Archaeological and Contemporary Evidence Indicates Low Sea Otter Prevalence on the Pacific Northwest Coast During the Late Holocene.

The historic extirpation and subsequent recovery of sea otters (Enhydra lutris) have profoundly changed coastal social-ecological systems across the northeastern Pacific. Today, the conservation status of sea otters is informed by estimates of population carrying capacity or growth rates independent of human impacts. However, archaeological and ethnographic evidence suggests that for millennia, complex hunting and management protocols by Indigenous communities limited sea otter abundance near human settlements to reduce the negative impacts of this keystone predator on shared shellfish prey. To assess relative sea otter prevalence in the Holocene, we compared the size structure of ancient California mussels (Mytilus californianus) from six archaeological sites in two regions on the Pacific Northwest Coast, to modern California mussels at locations with and without sea otters. We also quantified modern mussel size distributions from eight locations on the Central Coast of British Columbia, Canada, varying in sea otter occupation time. Comparisons of mussel size spectra revealed that ancient mussel size distributions are consistently more similar to modern size distributions at locations with a prolonged absence of sea otters. This indicates that late Holocene sea otters were maintained well below carrying capacity near human settlements as a result of human intervention. These findings illuminate the conditions under which sea otters and humans persisted over millennia prior to the Pacific maritime fur trade and raise important questions about contemporary conservation objectives for an iconic marine mammal and the social-ecological system in which it is embedded. Supplementary Information: The online version contains supplementary material available at 10.1007/s10021-021-00671-3.

Diagnostic Yield and Treatment Impact of Targeted Exome Sequencing in Early-Onset Epilepsy.

Targeted whole-exome sequencing (WES) is a powerful diagnostic tool for a broad spectrum of heterogeneous neurological disorders. Here, we aim to examine the impact on diagnosis, treatment and cost with early use of targeted WES in early-onset epilepsy. WES was performed on 180 patients with early-onset epilepsy (≤5 years) of unknown cause. Patients were classified as Retrospective (epilepsy diagnosis >6 months) or Prospective (epilepsy diagnosis <6 months). WES was performed on an Ion Proton™ and variant reporting was restricted to the sequences of 620 known epilepsy genes. Diagnostic yield and time to diagnosis were calculated. An analysis of cost and impact on treatment was also performed. A molecular diagnoses (pathogenic/likely pathogenic variants) was achieved in 59/180 patients (33%). Clinical management changed following WES findings in 23 of 59 diagnosed patients (39%) or 13% of all patients. A possible diagnosis was identified in 21 additional patients (12%) for whom supporting evidence is pending. Time from epilepsy onset to a genetic diagnosis was faster when WES was performed early in the diagnostic process (mean: 145 days Prospective vs. 2,882 days Retrospective). Costs of prior negative tests averaged $8,344 per patient in the Retrospective group, suggesting savings of $5,110 per patient using WES. These results highlight the diagnostic yield, clinical utility and potential cost-effectiveness of using targeted WES early in the diagnostic workup of patients with unexplained early-onset epilepsy. The costs and clinical benefits are likely to continue to improve. Advances in precision medicine and further studies regarding impact on long-term clinical outcome will be important.