Sustaining While Disrupting: The Challenge of Congregational Innovation

Review of Sustaining While Disrupting: The Challenge of Congregational Innovation by F. Douglas Powe Jr. and Lovett H. Weems Jr. (Minneapolis: Fortress Press, 2022

Metabolic variability in seafloor brines revealed by carbon and sulphur dynamics

Brine fluids that upwell from deep, hot reservoirs below the sea bed supply the sea floor with energy-rich substrates and nutrients that are used by diverse microbial ecosystems. Contemporary hypersaline environments formed by brine seeps may provide insights into the metabolism and distribution of microorganisms on the early Earth or on extraterrestrial bodies. Here we use geochemical and genetic analyses to characterize microbial community composition and metabolism in two seafloor brines in the Gulf of Mexico: an active mud volcano and a quiescent brine pool. Both brine environments are anoxic and hypersaline. However, rates of sulphate reduction and acetate production are much higher in the brine pool, whereas the mud volcano supports much higher rates of methane production. We find no evidence of anaerobic oxidation of methane, despite high methane fluxes at both sites. We conclude that the contrasting microbial community compositions and metabolisms are linked to differences in dissolved-organic-matter input from the deep subsurface and different fluid advection rates between the two sites. DOI: 10.1038/NGEO47

A real-world evidence study of CDK4/6 inhibitor treatment patterns and outcomes in metastatic breast cancer by g<i>BRCA</i> mutation status.

1563 Background: Limited data exist on the real-world treatment patterns and effectiveness of cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors in the germline BRCA (g BRCA) mutated breast cancer population. Methods: Adults with human epidermal growth factor receptor 2 negative (HER2-), hormone receptor positive (HR+) metastatic breast cancer (mBC) treated with a CDK4/6 inhibitor from 01Jan2013–31Jan2018 were retrospectively selected from the Flatiron Health Oncology electronic medical record database. Patients with known g BRCA status were classified as having g BRCA mutated (g BRCAm) or wild type (g BRCAwt) disease. Time to first subsequent therapy or death (TFST) and overall survival (OS) were calculated from start of the earliest line of therapy with a CDK4/6 inhibitor. Kaplan-Meier (KM) medians were estimated, and TFST and OS compared between g BRCA groups with Cox models stratified by line of therapy and adjusting for demographic and clinical characteristics that modified hazard ratios (HRs) for g BRCA status by &gt; 10%. Results: Of 2968 HER2- HR+ patients with mBC receiving a CDK4/6 inhibitor, g BRCA status was known for 859 (28.9%). Patients with g BRCAm and g BRCAwt received letrozole plus palbociclib (42.4 and 39.8%, respectively), fulvestrant plus palbociclib (32.9 and 30.7%), or other CDK4/6 regimens (24.7 and 29.5%) across all lines. The g BRCAm group had a non-significant, shorter TFST than g BRCAwt (stratified HR 1.24; 95% CI 0.96–1.59). OS was significantly shorter in g BRCAm than g BRCAwt patients (stratified HR 1.50; 95% CI 1.06–2.14). Conclusions: The results of this real-world study suggest that treatment outcomes with CDK4/6 inhibitors may be poorer in patients with g BRCAm compared with g BRCAwt disease. These findings indicate a higher unmet need among patients with g BRCAm, potentially requiring alternative treatment options. [Table: see text] </jats:p