Light availability controls in the benthic nearshore ecosystem of the Elwha River

The Elwha River Restoration Project was the largest US dam removal project to date, both in dam height and sediment released. During dam removal in 2011–2014, ~18 Mt of sediment washed downriver, and macroalgae virtually disappeared from the adjacent nearshore ecosystem. The link between current benthic light availability and sediment delivery and transport has been investigated in order to understand conditions during dam removal. Seven instrument platforms were deployed on the 10-m isobath along a 16 km transect centered on the river mouth for seven fortnightly periods in 2016 and 2017 to monitor near-bed photosynthetically available radiation (PAR), suspended sediment, wave climate, current velocity, temperature, and salinity. Water-column profiles, bed sediment, and water samples were collected during deployments. Seasonally variable chlorophyll-a and colored dissolved organic matter did not contribute substantially to light attenuation compared to suspended sediment. Along the 10-m isobath within 1.5 km of the river mouth, the greatest light attenuation occurred when wave events coincided with or followed periods of high river discharge. However, discharge events lasting attenuation; energetic tidal currents promote rapid sediment export out of the nearshore environment. In the buoyant plume, maximum light attenuation occurred within 1 m of the surface, reducing light through the rest of the water column. Benthic PAR varied more during spring tides when plume location was more variable. Alongshore 1.5 to 8 km from the river mouth, light availability was not directly coupled to river discharge. Light attenuation occurred throughout the water column, influenced by resuspension due to strong currents and wave events. This subsurface attenuation would not be captured by remote sensing. Predicting benthic light availability over event, tidal, and seasonal timescales will improve management strategies designed to limit ecosystem damage during other dam removals or sediment delivery events

Interpretable Subgroup Discovery in Treatment Effect Estimation with Application to Opioid Prescribing Guidelines

The dearth of prescribing guidelines for physicians is one key driver of the current opioid epidemic in the United States. In this work, we analyze medical and pharmaceutical claims data to draw insights on characteristics of patients who are more prone to adverse outcomes after an initial synthetic opioid prescription. Toward this end, we propose a generative model that allows discovery from observational data of subgroups that demonstrate an enhanced or diminished causal effect due to treatment. Our approach models these sub-populations as a mixture distribution, using sparsity to enhance interpretability, while jointly learning nonlinear predictors of the potential outcomes to better adjust for confounding. The approach leads to human-interpretable insights on discovered subgroups, improving the practical utility for decision suppor

The solution structure of the N-terminal domain of hepatocyte growth factor reveals a potential heparin-binding site

AbstractBackground: Hepatocyte growth factor (HGF) is a multipotent growth factor that transduces a wide range of biological signals, including mitogenesis, motogenesis, and morphogenesis. The N-terminal (N) domain of HGF, containing a hairpin-loop region, is important for receptor binding and the potent biological activities of HGF. The N domain is also the primary binding site for heparin or heparan sulfate, which enhances receptor/ligand oligomerization and modulates receptor-dependent mitogenesis. The rational design of artificial modulators of HGF signaling requires a detailed understanding of the structures of HGF and its receptor, as well as the role of heparin proteoglycan; this study represents the first step towards that goal.Results: We report here a high-resolution solution structure of the N domain of HGF. This first structure of HGF reveals a novel folding topology with a distinct pattern of charge distribution and indicates a possible heparin-binding site.Conclusions: The hairpin-loop region of the N domain plays a major role in stabilizing the structure and contributes to a putative heparin-binding site, which explains why it is required for biological functions. These results suggest several basic and/or polar residues that may be important for use in further mutational studies of heparin binding

Changes in Kelp and Other Seaweeds Following Elwha Dam Removal

Kelps are ecologically important seaweeds that dominated the nearshore vegetation community prior to dam removal on the Elwha River. Dam removal is expected to trigger a shift from kelps to vegetation types that are characteristic of soft-sediment communities through restoring natural sediment supply. This study is investigating how nearshore vegetation responds to restoration of the natural sediment regime, both initially when large amounts of sediment entrained in the reservoirs are released and over longer time periods. We assessed vegetation at multiple spatial scales using three approaches. First, we measured floating kelp canopy area using aerial photography. Second, we assessed the abundance of understory kelp and seagrasses with towed videography along 50 km of shoreline. Third, scuba divers recorded density of kelp species and other seaweeds along 10 km of shoreline bracketing the river mouth. Results show profound changes in vegetation and a strong gradient in magnitude of impact related to distance from the river mouth. Floating kelp canopy area decreased 74% in the Elwha Drift Cell in the first year following project initiation (year 1), with lower magnitude losses throughout the Strait of Juan de Fuca. Area of prostrate kelps decreased by 45% (400 ha) and of stipitate kelps by 30% (130 ha) in the Elwha Drift Cell in year 1. Mean kelp density near the river mouth decreased 77% in year 1 and 95% in year 2. While all 10 kelp species declined, annuals were more impacted than perennials. In contrast to the general decline, juveniles of several kelp species appeared in late August of year 2, a substantial delay compared to typical spring timing of juvenile growth. What caused the large kelp losses and apparent delay of juvenile growth? Likely candidates include light reduction from the river plume and scour, burial or settlement inhibition from deposition. These candidates will be explored using physical data from the multidisciplinary research effort

Centimeter to decimeter hollow concretions and voids in Gale Crater sediments, Mars

Voids and hollow spheroids between ∼1 and 23 cm in diameter occur at several locations along the traverse of the Curiosity rover in Gale crater, Mars. These hollow spherical features are significantly different from anything observed in previous landed missions. The voids appear in dark-toned, rough-textured outcrops, most notably at Point Lake (sols 302-305) and Twin Cairns Island (sol 343). Point Lake displays both voids and cemented spheroids in close proximity; other locations show one or the other form. The spheroids have 1-4 mm thick walls and appear relatively dark-toned in all cases, some with a reddish hue. Only one hollow spheroid (Winnipesaukee, sol 653) was analyzed for composition, appearing mafic (Fe-rich), in contrast to the relatively felsic host rock. The interior surface of the spheroid appears to have a similar composition to the exterior with the possible exceptions of being more hydrated and slightly depleted in Fe and K. Origins of the spheroids as Martian tektites or volcanic bombs appear unlikely due to their hollow and relatively fragile nature and the absence of in-place clearly igneous rocks. A more likely explanation to both the voids and the hollow spheroids is reaction of reduced iron with oxidizing groundwater followed by some re-precipitation as cemented rind concretions at a chemical reaction front. Although some terrestrial concretion analogs are produced from a precursor siderite or pyrite, diagenetic minerals could also be direct precipitates for other terrestrial concretions. The Gale sediments differ from terrestrial sandstones in their high initial iron content, perhaps facilitating a higher occurrence of such diagenetic reactions

Identification and Dynamics of a Heparin-Binding Site in Hepatocyte Growth Factor †

Hepatocyte growth factor (HGF) is a heparin-binding, multipotent growth factor that transduces a wide range of biological signals, including mitogenesis, motogenesis, and morphogenesis. Heparin or closely related heparan sulfate has profound effects on HGF signaling. A heparin-binding site in the N-terminal (N) domain of HGF was proposed on the basis of the clustering of surface positive charges [Zhou, H., Mazzulla, M. J., Kaufman, J. D., Stahl, S. J., Wingfield, P. T., Rubin, J. S., Bottaro, D. P., and Byrd, R. A. (1998) Structure 6, 109-116]. In the present study, we confirmed this binding site in a heparin titration experiment monitored by nuclear magnetic resonance spectroscopy, and we estimated the apparent dissociation constant (K(d)) of the heparin-protein complex by NMR and fluorescence techniques. The primary heparin-binding site is composed of Lys60, Lys62, and Arg73, with additional contributions from the adjacent Arg76, Lys78, and N-terminal basic residues. The K(d) of binding is in the micromolar range. A heparin disaccharide analogue, sucrose octasulfate, binds with similar affinity to the N domain and to a naturally occurring HGF isoform, NK1, at nearly the same region as in heparin binding. (15)N relaxation data indicate structural flexibility on a microsecond-to-millisecond time scale around the primary binding site in the N domain. This flexibility appears to be dramatically reduced by ligand binding. On the basis of the NK1 crystal structure, we propose a model in which heparin binds to the two primary binding sites and the N-terminal regions of the N domains and stabilizes an NK1 dimer

Weekly vs. Every-3-Week Paclitaxel and Carboplatin for Ovarian Cancer

BACKGROUND A dose-dense weekly schedule of paclitaxel (resulting in a greater frequency of drug delivery) plus carboplatin every 3 weeks or the addition of bevacizumab to paclitaxel and carboplatin administered every 3 weeks has shown efficacy in ovarian cancer. We proposed to determine whether dose-dense weekly paclitaxel and carboplatin would prolong progression-free survival as compared with paclitaxel and carboplatin administered every 3 weeks among patients receiving and those not receiving bevacizumab. METHODS We prospectively stratified patients according to whether they elected to receive bevacizumab and then randomly assigned them to receive either paclitaxel, administered intravenously at a dose of 175 mg per square meter of body-surface area every 3 weeks, plus carboplatin (dose equivalent to an area under the curve [AUC] of 6) for six cycles or paclitaxel, administered weekly at a dose of 80 mg per square meter, plus carboplatin (AUC, 6) for six cycles. The primary end point was progression-free survival. RESULTS A total of 692 patients were enrolled, 84% of whom opted to receive bevacizumab. In the intention-to-treat analysis, weekly paclitaxel was not associated with longer progression-free survival than paclitaxel administered every 3 weeks (14.7 months and 14.0 months, respectively; hazard ratio for disease progression or death, 0.89; 95% confidence interval [CI], 0.74 to 1.06; P=0.18). Among patients who did not receive bevacizumab, weekly paclitaxel was associated with progression-free survival that was 3.9 months longer than that observed with paclitaxel administered every 3 weeks (14.2 vs. 10.3 months; hazard ratio, 0.62; 95% CI, 0.40 to 0.95; P=0.03). However, among patients who received bevacizumab, weekly paclitaxel did not significantly prolong progression-free survival, as compared with paclitaxel administered every 3 weeks (14.9 months and 14.7 months, respectively; hazard ratio, 0.99; 95% CI, 0.83 to 1.20; P=0.60). A test for interaction that assessed homogeneity of the treatment effect showed a significant difference between treatment with bevacizumab and without bevacizumab (P=0.047). Patients who received weekly paclitaxel had a higher rate of grade 3 or 4 anemia than did those who received paclitaxel every 3 weeks (36% vs. 16%), as well as a higher rate of grade 2 to 4 sensory neuropathy (26% vs. 18%); however, they had a lower rate of grade 3 or 4 neutropenia (72% vs. 83%). CONCLUSIONS Overall, weekly paclitaxel, as compared with paclitaxel administered every 3 weeks, did not prolong progression-free survival among patients with ovarian cancer

Right coronary wall cmr in the older asymptomatic advance cohort: positive remodeling and associations with type 2 diabetes and coronary calcium

<p>Abstract</p> <p>Background</p> <p>Coronary wall cardiovascular magnetic resonance (CMR) is a promising noninvasive approach to assess subclinical atherosclerosis, but data are limited in subjects over 60 years old, who are at increased risk. The purpose of the study was to evaluate coronary wall CMR in an asymptomatic older cohort.</p> <p>Results</p> <p>Cross-sectional images of the proximal right coronary artery (RCA) were acquired using spiral black-blood coronary CMR (0.7 mm resolution) in 223 older, community-based patients without a history of cardiovascular disease (age 60-72 years old, 38% female). Coronary measurements (total vessel area, lumen area, wall area, and wall thickness) had small intra- and inter-observer variabilities (r = 0.93~0.99, all p < 0.0001), though one-third of these older subjects had suboptimal image quality. Increased coronary wall thickness correlated with increased coronary vessel area (p < 0.0001), consistent with positive remodeling. On multivariate analysis, type 2 diabetes was the only risk factor associated with increased coronary wall area and thickness (p = 0.03 and p = 0.007, respectively). Coronary wall CMR measures were also associated with coronary calcification (p = 0.01-0.03).</p> <p>Conclusions</p> <p>Right coronary wall CMR in asymptomatic older subjects showed increased coronary atherosclerosis in subjects with type 2 diabetes as well as coronary calcification. Coronary wall CMR may contribute to the noninvasive assessment of subclinical coronary atherosclerosis in older, at-risk patient groups.</p