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Currently, there are limited and conflicting reports on the prognostic utility of PIK3CAand associated pathway markers for cervical cancers treated with primary surgical management. Moreover, current studies are lacking complete characterization of adjuvant treatment with RT and/or chemotherapy. We aimed to document the prevalence, clinicopathologic, adjuvant treatment details, and prognostic value of PI3K/AKT pathway mutations and copy number variation and phosphorylated AKT status in patients with cervical cancers treated with primary surgery. A clinicopathologic review was performed on a retrospective cohort of 185 patients with cervical cancer, treated with primary surgery at a single tertiary institution. Next-generation sequencing and digital PCR was used to determine PI3K/AKT pathway mutational status and PIK3CAcopy number variation, respectively, and fluorescent immunohistochemistry measured phosphorylated AKT expression. In all, 179 of 185 (96.8%) of tumors were successfully sequenced; 48 (26.8%) were positive for PI3K/AKT pathway mutations—the majority (n=37, 77.1%) PIK3CAmutations. PIK3CAmutation was associated with pathologically positive lymph nodes [12 (32%) vs. 22 (16%); P=0.022] and indication for postoperative chemoradiotherapy [17 (45.9%) vs. 32 (22.5%); P=0.004]. On multivariable analysis, PIK3CAstatus was not associated with overall survival (P=0.103) or progression-free survival (P=0.240) at 5 yrs, nor was PIK3CAcopy number variation status. phosphorylated AKT ≤ median significantly predicted for progression-free survival [multivariable hazard ratio 0.39 (0.17–0.89; P=0.025)] but not overall survival (P=0.087). The correlation of PIK3CAwith pathologic positive lymph node status yet lack of association with survival outcomes may be due to the use of adjuvant postoperative therapy. PIK3CAassessment before radical hysterectomy may help identify patients with a higher risk of node-positive disease.

Microbes play a critical role in plant litter decomposition and influence the fate of carbon in rivers and riparian zones. When decomposing low‐nutrient plant litter, microbes acquire nitrogen (N) and phosphorus (P) from the environment (i.e., nutrient immobilization), and this process is potentially sensitive to nutrient loading and changing climate. Nonetheless, environmental controls on immobilization are poorly understood because rates are also influenced by plant litter chemistry, which is coupled to the same environmental factors. Here we used a standardized, low‐nutrient organic matter substrate (cotton strips) to quantify nutrient immobilization at 100 paired stream and riparian sites representing 11 biomes worldwide. Immobilization rates varied by three orders of magnitude, were greater in rivers than riparian zones, and were strongly correlated to decomposition rates. In rivers, P immobilization rates were controlled by surface water phosphate concentrations, but N immobilization rates were not related to inorganic N. The N:P of immobilized nutrients was tightly constrained to a molar ratio of 10:1 despite wide variation in surface water N:P. Immobilization rates were temperature‐dependent in riparian zones but not related to temperature in rivers. However, in rivers nutrient supply ultimately controlled whether microbes could achieve the maximum expected decomposition rate at a given temperature. Collectively, we demonstrated that exogenous nutrient supply and immobilization are critical control points for decomposition of organic matter. Bacteria and fungi contribute to the breakdown of leaf litter in rivers and floodplains. To break down leaf litter, these microbes need the nutrients nitrogen and phosphorus (P), and microbes can get nutrients either from the leaf litter itself or from the environment. Most leaf litter has low nutrient content and microbes must rely on the environment to supply nutrients. We studied microbial nutrient uptake from the environment during litter breakdown to determine whether it varies predictably across the globe and how it is influenced by changing climate and nutrient pollution. In 100 rivers and floodplains in 11 of Earth's major biomes we placed small strips of cotton as stand‐ins for leaf litter. Nutrient uptake was consistently greater on cotton strips that were submerged in the river compared to cotton on the floodplain. For microbes in the river, nutrient uptake was faster in instances where there was more P in the water. For microbes in the floodplain, nutrient uptake was faster where temperatures were warmer. Faster nutrient uptake by microbes was linked with faster cotton breakdown in rivers and floodplains. Our study shows that climate change and nutrient pollution can alter the activity of microbes in rivers and floodplains. Nitrogen (N) and phosphorus (P) immobilization was measured on organic matter (cotton) in 100 rivers and riparian zones representing 11 biomesElevated temperature in riparian zones and phosphate in rivers increased immobilization, and consequently accelerated decompositionN and P immobilization was strongly linked by microbial stoichiometry despite widely varied surface‐water nutrient ratios Nitrogen (N) and phosphorus (P) immobilization was measured on organic matter (cotton) in 100 rivers and riparian zones representing 11 biomes Elevated temperature in riparian zones and phosphate in rivers increased immobilization, and consequently accelerated decomposition N and P immobilization was strongly linked by microbial stoichiometry despite widely varied surface‐water nutrient ratios

Hydropower production is one of the greatest threats to fluvial ecosystems and freshwater biodiversity. Now that we have entered the Anthropocene, there is an opportunity to reflect on what might constitute a ‘sustainable’ Anthropocene in the context of hydropower and riverine fish populations. Considering elements of existing practices that promote favorable social-ecological outcomes (i.e., ‘bright spots’) is timely given that there are plans to expand hydropower capacity in previously undammed rivers, intensify dam development in some of the world's largest river systems, and re-license existing facilities. We approach this from a pragmatic perspective: for the foreseeable future, hydropower will likely remain an important source of renewable electricity. To offer support for moving toward a more ‘sustainable’ Anthropocene, we provide syntheses of best practices during the siting, design, construction, operation, and compensation phases of hydropower development to minimize impacts on inland fish. For each phase, we offer positive examples (or what might be considered ‘bright spots’) pertaining to some of the approaches described within our syntheses, acknowledging that these projects may not be viewed as without ecological and (or) societal detriment by all stakeholders. Our findings underscore the importance of protecting critical habitat and free-flowing river reaches through careful site selection and basin-scale planning, infrastructure designs that minimize reservoir effects and facilitate safe passage of fish, construction of hydropower plants using best practices that minimize long-term damage, operating guidelines that mimic natural flow conditions, and compensation that is lasting, effective, inclusive, and locally relevant. Learning from these ‘bright spots’ may require engagement of diverse stakeholders, professionals, and governments at scales that extend well beyond a given site, river, or even basin. Indeed, environmental planning that integrates hydropower development into broader discussions of conserving regional biodiversity and ecosystem services will be of utmost importance.

The aim of the study was to identify patients with NTRKfusion-positive or RETfusion/mutation-positive thyroid cancers, who could benefit from neurotrophic tyrosine kinase receptor (NTRK) or receptor tyrosine kinase (RET) inhibitors.Patients were identified in the Calgary prospective thyroid cancer database (N= 482). Patients were ‘pre-screened’ with clinically available MassARRAY® BRAF test, Colon Panel, Melanoma Panel, or ThyroSPEC™. Mutation-negative tumors were ‘screened’ for NTRKfusions and RETfusions/mutations with the Oncomine™ Comprehensive Assay v3 (OCAv3).A total of 86 patients were included in 1 of 2 separate analyses. Analysis A included 42 patients with radioactive iodine (RAI)-resistant distant metastases. After pre-screening, 20 BRAFand RASmutation-negative patients underwent OCAv3 screening, resulting in the detection of 4 patients with NTRKfusions and 4 patients with RETfusions (8/20, 40% of analyzed patients). Analysis B included 44 patients, 42 with American Thyroid Association (ATA) high and intermediate risk of recurrence and 2 with medullary thyroid carcinoma. During pre-screening, 1 patient with an NTRKfusion, 1 patient with a RETfusion, and 30 patients with BRAFmutations were identified. The remaining 9 patients received OCAv3 screening, resulting in detection of 1 patient with an NTRKfusion and 1 with aRETfusion (4/11, 36% of analyzed patients).Our findings indicate a higher rate of NTRKfusions and RETfusions in patients with thyroid cancer with RAI-resistant distant metastases and ATA high or intermediate risk of recurrence. This highlights the importance of early screening to enable intervention with a NTRK or RET inhibitor.