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Search Results: 1 - 10 of 140619 matches for " Emma K. Nickerson "
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Feasibility of Modified Surviving Sepsis Campaign Guidelines in a Resource-Restricted Setting Based on a Cohort Study of Severe S. Aureus Sepsis
Weera Mahavanakul, Emma K. Nickerson, Pramot Srisomang, Prapit Teparrukkul, Pichet Lorvinitnun, Mingkwan Wongyingsinn, Wirongrong Chierakul, Maliwan Hongsuwan, T. Eoin West, Nicholas P. Day, Direk Limmathurotsakul, Sharon J. Peacock
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0029858
Abstract: Background The Surviving Sepsis Campaign (SSC) guidelines describe best practice for the management of severe sepsis and septic shock in developed countries, but most deaths from sepsis occur where healthcare is not sufficiently resourced to implement them. Our objective was to define the feasibility and basis for modified guidelines in a resource-restricted setting. Methods and Findings We undertook a detailed assessment of sepsis management in a prospective cohort of patients with severe sepsis caused by a single pathogen in a 1,100-bed hospital in lower-middle income Thailand. We compared their management with the SSC guidelines to identify care bundles based on existing capabilities or additional activities that could be undertaken at zero or low cost. We identified 72 patients with severe sepsis or septic shock associated with S. aureus bacteraemia, 38 (53%) of who died within 28 days. One third of patients were treated in intensive care units (ICUs). Numerous interventions described by the SSC guidelines fell within existing capabilities, but their implementation was highly variable. Care available to patients on general wards covered the fundamental principles of sepsis management, including non-invasive patient monitoring, antimicrobial administration and intravenous fluid resuscitation. We described two additive care bundles, one for general wards and the second for ICUs, that if consistently performed would be predicted to improve outcome from severe sepsis. Conclusion It is feasible to implement modified sepsis guidelines that are scaled to resource availability, and that could save lives prior to the publication of international guidelines for developing countries.
Staphylococcus aureus Bacteraemia in a Tropical Setting: Patient Outcome and Impact of Antibiotic Resistance
Emma K. Nickerson, Maliwan Hongsuwan, Direk Limmathurotsakul, Vanaporn Wuthiekanun, Krupal R. Shah, Pramot Srisomang, Weera Mahavanakul, Therapon Wacharaprechasgul, Vance G. Fowler, T. Eoin West, Nitaya Teerawatanasuk, Harald Becher, Nicholas J. White, Wirongrong Chierakul, Nicholas P. Day, Sharon J. Peacock
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0004308
Abstract: Background Most information on invasive Staphylococcus aureus infections comes from temperate countries. There are considerable knowledge gaps in epidemiology, treatment, drug resistance and outcome of invasive S. aureus infection in the tropics. Methods A prospective, observational study of S. aureus bacteraemia was conducted in a 1000-bed regional hospital in northeast Thailand over 1 year. Detailed clinical data were collected and final outcomes determined at 12 weeks, and correlated with antimicrobial susceptibility profiles of infecting isolates. Principal Findings Ninety-eight patients with S. aureus bacteraemia were recruited. The range of clinical manifestations was similar to that reported from temperate countries. The prevalence of endocarditis was 14%. The disease burden was highest at both extremes of age, whilst mortality increased with age. The all-cause mortality rate was 52%, with a mortality attributable to S. aureus of 44%. Methicillin-resistant S. aureus (MRSA) was responsible for 28% of infections, all of which were healthcare-associated. Mortality rates for MRSA and methicillin-susceptible S. aureus (MSSA) were 67% (18/27) and 46% (33/71), respectively (p = 0.11). MRSA isolates were multidrug resistant. Only vancomycin or fusidic acid would be suitable as empirical treatment options for suspected MRSA infection. Conclusions S. aureus is a significant pathogen in northeast Thailand, with comparable clinical manifestations and a similar endocarditis prevalence but higher mortality than industrialised countries. S. aureus bacteraemia is frequently associated with exposure to healthcare settings with MRSA causing a considerable burden of disease. Further studies are required to define setting-specific strategies to reduce mortality from S. aureus bacteraemia, prevent MRSA transmission, and to define the burden of S. aureus disease and emergence of drug resistance throughout the developing world.
Factors Predicting and Reducing Mortality in Patients with Invasive Staphylococcus aureus Disease in a Developing Country
Emma K. Nickerson, Vanaporn Wuthiekanun, Gumphol Wongsuvan, Direk Limmathurosakul, Pramot Srisamang, Weera Mahavanakul, Janjira Thaipadungpanit, Krupal R. Shah, Arkhom Arayawichanont, Premjit Amornchai, Aunchalee Thanwisai, Nicholas P. Day, Sharon J. Peacock
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0006512
Abstract: Background Invasive Staphylococcus aureus infection is increasingly recognised as an important cause of serious sepsis across the developing world, with mortality rates higher than those in the developed world. The factors determining mortality in developing countries have not been identified. Methods A prospective, observational study of invasive S. aureus disease was conducted at a provincial hospital in northeast Thailand over a 1-year period. All-cause and S. aureus-attributable mortality rates were determined, and the relationship was assessed between death and patient characteristics, clinical presentations, antibiotic therapy and resistance, drainage of pus and carriage of genes encoding Panton-Valentine Leukocidin (PVL). Principal Findings A total of 270 patients with invasive S. aureus infection were recruited. The range of clinical manifestations was broad and comparable to that described in developed countries. All-cause and S. aureus-attributable mortality rates were 26% and 20%, respectively. Early antibiotic therapy and drainage of pus were associated with a survival advantage (both p<0.001) on univariate analysis. Patients infected by a PVL gene-positive isolate (122/248 tested, 49%) had a strong survival advantage compared with patients infected by a PVL gene-negative isolate (all-cause mortality 11% versus 39% respectively, p<0.001). Multiple logistic regression analysis using all variables significant on univariate analysis revealed that age, underlying cardiac disease and respiratory infection were risk factors for all-cause and S. aureus-attributable mortality, while one or more abscesses as the presenting clinical feature and procedures for infectious source control were associated with survival. Conclusions Drainage of pus and timely antibiotic therapy are key to the successful management of S. aureus infection in the developing world. Defining the presence of genes encoding PVL provides no practical bedside information and draws attention away from identifying verified clinical risk factors and those interventions that save lives.
Molecular evolution of urea amidolyase and urea carboxylase in fungi
Pooja K Strope, Kenneth W Nickerson, Steven D Harris, Etsuko N Moriyama
BMC Evolutionary Biology , 2011, DOI: 10.1186/1471-2148-11-80
Abstract: Among the 64 fungal species we examined, only those in two Ascomycota classes (Sordariomycetes and Saccharomycetes) had the urea amidolyase sequences. Urea carboxylase was found in many but not all of the species in the phylum Basidiomycota and in the subphylum Pezizomycotina (phylum Ascomycota). It was completely absent from the class Saccharomycetes (phylum Ascomycota; subphylum Saccharomycotina). Four Sordariomycetes species we examined had both the urea carboxylase and the urea amidolyase sequences. Phylogenetic analysis showed that these two enzymes appeared to have gone through independent evolution since their bacterial origin. The amidase domain and the urea carboxylase domain sequences from fungal urea amidolyases clustered strongly together with the amidase and urea carboxylase sequences, respectively, from a small number of beta- and gammaproteobacteria. On the other hand, fungal urea carboxylase proteins clustered together with another copy of urea carboxylases distributed broadly among bacteria. The urease proteins were found in all the fungal species examined except for those of the subphylum Saccharomycotina.We conclude that the urea amidolyase genes currently found only in fungi are the results of a horizontal gene transfer event from beta-, gamma-, or related species of proteobacteria. The event took place before the divergence of the subphyla Pezizomycotina and Saccharomycotina but after the divergence of the subphylum Taphrinomycotina. Urea carboxylase genes currently found in fungi and other limited organisms were also likely derived from another ancestral gene in bacteria. Our study presented another important example showing plastic and opportunistic genome evolution in bacteria and fungi and their evolutionary interplay.Fungi exhibit great metabolic flexibility in the diversity of carbon and nitrogen sources they can use. We have been especially interested in their nitrogen sources, most recently urea [1,2]. In a previous study [1], a dichotom
Intracluster Medium Abundances Revisited
Brad K. Gibson,Emma J. Woolaston
Physics , 1998,
Abstract: We examine the origin of heavy elements in the intracluster medium (ICM) of galaxy clusters, concentrating upon the roles played by supernovae (SNe) Types Ia and II. The most accurately determined elemental abundances, Si and Fe, imply a mild predominance of Type II SNe as the source of ICM Fe, contributing approximately 60-80% of its total (and approximately 100% of the alpha-elements). (Currently) intractable uncertainties in measuring X-ray alpha-element ICM abundances, the initial mass function (IMF), and stellar evolution ingredients, make a more precise determination of the Ia:II ICM iron ``ratio'' impossible.
Decreased Autocrine EGFR Signaling in Metastatic Breast Cancer Cells Inhibits Tumor Growth in Bone and Mammary Fat Pad
Nicole K. Nickerson,Khalid S. Mohammad,Jennifer L. Gilmore,Erin Crismore,Angela Bruzzaniti,Theresa A. Guise,John Foley
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0030255
Abstract: Breast cancer metastasis to bone triggers a vicious cycle of tumor growth linked to osteolysis. Breast cancer cells and osteoblasts express the epidermal growth factor receptor (EGFR) and produce ErbB family ligands, suggesting participation of these growth factors in autocrine and paracrine signaling within the bone microenvironment. EGFR ligand expression was profiled in the bone metastatic MDA-MB-231 cells (MDA-231), and agonist-induced signaling was examined in both breast cancer and osteoblast-like cells. Both paracrine and autocrine EGFR signaling were inhibited with a neutralizing amphiregulin antibody, PAR34, whereas shRNA to the EGFR was used to specifically block autocrine signaling in MDA-231 cells. The impact of these was evaluated with proliferation, migration and gene expression assays. Breast cancer metastasis to bone was modeled in female athymic nude mice with intratibial inoculation of MDA-231 cells, and cancer cell-bone marrow co-cultures. EGFR knockdown, but not PAR34 treatment, decreased osteoclasts formed in vitro (p<0.01), reduced osteolytic lesion tumor volume (p<0.01), increased survivorship in vivo (p<0.001), and resulted in decreased MDA-231 growth in the fat pad (p<0.01). Fat pad shEGFR-MDA-231 tumors produced in nude mice had increased necrotic areas and decreased CD31-positive vasculature. shEGFR-MDA-231 cells also produced decreased levels of the proangiogenic molecules macrophage colony stimulating factor-1 (MCSF-1) and matrix metalloproteinase 9 (MMP9), both of which were decreased by EGFR inhibitors in a panel of EGFR-positive breast cancer cells. Thus, inhibiting autocrine EGFR signaling in breast cancer cells may provide a means for reducing paracrine factor production that facilitates microenvironment support in the bone and mammary gland.
Ethics without Morality, Morality without Ethics—Politics, Identity, Responsibility in Our Contemporary World  [PDF]
Emma Palese
Open Journal of Philosophy (OJPP) , 2013, DOI: 10.4236/ojpp.2013.33055
Abstract: Ethics without morality and morality without ethics are the characteristics of two distinct eras: modernity and post-modernity. The duty to obey the law is an ethical act, but not always moral. Morality in fact is something more: a principle of responsibility and an index of humanity. This paper aims to explain the historical relationship between morality, ethics and politics up to the present day. The erosion of the nation-state, global capitalism, bio-economy leads us to rethink the meaning of ethics, morality and politics. A utilitarian ethics and a necessary morality may be the new frontiers of our contemporary world.
Effectiveness of Musculoskeletal Emergency Physiotherapy Practitioners  [PDF]
Emma Salt
Open Journal of Therapy and Rehabilitation (OJTR) , 2016, DOI: 10.4236/ojtr.2016.43013
Abstract: Relevance and Method: The purpose of this project was to evaluate the effectiveness of the Emergency Physiotherapy Practitioner (EPP) service against quality care indicators identified as part of the “gold standard” for emergency care in England. The study was prospective and evaluated time to initial assessment, total time in the emergency department and un-planned re-attendance rate within a seven-day period for all patients seen by the EPP’s over a period of one year. Outcomes: One thousand and seven patients were seen by EPPs in the emergency department. The median wait time for treatment by an EPP was 34.5 minutes (95th percentile = 122). Regional median wait time was 45 minutes (95th percentile = 138). National median wait time was 55 minutes (95th percentile = 192). Median total time spent in ED for patients seen by EPPs was 99 minutes (95th percentile = 224). Regional median total time in ED was 223 (95th percentile = 239). Nationally median total time in ED was 136 minutes (95th percentile = 336). Three percent of patients seen by an EPP returned to the ED, compared to 6% regionally and 7.5% nationally. Conclusions: EPPs excelled in all three indicators and exceeded regional and national figures. The re-return rate met the current standard of being less than 5%. It could be justified that the addition of the EPPs to the emergency department was an efficient and effective service development.
The Inadequate Treatment of Pain: Collateral Damage from the War on Drugs
Jason W. Nickerson ,Amir Attaran
PLOS Medicine , 2012, DOI: 10.1371/journal.pmed.1001153
Crohn's Disease-Associated Adherent-Invasive Escherichia coli Adhesion Is Enhanced by Exposure to the Ubiquitous Dietary Polysaccharide Maltodextrin
Kourtney P. Nickerson, Christine McDonald
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0052132
Abstract: Crohn's disease (CD) is associated with intestinal dysbiosis evidenced by an altered microbiome forming thick biofilms on the epithelium. Additionally, adherent-invasive E. coli (AIEC) strains are frequently isolated from ileal lesions of CD patients indicating a potential role for these strains in disease pathogenesis. The composition and characteristics of the host microbiome are influenced by environmental factors, particularly diet. Polysaccharides added to food as emulsifiers, stabilizers or bulking agents have been linked to bacteria-associated intestinal disorders. The escalating consumption of polysaccharides in Western diets parallels an increased incidence of CD during the latter 20th century. In this study, the effect of a polysaccharide panel on adhesiveness of the CD-associated AIEC strain LF82 was analyzed to determine if these food additives promote disease-associated bacterial phenotypes. Maltodextrin (MDX), a polysaccharide derived from starch hydrolysis, markedly enhanced LF82 specific biofilm formation. Biofilm formation of multiple other E. coli strains was also promoted by MDX. MDX-induced E. coli biofilm formation was independent of polysaccharide chain length indicating a requirement for MDX metabolism. MDX exposure induced type I pili expression, which was required for MDX-enhanced biofilm formation. MDX also increased bacterial adhesion to human intestinal epithelial cell monolayers in a mechanism dependent on type 1 pili and independent of the cellular receptor CEACAM6, suggesting a novel mechanism of epithelial cell adhesion. Analysis of mucosa-associated bacteria from individuals with and without CD showed increased prevalence of malX, a gene essential for MDX metabolism, uniquely in the ileum of CD patients. These findings demonstrate that the ubiquitous dietary component MDX enhances E. coli adhesion and suggests a mechanism by which Western diets rich in specific polysaccharides may promote dysbiosis of gut microbes and contribute to disease susceptibility.
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