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In resource-limited or point-of-care settings, rapid diagnostic tests (RDTs), that aim to simultaneously detect HIV antibodies and p24 capsid (p24CA) antigen with high sensitivity, can pose important alternatives to screen for early infections. We evaluated the performance of the antibody and antigen components of the old and novel version of the Determine™ HIV-1/2 Ag/Ab Combo RDTs in parallel to quantifications in a fourth-generation antigen/antibody immunoassay (4G-EIA), p24CA antigen immunoassay (p24CA-EIA), immunoblots, and nucleic acid quantification. We included plasma samples of acute, treatment-naïve HIV-1 infections (Fiebig stages I–VI, subtypes A1, B, C, F, CRF02_AG, CRF02_AE, URF) or chronic HIV-1 and HIV-2 infections. The tests’ antigen component was evaluated also for a panel of subtype B HIV-1 transmitted/founder (T/F) viruses, HIV-2 strains and HIV-2 primary isolates. Furthermore, we assessed the analytical sensitivity of the RDTs to detect p24CA using a highly purified HIV-1NL4-3 p24CA standard. We found that 77% of plasma samples from acutely infected, immunoblot-negative HIV-1 patients in Fiebig stages II–III were identified by the new RDT, while only 25% scored positive in the old RDT. Both RDTs reacted to all samples from chronically HIV-1-infected and acutely HIV-1-infected patients with positive immunoblots. All specimens from chronically infected HIV-2 patients scored positive in the new RDT. Of note, the sensitivity of the RDTs to detect recombinant p24CA from a subtype B virus ranged between 50 and 200 pg/mL, mirrored also by the detection of HIV-1 T/F viruses only at antigen concentrations tenfold higher than suggested by the manufacturer. The RTD failed to recognize any of the HIV-2 viruses tested. Our results indicate that the new version of the Determine™ HIV-1/2 Ag/Ab Combo displays an increased sensitivity to detect HIV-1 p24CA-positive, immunoblot-negative plasma samples compared to the precursor version. The sensitivity of 4G-EIA and p24CA-EIA to detect the major structural HIV antigen, and thus to diagnose acute infections prior to seroconversion, is still superior.
Vor zwei Monaten traf ich Sascia Bailer, die Künstlerischen Leiterin des M.1 der Arthur Boskamp-Stiftung in Hohenlockstedt, um über ihr Programm "Care" zu sprechen. Seitdem haben die dramatischen Geschehnisse uns gezwungen, die Realität neu zu überdenken. Bailers Konzept hat in der gegenwärtigen Krise nur an Aktualität gewonnen: Wir alle werden uns noch lange erinnern, wie sich die Care-Arbeitenden – Krankenschwestern, Pfleger*innen, Ärzt*innen und Sozialarbeiter*innen – in den Zeiten der höchsten Not, um uns gekümmert haben. Das Programm in der Ausstellungshalle M.1 hat das Ziel, die Unsichtbarkeit der Fürsorge und ihre Überlastung zu thematisieren und dieser entgegenzuwirken. Im Moment sind die Räume des M.1 sowie alle anderen Museen in Deutschland geschlossen, es lohnt sich aber, genau hinzuschauen, wie neue Dialoge in unserer Gemeinschaft hergestellt werden und welche Rolle dabei die Kunst spielen kann.
Household finance
(2020)
Household financial decisions are complex, interdependent, and heterogeneous, and central to the functioning of the financial system. We present an overview of the rapidly expanding literature on household finance (with some important exceptions) and suggest directions for future research. We begin with the theory and empirics of asset market participation and asset allocation over the lifecycle. We then discuss house-hold choices in insurance markets, trading behavior, decisions on retirement saving, and financial choices by retirees. We survey research on liabilities, including mortgage choice, refinancing, and default, and household behavior in unsecured credit markets, including credit cards and payday lending. We then connect the household to its social environment, including peer effects, cultural and hereditary factors, intra-household financial decision making, financial literacy, cognition and educational interventions. We also discuss literature on the provision and consumption of financial advice.
This essay discusses the current Europeanization of national museums in different European countries and considers it against the background of media theories and feminist epistemologies. Taking the example of the European Solidarity Centre Gdansk, the Deutsches Historisches Museum Berlin and the Musée des civilisations de l’Europe et de la Méditerranée Marseille, it suggests two approaches to the dynamics of travel and locatedness in the museum. Firstly, using the concept of what I call “Europoeic media” this essay shows how “Europe” as a travelling memory is shaped by and in media. Secondly, I argue that the locatedness both of memories and the memory researcher are not detrimental but instead produce “situated knowledges”. Thus, in combining media-sensitivity and standpoint-reflexivity, the paper proposes new ways of taking into account the travels and locatedness of both memories and memory research.
Der vorliegende Beitrag diskutiert, wie mithilfe von Unterrichtsvideographien die Reflexionskompetenz angehender Englischlehrkräfte bereits in der ersten Ausbildungsphase angebahnt und geschult werden kann. Er geht von der Annahme aus, dass praktizierenden Lehrkräften häufig die Gelegenheiten oder auch die Kompetenzen zur systematischen Reflexion fehlen (vgl. Kittel & Rollett, 2017) und diese bereits vorher grundgelegt werden müssen. Anhand von zwei Seminarbeispielen aus der Englischdidaktik, welche sich auf die disziplinspezifischen Heterogenitätsdimensionen Mehrsprachigkeit (vgl. u.a. Elsner & Wildemann, 2012; Niesen, 2018) und Transkulturalität (vgl. u.a. Viebrock, 2018; Kreft, 2019a, 2019b) beziehen, werden praktische Umsetzungsmöglichkeiten bzw. die wechselseitige Integration theoretischer Konzepte und unterrichtlicher Handlungen/Interaktionen illustriert. Die vorgestellten Aufgabenformate beziehen sich auf die kasuistische Fallarbeit (nach Lindow & Münch, 2014) sowie auf VierSchritt-Analysen (nach Santagata & Guarino, 2011). Als grundlegende Struktur für die Entwicklung von Reflexionskompetenz in videobasierten Lernsettings wird eine adaptierte Fassung des Modells von Aeppli und Lötscher (2016) mit den Verfahrensschritten „Erleben“, „Erkennen“, „Darstellen“, „Analysieren“ und „Alternative Szenarien entwickeln“ verwendet. Es zeigt sich, dass die gewählte Vorgehensweise Studierende in die Lage versetzt, die konzeptionelle und unterrichtspraktische Bedeutung von sprachlicher und kultureller Heterogenität im Englischunterricht zu erkennen und, in einem weiteren Schritt, Möglichkeiten zur Förderung von transkulturalitäts- bzw. mehrsprachigkeits-sensitivem Handeln zu identifizieren und somit ihre Reflexionskompetenzen zu schulen.
L'osservazione secondo la quale lo scarto come oggetto di ricerca sia allo stesso tempo un effetto della sua ricerca è ciò che l'articolo traccia in tre studi sulla spazzatura: Rubbish! di William Rathje e Cullen Murphy, Un mondo usa e getta di Guido Viale e Das Miill-System di Volker Grassmuck e Christian Unverzagt. Questi tre studi esemplificano tre modi di presentare lo scarto: esplorazione, problema e ricie/aggio. Guardarli come argomenti scientifici ci permette di discutere di ciò che è considerato scarto ponendo domande di presentazione testuale e, allo stesso tempo, di chiedere quali conseguenze abbia la presentazione per il concetto scientifico dello scarto.
This paper offers a description and account of the patterns of 'ex-situ' focus in Dagbani. We show that there are two syntactic strategies for creating 'ex-situ' focus in the language, one involving A’-movement to the left periphery, and the second involving base generation in the left periphery combined with coreference to a resumptive pronoun. Furthermore, we argue that subjects are difficult to move from Spec,TP to Spec,CP in the left-periphery because of 'anti-locality', which creates a tension when trying to focus subjects, which are required to derivationally fill the specifier of both positions. We further show that what looks to be a two-way distinction between the behaviour of subjects and non-subjects in the language is in fact a three-way distinction between subjects that are focussed to a local left-periphery, subjects that are focussed to a non-local left-periphery, and non-subjects. These distinctions arise due to there being two methods for Dagbani to resolve the antilocality problem of subject movement, and so local subjects solve the problem differently to non-local subjects.
At a site in the Bolivian Chiquitano region composed by a mosaic of pastureland and primary Chiquitano Dry Forest (CDF) we conducted a camera-trapping study to (1) survey the mammals, and (2) compare individual Jaguar numbers with other Chiquitano sites. Therefore, we installed 13 camera stations (450 ha polygon) over a period of six months. On 1,762 camera-days and in 1,654 independent capture events, we recorded 24 mammalian species that represent the native fauna of large and medium-sized mammals including apex-predators (Puma, Jaguar), meso-carnivores (Ocelot, Jaguarundi, Margay), and large herbivores (Tapir, Collared and White lipped Peccary). We identified six adult Jaguars and found indications of successful reproductive activity. Captures of Jaguars were higher in CDF than in altered habitats. In summary, we believe that (1) the mammal species richness, (2) the high capture numbers of indicator species, and (3) the high capture numbers of Jaguar indicate that our study area has a good conservation status. Future efforts should be undertaken to keep this, and monitoring programs in this region are necessary to further evaluate the potential importance of the Chiquitano region as a possible key region for mammals, especially Jaguars, in South America.
URPOSE: Today, the majority of medical graduates in countries such as the UK, the US or Germany are female. This poses a major problem for workforce planning especially in urology. We here use first the first time the previously established Brüggmann Groneberg (BG) index to assess if female academic career options advance in urology.
METHODS: Different operating parameters (student population, urology specialist population, urology chair female:male (f:m) ratio) were collected from the Federal Office of Statistics, the Federal Chamber of Physicians and the medical faculties of 36 German universities. Four time points were monitored (2000, 2005, 2010 and 2015). From these data, female to male (f:m) ratios and the recently established career advancement (BG) index have been calculated.
RESULTS: The German hospital urology specialists' f:m ratios were 0.257 (499 female vs. 1944 male) for 2015, 0.195 for 2010, 0.133 for 2005 and 0.12 for 2000. The career advancement (BG) index was 0.0007 for 2000, 0,0005 for 2005, 0.094 for 2010 and 0.073 for 2015. The decrease from 2010 to 2015 was due to an increase in the f:m ratio of hospital urologists and female medical students.
CONCLUSION: The BG index clearly illustrated that there is an urgent need for special academic career funding programs to counteract gender problems in urology. The BG index has been shown to be an excellent tool to assess female academic career options and will be very helpful to assess and document positive or negative changes in the next decades.
BACKGROUND: Although phosphodiesterase-4 (PDE4) inhibitors have been shown to reduce COPD exacerbation rate, their biological mechanism of action is not completely elucidated at the molecular level. We aimed to characterise the whole genome gene expression profile of the inhaled PDE4-inhibitor CHF6001 on top of triple therapy in sputum cells and whole blood of patients with COPD and chronic bronchitis.
METHODS: Whole genome gene expression analysis was carried out by microarray in 54 patients before and after 32 days treatment with CHF6001 800 and 1600 μg and placebo twice daily (BID) in a randomised crossover study.
RESULTS: CHF6001 had a strong effect in sputum, with 1471 and 2598 significantly differentially-expressed probe-sets relative to placebo (p-adjusted for False Discovery Rate < 0.05) with 800 and 1600 μg BID, respectively. Functional enrichment analysis showed significant modulation of key inflammatory pathways involved in cytokine activity, pathogen-associated-pattern-recognition activity, oxidative stress and vitamin D with associated inhibition of downstream inflammatory effectors. A large number of pro-inflammatory genes coding for cytokines and matrix-metalloproteinases were significantly differentially expressed for both doses; the majority (> 87%) were downregulated, including macrophage inflammatory protein-1-alpha and 1-beta, interleukin-27-beta, interleukin-12-beta, interleukin-32, tumour necrosis factor-alpha-induced-protein-8, ligand-superfamily-member-15, and matrix-metalloproteinases-7,12 and 14. The effect in blood was not significant.
CONCLUSIONS: Inhaled PDE4 inhibition by CHF6001 on top of triple therapy in patients with COPD and chronic bronchitis significantly modulated key inflammatory targets and pathways in the lung but not in blood. Mechanistically these findings support a targeted effect in the lung while minimising unwanted systemic class-effects.
TRIAL REGISTRATION: ClinicalTrial.gov, EudraCT, 2015-005550-35. Registered 15 July 2016.
Correction to: Scientifc Reports https://doi.org/10.1038/s41598-019-43857-5, published online 17 May 2019. In the original version of this Article, Jan-Hendrik Trösemeier was incorrectly affiliated with ‘Division of Allergology, Paul Ehrlich Institut, Langen, Germany’. Te correct afliations are listed below...
Biofabrication of SDF-1 functionalized 3D-printed cell-free scaffolds for bone tissue regeneration
(2020)
Large segmental bone defects occurring after trauma, bone tumors, infections or revision surgeries are a challenge for surgeons. The aim of our study was to develop a new biomaterial utilizing simple and cheap 3D-printing techniques. A porous polylactide (PLA) cylinder was printed and functionalized with stromal-derived factor 1 (SDF-1) or bone morphogenetic protein 7 (BMP-7) immobilized in collagen type I. Biomechanical testing proved biomechanical stability and the scaffolds were implanted into a 6 mm critical size defect in rat femur. Bone growth was observed via x-ray and after 8 weeks, bone regeneration was analyzed with µCT and histological staining methods. Development of non-unions was detected in the control group with no implant. Implantation of PLA cylinder alone resulted in a slight but not significant osteoconductive effect, which was more pronounced in the group where the PLA cylinder was loaded with collagen type I. Addition of SDF-1 resulted in an osteoinductive effect, with stronger new bone formation. BMP-7 treatment showed the most distinct effect on bone regeneration. However, histological analyses revealed that newly formed bone in the BMP-7 group displayed a holey structure. Our results confirm the osteoinductive character of this 3D-biofabricated cell-free new biomaterial and raise new options for its application in bone tissue regeneration.
Hepatocellular carcinoma (HCC) shows a remarkable heterogeneity and is recognized as a chemoresistant tumor with dismal prognosis. In previous studies, we observed significant alterations in the serum sphingolipids of patients with HCC. This study aimed to investigate the in vitro effects of sorafenib, which is the most widely used systemic HCC medication, on the sphingolipid pathway as well as the effects of inhibiting the sphingolipid pathway in HCC. Huh7.5 and HepG2 cells were stimulated with sorafenib, and inhibitors of the sphingolipid pathway and cell proliferation, viability, and concentrations of bioactive metabolites were assessed. We observed a significant downregulation of cell proliferation and viability and a simultaneous upregulation of dihydroceramides upon sorafenib stimulation. Interestingly, fumonisin B1 (FB1) and the general sphingosine kinase inhibitor SKI II were able to inhibit cell proliferation more prominently in HepG2 and Huh7.5 cells, whereas there were no consistent effects on the formation of dihydroceramides, thus implying an involvement of distinct metabolic pathways. In conclusion, our study demonstrates a significant downregulation of HCC proliferation upon sorafenib, FB1, and SKI II treatment, whereas it seems they exert antiproliferative effects independently from sphingolipids. Certainly, further data would be required to elucidate the potential of FB1 and SKI II as putative novel therapeutic targets in HCC.