On the isoperimetric problem for the Laplacian with Robin and Wentzell boundary conditions

Doctor of PhilosophyWe consider the problem of minimising the eigenvalues of the Laplacian with Robin boundary conditions $\frac{\partial u}{\partial \nu} + \alpha u = 0$ and generalised Wentzell boundary conditions $\Delta u + \beta \frac{\partial u}{\partial \nu} + \gamma u = 0$ with respect to the domain $\Omega \subset \mathbb R^N$ on which the problem is defined. For the Robin problem, when $\alpha > 0$ we extend the Faber-Krahn inequality of Daners [Math. Ann. 335 (2006), 767--785], which states that the ball minimises the first eigenvalue, to prove that the minimiser is unique amongst domains of class $C^2$. The method of proof uses a functional of the level sets to estimate the first eigenvalue from below, together with a rearrangement of the ball's eigenfunction onto the domain $\Omega$ and the usual isoperimetric inequality. We then prove that the second eigenvalue attains its minimum only on the disjoint union of two equal balls, and set the proof up so it works for the Robin $p$-Laplacian. For the higher eigenvalues, we show that it is in general impossible for a minimiser to exist independently of $\alpha > 0$. When $\alpha < 0$, we prove that every eigenvalue behaves like $-\alpha^2$ as $\alpha \to -\infty$, provided only that $\Omega$ is bounded with $C^1$ boundary. This generalises a result of Lou and Zhu [Pacific J. Math. 214 (2004), 323--334] for the first eigenvalue. For the Wentzell problem, we (re-)prove general operator properties, including for the less-studied case $\beta 0$ establish a type of equivalence property between the Wentzell and Robin minimisers for all eigenvalues. This yields a minimiser of the second Wentzell eigenvalue. We also prove a Cheeger-type inequality for the first eigenvalue in this case

Azole-Resistance in Aspergillus terreus and Related Species: An Emerging Problem or a Rare Phenomenon?

Raquel Sabino was not included as an author in the published article. It was corrected a posteriori.Erratum in - Corrigendum: Azole-Resistance in Aspergillus terreus and Related Species: An Emerging Problem or a Rare Phenomenon? [Front Microbiol. 2018] Front Microbiol. 2019 Jan 14;9:3245. doi: 10.3389/fmicb.2018.03245. eCollection 2018.Disponível em: https://www.frontiersin.org/articles/10.3389/fmicb.2018.03245/fullFree PMC Article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5882871/ | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6340063/Objectives: Invasive mold infections associated with Aspergillus species are a significant cause of mortality in immunocompromised patients. The most frequently occurring aetiological pathogens are members of the Aspergillus section Fumigati followed by members of the section Terrei. The frequency of Aspergillus terreus and related (cryptic) species in clinical specimens, as well as the percentage of azole-resistant strains remains to be studied. Methods: A global set (n = 498) of A. terreus and phenotypically related isolates was molecularly identified (beta-tubulin), tested for antifungal susceptibility against posaconazole, voriconazole, and itraconazole, and resistant phenotypes were correlated with point mutations in the cyp51A gene. Results: The majority of isolates was identified as A. terreus (86.8%), followed by A. citrinoterreus (8.4%), A. hortai (2.6%), A. alabamensis (1.6%), A. neoafricanus (0.2%), and A. floccosus (0.2%). One isolate failed to match a known Aspergillus sp., but was found most closely related to A. alabamensis. According to EUCAST clinical breakpoints azole resistance was detected in 5.4% of all tested isolates, 6.2% of A. terreus sensu stricto (s.s.) were posaconazole-resistant. Posaconazole resistance differed geographically and ranged from 0% in the Czech Republic, Greece, and Turkey to 13.7% in Germany. In contrast, azole resistance among cryptic species was rare 2 out of 66 isolates and was observed only in one A. citrinoterreus and one A. alabamensis isolate. The most affected amino acid position of the Cyp51A gene correlating with the posaconazole resistant phenotype was M217, which was found in the variation M217T and M217V. Conclusions:Aspergillus terreus was most prevalent, followed by A. citrinoterreus. Posaconazole was the most potent drug against A. terreus, but 5.4% of A. terreus sensu stricto showed resistance against this azole. In Austria, Germany, and the United Kingdom posaconazole-resistance in all A. terreus isolates was higher than 10%, resistance against voriconazole was rare and absent for itraconazole.This work was supported by ECMM, ISHAM, and EFISG and in part by an unrestricted research grant through the Investigator Initiated Studies Programof Astellas, MSD, and Pfizer. This study was fundet by the Christian Doppler Laboratory for invasive fungal infections.info:eu-repo/semantics/publishedVersio

Azole-resistance in Aspergillus terreus and related species: An emerging problem or a rare Phenomenon?

Objectives: Invasive mold infections associated with Aspergillus species are a significant cause of mortality in immunocompromised patients. The most frequently occurring aetiological pathogens are members of the Aspergillus section Fumigati followed by members of the section Terrei. The frequency of Aspergillus terreus and related (cryptic) species in clinical specimens, as well as the percentage of azole-resistant strains remains to be studied. Methods: A global set (n = 498) of A. terreus and phenotypically related isolates was molecularly identified (beta-tubulin), tested for antifungal susceptibility against posaconazole, voriconazole, and itraconazole, and resistant phenotypes were correlated with point mutations in the cyp51A gene. Results: The majority of isolates was identified as A. terreus (86.8), followed by A. citrinoterreus (8.4), A. hortai (2.6), A. alabamensis (1.6), A. neoafricanus (0.2), and A. floccosus (0.2). One isolate failed to match a known Aspergillus sp., but was found most closely related to A. alabamensis. According to EUCAST clinical breakpoints azole resistance was detected in 5.4 of all tested isolates, 6.2 of A. terreus sensu stricto (s.s.) were posaconazole-resistant. Posaconazole resistance differed geographically and ranged from 0 in the Czech Republic, Greece, and Turkey to 13.7 in Germany. In contrast, azole resistance among cryptic species was rare 2 out of 66 isolates and was observed only in one A. citrinoterreus and one A. alabamensis isolate. The most affected amino acid position of the Cyp51A gene correlating with the posaconazole resistant phenotype was M217, which was found in the variation M217T and M217V. Conclusions: Aspergillus terreus was most prevalent, followed by A. citrinoterreus. Posaconazole was the most potent drug against A. terreus, but 5.4 of A. terreus sensu stricto showed resistance against this azole. In Austria, Germany, and the United Kingdom posaconazole-resistance in all A. terreus isolates was higher than 10, resistance against voriconazole was rare and absent for itraconazole. © 2018 Zoran, Sartori, Sappl, Aigner, Sánchez-Reus, Rezusta, Chowdhary, Taj-Aldeen, Arendrup, Oliveri, Kontoyiannis, Alastruey-Izquierdo, Lagrou, Cascio, Meis, Buzina, Farina, Drogari-Apiranthitou, Grancini, Tortorano, Willinger, Hamprecht, Johnson, Klingspor, Arsic-Arsenijevic, Cornely, Meletiadis, Prammer, Tullio, Vehreschild, Trovato, Lewis, Segal, Rath, Hamal, Rodriguez-Iglesias, Roilides, Arikan-Akdagli, Chakrabarti, Colombo, Fernández, Martin-Gomez, Badali, Petrikkos, Klimko, Heimann, Uzun, Roudbary, de la Fuente, Houbraken, Risslegger, Lass-Flörl and Lackner

Corrigendum: Azole-resistance in aspergillus terreusand related species: An emerging problem or a rare phenomenon? (Frontiers in Microbiology (2018) 9 (516) DOI: 10.3389/fmicb.2018.00516)

Raquel Sabino was not included as an author in the published article. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated. © 2019 Zoran, Sartori, Sappl, Aigner, Sánchez-Reus, Rezusta, Chowdhary, Taj-Aldeen, Arendrup, Oliveri, Kontoyiannis, Alastruey-Izquierdo, Lagrou, Lo Cascio, Meis, Buzina, Farina, Drogari-Apiranthitou, Grancini, Tortorano, Willinger, Hamprecht, Johnson, Klingspor, Arsic-Arsenijevic, Cornely, Meletiadis, Prammer, Tullio, Vehreschild, Trovato, Lewis, Segal, Rath, Hamal, Rodriguez-Iglesias, Roilides, Arikan-Akdagli, Chakrabarti, Colombo, Fernández, Martin-Gomez, Badali, Petrikkos, Klimko, Heimann, Uzun, Roudbary, de la Fuente, Houbraken, Risslegger, Sabino, Lass-Flörl and Lackner

Azole-resistance in Aspergillus terreus and related species: An emerging problem or a rare Phenomenon?

Objectives: Invasive mold infections associated with Aspergillus species are a significant cause of mortality in immunocompromised patients. The most frequently occurring aetiological pathogens are members of the Aspergillus section Fumigati followed by members of the section Terrei. The frequency of Aspergillus terreus and related (cryptic) species in clinical specimens, as well as the percentage of azole-resistant strains remains to be studied. Methods: A global set (n = 498) of A. terreus and phenotypically related isolates was molecularly identified (beta-tubulin), tested for antifungal susceptibility against posaconazole, voriconazole, and itraconazole, and resistant phenotypes were correlated with point mutations in the cyp51A gene. Results: The majority of isolates was identified as A. terreus (86.8), followed by A. citrinoterreus (8.4), A. hortai (2.6), A. alabamensis (1.6), A. neoafricanus (0.2), and A. floccosus (0.2). One isolate failed to match a known Aspergillus sp., but was found most closely related to A. alabamensis. According to EUCAST clinical breakpoints azole resistance was detected in 5.4 of all tested isolates, 6.2 of A. terreus sensu stricto (s.s.) were posaconazole-resistant. Posaconazole resistance differed geographically and ranged from 0 in the Czech Republic, Greece, and Turkey to 13.7 in Germany. In contrast, azole resistance among cryptic species was rare 2 out of 66 isolates and was observed only in one A. citrinoterreus and one A. alabamensis isolate. The most affected amino acid position of the Cyp51A gene correlating with the posaconazole resistant phenotype was M217, which was found in the variation M217T and M217V. Conclusions: Aspergillus terreus was most prevalent, followed by A. citrinoterreus. Posaconazole was the most potent drug against A. terreus, but 5.4 of A. terreus sensu stricto showed resistance against this azole. In Austria, Germany, and the United Kingdom posaconazole-resistance in all A. terreus isolates was higher than 10, resistance against voriconazole was rare and absent for itraconazole. © 2018 Zoran, Sartori, Sappl, Aigner, Sánchez-Reus, Rezusta, Chowdhary, Taj-Aldeen, Arendrup, Oliveri, Kontoyiannis, Alastruey-Izquierdo, Lagrou, Cascio, Meis, Buzina, Farina, Drogari-Apiranthitou, Grancini, Tortorano, Willinger, Hamprecht, Johnson, Klingspor, Arsic-Arsenijevic, Cornely, Meletiadis, Prammer, Tullio, Vehreschild, Trovato, Lewis, Segal, Rath, Hamal, Rodriguez-Iglesias, Roilides, Arikan-Akdagli, Chakrabarti, Colombo, Fernández, Martin-Gomez, Badali, Petrikkos, Klimko, Heimann, Uzun, Roudbary, de la Fuente, Houbraken, Risslegger, Lass-Flörl and Lackner

European candidaemia is characterised by notable differential epidemiology and susceptibility pattern: Results from the ECMM Candida III study.

The objectives of this study were to assess Candida spp. distribution and antifungal resistance of candidaemia across Europe. Isolates were collected as part of the third ECMM Candida European multicentre observational study, conducted from 01 to 07-07-2018 to 31-03-2022. Each centre (maximum number/country determined by population size) included ∼10 consecutive cases. Isolates were referred to central laboratories and identified by morphology and MALDI-TOF, supplemented by ITS-sequencing when needed. EUCAST MICs were determined for five antifungals. fks sequencing was performed for echinocandin resistant isolates. The 399 isolates from 41 centres in 17 countries included C. albicans (47.1%), C. glabrata (22.3%), C. parapsilosis (15.0%), C. tropicalis (6.3%), C. dubliniensis and C. krusei (2.3% each) and other species (4.8%). Austria had the highest C. albicans proportion (77%), Czech Republic, France and UK the highest C. glabrata proportions (25-33%) while Italy and Turkey had the highest C. parapsilosis proportions (24-26%). All isolates were amphotericin B susceptible. Fluconazole resistance was found in 4% C. tropicalis, 12% C. glabrata (from six countries across Europe), 17% C. parapsilosis (from Greece, Italy, and Turkey) and 20% other Candida spp. Four isolates were anidulafungin and micafungin resistant/non-wild-type and five resistant to micafungin only. Three/3 and 2/5 of these were sequenced and harboured fks-alterations including a novel L657W in C. parapsilosis. The epidemiology varied among centres and countries. Acquired echinocandin resistance was rare but included differential susceptibility to anidulafungin and micafungin, and resistant C. parapsilosis. Fluconazole and voriconazole cross-resistance was common in C. glabrata and C. parapsilosis but with different geographical prevalence

Natural organic matter removal and fouling in a low pressure hybrid membrane systems.

The objective of this study was to investigate powdered activated carbon (PAC) contribution to natural organic matter (NOM) removal by a submerged MF and UF hybrid systems. It was found that filtration of surface waters by a bare MF and UF membranes removed negligible TOC; by contrast, significant amounts of TOC were removed when daily added PAC particles were predeposited on the membrane surfaces. These results support the assumption that the membranes surface properties and PAC layer structure might have considerably influential factor on NOM removal. Moreover, it was concluded that the dominant removal mechanism of hybrid membrane system is adsorption of NOM within PAC layer rather than size exclusion of NOM by both of membrane pores. Transmembrane pressure (TMP) increases with PAC membrane systems support the view that PAC adsorption pretreatment will not prevent the development of membrane pressure; on the contrary, PAC particles themselves caused membrane fouling by blocking the entrance of pores of MF and UF membranes. Although all three source waters have similar HPI content, it appears that the PAC interaction with the entrance of membrane pores was responsible for offsetting the NOM fractional effects on membrane fouling for these source waters

In vitro activities of antifungal drugs against environmental Exophiala isolates and review of the literature

PubMedID: 29611230Exophiala is a genus of black fungi isolated worldwide from environmental and clinical specimens. Data on antifungal susceptibility of Exophiala isolates are limited and the methodology on susceptibility testing is not yet standardised. In this study, we investigated in vitro antifungal susceptibilities of environmental Exophiala isolates. A total of 87 Exophiala isolated from dishwashers or railway ties were included. A CLSI M38-A2 microdilution method with modifications was used to determine antifungal susceptibility for fluconazole, voriconazole, posaconazole, itraconazole, amphotericin B and terbinafine. Minimum inhibitory concentration (MIC) values were determined visually at 48 hours, 72 hours and 96 hours. MIC-0 endpoint (complete inhibition of growth) was used for amphotericin B and azoles, except fluconazole, for which MIC-2 endpoint (~50% inhibition compared to growth control) was used. Both MIC-0 and MIC-1 (~80% inhibition compared to growth control) results were analysed for terbinafine to enable comparison with previous studies. Fungal growth was sufficient for determination of MICs at 48 hours for all isolates except two Exophiala dermatitidis strains. At 72 hours, most active antifungal agents according to GM MIC were voriconazole and terbinafine, followed by posaconazole, itraconazole and amphotericin B in rank order of decreasing activity. While amphotericin B displayed adequate in vitro activity despite relatively high MICs, fluconazole showed no meaningful antifungal activity against Exophiala. © 2018 Blackwell Verlag Gmb