简介:Objective:Anlotinibhydrochlorideisamultitargettyrosinekinaseinhibitorthattargetsvascularendothelialgrowthfactorreceptor,fibroblastgrowthfactorreceptor,platelet-derivedgrowthfactorreceptor,c-Kit,andc-MET;therefore,itexhibitsbothantitumorandanti-angiogeneticactivities.AphaseIIItrialhasshownthatanlotinibimprovedprogression-freesurvival(PFS)andoverallsurvival(OS)inpatientswithadvancednon-smallcelllungcancer(NSCLC),whopresentedwithprogressivediseaseorintoleranceafterstandardchemotherapy.Thisstudyaimedtoanalyzethecharacteristicsofpatientsreceivinganlotinibtreatmenttodeterminethedominantpopulationswhoarefitforthetreatment.Methods:DatawerecollectedfromMarch2015toJanuary2017fromarandomized,double-blind,placebo-controlled,multicenter,phaseIIItrialofanlotinib(ALTER0303).Atotalof437patientswereenrolledandrandomlyallocated(2:1)totheanlotinibandplacebogroups.Kaplan–Meieranalysisandlog-ranktestwereperformedtocomparePFSandOS.Coxproportionalhazardsmodelwasadoptedformultivariateprognosticanalysis.Results:Multivariateanalysisindicatedthathighpost-therapeuticperipheralbloodgranulocyte/lymphocyteratioandelevatedalkalinephosphataselevelswereindependentriskfactorsforPFS.Meanwhile,elevatedthyroid-stimulatinghormone,bloodglucose,andtriglyceridelevels;hypertension;andhand–footsyndromewereindependentprotectivefactorsofPFS.Highposttherapeuticperipheralbloodgranulocyte/lymphocyteratio,anEasternCooperativeOncologyGroup(ECOG)score≥2,andthesumofthemaximaltargetlesionlengthatbaselinewereindependentriskfactorsofOS,andhypertriglyceridemiawasanindependentprotectivefactorofOS.Conclusions:ThisstudypreliminarilyexploredthepossiblefactorsthataffectedPFSandOSafteranlotinibtreatmentinpatientswithadvancedrefractoryNSCLC,andthebaselinecharacteristicsofthetherapeuticallydominantpopulationswere
简介:WiththeendoftheColdWar,theconceptoftheThirdWorldhasgreatlychanged,andtheimportanceofthedevelopingstatesinU.S.newglobalstrategy,primacywithflexiblereactions,hasre-oriented.TheU.S.policytowardthesenationsalsohasbecomemorecomplicatedthanduringtheColdWarperiod.
简介:Researchongeomagneticreversalchronologyhasestablishedtheexistenceoftwosuperchrons,oneduringtheCretaceousandtheother(Kiaman)duringtheLatePaleozoic.Overthepastfewyears,wehaveperformedseveralmagnetostratigraphicstudiesonEarlyPaleozoic(CambrianandOrdovician)sedimentarysequencesfromSiberia.OurresultsshowhighmagneticreversalfrequenciesduringtheMiddleCambrian.Incontrast,severalrecordsshowtheoccurrenceofa-20MyrlongreversedpolarityintervalintheLowerandMiddleOrdovician,suggestingthepresenceofathirdsuperchron.Weproposetogivethenameof“Moyero”tothisnewsuperchron;thisnameisattributedtotheSiberiansectionwhichfirstyieldedacompleterecordofthisreversedpolarityinterval.
简介:Theconsequencesofglobalclimatechangepresentaseriousstrategicchallengeinoneofthemostremotepartsoftheworld.TheTibetanPlateauisthelargesthigh-altitudelandmassonearth,withmorethan45,000glaciersthatfeedthemajorriversystemsinAsia,which,inturn,support40percentoftheworld’spopulation.Temperaturesintheregionarerisingtwiceasfastastheglobalaverage,posingseriousriskstohydrologicalsystems,agriculture,andcriticalinfrastructure.Lookingatregionalcooperationthroughthelensofecologicalsecurityraisesimportantquestionsabouttheextenttowhichthethreatoflarge-scaleclimate-relateddisastercouldtriggernewformsofcooperativeaction.Thesoberingrealityisthatcurrentresponsesfallfarshortofensuringamutuallysecurefuture.
简介:ThestatusoftheThirdWorldinRussianforeignpolicyplummetedintheimmediatepost-Sovietyears,duringwhichMoscowpursueda"LookWest"policy.WhenthedesignoftheWesttocontainandweakenthecountrycametolighthowever,vigilanceheightenedinMoscowandtimelyforeignpolicyreadjustmentswereunderwaybyraisingtheweightoftheThirdWorld.Russiaintendstousetheresultingboostedtiesasaproptoitspursuitofanequalpartnershipwiththe
简介:SincetheendoftheColdWar,somenewfeatureshavebeenrevealedintheThirdWorld,which,referringtodevelopingnationsfordecades,especiallyintheColdWaryears,facessomeproblemsandchallengesunderheavyeconomicandpoliticalimpact.China,asabiggestmemberoftheThirdWorld,alsofacesnewenvironmentsandchallengesduringthe
简介:Thirdpartylitigationfunding(TPLF)isoneofthemostinnovativetrendsinlitigationfundingindustry.InaTPLFcontract,anexternalinvestor(thethirdpartyfunder)financiallysupportsalitiganttocoverlitigationexpenses.Iftheclaimisfinallysuccessful,ashareofrecoverieswillcometothefunderinreturn.Ontheotherhand,thethirdpartyfunderwillreceivenocompensationiftheplaintifflosesthesuit.Uptillnow,insomecommonlawjurisdictions(e.g.,Australia,theUK,andtheU.S.),TPLFhasbeenlegallyacceptedanddevelopsrapidly.Meanwhile,concernsabouttheuseofTPLFhavealsobeenraised.Forexample,whetherTPLFwillencouragefrivoloussuitsandunmeritoriousclaims;andwhethertheuseofTPLFwillbesociallydesirable.Inthisarticle,abasiceconomicmodelofTPLFwillbebuiltfirstly.Then,analysisbasedonthismodelwillbedeliveredandfurthersocialexternalitiesbroughtbytheuseofTPLFwillalsobeinvestigated.Finally,throughaneconomicanalysis,itisconcludedthatTPLFisgenerallysocialdesirablebutregulationsshouldbeimposed.
简介:ThethirdphaseengineeringofBaotouYunshengStrongMagneticMaterialsCo.,LtdstartedinBaotouRareEarthHi-TechZoneinAugust.Afterthecompletionoftheconstruction,theproduction(?)inecanproduce1,500tonsofhighperformanceNdFeBmagnetsperannum.Basedoncurrentproductionscale,NingboYunsheng
简介:Thisworkinvestigatestheflowofathirdgradefluidinarotatingframeofreference.Thefluidisincompressibleandmagnetohydrodynamic(MHD).Theflowisboundedbetweentwoporousplates,thelowerofwhichisshrinkinglinearly.Mathematicalmodellingoftheconsideredflowleadstoanonlinearproblem.Thesolutionofthisnonlinearproblemiscomputedbythehomotopyanalysismethod(HAM).Graphsarepresentedtodemonstratetheeffectofseveralemergingparameters,whichclearlydescribetheflowcharacteristics.
简介:Inthispaper,amodifiednonlineardynamicinequalityontimescalesisusedtostudytheboundednessofaclassofnonlinearthird-orderdynamicequationsontimescales.Thesetheoremscontainasspecialcasesresultsfordynamicdifferentialequations,differenceequationsandq-differenceequations.