University of East Anglia

About: University of East Anglia is a education organization based out in Norwich, Norfolk, United Kingdom. It is known for research contribution in the topics: Population & Climate change. The organization has 13250 authors who have published 37504 publications receiving 1669060 citations. The organization is also known as: UEA.

Cardiovascular efficacy and safety of bococizumab in high-risk patients

Abstract: BackgroundBococizumab is a humanized monoclonal antibody that inhibits proprotein convertase subtilisin–kexin type 9 (PCSK9) and reduces levels of low-density lipoprotein (LDL) cholesterol. We sought to evaluate the efficacy of bococizumab in patients at high cardiovascular risk. MethodsIn two parallel, multinational trials with different entry criteria for LDL cholesterol levels, we randomly assigned the 27,438 patients in the combined trials to receive bococizumab (at a dose of 150 mg) subcutaneously every 2 weeks or placebo. The primary end point was nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina requiring urgent revascularization, or cardiovascular death; 93% of the patients were receiving statin therapy at baseline. The trials were stopped early after the sponsor elected to discontinue the development of bococizumab owing in part to the development of high rates of antidrug antibodies, as seen in data from other studies in the program. The median follow-up was 10...

Analysis of the Streptomyces coelicolor sigE gene reveals the existence of a subfamily of eubacterial RNA polymerase sigma factors involved in the regulation of extracytoplasmic functions.

Abstract: sigma E, an RNA polymerase sigma factor of apparent M(r) 28,000, was previously identified by its ability to direct transcription from the P2 promoter of the agarose gene (dagA) of Streptomyces coelicolor. A degenerate oligonucleotide probe, designed from the N-terminal sequence of purified sigma E, was used to isolate the sigma E gene (sigE). The predicted sequence of sigma E shows greatest similarity to sequences of seven other proteins: Myxococcus xanthus CarQ, Pseudomonas aeruginosa AlgU, Pseudomonas syringae HrpL, Escherichia coli sigma E, Alcaligenes eutrophus CnrH, E. coli FecI, and Bacillus subtilis SigX, a protein of unknown function. These eight proteins define a subfamily of eubacterial RNA polymerase factors sufficiently different from other sigma s that, in many cases, they are not identified by standard similarity searching methods. Available information suggests that all of them regulate extracytoplasmic functions and that they function as effector molecules responding to extracytoplasmic stimuli. A. eutrophus CnrH appears to be a plasmid-encoded factor.

Computed tomographic pulmonary angiography vs ventilation-perfusion lung scanning in patients with suspected pulmonary embolism: a randomized controlled trial

Abstract: ContextVentilation-perfusion (/) lung scanning and computed tomographic pulmonary angiography (CTPA) are widely used imaging procedures for the evaluation of patients with suspected pulmonary embolism. Ventilation-perfusion scanning has been largely replaced by CTPA in many centers despite limited comparative formal evaluations and concerns about CTPA's low sensitivity (ie, chance of missing clinically important pulmonary embuli).ObjectivesTo determine whether CTPA may be relied upon as a safe alternative to / scanning as the initial pulmonary imaging procedure for excluding the diagnosis of pulmonary embolism in acutely symptomatic patients.Design, Setting, and ParticipantsRandomized, single-blinded noninferiority clinical trial performed at 4 Canadian and 1 US tertiary care centers between May 2001 and April 2005 and involving 1417 patients considered likely to have acute pulmonary embolism based on a Wells clinical model score of 4.5 or greater or a positive D-dimer assay result.InterventionPatients were randomized to undergo either / scanning or CTPA. Patients in whom pulmonary embolism was considered excluded did not receive antithrombotic therapy and were followed up for a 3-month period.Main Outcome MeasureThe primary outcome was the subsequent development of symptomatic pulmonary embolism or proximal deep vein thrombosis in patients in whom pulmonary embolism had initially been excluded.ResultsSeven hundred one patients were randomized to CTPA and 716 to / scanning. Of these, 133 patients (19.2%) in the CTPA group vs 101 (14.2%) in the / scan group were diagnosed as having pulmonary embolism in the initial evaluation period (difference, 5.0%; 95% confidence interval [CI], 1.1% to 8.9%) and were treated with anticoagulant therapy. Of those in whom pulmonary embolism was considered excluded, 2 of 561 patients (0.4%) randomized to CTPA vs 6 of 611 patients (1.0%) undergoing / scanning developed venous thromboembolism in follow-up (difference, −0.6%; 95% CI, −1.6% to 0.3%) including one patient with fatal pulmonary embolism in the / group.ConclusionsIn this study, CTPA was not inferior to / scanning in ruling out pulmonary embolism. However, significantly more patients were diagnosed with pulmonary embolism using the CTPA approach. Further research is required to determine whether all pulmonary emboli detected by CTPA should be managed with anticoagulant therapy.Trial Registrationisrctn.org Identifier: ISRCTN65486961