Institution
University of Alberta
Education•Edmonton, Alberta, Canada•
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.
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University of Tampere1, University of Helsinki2, University of New Mexico3, Chulalongkorn University4, Royal Children's Hospital5, Telethon Institute for Child Health Research6, Universidade Federal do Rio Grande do Sul7, Mexican Social Security Institute8, National Taiwan University9, Central Manchester University Hospitals NHS Foundation Trust10, State University of Campinas11, University of the Philippines12, Queen Mary University of London13, University of Alberta14, University of Manitoba15, University of Würzburg16, Katholieke Universiteit Leuven17, Federal University of Paraná18, University of Sydney19, GlaxoSmithKline20
TL;DR: End-of-study results show excellent vaccine efficacy against CIN3+ and AIS irrespective of HPV DNA in the lesion, suggesting population-based vaccination that incorporates the HPV-16/18 vaccine and high coverage of early adolescents might have the potential to substantially reduce the incidence of cervical cancer.
Abstract: Summary Background Cervical intraepithelial neoplasia grade 2 or greater (CIN2+) is the surrogate endpoint used in licensure trials of human papillomavirus (HPV) vaccines. Vaccine efficacy against CIN3+, the immediate precursor to invasive cervical cancer, is more difficult to measure because of its lower incidence, but provides the most stringent evidence of potential cancer prevention. We report vaccine efficacy against CIN3+ and adenocarcinoma in situ (AIS) in the end-of-study analysis of PATRICIA (PApilloma TRIal against Cancer In young Adults). Methods Healthy women aged 15–25 years with no more than six lifetime sexual partners were included in PATRICIA, irrespective of their baseline HPV DNA status, HPV-16 or HPV-18 serostatus, or cytology. Women were randomly assigned (1:1) to receive an HPV-16/18 AS04-adjuvanted vaccine or a control hepatitis A vaccine via an internet-based central randomisation system using a minimisation algorithm to account for age ranges and study sites. The patients and study investigators were masked to allocated vaccine. The primary endpoint of PATRICIA has been reported previously. In the present end-of-study analysis, we focus on CIN3+ and AIS in the populations of most clinical interest, the total vaccinated cohort (TVC) and the TVC-naive. The TVC comprised all women who received at least one vaccine dose, approximating catch-up populations and including sexually active women (vaccine n=9319; control=9325). The TVC-naive comprised women with no evidence of oncogenic HPV infection at baseline, approximating early adolescent HPV exposure (vaccine n=5824; control=5820). This study is registered with ClinicalTrials.gov, number NCT00122681. Findings Vaccine efficacy against CIN3+ associated with HPV-16/18 was 100% (95% CI 85·5–100) in the TVC-naive and 45·7% (22·9–62·2) in the TVC. Vaccine efficacy against all CIN3+ (irrespective of HPV type in the lesion and including lesions with no HPV DNA detected) was 93·2% (78·9–98·7) in the TVC-naive and 45·6% (28·8–58·7) in the TVC. In the TVC-naive, vaccine efficacy against all CIN3+ was higher than 90% in all age groups. In the TVC, vaccine efficacy against all CIN3+ and CIN3+ associated with HPV-16/18 was highest in the 15–17 year age group and progressively decreased in the 18–20 year and 21–25 year age groups. Vaccine efficacy against all AIS was 100% (31·0–100) and 76·9% (16·0–95·8) in the TVC-naive and TVC, respectively. Serious adverse events occurred in 835 (9·0%) and 829 (8·9%) women in the vaccine and control groups, respectively; only ten events (0·1%) and five events (0·1%), respectively, were considered to be related to vaccination. Interpretation PATRICIA end-of-study results show excellent vaccine efficacy against CIN3+ and AIS irrespective of HPV DNA in the lesion. Population-based vaccination that incorporates the HPV-16/18 vaccine and high coverage of early adolescents might have the potential to substantially reduce the incidence of cervical cancer. Funding GlaxoSmithKline Biologicals.
573 citations
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TL;DR: Although the majority of patients with sARF will die, most survivors will become independent from renal replacement therapy within a year and males, older patients, and those with underlying medical conditions are at greatest risk.
Abstract: Severe acute renal failure (sARF) is associated with considerable morbidity, mortality and use of healthcare resources; however, its precise epidemiology and long-term outcomes have not been well described in a non-specified population. Population-based surveillance was conducted among all adult residents of the Calgary Health Region (population 1 million) admitted to multidisciplinary and cardiovascular surgical intensive care units between May 1 1999 and April 30 2002. Clinical records were reviewed and outcome at 1 year was assessed. sARF occurred in 240 patients (11.0 per 100,000 population/year). Rates were highest in males and older patients (≥65 years of age). Risk factors for development of sARF included previous heart disease, stroke, pulmonary disease, diabetes mellitus, cancer, connective tissue disease, chronic renal dysfunction, and alcoholism. The annual mortality rate was 7.3 per 100,000 population with rates highest in males and those ≥65 years. The 28-day, 90-day, and 1-year case-fatality rates were 51%, 60%, and 64%, respectively. Increased Charlson co-morbidity index, presence of liver disease, higher APACHE II score, septic shock, and need for continuous renal replacement therapy were independently associated with death at 1 year. Renal recovery occurred in 78% (68/87) of survivors at 1 year. sARF is common and males, older patients, and those with underlying medical conditions are at greatest risk. Although the majority of patients with sARF will die, most survivors will become independent from renal replacement therapy within a year.
573 citations
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TL;DR: The structure of a synthetic peptide comprising the 28 amino-terminal residues of actin has been examined by 1H-NMR and CD spectroscopy and the significance of the TFE-induced peptide structure is discussed.
Abstract: The structure of a synthetic peptide comprising the 28 amino-terminal residues of actin has been examined by 1H-NMR and CD spectroscopy. The peptide is largely unstructured and flexible in solution but becomes increasingly structured at higher trifluoroethanol (TFE) concentrations. As judged by CD with the use of two additional peptides (actin 1-20 and actin 18-28), TFE induces formation of up to 48% helical content within residues 1-20, while residues 21-28 exhibit no helical propensity. Similar results were obtained by using NMR-derived distance information in restrained molecular dynamics calculations. The calculated structure of actin 1-28 peptide in 80% TFE is well defined for the first 23 residues with a backbone root mean square deviation of 0.5 A. Two helices are formed from residues 4-13 and 16-20, and a beta-turn is formed from residues 13-16. The N-terminal residues 1-3 exhibit increased flexibility and a helix-like conformation while the C-terminal residues 21-28 show no regular secondary structure. These results are compared with the predicted secondary structure and the structure of the corresponding sequence in the crystal structure of actin [Kabsch et al. (1990) Nature 347, 37-44]. The significance of the TFE-induced peptide structure is discussed.
573 citations
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573 citations
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TL;DR: Questioning the disruptive talk associated with digital transformation, it is suggested that the institutional perspective is a prolific lens to study digital innovation and transformation and that existing institutional arrangements are pivotal arbiters in deciding whether and how novel arrangements gain acceptance.
572 citations
Authors
Showing all 66027 results
Name | H-index | Papers | Citations |
---|---|---|---|
Salim Yusuf | 231 | 1439 | 252912 |
Yi Chen | 217 | 4342 | 293080 |
Robert M. Califf | 196 | 1561 | 167961 |
Douglas R. Green | 182 | 661 | 145944 |
Russel J. Reiter | 169 | 1646 | 121010 |
Jiawei Han | 168 | 1233 | 143427 |
Jaakko Kaprio | 163 | 1532 | 126320 |
Tobin J. Marks | 159 | 1621 | 111604 |
Josef M. Penninger | 154 | 700 | 107295 |
Subir Sarkar | 149 | 1542 | 144614 |
Gerald M. Edelman | 147 | 545 | 69091 |
Rinaldo Bellomo | 147 | 1714 | 120052 |
P. Sinervo | 138 | 1516 | 99215 |
David A. Jackson | 136 | 1095 | 68352 |
Andreas Warburton | 135 | 1578 | 97496 |