Timescales of population rarity and commonness in random environments

This paper investigates the influence of environmental noise on the characteristic timescale of the dynamics of density-dependent populations. General results are obtained on the statistics of time spent in rarity (i.e.\ below a small threshold on population density) and time spent in commonness (i.e. above a large threshold). The nonlinear stochastic models under consideration form a class of Markov chains on the state space $]0, \infty[$ which are transient if the intrinsic growth rate is negative and recurrent if it is positive or null. In the recurrent case, we obtain a necessary and sufficient condition for positive recurrence and precise estimates for the distribution of times of rarity and commonness. In the null recurrent, critical case that applies to ecologically neutral species, the distribution of rarity time is a universal power law with exponent $-3/2$. This has implications for our understanding of the long-term dynamics of some natural populations, and provides a rigorous basis for the statistical description of on-off intermittency known in physical sciences

On the functions counting walks with small steps in the quarter plane

Models of spatially homogeneous walks in the quarter plane ${\bf Z}_+^{2}$ with steps taken from a subset $\mathcal{S}$ of the set of jumps to the eight nearest neighbors are considered. The generating function $(x,y,z)\mapsto Q(x,y;z)$ of the numbers $q(i,j;n)$ of such walks starting at the origin and ending at $(i,j) \in {\bf Z}_+^{2}$ after $n$ steps is studied. For all non-singular models of walks, the functions $x \mapsto Q(x,0;z)$ and $y\mapsto Q(0,y;z)$ are continued as multi-valued functions on ${\bf C}$ having infinitely many meromorphic branches, of which the set of poles is identified. The nature of these functions is derived from this result: namely, for all the 51 walks which admit a certain infinite group of birational transformations of ${\bf C}^2$, the interval $]0,1/|\mathcal{S}|[$ of variation of $z$ splits into two dense subsets such that the functions $x \mapsto Q(x,0;z)$ and $y\mapsto Q(0,y;z)$ are shown to be holonomic for any $z$ from the one of them and non-holonomic for any $z$ from the other. This entails the non-holonomy of $(x,y,z)\mapsto Q(x,y;z)$, and therefore proves a conjecture of Bousquet-M\'elou and Mishna.Comment: 40 pages, 17 figure

Современное состояние антимикробной резистентности Streptococcus pneumoniae и специфической вакцинопрофилактики пневмококковой инфекции

The constant increase in the level of resistance of Streptococcus pneumoniae to antimicrobial drugs significantly affects the algorithms for the pharmacotherapy of pneumococcal infection, reduces the effectiveness of the therapy and increases the healthcare costs. In this regard, specific vaccine prevention of pneumococcal diseases is a socially significant and economically promising and profitable area.The aim of the study is to analyze the current status of antimicrobial resistance of S. pneumoniae in healthy carriers and patients with non-invasive and invasive pneumococcal infections, as well as specific vaccine prevention of pneumococcal infection.Conclusion. An increase in the number of pneumococcal strains resistant to macrolides and tetracycline has been noted, as well as a trend toward an increase in resistance to beta-lactam antibiotics. Given the spread of resistant strains of S. pneumoniae, a continuous epidemiological surveillance of pneumococcal infection with an assessment of the dynamics of pneumococcal serotype resistance and the effectiveness of vaccination is needed on a global scale.Постоянный рост уровня устойчивости Streptococcus pneumoniae к антимикробным препаратам существенно влияет на алгоритмы фармакотерапии пневмококковой инфекции, снижая эффективность проводимой терапии и увеличивая экономические затраты системы здравоохранения. В связи с этим специфическая вакцинопрофилактика заболеваний пневмококковой этиологии является социально значимым и экономически перспективным и выгодным направлением.Цель работы – проанализировать современное состояние антимикробной резистентности S. pneumoniae у здоровых носителей и пациентов с неинвазивной и инвазивной пневмококковой инфекцией, а также специфической вакцинопрофилактики пневмококковой инфекции.Заключение. Выявлено увеличение количества штаммов пневмококка, резистентных к макролидам и тетрациклину, а также обнаружена тенденция к росту устойчивости к бета-лактамным антибактериальным препаратам. Учитывая распространение резистентных штаммов S. pneumoniae, необходимо проведение непрерывного эпидемиологического мониторинга пневмококковой инфекции с оценкой динамики устойчивости серотипов пневмококка и эффективности вакцинопрофилактики во всем мире

ATHENA: A knowledge-based hybrid backpropagation-grammatical evolution neural network algorithm for discovering epistasis among quantitative trait Loci

<p>Abstract</p> <p>Background</p> <p>Growing interest and burgeoning technology for discovering genetic mechanisms that influence disease processes have ushered in a flood of genetic association studies over the last decade, yet little heritability in highly studied complex traits has been explained by genetic variation. Non-additive gene-gene interactions, which are not often explored, are thought to be one source of this "missing" heritability.</p> <p>Methods</p> <p>Stochastic methods employing evolutionary algorithms have demonstrated promise in being able to detect and model gene-gene and gene-environment interactions that influence human traits. Here we demonstrate modifications to a neural network algorithm in ATHENA (the Analysis Tool for Heritable and Environmental Network Associations) resulting in clear performance improvements for discovering gene-gene interactions that influence human traits. We employed an alternative tree-based crossover, backpropagation for locally fitting neural network weights, and incorporation of domain knowledge obtainable from publicly accessible biological databases for initializing the search for gene-gene interactions. We tested these modifications <it>in silico </it>using simulated datasets.</p> <p>Results</p> <p>We show that the alternative tree-based crossover modification resulted in a modest increase in the sensitivity of the ATHENA algorithm for discovering gene-gene interactions. The performance increase was highly statistically significant when backpropagation was used to locally fit NN weights. We also demonstrate that using domain knowledge to initialize the search for gene-gene interactions results in a large performance increase, especially when the search space is larger than the search coverage.</p> <p>Conclusions</p> <p>We show that a hybrid optimization procedure, alternative crossover strategies, and incorporation of domain knowledge from publicly available biological databases can result in marked increases in sensitivity and performance of the ATHENA algorithm for detecting and modelling gene-gene interactions that influence a complex human trait.</p

Mass measurements of As, Se and Br nuclei and their implication on the proton-neutron interaction strength towards the N=Z line

Mass measurements of the nuclides 69As, 70,71Se, and 71Br, produced via fragmentation of a 124Xe primary beam at the Fragment Separator (FRS) at GSI, have been performed with the multiple-reflection time-of-flight mass spectrometer (MR-TOF-MS) of the FRS Ion Catcher with an unprecedented mass resolving power of almost 1000000. Such high resolving power is the only way to achieve accurate results and resolve overlapping peaks of short-lived exotic nuclei, whose total number of accumulated events is always limited. For the nuclide 69As, this is the first direct mass measurement. A mass uncertainty of 22 keV was achieved with only ten events. For the nuclide 70Se, a mass uncertainty of 2.6 keV was obtained, corresponding to a relative accuracy of δm/m=4.0×10−8, with less than 500 events. The masses of the nuclides 71Se and 71Br have been measured with an uncertainty of 23 and 16 keV, respectively. Our results for the nuclides 70,71Se and 71Br are in good agreement with the 2016 Atomic Mass Evaluation, and our result for the nuclide 69As resolves the discrepancy between the previous indirect measurements. We measured also the mass of the molecule 14N15N40Ar (A=69) with a relative accuracy of δm/m=1.7×10−8, the highest yet achieved with an MR-TOF-MS. Our results show that the measured restrengthening of the proton-neutron interaction (δVpn) for odd-odd nuclei along the N=Z line above Z=29 (recently extended to Z=37) is hardly evident at the N−Z=2 line, and not evident at the N−Z=4 line. Nevertheless, detailed structure of δVpn along the N−Z=2 and N−Z=4 lines, confirmed by our mass measurements, may provide a hint regarding the ongoing ≈500 keV discrepancy in the mass value of the nuclide 70Br, which prevents including it in the world average of Ft value for superallowed 0+→0+β decays. The reported work sets the stage for mass measurements with the FRS Ion Catcher of nuclei at and beyond the N=Z line in the same region of the nuclear chart, including the nuclide 70Br.peerReviewe

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo