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Large wood is an integral part of many rivers, often defining river‐corridor morphology and habitat, but its occurrence, magnitude, and evolution in a river system are much less well understood than the sedimentary and hydraulic components, and due to methodological limitations, have seldom previously been mapped in substantial detail. We present a new method for this, representing a substantial advance in automated deep‐learning‐based image segmentation. From these maps, we measured large wood and sediment deposits from high‐resolution orthoimages to explore the dynamics of large wood in two reaches of the Elwha River, Washington, USA, between 2012 and 2017 as it adjusted to upstream dam removals. The data set consists of a time series of orthoimages (12.5‐cm resolution) constructed using Structure‐from‐Motion photogrammetry on imagery from 14 aerial surveys. Model training was optimized to yield maximum accuracy for estimated wood areas, compared to manually digitized wood, therefore model development and intended application were coupled. These fully reproducible methods and model resulted in a maximum of 15% error between observed and estimated total wood areas and wood deposit size‐distributions over the full spatio‐temporal extent of the data. Areal extent of wood in the channel margin approximately doubled in the years following dam removal, with greatest increases in large wood in wider, lower‐gradient sections. Large‐wood deposition increased between the start of dam removal (2011) and winter 2013, then plateaued. Sediment bars continued to grow up until 2016/17, assisted by a partially static wood framework deposited predominantly during the period up to winter 2013. Plain Language Summary: We measure the large wood in the Elwha River, Washington, USA, during and after dam removal. The presence of two dams had previously limited the movement of sediment and wood through the system. The removal of those dams liberated large amounts of sediment and wood from the former reservoir bottoms, which traveled downstream and deposited in the river channel. We develop an Artificial Intelligence (AI) model to measure all wood and sediment in the Elwha River corridor downstream of the two former dams, from a time‐series of high‐resolution imagery collected from aircraft. These measurements, accurate to within 15% of true values, provide a unique opportunity to understand how large wood occurs and behaves over multiple years and tens of kilometers. We found that the deposition of large wood on bars was coincident with and promoted the growth of sediment bars. The AI model we made could be powerful enough to find large wood in other places and images for similar purposes. Our data sets and models are made available to stimulate further studies of changes in river form resulting from interactions between water flow, wood, sediment, and vegetation. Key Points: We develop automated methods for detection and mapping of large wood, sediment, vegetation, and water from a time‐series of orthoimageryHigh‐resolution, reach‐wide measurements reveal wood dynamics in two Elwha River reaches adjusting to upstream dam removals over 5.5 yearsLarge wood deposition increased after dam removal, then plateaued, and bars continued to grow assisted by a partially static wood framework [ABSTRACT FROM AUTHOR]

The aim of this phase II trial was to estimate the objective response rate (ORR) of two different schedules of ixabepilone [weekly or every 3 weeks (Q3W)] combined with bevacizumab, relative to a reference arm of weekly paclitaxel and bevacizumab. Patients with human epidermal growth factor receptor 2-normal, chemotherapy-naïve metastatic breast cancer (MBC) were randomized 3:3:2 to ixabepilone 16 mg/m(2) weekly plus bevacizumab 10 mg/kg Q2W (Arm A: n = 46); ixabepilone 40 mg/m(2) Q3W (reduced to 32 mg/m(2) after four cycles of treatment) plus bevacizumab 15 mg/kg Q3W (Arm B: n = 45); or paclitaxel 90 mg/m(2) weekly plus bevacizumab 10 mg/kg intravenous infusion Q2W (Arm C: n = 32). Of 123 randomized patients, 122 were treated. All were followed for ≥19 months; 5 % of patients remained on study treatment at the time of this analysis. Grade 3 or 4 neutropenia was more common in Arm B (60 %) than Arms A (16 %) or C (22 %); other adverse events were similar. The investigator-assessed ORR was 48, 71, and 63 % for Arms A, B, and C, respectively. Median progression-free survival (randomized patients) was 9.6 months in Arm A, 11.9 months in Arm B, and 13.5 months in Arm C. In conclusion, ixabepilone Q3W plus bevacizumab has clinical activity as first-line therapy for MBC relative to paclitaxel plus bevacizumab, but with significantly greater risk of grade 3 or 4 neutropenia. In addition, these data suggest that weekly dosing of ixabepilone may be less active than Q3W dosing, but with less neutropenia.

Diabetic nephropathy (DN), the leading cause of end-stage renal failure, is clinically manifested by albuminuria and a progressive decline in glomerular filtration rate. The factors and mechanisms that contribute to progression of DN are still undefined. To address the contribution of [B.sub.2-kinin] receptors (B2KR) to the development of DN, we studied B2KR knockout mice ([B2KR.sup.-/-]) and their wild-type littermates ([B2KR.sup.+/+]). Diabetes was induced by daily injections of streptozotocin (50 mg/kg body wt) for 3-5 days. A total of 48 mice divided into 4 groups were used: group 1, wild-type control ([B2KR.sup.+/+] C); group 2, wild-type diabetic ([B2KR.sup.+/+] D); group 3, B2KR knockout control ([B2KR.sup.-/-] C); and group 4, B2KR knockout diabetic ([B2KR.sup.-/-] D). Glucose levels and albumin excretion rate (AER) were measured at predetermined intervals. Half of the mice were killed at 3 mo, and the remaining half, at 6 mo. Plasma glucose levels were markedly elevated in both [B2KR.sup.+/+] D and [B2KR.sup.-/-] D groups of mice compared with their controls. Diabetic [B2KR.sup.-/-] mice displayed reduced AER as well as reduced glomerular and tubular injury compared with diabetic [B2KR.sup.+/+] mice. The renoprotection conferred by deletion of B2KR was associated with increased renal expression of B1-kinin and angiotensin II [AT.sub.2] receptors and decreased expression of connective tissue growth factor. At a cellular level, our findings demonstrate that bradykinin downregulates the expression of [AT.sub.2] receptors in mesangial cells. These findings provide the first evidence that targeted deletion of B2KR protects against the development of DN. kinin receptors; albuminuria