ALBERT

Beschreibung: Journal of Physical Oceanography, Ahead of Print. 〈br/〉

Beschreibung: The relationship between net mixing and the estuarine exchange flow may be quantified using a salinity variance budget. Here “mixing” is defined as the rate of destruction of volume-integrated salinity variance, and the exchange flow is quantified using the total exchange flow. These concepts are explored using an idealized 3D model estuary. It is shown that in steady state (e.g., averaging over the spring–neap cycle) the volume-integrated mixing is approximately given by Mixing ≅ SinSoutQr, where Sin and Sout are the representative salinities of in- and outflowing layers at the mouth and Qr is the river volume flux. This relationship provides an extension of the familiar Knudsen relation, in which the exchange flow is diagnosed based on knowledge of these same three quantities, quantitatively linking mixing to the exchange flow.

Beschreibung: The roles of straining and dissipation in controlling stratification are derived analytically using a vertical salinity variance method. Stratification is produced by converting horizontal variance to vertical variance via straining, that is, differential advection of horizontal salinity gradients, and stratification is destroyed by the dissipation of vertical variance through turbulent mixing. A numerical model is applied to the Changjiang estuary in order to demonstrate the salinity variance balance and how it reveals the factors controlling stratification. The variance analysis reveals that dissipation reaches its maximum during spring tide in the Changjiang estuary, leading to the lowest stratification. Stratification increases from spring tide to neap tide because of the increasing excess of straining over dissipation. Throughout the spring–neap tidal cycle, straining is almost always larger than dissipation, indicating a net excess of production of vertical variance relative to dissipation. This excess is balanced on average by advection, which exports vertical variance out of the estuarine region into the plume. During neap tide, tidal straining shows a general tendency of destratification during the flood tide and restratification during ebb, consistent with the one-dimensional theory of tidal straining. During spring tide, however, positive straining occurs during flood because of the strong baroclinicity induced by the intensified horizontal salinity gradient. These results indicate that the salinity variance method provides a valuable approach for examining the spatial and temporal variability of stratification in estuaries and coastal environments.

Beschreibung: Observations and analyses of two tidally recurring, oblique, internal hydraulic jumps at a stratified estuary mouth (Columbia River, Oregon/Washington) are presented. These hydraulic features have not previously been studied due to the challenges of both horizontally resolving the sharp gradients and temporally resolving their evolution in numerical models and traditional observation platforms. The jumps, both of which recurred during ebb, formed adjacent to two engineered lateral channel constrictions and were identified in marine radar image time series. Jump occurrence was corroborated by (i) a collocated sharp gradient in the surface currents measured via airborne along-track interferometric synthetic aperture radar and (ii) the transition from supercritical to subcritical flow in the cross-jump direction via shipborne velocity and density measurements. Using a two-layer approximation, observed jump angles at both lateral constrictions are shown to lie within the theoretical bounds given by the critical internal long-wave (Froude) angle and the arrested maximum-amplitude internal bore angle, respectively. Also, intratidal and intertidal variability of the jump angles are shown to be consistent with that expected from the two-layer model, applied to varying stratification and current speed over a range of tidal and river discharge conditions. Intratidal variability of the upchannel jump angle is similar under all observed conditions, whereas the downchannel jump angle shows an additional association with stratification and ebb velocity during the low discharge periods. The observations additionally indicate that the upchannel jump achieves a stable position that is collocated with a similarly oblique bathymetric slope.

Beschreibung: High-resolution observations of velocity, salinity, and turbulence quantities were collected in a salt wedge estuary to quantify the efficiency of stratified mixing in a high-energy environment. During the ebb tide, a midwater column layer of strong shear and stratification developed, exhibiting near-critical gradient Richardson numbers and turbulent kinetic energy (TKE) dissipation rates greater than 10−4 m2 s−3, based on inertial subrange spectra. Collocated estimates of scalar variance dissipation from microconductivity sensors were used to estimate buoyancy flux and the flux Richardson number Rif. The majority of the samples were outside the boundary layer, based on the ratio of Ozmidov and boundary length scales, and had a mean Rif = 0.23 ± 0.01 (dissipation flux coefficient Γ = 0.30 ± 0.02) and a median gradient Richardson number Rig = 0.25. The boundary-influenced subset of the data had decreased efficiency, with Rif = 0.17 ± 0.02 (Γ = 0.20 ± 0.03) and median Rig = 0.16. The relationship between Rif and Rig was consistent with a turbulent Prandtl number of 1. Acoustic backscatter imagery revealed coherent braids in the mixing layer during the early ebb and a transition to more homogeneous turbulence in the midebb. A temporal trend in efficiency was also visible, with higher efficiency in the early ebb and lower efficiency in the late ebb when the bottom boundary layer had greater influence on the flow. These findings show that mixing efficiency of turbulence in a continuously forced, energetic, free shear layer can be significantly greater than the broadly cited upper bound from Osborn of 0.15–0.17.

Beschreibung: The linkage among total exchange flow, entrainment, and diffusive salt flux in estuaries is derived analytically using salinity coordinates, revealing the simple but important relationship between total exchange flow and mixing. Mixing is defined and quantified in this paper as the dissipation of salinity variance. The method uses the conservation of volume and salt to quantify and distinguish the diahaline transport of volume (i.e., entrainment) and diahaline diffusive salt flux. A numerical model of the Hudson estuary is used as an example of the application of the method in a realistic estuary with a persistent but temporally variable exchange flow. A notable finding of this analysis is that the total exchange flow and diahaline salt flux are out of phase with respect to the spring–neap cycle. Total exchange flow reaches its maximum near minimum neap tide, but diahaline salt transport reaches its maximum during the maximum spring tide. This phase shift explains the strong temporal variation of stratification and estuarine salt content through the spring–neap cycle. In addition to quantifying temporal variation, the method reveals the spatial variation of total exchange flow, entrainment, and diffusive salt flux through the estuary. For instance, the analysis of the Hudson estuary indicates that diffusive salt flux is intensified in the wider cross sections. The method also provides a simple means of quantifying numerical mixing in ocean models because it provides an estimate of the total dissipation of salinity variance, which is the sum of mixing due to the turbulence closure and numerical mixing.

Beschreibung: In this study, we investigate the skills of the regional climate model Consortium for Small-Scale Modeling in Climate Mode (CCLM) in reproducing historical climatic features and their added value to the driving global climate models (GCMs) of the Coordinated Regional Climate Downscaling Experiment—East Asia (CORDEX-EA) domain. An ensemble of climate simulations, with a resolution of 0.44°, was conducted by downscaling four GCMs: CNRM-CM5, EC-EARTH, HadGEM2, and MPI-ESM-LR. The CCLM outputs were compared with different observations and reanalysis datasets. Results showed strong seasonal variability of CCLM’s ability in reproducing climatological means, variability, and extremes. The bias of the simulated summer temperatures is generally smaller than that of the winter temperatures; in addition, areas where CCLM adds value to the driving GCMs in simulating temperature are larger in the winter than in the summer. CCLM outperforms GCMs in terms of generating climatological precipitation means and daily precipitation distributions for most regions in the winter, but this is not always the case for the summer. It was found that CCLM biases are partly inherited from GCMs and are significantly shaped by structural biases of CCLM. Furthermore, downscaled simulations show added value in capturing features of consecutive wet days for the tropics and of consecutive dry days for areas to the north of 30°N. We found considerable uncertainty from reanalysis and observation datasets in temperatures and precipitation climatological means for some regions that rival bias values of GCMs and CCLM simulations. We recommend carefully selecting reference datasets when evaluating modeled climate means.

Beschreibung: Salinity variance dissipation is related to exchange flow through the salinity variance balance equation, and meanwhile its magnitude is also proportional to the turbulence production and stratification inside the estuary. As river flow increases, estuarine volume-integrated salinity variance dissipation increases owing to more variance input from the open boundaries driven by exchange flow and river flow. This corresponds to the increased efficient conversion of turbulence production to salinity variance dissipation due to the intensified stratification with higher river flow. Through the spring–neap cycle, the temporal variation of salinity variance dissipation is more dependent on stratification than turbulence production, so it reaches its maximum during the transition from neap to spring tides. During most of the transition time from spring to neap tides, the advective input of salinity variance from the open boundaries is larger than dissipation, resulting in the net increase of variance, which is mainly expressed as vertical variance, that is, stratification. The intensified stratification in turn increases salinity variance dissipation. During neap tides, a large amount of enhanced salinity variance dissipation is induced by the internal shear stress near the halocline. During most of the transition time from neap to spring tides, dissipation becomes larger than the advective input, so salinity variance decreases and the stratification is destroyed.

Beschreibung: BACKGROUND: Symptom burden in essential thrombocythemia (ET) and polycythemia vera (PV) is severe even among individuals with low risk disease (Blood 2012. 12;123(24):3803-10). New therapies exist which alleviate the severe symptom burden and reduce splenomegaly in ET and PV patients (N Engl J Med 2015; 372:426-435). This analysis is the first to date to evaluate thresholds at which symptom-based treatment can be considered for ET and PV patients who are intolerant or resistant to hydroxyurea (HU). METHODS: Patient demographics, symptom burden, and disease traits were collected from ET and PV patients at a single time point during therapy. The MPN-10 total symptom score (TSS, JCO 2012;30(33)4098-103) was utilized to assess symptom burden. Symptom criteria models were determined as previously described among a population of MF patients (Scherber et. al. EHA 2016: a2250). Cutoffs were then evaluated in a cohort of ET and PV patients to assess for utility as a symptom model among this population. RESULTS: Demographics and symptom burden: 838 PV and 867 ET patients with previous hydroxyurea therapy were included in this analysis. Patients were of mean age (54.9 years ET, 64.0 years PV) and gender (69.2% female ET, 55.7% female). Mean disease duration was 6.0 years for ET and 7.3 years for PV.Among ET and PV patients, 15.0% and 24.2% had prior thrombosis respectively. In evaluating prognostic risk, ET patients tended to be low (45.5%) or intermediate risk (42.9%) with only a minority of patient meeting criteria forhigh risk disease (11.6%). Laboratory findings: ET patients had a mean platelet value of 598.7x 109/L(SD=283.4). Among PV patients, mean hematocrit was 45.8% (SD=8.1) and 42.6% of patients had a hematocrit of greater than 45%. White blood cell count was normal between the two groups (ET mean 8.3 x 109/L, PV mean 9.0 x 109/L). Symptoms: Mean worst symptom severity was 6.4 out of 10 (SD=2.7). Among ET patients, worst symptom was most frequently fatigue (32.7%, mean 5.0/10, SD=3.1, overall prevalence 88%) followed by night sweats (13.6%, mean 2.0/10, SD=3.0, overall prevalence 53%) and concentration difficulties (8.6%, mean 3.1/10, SD=3.0, overall prevalence 68%). For PV, worst individual symptom items were most frequently fatigue (29.2%, mean 5.2/10, SD=3.0, overall prevalence 91%), pruritus (14.1%, mean 3.2/10, SD=3.2, overall prevalence 69%), and night sweats (12.8%, mean 2.5/10, SD=3.0, overall prevalence 57%). Cutoff Scoring: 47.0% of ET patients fit criteria for TSSgreater than to equal to 20; 59.0%% had a single itemgreater than 5; and 45.7% had both a TSS greater than or equal to 20 and a single item greater than 5. Among PV participants, 54.5% had aTSS greater than to equal to 20; 66.1% had a single itemgreater than 5; and 51.5% had both a TSS greater than or equal to 20 and a single item greater than 5. Each scoring method was significantly associated with individual item scores (Table 1). Prognostic scoring was not significantly associated with any of the symptom cutoffs evaluated. Correlations: Among ET patients, a prior history of thrombosis was significantly associated with having a worst symptom item greater than 5 (p=0.043). ET patients with lower hemoglobin were significantly more likely to meet criteria for a MPN-10 score greater than or equal to 20 or to meet combined criteria for a MPN-10 greater than or equal to 20 and single worst item greater than 5 (for both p=0.01 or less). For PV, lower hematocrit levels were significantly associated with having an individual worst symptom score of greater than 5 (44.9% versus 46.7%, p=0.0376). CONCLUSION: Assessment of ET and PV symptoms, now measurable through standardized and practical instruments such as the MPN-10, is an integral part of determining therapeutic impact of newer therapies in both clinical practice and trial settings. In our modeling, patients with severe symptom burden profiles are well represented by utilizing cutoff criteria including aworst individual symptom item of greater than 5 out of 10, an MPN-10 score of greater than or equal to 20, or combined criteria of both cutoffs. These cutoffs can be considered when determiningwhich HU intolerant or resistant patients would most benefit fromsymptom orientedtreatment. Disclosures Kiladjian: AOP Orphan: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Research Funding. Schouten:Novartis: Consultancy; Sanofi: Consultancy. Etienne:BMS: Speakers Bureau; ARIAD: Speakers Bureau; Pfizer: Speakers Bureau; novartis: Consultancy, Speakers Bureau. Harrison:Incyte Corporation: Honoraria, Speakers Bureau; Shire: Honoraria, Speakers Bureau; Gilead: Honoraria, Speakers Bureau; Baxaltra: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Other: travel, accommodations, expenses, Research Funding, Speakers Bureau. Radia:Pfizer: Honoraria; Novartis: Honoraria. Cervantes:AOP Orphan: Membership on an entity's Board of Directors or advisory committees; Baxalta: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Vannucchi:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Mesa:Promedior: Research Funding; Celgene: Research Funding; CTI: Research Funding; Gilead: Research Funding; Incyte: Research Funding; Galena: Consultancy; Ariad: Consultancy; Novartis: Consultancy.

Beschreibung: Abstract 44 CALGB (now part of the Alliance for Clinical Trials in Oncology) performed a non-randomized phase II study testing one year (yr) of investigational maintenance therapy with decitabine for newly diagnosed adult AML patients (pts) 1 × 109/L, platelets 〉75 × 109/L, and be within 90 days after day 1 of the final consolidation. Decitabine 20mg/m2 was given IV over 1 hour for 4–5 days, every 6 weeks, for 8 cycles. 546 pts enrolled with a median age of 48 yrs (range, 17–60) and median presenting white blood count (WBC) of 12.6 × 109/L (range, 0.3–380 × 109/L). 75% achieved CR (412/546). Reasons for CR pts not receiving maintenance were mainly early relapse, alloHCT in 1st CR, inadequate count recovery, and patient refusal (Blum et al. ASH 2011). 33% of CR pts (134/412) received investigational maintenance. Of these, 46 (34%) were favorable risk; among the remaining 88 pts, 73 were consolidated with autoHCT, and 15 received HiDAC-based consolidation. The median time from initial study registration to initiation of maintenance therapy was 6.3 months. Pts receiving decitabine had a median age of 45 yrs (range, 18–60) and presenting WBC of 13.5 × 109/L (range, 0.4–221 × 109/L). Treatment with decitabine maintenance was feasible and reasonably well tolerated; the primary toxicity was myelosuppression. Preplanned dose reduction criteria for neutropenia were met after the first 20 pts had been treated. After this early timepoint, all subsequent pts who had been consolidated with autoHCT received only 4 days of decitabine per cycle (HiDAC consolidated pts continued to receive 5 days per cycle). The median number of cycles of decitabine received was 7 (range, 1–8); 46% of pts (62/134) received all 8 cycles, and 75% completed at least 4 cycles. Reasons for discontinuation of decitabine before completing 8 cycles included relapse (28%, 38/134), pt refusal (13%), adverse events (4%), and others. In this selected cohort of pts who received post-CR maintenance with decitabine, 1-yr and 3-yr overall survival (OS) were 96% and 66%; 1-yr and 3-yr disease-free survival (DFS) were 80% and 53%. 1-yr “failure-free survival” calculated from the time of registration to decitabine was 68% (70% for favorable risk, 68% for others). These results are similar to the outcomes for comparable pts enrolled on our prior CALGB study 19808 who received identical chemotherapy for induction and consolidation and then were randomized to observation or maintenance with interleukin-2 (3-yr OS 61% and 68%, 3-yr DFS 45% and 56%, for observation and IL-2 respectively). Post-consolidation maintenance with decitabine appears to provide only modest, if any, benefit overall. Correlative studies for CALGB 10503 are ongoing, including investigations into the impact of decitabine in unique molecular and cytogenetic subsets of disease, the prognostic/predictive value of aberrant methylation and other molecular markers, and assessment of minimal residual disease. Supported by CA33601 and CA128377. Disclosures: No relevant conflicts of interest to declare.