Separation, for Analytical Purpose, of Np Traces from different Solutions of Fuel Reprocessing

AbstractFour separation methods were developed for performance control of hydrometallurgical extraction processes as COEX™ or advanced PUREX. These methods used implemented the operations of radionuclides oxidation state adjustment and chromatographic separation using TEVA resin. Concerning FP raffinate, the method consisted in reducing Np traces to the valence IV by a mixture of ferrous sulfamate and ascorbic acid, to fix Np(IV) on “TEVA” resin and to eluate it by a nitrohydrofluoric acid solution. The Np recovery yield is 100%. The decontamination of Np is sufficiently high to allow its analysis by FXL (Zr/Np < 1). The study also showed that in presence of Zr and Tc, Pu behaved like Np. The mixture of ferrous sulfamate and ascorbic acid had surprisingly no action on Pu(IV). Concerning plutonium solution ([Pu] > 10g/L) and uranium solution ([U] > 100g/L), the same method used for Np recovery from FP raffinate led to an eluate containing 100% of the initial Np ([Np]: 10mg/L). The low concentration of U and Pu (< 100mg/L) allows the determination of Np by FXL. Concerning Pu(III)-U(IV) solution, the method, included 2 redox stages, the first one to oxidize all actinides to oxidation state VI et the second one to reduce Np and Pu respectively to IV and III oxidation state. Then Np(IV) was fixed on TEVA resin. The eluate contains 100% of the initial Np ([Np]: 10mg/L) and a low concentration of U and Pu ([U] < 20mg/L, [Pu] < 10mg/L). The next experiments will consist in consolidating these good results by working with real solutions of fuel reprocessing

Methods to Develop an Electronic Medical Record Phenotype Algorithm to Compare the Risk of Coronary Artery Disease across 3 Chronic Disease Cohorts

Background Typically, algorithms to classify phenotypes using electronic medical record (EMR) data were developed to perform well in a specific patient population. There is increasing interest in analyses which can allow study of a specific outcome across different diseases. Such a study in the EMR would require an algorithm that can be applied across different patient populations. Our objectives were: (1) to develop an algorithm that would enable the study of coronary artery disease (CAD) across diverse patient populations; (2) to study the impact of adding narrative data extracted using natural language processing (NLP) in the algorithm. Additionally, we demonstrate how to implement CAD algorithm to compare risk across 3 chronic diseases in a preliminary study. Methods and Results We studied 3 established EMR based patient cohorts: diabetes mellitus (DM, n = 65,099), inflammatory bowel disease (IBD, n = 10,974), and rheumatoid arthritis (RA, n = 4,453) from two large academic centers. We developed a CAD algorithm using NLP in addition to structured data (e.g. ICD9 codes) in the RA cohort and validated it in the DM and IBD cohorts. The CAD algorithm using NLP in addition to structured data achieved specificity >95% with a positive predictive value (PPV) 90% in the training (RA) and validation sets (IBD and DM). The addition of NLP data improved the sensitivity for all cohorts, classifying an additional 17% of CAD subjects in IBD and 10% in DM while maintaining PPV of 90%. The algorithm classified 16,488 DM (26.1%), 457 IBD (4.2%), and 245 RA (5.0%) with CAD. In a cross-sectional analysis, CAD risk was 63% lower in RA and 68% lower in IBD compared to DM (p<0.0001) after adjusting for traditional cardiovascular risk factors. Conclusions We developed and validated a CAD algorithm that performed well across diverse patient populations. The addition of NLP into the CAD algorithm improved the sensitivity of the algorithm, particularly in cohorts where the prevalence of CAD was low. Preliminary data suggest that CAD risk was significantly lower in RA and IBD compared to DM.National Institutes of Health (U.S.). Informatics for Integrating Biology and the Bedside Project (U54LM008748

The emerging landscape of health research based on biobanks linked to electronic health records: Existing resources, statistical challenges, and potential opportunities

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154448/1/sim8445_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154448/2/sim8445.pd

Chemotherapy effectiveness in trial-underrepresented groups with early breast cancer:A retrospective cohort study

BACKGROUND: Adjuvant chemotherapy in early stage breast cancer has been shown to reduce mortality in a large meta-analysis of over 100 randomised trials. However, these trials largely excluded patients aged 70 years and over or with higher levels of comorbidity. There is therefore uncertainty about whether the effectiveness of adjuvant chemotherapy generalises to these groups, hindering patient and clinician decision-making. This study utilises administrative healthcare data-real world data (RWD)-and econometric methods for causal analysis to estimate treatment effectiveness in these trial-underrepresented groups. METHODS AND FINDINGS: Women with early breast cancer aged 70 years and over and those under 70 years with a high level of comorbidity were identified and their records extracted from Scottish Cancer Registry (2001-2015) data linked to other routine health records. A high level of comorbidity was defined as scoring 1 or more on the Charlson comorbidity index, being in the top decile of inpatient stays, and/or having 5 or more visits to specific outpatient clinics, all within the 5 years preceding breast cancer diagnosis. Propensity score matching (PSM) and instrumental variable (IV) analysis, previously identified as feasible and valid in this setting, were used in conjunction with Cox regression to estimate hazard ratios for death from breast cancer and death from all causes. The analysis adjusts for age, clinical prognostic factors, and socioeconomic deprivation; the IV method may also adjust for unmeasured confounding factors. Cohorts of 9,653 and 7,965 were identified for women aged 70 years and over and those with high comorbidity, respectively. In the ≥70/high comorbidity cohorts, median follow-up was 5.17/6.53 years and there were 1,935/740 deaths from breast cancer. For women aged 70 years and over, the PSM-estimated HR was 0.73 (95% CI 0.64-0.95), while for women with high comorbidity it was 0.67 (95% CI 0.51-0.86). This translates to a mean predicted benefit in terms of overall survival at 10 years of approximately3% (percentage points) and 4%, respectively. A limitation of this analysis is that use of observational data means uncertainty remains both from sampling uncertainty and from potential bias from residual confounding. CONCLUSIONS: The results of this study, as RWD, should be interpreted with caution and in the context of existing and emerging randomised data. The relative effectiveness of adjuvant chemotherapy in reducing mortality in patients with early stage breast cancer appears to be generalisable to the selected trial-underrepresented groups.</p

Track D Social Science, Human Rights and Political Science

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138414/1/jia218442.pd

Using Ancillary Sociodemographic Data to Identify Sexual Minority Adults among Those Responding “Something Else” or “Don’t Know” to Sexual Orientation Questions

Background: General population surveys are increasingly offering broader response options for questions on sexual orientation—e.g., not only gay or lesbian, but also “something else” (SE) and “don’t know” (DK). However, these additional response options are potentially confusing for those who may not know what the terms mean. Researchers studying sexual orientation-based disparities face difficult methodological trade-offs regarding how best to classify respondents identifying with the SE and DK categories. Objectives: Develop respondent-level probabilities of sexual minority orientation without excluding or misclassifying the potentially ambiguous SE and DK responses. Compare three increasingly-inclusive analytic approaches for estimating health disparities using a single item: (a) omitting SE and DK respondents; (b) classifying SE as sexual minority and omitting DK; and (c) a new approach classifying only SE and DK respondents with >50% predicted probabilities of being sexual minorities as sexual minority. Methods: We used the sociodemographic information and follow-up questions for SE and DK respondents in the 2013-2014 NHIS to generate predicted probabilities of identifying as a sexual minority adult. Results: 94% of the 144 SE respondents and 20% of the 310 DK respondents were predicted to identify as a sexual minority adult, with higher probabilities for younger, wealthier, non-Hispanic white, and urban-dwelling respondents. Using a more specific definition of sexual minority orientation improved the precision of health and healthcare disparity estimates. Conclusions: Predicted probabilities of sexual minority orientation may be used in this and other surveys potentially to improve representation and categorization of those who identify as a sexual minority adult

Introduction of constrained Trp analogs in RW9 modulates structure and partition in membrane models

Over the past decades, many cell-penetrating peptides (CPP) have been studied for their capacity to cross cellular membranes, mostly in order to improve cellular uptake of therapeutic agents. Even though hydrophobic and anionic CPPs have been described, many of them are polycationic, due to the presence of several arginine (Arg) residues. Noteworthy, however, the presence of aromatic amino acids such as tryptophan (Trp) within CPPs seems to play an important role to reach high membranotropic activity. RW9 (RRWWRRWRR) is a designed CPP derived from the polyarginine R9 presenting both features. In general, when interacting with membranes, CPPs adopt an optimal conformation for membrane interactions – an amphipathic helical secondary structure in the case of RW9. Herein, we assumed that the incorporation of a locally constrained amino acid in the peptide sequence could improve the membranotropic activity of RW9, by facilitating its structuration upon contact with a membrane, while leaving a certain plasticity. Therefore, two cyclized Trp derivatives (Tcc and Aia) were synthesized to be incorporated in RW9 as surrogates of Trp residues. Thus, a series of peptides containing these building blocks has been synthesized by varying the type, position, and number of modifications. The membranotropic activity of the RW9 analogs was studied by spectrofluorescence titration of the peptides in presence of liposomes (DMPG), allowing to calculate partition coefficients (Kp). Our results indicate that the partitioning of the modified peptides depends on the type, the number and the position of the modification, with the best sequence being [Aia4]RW9. Interestingly, both NMR analysis and molecular dynamic (MD) simulations indicate that this analog presents an extended conformation similar to the native RW9, but with a much-reduced structural flexibility. Finally, cell internalization properties were also confirmed by confocal microscopy

Care integration within and outside health system boundaries

Objective: Examine care integration—efforts to unify disparate parts of health care organizations to generate synergy across activities occurring within and between them—to understand whether and at which organizational level health systems impact care quality and staff experience. Data Sources: Surveys administered to one practice manager (56/59) and up to 26 staff (828/1360) in 59 practice sites within 24 physician organizations within 17 health systems in four states (2017-2019). Study Design: We developed manager and staff surveys to collect data on organizational, social, and clinical process integration, at four organizational levels: practice site, physician organization, health system, and outside health systems. We analyzed data using descriptive statistics and regression. Principal Findings: Managers and staff perceived opportunity for improvement across most types of care integration and organizational levels. Managers/staff perceived little variation in care integration across health systems. They perceived better care integration within practice sites than within physician organizations, health systems, and outside health systems—up to 38 percentage points (pp) lower (P <.001) outside health systems compared to within practice sites. Of nine clinical process integration measures, one standard deviation (SD) (7.2-pp) increase in use of evidence-based care related to 6.4-pp and 8.9-pp increases in perceived quality of care by practice sites and health systems, respectively, and a 4.5-pp increase in staff job satisfaction; one SD (9.7-pp) increase in integration of social services and community resources related to a 7.0-pp increase in perceived quality of care by health systems; one SD (6.9-pp) increase in patient engagement related to a 6.4-pp increase in job satisfaction and a 4.6-pp decrease in burnout; and one SD (10.6-pp) increase in integration of diabetic eye examinations related to a 5.5-pp increase in job satisfaction (all P <.05). Conclusions: Measures of clinical process integration related to higher staff ratings of quality and experience. Action is needed to improve care integration within and outside health systems