Interferon-gamma release assays (IGRAs) in high-endemic settings: could they play a role in optimizing global TB diagnostics? Evaluating the possibilities of using IGRAs to diagnose active TB in a rural African setting

SummaryThe number of patients suffering from tuberculosis (TB) globally is increasing. Due to the HIV epidemic, most patients suffering from TB reside in sub-Saharan Africa. In order to improve TB diagnostics, new tests – interferon-gamma release assays (IGRAs) – have been developed over the last decade. In this paper we evaluate the possible use of these tests in diagnosing or excluding active TB in high HIV-burden, resource-limited settings. The inability to differentiate between active and latent TB, limited data on IGRA performance in HIV-infected patients, observed false-negative results, high costs, and logistic problems limit the potential benefit of IGRAs. We also present two theoretical study designs in order to further assess IGRAs. Setting up a study on this subject is complicated by the frequent unavailability of mycobacterial cultures, the difficulty in acquiring prospective data, and the impossibility of denying treatment to a patient suspected of having active TB. We feel that current evidence does not support the implementing of IGRAs in clinical practice in settings with high endemic latent TB infection (LTBI) and high HIV prevalence. As these settings are the ones that suffer the most from the TB epidemic, we believe that the role of IGRAs in global TB control is questionable

Swiss Marketing Leadership Studie 2018 : Geschwindigkeit vs. Beständigkeit

Der technologische Fortschritt sowie die Digitalisierung der Gesellschaft, aber auch der Unternehmen, sind ausschlaggebend für schnelle Innovationen und immer kürzer werdende Produkt- und Dienstleistungslebenszyklen (Wallmüller, 2017). Infolgedessen verändern sich auch die Bedürfnisse und das Verhalten der Kunden. Die sich stetig verändernden Umweltbedingungen stellen Unternehmen vor die Herausforderung, diese zunehmende Dynamik und Komplexität zu bewältigen (Schoeneberg, 2014). So bleibt auch das Marketing von dieser Herausforderung nicht unberührt. Da die verändernden Kundenanforderungen rechtzeitig erkannt und entsprechend passgenaue Massnahmen getroffen werden müssen, kommt ihr als Schnittstelle zum Markt eine immer bedeutsamere Rolle im Unternehmen zu. Um eine langfristige Wettbewerbsfähigkeit von Unternehmen gewährleisten zu können, sind rasche Reaktionszeiten sowie flexible Anpassungsmöglichkeiten zu zentralen Voraussetzungen geworden (Smart, 2016). Unter diesem Aspekt gewinnt die Geschwindigkeit bzw. die Agilität im Marketing für ein Unternehmen zunehmend an Bedeutung. Dies bestätigt ebenfalls eine aktuelle Studie von Fryrear (2018), in welcher über die steigende Bedeutung von Agilität im Kontext des Marketings diskutiert wird. Die Resultate zeigen, dass rund 37 Prozent der befragten Marketingteams bereits agile Prozesse anwenden, während sich rund 61 Prozent derzeit damit befassen, in naher Zukunft (innerhalb der nächsten 12 Monate) agiler zu werden. Agilität stellt somit nicht nur einen vorübergehenden Trend dar, sondern eine ernstzunehmende Thematik, welche im Marketing künftig eine immer zentralere Rolle einnehmen wird. Doch wird im Marketing überall mehr Geschwindigkeit benötigt oder gibt es Bereiche, in denen eher auf Beständigkeit und Kontinuität gesetzt werden sollte? Ist es ein «entweder oder» oder ein «sowohl als auch»? Mit diesen und weiteren Fragen beschäftigt sich auch das Institut für Marketing Management der ZHAW in seiner Forschung seit einiger Zeit

Gender Gap in Parental Leave Intentions: Evidence from 37 Countries

Despite global commitments and efforts, a gender-based division of paid and unpaid work persists. To identify how psychological factors, national policies, and the broader sociocultural context contribute to this inequality, we assessed parental-leave intentions in young adults (18–30 years old) planning to have children (N = 13,942; 8,880 identified as women; 5,062 identified as men) across 37 countries that varied in parental-leave policies and societal gender equality. In all countries, women intended to take longer leave than men. National parental-leave policies and women’s political representation partially explained cross-national variations in the gender gap. Gender gaps in leave intentions were paradoxically larger in countries with more gender-egalitarian parental-leave policies (i.e., longer leave available to both fathers and mothers). Interestingly, this cross-national variation in the gender gap was driven by cross-national variations in women’s (rather than men’s) leave intentions. Financially generous leave and gender-egalitarian policies (linked to men’s higher uptake in prior research) were not associated with leave intentions in men. Rather, men’s leave intentions were related to their individual gender attitudes. Leave intentions were inversely related to career ambitions. The potential for existing policies to foster gender equality in paid and unpaid work is discussed.Gender Gap in Parental Leave Intentions: Evidence from 37 CountriespublishedVersio

Gender Gap in Parental Leave Intentions: Evidence from 37 Countries

Despite global commitments and efforts, a gender-based division of paid and unpaid work persists. To identify how psychological factors, national policies, and the broader sociocultural context contribute to this inequality, we assessed parental-leave intentions in young adults (18–30 years old) planning to have children (N = 13,942; 8,880 identified as women; 5,062 identified as men) across 37 countries that varied in parental-leave policies and societal gender equality. In all countries, women intended to take longer leave than men. National parental-leave policies and women’s political representation partially explained cross-national variations in the gender gap. Gender gaps in leave intentions were paradoxically larger in countries with more gender-egalitarian parental-leave policies (i.e., longer leave available to both fathers and mothers). Interestingly, this cross-national variation in the gender gap was driven by cross-national variations in women’s (rather than men’s) leave intentions. Financially generous leave and gender-egalitarian policies (linked to men’s higher uptake in prior research) were not associated with leave intentions in men. Rather, men’s leave intentions were related to their individual gender attitudes. Leave intentions were inversely related to career ambitions. The potential for existing policies to foster gender equality in paid and unpaid work is discussed

Parâmetros hemato-imunológicos e perfil histológico de alguns tecidos de ostra do mangue Crassostrea rhizophorae

Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências Agrárias. Programa de Pós-Graduação em AquiculturaO objetivo do presente trabalho foi o de realizar um estudo inicial dos hemócitos e de alguns parâmetros hemolinfáticos da ostra do mangue Crassostrea rhizophorae, além de caracterizar histologicamente sua glândula digestiva e brânquias. Os animais foram coletados sazonalmente (n=30) no período de fevereiro a novembro de 2001, de uma estação de cultivo e de dois habitats naturais da ilha de Santa Catarina, Santa Catarina, Brasil. Foram identificados dois tipos celulares, hemócitos hialinos (HH) e hemócitos granulares (HG) na hemolinfa das ostras. Estas células mostraram conter carboidratos e glicogênio em seu citoplasma, quando submetidas ao método de PAS. A presença de fosfatase ácida intracelular, detectada pelo método de Gomori, sugeriu a presença de lisossomos e o potencial envolvimento dos hemócitos nas reações de fagocitose. Efetivamente, os hemócitos foram capazes de fagocitar in vitro partículas de zymosan, além de produzir moléculas citotóxicas, como ânion superóxido (redução do NBT) durante este processo. A contagem total de hemócitos (THC) variou de 1.100 a 4.000 (céls/mm3), havendo algumas diferenças significativas tanto em relação aos locais de coleta como em relação às estações do ano. Os valores mais elevados de THC ocorreram no verão e em relação aos três locais de coleta, os maiores valores foram geralmente encontrados nas ostras do manguezal. A porcentagem de HG variou de 34 a 82%, havendo diferenças significativas ao longo das estações e em relação aos três locais de coleta. Nas ostras coletadas no manguezal, os HG foram sempre predominantes (mais de 50%). A concentração de proteínas totais do plasma (CP), estimada pelo método de Bradford, variou de 0,11 a 3,0 mg/ml e mostrou um padrão sazonal similar nas ostras das três localidades. Os maiores valores foram atingidos no outono e os menores na primavera. O título aglutinante do plasma contra eritrócitos A humanos (2%) variou de 32 a 16.384, sendo os maiores valores sempre encontrados no cultivo. A análise histológica da glândula digestiva e das brânquias de C. rhizophorae revelou um padrão de organização semelhante ao de outras espécies de ostras. Além disso, não foram observadas alterações nas estruturas e arquitetura destes tecidos

Investigation of isolated compounds from spider caranguejeira Acanthoscurria natalensis Chamberlin, 1917 and its chemical and biological characterization

Tese (doutorado)—Universidade de Brasília, Instituto de Ciências Biológicas, Programa de Pós-Graduação em Biologia Animal, 2018.Texto parcialmente liberado. Conteúdo restrito: Parte II e III.A peçonha de aranhas é composta por uma mistura complexa de moléculas, como acilpoliaminas, peptídios e proteínas neurotóxicas e, enzimas, como hialuronidases. A caracterização destas moléculas tem possibilitado o desenvolvimento de diversas aplicações farmacológicas e biotecnológicas. Contudo, poucas moléculas foram estudadas em aranhas do gênero Acanthoscurria, inclusive em Acanthoscurria natalensis. Assim, o objetivo deste estudo foi a investigação de compostos presentes na peçonha de A. natalensis e sua caracterização química e biológica. A peçonha foi fracionada por cromatografia líquida (RP-HPLC) obtendo-se 18 frações principais. O screening de atividades biológicas da peçonha e/ou frações, identificou ação antimicrobiana pronunciada, manutenção da viabilidade celular e redução da produção de óxido nítrico, na fração composta por acilpoliaminas. A peçonha apresentou atividade hialuronidásica correspondente a fração 18 (AnHyal) e nenhuma atividade proteásica e fosfolipásica. A concentração inibitória mínima (CIM) das acilpoliaminas contra Staphylococcus aureus e Escherichia coli variou entre 128 e 256 μM, sem causar hemólise nestas mesmas concentrações. A estrutura química parcial das acilpoliaminas (614―756 Da) sugerida pelo espectro UV e padrão de fragmentação (ESI-MS/MS), compreende uma unidade tirosil ligada a uma cadeia poliamina, contendo ao menos uma espermidina. A caracterização da AnHyal indicou atividade máxima entre pH 4,0 e 6,0 e temperatura entre 30 e 60oC, degradando preferencialmente o ácido hialurônico. O sequenciamento parcial (LC-MS/MS e degradação de Edman) da AnHyal mostrou similaridades para a hialuronidase da aranha Brachipelma vagans e proteína CRISP de Grammostola rosea, com 64% e 79% de cobertura proteica, respectivamente. Análises por 1D e 2D BN-PAGE/SDS-PAGE/zimograma, mostraram que a AnHyal é composta pelas proteínas hialuronidade e CRISP, formando um complexo enzimaticamente ativo. Sua estrutura secundária contém 36,15% de α-hélice e a temperatura de desnaturação (Tm) foi de 46,37 °C, sendo esta irreversível. Em conclusão, este estudo possibilitou a identificação e caracterização parcial de acilpoliaminas com propriedades biológicas que podem contribuir para sua qualificação como possível agente terapêutico. Ainda, a AnHyal mostrou a presença de um complexo proteico enzimaticamente ativo entre as proteínas hialuronidase e CRISP, sendo este descrito pela primeira vez. Estudos adicionais poderão elucidar outras propriedades deste complexo, ampliando as possibilidades de aplicações biotecnológicas.Spider venom is composed of a complex mixture of molecules, such as acylpolyamines, peptides and neurotoxic proteins, and enzymes such as hyaluronidases. The characterization of these molecules has enabled the development of several pharmacological and biotechnological applications. However, few molecules have been studied in spiders of the genus Acanthoscurria, including Acanthoscurria natalensis. Thus, the objective of this study was the investigation of the compounds present in A. natalensis venom and its chemical and biological characterization. The venom was fractionated by liquid chromatography (RP-HPLC) obtaining 18 main fractions. The screening of biological activities of venom and/or fractions, identified pronounced antimicrobial action, maintenance of cellular viability and reduction of nitric oxide production, in the fraction composed of acylpolyamines. The venom presented hyaluronidase activity corresponding to fraction 18 (AnHyal) and no protease and phospholipase activity. The minimum inhibitory concentration (MIC) of the acylpolyamines against Staphylococcus aureus and Escherichia coli varied between 128 and 256 μM, without causing hemolysis at these same concentrations. The partial chemical structure of the acylpolyamine (614-756 Da) suggested by the UV spectrum and fragmentation standard (ESI-MS / MS) comprises a tyrosyl moiety attached to a polyamine chain containing at least one spermidine. The characterization of AnHyal indicated maximum activity between pH 4.0 and 6.0 and temperature between 30 and 60oC, preferentially degrading hyaluronic acid. AnHyal's partial sequencing (LC-MS / MS and degradation of Edman) showed similarities to the Brachipelma vagans spider hyaluronidase and Grammostola rosea CRISP protein, with 64% and 79% protein coverage, respectively. Analyzes by 1D and 2D BN-PAGE/SDS-PAGE/zymogram, showed that AnHyal is composed of hyaluron and CRISP proteins, forming an enzymatically active complex. Its secondary structure contains 36.15% α-helix and the denaturation temperature (Tm) was 46.37 ° C, which is irreversible. In conclusion, this study allowed the identification and partial characterization of acylpolyamines with biological properties that may contribute to its qualification as a possible therapeutic agent. Furthermore, AnHyal showed the presence of an enzymatically active protein complex between the hyaluronidase and CRISP proteins, which is described for the first time. Further studies may elucidate other properties of this complex, expanding the possibilities of biotechnological applications

Evaluation of some hemato-immunological parameters in the mangrove oyster

The main purpose of this study was to establish the pattern of variability of some hemato-immunological parameters in the mangrove oyster, Crassostrea rhizophorae, from 3 different environmental conditions in Santa Catarina Island: two natural habitats (mangrove and rocks of the coastal bay) and one oyster culture station. The water quality was adequate in all localities. The animals were collected seasonally over a period of one year (n = 30, per locality). The oyster hemolymph comprised two basic cell populations, hyaline (HH) and granular hemocytes (GH). Both cell populations contained carbohydrates and glycogen in their cytoplasm (periodic acid Schiff reaction, PAS staining) and the occurrence of lysosomes was suggested by the detection of acid phosphatase (Gomori's method). Both hemocyte populations were able of phagocytosis of zymosan particles in vitro and producing cytotoxic molecules, such as the superoxide anions (nitroblue-tetrazolium, NBT reduction). The oyster hemograms significantly differed in the different habitats and also among seasons. The total circulating hemocyte counts (THC) and the percentage of GH in the mangrove and rock oysters always differed from each other, but not from those of the cultured oysters. The highest THC and the lowest percentage of GH were always found in summer. The total plasma protein concentration (PC) exhibited a similar seasonal pattern in all oyster populations, with a marked decrease in spring. The PC of the cultured oysters was almost always significantly lower than that of the other oyster populations. The plasma agglutinating titer was higher in the cultured oysters regardless of season. The histological organization of the oyster digestive gland and gills was basically similar to that of other oyster species. Their structural aspect did not show any detectable alteration, corroborating that the oysters were in good health. The results of this study will serve as a basis for further analyses on the monitoring of C. rhizophorae health status and environmental quality in different aquatic habitats

Genome replication dynamics of a bacteriophage and its satellite reveal strategies for parasitism and viral restriction.

Phage-inducible chromosomal island-like elements (PLEs) are bacteriophage satellites found in Vibrio cholerae. PLEs parasitize the lytic phage ICP1, excising from the bacterial chromosome, replicating, and mobilizing to new host cells following cell lysis. PLEs protect their host cell populations by completely restricting the production of ICP1 progeny. Previously, it was found that ICP1 replication was reduced during PLE(+) infection. Despite robust replication of the PLE genome, relatively few transducing units are produced. We investigated if PLE DNA replication itself is antagonistic to ICP1 replication. Here we identify key constituents of PLE replication and assess their role in interference of ICP1. PLE encodes a RepA_N initiation factor that is sufficient to drive replication from the PLE origin of replication during ICP1 infection. In contrast to previously characterized bacteriophage satellites, expression of the PLE initiation factor was not sufficient for PLE replication in the absence of phage. Replication of PLE was necessary for interference of ICP1 DNA replication, but replication of a minimalized PLE replicon was not sufficient for ICP1 DNA replication interference. Despite restoration of ICP1 DNA replication, non-replicating PLE remained broadly inhibitory against ICP1. These results suggest that PLE DNA replication is one of multiple mechanisms contributing to ICP1 restriction

Common numerical methods & common experimental means for the demonstrators of the large passenger aircraft platforms

The integration of advanced propulsion systems into the aircraft, and the assessment of their benefits related to e.g. fuel burn, noise emission and potential further measures, is one of the major activities of the Large Passenger Aircraft (LPA) Platform 1 of the Clean Sky 2 initiative. In order to optimize and assess the potential of advanced propulsion integration, it is necessary to establish suitable design, evaluation, and measurement tools. The so-called Cross-Demonstrator-Capabilities (XDC-) activities have been set up to develop and demonstrate powerful numerical and experimental methods for aerodynamic, aeroacoustics and aeroelastic simulation and measurement tasks, supporting the dedicated demonstrators of LPA. The paper will give an overview of the XDC activities and some examples of the developments related to this demonstrator