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Background: The linear noise approximation (LNA) is commonly used to predict how noise is regulated and exploited at the cellular level. These predictions are exact for reaction networks composed exclusively of first order reactions or for networks involving bimolecular reactions and large numbers of molecules. It is however well known that gene regulation involves bimolecular interactions with molecule numbers as small as a single copy of a particular gene. It is therefore questionable how reliable are the LNA predictions for these systems.
Results: We implement in the software package intrinsic Noise Analyzer (iNA), a system size expansion based method which calculates the mean concentrations and the variances of the fluctuations to an order of accuracy higher than the LNA. We then use iNA to explore the parametric dependence of the Fano factors and of the coefficients of variation of the mRNA and protein fluctuations in models of genetic networks involving nonlinear protein degradation, post-transcriptional, post-translational and negative feedback regulation. We find that the LNA can significantly underestimate the amplitude and period of noise-induced oscillations in genetic oscillators. We also identify cases where the LNA predicts that noise levels can be optimized by tuning a bimolecular rate constant whereas our method shows that no such regulation is possible. All our results are confirmed by stochastic simulations.
Conclusion: The software iNA allows the investigation of parameter regimes where the LNA fares well and where it does not. We have shown that the parametric dependence of the coefficients of variation and Fano factors for common gene regulatory networks is better described by including terms of higher order than LNA in the system size expansion. This analysis is considerably faster than stochastic simulations due to the extensive ensemble averaging needed to obtain statistically meaningful results. Hence iNA is well suited for performing computationally efficient and quantitative studies of intrinsic noise in gene regulatory networks.
Research indicates that evidence-based policy making is most successful when public administrators refer to diversified information portfolios. With the rising prominence of social media in the last decade, this paper argues that governments can benefit from integrating this publically available, user-generated data through the technique of social media analytics (SMA). There are already several initiatives set up to predict future policy issues, e.g. for the policy fields of crisis mitigation or migrant integration insights. The authors analyse these endeavours and their potential for providing more efficient and effective public policies. Furthermore, they scrutinise the challenges to governmental SMA usage in particular with regards to legal and ethical aspects. Reflecting the latter, this paper provides forward-looking recommendations on how these technologies can best be used for future policy making in a legally and ethically sound manner.
Background: With increasing age neuromuscular deficits (e.g., sarcopenia) may result in impaired physical performance and an increased risk for falls. Prominent intrinsic fall-risk factors are age-related decreases in balance and strength / power performance as well as cognitive decline. Additional studies are needed to develop specifically tailored exercise programs for older adults that can easily be implemented into clinical practice. Thus, the objective of the present trial is to assess the effects of a fall prevention program that was developed by an interdisciplinary expert panel on measures of balance, strength / power, body composition, cognition, psychosocial well-being, and falls self-efficacy in healthy older adults. Additionally, the time-related effects of detraining are tested.
Methods/Design: Healthy old people (n = 54) between the age of 65 to 80 years will participate in this trial. The testing protocol comprises tests for the assessment of static / dynamic steady-state balance (i.e., Sharpened Romberg Test, instrumented gait analysis), proactive balance (i.e., Functional Reach Test; Timed Up and Go Test), reactive balance (i.e., perturbation test during bipedal stance; Push and Release Test), strength (i.e., hand grip strength test; Chair Stand Test), and power (i.e., Stair Climb Power Test; countermovement jump). Further, body composition will be analysed using a bioelectrical impedance analysis system. In addition, questionnaires for the assessment of psychosocial (i.e., World Health Organisation Quality of Life Assessment-Bref), cognitive (i.e., Mini Mental State Examination), and fall risk determinants (i.e., Fall Efficacy Scale -International) will be included in the study protocol. Participants will be randomized into two intervention groups or the control / waiting group. After baseline measures, participants in the intervention groups will conduct a 12-week balance and strength / power exercise intervention 3 times per week, with each training session lasting 30 min. (actual training time). One intervention group will complete an extensive supervised training program, while the other intervention group will complete a short version (` 3 times 3') that is home-based and controlled by weekly phone calls. Post-tests will be conducted right after the intervention period. Additionally, detraining effects will be measured 12 weeks after program cessation. The control group / waiting group will not participate in any specific intervention during the experimental period, but will receive the extensive supervised program after the experimental period.
Discussion: It is expected that particularly the supervised combination of balance and strength / power training will improve performance in variables of balance, strength / power, body composition, cognitive function, psychosocial well-being, and falls self-efficacy of older adults. In addition, information regarding fall risk assessment, dose-response-relations, detraining effects, and supervision of training will be provided. Further, training-induced health-relevant changes, such as improved performance in activities of daily living, cognitive function, and quality of life, as well as a reduced risk for falls may help to lower costs in the health care system. Finally, practitioners, therapists, and instructors will be provided with a scientifically evaluated feasible, safe, and easy-to-administer exercise program for fall prevention.
Open Government
(2013)
Bis heute gelingt es kaum, Begriffe rund um die Verwaltungsreform – von New Public Management bis zu den E-Modellen – schlüssig voneinander abzugrenzen. Dieses Defizit wird bei der Betrachtung des Konzepts Open Government erneut sichtbar. Der Begriff Open Government ist dabei nicht nur aus verwaltungswissenschaftlicher, sondern mit Blick auf die Instrumente der direkten Demokratie auch aus politikwissenschaftlicher Perspektive zu betrachten. Handelt es sich um einen Sammelbegriff für hauptsächlich schon Dagewesenes?
Was Bürger bem(a)erken
(2013)
Eingebettet in die aktuelle Open-Government-Debatte gewinnen E-Bürgerdienste weiter an Bedeutung. Zu den Vorreitern internetbasierter Bürgerdienste wird der Brandenburger Bürgerservice Maerker gezählt, da dieser eine einfache Möglichkeit der Kommunikation zwischen Bürger und Verwaltung über Infrastrukturprobleme in der Gemeinde bietet. Auf der Grundlage von Experteninterviews und einer Umfrage unter den teilnehmenden Kommunen evaluieren die Autoren die Einführung und Umsetzung des Maerker Brandenburgs. Im Ergebnis zeigen sich neben einer großen Breite an Akzeptanz und Zustimmung unter den beteiligten Akteuren auch unausgeschöpfte Potenziale zur Verbesserung der Prozesse innerhalb der Verwaltung. Dieser Artikel stellt die Ergebnisse der Evaluation des Maerkers dar und gibt einen Ausblick auf weitere Entwicklungspotenziale.
Background: Recent studies have demonstrated a superior diagnostic accuracy of cardiovascular magnetic resonance (CMR) for the detection of coronary artery disease (CAD). We aimed to determine the comparative cost-effectiveness of CMR versus single-photon emission computed tomography (SPECT).
Methods: Based on Bayes' theorem, a mathematical model was developed to compare the cost-effectiveness and utility of CMR with SPECT in patients with suspected CAD. Invasive coronary angiography served as the standard of reference. Effectiveness was defined as the accurate detection of CAD, and utility as the number of quality-adjusted life-years (QALYs) gained. Model input parameters were derived from the literature, and the cost analysis was conducted from a German health care payer's perspective. Extensive sensitivity analyses were performed.
Results: Reimbursement fees represented only a minor fraction of the total costs incurred by a diagnostic strategy. Increases in the prevalence of CAD were generally associated with improved cost-effectiveness and decreased costs per utility unit (Delta QALY). By comparison, CMR was consistently more cost-effective than SPECT, and showed lower costs per QALY gained. Given a CAD prevalence of 0.50, CMR was associated with total costs of (sic)6,120 for one patient correctly diagnosed as having CAD and with (sic)2,246 per Delta QALY gained versus (sic)7,065 and (sic)2,931 for SPECT, respectively. Above a threshold value of CAD prevalence of 0.60, proceeding directly to invasive angiography was the most cost-effective approach.
Conclusions: In patients with low to intermediate CAD probabilities, CMR is more cost-effective than SPECT. Moreover, lower costs per utility unit indicate a superior clinical utility of CMR.
We study origin, parameter optimization, and thermodynamic efficiency of isothermal rocking ratchets based on fractional subdiffusion within a generalized non-Markovian Langevin equation approach. A corresponding multi-dimensional Markovian embedding dynamics is realized using a set of auxiliary Brownian particles elastically coupled to the central Brownian particle (see video on the journal web site). We show that anomalous subdiffusive transport emerges due to an interplay of nonlinear response and viscoelastic effects for fractional Brownian motion in periodic potentials with broken space-inversion symmetry and driven by a time-periodic field. The anomalous transport becomes optimal for a subthreshold driving when the driving period matches a characteristic time scale of interwell transitions. It can also be optimized by varying temperature, amplitude of periodic potential and driving strength. The useful work done against a load shows a parabolic dependence on the load strength. It grows sublinearly with time and the corresponding thermodynamic efficiency decays algebraically in time because the energy supplied by the driving field scales with time linearly. However, it compares well with the efficiency of normal diffusion rocking ratchets on an appreciably long time scale.
During an unusually massive filament eruption on 7 June 2011, SDO/AIA imaged for the first time significant EUV emission around a magnetic reconnection region in the solar corona. The reconnection occurred between magnetic fields of the laterally expanding CME and a neighbouring active region. A pre-existing quasi-separatrix layer was activated in the process. This scenario is supported by data-constrained numerical simulations of the eruption. Observations show that dense cool filament plasma was re-directed and heated in situ, producing coronal-temperature emission around the reconnection region. These results provide the first direct observational evidence, supported by MHD simulations and magnetic modelling, that a large-scale re-configuration of the coronal magnetic field takes place during solar eruptions via the process of magnetic reconnection.
Understanding the magnetic configuration of the source regions of coronal mass ejections (CMEs) is vital in order to determine the trigger and driver of these events. Observations of four CME productive active regions are presented here, which indicate that the pre-eruption magnetic configuration is that of a magnetic flux rope. The flux ropes are formed in the solar atmosphere by the process known as flux cancellation and are stable for several hours before the eruption. The observations also indicate that the magnetic structure that erupts is not the entire flux rope as initially formed, raising the question of whether the flux rope is able to undergo a partial eruption or whether it undergoes a transition in specific flux rope configuration shortly
before the CME.
In Germany, active bat rabies surveillance was conducted between 1993 and 2012. A total of 4546 oropharyngeal swab samples from 18 bat species were screened for the presence of EBLV-1- , EBLV-2- and BBLV-specific RNA. Overall, 0 center dot 15% of oropharyngeal swab samples tested EBLV-1 positive, with the majority originating from Eptesicus serotinus. Interestingly, out of seven RT-PCR-positive oropharyngeal swabs subjected to virus isolation, viable virus was isolated from a single serotine bat (E. serotinus). Additionally, about 1226 blood samples were tested serologically, and varying virus neutralizing antibody titres were found in at least eight different bat species. The detection of viral RNA and seroconversion in repeatedly sampled serotine bats indicates long-term circulation of the virus in a particular bat colony. The limitations of random-based active bat rabies surveillance over passive bat rabies surveillance and its possible application of targeted approaches for future research activities on bat lyssavirus dynamics and maintenance are discussed.