Meta-analysis of statins in chronic kidney disease: who benefits?

Background: Attempts to reduce the burden of vascular disease in advanced chronic kidney disease (CKD) by control of lipids have not been as successful as predicted. Aim: To determine the extent to which the effectiveness of statins varies by kidney class. Design: Meta-analysis. Methods: We selected randomized trials of statin vs. placebo that gave outcomes for CKD3 (eGFR 30–59 ml/min), CKD4 (eGFR 15–29 ml/min), CKD5 (eGFR < 15 ml/min)/5D(dialysis) and transplant patients separately. Data sources were the Cholesterol Triallists’ Treatment Collaboration and previously published meta-analyses. Main outcome measures were major cardiovascular events (MACE), cardiovascular death and all-cause mortality (ACM). Results: A total of 13 studies provided 19 386 participants with CKD3, 2565 with CKD4, 7051 with CKD5/5D and 2102 with a functioning renal transplant. Statins reduced MACE (pooled HR 0.72, 95% CI 0.67–0.78) and ACM (0.82, 0.73–0.91) in CKD3; probably reduced MACE (0.78, 0.62–0.99) in CKD4; and probably reduced cardiovascular death (0.62, 0.40–0.96) in renal transplants. There were no cardiovascular or ACM data in CKD4; there was no convincing evidence of benefit for any outcome in CKD5/5D; and no significant reduction in MACE or ACM in patients with a functioning transplant. Conclusions: Statins are indicated in CKD3, probably indicated in CKD4, not indicated in CKD5/5D and probably indicated in patients with a functioning transplant. Too few patients with CKD4 and renal transplants have been included in lipid lowering trials for confident conclusions to be drawn

Electric birefringence studies of biopolymer systems

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.Important and novel electric birefringence measurements of immediate significance in the biomedical field are reported on a family of materials which form the major constituents of the cartilage connective tissue. Outstanding amongst the reported results is the confirmation of the Hardingham-Muir model for proteoglycan-hyaluronic acid aggregation, and the relative ease with which the technique was both able to substantiate the model, and, for the first time, to observe the gradual formation of the aggregate. The complex heteropolysaccharide, proteoglycan, has also been characterised by a wide ranging series of electric birefringence measurements. Other conformational changes studied by the technique on other cartilage materials and reported herein are the effects of pH changes on hyaluronic acid conformation, the enzymatic degradation of hyaluronic acid and the thermal denaturation of collagen. The work also considers aspects of the problems of application of theoretical models to flexible polymers and demonstrates what can be achieved on existing crude theories with the nitrocellulose in acetone system. Some exploratory measurements in the interfacial area between solute and solvent are reported for the bacterium E. coli and an aqueous suspension of PTFE particles. A diverse range of materials was studied with particular reference to the values of particle rotary diffusion constants derived from dispersion of birefringence with frequency and analysis of birefringence relaxation time decay rates following the application of a pulsed DC field. Comparisons are drawn between these values and explanations of the discrepancies observed are considered. Last, but not least, the design of an advanced and high sensitivity apparatus for the measurement of electric birefringence is reported. Unusually, the system adopts a vertical mode and the novel Kerr Cell design incorporated dispenses. with end windows. The use of this new compact design is suggested as the basis for commercial applications

Using xAU Tokens to Count Unique Active Users Per Epoch Without Cookies

User engagement and adoption is typically measured in terms of the number of users active during a given period, generally termed as xAU where x stands for the measurement time interval. Without third-party cookies, it is difficult to obtain xAU measures, especially when content is embedded within other applications and services. This disclosure describes cookieless techniques to determine a lower bound for various xAU measures. Upon receiving a request for content, a xAU token for the user agent is generated and cryptographically signed on the server and relayed to the user agent for local caching. Each xAU token can be a tuple of the form (period, nonce, cryptographic signature). Once the epoch corresponding to the period in the xAU token expires, the corresponding xAU token is sent back to the server via an out-of-band channel. The number of unique active users per epoch is obtained by counting the number of unique xAU tokens seen over the corresponding epoch. Implementation of the techniques with user permission enables reasonably accurate counts for unique active users during a given period, without requiring the use of third-party cookies