Fenómeno de Raynaud com isquémia acral – um caso de crioglobulinémia essencial

info:eu-repo/semantics/publishedVersio

Serum amyloid A proteins reduce bone mass during mycobacterial infections

IntroductionOsteopenia has been associated to several inflammatory conditions, including mycobacterial infections. How mycobacteria cause bone loss remains elusive, but direct bone infection may not be required. MethodsGenetically engineered mice and morphometric, transcriptomic, and functional analyses were used. Additionally, inflammatory mediators and bone turnover markers were measured in the serum of healthy controls, individuals with latent tuberculosis and patients with active tuberculosis. Results and discussionWe found that infection with Mycobacterium avium impacts bone turnover by decreasing bone formation and increasing bone resorption, in an IFN gamma- and TNF alpha-dependent manner. IFN gamma produced during infection enhanced macrophage TNF alpha secretion, which in turn increased the production of serum amyloid A (SAA) 3. Saa3 expression was upregulated in the bone of both M. avium- and M. tuberculosis-infected mice and SAA1 and 2 proteins (that share a high homology with murine SAA3 protein) were increased in the serum of patients with active tuberculosis. Furthermore, the increased SAA levels seen in active tuberculosis patients correlated with altered serum bone turnover markers. Additionally, human SAA proteins impaired bone matrix deposition and increased osteoclastogenesis in vitro. Overall, we report a novel crosstalk between the cytokine-SAA network operating in macrophages and bone homeostasis. These findings contribute to a better understanding of the mechanisms of bone loss during infection and open the way to pharmacological intervention. Additionally, our data and disclose SAA proteins as potential biomarkers of bone loss during infection by mycobacteria.This article is a result of the project HEALTH-UNORTE: Setting-up biobanks and regenerative medicine strategies to boost research in cardiovascular, musculoskeletal, neurological, oncological, immunological and infectious diseases (NORTE-01-0145-FEDER-000039), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). This work was supported by KOG-202108-00929 from the European Haematology Society, awarded to AG. Work in the MS lab was financed by FEDER - Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 - Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT - Fundacao para a Ciencia e a Tecnologia/Ministerio da Ciencia, Tecnologia e Ensino Superior in the framework of the project POCI-01-0145-FEDER-028955 (PTDC/SAU-INF/28955/2017). AG and MS are supported by an Individual Scientific Employment contract (CEECIND/00048/2017; CEECIND/00241/2017 respectively). DS acknowledges the Portuguese Foundation for Science and Technology (FCT) for the Post-Doc fellowship (SFRH/BPD/115341/2016). RP, DS and AF have PhD grants (SFRH/BD/145217/2019; SFRH/BD/143536/2019; 2020.05949.BD, respectively) financed by FCT

Supersymmetry Flows, Semi-Symmetric Space Sine-Gordon Models And The Pohlmeyer Reduction

We study the extended supersymmetric integrable hierarchy underlying the Pohlmeyer reduction of superstring sigma models on semi-symmetric superspaces F/G. This integrable hierarchy is constructed by coupling two copies of the homogeneous integrable hierarchy associated to the loop Lie superalgebra extension f of the Lie superalgebra f of F and this is done by means of the algebraic dressing technique and a Riemann-Hilbert factorization problem. By using the Drinfeld-Sokolov procedure we construct explicitly, a set of 2D spin \pm1/2 conserved supercharges generating supersymmetry flows in the phase space of the reduced model. We introduce the bi-Hamiltonian structure of the extended homogeneous hierarchy and show that the two brackets are of the Kostant-Kirillov type on the co-adjoint orbits defined by the light-cone Lax operators L_\pm. By using the second symplectic structure, we show that these supersymmetries are Hamiltonian flows, we compute part of the supercharge algebra and find the supersymmetric field variations they induce. We also show that this second Poisson structure coincides with the canonical Lorentz-Invariant symplectic structure of the WZNW model involved in the Lagrangian formulation of the extended integrable hierarchy, namely, the semi-symmetric space sine-Gordon model (SSSSG), which is the Pohlmeyer reduced action functional for the transverse degrees of freedom of superstring sigma models on the cosets F/G. We work out in some detail the Pohlmeyer reduction of the AdS_2xS^2 and the AdS_3xS^3 superstrings and show that the new conserved supercharges can be related to the supercharges extracted from 2D superspace. In particular, for the AdS_2xS^2 example, they are formally the same.Comment: V2: Two references added, V3: Modifications in section 2.6, V4: Published versio

An efficient semiparametric maxima estimator of the extremal index

The extremal index $\theta$, a measure of the degree of local dependence in the extremes of a stationary process, plays an important role in extreme value analyses. We estimate $\theta$ semiparametrically, using the relationship between the distribution of block maxima and the marginal distribution of a process to define a semiparametric model. We show that these semiparametric estimators are simpler and substantially more efficient than their parametric counterparts. We seek to improve efficiency further using maxima over sliding blocks. A simulation study shows that the semiparametric estimators are competitive with the leading estimators. An application to sea-surge heights combines inferences about $\theta$ with a standard extreme value analysis of block maxima to estimate marginal quantiles.Comment: 17 pages, 7 figures. Minor edits made to version 1 prior to journal publication. The final publication is available at Springer via http://dx.doi.org/10.1007/s10687-015-0221-

Game theory of mind

This paper introduces a model of ‘theory of mind’, namely, how we represent the intentions and goals of others to optimise our mutual interactions. We draw on ideas from optimum control and game theory to provide a ‘game theory of mind’. First, we consider the representations of goals in terms of value functions that are prescribed by utility or rewards. Critically, the joint value functions and ensuing behaviour are optimised recursively, under the assumption that I represent your value function, your representation of mine, your representation of my representation of yours, and so on ad infinitum. However, if we assume that the degree of recursion is bounded, then players need to estimate the opponent's degree of recursion (i.e., sophistication) to respond optimally. This induces a problem of inferring the opponent's sophistication, given behavioural exchanges. We show it is possible to deduce whether players make inferences about each other and quantify their sophistication on the basis of choices in sequential games. This rests on comparing generative models of choices with, and without, inference. Model comparison is demonstrated using simulated and real data from a ‘stag-hunt’. Finally, we note that exactly the same sophisticated behaviour can be achieved by optimising the utility function itself (through prosocial utility), producing unsophisticated but apparently altruistic agents. This may be relevant ethologically in hierarchal game theory and coevolution

Novel nonlinear method of heart rate variability analysis in exercise

Global chaotic analysis of heart rate variability (HRV) has been previously investigated. Preceding studies indicated impaired analysis in obese children and diabetic patients. However, its behaviour in response to exercise is not clear. We investigated the acute effects of physical exercise on global chaotic analysis of HRV. We investigated 35 healthy men aged between 18 and 35 years old. Volunteers were instructed not to drink alcohol, caffeine or other autonomic nervous system (ANS) stimulants for 24 hours before the evaluation. Volunteers performed physical exercise on treadmill with intensity of 6.0 km/hour + 1% slope in the first five minutes for physically "warming up". This was then followed by 25 minutes with intensity equivalent to 60% of V-max, with the same slope according to the Conconi threshold. HRV was analyzed in the following periods: (a) control protocol; the 10-minute periods before the performance of the exercise and (b) the 10-minute periods after the performance of the exercise. Both periods of exercise were analyzed by the chaotic global techniques. The number of RR-intervals derived from the PQRST-motif of the ECG signal was processed by the algorithms, and were always 750 RR-intervals for all subjects both experimenta

Study of recent and future trends in place of death in Belgium using death certificate data: a shift from hospitals to care homes

<p>Abstract</p> <p>Background</p> <p>Since most patients prefer out-of-hospital death, place of death can be considered an indicator of end-of-life care quality. The study of trends in place of death is necessary to examine causes of shifts, to evaluate efforts to alter place of death and develop future policies. This study aims to examine past trends and future projections of place of death.</p> <p>Methods</p> <p>Analysis of death certificates (decedents aged ≥ 1 year) in Belgium (Flanders and Brussels Capital region) 1998-2007. Trends in place of death were adjusted for cause of death, sociodemographic characteristics, environmental factors, numbers of hospital beds, and residential and skilled nursing beds in care homes. Future trends were based on age- and sex-specific mortality prognoses.</p> <p>Results</p> <p>Hospital deaths decreased from 55.1% to 51.7% and care home deaths rose from 18.3% to 22.6%. The percentage of home deaths remained stable. The odds of dying in a care home versus hospital increased steadily and was 1.65 (95%CI:1.53-1.78) in 2007 compared to 1998. This increase could be attributed to the replacement of residential beds by skilled nursing beds. Continuation of these trends would result in the more than doubling of deaths in care homes and a decrease in deaths at home and in hospital by 2040.</p> <p>Conclusions</p> <p>Additional end-of-life care resources in care homes largely explain the decrease in hospital deaths. Care homes will become the main locus of end-of-life care in the future. Governments should provide sufficient skilled nursing resources in care homes to fulfil the end-of-life care preferences and needs of patients.</p

IFNγ production in peripheral blood of early Lyme disease patients to hLFAα(L) (aa326-345)

BACKGROUND: It has been proposed that outer surface protein A (OspA) of Borrelia burgdorferi sensu stricto contains a T helper 1 (Th1) cell epitope that could play a role in an autoimmune response to hLFA1. METHODS: We used two peptides, hLFAα(L) (aa326-345) and Borrelia burgdorferi OspAB31 (aa164-183), as stimulating antigens to measure Th1 proinflammatory IFNγ cytokine production in peripheral blood of Lyme disease patients presenting with EM without history of arthritis, as well as in peripheral blood of healthy individuals. RESULTS: IFNγ responses to hLFA1 peptide were observed in 11 of 19 Lyme disease patients and in 3 of 15 healthy controls. In contrast, only 2 of 19 of the Lyme disease patients and none of the controls responded to the homologous OspAB31 peptide. CONCLUSIONS: IFNγ was produced in response to stimulation with peptide hLFAα(L) (aa326-345) in peripheral blood of 58% of patients with early Lyme disease without signs of arthritis, as well as in peripheral blood of 20% of healthy individuals, but not in response to stimulation with the homologous OspAB31 (aa164-183) peptide (p < 0.05). Our results suggest that reactivity to the hLFA1 peptide in peripheral blood may be the result of T cell degeneracy

Topologically Protected Quantum State Transfer in a Chiral Spin Liquid

Topology plays a central role in ensuring the robustness of a wide variety of physical phenomena. Notable examples range from the robust current carrying edge states associated with the quantum Hall and the quantum spin Hall effects to proposals involving topologically protected quantum memory and quantum logic operations. Here, we propose and analyze a topologically protected channel for the transfer of quantum states between remote quantum nodes. In our approach, state transfer is mediated by the edge mode of a chiral spin liquid. We demonstrate that the proposed method is intrinsically robust to realistic imperfections associated with disorder and decoherence. Possible experimental implementations and applications to the detection and characterization of spin liquid phases are discussed.Comment: 14 pages, 7 figure