MicroRNAs as Novel Biomarkers for Breast Cancer

Breast cancer is a complex phenotypically diverse genetic disease, involving a variety of changes in gene expression and structure. Recent advances in molecular profiling technology have made great progress in unravelling the molecular taxonomy of breast cancer, which has shed new light on the aetiology of the disease and also heralded great potential for the development of novel biomarkers and therapeutic targets. Mi(cro)RNAs are a contemporary class of small noncoding endogenous RNA molecules, generating great excitement in the clinical and scientific communities. The recent discovery that miRNA expression is frequently dysregulated in cancer has uncovered an entirely new repertoire of molecular factors upstream of gene expression, which warrants extensive investigation to further elucidate their precise role in malignancy. We present a comprehensive and timely review of the role of miRNAs in cancer: addressing miRNA function, their putative role as oncogenes or tumor suppressors, with a particular emphasis on breast cancer throughout. We discuss the recent discovery of quantifiable circulating cancer-associated miRNAs, which heralds immense potential for their use as novel minimally invasive biomarkers for breast and other cancers. Finally, we comment on the potential role of miRNAs in breast cancer management, particularly in improving current prognostic tools and achieving the goal of individualized cancer treatment

Primary care management for optimized antithrombotic treatment [PICANT]: study protocol for a cluster-randomized controlled trial

Background: Antithrombotic treatment is a continuous therapy that is often performed in general practice and requires careful safety management. The aim of this study is to investigate whether a best practice model that applies major elements of case management, including patient education, can improve antithrombotic management in primary health care in terms of reducing major thromboembolic and bleeding events. Methods: This 24-month cluster-randomized trial will be performed in 690 adult patients from 46 practices. The trial intervention will be a complex intervention involving general practitioners, health care assistants and patients with an indication for oral anticoagulation. To assess adherence to medication and symptoms in patients, as well as to detect complications early, health care assistants will be trained in case management and will use the Coagulation-Monitoring-List (Co-MoL) to regularly monitor patients. Patients will receive information (leaflets and a video), treatment monitoring via the Co-MoL and be motivated to perform self-management. Patients in the control group will continue to receive treatment-as-usual from their general practitioners. The primary endpoint is the combined endpoint of all thromboembolic events requiring hospitalization, and all major bleeding complications. Secondary endpoints are mortality, hospitalization, strokes, major bleeding and thromboembolic complications, severe treatment interactions, the number of adverse events, quality of anticoagulation, health-related quality of life and costs. Further secondary objectives will be investigated to explain the mechanism by which the intervention is effective: patients' assessment of chronic illness care, self-reported adherence to medication, general practitioners' and health care assistants' knowledge, patients' knowledge and satisfaction with shared decision making. Practice recruitment is expected to take place between July and December 2012. Recruitment of eligible patients will start in July 2012. Assessment will occur at three time points: baseline (T0), follow-up after 12 (T1) and after 24 months (T2). Discussion: The efficacy and effectiveness of individual elements of the intervention, such as antithrombotic interventions, self-management concepts in orally anticoagulated patients and the methodological tool, case-management, have already been extensively demonstrated. This project foresees the combination of several proven instruments, as a result of which we expect to profit from a reduction in the major complications associated with antithrombotic treatment

Functional analyses of <i>Agaricus bisporus </i>Serine Proteinase 1 (SPR1) reveals a role in utilisation of humic rich substrates and adaptation to the leaf-litter ecological niche

Agaricus bisporus is a secondary decomposer fungus and an excellent model for the adaptation, persistence and growth of fungi in humic‐rich environments such as soils of temperate woodland and pastures. The A. bisporus serine proteinase SPR1 is induced by humic acids and is highly expressed during growth on compost. Three Spr1 gene silencing cassettes were constructed around sense, antisense and non‐translatable‐stop strategies (pGRsensehph, pGRantihph and pGRstophph). Transformation of A. bisporus with these cassettes generated cultures showing a reduction in extracellular proteinase activity as demonstrated by the reduction, or abolition, of a clearing zone on plate‐based bioassays. These lines were then assessed by detailed enzyme assay, RT‐qPCR and fruiting. Serine proteinase activity in liquid cultures was reduced in 83% of transformants. RT‐qPCR showed reduced Spr1 mRNA levels in all transformants analysed, and these correlated with reduced enzyme activity. When fruiting was induced, highly‐silenced transformant AS5 failed to colonize the compost, whilst for those that did colonize the compost, 60% gave a reduction in mushroom yield. Transcriptional, biochemical and developmental observations, demonstrate that SPR1 has an important role in nutrient acquisition in compost and that SPR1 is a key enzyme in the adaptation of Agaricus to the humic‐rich ecological niche formed during biomass degradation

Is self monitoring of blood pressure in pregnancy safe and effective?

Guidelines encourage the use of self-monitoring of blood pressure in pregnancy, and research suggests that women prefer it. But the blood pressure monitoring in pregnancy group (BUMP) explain that our enthusiasm may run ahead of the evidence. They outline what is known and call for better understanding before self-monitoring is implemented

Development and validation of a novel non-contact monitor of nocturnal respiration for identifying sleep-disordered breathing in patients with heart failure

© 2016 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology. Aims: At least 50% of patients with heart failure (HF) may have sleep-disordered breathing (SDB). Overnight in-hospital polysomnography (PSG) is considered the gold standard for diagnosis, but a lack of access to such testing contributes to under-diagnosis of SDB. Therefore, there is a need for simple and reliable validated methods to aid diagnosis in patients with HF. The aim of this study was to investigate the accuracy of a non-contact type IV screening device, SleepMinderTM (SM), compared with in-hospital PSG for detecting SDB in patients with HF. Methods and results: The study included 75 adult patients with systolic HF and suspected SDB who underwent simultaneous PSG and SM recordings. An algorithm was developed from the SM signals, using digital signal processing and pattern recognition techniques to calculate the SM apnoea-hypopnoea index (AHI). This was then compared with expert-scored PSGAHI. The SM algorithm had 70% sensitivity and 89% specificity for identifying patients with clinically significant SDB (AHI ≥ 15/h). At this threshold, it had a positive likelihood ratio of 6.3 and a negative likelihood ratio of 0.16. The overall accuracy of the SMAHI algorithm was 85.8% as shown by the area under a receiver operator characteristic curve. The mean AHI with SM was 3.8/h (95% confidence interval 0.5–7.1) lower than that with PSG. Conclusions: The accuracy of the non-contact type IV screening device SM is good for clinically significant SDB in patients with systolic HF and could be considered as a simple first step in the diagnostic pathway

Possibility between earthquake and explosion seismogram differentiation by discrete stochastic non-Markov processes and local Hurst exponent analysis

The basic purpose of the paper is to draw the attention of researchers to new possibilities of differentiation of similar signals having different nature. One of examples of such kind of signals is presented by seismograms containing recordings of earthquakes (EQ's) and technogenic explosions (TE's). We propose here a discrete stochastic model for possible solution of a problem of strong EQ's forecasting and differentiation of TE's from the weak EQ's. Theoretical analysis is performed by two independent methods: with the use of statistical theory of discrete non-Markov stochastic processes (Phys. Rev. E62,6178 (2000)) and the local Hurst exponent. Time recordings of seismic signals of the first four dynamic orthogonal collective variables, six various plane of phase portrait of four dimensional phase space of orthogonal variables and the local Hurst exponent have been calculated for the dynamic analysis of the earth states. The approaches, permitting to obtain an algorithm of strong EQ's forecasting and to differentiate TE's from weak EQ's, have been developed.Comment: REVTEX +12 ps and jpg figures. Accepted for publication in Phys. Rev. E, December 200

Stochastic Resonance in Ion Channels Characterized by Information Theory

We identify a unifying measure for stochastic resonance (SR) in voltage dependent ion channels which comprises periodic (conventional), aperiodic and nonstationary SR. Within a simplest setting, the gating dynamics is governed by two-state conductance fluctuations, which switch at random time points between two values. The corresponding continuous time point process is analyzed by virtue of information theory. In pursuing this goal we evaluate for our dynamics the tau-information, the mutual information and the rate of information gain. As a main result we find an analytical formula for the rate of information gain that solely involves the probability of the two channel states and their noise averaged rates. For small voltage signals it simplifies to a handy expression. Our findings are applied to study SR in a potassium channel. We find that SR occurs only when the closed state is predominantly dwelled. Upon increasing the probability for the open channel state the application of an extra dose of noise monotonically deteriorates the rate of information gain, i.e., no SR behavior occurs.Comment: 10 pages, 2 figures, to appear in Phys. Rev.

Multifractal characterization of stochastic resonance

We use a multifractal formalism to study the effect of stochastic resonance in a noisy bistable system driven by various input signals. To characterize the response of a stochastic bistable system we introduce a new measure based on the calculation of a singularity spectrum for a return time sequence. We use wavelet transform modulus maxima method for the singularity spectrum computations. It is shown that the degree of multifractality defined as a width of singularity spectrum can be successfully used as a measure of complexity both in the case of periodic and aperiodic (stochastic or chaotic) input signals. We show that in the case of periodic driving force singularity spectrum can change its structure qualitatively becoming monofractal in the regime of stochastic synchronization. This fact allows us to consider the degree of multifractality as a new measure of stochastic synchronization also. Moreover, our calculations have shown that the effect of stochastic resonance can be catched by this measure even from a very short return time sequence. We use also the proposed approach to characterize the noise-enhanced dynamics of a coupled stochastic neurons model.Comment: 10 pages, 21 EPS-figures, RevTe

Changing emotional engagement with running through communal self-tracking: The implications of ‘teleoaffective shaping’ for public health,

Emerging research explores the role of self-tracking in supporting healthy behaviour. Self-tracking comprises a number of interrelated practices; some individual some communal. In this paper we focus on practices that enable interaction between self-trackers through data sharing and communication around personal data. For public health, communal self-tracking has been explored for the additional benefits it provides in addition to self-knowledge. However, under-explored is the emotional entanglement of self-tracking and tracked activities, or the role of practitioners in the dynamic evolution of tracked practices. Qualitative, mixed methods data was collected from leisure-time runners in the SW England who self-track using social fitness app ‘Strava’, and was interpreted through the lens of practice theory. We find that communal self-tracking affords the active shaping of the emotion and purpose of running. This ‘teleoaffective shaping’ allows practitioners to negotiate and reconstitute appealing meanings associated with running to protect their practice loyalty. We identify three mechanisms for teleoaffective shaping afforded by Strava: labelling, reward and materialising effort. Findings advance our understanding of how social fitness apps work to retain practitioners of physically active leisure practices. Future research should further explore the multiple ways that associations with tracked physical activity evolve through entanglement with self-tracking practices

Time correlations and 1/f behavior in backscattering radar reflectivity measurements from cirrus cloud ice fluctuations

The state of the atmosphere is governed by the classical laws of fluid motion and exhibits correlations in various spatial and temporal scales. These correlations are crucial to understand the short and long term trends in climate. Cirrus clouds are important ingredients of the atmospheric boundary layer. To improve future parameterization of cirrus clouds in climate models, it is important to understand the cloud properties and how they change within the cloud. We study correlations in the fluctuations of radar signals obtained at isodepths of winter and fall cirrus clouds. In particular we focus on three quantities: (i) the backscattering cross-section, (ii) the Doppler velocity and (iii) the Doppler spectral width. They correspond to the physical coefficients used in Navier Stokes equations to describe flows, i.e. bulk modulus, viscosity, and thermal conductivity. In all cases we find that power-law time correlations exist with a crossover between regimes at about 3 to 5 min. We also find that different type of correlations, including 1/f behavior, characterize the top and the bottom layers and the bulk of the clouds. The underlying mechanisms for such correlations are suggested to originate in ice nucleation and crystal growth processes.Comment: 33 pages, 9 figures; to appear in the Journal of Geophysical Research - Atmosphere