Minimal Brownian Ratchet: An Exactly Solvable Model

We develop an exactly-solvable three-state discrete-time minimal Brownian ratchet (MBR), where the transition probabilities between states are asymmetric. By solving the master equations we obtain the steady-state probabilities. Generally the steady-state solution does not display detailed balance, giving rise to an induced directional motion in the MBR. For a reduced two-dimensional parameter space we find the null-curve on which the net current vanishes and detailed balance holds. A system on this curve is said to be balanced. On the null-curve, an additional source of external random noise is introduced to show that a directional motion can be induced under the zero overall driving force. We also indicate the off-balance behavior with biased random noise.Comment: 4 pages, 4 figures, RevTex source, General solution added. To be appeared in Phys. Rev. Let

An analysis of C.difficile Environmental Contamination During and Following Treatment for C.difficile Infection

Background: Lower Clostridium difficile spore counts in feces from C difficile infection (CDI) patients treated with fidaxomicin versus vancomycin have been observed. We aimed to determine whether environmental contamination is lower in patients treated with fidaxomicin compared with those treated with vancomycin/metronidazole. Methods: The CDI cases were recruited at 4 UK hospitals (Leeds, Bradford, and London [2 centers]). Environmental samples (5 room sites) were taken pretreatment and at 2–3, 4–5, 6–8, and 9–12 days of treatment, end of treatment (EOT), and post-EOT. Fecal samples were collected at diagnosis and as often as produced thereafter. Swabs/feces were cultured for C difficile; percentage of C difficile-positive samples and C difficile bioburden were compared between different treatment arms at each time point. Results: Pre-EOT (n = 244), there was a significant reduction in environmental contamination (≥1 site positive) around fidaxomicin versus vancomycin/metronidazole recipients at days 4–5 (30% vs 50% recipients, P = .04) and at days 9–12 (22% vs 49%, P = .005). This trend was consistently seen at all other timepoints, but it was not statistically significant. No differences were seen between treatment groups post-EOT (n = 76). Fidaxomicin-associated fecal positivity rates and colony counts were consistently lower than those for vancomycin/metronidazole from days 4 to 5 of treatment (including post-EOT); however, the only significant difference was in positivity rate at days 9–12 (15% vs 55%, P = .03). Conclusions: There were significant reductions in C difficile recovery from both feces and the environment around fidaxomicin versus vancomycin/metronidazole recipients. Therefore, fidaxomicin treatment may lower the C difficile transmission risk by reducing excretion and environmental contamination

Monte-Carlo Simulations of the Dynamical Behavior of the Coulomb Glass

We study the dynamical behavior of disordered many-particle systems with long-range Coulomb interactions by means of damage-spreading simulations. In this type of Monte-Carlo simulations one investigates the time evolution of the damage, i.e. the difference of the occupation numbers of two systems, subjected to the same thermal noise. We analyze the dependence of the damage on temperature and disorder strength. For zero disorder the spreading transition coincides with the equilibrium phase transition, whereas for finite disorder, we find evidence for a dynamical phase transition well below the transition temperature of the pure system.Comment: 10 pages RevTeX, 8 Postscript figure

Critical behavior in 2+1 dimensional black holes

The critical behavior and phase transition in the 2+1 dimensional Ba\~nados, Teitelboim, and Zanelli (BTZ) black holes are discussed. By calculating the equilibrium thermodynamic fluctuations in the microcanonical ensemble, canonical ensemble, and grand canonical ensemble, respectively, we find that the extremal spinning BTZ black hole is a critical point, some critical exponents satisfy the scaling laws of the ``first kind'', and the scaling laws related to the correlation length suggest that the effective spatial dimension of extremal black holes is one, which is in agreement with the argument that the extremal black holes are the Bogomol'nyi saturated string states. In addition, we find that the massless BTZ black hole is a critical point of spinless BTZ black holes.Comment: RevTex, 9 pages, nofigur

Instantaneous Normal Mode Analysis of Supercooled Water

We use the instantaneous normal mode approach to provide a description of the local curvature of the potential energy surface of a model for water. We focus on the region of the phase diagram in which the dynamics may be described by the mode-coupling theory. We find, surprisingly, that the diffusion constant depends mainly on the fraction of directions in configuration space connecting different local minima, supporting the conjecture that the dynamics are controlled by the geometric properties of configuration space. Furthermore, we find an unexpected relation between the number of basins accessed in equilibrium and the connectivity between them.Comment: 5 pages, 4 figure

Optimal Renormalization Scale and Scheme for Exclusive Processes

We use the BLM method to fix the renormalization scale of the QCD coupling in exclusive hadronic amplitudes such as the pion form factor and the photon-to-pion transition form factor at large momentum transfer. Renormalization-scheme-independent commensurate scale relations are established which connect the hard scattering subprocess amplitudes that control exclusive processes to other QCD observables such as the heavy quark potential and the electron-positron annihilation cross section. The commensurate scale relation connecting the heavy quark potential, as determined from lattice gauge theory, to the photon-to-pion transition form factor is in excellent agreement with $\gamma e \to \pi^0 e$ data assuming that the pion distribution amplitude is close to its asymptotic form $\sqrt{3}f_\pi x(1-x)$. We also reproduce the scaling and normalization of the $\gamma \gamma \to \pi^+ \pi^-$ data at large momentum transfer. Because the renormalization scale is small, we argue that the effective coupling is nearly constant, thus accounting for the nominal scaling behavior of the data. However, the normalization of the space-like pion form factor $F_\pi(Q^2)$ obtained from electroproduction experiments is somewhat higher than that predicted by the corresponding commensurate scale relation. This discrepancy may be due to systematic errors introduced by the extrapolation of the $\gamma^* p \to \pi^+ n$ electroproduction data to the pion pole.Comment: 22 pages, Latex, 7 Latex figures. Several references added, discussion of scale fixing revised for clarity. Final version to appear in Phys. Rev.

A technical framework for costing health workforce retention schemes in remote and rural areas

<p>Abstract</p> <p>Background</p> <p>Increasing the availability of health workers in remote and rural areas through improved health workforce recruitment and retention is crucial to population health. However, information about the costs of such policy interventions often appears incomplete, fragmented or missing, despite its importance for the sound selection, planning, implementation and evaluation of these policies. This lack of a systematic approach to costing poses a serious challenge for strong health policy decisions.</p> <p>Methods</p> <p>This paper proposes a framework for carrying out a costing analysis of interventions to increase the availability of health workers in rural and remote areas with the aim to help policy decision makers. It also underlines the importance of identifying key sources of financing and of assessing financial sustainability.</p> <p>The paper reviews the evidence on costing interventions to improve health workforce recruitment and retention in remote and rural areas, provides guidance to undertake a costing evaluation of such interventions and investigates the role and importance of costing to inform the broader assessment of how to improve health workforce planning and management.</p> <p>Results</p> <p>We show that while the debate on the effectiveness of policies and strategies to improve health workforce retention is gaining impetus and attention, there is still a significant lack of knowledge and evidence about the associated costs. To address the concerns stemming from this situation, key elements of a framework to undertake a cost analysis are proposed and discussed.</p> <p>Conclusions</p> <p>These key elements should help policy makers gain insight into the costs of policy interventions, to clearly identify and understand their financing sources and mechanisms, and to ensure their sustainability.</p

Reactivation of a developmentally silenced embryonic globin gene

The α- and β-globin loci harbor developmentally expressed genes, which are silenced throughout post-natal life. Reactivation of these genes may offer therapeutic approaches for the hemoglobinopathies, the most common single gene disorders. Here, we address mechanisms regulating the embryonically expressed α-like globin, termed ζ-globin. We show that in embryonic erythroid cells, the ζ-gene lies within a ~65 kb sub-TAD (topologically associating domain) of open, acetylated chromatin and interacts with the α-globin super-enhancer. By contrast, in adult erythroid cells, the ζ-gene is packaged within a small (~10 kb) sub-domain of hypoacetylated, facultative heterochromatin within the acetylated sub-TAD and that it no longer interacts with its enhancers. The ζ-gene can be partially re-activated by acetylation and inhibition of histone de-acetylases. In addition to suggesting therapies for severe α-thalassemia, these findings illustrate the general principles by which reactivation of developmental genes may rescue abnormalities arising from mutations in their adult paralogues

Creating a FACETS digital toolkit to promote quality of life of people with multiple sclerosis through Participatory Design

In this paper, we report on the first stages of creating a stand-alone digital toolkit focusing on the homework elements of FACETS (Fatigue: Applying Cognitive behavioural and Energy effectiveness Techniques to lifeStyle). FACETS is an evidence-based face-to-face fatigue management group programme for people with multiple sclerosis. This paper details the participatory design process from requirements elicitation to initial prototyping and how offline activities linked to each session have been mapped in the digitised solution (mobile app)

Motor step size and ATP coupling efficiency of the dsDNA translocase EcoR124I

The Type I restriction-modification enzyme EcoR124I is an archetypical helicase-based dsDNA translocase that moves unidirectionally along the 3′–5′ strand of intact duplex DNA. Using a combination of ensemble and single-molecule measurements, we provide estimates of two physicochemical constants that are fundamental to a full description of motor protein activity—the ATP coupling efficiency (the number of ATP consumed per base pair) and the step size (the number of base pairs transported per motor step). Our data indicate that EcoR124I makes small steps along the DNA of 1 bp in length with 1 ATP consumed per step, but with some uncoupling of the ATPase and translocase cycles occurring so that the average number of ATP consumed per base pair slightly exceeds unity. Our observations form a framework for understanding energy coupling in a great many other motors that translocate along dsDNA rather than ssDNA