Association Between Chronic Hepatitis C Virus Infection and Myocardial Infarction Among People Living With HIV in the United States.

Hepatitis C virus (HCV) infection is common among people living with human immunodeficiency virus (PLWH). Extrahepatic manifestations of HCV, including myocardial infarction (MI), are a topic of active research. MI is classified into types, predominantly atheroembolic type 1 MI (T1MI) and supply-demand mismatch type 2 MI (T2MI). We examined the association between HCV and MI among patients in the Centers for AIDS Research (CFAR) Network of Integrated Clinical Systems, a US multicenter clinical cohort of PLWH. MIs were centrally adjudicated and categorized by type using the Third Universal Definition of Myocardial Infarction. We estimated the association between chronic HCV (RNA+) and time to MI while adjusting for demographic characteristics, cardiovascular risk factors, clinical characteristics, and history of injecting drug use. Among 23,407 PLWH aged ≥18 years, there were 336 T1MIs and 330 T2MIs during a median of 4.7 years of follow-up between 1998 and 2016. HCV was associated with a 46% greater risk of T2MI (adjusted hazard ratio (aHR) = 1.46, 95% confidence interval (CI): 1.09, 1.97) but not T1MI (aHR = 0.87, 95% CI: 0.58, 1.29). In an exploratory cause-specific analysis of T2MI, HCV was associated with a 2-fold greater risk of T2MI attributed to sepsis (aHR = 2.01, 95% CI: 1.25, 3.24). Extrahepatic manifestations of HCV in this high-risk population are an important area for continued research

Rational Herding in Microloan Markets

Microloan markets allow individual borrowers to raise funding from multiple individual lenders. We use a unique panel data set that tracks the funding dynamics of borrower listings on Prosper.com, the largest microloan market in the United States. We find evidence of rational herding among lenders. Well-funded borrower listings tend to attract more funding after we control for unobserved listing heterogeneity and payoff externalities. Moreover, instead of passively mimicking their peers (irrational herding), lenders engage in active observational learning (rational herding); they infer the creditworthiness of borrowers by observing peer lending decisions and use publicly observable borrower characteristics to moderate their inferences. Counterintuitively, obvious defects (e.g., poor credit grades) amplify a listing's herding momentum, as lenders infer superior creditworthiness to justify the herd. Similarly, favorable borrower characteristics (e.g., friend endorsements) weaken the herding effect, as lenders attribute herding to these observable merits. Follow-up analysis shows that rational herding beats irrational herding in predicting loan performance

The Feasibility, Tolerability, Safety, and Accuracy of Low-radiation Dynamic Computed Tomography Myocardial Perfusion Imaging With Regadenoson Compared With Single-photon Emission Computed Tomography

Objectives: Computed tomography (CT) myocardial perfusion imaging (CT-MPI) with hyperemia induced by regadenoson was evaluated for the detection of myocardial ischemia, safety, relative radiation exposure, and patient experience compared with single-photon emission computed tomography (SPECT) imaging. Materials and Methods: Twenty-four patients (66.5 y, 29% male) who had undergone clinically indicated SPECT imaging and provided written informed consent were included in this phase II, IRB-approved, and FDA-approved clinical trial. All patients underwent coronary CT angiography and CT-MPI with hyperemia induced by the intravenous administration of regadenoson (0.4 mg/5 mL). Patient experience and findings on CT-MPI images were compared to SPECT imaging. Results: Patient experience and safety were similar between CT-MPI and SPECT procedures and no serious adverse events due to the administration of regadenoson occurred. SPECT resulted in a higher number of mild adverse events than CT-MPI. Patient radiation exposure was similar during the combined coronary computed tomography angiography and CT-MPI (4.4 [2.7] mSv) and SPECT imaging (5.6 [1.7] mSv) (P-value 0.401) procedures. Using SPECT as the reference standard, CT-MPI analysis showed a sensitivity of 58.3% (95% confidence interval [CI]: 27.7-84.8), a specificity of 100% (95% CI: 73.5-100), and an accuracy of 79.1% (95% CI: 57.9-92.87). Low apparent sensitivity occurred when the SPECT defects were small and highly suspicious for artifacts. Conclusions: This study demonstrated that CT-MPI is safe, well tolerated, and can be performed with comparable radiation exposure to SPECT. CT-MPI has the benefit of providing both complete anatomic coronary evaluation and assessment of myocardial perfusion

Predictive Value of Cardiac CTA, Cardiac MRI, and Transthoracic Echocardiography for Cardioembolic Stroke Recurrence

Background: Transthoracic echocardiography (TTE) is the standard of care for initial evaluation of patients with suspected cardioembolic stroke. While TTE is useful for assessing certain sources of cardiac emboli, its diagnostic capability is limited in the detection of other sources, including left atrial thrombus and aortic plaques. Objectives: To investigate sensitivity, specificity and predictive value of cardiac CT angigography (cCTA), cardiac MRI (CMR), and TTE for recurrence in patients with suspected cardioembolic stroke. Methods: We retrospectively included 151 patients with suspected cardioembolic stroke who underwent TTE and either CMR (n=75) or cCTA (n=76) between January 2013 and May 2017. We evaluated for presence of left atrial thrombus, left ventricular thrombus, vulnerable aortic plaque, cardiac tumors, and valvular vegetation as causes of cardioembolic stroke. The end-point was stroke recurrence. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for recurrent stroke were calculated; the diagnostic accuracy of CMR, cCTA, and TTE was compared between and within groups using area under the curves (AUCs). Results: Twelve and 14 recurrent strokes occurred in the cCTA and CMR groups, respectively. Sensitivity, specificity, PPV and NPV were: 33.3%, 93.7%, 50.0%, and 88.2% for cCTA; 14.3%, 80.3%, 14.3%, and 80.3% for CMR; 14.3%, 83.6%, 16.7%, 80.9% for TTE in the CMR group, and 8.3%, 93.7%, 20.0% and 84.5% for TTE in the cCTA group. Accuracy was not different (p>0.05) between cCTA (0.63, 95% CI [0.49, 0.77]), CMR (0.53, [0.42, 0.63]), TTE in CMR group (0.51, [0.40, 0.61], and TTE in cCTA group (0.51, [0.42, 0.59]). In cCTA group, atrial and ventricular thrombus were detected by cCTA in 3 patients and TTE in 1 patient; in CMR group, thrombus was detected by CMR in 1 patient and TTE in 2 patients. Conclusion: cCTA, CMR, and TTE showed comparably high specificity and NPV for cardioembolic stroke recurrence. cCTA and CMR may be valid alternatives to TTE. cCTA may be preferred given potentially better detection of atrial and ventricular thrombus. Clinical impact: cCTA and CMR have similar clinical performance as TTE for predicting cardioembolic stroke recurrence. This observation may be especially important when TTE provides equivocal findings

Leadership Reconsidered: Engaging Higher Education in Social Change

Colleges and universities can provide effective environments for the development of future leaders. This book addresses the application of transformative leadership to higher education, identifies resources to use in the process, and..

Accuracy of an Artificial Intelligence Deep Learning Algorithm Implementing a Recurrent Neural Network With Long Short-term Memory for the Automated Detection of Calcified Plaques From Coronary Computed Tomography Angiography

Purpose: The purpose of this study was to evaluate the accuracy of a novel fully automated deep learning (DL) algorithm implementing a recurrent neural network (RNN) with long short-term memory (LSTM) for the detection of coronary artery calcium (CAC) from coronary computed tomography angiography (CCTA) data. Materials and Methods: Under an IRB waiver and in HIPAA compliance, a total of 194 patients who had undergone CCTA were retrospectively included. Two observers independently evaluated the image quality and recorded the presence of CAC in the right (RCA), the combination of left main and left anterior descending (LM-LAD), and left circumflex (LCx) coronary arteries. Noncontrast CACS scans were allowed to be used in cases of uncertainty. Heart and coronary artery centerline detection and labeling were automatically performed. Presence of CAC was assessed by a RNN-LSTM. The algorithm's overall and per-vessel sensitivity, specificity, and diagnostic accuracy were calculated. Results: CAC was absent in 84 and present in 110 patients. As regards CCTA, the median subjective image quality, signal-to-noise ratio, and contrast-to-noise ratio were 3.0, 13.0, and 11.4. A total of 565 vessels were evaluated. On a per-vessel basis, the algorithm achieved a sensitivity, specificity, and diagnostic accuracy of 93.1% (confidence interval [CI], 84.3%-96.7%), 82.76% (CI, 74.6%-89.4%), and 86.7% (CI, 76.8%-87.9%), respectively, for the RCA, 93.1% (CI, 86.4%-97.7%), 95.5% (CI, 88.77%-98.75%), and 94.2% (CI. 90.2%-94.6%), respectively, for the LM-LAD, and 89.9% (CI, 80.2%-95.8%), 90.0% (CI, 83.2%-94.7%), and 89.9% (CI, 85.0%-94.1%), respectively, for the LCx. The overall sensitivity, specificity, and diagnostic accuracy were 92.1% (CI, 92.1%-95.2%), 88.9% (CI. 84.9%-92.1%), and 90.3% (CI, 88.0%-90.0%), respectively. When accounting for image quality, the algorithm achieved a sensitivity, specificity, and diagnostic accuracy of 76.2%, 87.5%, and 82.2%, respectively, for poor-quality data sets and 93.3%, 89.2% and 90.9%, respectively, when data sets rated adequate or higher were combined. Conclusion: The proposed RNN-LSTM demonstrated high diagnostic accuracy for the detection of CAC from CCTA

Genomic Profiling of Childhood Tumor Patient-Derived Xenograft Models to Enable Rational Clinical Trial Design.

Accelerating cures for children with cancer remains an immediate challenge as a result of extensive oncogenic heterogeneity between and within histologies, distinct molecular mechanisms evolving between diagnosis and relapsed disease, and limited therapeutic options. To systematically prioritize and rationally test novel agents in preclinical murine models, researchers within the Pediatric Preclinical Testing Consortium are continuously developing patient-derived xenografts (PDXs)-many of which are refractory to current standard-of-care treatments-from high-risk childhood cancers. Here, we genomically characterize 261 PDX models from 37 unique pediatric cancers; demonstrate faithful recapitulation of histologies and subtypes; and refine our understanding of relapsed disease. In addition, we use expression signatures to classify tumors for TP53 and NF1 pathway inactivation. We anticipate that these data will serve as a resource for pediatric oncology drug development and will guide rational clinical trial design for children with cancer

Postcopulatory sexual selection

The female reproductive tract is where competition between the sperm of different males takes place, aided and abetted by the female herself. Intense postcopulatory sexual selection fosters inter-sexual conflict and drives rapid evolutionary change to generate a startling diversity of morphological, behavioural and physiological adaptations. We identify three main issues that should be resolved to advance our understanding of postcopulatory sexual selection. We need to determine the genetic basis of different male fertility traits and female traits that mediate sperm selection; identify the genes or genomic regions that control these traits; and establish the coevolutionary trajectory of sexes

Adaptations of Avian Flu Virus Are a Cause for Concern

We are in the midst of a revolutionary period in the life sciences. Technological capabilities have dramatically expanded, we have a much improved understanding of the complex biology of selected microorganisms, and we have a much improved ability to manipulate microbial genomes. With this has come unprecedented potential for better control of infectious diseases and significant societal benefit. However, there is also a growing risk that the same science will be deliberately misused and that the consequences could be catastrophic. Efforts to describe or define life-sciences research of particular concern have focused on the possibility that knowledge or products derived from such research, or new technologies, could be directly misapplied with a sufficiently broad scope to affect national or global security. Research that might greatly enhance the harm caused by microbial pathogens has been of special concern (1–3). Until now, these efforts have suffered from a lack of specificity and a paucity of concrete examples of “dual use research of concern” (3). Dual use is defined as research that could be used for good or bad purposes. We are now confronted by a potent, real-world example