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Evaluation of individual and ensemble probabilistic forecasts of COVID-19 mortality in the United States

Cramer, Estee Y; Ray, Evan L; Lopez, Velma K; Bracher, Johannes; Brennen, Andrea; Castro Rivadeneira, Alvaro J; Gerding, Aaron; Gneiting, Tilmann; House, Katie H; Huang, Yuxin; Jayawardena, Dasuni; Kanji, Abdul H; Khandelwal, Ayush; Le, Khoa; Mühlemann, Anja; Niemi, Jarad; Shah, Apurv; Stark, Ariane; Wang, Yijin; Wattanachit, Nutcha; Zorn, Martha W; Gu, Youyang; Jain, Sansiddh; Bannur, Nayana; Deva, Ayush; Kulkarni, Mihir; Merugu, Srujana; Raval, Alpan; Shingi, Siddhant; Tiwari, Avtansh; White, Jerome; Abernethy, Neil F; Woody, Spencer; Dahan, Maytal; Fox, Spencer; Gaither, Kelly; Lachmann, Michael; Meyers, Lauren Ancel; Scott, James G; Tec, Mauricio; Srivastava, Ajitesh; George, Glover E; Cegan, Jeffrey C; Dettwiller, Ian D; England, William P; Farthing, Matthew W; Hunter, Robert H; Lafferty, Brandon; Linkov, Igor; Mayo, Michael L; Parno, Matthew D; Rowland, Michael A; Trump, Benjamin D; Zhang-James, Yanli; Chen, Samuel; Faraone, Stephen V; Hess, Jonathan; Morley, Christopher P; Salekin, Asif; Wang, Dongliang; Corsetti, Sabrina M; Baer, Thomas M; Eisenberg, Marisa C; Falb, Karl; Huang, Yitao; Martin, Emily T; McCauley, Ella; Myers, Robert L; Schwarz, Tom; Sheldon, Daniel; Gibson, Graham Casey; Yu, Rose; Gao, Liyao; Ma, Yian; Wu, Dongxia; Yan, Xifeng; Jin, Xiaoyong; Wang, Yu-Xiang; Chen, YangQuan; Guo, Lihong; Zhao, Yanting; Gu, Quanquan; Chen, Jinghui; Wang, Lingxiao; Xu, Pan; Zhang, Weitong; Zou, Difan; Biegel, Hannah; Lega, Joceline; McConnell, Steve; Nagraj, V P; Guertin, Stephanie L; Hulme-Lowe, Christopher; Turner, Stephen D; Shi, Yunfeng; Ban, Xuegang; Walraven, Robert; Hong, Qi-Jun; Kong, Stanley; van de Walle, Axel; Turtle, James A; Ben-Nun, Michal; Riley, Steven; Riley, Pete; Koyluoglu, Ugur; DesRoches, David; Forli, Pedro; Hamory, Bruce; Kyriakides, Christina; Leis, Helen; Milliken, John; Moloney, Michael; Morgan, James; Nirgudkar, Ninad; Ozcan, Gokce; Piwonka, Noah; Ravi, Matt; Schrader, Chris; Shakhnovich, Elizabeth; Siegel, Daniel; Spatz, Ryan; Stiefeling, Chris; Wilkinson, Barrie; Wong, Alexander; Cavany, Sean; España, Guido; Moore, Sean; Oidtman, Rachel; Perkins, Alex; Kraus, David; Kraus, Andrea; Gao, Zhifeng; Bian, Jiang; Cao, Wei; Lavista Ferres, Juan; Li, Chaozhuo; Liu, Tie-Yan; Xie, Xing; Zhang, Shun; Zheng, Shun; Vespignani, Alessandro; Chinazzi, Matteo; Davis, Jessica T; Mu, Kunpeng; Pastore Y Piontti, Ana; Xiong, Xinyue; Zheng, Andrew; Baek, Jackie; Farias, Vivek; Georgescu, Andreea; Levi, Retsef; Sinha, Deeksha; Wilde, Joshua; Perakis, Georgia; Bennouna, Mohammed Amine; Nze-Ndong, David; Singhvi, Divya; Spantidakis, Ioannis; Thayaparan, Leann; Tsiourvas, Asterios; Sarker, Arnab; Jadbabaie, Ali; Shah, Devavrat; Della Penna, Nicolas; Celi, Leo A; Sundar, Saketh; Wolfinger, Russ; Osthus, Dave; Castro, Lauren; Fairchild, Geoffrey; Michaud, Isaac; Karlen, Dean; Kinsey, Matt; Mullany, Luke C; Rainwater-Lovett, Kaitlin; Shin, Lauren; Tallaksen, Katharine; Wilson, Shelby; Lee, Elizabeth C; Dent, Juan; Grantz, Kyra H; Hill, Alison L; Kaminsky, Joshua; Kaminsky, Kathryn; Keegan, Lindsay T; Lauer, Stephen A; Lemaitre, Joseph C; Lessler, Justin; Meredith, Hannah R; Perez-Saez, Javier; Shah, Sam; Smith, Claire P; Truelove, Shaun A; Wills, Josh; Marshall, Maximilian; Gardner, Lauren; Nixon, Kristen; Burant, John C; Wang, Lily; Gao, Lei; Gu, Zhiling; Kim, Myungjin; Li, Xinyi; Wang, Guannan; Wang, Yueying; Yu, Shan; Reiner, Robert C; Barber, Ryan; Gakidou, Emmanuela; Hay, Simon I; Lim, Steve; Murray, Chris; Pigott, David; Gurung, Heidi L; Baccam, Prasith; Stage, Steven A; Suchoski, Bradley T; Prakash, B Aditya; Adhikari, Bijaya; Cui, Jiaming; Rodríguez, Alexander; Tabassum, Anika; Xie, Jiajia; Keskinocak, Pinar; Asplund, John; Baxter, Arden; Oruc, Buse Eylul; Serban, Nicoleta; Arik, Sercan O; Dusenberry, Mike; Epshteyn, Arkady; Kanal, Elli; Le, Long T; Li, Chun-Liang; Pfister, Tomas; Sava, Dario; Sinha, Rajarishi; Tsai, Thomas; Yoder, Nate; Yoon, Jinsung; Zhang, Leyou; Abbott, Sam; Bosse, Nikos I; Funk, Sebastian; Hellewell, Joel; Meakin, Sophie R; Sherratt, Katharine; Zhou, Mingyuan; Kalantari, Rahi; Yamana, Teresa K; Pei, Sen; Shaman, Jeffrey; Li, Michael L; Bertsimas, Dimitris; Skali Lami, Omar; Soni, Saksham; Tazi Bouardi, Hamza; Ayer, Turgay; Adee, Madeline; Chhatwal, Jagpreet; Dalgic, Ozden O; Ladd, Mary A; Linas, Benjamin P; Mueller, Peter; Xiao, Jade; Wang, Yuanjia; Wang, Qinxia; Xie, Shanghong; Zeng, Donglin; Green, Alden; Bien, Jacob; Brooks, Logan; Hu, Addison J; Jahja, Maria; McDonald, Daniel; Narasimhan, Balasubramanian; Politsch, Collin; Rajanala, Samyak; Rumack, Aaron; Simon, Noah; Tibshirani, Ryan J; Tibshirani, Rob; Ventura, Valerie; Wasserman, Larry; O'Dea, Eamon B; Drake, John M; Pagano, Robert; Tran, Quoc T; Ho, Lam Si Tung; Huynh, Huong; Walker, Jo W; Slayton, Rachel B; Johansson, Michael A; Biggerstaff, Matthew; Reich, Nicholas G
SignificanceThis paper compares the probabilistic accuracy of short-term forecasts of reported deaths due to COVID-19 during the first year and a half of the pandemic in the United States. Results show high variation in accuracy between and within stand-alone models and more consistent accuracy from an ensemble model that combined forecasts from all eligible models. This demonstrates that an ensemble model provided a reliable and comparatively accurate means of forecasting deaths during the COVID-19 pandemic that exceeded the performance of all of the models that contributed to it. This work strengthens the evidence base for synthesizing multiple models to support public-health action.
PMID: 35394862
ISSN: 1091-6490
CID: 5207012

An unexpected upheaval: pediatric radiology fellows' experience during COVID-19 [Editorial]

Le, Viet T; Akbari, Yasmin S; El-Ali, Alexander M
PMCID:7791337
PMID: 33416923
ISSN: 1432-1998
CID: 4868002

Solitary long-bone epiphyseal lesions in children: radiologic-pathological correlation and epidemiology

El-Ali, Alexander M; Coblentz, Ailish; Degnan, Andrew J
BACKGROUND:Solitary epiphyseal lesions are rare and present with nonspecific imaging features. Knowledge regarding etiologies of pediatric epiphyseal lesions is limited to small studies. OBJECTIVE:The purpose of this study was to determine the relative incidence of pathologies affecting the pediatric epiphysis based on biopsy-proven cases with imaging. MATERIALS AND METHODS/METHODS:We conducted a retrospective review of imaging studies including the terms "biopsy" or "resection" and entities known to affect the epiphysis and cross-referenced these with pathology reports, recording the relevant clinical data. Two radiologists performed comprehensive imaging review and recorded relevant features. RESULTS:Forty-nine children and adolescents met inclusion criteria. The long-bone epiphyseal lesion etiologies included chondroblastoma (n=22, 45%), nonspecific nonmalignant pathology (n=11, 22%), osteomyelitis (n=9, 18%), lymphoma (n=2, 4%) and 1 case of each of aneurysmal bone cyst, chondrosarcoma, enchondroma, hemangioendothelioma, and non-Langerhans cell histiocytosis. Median age was 13.1 years old (range 1.5-18.6 years). We performed comparative analysis of the two most common lesions in our series, chondroblastoma and osteomyelitis. Chondroblastoma was significantly more likely to be peripherally located (94% vs. 33%, P=0.002) and to demonstrate a discrete T1-weighted hypointense rim (94% vs. 33%, P=0.002); there were no significant differences in enhancement or intrinsic signal properties. Children with chondroblastoma were older (15.1 years vs. 7.3 years, P=0.001), and chondroblastoma lesions were significantly larger, with mean maximum lesion diameter of 25 mm (interquartile range [IQR] 20-30) vs. 12 mm (IQR 11-18) (P=0.001) and lesion volumes of 4.4 mL (IQR 2.4-7.9) vs. 0.4 mL (IQR 0.2-1.4) (P=0.01). CONCLUSION/CONCLUSIONS:This study reports the relative frequency of pathology of pediatric solitary epiphyseal lesions and describes several features that might assist in differentiating between chondroblastoma and osteomyelitis.
PMID: 32638051
ISSN: 1432-1998
CID: 4533222

Feasibility and reproducibility of shear wave elastography in pediatric cranial ultrasound

El-Ali, Alexander M; Subramanian, Subramanian; Krofchik, Lisa M; Kephart, Morie C; Squires, Judy H
BACKGROUND:Head ultrasound (US) is commonly used to evaluate the neonatal brain but may be limited by its lack of sensitivity and specificity. Ultrasound shear wave elastography (SWE) might provide additional information to conventional gray-scale imaging. OBJECTIVE:To assess whether SWE of brain parenchyma can be (1) successfully performed at a large academic medical center where US technologists perform the majority of examinations and (2) used to detect intracranial pathology. MATERIALS AND METHODS/METHODS:Pediatric patients undergoing head ultrasound underwent simultaneous SWE examination. We included normal examinations (n=70) and those with intracranial pathology (n=8) for analysis. We analyzed inter-reader variability and examination success rates and assessed the stiffness of white matter and deep gray nuclei in normal and pathological states across multiple gestational age groups. RESULTS:Average gestational age of the term, pre-term and extreme pre-term groups were 38.4±1.2 weeks, 29.0±3.7 weeks and 28.3±3.1 weeks, respectively. Overall examination success rate was 79.5%. We observed a decrease in the SWE examination time from the first month (5.9±3.7 min) to the second month (4.1±1.7 min; P=0.01). Forty-one repeat examinations were performed on 14 children by different technologists, with an intraclass correlation coefficient (ICC) of 0.91. Mean stiffness in the periventricular white matter was lower than in the deep gray nuclei in all gestational age groups: term group (1.3 m/s vs. 1.5 m/s, P<0.001), pre-term (1.3 m/s vs. 1.4 m/s P=0.12), and extremely preterm group (1.2 m/s vs. 1.4 m/s, P=0.001). Mean stiffness for the deep gray nuclei differed between the term (1.5±0.3 m/s) and pre-term (1.4±0.2 m/s) groups (P<0.01). No significant differences in white matter stiffness were seen in relation to gestational age. Infants with large intraparenchymal hemorrhage had increased white matter stiffness (1.3±0.1 m/s) and deep gray nuclei stiffness (1.6±0.2 m/s) compared to full-term infants with normal head ultrasounds. These differences approached statistical significance with P=0.09 and P=0.06, respectively. CONCLUSION/CONCLUSIONS:We demonstrated that SWE performed by pediatric sonography technologists is reproducible. We found differences in stiffness between deep gray nuclei and periventricular white matter across multiple age groups.
PMID: 31863191
ISSN: 1432-1998
CID: 4344302

Contrast-Enhanced Ultrasound of Congenital and Infantile Hemangiomas: Preliminary Results From a Case Series

El-Ali, Alexander Maad; McCormick, Andrew; Thakrar, Darshit; Yilmaz, Sabri; Malek, Marcus M; Squires, Judy H
OBJECTIVE. The contrast-enhanced ultrasound (CEUS) imaging features of hepatic vascular tumors in infants, including infantile hemangioma (IH) and congenital hemangioma (CH), are not well reported. Frequent inaccurate use of lesion terminology in the literature has created diagnostic confusion. The purpose of this study is to describe the CEUS features of IH and CH. MATERIALS AND METHODS. Ten patients, ranging in age from 8 days to 16 months, with hepatic vascular tumors were included for retrospective analysis. Gray-scale ultrasound, color Doppler ultrasound, and CEUS features were reviewed, and interobserver kappa coefficients were calculated. Final diagnoses were clinically determined by a pediatrician with expertise in vascular anomalies except in one patient who underwent surgical excision. RESULTS. Of the 10 patients, five had CHs and five had IHs. All 10 lesions were hyperenhancing in the early arterial phase. In the portal venous phase, four of five (80%) CHs showed hyperenhancement relative to normal liver parenchyma, whereas four of five (80%) IHs showed isoenhancement. In the late phase, washout of contrast material was seen in three of five (60%) IHs, whereas one IH remained isoenhancing and one IH was hyperenhancing. None of the CHs showed late washout. Interobserver kappa coefficients for CEUS features ranged from 0.60 to 1.00. CONCLUSION. Except for the CEUS feature portal venous phase enhancement (κ = 0.60), good to excellent (κ = 0.74-1.00) agreement about CEUS features of IHs and CHs was observed. A significant proportion of IHs (60%) showed washout at delayed phase imaging, which has also been reported with malignancies. Recognition of the overlap in imaging appearance of these two entities is vital to preventing misdiagnosis of malignancy.
PMID: 31967502
ISSN: 1546-3141
CID: 4344312

Contrast-enhanced ultrasound of liver lesions in children

El-Ali, Alexander M; Davis, James C; Cickelli, Jennifer M; Squires, Judy H
Initial pediatric imaging of the liver heavily relies on ultrasonography (US) because it is free of ionizing radiation, easily portable and readily available. Although conventional US (gray-scale and color Doppler) is often an excellent screening tool, its relative low specificity compared to CT/MRI limits liver lesion characterization. The United States Food and Drug Administration's recent approval of an intravenous US contrast agent for pediatric liver lesion characterization (sulfur hexafluoride lipid-type A microspheres) and its excellent safety profile have spurred increased interest in contrast-enhanced US for definitive diagnosis of pediatric liver lesions. This review focuses on the safety of contrast-enhanced US, role of contrast-enhanced US in the evaluation of focal liver lesions, basic contrast-enhanced US technique for liver imaging, and interpretation principles. The authors review common focal liver lesions, with special attention to the role of contrast-enhanced US in the pediatric oncology population.
PMID: 31620843
ISSN: 1432-1998
CID: 4344292

Comparison of Traditional and Web-Based Medical Student Teaching by Radiology Residents

El-Ali, Alexander; Kamal, Fariha; Cabral, C Lynn; Squires, Judy H
PURPOSE/OBJECTIVE:Web-based learning tools are increasingly available for use and have been described in the pedagogical literature. However, rigorous comparisons between traditional learning methods and newer collaborative online tools have not been performed. Herein, we describe a web-based curriculum hosted on the collaborative Radiopaedia.org website. This curriculum was compared with traditional learning tools in a randomized, controlled fashion. MATERIALS AND METHODS/METHODS:Medical students rotating through inpatient pediatrics were offered a 1-hour case-based learning session led by radiology residents. Students were randomized to receive online (Radiopaedia.org) versus traditional supplemental educational materials (reading material covering the same content) for review before the in-class session. A 15-point questionnaire was administered at two different points during the rotation: at the beginning of the clinical rotation and at the end of the classroom session. RESULTS:Fifty-eight students were approached for enrollment and a total of 47 (81%) consented to participation and completed the study requirements. Students who completed the web-based module had higher mean knowledge scores (74%) compared with those who were provided the traditional learning material (68%) (P = .06). Specifically, they demonstrated increased knowledge of the ACR Appropriateness Criteria and the "silhouette sign." CONCLUSIONS:A randomized, controlled, nonblinded evaluation of a novel radiology curriculum intervention hosted on Radiopaedia.org demonstrates improved test scores compared with traditional teaching methods.
PMID: 30449521
ISSN: 1558-349x
CID: 4344232

Clinical metric for differentiating intracranial hemangiopericytomas from meningiomas using diffusion weighted MRI

El-Ali, Alexander M; Agarwal, Vikas; Thomas, Andrew; Hamilton, Ronald L; Filippi, Christopher G
PURPOSE/OBJECTIVE:Intracranial Hemangiopericytomas (IHP) are dural based tumors that frequently recur/metastasize. Unfortunately, their imaging appearance overlaps significantly with more benign meningiomas. We evaluated the use of diffusion weighted imaging (DWI) to differentiate IHP from meningioma. METHODS:We compared MRI of IHP tumors (WHO Grades II/III) (n = 20) to meningioma (n = 48, WHO Grade I/II). FINDINGS/RESULTS:ADC values differed between IHP (1.05 × 10-3 mm2/s) and meningiomas (0.89 × 10-3 mm2/s) (p = 0.05). Normalized ADC ratios (nADC), differed between IHP and meningiomas (1.30 vs 1.07, p = 0.03). CONCLUSION/CONCLUSIONS:Importantly, a nADC cutoff of >1.3 was specific (96%) but not sensitive (35%) for identifying IHP.
PMID: 30469018
ISSN: 1873-4499
CID: 4344282

Contractile force is enhanced in Aortas from pendrin null mice due to stimulation of angiotensin II-dependent signaling

Sutliff, Roy L; Walp, Erik R; Kim, Young Hee; Walker, Lori A; El-Ali, Alexander M; Ma, Jing; Bonsall, Robert; Ramosevac, Semra; Eaton, Douglas C; Verlander, Jill W; Hansen, Laura; Gleason, Rudolph L; Pham, Truyen D; Hong, Seongun; Pech, Vladimir; Wall, Susan M
Pendrin is a Cl-/HCO3- exchanger expressed in the apical regions of renal intercalated cells. Following pendrin gene ablation, blood pressure falls, in part, from reduced renal NaCl absorption. We asked if pendrin is expressed in vascular tissue and if the lower blood pressure observed in pendrin null mice is accompanied by reduced vascular reactivity. Thus, the contractile responses to KCl and phenylephrine (PE) were examined in isometrically mounted thoracic aortas from wild-type and pendrin null mice. Although pendrin expression was not detected in the aorta, pendrin gene ablation changed contractile protein abundance and increased the maximal contractile response to PE when normalized to cross sectional area (CSA). However, the contractile sensitivity to this agent was unchanged. The increase in contractile force/cross sectional area observed in pendrin null mice was due to reduced cross sectional area of the aorta and not from increased contractile force per vessel. The pendrin-dependent increase in maximal contractile response was endothelium- and nitric oxide-independent and did not occur from changes in Ca2+ sensitivity or chronic changes in catecholamine production. However, application of 100 nM angiotensin II increased force/CSA more in aortas from pendrin null than from wild type mice. Moreover, angiotensin type 1 receptor inhibitor (candesartan) treatment in vivo eliminated the pendrin-dependent changes contractile protein abundance and changes in the contractile force/cross sectional area in response to PE. In conclusion, pendrin gene ablation increases aorta contractile force per cross sectional area in response to angiotensin II and PE due to stimulation of angiotensin type 1 receptor-dependent signaling. The angiotensin type 1 receptor-dependent increase in vascular reactivity may mitigate the fall in blood pressure observed with pendrin gene ablation.
PMCID:4141771
PMID: 25148130
ISSN: 1932-6203
CID: 4344272

Red blood cells stored for increasing periods produce progressive impairments in nitric oxide-mediated vasodilation

Alexander, Jason T; El-Ali, Alexander M; Newman, James L; Karatela, Sulaiman; Predmore, Benjamin L; Lefer, David J; Sutliff, Roy L; Roback, John D
BACKGROUND:Clinical outcomes in transfused patients may be affected by the duration of blood storage, possibly due to red blood cell (RBC)-mediated disruption of nitric oxide (NO) signaling, a key regulator of vascular tone and blood flow. STUDY DESIGN AND METHODS/METHODS:AS-1 RBC units stored up to 42 days were sampled at selected storage times. Samples were added to aortic rings ex vivo, a system where NO-mediated vasodilation could be experimentally controlled. RESULTS:RBC units showed storage-dependent changes in plasma hemoglobin (Hb), RBC 2,3-diphosphoglycerate acid, and RBC adenosine triphosphate conforming to expected profiles. When freshly collected (Day 0) blood was added to rat aortic rings, methacholine (MCh) stimulated substantial NO-mediated vasodilation. In contrast, MCh produced no vasodilation in the presence of blood stored for 42 days. Surprisingly, the vasoinhibitory effects of stored RBCs were almost totally mediated by RBCs themselves: removal of the supernatant did not attenuate the inhibitory effects, while addition of supernatant alone to the aortic rings only minimally inhibited MCh-stimulated relaxation. Stored RBCs did not inhibit vasodilation by a direct NO donor, demonstrating that the RBC-mediated vasoinhibitory mechanism did not work by NO scavenging. CONCLUSIONS:These studies have revealed a previously unrecognized vasoinhibitory activity of stored RBCs, which is more potent than the described effects of free Hb and works through a different mechanism that does not involve NO scavenging but may function by reducing endothelial NO production. Through this novel mechanism, transfusion of small volumes of stored blood may be able to disrupt physiologic vasodilatory responses and thereby possibly cause adverse clinical outcomes.
PMID: 23480490
ISSN: 1537-2995
CID: 4344252