Defects in memory B-cell and plasma cell subsets expressing different immunoglobulin-subclasses in patients with CVID and immunoglobulin subclass deficiencies

Background: Predominantly antibody deficiencies (PADs) are the most prevalent primary immunodeficiencies, but their B-cell defects and underlying genetic alterations remain largely unknown. Objective: We investigated patients with PADs for the distribution of 41 blood B-cell and plasma cell (PC) subsets, including subsets defined by expression of distinct immunoglobulin heavy chain subclasses. Methods: Blood samples from 139 patients with PADs, 61 patients with common variable immunodeficiency (CVID), 68 patients with selective IgA deficiency (IgAdef), 10 patients with IgG subclass deficiency with IgA deficiency, and 223 agematched control subjects were studied by using flow cytometry with EuroFlow immunoglobulin isotype staining. Patients were classified according to their B-cell and PC immune profile, and the obtained patient clusters were correlated with clinical manifestations of PADs. Results: Decreased counts of blood PCs, memory B cells (MBCs), or both expressing distinct IgA and IgG subclasses were identified in all patients with PADs. In patients with IgAdef, B-cell defects were mainly restricted to surface membrane (sm)IgA1 PCs and MBCs, with 2 clear subgroups showing strongly decreased numbers of smIgA1 PCs with mild versus severe smIgA1 MBC defects and higher frequencies of nonrespiratory tract infections, autoimmunity, and affected family members. Patients with IgG subclass deficiency with IgA deficiency and those with CVID showed defects in both smIgA1 and smIgG1 MBCs and PCs. Reduced numbers of switched PCs were systematically found in patients with CVID (absent in 98%), with 6 different defective MBC (and clinical) profiles: (1) profound decrease in MBC numbers; (2) defective CD271 MBCs with almost normal IgG3 1 MBCs; (3) absence of switched MBCs; and (4) presence of both unswitched and switched MBCs without and; (5) with IgG2 1 MBCs; and (6) with IgA

Estimación de la concentración media diaria de material particulado fino en la región del Complejo Industrial y Portuario de Pecém, Ceará, Brasil

A exposição ao material particulado fino (MP2,5) está associada a inúmeros desfechos à saúde. Desta forma, monitoramento da concentração ambiental do MP2,5 é importante, especialmente em áreas amplamente industrializadas, pois abrigam potenciais emissores do MP2,5 e de substâncias com potencial de aumentar a toxicidade de partículas já suspensas. O objetivo desta pesquisa é estimar a concentração diária do MP2,5 em três áreas de influência do Complexo Industrial e Portuário do Pecém (CIPP), Ceará, Brasil. Foi aplicado um modelo de regressão não linear para a estimativa do MP2,5, por meio de dados de profundidade óptica monitorados por satélite. As estimativas foram realizadas em três áreas de influência (Ai) do CIPP (São Gonçalo do Amarante – Ai I, Paracuru e Paraipaba – Ai II e Caucaia – Ai III, no período de 2006 a 2017. As médias anuais das concentrações estimadas foram inferiores ao estabelecido pela legislação nacional em todas as Ai (8µg m-3). Em todas as Ai, os meses referentes ao período de seca (setembro a fevereiro) apresentaram as maiores concentrações e uma predominância de ventos leste para oeste. Os meses que compreendem o período de chuva (março a agosto) apresentaram as menores concentrações e ventos menos definidos. As condições meteorológicas podem exercer um papel importante nos processos de remoção, dispersão ou manutenção das concentrações do material particulado na região. Mesmo com baixas concentrações estimadas, é importante avaliar a constituição das partículas finas dessa região, bem como sua possível associação a efeitos adversos à saúde da população local.Exposure to fine particulate matter (PM2.5) is associated with numerous negative health outcomes. Thus, monitoring the environmental concentration of PM2.5 is important, especially in heavily industrialized areas, since they harbor potential emitters of PM2.5 and substances with the potential to increase the toxicity of already suspended particles. This study aims to estimate daily concentrations of PM2.5 in three areas under the influence of the Industrial and Port Complex of Pecém (CIPP), Ceará State, Brazil. A nonlinear regression model was applied to estimate PM2.5, using satellitemonitored optical depth data. Estimates were performed in three areas of influence (Ai) of the CIPP (São Gonçalo do Amarante – AiI, Paracuru and Paraipaba – AiII, and Caucaia – AiIII), from 2006 to 2017. Estimated mean annual concentrations were lower than established by Brazil’s national legislation in all three Ai (8µg m-³). In all the Ai, the months of the dry season (September to February) showed the highest concentrations and a predominance of east winds, while the months of the rainy season (March to August) showed the lowest concentrations and less defined winds Weather conditions can play an important role in the removal, dispersal, or maintenance of concentrations of particulate matter in the region. Even at low estimated concentrations, it is important to assess the composition of fine participles in this region and their possible association with adverse health outcomes in the local population.La exposición al material particulado fino (MP2,5) está asociada a innumerables problemas de salud. Por ello, la supervisión de la concentración ambiental del MP2,5 es importante, especialmente en áreas ampliamente industrializadas, puesto que albergan potenciales emisores de MP2,5 y de sustancias con potencial de aumentar la toxicidad de partículas ya suspendidas. El objetivo de esta investigación es estimar la concentración diaria del MP2,5 en tres áreas de influencia del Complejo Industrial y Portuario de Pecém (CIPP), Ceará, Brasil. Se aplicó un modelo de regresión no lineal para la estimación del MP2,5, mediante datos de profundidad óptica supervisados por satélite. Las estimaciones fueron realizadas en tres áreas de influencia (Ai) del CIPP (São Gonçalo do Amarante – Ai I, Paracuru y Paraipaba – Ai II y Caucaia – Ai III en el período de 2006 a 2017. Las medias anuales de las concentraciones estimadas fueron inferiores a lo establecido por la legislación nacional en todas las Ai (8µg m-³). En todas las Ai, los meses referentes al período de sequía (de setiembre a febrero) presentaron las mayores concentraciones y una predominancia de vientos este a oeste, los meses que comprenden el período de lluvia (marzo a agosto) presentaron las menores concentraciones y vientos menos definidos. Las condiciones meteorológicas pueden ejercer un papel importante en los procesos de eliminación, dispersión o mantenimiento de las concentraciones del material particulado en la región. Incluso con bajas concentraciones estimadas es importante que se evalúe la constitución de las partículas finas de esta región, así como su posible asociación con efectos adversos para la salud de la población local

25 Years of Self-organized Criticality: Concepts and Controversies

Introduced by the late Per Bak and his colleagues, self-organized criticality (SOC) has been one of the most stimulating concepts to come out of statistical mechanics and condensed matter theory in the last few decades, and has played a significant role in the development of complexity science. SOC, and more generally fractals and power laws, have attracted much comment, ranging from the very positive to the polemical. The other papers (Aschwanden et al. in Space Sci. Rev., 2014, this issue; McAteer et al. in Space Sci. Rev., 2015, this issue; Sharma et al. in Space Sci. Rev. 2015, in preparation) in this special issue showcase the considerable body of observations in solar, magnetospheric and fusion plasma inspired by the SOC idea, and expose the fertile role the new paradigm has played in approaches to modeling and understanding multiscale plasma instabilities. This very broad impact, and the necessary process of adapting a scientific hypothesis to the conditions of a given physical system, has meant that SOC as studied in these fields has sometimes differed significantly from the definition originally given by its creators. In Bak’s own field of theoretical physics there are significant observational and theoretical open questions, even 25 years on (Pruessner 2012). One aim of the present review is to address the dichotomy between the great reception SOC has received in some areas, and its shortcomings, as they became manifest in the controversies it triggered. Our article tries to clear up what we think are misunderstandings of SOC in fields more remote from its origins in statistical mechanics, condensed matter and dynamical systems by revisiting Bak, Tang and Wiesenfeld’s original papers

Search for invisible decays of the Higgs boson produced via vector boson fusion in proton-proton collisions at s\sqrt{s} = 13 TeV

A search for invisible decays of the Higgs boson produced via vector boson fusion (VBF) has been performed with 101  fb$^{-1}$ of proton-proton collisions delivered by the LHC at $\sqrt{s}$ =13  TeV and collected by the CMS detector in 2017 and 2018. The sensitivity to the VBF production mechanism is enhanced by constructing two analysis categories, one based on missing transverse momentum and a second based on the properties of jets. In addition to control regions with Z and W boson candidate events, a highly populated control region, based on the production of a photon in association with jets, is used to constrain the dominant irreducible background from the invisible decay of a Z boson produced in association with jets. The results of this search are combined with all previous measurements in the VBF topology, based on data collected in 2012 (at $\sqrt{s}$ =8  TeV), 2015, and 2016, corresponding to integrated luminosities of 19.7, 2.3, and 36.3  fb$^{-1}$, respectively. The observed (expected) upper limit on the invisible branching fraction of the Higgs boson is found to be 0.18 (0.10) at the 95% confidence level, assuming the standard model production cross section. The results are also interpreted in the context of Higgs-portal models