University of Alberta

About: University of Alberta is a education organization based out in Edmonton, Alberta, Canada. It is known for research contribution in the topics: Population & Health care. The organization has 65403 authors who have published 154847 publications receiving 5358338 citations. The organization is also known as: Ualberta & UAlberta.

Density-based clustering based on hierarchical density estimates

Abstract: We propose a theoretically and practically improved density-based, hierarchical clustering method, providing a clustering hierarchy from which a simplified tree of significant clusters can be constructed. For obtaining a “flat” partition consisting of only the most significant clusters (possibly corresponding to different density thresholds), we propose a novel cluster stability measure, formalize the problem of maximizing the overall stability of selected clusters, and formulate an algorithm that computes an optimal solution to this problem. We demonstrate that our approach outperforms the current, state-of-the-art, density-based clustering methods on a wide variety of real world data.

Adverse effects of nonsteroidal antiinflammatory drugs: an update of gastrointestinal, cardiovascular and renal complications.

Abstract: Non-steroidal anti-inflammatory drugs (NSAIDs) are used chronically to reduce pain and inflammation in patients with arthritic conditions, and also acutely as analgesics by many patients Both therapeutic and adverse effects of NSAIDs are due to inhibition of cyclooxygenase (COX) enzyme NSAIDs are classified as non-selective and COX-2-selective inhibitors (COXIBS) based on their extent of selectivity for COX inhibition However, regardless of their COX selectivity, reports are still appearing on the GI side effect of NSAIDs particularly on the lower gastrointestinal (GI) tract and the harmful role of their controlled release formulations In addition, previously unpublished data stored in the sponsor’s files, question the GI sparing properties of rofecoxib, a COXIB that has been withdrawn due to cardiovascular (CV) side effects Presently, the major side effects of NSAIDs are the GI complications, renal disturbances and CV events There is a tendency to believe that all NSAIDs are associated with renal and CV side effects, a belief that is not supported by solid evidence Indeed, lower but still therapeutics doses of some NSAIDs may be cardioprotective In this review, we briefly discuss the GI toxicity of the NSAIDs and assess their renal and CV adverse effects in more detail This article is open to POST-PUBLICATION REVIEW Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page

Mutations in kelch-like 3 and cullin 3 cause hypertension and electrolyte abnormalities

Abstract: Hypertension affects one billion people and is a principal reversible risk factor for cardiovascular disease. Pseudohypoaldosteronism type II (PHAII), a rare Mendelian syndrome featuring hypertension, hyperkalaemia and metabolic acidosis, has revealed previously unrecognized physiology orchestrating the balance between renal salt reabsorption and K(+) and H(+) excretion. Here we used exome sequencing to identify mutations in kelch-like 3 (KLHL3) or cullin 3 (CUL3) in PHAII patients from 41 unrelated families. KLHL3 mutations are either recessive or dominant, whereas CUL3 mutations are dominant and predominantly de novo. CUL3 and BTB-domain-containing kelch proteins such as KLHL3 are components of cullin-RING E3 ligase complexes that ubiquitinate substrates bound to kelch propeller domains. Dominant KLHL3 mutations are clustered in short segments within the kelch propeller and BTB domains implicated in substrate and cullin binding, respectively. Diverse CUL3 mutations all result in skipping of exon 9, producing an in-frame deletion. Because dominant KLHL3 and CUL3 mutations both phenocopy recessive loss-of-function KLHL3 mutations, they may abrogate ubiquitination of KLHL3 substrates. Disease features are reversed by thiazide diuretics, which inhibit the Na-Cl cotransporter in the distal nephron of the kidney; KLHL3 and CUL3 are expressed in this location, suggesting a mechanistic link between KLHL3 and CUL3 mutations, increased Na-Cl reabsorption, and disease pathogenesis. These findings demonstrate the utility of exome sequencing in disease gene identification despite the combined complexities of locus heterogeneity, mixed models of transmission and frequent de novo mutation, and establish a fundamental role for KLHL3 and CUL3 in blood pressure, K(+) and pH homeostasis.