160 research outputs found

    Treatment of acquired aplastic anemia

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    Foundations of Dissipative Particle Dynamics

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    We derive a mesoscopic modeling and simulation technique that is very close to the technique known as dissipative particle dynamics. The model is derived from molecular dynamics by means of a systematic coarse-graining procedure. Thus the rules governing our new form of dissipative particle dynamics reflect the underlying molecular dynamics; in particular all the underlying conservation laws carry over from the microscopic to the mesoscopic descriptions. Whereas previously the dissipative particles were spheres of fixed size and mass, now they are defined as cells on a Voronoi lattice with variable masses and sizes. This Voronoi lattice arises naturally from the coarse-graining procedure which may be applied iteratively and thus represents a form of renormalisation-group mapping. It enables us to select any desired local scale for the mesoscopic description of a given problem. Indeed, the method may be used to deal with situations in which several different length scales are simultaneously present. Simulations carried out with the present scheme show good agreement with theoretical predictions for the equilibrium behavior.Comment: 18 pages, 7 figure

    Deep-phenotyping of Tregs identifies an immune signature for idiopathic aplastic anemia and predicts response to treatment

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    Idiopathic aplastic anemia (AA) is an immune-mediated and serious form of bone marrow failure. Akin to other autoimmune diseases, we have previously shown that in AA regulatory T-cells (Tregs) are reduced in number and function. The aim of this study was to further characterize Treg subpopulations in AA and investigate the potential correlation between specific Treg subsets and response to immunosuppressive therapy (IST) as well as their in-vitro expandability for potential clinical use. Using mass cytometry (CyTOF) and an unbiased multidimensional analytical approach, we identified two specific human Treg subpopulations (Treg A and Treg B) with distinct phenotypes, gene-expression, expandability and function. Treg subpopulation B, predominates in IST responder patients, has a memory/activated phenotype (with higher expression of CD95, CCR4 and CD45RO within FOXP3hi, CD127lo Tregs), expresses the IL- 2/STAT5 pathway and cell-cycle commitment genes. Furthermore, in-vitro expanded Tregs become functional and with the characteristics of Treg subpopulation B. Collectively, this study identifies human Treg subpopulations that can be used as predictive biomarkers for response to IST in AA and potentially other autoimmune diseases. We also show that Tregs from AA patients are IL-2 sensitive and expandable in-vitro, suggesting novel therapeutic approaches such as low dose IL-2 therapy and/or expanded autologous Tregs and meriting further exploration

    Subword complexes, cluster complexes, and generalized multi-associahedra

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    In this paper, we use subword complexes to provide a uniform approach to finite type cluster complexes and multi-associahedra. We introduce, for any finite Coxeter group and any nonnegative integer k, a spherical subword complex called multi-cluster complex. For k=1, we show that this subword complex is isomorphic to the cluster complex of the given type. We show that multi-cluster complexes of types A and B coincide with known simplicial complexes, namely with the simplicial complexes of multi-triangulations and centrally symmetric multi-triangulations respectively. Furthermore, we show that the multi-cluster complex is universal in the sense that every spherical subword complex can be realized as a link of a face of the multi-cluster complex.Comment: 26 pages, 3 Tables, 2 Figures; final versio

    Paleobiology of titanosaurs: reproduction, development, histology, pneumaticity, locomotion and neuroanatomy from the South American fossil record

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    Fil: García, Rodolfo A.. Instituto de Investigación en Paleobiología y Geología. Museo Provincial Carlos Ameghino. Cipolletti; ArgentinaFil: Salgado, Leonardo. Instituto de Investigación en Paleobiología y Geología. General Roca. Río Negro; ArgentinaFil: Fernández, Mariela. Inibioma-Centro Regional Universitario Bariloche. Bariloche. Río Negro; ArgentinaFil: Cerda, Ignacio A.. Instituto de Investigación en Paleobiología y Geología. Museo Provincial Carlos Ameghino. Cipolletti; ArgentinaFil: Carabajal, Ariana Paulina. Museo Carmen Funes. Plaza Huincul. Neuquén; ArgentinaFil: Otero, Alejandro. Museo de La Plata. Universidad Nacional de La Plata; ArgentinaFil: Coria, Rodolfo A.. Instituto de Paleobiología y Geología. Universidad Nacional de Río Negro. Neuquén; ArgentinaFil: Fiorelli, Lucas E.. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica. Anillaco. La Rioja; Argentin

    Representational predicaments for employees: Their impact on perceptions of supervisors\u27 individualized consideration and on employee job satisfaction

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    A representational predicament for a subordinate vis-à-vis his or her immediate superior involves perceptual incongruence with the superior about the subordinate\u27s work or work context, with unfavourable implications for the employee. An instrument to measure the incidence of two types of representational predicament, being neglected and negative slanting, was developed and then validated through an initial survey of 327 employees. A subsequent substantive survey with a fresh sample of 330 employees largely supported a conceptual model linking being neglected and negative slanting to perceptions of low individualized consideration by superiors and to low overall job satisfaction. The respondents in both surveys were all Hong Kong Chinese. Two case examples drawn from qualitative interviews illustrate and support the conceptual model. Based on the research findings, we recommend some practical exercises to use in training interventions with leaders and subordinates. © 2013 Copyright Taylor and Francis Group, LLC

    The SUrvey for Pulsars and Extragalactic Radio Bursts – II. New FRB discoveries and their follow-up

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    We report the discovery of four Fast Radio Bursts (FRBs) in the ongoing SUrvey for Pulsars and Extragalactic Radio Bursts at the Parkes Radio Telescope: FRBs 150610, 151206, 151230 and 160102. Our real-time discoveries have enabled us to conduct extensive, rapid multimessenger follow-up at 12 major facilities sensitive to radio, optical, X-ray, gamma-ray photons and neutrinos on time-scales ranging from an hour to a few months post-burst. No counterparts to the FRBs were found and we provide upper limits on afterglow luminosities. None of the FRBs were seen to repeat. Formal fits to all FRBs show hints of scattering while their intrinsic widths are unresolved in time. FRB 151206 is at low Galactic latitude, FRB 151230 shows a sharp spectral cut-off, and FRB 160102 has the highest dispersion measure (DM = 2596.1 ± 0.3 pc cm−3) detected to date. Three of the FRBs have high dispersion measures (DM > 1500 pc cm−3), favouring a scenario where the DM is dominated by contributions from the intergalactic medium. The slope of the Parkes FRB source counts distribution with fluences >2 Jy ms is α=−2.2+0.6−1.2 and still consistent with a Euclidean distribution (α = −3/2). We also find that the all-sky rate is 1.7+1.5−0.9×103 FRBs/(4π sr)/day above ∼2Jyms and there is currently no strong evidence for a latitude-dependent FRB sky rate

    Viral coinfections in hospitalized coronavirus disease 2019 patients recruited to the international severe acute respiratory and emerging infections consortium WHO clinical characterisation protocol UK study

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    Background We conducted this study to assess the prevalence of viral coinfection in a well characterized cohort of hospitalized coronavirus disease 2019 (COVID-19) patients and to investigate the impact of coinfection on disease severity. Methods Multiplex real-time polymerase chain reaction testing for endemic respiratory viruses was performed on upper respiratory tract samples from 1002 patients with COVID-19, aged <1 year to 102 years old, recruited to the International Severe Acute Respiratory and Emerging Infections Consortium WHO Clinical Characterisation Protocol UK study. Comprehensive demographic, clinical, and outcome data were collected prospectively up to 28 days post discharge. Results A coinfecting virus was detected in 20 (2.0%) participants. Multivariable analysis revealed no significant risk factors for coinfection, although this may be due to rarity of coinfection. Likewise, ordinal logistic regression analysis did not demonstrate a significant association between coinfection and increased disease severity. Conclusions Viral coinfection was rare among hospitalized COVID-19 patients in the United Kingdom during the first 18 months of the pandemic. With unbiased prospective sampling, we found no evidence of an association between viral coinfection and disease severity. Public health interventions disrupted normal seasonal transmission of respiratory viruses; relaxation of these measures mean it will be important to monitor the prevalence and impact of respiratory viral coinfections going forward
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