Demens är en växande sjukdom världen över. Vid demens kan den drabbade få svårigheter att utföra aktiviteter i det dagliga livet på samma sätt som innan sjukdomen. Arbetsterapeuter arbetar med att hjälpa personer med demens att öka eller bibehålla funktioner i dagliga aktiviteter. I och med att demens ökar världen över kommer behovet av arbetsterapi öka för målgruppen. Syftet med denna studie var därför att undersöka arbetsterapeutiska interventioner för personer med demens samt vilket utfall dessa interventioner haft i utförandet av dagliga aktiviteter. I studien användes en systematisk litteraturstudie som metod för att få svar på syftet. Genom sökningar i databaserna Cinahl, Pubmed, Medline, Psycinfo, Scopus, OT-seeker och Swemed+ framkom nio artiklar med kvantitativ ansats som svarade på syftet. I studien framkom olika arbetsterapeutiska interventioner som strukturerades upp enligt OTIPM. Arbetsterapeuter använde sig av olika varianter av kompensationer, aktivitetsträning och förbättring av personliga faktorer och kroppsfunktioner för att förbättra personernas utförande i dagliga aktiviteter. Kompensationer handlade om att arbetsterapeuten hjälpte den demenssjuke att finna strategier eller att genomföra anpassningar av den fysiska och sociala miljön. Aktivitetsträning involverade träning i personlig- och instrumentell ADL och fritidsaktiviteter. Vid förbättringar av personliga faktorer och kroppsfunktioner använde arbetsterapeuterna sig av kognitiv träning, fysisk aktivering och avslappning samt träning av den sociala rollfunktionen. Huvudparten av interventionerna visade sig ge positiva förändringar vid utförandet av dagliga aktiviteter. Däremot var det två studier som visade på försämrade utfall. Resultatet indikerar på att arbetsterapeutiska interventioner kan ha en positiv inverkan på utförandet av dagliga aktiviteter hos personer med demens. Interventionernas längd och intensitet kan påverka utfallet . Ytterligare en faktor som kan påverka är att sjukdomen progreiderar.

There has in recent years been interdisciplinary research on utilizing machine learning for detecting and classifying neurodegenerative disorders with the sole goal of outperforming state-of-the-art models in terms of metrics such as accuracy, specificity, and sensitivity. Specifically, these studies have been conducted using existing networks on ”novel” methods of pre-processing data or by developing new convolutional neural networks. As of now, no work has looked into how different normalization techniques affect a deep or shallow convolutional neural network in terms of numerical stability, its performance, explainability, and interpretability. This work delves into what normalization technique is most suitable for deep and shallow convolutional neural networks. Two baselines were created, one shallow and one deep, and applied eight different normalization techniques to these model architectures. Conclusions were drawn based on our analysis of numerical stability, performance (metrics), and methods of Explainable Artificial Intelligence. Our findings indicate that normalization techniques affect models differently regarding the mentioned aspects of our analysis, especially numerical stability and explainability. Moreover, we show that there should indeed be a preference to select one method over the other in future studies of this interdisciplinary field.

Submitted by Cleide Dantas (cleidedantas@ufpa.br) on 2014-02-26T16:00:26Z No. of bitstreams: 2 license_rdf: 23898 bytes, checksum: e363e809996cf46ada20da1accfcd9c7 (MD5) Dissertacao_AnaliseCitogeneticaBioindicador.pdf: 2113257 bytes, checksum: dceaa9fd4dd39bca09223f354aac4f45 (MD5) / Approved for entry into archive by Irvana Coutinho (irvana@ufpa.br) on 2014-03-13T13:35:31Z (GMT) No. of bitstreams: 2 license_rdf: 23898 bytes, checksum: e363e809996cf46ada20da1accfcd9c7 (MD5) Dissertacao_AnaliseCitogeneticaBioindicador.pdf: 2113257 bytes, checksum: dceaa9fd4dd39bca09223f354aac4f45 (MD5) / Made available in DSpace on 2014-03-13T13:35:31Z (GMT). No. of bitstreams: 2 license_rdf: 23898 bytes, checksum: e363e809996cf46ada20da1accfcd9c7 (MD5) Dissertacao_AnaliseCitogeneticaBioindicador.pdf: 2113257 bytes, checksum: dceaa9fd4dd39bca09223f354aac4f45 (MD5) Previous issue date: 2013 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / A doença de Alzheimer (DA) é uma doença neurodegenerativa que provoca morte neuronal e consequente perda progressiva das funções cognitivas, reduzindo as capacidades de trabalho, interferindo na relação social e no comportamento do paciente. Entre as doenças causadoras de demência, a DA é a mais incidente que as de cunho vascular, numa proporção de 4:1, respectivamente. Além das terapias farmacológicas, os métodos diagnósticos auxiliam na identificação precoce da doença auxiliando o tratamento prévio, assim diminuído a progressão da doença. Atualmente estudos citogenéticos vêm demonstrando alterações cromossômicas em portadoras da DA e podem auxiliar no diagnósticos da doença. O objetivo desse trabalho foi verificar o potencial da análise cariotípica de linfócitos do sangue periférico como bioindicador diagnostico da doença de Alzheimer. Para a realização deste trabalho, utilizamos dois grupos de mulheres com 65 anos ou mais, sendo um grupo com (10) portadoras de DA e outro grupo (10) normais. Cada indivíduo foi submetida ao questionário socioeconômico, teste de rastreio cognitivo (MEEM) e à coleta de sangue venoso para cultura de linfócitos e análise cromossômica. Nossos resultados demonstram que o grupo de mulheres portadoras da DA apresentaram elevada taxa de monossomia e trissomia em relação às mulheres normais. Através de estudo de anamnese via questionário, verificamos o estilo de vida de ambos os grupos. Quando comparado a relação das alterações cromossômicas com o nível cognitivo do grupo DA, nós evidenciamos uma tendência inversamente proporcional entre o número de monossomia/trissomia e o desempenho cognitivo. Outro aspecto de nossas análises foi o papel de cada cromossomo ligado à DA. Os cromossomos 1, 14 e 21 não apresentaram trissomia e na verificação da frequência de monossomia, cada cromossomo possui frequência abaixo de 3 % de aneuploidia, ou seja, os cromossomos estudados não possuem uma grande representatividade nas alterações cromossômicas encontradas no estudo. / Alzheimer's disease (AD) is a neurodegenerative disease that causes neuronal death and consequent progressive loss of cognitive functions, reducing the capacity for work, interfering with social relationships and behavior of the patient. Among the diseases that cause dementia, AD is the most frequent nature of the vascular a ratio of 4:1, respectively. In addition to the pharmacological therapies, diagnostic methods assist in the early identification of the disease by helping the pretreatment, thus reduced disease progression. Currently cytogenetic studies have demonstrated chromosomal abnormalities in individuals with AD and may aid in the diagnosis of disease. The aim of this study was to investigate the potential of karyotype analysis of peripheral blood lymphocytes as a diagnostic biomarker of Alzheimer's disease. For this work, we used two groups of women aged 65 or more, one group (10) suffering from AD and other normal group (10). Each subject was submitted to the socioeconomic survey, a cognitive screening test (MMSE) and the Venous blood lymphocyte culture and chromosome analysis. Our results demonstrate that the group of women with AD showed high rate of monosomy and trisomy compared to normal women. Through the study of history via questionnaire, we found the lifestyle of both groups. Compared the relationship of chromosomal abnormalities with the cognitive level of the AD group, we evidenced an inverse trend between the number of monosomy / trisomy and cognitive performance. Another aspect of our analysis was the role of each chromosome linked to AD. Chromosomes 1, 14 and 21 showed no trisomy and verify the frequency of monosomy, each chromosome has frequency below 3 % of aneuploidy, i.e., the chromosomes studied did not have a great importance in chromosomal alterations found in the study.

SAMMANFATTNING Bakgrund: Vid hjärnundersökningar finns även andra strukturer utanför hjärnan som är innerverade av nervsystemet. Det är möjligt att sjukdomen i hjärnan avspeglas där också. Det finns många sjukdomar och tillstånd med liknande symptom och att ställa rätt diagnos kan vara svårt. Många sjukdomar påverkar det autonoma nervsystemet och ett sätt att hitta rätt diagnos kan vara att undersöka hur det fungerar.  Syfte: Att se vilka variationer av radioaktivitetsupptag som fanns i parotiskörtlarna mellan patienterna som avbildades med 11C-PE2I PET/DT. Samt att kunna se om denna information kan utnyttjas till att identifiera dysfunktion av autonoma nervsystemet (MRT-bilder är även en tillhjälps verktyg). Metod: Studiedesignen var en retrospektiv kvantitativ studie. Hundra (konsekutiva) patienter indelades i grupper så som: normal, Parkinsons, Parkinsons sjukdom med kombination av vaskulära förändringar och atypisk Parkinson sjukdom. Isotopupptag i basala ganglier och parotiskörtlar har mätts. Några patienters MRT- bilder var tillgängligt till kvantifiering.   Resultat: kombinerade gruppen med Parkinsons sjukdom, atypisk Parkinsons sjukdom och vaskulära förändringar har en uppreglering av antalet fria dopaminreceptorer i parotis jämfört med friska (även i bara PSP samt bara vaskulära grupper) med (p <0.05).   Slutsats: Det finns variation av upptaget mellan en del av grupper därmed kan sjukdomen i hjärnan avspeglas i körtlar också.   Nyckelord: Neurodegenerativa sjukdomar, Autonom dysfunktion, 11CPE2I-PET/DT, parotiskörtlar, basala ganglier / ABSTRACT Background: At brain examination, there are also other structures outside the brain that are innervated by the nervous system. It is possible that the disease of the brain is reflected there as well. There are many diseases and conditions with similar symptoms and making the right diagnosis can be difficult. Many diseases affect the autonomic nervous system and one way to find the right diagnosis may be to investigate how it works.     Purpose: to see what variations in radioactivity uptake were found in the parotic glands between the patients depicted with the 11C-PE2I PET/CT. As well as being able to see how valuable this information is in being used to identify dysfunction of the autonomic nervous system (MRT- images are also an aids tool).   Method: The study design was a retrospective quantitative study. One hundred (consecutive) patients were divided in groups such as normal, Parkinson's, Parkinson's disease with combination of vascular changes and atypical Parkinson's disease. Isotope uptake in basal ganglia and parotic glands has been measured. Some patients' MRT images were available for quantification.     Result: the results show that the combined group of Parkinson's disease, atypical Parkinson's disease and vascular changes has an upregulation of the number of free dopamine receptors in parotid compared to healthy ones (also in PSP only and only vascular groups) with (p <0.05).    Conclusion: There is variation of uptake between some of the groups thus the disease in the brain can be reflected in glands as well.     Keywords: Neurodegenerative Diseases, Autonomic Dysfunction, 11CPE2I-PET/CT, Parotid Glands, Basal Ganglia

As the aging population is increasing worldwide, so is the prevalence of neurodegenerativediseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), frontotemporal dementia(FTD) and amyotrophic lateral sclerosis (ALS). Reliable biomarkers able to aid the diagnosis anddifferentiation of these diseases are needed in order to start the right treatment as early as possible.Due to its representative state of the central nervous system, cerebrospinal fluid (CSF) is afavorable sample material for biomarker discovery within neurodegenerative diseases. Alteredprotein levels of this body fluid might serve as a biomarker, but further validation of earlierfindings is needed. The aim of this project was to validate earlier studies suggesting potentialprotein biomarkers in CSF. From a list of 80 potential biomarkers in the CSF of patient samples,eight were chosen to be included in this validation effort. By utilizing a suspension bead array ina sandwich assay setup, 21 antibodies were tested in an initial screening. Antibody pairs that couldmeasure the protein levels in a dilution dependent manner was further optimized before individualpatient samples were analyzed. Sandwich assays targeting the three proteins Amphiphysin(AMPH), Chitotriosidase-1 (CHIT1) and Beta-synuclein (SNCB) were successfully developed andcorrelated to earlier generated data using a suspension bead array with a single binder setup.Therefore, the earlier findings of elevated levels of AMPH and SNCB in AD patients and CHIT1in ALS patients were successfully validated. / Prevalensen av neurodegenerativa sjukdomar såsom Alzheimers sjukdom (AD), Parkinsonssjukdom (PD), frontallobsdemens (FTD) och amyotrofisk lateralskleros (ALS) ökar i takt med denåldrande populationen. Pålitliga biomarkörer som kan hjälpa till vid diagnostiseringen av dessasjukdomar behövs för att starta rätt behandling så tidigt som möjligt. Ryggmärgsvätska, enkroppsvätska tillhörande det centrala nervsystemet, kan ge en inblick i det centrala nervsystemetstillstånd. Förändrade proteinnivåer i denna kroppsvätska skulle därför kunna fungera sombiomarkörer. Målet i detta projekt var att validera tidigare föreslagna proteinbiomarkörer iryggmärgsvätska. Utifrån en lista av 80 tidigare analyserade proteiner i ryggmärgsvätska hospatienter, inkluderades åtta proteiner i detta valideringsförsök. En antikroppsbaserad så kalladsandwich assay användes i en suspension bead array för att testa 21 stycken antikroppar i ett initialtscreeningsförsök. Antikroppspar som kunde mäta proteinnivåer på ett spädningsberoende vis i detinitiala screeningsförsöket optimerades vidare innan den utvecklade sandwich assayn användes föratt analysera proteinnivåer i individuella prover. Sandwich assays gentemot Amphiphysin(AMPH), Chitotriosidase-1 (CHIT1) och Beta-synuclein (SNCB) kunde bli framtagna ochkorrelerade gentemot tidigare genererat data från en single binder assay på ett framgångsrikt sätt.Projektet kunde därmed validera tidigare fynd som indikerat förhöjda nivåer av AMPH och SNCBi AD patienter, samt förhöjda nivåer av CHIT1 i ALS patienter.

Submitted by Hellen Luz (hellencrisluz@gmail.com) on 2018-02-26T19:14:41Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertacao_CorrelacaoMedidasQuantitativas.pdf: 4931104 bytes, checksum: 89eb8efff7aef9a8c3382319a847ac48 (MD5) / Approved for entry into archive by Edisangela Bastos (edisangela@ufpa.br) on 2018-03-08T15:47:29Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertacao_CorrelacaoMedidasQuantitativas.pdf: 4931104 bytes, checksum: 89eb8efff7aef9a8c3382319a847ac48 (MD5) / Made available in DSpace on 2018-03-08T15:47:29Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertacao_CorrelacaoMedidasQuantitativas.pdf: 4931104 bytes, checksum: 89eb8efff7aef9a8c3382319a847ac48 (MD5) Previous issue date: 2017-10-17 / Atualmente, com o aumento na expectativa de vida das populações humanas, as doenças neurodegenerativas, de comum ocorrência com o avançar da idade, tornaram-se fonte de serias preocupações. Deste modo, tem sido fomentado em todo o mundo a investigação de novos meios de diagnóstico precoce de transtornos neurocognitivos associados a doenças como a de Alzheimer e de Parkinson, assim como a melhoria do entendimento dos métodos de diagnóstico clinico neurológico atualmente disponíveis. Neste sentido, este trabalho propõe investigar a existência de possíveis correlações entre os resultados de exames utilizados na investigação clínica neurológica de pacientes diagnosticados com transtorno neurocognitivo associado a essas importantes doenças neurodegenerativas (doenças de Alzheimer e Parkinson). Os resultados mostram que a medida da espessura da camada de fibras nervosas da retina perimacular, realizada por tomografia de coerência óptica, é um parâmetro que pode não diferir de modo relevante entre grupos de pacientes e sujeitos saudáveis. Por outro lado, a medida da amplitude dos sinais espectroscópicos gerados por metabólitos encefálicos, realizada por espectroscopia de prótons em ressonância magnética, revela alterações encefálicas que variam de região para região. Além disso, a medida neuropsicológica de funções cognitivas, realizada pela aplicação da bateria automatizada CANTAB, revela que diversos aspectos dessas funções estão prejudicados nesses pacientes. Finalmente, a Análise de Componente Principal mostra que, considerando o conjunto de variáveis obtidos pelas medidas tomográficas e neuropsicológicas, é possível observar uma correlação entre várias dessas variáveis. Deste modo, conclui-se que correlacionando os resultados obtidos por diferentes abordagens pode agregar potencial na interpretação dessa casuística, o que não seria possível se considerarmos tais dados de modo isolado. / Currently, with the increase in life expectancy of human populations, neurodegenerative diseases, commonly occurring with the advancing age, have become a source of serious concern. Thus, research into new ways of early diagnosis of neurocognitive disorders associated with diseases such as Alzheimer's and Parkinson's, as well as the improvement of the understanding of currently available clinical neurological diagnostic methods, has been promoted throughout the world. In this sense, this work proposes to investigate the existence of possible correlations between the results of exams used in clinical neurological investigation of patients diagnosed with neurocognitive disorder associated with these important neurodegenerative diseases (Alzheimer's and Parkinson's diseases). The results show that the measurement of the thickness of the nerve fiber layer of the perimacular retina, performed by optical coherence tomography, is a parameter that may not differ significantly between groups of patients and healthy subjects. On the other hand, the measurement of the amplitude of the spectroscopic signals generated by encephalic metabolites, performed by magnetic resonance proton spectroscopy, reveals encephalic changes that vary from region to region. In addition, the neuropsychological measure of cognitive functions, performed by the automated CANTAB battery, reveals that several aspects of these functions are impaired in these patients. Finally, Principal Component Analysis shows that, considering the set of variables obtained by tomographic and neuropsychological measurements, it is possible to observe a correlation between several of these variables. Thus, it is concluded that correlating the results obtained by different approaches may add potential in the interpretation of this casuistry, which would not be possible if we consider such data in an isolated way.

<p>QC 20110615</p>

Mänsklig utforskning av månen och Mars innebär stora utmaningar för människans fysiologi och hälsa på grund av de unika miljöfaktorer som följer av långvariga rymduppdrag. Rymdbiologiska experiment har blivit ett viktigt verktyg för att studera effekterna som mikrogravitation och rymdstrålning har på levande organismer, i syfte att förstå och minska dessa utmaningar. Sådana experiment ger forskarna möjlighet att få insikt i rymduppdragens inverkan på människans fysiologi och utveckla strategier för att motverka eventuella skadliga effekter. Dessutom ger rymdbiologiska experiment möjlighet att öka vår förståelse av grundläggande biologiska processer, inklusive mikrogravitationens effekter på celldifferentiering och vävnadsregeneration, med potentiella tillämpningar för både rymdforskning och för att förbättra människors hälsa på jorden. Särskilt studier av mikrogravitationens effekter på hjärncellerna har potentiella konsekvenser för neurodegenerativa sjukdomar som Alzheimers och Parkinsons sjukdom. Genom att analysera data som genererats från hjärnor hos möss som skickats ut i rymden med en ny R-mjukvara, ArchR, är det möjligt att belysa de mekanismer som ligger till grund för förändringar i hjärnans funktion och beteende hos astronauter under långvariga rymduppdrag. Genom att förstå dessa mekanismer kan man utveckla nya terapeutiska metoder för att behandla eller till och med förebygga dessa sjukdomstillstånd. Fortsatta investeringar i rymdbiologisk forskning är avgörande för att garantera säkerheten och framgången för framtida, långvariga rymdforskningsuppdrag för människor. Genom att integrera avancerad teknik, t.ex. användning av spatiell transkriptomik eller sekvensering med encellsupplösning, kan en omfattande förståelse av komplexa biologiska system tolkas. De potentiella fördelarna med rymdbiologisk forskning sträcker sig längre än till att bara förstå effekterna av rymdfärder på människans fysiologi, med konsekvenser för grundläggande biologiska processer och behandling av en rad neurologiska sjukdomar. / Human exploration of the Moon and Mars poses significant challenges to human physiology and health due to the unique environmental factors that accompany long-duration space missions. Space biology experiments have emerged as an essential tool for studying the effects of microgravity and space radiation on living organisms, in order to understand and mitigate these challenges. Such experiments provide researchers with the opportunity to gain insights into the impacts of prolonged exposure to outer space on human physiology, and develop strategies to counteract any harmful effects. Additionally, space biology experiments offer the potential to enhance our understanding of fundamental biological processes, including the effects of microgravity on cell differentiation and tissue regeneration, with potential applications for both space exploration and improving human health on Earth. Previous research indicated the regulation of similar biomarkers, studying the effects of microgravity on brain cells could offer valuable insights into the potential impact on neurodegenerative conditions such as Alzheimer’s and Parkinson’s diseases. By analyzing data generated from the brains of mice that have been sent to space with a new R-software tool called ArchR, it is possible to elucidate the mechanisms underlying changes in brain function and behavior in astronauts during long-duration space missions. Understanding these mechanisms can inform the development of new therapeutic approaches to treating or even preventing these conditions. Continued investment in space biology research is critical to ensuring the safety and success of future long-term human space exploration missions. By integrating advanced technologies, such as the use of spatial transcriptomics or sequencing at the single-cell resolution, comprehensive understanding of complex biological systems can be interpreted. The potential benefits of space biology research extend beyond just understanding the effects of spaceflight on human physiology, with implications for fundamental biological processes and the treatment of a range of neurological diseases.