Digital Commons Network^™

Nitrate And Nitrite Ingestion And Risk Of Ovarian Cancer Among Postmenopausal Women In Iowa, Maki Inoue-Choi, Rena R. Jones, Kristin E. Anderson, Kenneth P. Cantor, James R. Cerhan, Stuart Krasner, Kimberly Robien, Peter J. Weyer, Mary H. Ward

Epidemiology Faculty Publications

Nitrate and nitrite are precursors in the endogenous formation of N-nitroso compounds (NOC), potential human carcinogens. We evaluated the association of nitrate and nitrite ingestion with postmenopausal ovarian cancer risk in the Iowa Women's Health Study. Among 28,555 postmenopausal women, we identified 315 incident epithelial ovarian cancers from 1986 to 2010. Dietary nitrate and nitrite intakes were assessed at baseline using food frequency questionnaire data. Drinking water source at home was obtained in a 1989 follow-up survey. Nitrate-nitrogen (NO₃-N) and total trihalomethane (TTHM) levels for Iowa public water utilities were linked to residences and average levels were …

Pregnancy Apps: A Closer Look At The Implications For Childbirth Educators, Christine Frazer, Leslie Hussey, Emily Bosch, Michelle Squire

Walden Faculty and Staff Publications

Most pregnant women download an average of three pregnancy apps during their gestational period. There are no set standards in place for what needs to be included in an app’s description leaving consumers to decide for themselves when it comes to selecting the right app to download. The childbirth educator must be knowledgeable about pregnancy apps, in-tune as to what apps their clientele download, and how to analyze them for credibility. This article presents characteristics associated with women of childbearing age (i.e. Millennial/Net generation); the reasons why pregnant women are turning to apps; the limitations of apps, and the childbirth …

Current Management Of Heart Failure: When To Refer To Heart Failure Specialist And When Hospice Is The Best Option., Behnam Bozorgnia, Paul J. Mather

Division of Cardiology Faculty Papers

Heart failure is a common syndrome caused by different abnormalities of the cardiovascular system that result in impairment of the ventricles in filling or ejecting blood. It is one of the most common causes of hospitalization in the United States, with a very high cost to the health care system. This article focuses on the causes of left ventricle dysfunction and the presentation and management of heart failure, both acute and chronic.

Risk Analysis Of Prostate Cancer In Practical, A Multinational Consortium, Using 25 Known Prostate Cancer Susceptibility Loci., Ali Amin Al Olama, Sara Benlloch, Antonis C Antoniou, Graham G Giles, Gianluca Severi, David E Neal, Freddie C Hamdy, Jenny L Donovan, Kenneth Muir, Johanna Schleutker, Brian E Henderson, Christopher Haiman, Fredrick R Schumacher, Nora Pashayan, Paul D P Pharoah, Elaine A Ostrander, Janet L Stanford, Jyotsna Batra, Judith A Clements, Suzanne K Chambers, Maren Weischer, Børge G Nordestgaard, Sue A Ingles, Karina D Sorensen, Torben F Orntoft, Jong Y Park, Cezary Cybulski, Christiane Maier, Thilo Doerk, Joanne L Dickinson, Lisa Cannon-Albright, Hermann Brenner, Timothy R Rebbeck, Charnita Zeigler-Johnson, Tomonori Habuchi, Stephen N Thibodeau, Kathleen A Cooney, Pierre O Chappuis, Pierre Hutter, Radka P Kaneva, William D Foulkes, Maurice P Zeegers, Yong-Jie Lu, Hong-Wei Zhang, Robert Stephenson, Angela Cox, Melissa C Southey, Amanda B Spurdle, Liesel Fitzgerald, Daniel Leongamornlert, Edward Saunders, Malgorzata Tymrakiewicz, Michelle Guy, Tokhir Dadaev, Sarah J Little, Koveela Govindasami, Emma Sawyer, Rosemary Wilkinson, Kathleen Herkommer, John L Hopper, Aritaya Lophatonanon, Antje E Rinckleb, Zsofia Kote-Jarai, Rosalind A Eeles, Douglas F Easton

Department of Medical Oncology Faculty Papers

BACKGROUND: Genome-wide association studies have identified multiple genetic variants associated with prostate cancer risk which explain a substantial proportion of familial relative risk. These variants can be used to stratify individuals by their risk of prostate cancer.

METHODS: We genotyped 25 prostate cancer susceptibility loci in 40,414 individuals and derived a polygenic risk score (PRS). We estimated empirical odds ratios (OR) for prostate cancer associated with different risk strata defined by PRS and derived age-specific absolute risks of developing prostate cancer by PRS stratum and family history.

RESULTS: The prostate cancer risk for men in the top 1% of the …

College Students As Facilitators In Reducing Adolescent Obesity Disparity In Southern Appalachia: Team Up For Healthy Living, Deborah Slawson, William T. Dalton, Taylor Mckeehan Dula, Jodi Southerland, Liang Wang, Mary Ann Littleton, Diana Mozen, George Relyea, Karen Schetzina, Elizabeth F. Lowe, James M. Stoots, Tiejian Wu

ETSU Faculty Works

The proportion of obese adolescents in Southern Appalachia is among the highest in the nation. Through funding from the National Institute on Minority Health and Health Disparities — National Institutes of Health, the Team Up for Healthy Living project was a cluster-randomized trial targeting obesity prevention in adolescents through a cross-peer intervention. The specific aims of the project were to: 1) develop a peer-based health education program focusing on establishing positive peer norms towards healthy eating and physical activity (PA) among high school students, 2) test program efficacy, and 3) explore mechanisms underlying the program. The study was guided by …

Landscape Analysis Of Multi-Sectoral Initiatives For Under-Nutrition In Pakistan, Zulfiqar Ahmed Bhutta, Albertha Nyaku, Jane Keylock, Shehla Zaidi, Jai Das

Community Health Sciences

Mapping of Multi-Sectoral Initiatives for Nutrition in Pakistan, Challenges faced, Opportunities, and potential for Cross- Sectoral Synergies.

Labrad : Vol 41, Issue 2 - July 2015, Aga Khan Universiity Hospital, Karachi

LABRAD - Departments of Pathology & Laboratory Medicine and Radiology Archives

• An Overview of Immunoglobulin G4-Related Disease
• Plasma Neutrophil Gelatinase Associated Lipocalin (NGAL) a Marker of Acute Kidney Injury
• Celiac Disease: Biomarkers for Diagnosis and Monitoring
• Pathophysiology of Paroxysmal Nocturnal Haemoglobinuria and Diagnosis by Flowcytommetry
• Pathological Changes in Renal Transplant Biopsies not Related to Allo-Immune Mechanisms
• Myelodysplastic Syndromes
• Fluorescent Optical Method for Platelet Estimation: An Advanced Clinical Parameter in Laboratory Hematology
• Introduction of Beta-D-Glucan and Galactomannan - Testing for Diagnosis of Invasive Fungal Infections
• Basic Concepts in Hematopoietic Stem Cell Transplantation

Nrg Oncology/Rtog 0921: A Phase 2 Study Of Postoperative Intensity-Modulated Radiotherapy With Concurrent Cisplatin And Bevacizumab Followed By Carboplatin And Paclitaxel For Patients With Endometrial Cancer., Akila N. Viswanathan, Jennifer Moughan, Brigitte E. Miller, Ying Xiao, Anuja Jhingran, Lorraine Portelance, Walter R. Bosch, Ursula A. Matulonis, Neil S. Horowitz, Robert S S. Mannel, Luis Souhami, Beth A. Erickson, Kathryn A. Winter, William Small, David K. Gaffney

Department of Radiation Oncology Faculty Papers

BACKGROUND: The current study was conducted to assess acute and late adverse events (AEs), overall survival (OS), pelvic failure, regional failure, distant failure, and disease-free survival in a prospective phase 2 clinical trial of bevacizumab and pelvic intensity-modulated radiotherapy (IMRT) with chemotherapy in patients with high-risk endometrial cancer.

METHODS: Patients underwent a hysterectomy and lymph node removal, and had ≥1 of the following high-risk factors: grade 3 carcinoma with >50% myometrial invasion, grade 2 or 3 disease with any cervical stromal invasion, or known extrauterine extension confined to the pelvis. Treatment included pelvic IMRT and concurrent cisplatin on days 1 …

Clinical Characteristics And Risk Factors Of Candidemia In Tertiary Care Hospital, Iffat Khanum, Syed Faisal Mahmood, Farheen Ali, Hafsa Waqar, Safia Awan

Department of Medicine

Introduction: During the past two decades, the incidence of candidemia has doubled and Candida spp. currently ranks in top blood stream pathogen in developed countries. Given the need to ensure appropriate and timely antifungal therapy, there is need to identify these patients as early as possible and therefore a risk stratification for candidemia is imperative. We aim to identify the risk factors of candidemia in patients admitted at our tertiary care center.

Methods: A retrospective case control study were conducted on adult patients (15 years. or more) admitted to Aga Khan University Hospital between 2009 and 2013 who developed candidemia …

Obesity Early In Adulthood Increases Risk But Does Not Affect Outcomes Of Hepatocellular Carcinoma, Manal M. Hassan, Reham Abdel-Wahab, Ahmed Kaseb, Ahmed Shalaby, Alexandria Phan, Hashem El-Serag, Ernest Hawk, Jeff Morris, Kanwal Pratap Singh Raghav, Ju-Seog Lee, Jean-Nicolas Vauthey, Gehan Bortus, Harrys Torres, Christopher Amos, Robert Wolff, Donghui Li

Dartmouth Scholarship

Despite the significant association between obesity and several cancers, it has been difficult to establish an association between obesity and hepatocellular carcinoma (HCC). Patients with HCC often have ascites, making it a challenge to accurately determine body mass index (BMI), and many factors contribute to the development of HCC. We performed a case–control study to investigate whether obesity early in adulthood affects risk, age of onset, or outcomes of patients with HCC.

Exogenous 17-Β Estradiol Administration Blunts Progression Of Established Angiotensin Ii-Induced Abdominal Aortic Aneurysms In Female Ovariectomized Mice, Sean E. Thatcher, Xuan Zhang, Shannon Woody, Yu Wang, Yasir Alsiraj, Richard Charnigo, Alan Daugherty, Lisa A. Cassis

Saha Cardiovascular Research Center Faculty Publications

BACKGROUND: Abdominal aortic aneurysms (AAAs) occur predominately in males. However, AAAs in females have rapid growth rates and rupture at smaller sizes. Mechanisms contributing to AAA progression in females are undefined. We defined effects of ovariectomy, with and without 17-β estradiol (E2), on progression of established angiotensin II (AngII)-induced AAAs in female mice.

METHODS: We used neonatal testosterone exposures at 1 day of age to promote susceptibility to AngII-induced AAAs in adult female Ldlr^-/- mice. Females were infused with AngII for 28 days to induce AAAs, and then stratified into groups that were sham, ovariectomized (Ovx, vehicle), or Ovx …

Inotropes Are Not Linked To Increased Mortality In Heart Failure, Maya Guglin

The VAD Journal

How to use inotropes is one of the most controversial topics in the management of heart failure. While most clinicians use these drugs, and recognize the state of inotrope dependency, current guidelines recommend them onlu as a bridge or palliation. Thus, inotropes are considered either neutral or detrimental in terms of outcomes. Meanwhile, properly designed randomized clinical trials testing the outcomes on inotropes, have never been performed and it is unlikely that they will ever be attempted. These trials would require randomizing patients with advanced heart failure, low output syndrome, and impaired end-organ perfusion into groups that received or not …

Non-Operative Management Of Hip Osteoarthritis, Ray Marks

Publications and Research

This paper reviews several non-operative and non-pharmacologic management strategies advocated for alleviating the pain and disability experienced by people with hip osteoarthritis. It analyzes whether painful debilitating hip osteoarthritis, which has no effective cure and is often progressive, may be affected positively by non-operative interventions designed to control osteoar- thritis pain. Finally, it provides an integrated plan of management for ameliorating hip osteoar- thritis pain and disability in light of this knowledge.

Procollagen C-Endopeptidase Enhancer Protein 2 (Pcpe2) Reduces Atherosclerosis In Mice By Enhancing Scavenger Receptor Class B1 (Sr-Bi)-Mediated High-Density Lipoprotein (Hdl)-Cholesteryl Ester Uptake, Ricquita D. Pollard, Christopher N. Blesso, Manal Zabalawi, Brian Fulp, Mark Gerelus, Xuewei Zhu, Erica W. Lyons, Nebil Nuradin, Omar L. Francone, Xiang-An Li, Daisy Sahoo, Michael J. Thomas, Mary G. Sorci-Thomas

Pediatrics Faculty Publications

Studies in human populations have shown a significant correlation between procollagen C-endopeptidase enhancer protein 2 (PCPE2) single nucleotide polymorphisms and plasma HDL cholesterol concentrations. PCPE2, a 52-kDa glycoprotein located in the extracellular matrix, enhances the cleavage of C-terminal procollagen by bone morphogenetic protein 1 (BMP1). Our studies here focused on investigating the basis for the elevated concentration of enlarged plasma HDL in PCPE2-deficient mice to determine whether they protected against diet-induced atherosclerosis. PCPE2-deficient mice were crossed with LDL receptor-deficient mice to obtain LDLr^-/-, PCPE2^-/- mice, which had elevated HDL levels compared with LDLr^-/- mice with similar …

Doxycycline Down-Regulates Dna-Pk And Radiosensitizes Tumor Initiating Cells: Implications For More Effective Radiation Therapy., Rebecca Lamb, Marco Fiorillo, Amy Chadwick, Bela Ozsvari, Kimberly J Reeves, Duncan L Smith, Robert B Clarke, Sacha J Howell, Anna Rita Cappello, Ubaldo E. Martinez-Outshoorn, Md, Maria Peiris-Pagès, Federica Sotgia, Michael P Lisanti

Kimmel Cancer Center Faculty Papers

DNA-PK is an enzyme that is required for proper DNA-repair and is thought to confer radio-resistance in cancer cells. As a consequence, it is a high-profile validated target for new pharmaceutical development. However, no FDA-approved DNA-PK inhibitors have emerged, despite many years of drug discovery and lead optimization. This is largely because existing DNA-PK inhibitors suffer from poor pharmacokinetics. They are not well absorbed and/or are unstable, with a short plasma half-life. Here, we identified the first FDA-approved DNA-PK inhibitor by "chemical proteomics". In an effort to understand how doxycycline targets cancer stem-like cells (CSCs), we serendipitously discovered that doxycycline …

Akt Inhibition Overcomes Rapamycin Resistance By Enhancing The Repressive Function Of Pras40 On Mtorc1/4e-Bp1 Axis, Wenting Mi, Qing Ye, Side Liu, Qing-Bai She

Markey Cancer Center Faculty Publications

The mTORC1 inhibitors, rapamycin and its analogs, are known to show only modest antitumor activity in clinic, but the underlying mechanisms remain largely elusive. Here, we found that activated AKT signaling is associated with rapamycin resistance in breast and colon cancers by sustained phosphorylation of the translational repressor 4E-BP1. Treatment of tumor cells with rapamycin or the AKT inhibitor MK2206 showed a limited activity in inhibiting 4E-BP1 phosphorylation, cap-dependent translation, cell growth and motility. However, treatment with both drugs resulted in profound effects in vitro and in vivo. Mechanistic investigation demonstrated that the combination treatment was required to effectively …

Calcium Channel Blockers, Progression To Dementia, And Effects On Amyloid Beta Peptide Production, Mark A. Lovell, Erin Abner, Richard Kryscio, Liou Xu, Shuling X. Fister, Bert C. Lynn

Sanders-Brown Center on Aging Faculty Publications

Previous epidemiologic studies suggest that antihypertensive drugs may be protective against cognitive decline. To determine if subjects enrolled in the University of Kentucky longitudinal aging study who used antihypertensive drugs showed diminished progression to dementia, we used a 3-parameter logistic regression model to compare the rate of progression to dementia for subjects who used any of the five common categories of antihypertensive drugs to those with similar demographic characteristics but who did not use antihypertensives. Regression modeling showed that subjects who used calcium channel blockers (CCBs) but not the other classes of antihypertensives showed a significant decrease in the rate …

An Uncommon Clinical Presentation Of Relapsing Dilated Cardiomyopathy With Identification Of Sequence Variations In Mynpc3, Kcnh2 And Mitochondrial Trna Cysteine, M. J. Guillen Sacoto, Kimberly A. Chapman, D. Heath, M. B. Seprish, Dina Zand

Pediatrics Faculty Publications

We describe a young girl with dilated cardiomyopathy, long QT syndrome, and possible energy deficiency. Two major sequence changes were identified by whole exome sequencing (WES) and mitochondrial DNA analysis that were interpreted as potentially causative. Changes were identified in the KCNH2 gene and mitochondrial tRNA for cysteine. A variation was also seen in MYPBC3. Since the launch of WES as a clinically available technology in 2010, there has been concern regarding the identification of variants unrelated to the patient's phenotype. However, in cases where targeted sequencing fails to explain the clinical presentation, the underlying etiology could be more complex …

Thyroxine Replacement In Patients On Parenteral Nutrition: A Clinical Conundrum, Abdul Rehman, Noor Ul-Ain Baloch, Muhammad Awais

Department of Biological & Biomedical Sciences

No abstract provided.

Funding And Other Resources For Beginning Researchers, Jane Z. Dumsha, David Yens, Grace Brannan

PCOM Scholarly Works

Despite the fact that osteopathic research is essential for the continued advancement of our profession, such research is lacking. One barrier is the attainment of funding resources to launch and continue quality research studies. In the present article, the authors outline resources for the early stages of research and provide guidance for grant proposal preparation, if it is determined that external funding is needed. Free and low-cost resources for obtaining preliminary data and sources of external funds are described. An overview of grant writing and information on where to obtain training is presented. Information on proposal writing basics, tips to …

Oncolog, Volume 60, Number 06, June 2015, Bryan Tutt, Joe Munch, U. Arizor

OncoLog MD Anderson's Report to Physicians (All issues) Archives

• New Breast Imaging Modalities Show promise for Cancer Screening and Staging: New technology to supplement digital mammography may improve breast cancer screening and diagnosis. Although some of these new imaging modalities are still under development, others are already in clinical use as adjuncts to mammography for breast cancer screening and staging.
• Addressing Sexual Dysfunction in Cancer Survivors: Cancer treatments carry a host of side effects that can affect patients' ability to have and enjoy sex. The sexual dysfunction arising from these side effects, which include functional changes, can often be addressed, but uncovering sexual dysfunction can prove challenging.
• HOUSE CALL: …

Postpartum Contraceptive Use And Unmet Need For Family Planning In Five Low-Income Countries., Omrana Pasha, Shivaprasad S. Goudar, Archana Patel, Ana Garces, Fabian Esamai, Elwyn Chomba, Janet L. Moore, Bhalchandra S. Kodkany, Sarah Saleem, Richard J. Derman, Edward A. Liechty, Patricia L. Hibberd, K. Michael Hambidge, Nancy F. Krebs, Waldemar A. Carlo, Elizabeth M. Mcclure, Marion Koso-Thomas, Robert L. Goldenberg

Community Health Sciences

BACKGROUND:

During the post-partum period, most women wish to delay or prevent future pregnancies. Despite this, the unmet need for family planning up to a year after delivery is higher than at any other time. This study aims to assess fertility intention, contraceptive usage and unmet need for family planning amongst women who are six weeks postpartum, as well as to identify those at greatest risk of having an unmet need for family planning during this period.

METHODS:

Using the NICHD Global Network for Women's and Children's Health Research's multi-site, prospective, ongoing, active surveillance system to track pregnancies and births …

Association Of Vitamin D With Statin Induced Myalgia, Ayla K. Zubair, Imran N Ahmad, Arsalan Ahmad Md

Pakistan Journal of Neurological Sciences (PJNS)

Objective:
To determine the association of serum 25-hydroxy vitamin D (25(OH) Vitamin D) deficiency with the occurrence of myalgia in patients on statin therapy.

Methods:
The pathology laboratory database was reviewed to identify patients tested for serum 25(OH) Vitamin D and creatine kinase. A retrospective chart review was then conducted to ascertain statin use and reporting of myalgia for patients tested concurrently for serum 25(OH) vitamin D and creatinekinase levels between January 1, 2013 and December 31, 2013.

Results:
Of the 825 patients tested for creatine kinase and 25 (OH) Vitamin D in 2013, 49 met the study criteria.The …

Hepatic Encephalopathy In Chronic Liver Disease: Predisposing Factors In A Developing Country, Fakhar Qazi, Shameem Behram Khan, Anam Umar

Section of Gastroenterology

Objective: To fi nd out the risk factors for developing Hepatic Encephalopathy in patients suffering from Chronic liver disease.

Background: Hepatic encephalopathy (HE) is a neuropsychiatric disorder that is caused by liver damage. In its pathology, alterations in normal brain function are associated with an increase in blood ammonia, benzodiazepine like substances, products of neurotoxic fatty acids, and other gut derived toxins, which gain access to the brain as a result of liver dysfunction.

Study Design: Hospital based descriptive, cross sectional study.

Settings: Medical Unit 1, Ward- 5, Jinnah Post Graduate Medical Centre, Karachi.

Duration: July 2013 to December 2013. …

Environmental And Food Allergens Reactivity And Its Association With Total Ige, Age And Gender In Karachi, Pakistan, Noreen Abbas, Ahmed Raheem, Farooq Ghani

Department of Pathology and Laboratory Medicine

Aim: The aim of this study is to assess the frequency of food and environmental allergens reactivity and its association in with age, gender and total IgE levels
Material and Methods: The study population consisted of 88 individuals including children and adults (male: 47 and female: 41). The study was conducted in the clinical laboratory, Department of Pathology and Laboratory Medicine, Aga Khan University Hospital from May 2009 till May 2010. Sera of patients positive for total IgE were tested for allergen specific IgE levels by Immulite 2000, 3gAllergyTM. We divided allergens into two panels, namely food and environmental.
Results: …

Understanding Nucleus Pulposus Cell Phenotype: A Prerequisite For Stem Cell Based Therapies To Treat Intervertebral Disc Degeneration., Hyowon Choi, Zariel I. Johnson, Makarand V. Risbud

Department of Orthopaedic Surgery Faculty Papers

Intervertebral disc (IVD) degeneration and associated low back pain (LBP) remains a major burden to our society without significant improvements in treatment strategies or patient's quality of life. While the recent cell-transplantation studies for treatment of degenerative disc disease have shown promising results, to better gauge the success and functional outcomes of these therapies, it is crucial to understand if transplanted cells give rise to healthy nucleus pulposus (NP) tissue. NP cell phenotype is unique and is defined by expression of a characteristic set of markers that reflect specialized physiology and function. This review summarizes phenotypic markers that mirror the …

Promoting Completion Of Advance Directives In A Hispanic Religious Congregation: An Evidence-Based Practice Project, Luis Daniel San Miguel, Mary Jo Clark

Doctor of Nursing Practice Final Manuscripts

Background: Hispanics utilize more aggressive medical treatment at the end of life and are less likely to receive end-of-life care consistent with their wishes than nonHispanic Whites. Hispanics are less likely than nonHispanic Whites to have an advance directive (AD). Increasing AD completion among Hispanics can promote end-of-life care consistent with their wishes, diminish healthcare disparities, and eliminate unnecessary healthcare spending. Objectives: To promote completion of advance directives by increasing knowledge, positive attitudes, and comfort with advance care planning (ACP) among Hispanics through culturally sensitive interventions. Intervention: The project was conducted in Spanish and implemented among a …

Value-Based Medicine: The Financial Impact Of A Pressure Ulcer Prevention Program On A Trauma Population, Jayme D. Lieberman Md, Patrick S. Duffy Md, Kai L. Bortz Rn, Rovinder S. Sandhu Md, Michael D. Pasquale Md, Facs, Fccm, Michael M. Badellino Md

Department of Surgery

No abstract provided.

Preop Evaluation/Post Operative Care (Nutrition, Pain Management), Malia Eischen Md, Meghan L. Good Md, Lung-Ching Lee Md

Department of Surgery

No abstract provided.

Amyotrophic Lateral Sclerosis, The Primary Motor Neuron Disease, Jacob P. Naumann

The Downtown Review: An Interdisciplinary Journal Written and Peer-Reviewed by Mandel Honors College Students at Cleveland State University

Amyotrophic lateral sclerosis is a degenerative neurological disease that damages nerve cells in the brain, in particular the neurons that are involved in voluntary muscle movements. Internationally the disorder is also known as Charcot’s disease and motor neuron disease. In the United States, amyotrophic lateral sclerosis is often referred to as Lou Gehrig’s disease, motor neuron disease, and more colloquially ALS. Amyotrophic Lateral Sclerosis is the most prominent of the five motor neuron diseases, distinguishing itself from the others through degeneration of both upper motor neurons (UMN) and lower motor neurons (LMN) respectively. The “Father of neurology” Jean-Marie Charcot founded …