High-Throughput In-Use and Stress Size Stability Screening of Protein Therapeutics Using Algorithm-Driven Dynamic Light Scattering

Stability of therapeutic proteins (TPs) is a critical quality attribute that impacts both safety and efficacy of the drug. Size stability is routinely performed during and after biomanufacturing. Dynamic light scattering (DLS) is a commonly used technique to characterize hydrodynamic size of the TPs. Herein, we have developed a novel method to evaluate in-use and thermal stress stability of TPs using algorithm-driven high-throughput DLS. Five marketed TPs were tested under the guidance of customized algorithms. The TPs were evaluated at relevant temperature conditions as well as under dilution and thermal stress for size stability. We found that the TPs were stable under the in-use conditions tested; however, sample loss due to evaporation can lead to large protein aggregates. A combined assessment of autocorrelation function and photos of sample well could be useful in formulation screening. Dilution of TPs also has an impact on the hydrodynamic size. Thermal stress experiments showed the importance of using different data processing methods to access size distribution. Polydispersity index was useful in evaluating sample heterogeneity. Herein, we show that algorithm-driven high-throughput DLS can provide additional supportive information during and after biomanufacturing and the potential to be used in a quality control environment.     

Evidence for an own-age bias in age estimation from voices in older persons

Previous studies have investigated the effect of ageing on age estimation from faces as well as the occurrence of an own-age bias in such age estimation from faces. To the best of our knowledge, the occurrence of an own age effect on age estimation from voices has never been examined earlier using an experimental design in which the age of participants (young vs. old) and the age of voice stimuli (young vs. old) were crossed. Results revealed an own-age bias in older adults only. In comparison with younger adults, older participants showed age estimation abilities that are preserved for voices from their own age group and impaired for younger voices. This own age bias was absent in younger participants.     

Reappraisal of the Traditional Wenckebach Phenomenon with a Modified Ladder Diagram

Understanding of the traditional Wenckebach phenomenon is enhanced by using a modified ladder diagram where AV conduction in any cycle is represented by a slanted line in the AV bar together with similar AV conduction lines of all the preceding cycles. The diagram facilitates calculation of the duration of RR intervals (equal to the basic PP or sinus interval minus the PR or AV increment applied to this particular cycle) and the duration of the pause (equal to 2 × PP or sinus interval minus the sum of all the increments applied to the AV delay). The modified Wenckebach diagram should help students understand the mysterious clustering of QRS complexes or “paradoxical” increase of the ventricular rate that occurs during a Wenckebach sequence. Ann Noninvasive Electrocardiol 2012;17(1):3–7