Geographic and taxonomic variation in adaptive capacity among mountain-dwelling small mammals: Implications for conservation status and actions

Contemporary climate change is modifying the distribution, morphology, phenology, physiology, evolution, and interspecific interactions of species. Effects of climate change are mediated not only through the magnitude of change experienced (exposure) and an animal\u27s sensitivity to such changes, but also through the ability of the population or species to adjust to climatic variability and change genetically, behaviorally, or spatially (via its distribution) (i.e., adaptive capacity; AC). Here, we used an attribute-based framework to systematically evaluate and compare the AC of American pikas (Ochotona princeps) against four other mountain-dwelling small mammals of North America to determine whether pikas are disproportionately vulnerable to climate change, as has been postulated. Unlike previous analyses, we also compared AC across O. princeps lineages and across three taxonomic (and thus, spatial) scales. Our results indicate that pikas have markedly lower adaptive capacity than all compared species except bushy-tailed woodrats (Neotoma cinerea), and that our assessments of species generally align with earlier characterizations of climate-change vulnerability based on life-history characteristics. Although AC did not differ dramatically among pika lineages, some attributes are likely constraining AC differently in various parts of the geographic range. Comparisons across taxonomic levels of pikas illustrated that, although AC levels were comparable in pika lineages versus range-wide, AC was assessed as lower in interior-Great-Basin pikas than across the entire O.p. schisticeps lineage. We conclude that the comparatively lower AC of pikas results in particularly high susceptibility to anthropogenic climate change, corroborating results from numerous other recent investigations of pikas\u27 climate-responsiveness. Adaptive-capacity evaluations appear useful as a consistent way to identify sentinel species or populations and for conservation prioritization

Clinical importance of clonal hematopoiesis in metastatic gastrointestinal tract cancers

IMPORTANCE: Clonal hematopoiesis (CH) has been associated with development of atherosclerosis and leukemia and worse survival among patients with cancer; however, the association with cancer therapy efficacy, in particular immune checkpoint blockade (ICB), and toxicity has not yet been established. Given the widespread use of ICB and the critical role hematopoietic stem cell-derived lymphocytes play in mediating antitumor responses, CH may be associated with therapeutic efficacy and hematologic toxicity. OBJECTIVE: To determine the association between CH and outcomes, hematologic toxicity, and therapeutic efficacy in patients with metastatic gastrointestinal tract cancers being treated with systemic therapy, both in the first-line metastatic treatment setting and in ICB. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included 633 patients with stage IV colorectal (CRC) and esophagogastric (EGC) cancer who were treated with first-line chemotherapy and/or ICB at Memorial Sloan Kettering Cancer Center. Patients underwent matched tumor and peripheral blood DNA sequencing using the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets next-generation sequencing assay between January 1, 2006, and December 31, 2020. EXPOSURES: Clonal hematopoiesis-related genetic alterations were identified by next-generation sequencing of patients\u27 tumor and normal blood buffy coat samples, with a subset of these CH alterations annotated as likely putative drivers (CH-PD) based upon previously established criteria. MAIN OUTCOMES AND MEASURES: Patients with CH and CH-PD in peripheral blood samples were identified, and these findings were correlated with survival outcomes (progression-free survival [PFS] and overall survival [OS]) during first-line chemotherapy and ICB, as well as baseline white blood cell levels and the need for granulocyte colony-stimulating factor (G-CSF) support. RESULTS: Among the 633 patients included in the study (390 men [61.6%]; median age, 58 [IQR, 48-66] years), the median age was 52 (IQR, 45-63) years in the CRC group and 61 (IQR, 53-69) years in the EGC group. In the CRC group, 161 of 301 patients (53.5%) were men, compared with 229 of 332 patients (69.0%) in the EGC group. Overall, 62 patients (9.8%) were Asian, 45 (7.1%) were Black or African American, 482 (76.1%) were White, and 44 (7.0%) were of unknown race or ethnicity. Presence of CH was identified in 115 patients with EGC (34.6%) and 83 with CRC (27.6%), with approximately half of these patients harboring CH-PD (CRC group, 44 of 83 [53.0%]; EGC group, 55 of 115 [47.8%]). Patients with EGC and CH-PD exhibited a significantly worse median OS of 16.0 (95% CI, 11.6-22.3) months compared with 21.6 (95% CI, 19.6-24.3) months for those without CH-PD (P = .01). For patients with CRC and EGC, CH and CH-PD were not associated with PFS differences in patients undergoing ICB or first-line chemotherapy. Neither CH nor CH-PD were correlated with baseline leukocyte levels or increased need for G-CSF support. CONCLUSIONS AND RELEVANCE: These findings suggest CH and CH-PD are not directly associated with the treatment course of patients with metastatic gastrointestinal tract cancer receiving cancer-directed therapy

A global multicohort study to map subcortical brain development and cognition in infancy and early childhood

The human brain grows quickly during infancy and early childhood, but factors influencing brain maturation in this period remain poorly understood. To address this gap, we harmonized data from eight diverse cohorts, creating one of the largest pediatric neuroimaging datasets to date focused on birth to 6 years of age. We mapped the developmental trajectory of intracranial and subcortical volumes in ∼2,000 children and studied how sociodemographic factors and adverse birth outcomes influence brain structure and cognition. The amygdala was the first subcortical volume to mature, whereas the thalamus exhibited protracted development. Males had larger brain volumes than females, and children born preterm or with low birthweight showed catch-up growth with age. Socioeconomic factors exerted region- and time-specific effects. Regarding cognition, males scored lower than females; preterm birth affected all developmental areas tested, and socioeconomic factors affected visual reception and receptive language. Brain-cognition correlations revealed region-specific associations