1,374 research outputs found

    Poverty traps in Markov models of the evolution of wealth

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    Poverty trap models are dynamical systems with more than one attractor. Similar dynamical systems arise in optimal growth and macroeconomic models. These systems are often studied empirically by ad hoc methods relying on intuition from deterministic systems, such as looking for multiple peaks in the stationary distribution of states. We develop Markov wealth processes in which parents' investments in children stochastically determine children's wealth, and consequently their own investment choices. We show that, relative to a zero-shock process, some of the multiple attractors are less fragile than are others, and that their presence dominates the stationary behavior of the wealth distribution. Typically, mass accumulates around attractors. An only slightly stochastically perturbed deterministic system will have an invariant distribution which puts close to probability 1 on a single steady state rather than having significant mass distributed among several attractors. We also examine how policy effects the shape of the invariant distribution

    Pregnancy outcome in women with Gaucher disease type 1 who had unplanned pregnancies during eliglustat clinical trials

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    Gaucher disease type 1 (GD1) is an inherited lysosomal storage disorder caused by deficient enzymatic activity of acid β-glucosidase, resulting in accumulation of its substrate glucosylceramide, leading to debilitating visceral, hematologic, and skeletal manifestations. Women with GD1 are at increased risk for complications during pregnancy, delivery, and postpartum. Treatment with enzyme replacement therapy is generally recommended before and during pregnancy to reduce risks. Eliglustat, an oral substrate-reduction therapy, is a first-line treatment for adults with GD1 adults who have extensive, intermediate, or poor CYP2D6-metabolizer phenotypes (>90% of patients). We report on pregnancy outcomes among women in eliglustat trials who had unplanned pregnancies and female partners of men in the trials. In four phase 2 and 3 eliglustat trials of 393 adults with GD1, women of childbearing potential were required to use contraception, have monthly pregnancy tests, and discontinue eliglustat promptly if pregnant. In phase 2 and 3 trials, 18 women had 19 pregnancies, resulting in 14 healthy infants from 13 pregnancies (one set of twins), three elective terminations, one ectopic pregnancy, one spontaneous abortion, and one in utero death. Median estimated eliglustat exposure duration during pregnancy was 38 days. In phase 1 trials (non-GD1 subjects), one woman had a spontaneous abortion. Partners of 16 eliglustat-treated men with GD1 had 18 pregnancies, all resulting in healthy infants. Eliglustat is not approved during pregnancy due to limited data. Guidelines for clinicians and patients with GD that address use of eliglustat in women of childbearing potential are needed

    Parameter-Independent Strategies for pMDPs via POMDPs

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    Markov Decision Processes (MDPs) are a popular class of models suitable for solving control decision problems in probabilistic reactive systems. We consider parametric MDPs (pMDPs) that include parameters in some of the transition probabilities to account for stochastic uncertainties of the environment such as noise or input disturbances. We study pMDPs with reachability objectives where the parameter values are unknown and impossible to measure directly during execution, but there is a probability distribution known over the parameter values. We study for the first time computing parameter-independent strategies that are expectation optimal, i.e., optimize the expected reachability probability under the probability distribution over the parameters. We present an encoding of our problem to partially observable MDPs (POMDPs), i.e., a reduction of our problem to computing optimal strategies in POMDPs. We evaluate our method experimentally on several benchmarks: a motivating (repeated) learner model; a series of benchmarks of varying configurations of a robot moving on a grid; and a consensus protocol.Comment: Extended version of a QEST 2018 pape

    Presenting signs and patient co-variables in Gaucher disease : outcome of the Gaucher Earlier Diagnosis Consensus (GED-C) Delphi initiative

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    © 2018 The Authors. Internal Medicine Journal by Wiley Publishing Asia Pty Ltd on behalf of Royal Australasian College of Physicians.Background: Gaucher disease (GD) presents with a range of signs and symptoms. Physicians can fail to recognise the early stages of GD owing to a lack of disease awareness, which can lead to significant diagnostic delays and sometimes irreversible but avoidable morbidities. Aim: The Gaucher Earlier Diagnosis Consensus (GED-C) initiative aimed to identify signs and co-variables considered most indicative of early type 1 and type 3 GD, to help non-specialists identify ‘at-risk’ patients who may benefit from diagnostic testing. Methods: An anonymous, three-round Delphi consensus process was deployed among a global panel of 22 specialists in GD (median experience 17.5 years, collectively managing almost 3000 patients). The rounds entailed data gathering, then importance ranking and establishment of consensus, using 5-point Likert scales and scoring thresholds defined a priori. Results: For type 1 disease, seven major signs (splenomegaly, thrombocytopenia, bone-related manifestations, anaemia, hyperferritinaemia, hepatomegaly and gammopathy) and two major co-variables (family history of GD and Ashkenazi-Jewish ancestry) were identified. For type 3 disease, nine major signs (splenomegaly, oculomotor disturbances, thrombocytopenia, epilepsy, anaemia, hepatomegaly, bone pain, motor disturbances and kyphosis) and one major co-variable (family history of GD) were identified. Lack of disease awareness, overlooking mild early signs and failure to consider GD as a diagnostic differential were considered major barriers to early diagnosis. Conclusion: The signs and co-variables identified in the GED-C initiative as potentially indicative of early GD will help to guide non-specialists and raise their index of suspicion in identifying patients potentially suitable for diagnostic testing for GD.Peer reviewedFinal Published versio

    Genetic diversity of barley accessions from East Asian countries in terms of resistance to powdery mildew

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    Background. Barley is an ancient crop currently cultivated in more than 100 countries. High adaptability makes it possible to cultivate it in environments unfavorable for many other crops. At the same time, fungal diseases can have a negative impact on its grain yield and quality. One of the most harmful is the fungus Blumeria graminis (DC.) Golovin ex Speer f. sp. hordei Marchal. The pathogen can overcome a cultivar’s resistance, resulting in significant harvest losses. There is a need for a constant search for new effective sources of resistance to powdery mildew for barley breeding.Materials and methods. A set of 950 barley accessions from the East Asian center of the crop’s morphogenesis were studied at the adult stage of plant development. They were screened and crossed in the fields of Pushkin and Pavlovsk Laboratories of VIR (St. Petersburg, Russia). Genetic control of barley resistance to B. graminis was analyzed in a climate chamber under artificial infection pressure with the northwestern population of the fungus. Scoring scales were used for screening.Results and conclusions. Weak development of B. graminis during the heading phase was observed on plants of 38 barley accessions from the East Asian center. High resistance at all stages of development was manifested by 20 genotypes that can be used in breeding programs. Resistance genes in 18 selected forms differed in their effectiveness at the seedling stage of development and during the heading phase. Accessions k-3433, k-10931, k-10934, k-11608, k-17545, k-20272, k-20279, k-20354 and k-27867 had one dominant resistance gene each. Accessions k-11608, k-12278, and k-17545 are protected by the identical gene, while the resistance of k-3433 is induced by a gene that differs from the genes present in accessions k-10931 and k-20279

    Smoking and response to rituximab in rheumatoid arthritis : results from an international European collaboration

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    Objectives: To investigate whether smoking habits predict response to rituximab (RTX) in rheumatoid arthritis (RA). Method: We included patients from the CERERRA international cohort receiving the first treatment cycle with available smoking status (n = 2481, smokers n = 528, non-current smokers n = 1953) and at least one follow-up visit. Outcome measures were change in Disease Activity Score based on 28-joint count (Delta DAS28) and European League Against Rheumatism (EULAR) good response at 6 months, with non-current smokers as the referent group. Results: Compared with non-smokers at baseline, smokers were more often rheumatoid factor (RF)/anti-citrullinated protein antibody (ACPA) positive and males, had shorter disease duration, lower DAS28 and Health Assessment Questionnaire (HAQ) score, a higher number of prior biological disease-modifying anti-rheumatic drugs, and were more likely to receive concomitant conventional synthetic disease-modifying anti-rheumatic drug (csDMARDs). Disease activity had decreased less in smokers at 6 months (Delta DAS28 = 1.5 vs 1.7, p = 0.006), although the difference was no longer significant after correction for baseline DAS28 (p = 0.41). EULAR good response rates did not differ between smokers and non-smokers overall or stratified by RF/ACPA status, although smokers had lower good response rates among seronegative patients (ACPA-negative: 6% vs 14%, RF-negative: 11% vs 18%). Smoking did not predict good response [odds ratio (OR) = 1.04, 95% confidence interval (CI) = 0.76-1.41], while ACPA, DAS28, HAQ, and concomitant csDMARDs were significant predictors for good response. However, when stratified by country, smokers were less likely to achieve good response in Sweden (unadjusted OR = 0.24, 95% CI = 0.07-0.89), and a trend was seen in the Czech Republic (OR = 0.45, 95% CI = 0.16-1.02). Conclusion: In this large, observational, multinational RA cohort, smokers starting RTX differed from non-smokers by having shorter disease duration and lower disease activity, but more previous treatments. The overall results do not support smoking as an important predictor for response to RTX in patients with RA.Peer reviewe

    A comparative study of Epipactis atrorubens in two different forest communities of the Middle Urals, Russia

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    The objective of this study was to compare eco-physiological and morphological parameters of a regionally endangered orchid species, Epipactis atrorubens (Hoffm. ex Bernh.) Bess., growing in two forest communities (on serpentine and granite outcrops) of the Middle Urals, Russia. Biodiversity, dominance, and phytocoenosis studies showed the colonization of a wide range of plant species on both sites. The physicochemical properties of the soil, chemical composition and morphological features of E. atrorubens, growing under technogenic conditions (asbestos deposits), on serpentine outcrops and in the natural environment of the granite massif were studied for the first time. The serpentine substrate differed from the granite one by its greater stoniness, circumneutral pH and lower contents of available nitrogen and phosphorus. Extremely high concentrations of magnesium were found in the serpentine soil, some 79 times higher than in the granite substrate. High concentrations of nickel (94 times), chromium (59 times), cobalt (17 times), and iron (4 times) were found in the serpentine substrate, higher than in the granite substrate. The differences between the sites for available metal contents and for root and shoot metal contents were significantly less. Concentrations of most of the metals in the roots were higher than in the shoots. Despite higher metal concentrations and lower nitrogen and phosphorus levels in serpentine soils, E. atrorubens had a larger population and greater viability compared to those growing on granite. Plants on serpentine outcrops were characterized by the formation of a larger number of fruits, greater root lengths and thicker leaf blades, compared to plants on granites. The well-developed orchid mycorrhizae contributed to the survival of this species under unfavorable serpentine conditions. Hence, serpentine outcrops formed due to the mining of asbestos could be a suitable substrate for the light-demanding E. atrorubens due to its capacity to adapt to dry, rocky, nutrient-depleted soils and limited competition from other plants. © 2019, The Author(s).The work was supported by the Ministry of Science and Higher Education of the Russian Federation in the framework of the State Task of UrFU No. 6.7696.2017

    Adaptive morphophysiological features of neottia ovata (Orchidaceae) contributing to its natural colonization on fly ash deposits

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    In previous decades, some species of the Orchidaceae family have been found growing in man-made habitats. Neottia ovata is one of the most widespread orchids in Europe, however it is quite rare in Russia and is included in several regional Red Data Books. The purpose of this study was to compare the chemical composition and morphophysiological parameters of N. ovata from two forest communities of the Middle Urals, Russia: natural and transformed (fly ash dump of Verkhnetagil’skaya Thermal Power Station) for determining orchid adaptive features. The content of most of the studied metals in the underground parts (rhizome + roots) of N. ovata was considerably higher than in the leaves, which diminished the harmful effect of toxic metals on the aboveground organs. The adaptive changes in the leaf mesostructure of N. ovata such as an increase in epidermis thickness, the number of chloroplasts in the cell, and the internal assimilating surface were found for the first time. The orchids from the fly ash deposits were characterized by a higher content of chlorophyll b and carotenoids than plants from the natural forest community that evidenced the compensatory response on the decrease in chlorophyll a. The ability of N. ovata from the transformed habitat to maintain a relatively favorable water balance and stable assimilation indexes further contribute to its high viability. The study of orchid adaptive responses to unfavorable factors is necessary for their successful naturalization and introduction into a new environment. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.The reported study was partly funded by RFBR and the Government of Sverdlovsk region, project number 20-44-660011 and the Ministry of Science and Higher Education of the Russian Federation as part of state task of the Ural Federal University, FEUZ-2020-0057
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