Novel complexing agents for the efficient separation of actinides and remediation of actinide-contaminated sites

Research into the coordination chemistry of transactinide elements should provide us with new fundamental knowledge about structure, geometry, and stability of these metal complexes. Our approach involves the design, synthesis, and characterization of {open_quotes}expanded porphyrin{close_quotes} macrocyclic ligands which coordinate the actinide metal cations with high thermodynamic affinity and kinetic stability. We can use the knowledge from understanding the fundamental coordination chemistry of these elements as a stepping stone to heavy metal detoxification, radioactive waste cleanup, and possibly radioactive isotope separation. The critical components of this research endeavor, along with the viability of metal complex formation, will be correlated to ring size and core geometry of the ligand and, the atomic radius, oxidation state, coordination geometry and coordination number of the transactinium metal ion. These chelating agents may have certain applications to the solution of some radioactive waste problems if they can be attached to polymer supports and used to chemically separate the radioactive components in waste

Sex Affects Myocardial Blood Flow and Fatty Acid Substrate Metabolism in Humans with Nonischemic Heart Failure

In animal models of heart failure (HF), myocardial metabolism shifts from the normal preference for high-energy fatty acid (FA) metabolism towards the more efficient fuel, glucose. However, FA (vs. glucose) metabolism generates more ATP/mole; thus FA metabolism may be especially advantageous in HF. Sex modulates myocardial blood flow (MBF) and substrate metabolism in normal humans. Whether sex affects MBF and metabolism in patients with HF is unknown. We studied 19 well-matched men and women with nonischemic HF with similar ejection fractions (all ≤ 35%). MBF and myocardial substrate metabolism were quantified using positron emission tomography. Women had higher MBF (mL/g/min), FA uptake (mL/g/min), utilization (nmol/g/min) (P<0.005, <0.005, <0.05, respectively) and trended towards higher FA oxidation than men (P=0.09). These findings were independent of age, obesity, and insulin resistance. There were no sex-related differences in fasting myocardial glucose uptake or metabolism. In an exploratory analysis of the longitudinal follow-up of these subjects (mean 7 y), we found that 4 men had a major cardiovascular event, while one woman died of non-cardiac causes. Higher MBF related to improved event-free survival (HR=0.31, P=0.02). In sum, in nonischemic HF, women have higher MBF and FA uptake and metabolism than men, and these changes are not due to differences in other variables that can affect myocardial metabolism (e.g., age, obesity, or insulin resistance). Moreover, higher MBF portends a better prognosis. These sex-related differences should be taken into account in the development and targeting of novel agents aimed at modulating in MBF and metabolism in HF

Endovascular and Surgical Treatment of Unruptured MCA Aneurysms: Meta-Analysis and Review of the Literature

Introduction. The best treatment for unruptured middle cerebral artery (MCA) aneurysms is unclear. We perform a meta-analysis of recent publications to evaluate the results of unruptured MCA aneurysms treated with surgical clipping and endovascular coiling. Methods. A PubMed search for articles published between January 2004 and November 2013 was performed. The R statistical software package was used to create a random effects model for each desired incidence rate. Cochran&apos;s Q test was used to evaluate possible heterogeneity among the rates observed in each study. Results. A total of 1891 unruptured MCA aneurysms, 1052 clipped and 839 coiled, were included for analysis. The complete occlusion rate at 6-9 months mean follow-up was 95.5% in the clipped group and 67.8% in the coiled group ( &lt; 0.05). The periprocedural thromboembolism rate in the clipping group was 1.8% compared with 10.7% in the aneurysms treated by coiling ( &lt; 0.05). The recanalization rate was 0% for clipping and 14.3% for coiling ( = 0.05). Modified Rankin scores of 0-2 were obtained in 98.9% of clipped patients compared to 95.5% of coiled (NS). Conclusions. This review weakly supports clipping as the preferred treatment of unruptured MCA aneurysms. Clinical outcomes did not differ significantly between the two groups

Use of Quantitative Pharmacology in the Development of HAE1, a High-Affinity Anti-IgE Monoclonal Antibody

HAE1, a high-affinity anti-IgE monoclonal antibody, is discussed here as a case study in the use of quantitative pharmacology in the development of a second-generation molecule. In vitro, preclinical, and clinical data from the first-generation molecule, omalizumab, were heavily leveraged in the HAE1 program. A preliminary mechanism-based pharmacokinetic/pharmacodynamic (PK/PD) model for HAE1 was developed using an existing model for omalizumab, together with in vitro binding data for HAE1 and omalizumab. When phase I data were available, the model was refined by simultaneously modeling PK/PD data from omalizumab studies with the available HAE1 phase I data. The HAE1 clinical program was based on knowledge of the quantitative relationship between a pharmacodynamic biomarker, suppression of free IgE, and clinical response (e.g., lower exacerbation rates) obtained in pivotal studies with omalizumab. A clinical trial simulation platform was developed to predict free IgE levels and clinical responses following attainment of a target free IgE level (≤10 IU/ml). The simulation platform enabled selection of four doses for the phase II dose-ranging trial by two independent methods: dose-response non-linear fitting and linear mixed modeling. Agreement between the two methods provided confidence in the doses selected. Modeling and simulation played a large role in supporting acceleration of the HAE1 program by enabling data-driven decision-making, often based on confirmation of projections and/or learning from incoming new data

Wrist-Worn Wearables Based on Force Myography: On the Significance of User Anthropometry

Background Force myography (FMG) is a non-invasive technology used to track functional movements and hand gestures by sensing volumetric changes in the limbs caused by muscle contraction. Force transmission through tissue implies that differences in tissue mechanics and/or architecture might impact FMG signal acquisition and the accuracy of gesture classifier models. The aim of this study is to identify if and how user anthropometry affects the quality of FMG signal acquisition and the performance of machine learning models trained to classify different hand and wrist gestures based on that data. Methods Wrist and forearm anthropometric measures were collected from a total of 21 volunteers aged between 22 and 82 years old. Participants performed a set of tasks while wearing a custom-designed FMG band. Primary outcome measure was the Spearman’s correlation coefficient (R) between the anthropometric measures and FMG signal quality/ML model performance. Results Results demonstrated moderate (0.3&thinsp;≤|R|&thinsp;&lt;&thinsp;0.67) and strong (0.67&thinsp;≤&thinsp;|R|) relationships for ratio of skinfold thickness to forearm circumference, grip strength and ratio of wrist to forearm circumference. These anthropometric features contributed to 23–30% of the variability in FMG signal acquisition and as much as 50% of the variability in classification accuracy for single gestures. Conclusions Increased grip strength, larger forearm girth, and smaller skinfold-to-forearm circumference ratio improve signal quality and gesture classification accuracy