The purpose with this study is to describe what individual pupils with neuropsychiatric disorders, such as Asperger syndrome and ADHD (Attention Deficit/Hyperactivity Disorder), think of their time in the nine-year compulsory school. The intention is to, from a social and spatial point of view elucidate their experiences, on the basis of their specific needs and the commission and the curriculum of the compulsory school. This study have a qualitative approach where I on two occasions have talked to three upper secondary school pupils with neuropsychiatric disorders about their time in the compulsory school. The work method for this study is life stories, a kind of interview that allows the pupils to speak more freely, and where the definitive question formulation appears gradually. The result shows that the pupils in many ways experience that they have been misunderstood by both teachers and other pupils, first and foremost regarding teachers not having enough knowledge about how people with Asperger syndrome think and acts. In addition, all three have experiences of being bullied. At the same time the result shows that special adjustments to the pupils’ specific needs works and is a good thing, if they are based upon knowledge and understanding. The conclusion is that genuine knowledge about neuropsychiatric disorders and the will to understand among the teachers is very important, and that adjustments of resources, demands and conditions is a good thing, and many times necessary. Many teachers do not have the adequate knowledge and the support to the students is inadequate. A proper, comprehensive and correct diagnosis is important to create knowledge of the specific individual needs. / Syftet med studien är att beskriva hur enskilda elever med neuropsykiatriska funktionsnedsättningar, i första hand Aspergers syndrom och ADHD (Attention Deficit/Hyperactivity Disorder), har upplevt sin tid i det obligatoriska skolväsendet. Avsikten är att ur ett socialt och ett rumsligt perspektiv belysa hur de upplevt sin skoltid, utifrån de specifika behoven och skolans uppdrag enligt Lpo94. Studien har en kvalitativ ansats där jag vid två tillfällen samtalat med tre ungdomar i gymnasieåldern med diagnostiserade neuropsykiatriska funktionsnedsättningar om deras grundskoletid. Den metod som använts för genomförandet av studien är livsberättelse, en form av intervju som tillåter den intervjuade att berätta mer fritt, och där de definitiva frågeställningarna infinner sig efter hand. Resultatet visar att eleverna på många sätt upplever att de blivit missförstådda av både lärare och andra elever, framför allt handlar det om att lärare inte haft tillräcklig kunskap om hur elever med Aspergers syndrom tänker och fungerar. Alla tre upplever dessutom att de varit utsatta för mobbing. Samtidigt visar resultatet att särskilda lösningar och anpassningar efter elevens specifika behov är bra och fungerar, om de bygger på kunskap och förståelse. Slutsatser blir att gedigen kunskap om neuropsykiatriska funktionsnedsättningar och vilja till förståelse hos personalen är mycket viktigt, och att anpassningar av resurser, krav och villkor är bra och ofta nödvändigt. Många lärare saknar tillräcklig kunskap och stödet till eleverna är bristfälligt. En ordentlig, fullständig och korrekt diagnostisering är viktigt för att skapa kunskap om de specifika individuella behoven.

No description available.

Στην καθημερινή ιατρική πρακτική υπάρχουν δυσκολίες κατά την επιλογή του κατάλληλου θεραπευτικού σχήματος που ωφελεί ατομικά τον ασθενή, ο οποίος αποτελεί μία ξεχωριστή και μοναδική οντότητα. Η διαδικασία που ακολουθεί ένα φάρμακο από τη στιγμή που λαμβάνεται ακολουθεί τους κανόνες της φαρμακοκινητικής και φαρμακοδυναμικής, που με τη σειρά τους εξαρτώνται από παράγοντες όπως είναι η ηλικία, το φύλο, το περιεχόμενο του γαστρεντερικού σωλήνα (ΓΕΣ), ο τρόπος ζωής του ατόμου, οι συνήθειές του, οι συμπαρομαρτούσες νόσοι καθώς και άλλα φάρμακα που μπορεί να συγχορηγούνται. Οι μοριακοί μεσολαβητές όλων αυτών των παραγόντων υπόκεινται σε διακύμανση που απορρέει από την ύπαρξη γενετικών πολυμορφισμών. Γενετικοί πολυμορφισμοί σε γονίδια που κωδικοποιούν πρωτεΐνες-μεταφορείς διαδραματίζουν πολύ σημαντικό ρόλο. Οι παράγοντες αυτοί συνολικά επηρεάζουν την «τύχη» του φαρμάκου στον οργανισμό μέσω προαγωγής ή αναστολής μεταφορέων του τοιχώματος του ΓΕΣ, μέσω μεταβολής του pH ή της βακτηριακής χλωρίδας, μέσω αναστολής ή προαγωγής του μεταβολισμού του στο ήπαρ ή και μέσω της επιρροής της απέκκρισης και της κατανομής του φαρμάκου. Όσον αφορά την φαρμακοδυναμική, δηλαδή το αποτέλεσμα του ιδίου του φαρμάκου στον οργανισμό, επίσης εξαρτάται από τους παραπάνω παράγοντες όπως η ηλικία, το φύλο, συνοδές παθήσεις, άλλα φάρμακα ή χημικές ουσίες (που τυχόν δρουν ως ανταγωνιστές της θέσης δράσης) και φυσικά, οι γενετικοί πολυμορφισμοί των υποδοχέων θέσεων δράσης. Στην ιατρική πράξη και κατά τη συνταγογράφηση πρέπει να λαμβάνονται υπόψη όλα τα προαναφερθέντα στοιχεία. Φυσικά, η πολυπλοκότητα αυτού κάνει κάτι τέτοιο να φαίνεται αδύνατο για έναν ιατρό. Για το λόγο αυτό, θα επιχειρηθεί ο θεωρητικός σχεδιασμός ενός υπολογιστικού συστήματος-λογισμικού που θα υλοποιήσει τον μέχρι τώρα ακατόρθωτο συνδυασμό όλων αυτών των αποσπασματικών παραμέτρων που επηρεάζουν την δράση των φαρμάκων και συγκεκριμένα των νευροψυχιατρικών. Η υλοποίηση ξεκινά με τη συλλογή των δεδομένων που στο εξής ονομάζονται παράμετροι-μεταβλητές του συστήματος και των οποίων ο συνδυασμός θα δίνει το αναμενόμενο αποτέλεσμα της χρήσης ενός νευροψυχιατρικού φαρμάκου σε κάθε ασθενή ξεχωριστά, αναλόγως της ηλικίας, του φύλου, του τρόπου ζωής, τις συνοδές παθήσεις, συγχορηγούμενα φάρμακα και τυχόν γνωστών γενετικών πολυμορφισμών. Το σύστημα θα είναι έτσι σχεδιασμένο, ώστε ανά πάσα στιγμή θα μπορούν να διοχετευθούν νέα δεδομένα, ανάλογα με την πρόοδο της έρευνας. Στο μέλλον, θα μπορούσε η μελέτη αυτή να θέσει τις βάσεις για ένα πλήρες σύστημα πρόβλεψης της δράσης όλων των κατηγοριών των φαρμάκων για τον ξεχωριστό ασθενή με απώτερο σκοπό την αποτελεσματικότερη και ασφαλέστερη ατομική θεραπεία. / -

Syftet med denna undersökning är att ta del av hur fritidspedagoger arbetar med elever som har en neuropsykiatriska funktionsnedsättningar i fritidshem. Neuropsykiatrisk funktionsnedsättning innefattar olika diagnoser exempelvis ADHD och autismspektrumtillstånd. Det finns olika metoder att hjälpa dessa elever på, som exempelvis bemötandet, inredningen samt miljön på fritidshemmen. Tanken är att det ska vara en skola för alla där alla elever blir inkluderade, oavsett om eleven har en nedsättning eller inte. Som det ser ut idag blir många elever exkluderade på grund av bland annat att eleverna inte klarar av att vara i storgrupp. Undersökningen baseras på en kvalitativ metod med semistrukturerade frågeställningar. Respondenterna använder sig av olika hjälpmedel för att eleverna ska få en lugn effekt samt få en högre koncentrationsförmåga. Vissa skolor får handledning genom stöd från rektor eller en person från en organisation hur personalen ska bemöta dessa elever. Något som genomsyrar resultatet i denna undersökning är tydlighet. Respondenterna anser att de måste vara tydliga för att eleverna ska kunna ta in vad pedagogerna säger samt förstå det.

The current work entails the development of a novel high content platform for the measurement of kinetic ligand responses across cell signalling networks at the single-cell level in distinct PBMC subtypes ex vivo. Using automated sample preparation, fluorescent cellular barcoding and flow cytometry the platform is capable of detecting 21, 840 parallel cell signalling responses in each PBMC sample. We apply this platform to characterize the effects of neuropsychiatric treatments and CNS ligands on the T cell signalling repertoire. We apply it to define cell signalling network abnormalities in PBMCs from drug-naïve first-onset schizophrenia patients (n=12) relative to healthy controls (n=12) which are subsequently normalized in PBMCs from the same patients (n=10) after a six week course of clinical treatment with the atypical antipsychotic olanzapine. We then validate the abnormal cell signalling responses in PBMCs from an independent cohort of drug-naïve first-onset schizophrenia patients (n=25) relative to controls (n=25) and investigate the specificity of the abnormal PBMC responses in schizophrenia as compared to major depression (n=25), bipolar disorder (n=25) and autism spectrum disorder (n=25). Subsequently we conduct a phenotypic drug screen using the US Food and Drug Administration (FDA) approved compound library, in addition to experimental neuropsychiatric drug candidates and nutraceuticals, to identify compounds which selectively normalize the schizophrenia-associated cell signalling response. Finally these candidate compounds are characterized using structure-activity relationships to reveal specific chemical moieties implicated in the putative therapeutic effect.

Bakgrund: Skolsköterskan och elevhälsan har ett grundläggande uppdrag i att främja och stödja elevers hälsa för att möjliggöra goda skolresultat. Elever med koncentrationssvårigheter utan hyperaktivitet kan vara svåra att upptäcka då eleven inte stör andra men har svårt att tillgodogöra sig undervisningen. Elever med detta funktionshinder upplever varierat stöd från skolan vilket kan få negativa konsekvenser på skolresultat och självkänsla. Syfte: Att beskriva hur skolsköterskor upplever sig stödja elever med ADD.  Metod: En empirisk intervjustudie genomfördes med semistrukturerade frågor som ställdes till nio skolsköterskor verksamma inom grund- och gymnasieskolor. En kvalitativ innehållsanalys användes för analys av insamlad data. Resultat: Tre kategorier framkom ur resultatet: ”Att finnas där för eleven”, ”Att samverka i EHT” samt ”Att fungera som en informerande länk”. Ett övergripande tema framkom som ”Stöd byggt på kunskap och förståelse”   Slutsats: Skolsköterskan stödjer elev med ADD genom att arbeta hälsofrämjande med att finnas tillgänglig och vara lyhörd för elev samt lyfta behov till elevhälsoteamet. Hen arbetar dessutom som en samverkande länk mellan alla inblandade aktörer. Dock krävs det viss kunskap om ADD för att kunna vara ett stöd. / Background: The school nurse and the student health service have a fundamental mission to promote students health to enforce school performance. Students with attention deficit without hyperactivity can be difficult to detect as the pupil does not disturb others but find it difficult to follow the education. Students with these disabilities are experiencing varied support from the school which can have a negative impact on academic performance and self-esteem. Aim: To describe school nurses experience of how to support students with ADD.  Method: An empirical interview study was conducted using semi-structured questions asked to nine school nurses working in elementary and secondary schools. A qualitative content analysis was used for the analysis of the collected data. Result: Three categories emerged from the result: "To be there for the student", "To interact in the school health team", and "To act as an informative link". An overall theme emerged as "Support built on knowledge and understanding”.  Conclusion: The school nurse supports students with ADD by working health promoting through being available, be responsive to student needs and by lifting student needs to the school health team. He/she also works as a collaborative link between all participants to follow up the support over time. However it requires some knowledge about ADD to be able to provide support for these students.

Submitted by Fabio Sobreira Campos da Costa (fabio.sobreira@ufpe.br) on 2016-09-21T12:07:22Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Jeyzon Valeriano-Dissertacao-2016.pdf: 2220289 bytes, checksum: ac06db6f610b526f0d583eff5e7b11d0 (MD5) / Made available in DSpace on 2016-09-21T12:07:22Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Jeyzon Valeriano-Dissertacao-2016.pdf: 2220289 bytes, checksum: ac06db6f610b526f0d583eff5e7b11d0 (MD5) Previous issue date: 2016-03-09 / CAPES / CNPq / FACEPE / A Terapia Antirretroviral Altamente Ativa (HAART) foi uma revolução que mudou drasticamente a evolução da infecção pelo HIV, transformando uma doença fatal em uma doença crônica. Efavirenz é um antirretroviral muito eficaz, mundialmente prescrito, presente no tratamento de primeira linha HAART, mas que apresenta uma alta frequência de efeitos neuropsiquiátricos que afetam a adesão ao tratamento, prejudicam a saúde e a qualidade de vida dos pacientes. Neste sentido, este estudo visa identificar polimorfismos genéticos associados à ocorrência de efeitos neuropsiquiátricos relatados no tratamento com Efavirenz em doses padrão. Através da análise retrospectiva dos prontuários dos 162 pacientes HIV positivos que utilizavam Efavirenz, 82 (50,6%) apresentaram efeitos adversos neuropsiquiátricos relacionados, dentre os quais: tonturas, cefaleia, insônia e depressão se mostraram os mais frequentes. Foi demonstrado que o uso da Zidovudina combinado ao Efavirenz, ao invés de Tenofovir (HR: 2,7; p-valor: 0,04), e o sexo feminino (HR: 3,5; p-valor: 0,05) aumentam o risco de tonturas e depressão, respectivamente, ao longo do tempo. Dez sete genes (CYP2B6, ABCB1, ABCC1, ABCC2, ABCC10, NR1I 2p oeli mNoRr1fiIs3m) ofosr eamm analisados. Apenas o polimorfismo no gene ABCC10 (rs2125739), alelo C, foi associado à ocorrência de efeitos adversos neuropsiquiátricos no tratamento com Efavirenz (OR: 2,6; p-valor: 0,03). Análises por regressão logística ajustada para variáveis demográficas, clínicas e genéticas, esta última relacionada ao aumento nas concentrações plasmáticas do Efavirenz, mostraram que os genótipos CT ou CC no rs2125739 estavam ainda mais associados com um risco elevado (OR: 5,1; p-valor: 0,007). Os resultados poderão contribuir para minimizar os riscos de eofceotrivrêidnacdiae ,d eid eefnetiitfoicsa nndeou roppasciqieuniátetrsi cossu sncae ptetírvaepiisa ceo mau Exiflaiavnirdeon z,n am aensteconldhoa sudaa HAART combinada. / Highly Active Antiretroviral Therapy (HAART) was a revolution that changed the HIV dynamic infection, turning a fatal disease into a chronic one. Efavirenz is a very efficient globally prescribed antiretroviral, present in first line of HAART treatment, but which presents a high frequency of neuropsychiatric adverse effects that affect treatment adherence, damaging the patients’ health and their quality of life. Thus, this study aims to identify genetic polymorphism associated with the occurrence of neuropsychiatric adverse effects in HIV-positive patients submitted to Efavirenz therapy in standard oral doses. Through retrospective analysis of medical records of 162 of these patients, 82 (50,6%) had neuropsychiatric adverse effects related, such as: dizziness, headache, depression and insomnia. Survival analysis demonstrated that the combined use of Efavirenz with Zidovudine instead of Tenofovir increases the dizziness risk (HR: 2.7; p value: 0.04), as well as female sex increases the depression risk (HR: 3.5; p-value: 0.05), both polymorphisms in seven genes (CYP2B6, ABCB1, ABCC1, AB CoCve2r, tAimBeC. CT1e0n, NR1I2 and NR1I3) were genotyped. Only a polymorphism on ABCC10 gene (rs2125739) was associated (C allele) with the neuropsychiatric adverse effects occurrence in treatment with Efavirenz (OR 2.6; p value: 0.03). Logistic regression analysis, adjusted to demographic, clinical and genetic variables related to increased plasma concentrations of Efavirenz, showed that the CT or CC genotypes at rs2125739 were even more significantly associated to a higher risk of neuropsychiatric effects (OR 5.1; p -value: 0.007). The results may help to minimize the neuropsychiatric effects risk in therapy with Efavirenz maintaining its effectiveness by identifying susceptible patients and assisting in the choice of combin ed HAART.

Orientador: Simone Appenzeller / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-19T11:05:02Z (GMT). No. of bitstreams: 1 Aldar_Henrique_M.pdf: 1202072 bytes, checksum: f32d5c89beb6e8a3a6884266359ea535 (MD5) Previous issue date: 2011 / Resumo: O Lúpus Eritematoso Sistêmico Juvenil (LESJ) é uma doença inflamatória crônica, de etiologia desconhecida e natureza autoimune com início até os 16 anos de idade. O comprometimento do sistema nervoso central (SNC) é difícil de ser avaliado no LESJ. Os anticorpos anti-P ribossomal são autoanticorpos dirigidos contra epítopos de fosfoproteínas do complexo ribonucleoproteico ribossomal e com maior prevalência em pacientes com até 18 anos de idade. A proteína S100? tem baixo peso molecular, sendo composta de 91 aminoácidos e localizada principalmente nas células da neuroglia, células de Schwann e na maioria dos nervos sensoriais do tronco cerebral. Os objetivos deste trabalho foram determinar a associação entre anticorpos anti-P ribossomal e a proteína S100? com manifestações clínicas e laboratoriais no LESJ; avaliar a prevalência dos anticorpos anti-P ribossomal em pacientes com LESJ, familiares de primeiro grau e indivíduos controles saudáveis; e avaliar os níveis de proteína S100? em pacientes com LESJ e indivíduos controles saudáveis. Foram selecionados pacientes consecutivos com LESJ acompanhados na Reumatologia Pediátrica da Universidade Estadual de Campinas entre 2009/2010. Familiares aparentados em primeiro grau com os pacientes também foram incluídos. Os indivíduos do grupo controle foram pareados por idade, sexo e antecedentes demográficos. Manifestações clínicas, laboratoriais, atividade da doença [SLE Disease Activity Index (SLEDAI)], dano cumulativo [Lupus International Collaborating Clinics / American College of Rheumatology Damage Index (SDI)] e medicação em uso foram avaliados. Incluímos 50 pacientes com LESJ (média de idade de 16,82 ± 3,46 anos), 35 familiares (média de idade de 38,73 ± 3,89 anos), e 20 controles saudáveis (média de idade de 18,3 ± 4,97 anos). Observamos os anticorpos anti-P ribossomal em 13 (26%) dos pacientes com LESJ, e em nenhum familiar (p<0,01) ou controle (p<0,01). A presença dos anticorpos anti-P ribossomal esteve associada à presença de ansiedade no LESJ (p<0,002). Pacientes com distúrbio cognitivo (mediana=38,08) apresentaram níveis de S100? significativamente maiores quando comparados aos pacientes sem distúrbio cognitivo (mediana=16,12; p=0,01) e indivíduos controles (mediana=23,62; p<0,05). Nenhuma outra manifestação clínica, laboratorial, e de tratamento esteve associada com o anticorpo anti-P ribossomal ou com a proteína S100? no LESJ. A partir destes dados concluímos que os anticorpos anti-P ribossomal são frequentemente observados em pacientes com LESJ e estiveram associados com a presença de ansiedade neste grupo de pacientes; e que a presença de distúrbio cognitivo esteve associada com níveis elevados de S100?, indicando a presença de lesão neuronal nestes pacientes / Abstract: Childhood-onset systemic lupus erythematosus (cSLE) is a chronic inflammatory disease of unknown etiology and autoimmune nature, with disease onset until 16 years of age. It is difficult to assess the central nervous system involvement in cSLE. The antiribosomal P antibodies are autoantibodies directed against epitopes of ribosomal phosphoproteins from the ribonucleoprotein complex and more frequently observed in patients with up to 18 years old. The S100? protein has a low molecular weight, being composed of 91 amino acids and mainly located in the cells of the neuroglia, Schwann cells and sensory nerves in most of the brainstem. Our objectives were to determine the association between antiribosomal P antibodies and S100? protein with clinical and laboratory manifestations in cSLE; to assess the prevalence of antiribosomal P antibodies in patients with cSLE, first-degree relatives and healthy control subjects; and to evaluate S100? protein levels in cSLE patients and healthy control subjects. Consecutive cSLE patients followed in Pediatric Rheumatology at the University of Campinas between 2009/2010 were selected for this study. First-degree relatives were also included in this work. The control group was matched for age, gender and demographic background. Clinical, laboratory, disease activity [SLE Disease Activity Index (SLEDAI)], cumulative damage [Systemic Lupus International Collaborating Clinics /American College of Rheumatology Damage Index (SDI)] and medication in use were assessed. Fifty cSLE patients, (mean age of 16.82 ± 3.46 years), 35 relatives (mean age of 38.73 ± 3.89 years) and 20 healthy controls (mean age 18.3 ± 4.97 years) were selected. Thirteen (26%) cSLE patients presented the antiribosomal P antibodies, no first-degree relative (p<0.01) or control (p<0.01) presented antiribosomal P antibodies. Antiribosomal P antibodies were associated to anxiety in this cohort of cSLE patients (p<0.02). Patients with cognitive impairment (median = 38.08) had significantly higher levels of S100? compared to patients without cognitive impairment (median = 16.12, p = 0.001) and controls (median = 23.62, p <0.05 ).No other clinical, laboratory, and treatment were associated with the antiribosomal P antibodies or S100? protein in cSLE. These data shows that the antiribosomal P antibodies are often observed in cSLE patients and that it was associated with the presence of anxiety in this group of patients. The presence of cognitive impairment was associated with elevated levels of S100?, suggesting neuronal damage in these patients / Mestrado / Ciencias Basicas / Mestre em Clinica Medica

Syftet med denna kvalitativa studie är att undersöka om gymnasielärare i instrument/sång-kurser tycker att de fått tillräcklig utbildning från sina högskoleutbildningar samt fortbildning från sina arbetsgivare för att kunna bemöta elever med neuropsykiatriska funktionsnedsättningar på ett lämpligt sätt. Frågeställningarna handlar om vad lärare i INSÅ behöver tänka på i sin undervisning av elever med NPF, samt vilken utbildning/fortbildning de fått för att kunna möta och undervisa dessa elever. Intervjuer har genomförts med 9 musiklärare som alla undervisar i INSÅ på estetiska programmet inriktning musik. Resultatet, som har analyserats ur ett sociokulturellt perspektiv, visar att endast en av lärarna under sin lärarutbildning fått en kurs i specialpedagogik, och att ingen av de intervjuade lärarna fått någon fortbildning av betydelse från sin arbetsgivare. Samtliga lärare önskar fortbildning från sin arbetsgivare om NPF, då de alla möter och undervisar elever med dessa diagnoser. De upplever att den kunskap de har idag beror mycket på lärarens eget intresse och de önskar djupare kunskap om hur de kan känna igen och bemöta NPF.

In the UK, dipping sheep with pesticides for treating ectoparasites has been one of the main pesticide applications and it was compulsory between 1984 and 1991 when organophosphates (OPs) were the main ingredients of sheep dips. As a result many current elderly sheep farmers have been exposed to OPs. The acute health effects of many pesticides especially OPs are very well documented, while the effects of long-term exposure are still unclear. Difficulties in assessing past pesticide exposure have been suggested to be one of the main reasons for this uncertainty. The overall aim of this PhD was to develop long-term occupational pesticide exposure models for UK farmers, specifically for OP exposure among sheep dippers, and to apply them to the Study of Health in Agricultural Work (SHAW) in order to examine the associations between long-term pesticide exposure and neuropsychiatric ill-health. A comprehensive conceptual exposure model to assess pesticide exposure during sheep dipping was developed and included five sources of pesticide exposure; handling the concentrate, dipping sheep in the bath, handling sheep after dipping, disposal of sheep dip, and any incidental exposure. Dermal, ingestion and inhalation routes were described for each source and different modifying factors for each route were identified. A semi-quantitative exposure algorithm was developed and all sources, routes and modifying factors were assigned scores and weights by assessment of the literature and expert judgement. The new model was evaluated by comparing its estimates of diazinon exposure among dippers who participated in the Health and Sheep Dipping Survey (HSDS) with diazinon urinary metabolite levels in spot urines collected after the dipping session. The model estimates generally did not correlate well with metabolite levels though there was evidence of an association between total metabolites and ordinal categories of exposure intensity. The uncontrolled conditions of the HSDS and the lack of 24 hr urine collections may have contributed to these results. A probabilistic model was also developed from the conceptual model and indicated that although handling the concentrate and dipping sheep are the most important exposure sources, other sources like handling dipped sheep and disposal of sheep dip should not be neglected. This probabilistic model was applied to different scenarios: probabilistic estimates may give a more comprehensive description of exposures than deterministic estimates as they take into account all conceptual variables. Occupational pesticide exposure among UK farmers in the SHAW study was then estimated using simple surrogates and more sophisticated models. The validity of self-reported exposure history among SHAW farmers was investigated by making comparison with data collected contemporaneously by the June Census. Farmers recall was generally reliable especially for a specific type of livestock or crop rather than the number of livestock or acreage. Associations between screen-identified ill-health and pesticide exposure were only demonstrated by using more developed metrics. Exposure to pesticides but not specifically OPs in sheep farming was associated with neuropathy and Parkinsonism. Exposure to OPs in sheep dipping was associated with a decrease risk of dementia. Depression was not associated with any exposure. In conclusion, this thesis developed a comprehensive model for pesticide exposure from sheep dipping and simpler exposure models for other farming sectors. The application of these models to the SHAW study suggests that long term pesticide exposure among farmers mainly via sheep dipping may result in ill- health; however the associations between exposure and outcomes may only be revealed by the use of more sophisticated exposure models rather than simple exposure surrogates. The study also indicates that even the use of well-derived deterministic estimates might lead to exposure misclassification. This misclassification may be investigated by using probabilistic approaches.