Supporting Information from Leveraging genome-wide datasets to quantify the functional role of the anti-Shine–Dalgarno sequence in regulating translation efficiency

10 total supplementary figures that support and extend the results from the Main Tex

Validation of a tool for estimating clinician recognition of ARDS using data from the international LUNG SAFE study.

Under-recognition of acute respiratory distress syndrome (ARDS) by clinicians is an important barrier to adoption of evidence-based practices such as low tidal volume ventilation. The burden created by the COVID-19 pandemic makes it even more critical to develop scalable data-driven tools to improve ARDS recognition. The objective of this study was to validate a tool for accurately estimating clinician ARDS recognition rates using discrete clinical characteristics easily available in electronic health records. We conducted a secondary analysis of 2,705 ARDS and 1,261 non-ARDS hypoxemic patients in the international LUNG SAFE cohort. The primary outcome was validation of a tool that estimates clinician ARDS recognition rates from health record data. Secondary outcomes included the relative impact of clinical characteristics on tidal volume delivery and clinician documentation of ARDS. In both ARDS and non-ARDS patients, greater height was associated with lower standardized tidal volume (mL/kg PBW) (ARDS: adjusted β = -4.1, 95% CI -4.5 --3.6; non-ARDS: β = -7.7, 95% CI -8.8 --6.7, P<0.00009 [where α = 0.01/111 with the Bonferroni correction]). Standardized tidal volume has already been normalized for patient height, and furthermore, height was not associated with clinician documentation of ARDS. Worsening hypoxemia was associated with both increased clinician documentation of ARDS (β = -0.074, 95% CI -0.093 --0.056, P<0.00009) and lower standardized tidal volume (β = 1.3, 95% CI 0.94-1.6, P<0.00009) in ARDS patients. Increasing chest imaging opacities, plateau pressure, and clinician documentation of ARDS also were associated with lower tidal volume in ARDS patients. Our EHR-based data-driven approach using height, gender, ARDS documentation, and lowest standardized tidal volume yielded estimates of clinician ARDS recognition rates of 54% for mild, 63% for moderate, and 73% for severe ARDS. Our tool replicated clinician-reported ARDS recognition in the LUNG SAFE study, enabling the identification of ARDS patients at high risk of being unrecognized. Our approach can be generalized to other conditions for which there is a need to increase adoption of evidence-based care

Adoption of a High-Impact Innovation in a Homogeneous Population

Adoption of innovations, whether new ideas, technologies, or products, is crucially important to knowledge societies. The landmark studies of adoption dealt with innovations having great societal impact (such as antibiotics or hybrid crops) but where determining the utility of the innovation was straightforward (such as fewer side effects or greater yield). Recent large-scale studies of adoption were conducted within heterogeneous populations and focused on products with little societal impact. Here, we focus on a case with great practical significance: adoption by small groups of highly trained individuals of innovations with large societal impact but for which it is impractical to determine the true utility of the innovation. Specifically, we study experimentally the adoption by critical care physicians of a diagnostic assay that complements current protocols for the diagnosis of life-threatening bacterial infections and for which a physician cannot estimate the true accuracy of the assay based on personal experience. We show through computational modeling of the experiment that infection-spreading models—which have been formalized as generalized contagion processes—are not consistent with the experimental data, while a model inspired by opinion models is able to reproduce the empirical data. Our modeling approach enables us to investigate the efficacy of different intervention schemes on the rate and robustness of innovation adoption in the real world. While our study is focused on critical care physicians, our findings have implications for other settings in education, research, and business, where small groups of highly qualified peers make decisions about the adoption of innovations whose utility is difficult if not impossible to gauge

A quantitative approach for the analysis of clinician recognition of acute respiratory distress syndrome using electronic health record data - data repository

ImportanceDespite its efficacy, low tidal volume ventilation (LTVV) remains severely underutilized for patients with acute respiratory distress syndrome (ARDS). Physician under-recognition of ARDS is a significant barrier to LTVV use. We propose a computational method that addresses some of the limitations of the current approaches to automated measurement of whether ARDS is recognized by physicians.ObjectiveTo quantify patient and physician factors affecting physicians' tidal volume selection and to build a computational model of physician recognition of ARDS that accounts for these factors.Design, setting, and participantsIn this cross-sectional study, electronic health record data were collected for 361 ARDS patients and 388 non-ARDS hypoxemic (control) patients in nine adult intensive care units at four hospitals between June 24 and December 31, 2013.MethodsStandardized tidal volumes (mL/kg predicted body weight) were chosen as a proxy for physician decision-making behavior. Using data-science approaches, we quantified the effect of eight factors (six severity of illness, two physician behaviors) on selected standardized tidal volumes in ARDS and control patients. Significant factors were incorporated in computational behavioral models of physician recognition of ARDS.ResultsHypoxemia severity and ARDS documentation in physicians' notes were associated with lower standardized tidal volumes in the ARDS cohort. Greater patient height was associated with lower standardized tidal volumes (which is already normalized for height) in both ARDS and control patients. The recognition model yielded a mean (99% confidence interval) physician recognition of ARDS of 22% (9%-42%) for mild, 34% (19%-49%) for moderate, and 67% (41%-100%) for severe ARDS.Conclusions and relevanceIn this study, patient characteristics and physician behaviors were demonstrated to be associated with differences in ventilator management in both ARDS and control patients. Our model of physician ARDS recognition measurement accounts for these clinical variables, providing an electronic approach that moves beyond relying on chart documentation or resource intensive approaches

A quantitative approach for the analysis of clinician recognition of acute respiratory distress syndrome using electronic health record data.

ImportanceDespite its efficacy, low tidal volume ventilation (LTVV) remains severely underutilized for patients with acute respiratory distress syndrome (ARDS). Physician under-recognition of ARDS is a significant barrier to LTVV use. We propose a computational method that addresses some of the limitations of the current approaches to automated measurement of whether ARDS is recognized by physicians.ObjectiveTo quantify patient and physician factors affecting physicians' tidal volume selection and to build a computational model of physician recognition of ARDS that accounts for these factors.Design, setting, and participantsIn this cross-sectional study, electronic health record data were collected for 361 ARDS patients and 388 non-ARDS hypoxemic (control) patients in nine adult intensive care units at four hospitals between June 24 and December 31, 2013.MethodsStandardized tidal volumes (mL/kg predicted body weight) were chosen as a proxy for physician decision-making behavior. Using data-science approaches, we quantified the effect of eight factors (six severity of illness, two physician behaviors) on selected standardized tidal volumes in ARDS and control patients. Significant factors were incorporated in computational behavioral models of physician recognition of ARDS.ResultsHypoxemia severity and ARDS documentation in physicians' notes were associated with lower standardized tidal volumes in the ARDS cohort. Greater patient height was associated with lower standardized tidal volumes (which is already normalized for height) in both ARDS and control patients. The recognition model yielded a mean (99% confidence interval) physician recognition of ARDS of 22% (9%-42%) for mild, 34% (19%-49%) for moderate, and 67% (41%-100%) for severe ARDS.Conclusions and relevanceIn this study, patient characteristics and physician behaviors were demonstrated to be associated with differences in ventilator management in both ARDS and control patients. Our model of physician ARDS recognition measurement accounts for these clinical variables, providing an electronic approach that moves beyond relying on chart documentation or resource intensive approaches

Engraved portrait of Carleton, Dudley, Viscount Dorchester (1574–1632)

Line engraving of Carleton, Dudley, Viscount Dorchester (1574–1632), diplomat and letter write

Phytochemical investigation of the leaves of tetracera scandens Linn and in vitro antidiabetic activity of hypoletin

Tetracera scandens Linn. (Dilleniaceae), locally known as Mempelas Kasar, is traditionally used in folk remedies by various indigenous people in different countries including Malaysia for the treatment of rheumatism, inflammatory diseases, hepatitis, internal pains, urinary disorders, dysentery, sore throat, gout and diabetes infirmities; for lowering hypertension; and for child birth. In this study, phytochemical analysis of T. scandens leaf methanol (MeOH) extract was carried out for the first time and afforded three terpenoids (stigmasterol, betulinic acid and an isomeric mixture of sitosterol (∆5) glycoside and stigmasterol (∆5,22) glycoside) and six flavonoids (namely, kaempferol, quercetin, isoscutellarein, hypoletin, astragalin and kaempferol-3-O-(6″-O-p-trans-coumaroyl) glucoside, a rare compound which has been isolated for the first time from family Dilleniaceae). Structures of all compounds were elucidated through extensive UV–Vis, mass, IR and NMR spectral analysis. The occurrence of all these compounds is being reported for the first time from this plant. Due to the rare occurrence of hypoletin (3′,4′,5,7,8-pentahydroxyflavone) in plants, its in vitro antidiabetic effect was explored. Hence, the treatment of hypoletin in a dose-dependent manner was examined on the induction of lipid accumulation by using Oil Red O staining and glucose regulation in 3T3-L1 adipocytes in vitro with regard to its preventive role in the management of diabetes. After 8 days, morphological changes and high lipid accumulation activity were observed in cells treated with 10 μg/mL of hypoletin concentration (P < 0.01). In addition, the intracellular fat accumulation increased by up to 79.7 % relative to MDI-treated control cells at a dose of 10 μg/mL. Furthermore, insulin-induced 2-deoxy-d-[3H] glucose uptake was significantly increased (P < 0.001) in hypoletin-treated cells as compared to control (DMSO cells). Our results suggest that hypoletin could be useful for the management of type 2 diabetes due to its adipocyte stimulation and glucose uptake activity