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David W. Johnson

Bio: David W. Johnson is an academic researcher from University of Queensland. The author has contributed to research in topics: Peritoneal dialysis & Kidney disease. The author has an hindex of 160, co-authored 2714 publications receiving 140778 citations. Previous affiliations of David W. Johnson include Minnesota Department of Transportation & Open University.


Papers
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Journal ArticleDOI
TL;DR: Tolevamer, a novel polystyrene binder of C. difficile toxins A and B, effectively treats mild to moderate C.difficile diarrhea and merits further clinical development.
Abstract: BACKGROUND Current antibiotic therapies for Clostridium difficile-associated diarrhea have limitations, including progression to severe disease, recurrent C. difficile-associated diarrhea, and selection for nosocomial pathogens. Tolevamer, a soluble, high-molecular weight, anionic polymer that binds C. difficile toxins A and B is a unique nonantibiotic treatment option. METHODS In this 3-arm, multicenter, randomized, double-blind, active-controlled, parallel-design phase II study, patients with mild to moderately severe C. difficile-associated diarrhea were randomized to receive 3 g of tolevamer per day (n = 97), 6 g of tolevamer per day (n = 95), or 500 mg of vancomycin per day (n = 97). The primary efficacy parameter was time to resolution of diarrhea, defined as the first day of 2 consecutive days when the patient had hard or formed stools (any number) or < or = 2 stools of loose or watery consistency. RESULTS In the per-protocol study population, resolution of diarrhea was achieved in 48 (67%) of 72 patients receiving 3 g of tolevamer per day (median time to resolution of diarrhea, 4.0 days; 95% confidence interval, 2.0-6.0 days), in 58 (83%) of 70 patients receiving 6 g of tolevamer per day (median time to resolution of diarrhea, 2.5 days; 95% confidence interval, 2.0-3.0 days), and in 73 (91%) of 80 patients receiving vancomycin (median time to resolution of diarrhea, 2.0 days; 95% confidence interval, 1.0-3.0 days). Tolevamer administered at a dosage of 6 g per day was found to be noninferior to vancomycin administered at a dosage of 500 mg per day with regard to time to resolution of diarrhea (P = .02) and was associated with a trend toward a lower recurrence rate. Tolevamer was well tolerated but was associated with an increased risk of hypokalemia. CONCLUSIONS Tolevamer, a novel polystyrene binder of C. difficile toxins A and B, effectively treats mild to moderate C. difficile diarrhea and merits further clinical development.

219 citations

Journal ArticleDOI
TL;DR: Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong; Department of Nephrology, University of Queensland at Princess Alexandra Hospital, Brisbane, Australia; Renal Electrolyte Division.
Abstract: Peritoneal dialysis (PD) catheter-related infections are a major predisposing factor to PD-related peritonitis (1–3). The primary objective of preventing and treating catheter-related infections is to prevent peritonitis.Recommendations on the prevention and treatment of catheter-related infections were published previously together with recommendations on PD peritonitis under the auspices of the International Society for Peritoneal Dialysis (ISPD) in 1983 and revised in 1989, 1993, 1996, 2000, 2005, and 2010 (4–9). The present recommendations, however, focus on catheter-related infections, while peritonitis will be covered in a separate guideline.These recommendations are evidence-based where such evidence exists. The bibliography is not intended to be comprehensive. When there are many similar reports on the same area, the committee prefers to refer to the more recent publications. In general, these recommendations follow the Grades of Recommendation Assessment, Development and Evaluation (GRADE) system for classification of the level of evidence and grade of recommendations in clinical guideline reports (10). Within each recommendation, the strength of recommendation is indicated as Level 1 (We recommend), Level 2 (We suggest), or Not Graded, and the quality of the supporting evidence is shown as A (high quality), B (moderate quality), C (low quality), or D (very low quality). The recommendations are not meant to be implemented in every situation indiscriminately. Each PD unit should examine its own pattern of infection, causative organisms, and sensitivities and adapt the protocols according to local conditions as necessary. Although many of the general principles presented here could be applied to pediatric patients, we focus on catheter-related infections in adult patients. Clinicians who take care of pediatric PD patients should refer to the latest consensus guideline in this area for detailed treatment regimen and dosage (11).

218 citations

Journal ArticleDOI
17 Dec 2015-Blood
TL;DR: The combination of idelalisib and rituximab was highly active, resulting in durable disease control in treatment-naïve older patients with CLL, and support the further development of idELalisib as initial treatment of CLL.

216 citations

Journal ArticleDOI
TL;DR: Results from a systematic investigation of mercury (Hg) concentrations across 14 forest sites in the United States show highest concentrations in litter layers, strongly enriched in Hg compared to aboveground tissues and indicative of substantial postdepositional sorption of Hg.
Abstract: Results from a systematic investigation of mer- cury (Hg) concentrations across 14 forest sites in the United States show highest concentrations in litter layers, strongly enriched in Hg compared to aboveground tissues and indicative of substantial postdepositional sorption of Hg Soil Hg con- centrations were lower than in litter, with highest concentra- tions in surface soils Aboveground tissues showed no detectable spatial patterns, likely due to 17 different tree species present across sites Litter and soil Hg concentrations positively correlated with carbon (C), latitude, precipitation, and clay (in soil), which together explained up to 94% of concentration variability We observed strong latitudinal increases in Hg in soils and litter, in contrast to inverse latitudinal gradients of atmospheric deposition measures Soil and litter Hg concentrations were closely linked to C contents, consistent with well-known associations between organic matter and Hg, and we propose that C also shapes distribution of Hg in forests at continental scales TheconsistentlinkbetweenCandHgdistributionmayreflectalong-termlegacywherebyold,C-richsoilandlitterlayerssequester atmospheric Hg depositions over long time periods Based on a multiregression model, we present a distribution map of Hg concentrations in surface soils of the United States

215 citations

Journal ArticleDOI
01 Aug 2014-Leukemia
TL;DR: This study confirms that myeloma subclones exhibit different survival properties during treatment or mouse engraftment, and concludes that clonal diversity combined with varying selective pressures is the essential foundation for tumor progression and treatment resistance in Myeloma.
Abstract: Although intratumor heterogeneity has been inferred in multiple myeloma (MM), little is known about its subclonal phylogeny. To describe such phylogenetic trees in a series of patients with MM, we perform whole-exome sequencing and single-cell genetic analysis. Our results demonstrate that at presentation myeloma is composed of two to six different major clones, which are related by linear and branching phylogenies. Remarkably, the earliest myeloma-initiating clones, some of which only had the initiating t(11;14), were still present at low frequencies at the time of diagnosis. For the first time in myeloma, we demonstrate parallel evolution whereby two independent clones activate the RAS/MAPK pathway through RAS mutations and give rise subsequently to distinct subclonal lineages. We also report the co-occurrence of RAS and interferon regulatory factor 4 (IRF4) p.K123R mutations in 4% of myeloma patients. Lastly, we describe the fluctuations of myeloma subclonal architecture in a patient analyzed at presentation and relapse and in NOD/SCID-IL2Rγ(null) xenografts, revealing clonal extinction and the emergence of new clones that acquire additional mutations. This study confirms that myeloma subclones exhibit different survival properties during treatment or mouse engraftment. We conclude that clonal diversity combined with varying selective pressures is the essential foundation for tumor progression and treatment resistance in myeloma.

214 citations


Cited by
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Journal ArticleDOI
Eric S. Lander1, Lauren Linton1, Bruce W. Birren1, Chad Nusbaum1  +245 moreInstitutions (29)
15 Feb 2001-Nature
TL;DR: The results of an international collaboration to produce and make freely available a draft sequence of the human genome are reported and an initial analysis is presented, describing some of the insights that can be gleaned from the sequence.
Abstract: The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.

22,269 citations

28 Jul 2005
TL;DR: PfPMP1)与感染红细胞、树突状组胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作�ly.
Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1(PfPMP1)与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用,在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员,通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

18,940 citations

Book ChapterDOI
09 Jan 2004
TL;DR: A theory of intergroup conflict and some preliminary data relating to the theory is presented in this article. But the analysis is limited to the case where the salient dimensions of the intergroup differentiation are those involving scarce resources.
Abstract: This chapter presents an outline of a theory of intergroup conflict and some preliminary data relating to the theory. Much of the work on the social psychology of intergroup relations has focused on patterns of individual prejudices and discrimination and on the motivational sequences of interpersonal interaction. The intensity of explicit intergroup conflicts of interests is closely related in human cultures to the degree of opprobrium attached to the notion of "renegade" or "traitor." The basic and highly reliable finding is that the trivial, ad hoc intergroup categorization leads to in-group favoritism and discrimination against the out-group. Many orthodox definitions of "social groups" are unduly restrictive when applied to the context of intergroup relations. The equation of social competition and intergroup conflict rests on the assumptions concerning an "ideal type" of social stratification in which the salient dimensions of intergroup differentiation are those involving scarce resources.

14,812 citations

Journal ArticleDOI
TL;DR: In this paper, Imagined communities: Reflections on the origin and spread of nationalism are discussed. And the history of European ideas: Vol. 21, No. 5, pp. 721-722.

13,842 citations

Journal ArticleDOI
TL;DR: Reading a book as this basics of qualitative research grounded theory procedures and techniques and other references can enrich your life quality.

13,415 citations