Brownian motion.

Thesis (M.A.)--Boston Universit

Evaluation of Standard- and High-Dose Daptomycin versus Linezolid against Vancomycin-Resistant Enterococcus Isolates in an In Vitro Pharmacokinetic/Pharmacodynamic Model with Simulated Endocardial Vegetations

Daptomycin MICs for enterococci are typically 1- to 2-fold higher than those for Staphylococcus aureus, and there is an imminent need to establish the optimal dose for appropriate treatment of enterococcal infections. We investigated the bactericidal activity of daptomycin at various dose exposures compared to that of linezolid against vancomycin-resistant enterococcus (VRE) in an in vitro pharmacokinetic/pharmacodynamic model utilizing simulated endocardial vegetations over 96 h. Daptomycin at doses of 6, 8, 10, and 12 mg/kg of body weight/day and linezolid at a dose of 600 mg every 12 h were evaluated against two clinical vancomycin-resistant Enterococcus faecium strains (EFm11499 and 09-184D1051), one of which was linezolid resistant (09-184D1051), and one clinical vancomycin-resistant Enterococcus faecalis strain (EFs11496). Daptomycin MICs were 4, 2, and 0.5 μg/ml for EFm11499, 09-184D1051, and EFs11496, respectively. Bactericidal activity, defined as a ≥3 log10 CFU/g reduction from the initial colony count, was demonstrated against all three isolates with all doses of daptomycin; however, bactericidal activity was not sustained with the daptomycin 6- and 8-mg/kg/day regimens. Linezolid was bacteriostatic against EFm11499 and displayed no appreciable activity against 09-184D1051 or EFs11496. Concentration-dependent killing was displayed with more sustained reduction in colony count (3.58 to 6.46 and 5.89 to 6.56 log10 CFU/g) at 96 h for the simulated regimen of daptomycin at doses of 10 and 12 mg/kg/day, respectively (P ≤ 0.012). No E. faecium mutants with reduced susceptibility were recovered at any dosage regimen; however, the E. faecalis strain developed reduced daptomycin susceptibility with daptomycin at 6, 8, and 10 but not at 12 mg/kg/day. Daptomycin displayed a dose-dependent response against three VRE isolates, with high-dose daptomycin producing sustained bactericidal activity. Further research is warranted.This investigator-initiated study was funded by a research grant from Cubist Pharmaceuticals. We are grateful to Audrey Wanger for providing isolate 09-184D1051 and to Marcus Zervos for providing isolates SF11496 and SF11499. M.J.R. has received grant support, has served as a consultant, or has participated as a speaker for Astellas, Cubist, Forest Laboratories, Pfizer, Rib-X, and Novartis and is supported in part by grant R21AI092055 from the NIAID. C.A.A. has received lecture fees, research support, and consulting fees from Pfizer, Inc., and Cubist and has served as a speaker for Novartis. C.A.A. is supported in part by NIH grants R00 AI72961 and R01 AI093749 from the NIAID. B.E.M. has received grant support from Johnson & Johnson, Astellas, Palumed, Intercell, and Cubist, has served as a consultant for Astellas, Cubist, The Medicines Company, Pfizer, Rib-X, AstraZeneca, and Duranta Therapeutics, and was supported in part by NIH grant R01 AI72961

Management of the Brown-Headed Cowbird: Implications for Endangered Species and Agricultural Damage Mitigation

The brown-headed cowbird (Molothrus ater; cowbird) is unique among North American blackbirds (Icteridae) because it is managed to mitigate the negative effects on endangered songbirds and economic losses in agricultural crops. Cowbird brood parasitism can further affect species that are considered threatened or endangered due to anthropogenic land uses. Historically, cowbirds have often been culled without addressing ultimate causes of songbird population declines. Similar to other North American blackbirds, cowbirds depredate agricultural crops, albeit at a lower rate reported for other blackbird species. Conflicting information exists on the extent of agricultural damage caused by cowbirds and the effectiveness of mitigation measures for application to management. In this paper, we reviewed the progress that has been made in cowbird management from approximately 2005 to 2020 in relation to endangered species. We also reviewed losses to the rice (Oryza sativa) crop attributed to cowbirds and the programs designed to reduce depredation. Of the 4 songbird species in which cowbirds have been managed, both the Kirtland’s warbler (Dendroica kirtlandii) and black-capped vireo (Vireo atricapilla) have been removed from the endangered species list following population increases in response to habitat expansion. Cowbird trapping has ceased for Kirtland’s warbler but continues for the vireo. In contrast, least Bell’s vireo (V. bellii pusillus) and southwestern willow flycatcher (Empidonax traillii extimus) still require cowbird control after modest increases in suitable habitat. Our review of rice depredation by cowbirds revealed models that have been created to determine the number of cowbirds that can be taken to decrease rice loss have been useful but require refinement with new data that incorporate cowbird population changes in the rice growing region, dietary preference studies, and current information on population sex ratios and female cowbird egg laying. Once this information has been gathered, bioenergetic and economic models would increase our understanding of the damage caused by cowbirds

Trends in the Population Prevalence of People Who Inject Drugs in US Metropolitan Areas 1992–2007

Background: People who inject drugs (PWID) have increased risk of morbidity and mortality. We update and present estimates and trends of the prevalence of current PWID and PWID subpopulations in 96 US metropolitan statistical areas (MSAs) for 1992–2007. Current estimates of PWID and PWID subpopulations will help target services and help to understand long-term health trends among PWID populations. Methodology: We calculated the number of PWID in the US annually from 1992–2007 and apportioned estimates to MSAs using multiplier methods. We used four types of data indicating drug injection to allocate national annual totals to MSAs, creating four distinct series of component estimates of PWID in each MSA and year. The four component estimates are averaged to create the best estimate of PWID for each MSA and year. We estimated PWID prevalence rates for three subpopulations defined by gender, age, and race/ethnicity. We evaluated trends using multi-level polynomial models. Results: PWID per 10,000 persons aged 15–64 years varied across MSAs from 31 to 345 in 1992 (median 104.4) to 34 to 324 in 2007 (median 91.5). Trend analysis indicates that this rate declined during the early period and then was relatively stable in 2002–2007. Overall prevalence rates for non-Hispanic black PWID increased in 2005 as compared to other racial/ethnic groups. Hispanic prevalence, in contrast, declined across time. Importantly, results show a worrisome trend in young PWID prevalence since HAART was initiated – the mean prevalence was 90 to 100 per 10,000 youth in 1992–1996, but increased to >120 PWID per 10,000 youth in 2006–2007. Conclusions: Overall, PWID rates remained constant since 2002, but increased for two subpopulations: non-Hispanic black PWID and young PWID. Estimates of PWID are important for planning and evaluating public health programs to reduce harm among PWID and for understanding related trends in social and health outcomes

Characterisation of the Immunophenotype of Dogs with Primary Immune-Mediated Haemolytic Anaemia

Immune-mediated haemolytic anaemia (IMHA) is reported to be the most common autoimmune disease of dogs, resulting in significant morbidity and mortality in affected animals. Haemolysis is caused by the action of autoantibodies, but the immunological changes that result in their production have not been elucidated.To investigate the frequency of regulatory T cells (Tregs) and other lymphocyte subsets and to measure serum concentrations of cytokines and peripheral blood mononuclear cell expression of cytokine genes in dogs with IMHA, healthy dogs and dogs with inflammatory diseases.19 dogs with primary IMHA, 22 dogs with inflammatory diseases and 32 healthy control dogs.Residual EDTA-anti-coagulated blood samples were stained with fluorophore-conjugated monoclonal antibodies and analysed by flow cytometry to identify Tregs and other lymphocyte subsets. Total RNA was also extracted from peripheral blood mononuclear cells to investigate cytokine gene expression, and concentrations of serum cytokines (interleukins 2, 6 10, CXCL-8 and tumour necrosis factor α) were measured using enhanced chemiluminescent assays. Principal component analysis was used to investigate latent variables that might explain variability in the entire dataset.There was no difference in the frequency or absolute numbers of Tregs among groups, nor in the proportions of other lymphocyte subsets. The concentrations of pro-inflammatory cytokines were greater in dogs with IMHA compared to healthy controls, but the concentration of IL-10 and the expression of cytokine genes did not differ between groups. Principal component analysis identified four components that explained the majority of the variability in the dataset, which seemed to correspond to different aspects of the immune response.The immunophenotype of dogs with IMHA differed from that of dogs with inflammatory diseases and from healthy control dogs; some of these changes could suggest abnormalities in peripheral tolerance that permit development of autoimmune disease. The frequency of Tregs did not differ between groups, suggesting that deficiency in the number of these cells is not responsible for development of IMHA

Macrophages enhance Vegfa-driven angiogenesis in an embryonic zebrafish tumour xenograft model

Tumour angiogenesis has long been a focus of anti-cancer therapy; however, anti-angiogenic cancer treatment strategies have had limited clinical success. Tumour-associated myeloid cells are believed to play a role in the resistance of cancer towards anti-angiogenesis therapy, but the mechanisms by which they do this are unclear. An embryonic zebrafish xenograft model has been developed to investigate the mechanisms of tumour angiogenesis and as an assay to screen anti-angiogenic compounds. In this study, we used cell ablation techniques to remove either macrophages or neutrophils and assessed their contribution towards zebrafish xenograft angiogenesis by quantitating levels of graft vascularisation. The ablation of macrophages, but not neutrophils, caused a strong reduction in tumour xenograft vascularisation and time-lapse imaging demonstrated that tumour xenograft macrophages directly associated with the migrating tip of developing tumour blood vessels. Finally, we found that, although macrophages are required for vascularisation in xenografts that either secrete VEGFA or overexpress zebrafish vegfaa, they are not required for the vascularisation of grafts with low levels of VEGFA, suggesting that zebrafish macrophages can enhance Vegfa-driven tumour angiogenesis. The importance of macrophages to this angiogenic response suggests that this model could be used to further investigate the interplay between myeloid cells and tumour vascularisation

Atmospheric Acetaldehyde: Importance of Air-Sea Exchange and a Missing Source in the Remote Troposphere.

We report airborne measurements of acetaldehyde (CH3CHO) during the first and second deployments of the National Aeronautics and Space Administration (NASA) Atmospheric Tomography Mission (ATom). The budget of CH3CHO is examined using the Community Atmospheric Model with chemistry (CAM-chem), with a newly-developed online air-sea exchange module. The upper limit of the global ocean net emission of CH3CHO is estimated to be 34 Tg a-1 (42 Tg a-1 if considering bubble-mediated transfer), and the ocean impacts on tropospheric CH3CHO are mostly confined to the marine boundary layer. Our analysis suggests that there is an unaccounted CH3CHO source in the remote troposphere and that organic aerosols can only provide a fraction of this missing source. We propose that peroxyacetic acid (PAA) is an ideal indicator of the rapid CH3CHO production in the remote troposphere. The higher-than-expected CH3CHO measurements represent a missing sink of hydroxyl radicals (and halogen radical) in current chemistry-climate models

A Prompt to the Web: The Media and Health Information Seeking Behaviour

UNLABELLED: OBJECTIVE, DESIGN, SETTING AND PARTICIPANTS: The objective was to investigate media influence on consumers' health related behaviours. A cross-sectional survey of randomly selected adults (18+ years) residing in the Hunter Region of New South Wales Australia was conducted. The sample was selected using a combination of the white pages and random digit dialling. MAIN OUTCOME MEASURES: The proportions of respondents who recalled seeing or hearing about conditions or treatments in the media over the 12 months prior to interview (August 2009-August 2010) and their subsequent health related behaviour. RESULTS: Although most survey participants reported seeking health information from their doctors, around two-thirds of survey participants (551, 68.8%) recalled hearing, seeing or reading about one or more medical conditions (total = 1097 instances) in the mainstream media over the past 12 months. Almost 40% of respondents (307, 38.4%) stated that they had looked for more information about a condition as a result of hearing about it in the media, and most used the internet (269, 87.4%). More than a quarter of respondents (215, 26.9%) indicated that they had asked their doctor about a condition they had heard about in the media. Around half of those who asked their doctor (109, 50.6%) reported that their inquiry resulted in them receiving treatment, of whom almost half (53, 48.3%) reported being prescribed a medicine. CONCLUSION: The survey results show that consumers become aware of medicines through traditional media and then to learn more often turn to the internet where quality of information may be poor

The KIC 8462852 light curve from 2015.75 to 2018.18 shows a variable secular decline

The star KIC 8462852 (Boyajian's Star) displays both fast dips of up to 20% on time scales of days, plus long-term secular fading by up to 19% on time scales from a year to a century. We report on CCD photometry of KIC 8462852 from 2015.75 to 2018.18, with 19,176 images making for 1,866 nightly magnitudes in BVRI. Our light curves show a continuing secular decline (by 0.023±0.003 mags in the B-band) with three superposed dips with duration 120-180 days. This demonstrates that there is a continuum of dip durations from a day to a century, so that the secular fading is seen to be by the same physical mechanism as the short-duration Kepler dips. The BVRI light curves all have the same shape, with the slopes and amplitudes for VRI being systematically smaller than in the B-band by factors of 0.77±0.05, 0.50±0.05, and 0.31±0.05. We rule out any hypothesis involving occultation of the primary star by any star, planet, solid body, or optically thick cloud. But these ratios are the same as that expected for ordinary extinction by dust clouds. This chromatic extinction implies dust particle sizes going down to ˜0.1 micron, suggesting that this dust will be rapidly blown away by stellar radiation pressure, so the dust clouds must have formed within months. The modern infrared observations were taken at a time when there was at least 12.4%±1.3% dust coverage (as part of the secular dimming), and this is consistent with dimming originating in circumstellar dust