The aim of this paper is to analyse how a group of Spanish public research organisations affected by.docx

The aim of this paper is to analyse how a group of Spanish public research organisations affected by.docx

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TheaimofthispaperistoanalysehowagroupofSpanishpublicresearchorganisationsaffectedby

TheoveralleffectsofNCMSonprivatecoverageweremodest.►NCMShadapositiveeffectonadultprivatecoverage.►NCMScrowdedoutchildprivatecoverageinlowerincomegroups.►RiskpreferencesandSESareimportantpredictorsofprivateinsurancetake-up.►Noevidenceforadverseselectioninthedemandforprivatehealthinsurance.

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PublicHealthSignificanceofNeuroticism  OriginalResearchArticle

AmericanPsychologist,Volume64,Issue4,May-June2009,Pages241-256

BenjaminB.Lahey

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AbstractAbstract|ReferencesReferences

Thepersonalitytraitofneuroticismreferstorelativelystabletendenciestorespondwithnegativeemotionstothreat,frustration,orloss.Individualsinthepopulationvarymarkedlyonthistrait,rangingfromfrequentandintenseemotionalreactionstominorchallengestolittleemotionalreactioneveninthefaceofsignificantdifficulties.Althoughnotwidelyappreciated,thereisgrowingevidencethatneuroticismisapsychologicaltraitofprofoundpublichealthsignificance.Neuroticismisarobustcorrelateandpredictorofmanydifferentmentalandphysicaldisorders,comorbidityamongthem,andthefrequencyofmentalandgeneralhealthserviceuse.Indeed,neuroticismapparentlyisapredictorofthequalityandlongevityofourlives.Achievingafullunderstandingofthenatureandoriginsofneuroticism,andthemechanismsthroughwhichneuroticismislinkedtomentalandphysicaldisorders,shouldbeatoppriorityforresearch.Knowingwhyneuroticismpredictssuchawidevarietyofseeminglydiverseoutcomesshouldleadtoimprovedunderstandingofcommonalitiesamongthoseoutcomesandimprovedstrategiesforpreventingthem.

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237

Intelligenttransportationsystems—Enablingtechnologies  OriginalResearchArticle

MathematicalandComputerModelling,Volume22,Issues4-7,August-October1995,Pages11-81

A.García-Ortiz,S.M.Amin,J.R.Wootton

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AbstractAbstract|ReferencesReferences

Abstract

Intelligenttransportationprogramstakemanydifferentnamesthroughouttheworld;intheUnitedStatesitisITS,inEuropeitisPrometheus,andinJapanitisAMTICSandRACS.Allofthemshareverysimilarobjectives,i.e.,thedevelopmentofadvancedTrafficManagementSystems,TravelerInformationSystems,VehicleControlSystems,CommercialVehicleOperations,PublicTransportationSystems,andRuralTransportationSystems.Severalkeytechnologiesstandtoservethesynthesisofeachandeveryoneoftheseobjectives.Thesetechnologiesare:

DigitalMaps,Computers,PathPlanning,HumanFactors,Sensors,Communications,VehicleControl,andTrafficControl.Thispaperdiscusseseachoneofthesesubjectsinenoughdetailtoprovidethereaderwithanintroductiontoboththetechnologyanditsstate-of-the-art.Inaddition,thepaperdiscussessocio-politico-economicissuesassociatedwiththeimplementationofthevariousprograms.Webelievethatthishighlyneglectedsubjectwillservetotemperthedevelopmentanddeploymentoftheseprograms.

ArticleOutline

•References

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238

Methodsofinvitrotoxicology  ReviewArticle

FoodandChemicalToxicology,Volume40,Issues2-3,February-March2002,Pages193-236

GEisenbrand,BPool-Zobel,VBaker,MBalls,B.JBlaauboer,ABoobis,ACarere,SKevekordes,J.-CLhuguenot,RPieters,JKleiner

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AbstractAbstract|Figures/TablesFigures/Tables|ReferencesReferences

Abstract

Invitromethodsarecommonandwidelyusedforscreeningandrankingchemicals,andhavealsobeentakenintoaccountsporadicallyforriskassessmentpurposesinthecaseoffoodadditives.However,therangeoffood-associatedcompoundsamenabletoinvitrotoxicologyisconsideredmuchbroader,comprisingnotonlynaturalingredients,includingthosefromfoodpreparation,butalsocompoundsformedendogenouslyafterexposure,permissible/authorisedchemicalsincludingadditives,residues,supplements,chemicalsfromprocessingandpackagingandcontaminants.Amajorpromiseofinvitrosystemsistoobtainmechanism-derivedinformationthatisconsideredpivotalforadequateriskassessment.Thispapercriticallyreviewstheentireprocessofriskassessmentbyinvitrotoxicology,encompassingongoingandfuturedevelopments,withmajoremphasisoncytotoxicity,cellularresponses,toxicokinetics,modelling,metabolism,cancer-relatedendpoints,developmentaltoxicity,predictionofallergenicity,andfinally,developmentandapplicationofbiomarkers.Itdescribesindepththeuseofinvitromethodsinstrategiesforcharacterisingandpredictinghazardstothehuman.Majorweaknessesandstrengthsoftheseassaysystemsareaddressed,togetherwithsomekeyissuesconcerningmajorresearchprioritiestoimprovehazardidentificationandcharacterisationoffood-associatedchemicals.

ArticleOutline

1.Introduction

2.Invitroassessmentofgeneraltoxicity

2.1.Cytotoxicity

2.1.1.Introduction

2.1.2.Stateoftheart

2.1.2.1.Theuseofcytotoxicitydataasapredictorofacutesystemictoxicity

2.1.2.2.Relevantendpoints

2.1.3.Newdevelopmentsandresearchgaps

2.2.Cellularresponses

2.2.1.Genomics,transcriptomicsandproteomics

2.2.1.1.Introduction

2.2.1.2.Stateoftheart—thetechnologiesofgenomics,transcriptomics,proteomicsandbioinformatics

2.2.1.2.1.Genomicsandtranscriptomics

2.2.1.2.2.DNA/oligonucleotidemicroarrays

2.2.1.2.3.Proteomics

2.2.1.2.4.Bioinformatics

2.2.1.3.Applicationsoftranscriptomicsandproteomicstohazardidentification

2.2.1.3.1.Transcriptomicsappliedtotoxicologicalhazardidentification

2.2.1.3.2.Proteomicsappliedtotoxicologicalhazardidentification

2.2.1.3.3.Transcriptomicsandproteomics—acombinedapproach

2.2.1.4.Challengesandresearchgaps

2.2.1.4.1.Microarraytechnologyandexperimentalprocedures

2.2.1.4.2.Proteomictechnology

2.2.1.4.3.Datahandlingandinterpretation—bioinformatics

2.2.1.4.4.Buildingreferencedatasetsandcorrelationwithclassicendpointsoftoxicity

2.2.1.5.Conclusionsandfuturepriorities

2.2.2.Functionalresponses

2.2.2.1.Introduction

2.2.2.2.Stateoftheart—cellularresponsesasearlymarkersoftoxicity

2.2.2.2.1.Genotoxicity（seesection3.1.2,Genotoxicity）

2.2.2.2.2.Oxidativestressandglutathionehomeostasis

2.2.2.2.3.Calciumregulationandtheendoplasmicreticulum

2.2.2.2.4.Heatshockproteins

2.2.2.2.5.Stress-activatedproteinkinases（SAPKs）

2.2.2.2.6.Metallothioneins

2.2.2.2.7.Adaptiveresponses

2.2.2.3.Conclusionsandfuturepriorities

2.2.3.Perspectivesforusinginvitromethodstoevaluatechronictoxicityofcompounds

2.3.Toxicokineticmodellingandmetabolism

2.3.1.Extrapolationofkineticbehaviourfromtheinvitrototheinvivosituation

2.3.2.Obtainingcompound-specificparametersforPB-TKmodellingfrominvitrostudiesorothernon-animalmodels

2.3.2.1.Absorption

2.3.2.1.1.Tissue–bloodpartitioning

2.3.2.2.Metabolism

3.Theuseofinvitromethodsinstrategiesforcharacterisingandpredictinghazardstothehuman

3.1.Parallelogramapproach

3.2.Integratedteststrategy

3.2.1.Anticipatedexposurelevels

3.2.2.Existingtoxicologicalknowledge

3.2.3.Applicationofdataonphysicochemicalproperties

3.2.4.Toxicokinetics

3.2.5.Basalcytotoxicity

3.2.6.Specifictoxicity

3.2.7.Specificrequirements

4.Endpointsofinvitrotoxicologysystems

4.1.Cancer-relatedendpoints

4.1.1.Introduction

4.1.2.Genotoxicity

4.1.2.1.Introduction

4.1.2.2.Stateoftheart

4.1.2.3.Testingstrategy

4.1.2.4.Testmethods

4.1.2.5.Noveldevelopments

4.1.3.Non-genotoxiccancerendpoints

4.1.3.1.Stateoftheart

4.1.3.1.1.Persistentcytotoxicityaccompaniedbyproliferativeregeneration.

4.1.3.1.2.Chronicinflammation

4.1.3.1.3.Hormones

4.1.3.1.4.Ligandsforxenobioticinductionreceptors

4.1.3.1.5.DNAmethylation

4.1.3.2.Limitations

4.1.3.3.Noveldevelopments

4.1.3.3.1.Developmentofinvitrosystemstodetectcompoundsactingbythemajormechanismsinvolvedinnon-genotoxiccarcinogenesis

4.1.3.4.Conclusion

4.2.Developmentaltoxicity

4.2.1.Introduction

4.2.2.Celllinesandembryonicstemcells

4.2.3.Aggregateandmicromasscultures

4.2.4.Embryosoflowerorderspecies

4.2.5.Avianandmammalianwholeembryoculture

4.2.6.Validation

4.2.7.Futuredevelopments

4.3.Predictionofallergenicity

4.3.1.Introduction

4.3.1.1.BasicsofTcellsensitisation

4.3.2.Stateoftheart

4.3.2.1.Applicabilityandlimitationsofinvitrotesting

4.3.2.2.DetectionofsensitisingpotentialofHMWCinthefood

4.3.3.Futureprospectsforthepremarkethazardidentification

5.Invitroapproachesfordevelopmentofbiomarkers

5.1.Introduction

5.2.Stateoftheartandpotentialroleofinvitrotests

5.2.1.Definitionandrole

5.3.Typesofbiomarkers

5.3.1.Biomarkersofexposure

5.3.1.1.Challengeassaystoassessimpactsofbodyfluidsinmodelcellcultures

5.3.2.Biomarkersofeffect

5.3.2.1.Humantissuesastargetsforbiomarkersandtoidentifynewparametersofeffect

5.3.3.Susceptibilitybiomarkers

5.3.3.1.Studyingtheimpactofhazardouschemicalsonthebasisofsusceptibilityfactors

5.4.Conclusion

6.Generalsummaryandconclusions

6.1.Weaknesses

6.2.Strengths

6.3.Keyfeaturesofinvitrosystems

6.4.Priorityresearchneeds

References

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