Isotopic variations of meltwater from ice by isotopic exchange between liquid water and ice

Predicting the isotopic modification of ice by melting processes is important for improving the accuracy in paleoclimate reconstruction. To this end, we present results from cold room laboratory observations of changes in the isotopic ratio (D/H and 18O/16O) of ice cubes by isotopic exchange between liquid water and ice in nearly isothermal conditions. A 1-D model was fit to the isotopic results by adjusting the values of two parameters, the isotopic exchange rate constant (kr) and the fraction of ice participating in the exchange (f). We found that the rate constant for hydrogen isotopic exchange between liquid water and ice may be greater (up to 40%) than that for the oxygen isotopic exchange. The range of the rate constant obtained from four melt experiments is from 0.21 to 0.82 h–1. The model results also suggest that f decreases with the increasing wetness of the ice. This is because with increasing water saturation in ice, water may be present only in the small pores or some of the water that was exchanged with ice may be bypassed, decreasing the effective surface area over which the isotopic exchange can occur. The relationship between the two water isotopes (δ18O vs δD) was observed and modeled and the slope was <8, which is significantly different from the slope of the meteoric waterline. We note that these slopes were obtained without considering the sublimation process.

Prognostic Significance Of Parameters Of Dynamic Contrast-Enhanced MRI Detecting Increased Bone Marrow Microcirculation In Monoclonal Plasma Cell Disorders

Introduction Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) is a non-invasive imaging technique allowing the detection of changes in local microcirculation reflecting increased angiogenesis. DCE-MRI parameters Amplitude A (reflecting blood volume) and exchange rate constant kep (reflecting vascular permeability) are increased in bone marrow exams of patients with active multiple myeloma (MM) compared to healthy controls. In the current prospective study we analyzed the prognostic significance of the DCE-MRI parameters in 289 patients with monoclonal plasma cell disorders and 33 healthy controls. Methods The patient group consisted of 68 individuals with monoclonal gammopathy of undetermined significance (MGUS), 90 patients with smoldering MM (sMM) and 131 patients with symptomatic MM according to IMWG criteria. All patients and controls underwent standardized DCE-MRI with high temporal resolution (T1w-turboFLASH) of the lumbar spine (symptomatic patients before start of therapy). Regions of interest were drawn manually on T1-weighted images encompassing the bone marrow of each of the 5 lumbar vertebrae sparing the vertebral vessel. Values of the DCE-MRI parameters of the 5 lumbar vertebrae were summarized per patient in median values. Log transformation was used for median kep values. Results Significant differences in Amplitude A were found between sMM and controls (P=0.004), sMM and MGUS (P=0.01), and MM and all other groups (P<0.001 respectively). For exchange rate constant kep differences were significant between sMM and controls (P=0.01), sMM and MGUS (P=0.01) and MM and all other groups (P<0.001 respectively). P-values were adjusted for multiple testing by Holm's method. Comparison of DCE-MRI- and clinical parameters revealed a significant positive correlation of Amplitude A with beta2-microglobulin (P<0.001), high risk cytogenetics (P=0.009), immunoparesis (P<0.001) and a negative correlation with albumin, hemoglobin and age (P<0.001, respectively). For exchange rate constant kep the following significant correlation were found: positive correlation with beta2-microglobulin (P<0.001), LDH (P=0.03), immunoparesis (P<0.001) and negative correlation with albumin (P=0.03), hemoglobin (P<0.001) and age (P=0.03). Application of univariate and multivariate Cox models revealed a significant prognostic impact for median of DCE-MRI parameter Amplitude A for progression free survival of patients with MGUS (univariate P=0.02), sMM (univariate P=0.002; multivariate P=0.03) and for overall survival of MM patients (multivariate P=0.05). Log transformed arameter kep showed prognostic significance for PFS of MM patients (univariate P=0.04). The multivariate Cox model was adjusted for the following additional factors: plasma cells in bone marrow, M-Protein, IgG-subtype, presence of immunoparesis and age. M-protein (P=0.004), age (P=0.03) and a non-IgG-type (P=0.006) also were revealed as significant prognostic factors. Conclusion DCE-MRI is a non-invasive imaging tool delivering parameters on bone marrow microcirculation which are correlated to clinical markers of disease activity as well stage of disease. In all groups of patients especially DCE-MRI parameter Amplitude A is of significant prognostic value for progression free and in symptomatic patients also for overall survival. Disclosures: No relevant conflicts of interest to declare.

Electron transfer in non-oxovanadium(IV) and (V) complexes: Kinetic studies of an amavadin model

Electron-transfer reactions of the eight-coordinate vanadium complex, bis-(N-hydroxyiminodiacetate)vanadium(IV) [V(HIDA)2]2–, a synthetic analog of amavadin with ascorbic acid and hexachloroiridate(IV), have been studied. The self-exchange rate constant for this analog has been calculated from oxidation and reduction cross-reactions using Marcus theory and directly measured using 51V NMR paramagnetic line-broadening techniques. The average self-exchange rate constant for the bis-HIDA vanadium(IV/V) couple equals 1.5 × 105 M–1 s–1. The observed rate enhancements are proposed to be due to the small structural differences between the oxidized and reduced forms of the HIDA complex and inner-sphere reorganizational energies. The electron-transfer reaction of this synthetic analog is experimentally indistinguishable from amavadin itself, although significant differences exist in the reduction potential of these compounds. This suggests that ligand modification effects the thermodynamic driving force and not the self-exchange process.

Dynamic Contrast-Enhanced MRI Identifies a Distinct Group of Asymptomatic Myeloma Patients with Increased Bone Marrow Microcirculation.

Introduction: Dynamic contrast enhanced MRI (dceMRI) is an imaging technique detecting changes in local microcirculation reflecting increased angiogenesis. The dceMRI parameters Amplitude A and exchange rate constant kep have been shown to be significantly increased in patients with active multiple myeloma (MM) compared to healthy controls and to correlate with osteolytic bone involvement and prognosis. We now compared the parameters and infiltration patterns of dceMRI in patients with monoclonal gammopathy of undetermined significance (MGUS) as well as in patients with asymptomatic MM not requiring chemotherapy (NRC-group) with those in patients with symptomatic MM requiring chemotherapy according to international standards. Methods: The NRC group contained 71 patients: 29 patients with MGUS, 39 patients with MM stage I and 3 patients with MM stage IIA according to Durie and Salmon. 24 patients had a diagnosis of a MM in stage II in progression (n = 3) or stage III (n = 21). All patients underwent standardized dceMRI with high temporal resolution (T1w-turboFLASH) of the lumbar spine before start of therapy. Color coded pharmacokinetic maps of imaged area were classified according to three distinct patterns of microcirculation: “normal” (as in healthy controls), “diffuse” or “focal”. The contrast uptake was quantified using a two compartment model with the output parameters Amplitude A and distribution constant rate kep reflecting bone marrow microcirculation. Results: 63 % of patients in the NRC group were found to have changes in the microcirculation pattern with 26 patients (37%) displaying a normal, 43 (60%) a diffuse and 2 (3%) a focal pattern. Within the NRC group 11 MGUS patients (38%) were found to have a normal pattern, 17 patients (59%) had a diffuse and 1 patient (3%) presented with a focal pattern. 79 % of patients with symptomatic MM had an abnormal microcirculation pattern with 5 (21%) MM patients showing a normal, 12 (50%) a diffuse and 7 (29%) a focal pattern. Statistical comparison did not reveal a significant difference in the total incidence between NRC and symptomatic MM group. Comparison of quantitative microcirculation parameters did not show a significant difference of Amplitude A (p=0.87) and exchange rate constant kep (p=0.3) in MGUS patients compared to patients with asymptomatic MM. Comparing the NRC group with the symptomatic myeloma group revealed a significant higher Amplitude A in the symptomatic MM group (p=0.01). There was no significant difference in exchange rate constant kep. Conclusion: Our investigations revealed a group of patients with asymptomatic myeloma and MGUS that display significant increase in bone marrow microcirculation. Our findings could be the basis for stratified treatment of patients with novel therapeutics targeting the vascular system. Prognostic implications for systemic and local development of the malignant disease are topic of current investigations.