60 research outputs found
An experimental investigation of the aerodynamic characteristics of slanted base ogive cylinders using magnetic suspension technology
An experimental investigation is reported on slanted base ogive cylinders at zero incidence. The Mach number range is 0.05 to 0.3. All flow disturbances associated with wind tunnel supports are eliminated in this investigation by magnetically suspending the wind tunnel models. The sudden and drastic changes in the lift, pitching moment, and drag for a slight change in base slant angle are reported. Flow visualization with liquid crystals and oil is used to observe base flow patterns, which are responsible for the sudden changes in aerodynamic characteristics. Hysteretic effects in base flow pattern changes are present in this investigation and are reported. The effect of a wire support attachment on the 0 deg slanted base model is studied. Computational drag and transition location results using VSAERO and SANDRAG are presented and compared with experimental results. Base pressure measurements over the slanted bases are made with an onboard pressure transducer using remote data telemetry
A Multivariate Analysis of Two Types of Conformity Behaviors
A review of research concerning conformity behaviors revealed a need for large sample, multivariate approaches. To that end, seventeen variables were utilized (birth order, chronological agev sex, race, IQ, socioeconomic status, geographic area uf residencer religion, anxiety, dogmatism, rigidity, acquiescence, ego strength, confidence, extroversion/ introversion, impulsivity, and neuroticism) to describe the behaviors of 104 subjects in a Tuddenham-type setting wherein the subjects were randomly assigned to either Asch-type (group pressure) or Crutchfield-type (expert pressure) treatment conditions. Utilizing a stepwise multiple discriminant function analysis, discriminant weights were derived. The variable of rigidity was not found to be a valid predictor. With the discriminant weights and the sixteen predictive second-order variables, 218 subjects were randomly assigned to treatment conditions end their conforming or not-conforming behaviors were predicted. The data of eleven subjects who correctly perceived the contrived nature of the exper\u27iment were· not included. Of the 123 subjects subjected to expert pressure, 85 were not-conformers. Chi-Square analysis of the expert pressure data yields c significant difference at the . 20 Level of Confidence. Of the 95 subjects subjected to group pressure, 45 were conformers and 50 were not-conformers. Chi-Square was not significant.. Conformers to expert pressure were correctly identified 74 per cent of the time; conformers to grcup pressure were correctly identified 62 per cent of the time. Thus, it appears that conforming behaviors are predictable providing a multivariate method is used conjointly with a discriminant function analysis of the data. The most difficult behavior to correctly predict is not-conforming to expert pressure, 11 with but 32 per cent correct. Too, but 40 per cent of the not-conforming to group pressure 11 was correct! y p;edi cted. Conformers to 11expert pressure were seen as typically being first-born, 20.8 year old Caucasian males or females with an IQ of 114. Their parents were high school graduates or above, and were either professional persons, business proprietors, or managers, etcetera. Their geographic area of residence was Rural East North Central United States, but this finding may be due to sampling error. Protestants were more frequently observed (n = 54) than Roman Catholics (n = 28). The conformers were slightly above average in anxiety and dogmatism. Average acquiescence 1 ego strength, and confidence were noted. low impulsivity was seen, and they were slightly extroverted. As a group, they were more neurotic than an average subject. Not-con formers to expert pressure were seen as first-born 21.5 year old Caucasian maler. with an IQ of 119. No clear socioeconomic status was noted due to extreme scatter. The geographic area of residence was Rural East North Central United States. They were predominantly Prctestant subjects. They were less anxious than conforn.ers, less dogmatic, and less acquiescent. They did not differ significantly in ego strength, confidence or impulsivity. However, they were more introverted and decidedly less neurotic than their conformer counterpart. Conformers to group pressure were equally likely to be either a first or second-born 21 year old male or female Caucasian Protestant with an IQ of 116. They were more anxious than an average subject. Dogmatism, acquiescence, ego strength, neuroticism, and extroversion/introversion were average. As a group, they were slightly more confident. Subjects who were not-conformers to group pressure were seen as secondborn 21.5 year old females with an IQ of 116. Two-thirds of these subjects were Protestant; one-third were Roman Catholic. No obvious socioeconomic status could be ascertained. They were less anxious than conformers to group pressure. No significant differences were noted in dogmatism, acquiescence, ego strength, confidence, impulsivity or extroversion/introversion. They were less neurotic than their conformer counterpart
Boundary Layer influences on the Subsonic Near-Wake of a Family of Three-Dimensional Bluff Bodies
A study is reported on subsonic bluff body near-wake flows. It has been determined that one family of bluff bodies, namely slanted-base ogive cylinders, can experience either a closed recirculating near-wake, or a longitudinal vortex near-wake depending on the base slant-angle and the Reynolds number. This suggests a dependence of near-wake parameters on the state of the boundary layer ahead of separation. This report addresses the influence of the boundary layer on the near-wake of slanted-base bluff bodies. Experiments were conducted in two facilities, the 6-inch Magnetic Suspension and Balance System (MSBS) at NASA Langley Research Center and the Old Dominion University low-speed wind tunnel. Interference-free drag measurements in the 6-inch MSBS validated previous drag results. Measurements in the ODU facility were made to determine base pressures, wake stagnation point locations, and boundary layer velocity profiles. Furthermore, spectral and cross-spectral analyses of the fluctuating streamwise velocity in the near-wake were performed to determine frequencies and coherence of large-scale structures. It was determined that despite variations in the boundary layer state, base pressures and wake stagnation point locations correlate with the Reynolds number based on the boundary layer momentum thickness as the independent variable. Variations in the frequency and coherence of large-scale structures were shown to exist with fixed boundary layer transition. A two-dimensional representation of a slanted-base configuration was studied analytically using classical theories and computationally using an existing finite element package. This study confirmed that the sudden changeover in wake structure is a result of flow reattachment onto the slanted-base
Subsonic sting interference on the aerodynamic characteristics of a family of slanted-base ogive-cylinders
Support interference free drag, lift, and pitching moment measurements on a range of slanted base ogive cylinders were made using the NASA Langley 13 inch magnetic suspension and balance system. Typical test Mach numbers were in the range 0.04 to 0.2. Drag results are shown to be in broad agreement with previous tests with this configuration. Measurements were repeated with a dummy sting support installed in the wind tunnel. Significant support interferences were found at all test conditions and are quantified. Further comparison is made between interference free base pressures, obtained using remote telemetry, and sting cavity pressures
HIV infection and cardiovascular disease in women
Background HIV infection is associated with increased risk of cardiovascular disease (CVD) in men. Whether HIV is an independent risk factor for CVD in women has not yet been established. Methods and Results We analyzed data from the Veterans Aging Cohort Study on 2187 women (32% HIV infected [HIV+]) who were free of CVD at baseline. Participants were followed from their first clinical encounter on or after April 01, 2003 until a CVD event, death, or the last follow‐up date (December 31, 2009). The primary outcome was CVD (acute myocardial infarction [AMI], unstable angina, ischemic stroke, and heart failure). CVD events were defined using clinical data, International Classification of Diseases, Ninth Revision, Clinical Modification codes, and/or death certificate data. We used Cox proportional hazards models to assess the association between HIV and incident CVD, adjusting for age, race/ethnicity, lipids, smoking, blood pressure, diabetes, renal disease, obesity, hepatitis C, and substance use/abuse. Median follow‐up time was 6.0 years. Mean age at baseline of HIV+ and HIV uninfected (HIV−) women was 44.0 versus 43.2 years (PP=0.11). There were 86 incident CVD events (53%, HIV+): AMI, 13%; unstable angina, 8%; ischemic stroke, 22%; and heart failure, 57%. Incident CVD/1000 person‐years was significantly higher among HIV+ (13.5; 95% confidence interval [CI]=10.1, 18.1) than HIV−women (5.3; 95% CI=3.9, 7.3; P+ women had an increased risk of CVD, compared to HIV− (hazard ratio=2.8; 95% CI=1.7, 4.6; P\u3c0.001). Conclusions HIV is associated with an increased risk of CVD in women
Jun N-terminal kinase 1 regulates epithelial-to-mesenchymal transition induced by TGF-beta1
Transforming growth factor beta1 (TGF-beta1) is a cardinal cytokine in the pathogenesis of airway remodeling, and promotes epithelial-to-mesenchymal transition (EMT). As a molecular interaction between TGF-beta1 and Jun N-terminal kinase (JNK) has been demonstrated, the goal of this study was to elucidate whether JNK plays a role in TGF-beta1-induced EMT. Primary cultures of mouse tracheal epithelial cells (MTEC) from wild-type, JNK1-/- or JNK2-/- mice were comparatively evaluated for their ability to undergo EMT in response to TGF-beta1. Wild-type MTEC exposed to TGF-beta1 demonstrated a prominent induction of mesenchymal mediators and a loss of epithelial markers, in conjunction with a loss of trans-epithelial resistance (TER). Significantly, TGF-beta1-mediated EMT was markedly blunted in epithelial cells lacking JNK1, while JNK2-/- MTEC underwent EMT in response to TGF-beta1 in a similar way to wild-type cells. Although Smad2/3 phosphorylation and nuclear localization of Smad4 were similar in JNK1-/- MTEC in response to TGF-beta1, Smad DNA-binding activity was diminished. Gene expression profiling demonstrated a global suppression of TGF-beta1-modulated genes, including regulators of EMT in JNK1-/- MTEC, in comparison with wild-type cells. In aggregate, these results illuminate the novel role of airway epithelial-dependent JNK1 activation in EMT
Pharmacogenomics driven decision support prototype with machine learning: A framework for improving patient care
Introduction: A growing number of healthcare providers make complex treatment decisions guided by electronic health record (EHR) software interfaces. Many interfaces integrate multiple sources of data (e.g., labs, pharmacy, diagnoses) successfully, though relatively few have incorporated genetic data.
Method: This study utilizes informatics methods with predictive modeling to create and validate algorithms to enable informed pharmacogenomic decision-making at the point of care in near real-time. The proposed framework integrates EHR and genetic data relevant to the patient's current medications including decision support mechanisms based on predictive modeling. We created a prototype with EHR and linked genetic data from the Department of Veterans Affairs (VA), the largest integrated healthcare system in the US. The EHR data included diagnoses, medication fills, and outpatient clinic visits for 2,600 people with HIV and matched uninfected controls linked to prototypic genetic data (variations in single or multiple positions in the DNA sequence). We then mapped the medications that patients were prescribed to medications defined in the drug-gene interaction mapping of the Clinical Pharmacogenomics Implementation Consortium's (CPIC) level A (i.e., sufficient evidence for at least one prescribing action) guidelines that predict adverse events. CPIC is a National Institute of Health funded group of experts who develop evidence based pharmacogenomic guidelines. Preventable adverse events (PAE) can be defined as a harmful outcome from an intervention that could have been prevented. For this study, we focused on potential PAEs resulting from a medication-gene interaction.
Results: The final model showed AUC scores of 0.972 with an F1 score of 0.97 with genetic data as compared to 0.766 and 0.73 respectively, without genetic data integration.
Discussion: Over 98% of people in the cohort were on at least one medication with CPIC level a guideline in their lifetime. We compared predictive power of machine learning models to detect a PAE between five modeling methods: Random Forest, Support Vector Machine (SVM), Extreme Gradient Boosting (XGBoost), K Nearest neighbors (KNN), and Decision Tree. We found that XGBoost performed best for the prototype when genetic data was added to the framework and improved prediction of PAE. We compared area under the curve (AUC) between the models in the testing dataset
HIV Infection and the Risk of World Health Organization-Defined Sudden Cardiac Death
Background
People living with HIV have higher sudden cardiac death (SCD) rates compared with the general population. Whether HIV infection is an independent SCD risk factor is unclear.
Methods and Results
This study evaluated participants from the Veterans Aging Cohort Study, an observational, longitudinal cohort of veterans with and without HIV infection matched 1:2 on age, sex, race/ethnicity, and clinical site. Baseline for this study was a participant\u27s first clinical visit on or after April 1, 2003. Participants were followed through December 31, 2014. Using Cox proportional hazards regression, we assessed whether HIV infection, CD4 cell counts, and/or HIV viral load were associated with World Health Organization (WHO)–defined SCD risk. Among 144 336 participants (30% people living with HIV), the mean (SD) baseline age was 50.0 years (10.6 years), 97% were men, and 47% were of Black race. During follow‐up (median, 9.0 years), 3035 SCDs occurred. HIV infection was associated with increased SCD risk (hazard ratio [HR], 1.14; 95% CI, 1.04–1.25), adjusting for possible confounders. In analyses with time‐varying CD4 and HIV viral load, people living with HIV with CD4 counts \u3c 200 cells/mm3 (HR, 1.57; 95% CI, 1.28–1.92) or viral load \u3e 500 copies/mL (HR, 1.70; 95% CI, 1.46–1.98) had increased SCD risk versus veterans without HIV. In contrast, people living with HIV who had CD4 cell counts \u3e 500 cells/mm3 (HR, 1.03; 95% CI, 0.90–1.18) or HIV viral load \u3c 500 copies/mL (HR, 0.97; 95% CI, 0.87–1.09) were not at increased SCD risk.
Conclusions
HIV infection is associated with increased risk of WHO‐defined SCD among those with elevated HIV viral load or low CD4 cell counts
Early initiation of prophylactic anticoagulation for prevention of coronavirus disease 2019 mortality in patients admitted to hospital in the United States: cohort study.
OBJECTIVE: To evaluate whether early initiation of prophylactic anticoagulation compared with no anticoagulation was associated with decreased risk of death among patients admitted to hospital with coronavirus disease 2019 (covid-19) in the United States. DESIGN: Observational cohort study. SETTING: Nationwide cohort of patients receiving care in the Department of Veterans Affairs, a large integrated national healthcare system. PARTICIPANTS: All 4297 patients admitted to hospital from 1 March to 31 July 2020 with laboratory confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and without a history of anticoagulation. MAIN OUTCOME MEASURES: The main outcome was 30 day mortality. Secondary outcomes were inpatient mortality, initiating therapeutic anticoagulation (a proxy for clinical deterioration, including thromboembolic events), and bleeding that required transfusion. RESULTS: Of 4297 patients admitted to hospital with covid-19, 3627 (84.4%) received prophylactic anticoagulation within 24 hours of admission. More than 99% (n=3600) of treated patients received subcutaneous heparin or enoxaparin. 622 deaths occurred within 30 days of hospital admission, 513 among those who received prophylactic anticoagulation. Most deaths (510/622, 82%) occurred during hospital stay. Using inverse probability of treatment weighted analyses, the cumulative incidence of mortality at 30 days was 14.3% (95% confidence interval 13.1% to 15.5%) among those who received prophylactic anticoagulation and 18.7% (15.1% to 22.9%) among those who did not. Compared with patients who did not receive prophylactic anticoagulation, those who did had a 27% decreased risk for 30 day mortality (hazard ratio 0.73, 95% confidence interval 0.66 to 0.81). Similar associations were found for inpatient mortality and initiation of therapeutic anticoagulation. Receipt of prophylactic anticoagulation was not associated with increased risk of bleeding that required transfusion (hazard ratio 0.87, 0.71 to 1.05). Quantitative bias analysis showed that results were robust to unmeasured confounding (e-value lower 95% confidence interval 1.77 for 30 day mortality). Results persisted in several sensitivity analyses. CONCLUSIONS: Early initiation of prophylactic anticoagulation compared with no anticoagulation among patients admitted to hospital with covid-19 was associated with a decreased risk of 30 day mortality and no increased risk of serious bleeding events. These findings provide strong real world evidence to support guidelines recommending the use of prophylactic anticoagulation as initial treatment for patients with covid-19 on hospital admission
Early initiation of prophylactic anticoagulation for prevention of COVID-19 mortality: a nationwide cohort study of hospitalized patients in the United States.
Importance: Deaths among patients with coronavirus disease 2019 (COVID-19) are partially attributed to venous thromboembolism and arterial thromboses. Anticoagulants prevent thrombosis formation, possess anti-inflammatory and anti-viral properties, and may be particularly effective for treating patients with COVID-19. Objective: To evaluate whether initiation of prophylactic anticoagulation within 24 hours of admission is associated with decreased risk of death among patients hospitalized with COVID-19. Design: Observational cohort study. Setting: Nationwide cohort of patients receiving care in the Department of Veterans Affairs, the largest integrated healthcare system in the United States. Participants: All patients hospitalized with laboratory-confirmed SARS-CoV-2 infection March 1 to July 31, 2020, without a history of therapeutic anticoagulation. Exposures: Prophylactic doses of subcutaneous heparin, low-molecular-weight heparin, or direct oral anticoagulants. Main Outcomes and Measures: 30-day mortality. Secondary outcomes: inpatient mortality and initiating therapeutic anticoagulation. Results: Of 4,297 patients hospitalized with COVID-19, 3,627 (84.4%) received prophylactic anticoagulation within 24 hours of admission. More than 99% (n=3,600) received subcutaneous heparin or enoxaparin. We observed 622 deaths within 30 days of admission, 513 among those who received prophylactic anticoagulation. Most deaths (510/622, 82%) occurred during hospitalization. In inverse probability of treatment weighted analyses, cumulative adjusted incidence of mortality at 30 days was 14.3% (95% CI 13.1-15.5) among those receiving prophylactic anticoagulation and 18.7% (95% CI 15.1-22.9) among those who did not. Compared to patients who did not receive prophylactic anticoagulation, those who did had a 27% decreased risk for 30-day mortality (HR 0.73, 95% CI 0.66-0.81). Similar associations were found for inpatient mortality and initiating therapeutic anticoagulation. Quantitative bias analysis demonstrated that results were robust to unmeasured confounding (e-value lower 95% CI 1.77). Results persisted in a number of sensitivity analyses. Conclusions and Relevance: Early initiation of prophylactic anticoagulation among patients hospitalized with COVID-19 was associated with a decreased risk of mortality. These findings provide strong real-world evidence to support guidelines recommending the use of prophylactic anticoagulation as initial therapy for COVID-19 patients upon hospital admission
- …