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.

PET Imaging of Osteomyelitis. Feasibility of 18F-FDG, 68Ga-Chloride and 68Ga-DOTAVAP-P1 Tracers in Staphylococcal Bone Infections

Due to technical restrictions of the database system the title of the thesis does not show corretly on this page. Numbers in the title are in superscript. Please see the PDF-file for correct title. ---- Osteomyelitis is a progressive inflammatory disease of bone and bone marrow that results in bone destruction due to an infective microorganism, most frequently Staphylococcus aureus. Orthopaedic concern relates to the need for reconstructive and trauma-related surgical procedures in the fast grow¬ing population of fragile, aged patients, who have an increased susceptibility to surgical site infections. Depending on the type of osteomyelitis, infection may be acute or a slowly progressing, low-grade infection. Peri-implant infections lead to implant loosening. The emerging antibiotic resistance of com¬mon pathogens further complicates the situation. With current imaging methods, significant limitations exist in the diagnosing of osteomyelitis and implant-related infections. Positron emission tomography (PET) with a glucose analogue, 18F-fluoro¬deoxyglucose (18F-FDG), seems to facilitate a more accurate diagnosis of chronic osteomyelitis. The method is based on the increased glucose consumption of activated inflammatory cells. Unfortunately, 18F-FDG accumulates also in sterile inflammation regions and causes false-positive findings, for exam¬ple, due to post-operative healing processes. Therefore, there is a clinical need for new, more infection-specific tracers. In addition, it is still unknown why 18F-FDG PET imaging is less accurate in the detec¬tion of periprosthetic joint infections, most frequently due to Staphylococcus epidermidis. This doctoral thesis focused on testing novel PET tracers (68Ga-chloride and 68Ga-DOTAVAP-P1) for early detections of bone infections and evaluated the role of pathogen-related factors in the appli¬cations of 18F-FDG PET in the diagnostics of bone infections. For preclinical models of S. epidermidis and S. aureus bone/implant infections, the significance of the causative pathogen was studied with respect to 18F-FDG uptake. In a retrospective analysis of patients with confirmed bone infections, the significance of the presence or absence of positive bacterial cultures on 18F-FDG uptake was evalu¬ated. 18F-FDG and 68Ga-chloride resulted in a similar uptake in S. aureus osteomyelitic bones. However, 68Ga-chloride did not show uptake in healing bones, and therefore it may be a more-specific tracer in the early post-operative or post-traumatic phase. 68Ga-DOTAVAP-P1, a novel synthetic peptide bind¬ing to vascular adhesion protein 1 (VAP-1), was able to detect the phase of inflammation in healing bones, but the uptake of the tracer was elevated also in osteomyelitis. Low-grade peri-implant infec¬tions due to S. epidermidis were characterized by a low uptake of 18F-FDG, which reflects the virulence of the causative pathogen and the degree of leukocyte infiltration. In the clinical study, no relationship was found between the level of 18F-FDG uptake and the presence of positive or negative bacterial cul¬tures. Thus 18F-FDG PET may help to confirm metabolically active infection process in patients with culture-negative, histologically confirmed, low-grade osteomyelitis.

Kone- ja laitesuunnittelupalvelun nykytilanteen kartoitus ja kehittämisen lähtökohdat muuttuvassa asiakasympäristössä

Haastattelututkimus on menetelmä, jolla voidaan kerätä yrityksen asiakaskunnalta asiakas-palaute ja tulokseksi saadaan yrityksen laatujohtamiseen kuuluva tieto asiakastyytyväisyy-destä. Asiakastyytyväisyystutkimus on yrityksen päätöksentekoa tukeva työkalu. Rejlers Oy:n tavoitteena oli selvittää mahdollisuus yritystoiminnan tehostamiseen yrityksen Itä-Suomen kone- ja laitesuunnittelun osastolla. Työssä tavoite pyrittiin saavuttamaan haastattelun kysymyksenasettelujen kohdistuessa niin yrityksen nykyiseen toimintaan kuin asiakaskunnassa mahdollisesti tapahtuviin muutoksiin. Kirjallisuuden perusteella selvitettiin asiakastyytyväisyystutkimuksen peruskäsitteitä, joita käytettiin työn suorittamisessa. Työn haastattelut suoritettiin Rejlers Oy:n asiakaskunnasta suunnittelupalvelujen volyymiin perustuen valittujen asiakkaiden luona. Haastatteluvastausten tietokoneavusteisesta analyysistä muodostettiin työssä tutkimuksen tulos. Tutkimustuloksesta todetaan, että Rejlers Oy:n nykyiseen toimintaan ei asiakaskunnassa nähdä tarvetta muutoksiin. Palvelutarpeiden mahdollisesti muuttuessa, nousi tutkimustu-loksessa merkittävimmäksi asiakaskuntaa kiinnostavaksi kehitettäväksi palveluksi cleantech-teknologian laaja-alainen osaaminen. Työssä on luotu lähtökohta Rejlers Oy:n käyttöön soveltuvalle asiakastyytyväisyystutki-mukselle. Haastattelututkimuksena suoritettavan asiakastyytyväisyystutkimuksen kehittä-misellä pyritään tehostamaan Rejlers Oy:n yritystoimintaa.

Elever syns på nätet : multimodala texter och autentiska mottagare

This study is based on the notion that all students are likely to have a computer of some kind as their primary tool at school within a few years. The overall aim is to contribute to the knowledge of what this development of computer-assisted multimodal text production and communication on and over the net may entail in a school context. The study has an abductive approach drawing on theory from Media and Communication studies and from Pedagogy - particularly on media peda-gogy, multimodality, storytelling, conversation research and deliberative democracy – and is based on a DBR project in three schools. The empirical data are retrieved from four school classes, school years 4 and 5, with good access to computers and digital cameras. The classes have used the class blogs to tell the blog visitors about their school work and Skype to communicate with other classes in Sweden and Tanzania. A variety of research methods was employed: content analysis of texts, observations with field notes and camera documentation, interviews with individual students, group interviews with teachers and students, and a small survey. The study is essentially qualitative, focusing on students’ different perceptions. A small quantitative study was conducted to determine if any factors and variables could be linked to each other and to enable comparisons of the surveyed group with other research results. The results suggest that more computers at school offer more opportunities for real-life assignments and the chance to secure an authentic audience to the students’ production; primarily the students’ parents and relatives, students in the same class and at other schools. A theoretical analysis model to determine the degree of reality and authenticity in various school assignments was developed. The results also indicate that having access to cameras for documenting various events in the classes and to an authentic audience can create new opportunities for storytelling that have not been practiced previously at school. The documentary photo invites a viewer into the present tense of the image and the location where the picture was taken, whoever took the picture. It is used by the students and here too, a model has been developed to describe this relationship. The study also focuses on the freedom of expression and democracy. One of the more unexpected findings is that the students in the study did not see that they can influence other people’s perceptions or change various power structures through communication on the web, neither in nor outside of school.

Neurobiological Correlates of Personality Traits: A Study on Harm Avoidance and Neuroticism

Harm Avoidance and Neuroticism are traits that predispose to mental illnesses. Studying them provides a unique way to study predisposition of mental illnesses. Understanding the biological mechanisms that mediate vulnerability could lead to improvement in treatment and ultimately to pre-emptive psychiatry. These personality traits describe a tendency to feel negative emotions such as fear, shyness and worry. Previous studies suggest these traits are regulated by serotonin and opiate pathways. The aim of this thesis was to test the following hypotheses using personality trait measures and positron emission tomography (PET): 1) Brain serotonin transporter density in vivo is associated with Harm Avoidance and Neuroticism traits. 2) μ-opioid receptor binding is associated with Harm Avoidance. In addition, we developed a methodology for studying neurotransmitter interactions in the brain using the opiate and serotonin pathways. 32 healthy subjects who were consistently in either the highest or lowest quartile of the Harm Avoidance trait were recruited from a population-based cohort. Each subject underwent two PET scans, serotonin transporter binding was measured with [11C] MADAM and μ-opioid receptor binding with [11C]carfentanil. We found that the serotonin transporter is not associated with anxious personality traits. However, Harm Avoidance positively correlated with μ-opioid receptor availability. Particularly the tendency to feel shy and the inability to cope with stress were associated μ-opioid receptor availability. We also demonstrated that serotonin transporter binding correlates with μ-opioid receptor binding, suggesting interplay between the two systems. These findings shed light on the neurobiological correlates of personality and have an impact on etiological considerations of affective disorders.

Characterisation of Functional Brown Adipose Tissue In Adult Humans

The white adipose tissue mainly serves the purpose of energy storage, while brown adipose tissue (BAT) has the capacity to generate heat under cold conditions in mammals and in human infants. BAT is controlled by the central nervous system, and BAT function is accompanied by increased energy expenditure. However, it was not previously certain whether adult humans also have functional BAT. The aim of this doctoral work was to identify functional BAT in adult humans and to characterise its glucose uptake and blood flow under cold and insulin stimulation conditions in lean and in obese humans, by using positron emission tomography. Further, the impact of weight loss on BAT glucose uptake was assessed. Cerebral glucose uptake was also studied in relation to BAT function and cold exposure. The results showed that healthy adult humans have functional BAT, as assessed by the intense cold-induced glucose uptake and by biopsies. BAT was also found to be a highly insulinsensitive tissue in lean humans, but the effects of insulin and cold exposure were attenuated in obese humans, although the glucose uptake capacity of cold-activated BAT might be increased by weight loss. Blood flow in the BAT of lean humans was associated with whole-body energy expenditure. The presence of cold-activated BAT was related to lower body mass index and higher insulin sensitivity. Finally, BAT activation was linked to the activity of the cerebellum, the thalamus and certain neocortical regions. The cold-induced cerebral glucose uptake was also lower in obese than in lean adult humans.

Target audience analysis in cyber domain

This thesis aims to find an effective way of conducting a target audience analysis (TAA) in cyber domain. There are two main focal points that are addressed; the nature of the cyber domain and the method of the TAA. Of the cyber domain the object is to find the opportunities, restrictions and caveats that result from its digital and temporal nature. This is the environment in which the TAA method is examined in this study. As the TAA is an important step of any psychological operation and critical to its success, the method used must cover all the main aspects affecting the choice of a proper target audience. The first part of the research was done by sending an open-ended questionnaire to operators in the field of information warfare both in Finland and abroad. As the results were inconclusive, the research was completed by assessing the applicability of United States Army Joint Publication FM 3-05.301 in the cyber domain via a theory-based content analysis. FM 3- 05.301 was chosen because it presents a complete method of the TAA process. The findings were tested against the results of the questionnaire and new scientific research in the field of psychology. The cyber domain was found to be “fast and vast”, volatile and uncontrollable. Although governed by laws to some extent, the cyber domain is unpredictable by nature and not controllable to reasonable amount. The anonymity and lack of verification often present in the digital channels mean that anyone can have an opinion, and any message sent may change or even be counterproductive to the original purpose. The TAA method of the FM 3-05.301 is applicable in the cyber domain, although some parts of the method are outdated and thus suggested to be updated if used in that environment. The target audience categories of step two of the process were replaced by new groups that exist in the digital environment. The accessibility assessment (step eight) was also redefined, as in the digital media the mere existence of a written text is typically not enough to convey the intended message to the target audience. The scientific studies made in computer sciences and both in psychology and sociology about the behavior of people in social media (and overall in cyber domain) call for a more extensive remake of the TAA process. This falls, however, out of the scope of this work. It is thus suggested that further research should be carried out in search of computer-assisted methods and a more thorough TAA process, utilizing the latest discoveries of human behavior. ---------------------------------------------------------------------------------------------------------------------------------- Tämän opinnäytetyön tavoitteena on löytää tehokas tapa kohdeyleisöanalyysin tekemiseksi kybertoimintaympäristössä. Työssä keskitytään kahteen ilmiöön: kybertoimintaympäristön luonteeseen ja kohdeyleisöanalyysin metodiin. Kybertoimintaympäristön osalta tavoitteena on löytää sen digitaalisesta ja ajallisesta luonteesta juontuvat mahdollisuudet, rajoitteet ja sudenkuopat. Tämä on se ympäristö jossa kohdeyleisöanalyysiä tarkastellaan tässä työssä. Koska kohdeyleisöanalyysi kuuluu olennaisena osana jokaiseen psykologiseen operaatioon ja on onnistumisen kannalta kriittinen tekijä, käytettävän metodin tulee pitää sisällään kaikki oikean kohdeyleisön valinnan kannalta merkittävät osa-alueet. Tutkimuksen ensimmäisessä vaiheessa lähetettiin avoin kysely informaatiosodankäynnin ammattilaisille Suomessa ja ulkomailla. Koska kyselyn tulokset eivät olleet riittäviä johtopäätösten tekemiseksi, tutkimusta jatkettiin tarkastelemalla Yhdysvaltojen armeijan kenttäohjesäännön FM 3-05.301 soveltuvuutta kybertoimintaympäristössä käytettäväksi teorialähtöisen sisällönanalyysin avulla. FM 3-05.301 valittiin koska se sisältää kokonaisvaltaisen kohdeyleisöanalyysiprosessin. Havaintoja verrattiin kyselytutkimuksen tuloksiin ja psykologian uusiin tutkimuksiin. Kybertoimintaympäristö on tulosten perusteella nopea ja valtava, jatkuvasti muuttuva ja kontrolloimaton. Vaikkakin lait hallitsevat kybertoimintaympäristöä jossakin määrin, on se silti luonteeltaan ennakoimaton eikä sitä voida luotettavasti hallita. Digitaalisilla kanavilla usein läsnäoleva nimettömyys ja tiedon tarkastamisen mahdottomuus tarkoittavat että kenellä tahansa voi olla mielipide asioista, ja mikä tahansa viesti voi muuttua, jopa alkuperäiseen tarkoitukseen nähden vastakkaiseksi. FM 3-05.301:n metodi toimii kybertoimintaympäristössä, vaikkakin jotkin osa-alueet ovat vanhentuneita ja siksi ne esitetään päivitettäväksi mikäli metodia käytetään kyseisessä ympäristössä. Kohdan kaksi kohdeyleisökategoriat korvattiin uusilla, digitaalisessa ympäristössä esiintyvillä ryhmillä. Lähestyttävyyden arviointi (kohta 8) muotoiltiin myös uudestaan, koska digitaalisessa mediassa pelkkä tekstin läsnäolo ei sellaisenaan tyypillisesti vielä riitä halutun viestin välittämiseen kohdeyleisölle. Tietotekniikan edistyminen ja psykologian sekä sosiologian aloilla tehty tieteellinen tutkimus ihmisten käyttäytymisestä sosiaalisessa mediassa (ja yleensä kybertoimintaympäristössä) mahdollistavat koko kohdeyleisöanalyysiprosessin uudelleenrakentamisen. Tässä työssä sitä kuitenkaan ei voida tehdä. Siksi esitetäänkin että lisätutkimusta tulisi tehdä sekä tietokoneavusteisten prosessien että vielä syvällisempien kohdeyleisöanalyysien osalta, käyttäen hyväksi viimeisimpiä ihmisen käyttäytymiseen liittyviä tutkimustuloksia.

Sähköisen taloushallinnon kehityksen vaikutukset tilintarkastukseen ammattilehtikirjoittelussa vuosina 2003-2013

Tutkielman tavoitteena on tutkia, miten sähköisen taloushallinnon kehitys on vaikuttanut tilintarkastukseen ja miten se näkyy ammattilehtien kirjoittelussa vuosina 2003-2013. Alatavoitteina tutkitaan, mitä sähköisen taloushallinnon kehityksen tuomia hyötyjä ja haasteita on havaittu tarkastellussa suomalaisessa sekä kansainvälisessä ammattilehtikirjoittelussa tilintarkastuksen näkökulmasta. Kyseessä on laadullinen tutkimus ja tutkimusmetodologiana käytetään sisällönanalyysia. Tietokoneavusteisten tilintarkastuksen tekniikoiden kehityksen seurauksena tekniikoita voidaan kehittää kohti jatkuvaa tilintarkastusta. Kannettavien tietokoneiden ja pilvipalveluiden seurauksena tilintarkastuksesta on tullut enemmän ajasta ja paikasta riippumatonta. XBRL:n avulla tietojen vertailtavuus, luotettavuus ja tarkkuus ovat parantuneet. Haasteina voidaan nähdä tilintarkastajien IT-taitojen kehittämisen tarve sekä asiakkaan ja tilintarkastusyhteisön tietojärjestelmien yhteensopivuus. Hyvätkin ohjelmistot voivat altistaa väärinkäytöksille, jolloin tarvitaan uusia innovatiivisia tekniikoita väärinkäytösten havaitsemiseen. Tutkielman empiirisen osion luotettavuus perustuu ammattilehtien artikkeleiden kirjoittajien näkökulmiin. Tilintarkastusalan kehittyminen tulevaisuudessa on kiinni kehittyvän tekniikan lisäksi asenteista.

Advanced epithelial ovarian cancer – studies on preoperative [18F] FDG PET/CT and HE4 profile during primary chemotherapy

Epithelial ovarian cancer (EOC) is usually diagnosed in an advanced stage. The prognosis depends highly on the amount of the residual tumor in surgery. In patients with extensive disease, neoadjuvant chemotherapy (NACT) is used to diminish the tumor load before debulking surgery. New non-invasive methods are needed to preoperatively evaluate the disease dissemination and operability. [18F] FDG PET/CT (Positron emission tomography/computed tomography) is a promising method for cancer diagnostics and staging. The biomarker profiles during treatment can predict patient’s outcome. This prospective study included 41 EOC patients, 21 treated with primary surgery and 20 with NACT and interval surgery. The performances of preoperative contrast enhanced PET/CT (PET/ceCT) and diagnostic CT (ceCT) were compared. Perioperative visual estimation of tumor spread was studied in primary and interval surgery. The profile of the serum marker HE4 (Human epididymis 4) during primary chemotherapy was evaluated. In primary surgery, surgical findings were found to form an adequate reference standard for imaging studies. After NACT, the sensitivity for visual estimation of cancer dissemination was significantly worse. Preoperative PET/ceCT was more effective than ceCT alone in detecting extra-abdominal disease spread. The high number of supradiaphragmatic lymph node metastases detected by PET/ceCT at the time of diagnosis brings new insight in EOC spread patterns. The sensitivity of both PET/CT and ceCT remained modest in intra-abdominal areas important to operability. The HE4 profile was in concordance with the CA125 profile during primary chemotherapy. Its role in the evaluation of EOC chemotherapy response will be clarified in further studies.

New [18F]Tracers for Alzheimer's Disease Imaging. Labeling Synthesis And Biological Testing

Alzheimer’s disease (AD) is the most common form of dementia. Characteristic changes in an AD brain are the formation of β-amyloid protein (Aβ) plaques and neurofibrillary tangles, though other alterations in the brain have also been connected to AD. No cure is available for AD and it is one of the leading causes of death among the elderly in developed countries. Liposomes are biocompatible and biodegradable spherical phospholipid bilayer vesicles that can enclose various compounds. Several functional groups can be attached on the surface of liposomes in order to achieve long-circulating target-specific liposomes. Liposomes can be utilized as drug carriers and vehicles for imaging agents. Positron emission tomography (PET) is a non-invasive imaging method to study biological processes in living organisms. In this study using nucleophilic 18F-labeling synthesis, various synthesis approaches and leaving groups for novel PET imaging tracers have been developed to target AD pathology in the brain. The tracers were the thioflavin derivative [18F]flutemetamol, curcumin derivative [18F]treg-curcumin, and functionalized [18F]nanoliposomes, which all target Aβ in the AD brain. These tracers were evaluated using transgenic AD mouse models. In addition, 18F-labeling synthesis was developed for a tracer targeting the S1P3 receptor. The chosen 18F-fluorination strategy had an effect on the radiochemical yield and specific activity of the tracers. [18F]Treg-curcumin and functionalized [18F]nanoliposomes had low uptake in AD mouse brain, whereas [18F]flutemetamol exhibited the appropriate properties for preclinical Aβ-imaging. All of these tracers can be utilized in studies of the pathology and treatment of AD and related diseases.

Experimental Studies on Non-Metallic Composite Bone Implants With a Special Reference to Staphylococcal Biofilm Infection

Non-metallic implants made of bioresorbable or biostable synthetic polymers are attractive options in many surgical procedures, ranging from bioresorbable suture anchors of arthroscopic surgery to reconstructive skull implants made of biostable fiber-reinforced composites. Among other benefits, non-metallic implants produce less interference in imaging. Bioresorbable polymer implants may be true multifunctional, serving as osteoconductive scaffolds and as matrices for simultaneous delivery of bone enhancement agents. As a major advantage for loading conditions, mechanical properties of biostable fiber-reinforced composites can be matched with those of the bone. Unsolved problems of these biomaterials are related to the risk of staphylococcal biofilm infections and to the low osteoconductivity of contemporary bioresorbable composite implants. This thesis was focused on the research and development of a multifunctional implant model with enhanced osteoconductivity and low susceptibility to infection. In addition, the experimental models for assessment, diagnostics and prophylaxis of biomaterial-related infections were established. The first experiment (Study I) established an in vitro method for simultaneous evaluation of calcium phosphate and biofilm formation on bisphenol-Aglycidyldimethacrylate and triethylenglycoldimethacrylate (BisGMA-TEGDMA) thermosets with different content of bioactive glass 45S5. The second experiment (Study II) showed no significant difference in osteointegration of nanostructured and microsized polylactide-co-glycolide/β-tricalcium phosphate (PLGA /β-TCP) composites in a minipig model. The third experiment (Study III) demonstrated that positron emission tomography (PET) imaging with the novel 68Ga labelled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) CD33 related sialic-acid immunoglobulin like lectins (Siglec-9) tracer was able to detect inflammatory response to S. epidermidis and S. aureus peri-implant infections in an intraosseous polytetrafluoroethylene catheter model. In the fourth experiment (Study IV), BisGMATEGDMA thermosets coated with lactose-modified chitosan (Chitlac) and silver nanoparticles exhibited antibacterial activity against S. aureus and P. aeruginosa strains in an in vitro biofilm model and showed in vivo biocompatibility in a minipig model. In the last experiment (Study V), a selective androgen modulator (SARM) released from a poly(lactide)-co-ε-caprolactone (PLCL) polymer matrix failed to produce a dose-dependent enhancement of peri-implant osteogenesis in a bone marrow ablation model.

Validation of a simple and inexpensive method for the quantitation of infarct in the rat brain

A gravimetric method was evaluated as a simple, sensitive, reproducible, low-cost alternative to quantify the extent of brain infarct after occlusion of the medial cerebral artery in rats. In ether-anesthetized rats, the left medial cerebral artery was occluded for 1, 1.5 or 2 h by inserting a 4-0 nylon monofilament suture into the internal carotid artery. Twenty-four hours later, the brains were processed for histochemical triphenyltetrazolium chloride (TTC) staining and quantitation of the schemic infarct. In each TTC-stained brain section, the ischemic tissue was dissected with a scalpel and fixed in 10% formalin at 0ºC until its total mass could be estimated. The mass (mg) of the ischemic tissue was weighed on an analytical balance and compared to its volume (mm³), estimated either by plethysmometry using platinum electrodes or by computer-assisted image analysis. Infarct size as measured by the weighing method (mg), and reported as a percent (%) of the affected (left) hemisphere, correlated closely with volume (mm³, also reported as %) estimated by computerized image analysis (r = 0.88; P < 0.001; N = 10) or by plethysmography (r = 0.97-0.98; P < 0.0001; N = 41). This degree of correlation was maintained between different experimenters. The method was also sensitive for detecting the effect of different ischemia durations on infarct size (P < 0.005; N = 23), and the effect of drug treatments in reducing the extent of brain damage (P < 0.005; N = 24). The data suggest that, in addition to being simple and low cost, the weighing method is a reliable alternative for quantifying brain infarct in animal models of stroke.

Decision support system for the diagnosis of schizophrenia disorders

Clinical decision support systems are useful tools for assisting physicians to diagnose complex illnesses. Schizophrenia is a complex, heterogeneous and incapacitating mental disorder that should be detected as early as possible to avoid a most serious outcome. These artificial intelligence systems might be useful in the early detection of schizophrenia disorder. The objective of the present study was to describe the development of such a clinical decision support system for the diagnosis of schizophrenia spectrum disorders (SADDESQ). The development of this system is described in four stages: knowledge acquisition, knowledge organization, the development of a computer-assisted model, and the evaluation of the system's performance. The knowledge was extracted from an expert through open interviews. These interviews aimed to explore the expert's diagnostic decision-making process for the diagnosis of schizophrenia. A graph methodology was employed to identify the elements involved in the reasoning process. Knowledge was first organized and modeled by means of algorithms and then transferred to a computational model created by the covering approach. The performance assessment involved the comparison of the diagnoses of 38 clinical vignettes between an expert and the SADDESQ. The results showed a relatively low rate of misclassification (18-34%) and a good performance by SADDESQ in the diagnosis of schizophrenia, with an accuracy of 66-82%. The accuracy was higher when schizophreniform disorder was considered as the presence of schizophrenia disorder. Although these results are preliminary, the SADDESQ has exhibited a satisfactory performance, which needs to be further evaluated within a clinical setting.

Imaging Neuroinflammation in Progressive Multiple Sclerosis

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system CNS), where inflammation and neurodegeneration lead to irreversible neuronal damage. In MS, a dysfunctional immune system causes auto‐reactive lymphocytes to migrate into CNS where they initiate an inflammatory cascade leading to focal demyelination, axonal degeneration and neuronal loss. One of the hallmarks of neuronal injury and neuroinflammation is the activation of microglia. Activated microglia are found not only in the focal inflammatory lesions, but also diffusely in the normal‐appearing white matter (NAWM), especially in progressive MS. The purine base, adenosine is a ubiquitous neuromodulator in the CNS and also participates in the regulation of inflammation. The effect of adenosine mediated via adenosine A2A receptors has been linked to microglial activation, whereas modulating A2A receptors may exert neuroprotective effects. In the majority of patients, MS presents with a relapsing disease course, later advancing to a progressive phase characterised by a worsening, irreversible disability. Disease modifying treatments can reduce the severity and progression in relapsing MS, but no efficient treatment exists for progressive MS. The aim of this research was to investigate the prevalence of adenosine A2A receptors and activated microglia in progressive MS by using in vivo positron emission tomography (PET) imaging and [11C]TMSX and [11C](R)‐PK11195 radioligands. Magnetic resonance imaging (MRI) with diffusion tensor imaging (DTI) was performed to evaluate structural brain damage. Non‐invasive input function methods were also developed for the analyses of [11C]TMSX PET data. Finally, histopathological correlates of [11C](R)‐PK11195 radioligand binding related to chronic MS lesions were investigated in post‐mortem samples of progressive MS brain using autoradiography and immunohistochemistry. [11C]TMSX binding to A2A receptors was increased in NAWM of secondary progressive MS (SPMS) patients when compared to healthy controls, and this correlated to more severe atrophy in MRI and white matter disintegration (reduced fractional anisotropy, FA) in DTI. The non‐invasive input function methods appeared as feasible options for brain [11C]TMSX images obviating arterial blood sampling. [11C](R)‐PK11195 uptake was increased in the NAWM of SPMS patients when compared to patients with relapsing MS and healthy controls. Higher [11C](R)‐PK11195 binding in NAWM and total perilesional area of T1 hypointense lesions was associated with more severe clinical disability, increased brain atrophy, higher lesion load and reduced FA in NAWM in the MS patients. In autoradiography, increased perilesional [11C](R)‐PK11195 uptake was associated with increased microglial activation identified using immunohistochemistry. In conclusion, brain [11C]TMSX PET imaging holds promise in the evaluation of diffuse neuroinflammation in progressive MS. Being a marker of microglial activation, [11C](R)‐ PK11195 PET imaging could possibly be used as a surrogate biomarker in the evaluation of the neuroinflammatory burden and clinical disease severity in progressive MS.

Computerized invasive measurement of time-dependent intraocular pressure

Several methods have been described to measure intraocular pressure (IOP) in clinical and research situations. However, the measurement of time varying IOP with high accuracy, mainly in situations that alter corneal properties, has not been reported until now. The present report describes a computerized system capable of recording the transitory variability of IOP, which is sufficiently sensitive to reliably measure ocular pulse peak-to-peak values. We also describe its characteristics and discuss its applicability to research and clinical studies. The device consists of a pressure transducer, a signal conditioning unit and an analog-to-digital converter coupled to a video acquisition board. A modified Cairns trabeculectomy was performed in 9 Oryctolagus cuniculus rabbits to obtain changes in IOP decay parameters and to evaluate the utility and sensitivity of the recording system. The device was effective for the study of kinetic parameters of IOP, such as decay pattern and ocular pulse waves due to cardiac and respiratory cycle rhythm. In addition, there was a significant increase of IOP versus time curve derivative when pre- and post-trabeculectomy recordings were compared. The present procedure excludes corneal thickness and error related to individual operator ability. Clinical complications due to saline infusion and pressure overload were not observed during biomicroscopic evaluation. Among the disadvantages of the procedure are the requirement of anesthesia and the use in acute recordings rather than chronic protocols. Finally, the method described may provide a reliable alternative for the study of ocular pressure dynamic alterations in man and may facilitate the investigation of the pathogenesis of glaucoma.