Avaliação de métodos alternativos à citologia no rastreamento de lesões cervicais: detecção de DNA-HPV e inspeção visual

OBJETIVO: avaliar o desempenho da citologia oncológica (CO), de captura híbrida II (CH II) e da inspeção visual com ácido acético na detecção de lesões pré-neoplásicas e neoplásicas cervicais. MÉTODOS: 2281 mulheres foram submetidas a exame clínico além da coleta de material para citologia, para CH II para detecção de DNA-HPV. Foi feita a inspeção visual do colo após aplicação do ácido acético a 5% (IVA). As mulheres com pelo menos um exame positivo eram convocadas para colposcopia, que também foi realizada em 420 mulheres com todos os exames normais. O desempenho dos testes foi calculado utilizando como padrão ouro a colposcopia com ou sem biopsia. RESULTADOS: a CO foi anormal em 209 mulheres (9,2%); a CH II foi positiva em 399 (17,5%) e em 249 (10,9%) foram encontradas alterações na IVA. Entre as 2281 mulheres avaliadas, 671 (29,4%) apresentaram pelo menos um resultado de exame positivo, embora apenas 82 (3,6%) apresentassem doença confirmada histologicamente (50 NIC1, 20 NIC2, sete NIC3 e cinco carcinomas invasores). As sensibilidades da IVA e da CH II foram semelhantes e significativamente maiores que a da CO. A especificidade da CO foi maior que a da IVA e da CH II. Nos casos com resultado de CO negativo, a IVA apresentou melhor desempenho comparada à CH II. CONCLUSÃO: o desempenho da CO associada à IVA foi melhor que o da CO associada à CH II e do que o da CO isolada.

Inspeção visual do colo uterino após aplicação de ácido acético no rastreamento das neoplasias intra-epiteliais e lesões induzidas por HPV

OBJETIVO: estimar a validade da inspeção visual após aplicação de ácido acético (IVA) no rastreamento das neoplasias intra-epiteliais cervicais (NIC) e lesões induzidas por HPV, comparando seu desempenho com o da colpocitologia e da colposcopia. MÉTODOS: estudo de validação de teste diagnóstico realizado em 893 mulheres de 18 a 65 anos, rastreadas simultaneamente com colpocitologia, IVA e colposcopia, em unidade de saúde pública de Recife, PE. A IVA foi realizada por embrocação do colo com ácido acético a 5% e observação a olho nu, com auxílio de foco clínico comum. Considerou-se como positividade o achado de qualquer lesão aceto-branca no colo. O padrão-ouro foi o histopatológico de biópsia cervical, realizado sempre que qualquer um dos três testes resultasse anormal. Foram estimados e comparados os indicadores de validade de cada teste, com os respectivos intervalos de confiança a 95%. A concordância entre os resultados dos testes foi avaliada pelo coeficiente kappa (k). RESULTADOS: das 303 mulheres biopsiadas, o estudo histopatológico foi anormal em 24. Deste total, a IVA foi positiva em 22, conferindo-lhe sensibilidade estimada de 91,7%, especificidade de 68,9%, valor preditivo positivo de 7,5% e valor preditivo negativo de 99,7%. Comparando-se os intervalos de confiança a 95%, a IVA mostrou maior sensibilidade que a colpocitologia, mas com menores especificidade e valor preditivo positivo. Houve fraca concordância entre os resultados da IVA e da colpocitologia (k=0,02) e excelente concordância com os da colposcopia (k=0,93). CONCLUSÃO: a IVA foi muito mais sensível que a colpocitologia no rastreamento das NIC e lesões HPV-induzidas e teve o mesmo desempenho da colposcopia. Sua baixa especificidade foi responsável por um elevado número de resultados falso-positivos.

The Effects of Anesthetic Induced Loss of Consciousness on Quantitative Electroen Cephalogram, and Bispectral and Spectral Entropy Indices. Studies on Healthy Male

Changes in the electroencephalography (EEG) signal have been used to study the effects of anesthetic agents on the brain function. Several commercial EEG based anesthesia depth monitors have been developed to measure the level of the hypnotic component of anesthesia. Specific anesthetic related changes can be seen in the EEG, but still it remains difficult to determine whether the subject is consciousness or not during anesthesia. EEG reactivity to external stimuli may be seen in unconsciousness subjects, in anesthesia or even in coma. Changes in regional cerebral blood flow, which can be measured with positron emission tomography (PET), can be used as a surrogate for changes in neuronal activity. The aim of this study was to investigate the effects of dexmedetomidine, propofol, sevoflurane and xenon on the EEG and the behavior of two commercial anesthesia depth monitors, Bispectral Index (BIS) and Entropy. Slowly escalating drug concentrations were used with dexmedetomidine, propofol and sevoflurane. EEG reactivity at clinically determined similar level of consciousness was studied and the performance of BIS and Entropy in differentiating consciousness form unconsciousness was evaluated. Changes in brain activity during emergence from dexmedetomidine and propofol induced unconsciousness were studied using PET imaging. Additionally, the effects of normobaric hyperoxia, induced during denitrogenation prior to xenon anesthesia induction, on the EEG were studied. Dexmedetomidine and propofol caused increases in the low frequency, high amplitude (delta 0.5-4 Hz and theta 4.1-8 Hz) EEG activity during stepwise increased drug concentrations from the awake state to unconsciousness. With sevoflurane, an increase in delta activity was also seen, and an increase in alpha- slow beta (8.1-15 Hz) band power was seen in both propofol and sevoflurane. EEG reactivity to a verbal command in the unconsciousness state was best retained with propofol, and almost disappeared with sevoflurane. The ability of BIS and Entropy to differentiate consciousness from unconsciousness was poor. At the emergence from dexmedetomidine and propofol induced unconsciousness, activation was detected in deep brain structures, but not within the cortex. In xenon anesthesia, EEG band powers increased in delta, theta and alpha (8-12Hz) frequencies. In steady state xenon anesthesia, BIS and Entropy indices were low and these monitors seemed to work well in xenon anesthesia. Normobaric hyperoxia alone did not cause changes in the EEG. All of these results are based on studies in healthy volunteers and their application to clinical practice should be considered carefully.

Lean daily management, visual management and continuous improvement

This thesis was part of lean adaptation project started at Outotec Lappeenranta factory in early 2013. The purpose of this thesis was to develop and propose lean tools that could be used in daily management, visual management and continuous improvement. This thesis was “outsiders” view, and as such, did not study the current processes deeply. As result of this thesis, two different Daily Management -boards were designed, one for parallel processes and one for sequential processes. In addition, methods of doing continuous improvement and daily task accountability were framed and standard work for the leaders outlined. The tools presented in this thesis are general tools which support work in lean environment. They are visual and, if used correctly, they provide a basis from which continuous improvement can be done. Lean philosophy emphasizes the deep understanding of the current situation and it would be against the lean principles to blindly implement anything developed “on the outside”. The tools presented should be reviewed and modified further by the people working on the factory floor.

Visual customer segmentation and behavior analysis : a SOM-based approach

Ett ämne som väckt intresse både inom industrin och forskningen är hantering av kundförhållanden (CRM, eng. Customer Relationship Management), dvs. en kundorienterad affärsstrategi där företagen från att ha varit produktorienterade väljer att bli mera kundcentrerade. Numera kan kundernas beteende och aktiviteter lätt registreras och sparas med hjälp av integrerade affärssystem (ERP, eng. Enterprise Resource Planning) och datalager (DW, eng. Data Warehousing). Kunder med olika preferenser och köpbeteende skapar sin egen ”signatur” i synnerhet via användningen av kundkort, vilket möjliggör mångsidig modellering av kundernas köpbeteende. För att få en översikt av kundernas köpbeteende och deras lönsamhet, används ofta kundsegmentering som en metod för att indela kunderna i grupper utgående från deras likheter. De mest använda metoderna för kundsegmentering är analytiska modeller konstruerade för en viss tidsperiod. Dessa modeller beaktar inte att kundernas beteende kan förändras med tiden. I föreliggande avhandling skapas en holistisk översikt av kundernas karaktär och köpbeteende som utöver de konventionella segmenteringsmodellerna även beaktar dynamiken i köpbeteendet. Dynamiken i en kundsegmenteringsmodell innefattar förändringar i segmentens struktur och innehåll, samt förändringen av individuella kunders tillhörighet i ett segment (s.k migrationsanalyser). Vardera förändringen modelleras, analyseras och exemplifieras med visuella datautvinningstekniker, främst med självorganiserande kartor (SOM, eng. Self-Organizing Maps) och självorganiserande tidskartor (SOTM), en vidareutveckling av SOM. Visualiseringen anteciperas underlätta tolkningen av identifierade mönster och göra processen med kunskapsöverföring mellan den som gör analysen och beslutsfattaren smidigare. Asiakkuudenhallinta (CRM) eli organisaation muuttaminen tuotepainotteisesta asiakaskeskeiseksi on herättänyt mielenkiintoa niin yliopisto- kuin yritysmaailmassakin. Asiakkaiden käyttäytymistä ja toimintaa pystytään nykyään helposti tallentamaan ja varastoimaan toiminnanohjausjärjestelmien ja tietovarastojen avulla; asiakkaat jättävät jatkuvasti piirteistään ja ostokäyttäytymisestään kertovia tietojälkiä, joita voidaan analysoida. On tavallista, että asiakkaat poikkeavat toisistaan eri tavoin, ja heidän mieltymyksensä kuten myös ostokäyttäytymisensä saattavat olla hyvinkin erilaisia. Asiakaskäyttäytymisen monimuotoisuuteen ja tuottavuuteen paneuduttaessa käytetäänkin laajalti asiakassegmentointia eli asiakkaiden jakamista ryhmiin samankaltaisuuden perusteella. Perinteiset asiakassegmentoinnin ratkaisut ovat usein yksittäisiä analyyttisia malleja, jotka on tehty tietyn aikajakson perusteella. Tämän vuoksi ne monesti jättävät huomioimatta sen, että asiakkaiden käyttäytyminen saattaa ajan kuluessa muuttua. Tässä väitöskirjassa pyritäänkin tarjoamaan holistinen kuva asiakkaiden ominaisuuksista ja ostokäyttäytymisestä tarkastelemalla kahta muutosvoimaa tiettyyn aikarajaukseen perustuvien perinteisten segmentointimallien lisäksi. Nämä kaksi asiakassegmentointimallin dynamiikkaa ovat muutokset segmenttien rakenteessa ja muutokset yksittäisten asiakkaiden kuulumisessa ryhmään. Ensimmäistä dynamiikkaa lähestytään ajallisen asiakassegmentoinnin avulla, jossa visualisoidaan ajan kuluessa tapahtuvat muutokset segmenttien rakenteissa ja profiileissa. Toista dynamiikkaa taas lähestytään käyttäen nk. segmenttisiirtymien analyysia, jossa visuaalisin keinoin tunnistetaan samantyyppisesti segmentistä toiseen vaihtavat asiakkaat. Visualisoinnin tehtävänä on tukea havaittujen kaavojen tulkitsemista sekä helpottaa tiedonsiirtoa analysoijan ja päättäjien välillä. Visuaalisia tiedonlouhintamenetelmiä, kuten itseorganisoivia karttoja ja niiden laajennuksia, käytetään osoittamaan näiden menetelmien hyödyllisyys sekä asiakkuudenhallinnassa yleisesti että erityisesti asiakassegmentoinnissa.

Visual Arts Data Skills for Researchers (VADS4R)

Workshop at Open Repositories 2014, Helsinki, Finland, June 9-13, 2014

From KAPTUR to VADS4R: Exploring Research Data Management in the Visual Arts

Presentation at Open Repositories 2014, Helsinki, Finland, June 9-13, 2014

From KAPTUR to VADSR: Exploring Research Data Management in the Visual Arts

Poster at Open Repositories 2014, Helsinki, Finland, June 9-13, 2014

Alterations in The States and Contents of Consciousness: Empirical and Theoretical Aspects

The main purpose of the present doctoral thesis is to investigate subjective experiences and cognitive processes in four different types of altered states of consciousness: naturally occurring dreaming, cognitively induced hypnosis, pharmacologically induced sedation, and pathological psychosis. Both empirical and theoretical research is carried out, resulting in four empirical and four theoretical studies. The thesis begins with a review of the main concepts used in consciousness research, the most influential philosophical and neurobiological theories of subjective experience, the classification of altered states of consciousness, and the main empirical methods used to study consciousness alterations. Next, findings of the original studies are discussed, as follows. Phenomenal consciousness is found to be dissociable from responsiveness, as subjective experiences do occur in unresponsive states, including anaesthetic-induced sedation and natural sleep, as demonstrated by post-awakening subjective reports. Two new tools for the content analysis of subjective experiences and dreams are presented, focusing on the diversity, complexity and dynamics of phenomenal consciousness. In addition, a new experimental paradigm of serial awakenings from non-rapid eye movement sleep is introduced, which enables more rapid sampling of dream reports than has been available in previous studies. It is also suggested that lucid dreaming can be studied using transcranial brain stimulation techniques and systematic analysis of pre-lucid dreaming. For blind judges, dreams of psychotic patients appear to be indistinguishable from waking mentation reports collected from the same patients, which indicates a close resemblance of these states of mind. However, despite phenomenological similarities, dreaming should not be treated as a uniform research model of psychotic or intact consciousness. Contrary to this, there seems to be a multiplicity of routes of how different states of consciousness can be associated. For instance, seemingly identical time perception distortions in different alterations of consciousness may have diverse underlying causes for these distortions. It is also shown that altered states do not necessarily exhibit impaired cognitive processing compared to a baseline waking state of consciousness: a case study of time perception in a hypnotic virtuoso indicates a more consistent perceptual timing under hypnosis than in a waking state. The thesis ends with a brief discussion of the most promising new perspectives for the study of alterations of consciousness.

Distribution of AMPA-type glutamate receptor subunits in the chick visual system

Several glutamate receptor (GluR) subunits have been characterized during the past few years. In the present study, subunit-specific antisera were used to determine the distribution of the AMPA-type glutamate receptor subunits GluR1-4 in retinorecipient areas of the chick brain. Six white leghorn chicks (Gallus gallus, 7-15 days old, unknown sex) were deeply anesthetized and perfused with 4% buffered paraformaldehyde and brain sections were stained using immunoperoxidase techniques. The AMPA-type glutamate receptor subunits GluR1, GluR2/3 and GluR4 were present in several retinorecipient areas, with varying degrees of colocalization. For example, perikarya in layers 2, 3, and 5 of the optic tectum contained GluR1, whereas GluR2/3 subunits appeared mainly in neurons of layer 13. The GluR4 subunit was only detected in a few cells of the tectal layer 13. GluR1 and GluR2/3 were observed in neurons of the nucleus geniculatus lateralis ventralis, whereas GluR4 was only present in its neuropil. Somata in the accessory optic nucleus appeared to contain GluR2/3 and GluR4, whereas GluR1 was the dominant subunit in the neuropil of this nucleus. These results suggest that different subpopulations of visual neurons might express different combinations of AMPA-type GluR subunits, which in turn might generate different synaptic responses to glutamate derived from retinal ganglion cell axons

NADPH-diaphorase activity in area 17 of the squirrel monkey visual cortex: neuropil pattern, cell morphology and laminar distribution

We studied the distribution of NADPH-diaphorase activity in the visual cortex of normal adult New World monkeys (Saimiri sciureus) using the malic enzyme "indirect" method. NADPH-diaphorase neuropil activity had a heterogeneous distribution. In coronal sections, it had a clear laminar pattern that was coincident with Nissl-stained layers. In tangential sections, we observed blobs in supragranular layers of V1 and stripes throughout the entire V2. We quantified and compared the tangential distribution of NADPH-diaphorase and cytochrome oxidase blobs in adjacent sections of the supragranular layers of V1. Although their spatial distributions were rather similar, the two enzymes did not always overlap. The histochemical reaction also revealed two different types of stained cells: a slightly stained subpopulation and a subgroup of deeply stained neurons resembling a Golgi impregnation. These neurons were sparsely spined non-pyramidal cells. Their dendritic arbors were very well stained but their axons were not always evident. In the gray matter, heavily stained neurons showed different dendritic arbor morphologies. However, most of the strongly reactive cells lay in the subjacent white matter, where they presented a more homogenous morphology. Our results demonstrate that the pattern of NADPH-diaphorase activity is similar to that previously described in Old World monkeys

Distribution of calcium-binding proteins in the chick visual system

The calcium-binding proteins calbindin (CB), calretinin (CR), and parvalbumin (PV) have been extensively studied over the last decade since they appear to be important as buffers of intracellular calcium. In the present study we investigated the distribution of these proteins in the chick visual system by means of conventional immunocytochemistry. The results indicated that CB, CR, and PV are widely distributed in retinorecipient areas of the chick brain. In some regions, all three calcium-binding proteins were present at different intensities and often in different neurons such as in the dorsolateral thalamic complex. In other areas, such as the nucleus geniculatus lateralis ventralis, only CB and CR were detected, whereas PV was absent. These results show that these three calcium-binding proteins are differentially distributed in the visual system of the chick, with varying degrees of co-localization

Signaled two-way avoidance learning using electrical stimulation of the inferior colliculus as negative reinforcement: effects of visual and auditory cues as warning stimuli

The inferior colliculus is a primary relay for the processing of auditory information in the brainstem. The inferior colliculus is also part of the so-called brain aversion system as animals learn to switch off the electrical stimulation of this structure. The purpose of the present study was to determine whether associative learning occurs between aversion induced by electrical stimulation of the inferior colliculus and visual and auditory warning stimuli. Rats implanted with electrodes into the central nucleus of the inferior colliculus were placed inside an open-field and thresholds for the escape response to electrical stimulation of the inferior colliculus were determined. The rats were then placed inside a shuttle-box and submitted to a two-way avoidance paradigm. Electrical stimulation of the inferior colliculus at the escape threshold (98.12 ± 6.15 (A, peak-to-peak) was used as negative reinforcement and light or tone as the warning stimulus. Each session consisted of 50 trials and was divided into two segments of 25 trials in order to determine the learning rate of the animals during the sessions. The rats learned to avoid the inferior colliculus stimulation when light was used as the warning stimulus (13.25 ± 0.60 s and 8.63 ± 0.93 s for latencies and 12.5 ± 2.04 and 19.62 ± 1.65 for frequencies in the first and second halves of the sessions, respectively, P<0.01 in both cases). No significant changes in latencies (14.75 ± 1.63 and 12.75 ± 1.44 s) or frequencies of responses (8.75 ± 1.20 and 11.25 ± 1.13) were seen when tone was used as the warning stimulus (P>0.05 in both cases). Taken together, the present results suggest that rats learn to avoid the inferior colliculus stimulation when light is used as the warning stimulus. However, this learning process does not occur when the neutral stimulus used is an acoustic one. Electrical stimulation of the inferior colliculus may disturb the signal transmission of the stimulus to be conditioned from the inferior colliculus to higher brain structures such as amygdala