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.

The Current State of Peritoneal Dialysis

Abstract: Technical innovations in peritoneal dialysis (PD), now used widely for the long-term treatment of ESRD, have significantly reduced therapy-related complications, allowing patients to be maintained on PD for longer periods. Indeed, the survival rate for patients treated with PD is now equivalent to that with in-center hemodialysis. In parallel, changes in public policy have spurred an unprecedented expansion in the use of PD in many parts of the world. Meanwhile, our improved understanding of the molecular mechanisms involved in solute and water transport across the peritoneum and of the pathobiology of structural and functional changes in the peritoneum with long-term PD has provided new targets for improving efficiency and for intervention. As with hemodialysis, almost half of all deaths on PD occur because of cardiovascular events, and there is great interest in identifying modality-specific factors contributing to these events. Notably, tremendous progress has been made in developing interventions that substantially reduce the risk of PD-related peritonitis. Yet the gains have been unequal among individual centers, primarily because of unequal clinical application of knowledge gained from research. The work to date has further highlighted the areas in need of innovation as we continue to strive to improve the health and outcomes of patients treated with PD.

Factors influencing success of clinical genome sequencing across a broad spectrum of disorders

Abstract: To assess factors influencing the success of whole-genome sequencing for mainstream clinical diagnosis, we sequenced 217 individuals from 156 independent cases or families across a broad spectrum of disorders in whom previous screening had identified no pathogenic variants. We quantified the number of candidate variants identified using different strategies for variant calling, filtering, annotation and prioritization. We found that jointly calling variants across samples, filtering against both local and external databases, deploying multiple annotation tools and using familial transmission above biological plausibility contributed to accuracy. Overall, we identified disease-causing variants in 21% of cases, with the proportion increasing to 34% (23/68) for mendelian disorders and 57% (8/14) in family trios. We also discovered 32 potentially clinically actionable variants in 18 genes unrelated to the referral disorder, although only 4 were ultimately considered reportable. Our results demonstrate the value of genome sequencing for routine clinical diagnosis but also highlight many outstanding challenges.

Relationship between Dialysis Modality and Mortality

Abstract: Mortality differences between peritoneal dialysis (PD) and hemodialysis (HD) are widely debated. In this study, mortality was compared between patients treated with PD and HD (including home HD) using data from 27,015 patients in the Australia and New Zealand Dialysis and Transplant Registry, 25,287 of whom were still receiving PD or HD 90 d after entry into the registry. Overall mortality rates were significantly lower during the 90- to 365-d period among those being treated with PD at day 90 (adjusted hazard ratio [HR] 0.89; 95% confidence interval [CI] 0.81 to 0.99]; P < 0.001). This effect, however, varied in direction and size with the presence of comorbidities: Younger patients without comorbidities had a mortality advantage with PD treatment, but other groups did not. After 12 mo, the use of PD at day 90 was associated with significantly increased mortality (adjusted HR 1.33; 95% CI 1.24 to 1.42; P < 0.001). In a supplementary as-treated analysis, PD treatment was associated with lower mortality during the first 90 d (adjusted HR 0.67; 95% CI 0.56 to 0.81; P < 0.001). These data suggest that the effect of dialysis modality on survival for an individual depends on time, age, and presence of comorbidities. Treatment with PD may be advantageous initially but may be associated with higher mortality after 12 mo.

Comparison of Clinical Outcomes and Adverse Events Associated With Glucose-Lowering Drugs in Patients With Type 2 Diabetes: A Meta-analysis.

Abstract: Importance Numerous glucose-lowering drugs are used to treat type 2 diabetes. Objective To estimate the relative efficacy and safety associated with glucose-lowering drugs including insulin. Data Sources Cochrane Library Central Register of Controlled Trials, MEDLINE, and EMBASE databases through March 21, 2016. Study Selection Randomized clinical trials of 24 weeks’ or longer duration. Data Extraction and Synthesis Random-effects network meta-analysis. Main Outcomes and Measures The primary outcome was cardiovascular mortality. Secondary outcomes included all-cause mortality, serious adverse events, myocardial infarction, stroke, hemoglobin A 1c (HbA 1C ) level, treatment failure (rescue treatment or lack of efficacy), hypoglycemia, and body weight. Results A total of 301 clinical trials (1 417 367 patient-months) were included; 177 trials (56 598 patients) of drugs given as monotherapy; 109 trials (53 030 patients) of drugs added to metformin (dual therapy); and 29 trials (10 598 patients) of drugs added to metformin and sulfonylurea (triple therapy). There were no significant differences in associations between any drug class as monotherapy, dual therapy, or triple therapy with odds of cardiovascular or all-cause mortality. Compared with metformin, sulfonylurea (standardized mean difference [SMD], 0.18 [95% CI, 0.01 to 0.34]), thiazolidinedione (SMD, 0.16 [95% CI, 0.00 to 0.31]), DPP-4 inhibitor (SMD, 0.33 [95% CI, 0.13 to 0.52]), and α-glucosidase inhibitor (SMD, 0.35 [95% CI, 0.12 to 0.58]) monotherapy were associated with higher HbA 1C levels. Sulfonylurea (odds ratio [OR], 3.13 [95% CI, 2.39 to 4.12]; risk difference [RD], 10% [95% CI, 7% to 13%]) and basal insulin (OR, 17.9 [95% CI, 1.97 to 162]; RD, 10% [95% CI, 0.08% to 20%]) were associated with greatest odds of hypoglycemia. When added to metformin, drugs were associated with similar HbA 1C levels, while SGLT-2 inhibitors offered the lowest odds of hypoglycemia (OR, 0.12 [95% CI, 0.08 to 0.18]; RD, −22% [−27% to −18%]). When added to metformin and sulfonylurea, GLP-1 receptor agonists were associated with the lowest odds of hypoglycemia (OR, 0.60 [95% CI, 0.39 to 0.94]; RD, −10% [95% CI, −18% to −2%]). Conclusions and Relevance Among adults with type 2 diabetes, there were no significant differences in the associations between any of 9 available classes of glucose-lowering drugs (alone or in combination) and the risk of cardiovascular or all-cause mortality. Metformin was associated with lower or no significant difference in HbA 1C levels compared with any other drug classes. All drugs were estimated to be effective when added to metformin. These findings are consistent with American Diabetes Association recommendations for using metformin monotherapy as initial treatment for patients with type 2 diabetes and selection of additional therapies based on patient-specific considerations.

Initial sequencing and analysis of the human genome.

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.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

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。

The social identity theory of intergroup behavior

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.