Utilizing patient advocates in Parkinson's disease: A proposed framework for patient engagement and the modern metrics that can determine its success.

The wide application of patient engagement and its associated benefits has increased across government, academic and pharmaceutical research. However, neither an identified standard practice for the process of engagement, nor utilization of common metrics to assess associated outcomes, exists. Parkinson's Foundation developed a patient engagement framework and metrics to assess engagement within the academic research and drug development sectors. This approach was developed over the course of several years through assessing the literature, acquiring feedback from researchers and people with Parkinson's disease and adapting practices to be relevant and generalizable across patient engagement projects. This framework includes the: 1) creation of a scope of work, 2) establishment of guiding principles, 3) selection and training of participants, 4) co-determination of project metrics, 5) execution of the project and 6) dissemination of project findings. Parkinson's Foundation has also worked with academic, government and pharmaceutical stakeholders to identify metrics that assess both the quality of patient engagement and outcomes associated with patient engagement on projects. By improving patient engagement project methodologies and metrics, global clinical trials can have access to evidence-based patient engagement practices to more efficiently capture the needs of, and potentially benefit, the patient community.

Recombination-Mediated Telomere Maintenance in Saccharomyces cerevisiae Is Not Dependent on the Shu Complex.

In cells lacking telomerase, telomeres shorten progressively during each cell division due to incomplete end-replication. When the telomeres become very short, cells enter a state that blocks cell division, termed senescence. A subset of these cells can overcome senescence and maintain their telomeres using telomerase-independent mechanisms. In Saccharomyces cerevisiae, these cells are called 'survivors' and are dependent on Rad52-dependent homologous recombination and Pol32-dependent break-induced replication. There are two main types of survivors: type I and type II. The type I survivors require Rad51 and maintain telomeres by amplification of subtelomeric elements, while the type II survivors are Rad51-independent, but require the MRX complex and Sgs1 to amplify the C1-3A/TG1-3 telomeric sequences. Rad52, Pol32, Rad51, and Sgs1 are also important to prevent accelerated senescence, indicating that recombination processes are important at telomeres even before the formation of survivors. The Shu complex, which consists of Shu1, Shu2, Psy3, and Csm2, promotes Rad51-dependent homologous recombination and has been suggested to be important for break-induced replication. It also promotes the formation of recombination intermediates that are processed by the Sgs1-Top3-Rmi1 complex, as mutations in the SHU genes can suppress various sgs1, top3, and rmi1 mutant phenotypes. Given the importance of recombination processes during senescence and survivor formation, and the involvement of the Shu complex in many of the same processes during DNA repair, we hypothesized that the Shu complex may also have functions at telomeres. Surprisingly, we find that this is not the case: the Shu complex does not affect the rate of senescence, does not influence survivor formation, and deletion of SHU1 does not suppress the rapid senescence and type II survivor formation defect of a telomerase-negative sgs1 mutant. Altogether, our data suggest that the Shu complex is not important for recombination processes at telomeres.