Range-wide persistence of the endangered arroyo toad (Anaxyrus californicus) for 20+ years following a prolonged drought.

Prolonged drought due to climate change has negatively impacted amphibians in southern California, U.S.A. Due to the severity and length of the current drought, agencies and researchers had growing concern for the persistence of the arroyo toad (Anaxyrus californicus), an endangered endemic amphibian in this region. Range-wide surveys for this species had not been conducted for at least 20 years. In 2017-2020, we conducted collaborative surveys for arroyo toads at historical locations. We surveyed 88 of the 115 total sites having historical records and confirmed that the arroyo toad is currently extant in at least 61 of 88 sites and 20 of 25 historically occupied watersheds. We did not detect toads at almost a third of the surveyed sites but did detect toads at 18 of 19 specific sites delineated in the 1999 Recovery Plan to meet one of four downlisting criteria. Arroyo toads are estimated to live 7-8 years, making populations susceptible to prolonged drought. Drought is estimated to increase in frequency and duration with climate change. Mitigation strategies for drought impacts, invasive aquatic species, altered flow regimes, and other anthropogenic effects could be the most beneficial strategies for toad conservation and may also provide simultaneous benefits to several other native species that share the same habitat.

The Translational and Regulatory Development of an Implantable Microdevice for Multiple Drug Sensitivity Measurements in Cancer Patients.

OBJECTIVE: The purpose of this article is to report the translational process of an implantable microdevice platform with an emphasis on the technical and engineering adaptations for patient use, regulatory advances, and successful integration into clinical workflow. METHODS: We developed design adaptations for implantation and retrieval, established ongoing monitoring and testing, and facilitated regulatory advances that enabled the administration and examination of a large set of cancer therapies simultaneously in individual patients. RESULTS: Six applications for oncology studies have successfully proceeded to patient trials, with future applications in progress. CONCLUSION: First-in-human translation required engineering design changes to enable implantation and retrieval that fit with existing clinical workflows, a regulatory strategy that enabled both delivery and response measurement of up to 20 agents in a single patient, and establishment of novel testing and quality control processes for a drug/device combination product without clear precedents. SIGNIFICANCE: This manuscript provides a real-world account and roadmap on how to advance from animal proof-of-concept into the clinic, confronting the question of how to use research to benefit patients.

Preparation and sterilization of an implantable drug-delivery microdevice for clinical use.

Implantable drug-delivery microdevices are a key diagnostic and therapeutic tool in medicine with increasing applications. Preparation of such combination drug-delivery devices for human studies requires the development of methods to ensure sterility, safety and integrity on both the device and drug side. Despite growing applications for these technologies, there has been a lack of clear methodology regarding sterilization and preparation to meet strict guidelines set forth by the Food and Drug Administration (FDA). Our laboratory developed a set of widely applicable and straightforward procedures to prepare drug-device combination products for clinical use that consistently achieve the high-quality standards provided by the FDA. This includes several newly developed methods for preparation of the implant including endotoxin removal, appropriate sterilization of raw materials, formulation of novel pharmaceutical agents, and loading of agents into drug delivery reservoirs. We also discuss protocols and methods developed with FDA to meet regulatory guidelines to ensure continual sterility and endotoxin testing, as well as longer-term stability testing of drugs and biologic agents.•Endotoxin removal and sterilization of raw materials for clinical use.•Formulation and device loading of novel pharmaceutical agents.•Continued testing of pharmaceutical agents and devices to meet regulatory guidelines.