Medical Specialties Commons^™

Effect Of Awake Prone Positioning On Endotracheal Intubation In Patients With Covid-19 And Acute Respiratory Failure: A Randomized Clinical Trial, Waleed Alhazzani, Ken Kuljit S Parhar, Jason Weatherald, Zainab Al Duhailib, Mohammed Alshahrani, Abdulrahman Al-Fares, Sarah Buabbas, Sujith V Cherian, Laveena Munshi, Eddy Fan, Fahad Al-Hameed, Jamal Chalabi, Amera A Rahmatullah, Erick Duan, Jennifer L Y Tsang, Kimberley Lewis, François Lauzier, John Centofanti, Bram Rochwerg, Sarah Culgin, Katlynne Nelson, Sheryl Ann Abdukahil, Kirsten M Fiest, Henry T Stelfox, Haytham Tlayjeh, Maureen O Meade, Dan Perri, Kevin Solverson, Daniel J Niven, Rachel Lim, Morten Hylander Møller, Emilie Belley-Cote, Lehana Thabane, Hani Tamim, Deborah J Cook, Yaseen M Arabi, Covi-Prone Trial Investigators And The Saudi Critical Care Trials Group

Faculty, Staff and Student Publications

Importance: The efficacy and safety of prone positioning is unclear in nonintubated patients with acute hypoxemia and COVID-19.

Objective: To evaluate the efficacy and adverse events of prone positioning in nonintubated adult patients with acute hypoxemia and COVID-19.

Design, setting, and participants: Pragmatic, unblinded randomized clinical trial conducted at 21 hospitals in Canada, Kuwait, Saudi Arabia, and the US. Eligible adult patients with COVID-19 were not intubated and required oxygen (≥40%) or noninvasive ventilation. A total of 400 patients were enrolled between May 19, 2020, and May 18, 2021, and final follow-up was completed in July 2021.

Intervention: Patients were …

Malinc1 An Immune-Related Long Non-Coding Rna Associated With Early-Stage Breast Cancer Progression, María Laura Fabre, Romina Canzoneri, Agustina Gurruchaga, Jaeho Lee, Pradeep Tatineni, Hyunsuk Kil, Ezequiel Lacunza, C Marcelo Aldaz, Martín Carlos Abba

Faculty, Staff and Student Publications

Simple Summary

Here we characterize the phenotypic and molecular effects of MALINC1, a long non-coding RNA (lncRNA) that we found significantly upregulated in premalignant ductal carcinoma in-situ lesions. We provide evidence that MALINC1 behaves as an oncogenic and immune-related lncRNA involved with early-stage breast cancer progression, showing prognostic and predictive value to immunotherapy in invasive breast carcinomas.

Abstract

Long non-coding RNAs are increasingly being recognized as cancer biomarkers in various malignancies, acting as either tumor suppressors or oncogenes. The long non-coding MALINC1 intergenic RNA was identified as significantly upregulated in breast ductal carcinoma in situ. The aim of this …

Respiratory Morbidity And Neurodevelopmental Outcomes In Infants Born Preterm: A Complex Web, Anna Maria Hibbs

Faculty Scholarship

This commentary is on the original article by Yu et al. on pages 1246–1253 of this issue.

Temporal Changes In Gastrointestinal Fungi And The Risk Of Autoimmunity During Early Childhood: The Teddy Study, Thomas A Auchtung, Christopher J Stewart, Daniel P Smith, Eric W Triplett, Daniel Agardh, William A Hagopian, Anette G Ziegler, Marian J Rewers, Jin-Xiong She, Jorma Toppari, Åke Lernmark, Beena Akolkar, Jeffrey P Krischer, Kendra Vehik, Jennifer M Auchtung, Nadim J Ajami, Joseph F Petrosino

Faculty, Staff and Students Publications

Fungal infections are a major health problem that often begin in the gastrointestinal tract. Gut microbe interactions in early childhood are critical for proper immune responses, yet there is little known about the development of the fungal population from infancy into childhood. Here, as part of the TEDDY (The Environmental Determinants of Diabetes in the Young) study, we examine stool samples of 888 children from 3 to 48 months and find considerable differences between fungi and bacteria. The metagenomic relative abundance of fungi was extremely low but increased while weaning from milk and formula. Overall fungal diversity remained constant over …

Right Superior Vena Cava Connected Left Atrium With Partial Anomalous Pulmonary Venous Return And Intact Atrial Septum: An Unusual Cause Of Paradoxical Embolism, Abdullah Al-Sehly, Abdah Hrfi, Ahmed Binsalahuddin

Journal of the Saudi Heart Association

A six-month-old girl presented with history of convulsion and cyanosis, was eventually found to have a right superior vena cava connected to left atrium with anomalous upper right pulmonary vein return and without atrial septal defect. Diagnosis was confirmed by cardiac magnetic resonance imaging. The patient underwent a successful cardiac surgery correction, routing SVC to right atrium and repair of right upper pulmonary vein to left atrium.

Secondary School Athletic Trainers’ Perceived Confidence In Providing Independent Medical Care Within Differing Healthcare Delivery Models, Sam G. Arredondo Dat, Atc, Matthew J. Rivera Dat, Lat, Atc, Lindsey E. Eberman Phd, Lat, Atc

Journal of Sports Medicine and Allied Health Sciences: Official Journal of the Ohio Athletic Trainers Association

ABSTRACT

Purpose: The aim of this study was to evaluate athletic trainers’ confidence and ability to deliver independent medical care in the secondary school setting. Methods: A cross-sectional survey design was used with open- and closed-ended questions using a tool that was modified from a previously validated tool used within the collegiate setting; the tool was adapted through content expert validation. Results: Athletic trainers perceived themselves as confident in providing independent medical care through the school district healthcare delivery model (n=109/121, 90%) more often than those functioning within the hospital/clinic outreach model (n=85/130, 65%). Conclusions: Despite not having nationalized legislation …

Effects Of A 4-Week Heart Rate Variability Biofeedback Intervention On Psychological And Performance Variables In Student-Athletes: A Pilot Study, Samantha R. Weber, Zachary K. Winkelmann, Eva V. Monsma, Shawn M. Arent, Toni Torres-Mcgehee

Journal of Sports Medicine and Allied Health Sciences: Official Journal of the Ohio Athletic Trainers Association

PURPOSE: To examine the effects of a 4-week biofeedback intervention on coherence, psychological, and performance variables in collegiate student-athletes. METHODS: Thirteen student-athletes were randomly assigned to the intervention (one weekly biofeedback session for 4-weeks) or control group (no sessions). Data were collected at pre and post-intervention using weekly averaged coherence scores, psychological measures for depression, arousal, stress, resiliency, and performance outcome measures. RESULTS: A 3 (Time) x 4 (Week average) repeated measures ANOVA was independently conducted to examine differences between time and weekly coherence average for coherence scores. No significant differences were found for “at rest”, pre, or post-practice coherence …

The Effects Of Vitamin D Supplementation On Athletic Performance And Injury Prevention, Amani Adeeb Abushamma

Journal of Sports Medicine and Allied Health Sciences: Official Journal of the Ohio Athletic Trainers Association

Vitamin D supplementation has numerous effects on athletic performance and plays a significant role in preventing an athlete’s risk of getting injuries. Vitamin D has an impact on numerous physiological functions such as: bone health, muscle function, inflammatory response, and immune function. An athlete’s bone and muscle health are essential for maximum performance and career success. A bone fracture due to vitamin D deficiency can delay an athlete’s training and ultimately inhibit obtaining a collegiate scholarship and/or contract. A cross sectional study found that more than half of athletic trainers did not view 25-hydroxyvitamin D(25[OH]) testing and vitamin D supplementation …

An Infrapatellar Fat Pad Tear In A High School Football Player: A Case Report, Brian D. Seiler

Journal of Sports Medicine and Allied Health Sciences: Official Journal of the Ohio Athletic Trainers Association

Objective: To present a clinical case exploring the occurrence and management of a tear to the infrapatellar fat pad IFP of a high school football player. Background: Acute tears to the IFP are rare. Typically, the IFP becomes impinged (i.e., Hoffa’s disease) through a fall, direct knee trauma, or surgical complications, and requires conservative treatment. Treatment: A 15-year-old high school football player reported to the athletic training clinical complaining of right knee discomfort and the inability to fully flex the knee. The patient stated that during a field goal attempt he missed the ball and hyperextended his right knee. Hoffa’s …

Cxcr5, Pd-1, And Icos Expressing Tumor Reactive Cd4 T Cells And Thier Use, Andrew D Weinberg, Thomas Duhen, Rebekka Duhen, Jacob Moses

Technology Transfer - Patents

No abstract provided.

Phosphorylation And Stabilization Of Pd-L1 By Ck2 Suppresses Dendritic Cell Function, Xixi Zhao, Yongkun Wei, Yu-Yi Chu, Yintao Li, Jung-Mao Hsu, Zhou Jiang, Chunxiao Liu, Jennifer L Hsu, Wei-Chao Chang, Riyao Yang, Li-Chuan Chan, Jingkun Qu, Shuqun Zhang, Haoqiang Ying, Dihua Yu, Mien-Chie Hung

Faculty, Staff and Student Publications

UNLABELLED: Targeting immune checkpoints such as programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) has transformed cancer treatment, with durable clinical responses across a wide range of tumor types. However, a high percentage of patients fail to respond to anti-PD-1/PD-L1 treatment. A greater understanding of PD-L1 regulation is critical to improving the clinical response rate of PD-1/PD-L1 blockade. Here, we demonstrate that PD-L1 is phosphorylated and stabilized by casein kinase 2 (CK2) in cancer and dendritic cells (DC). Phosphorylation of PD-L1 at Thr285 and Thr290 by CK2 disrupted PD-L1 binding with speckle-type POZ protein, an adaptor …

My Journey With The Heartware Ventricular Assist Device- An Obituary, Georg M. Wieselthaler

The VAD Journal

None

Evaluation Of Surgical Skill Using Machine Learning With Optimal Wearable Sensor Locations, Rahul Soangra, R. Sivakumar, E. R. Anirudh, Sai Viswanth Reddy Y., Emmanuel B. John

Physical Therapy Faculty Articles and Research

Evaluation of surgical skills during minimally invasive surgeries is needed when recruiting new surgeons. Although surgeons’ differentiation by skill level is highly complex, performance in specific clinical tasks such as pegboard transfer and knot tying could be determined using wearable EMG and accelerometer sensors. A wireless wearable platform has made it feasible to collect movement and muscle activation signals for quick skill evaluation during surgical tasks. However, it is challenging since the placement of multiple wireless wearable sensors may interfere with their performance in the assessment. This study utilizes machine learning techniques to identify optimal muscles and features critical for …

De Novo Fzr1 Loss-Of-Function Variants Cause Developmental And Epileptic Encephalopathies, Sathiya N Manivannan, Jolien Roovers, Noor Smal, Candace T Myers, Dilsad Turkdogan, Filip Roelens, Oguz Kanca, Hyung-Lok Chung, Tasja Scholz, Katharina Hermann, Tatjana Bierhals, Hande S Caglayan, Hannah Stamberger, Mae Working Group Of Euroepinomics Res Consortium, Heather Mefford, Peter De Jonghe, Shinya Yamamoto, Sarah Weckhuysen, Hugo J Bellen

Duncan NRI Faculty and Staff Publications

FZR1, which encodes the Cdh1 subunit of the anaphase-promoting complex, plays an important role in neurodevelopment by regulating the cell cycle and by its multiple post-mitotic functions in neurons. In this study, evaluation of 250 unrelated patients with developmental and epileptic encephalopathies and a connection on GeneMatcher led to the identification of three de novo missense variants in FZR1. Whole-exome sequencing in 39 patient-parent trios and subsequent targeted sequencing in an additional cohort of 211 patients was performed to identify novel genes involved in developmental and epileptic encephalopathy. Functional studies in Drosophila were performed using three different mutant alleles of …

Trust-Ii: A Global Phase Ii Study For Taletrectinib In Ros1 Fusion-Positive Lung Cancer And Other Solid Tumors, Misako Nagasaka, Shunichi Sugawara, Chang-Min Choi, Tatsuro Okamoto, Noriko Yangitani, Kaname Nosaki, Toshiaki Takahashi, Yutaka Fujiwara, John Khoury, Jorge J. Nieva

Conference Presentation Abstracts

Background: Taletrectinib (AB-106/DS-6051b) is a next-generation, brain-penetrant, ROS1/ NTRK tyrosine kinase inhibitor (TKI) and has shown clinically meaningful effect and safety profile in ROS1+ Non-Small Cell Lung Cancer (NSCLC) patients in phase 1 studies (Fujiwara et al, Oncotarget 2018; 9(34): 23729-23737; Ou et al, JTO Clin Res Rep. 2020 Oct 21;2(1):100108). Taletrectinib has also demonstrated activity against ROS1 G2032R resistance mutation and CNS metastases in the ongoing phase 2 TRUST study (NCT04395677) in China. Also, taletrectinib has shown preliminary efficacy against NTRK positive solid tumors in an ongoing phase 2 study (NCT04617054). Methods: TRUST-II study (NCT04919811) is a phase 2, …

Clinical Features And Body Composition In Men With Hormone-Sensitive Metastatic Prostate Cancer: A Pilot Study Examining Differences By Race, Patricia M. Sheean, Paula O'Connor, Cara Joyce, Vasilios Vasilopoulos, Ami Badami, Melinda Stolley

Biostatistics Collaborative Core: Faculty Publications and Other Works

Black men treated with frontline therapies for metastatic prostate cancer (MPC) show better clinical outcomes than non-Black men receiving similar treatments. Variations in body composition may contribute to these findings. However, preliminary data are required to support this concept. We conducted a retrospective cohort study for all men with MPC evaluated at our center over a 4-year period, collecting demographic and clinical data (N = 74). Of these, 55 men had diagnostic computed tomography images to quantify adipose tissue and skeletal muscle, specifically sarcopenia and myosteatosis. Nineteen men had repeat imaging to explore changes over time. Frequencies, medians, interquartile ranges, …

Structural Characterization Of Dicyanopyridine Containing Dnmt1-Selective, Non-Nucleoside Inhibitors, John R Horton, Sarath Pathuri, Kristen Wong, Ren Ren, Lourdes Rueda, David T Fosbenner, Dirk A Heerding, Michael T Mccabe, Melissa B Pappalardi, Xing Zhang, Bryan W King, Xiaodong Cheng

Faculty, Staff and Student Publications

DNMT1 maintains the parental DNA methylation pattern on newly replicated hemimethylated DNA. The failure of this maintenance process causes aberrant DNA methylation that affects transcription and contributes to the development and progression of cancers such as acute myeloid leukemia. Here, we structurally characterized a set of newly discovered DNMT1-selective, reversible, non-nucleoside inhibitors that bear a core 3,5-dicyanopyridine moiety, as exemplified by GSK3735967, to better understand their mechanism of inhibition. All of the dicyanopydridine-containing inhibitors examined intercalate into the hemimethylated DNA between two CpG base pairs through the DNA minor groove, resulting in conformational movement of the DNMT1 active-site loop. In …

Beyond The Backbone: The Next Generation Of Pathwalking Utilities For Model Building In Cryoem Density Maps, Corey F Hryc, Matthew L Baker

Faculty, Staff and Student Publications

Single-particle electron cryomicroscopy (cryoEM) has become an indispensable tool for studying structure and function in macromolecular assemblies. As an integral part of the cryoEM structure determination process, computational tools have been developed to build atomic models directly from a density map without structural templates. Nearly a decade ago, we created Pathwalking, a tool for de novo modeling of protein structure in near-atomic resolution cryoEM density maps. Here, we present the latest developments in Pathwalking, including the addition of probabilistic models, as well as a companion tool for modeling waters and ligands. This software was evaluated on the 2021 CryoEM Ligand …

Predictive Performance Of Different Ntcp Techniques For Radiation-Induced Esophagitis In Nsclc Patients Receiving Proton Radiotherapy, Mei Chen, Zeming Wang, Shengpeng Jiang, Jian Sun, Li Wang, Narayan Sahoo, G Brandon Gunn, Steven J Frank, Cheng Xu, Jiayi Chen, Quynh-Nhu Nguyen, Joe Y Chang, Zhongxing Liao, X Ronald Zhu, Xiaodong Zhang

Faculty, Staff and Student Publications

This study aimed to compare the predictive performance of different modeling methods in developing normal tissue complication probability (NTCP) models for predicting radiation-induced esophagitis (RE) in non-small cell lung cancer (NSCLC) patients receiving proton radiotherapy. The dataset was composed of 328 NSCLC patients receiving passive-scattering proton therapy and 41.6% of the patients experienced ≥ grade 2 RE. Five modeling methods were used to build NTCP models: standard Lyman-Kutcher-Burman (sLKB), generalized LKB (gLKB), multivariable logistic regression using two variable selection procedures-stepwise forward selection (Stepwise-MLR), and least absolute shrinkage and selection operator (LASSO-MLR), and support vector machines (SVM). Predictive performance was internally …

Precision Combination Therapies Based On Recurrent Oncogenic Coalterations, Xubin Li, Elisabeth K Dowling, Gonghong Yan, Zeynep Dereli, Behnaz Bozorgui, Parisa Imanirad, Jacob H Elnaggar, Augustin Luna, David G Menter, Patrick G Pilié, Timothy A Yap, Scott Kopetz, Chris Sander, Anil Korkut

Faculty, Staff and Student Publications

UNLABELLED: Cancer cells depend on multiple driver alterations whose oncogenic effects can be suppressed by drug combinations. Here, we provide a comprehensive resource of precision combination therapies tailored to oncogenic coalterations that are recurrent across patient cohorts. To generate the resource, we developed Recurrent Features Leveraged for Combination Therapy (REFLECT), which integrates machine learning and cancer informatics algorithms. Using multiomic data, the method maps recurrent coalteration signatures in patient cohorts to combination therapies. We validated the REFLECT pipeline using data from patient-derived xenografts, in vitro drug screens, and a combination therapy clinical trial. These validations demonstrate that REFLECT-selected combination therapies …

Identification Of Functional Heterogeneity Of Carcinoma-Associated Fibroblasts With Distinct Il6-Mediated Therapy Resistance In Pancreatic Cancer, Kathleen M Mcandrews, Yang Chen, J Kebbeh Darpolor, Xiaofeng Zheng, Sujuan Yang, Julienne L Carstens, Bingrui Li, Huamin Wang, Toru Miyake, Pedro Correa De Sampaio, Michelle L Kirtley, Mariangela Natale, Chia-Chin Wu, Hikaru Sugimoto, Valerie S Lebleu, Raghu Kalluri

Faculty, Staff and Student Publications

The tumor microenvironment in pancreatic ductal adenocarcinoma (PDAC) involves a significant accumulation of fibroblasts as part of the host response to cancer. Employing single-cell RNA-sequencing, multiplex immunostaining, and several genetic mouse models, we identify carcinoma-associated fibroblasts (CAFs) with opposing functions in PDAC progression. Depletion of fibroblast activation protein (FAP)+ CAFs results in increased survival, in contrast to depletion of alpha smooth muscle actin (αSMA)+ CAFs that leads to decreased survival. Tumor-promoting FAP+ CAFs (TP-CAFs) and tumor-restraining αSMA+ CAFs (TR-CAFs) differentially regulate cancer-associated pathways and accumulation of Tregs. Improved efficacy of gemcitabine is observed when IL-6 is deleted from αSMA+ CAFs …

Pathological Response And Immune Biomarker Assessment In Non-Small-Cell Lung Carcinoma Receiving Neoadjuvant Immune Checkpoint Inhibitors, Frank Rojas, Edwin Roger Parra, Ignacio Ivan Wistuba, Cara Haymaker, Luisa Maren Solis Soto

Faculty, Staff and Student Publications

Lung cancer is the leading cause of cancer incidence and mortality worldwide. Adjuvant and neoadjuvant chemotherapy have been used in the perioperative setting of non-small-cell carcinoma (NSCLC); however, the five-year survival rate only improves by about 5%. Neoadjuvant treatment with immune checkpoint inhibitors (ICIs) has become significant due to improved survival in advanced NSCLC patients treated with immunotherapy agents. The assessment of pathology response has been proposed as a surrogate indicator of the benefits of neaodjuvant therapy. An outline of recommendations has been published by the International Association for the Study of Lung Cancer (IASLC) for the evaluation of pathologic …

Synchronized Diaphragmatic Stimulation: A Case Report Of A Novel Extra-Cardiac Intervention For Chronic Heart Failure., Lee R Goldberg, Ana Jorbenadze, Tamaz Shaburishvilli, Michael Mirro Md, Marat Fudim, Michel Zuber, Simon F Stämpfli, Felix C Tanner, Paul Erne, John G Cleland

Parkview Heart Institute

Synchronized diaphragmatic stimulation (SDS) is a novel extra-cardiac device-based therapy for symptomatic heart failure with reduced ejection fraction. SDS provides imperceptible chronic stimulation of the diaphragm through a laparoscopically implanted system consisting of an implantable pulse generator and two sensing/stimulating leads affixed to the inferior surface of the diaphragm delivering imperceptible R-wave gaited pulses that alter intrathoracic pressure improving ventricular filling and cardiac output. We describe, in a man with a history of myocardial infarctions resulting in heart failure and persistent New York Heart Association Class III symptoms despite standard therapies, the successful implantation of SDS resulting in improved quality …

Acute Otitis Media: Antibiotic Length, Children's Mercy Kansas City

Clinical Critically Appraised Topics

No abstract provided.

Asthma Exacerbation, Children's Mercy Kansas City

Clinical Pathways (Formally Known As Clinical Practice Guidelines)

No abstract provided.

The Urinary Microbiome And Biological Therapeutics: Novel Therapies For Urinary Tract Infections, Ciara Kenneally, Craig P. Murphy, Roy D. Sleator, Eamonn P. Culligan

Department of Biological Sciences Publications

The discovery of microbial communities in the urinary tract (the urobiome) has fundamentally altered the previous doctrine regarding urine sterility and associated urinary disorders. Recent advances in culturing and culture-independent DNA sequencing technologies have characterised the resident microbial community in the urobiome, and has, in turn, demonstrated how community imbalances potentially contribute to infection and disease. As we enter a post-antibiotic era, the effectiveness of standard antimicrobial treatments against multi-drug resistant (MDR) uropathogens is vastly diminished. Preliminary research is accumulating surrounding microbiome-based therapies, and their potential as non-antibiotic therapeutics. In this context, the urobiome is significantly underexplored, and knowledge regarding …

Rural-Urban Trends In Congenital Heart Disease-Related Mortality In The United States, 1999 To 2019, Abdul Mannan Khan Minhas, Rachel A. Wyand, Robert W. Ariss, Salik Nazir, Vardhmaan Jain, Sadeer G. Al-Kindi, Michael D. Shapiro, William Campbell, Laurence Sperling, Salim S. Virani

Office of the Provost

No abstract provided.

Prevalence & Factors Associated With Acute Kidney Injury In Patients Undergoing Percutaneous Coronary Intervention At A Tertiary Healthcare Facility In Tanzania, Faisal Hooda

Master of Medicine in Internal Medicine

Background: Acute kidney injury is a potentially fatal but preventable outcome of percutaneous coronary intervention: the most plausible cause being radiocontrast-induced nephropathy; others include: pre-existing renal insufficiency from underlying illnesses and also acute renal insult caused by hypoperfusion from cardiac causes. The prevalence, associated risk factors and outcomes of AKI post-PCI are unclear and unexplored in our setting. Objectives: The study sought to determine the prevalence of acute kidney injury post-percutaneous coronary intervention at The Aga Khan Hospital, Dar es Salaam, Tanzania. Secondary objectives included: factors associated, with and outcomes of acute kidney injury (AKI) post percutaneous coronary intervention (PCI). …

Churg Strauss Syndrome With Neuropathy: A Case Report, Zaid Waqar

Pakistan Journal of Neurological Sciences (PJNS)

A 24 years old man with known history of asthma came with acute presentation of ascending weakness for four days following flu like symptoms and worsening of asthma. His complete blood counts showed elevated eosinophil count. Nerve conduction showed neuropathy. He was diagnosed as Churg Strauss syndrome due to presence of asthma, eosinophilia, neuropathy and pulmonary infiltrates. Churg Strauss is a systemic eosinophilic vasculitis involving multiple organ systems that may present with neuropathy, as in this case.

Post Covid-19 Vaccine (Sinovac) Cerebral Venous Sinus Thrombosis, Soban Khan, Maryam Khalil, Zaid Waqar

Pakistan Journal of Neurological Sciences (PJNS)

SINOVAC is an inactivated virus COVID 19 vaccine given emergency authorization for COVID-19 Pandemic. Different adverse reactions have been seen in after-marketing of COVID-19 vaccines. Here we present a case of patient who developed cerebral venous sinus thrombosis two weeks after the first dose of SINOVAC vaccine.