impact of Disease-Modifying Therapy Access Barriers on People With Multiple Sclerosis: Mixed-Methods Study.

BACKGROUND: In the United States, people with relapsing-remitting multiple sclerosis (RRMS) can face difficulty accessing disease-modifying therapies (DMTs) because of insurance, pharmacy, or provider policies. These barriers have been associated with poor adherence and negative health outcomes. OBJECTIVE: The goals of this study were to describe the overall occurrence of difficulties and delays associated with gaining access to DMTs among people with RRMS, to assess DMT adherence during periods of reduced access, and to contextualize the patients\u27 journey from receipt of a prescription for DMT to obtaining and taking their medication when faced with access barriers. METHODS: We recruited US-based adults self-reporting RRMS from a Web-based health data-sharing social network, PatientsLikeMe. Individuals were invited to complete a Web-based survey if they reported a diagnosis of RRMS and were prescribed a DMT for MS. Follow-up phone interviews were conducted with 10 respondents who reported experiencing an MS-related relapse during the time they had experienced challenges accessing DMTs. RESULTS: Among 507 survey completers, nearly half were either currently experiencing an issue related to DMT assess or had difficulty accessing a DMT in the past (233/507, 46.0%). The most frequently reported reasons for access difficulty were authorization requirements by insurance companies (past issues: 78/182, 42.9%; current issues: 9/42, 21%) and high out-of-pocket costs (past issues: 54/182, 29.7%; current issues: 13/42, 31%). About half (20/39, 51%) of participants with current access issues and over a third (68/165, 41.2%) of those with past issues went without their medication until they could access their prescribed DMT. Relapses were reported during periods of reduced DMT access for almost half (56/118, 47.5%) of those with past issues and nearly half (22/45, 49%) of those with current issues. Resolving access issues involved multiple stakeholder agents often coordinated in a patient-led effort. Among those who had resolved issues, about half (57/119, 47.9%) reported that doctors or office staff were involved, under half (48/119, 40.3%) were involved themselves, and about a third (39/119, 32.8%) reported the drug manufacturer was involved in resolving the issue. Follow-up interviews revealed that the financial burden associated with obtaining a prescribed DMT led to nonadherence. Additionally, participants felt that DMT treatment delays and stress associated with obtaining the DMT triggered relapses or worsened their MS. CONCLUSIONS: This study expands current research by using a patient-centered, mixed-methods approach to describe barriers to MS treatment, the process to resolve barriers, and the perceived impact of treatment barriers on outcomes. Issues related to DMT access occur frequently, with individuals often serving as their own agents when navigating access difficulties to obtain their medication(s). Support for resolution of DMT access is needed to prevent undue stress and nonadherence

Spontaneous Ratchet Effect in a Granular Gas

The spontaneous clustering of a vibrofluidized granular gas is employed to generate directed transport in two different compartmentalized systems: a "granular fountain" in which the transport takes the form of convection rolls, and a "granular ratchet" with a spontaneous particle current perpendicular to the direction of energy input. In both instances, transport is not due to any system-intrinsic anisotropy, but arises as a spontaneous collective symmetry breaking effect of many interacting granular particles. The experimental and numerical results are quantitatively accounted for within a flux model.Comment: 4 pages, 5 figures; Fig. 4 has been reduced in size and qualit

Lymphotoxins and cytomegalovirus cooperatively induce interferon-beta, establishing host-virus détente

Tumor necrosis factor (TNF)-related cytokines regulate cell death and survival and provide strong selective pressures for viruses, such as cytomegalovirus (CMV), to evolve counterstrategies in order to persist in immune-competent hosts. Signaling by the lymphotoxin (LT)-β receptor or TNF receptor-1, but not Fas or TRAIL receptors, inhibits the cytopathicity and replication of human CMV by a nonapoptotic, reversible process that requires nuclear factor κB (NF-κB)-dependent induction of interferon-β (IFN-β). Efficient induction of IFN-β requires virus infection and LT signaling, demonstrating the need for both host and viral factors in the curtailment of viral replication without cellular elimination. LTα-deficient mice and LTβR-Fc transgenic mice were profoundly susceptible to murine CMV infection. Together, these results reveal an essential and conserved role for LTs in establishing host defense to CMV

Thermal Charm Production in Quark-Gluon Plasma at LHC

Charm production from the quark-gluon plasma created in the midrapidity of central heavy ion collisions at the Large Hadron Collider (LHC) is studied in the next-to-leading order in QCD. Using a schematic longitudinally boost-invariant and transversally expanding fire-cylinder model, we find that charm production could be appreciably enhanced at LHC as a result of the high temperature that is expected to be reached in the produced quark-gluon plasma. Sensitivities of our results to the number of charm quark pairs produced from initial hard scattering, the initial thermalization time and temperature of the quark-gluon plasma, and the charm quark mass are also studied.Comment: 8 pages, 9 figures; adding a figure and relevant discussion on the sensitivity of our results to the number of charm quark pairs produced from initial hard scattering. Version accepted for publication in PR

Antrodia cinnamomea reduces obesity and modulates the gut microbiota in high-fat diet-fed mice.

BackgroundObesity is associated with gut microbiota dysbiosis, disrupted intestinal barrier and chronic inflammation. Given the high and increasing prevalence of obesity worldwide, anti-obesity treatments that are safe, effective and widely available would be beneficial. We examined whether the medicinal mushroom Antrodia cinnamomea may reduce obesity in mice fed with a high-fat diet (HFD).MethodsMale C57BL/6J mice were fed a HFD for 8 weeks to induce obesity and chronic inflammation. The mice were treated with a water extract of A. cinnamomea (WEAC), and body weight, fat accumulation, inflammation markers, insulin sensitivity and the gut microbiota were monitored.ResultsAfter 8 weeks, the mean body weight of HFD-fed mice was 39.8±1.2 g compared with 35.8±1.3 g for the HFD+1% WEAC group, corresponding to a reduction of 4 g or 10% of body weight (P<0.0001). WEAC supplementation reduced fat accumulation and serum triglycerides in a statistically significant manner in HFD-fed mice. WEAC also reversed the effects of HFD on inflammation markers (interleukin-1β, interleukin-6, tumor necrosis factor-α), insulin resistance and adipokine production (leptin and adiponectin). Notably, WEAC increased the expression of intestinal tight junctions (zonula occludens-1 and occludin) and antimicrobial proteins (Reg3g and lysozyme C) in the small intestine, leading to reduced blood endotoxemia. Finally, WEAC modulated the composition of the gut microbiota, reducing the Firmicutes/Bacteroidetes ratio and increasing the level of Akkermansia muciniphila and other bacterial species associated with anti-inflammatory properties.ConclusionsSupplementation with A. cinnamomea produces anti-obesogenic, anti-inflammatory and antidiabetic effects in HFD-fed mice by maintaining intestinal integrity and modulating the gut microbiota

The Electromagnetic Mass Differences of Pions and Kaons

We use the Cottingham method to calculate the pion and kaon electromagnetic mass differences with as few model dependent inputs as possible. The constraints of chiral symmetry at low energy, QCD at high energy and experimental data in between are used in the dispersion relation. We find excellent agreement with experiment for the pion mass difference. The kaon mass difference exhibits a strong violation of the lowest order prediction of Dashen's theorem, in qualitative agreement with several other recent calculations.Comment: 40 pages, Latex, needs axodraw. and psfig. macros, 4 figure

Discrete Morse functions for graph configuration spaces

We present an alternative application of discrete Morse theory for two-particle graph configuration spaces. In contrast to previous constructions, which are based on discrete Morse vector fields, our approach is through Morse functions, which have a nice physical interpretation as two-body potentials constructed from one-body potentials. We also give a brief introduction to discrete Morse theory. Our motivation comes from the problem of quantum statistics for particles on networks, for which generalized versions of anyon statistics can appear.Comment: 26 page

Hadron widths in mixed-phase matter

We derive classically an expression for a hadron width in a two-phase region of hadron gas and quark-gluon plasma (QGP). The presence of QGP gives hadrons larger widths than they would have in a pure hadron gas. We find that the $\phi$ width observed in a central Au+Au collision at $\sqrt{s}=200$ GeV/nucleon is a few MeV greater than the width in a pure hadron gas. The part of observed hadron widths due to QGP is approximately proportional to $(dN/dy)^{-1/3}$.Comment: 8 pages, latex, no figures, KSUCNR-002-9

Color-octet mechanism and J/psi polarization at LEP

Polarized heavy quarkonium productions in $Z^0$ decays are considered. We find that polarizations of the produced quarkonia are independent of that of the parent Z^0 provided that one considers the energy distribution or the total production rate. Produced J/psi's via the color-octet and the color- singlet mechanisms are expected to be 19% and 29% longitudinally polarized, respectively. The energy dependence of eta_{1,8}(x)=\frac{dGamma_{1,8}^L}{dx} /\frac{dGamma_{1,8}}{d x} is very sensitive to the production mechanism, and therefore the measurement of \eta(x)_exp will be an independent probe of the color-octet mechanism.Comment: 15 pages, minor changes, version to be published in Phys. Rev.

A fast ILP-based Heuristic for the robust design of Body Wireless Sensor Networks

We consider the problem of optimally designing a body wireless sensor network, while taking into account the uncertainty of data generation of biosensors. Since the related min-max robustness Integer Linear Programming (ILP) problem can be difficult to solve even for state-of-the-art commercial optimization solvers, we propose an original heuristic for its solution. The heuristic combines deterministic and probabilistic variable fixing strategies, guided by the information coming from strengthened linear relaxations of the ILP robust model, and includes a very large neighborhood search for reparation and improvement of generated solutions, formulated as an ILP problem solved exactly. Computational tests on realistic instances show that our heuristic finds solutions of much higher quality than a state-of-the-art solver and than an effective benchmark heuristic.Comment: This is the authors' final version of the paper published in G. Squillero and K. Sim (Eds.): EvoApplications 2017, Part I, LNCS 10199, pp. 1-17, 2017. DOI: 10.1007/978-3-319-55849-3\_16. The final publication is available at Springer via http://dx.doi.org/10.1007/978-3-319-55849-3_1