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2. A Comparison of Resampling and Recursive Partitioning Methods in Random Forest for Estimating the Asymptotic Variance Using the Infinitesimal Jackknife

Author

Brokamp, Cole, Rao, MB, Ryan, Patrick, and Jandarov, Roman

Subjects
Statistics - Machine Learning
Abstract

The infinitesimal jackknife (IJ) has recently been applied to the random forest to estimate its prediction variance. These theorems were verified under a traditional random forest framework which uses classification and regression trees (CART) and bootstrap resampling. However, random forests using conditional inference (CI) trees and subsampling have been found to be not prone to variable selection bias. Here, we conduct simulation experiments using a novel approach to explore the applicability of the IJ to random forests using variations on the resampling method and base learner. Test data points were simulated and each trained using random forest on one hundred simulated training data sets using different combinations of resampling and base learners. Using CI trees instead of traditional CART trees as well as using subsampling instead of bootstrap sampling resulted in a much more accurate estimation of prediction variance when using the IJ. The random forest variations here have been incorporated into an open source software package for the R programming language.

Published
2017
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18. Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Author

Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, Fonseca F, Nicolau J, Koenig W, Anker SD, Kastelein JJP, Cornel JH, Pais P, Pella D, Genest J, Cifkova R, Lorenzatti A, Forster T, Kobalava Z, Vida-Simiti L, Flather M, Shimokawa H, Ogawa H, Dellborg M, Rossi PRF, Troquay RPT, Libby P, Glynn RJ, Novo S, Krum H, Varigos J, Siostrzonek P, Sinnaeve P, Gotcheva N, Yong H, Urina-Triana M, Milicic D, Vettus R, Manolis AJ, Wyss F, Sigurdsson A, Fucili A, Veze I, Petrauskiene B, Salvador L, Klemsdal TO, Medina F, Budaj A, Otasevic P, Lainscak M, Seung KB, Commerford P, Donath M, Hwang JJ, Kultursay H, Bilazarian S, East C, Forgosh L, Harris B, Ligueros M, Bohula E, Charmarthi B, Cheng S, Chou S, Danik J, McMahon G, Maron B, Ning M, Olenchock B, Pande R, Perlstein T, Pradhan A, Rost N, Singhal A, Taqueti V, Wei N, Burris H, Cioffi A, Dalseg AM, Ghosh N, Gralow J, Mayer T, Rugo H, Fowler V, Limaye AP, Cosgrove S, Levine D, Lopes R, Scott J, Hilkert R, Tamesby G, Mickel C, Manning B, Woelcke J, Tan M, Manfreda S, Ponce T, Kam J, Saini R, Banker K, Salko T, Nandy P, Tawfik R, O’Neil G, Manne S, Jirvankar P, Lal S, Nema D, Jose J, Collins R, Bailey K, Blumenthal R, Colhoun H, Gersh B, Abreu M, Actis MV, Aiub J, Aiub F, Albisu J, Alvarisqueta A, Avalos V, Barreto M, Berli MA, Blumberg C, Bocanera M, Botta C, Bowen L, Budassi N, Buhlman S, Westberg JC, Carabajal T, Caruso G, Casala J, Cendali G, Coloma G, Berra FC, Cuneo C, Degennaro N, Dellasa M, Diaz M, Dos Santos P, Espinosa V, Facello A, Facello M, Farias E, Fernandez AA, Ferrari V, Pacora FF, Flores GS, Franco M, Gabito A, Viola HG, Garcia F, Garcia Duran R, Garcia Pinna J, Glenny J, Godoy Sanchez M, Grosse A, Guzman P, Hasbani E, Hominal M, Ibañez J, Jure H, Jure D, Vico ML, Liniado G, Luciardi H, Luquez H, Maehara G, Maffei L, Majul C, Mallagray M, Marinaro S, Martinez J, Massaccesi R, De Los Milagros Had M, Azize GM, Montana O, Montenegro E, Morell Y, Muntaner J, Navarrete S, Olmedo M, Paganini M, Paz S, Perez Manghi F, Piskorz D, Polato C, Recoaro R, Romano A, Salinger M, Sanchez A, Saravia MA, Sarjanovich R, Scaro G, Schiavi LB, Soler J, Tinnirello V, Tomassi A, Valle M, Vallejo MA, Venturini C, Marcela Wenetz LM, Yossen M, Zaidman C, Zalazar L, Zangroniz P, Amerena J, Brady L, Colquhoun D, Eccleston D, Ferreira-Jardim A, French J, Jayasinghe R, Mcintosh C, Ord M, Plotz M, Purnell P, Roberts-Thomson P, Schultz C, Shanahan T, Tan R, Taverner P, Turner F, Vibert J, Vorster M, William M, Youssef G, Bergler-Klein J, Brath H, Brodmann M, Fliesser-Goerzer E, Haider K, Heeren G, Hiden C, Mandic L, Paulweber B, Ploechl A, Prenner A, Steringer-Mascherbauer R, Strohner-Kaestenbauer H, Barbato E, Bouvy C, Briké C, Charlier F, Cools F, De Knijf K, De Wolf L, Delforge M, Deweerdt N, Gits F, Goffinet C, Hermans K, Hollanders G, Mestdagh I, Pirenne B, Servaes V, Simons N, Tahon S, Theunissen E, Van Genechten G, Vervoort G, Vissers C, Vranckx P, Vrolix M, Abib E Jr, Abrantes J, Araujo Fonseca M, Barbosa E, Barroso W, Barroso A, Bodanese L, Botelho R, Costa Amorim R, Da Costa F, Da Silva A, Da Silva O Jr, Da Silva D Jr, Ferreira Dos Santos T, Dos Santos F, Dos Santos A, Duda N, Feitosa G, Felario Junior GA, Ferraz R, Filho P, Fonseca A, Wanderley FF, Freitas E, Fucci F, Marengo Garcia De Carvalho L, Hernandez M, Hettwer Magedanz E, Julião K, Kormann A, Lameira A, Lima F, Lino E, Maia L, Manenti E, Marchi AL, Fischer SM, Michalaros Y, Moraes J Jr, Moreira L, Pagnan M, Pesce F, Pinheiro L, Rassi S, Reis G, Reis H, Resende I, Roel A, Ruschel K, Saporito W, Saraiva JF, Seroqui M, Silva R, Unterkircher B, Vicente C, Vieira N, Xavier JP, Zucchetti C, Angelova I, Dimitrov G, Genova D, Gospodinov K, Goudev A, Grigorova V, Hristova K, Makedonska JJ, Katova T, Kostov K, Lazov P, Manov E, Manukov I, Manukov D, Milanova M, Kabakchieva VM, Petrov D, Petrusheva T, Pramatarova I, Raev D, Runev N, Sirakova-Taseva A, Tisheva-Gospodinova S, Todorova A, Tzekova M, Yakovova S, Yanev T, Abulencia K, Arora S, Baker A, Bata IR, Beaudry M, Belle Isle J, Bilodeau N, Boivin MC, Bolduc H, Bourgeois S, Brons S, Cantor W, Chaussé I, Chhabra A, Chouinard G, Cleveland T, Dattani D, Deslongchamps F, Diodati J, Drouin K, Duchesne L, Fontaine S, d'Amours DG, Gervais B, Gosselin G, Graham J, Grover A, Gupta A, Haldane H, Hartleib M, Hickey L, Huynh T, Johnston J, Julien VE, Lachance P, Lake J, Lamontagne C, Lauzon C, Lepage S, Maheux K, Manyari D, Martin E, McPherson C, Mehta S, Michaud N, Kouz SM, Murphy G, OKeefe D, Otis R, Ouimet F, Pandey S, Peck C, Perkins L, Richert L, Robbins K, Robinson S, Cabau JR, Ross B, Roy C, Roy M, Roy A, Rupka D, Affaki GS, Saunders K, Savard D, Soucy D, St Amour E, Thiessen S, Vertes G, Vezina M, Vincelli G, Weisnagel SJ, Zadra R, Chen J, Chen Y, Dong X, Feng Y, Feng Z, Fu G, Han B, Hao Y, He Y, He Z, Hong T, Jia Z, Jiang T, Jiang J, Jiang X, Ke Y, Li Y, Li Z, Li W, Li X, Liu P, Liu Y, Liu B, Liu S, Liu L, Lu Z, Lv Y, Ma C, Ma G, Peng L, Qing L, Ren L, Sang X, Song M, Sun Z, Wang J, Wang Y, Wei J, Wu W, Wu J, Xu H, Yan J, Yang P, Yang K, Yao Z, Yaoqing H, Yuan Z, Zhai Z, Zhang J, Zhang Y, Zhao R, Zhou H, Accini Mendoza JL, Aparicio CV, Castillo T, Chaverra I, Conrado Y, Coronel J, Cotes C, Cuentas I, Cuervo A, Dussan MA, Echeverria L, Hernandez E, Ibarra J, Isaza D, Jimenez D, Lopez P, Manzur F, Mejia I, Mendoza Y, Molina DI, Patino JM, Rodriguez D, Rodriguez LM, Rodriguez SM, Sanchez Vallejo G, Luz Serrano H, Sotomayor A, Urina M, Vesga B, Yupanqui H, Akrap B, Busic N, Ciglenecki N, Cmrecnjak J, Fucak E, Gabor M, Jeric M, Jutrisa N, Kordic K, Planinc I, Popovic Z, Radeljic V, Sesto I, Sutalo K, Tusek S, Belohlavek J, Budkova J, Busak L, Capova L, Cech V, Cermak O, Coufalova Z, Cyprian R, Dedek V, Dedkova S, Ferkl R, Hanak P, Hanustiakova A, Homza M, Horackova K, Houra M, Iveta H, Kaiserova L, Kala P, Karel I, Kellnerova I, Koleckar P, Kreckova M, Krupicka J, Lorenc Z, Machova V, Malik J, Masarikova L, Matyasek I, Mikus M, Mikusova T, Ondrasik J, Otava M, Palubova L, Pavlickova L, Peterka M, Petrova I, Pokorna B, Povolny P, Radvan M, Reznakova S, Rickova Z, Roszkowska P, Rotreklova M, Samkova D, Skalicka H, Slechticka A, Sternthal P, Telekes P, Tesak M, Vesely P, Vesely J, Vins P, Vitovec M, Vodnansky P, Zidova M, Keba E, Laane E, Pool T, Randvee L, Ratnik E, Reimand M, Reinmets S, Rivis L, Siemann M, Stern M, Toom M, Vahula V, Apel T, Axthelm C, Ayasse D, Ayasse M, Baar M, Baeumer A, Bagi ES, Becker B, Binder A, Blankenberg S, Braun P, Johansen BB, Contzen C, Delfonso F, Denecke C, Dengler T, Donaubauer T, Eichinger G, Englmann E, Erhard M, Faghih M, Foerster A, Frankenstein L, Fuchs R, Furch G, Gaeb-Strasas B, Germann H, Giese C, Goette A, Gravenhorst-Muenter U, Haege R, Haenel T, Hagemann D, Hagenow A, Hanefeld M, Heider J, Heisters J, Hennig D, Hielscher S, Himpel-Boenninghoff A, Holscher A, Hornig M, Jeserich M, Kaczmarek N, Kanitz S, Kara YD, Khariouzov A, Kiefer R, Kiroglu K, Klamm M, Klein C, Korth-Wiemann B, Krapivsky A, Kuenzler J, Kuntzsch A, Landers B, Lappo M, Laube S, Leggewie S, Lehmann D, Lepp H, Lierse T, Lindner C, Luecke-Uzar M, Luedemann J, Marschke T, Maruzzo S, Mauersberger K, Maus O, Meinrich M, Meissner A, Moehring B, Muehlhaus J, Mueller S, Muenter KC, Muenzel T, Naumann R, Nebel J, Neumann J, Nuding S, Overhoff U, Papke B, Pencz I, Peter Y, Peukert AM, Radde I, Rau T, Regner S, Reichenbach D, Reimer D, Rinke A, Roettges R, Romanski A, Rummel R, Samer H, Sanuri M, Sarnighausen HE, Schäfer B, Scheibner T, Schermaul KH, Schindler A, Schlundt C, Schmidt E, Schmidt K, Schnabel A, Schoen N, Schorn K, Schroeder T, Schulenburg D, Schulz M, Schulze U, Schulze J, Schumacher M, Schwerin G, Schwerin M, Stadelmeier S, Stahl HD, Stahl A, Stockhausen J, Stockhausen G, Stoessel J, Stolze K, Stratmann M, Szymanowski N, Teschner AB, Teske A, Uecker C, Veit S, Voeller H, Walter I, Walter J, Walther I, Weber HG, Weimer J, Wichterich K, Wiebusch A, Willmerdinger M, Willner C, Winkelmann B, Winkler J, Wistuba T, Woehrle J, Wohnlich T, Wolf S, Woyczak D, Wrage P, Zirlik A, Anadiotis A, Chachalis G, Dermitzakis A, Kafarakis P, Kaldara E, Kolokathis F, Kostakou P, Lekakis J, Manolis A, Mantas I, Megalou A, Milkas A, Nanas J, Olympios CD, Patsilinakos S, Perperis A, Poulimenos L, Saloustros I, Tsioufis K, Tsorbatzoglou K, Vardas P, Zarifis I, Aguilar M, Arango JL, Borrayo NA, Corona V, Guerrero A, Guzman I, Haase F, De Krumbach L, Montenegro P, Munoz R, Munoz N, Paniagua A, Solares A, Vogel M, Anita S, Blazsek Z, Decsi K, Fulop T, Hangyal T, Hegedus V, Kalina A, Karakai H, Katona A, Kiss RG, Kovacs A, Laszlo Z, Lupkovics G, Medvegy M, Merkely B, Mihaly N, Nagy AC, Dékány JN, Nikoletta P, Noori E, Penzes J, Poor F, Sarszegi Z, Simay A, Simon J, Szakal I, Szatmarine V, Szocs A, Zilahi Z, Karsai XZ, Andersen K, Sigurdadottir E, Skuladottir F, Abdullakutty J, Abhaichand R, Abhyankar A, Agarwal DK, Aggarwal RK, Ahire N, Awasthi AK, Babu R, Bai A, Bali HK, Banker D, Bhadade S, Bisne V, Bohra P, Raghu C, Chauhan D, Chauhan H, Chavada J, Chaware G, Chella S, Chintala P, Dash D, Desai D, Devasia T, Dhanak R, Dobariya H, Dudhatra N, Duhan S, Fulwani M, Ghondale N, Ghosh S, Gohel P, Govindaraj D, Goyal B, Goyal S, Gundala AK, Gupta M, Hardas S, Iby M, Jagtap P, Jain A, Joshi U, Karpuram M, Kaur H, Khan A, Khan R, Kodem DR, Koeitti P, Kulkarni L, Kullal P, Kumar KS, Kumbla M, Latheef K, Lohkare M, Santosh MJ, Makhe B, Mandati M, Mehta A, Minocha G, Mittal A, Modi R, Mohan K, Oomman A, Pai R, Pai V, Palaniswami N, Pansheriya A, Parekh N, Patel J, Patel R, Patole T, Praveen M, Radhakrishnan V, Rajan B A, Rajasekhar D, Rao M, Rao MB, Rao NM, Rathnavel S, Rathore A, Rathore SRS, Rawat S, Reddy NC, Sarma R, Sathe S, Shah J, Shaikh P, Sharma K, Sharma S, Sharma T, Shetty P, Sidhu G, Singh V, Sohi GS, Srinath VS, Raju SS, Taran A, Thakkar B, Velusamy K, Vijan V, Vora V, Vuriya AK, Agosta GF, Antonicelli R, Ardissino D, Argiolas G, Baldin MG, Benedetti G, Berti S, Bevilacqua MT, Bolognesi MG, Dessalvi CC, Calabrese A, Campanale EG, Candusso R, Caso P, Cosmi F, Crea F, Crocamo A, De Caterina R, De Rosa S, Destro M, Di Biase M, Dognini GP, Eleuteri E, Fedele F, Ferrario M, Gabrielli D, Gamba C, Ganau A, Gravellone M, Iannopollo G, Indolfi C, Infusino F, Invitti C, Landolfi A, Lembo G, Liberato NL, Mannucci E, Marino P, Mariottoni B, Marziali A, Mercuro G, Monti L, Mos L, Mureddu V, Musumeci MB, Panzarino C, Parente A, Perotti M, Filardi PP, Petrillo C, Piatti P, Priori S, Racca V, Ragghianti B, Renda G, Righini V, Sarcone M, Senni M, Soro E, Tamburrini P, Vallone L, Villani GQ, Volpe M, Ajioka M, Akai Y, Ashino K, Baden M, Doi M, Eki Y, Endo T, Fukuike C, Hagiwara Y, Hasegawa K, Higuchi Y, Higuchi T, Hioki M, Hirayama A, Hiroma J, Hosokawa S, Ichisawa M, Iijima T, Inada T, Inagaki M, Ito K, Kaigawa K, Kajihara S, Kamiya H, Kamiya J, Kaneno Y, Katahira K, Kataoka M, Kawai M, Kawasaki T, Kojima E, Komura Y, Kuramochi T, Kuruma T, Kyo E, Mani H, Miyamoto T, Morii I, Morinaga Y, Morisawa T, Nagai Y, Naka T, Nakamura Y, Nakamura S, Nakayoshi K, Nishibe A, Ogawa M, Okada Y, Okawa M, Sakamoto Y, Sakurada M, Sasaki S, Seki S, Shimomura H, Shinozaki T, Sugimoto N, Suzuki A, Taguchi S, Takahashi J, Takase S, Tanabe K, Tanaka A, Tani S, Tomioka J, Tsuboi H, Tsuji M, Tsujita K, Tsujiyama S, Umesu A, Yamada T, Yamaguchi E, Yamamoto H, Yamamoto T, Yamane M, Yanase T, Yasuoka S, Yasutake M, Yokoyama M, Yoshida M, Yoshimoto E, Yunoki C, Balode A, Dormidontova G, Flaksa I, Nagele-Luse I, Rancane G, Sime I, Bartuseviciene S, Cepinskiene L, Dobilas V, Grigaraviciene I, Marcinkeviciene J, Mazutavicius R, Miliuniene R, Motiejuniene R, Norkiene S, Norkute-Macijauske U, Rudys A, Slapikas R, Stonkute K, Strazdiene D, Tijuneliene E, Urbonas G, Vanagiene S, Viezelis M, Arenas Leon JL, Bayram E, Carrillo J, Davalos C, De Los Rios M, Delgadillo T, Hernández N, Leon S, Mendoza N, Muñoz W, Ramos G, Anneveldt A, Bakker H, Brouwer M, Bunschoten P, De Boer P, De Jong C, De Vos A, Den Hartog F, Doesborg L, Dommerholt R, Drost I, Ellenbroek D, Engelen W, Folkeringa RJ, Hamer BJB, Herrman JP, Hoogslag PAM, Jansen M, Jerzewski A, Joosten C, Kalkman C, Kietselaer B, Kok M, Kooiman E, Kose V, Lardinois R, Lenderink T, Lok DJA, Lousberg A, Meijlis P, Mulder R, Singerling M, Smeele F, Stroes E, Swart HP, Ten Holt W, Van Der Wal M, Van Der Zwaan C, Van Kempen WW, Van Maarseveen M, Van Stein I, Viergever EP, Visseren FLJ, Voors C, Nugteren SKZ, Ata B, Berulfsen A, Rønnevik TD, Dickstein K, Furuseth B, Grundtvig M, Hansen H, Hofsoey K, Høivik HO, Bøen RH, Hurtig U, Pettersen KI, Johansen E, Kleve R, Kolleroy C, Moen S, Nilsen V, Norin V, Otterstad JE, Risberg K, Rønnevik P, Sirnes PA, Skjelvan G, Strand S, Szacinski G, Vegsundvåg J, Alcalde JM, Gomez Sanchez J, Rodriguez J, Rodriguez A, Zena N, Baszak J, Cymerman K, Czerski T, Fratczak M, Jaguszewska G, Kawka-Urbanek T, Koba M, Kopaczewski J, Kopczyńska M, Laniec M, Lysek R, Sciborski R, Szpajer M, Torun A, Wujkowski M, Zielinski M, Ahn Y, Baek C, Bang SA, Chang K, Choi AJ, Han S, Hyun K, Kim M, Kim KS, Kim B, Lee SH, Lee J, Lee HN, Lee JH, Lee KR, Moon K, Park B, Park C, Tahk S, Yim KH, Yim S, Tase T, Andor M, Aron G, Badea C, Casoinic F, Clocotan M, Coman S, Emil B, Imre BS, Istratoaie O, Liviu C, Maximov D, Militaru C, Minescu B, Istvan KP, Parepa I, Petrescu L, Podoleanu C, Pop CF, Popa V, Popescu E, Radoi M, Sarbu I, Socoteanu E, Socoteanu G, Sorodoc L, Spiridon M, Stanciulescu G, Stefanescu M, Tanaseanu C, Tudoran M, Zdrenghea D, Agafina A, Akatova E, Avdonina N, Balukova E, Barbarash OL, Bartosh L, Boyarkin M, Bulashova O, Burova N, Churina S, Demidova M, Dorogova I, Dovgalevskiy Y, Dovgolis S, Dudarev M, Fitilev S, Gapon L, Gazizianova V, Gordeev I, Ivanov I, Izmozherova N, Kazanskay E, Khirmanov V, Khromtsova O, Konradi A, Kosmacheva E, Kozlova S, Kulibaba E, Kuzin A, Libov I, Lipchenko A, Lozhkina N, Malchikova S, Morozov E, Myslyaeva L, Onuchina E, Palatkina T, Panov A, Parmon E, Petelina T, Repin A, Reznik I, Sazonova E, Sergienko T, Shaposhnik I, Shapovalova Y, Shustov S, Shvarts Y, Skopets I, Skuratova M, Smolenskaya O, Solovev O, Trofimov V, Vasiliev M, Vezikova N, Vozzhaev A, Yakushin S, Zadionchenko V, Apostolovic S, Adjic NC, Ilic I, Ilic S, Nikolic L, Pupic L, Stokuca-Korac N, Antalik L, Bugan V, Csala L, Dokupilova A, Dzupina A, Forgon T, Fulop P, Gonsorcik J, Gyorgyova E, Holoubek D, Horvat P, Kamensky G, Kolikova V, Krupciakova B, Lenner E, Lennerova J, Lukac J, Majercak I, Mancikova I, Micko K, Nociar J, Pales J, Palka J Jr, Poliacik P, Ruffini L, Sabo L, Skubova K, Slanina M, Smik R, Srdos V, Stitova M, Stofkova D, Strbova J, Such S, Toth P, Urgeova L, Vinanska D, Zareczky P, Flezar M, Kovacic D, Marcun R, Zagozen P, Bolsmann C, Conradie C, Dawood SY, Decsi KL, Ebrahim I, Henley L, Horak A, Kapp I, Komati S, Lock E, Maboyi S, Makotoko E, Manga P, Page A, Ramdas S, Ranjith N, Roos J, Talliard C, Ajax K, Al-Khalili F, Assarsson E, Bergholtz T, Blom KB, Boman K, Boström PÅ, Curiac D, Jensen ED, Dahlen G, Davidsson K, Duckert A, Hansson A, Härstedt N, Henriksson A, Olsson GH, Johansson K, Jonsson JE, Knutsson A, Lindholm CJ, Lönnberg I, Lundqvist M, Mellberg L, Moodh J, Mooe T, Olofsson M, Risenfors M, Rönndahl M, Sundelin R, Suorra I, Torgersruud M, Torstensson I, Chang KC, Chen CP, Chen ZC, Chen MH, Cheng SM, Cheng JJ, Fang CY, Ho CJ, Hsieh IC, Huang PH, Huang A, Kuo JY, Lai WT, Lee SC, Li YH, Lin T, Liu HM, Tsai MC, Tsao HM, Tzong L, Ueng KC, Wang YL, Wang HC, Wang CP, Yang CC, Abaci F, Birdane A, Yilmaz MB, Asim Oktay AO, Kan G, Koldas N, Ozcan IT, Sahin M, Sahin T, Saka B, Tekten T, Ucar N, Uresin S, Yigit Z, Arif I, Bakhai A, Baksi A, Blagdon M, Brickman T, Brown N, Burton M, Burton J, Chaggar S, Chung A, Collier D, Covell W, Crawford G, Davies N, Davies M, Dayer M, Doughty A, Duff J, Dwenger E, Fisher J, Fitzpatrick L, Garner K, Glover J, Haughton G, Ilsley M, Ivan P, Voyzey EJ, Keenan S, Kelt T, Knight J, 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Lee J, Lee HN, Lee JH, Lee KR, Moon K, Park B, Park C, Tahk S, Yim KH, Yim S, Tase T, Andor M, Aron G, Badea C, Casoinic F, Clocotan M, Coman S, Emil B, Imre BS, Istratoaie O, Liviu C, Maximov D, Militaru C, Minescu B, Istvan KP, Parepa I, Petrescu L, Podoleanu C, Pop CF, Popa V, Popescu E, Radoi M, Sarbu I, Socoteanu E, Socoteanu G, Sorodoc L, Spiridon M, Stanciulescu G, Stefanescu M, Tanaseanu C, Tudoran M, Zdrenghea D, Agafina A, Akatova E, Avdonina N, Balukova E, Barbarash OL, Bartosh L, Boyarkin M, Bulashova O, Burova N, Churina S, Demidova M, Dorogova I, Dovgalevskiy Y, Dovgolis S, Dudarev M, Fitilev S, Gapon L, Gazizianova V, Gordeev I, Ivanov I, Izmozherova N, Kazanskay E, Khirmanov V, Khromtsova O, Konradi A, Kosmacheva E, Kozlova S, Kulibaba E, Kuzin A, Libov I, Lipchenko A, Lozhkina N, Malchikova S, Morozov E, Myslyaeva L, Onuchina E, Palatkina T, Panov A, Parmon E, Petelina T, Repin A, Reznik I, Sazonova E, Sergienko T, Shaposhnik I, Shapovalova Y, Shustov S, Shvarts Y, Skopets I, Skuratova M, Smolenskaya O, Solovev O, Trofimov V, Vasiliev M, Vezikova N, Vozzhaev A, Yakushin S, Zadionchenko V, Apostolovic S, Adjic NC, Ilic I, Ilic S, Nikolic L, Pupic L, Stokuca-Korac N, Antalik L, Bugan V, Csala L, Dokupilova A, Dzupina A, Forgon T, Fulop P, Gonsorcik J, Gyorgyova E, Holoubek D, Horvat P, Kamensky G, Kolikova V, Krupciakova B, Lenner E, Lennerova J, Lukac J, Majercak I, Mancikova I, Micko K, Nociar J, Pales J, Palka J Jr, Poliacik P, Ruffini L, Sabo L, Skubova K, Slanina M, Smik R, Srdos V, Stitova M, Stofkova D, Strbova J, Such S, Toth P, Urgeova L, Vinanska D, Zareczky P, Flezar M, Kovacic D, Marcun R, Zagozen P, Bolsmann C, Commerford P, Conradie C, Dawood SY, Decsi KL, Ebrahim I, Henley L, Horak A, Kapp I, Komati S, Lock E, Maboyi S, Makotoko E, Manga P, Page A, Ramdas S, Ranjith N, Roos J, Talliard C, Ajax K, Al-Khalili F, Assarsson E, Bergholtz T, Blom KB, Boman K, Boström PÅ, Curiac D, Jensen ED, Dahlen G, Davidsson K, Duckert A, Hansson A, Härstedt N, Henriksson A, Olsson GH, Johansson K, Jonsson JE, Knutsson A, Lindholm CJ, Liu B, Lönnberg I, Lundqvist M, Mellberg L, Moodh J, Mooe T, Olofsson M, Risenfors M, Rönndahl M, Sundelin R, Suorra I, Torgersruud M, Torstensson I, Chang KC, Chen CP, Chen ZC, Chen MH, Cheng SM, Cheng JJ, Fang CY, Ho CJ, Hsieh IC, Huang PH, Huang A, Hwang JJ, Kuo JY, Lai WT, Lee SC, Li YH, Lin T, Liu HM, Tsai MC, Tsao HM, Tzong L, Ueng KC, Wang YL, Wang HC, Wang CP, Yang CC, Abaci F, Birdane A, Yilmaz MB, Asim Oktay AO, Kan G, Koldas N, Ozcan IT, Sahin M, Sahin T, Saka B, Tekten T, Ucar N, Uresin S, Yigit Z, Arif I, Bakhai A, Baksi A, Blagdon M, Brickman T, Brown N, Burton M, Burton J, Chaggar S, Chung A, Collier D, Covell W, Crawford G, Davies N, Davies M, Dayer M, Doughty A, Duff J, Dwenger E, Fisher J, Fitzpatrick L, Garner K, Glover J, Haughton G, Ilsley M, Ivan P, Voyzey EJ, Keenan S, Kelt T, Knight J, Kondagunta V, Lang C, Lee K, Lim L, Macdonald J, Mathew A, Mckenzie A, Mckibbin A, Michalska A, Pagett K, Pogson A, Price R, Price D, Procter K, Pye M, Redfearn H, Rewbury J, Ryding A, Sattar N, Sharp A, Shaw P, Simpson H, Smith W, Squire I, Storey R, Teenan M, Thomas H, Townend J, Trevelyan J, Wakeling J, Walukiewicz P, Wilkinson S, Zaman A, Acevedo L, Benton J, Abbate A, Aboufakher R, Acampora M, Acampora D, Aceto L, Acevedo B, Acheatel R, Adams M, Adams A, Ahmad I, Ahmed SH, Aish B, Akyea-Djamson A, Al Joundi T, Alcide P, Alfieri A, Alfonso T, Alfrey A, Allen J, Alllison DC, Almaliky T, Amos A, Angiolillo D, Antolick A, Ara M, Aragorn L, Arevalo S, Armas E, Arthur A, Asafu-Adjaye N, Ashcom T, Ashford M, Aslam A, Ather N, Atieh M, Aull L, Ayala M, Azizad M, Backer T, Baehl S, Bailey S, Bair S, Baker C, Ballmajo M, Pieretti HB, Baquero A, Barnett S, Baron S, Bartkowiak A, Bashir K, Beall K, Beauregard LA, Sarah S, Beckett L, Belejchak P, Bendelow T, Bender D, Benjamin S, Berdoff R, Berger V, Bergeron P, Berk M, Bernstein M, Binns Y, Bitzer V, Blahey M, Bloch S, Bluemel J, Boffetti P, Boley K, Bonner J, Boudreaux R, Boulanger K, Bradley A, Bramlet D, Bredlau C, Briggs S, Brousalis L, Brown S, Brown C, Buchannan C, Burke W, Burley T, Burton C, Burtt D, Byars W, Caballero-Valiente B, Carr K, Halliwell TC, Castillo J, Cei L, Cerda L, Chambers J, Chamblee T, Chattin W, Chee L, Chen YC, Cherlin R, Cheung D, Chiodi L, Christensen L, Christenson S, Cislowski D, Clavier-Firmin C, Colfer H, Colvin T, Cosgrove N, Covert C, Cox B, Cox R, Craig W, Crandall L, Crepps K, Cromer M, Cruz H, Cruz H, Cruz M, Cucher F, Damron M, Dave K, Dave B, Davis M, Davis B, Dawkins-Hughes S, Dean J, Debnam S, Defosse C, Dehning M, Dela Llana A, Dellorso M, Denham D, Desalle D, Dettmer M, Dhawan M, Diago M, Dicken T, Diederich C, Diederich M, Diehl R, Digangi D, Diller P, Dimattia M, Dodds G, Doggett J, Donahue K, Doughty L, Dragutksy B, Dreese M, Dunhurst F, Dunn D, Dutka C, Earl J, Eaton C, Eaves W, Ebeling K, Eder F, Edgerton L, Edillo C, Edwards J, Edwards T, Einhorn D, El Hafi S, Ellis M, Erickson B, Ervin W, Eskridge L, Fail P, Falcon D, Fang C, Fattal P, Fawson A, Felix L, Ferdinand K, Fien E, Fintel D, Firek C, Fitz-Patrick D, Flores E, Flores E, Flores H, Floro T, Forker A, Foster M, Foucauld J, Lehman KF, Fox B, Francoeur L, Frandsen B, Frandsen B, Frivold G, Fruchter G, Fullerton D, Gabriel J, Gacioch G, Garas S, Garcia N, Garcia Rinaldi R, Garcia-Fragoso V, Garcia-Portela M, Gelb R, George F, Ghali J, Gilbert J, Gilley J, Glancy R, Goff R, Goldberg N, Gonzales D, Gonzales V, Gonzalez E, Gorges R, Gould R, Grabeau R, Grable M, Graham JA, Graif J, Green E, Greener R, Greenway F, Grieshaber V, Griffin S, Gros C, Gudipati RVC, Guillinta P, Gupta V, Gutmann J, Gwyn M, El Hachem M, Hage F, Hageman T, Haidar A, Hakas J, Haldis T, Hall L, Hall C, Hall S, Halpern S, Hamud-Socoro A, Hardee L, Harrell W, Harrington A, Hartwell J, Hasan F, Hattler B, Haught H, Haynes E, Haywood A, Heaney L, Hecht J, Hernandez I, Herzog W, Hess E, Hill H, Hilton T, Hinderaker P, Hodnett P, Hoffman M, Hogan C, Holmes Z, Rees DH, Hotchkiss D, Huang P, Humbert J, Hutchens E, Iachini K, Ibarra M, Igbokidi O, Ilahi T, Imbrognio M, Ipp E, Iteld B, Jacques G, Jafri A, Jafry B, Jardula M, Jefferson D, Jenkins R, Johnson E, Johnson J, Jones S, Kawahara M, Kelehan S, Kelly R, Kendall T, Kereiakes D, Khan M, Khan S, Kick J, Kimmel M, King T, King A, Kirkland S, Kissel S, Kitchens D, Klein P, Klugherz B, Korban E, Koren M, Korte M, Kostis J, Kotek L, Kozak M, Kreutter F, Kusnick B, Labovitz R, Lail J, Lamance J, Lamas G, Lambert J, Lambert C, Landzberg J, Langdon J, Lavoie W, Ledger G, Lee T, Lee K, Lehman R, Leimbach W, Lennard M, Lepor N, Lester F, Levin P, Levinson L, Lewis D, Lillo J, Link L, Long C, Longaker R, Lorch G, Lucksinger G, Lynd S, Rhudy JM, Madder R, Magness K, Maheshwari A, Alan A, Malek M, Maletz L, Malhotra V, Malhotra S, Mandviwala M, Mani CK, Manuel J, Marchelletta N, Marshall L, Marsters M, Martin L, Martinez E, Mavromatis K, Maynard R, Mays M, Mays B, Mbulaiteye A, Mcalister R, Mccoy C, Mccrary D Jr, Mccullough-O'Brien H, Mcdonald M, Mcgill J, Mcgrew F, Mckenzie C, Mclaurin B, Mclellan BA, Mcneil D, Mcneill R, Mehrle A, Melbie K, Melliza T, Messina T, Meyer R, Michel K, Mikdadi G, Miller C, Miller R, Miller A, Miller G, Miller W, Mitchell J, Moats DJR, Mody F, Moffat J, Molk B, Molter D, Monroe T, Montero H, Montgomery R, Mookherjee D, Moran J, Moriarty P, Morrison J, Morton D, Moshayedi P, Mosley J, Moustafa M, Munshi K, Murray A, Mustafa J, Nadar V, Naidu R, Nalley J, Navy S, Neil L, Neutel JM, Niblack P, Nicely V, Nicolai M, Nijmeh G, Nikas A, Nikyar A, Nixon S, Norman L, Noto G, Nour K, Nugent A, Ocman B, Odegard A, Olsen S, Ortiz-Carrasquillo R, Ossino N, Paez H, Palchick B, Paliwal Y, Pannell R, Parfait V, Partridge J, Patel B, Patel R, Patel M, Patel S, Paysor C, Pena A, Pereira S, Perez M, Perez A, Perkins H, Perry B, Peters P, Phillippi C, Phillips A, Phillips A, Piacente R, Pintado M, Pish R, Pitt W, Poling T, Pomposini D, Poock J, Potts J, Poudrier R, Prior J, Pritchard C, Purighalla R, Quddusi K, Quinones J, Quinton D, Radin M, Radojcsics B, Rajput B, Rama B, Ramos M, Rauch R, Raynes K, Reber AM, Reddy J, Reeves M, Reilly K, Renaud K, Resnick H, Reyes R, Richardson M, Riethof M, Riser J, Rodero M, Rodriguez Araya E, Roper L, Rozeman P, Ruder D, Runquist L, Sack G, Saint-Jacques H, Salfity M, Sall N, Sam K, Samal A, Sanchez D, Santiago J Jr, Savignano C, Saylor R, Scheffel M, Schifferdecker B, Schindler E, Schneider P, Schneider R, Schnitzler R, Schrager B, Schwartz A, Scott R, Seals A, Shah AV, Shah A, Shatsky K, Shayani S, Shealy N, Sheets L, Shelley J, Shepard P, Shetty S, Silver K, Simon M, Singh K, Singh N, Sizemore BC, Skatrud L, Slayton C, Slimak V, Sloane G, Smallwood B, Smith P, Smith M, Smith T, Smith G, Smith B, Smith W, Smith M, Smith J, Smith J, Soca Y, Sofley C, Sopko K, Sosa-Padilla M, Sotolongo R, Sprinkle B, Srivastava S, Starzec M, Steinhoff J, Stelly L, Stinson J, Stoddard M, Stoltz S, Stone B, Stover T, Strain J, Strugatsky S, Stys T, Suleman A, Sullivan P, Tamez W, Tandon N, Teltser M, Terry PS, Terry K, Tessmar C, Thekkoott D, Thomas D, Thomas DM, Thompson E, Thompson J, Thornton A, Tjaden T, Tobias C, Topper J, Tran A, Treasure C, Trenkamp P, Trevino M, Tsou L, Tuholske C, Uy W, Vahtel M, Vaid B, Valenzuela M, Vance A, Vandam J, Vanhecke T, Vanness WC III, Vargas R, Vaz S, Vazquez Tanus J, Veerina K, Vega J, Vento A, Vijay N, Voelker F, Vogt E, Vold D, Vora K, Wade RD, Wadell C, Waksman R, Walker K, Walker K, Wallace K, Warren M, Washam M, Watson B, Webel R, Wells T, West M, Whitaker J, White J, White C, White A, White A, Wilhoit G, Wilkins M, Willingham K, Wilson S, Wilson V, Wise J, Woodall S, Woods A, Wright J, Wu J, Xu ZJ, Yarows S, Young A, Younis L, Zarate J, Zebrack J, Zhang W, Zieve F, Zineldine A, Ridker, P. M., Everett, B. M., Thuren, T., Macfadyen, J. G., Chang, W. H., Ballantyne, C., FONSECA E PIRES, CARLOS EDUARDO, Nicolau, J., Koenig, W., Anker, S. D., Kastelein, J. J. P., Cornel, J. H., Pais, P., Pella, D., Genest, J., Cifkova, R., Lorenzatti, A., Forster, T., Kobalava, Z., Vida-Simiti, L., Flather, M., Shimokawa, H., Ogawa, H., Dellborg, M., Rossi, P. R. F., Troquay, R. P. T., Libby, P., Glynn R., J, CANTOS Trial, Group, Perrone, Filardi, P, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, ACS - Pulmonary hypertension & thrombosis, and ACS - Atherosclerosis & ischemic syndromes

Subjects
0301 basic medicine, 030204 cardiovascular system & hematology, law.invention, 0302 clinical medicine, c-reactive protein, Randomized controlled trial, law, Cardiovascular Disease, middle aged, double-blind method, antibodies, Myocardial infarction, humans, Stroke, interleukin-1beta, biology, Antibodies, Monoclonal, drug, General Medicine, Lipid, Aged, anti-inflammatory agents, monoclonal, humanized, atherosclerosis, cardiovascular diseases, dose-response relationship, female, incidence, infections, lipids, male, myocardial infarction, neutropenia, secondary prevention, stroke, Anti-Inflammatory Agent, aged, Editorial, Atherosclerosi, Monoclonal, Human, medicine.drug, medicine.medical_specialty, Neutropenia, Antibodies, Monoclonal, Humanized, Infections, Placebo, antibodies, monoclonal, dose-response relationship, drug, infection, medicine (all), 03 medical and health sciences, Internal medicine, medicine, Dose-Response Relationship, Drug, business.industry, Antiinflammatory Therapy, Canakinumab, for Atherosclerotic Disease, C-reactive protein, medicine.disease, Surgery, Canakinumab, 030104 developmental biology, biology.protein, business
Abstract

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.)

Published
2017

20. Procedural Sedation and Analgesia in Emergency Department: A Review and Update

Author

Upadhyay Sp, Rao Mb, Singh Ak, Varma M, and Mallick Np

Subjects
medicine.medical_specialty, business.industry, medicine.drug_class, Sedation, medicine.medical_treatment, 030208 emergency & critical care medicine, Emergency department, Emergency procedure, Advanced life support, 03 medical and health sciences, 0302 clinical medicine, Sedative, Procedural sedation and analgesia, Medicine, Airway management, 030212 general & internal medicine, medicine.symptom, business, Adverse effect, Intensive care medicine
Abstract

Procedural sedation and analgesia is one of the common clinical practices in the emergency department. The level of sedation must be adjusted in such a way that it allows patient to tolerate unpleasant procedures while maintaining normal physiologic reflexes and consciousness and able to understand and respond to verbal or light tactile stimulus. Although drugs used for procedural sedation has wide margin of safety but inappropriate monitoring or dosing may cause serious adverse event. Procedural sedation in emergency department is not without risk. Proper monitoring; provision of readily available access to resuscitation facility and continuous presence of trained staffs capable for airway management and providing advanced life support measure contributes reduction in adverse outcome. Pre-procedural evaluation is done to screen for suitability for procedural sedation and assesses the risk factors. Patients with full stomach, difficult airway or significant medical illness requiring more than mild sedation, alternative to procedural sedation should be considered. Clinician performing procedural sedation should have through knowledge of action, dose, side effects and antidote of commonly used sedative analgesics. Newer and innovative techniques have been evolved recently including transmucosal, Tran’s nasal, inhalation anaesthetic, patient controlled sedation, target controlled sedation. All patients after procedural sedation should be monitored in a designated recovery area and should not be discharged until they meet all the discharge criteria and while sending home, proper written discharge instruction should be provided to all.

Published
2016

27. Studies on the site and mechanism of action of phenformin. I. Evidence for significant 'nonperipheral' effects of phenformin on glucose metabolism in normal subjects

Author

Hollobaugh Sl, Rao Mb, and Kruger Fa

Subjects
Drug, Adult, Male, medicine.medical_specialty, Intravenous Glucose Tolerance, Endocrinology, Diabetes and Metabolism, media_common.quotation_subject, Phenformin, Carbohydrate metabolism, chemistry.chemical_compound, Internal medicine, Insulin response, Intestine, Small, Internal Medicine, Medicine, Humans, Inhibitory effect, media_common, business.industry, Glucose Tolerance Test, Endocrinology, Glucose, chemistry, Mechanism of action, Intestinal Absorption, Intravenous glucose, Injections, Intravenous, Female, medicine.symptom, business
Abstract

Oral and intravenous glucose tolerance tests were performed in ten normal subjects. Phenformin pretreatment flattened the glucose and insulin response to oral glucose loading but did not significantly alter the response to intravenous glucose. It is suggested that these results can best be explained by an inhibitory effect of the drug on the rate of intestinal glucose absorption.

Published
1970

28. Robust identification of environmental exposures and community characteristics predictive of rapid lung disease progression.

Author

Peterson CJ, Rao MB, Palipana A, Manning ER, Vancil A, Ryan P, Brokamp C, Kramer E, Szczesniak RD, and Gecili E

Subjects
Humans, Female, Male, Retrospective Studies, Adolescent, Child, Young Adult, Disease Progression, Air Pollution statistics & numerical data, Longitudinal Studies, Cystic Fibrosis, Lung Diseases epidemiology, Air Pollutants analysis, Environmental Exposure statistics & numerical data, Bayes Theorem
Abstract

Environmental exposures and community characteristics have been linked to accelerated lung function decline in people with cystic fibrosis (CF), but geomarkers, the measurements of these exposures, have not been comprehensively evaluated in a single study. To determine which geomarkers have the greatest predictive potential for lung function decline and pulmonary exacerbation (PEx), a retrospective longitudinal cohort study was performed using novel Bayesian joint covariate selection methods, which were compared with respect to PEx predictive accuracy. Non-stationary Gaussian linear mixed effects models were fitted to data from 151 CF patients aged 6-20 receiving care at a CF Center in the midwestern US (2007-2017). The outcome was forced expiratory volume in 1 s of percent predicted (FEV1pp). Target functions were used to predict PEx from established criteria. Covariates included 11 routinely collected clinical/demographic characteristics and 45 geomarkers comprising 8 categories. Unique covariate selections via four Bayesian penalized regression models (elastic-net, adaptive lasso, ridge, and lasso) were evaluated at both 95 % and 90 % credible intervals (CIs). Resultant models included one to 6 geomarkers (air temperature, percentage of tertiary roads outside urban areas, percentage of impervious nonroad outside urban areas, fine atmospheric particulate matter, fraction achieving high school graduation, and motor vehicle theft) representing weather, impervious descriptor, air pollution, socioeconomic status, and crime categories. Adaptive lasso had the lowest information criteria. For PEx predictive accuracy, covariate selection from the 95 % CI elastic-net had the highest area under the receiver-operating characteristic curve (mean ± standard deviation; 0.780 ± 0.026) along with the 95 % CI ridge and lasso methods (0.780 ± 0.027). The 95 % CI elastic-net had the highest sensitivity (0.773 ± 0.083) while the 95 % CI adaptive lasso had the highest specificity (0.691 ± 0.087), suggesting the need for different geomarker sets depending on monitoring goals. Surveillance of certain geomarkers embedded in prediction algorithms can be used in real-time warning systems for PEx onset., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Published
2024
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29. Vaping: The Key to Quitting Cigarettes or a Gateway to Addiction?

Author

Hill JE, Rao MB, and Guan T

Subjects
Humans, Adolescent, Male, Female, Cross-Sectional Studies, Surveys and Questionnaires, Smoking Cessation psychology, Smoking Cessation statistics & numerical data, Smoking Cessation methods, Electronic Nicotine Delivery Systems statistics & numerical data, United States epidemiology, Adolescent Behavior psychology, Logistic Models, Vaping psychology, Vaping epidemiology
Abstract

Background and Objectives : In 2022, the Centers for Disease Control and Prevention (CDC) discovered that 2.55 million middle and high school students were using electronic cigarettes (e-cigarettes) in the US alone. E-cigarettes allow people to inhale a nicotine solution (e-liquid) into their bodies. While e-cigarettes are often advertised as a way to help people quit traditional tobacco products, the World Health Organization (WHO) has stated that there is no proof of e-cigarettes being effective at reducing an individual's tobacco use. The objective of this study is to determine why adolescents start smoking e-cigarettes. Materials and Methods : For the following study, the National Youth Tobacco Survey (NYTS) 2021 was used. This is a nationally representative cross-sectional survey that includes middle and high school students. The data were analyzed using SAS v.9.4. The odds ratio for smoking e-cigarettes was evaluated for both sex and race via a logistic regression. Results : It was discovered that the percentage of only e-cigarette smokers (12.10%) was 5.5 times the percentage of only traditional smokers (2.19%). Additionally, the median age at which adolescents started smoking e-cigarettes was fifteen years with an IQR (Inter Quartile Range) of two. We used a logistic regression to show that biological sex and race were significant predictors of e-cigarette usage. Conclusions : In general, we saw that adolescents were mostly starting to smoke e-cigarettes because their friends were doing it, out of curiosity, they were depressed or anxious, and/or to get a "high", implying that adolescents mostly started smoking in order to fit in and/or to numb themselves. Interestingly, reasons like cost, using them to quit smoking, seeing them in the media, and ease of attainment were ranked the lowest when it came to smoking e-cigarettes. However, their lower costs naturally lead to increased accessibility compared to traditional cigarettes, making them easier to reach the hands of teenagers. Overall, in this paper, we aim to identify if adolescents are choosing e-cigarettes as their first foray into tobacco products and why.

Published
2024
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30. A risk stratification analysis of atherosclerotic cardiovascular disease events post-statin discontinuation in patients who underwent sleeve gastrectomy or Roux-en-Y gastric bypass bariatric/metabolic surgeries.

Author

Alsuhibani AA, Al-Kadi A, Wigle PR, Guo JJ, Lin AC, Rao MB, and Hincapie AL

Subjects
Humans, Female, Male, Middle Aged, Retrospective Studies, Adult, Risk Assessment methods, Obesity, Morbid surgery, Obesity, Morbid complications, Bariatric Surgery adverse effects, United States epidemiology, Aged, Secondary Prevention methods, Primary Prevention methods, Withholding Treatment statistics & numerical data, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Hydroxymethylglutaryl-CoA Reductase Inhibitors administration & dosage, Atherosclerosis prevention & control, Gastrectomy adverse effects, Gastrectomy methods, Gastric Bypass methods, Gastric Bypass adverse effects
Abstract

Background: Cardiovascular disease remains a leading cause of mortality globally, and its prevalence is notably elevated in individuals with obesity. Bariatric surgery is an effective intervention to reduce obesity-related health risks. However, the implications of discontinuing statin therapy, particularly post-bariatric surgery, among those with a history of atherosclerotic cardiovascular disease have yet to be clarified. We aimed to ascertain the risk of atherosclerotic cardiovascular disease events following statin cessation after bariatric surgery and to delineate the variance in outcomes between primary and secondary prevention cohorts., Methods: The TriNetX database, encompassing electronic medical records from 69 United States healthcare institutions, spanning 2012 to 2021. Using a retrospective cohort design, patients aged ≥18 years who underwent bariatric surgery and were concurrently on statin therapy were selected. Discontinuation was defined as a 90-day lapse after the last statin prescription. Patients were categorized as "primary" or "secondary" prevention based on their atherosclerotic cardiovascular disease history. The primary outcome was the occurrence of an atherosclerotic cardiovascular disease event post-statin cessation. Multivariable Cox proportional hazards models discerned factors influencing this outcome., Results: Of the 453 statin users who underwent bariatric surgery, 332 (73.1%) were in the primary prevention group and 121 (26.7%) in the secondary prevention group. At 1-year post-surgery, atherosclerotic cardiovascular disease event-free rates were 93% for primary and 68% for secondary prevention groups. Primary prevention patients showed an 82% reduced risk of post-statin cessation atherosclerotic cardiovascular disease events than secondary prevention patients (hazard ratio, 0.181; 95% confidence interval, 0.119-0.274). Additionally, Hispanic/Latino patients had heightened post-statin cessation atherosclerotic cardiovascular disease risks compared to non-Hispanic/Latino peers., Conclusion: Post-bariatric surgery statin discontinuation can pose significant risks, especially for those with atherosclerotic cardiovascular disease history and certain demographic groups, such as those over age 40 with diabetes. Ethnic disparities in outcomes necessitate individualized, equitable healthcare strategies. Optimal decisions about statin cessation necessitate comprehensive evaluations of cardiovascular determinants, with future research crucial to refine therapeutic approaches based on these insights., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Published
2024
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31. Surgical outcomes of trigonal intraventricular meningiomas: a single-centre study.

Author

Sadashiva N, Goyal-Honavar A, Nadeem M, Phaneendra GS, Konar S, Prabhuraj AR, Shukla D, Rao MB, Vazhayil V, Beniwal M, and Arimappamagan A

Subjects
Humans, Female, Male, Middle Aged, Adult, Aged, Treatment Outcome, Retrospective Studies, Cerebral Ventricle Neoplasms surgery, Young Adult, Meningioma surgery, Meningioma complications, Meningeal Neoplasms surgery, Neurosurgical Procedures methods, Postoperative Complications epidemiology
Abstract

Trigonal meningiomas are rare intraventricular tumours that present a surgical challenge. There is no consensus on the optimal surgical approach to these lesions, though the transtemporal and transparietal approaches are most frequently employed. We aimed to examine the approach-related morbidity and surgical nuances in treating trigonal meningiomas. This retrospective review assimilated data from 64 trigonal meningiomas operated over 15 years. Details of clinicoradiological presentation, surgical approach and intraoperative impression, pathology and incidence of various postoperative deficits were recorded. In our study, Trigonal meningiomas most frequently presented with headache and visual deterioration. The median volume of tumours was 63.6cc. Thirty-one meningiomas each (48.4%) were WHO Grade 1 and WHO Grade 2, while 2 were WHO Grade 3. The most frequent approach employed was transtemporal (38 patients, 59.4%), followed by transparietal (22 patients, 34.4%). After surgery features of raised ICP and altered mental status resolved in all patients, while contralateral limb weakness resolved in 80%, aphasia in 60%, seizures in 70%, and vision loss in 46.2%. Eighteen patients (28.13%) developed transient postoperative neurological deficits, with one patient (1.5%) developing permanent morbidity. Surgery for IVMs results in rapid improvement of neurological status, though visual outcomes are poorer in patients with low vision prior to surgery, longer duration of complaints and optic atrophy. The new postoperative deficits in some patients tend to improve on follow up. Transtemporal and transparietal approaches may be employed, based on multiple factors like tumour extension, loculation of temporal horn, size of lesion with no significant difference in their safety profile., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Published
2024
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32. Antiresorptive and anti-angiogenic drug therapy in the pediatric population with reference to medication-related osteonecrosis of the jaw.

Author

McLaurin WS, Francisco BJ, Hooker KJ, Sheshashayee N, Khan MTF, Triana RR, Rao MB, Pressey JG, and Krishnan DG

Subjects
Humans, Retrospective Studies, Child, Male, Female, Adolescent, Child, Preschool, Bisphosphonate-Associated Osteonecrosis of the Jaw epidemiology, Prevalence, Osteonecrosis chemically induced, Jaw Diseases chemically induced, Jaw Diseases epidemiology, Infant, Angiogenesis Inhibitors adverse effects, Bone Density Conservation Agents adverse effects
Abstract

The objective of this study was to identify the prevalence of osteonecrosis of the jaw in a pediatric population with systemic therapeutic exposure to an antiresorptive, anti-angiogenic, and/or immunomodulating drug (ARAID), and in particular in the subgroup of patients who had undergone invasive dental treatment. This was a retrospective cohort study performed at a single center. The investigation included pediatric patients who had undergone systemic therapy with ARAIDs and who began receiving ARAID therapy at ≤16 years of age. The study included 482 patients who received ARAIDs between January 2011 and January 2021. The most common medication class was bisphosphonates (45.0%), followed by mTOR inhibitors (30.1%) and anti-angiogenics (17.8%). No diagnosis of osteonecrosis of the jaw was observed. From this population, 26 patients were noted to have undergone invasive dental treatment. The duration from treatment to the invasive procedure ranged from 0 to 5.9 years. Medication-related osteonecrosis of the jaw is extremely rare among the pediatric population - much less common when compared to the adult population. Prospective cohort studies and continued evaluation will help determine the incidence and prevalence of medication-related osteonecrosis of the jaw in pediatric patients., (Copyright © 2023 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Published
2024
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33. Intentional Insertion of Air to Predict the Diagnostic Accuracy of Stereotactic Biopsy and a Uniform Grading System for Reporting.

Author

Deora H, Nadeem M, Shashidhar A, Arivazaghan A, and Rao MB

Subjects
Humans, Female, Male, Middle Aged, Biopsy methods, Child, Adult, Child, Preschool, Aged, Adolescent, Brain Neoplasms pathology, Brain Neoplasms diagnostic imaging, Brain Neoplasms diagnosis, Young Adult, Stereotaxic Techniques, Air, Tomography, X-Ray Computed
Abstract

Background and Objectives: Stereotactic biopsies are a relatively safe and reliable way of tissue diagnosis and characterization of eloquent area lesions/neoplasm. However, predicting the accuracy of the site of biopsy with the desired/planned site is not always possible. We describe a technique to identify the precise location of the biopsy site in the post-operative computed tomography (CT) scan using the injection of a low volume of air into the biopsy cannula., Methods: Hundred consecutive biopsies were performed in 80 adults/20 children (59 males/41 females, median age 51 years) over 3 years, consisting of 75 frameless and 25 frame-based stereotactic biopsies. After the biopsy specimens had been collected, a small volume of air (median 1 cc) was injected into the site. Post-operative CT was done within 4 hours of the biopsy to see the site of the air bubble, and the same was correlated with the histopathological accuracy., Results: Intra-cranial air in the selected target was present in 95 patients (Grade 1 and 2), while the air was seen in the track (Grade 3) in 3% and at an unrelated site (Grade 4) in 2% of cases. Both Grade 4 biopsies were negative on histopathology (diagnostic yield = 98%). Two negative biopsies were reported, which were both predicted with the Grade 4 biopsy. The grading allowed uniform reporting across series and eliminated the chance of upgrading/downgrading the report due to wrong site sampling within the lesion/neoplasm., Conclusion: The air-injection manoeuvre proposed for use in stereotactic biopsies of intra-cranial mass lesions is a safe and reliable technique that allows the exact biopsy site to be located without any related complications., (Copyright © 2024 Copyright: © 2024 Neurology India, Neurological Society of India.)

Published
2024
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34. Factors Associated with Statin Discontinuation Following Metabolic and Bariatric Surgery: A Retrospective Analysis of 2012-2021 Electronic Medical Records Network Data.

Author

Alsuhibani AA, Al-Obeed OA, Wigle PR, Alsultan MM, Guo JJ, Lin AC, Rao MB, and Hincapie AL

Subjects
Humans, Retrospective Studies, Electronic Health Records, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Obesity, Morbid surgery, Bariatric Surgery, Atherosclerosis, Cardiovascular Diseases prevention & control
Abstract

Background: Bariatric surgery has been shown to improve hyperlipidemia, decreasing the need for statin medications. Although maintaining statin therapy post-surgery for those with a history of atherosclerotic cardiovascular disease (ASCVD) is advised, it is uncertain if discontinuation risks differ between those with and without ASCVD history., Aim: The study aims to analyze the rate and reasons for statin cessation post-bariatric surgery in the US using real-world data., Methods: Using the TriNetX electronic medical records network from 2012 to 2021, the study involved patients aged 18 or older on statins at the time of bariatric surgery. They were categorized into primary and secondary prevention groups based on prior ASCVD. Statin discontinuation was defined as a 90-day gap post the last statin dosage. The Cox model assessed factors influencing statin cessation., Results: Seven hundred and thirty-three statin users undergoing bariatric surgery were identified, with 564 (77%) in primary prevention. Six months post-surgery, 48% of primary prevention patients and 34.5% of secondary ones stopped statins. Primary prevention patients had a 30% higher likelihood of cessation compared to secondary prevention (hazard ratio, 1.30; 95% CI, 1.06-1.60) as shown by multivariable analysis., Conclusions: Post-bariatric surgery, primary prevention patients are more likely to discontinue statins than secondary prevention patients., (© 2024. The Author(s).)

Published
2024
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35. Profile of a Multivariate Observation under Destructive Sampling-A Monte Carlo Approach to a Case of Spina Bifida.

Author

Guan T, Tatu R, Wima K, Oria M, Peiro JL, Lin CY, and Rao MB

Abstract

A biodegradable hybrid polymer patch was invented at the University of Cincinnati to cover gaps on the skin over the spinal column of a growing fetus, characterized by the medical condition spina bifida. The inserted patch faces amniotic fluid (AF) on one side and cerebrospinal fluid on the other side. The goal is to provide a profile of the roughness of a patch over time at 0, 4, 8, 12, and 16 weeks with a 95% confidence band. The patch is soaked in a test tube filled with either amniotic fluid (AF) or phosphate-buffered saline (PBS) in the lab. If roughness is measured at any time point for a patch, the patch is destroyed. Thus, it is impossible to measure roughness at all weeks of interest for any patch. It is important to assess the roughness of a patch because the rougher the patch is, the faster the skin grows under the patch. We use a model-based approach with Monte Carlo simulations to estimate the profile over time with a 95% confidence band. The roughness profiles are similar with both liquids. The profile can be used as a template for future experiments on the composition of patches.

Published
2024
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36. Krause approach to pineal tumour with intraoperative oculomotor nerve monitoring.

Author

Thombre B, Deora H, Bharadwaj S, and Rao MB

Abstract

Background: The supra-cerebellar infratentorial approach to pineal region tumours is versatile and safe corridor to lesions located below the deep veins. Monitoring of the extra-ocular muscle pathways using the evoked compound muscle action potential can lead to safer resections., Technical Note: To describe the use of electrooculography and a three handed retractor less method for pineal region tumour surgeries., Material and Methods: Intraoperative electrooculography uses recording done from two channels (horizontal and vertical)by inserting disposable subdermal needle electrodes along the periorbital area. The oculomotor nerve is being monitored as it exits the midbrain. Retractor-less three-handed-technique allows for minimal handling of the cerebellum while maximizing the operative corridor., Result: The oculomotor nerve was stimulated post resection and correspondingly led to improved symptoms post-operatively., Discussion and Conclusion: We demonstrate a method for the intraoperative monitoring of the continuity of the oculomotor tracts and a three handed retractor-less method of resection of pineal region tumours. The placement of electrodes and area of stimulation need sound knowledge of anatomy of the region. Haemostasis at every step is absolutely essential to be able to visualize in the narrow corridor., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Published
2024
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37. Bell's mania as a clinical presentation in a neurosurgical setting from a tertiary care neuropsychiatric hospital in India.

Author

Mamtani H, Utagi S, Chaurasia KK, Reddy PV, Arasappa R, Prasad C, Srinivas D, Rao MB, and Thippeswamy H

Abstract

Bell's mania is the co-occurrence of delirium and mania. We present two cases of Bell's mania in a neurosurgical setting. The first case is of a 52-year-old male who presented with holocranial headache, disorientation, and manic symptoms for five months. He was found to have suprasellar craniopharyngioma. He significantly improved with olanzapine, but re-emergence of mood symptoms was noted after surgery. The second case is of a 42-year-old male who presented with a 15-day history of seizures and disorientation. He was found to have a dural arteriovenous fistula. He developed Bell's mania in the post-procedural period, which improved with olanzapine. Compression of the hypothalamo-pituitary stalk in the first case and vascular and inflammatory changes in the second case could have led to Bell's mania. Atypical age of onset and presence of neurological symptoms in patients presenting with psychiatric symptoms should raise the suspicion of an underlying organicity. Atypical anti-psychotics can be a useful management strategy for Bell's mania., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Indian Journal of Psychiatry.)

Published
2024
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38. Reliability of Systematic and Targeted Biopsies versus Prostatectomy.

Author

Guan T, Sidana A, and Rao MB

Abstract

Systematic Biopsy (SBx) has been and continues to be the standard staple for detecting prostate cancer. The more expensive MRI guided biopsy (MRITBx) is a better way of detecting cancer. The prostatectomy can provide an accurate condition of the prostate. The goal is to assess how reliable SBx and MRITBx are vis à vis prostatectomy. Graded Gleason scores are used for comparison. Cohen's Kappa index and logistic regression after binarization of the graded Gleason scores are some of the methods used to achieve our goals. Machine learning methods, such as classification trees, are employed to improve predictability clinically. The Cohen's Kappa index is 0.31 for SBx versus prostatectomy, which means a fair agreement. The index is 0.34 for MRITBx versus prostatectomy, which again means a fair agreement. A direct comparison of SBx versus prostatectomy via binarized graded scores gives sensitivity 0.83 and specificity 0.50. On the other hand, a direct comparison of MRITBx versus prostatectomy gives sensitivity 0.78 and specificity 0.67, putting MRITBx on a higher level of accuracy. The SBx and MRITBx do not yet match the findings of prostatectomy completely, but they are useful. We have developed new biomarkers, considering other pieces of information from the patients, to improve the accuracy of SBx and MRITBx. From a clinical point of view, we provide a prediction model for prostatectomy Gleason grades using classification tree methodology.

Published
2023
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39. Metabolic and Bariatric Surgery Utilization Trends in the United States: Evidence From 2012 to 2021 National Electronic Medical Records Network.

Author

Alsuhibani A, Thompson JR, Wigle PR, Guo JJ, Lin AC, Rao MB, and Hincapie AL

Abstract

Background: Bariatric surgery has evolved over the past 2 decades yet assessing trends of bariatric surgery utilization in the growing eligible population is lacking., Aim: This study aimed to update the trends in bariatric surgery utilization, changes in types of procedures performed, and the characteristics of patients who underwent bariatric surgery in the United States, using real-world data., Method: This retrospective descriptive observational study was conducted using the TriNetX, a federated electronic medical records network from 2012 to 2021, for adult patients 18 years old or older who had bariatric surgery. Descriptive statistical analysis was conducted to assess patients' demographics and characteristics. Annual secular trend analyses were conducted for the annual rate of bariatric surgery, and the specific procedural types and proportions of laparoscopic surgeries., Results: A steady increase in the number of procedures performed in the United States over the first 6 years of the study, a plateau for the following 2 years, and then a decline in 2020 and 2021 (during the coronavirus disease 2019 pandemic). The annual rate of bariatric surgery was lowest in 2012 at 59.2 and highest in 2018 at 79.6 surgeries per 100,000 adults. During the study period, 96.2% to 98.8% of procedures performed annually were conducted laparoscopically as opposed to the open technique. Beginning in 2012, the Roux-en-Y gastric bypass (RYGB) procedure fell to represent only 17.1% of cases in 2018, along with a sharp decline in the adjustable gastric band (AGB) procedure, replaced by a sharp increase in the sleeve gastrectomy (SG) procedure to represent over 74% of cases in 2018., Conclusions: Bariatric surgery utilization in the United States showed a moderate decline in the number of RYGB procedures, which was offset by a substantial increase in the number of SG procedures and a precipitous drop in the annual number of AGB procedures., Competing Interests: Disclosure: The authors declare that they have nothing to disclose., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Published
2023
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40. Role of magnetoencephalography in predicting the epileptogenic zone and post-operative seizure outcome - A retrospective study.

Author

Sindhu DM, Mundlamuri RC, Goutham B, Narayanan M, Raghavendra K, Asranna A, Vishwanathan LG, Kulanthaivelu K, Saini J, Mangalore S, Bharath RD, Sadashiva N, Mahadevan A, Jamuna R, Arivazhagan A, Rao MB, and Sinha S

Subjects
Humans, Infant, Child, Preschool, Child, Adolescent, Retrospective Studies, Treatment Outcome, Seizures diagnosis, Seizures surgery, Magnetic Resonance Imaging, Magnetoencephalography, Electroencephalography
Abstract

Purpose: Study assessed the role of MSI in predicting the post-operative seizure outcome., Methods: This retrospective study included patients who underwent MEG and epilepsy surgery and had a minimum 6 months of postoperative follow-up. Concordance of MEG cluster with post-surgical resection cavity was classified as follows Class I) Concordant and region-specific, Class II) Concordant and region non-specific, Class III) Concordant lateralization only and Class IV) Discordant lateralization. The relationship between MSI concordance and post-operative seizure outcome was assessed., Results: A total of 183 patients (M: F = 109:74) were included. The mean age at onset of seizures: 8.0 ± 6.4 years. The dipoles were frequent in 123(67.2 %). The primary cluster orientation was regular in 59 (32.2 %) and mixed in 124 (67.8 %) patients. Concordance between MEG and resection cavity: Class I - 124 (67.8 %), class II- 30 (16.4 %), class III- 23 (12.6 %), and class IV- 6 (3.3 %). The post-surgically mean duration of follow-up was 19.52 ± 11.27 months. At 6-month follow-up period, 144 (78.7 %) patients had complete seizure freedom out of which 106 (73.6 %) had class I concordance. Concordance of MEG with resection cavity was associated with a good outcome at 6 months (p = 0.001), 1 year (p = 0.001), 2 years (p = 0.0005) and 5 years (p = 0.04). MEG cluster characteristics had no association with seizure outcome except the strength of the cluster and outcome at 3 years (p = 0.02) follow-up., Conclusion: The study supports that the complete resection of the MEG cluster had high chance of seizure-freedom and can be used as a complementary noninvasive presurgical evaluation tool., Competing Interests: Declaration of Competing Interest Dodmalur Mallikarjuna Sindhu: No conflicts of interest to disclose Ravindranadh Chowdary Mundlamuri: No conflicts of interest to disclose Bhargava Goutham: No conflicts of interest to disclose Mariyappa Narayanan: No conflicts of interest to disclose Kenchaiah Raghavendra: No conflicts of interest to disclose Ajay Asranna : No conflicts of interest to disclose Lakshminarayanapuram Gopal Vishwanathan: No conflicts of interest to disclose Karthik Kulanthaivelu : No conflicts of interest to disclose Jitender Saini: No conflicts of interest to disclose Sandhya Mangalore (3) Sandhya Mangalore: No conflicts of interest to disclose Rose Dawn Bharath: No conflicts of interest to disclose Nishanth Sadashiva: No conflicts of interest to disclose Anita Mahadevan: No conflicts of interest to disclose Rajeswaran Jamuna: No conflicts of interest to disclose Arimappamagan Arivazhagan: No conflicts of interest to disclose Malla Bhaskara Rao: No conflicts of interest to disclose Sanjib Sinha: No conflicts of interest to disclose, (Copyright © 2023 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Published
2023
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41. A framework to identify functional interactors that contribute to disrupted early retinal development in Vsx2 ocular retardation J mice.

Author

Leung AM, Rao MB, Raju N, Chung M, Klinger A, Rowe DJ, Li X, and Levine EM

Subjects
Mice, Animals, Amyloid Precursor Protein Secretases genetics, Retina, Neurogenesis physiology, Transcription Factors genetics, Homeodomain Proteins genetics
Abstract

Background: A goal of developmental genetics is to identify functional interactions that underlie phenotypes caused by mutations. We sought to identify functional interactors of Vsx2, which when mutated, disrupts early retinal development. We utilized the Vsx2 loss-of-function mouse, ocular retardation J (orJ), to assess interactions based on principles of positive and negative epistasis as applied to bulk transcriptome data. This was first tested in vivo with Mitf, a target of Vsx2 repression, and then to cultures of orJ retina treated with inhibitors of Retinoid-X Receptors (RXR) to target Rxrg, an up-regulated gene in the orJ retina, and gamma-Secretase, an enzyme required for Notch signaling, a key mediator of retinal proliferation and neurogenesis., Results: Whereas Mitf exhibited robust positive epistasis with Vsx2, it only partially accounts for the orJ phenotype, suggesting other functional interactors. RXR inhibition yielded minimal evidence for epistasis between Vsx2 and Rxrg. In contrast, gamma-Secretase inhibition caused hundreds of Vsx2-dependent genes associated with proliferation to deviate further from wild-type, providing evidence for convergent negative epistasis with Vsx2 in regulating tissue growth., Conclusions: Combining in vivo and ex vivo testing with transcriptome analysis revealed quantitative and qualitative characteristics of functional interaction between Vsx2, Mitf, RXR, and gamma-Secretase activities., (© 2023 The Authors. Developmental Dynamics published by Wiley Periodicals LLC on behalf of American Association for Anatomy.)

Published
2023
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43. Sample Size Calculations in Simple Linear Regression: A New Approach.

Author

Guan T, Alam MK, and Rao MB

Abstract

The problem tackled is the determination of sample size for a given level and power in the context of a simple linear regression model. The standard approach deals with planned experiments in which the predictor X is observed for a number n of times and the corresponding observations on the response variable Y are to be drawn. The statistic that is used is built on the least squares' estimator of the slope parameter. Its conditional distribution given the data on the predictor X is utilized for sample size calculations. This is problematic. The sample size n is already presaged and the data on X is fixed. In unplanned experiments, in which both X and Y are to be sampled simultaneously, we do not have data on the predictor X yet. This conundrum has been discussed in several papers and books with no solution proposed. We overcome the problem by determining the exact unconditional distribution of the test statistic in the unplanned case. We have provided tables of critical values for given levels of significance following the exact distribution. In addition, we show that the distribution of the test statistic depends only on the effect size, which is defined precisely in the paper.

Published
2023
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44. Resting-State Functional MRI/PET Profile as a Potential Alternative to Tri-Modality EEG-MR/PET Imaging: An Exploratory Study in Drug-Refractory Epilepsy.

Author

Mangalore S, Peer S, Khokhar SK, Bharath RD, Kulanthaivelu K, Saini J, Sinha S, Kishore VK, Mundlamuri RC, Asranna A, Lakshminarayanapuram Gopal V, Kenchaiah R, Arimappamagan A, Sadashiva N, Rao MB, Mahadevan A, Rajeswaran J, Kumar K, and Thennarasu K

Abstract

Objective  The study explores whether the epileptic networks associate with predetermined seizure onset zone (SOZ) identified from other modalities such as electroencephalogram/video electroencephalogram/structural MRI (EEG/VEEG/sMRI) and with the degree of resting-state functional MRI/positron emission tomography (RS-fMRI/PET) coupling. Here, we have analyzed the subgroup of patients who reported having a seizure on the day of scan as postictal cases and compared the findings with interictal cases (seizure-free interval). Methods  We performed independent component analysis (ICA) on RS-fMRI and 20 ICA were hand-labeled as large scale, noise, downstream, and epilepsy networks (Epinets) based on their profile in spatial, time series, and power spectrum domains. We had a total of 43 cases, with 4 cases in the postictal group (100%). Of 39 cases, 14 cases did not yield any Epinet and 25 cases (61%) were analyzed for the final study. The analysis was done patient-wise and correlated with predetermined SOZ. Results  The yield of finding Epinets on RS-fMRI is more during the postictal period than in the interictal period, although PET and RS-fMRI spatial, time series, and power spectral patterns were similar in both these subgroups. Overlaps between large-scale and downstream networks were noted, indicating that epilepsy propagation can involve large-scale cognition networks. Lateralization to SOZ was noted as blood oxygen level-dependent activation and correlated with sMRI/PET findings. Postoperative surgical failure cases showed residual Epinet profile. Conclusion  RS-fMRI may be a viable option for trimodality imaging to obtain simultaneous physiological information at the functional network and metabolic level., Competing Interests: Conflict of Interest None declared., (Asian Congress of Neurological Surgeons. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Published
2023
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45. Disorientation effects, circulating small ribonucleic acid, and genetic susceptibility on static postural stability.

Author

Turner A, Markey M, Le P, Reiter A, Cox C, Simmons S, Rao MB, Altman L, Davis K, Huber D, Dufour JS, Marras W, and Bhattacharya A

Abstract

Background: Motion Sickness increases risk of performance deficits and safety of flight concerns. The etiology of motion sickness is poorly understood. Here, we attempted to quantify the physiological effects of motion sickness on static balance and determine the genetic predictors associated with these effects., Methods: 16 subjects underwent a disorientation stimulus to induce motion sickness. Motion sickness susceptibility was identified using the Motion Sickness Susceptibility Questionnaire. Postural balance outcomes were measured using two tasks, and small ribonucleic acid profiles were assessed with blood draws before motion sickness stimulus. Differences in postural sway before and after the stimulus as well as effect modification of susceptibility were assessed. A random forest followed by regression tree analysis was constructed for each postural sway variable to determine top genetic and covariate predictors., Findings: Significant differences existed in mean postural balance responses between before and after stimulus. Individuals with longer stimulus survival experienced a greater (but insignificant) perception of sway, even if not displaying increased sway for all conditions. Circulation small ribonucleic acids were differentially expressed between individuals with long and short stimulus survival, many of these microRNA have purported targets in genes related to vestibular disorders., Interpretation: We found motion sickness produces transient motor dysfunction in a healthy military population. Small ribonucleic acids were differentially expressed between subjects with long and short stimulus survival times., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors.)

Published
2023
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46. Corpus Callosotomy for Non-Localizing Drug Resistant Epilepsy with Drop Attacks.

Author

Sadashiva N, Kadam R, Arimappamagan A, Rao MB, Mundlamuri RC, Raghavendra K, Asranna A, Viswanathan LG, Mariyappa N, Kulanthaivelu K, Mangalore S, Nagaraj C, Saini J, Bharath RD, Rajeswaran J, Mahadevan A, Satishchandra P, and Sinha S

Subjects
Humans, Male, Female, Child, Retrospective Studies, Seizures surgery, Syncope surgery, Corpus Callosum surgery, Treatment Outcome, Drug Resistant Epilepsy surgery, Psychosurgery methods
Abstract

Background: Corpus callosotomy (CC) is a surgical palliative procedure done for a selected group of patients with drug resistant epilepsy (DRE) to stop drop attacks and prevent falls., Methods: We performed a retrospective chart review of consecutive patients who underwent CC for DRE with drop attacks at our center between 2015 and 2019. Clinical, imaging details and surgical findings were noted. Clinical outcomes and functional status were evaluated., Results: During the study period, 17 patients underwent corpus callosotomy (Male: Female 14:3). The mean age at surgery was 10.3 years (standard deviation - 5.85, interquartile range [IQR] = 6.5). The mean age at onset of seizure was 2.23 years (standard deviation - 3.42, IQR = 1.5). Preoperative seizure frequency ranged from 2 to 60 attacks per day (median: 20, IQR= 36). All patients had atonic seizures/drop attacks. One patient underwent anterior CC and 16 underwent complete CC. Three patients had complications in the postoperative period. The median follow-up was 26 months. All patients had cessation of drop attacks immediately following surgery. One patient with anterior CC had a recurrence of drop attacks for which she underwent completion CC. Another patient had recurrent drop attacks 3 years later and was found to have a residual callosal connection. Three patients had complete seizure freedom and 4 patients had a <50% reduction in seizure frequency., Conclusions: Our study lends additional support to the efficacy of CC in patients with DRE, with the cessation of drop attacks. It also provided a reasonable reduction in seizure frequency. Complete CC led to better control of drop attacks., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Published
2023
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47. Avoidance of Pitfalls and Complications During Surgery for Temporal Lobe Epilepsy.

Author

Arivazhagan A, Sinha S, and Rao MB

Subjects
Humans, Quality of Life, Treatment Outcome, Seizures complications, Seizures surgery, Anterior Temporal Lobectomy adverse effects, Hippocampus surgery, Postoperative Complications epidemiology, Postoperative Complications etiology, Epilepsy, Temporal Lobe surgery, Epilepsy, Temporal Lobe complications
Abstract

Anterior temporal lobectomy with amygdalohippocampectomy is the most common epilepsy surgery, which, in cases of mesial temporal lobe epilepsy caused by mesial temporal sclerosis, usually leads to improvements in seizure control, cognitive function, and quality of life. Nevertheless, while the primary goal of intervention is achieved in a large majority of patients, a small number of them, unfortunately, encounter complications. Some morbidity is nonspecific and may be noted after any craniotomy (e.g., surgical site infections, meningitis, bone flap osteomyelitis, and operative site or craniotomy-related hematomas). On the other hand, certain complications are specifically associated with surgery for temporal lobe epilepsy and can be discussed from the etiological standpoint: mechanical injuries of the brain; injury of eloquent neuronal structures; arterial and venous injuries; cerebral venous thrombosis; remote cerebellar hemorrhage; and postoperative hydrocephalus, seizures, and psychiatric disorders. In many cases, these complications are manifested in the early postoperative period by alterations of consciousness and a focal neurological deficit, and it may require immediate decisions on their appropriate management., (© 2023. Springer Nature Switzerland AG.)

Published
2023
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48. Evaluating the Role of Perilesional Tissue in Pathobiology of Epileptogenesis of Vascular Malformations of the Central Nervous System.

Author

Rajeswarie RT, Aravinda HR, Arivazhagan A, Bevinahalli NN, Rao MB, and Mahadevan A

Abstract

Background and Purpose: Seizures are common presentation of cerebral vascular malformation (CVM). Topography and haemodynamic alterations are proposed as mechanisms for epileptogenesis, but the role of glial/neuronal alterations in perilesional tissue has not received much attention. Identification of the exact pathophysiologic basis could have therapeutic implications. To evaluate whether angioarchitectural factors of CVM or alterations in neuroglial/stroma of the adjacent cortex contribute to seizures., Method: The clinical, imaging and histological characteristics of arteriovenous malformation (AVM) and cerebral cavernous malformation (CCM) with and without seizures was evaluated using neuroimaging imaging and digital subtraction angiography parameters and histopathology by morphology and immunohistochemistry., Results: Fifty-six cases of CVM were diagnosed over a 2-year study period. Of these, 32 had adequate perilesional tissue for evaluation (AVM, 24; CCM, 8). Seizures at presentation was seen in 12/24 (50%) of AVM and 5/8 (62.5%) CCM. In AVM, hemosiderin deposition and gliosis in parenchyma ( p =0.01) had significant association with seizure. Siderotic vessels in the adjacent cortex was exclusively seen only in CCM with seizures ( p =0.018). Angioarchitectural features of CVM on imaging and neuronal alterations in adjacent cortex on histology failed to show any statistically significant difference between the two groups ( p >0.05)., Conclusions: We propose that changes in adjacent cortex appear to be epileptogenic rather than the malformation per se. Reactive gliosis and hemosiderin deposits in perilesional tissue in AVM and siderotic vessels in CCM were associated with seizure. This explains the better outcomes following extended lesionectomy that includes epileptogenic perilesional tissues., (Copyright © 2022 Korean Epilepsy Society.)

Published
2022
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49. Identification of microbial agents in culture-negative brain abscess samples by 16S/18S rRNA gene PCR and sequencing.

Author

John DV, Aryalakshmi B, Deora H, Purushottam M, Raju R, Mahadevan A, Rao MB, and Patil SA

Subjects
Humans, RNA, Ribosomal, 16S genetics, RNA, Ribosomal, 18S genetics, Genes, rRNA, Bacteria genetics, Polymerase Chain Reaction methods, Streptococcus genetics, DNA, Bacterial genetics, Acanthamoeba, Brain Abscess diagnosis, Brain Abscess genetics, Brain Abscess microbiology
Abstract

Despite clinical suspicion of an infection, brain abscess samples are often culture-negative in routine microbiological testing. Direct PCR of such samples enables the identification of microbes that may be fastidious, non-viable, or unculturable. Brain abscess samples (n = 217) from neurosurgical patients were subjected to broad range 16S rRNA gene PCR and sequencing for bacteria. All these samples and seven formalin-fixed paraffin-embedded tissue (FFPE) samples were subjected to species-specific 18S rRNA PCR for neurotropic free-living amoeba that harbour pathogenic bacteria. The concordance between smear and/or culture and PCR was 69%. One-third of the samples were smear- and culture-negative for bacterial agents. However, 88% of these culture-negative samples showed the presence of bacterial 16S rRNA by PCR. Sanger sequencing of 27 selected samples showed anaerobic/fastidious gram negative bacteria (GNB, 38%), facultative Streptococci (35%), and aerobic GNB (27%). Targeted metagenomics sequencing of three samples showed multiple bacterial species, including anaerobic and non-culturable bacteria. One FFPE tissue revealed the presence of Acanthamoeba 18S rRNA. None of the frozen brain abscess samples tested was positive for 18S rRNA of Acanthamoeba or Balamuthia mandrillaris. The microbial 16/18S rRNA PCR and sequencing outperformed culture in detecting anaerobes, facultative Streptococci and FLA in brain abscess samples. Genetic analyses of 16S/18S sequences, either through Sanger or metagenomic sequencing, will be an essential diagnostic technology to be included for diagnosing culture-negative brain abscess samples. Characterizing the microbiome of culture-negative brain abscess samples by molecular methods could enable detection and/or treatment of the source of infection.

Published
2022
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50. Impact of Ergonomic Posture on the Chemical Exposure of Workers in the Petroleum and Chemical Industry.

Author

Whitehead C, Maier MA, Rao MB, Eturki M, Snawder JE, and Davis KG

Subjects
Chemical Industry, Ergonomics, Female, Humans, Male, Methane, Posture, Sulfur Hexafluoride, Occupational Exposure, Petroleum
Abstract

Objectives: Despite a rise in automation, workers in the petroleum refining and petrochemical manufacturing industry are potentially exposed to various chemicals through inhalation while performing routine job duties. Many factors contribute to the degree of exposure experienced in this setting. The study objective was to characterize the impact of workplace conditions, anthropometric variability, and task orientation on exposure for a simulated routine operations task., Methods: A chemical exposure laboratory simulation study was designed to evaluate the dependent variable of chemical exposure level in the breathing zone for methane and sulfur hexafluoride. The independent variables were (i) posture of the worker, (ii) worker anthropometry, (iii) process configuration, and (iv) gas density., Results: Pipe height was a significant predictor of gas concentration measured in the breathing zone when located in a position that encouraged the gas to enter the breathing zone of the worker. Worker anthropometry had a major impact; tall worker's (male) chemical concentrations exceeded those of the short worker (female) for methane simulations but the opposite resulted for sulfur hexafluoride. Also, worker posture had a significant impact on gas exposure where nonneutral postures were found to have higher levels of chemical concentration., Conclusions: The study findings indicate that the breathing zone location is altered by posture and worker height, which changes the exposures relative to the emission source depending on the gas density of the chemicals that are present. As a result, qualitative risk assessment cannot be performed accurately without accounting for these factors. Practically, controls may need to account for worker size differences and posture adaptations., (Published by Oxford University Press on behalf of The British Occupational Hygiene Society 2022.)

Published
2022
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