The NLRP3 inflammasome is differentially activated by pneumolysin variants and contributes to host defense in pneumococcal pneumonia.

Streptococcus pneumoniae is a leading cause of pneumonia, meningitis, and sepsis. Pneumococci can be divided into >90 serotypes that show differences in the pathogenicity and invasiveness. We tested the hypotheses that the innate immune inflammasome pathway is involved in fighting pneumococcal pneumonia and that some invasive pneumococcal types are not recognized by this pathway. We show that human and murine mononuclear cells responded to S. pneumoniae expressing hemolytic pneumolysin by producing IL-1β. This IL-1β production depended on the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome. Some serotype 1, serotype 8, and serotype 7F bacteria, which have previously been associated with increased invasiveness and with production of toxins with reduced hemolytic activity, or bacterial mutants lacking pneumolysin did not stimulate notable IL-1β production. We further found that NLRP3 was beneficial for mice during pneumonia caused by pneumococci expressing hemolytic pneumolysin and was involved in cytokine production and maintenance of the pulmonary microvascular barrier. Overall, the inflammasome pathway is protective in pneumonia caused by pneumococci expressing hemolytic toxin but is not activated by clinically important pneumococcal sequence types causing invasive disease. The study indicates that a virulence factor polymorphism may substantially affect the recognition of bacteria by the innate immune system.

Consolidation with Radioimmunotherapy May Prolong Survival in First Remission of Mantle Cell Lymphoma Patients Uneligible for Stem Cell Transplantation, An Analysis of the International RIT-Network

Background: Mantle cell lymphoma (MCL) is a rare subtype (3-9%) of Non Hodgkin Lymphoma (NHL) with a relatively poor prognosis (5-year survival < 40%). Although consolidation of first remission with autologous stem cell transplantation (ASCT) is regarded as "golden standard", less than half of the patients may be subjected to this intensive treatment due to advanced age and co-morbidities. Standard-dose non-myeloablative radioimmunotherapy (RIT) seems to be a very efficient approach for treatment of certain NHL. However, there are almost no data available on the efficacy and safety of RIT in MCL. Methods and Patients: In the RIT-Network, a web-based international registry collecting real observational data from RIT-treated patients, 115 MCL patients treated with ibritumomab tiuxetan were recorded. Most of the patients were elderly males with advanced stage of the disease: median age - 63 (range 31-78); males - 70.4%, stage III/IV - 92%. RIT (i.e. application of ibritumomab tiuxetan) was a part of the first line therapy in 48 pts. (43%). Further 38 pts. (33%) received ibritumomab tiuxetan after two previous chemotherapy regimens, and 33 pts. (24%) after completing 3-8 lines. In 75 cases RIT was applied as a consolidation of chemotherapy induced response; the rest of the patients received ibritumomab tiuxetan because of relapse/refractory disease. At the moment follow up data are available for 74 MCL patients. Results: After RIT the patients achieved high response rate: CR 60.8%, PR 25.7%, and SD 2.7%. Only 10.8% of the patients progressed. For survival analysis many data had to be censored since the documentation had not been completed yet. The projected 3-year overall survival (OAS, fig.1 - image 001.gif) after radioimmunotherapy was 72% for pts. subjected to RIT consolidation versus 29% for those treated in relapse/refractory disease (p=0.03). RIT was feasible for almost all patients; only 3 procedure-related deaths were reported in the whole group. The main adverse event was hematological toxicity (grade III/IV cytopenias) showing a median time of recovery of Hb, WBC and Plt of 45, 40 and 38 days respectively. Conclusion: Standard-dose non-myeloablative RIT is a feasible and safe treatment modality, even for elderly MCL pts. Consolidation radioimmunotherapy with ibritumomab tiuxetan may prolong survival of patients who achieved clinical response after chemotherapy. Therefore, this consolidation approach should be considered as a treatment strategy for those, who are not eligible for ASCT. RIT also has a potential role as a palliation therapy in relapsing/resistant cases.

Nonperturbative semiclassical stability of de Sitter spacetime for small metric deviations

We consider the linearized semiclassical Einstein equations for small deviations around de Sitter spacetime including the vacuum polarization effects of conformal fields. Employing the method of order reduction, we find the exact solutions for general metric perturbations (of scalar, vector and tensor type). Our exact (nonperturbative) solutions show clearly that in this case de Sitter is stable with respect to small metric deviations and a late-time attractor. Furthermore, they also reveal a breakdown of perturbative solutions for a sufficiently long evolution inside the horizon. Our results are valid for any conformal theory, even self-interacting ones with arbitrarily strong coupling.

Amplification and displacement of chaotic attractors by means of unidirectional chaotic driving

Chaotic systems, when used to drive copies of themselves (or parts of themselves) may induce interesting behaviors in the driven system. In case the later exhibits invariance under amplification or translation, they may show amplification (reduction), or displacement of the attractor. It is shown how the behavior to be obtained is implied by the symmetries involved. Two explicit examples are studied to show how these phenomena manifest themselves under perfect and imperfect coupling.

Observation of a continuous interior crisis in the Hindmarsh-Rose neuron model.

Interior crises are understood as discontinuous changes of the size of a chaotic attractor that occur when an unstable periodic orbit collides with the chaotic attractor. We present here numerical evidence and theoretical reasoning which prove the existence of a chaos-chaos transition in which the change of the attractor size is sudden but continuous. This occurs in the Hindmarsh¿Rose model of a neuron, at the transition point between the bursting and spiking dynamics, which are two different dynamic behaviors that this system is able to present. Moreover, besides the change in attractor size, other significant properties of the system undergoing the transitions do change in a relevant qualitative way. The mechanism for such transition is understood in terms of a simple one-dimensional map whose dynamics undergoes a crossover between two different universal behaviors

Parâmetros zootécnicos de juvenis de pacu alimentados a diferentes frequências de arraçoamento em tanques-rede

O objetivo deste trabalho foi avaliar o desempenho zootécnico e as características bromatológicas e hematológicas de pacus alimentados a diferentes frequências de arraçoamento. Três mil e duzentos peixes, com peso inicial médio de 65,9±2,36 g, foram distribuídos em 16 tanques-rede de 5 m³ de volume útil. Durante 65 dias, foram avaliadas quatro frequências de arraçoamento (tratamentos): T1, às 12:00 h; T2, às 8:00 e às 17:00 h; T3, às 8:00, 12:00 e 17:00 h; e T4, às 8:00, 11:00, 14:00 e 17:00 h. Utilizou-se o delineamento experimental inteiramente casualizado, com quatro repetições. Analisaram-se parâmetros de desempenho produtivo, índices de gordura visceral e hepatossomático, composição centesimal da carcaça e parâmetros hematológicos e bioquímicos. Quanto ao ganho de peso, as frequências T3 e T4 proporcionaram melhores resultados do que T1 e T2. Embora a proteína, o colesterol e os eritrócitos tenham apresentado diferenças entre os tratamentos, permaneceram dentro dos valores de referência para pacus cultivados em tanques-rede. A frequência de três arraçoamentos diários resultou em maior ganho de peso, em comparação aos demais tratamentos, sem interferir na saúde e na composição centesimal das carcaças dos animais.

Torque vibration model of axial-flux surface-mounted permanent magnet synchronous machine

In order that the radius and thus ununiform structure of the teeth and otherelectrical and magnetic parts of the machine may be taken into consideration the calculation of an axial flux permanent magnet machine is, conventionally, doneby means of 3D FEM-methods. This calculation procedure, however, requires a lotof time and computer recourses. This study proves that also analytical methods can be applied to perform the calculation successfully. The procedure of the analytical calculation can be summarized into following steps: first the magnet is divided into slices, which makes the calculation for each section individually, and then the parts are submitted to calculation of the final results. It is obvious that using this method can save a lot of designing and calculating time. Thecalculation program is designed to model the magnetic and electrical circuits of surface mounted axial flux permanent magnet synchronous machines in such a way, that it takes into account possible magnetic saturation of the iron parts. Theresult of the calculation is the torque of the motor including the vibrations. The motor geometry and the materials and either the torque or pole angle are defined and the motor can be fed with an arbitrary shape and amplitude of three-phase currents. There are no limits for the size and number of the pole pairs nor for many other factors. The calculation steps and the number of different sections of the magnet are selectable, but the calculation time is strongly depending on this. The results are compared to the measurements of real prototypes. The permanent magnet creates part of the flux in the magnetic circuit. The form and amplitude of the flux density in the air-gap depends on the geometry and material of the magnetic circuit, on the length of the air-gap and remanence flux density of the magnet. Slotting is taken into account by using the Carter factor in the slot opening area. The calculation is simple and fast if the shape of the magnetis a square and has no skew in relation to the stator slots. With a more complicated magnet shape the calculation has to be done in several sections. It is clear that according to the increasing number of sections also the result will become more accurate. In a radial flux motor all sections of the magnets create force with a same radius. In the case of an axial flux motor, each radial section creates force with a different radius and the torque is the sum of these. The magnetic circuit of the motor, consisting of the stator iron, rotor iron, air-gap, magnet and the slot, is modelled with a reluctance net, which considers the saturation of the iron. This means, that several iterations, in which the permeability is updated, has to be done in order to get final results. The motor torque is calculated using the instantaneous linkage flux and stator currents. Flux linkage is called the part of the flux that is created by the permanent magnets and the stator currents passing through the coils in stator teeth. The angle between this flux and the phase currents define the torque created by the magnetic circuit. Due to the winding structure of the stator and in order to limit the leakage flux the slot openings of the stator are normally not made of ferromagnetic material even though, in some cases, semimagnetic slot wedges are used. In the slot opening faces the flux enters the iron almost normally (tangentially with respect to the rotor flux) creating tangential forces in the rotor. This phenomenon iscalled cogging. The flux in the slot opening area on the different sides of theopening and in the different slot openings is not equal and so these forces do not compensate each other. In the calculation it is assumed that the flux entering the left side of the opening is the component left from the geometrical centre of the slot. This torque component together with the torque component calculated using the Lorenz force make the total torque of the motor. It is easy to assume that when all the magnet edges, where the derivative component of the magnet flux density is at its highest, enter the slot openings at the same time, this will have as a result a considerable cogging torque. To reduce the cogging torquethe magnet edges can be shaped so that they are not parallel to the stator slots, which is the common way to solve the problem. In doing so, the edge may be spread along the whole slot pitch and thus also the high derivative component willbe spread to occur equally along the rotation. Besides forming the magnets theymay also be placed somewhat asymmetric on the rotor surface. The asymmetric distribution can be made in many different ways. All the magnets may have a different deflection of the symmetrical centre point or they can be for example shiftedin pairs. There are some factors that limit the deflection. The first is that the magnets cannot overlap. The magnet shape and the relative width compared to the pole define the deflection in this case. The other factor is that a shifting of the poles limits the maximum torque of the motor. If the edges of adjacent magnets are very close to each other the leakage flux from one pole to the other increases reducing thus the air-gap magnetization. The asymmetric model needs some assumptions and simplifications in order to limit the size of the model and calculation time. The reluctance net is made for symmetric distribution. If the magnets are distributed asymmetrically the flux in the different pole pairs will not be exactly the same. Therefore, the assumption that the flux flows from the edges of the model to the next pole pairs, in the calculation model from one edgeto the other, is not correct. If it were wished for that this fact should be considered in multi-pole pair machines, this would mean that all the poles, in other words the whole machine, should be modelled in reluctance net. The error resulting from this wrong assumption is, nevertheless, irrelevant.

Análisis de la concentración de los Fondos Estructurales por Comunidades Autónomas

En este trabajo se analiza la distribución en España de las ayudas estructurales comuni- tarias del FEDER por Comunidades Autónomas y para dos períodos quinquenales, el primero correspondiente a los años 1989-1993 y el segundo entre 1994 y 1999. En concreto se obtienen medidas de concentración para destacar las diferencias en el FEDER per capita asignado a las poblaciones elegibles por la Unión Europea. Los indicadores que se presentan derivan del diagrama de Lorenz. Por un lado, la superficie que separa la recta imaginaria de equidistribución de la curva es una buena medida de concentración de la variable, y por otro, en la misma representación surgen distancias de interés que reflejan la desigualdad en el reparto de los fondos FEDER per capita de la población asignada por los objetivos 1, 2 y 5b. Las curvas teóricas de concentración que se utilizan en este estudio (modelo de Kakwani-Podder, modelo de Kakwani y modelo de Gupta) se estiman a partir de los datos de la variable económica. Con las estimaciones se calculan las medidas de desigualdad que permitirán el cálculo cuantitativo de la concentración de los fondos comunitarios.

Assessment of inflammatory Bowel Disease patient's needs and problems from a nursing perspective

BACKGROUND: In this study, we aimed at assessing Inflammatory Bowel Disease patients' needs and current nursing practice to investigate to what extent consensus statements (European Crohn's and Colitis Organization) on the nursing roles in caring for patients with IBD concur with local practice. METHODS: We used a mixed-method convergent design to combine quantitative data prospectively collected in the Swiss IBD cohort study and qualitative data from structured interviews with IBD healthcare experts. Symptoms, quality of life, and anxiety and depression scores were retrieved from physician charts and patient self-reported questionnaires. Descriptive analyses were performed based on quantitative and qualitative data. RESULTS: 230 patients of a single center were included, 60% of patients were males, and median age was 40 (range 18-85). The prevalence of abdominal pain was 42%. Self-reported data were obtained from 75 out of 230 patients. General health was perceived significantly lower compared with the general population (p < 0.001). Prevalence of tiredness was 73%; sleep problems, 78%; issues related to work, 20%; sexual constraints, 35%; diarrhea, 67%; being afraid of not finding a bathroom, 42%; depression, 11%; and anxiety symptoms, 23%. According to experts' interviews, the consensus statements are found mostly relevant with many recommendations that are not yet realized in clinical practice. CONCLUSION: Identified prevalence may help clinicians in detecting patients at risk and improve patient management. © 2015 S. Karger AG, Basel.

Fenologia e acúmulo de graus-dia da videira 'Niagara Rosada' cultivada ao noroeste do estado de São Paulo

Este trabalho teve por objetivo avaliar a influência dos porta-enxertos 'IAC 766', 'IAC 572', 'IAC 313' e 'IAC 571-6' na duração dos estádios fenológicos e no acúmulo de graus- dia pela videira 'Niagara Rosada', cultivada em Votuporanga-SP. O delineamento estatístico utilizado foi em blocos inteiramente casualizados, com parcelas subdivididas, cinco repetições, sendo as parcelas representadas pelos porta-enxertos, e as subparcelas, pelos dois ciclos de produção. Após a poda da videira, foram realizadas avaliações dos estádios fenológicos, utilizando-se do critério de Eichhon e Lorenz (1984). Baseado nos estádios fenológicos, calculou-se a duração dos períodos: poda ao início da brotação; poda ao início do florescimento; poda ao início da frutificação; poda ao início da maturação dos cachos; poda ao início da colheita. Tomando-se por base a duração do ciclo da videira e as temperaturas médias diárias, calculou-se o acúmulo de graus-dia. Obteve-se maior duração do ciclo e do acúmulo de graus-dia da cultivar Niagara Rosada com os porta-enxertos 'IAC 572' e 'IAC 571-6', e a menor, com o porta-enxerto 'IAC 766'. Evidenciou-se a influência do clima na duração dos estádios fenológicos da videira.

Desenvolvimento e ocorrência de pérola-da-terra em videiras rústicas e finas enxertadas sobre os porta-enxertos 'VR 043-43' e 'Paulsen 1103'

Este trabalho teve por objetivo avaliar a ocorrência de pérola-da-terra (Eurhizococcus brasiliensis) (Hemiptera: Margarodidae), bem como o desenvolvimento vegetativo e a fenologia das videiras 'Isabel', 'Bordô (Vitis labrusca L.), 'Cabernet Sauvignon', 'Malbec' e 'Merlot' (Vitis vinifera L.) enxertadas sobre os porta-enxertos 'Paulsen 1103' e 'VR 043-43'. O experimento foi conduzido no pomar experimental do Departamento de Agronomia da Universidade Estadual do Centro-Oeste (Unicentro), localizado em Guarapuava-PR, durante a safra de 2010/2011. O delineamento experimental adotado foi em blocos casualizados, em esquema fatorial 5 x 2 (cultivares x porta-enxerto), com o total de 10 tratamentos, cinco repetições e três plantas por parcela experimental. Cada bloco foi constituído por uma linha de plantio. Foram avaliados: as massas fresca (MFP) e seca (MSP) do material oriundo da poda de produção. Logo após a colheita dos frutos, as plantas foram retiradas do solo e, posteriormente, quantificou-se o número de pérola-da-terra por planta (NP), as massas fresca (MFR) e seca (MSR) de raízes, as massas fresca (MFC) e seca (MSC) do caule. Além disso, também foi avaliada a duração dos estádios fenológicos baseados na metodologia de Eichhorn e Lorenz (1984). Verificou-se que as videiras enxertadas sobre o 'VR 043-43' apresentaram menor quantidade de cistos de pérola-da-terra, no entanto este fator influenciou positivamente apenas no desenvolvimento vegetativo das cultivares americanas, sendo que, para as demais variáveis analisadas, não houve influência do porta-enxerto.