Tracking daily fatigue fluctuations in multiple sclerosis : ecological momentary assessment provides unique insights

The preparation of this manuscript was supported by a UK Economic and Social Research Council (ESRC) PhD studentship (ES/1026266/1) awarded to DP. The study was funded by the Psychology Unit at the University of Southampton. The authors declare that they have no conflict of interest. The authors thank all participants of this study. Open access via Springer Compact Agreement.Peer reviewedPublisher PD

Prompting consumers to make healthier food choices in hospitals : a cluster randomised controlled trial

Funding The study was funded by the Royal Society of Edinburgh through a Sabbatical Research Award to JA (Award ID: 59117). DP is supported by the strategic research programme funded by the Scottish Government’s Rural and Environment Science and Analytical Services Division Acknowledgements The authors wish to thank the Royal Voluntary Service for hosting the study and in particular Andrew Roberts, Philip Hurley and Steven Waite for enabling access to the necessary sites, retail staff and purchasing data.Peer reviewedPublisher PD

Univariate Probability Distributions

We describe a web-based interactive graphic that can be used as a resource in introductory classes in mathematical statistics. This interactive graphic presents 76 common univariate distributions and gives details on (a) various features of the distribution such as the functional form of the probability density function and cumulative distribution function, graphs of the probability density function for various parameter settings, and values of population moments; (b) properties that the distribution possesses, for example, linear combinations of independent random variables from a particular distribution family also belong to the same distribution family; and (c) relationships between the various distributions, including special cases, transformations, limiting distributions, and Bayesian relationships. The interactive graphic went online on 11/30/12 at the URL www.math.wm.edu/ leemis/chart/UDR/UDR.html

DEVELOPMENTAL ORIGINS OF METABOLIC DISEASES

Almost 2 billion adults in the world are overweight, and more than half of them are classified as obese, while nearly one-third of children globally experience poor growth and development. Given the vast amount of knowledge that has been gleaned from decades of research on growth and development, a number of questions remain as to why the world is now in the midst of a global epidemic of obesity accompanied by the “double burden of malnutrition,” where overweight coexists with underweight and micronutrient deficiencies. This challenge to the human condition can be attributed to nutritional and environmental exposures during pregnancy that may program a fetus to have a higher risk of chronic diseases in adulthood. To explore this concept, frequently called the developmental origins of health and disease (DOHaD), this review considers a host of factors and physiological mechanisms that drive a fetus or child toward a higher risk of obesity, fatty liver disease, hypertension, and/or type 2 diabetes (T2D). To that end, this review explores the epidemiology of DOHaD with discussions focused on adaptations to human energetics, placental development, dysmetabolism, and key environmental exposures that act to promote chronic diseases in adulthood. These areas are complementary and additive in understanding how providing the best conditions for optimal growth can create the best possible conditions for lifelong health. Moreover, understanding both physiological as well as epigenetic and molecular mechanisms for DOHaD is vital to most fully address the global issues of obesity and other chronic diseases

A Brachistochrone Approach to Reconstruct the Inflaton Potential

We propose a new way to implement an inflationary prior to a cosmological dataset that incorporates the inflationary observables at arbitrary order. This approach employs an exponential form for the Hubble parameter $H(\phi)$ without taking the slow-roll approximation. At lowest non-trivial order, this $H(\phi)$ has the unique property that it is the solution to the brachistochrone problem for inflation.Comment: 13 pages, 2 figures, version matches published versio

Plans, Takes, and Mis-takes

This paper analyzes what may have been a mistake bypianist Thelonious Monk playing a jazz solo in 1958.Even in a Monk composition designed for patternedmayhem, a note can sound out of pattern. We reframethe question of whether the note was a mistake and askinstead about how Monk handles the problem. Amazingly,he replays the note into a new pattern that resituatesits jarring effect in retrospect. The mistake, orbetter, the mis-take, was “saved” by subsequent notes.Our analysis, supported by reflections from jazz musiciansand the philosopher John Dewey, encourages areformulation of plans, takes, and mis-takes as categoriesfor the interpretation of contingency, surprise, andrepair in all human activities. A final section suggeststhat mistakes are essential to the practical plying andplaying of knowledge into performances, particularlythose that highlight learning

CAR-T Cells Hit the Tumor Microenvironment: Strategies to Overcome Tumor Escape

Chimeric antigen receptor (CAR) T cell therapies have demonstrated remarkable efficacy for the treatment of hematological malignancies. However, in patients with solid tumors, objective responses to CAR-T cell therapy remain sporadic and transient. A major obstacle for CAR-T cells is the intrinsic ability of tumors to evade immune responses. Advanced solid tumors are largely composed of desmoplastic stroma and immunosuppressive modulators, and characterized by aberrant cell proliferation and vascularization, resulting in hypoxia and altered nutrient availability. To mount a curative response after infusion, CAR-T cells must infiltrate the tumor, recognize their cognate antigen and perform their effector function in this hostile tumor microenvironment, to then differentiate and persist as memory T cells that confer long-term protection. Fortunately, recent advances in synthetic biology provide a wide set of tools to genetically modify CAR-T cells to overcome some of these obstacles. In this review, we provide a comprehensive overview of the key tumor intrinsic mechanisms that prevent an effective CAR-T cell antitumor response and we discuss the most promising strategies to prevent tumor escape to CAR-T cell therapy