New Enantio- and Diastereoselective Carbon-Carbon Bond Forming Methodologies Utilizing 1,1-Organodiboronate Esters

I. Stereoselective Cu-Catalyzed Synthesis of 1,3-Hydroxyboronate Esters Employing 1,1-Diborylmethane A three component bis-electrophile coupling with 1,1-diborylmethane is reported. The reaction is stereoselective and proceeds through a Cu-catalyzed process. This methodology forms two carbon-carbon bonds, generates one new stereogenic center, and installs a stereodefined sp3 boronate ester for further functionalization, such as applications to bioactive molecule synthesis and for the construction of polyol scaffolds. II. Enantioselective Rh-Catalyzed Synthesis of 1,4-Ketoalkenylboronate Esters and 1,4-Diketones Utilizing 1,1-Diborylalkenes An enantioselective Rh-catalyzed conjugate addition of 1,1-diborylalkenes and α,β-unsaturated ketones is disclosed. This reaction forms one carbon-carbon bond, a stereogenic center, and an sp2 boronate ester. The substrate scope encompasses a variety of cyclic enones and 1,1-organodiboron reagents, and results in applications to 1,4-dicarbonyl synthesis as well as other transformations of the sp2 boronate ester moiety. Mechanistic studies via mass spectral analysis reveal a non-site selective transmetalation event. III. Diastereoselective Synthesis of 1,6-Ketoalkenylboronate Esters Containing a Quaternary Carbon Stereogenic Center via Conjugate Allylation of 1,1-Allyldiborons A method for the synthesis of 1,6-ketoalkenylboronate esters is described via CsF initiated diastereoselective conjugate allylation of 1,1-diborylallyls to α,β-unsaturated ketones is described. This process forms one now carbon-carbon bond, vicinal tertiary and quaternary all-carbon stereogenic centers, and an sp2 boronate ester. The substrate scope demonstrates compatibility with a range of α,β-unsaturated ketones and 1,1-diborylallyl reagents, with further transformations to demonstrate synthetic utility and applicability to the synthesis of stereochemically rich carbocycles. Mechanistic probes illuminate a proposed mechanism with potential for further reaction development. IV. Studies Toward Catalytic Enantioselective Conjugate Allylation of α,β-Unsaturated Ketones with γ,γ-Disubstituted Allyldiborons via Phase-Transfer Catalysis Studies toward the enantioselective conjugate allylation of α,β-unsaturated carbonyls with 1,1-diborylallyls are discussed. Multiple catalytic pathways are investigated, including counterion control, Lewis base activation, cation sequestration, and phase-transfer catalysis strategies. Phase-transfer catalysts and noncanonical activators were synthesized and investigated in the proposed reaction. Nascent enantioenrichment and regioselectivity obtained through these studies lay a roadmap for further development of this reaction.Doctor of Philosoph

Prevalence and incidence of diagnosed hypertension in Alberta, Canada

Introduction The prevalence of diagnosed hypertension in Canada is projected to increase despite the incidence rate decreasing. Previous work around the world has utilized survey data to provide estimates of prevalence and incidence. Administrative data is population-level, and may provide more reliable estimates of provincial prevalence and incidence than could be achieved using survey data.  Objectives and Approach • To produce age and sex-specific prevalence and incidence estimates of diagnosed hypertension in Alberta from 2007 to 2015, • To project estimates to the fiscal year of 2019/2020. Data from the Discharge Abstract Database, physician claims database, National Ambulatory Care Reporting System, and provincial health insurance registry will be linked using unique anonymous personal identifier and gender. A validated case definition of diagnosed hypertension for use in administrative datasets will be used to identify annual prevalent and incident cases from claims data. Obstetric cases will be excluded. The provincial health insurance registry will be used to estimate denominator values. Results Results of this analysis are not available for the time of abstract submission as the timeline for this analysis projects completion in April 2018. Conclusion/Implications Maintained surveillance of diagnosed hypertension is important to inform health policy and spending decisions, to monitor efficacy of public health interventions, and to inform patient care. Furthermore, diagnosis guidelines have been updated since 2017. Providing estimates for the prevalence of diagnosed hypertension in Alberta five years into the future to compare to actual prevalence estimates may indicate whether changes in prevalence are due to actual changes in health status or to changes in diagnosis guidelines

Improving the Coding Completeness of Hypertension in Inpatient Administrative Health Data Using Machine Learning Methods

Introduction The Discharge Abstract Database (DAD) associates ICD-10-CA diagnosis codes with inpatient care episodes at acute-care facilities. Codes are assigned by human coders, based on chart review. Coding guidelines stipulate mandatory coding of major and fatal conditions but only optional coding of secondary conditions, which results in undercoding for many conditions. Objectives and Approach This research evaluates machine learning approaches for identifying and completing records with missing codes, to improve data quality. The Alberta Hospital DAD for 2013-14 was used in this study. We assumed that the existing ICD-10-CA codes in the DAD are correct, and used them as training examples. Several ML classifiers, including logistic regression and random forest, were used to develop models to assess the coding probability, using existing codes and demographic information. 3300 chart-review records were used as the reference standard. We focused on hypertension-related codes. Validity of raw diagnosis codes in the DAD was used as the baseline. Results A record is deemed to have a missing hypertension diagnosis code if the predicted probability is high, but without the diagnosis codes having been assigned by the coders. In the baseline, the original hypertension codes have high PPV (ranging from 0.902 for the age group 35-54 to 1.000 for the age group 18-34) but low sensitivity (ranging from 0.200 for the age group 18-34 to 0.565 for the age group 75+). The most successful models that we have tested so far have provided improvements of 2-6% in the sensitivity, while maintaining the PPV. More improvement is generally seen for the younger age groups. Initial experiments indicate greater improvements in sensitivity may be possible for other conditions, such as peptic ulcer disease and cerebrovascular disease. Conclusion/Implications Machine learning approaches can be useful and cost-effective for improving data quality in DAD. While the improvements in sensitivity relative to the baseline are modest at present, further experiments with different models and feature sets are warranted. Experiments with other conditions may also be fruitful

Liquid metal embrittlement of a dual-phase Al0.7CoCrFeNi high-entropy alloy exposed to oxygen-saturated lead-bismuth eutectic

This paper reports a new liquid metal embrittlement (LME) system in which a dual-phase Al0.7CoCrFeNi (equimolar fraction) high-entropy alloy (HEA) is embrittled by lead-bismuth eutectic (LBE) at 350 and 500°C. At 350°C, (Ni, Al)-rich BCC phase is embrittled, leading to intragrain cracking within this phase, while the predominant cracking mode changes to BCC/FCC phase boundary decohesion at 500°C. At both temperatures, cracks are rarely seen in the (Co, Cr, Fe)-rich FCC phase, indicating that this phase is immune to LME. Furthermore, the results suggest a transition from an adsorption-dominated LME mechanism at 350°C to a phase boundary wetting-dominated LME mechanism at 500°C

Patient-Reported Outcomes Improves the Prediction of In-patient and Emergency Department Readmission Risks in Coronary Artery Disease

Introduction Coronary Artery Disease (CAD) patients are known to report higher healthcare resource use, such as inpatient [IP] and emergency department [ED] readmissions, than the general population. We investigate if the patient reported outcome measures (PROMs) improve the accuracy of readmissions risk prediction models in CAD. Objectives and Approach Patients enrolled in the Alberta Provincial Project for Outcomes Assessment in Coronary Heart Disease (APPROACH) registry between 1995 and 2014 who received catheterization (CATH) and completed baseline PROMs were linked to discharge abstract data and national ambulatory data. Logistic regression (LR) was used to develop 30-day and 1-year readmissions risk prediction models adjusting for patients’ demographic, clinical, and self-reported characteristics. PROM was measured using the 19-item Seattle Angina Questionnaire (SAQ). The discriminatory performance of each prediction model was assessed using the Harrel’s c-statistic for LR. Results Of the 13,264 patients who completed baseline SAQ, 59 (0.3%) had IP readmissions or ED visits within 30 days, and up to 356 (1.9%) within 1 year of baseline survey. The C-statistics for one-year readmissions risk prediction models that only adjusted for demographic and clinical variables only ranged between 56.4% and 61.2%. The prognostic improvement in the discrimination of these models ranged between 2% to 10% when patient-reported SAQ was included as predictor. The addition of SAQ improves the model discrimination in all types of admission. Conclusion/Implications The addition of PROMs improves the moderate accuracy of readmissions risk prediction models. These findings highlight the need for routine collection of PROMs in clinical settings and their potential use for aiding clinical and policy decision-making and post-discharge outcomes monitoring in the management of cardiovascular diseases

Immune Protection Induced on Day 10 Following Administration of the 2009 A/H1N1 Pandemic Influenza Vaccine

BACKGROUND: The 2009 swine-origin influenza virus (S-OIV) H1N1 pandemic has caused more than 18,000 deaths worldwide. Vaccines against the 2009 A/H1N1 influenza virus are useful for preventing infection and controlling the pandemic. The kinetics of the immune response following vaccination with the 2009 A/H1N1 influenza vaccine need further investigation. METHODOLOGY/PRINCIPAL FINDINGS: 58 volunteers were vaccinated with a 2009 A/H1N1 pandemic influenza monovalent split-virus vaccine (15 µg, single-dose). The sera were collected before Day 0 (pre-vaccination) and on Days 3, 5, 10, 14, 21, 30, 45 and 60 post vaccination. Specific antibody responses induced by the vaccination were analyzed using hemagglutination inhibition (HI) assay and enzyme-linked immunosorbent assay (ELISA). After administration of the 2009 A/H1N1 influenza vaccine, specific and protective antibody response with a major subtype of IgG was sufficiently developed as early as Day 10 (seroprotection rate: 93%). This specific antibody response could maintain for at least 60 days without significant reduction. Antibody response induced by the 2009 A/H1N1 influenza vaccine could not render protection against seasonal H1N1 influenza (seroconversion rate: 3% on Day 21). However, volunteers with higher pre-existing seasonal influenza antibody levels (pre-vaccination HI titer ≥1∶40, Group 1) more easily developed a strong antibody protection effect against the 2009 A/H1N1 influenza vaccine as compared with those showing lower pre-existing seasonal influenza antibody levels (pre-vaccination HI titer <1∶40, Group 2). The titer of the specific antibody against the 2009 A/H1N1 influenza was much higher in Group 1 (geometric mean titer: 146 on Day 21) than that in Group 2 (geometric mean titer: 70 on Day 21). CONCLUSIONS/SIGNIFICANCE: Recipients could gain sufficient protection as early as 10 days after vaccine administration. The protection could last at least 60 days. Individuals with a stronger pre-existing seasonal influenza antibody response may have a relatively higher potential for developing a stronger humoral immune response after vaccination with the 2009 A/H1N1 pandemic influenza vaccine

Precise Measurements of Branching Fractions for Ds+D_s^+ Meson Decays to Two Pseudoscalar Mesons

We measure the branching fractions for seven $D_{s}^{+}$ two-body decays to pseudo-scalar mesons, by analyzing data collected at $\sqrt{s}=4.178\sim4.226$ GeV with the BESIII detector at the BEPCII collider. The branching fractions are determined to be $\mathcal{B}(D_s^+\to K^+\eta^{\prime})=(2.68\pm0.17\pm0.17\pm0.08)\times10^{-3}$, $\mathcal{B}(D_s^+\to\eta^{\prime}\pi^+)=(37.8\pm0.4\pm2.1\pm1.2)\times10^{-3}$, $\mathcal{B}(D_s^+\to K^+\eta)=(1.62\pm0.10\pm0.03\pm0.05)\times10^{-3}$, $\mathcal{B}(D_s^+\to\eta\pi^+)=(17.41\pm0.18\pm0.27\pm0.54)\times10^{-3}$, $\mathcal{B}(D_s^+\to K^+K_S^0)=(15.02\pm0.10\pm0.27\pm0.47)\times10^{-3}$, $\mathcal{B}(D_s^+\to K_S^0\pi^+)=(1.109\pm0.034\pm0.023\pm0.035)\times10^{-3}$, $\mathcal{B}(D_s^+\to K^+\pi^0)=(0.748\pm0.049\pm0.018\pm0.023)\times10^{-3}$, where the first uncertainties are statistical, the second are systematic, and the third are from external input branching fraction of the normalization mode $D_s^+\to K^+K^-\pi^+$. Precision of our measurements is significantly improved compared with that of the current world average values

Spatially different responses of nitrogen processing to precipitation during glacial-interglacial cycles on the Chinese Loess Plateau

Terrestrial nitrogen (N) cycling is closely associated with precipitation and crucial to ecosystem, which has been receiving great concerns at the backdrop of global climate change. In addition to modern investigations, paleo record of N cycling may provide valuable clues about how ecosystem N responds to climate change. Here we measured soil organic nitrogen (TON) and its isotope value (delta N-15(org)) in two loess-paleosol sequences (LPS), i.e. the Yuanbao (YB) and Luochuan (LC) sequences, on the Chinese Loess Plateau (CLP) accumulated during the glacial-interglacial cycles. Both sequences showed higher magnetic susceptibility in paleosol and lower in loess, but with overall higher values in the wetter site of LC, suggesting higher precipitation during warm periods for both sites, as well as higher precipitation at site LC than at site YB. TON increased with increase of paleo-precipitation in both sequences, but the fraction of microbial derived ON, estimated from (C/N)(org), increased faster than plant-derived ON at site YB but slower at site LC. delta N-15(org) was used to estimate microbial mediated gaseous N loss, showing greater losses at higher paleo-precipitation at site YB and a reverse trend at site LC. Thereby, both (C/N)(org) and delta N-15(org) suggest a quicker response of microbes than plants to precipitation at the drier site YB but conversely at the wetter site LC. Such a spatially different responses of nitrogen processing to precipitation would be a reference for projection of future terrestrial ecosystem response to climate change