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Mentor Name: Mentor Department Title of Proposed Project Hypothesis/Specific Aim Rami Hallac Analytical Imaging and Modeling Automatic Classification of Normal and Cleft Lip Photos using Computer Vision Hypothesis Compared to manual human segmentation, the CADe system will accurately segment the lip in normal subjects and patients with cleft lip and/or palate to automatically categorize the patients' condition based on shape analysis, removing bias and improving the classification, detection, and efficacy of cleft lip surgery procedures, ultimately improving patient satisfaction. Tiffany Moon Anesthesiology & Pain Management Outcomes of General Anesthesia in Patients with a History of Cocaine Use: A Retrospective Review Hypothesis: We seek to evaluate the claim that patients who test positive for cocaine metabolites, but do not appear acutely toxic and have a normal ECG and vital signs within the normal range, will not have an increased rate of perioperative complications during elective surgery compared to similar patients with negative urine cocaine screening tests. However, it is possible that patients who are chronic cocaine users may have a higher anesthetic requirement. Specific Aim: The goal of the summer research fellowship will be to enroll 40 patients in a pilot study at Parkland Memorial Hospital. An analysis of the pilot study data will provide critical data on a patient population, which has historically been reluctant to self-report. The information that we obtain will be used to inform the implementation of a greater IRB-approved study by determining the true incidence of this phenomenon at our institution, planning future enrollment through a power analysis, identifying trends in the data, and generating new hypotheses for future research efforts. Tiffany Moon Anesthesiology & Pain Management The Difficult Airway: Incidence and Predictors in Lean vs. Obese Patients in a Large Public Teaching Hospital Our hypothesis is that BMI alone is a weak predictor for difficult intubation in obese individuals. Other factors such as neck circumference (NC), thyromental distance (TMD), the NC/TMD ratio, presence of OSA, inter incisor distance (IID), upper lip bite test (ULBT) and Mallampati (MP) score may be more predictive of difficult intubation in obese individuals. Specific Aim: To assess the difficulty of intubation using the intubation difficulty scale (IDS), a previously validated tool to assess the difficulty of intubation (Adnet et al., 1997). Jarett Berry Cardiology The Association between Physical Fitness and Longevity Specific Aim: To characterize the association between exercise training on measures of LV strain. We hypothesize that exercise training will be associated with improvement in left ventricular strain after six months of exercise training.

2016 Summer Research Projects

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MentorName: MentorDepartment TitleofProposedProject Hypothesis/SpecificAim RamiHallac AnalyticalImagingand

ModelingAutomaticClassificationofNormalandCleftLipPhotosusingComputerVision

HypothesisComparedtomanualhumansegmentation,theCADesystemwillaccuratelysegmentthelipinnormalsubjectsandpatientswithcleftlipand/orpalatetoautomaticallycategorizethepatients'conditionbasedonshapeanalysis,removingbiasandimprovingtheclassification,detection,andefficacyofcleftlipsurgeryprocedures,ultimatelyimprovingpatientsatisfaction.

TiffanyMoon Anesthesiology&PainManagement

OutcomesofGeneralAnesthesiainPatientswithaHistoryofCocaineUse:ARetrospectiveReview

Hypothesis:Weseektoevaluatetheclaimthatpatientswhotestpositiveforcocainemetabolites,butdonotappearacutelytoxicandhaveanormalECGandvitalsignswithinthenormalrange,willnothaveanincreasedrateofperioperativecomplicationsduringelectivesurgerycomparedtosimilarpatientswithnegativeurinecocainescreeningtests.However,itispossiblethatpatientswhoarechroniccocaineusersmayhaveahigheranestheticrequirement.SpecificAim:Thegoalofthesummerresearchfellowshipwillbetoenroll40patientsinapilotstudyatParklandMemorialHospital.Ananalysisofthepilotstudydatawillprovidecriticaldataonapatientpopulation,whichhashistoricallybeenreluctanttoself-report.TheinformationthatweobtainwillbeusedtoinformtheimplementationofagreaterIRB-approvedstudybydeterminingthetrueincidenceofthisphenomenonatourinstitution,planningfutureenrollmentthroughapoweranalysis,identifyingtrendsinthedata,andgeneratingnewhypothesesforfutureresearchefforts.

TiffanyMoon Anesthesiology&PainManagement

TheDifficultAirway:IncidenceandPredictorsinLeanvs.ObesePatientsinaLargePublicTeachingHospital

OurhypothesisisthatBMIaloneisaweakpredictorfordifficultintubationinobeseindividuals.Otherfactorssuchasneckcircumference(NC),thyromentaldistance(TMD),theNC/TMDratio,presenceofOSA,interincisordistance(IID),upperlipbitetest(ULBT)andMallampati(MP)scoremaybemorepredictiveofdifficultintubationinobeseindividuals.SpecificAim:Toassessthedifficultyofintubationusingtheintubationdifficultyscale(IDS),apreviouslyvalidatedtooltoassessthedifficultyofintubation(Adnetetal.,1997).

JarettBerry Cardiology TheAssociationbetweenPhysicalFitnessandLongevity

SpecificAim:TocharacterizetheassociationbetweenexercisetrainingonmeasuresofLVstrain.Wehypothesizethatexercisetrainingwillbeassociatedwithimprovementinleftventricularstrainaftersixmonthsofexercisetraining.

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SubhashBanerjee Cardiology VeteransAorticAneurysmCardiovascularOutcomeStudy

Secondaryendpoints:1.Tocomparetheprevalenceofatherothromboticriskfactors;concomitantnon-aorticCV)disease;PAD,andmajoradverseCVeventrates(MACE)inpatientswiththoracicorabdominalaorticaneurysms2.TocomparetheprevalenceofPAD,andmajoradverseCVeventrates(MACE)inpatientswithpatientswithaorticaneurysmsandthosewithoutaorticaneurysmHypothesis:Wehypothesizethatgiventheoverlappingrisksbetweenaorticaneurysmsandcoronaryarterydisease(CAD),especiallyhistoryoftobaccouseandhypertension,inapredominantlymaleveteranpopulation,theprevalenceofatherothromboticriskfactors;concomitantnon-aorticCV)disease;PAD,andmajoradverseCVeventrates(MACE)willbesimilarbetweenpatientswithaorticrootandotherthoracicorabdominalaneurysms.

JohnAbrams CellBiology TheRoleofTumorSuppressorp53inRestraintofRetrotransposonActivity

Hypothesis:Usingcomplementationassays,Abramslabrecentlydiscoveredthatnormalp53allelessuppresstransposonsbutmutantp53allelesfromcancerpatientscouldnot(Wylieetal,2016)..Inaddition,unrestrainedretrotransposonshavebeenobservedinp53drivenhumanandmousecancers.Thisprojectseekstoadvanceourunderstandingofthelinkbetweenthebiologyofp53andthebiologyoftransposons.Specifically,Iwilltestthehypothesisthattumorsuppressionbyp53isfundamentallycoupledtosystemsthatrestrainretrotransposonactivity.

MarcDiamond CenterforAlzheimer'sandNeurodegenerativeDiseases

TargetingDistinctTauStrainswithHeparinoidstoDetermineBindingSpecificityandUltimatelyPreventTauPropagationBetweenCells

Hypothesis:Heparinoidswilldifferentiallytargetdistincttaustrains.

RalphDeberardinis

Children'sMedicalCenterResearchInstitute

FeasibilityStudyUsingImagingBiomarkersinLungCancer

WehypothesizethatthesetumorcellsareusinglactateasanalternativefuelsourcefortheTCAcycle.Effectiveutilizationoflactatemightenabletumorcellstoresistglucosedeprivation;infact,asymbioticrelationshiphasbeenproposedbetweenwell-perfusedandpoorly-perfusedareasinthetumor,withpoorlyperfusedcellsconvertingglucosetolactateviaglycolysisandwell-perfusedcellsoxidizinglactateforenergy(5).

AmitPandya Dermatology ValidationoftheVitiligoDiseaseActivityIndex

Hypothesis:WehypothesizethatthesubjectiveVIDAscorecorrelatespoorlywithchangeinvitiligolesionsasmeasuredobjectivelybyinvestigatorsovertime.

AmitPandya Dermatology DeterminationofthelevelsofCXCL9and HypothesisWehypothesizethatchemokinelevelsdecreasein

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10intheinterstitialfluidoftheskinofpatientswithvitiligoundergoingtreatmentusinganovelblisteringtechnique

theskinofpatientswithvitiligowithtreatment.

MelissaMauskar Dermatology PredictorsofMortalityinPatientsWithSystemicCalciphylaxisandEndStageRenalDisease

Wehopetolookatclinicaldatatodetermineifthereareanypredictorsthatwouldindicatetheusefulnessofearlyinterventionordifferentmanagementprotocolsforpatientswithendstagerenaldiseasewhodevelopsystemiccalciphylaxis.Ourhypothesisisthatthesepatientshaveahighermortalityrate.

DonaldGlass Dermatology EvaluationoftheSafety,Efficacy,andIndicationsforUseofPentoxifyllineasaPost-SurgicalKeloidTreatmentOption

Hypothesis:Theuseofpentoxifyllineinpost-surgicalkeloidtreatmentwillbebeneficialindecreasingkeloidrecurrenceandwillbewell-toleratedbypatients.SpecificAims:Thisstudywillevaluatethesafetyandefficacyoforalpentoxifyllineinthetreatmentofkeloidsthroughevaluationofthefollowingfactors:1)Thenumberofpatientsgivenpentoxifyllineatoraroundthetimeofsurgery2)Thenumberofpatientswhodiscontinuedthemedication,andifso,whatwasthereason3)Therecurrencerateat6monthspost-surgeryforpatientswhotoleratedpentoxifylline,comparedtokeloidrecurrenceratescitedintheliteratureandforpost-surgicalpatientsseeninclinicwhodidnotuseortoleratepentoxifylline4)Thecriteriausedtoselectpatientsputonpentoxifyllineversusthosewhowerenot,suchashistoryofrecurrence,previoussurgery,numberoflesions,locationoflesions,andpainorpruritus

AmitPandya Dermatology Immunologicalprofileofinflammatorycellsintheskinofpatientswithvitiligoundergoingtreatment

WehypothesizethatCD8+andCD4+TcellsdiminishovertimeintheskinofpatientswithvitiligowithtreatmentwhileTregcellsincrease.

KimberlyReynolds GreenCenterforSystemsBiology,Biophysics

EvolutionofHighEfficiencyAllostericSwitches

HYPOTHESISTheengineeredDHFR/LOV2fusionswereconstructedwithoutanyoptimization,andshowedmodestregulation(2-foldchangeinenzymeactivity)inresponsetolight.Wenowaskhowthesectorarchitectureinfluencesoptimizationoftheseswitches.Wehypothesizethatthesectorarchitectureprovidesapre-wiredevolutionarypathforthegainofallostericregulation.Accordingly,shortpathsofpointmutationsshouldallowfortheoptimizationofallostericregulationdisplayedbysector-connectedDHFR/LOV2mutantswhilenon-sectorconnectedmutantsshouldremainresistanttoallostericcommunicationdespitefurthermutation.AIMS1.Measuretheeffectofeachmutationonregulationusingahighthroughputin

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vivoscreen.Todothis,IwilltransformeachlibraryintoanE.coliknock-outstrainmissingDHFR(ER2566ΔfolAΔthyA),growtheminselectivemediaunderlitanddarkconditions,andconductatimecourseexperimentinwhichsamplesareremovedfromthemixedcultureandtherelativefrequenciesofeachmutantalleleinthepopulationarequantifiedusingnext-generationsequencing.2.Identifymutantallelesthataltergrowthratesinlitversusdarkconditions,quantifytheiractivitythroughenzymekineticmeasurements,mapthesemutantallelesontotheDHFRstructure,andstatisticallycomparethesepositionstotheallostericnetworkdefinedbythesector.3.Solvehighresolutioncrystalstructuresofthemutantsdisplayingthegreatestmagnitudeinallostericregulationtobetterunderstandwhatstructuralchangesunderliethechangesinfunction.

JeffreyZigman HypothalmicResearch InvestigatingtheRoleofGhrelininPrader-WilliSyndrome

TheoverallgoalofthisSummerProjectistodirectlytestamodelpredictingnovelrolesofghrelininPWS.IncontrasttotheprevailingviewthatghrelinisdetrimentalinPWS,wenowproposethatghrelinelevationinPWSisprotective,preventingprematuredeathinchildrenwithPWSwhilealsohelpingtopreserveGHsecretionandmusclefunction,limitdepressionandanxiety,andensuresurvivalinadultswithPWS.WehypothesizethattheelevatedghrelininPWSisprotective,defendingagainstexaggerateddegreesofGHdeficiency,hypotonia,andhypoglycemia-ultimatelypreventingdeathofPWSneonates.Todirectlytestthishypothesis,wewilldetermineifcrossingSnord116delmicetoghrelin-KOmicereproducesthestrikingphenotypeobtainedusingSnord116del/GHSR-nullmice.Also,wewilldetermineifadministeringghrelinrescuesorimprovestheoutcomeofPWSmiceontheghrelin-deficientoronghrelin-repletebackgrounds,respectively.

IanNeeland InternalMedicine ImpactofVisceralAdiposityonGlycerolMetabolisminGluconeogenesisamongNon-DiabeticObeseAdults

ThefirsthypothesisisthatparticipantswithhighervisceralfatcontentbyMRIwillhaveagreaterrelativecontributionofunlabeledglyceroltoglucosecomparedwithage,sex,andbodymassindex(BMI)-matchedparticipantswithlowervisceralfat.Thesecondhypothesisisthatparticipantsinthefasting-refedstatewillhaveagreaterrelativecontributionofadiposetissuederivedglycerol(measuredby13Cnuclearmagneticresonancespectroscopyanalysis)tohepaticgluconeogenesiscomparedwithparticipantsinthefastingstate.

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RicardaLaHozDavidGreenberg

InternalMedicine EpidemiologyofBlood-BorneInfectionsinSolidOrganTransplantRecipients

HypothesisTheincidenceofbloodstreaminfectionsishigheramongsttransplantrecipientsthaninthegeneralpopulation.Wepredictthatthemostcommonmicroorganismsassociatedwithbloodstreaminfectionsamongstsolidorgantransplantrecipientstobe:CoagulasenegativeStaphylococci,Staphylococcusaureus,Enterococcusspecies,Escherichiacoli,KlebsiellaspeciesandCandidaspecies.Transplantrecipientswillhaveahigherprevalenceofmulti-drugresistantorganismsthanthegeneralpopulation.SpecificAims1.Describetheepidemiologyofbloodstreaminfectionsinsolidandstemcelltransplantrecipients.a.Identifythemostcommonorganismsresponsibleforbloodstreaminfectionsinallsolidorgantransplantrecipientsandbyorgantype(lung,heart,liver,andkidney).b.Identifythemostcommonorganismsresponsibleforbloodstreaminfectionsinstemcelltransplantrecipientsbothautologousandstemcelltransplantrecipients.c.Describetheprevalenceofmulti-drugresistantorganismsasacauseofbloodstreaminfections.

AmitSingal InternalMedicine AccuracyofUltrasoundasScreeningModalityforDetectingHepatocellularCarcinomainPatientswithCirrhosis

Specificaims/Hypothesis:Toidentifypatientcharacteristicsassociatedwithsensitivityofultrasoundforearly-stagedetectionofhepatocellularcarcinoma.Wehypothesizepatientfactorsincludingbodymassindex,presenceofascites,anddegreeofliverdysfunction/nodularityareassociatedwithlowerultrasoundsensitivityfordetectingHCCnodules.

DavidGerber InternalMedicine Clinicaltrialdesignandconducttooptimizeaccrualandquality

Aim1.ThisresearchprojectwilluseadatasetofpublicallyavailableNCI-sponsoredlungcancerclinicaltrialprotocols(N=73)andprotocolsummariesontheclinicaltrials.govwebsitetodeterminepredictorsandtrendsinthetotalnumberofeligibilitycriteriaandpharmacy-relatedeligibilitycriteria(CYP3A4metabolism,QTcprolongation).Protocolswillbecharacterizedaccordingtoactivationyear,principaltreatmentmodality,diseasehistologyandstage,trialphase,andtotalenrollmentnumber.TheassociationbetweentrialcharacteristicsandeligibilitycriteriawillbeassessedbyChi-Squareanalysis.Aim2.WorkingwithprimarymentorDr.GerberandcollaboratorDr.SimonLee,Ms.Garciawill(1)conductarelevantliteraturesearchfocusingoninteractionsbetweenclinicalresearchteamsandclinicstaff,(2)reviewtranscriptsfrompreviouslyconductedfocusgroupswithclinicalresearchandclinicstaff,and(3)developsurveysandquestionnairestobe

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administeredtostaff,providers,andpatients.Theseinstrumentswillbedesignedtodetermineperceptionsofrolesandresponsibilitiesandopportunitiestoenhancethefunctionofthismulti-teamsystem.

AnneSatterthwaite

InternalMedicine-DivisionofRheumatology

RoleofFoxo3inBCellTolerance Hypothesis:Foxo3promotesdeletionofimmatureBcellsthatremainauto-reactiveafterreceptorediting.SpecificAim1:DefinethemechanismbywhichFoxo3mediatesimmatureBcellapoptosisanddeterminetheconsequencesofthisfortheeliminationofauto-reactiveBcells.SpecificAim2:DeterminewhetheraFoxo3-deficiencyresultsinincreasedreceptoreditingduetoalongereditingwindowandassesstheconsequencesforBcellauto-reactivity.

ChrisChen Orthopedics TentativeTitle:Efficacyofintra-articularadministrationofEPOandBMP2fromHAmicroscaffoldsonautologousMSCrecruitment,localinflammatoryresponsesinsynovialspace,andcartilageregeneration.

HYPOTHESIS:Theintra-articularadministrationofEPOandBMP2fromHAmicroscaffoldswillenhanceautologousMSCrecruitment,reducelocalizedinflammatoryresponsesinthesynovialspaceandpromotecartilageregeneration.SPECIFICAIM:Totesttheabilityofintra-articularinjectionofEPO-HAandBMP2-HAmicroscaffoldsinpreventingthedevelopmentofPTOAinrabbits.

WilliamM.Lee InternalMedicine-Hepatology

HistologicalFindingsintheTwoSubtypesofHepatitisB-RelatedAcuteLiverFailure

Hypothesis:WehypothesizethatpatientswithacuteHBV-acuteliverfailurewilldemonstrate,onlivertissuestaining,qualitativeand/orquantitativedifferencesinHBcAgexpressionand/orHBsAgexpression,aswellasmorphologicaldifferencesonH&EstainfromthosewithchronicHBV-ALF.SpecificAims:Bydeterminingthatthereareantigenicand/ormorphologicaldifferencesbetweenthesubtypesofHBV-ALFandspecifyingwhattheyare,weexpandourknowledgeofthedifferencebetweenacuteandchronicHBVasitrelatestoacuteliverfailure.Thisisusefulforestablishingpotentialtherapeutictargetsthatmaymodifythecourseofthediseaseorallowforstratificationofriskwithineachcategory.

DavidGreenberg InternalMedicine,Microbiology

DevelopmentofNovelGene-SilencingTherapeuticsforPseudomonasaeruginosaBiofilms

Hypothesis:PPMOstargetingthequorumsensingproteinlasRwhenco-incubatedwithtraditionalantibioticswillprovidesynergisticeffectsinboththepreventionand/orbreakdownofP.aeruginosabiofilm.SpecificAims:1)UtilizetheLasRPPMOwithtraditionalantibioticsinastraincollectionofP.aeruginosaandmeasuretheabilitytopreventbiofilmformationinbothantibiotic-sensitiveandantibiotic-resistantstrains.2)UtilizetheLasRPPMOwithtraditionalantibioticsinastraincollectionofP.aeruginosaandmeasurethebreakdownofpre-formedbiofilms

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inbothantibiotic-sensitiveandantibiotic-resistantstrains.DavidGreenberg InternalMedicine,

MicrobiologyDevelopmentofNovelGene-SilencingTherapeuticsforAcinetobacterbaumanniiBiofilms

WehypothesizethatPPMOstargetingtheattachmentproteinCsuEwhenco-incubatedwithtraditionalantibioticswillprovidesynergisticeffectsinboththepreventionand/orbreakdownofA.baumanniibiofilm.

DharamKumbhani Cardiology AssessingthequalityoftreatmentintheuseofvascularinterventioninpatientswithPVDcomplicatedbyfootulcer

SpecificAim:TocreateandanalyzeauniquedatabaseconsistingofpatientdatafromParklandpatientsfromtheASCFootWoundClinic(includinglimiteddemographicdata,historyofdiagnosticandprognosticcareregardingvascularassessmentandintervention,dataonhemoglobinA1C,comorbidities,andoutcomes)ofapproximately600patientsovera6-monthtimeperiodtoassessdifferentoutcomesandthequalityandinclusionofvascularinterventioninpatientspresentingwithfootulcers.

PeterDouglas MolecularBiology MediatingNeuronalProtectionagainstTraumaticInjurythroughMitochondrialMetabolism

Theaimsofthisresearchprojectarethreefold.First,wewillassesswhetherapplicationofcco-1RNAiknockdowntreatmentsreversetheshort-termeffectsoftrauma,whichwillbemeasuredbyparalysisduration,ERK1/2phosphorylationlevels,levelsofoxidativedamageandrespirationratesobtainedviaaSeaHorseeffluxanalyzer.Second,wewilldetermineifthecco-1RNAitreatmentcanpreventthelong-termconsequencesofearlyadulthoodbluntforcetraumabymeasuringthedegreeofneurodegenerationinwormfood-sensingneuronsandtheaccumulationoftoxicproteinaggregatessuchasneuronalpolyglutamineexpansionproteinssuchasQ67,muscle-expressedamyloidbeta(linkedtoAlzheimer'sdisease),andtheALSlinkedgene,TDP-43.Third,wewilldeterminetheprecisespatiotemporalrequirementsforcco-1RNAitreatmentadministration.

RueylingLin MolecularBiology RoleoftheendogenoussiRNApathwayinmRNAclearanceandcellularreprogramming.

Theaimofthisprojectistobegintestingthehypothesisthattheendo-siRNApathwayhasanimportantfunctionduringthereprogrammingofmammaliancellsbygeneratingtheblankslateforthenewdevelopmentalprogram.Specifically,wewilltesttheroleofendo-siRNAinwell-developedreprogrammingprotocolsbyusingeitherectopicexpressionorknockdownofendo-siRNApathwaycomponents.Ourhypothesispredictsthatenhancingtheendo-siRNApathwayshouldimprovereprogramming(measuredasefficiencyand/ortimerequired),andconversely,inactivatingthepathwayshouldnegatively

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reprogramming.JoachimHerz MolecularGenetics InducibleMouseModelforAmyloid

PrecursorProteinHypothesis:BycreatingamousemodelthatallowsinducibleoverexpressionofendogenousAPPinatimely,regulated,andreversiblemannerweareabletocircumventseveralflawsofcurrentADmousemodels.OurtransgenicmousewillbecrossedwithwildtypeanddifferentavailableAPP-knockinmiceallowingustostudytheeffectofinducibleupanddownregulationofendogenouswildtypeandhumanAPP.SpecificAims:OurmodelmakesuseofatranscriptionfactorfusionproteinthatisdesignedtospecificallybindtothemouseendogenousAPPpromoter.Atransgenicmouseline,whichexpressessuchatranscriptionfactorinaninduciblemanner,canbeusedtostudythephysiologicalfunctionofmousewildtypeAPP,whichiscurrentlynotverywellunderstood.Geneoverexpressionstudiesandsubsequentreversiontonormallevelswillgiveimportantinsightinproteinfunctioninvivo.Thefuturemousemodelwillbesuitedtostudysynapseformationandfunction.Furthermore,breedingthistransgenicmouselinewithavailablehumanAPPknockinmicewillrevealfurtherinsightsintothepathogenesisofADundermorephysiologicalconditionsthancurrentADmousemodelsallow.Inourmousemodelwecircumventtheproblemoflackinguntranslatedregions(UTRs)intheAPPmRNAtranscript,suchimportantregulatoryelementsaredisregardedincurrentAPPoverexpressionmodels.SincethesubcellularlocalizationofmRNAandtranscriptionalregulationwillbeunaffectedinourmodelitreflectsthepathogenesisinthehumanbrainmorepreciselythancurrentmodels.Insummary,thismousemodelallowsustostudytheeffectofreversibleoverexpressionofendogenouswholelengthsAPPtodiscoverAPPfunctioninhealthanddisease.

JuanPascual Neurology&Neurotherapeutic

AnalysisoftheglucosetransportertypeIdeficiencyregistry

ThepurposeoftheGlucoseTransporterType1Deficiency(G1D)RegistryistoexpandtheknowledgeofthenaturalcourseofG1D,improveclinicalcare,andprovidedirectionforfutureresearch.TheG1DRegistryhasbeencreatedandfundedbytheDepartmentofNeurologyandNeurotherapeuticsatUTSouthwesternMedicalCenterundertheguidanceofDr.JuanPascual.Patientsandfamiliesdirectlyentertheirdataintheregistrybyansweringaseriesofquestions.Theregistrycontainsinformationaboutdiagnosis,symptoms,medicalandfamily

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history,treatmentsandmedications,laboratoryandimagingtests,andthehistoryofpatient'smedicalcare.Itisexpectedthataddressingcertainquestionsmayultimatelyresultinasignificantchangeinthestandardofcare.

CraigPowell Neurology&Neurotheraputics

Insulin-LikeGrowthFactor1(IGF-1)therapyinrestoringhippocampalneuronsinaGulfWarIllnessmodel

Objective/HypothesisWehypothesizethatthedelayed-onsetdecreaseinsynapsenumbercanbereversedwithdrugsalreadyinclinicaluseorclinicaltrials.TheneurotrophicfactorIGF-1,FDAapprovedforuseeveninchildren,stimulatessynapticspineandsynapseformationduringdevelopment,duringnormalaging,andwhenadministeredinpreclinicalstudiesofhumanneurologicaldisorders.ThisprojectwillevaluatetheeffectivenessofIGF-1therapyinrestoringnormalsynapsestructureandfunctioninourGWImousemodelusingextracellular'field'electrophysiology,neuronreconstructiontechniques,andimmunohistochemistry(IHC).

ShilpaChitnis Neurology&Neurotheraputics

PatientPerceptionsandKnowledgeofParkinsonDiseaseandTreatment

ThepurposeofthisstudyistosurveypatientsabouttheirknowledgeofPDandavailabletherapeuticoptions.Theresultsfromthissurveywillbeusefultoidentifypossibledeficienciesinpatienteducationandhelpdevelopatargetedpatienteducationprotocol,withtheultimategoalofimprovingoutcomesandprovidingreasonablequalityoflifeforPDpatientsdependingonthestageoftheirdisease.

MunroCullum Neuropsychiatry AgeofDiagnosisofMildCognitiveImpairmentbyRace:TheEffectofTraumaticBrainInjuryHistoryandApolipoproteinε4

Hypothesis:ItispredictedthattheinteractionbetweenApo-E4andahistoryofTBIwillbeassociatedwithasignificantlyearlierageofMCIdiagnosisinCaucasiansandnotinAfricanAmericannorHispanicindividuals.

JerryNiederkorn Ophthalmology MechanismsLeadingtoReducedLiverMetastasisinMicewithDefectiveFasL(CD95L)

Experiment1Hypothesis:Althoughgld/gldmicehavenon-functionalFasL,theymayhaveotheranomaliesthataffecthomingofblood-bornemelanomacellstotheliver.Rationale:Homingofblood-bornemelanomacellstothelivercorrelateswithmetastasis.Design:HomingofradiolabeledB16LS9melanomacellstotheliverwillbeassessedinWTandgld/gldmice.Outcomeifhypothesisiscorrect:LiverhomingwillbehigherinWTmice.Experiment2Hypothesis:FasL-FasRinteractionmaypromotetumormetastasisthroughincreasedliversecretionofc-met.Rationale:C-metisthemajorchemokineintheliverthatisassociatedwithlivermetastasisinhumanUMpatients.Design:LiversfromWTandgldmiceharboringlivermetastaseswillbeanalyzedbywesternblotandELISAtodeterminec-metproteinlevels.Liversupernatantsfrom

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WTandgldmicewillalsobeanalyzedfordifferencesintumorcellchemotacticresponsesinvitro.Outcomeifhypothesisiscorrect:WTmouseliverswillhavegreaterc-metlevelsandwillproducegreatertumorcellchemotacticresponses.Experiment3Hypothesis:AbsenceoffunctionalFasLmayenhanceliverNKcellcytotoxicity.Rationale:StudieshavereportedthatFasRcandampenimmuneresponsesbytransmittingsignalsintoFasL-bearingNKcells,viaamechanismknownas'reversesignaling.'Design:LiverNKcellcytotoxicitywillbeassessedinWTandgldmice.Outcomeifhypothesisiscorrect:gldmicewillhavehigherNKcytolyticactivitythanWTmice.Experiment4Hypothesis:InadditiontodefectiveFasL,gldmicemayhaveananomaloushigherproductionofinterferon-gamma(IFN-)orperforin.Rationale:IFN-andperforinareimportantmediatorsfortheanti-tumoreffectsofNKcells.Design:IFN-andperforinlevelswillbemeasuredbyELISAsintheliversremovedfromtumor-bearinggldandWTmice.Outcomeifhypothesisiscorrect:IFN-orperformlevelswillbehigheringldmice.Experiment5Hypothesis:FasL-FasRinteractionsmaypromoteangiogenesisthroughincreasedVEGFsynthesisintheliver.Rationale:AngiogenesismediatedbyVEGFisanimportantstepintheestablishmentoflivermetastases.

KaranjitKooner Ophthalmology RedefiningGlaucomaDamage Hypothesis:NFLanalysiswillprovidemoresensitive,reliableandearlyevidenceofopticnervedamagethanthecurrentVFtests.Specificaims:1.todetermineifNFLanalysisagreeswiththecurrentdefinitionsofVFdefectsbytheHodapp-Parrish-Andersoncriteria.2.DoesthethicknessoflaminacribrosacorrelatewithCCTorfamilyhistoryofglaucoma?

RonaldMancini Ophthalmology Examiningcorrelationsbetweenpreoperativebasalandsquamouscellcarcinomalesionsoftheeyelidandpostoperativerepairs

HYPOTHESIS1.Ourfirsthypothesisisthatpreoperativeappearanceofthelesionisapoorpredictoroffinallesion/defectsize.Weexpectthatthevisibletumorontheeyelidwillultimatelyrevealtobemuchlargerunderthesurface,requiringmoresurgicalinterventionthaninitiallyanticipated.2.Oursecondhypothesisisthatsquamouscellcarcinoma,amoreaggressivetumorthanbasalcellcarcinoma,willlikelyresultinalargerpostoperativedefect.3.Basalandsquamouscellcarcinomahaveapredilectionforthelowereyelidovertheuppereyelidduetomoresunexposureonthelowereyelidsurface.Wehypothesizetofindasimilarcorrelationwiththepopulationinourstudy.III.SPECIFCAIMSBylookingat

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preoperativephotographsandinitialclinicalexaminationofthepatientsinourstudy,wewilldeterminewhetherornotandtowhatdegreewewereabletopredictthedefectsizefollowingsurgicalremovalofthelesion.Wewillalsodeterminewhetherthetypeofcancer,basalvssquamouscellcarcinoma,hasaneffectontheultimatedefectsizeandourabilitytopredictdefectsizefrominitialexamination.Lastly,wewilldeterminewhetherornotourpopulationfitswithpriorreportedstudiesthatshowskincancershaveapropensityforthelowereyelidasopposedtotheuppereyelid.

DavidBirch Ophthalmology EvaluatingPossibleMechanismsofAgeRelatedMacularDegenerationwithReticularPseudodrusen

Hypothesis:RPDactsasadiffusionalblockthatphysicallylimitstheexchangeofretinolbetweenRPEandphotoreceptors.Specificaims:(1)TodeterminetheextentandprogressionofrodsensitivitylossinintermediateAMDwithRPD(2)TorelatetheextentofrodandconesensitivitylosstoenfacefdOCTstructuralmeasures.

W.MatthewPetroll

Ophthalmology ModulationofCornealWoundHealingfollowingPhotorefractiveKeratectomy

Hypothesis:WehypothesizethattopicalapplicationofQuercetinwillreducecornealfibrosisandhazefollowingphotorefractivekeratectomysurgeryintherabbit.SpecificAims:Totestthishypothesis,wewillassesstheeffectsofQuercetinonkeratocytebackscattering,alignment,morphologyandconnectivityinvivofollowingakeratectomyinjury(photorefractivekeratectomy,PRK)whichproducesafibroticresponseontopoftheinjuredstroma.CorneaswillbeevaluatedusingtheHeidelbergRetinaTomographRostockCorneaModule(HRT-RCM)clinicalconfocalmicroscope,andthesefindingswillbecorrelatedwithenbloc3-Dconfocalfluorescenceandsecondharmonicgeneration(SHG)imaging.

DanielleRobertson

Ophthalmology Impactofinsulin,IGF-1,andhyperglycemiaonautophagyinthecornealepitheliumandwouldhealing

Hypothesis:Thathyperglycemia-inducedalterationsinautophagyplaysapivotalroleinthedevelopmentofcornealepithelialcomplicationsandimpairedwoundhealingindiabetes.SpecificAims:Wewilltestthishypothesisinthefollowingtwospecificaims:1.(a)Wewillexaminetheroleofinsulininmediatingautophagyinthecornealepithelium.(b)Wewillthentesttheeffectsofhyperglycemiaonautophagyinthecornealepithelium.2.Wewillcomparethelevelofautophagyinnormalversusdiabeticcornealepithelialcellsobtainedbyprimarycultureofhumandonoreyebankcorneas.

JohnHulleman Ophthalmology Developmentofaprimaryretinalcellculturemodeltoidentifythecause(s)of

WehypothesizethathfRPEcellscanbeusedtogenerateaprimaryRPEmodelthatrecapitulatestheformationofsub-RPE

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theraremaculardystrophy,MalattiaLeventinese

proteindepositsreminiscentofML/AMD.SpecificAims.1.)ToestablishanhfRPEwhichdevelopssub-RPEproteindeposits.2.)Totestanumberofgeneticandpharmacologicmanipulationsinthiscellculturemodeltodeterminetheireffectonrescuingproteindepositformation.

RonaldMancini Ophthalmology Riskfactorscontributingtopathophysiologyofprimaryacquirednasolacrimalductobstruction

WehypothesizeriskfactorsexistthatmaycontributetothepathophysiologyofPANDO,suchasuseofglaucomamedications,environmentalfactors(i.e.cosmeticuse),gender,medicalco-morbidities,andmetabolicdisturbancesparticularlyinvolvingNa+,K+,Cl-,Ca++whichmaybeassociatedwithstoneformationsometimesnotedinPANDO.WewillaimtoidentifypotentialriskfactorsthatleadtoPANDObylookingforanypossiblestatisticallysignificantcorrelationbetweenfactorsanddisease.

DanielleRobertson

Ophthalmology PseudomonasaeruginosaTypeVIsecretionsystemonneutrophilactinpolymerization

SpecificAim:ToassesstheabilityofP.aeruginosatoevadetheinnateimmunesystembycomparingthepotentialforwildtype(PA01)andH2-T6SSmutant(PA01ΔclpV2)toinduceactinpolymerizationinhumanneutrophilsandinhibitfurtherphagocytosisinvitro.Hypothesis:ATypeVIsecretionsystemisutilizedbyPseudomonasaeruginosatointerferewithneutrophilactincytoskeleton,thushinderingitsphagocyticcapabilities.

PaulaHernandezValdez

OrthopaedicSurgery MolecularandMorphologicalResponsestoSevereBurnInjuryinRatAchillesTendonandIntervertebralDisks

Hypothesis:TheAchillestendonwillbeaffectedbysystemicexpressionofpro-inflammatorycytokinesalteringitsremodelingbalance.Also,NPcellsintheIVDswillbealteredbothmorphologicallyandinproteinexpression.SpecificAims:Aim1:Tostudygeneandproteinexpressionofpro-inflammatorycytokines,CollagenI,CollagenIIIandMMPsinAchillestendonafterskinburnaswellastocharacterizechangesinfiberalignment.Aim2:TostudyproteinexpressioninNPcellsfromIVDs,comparingareasimmediatelybelowthesiteofburninjurywiththosethataremoredistant.Wewillalsocomparetheequivalentdiscsofnon-burnedcontrolratsandobserveformorphologicalchangesinNPcellsafterburning.

MichaelKhazzam OrthopaedicSurgery EffectivenessofCorticosteroidvs.KetorolacShoulderInjections:AProspectiveDouble-BlindedRandomizedTrial

ThegoalofthisstudyistotesttheefficacyofintraarticularinjectionsofKetorolacvs.Corticosteroidonrotatorcuffshoulderpathologies,specificallyrotatorcufftearsandtendonitis.WehypothesizethatsubacromialinjectionsofKetorolacwillbemoreeffectivethancorticosteroidinjectionsinpainrelieftreatmentforshoulderpathologies.

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MohammedKhaleel

OrthopaedicSurgery SleepDisturbanceinPatientswithOperativeSpinePathology

Hypothesis:Spinepathologyhasanegativeimpactonsleepquality,andsurgicaltreatmentwillincreasethequalityofsleepinpatientswithoperativespinepathology.

MichaelHuo OrthopaedicSurgery RetrospectiveDatabaseforTotalKneeArthroplasty(TKA)

SpecificAim:TocollectclinicalandradiographicdatainconsecutivepatientswhohaveundergoneprimaryandrevisionTKAsatUTSouthwesternMedicalCenteranditsaffiliatesandParklandHealthandHospitalSystem.

HarryKim Orthopaedics Proximalfemoralgrowthmodulationusingpercutaneoustrans-physealscrewplacement

Specificaim.Wewilldeterminetheeffectsofaneccentricallyplacedtrans-physealscrewoninducingavarusorvalgusangulationoftheproximalfemurinalargegrowinganimalmodel.Hypothesis.Wehypothesizethatamediallyorlaterallyplacedproximalfemoraltrans-physealscrewwillserveasagrowthtetherandproduceavarusorvalgusangulationoftheproximalfemur,respectively.

MichaelKhazzam OrthopedicSurgery EffectivenessofCorticosteroidvs.KetorolacShoulderInjections:AProspectiveDouble-BlindedRandomizedTrial

SpecificAim:IwillbeassistingDr.MichaelKhazzaminaprospective,randomizeddouble-blindedstudythataimstocomparetheeffectivenessofketorolacorcorticosteroidinjectionsinindividualswhohaveacquiredshoulderpathologiesincludingatraumaticfullthicknessrotatorcufftearsandrotatorcufftendinitis.ThehypothesisstatesshoulderinjectionswithKetorolacwillbemoreeffectivethancorticosteroidinjections.

PaulaHernandez Orthopedics TheroleofHtrA1inthemorphologicchangesofchondrocytemorphologyseeninOsteoarthritis.

Hypothesis:chondrocytephenotypicregulationisdisruptedbyoverexpressionofHtrA1,leadingtochangesobservedinOA.SpecificAims:Aim1:tocompareOAsampleswithcontrolin(i)HtrA1expressionusingqPCRandWesternblot,(ii)HtrA1associationwithcytoskeletonusingco-immunoprecipitationandimmunofluorescence,and(iii)analysisofcellmorphologyparameterssuchascellcircularity,perimeter,andattachmentsinordertostudychangesinphenotype.Aim2:TocomparecontrolchondrocytesversusOAchondrocytesresponsetoCytochalasinDtreatment,usingcellmorphologyparameters.LowdosesofCytochalasinDwillcausecytoskeletaldisruption,particularlyinactinfilaments.

KennethLee Otolaryngology ImprovingPatientHearingOutcomesbyMinimizingInsertionTraumawithaShapeMemoryPolymerCochlearImplantArray

Hypothesis:Novelself-coilingelectrodearraysmadeofshapememorypolymerallowforatraumaticimplantationofcochlearimplants,minimizinglossofresidualhearingandmaximizinghearingoutcomesincochlearimplantpatients.

RonMitchell Otolaryngology PolysomnographicvariationandAdenotonsillectomyoutcomesinthe

Hypothesis:AmongchildrenwithDownsyndrome,obesity,ageandethnicityunfavorablypredictsoutcomesofT&Ainchildren

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pediatricpopulationwithDownsyndrome

SpecificAims:ThespecificaimsofthisprojectaretocorrelatedemographicsandespeciallyweightwiththeoutcomesofT&AinchildrenwithDownsyndromeandOSA.ThegoalisidentifypredictorsofresolutionofOSAinchildrenwithDownsyndromebasedondemographics,clinicalandpolysomnographicparameters.

RonMitchell OtolaryngologyHeadandNeckSurgery

OutcomesofT&Ainoverweightandobesepediatricpatientswithobstructivesleepapnea

WehypothesizethatT&AwillresultinimprovementorresolutionofOSAinoverweightandobesepatientsbuttheresponsewillnotbeuniform.Wealsohypothesizethatsomepredictorsofoutcomewouldincludeage,BMIz-score(specificallyweightincrease)andethnicity.

RonMitchell Otolaryngology,Pediatrics

CorrelatestoWeightGaininChildrenwithObstructiveSleepApneafollowingTonsillectomy

Manypediatriccasesofobstructivesleepapnea(OSA)occurduetotonsillitis,whichmaybetreatedwitharoutinetonsillectomy.However,manychildrenrelapseintoOSAaftertonsillectomydespitetemporaryreliefofsymptoms.Onepossiblecauseofthismaybeduetotheassociationbetweentonsillectomiesandpost-operativeweightgain,asobservedbyLewiset.al.in'Weightgainafteradenotonsillectomy:acasecontrolstudy'(2015).Inobesepatients,excessiveaccumulationofadiposetissuearoundtheneckcanleadtoairwayobstruction,thusresultinginOSA.Thegoalofthisprojectwillbetoperformaretrospectivemultivariateanalysisusingdemographicandotherpatientdata(fromtheChildren'sHealthEPICpatientrecords)toidentifyfactorsrelatingtoweightgainfollowingatonsillectomy.

JamesMalter Pathology IdentifyingrecombinantPIN1proteinsatspecificphospho-serinesitesandestablishingifsensitivetoB-amyloid

Pin1isacis-transpeptidylisomerasewithspecificityforserine-prolineorthreonine-prolinepeptidebonds,Pin1targetsincludeAPP,tau,4EBP1andavarietyofothersignalingproteinsinvolvedinneuronalfunctionandhomeostasis,leadingtothehypothesisthatPin1isinvolvedinADpathology.Pin1islostearlyinADevolutionpossiblyviaoxidationandacceleratedclearance.WhenboundtoAPPortau,Pin1acceleratesnon-amyloidogenicprocessingviaanalpha-secretasepathwayandhelpsmaintaintauinanon-phosphorylatedstate.WhetherorhowPin1enzymaticactivityisacutelyorchronicallyaffectedbyB-amyloid,thelikelycausalagentinAD,isunknown.Recently,wehaveidentifiedanewroleforPin1inthemaintenanceofdendriticspines.IntheabsenceofPin1,spinesarereducedinnumberandcomplexity.Ofnote,spinesarelostduringevolvingADthatmayaccountfortheprominentmemorylossesandbehavioralchangesseenearlyinthedisease.Therefore,itwas

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hypothesizedthatPin1loss/inhibitionwasresponsibleforthereductioninspinesseeninneuronstreatedwith/exposedtoB-amyloid.

MohammadTariqueHussain

PediatricCardiology ClinicalOutcomesandUtilityofCardiacCatheterizationPriortoFontanCompletionintheCurrentEra

Hypothesisandspecificaims:Ourgoalistoconductaretrospective,observationalstudyinwhichweexaminetheoutcomesofthepatientsatChildren'sMedicalCentereligiblefortheGlennproceduretodetermineunderwhatcircumstancespatientsproceededandunderwenttheGlenn;whatcircumstancespatientswererecommendedforandreceivedhearttransplantationandwhatcircumstancesresultedinnofurthertherapeuticoptionsbeingavailabletothem.WehypothesizethatpatientsarenotexcludedfromtheFontanprocedurebasedonhemodynamicdatathatwasnototherwisefoundinahistoryorechocardiogram.

HannahPiper PediatricSurgery Evaluationofurinarysodium,dietarysodiumintake,andsomaticgrowthinchildrenwithshortbowelsyndrome

HypothesisChildrenwithshortbowelsyndromewhoarereceivingsufficientdietarysodiumtomaintainaurinesodiumconcentration≥60meq/Lwillhavebetterweightgainandlineargrowthcomparedtochildrenwithurinesodium<60meq/Lreceivingsimilarkcal/kg.SpecificAims1.Tocorrelateurinesodiumconcentration(mmol/L)inchildrenwithSBSwithaveragedailyweightgain(g/kg/d),lineargrowth,anddailysodiumintake(mEq/kg/d)2.Todevelopaguidelineformonitoringurinarysodiumconcentrationanddietarysodiumsupplementationtoachievesufficientsomaticgrowth

FaisalQureshi PediatricSurgery AreviewofthetreatmentofspleniccystsatChildren'sMedicalCenter

Hypothesis:Wehypothesizethatthetreatmentofspleniccystswithaspirationandsclerotherapywillhavefewercomplicationsandalowerfailureratethanothertreatmentmodalities.

JosephMurphy PediatricSurgery IVCTumorThrombus-Identification,ManagementandConsequences

OurhypothesisisthosepatientswithIVCtumorthrombidoworsethanthoseIVCpatientsarewithoutthrombi.SpecificAims:Theaimofthisstudyistoidentifychildrenwithinferiorvenacava(IVC)tumorthrombi,describetheirsurgicalexperienceanddetailtheirlong-termoncologicandphysiologicoutcomes.

LindaBaker PediatricUrology NovelSurgicalTechniqueforDrainageofObstructedUterovaginalDuplication

HYPOTHESIS:Percutaneousobstructedhemivaginaaccess(POHVA)leadstominimallyinvasiveidentificationandsafeentrytothedifficultOHcomparedtoblinddissectionandsuccessfullyidentifiesthedifficultOHinover50%ofcasesSPECIFICAIMS:1.Reportthenoveltechniqueofpercutaneousobstructedhemivaginaaccess,POHVA.2.FindsuccessrateofPOHVAin

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identificationofandsafeentrytothedifficultOHinallpastcases.3.DeterminecomplicationsifanythatarosesecondarytothePOHVAtechnique

ChristyTurer Pediatrics AutomatingClinicalDecisionSupporttoImprovePediatricHypertensionIdentificationandManagement:AnEvaluationofDiagnosticSensitivity,ComputationalEfficiency,andCostofThreeProposedMethods

Wehypothesizethatthethird(Cache)methodwillbethemostsensitivefordiagnosingpediatrichypertension,followedbyuseofSDEs,andfinally,thesubstitutionofpoint-of-careheightandagemeasuresformissingorinaccuratehistoricalvalues(COCB).

DarrylMiles Pediatrics AStudyofOpticNerveSheathDiametertoPredictIntracranialHypertensioninPediatricBrainInjuredPatients

SpecificAims:Aim1:CompileastandardizednormativedatasetofONSDsinchildrenrangingfrominfancyto18years.Impact:Thisnormativedatacanbeusedbyfuturepediatricphysiciansacrossthecountrytoinformthemwhethertheirpatienthasnormallevelsofpressureornot.ThiscouldpreventunnecessarysurgicalproceduresandCTscans.Aim2:DeterminethesensitivityandspecificityoftheONSDproceduretopredictpathologicalchangesinICPinpediatricpatients.Impact:Ifproven,thisprocedurecoulddetectelevatedICPnon-invasivelyandhelpphysiciansmonitorpressurelevelsintheirpatientsonceadmittedtothePICUwithoutinvasivemonitoring.Thistechniquecouldthenbeusedonawiderangeofpediatricpatientswithacuteneurologicinjury.Hypothesis:Wehypothesizethatanultrasoundbased-measurementONSDof>4.5mminchildrenwillcorrelatewithanICPofgreaterthan20mmHgwithinvasivemonitoringmethods.

MayLau Pediatrics UniqueFactorsofDatingViolenceinAsianAmericanAdolescents

Hypothesis:1.Asian-Americanadolescentswillhavedatingviolenceratesequivalenttootherraces.2.UniquefactorswillbeidentifiedthatexplaintheequivalentdatingviolenceratesinAsian-AmericansSpecificaims:Thespecificaimsofthisstudyis:1.ToexamineratesofdatingviolenceamongAsianAmericansadolescentsandyoungadults2.Toidentifysociodemographic,academic,violence-related,drug-related,andmentalhealthfactorsthatareassociatedwithdatingviolenceinAsianAmericanadolescents

JamesCollins Pharmacology AnalysisofneoblastgeneexpressionandfunctioninSchistosomaflatworms

Wehypothesizethatneoblast-driventegumentrenewalisessentialtoprotecttheschistosomefromthehost'simmunesystem.Specificaims:Totestourmainhypothesis,werequireanin-depthunderstandingofthemoleculareventsthatcoordinatethedifferentiationofneoblastsintotegumentalcells.Therefore,wewillclonecDNAsfor20-30stemcell

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associatedgenesandperformdoublefluorescentinsituhybridizationexperimentswithknownneoblastmarkerstoconfirmthesegenesareexpressedinstemcells.

ElisabethMartinez Pharmacology TheeffectsofJumonjihistonelysinedemethylasesontheP.falciparumlifecycle

IhypothesizethatJumonjihistonelysinedemethylasesplayacriticalroleinregulatinggenetranscriptioninP.falciparumandthusmediatingparasitevirulence,andthatdisruptionofthisregulatorymechanismwilldisruptitsvirulence.SpecificAims•TodeterminehowtheredbloodcellstagesofP.falciparumareaffectedbyhistonedemethylaseinhibitors.Morespecifically,IaimtocharacterizeJIB-04-treatedbloodstageparasitestodetermine:1.whenmorphologicalchangesbecomeapparent,2.whetherthebloodcellstageoftheparasiteimpactstheabilityofdemethylaseinhibitorstoimpedelifecycleprogression3.howquicklydemethylaseinhibitorskilltheparasite•ToidentifychangesingeneexpressionmediatedbyJIB-04

JoyceRepa Physiology EvaluatingtherapiesforNiemann-PicktypeCdisease

WehypothesizethatLXRagonistsand/oranewtherapy,triglycerolacetate,mayimprovehearingfunctionandlungdiseaseinNPC.SpecificAim1.DeterminewhetherLXRactivityimpactshearing.a)PerformAuditoryBrainstemResponse(ABR)testsinwildtype,Lxralpha-/-,Lxrbeta-/-,andLxralpha/beta-/-mice.b)PerformABRtestingofNpc1+/+andNpc1-/-micetreatedwiththeLXRagonistT0901317.SpecificAim2.CharacterizethepulmonarydysfunctioninNPCdisease,andevaluatetheimpactoftherapies(T0901317,cyclodextrin,andtriglycerol-acetate)onlungphenotypesintheNpc1-/-mouse.a)PerformMS-MSALLlipidomicsanalysesonlungtissuesfromtreatedNpc1+/+andNpc1-/-mice.b)Usequantitativereal-timePCRtomeasuretheexpressionofgenesrelevanttopulmonarycelltypesandfunction(e.g.surfactants),inflammation,andlipidmetabolismusinglungtissuesfromthesemice.

ChristopherDerderian

PediatricPlasticandCraniofacialSurgery

Determiningthecraniofaciallandmarksimportantinassessingheadshape:Astudyusingeyetrackingtechnology

Wehypothesizethatthereareimportantreferencepointsintheheadandfacethatindividualscompareagainstthresholdsofnormalandabnormalandusetomakethesocialdeterminationofdeformity.Wefurtherhypothesizethatthesereferencepoints,andtheprocessofevaluation,areconservedbetweenindividuals.SpecificAims1.Assesstheeyemovementsusedinnormalheadshapeevaluationtodeterminetheoverallprocessofevaluationofnormalheadshape.2.Determinehoweyemovementsdeviatefromtheprocessofnormalheadshape

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evaluationintheevaluationofabnormalheadshape.BardiaAmirlak PlasticSurgery Retrospectivestudytomeasureefficacy

ofonabotulinumtoxinAinthecontextofchronicmigraineheadaches.

WepredictthataccurateinjectionofonabotulinumtoxinAintocarefullystudiedanatomicalsitesareeffectiveinreducingdiseaseburden.Inthisstudy,aretrospectivereviewofpatientsforheadachecharacteristicswillbeconductedtomeasurepreandposttreatmentchanges.Suchcharacteristicsincludefrequency,duration,andseverity.

NicholasHaddock PlasticSurgery Co-surgeonsinBreastReconstructiveMicrosurgery:WhatDoTheyBringtoTheTableinanAcademicInstitution?

Hypothesis:TheadditionofaCo-surgeonwebelievewillreduceoperativetime,averagepatientLOS,andsomepost-operativecomplications.Webelievethattheco-surgerymodelisassociatedwithincreasedoperativeefficiencyforBilateralDIEPBreastReconstruction.

JeffreyKenkel PlasticSurgery ClinicalAssessmentofthePerformanceofCombination1470nm/2940nmLaserTherapyforImprovedFacialSkinTexture,Tone,andReductionofSkinPoreSize

Ideally,non-surgicalskinrejuvenationwillmovetowardslasertreatmentsthatachievetheresultsofablativetherapieswithouttheunfavorablerecoverytimesandrisks.Inoursummerproject,wewillinitiallydefinewhatyouthfulskinlookslikeusingnon-invasivetechniquessuchashighresolutionphotography,3-dimensionalphotography,UVlightevaluation,high-resolutionultrasound(HRUS),elasticitymeasurements,andvariouspolarizedlights.Specifically,3D-photographywillbeusedtoevaluateimprovementsinskintone,texture,andporesize.UVlightevaluationwillbeusedtoassessimprovementsinactinicsundamage.HRUSwillbeusedtomeasureincreasesincollagenthickness.Wewilltheninvestigateskinultrastructureevaluatingcollagen,elastin,andglycosaminoglycansusingelectronandconfocalmicroscopy.Inaddition,wewillconsiderthegeneexpressionusingRNAsequencingandMassspectroscopy.

SumeetTeotaNicholasHaddock

PlasticSurgery The2stagedimplantbasedreconstructionwithanatomictexturedimplantsinNipple-sparingmastectomy

Wehypothesizethatstrictadherancetoprotocolfortexturedimplantsisnecessarytooptimizepatientoutcome.Furthermorecertaintechniquesofmanipulationofexpandersizemayreducethecomplicationrateandresultinhigherpatientsatisfaction.

SumeetTeotia PlasticSurgery Challengesinradiationofpatientswithbreastcancer,QuantitativeAnalysisinoutcomesofseven-hundredconsecutiveautologousbreastreconstructionsatUTSW

Hypothesis:Refinementsinmultiple-freeflapbreastreconstructionsproducebetteraestheticoutcomesandpatientsatisfactioninpost-radiation,post-mastectomy,patients.

CarolNorth Psychiatry SecondaryAnalysisSUNCODAStudyDataonHomelessServiceUse

ScientificaimsandhypothesesAim1.ToexaminetheSUNCODAmodel,exploringtherelationshipsamongpredisposing,enabling,andneedfactors,serviceuse,andcostof

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servicesassociatedwithdrugabuseandotherhealthconditions,andhowthesefactorsandserviceuseareassociatedwithchangesinstatusovertimeinadrugabusinghomelesspopulation.These'changeinstatus'variablesincludeddruguse,housing,consequencesofdruguse,andHIVriskbehaviors.Aim1pertainstotheSUNCODAmodel'sabilitytopredictserviceuseandsubsequentstatuschanges.Thesestatuschangesincludeachievementofstablehousing,changesinsubstanceusepatternsandtheirconsequences,changesinpsychiatricstatus,changesinHIVriskbehaviors,andchangesinotherbehaviorsassociatedwithhomelessnessandsubstanceusedisordersandtheirconsequences(e.g.,employment,entitlementuse,childcustodystatus).ThedatasetcollectedfortheSUNCODAprojectprovidesarichsourceofmaterialforinvestigationoftherelativedirectcostsofserviceuseandtheirrelationtostatuschanges.AnalysesrelatedtospecificcomponentsoftheSUNCODAmodelarepredictionofhousingoutcomesfromdrugabusestatusandtreatmentutilized.AnalysisofdatafortheSUNCODAhomelessmodelonwhichthedatafromthisprojectarestructuredpermitscombiningattributesofstructuralanalysis(pathanalytic)modelswithrepeatedmeasurestoexaminecomponentsofthemodelsimultaneously.TheseanalysesareongoingandwillprovideyearsofproductiveanalysisandpublicationoffindingsfromtheSUNCODAdatabases.Aim2.Toexaminetheassociationofdrugabuseandthecourseofhomelessnessbycomparingdrugabusingandnon-drugabusinghomelessindividualsovertimeintermsofstatuschangeassociatedwithserviceusewithintheSUNCODAhomelessmodel.Hypothesis1:Drugabusinghomelessindividualswillnotonlybemorelikelytousedrug-relatedservices,theseindividualswillalsobemorelikelytouseavarietyofservicesmoreextensivelythanwilltheirnon-drugabusingcounterparts,includingalcoholtreatmentandotherpsychiatric,medical,andsocialservices.Hypothesis2:Controllingfortheextentandtypesofservicesused,drugabusingindividualswillhaveworseconsequencesthantheirnon-drugabusingcounterparts.Serviceuseandextentofusewillbelesspredictiveofstatuschanges(e.g.,exitinghomelessness)indrugabusinghomelessindividualsthaninthenon-drugabusinghomelesscomparisonpopulation.

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SherwoodBrown Psychiatry RelationshipBetweenDepressionandBoneDensityintheDallasHeartStudy.

Hypothesis:CurrentdepressivesymptomseveritywillbeinverselyrelatedtoBMDSpecificAims:PrimaryAim:DeterminewhethercurrentdepressivesymptomseverityisinverselyrelatedtoBMDinparticipantsintheDHS.SecondaryAims:1)ExploreracialandethnicdifferencesintherelationshipbetweencurrentdepressivesymptomseverityandBMD.2)DeterminewhetherantidepressantuseinfluencestherelationshipbetweendepressivesymptomsandBMD.

XuejunGu RadiationOncology AutomaticSegmentationforBrainTumorsinStereotacticRadiosurgeryApplications

SpecificAims:Thegoalofthisprojectistodevelopanauto-segmentationclinicaltoolthatcanhelpalleviatetheworkloadofmanualcontouringduringSRSplanning,providegoodbasecontoursforphysicianstorefine,andreduceinter-observercontouringvariability.

KevinAlbuquerque

RadiationOncology HematologicToxicityinIntactCervicalCancerPatientswhohaveUndergoneIntensity-ModulatedRadiationTherapywithandwithoutBoneMarrowSparing

SpecificAimsAim1:ComparetheHToccurrenceratebetweenpatientsirradiatedbynormal-IMRT,BMS-IMRTand3D-CRTinanindigentpatientpopulation.Aim2:DeterminethepredictorsofHTincervicalcancerpatientsreceivingIMRT.Aim3:ReportoutcomesofpatientsreceivingIMRTforintactcervicalcancer.HypothesisWehypothesizethatBMS-IMRTpatientswillhavetheleastriskofHTwhile3D-CRTpatientswillhavethehighestriskforHT,becauseBMS-IMRTwillirradiateaslittleofthebonemarrowaspossiblewhereasthe3D-CRTpatientswillreceivethegreatestamountofirradiationtothepelvicbonemarrow.WehypothesizethattheoutcomeofpatientsreceivingIMRTforintactcervicalcancerwillnotbeasfavorableasthosereceiving3D-CRT,becausewhileIMRTisveryeffectiveindefiningthebordersofthetumor,thetumorcouldmoveduringtreatment,leadingtoineffectiveirradiationofthetumorsincetheboundarieshavechanged.

IvanPedrosa Radiology Identifyinghistologicandgeneticfactorsexplainingcorrelationbetweenmagneticresonanceimagingphenotypesandpapillaryrenalcellcarcinomaprognosis

Hypothesis:BecauseithasbeenshownthatimagingphenotypesarebetterpredictorsforassessingprognosisofpapillaryRCCs,thehypothesisunderstudyisthattherearespecificMRIimagingphenotypesthatcorrelatewithspecifichistologicalfindingsindicativeofpapillaryRCCs,suchasthepresenceofinfiltrationoftheadjacentrenalparenchymaand/orperirenalfatathistopathology.ArecentstudyhasalsoelucidatedacollectionofgeneticmutationsthatcorrelatewithdiagnosisofpRCC.AnotherhypothesistobeinvestigatedinthisprojectiswhethertherearespecificmolecularandgeneticfeaturesthatcanbeidentifiedandcorrelatedwiththeMRimagingphenotypesandtheir

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prognosticpredictions.ByidentifyingthesehistologicalandgeneticfeaturesandexplainingiftheycorrelatewithMRimagingphenotypes,wecanbetterunderstandandexplainwhyMRIphenotypesmaybeaccurateandeffectiveindicatorsofpapillaryRCCprognosis.

DanielCosta Radiology Anovelmodel-independentDWIinterpretationmethodforthediagnosisofprostatecancer

HypothesisThemodel-independentDWIratioimage(lowbvaluedividedbyhighbvalue)isnoninferiortothatofthecurrentgoldstandardofADCfordiagnosisofprostatecancer.SpecificAimsInordertosupporttheuseoftheb-valueratioasamethodforevaluationofprostatecancer,theinvestigationmustcomparetheaccuracyofGleasonscoringbetweenusingtheb-valueratioandADCmeasurement.

RalphMason Radiology Evaluatingphotoacoustictomography(PAT)inbreasttumoroxygenation

HypothesisPhotoacoustictomographywillrevealheterogeneityintumoroxygenationwithrespecttorespiratorychallenges.SpecificaimsAssessabilityofphotoacoustictomographytodetectchangesinbreasttumoroxygenation

DavidBoothman SimmonsComprehensiveCancerCenter,Pharmacology,RadiationOncology

RoleofMTH1inpotentiatingb-lapachonetumorselectivedeathinpancreaticductaladenocarcinomas

Hypothesis:Webelievethatinhibitionofproteinsparticipatinginbaseexcisionrepair(BER),specificallyMTH1,willenhanceb-lapachoneefficacyandimprovepatientoutcomeswithpancreaticductaladenocarcinomasbyallowingustouselowerdosesofb-lapachoneandtherebyreducepatienttoxicityintheformofmethemaglobinemia.ThisprojectwillfocusonthemechanismofactionofMTH1potentiatingb-lapachoneusingPDAcelllinecultures.SpecificAims:InhibitingBERspecificproteins,mainlyMTH1,andallowingforprolongedapyrimidinic/apurinic(AP)sitehalf-lifewhichwillfurtherpotentiatePARP1hyperactivationandtumorcelldeath.SinceMTH1isinvolvedinpreventingtheincorporationofDNAdamagingmolecules,weexpecttoseeincreasedDNAdamage,subsequenthyperactivationofPARP1,andeventualcelldeathbyknockingdownMTH1activity.SpecificAim1:ToexploretheinvitroeffectofMTH1inhibitiononb-lapachoneefficacyinPDAtumorsusingNQO1+vsNQO1-MiaPaca2celllines.OtherPDAcelllineswithvariedNQO1levelswillalsobeexplored.SpecificAim2:ToelucidatethemechanismofactionofMTH1inhibitiontoincreasethepotencyofb-lapachoneinNQO1+PDAcellsinvitro.Aim1:MTH1expressionwillbeknockeddownintheNQO1+vsNQO1-MiaPaca2pancreatictumorcelllineusingthreedifferentmethods:transientsiRNA,stableshRNA,andMTH1inhibitor.Knockdownwillthenbeconfirmedusing

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WesternblottingorReal-TimePCRexpressionanalyses.Cellsurvivalassays,includingDNAandcolonyformingassessmentswillthenbeperformedtoascertaintheeffectsthatknockdownofMTH1willhaveon-lapachoneactivity.OtherPDAcells(12totalcelllines)willthenbetested.IexpectNQO1+,MTH1-cellswillhavethegreatestlossofoverallsurvival,withnoalterationsincellcyclestatusesasnotedpreviously.Aim2:CelldeathpotentiatedbyMTH1inhibitionincombinationwithsub-lethaldosesb-lapachoneshouldbeaccompaniedbyincreasedDNAdamage.Usingnontoxicdosesofb-lapachone,IwilltestforexpectedlossesinglycolysisandTCAcyclemetabolism.Additionally,Iwillmonitorforarisein8-oxo-dGTPincorporation,increasedDNAdamage(bycometandyH2AX/53BP1fociformationassays),andelevatedlevelsofPARformation.

StevenWolf Surgery Combinationtherapeuticstrategyofmusclefunctionimprovement

Hypothesis:AgrowthresponseintheskeletalmusclecellswithfunctionalimprovementthroughtheuseofmesenchymalstemcellsandUBM,characterizedthroughsystemicmorphologicalchangesincludinglipogenesis,fibrosis,musclefiberstructure,andangiogenesis.

PatricioM.Polanco

Surgery FailuretoRescueafterCytoreductiveSurgeryandHyperthermicIntraperitonealChemotherapytoTreatPeritonealCarcinomatosis

WeaimtodefinetherelationshipbetweensurgeonandhospitaloperativevolumesofCRS/HIPECandFTRafterthisprocedureusingtheNationalInpatientSample(NIS)dataset.Wealsoaimtoidentifypatients'riskfactorsandcomorbiditiesassociatedwithFTRfollowingCRS/HIPECusingtheNationalSurgicalQualityImprovementProgramdatabase(NSQIP).NISandNSQIParetwolargenationaldatasets.WehypothesizethatmorbidityandmortalityfollowingCRS/HIPECareassociatedwithindividualsurgeons'andinstitutionalpatientvolumes.WealsohypothesizethatFTRispredictableinpatientspresentingwithspecificriskfactorsandco-morbiditiesundergoingCRS/HIPEC.

StevenWolf Surgery Theroleofmyokinemusclininmuscleatrophyafterburn

Theaimofthestudyistoinvestigatetheroleofmusclininmuscleatrophyinresponsetosevereinjury.Thehypothesisofthestudyisthatmusclinisnecessaryformusclehomeostasis,muscleatrophyfollowingmuscleatrophyisatleastpartlythroughmusclinsignaling.Thespecificaimsofstudyareto1)todetectmusclinlevelinresponsetoburn;2)toidentifythemusclininregulatingmitochondrialimpairmentinmuscleafterburn;3)toinvestigatetheeffectofmuscledisuse,exerciseandinsulininmusclinexpressions.

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StevenWolf Surgery CholecystitisandtheMicrobiomeoftheGallBladder

HYPOTHESIS:Themicrobiotacompositioninsevereacutecholecystitiswillbecomplexandtheseveritygradesofcholecystitiswillhavesignificantdifferencesintheirmicrobiotaprofiles.SPECIFICAIM:Determinethemicrobiomeprofileofthegallbladderinacutecholecystitis.

Stevenwolf Surgery ChangesinWeightDuringAcuteHospitalisationintheSeverelyBurned:ModernClinicalPracticeandPotentialPitfalls

Ourgeneralhypothesisisthatweightlossiscommonintheseverelyburnedandfollowsapredictablepattern.

AdamAlder Surgery AReviewofIntervalAppendectomy Weaimtouseamatchedcase-controlapproachtocomparetheclinicaloutcomesofpatientswithcomplicatedappendicitiswhowereselectedforfirst-lineantibioticversusfirst-lineappendectomyapproachestomanagement.Wehypothesizethatafirst-lineantibioticapproachtocomplicatedacuteappendicitisinchildrenwillnotbeassociatedwithanincreaseinEDvisitsandCTscanscomparedtoafirst-lineappendectomyapproach.

SergioHuerta Surgery Predictorsofmorbidityandmortalityinpatientsundergoingcholecystectomyinveteranpatients

ThemaingoalofthisstudyistoidentifyoutcomesofveteranpatientsundergoingcholecystectomiesattheVAhospital.Wehypothesizethatwhilethenumberofcomorbidconditionsinourpatientpopulationisincreasing,thecomplicationrateandmortalityremainsthesame.Further,thisanalysiswillallowustoidentifyfactorsthatmightpreventadverseoutcomesinthosethathavethem.

StevenWolf Surgery Testinginflammatorycytokinesandmitochondrialproteinsandhowtheyaffectmitochondrialdynamicsinresponsetoburn

Hypothesis:BurnresultedmusclecelldeathisdependofIL-6andTNF-alphastimulation;intracellularpathwayisassociatedwithmitochondrialfission/fusioncycleregulatedbyDrp1/Mfn1signals.Forspecificaim1,wearegoingtorepeatburnserumstimulationofnormalC2C12musclecells,butaddanIL-6andTNF-alphapostburnserumstimulation,sothatwemayobservetheeffectsonmitochondrialmorphology.Inadditional,wearegoingtotestmitochondrialdynamicsinprimarymurinemyoblast.Forspecificaim2,wearegoingtoknockoutDrp1andMfn1inC2C12musclecelllinesbyusingcrispr/cas9andlentiviraltransfectioninvitro.

MichaelChoti Surgery Theroleoftheintestinalmicrobiotainpostoperativeoutcomesfollowingpancreaticcancersurgery

Inthisstudy,wewillinvestigatewhetherthereisacorrelationbetweenintestinaldysbiosisandpost-operativeclinicalsymptomsafterpancreaticsurgery.Todeterminethiswewillusestepwiseforwardlogisticregressionanalysisofclinical

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characteristicstomodeltheindependentpredictorsforpost-operativegastrointestinalsymptoms.Inthisstudy,wewillalsocharacterizetheintestinalmicrobiotainpatientsthathaveundergonepancreaticoduodenectomycomparedtopatientswhohaveundergodistalpancreatectomy.

RoshniRao Surgery EvaluationoftheCedilleIncisioninSkin-SparingTotalMastectomy

Purpose:ToevaluatewhethertheCédilleincisionforperformanceofskinsparingmastectomyprovidessuperiorresultswhencomparedtostandard'tennisracket'incisions.

JoselinAnandamArtiBarnes

SurgeryandInfectiousDiseases

InvestigationofeffectivenessofscreeningforanalcanceramongHIVpatientsintheParklandpatientpopulation

SpecificAims:Thefollowingspecificaimsaredefinedforthisproject1.Estimatethecurrentannual-screeningrateachieved(viaanalPaptesting)forParklandHIVpatientsanddetermineifthatscreeningratevariesacrossprovidersand/oracrosspatientdemographicsubgroups.2.EstimatethefractionofpatientswithpositiveanalPapresultsthathaveappropriateandtimelyfollow-upfordiagnosticconfirmation.3.EstimatethedistributionofstageatdiagnosisforHIVpatientsscreenedviaPaptestingandultimatelydiagnosedwithanalcancer,andcomparethatstagedistribution(afterdemographicadjustment)tounscreenedHIVpatientswithanalcancerdiagnoses.4.Estimatetheeffectoflife-yearsofannualanalcancerscreeningviaanalPaptesting,ascomparedtonoanalPaptesting.

BrianWilliams Surgery,DivisionofBurn/Trauma/CriticalCare

PosttraumaticStressDisorder(PTSD)intheprimarycaregiverofcriticallypatientsintheSurgical/TraumaICU

Individualswhowitness,orlearnof,traumaticeventshappeningtoaclosefamilymemberorfriendarealsoatriskofdevelopingPTSDsymptoms.ThismayincludefamilymembersoftraumapatientswhoareadmittedtoIntensiveCareUnits.Inthisprospectivepilotstudy,wewillestimatetheprevalenceofPTSDinthefamilymemberwhoistheprimarycaregiverofcriticallyillpatientsintheSurgical/TraumaIntensiveCareUnit(SICU).ThisobservationalpilotstudywilldetermineifusingavalidatedPTSDself-reportquestionnaireforthemaincaregiverofcriticallyillSICUpatientsisfeasibleandinvestigatewhetherthereisanotableprevalenceofPTSDwithinthispopulation.Withthisdata,wewillexpandourinvestigationtoevaluatepatternsofPTSDbasedonsocioeconomicstatus,immigrantstatus,mechanismoftrauma,andneedforemergencysurgery.Theprimarygoalistoimproveoutcomesforpatientsandfamilymembersofcriticallyillpatients.

MalcolmMacConmara

SurgicalTransplant 'DiscardedDonorOrgans-CanWeDoBetter?'

Thisresearchprojectaimstoexaminetheimpactofemployingsurgeonsdedicatedonlytotheprocurementoftheseorgansandtoseeifthishasledtoimprovedutilizationbytransplant

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programsinthearea,especiallyatUTSouthwesternMedicalCenter.Thespecificaimsoftheprojectareto:(1)identifytheincidenceoforgandiscardandthecausativefactorsintheNorthTexasDSA,(2)examinetheimpactofanindependentdonorsurgeonontherateandpatternsoforgandiscards,and(3)determineintheeventoforganreallocationiftheindependentsurgeonmodelhasimprovedrecipientoutcomes.Thegoalofthisresearchistobetterunderstandtheeventsandfactorsthatleadtoorgansbeingdiscardedandspecificallytoassessifbetterorganizationwithintheorgansharingsystemmightincreasethenumberoforgansused.

KempKernstine ThoracicSurgery CostandClinicalOutcomesforPulmonaryLobectomy:AssessingtheComparativeEffectivenessforOpen,Video-Assisted,andRoboticProcedures

Ourspecificaimforthisprojectistoprovideagreaterunderstandingoftheapplicationoftheseprocedurestoachieveoptimalcosteffectiveoutcomesinpulmonarylobectomy,perhapsofferinginsightintothelevelanddepthoftrainingrequiredtomaximizeproficiency.Onalargerscale,thisstudywillattempttobetterinformbothsurgeonsandinstitutionsofthebenefitsofparticulartechniquesthatimpactpatientsafety,performance,andcost-of-care.

GaryLemack Urology RiskFactorsPredictingComplicationsintheAdultSpinaBifidaPatient

Hypothesis:Wehypothesizethatadultpatientswithspinabifidapresentingwithcomplexpriorurologichistoryareatincreasedriskofcomplicationslong-term.SpecificAims:Theaimofthisprojectistoidentifymodifiableriskfactorsinthispopulationtopredictlong-termcomplications.Asecondaryaimistocharacterizetheurologicmanagement,qualityoflife(QOL)andsexualfunctioninthispopulationtoassistinguidelinesfortheirevaluationandmanagement.

PhilippeZimernn Urology CollegialityandTransparency:Howtoinformacolleagueaboutadelayedcomplicationofameshimplanteddevicetocorrectstressurinaryincontinenceand/orpelvicorganprolapse?

Itisourbeliefthatlong-termoutcomedataiscrucialforre-evaluationofcurrentsurgicalpracticeandwefeelsurgeonswithadverseeventsmaybenefitfromthisfeedback.

PhilippeZimmern Urology UrinaryAntibioticConcentrationInWomenNotRespondingtoUrinaryCulture-GuidedAntibioticTherapy

Unresolvedinfectionscouldbeduetoavarietyoffactorssuchas:-anincreaseinantibiotic-resistantUPEC,-adifferentbacteriaserotypethantheoneoriginallyidentified,-thedevelopmentofintracellularbacterialcommunities(IBC)asprovenintheurinesedimentofwomenexperiencingacuteandrecurrentUTI's,-anunder-dosingoftheadministeredantibiotic-oratreatmenttooshort.Severalmechanismsmaybeatplaytoexplainthissurprisingandunexpectedcourseofantibioticnon-

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responsedespiteanappropriatelyselectedurineculture-directedantibioticselection.AmongtheplausibleexplanationsforthislackofclinicaleffectivenessleadingtoanunresolvedUTIisthepossibilitythattheantibioticdosingisinsufficient,resultinginnon-bactericidalurinaryconcentrations.Itisnotcleariftheroleoffluidintakeandurinedilutioncouldbeaffectingtheefficacyoftheantibiotictreatmentatthebladderlevelaswell.AcreatinineurinevaluetoevaluatethelevelofurinaryconcentrationandurinaryantibioticconcentrationwillbeobtainedonaurinesampleatthecompletionofantibiotictreatmenttoverifyresolutionofinfectionandstudytheantibioticconcentrationvariabilityinalargecohortofolderwomenwithRUTI.

PhilippeZimmern Urology BacterialandPhageSurveyofUrinefromPostmenopausalUTIpatients

Studyaims/hypothesisWeareinterestedinthefollowingissues:ArebacteriainUTIclonal?WhilemanyUTIpathogenshavebeencharacterizedheretofore,thegeneticrelatednessofpathogensinthesamebladderisnotknown.If,forinstance,aUTIincludesmultipleUPECstrains,thenphage-basedantibacterialinterventionswouldneedtobeinformedbythisknowledge.Doesthepresenceofprophageinanystrainmakeitlesssusceptibletolyticbacteriophage?CRISPRandrestrictionsystemsarecommoninphageresistantstrains.ThemovementofCRISPRonprophageisnotknown,butCRISPRelementsdoinfluencetheretentionofpathogenicityislands,whichfacilitatephageresistance.Thesimultaneouspresenceofactiveprophageinphageresistantstrainswillprovideopportunitiestoexploremechanismsoflateraltransferofphageresistancebyprophage.Doprophageshaverecipientstrainsinthesamebladderisolatesastheirhosts?Thepresenceofsusceptiblestrainswillfacilitatecharacterizationofprophages,butmoreoveritmaysuggestpathwaysofgenetransmissionandsharingamonglike/unlikespecies.Whatistherateofspontaneousinductionofurine-derived-prophage-carrier-strains?TheabilityofphageDNAtobemobilizedthroughtransductionissalienttotheevolutionoflong-termandchronicinfectionsinpatients.Iftransductionhappensinthebladder,thenaresidentinfectionmaybecomemorerecalcitranttotherapywhenlysogenizedbyatransientandlessadaptedpathogenthatactsasaprophagedonor.

GregoryModrall VascularSurgery Renalatrophyandlong-termsurvivalinpatientswithrenalarterystenosisand

Hypothesis.Wehypothesizethatrenalarterystentingisassociatedwithlessrenalparenchymalatrophy,comparedto

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renalstenting patientswithrenalarterystenosisandnostenting.Wefurtherhypothesizethattherewillbenodifferenceinlong-termrenalfunctionorsurvivalbetweenthetwogroups(stentedversusunstented).SpecificAims.ThetwoSpecificAimsoftheprojectareto:1)Comparelongitudinalrenalvolume(overtime)intwogroupswithrenalarterystenosis:stentedversusunstentedgroups.2)Comparechangesinrenalfunctionovertimeandlong-termsurvivaloftwogroupswithrenalarterystenosis:stentedversusunstentedgroups.