Far-from-equilibrium distribution from near-steady-state work fluctuations

A long-standing goal of nonequilibrium statistical mechanics has been to extend the conceptual power of the Boltzmann distribution to driven systems. We report some new progress towards this goal. Instead of writing the nonequilibrium steady-state distribution in terms of perturbations around thermal equilibrium, we start from the linearized driven dynamics of observables about their stable fixed point, and expand in the strength of the nonlinearities encountered during typical fluctuations away from the fixed point. The first terms in this expansion retain the simplicity of known expansions about equilibrium, but can correctly describe the statistics of a certain class of systems even under strong driving. We illustrate this approach by comparison with a numerical simulation of a sheared Brownian colloid, where we find that the first two terms in our expansion are sufficient to account for the shear thinning behavior at high shear rates.American Society for Engineering Education. National Defense Science and Engineering Graduate Fellowship (32 CRF 168a

Current understanding of the bi-directional relationship of major depression with inflammation

Consistent evidence links major depression and its affective components to negative health outcomes. Although the pathways of these effects are likely complex and multifactorial, recent evidence suggests that innate inflammatory processes may play a role. An overview of current literature suggests that pathways between negative moods and inflammation are bi-directional. Indeed, negative moods activate peripheral physiologic mechanisms that result in an up regulation of systemic levels of inflammation. Conversely, peripheral inflammatory mediators signal the brain to affect behavioral, affective and cognitive changes that are consistent with symptoms of major depressive disorder. It is likely that these pathways are part of a complex feedback loop that involves the nervous, endocrine, and immune systems and plays a role in the modulation of peripheral inflammatory responses to central and peripheral stimuli, in central responses to peripheral immune activation and in the maintenance of homeostatic balance. Further research is warranted to fully understand the role of central processes in this feedback loop, which likely contributes to the pathophysiology of mental and physical health

Statistical Physics of Adaptation

Whether by virtue of being prepared in a slowly relaxing, high-free energy initial condition, or because they are constantly dissipating energy absorbed from a strong external drive, many systems subject to thermal fluctuations are not expected to behave in the way they would at thermal equilibrium. Rather, the probability of finding such a system in a given microscopic arrangement may deviate strongly from the Boltzmann distribution, raising the question of whether thermodynamics still has anything to tell us about which arrangements are the most likely to be observed. In this work, we build on past results governing nonequilibrium thermodynamics and define a generalized Helmholtz free energy that exactly delineates the various factors that quantitatively contribute to the relative probabilities of different outcomes in far-from-equilibrium stochastic dynamics. By applying this expression to the analysis of two examples—namely, a particle hopping in an oscillating energy landscape and a population composed of two types of exponentially growing self-replicators—we illustrate a simple relationship between outcome-likelihood and dissipative history. In closing, we discuss the possible relevance of such a thermodynamic principle for our understanding of self-organization in complex systems, paying particular attention to a possible analogy to the way evolutionary adaptations emerge in living things.United States. Air Force Office of Scientific Research (32 CFR 168a

Geodesic Warps by Conformal Mappings

In recent years there has been considerable interest in methods for diffeomorphic warping of images, with applications e.g.\ in medical imaging and evolutionary biology. The original work generally cited is that of the evolutionary biologist D'Arcy Wentworth Thompson, who demonstrated warps to deform images of one species into another. However, unlike the deformations in modern methods, which are drawn from the full set of diffeomorphism, he deliberately chose lower-dimensional sets of transformations, such as planar conformal mappings. In this paper we study warps of such conformal mappings. The approach is to equip the infinite dimensional manifold of conformal embeddings with a Riemannian metric, and then use the corresponding geodesic equation in order to obtain diffeomorphic warps. After deriving the geodesic equation, a numerical discretisation method is developed. Several examples of geodesic warps are then given. We also show that the equation admits totally geodesic solutions corresponding to scaling and translation, but not to affine transformations

Retrospective case note review of chronic spontaneous urticaria outcomes and adverse effects in patients treated with omalizumab or ciclosporin in UK secondary care.

BACKGROUND: Omalizumab is approved in the UK as add-on treatment for chronic spontaneous urticaria (CSU) in patients with inadequate response to H1-antihistamines. Ciclosporin is an established but unlicensed 3rd line option for CSU. Two parallel retrospective observational studies were conducted to describe outcomes of treatment and adverse events with omalizumab or ciclosporin for CSU treatment. METHODS: Data from UK specialist centres prescribing omalizumab (five centres) or ciclosporin (three centres) in CSU patients were collected from hospital records by clinical staff and pooled for analysis. RESULTS: Forty-six patients prescribed omalizumab and 72 patients prescribed ciclosporin were included. Twenty-two (48%) omalizumab-treated patients had paired Urticaria Activity Scores (UAS7), showing a 25.4 point improvement during treatment (P < 0.0001). Paired Dermatology Life Quality Index (DLQI) was available in 28 (61%) omalizumab-treated and 17 (24%) ciclosporin-treated patients. At least a 75% improvement in DLQI score was observed in 79% of omalizumab-treated and 41% of ciclosporin-treated patients, and 65% of omalizumab-treated patients had complete resolution of their quality-of-life impairment (DLQI 0-1) versus 21% of ciclosporin-treated patients. Clinician comments reported symptom clearance in 15/36 (42%) omalizumab-treated and 10/60 (17%) ciclosporin-treated patients. Proportions of patients with adverse events were similar but those for omalizumab resembled CSU symptoms, making causality assignment difficult, whereas those for ciclosporin were consistent with its known adverse effect profile. CONCLUSIONS: Validated patient-reported measures of disease severity and quality of life should be used routinely in CSU management. Based on clinician comments and DLQI scores, symptoms and quality of life showed a greater improvement in the omalizumab-treated cohort than in the ciclosporin-treated cohort

Coping strategies adopted by small-scale farmers in Tanzania and Kenya to counteract problems caused by storage pests, particularly the Larger Grain Borer

Final Technical Report, Project R 6952 (1 May 1997 - 31 December 1998)

The Intestinal Microbiota Contributes to the Ability of Helminths to Modulate Allergic Inflammation

We thank Manuel Kulagin for technical help, Pierre Bonnaventure for portal vein blood sampling, Francisco Sepulveda for technical assistance in GS-MS acquisition, and Dorothee Hahne (Metabolomics Australia, University of Western Australia) for human samples SCFA isolation, acquisition, and analysis. We also thank Cristina Cartoni (Phenotyping Unit, EPFL) for Milliplex analysis, Jessica Dessimoz and her team from the Histology Core Facility (EPFL), Miguel Garcia and his team from the Flow Cytometry Core Facility (EPFL), and staff from the EPFL CPG animal house for excellent animal care. The computations were partially performed at the Vital-IT Center for high-performance computing of the SIB Swiss Institute of Bioinformatics (http://www.vital-it.ch). The research leading to these results has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP/2007-2013) / ERC Grant Agreement n. 310948. Funding for A.W.W. and a subset of the 16S rRNA gene sequencing was provided by the Wellcome Trust (grant number WT 098051). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Diabetes UK evidence-based nutrition guidelines for the prevention and management of diabetes

A summary of the latest evidence‐based nutrition guidelines for the prevention and management of diabetes is presented. These guidelines are based on existing recommendations last published in 2011, and were formulated by an expert panel of specialist dietitians after a literature review of recent evidence. Recommendations have been made in terms of foods rather than nutrients wherever possible. Guidelines for education and care delivery, prevention of Type 2 diabetes, glycaemic control for Type 1 and Type 2 diabetes, cardiovascular disease risk management, management of diabetes‐related complications, other considerations including comorbidities, nutrition support, pregnancy and lactation, eating disorders, micronutrients, food supplements, functional foods, commercial diabetic foods and nutritive and non‐nutritive sweeteners are included. The sections on pregnancy and prevention of Type 2 diabetes have been enlarged and the weight management section modified to include considerations of remission of Type 2 diabetes. A section evaluating detailed considerations in ethnic minorities has been included as a new topic. The guidelines were graded using adapted ‘GRADE’ methodology and, where strong evidence was lacking, grading was not allocated. These 2018 guidelines emphasize a flexible, individualized approach to diabetes management and weight loss and highlight the emerging evidence for remission of Type 2 diabetes. The full guideline document is available at www.diabetes.org.uk/nutrition-guidelines

The over-reset phenomenon in Ta2O5 RRAM device investigated by the RTN-based defect probing technique

IEEE Despite the tremendous efforts in the past decade devoted to the development of filamentary resistive-switching devices (RRAM), there is still a lack of in-depth understanding of its over-reset phenomenon. At higher reset stop voltages that exceed a certain threshold, the resistance at high resistance state reduces, leading to an irrecoverable window reduction. The over-reset phenomenon limits the maximum resistance window that can be achieved by using a higher Vreset, which also degrades its potential in applications such as multi-level memory and neuromorphic synapses. In this work, the over-reset is investigated by cyclic reset operations with incremental stop voltages, and is explained by defect generation in the filament constriction region of Ta2O5 RRAM devices. This is supported by the statistical spatial defects profile obtained from the random telegraph noise based defect probing technique. The impact of forming compliance current on the over-reset is also evaluated

CD4+ and CD8+ T cells exhibit differential requirements for CCR7-mediated antigen transport during influenza infection

Upon encounter of viral Ags in an inflammatory environment, dendritic cells up-regulate costimulatory molecules and the chemokine receptor CCR7, with the latter being pivotal for their migration to the lymph node. By utilizing mice deficient in CCR7, we have examined the requirement of dendritic cell-mediated Ag transport from the lung to the draining lymph node for the induction of anti-influenza immune responses in vivo. We found that CCR7-mediated migration of dendritic cells was more crucial for CD8(+) T cell than CD4(+) T cell responses. While no specific CD8(+) T cell response could be detected in the airways or lymphoid tissues during the primary infection, prolonged infection in CCR7-deficient mice did result in a sustained inflammatory chemokine profile, which led to nonspecific CD8(+) T cell recruitment to the airways. The recruitment of influenza-specific CD4(+) T cells to the airways was also below levels of detection in the absence of CCR7 signaling, although a small influenza-specific CD4(+) T cell population was detectable in the draining lymph node, which was sufficient for the generation of class-switched anti-influenza Abs and a normal CD4(+) T cell memory population. Overall, our data show that CCR7-mediated active Ag transport is differentially required for CD4(+) and CD8(+) T cell expansion during influenza infection