832 research outputs found

    High-sensitivity diamond magnetometer with nanoscale resolution

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    We present a novel approach to the detection of weak magnetic fields that takes advantage of recently developed techniques for the coherent control of solid-state electron spin quantum bits. Specifically, we investigate a magnetic sensor based on Nitrogen-Vacancy centers in room-temperature diamond. We discuss two important applications of this technique: a nanoscale magnetometer that could potentially detect precession of single nuclear spins and an optical magnetic field imager combining spatial resolution ranging from micrometers to millimeters with a sensitivity approaching few femtotesla/Hz1/2^{1/2}.Comment: 29 pages, 4 figure

    Modeling human mobility responses to the large-scale spreading of infectious diseases

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    Current modeling of infectious diseases allows for the study of realistic scenarios that include population heterogeneity, social structures, and mobility processes down to the individual level. The advances in the realism of epidemic description call for the explicit modeling of individual behavioral responses to the presence of disease within modeling frameworks. Here we formulate and analyze a metapopulation model that incorporates several scenarios of self-initiated behavioral changes into the mobility patterns of individuals. We find that prevalence-based travel limitations do not alter the epidemic invasion threshold. Strikingly, we observe in both synthetic and data-driven numerical simulations that when travelers decide to avoid locations with high levels of prevalence, this self-initiated behavioral change may enhance disease spreading. Our results point out that the real-time availability of information on the disease and the ensuing behavioral changes in the population may produce a negative impact on disease containment and mitigation

    Empirical estimates of prostate cancer overdiagnosis by age and prostate-specific antigen

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    Background: Prostate cancer screening depends on a careful balance of benefits, in terms of reduced prostate cancer mortality, and harms, in terms of overdiagnosis and overtreatment. We aimed to estimate the effect on overdiagnosis of restricting prostate specific antigen (PSA) testing by age and baseline PSA.Methods: Estimates of the effects of age on overdiagnosis were based on population based incidence data from the US Surveillance, Epidemiology and End Results database. To investigate the relationship between PSA and overdiagnosis, we used two separate cohorts subject to PSA testing in clinical trials (n = 1,577 and n = 1,197) and a population-based cohort of Swedish men not subject to PSA-screening followed for 25 years (n = 1,162).Results: If PSA testing had been restricted to younger men, the number of excess cases associated with the introduction of PSA in the US would have been reduced by 85%, 68% and 42% for age cut-offs of 60, 65 and 70, respectively. The risk that a man with screen-detected cancer at age 60 would not subsequently lead to prostate cancer morbidity or mortality decreased exponentially as PSA approached conventional biopsy thresholds. For PSAs below 1 ng/ml, the risk of a positive biopsy is 65 (95% CI 18.2, 72.9) times greater than subsequent prostate cancer mortality.Conclusions: Prostate cancer overdiagnosis has a strong relationship to age and PSA level. Restricting screening in men over 60 to those with PSA above median (>1 ng/ml) and screening men over 70 only in selected circumstances would importantly reduce overdiagnosis and change the ratio of benefits to harms of PSA-screening

    Real-time numerical forecast of global epidemic spreading: Case study of 2009 A/H1N1pdm

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    Background Mathematical and computational models for infectious diseases are increasingly used to support public-health decisions; however, their reliability is currently under debate. Real-time forecasts of epidemic spread using data-driven models have been hindered by the technical challenges posed by parameter estimation and validation. Data gathered for the 2009 H1N1 influenza crisis represent an unprecedented opportunity to validate real-time model predictions and define the main success criteria for different approaches. Methods We used the Global Epidemic and Mobility Model to generate stochastic simulations of epidemic spread worldwide, yielding (among other measures) the incidence and seeding events at a daily resolution for 3,362 subpopulations in 220 countries. Using a Monte Carlo Maximum Likelihood analysis, the model provided an estimate of the seasonal transmission potential during the early phase of the H1N1 pandemic and generated ensemble forecasts for the activity peaks in the northern hemisphere in the fall/winter wave. These results were validated against the real-life surveillance data collected in 48 countries, and their robustness assessed by focusing on 1) the peak timing of the pandemic; 2) the level of spatial resolution allowed by the model; and 3) the clinical attack rate and the effectiveness of the vaccine. In addition, we studied the effect of data incompleteness on the prediction reliability. Results Real-time predictions of the peak timing are found to be in good agreement with the empirical data, showing strong robustness to data that may not be accessible in real time (such as pre-exposure immunity and adherence to vaccination campaigns), but that affect the predictions for the attack rates. The timing and spatial unfolding of the pandemic are critically sensitive to the level of mobility data integrated into the model. Conclusions Our results show that large-scale models can be used to provide valuable real-time forecasts of influenza spreading, but they require high-performance computing. The quality of the forecast depends on the level of data integration, thus stressing the need for high-quality data in population-based models, and of progressive updates of validated available empirical knowledge to inform these models

    Insights into the function of ion channels by computational electrophysiology simulations

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    Ion channels are of universal importance for all cell types and play key roles in cellular physiology and pathology. Increased insight into their functional mechanisms is crucial to enable drug design on this important class of membrane proteins, and to enhance our understanding of some of the fundamental features of cells. This review presents the concepts behind the recently developed simulation protocol Computational Electrophysiology (CompEL), which facilitates the atomistic simulation of ion channels in action. In addition, the review provides guidelines for its application in conjunction with the molecular dynamics software package GROMACS. We first lay out the rationale for designing CompEL as a method that models the driving force for ion permeation through channels the way it is established in cells, i.e., by electrochemical ion gradients across the membrane. This is followed by an outline of its implementation and a description of key settings and parameters helpful to users wishing to set up and conduct such simulations. In recent years, key mechanistic and biophysical insights have been obtained by employing the CompEL protocol to address a wide range of questions on ion channels and permeation. We summarize these recent findings on membrane proteins, which span a spectrum from highly ion-selective, narrow channels to wide diffusion pores. Finally we discuss the future potential of CompEL in light of its limitations and strengths. This article is part of a Special Issue entitled: Membrane Proteins edited by J.C. Gumbart and Sergei Noskov

    Physics of Neutron Star Crusts

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    The physics of neutron star crusts is vast, involving many different research fields, from nuclear and condensed matter physics to general relativity. This review summarizes the progress, which has been achieved over the last few years, in modeling neutron star crusts, both at the microscopic and macroscopic levels. The confrontation of these theoretical models with observations is also briefly discussed.Comment: 182 pages, published version available at <http://www.livingreviews.org/lrr-2008-10

    Efficient Finite Groups Arising in the Study of Relative Asphericity

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    We study a class of two-generator two-relator groups, denoted Jn(m, k), that arise in the study of relative asphericity as groups satisfying a transitional curvature condition. Particular instances of these groups occur in the literature as finite groups of intriguing orders. Here we find infinite families of non-elementary virtually free groups and of finite metabelian non-nilpotent groups, for which we determine the orders. All Mersenne primes arise as factors of the orders of the non-metacyclic groups in the class, as do all primes from other conjecturally infinite families of primes. We classify the finite groups up to isomorphism and show that our class overlaps and extends a class of groups Fa,b,c with trivalent Cayley graphs that was introduced by C.M.Campbell, H.S.M.Coxeter, and E.F.Robertson. The theory of cyclically presented groups informs our methods and we extend part of this theory (namely, on connections with polynomial resultants) to ?bicyclically presented groups? that arise naturally in our analysis. As a corollary to our main results we obtain new infinite families of finite metacyclic generalized Fibonacci groups

    Changing behaviour 'more or less'-do theories of behaviour inform strategies for implementation and de-implementation? A critical interpretive synthesis

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    BACKGROUND: Implementing evidence-based care requires healthcare practitioners to do less of some things (de-implementation) and more of others (implementation). Variations in effectiveness of behaviour change interventions may result from failure to consider a distinction between approaches by which behaviour increases and decreases in frequency. The distinction is not well represented in methods for designing interventions. This review aimed to identify whether there is a theoretical rationale to support this distinction. METHODS: Using Critical Interpretative Synthesis, this conceptual review included papers from a broad range of fields (biology, psychology, education, business) likely to report approaches for increasing or decreasing behaviour. Articles were identified from databases using search terms related to theory and behaviour change. Articles reporting changes in frequency of behaviour and explicit use of theory were included. Data extracted were direction of behaviour change, how theory was operationalised, and theory-based recommendations for behaviour change. Analyses of extracted data were conducted iteratively and involved inductive coding and critical exploration of ideas and purposive sampling of additional papers to explore theoretical concepts in greater detail. RESULTS: Critical analysis of 66 papers and their theoretical sources identified three key findings: (1) 9 of the 15 behavioural theories identified do not distinguish between implementation and de-implementation (5 theories were applied to only implementation or de-implementation, not both); (2) a common strategy for decreasing frequency was substituting one behaviour with another. No theoretical basis for this strategy was articulated, nor were methods proposed for selecting appropriate substitute behaviours; (3) Operant Learning Theory makes an explicit distinction between techniques for increasing and decreasing frequency. DISCUSSION: Behavioural theories provide little insight into the distinction between implementation and de-implementation. Operant Learning Theory identified different strategies for implementation and de-implementation, but these strategies may not be acceptable in health systems. Additionally, if behaviour substitution is an approach for de-implementation, further investigation may inform methods or rationale for selecting the substitute behaviour

    Priority focus areas for a sub-national response to climate change and health: A South African provincial case study

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    Introduction: The intersection of health and climate change is often absent or under-represented in sub-national government strategies. This analysis of the literature, using a new methodological framework, highlights priority focus areas for a sub-national government response to health and climate change, using the Western Cape (WC) province of South Africa as a case study. Methods: A methodological framework was created to conduct a review of priority focus areas relevant for sub-national governments. The framework encompassed the establishment of a Project Steering Group consisting of relevant, sub-national stakeholders (e.g. provincial officials, public and environmental health specialists and academics); an analysis of local climatic projections as well as an analysis of global, national and sub-national health risk factors and impacts. Results: Globally, the discussion of health and climate change adaptation strategies in sub-national, or provincial government is often limited. For the case study presented, multiple health risk factors were identified. WC climatic projections include a warmer and potentially drier future with an increased frequency and intensity of extreme weather events. WC government priority focus areas requiring further research on health risk factors include: population migration and environmental refugees, land use change, violence and human conflict and vulnerable groups. WC government priority focus areas for further research on health impacts include: mental ill-health, non-communicable diseases, injuries, poisonings (e.g. pesticides), food and nutrition insecurity-related diseases, water- and food-borne diseases and reproductive health. These areas are currently under-addressed, or not addressed at all, in the current provincial climate change strategy. Conclusions: Sub-national government adaptation strategies often display limited discussion on the health and climate change intersect. The methodological framework presented in this case study can be globally utilized by other sub-national governments for decision-making and development of climate change and health adaptation strategies. Additionally, due to the broad range of sectoral issues identified, a primary recommendation from this study is that sub-national governments internationally should consider a “health and climate change in all policies” approach when developing adaptation and mitigation strategies to address climate change
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