Improving SWE Estimation with Data Assimilation: The Influence of Snow Depth Observation Timing and Uncertainty

Snow depth observations can be leveraged with data assimilation (DA) to improve estimation of snow density and snow water equivalent (SWE). A key consideration for mission and campaign design is how snow depth retrieval characteristics (including observation timing/frequency and sampling error) influence SWE accuracy and uncertainty in a DA framework. To quantify these effects, we implement a particle filter (PF) assimilation technique to assimilate depth and validate this approach against observed snow density and SWE at 49 snow telemetry sites across 9 years. We sample from continuous in-situ snow depth records to test a range of measurement timing scenarios and two sampling error scenarios representative of remote sensing capabilities. Assimilation reduces density bias by over 40% and SWE bias by over 70% across climate zones and in both wet and dry years. There is little incremental benefit to SWE accuracy when assimilating more than one depth observation near peak accumulation. SWE estimates are less sensitive to observation timing than sampling error. Alternatively, more frequent depth observations improve melt-out date timing and reduce SWE uncertainty, a key consideration when evaluating the operational utility of DA. In matching depth observations, the PF mostly acts to increase precipitation inputs to the model, while not systematically shifting other parameter values or forcings across the climate zones represented with the study sites. This demonstrates that precipitation is the largest source of model error. With DA, density errors are still nontrivial, illuminating the need for further improvements to modeled density to achieve SWE error targets.</div

State of the Art in Large-Scale Soil Moisture Monitoring

Soil moisture is an essential climate variable influencing land atmosphere interactions, an essential hydrologic variable impacting rainfall runoff processes, an essential ecological variable regulating net ecosystem exchange, and an essential agricultural variable constraining food security. Large-scale soil moisture monitoring has advanced in recent years creating opportunities to transform scientific understanding of soil moisture and related processes. These advances are being driven by researchers from a broad range of disciplines, but this complicates collaboration and communication. For some applications, the science required to utilize large-scale soil moisture data is poorly developed. In this review, we describe the state of the art in large-scale soil moisture monitoring and identify some critical needs for research to optimize the use of increasingly available soil moisture data. We review representative examples of 1) emerging in situ and proximal sensing techniques, 2) dedicated soil moisture remote sensing missions, 3) soil moisture monitoring networks, and 4) applications of large-scale soil moisture measurements. Significant near-term progress seems possible in the use of large-scale soil moisture data for drought monitoring. Assimilation of soil moisture data for meteorological or hydrologic forecasting also shows promise, but significant challenges related to model structures and model errors remain. Little progress has been made yet in the use of large-scale soil moisture observations within the context of ecological or agricultural modeling. Opportunities abound to advance the science and practice of large-scale soil moisture monitoring for the sake of improved Earth system monitoring, modeling, and forecasting

Antithrombotic Treatment in Transcatheter Aortic Valve Implantation Insights for Cerebrovascular and Bleeding Events

Transcatheter aortic valve implantation (TAVI) has emerged as a therapeutic alternative for patients with symptomatic aortic stenosis at high or prohibitive surgical risk. However, patients undergoing TAVI are also at high risk for both bleeding and stroke complications, and specific mechanical aspects of the procedure itself can increase the risk of these complications. The mechanisms of periprocedural bleeding complications seem to relate mainly to vascular/access site complications (related to the use of large catheters in a very old and frail elderly population), whereas the pathophysiology of cerebrovascular events remains largely unknown. Further, although mechanical complications, especially the interaction between the valve prosthesis and the native aortic valve, may play a major role in events that occur during TAVI, post-procedural events might also be related to a prothrombotic environment or state generated by the implanted valve, the occurrence of atrial arrhythmias, and associated comorbidities. Antithrombotic therapy in the setting of TAVI has been empirically determined, and unfractionated heparin during the procedure followed by dual antiplatelet therapy with aspirin (indefinitely) and clopidogrel (1 to 6 months) is the most commonly recommended treatment. However, bleeding and cerebrovascular events are common; these may be modifiable with optimization of periprocedural and post-procedural pharmacology. Further, as the field of antiplatelet and anticoagulant therapy evolves, potential drug combinations will multiply, introducing variability in treatment. Randomized trials are the best path forward to determine the balance between the efficacy and risks of antithrombotic treatment in this high risk-population

Induction of \u3cem\u3eIL19\u3c/em\u3e Expression through JNK and cGAS-STING Modulates DNA Damage–Induced Cytokine Production

Cytokine production is a critical component of cell-extrinsic responses to DNA damage and cellular senescence. Here, we demonstrated that expression of the gene encoding interleukin-19 (IL-19) was enhanced by DNA damage through pathways mediated by c-Jun amino-terminal kinase (JNK) and cGAS-STING and that IL19 expression was required for the subsequent production of the cytokines IL-1, IL-6, and IL-8. IL19 expression was stimulated by diverse cellular stresses, including inhibition of the DNA replication checkpoint kinase ATR (ataxia telangiectasia and Rad3-related protein), oncogene expression, replicative exhaustion, oxidative stress, and DNA double-strand breaks. Unlike the production of IL-6 and IL-8, IL19 expression was not affected by abrogation of signaling by the IL-1 receptor (IL-1R) or the mitogen-activated protein kinase p38. Instead, the DNA damage–induced production of IL-1, IL-6, and IL-8 was substantially reduced by suppression of IL19 expression. The signaling pathways required to stimulate IL19 expression selectively depended on the type of DNA-damaging agent. Reactive oxygen species and the ASK1-JNK pathway were critical for responses to ionizing radiation (IR), whereas the cGAS-STING pathway stimulated IL19 expression in response to either IR or ATR inhibition. Whereas induction of IL1, IL6, and IL8 by IR depended on IL19 expression, the cGAS-STING–dependent induction of the immune checkpoint gene PDL1 after IR and ATR inhibition was independent of IL19. Together, these results suggest that IL-19 production by diverse pathways forms a distinct cytokine regulatory arm of the response to DNA damage

A phase 2 study of estramustine, docetaxel, and bevacizumab in men with castrate-resistant prostate cancer: Results from Cancer and Leukemia Group B Study 90006

The use of docetaxel prolongs survival for patients with castrate resistant prostate cancer (CRPC). Inhibition of vascular endothelial growth factor (VEGF) with bevacizumab may further enhance the anti-tumor effect of docetaxel and estramustine in patients with CRPC

ECOHYDROLOGICAL IMPLICATIONS OF WOODY PLANT ENCROACHMENT

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Transcriptional profiling identifies an androgen receptor activity-low, stemness program associated with enzalutamide resistance.

The androgen receptor (AR) antagonist enzalutamide is one of the principal treatments for men with castration-resistant prostate cancer (CRPC). However, not all patients respond, and resistance mechanisms are largely unknown. We hypothesized that genomic and transcriptional features from metastatic CRPC biopsies prior to treatment would be predictive of de novo treatment resistance. To this end, we conducted a phase II trial of enzalutamide treatment (160 mg/d) in 36 men with metastatic CRPC. Thirty-four patients were evaluable for the primary end point of a prostate-specific antigen (PSA)50 response (PSA decline ≥50% at 12 wk vs. baseline). Nine patients were classified as nonresponders (PSA decline &lt;50%), and 25 patients were classified as responders (PSA decline ≥50%). Failure to achieve a PSA50 was associated with shorter progression-free survival, time on treatment, and overall survival, demonstrating PSA50's utility. Targeted DNA-sequencing was performed on 26 of 36 biopsies, and RNA-sequencing was performed on 25 of 36 biopsies that contained sufficient material. Using computational methods, we measured AR transcriptional function and performed gene set enrichment analysis (GSEA) to identify pathways whose activity state correlated with de novo resistance. TP53 gene alterations were more common in nonresponders, although this did not reach statistical significance (P = 0.055). AR gene alterations and AR expression were similar between groups. Importantly, however, transcriptional measurements demonstrated that specific gene sets-including those linked to low AR transcriptional activity and a stemness program-were activated in nonresponders. Our results suggest that patients whose tumors harbor this program should be considered for clinical trials testing rational agents to overcome de novo enzalutamide resistance

Recurrent Modification of a Conserved Cis-Regulatory Element Underlies Fruit Fly Pigmentation Diversity

The development of morphological traits occurs through the collective action of networks of genes connected at the level of gene expression. As any node in a network may be a target of evolutionary change, the recurrent targeting of the same node would indicate that the path of evolution is biased for the relevant trait and network. Although examples of parallel evolution have implicated recurrent modification of the same gene and cis-regulatory element (CRE), little is known about the mutational and molecular paths of parallel CRE evolution. In Drosophila melanogaster fruit flies, the Bric-à-brac (Bab) transcription factors control the development of a suite of sexually dimorphic traits on the posterior abdomen. Female-specific Bab expression is regulated by the dimorphic element, a CRE that possesses direct inputs from body plan (ABD-B) and sex-determination (DSX) transcription factors. Here, we find that the recurrent evolutionary modification of this CRE underlies both intraspecific and interspecific variation in female pigmentation in the melanogaster species group. By reconstructing the sequence and regulatory activity of the ancestral Drosophila melanogaster dimorphic element, we demonstrate that a handful of mutations were sufficient to create independent CRE alleles with differing activities. Moreover, intraspecific and interspecific dimorphic element evolution proceeded with little to no alterations to the known body plan and sex-determination regulatory linkages. Collectively, our findings represent an example where the paths of evolution appear biased to a specific CRE, and drastic changes in function were accompanied by deep conservation of key regulatory linkages. © 2013 Rogers et al