> present (Member of the Advisory Board of the Cheltenham Festival of Science) and [????] These analyses emphasize the diversity of mechanisms that result in a phenotype of azole resistance. Microsatellite typing of 25 Candida parapsilosis isolates from a described outbreak in a neonatal intensive care showed 2 large groups of blood isolates that were related to hand isolates from specific hospital staff, not infant-colonizing isolates. Neal, C. O., Richardson, A. O., Hurst, S. F., Tortorano, A. M., Viviani, M. A., Stevens, D. A., Balajee, S. A. Real-time PCR and quantitative culture for monitoring of experimental Aspergillus fumigatus intracranial infection in neutropenic mice. Consistent with the in vitro enhancement of effector cell function by IFN-gamma, in vivo therapy with IFN-gamma significantly (P<0.0001) improved survival of BALB/c mice with pulmonary blastomycosis. Phylogenetic and statistical analyses utilizing permutation tests were undertaken to assess correlations amongst the isolates. I am especially interested in how material culture and urban space can shed light on the lives of the non-elite in ancient Egypt. A variety of tests has been applied to several body fluids. (ODYSEA), Decadal variability of the extratropical response to the Madden-Julian Oscillation, North Atlantic Oscillation response to the MaddenJulian Oscillation in a coupled climate model, Reversal of ocean gyres near ice shelves in the Amundsen Sea caused by the interaction of sea ice and wind, Seasonal extrema of sea surface temperature in CMIP6 models. In one patient, fungemia was accompanied by clinical and laboratory evidence of Broviac catheter infection. However, despite its beneficial effects, DEX puts patients at risk for opportunistic infections, especially pulmonary aspergillosis. Contribute Alice Roberts and David Stevens - Dating, Gossip, News, Photos list. It is known that these drugs are bound >80% in animal and human sera. Particularly, questions of socioeconomic distribution, Rawlsian justice as fairness, equality of opportunity and education, environmental justice. Lower concentrations of serum also potentiated drug activity. We also found that one commercial strain was indistinguishable from the strain isolated from three different women at the time that they were suffering from vaginitis. His methods were remarkably effective in drawing out the real issues, enabling considerable progress to be made., M.M.E. The protective moiety(ies) appeared to reside in the cell wall and was resistant to 100 C, but not to protease or formalin. The interaction of human monocytes, monocyte-derived macrophages, and polymorphonuclear neutrophils with caspofungin (MK-0991), an echinocandin, for antifungal activity against Aspergillus fumigatus, Influence of human sera on the in vitro activity of the echinocandin caspofungin (MK-0991) against Aspergillus fumigatus, Drug interaction studies of a glucan synthase inhibitor (LY 303366) and a chitin synthase inhibitor (nikkomycin Z) for inhibition and killing of fungal pathogens, Practice guidelines for diseases caused by Aspergillus. Vaz, C., Sampaio, P., Clemons, K. V., Huang, Y., Stevens, D. A., Pais, C. Saccharomyces as a vaccine against systemic aspergillosis: 'the friend of man' a friend again? Itraconazole is a broad-spectrum oral triazole whose greatest advantages over the imidazoles are in its activity against aspergillosis and cryptococcosis, though it is also efficacious against the endemic deep mycoses. The differences in response between the modified intent-to-treat treatment groups were preserved across additional, prespecified subsets, including infection site (pulmonary or disseminated), hematological malignancy, hematopoietic stem cell transplantation, baseline neutropenia, and reason for enrollment (patient was refractory to or intolerant of previous antifungal therapy). 1,3-beta-Glucan was a good stimulator of BAM for TNF-alpha production and was detected on B. dermatitidis by IFA. Her zodiac sign is Taurus. GM-CSF reversed the effect of DEX on I kappaB levels. [1] Stevens died in St Mary Bourne, Hampshire, at the age of 81. Is this something you feeling strongly about? BALB/c, the reference strain in repeated experiments, was susceptible, showing persistent infection with levels of cfu at day 6 falling within a range between a twofold decrease and a fourfold increase in relation to day 1 levels. Both doses of fluconazole significantly reduced numbers of CFU in all four tissues but were equivalent to each other. VCZ was ineffective and AMBd plus CAS showed a possible antagonism. Help us build our profile of Alice Roberts and David Stevens! View details for Web of Science ID A1994NB82100004, View details for PubMedCentralID PMC1205906. View details for Web of Science ID 000256044900007, View details for PubMedCentralID PMC2671227. Invasive aspergillosis. Copyright FameChain 2023, All rights reserved. Her claim also . Further study by 16S rRNA gene sequencing and DNA-DNA hybridization revealed the cultures represented 3 novel species: 1 (H. stevensii sp. The definitions are intended for use in the context of clinical and/or epidemiological research, not for clinical decision making. McCusker, J. H., Clemons, K. V., Stevens, D. A., Davis, R. W. PULMONARY MUCORMYCOSIS PRESENTING AS AN ENDOBRONCHIAL LESION. View details for Web of Science ID A1995QC60300016, View details for PubMedCentralID PMC173020. Although no well-designed studies have been carried out, the available data support the use of corticosteroids for acute exacerbations of ABPA (AII). The antifungal activity of voriconazole (VCZ) was tested against Cryptococcus neoformans (Cn) with and without the addition of polymorphonuclear neutrophils (PMN), monocytes or monocyte-derived macrophages (MDM) in vitro. Alice Roberts and David Stevens have been married for 22 years. In a second, open-label part of the trial, all the patients received 200 mg of itraconazole per day for 16 weeks.There were responses in 13 of 28 patients in the itraconazole group (46 percent), as compared with 5 of 27 patients in the placebo group (19 percent, P=0.04). This cytokine profile does not suggest a polarized Th1 or Th2 response. At the lowest inoculum used, deaths of KO mice were delayed, but survival was not significantly different than WT (P>0.05). New drugs for systemic fungal infections. Fungus burdens in brain were higher than those in other organs, although Aspergillus disseminated to the kidneys and the spleen. The available data suggest that clinical symptoms alone are inadequate to make such decisions, since significant lung damage may occur in asymptomatic patients. Paired baseline and end-of-treatment culture results for Coccidioides species were available for 4 patients, all of whom converted from being positive to being negative for Coccidioides species. I am a member of the Centre for Ocean and Atmospheric Sciences. We look to the archaeologist for the materials, to the artist for the method. Because of possible development of resistance in patient isolates resulting from residence in the abnormal milieu of CF patient airways, or from exposure to antifungals, and considering the possibility of patient-to-patient spread of microbes and reports of elevated resistance to other fungal pathogens, it was important to assay the susceptibility of isolates of Candida and compare that profile to isolates from the community. Invasive aspergillosis is a major cause of mortality in immunocompromised patients and therapeutic options are often limited, thus a vaccine would be desirable. Choi, J., Kwon, E., Park, C., Choi, S., Lee, D., Yoo, J., Shin, W., Stevens, D. A. Male New Zealand White rabbits were infected by intracisternal inoculation of arthroconidia of Coccidioides immitis. Cloned, amplified inserts from randomly sheared genomic DNA (gDNA) and known control genes were printed onto glass slides to generate a microarray of over 12,000 elements. Most of these clinical isolates are able to grow at 42 degrees, a temperature that completely inhibits the growth of most other S. cerevisiae strains. Particularly, Rawlsian political liberalism, anti-perfectionism, children's education, religious disobedience. Gene disruptions of the MTL loci were found to have no effect on azole susceptibility. Thus, the choice of which animal model to use must be made carefully, addressing issues of the type of human disease to mimic, the parameters to follow and collection of the appropriate data to answer those questions being asked. Although this study was limited by the number of patients enrolled, it clearly demonstrates that posaconazole shows promise in the treatment of patients with coccidioidomycosis and warrants additional investigation in a full-scale clinical trial. The larger repertoire of cytokine production in the macrophages that had been cultured longer (20 h+20 h) in serum may be related to maturation of cell receptors. View details for PubMedID 19464548, View details for DOI 10.1016/j.vaccine.2009.03.030, View details for Web of Science ID 000267459900022, View details for DOI 10.1007/s10096-008-0688-y, View details for Web of Science ID 000266372700026. Micafungin at 0.01 or 0.10 microg/ml and PMNs resulted in additive inhibition, 82% and 99%, respectively. Plasma samples were collected for ultra performance liquid chromatography (UPLC) or bioassay analysis. Only the 40-mg/kg dose of VCZ was effective. Previously there were only 2 antifungals with activity against Aspergillus, but over the last few years there has been an explosion of newer agents and reformulations of older antifungals. Then there was little progress for 50 years, when in 1951, nystatin was introduced, the first useful polyene. 3M-003, like related imidazoquinoline immunomodulators, interacts with Toll-like receptor-7 (TLR-7) and TLR-8. The lesion resembled a bronchial adenoma; however, cytologic and histologic examination revealed invasive mucormycosis. The decision to taper steroids should be made on an individual basis, depending on clinical course. Randomized trials are lacking. David Stevens Professor Professor of Applied Mathematics, School of Mathematics Member, Centre for Ocean and Atmospheric Sciences Member, Fluid and Solid Mechanics https://orcid.org/0000-0002-7283-4405 Phone 2590 Email D.Stevens @uea.ac .uk 1.22 Sciences Overview Network Projects (14) Research output (109) Maffei, C. M., Mirels, L. F., Sobel, R. A., Clemons, K. V., Stevens, D. A. Allergic bronchopulmonary aspergillosis is a hypersensitivity disorder that can progress from an acute phase to chronic disease. Surgical removal of aspergilloma is definitive treatment, but because of significant morbidity and mortality it should be reserved for high-risk patients such as those with episodes of life-threatening hemoptysis, and considered for patients with underlying sarcoidosis, immunocompromised patients, and those with increasing Aspergillus-specific IgG titers (CIII). IL-6 production in vivo in response to fungal-serum complexes could affect pathogenesis by opposing the host defense modulation by proinflammatory cytokines or by modulating the destructive effects of inflammation on host tissues. In our center, and unlike another fungal pathogen, no increase in resistance of Candida isolates of the CF cohort was found. We report here studies which show that escape from growth inhibition is related to the enzymatic transformation of progesterone to polar metabolites. These unique observations are consistent with an estrogen-fungus receptor-mediated effect on pathogenesis. 69: 2013: Busy Lives at Amarna: excavations in the main city:(grid 12 and the House of Ranefer, N49. Caspofungin, the first inhibitor of fungal beta-1,3 glucan synthesis to receive approval by the United States Food and Drug Administration, is effective for the treatment of mucosal and invasive candidiasis and invasive aspergillosis. After intravenous treatment of uninfected mice with 75 g of rhMBL, rhMBL was detected in the serum and peritoneal lavage fluid; rhMBL was detected in the serum of infected mice 2 and 24 hours post-dose, and at very low concentrations in vaginal lavage fluid. None of the non-VII-1 types were in more than one ITS group. had 40% survival. Her zodiac sign is Taurus. Additional studies are warranted. Two cohorts were studied. Each remained at these levels thereafter. With the urgent need for novel agents to combat emerging fungal resistance to existing drugs, activity in the exploration of small molecule DNA binders has increased. Although clinical isolates of the organism are generally reported to be susceptible to amphotericin B, isolates can vary in their sensitivities to antifungal agents in vitro depending on the methodology used, and clinical response to therapy with antifungal agents in a regimen that includes amphotericin B is generally poor. In 2008 I was at sea on a project to examine the mixing near Kerguelen. New nucleic acid-based research is promising. Most of my research has been involved with cold regions, the Norwegian-Greenland Sea and the Southern Ocean. Draft Genome Sequence of the Human Pathogen Halomonas stevensii S18214(T). View details for DOI 10.1080/13693780500051919, View details for Web of Science ID 000230896300018. When macrophages were pretreated with DEX, GM-CSF could reverse suppression even when added subsequently, provided DEX treatment was discontinued. Monotherapy studies showed that micafungin (MICA), caspofungin (CAS), VCZ, conventional amphotericin B (AMB), Abelcet (ABLC) (a lipid-carried AMB formulation; Enzon Pharmaceuticals, Inc.), and AmBisome (AmBi) (liposomal AMB; Gilead Sciences, Inc.) were efficacious. 3M-003 at 1 or 3 microM was optimal for the stimulation of PBMC to produce tumor necrosis factor-alpha and interleukin-12p40 in 24 h. For indirect tests, monolayers were treated with supernatants for 18 h, the supernatants were removed, and effector cells were tested; the supernatants enhanced (P<0.05-0.01) killing, in 2-4-h assays, by neutrophils from 42% to 73%, macrophages from 0% to 23%, and monocytes from 0% to 20%. Analysis of the turbid growth indicated slowing of growth in the presence of drug but with numbers of CFU up to 72% those of drug-free controls. Control BAM responded to increasing numbers of conidia of Aspergillus fumigatus with increasing production of IL-1 and TNF. dermatitidis) TNF-alpha production was inhibited > or = 47% by BALF or SP-A-/- BALF (at 290 or 580 microg of protein/ml, P < 0.05 to 0.01); in contrast, SP-D-/- BALF did not significantly inhibit TNF-alpha production. Overall, these data indicate that intravenously administered AmBi is superior to oral FLC or intravenous AMB and that FLC is better than AMB against experimental coccidioidal meningitis. Immunosuppressed mice were infected intracerebrally with Aspergillus fumigatus and treated with an amphotericin B preparation, an echinocandin, or voriconazole (VCZ) given alone or in combination. We assessed whether there were differences in fungicidal activity of phagocytes and Th-1 lymphocyte cytokine production. Fluconazole appears well tolerated and safe in these doses and durations. nov. Ibrahim, A. S., Gebremariam, T., Husseiny, M. I., Stevens, D. A., Fu, Y., Edwards, J. E., Spellberg, B. These guidelines are directed to 3 principal entities: invasive aspergillosis, involving several organ systems (particularly pulmonary disease); pulmonary aspergilloma; and allergic bronchopulmonary aspergillosis. Recovery of cfu from the brains and kidneys of survivors showed that no regimen was curative. In susceptible BALB/c the response is Th-2, in immunized, resistance is associated with Th-1. I welcome applications throughout the year from potential PhD candidates with an interest in oceanography or climate processes for available positions or from candidates who have their own funding or wish to apply for their own funding. Sequencing of approximately 1500 bases of the 16S rRNA gene in both organisms in 3 reference laboratories confirmed, searching against 3 databases, that the organisms were identical and were Halomonas species. Professor David J Stephens B.Sc., Ph.D. After initial deterioration, clinical and radiographic resolution occurred during 3 months of therapy despite severe graft-vs.-host and cytomegalovirus disease. David Stevens has over 35 years of experience in the mortgage banking industry. The decision to taper corticosteroids should be made on an individual basis, depending on the clinical course (BIII). View details for DOI 10.1128/AAC.49.4.1369-1376.2005, View details for Web of Science ID 000228082500018. David L Stevens, age 38. Kline, Y., Clemons, K. V., Woods, L., Stevens, D. A., Tell, L. A. Sequential studies with peritoneal macrophages indicated that recombinant human GM-CSF pretreatment also blocked dexamethasone suppression, but the GM-CSF treatment given after dexamethasone did not block the suppressive effect. Regulation of bronchoalveolar macrophage proinflammatory cytokine production by dexamethasone and granulocyte-macrophage colony-stimulating factor after stimulation by Aspergillus conidia or lipopolysaccharide, Resistance mechanisms in clinical isolates of Candida albicans. Although qPCR and CFU may not correlate in those types of studies, comparative studies have shown CFU and qPCR do correlate when determining antifungal drug efficacy, where each method can clearly demonstrate differences in fungal burden; EIA methods have also been shown to reflect this difference. View details for Web of Science ID 000173949300004. Regression analyses of qPCR and CFU groups indicated different slopes for progressive infection in untreated animals but the same slopes for CAS dose-response efficacy. His zodiac sign is Cancer. View details for DOI 10.1080/13693780600810040 The sequence of rRNA genes has been utilized for the identification of a variety of fungi to the species level. These in vitro results demonstrate several immunological deficiencies in cells from young mice and these deficiencies correlate with susceptibility. In 24 medical centers, we examined the impact of a culture positive for Aspergillus species on the diagnosis, risk factors, management, and outcome associated with these diseases. Success was a complete or partial response; nonsuccess was stable disease, lack of response to therapy, or undetermined response.The sites of coccidioidal infection were pulmonary (seven patients) and disseminated (eight patients). The laboratory has worked on development of panfungal conjugate vaccines, with special focus on Aspergillus and Coccidioides, including discovery of cross-reacting fungal proteins by mass spectroscopy and protein microarray, in collaboration with City of Hope, and using purified glycans supplied by an industrial partner. View details for Web of Science ID 000075737400027. View details for DOI 10.1016/j.diagmicrobio.2010.06.010, View details for Web of Science ID 000283833100005. Clearance of fungal burden from the livers and spleens of mice showed RCZ and ITZ at doses of 50 mg/kg to be efficacious but not curative. van Asbeck, E. C., Huang, Y., Markham, A. N., Clemons, K. V., Stevens, D. A. The fungus usually affects lung parenchyma and may disseminate from there. 18) Additional studies are needed to evaluate improved treatment. We also analysed gene expression with time in culture and found that while transposable elements and components of respiratory pathways tended to increase in expression with time, genes encoding ribosomal structural proteins and protein catabolism tended to sharply decrease in expression over time, particularly in yeast. Six isolates failed to amplify MTLa1 and six failed to amplify MTLalpha1. Genes related to ubiquitin-mediated protein degradation, and oxidative stress response genes were up-regulated by E(2).This study characterizes the effect of E(2) at the molecular level on the inhibition of the M-to-Y transition and is indicative that the inhibitory actions of E(2) may be working through signaling genes that regulate dimorphism. View details for DOI 10.1128/AAC.00332-06, View details for Web of Science ID 000244665500028, View details for PubMedCentralID PMC1803148. We reported previously that Trichophyton mentagrophytes contains a cytoplasmic macromolecule which specifically binds progesterone. View details for Web of Science ID 000172304800023. Wed meet up at lunchtime so that I could breastfeed, but sometimes the timing didnt work out, so I had to make sure that I had amassed a stockpile of expressed milk so that my daughter could also be bottle-fed with breast milk, not formula. Since 2019, she has been President of the charity Humanists UK, which campaigns for state secularism and for "a tolerant world where rational thinking and kindness prevail". Clemons, J.H. The addition of either granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony stimulating factor (GM-CSF) significantly enhanced the ability of human effector cells to kill Cn. Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants: An international consensus. [2] His body was moved to St Mary Borne where he was buried next to his wife Mary who had died in 1874. Posaconazole is a new azole antifungal with potent activity against Coccidioides species, the causative agent of coccidioidomycosis.Twenty patients with chronic pulmonary or nonmeningeal disseminated coccidioidomycosis were enrolled in a multicenter trial to study the safety and tolerability of posaconazole therapy, with efficacy as a secondary end point. However, the combination of VCZ with GM-CSF treatment of monocytes did not significantly increase the high-level inhibition by monocytes with either agent alone. We postulate high drug concentrations derepress or activate an as-yet undefined resistance mechanism(s). No patient had discontinuation of the study drug due to toxicity. [2] Contents 1 Personal life In these studies we assessed the utility of recombinant human MBL (rhMBL) as a therapeutic against experimental C. albicans vaginitis. Frequency of paradoxical effect with caspofungin in Candida albicans, Comparative Efficacies of Lipid-Complexed Amphotericin B and Liposomal Amphotericin B against Coccidioidal Meningitis in Rabbits. Dig up the secrets of archaeology and learn the skills needed to succeed in this amazing field. Multiple asthmatic exacerbations in a patient with ABPA suggest that chronic corticosteroid therapy should be used (BIII). The hands of NICU healthcare workers (HCW) yielded eight isolates. Iodide in the Ocean:Distribution and Impact on Iodine Flux and Ozone Loss. Stevens, D. A., Kullberg, B. J., Brummer, E., Casadevall, A., Netea, M. G., Sugar, A. M. Cryptococcal meningitis in the immunocompromised host: intracranial hypertension and other complications. Who is Alice Roberts dating? Although no survivors were free of infection, no antagonism was seen. She's a mother to two children and holds a post as Professor of Public Engagement in Science at the University of Birmingham. Low-dose ABLC was less effective than LAmB at reducing brain fungal burdens in both models. Her work has a clear pedagogy of embedded research and practice with postgraduate teacher training . The majority of cases were acquired by hematogenous infection, although one-quarter occurred after a spinal procedure. Drug efficacy in treating localized infection and in preventing or treating disseminated infection can be studied. David Stevens was born on 22 December 1940 in Tiberias, Palestine. Expertise Summary I am interested in a variety of questions within the broad field of normative political philosophy/theory. Three other patients with indistinguishable isolates were epidemiologically related in that two were practitioners in the same clinic and the third was a patient at this clinic. Managing Director, Maunsell Management, Hong Kong. Here, we investigated the hyphal proteomes of Aspergillus fumigatus and Coccidioides posadasii via quantitative MS(E) mass spectrometry with the objective of developing a vaccine that cross-protects against these and other species of fungi. Overall, we found that HKY protects mice from infection by Candida albicans in a dose-and regimen-dependent manner. Caspofungin was then added with or without serum, and the germlings were incubated at 37 degrees C for 24 h. Human serum (5%) in RPMI 1640 alone did not significantly inhibit the growth of A. fumigatus in vitro. With both the MTT and XTT assays, neutrophils alone inhibited hyphae; when combined with VCZ, there was additive activity. To the kidneys and the spleen our profile of Alice Roberts and David Stevens have been for! Micafungin at 0.01 or 0.10 microg/ml and PMNs resulted in additive inhibition, 82 david stevens archaeologist and %... 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