Evaluation of driving ability of the disabled persons in the context of the psychological activity theory

In the future the number of the disabled drivers requiring a special evaluation of their driving ability will increase due to the ageing population, as well as the progress of adaptive technology. This places pressure on the development of the driving evaluation system. Despite quite intensive research there is still no consensus concerning what is the factual situation in a driver evaluation (methodology), which measures should be included in an evaluation (methods), and how an evaluation has to be carried out (practise). In order to find answers to these questions we carried out empirical studies, and simultaneously elaborated upon a conceptual model for driving and a driving evaluation. The findings of empirical studies can be condensed into the following points: 1) A driving ability defined by the on-road driving test is associated with different laboratory measures depending on the study groups. Faults in the laboratory tests predicted faults in the on-road driving test in the novice group, whereas slowness in the laboratory predicted driving faults in the experienced drivers group. 2) The Parkinson study clearly showed that even an experienced clinician cannot reliably accomplish an evaluation of a disabled person’s driving ability without collaboration with other specialists. 3) The main finding of the stroke study was that the use of a multidisciplinary team as a source of information harmonises the specialists’ evaluations. 4) The patient studies demonstrated that the disabled persons themselves, as well as their spouses, are as a rule not reliable evaluators. 5) From the safety point of view, perceptible operations with the control devices are not crucial, but correct mental actions which the driver carries out with the help of the control devices are of greatest importance. 6) Personality factors including higher-order needs and motives, attitudes and a degree of self-awareness, particularly a sense of illness, are decisive when evaluating a disabled person’s driving ability. Personality is also the main source of resources concerning compensations for lower-order physical deficiencies and restrictions. From work with the conceptual model we drew the following methodological conclusions: First, the driver has to be considered as a holistic subject of the activity, as a multilevel hierarchically organised system of an organism, a temperament, an individuality, and a personality where the personality is the leading subsystem from the standpoint of safety. Second, driving as a human form of a sociopractical activity, is also a hierarchically organised dynamic system. Third, in an evaluation of driving ability it is a question of matching these two hierarchically organised structures: a subject of an activity and a proper activity. Fourth, an evaluation has to be person centred but not disease-, function- or method centred. On the basis of our study a multidisciplinary team (practitioner, driving school teacher, psychologist, occupational therapist) is recommended for use in demanding driver evaluations. Primary in a driver’s evaluations is a coherent conceptual model while concrete methods of evaluations may vary. However, the on-road test must always be performed if possible.

"Do Not Celebrate Your Feast without Your Neighbours" : A Study of References to Feasts and Festivals in Non-Literary Documents from Ramesside Period Deir el-Medina

This dissertation is a study of the forms and functions of feasts and feasting in the ancient Egyptian village of Deir el-Medina in Thebes (modern Luxor). This particular village, during the New Kingdom (c. 1550 1069 BC), was inhabited by the men (and their families) who constructed the Royal Tombs in the Valley of the Kings and the Valley of the Queens. The royal artisans were probably more literate than the average Egyptians and the numerous Ramesside Period (c. 1295 1069 BC) non-literary texts found in the excavations of the village and its surroundings form the source material for this study. In this study, the methods used are mainly Egyptological and the references to feasts and feasting are considered in view of what is known of New Kingdom Egypt, Thebes, and Deir el-Medina. Nevertheless, it is the use of the methodological concept local vernacular religion that has resulted in the division of the research findings into two sections, i.e., references to feasts celebrated both in and outside the community and other references to feasts and feasting in the village. When considering the function of the feasts celebrated at Deir el-Medina, a functional approach to feasts introduced by anthropologists and archaeologists is utilized. The Deir el-Medina feasts which were associated with the official religion form a festival calendar of feasts celebrated annually on the same civil calendar day. The reconstructed festival calendar of Deir el-Medina reflects the feasts celebrated around Thebes or, at least, in Western Thebes. The function of the nationally and regionally observed feasts (which, at least at Deir el-Medina, resulted in a work-free day) may have been to keep people content so that they would continue to work which was to the advantage of the king and the elite surrounding him. Local feasts appear to have been observed more irregularly at Deir el-Medina or perhaps according to the lunar calendar. Feasts celebrated by the community as a whole served to maintain the unity of the group. In addition to feasts celebrated by the entire community, the inhabitants of Deir el-Medina could mark their own personal feasts and organize small gatherings during public feasts. Through such feasts, an individual man might form alliances and advance his chances of a favourable marriage or of acquiring a position on the work crew.

Fatigued driving : prevalence, risk factors and groups, and the law

Fatigue and sleepiness are major causes of road traffic accidents. However, precise data is often lacking because a validated and reliable device for detecting the level of sleepiness (cf. the breathalyzer for alcohol levels) does not exist, nor does criteria for the unambiguous detection of fatigue/sleepiness as a contributing factor in accident causation. Therefore, identification of risk factors and groups might not always be easy. Furthermore, it is extremely difficult to incorporate fatigue in operationalized terms into either traffic or criminal law. The main aims of this thesis were to estimate the prevalence of fatigue problems while driving among the Finnish driving population, to explore how VALT multidisciplinary investigation teams, Finnish police, and courts recognize (and prosecute) fatigue in traffic, to identify risk factors and groups, and finally to explore the application of the Finnish Road Traffic Act (RTA), which explicitly forbids driving while tired in Article 63. Several different sources of data were used: a computerized database and the original folders of multidisciplinary teams investigating fatal accidents (VALT), the driver records database (AKE), prosecutor and court decisions, a survey of young male military conscripts, and a survey of a representative sample of the Finnish active driving population. The results show that 8-15% of fatal accidents during 1991-2001 were fatigue related, that every fifth Finnish driver has fallen asleep while driving at some point during his/her driving career, and that the Finnish police and courts punish on average one driver per day on the basis of fatigued driving (based on the data from the years 2004-2005). The main finding regarding risk factors and risk groups is that during the summer months, especially in the afternoon, the risk of falling asleep while driving is increased. Furthermore, the results indicate that those with a higher risk of falling asleep while driving are men in general, but especially young male drivers including military conscripts and the elderly during the afternoon hours and the summer in particular; professional drivers breaking the rules about duty and rest hours; and drivers with a tendency to fall asleep easily. A time-of-day pattern of sleep-related incidents was repeatedly found. It was found that VALT teams can be considered relatively reliable when assessing the role of fatigue and sleepiness in accident causation; thus, similar experts might be valuable in the court process as expert witnesses when fatigue or sleepiness are suspected to have a role in an accident’s origins. However, the application of Article 63 of the RTA that forbids, among other things, fatigued driving will continue to be an issue that deserves further attention. This should be done in the context of a needed attitude change towards driving while in a state of extreme tiredness (e.g., after being awake for more than 24 hours), which produces performance deterioration comparable to illegal intoxication (BAC around 0.1%). Regarding the well-known interactive effect of increased sleepiness and even small alcohol levels, the relatively high proportion (up to 14.5%) of Finnish drivers owning and using a breathalyzer raises some concern. This concern exists because these drivers are obviously more focused on not breaking the “magic” line of 0.05% BAC than being concerned about driving impairment, which might be much worse than they realize because of the interactive effects of increased sleepiness and even low alcohol consumption. In conclusion, there is no doubt that fatigue and sleepiness problems while driving are common among the Finnish driving population. While we wait for the invention of reliable devices for fatigue/sleepiness detection, we should invest more effort in raising public awareness about the dangerousness of fatigued driving and educate drivers about how to recognize and deal with fatigue and sleepiness when they ultimately occur.

LKB1 tumor suppression in Peutz-Jeghers Syndrome

Kasvainten, ajatellaan syntyvän yksittäisen solun perimän mutaatioista, jonka seurauksena tuon solun kasvu häiriintyy. Ruoansulatuskanavan polyyppien syntyä käytetään usein mallina siitä, miten nämä epiteelisoluun kerääntyvät mutaatiot aiheuttavat asteittain pahenevan kasvuhäiriön. Peutz–Jeghersin oireyhtymä (PJS) on perinnöllinen polypoosisyndrooma, jossa oireita aiheuttavat erityisesti maha-suolikanavan hamartomatoottiset polyypit. Noin puolella PJS potilaista havaitaan mutaatioita LKB1 kasvunrajoite geenissä. Hiirille joilta toinen Lkb1 alleeli on poistettu (Lkb1+/-) kehittyy PJS-tyypin maha-suolikanavan polyyppeja, joissa on epiteelin liikakasvun lisäksi merkittävä sileälihaskomponentti, aivan kuten PJS polyypeissa. Kuten myös muissa ruoansulatuskanavan polypooseissa, sekä PJS että hiirten polyypeissa Cyclo-oxygenaasi-2:n (COX-2) määrä on usein kohonnut. PJS-polyyppien kehittymisen molekulaarinen mekanismi on kuitenkin selvittämättä. Koska vain osa PJS potilaista kantaa LKB1 mutaatioita, mutaatiot jossakin toisessa lokuksessa saattaisivat selittää osan PJS tapauksista. Jotta PJS:n geneettinen tausta selviäisi, seulottiin kolmen LKB1:n kanssa interaktoivan proteiinin (BRG1, STRADα ja MO25α) geenit PJS potilaista joilla ei ole havaittu LKB1 mutaatioita. Yhdessäkään tutkituista geeneistä ei havaittu tautia aiheuttavia mutaatioita. Näiden kolmen geenin pois sulkeminen, ja uusien menetelmien ansiosta kasvanut havaittujen Lkb1 mutaatioden määrä viittaavat LKB1:n olevan useimpien PJS tapausten taustalla. COX-2:n estäjien käyttö on tehokkaasti vähentänyt polyyppien määrää familiaarisessa adenomatoottisessa polypoosissa. Tästä johtuen COX-2:n eston tehokkuutta tutkittiin PJS polypoosissa. PJS-tyypin polypoosin havaittin pienenevän merkittävästi Lkb1+/- hiirissä, joilta oli lisäksi poistettu toinen tai molemmat COX-2:n alleeleista. Lisäksi farmakologinen COX-2:n esto Celecoxib:lla vähensi polypoosia tehokkaasti. Näin ollen COX-2:n eston tehokkuutta tutkittiin seuraavaksi PJS potilaissa. Kuuden kuukauden Celecoxib hoidon jälkeen polypoosin havaittiin vähentyneen merkittävästi osalla potilaista (2/6). Nämä tulokset osoittavat COX-2:n roolin PJS-polyyppien kehityksessä, ja viittaavat COX-2:n eston vähentävän polypoosia. Kasvunrajoitegeenin klassisen määritelmän mukaan kasvaimen kehitys vaatii perinnöllisen mutaation lisäksi geenin toisenkin alleelin mutaation, mutta PJS-polyyppien häiriintyneestä epiteelistä ei kuitenkaan systemaattisesti löydy toista LKB1:n mutaatiota. Havainto johti tutkimukseen, jossa selvitettiin voisiko LKB1:n kasvun rajoitus välittyäkin epäsuorasti tukikudokseksi ajatelluista sileälihassoluista. Tätä tutkittiin kehittämällä poistogeeninen hiirimalli jossa Lkb1 on mutatoitunut vain sileälihassoluissa. Näille hiirille kehittyi polyyppeja, jotka ovat kaikin tavoin PJS-polyyppien kaltaisia. Lkb1:n menettäneiden solujen havaittiin tuottavan vähemmän transformoivaa kasvutekijä beetaa (TGFß), joka aiheutti solujen välisen viestinnän heikentymisen ja mahdollisesti viereisten epiteelisolujen liikakasvun. Vastaava häiriö havaittiin myös PJS-potilaiden polyypeissa, mikä viittaa siihen, että potilaillakin sileälihassolujen häiriö on polyyppien taustalla. Havainto suuntaa täten hoitokohteiden etsintää ja osoittaa että LKB1 toimii kasvunrajoittajana epätyypillisellä tavalla pitäen naapurisolujen kasvun kurissa.

Self-reported bruxism : Associated factors among media personnel with or without irregular shift work

Tutkimuksen kohderyhmänä oli mediatyöntekijöitä, joiden toimenkuva on viime vuosina muuttunut yhä kuormittavammaksi epäsäännöllisen vuorotyön sekä jatkuvien teknisten, organisatoristen ja taloudellisten tekijöiden ristipaineessa. Väitöskirjatutkimus on osa laajempaa tutkimushanketta, joka suunniteltiin selvittämään epäsäännöllisen vuorotyön mahdollisia haittoja. Tutkimusta tukivat taloudellisesti Työsuojelurahasto ja Suomen Hammaslääkäriseura Apollonia sekä resurssipanostuksin Hammaslääketieteen laitos (HY), Työterveyslaitos ja Yleisradio Oy. Bruksismi on tahdosta riippumatonta hampaiden narskuttelua tai yhteenpuristamista. Hampaiden narskuttelu on rytmistä jaksoittain toistuvaa puremalihasten toimintaa, joka esiintyy nukkuessa -tavallisimmin kevyen unen ja havahtumisjaksojen yhteydessä. Valveilla ollessa bruksismi on terveillä ihmisillä lähinnä hampaiden yhteenpuristamista. Yleisen käsityksen mukaan toistuvaa unibruksismia esiintyy noin 10 %:lla ja valveilla tapahtuvaa hampaiden yhteenpuristamista noin 20 %:lla. Aiemmin bruksismi kuului kansainvälisen unihäiriöluokituksen (ICSD 1997) mukaan unen erityishäiriöihin, mutta tuorein luokitus (ICSD 2005) listaa sen unen liikehäiriöihin. Väitöstutkimuksen yleisenä tavoitteena oli kartoittaa koetun bruksismin ja uni- valvehäiriöiden yhteyttä. Tutkimus oli poikittainen vertailututkimus epäsäännöllistä vuorotyötä ja säännöllisiä päivävuoroja tekevien välillä. Mielenkiinto kohdistui myös bruksismin ja kasvojen alueen kivun mahdolliseen yhteyteen. Lisäksi tutkimuksessa selvitettiin joidenkin tunnetusti unen laatua huonontavien psykososiaalisten, neurologisten ja fysiologisten tekijöiden yhteyttä koettuun bruksismiin. Tutkimuksen kohderyhmän muodosti 750 Yleisradion epäsäännöllistä vuorotyötä tekevää työntekijää. Vertailuryhmänä käytettiin samansuuruista satunnaistetusti valittua kaltaistettua Yleisradion työntekijäjoukkoa, joka tekee samankaltaista työtä, mutta säännöllisenä päivätyönä. Kohderyhmälle lähetettiin kyselylomakkeet, jotka kartoittivat koetun bruksismin lisäksi mm. tutkittavien taustatiedot, yleisen terveydentilan, yleisiä koettuja stressioireita ja tuntemuksia, kipuoireita, sekä unen laatua. Lisäksi esitettiin jaksamista ja työympäristöä koskevia kysymyksiä. Kyselyyn vastasi kaikkiaan 874 henkilöä. Kokonaisvastausprosentti oli 58,3 % (53,7 % miehiä). Epäsäännöllistä vuorotyötä tekevien vastausprosentti oli 82,3 % ja säännöllistä päivätyötä tekevien ryhmässä 34,3 %. Työtehtävät sisälsivät ohjelmien toimitus- ja tuottamistyötä, teknistä tuotanto- ja tukityötä, sekä esimies- ja hallintotyötä. Miesten keski-ikä vuorotyöryhmässä oli 45,0 (± 10,6) vuotta ja naisten keski-ikä 42,6 (± 10,7) vuotta, vastaavat luvut päivätyötä tekeville olivat 47,4 (± 9,7) ja 45,5 (± 10,1) vuotta. Vuorotyötä tekevistä oli miehiä 56,6 %, päivätyöryhmässä miehien osuus oli 46,7 %. Usein koettua bruksismia havaittiin koko tutkimusjoukossa 10,6 %:lla. Bruksismin esiintyvyydessä ei ollut merkitsevää eroa epäsäännöllistä vuorotyötä ja päivätyötä tekevien välillä. Kun bruksismia ja stressiä arvioitiin suhteessa tyytyväisyyteen nykyiseen työaikamuotoon, molemmat olivat merkitsevästi vallitsevimpia niillä, jotka halusivat vaihtaa nykyistä työaikamuotoaan. Epäsäännöllistä vuorotyötä tekevät lisäksi ilmoittivat kokevansa enemmän stressiä kuin päivätyötä tekevät sekä olivat tyytymättömämpiä työaikamuotoonsa. Tutkittavista henkilöistä katkonaista unta esiintyi 43,6 %:lla sekä 36,2 % koki unensa virkistämättömäksi. Kasvokipua esiintyi 19,6 %:lla. Usein toistuva bruksaus sekä tyytymättömyys työaikamuotoon olivat erittäin merkitsevästi yhteydessä unihäiriöiden sekä riittämättömän unen oireiden kanssa. Bruksismi ja katkonainen uni osoittautuivat myös kasvokivun taustatekijöiksi. Tutkimus osoitti, että koetulla bruksismilla oli merkitsevä yhteys unihäiriöihin, kasvokipuun, koettuun stressiin ja ahdistuneisuuteen, nuorempaan ikään, runsaampiin hammaslääkäri- ja lääkärikäynteihin sekä siihen että oli tyytymätön työaikamuotoonsa (itse työaikamuoto ei ollut merkitsevä tekijä). Tutkimuksen yhtenä johtopäätöksenä todettiin, että koettu bruksismi voi terveillä työikäisillä henkilöillä olla osa stressaavaa tilannetta ja siihen liittyvää käyttäytymistä. Tämän tiedostaminen terveydenhuollossa voisi olla hyödyllistä.

Drug Analysis without Primary Reference Standards : Application of LC-TOFMS and LC-CLND to Biofluids and Seized Material

Drug Analysis without Primary Reference Standards: Application of LC-TOFMS and LC-CLND to Biofluids and Seized Material Primary reference standards for new drugs, metabolites, designer drugs or rare substances may not be obtainable within a reasonable period of time or their availability may also be hindered by extensive administrative requirements. Standards are usually costly and may have a limited shelf life. Finally, many compounds are not available commercially and sometimes not at all. A new approach within forensic and clinical drug analysis involves substance identification based on accurate mass measurement by liquid chromatography coupled with time-of-flight mass spectrometry (LC-TOFMS) and quantification by LC coupled with chemiluminescence nitrogen detection (LC-CLND) possessing equimolar response to nitrogen. Formula-based identification relies on the fact that the accurate mass of an ion from a chemical compound corresponds to the elemental composition of that compound. Single-calibrant nitrogen based quantification is feasible with a nitrogen-specific detector since approximately 90% of drugs contain nitrogen. A method was developed for toxicological drug screening in 1 ml urine samples by LC-TOFMS. A large target database of exact monoisotopic masses was constructed, representing the elemental formulae of reference drugs and their metabolites. Identification was based on matching the sample component s measured parameters with those in the database, including accurate mass and retention time, if available. In addition, an algorithm for isotopic pattern match (SigmaFit) was applied. Differences in ion abundance in urine extracts did not affect the mass accuracy or the SigmaFit values. For routine screening practice, a mass tolerance of 10 ppm and a SigmaFit tolerance of 0.03 were established. Seized street drug samples were analysed instantly by LC-TOFMS and LC-CLND, using a dilute and shoot approach. In the quantitative analysis of amphetamine, heroin and cocaine findings, the mean relative difference between the results of LC-CLND and the reference methods was only 11%. In blood specimens, liquid-liquid extraction recoveries for basic lipophilic drugs were first established and the validity of the generic extraction recovery-corrected single-calibrant LC-CLND was then verified with proficiency test samples. The mean accuracy was 24% and 17% for plasma and whole blood samples, respectively, all results falling within the confidence range of the reference concentrations. Further, metabolic ratios for the opioid drug tramadol were determined in a pharmacogenetic study setting. Extraction recovery estimation, based on model compounds with similar physicochemical characteristics, produced clinically feasible results without reference standards.

Homoclinic Splitting without Trees

We study a Hamiltonian describing a pendulum coupled with several anisochronous oscillators, giving a simple construction of unstable KAM tori and their stable and unstable manifolds for analytic perturbations. When the coupling takes place through an even trigonometric polynomial in the angle variables, we extend analytically the solutions of the equations of motion, order by order in the perturbation parameter, to a large neighbourhood of the real line representing time. Subsequently, we devise an asymptotic expansion for the splitting (matrix) associated with a homoclinic point. This expansion consists of contributions that are manifestly exponentially small in the limit of vanishing gravity, by a shift-of-countour argument. Hence, we infer a similar upper bound for the splitting itself. In particular, the derivation of the result does not call for a tree expansion with explicit cancellation mechanisms.

Evaluation of methods and applications for behavioural profiling of transgenic mice

During the last 10-15 years interest in mouse behavioural analysis has evolved considerably. The driving force is development in molecular biological techniques that allow manipulation of the mouse genome by changing the expression of genes. Therefore, with some limitations it is possible to study how genes participate in regulation of physiological functions and to create models explaining genetic contribution to various pathological conditions. The first aim of our study was to establish a framework for behavioural phenotyping of genetically modified mice. We established comprehensive battery of tests for the initial screening of mutant mice. These included tests for exploratory and locomotor activity, emotional behaviour, sensory functions, and cognitive performance. Our interest was in the behavioural patterns of common background strains used for genetic manipulations in mice. Additionally we studied the behavioural effect of sex differences, test history, and individual housing. Our findings highlight the importance of careful consideration of genetic background for analysis of mutant mice. It was evident that some backgrounds may mask or modify the behavioural phenotype of mutants and thereby lead to false positive or negative findings. Moreover, there is no universal strain that is equally suitable for all tests, and using different backgrounds allows one to address possible phenotype modifying factors. We discovered that previous experience affected performance in several tasks. The most sensitive traits were the exploratory and emotional behaviour, as well as motor and nociceptive functions. Therefore, it may be essential to repeat some of the tests in naïve animals for assuring the phenotype. Social isolation for a long time period had strong effects on exploratory behaviour, but also on learning and memory. All experiments revealed significant interactions between strain and environmental factors (test history or housing condition) indicating genotype-dependent effects of environmental manipulations. Several mutant line analyses utilize this information. For example, we studied mice overexpressing as well as those lacking extracellular matrix protein heparin-binding growth-associated molecule (HB-GAM), and mice lacking N-syndecan (a receptor for HB-GAM). All mutant mice appeared to be fertile and healthy, without any apparent neurological or sensory defects. The lack of HB-GAM and N-syndecan, however, significantly reduced the learning capacity of the mice. On the other hand, overexpression of HB-GAM resulted in facilitated learning. Moreover, HB-GAM knockout mice displayed higher anxiety-like behaviour, whereas anxiety was reduced in HB-GAM overexpressing mice. Changes in hippocampal plasticity accompanied the behavioural phenotypes. We conclude that HB-GAM and N-syndecan are involved in the modulation of synaptic plasticity in hippocampus and play a role in regulation of anxiety- and learning-related behaviour.

Corneal recovery after uncomplicated and complicated PRK and LASIK

Refractive errors, especially myopia, seem to increase worldwide. Concurrently, the number of surgical refractive corrections has increased rapidly, with several million procedures performed annually. However, excimer laser surgery was introduced after a limited number of studies done with animals and to date there still are only few long-term follow-up studies of the results. The present thesis aims to evaluate the safety and functional outcome of, as well as to quantify the cellular changes and remodelling in the human cornea after, photorefractive keratectomy (PRK) and laser assisted in situ keratomileusis (LASIK). These procedures are the two most common laser surgical refractive methods. In Study I, myopic ophthalmic residents at Helsinki University Eye Hospital underwent a refractive correction by PRK. Five patients were followed up for 6 months to assess their subjective experience in hospital work and their performance in car driving simulator and in other visuomotor functions. Corneal morphological changes were assessed by in vivo confocal microscopy (ivCM). Study II comprised 14 patients who had undergone a PRK operation in 1993-1994. Visual acuity was examined and ivCM examinations performed 5 years postoperatively. In Study III 15 patients received LASIK refractive correction for moderate to high myopia (-6 - -12 D). Their corneal recovery was followed by ivCM for 2 years. Diffuse lamellar keratitis (DLK) is a common but variable complication of LASIK. Yet, its aetiology remains unknown. In Study IV we examined six patients who had developed DLK as a consequence of formation of an intraoperative or post-LASIK epithelial defect, to assess the corneal and conjunctival inflammatory reaction. In the whole series, the mean refractive correction was -6.46 diopters. The best spectacle corrected visual acuity (BSCVA) improved in 30 % of patients, whereas in four patients BSCVA decreased slightly. The mean achieved refraction was 0.35 D undercorrected. After PRK, the stromal scar formation was highest at 2 to 3 months postoperatively and subsequently decreased. At 5 years increased reflectivity in the subepithelial stroma was observed in all patients. Interestingly, no Bowman s layer was detected in any patient. Subbasal nerve fiber bundle(snfb) regeneration could be observed already at 2 months in 2 patients after PRK. After 5 years, all corneas presented with snfb, the density of which, however, was still lower than in control corneas. LASIK induced a hypocellular area on both sides of the flap interface. A decrease of the most anterior keratocyte density was also observed. In the corneas that developed DLK, inflammatory cell-type objects were present in the flap interface in half of the patients. The other patients presented only with keratocyte activation and highly reflective extracellular matrix. These changes resolved completely with medication and time. Snfb regeneration was first detected at one month post-LASIK, but still after two years the density of snfb, however, was only 64 % of the preoperative values. The performance of ophthalmological examinations and microsurgery without spectacles was easier postoperatively, which was appreciated by the residents. Both PRK and LASIK showed moderate to good accuracy and high safety. In terms of visual perception and subjective evaluation, few patients stated any complaints in the whole series of studies. Instead, the majority of patients experienced a marked improvement in everyday life and work performance. PRK and LASIK have shown similar results, with good long term morphological healing. It seems evident that, even without the benefit of over-20-year follow-up results, these procedures are sufficiently safe and accurate for refractive corrections and corneal reshaping.

Atomic scale engineering of carbon nanotubes

Carbon nanotubes, seamless cylinders made from carbon atoms, have outstanding characteristics: inherent nano-size, record-high Young’s modulus, high thermal stability and chemical inertness. They also have extraordinary electronic properties: in addition to extremely high conductance, they can be both metals and semiconductors without any external doping, just due to minute changes in the arrangements of atoms. As traditional silicon-based devices are reaching the level of miniaturisation where leakage currents become a problem, these properties make nanotubes a promising material for applications in nanoelectronics. However, several obstacles must be overcome for the development of nanotube-based nanoelectronics. One of them is the ability to modify locally the electronic structure of carbon nanotubes and create reliable interconnects between nanotubes and metal contacts which likely can be used for integration of the nanotubes in macroscopic electronic devices. In this thesis, the possibility of using ion and electron irradiation as a tool to introduce defects in nanotubes in a controllable manner and to achieve these goals is explored. Defects are known to modify the electronic properties of carbon nanotubes. Some defects are always present in pristine nanotubes, and naturally are introduced during irradiation. Obviously, their density can be controlled by irradiation dose. Since different types of defects have very different effects on the conductivity, knowledge of their abundance as induced by ion irradiation is central for controlling the conductivity. In this thesis, the response of single walled carbon nanotubes to ion irradiation is studied. It is shown that, indeed, by energy selective irradiation the conductance can be controlled. Not only the conductivity, but the local electronic structure of single walled carbon nanotubes can be changed by the defects. The presented studies show a variety of changes in the electronic structures of semiconducting single walled nanotubes, varying from individual new states in the band gap to changes in the band gap width. The extensive simulation results for various types of defect make it possible to unequivocally identify defects in single walled carbon nanotubes by combining electronic structure calculations and scanning tunneling spectroscopy, offering a reference data for a wide scientific community of researchers studying nanotubes with surface probe microscopy methods. In electronics applications, carbon nanotubes have to be interconnected to the macroscopic world via metal contacts. Interactions between the nanotubes and metal particles are also essential for nanotube synthesis, as single walled nanotubes are always grown from metal catalyst particles. In this thesis, both growth and creation of nanotube-metal nanoparticle interconnects driven by electron irradiation is studied. Surface curvature and the size of metal nanoparticles is demonstrated to determine the local carbon solubility in these particles. As for nanotube-metal contacts, previous experiments have proved the possibility to create junctions between carbon nanotubes and metal nanoparticles under irradiation in a transmission electron microscope. In this thesis, the microscopic mechanism of junction formation is studied by atomistic simulations carried out at various levels of sophistication. It is shown that structural defects created by the electron beam and efficient reconstruction of the nanotube atomic network, inherently related to the nanometer size and quasi-one dimensional structure of nanotubes, are the driving force for junction formation. Thus, the results of this thesis not only address practical aspects of irradiation-mediated engineering of nanosystems, but also contribute to our understanding of the behaviour of point defects in low-dimensional nanoscale materials.

Aspects of Inflationary Models at Low Energy Scales

Cosmological inflation is the dominant paradigm in explaining the origin of structure in the universe. According to the inflationary scenario, there has been a period of nearly exponential expansion in the very early universe, long before the nucleosynthesis. Inflation is commonly considered as a consequence of some scalar field or fields whose energy density starts to dominate the universe. The inflationary expansion converts the quantum fluctuations of the fields into classical perturbations on superhorizon scales and these primordial perturbations are the seeds of the structure in the universe. Moreover, inflation also naturally explains the high degree of homogeneity and spatial flatness of the early universe. The real challenge of the inflationary cosmology lies in trying to establish a connection between the fields driving inflation and theories of particle physics. In this thesis we concentrate on inflationary models at scales well below the Planck scale. The low scale allows us to seek for candidates for the inflationary matter within extensions of the Standard Model but typically also implies fine-tuning problems. We discuss a low scale model where inflation is driven by a flat direction of the Minimally Supersymmetric Standard Model. The relation between the potential along the flat direction and the underlying supergravity model is studied. The low inflationary scale requires an extremely flat potential but we find that in this particular model the associated fine-tuning problems can be solved in a rather natural fashion in a class of supergravity models. For this class of models, the flatness is a consequence of the structure of the supergravity model and is insensitive to the vacuum expectation values of the fields that break supersymmetry. Another low scale model considered in the thesis is the curvaton scenario where the primordial perturbations originate from quantum fluctuations of a curvaton field, which is different from the fields driving inflation. The curvaton gives a negligible contribution to the total energy density during inflation but its perturbations become significant in the post-inflationary epoch. The separation between the fields driving inflation and the fields giving rise to primordial perturbations opens up new possibilities to lower the inflationary scale without introducing fine-tuning problems. The curvaton model typically gives rise to relatively large level of non-gaussian features in the statistics of primordial perturbations. We find that the level of non-gaussian effects is heavily dependent on the form of the curvaton potential. Future observations that provide more accurate information of the non-gaussian statistics can therefore place constraining bounds on the curvaton interactions.

Essays on Stock Options, Incentives, and Managerial Action

Executive compensation and managerial behavior have received an increasing amount of attention in the financial economics literature since the mid 1970s. The purpose of this thesis is to extend our understanding of managerial compensation, especially how stock option compensation is linked to the actions undertaken by the management. Furthermore, managerial compensation is continuously and heatedly debated in the media and an emerging consensus from this discussion seems to be that there still exists gaps in our knowledge of optimal contracting. In Finland, the first executive stock options were introduced in the 1980s and throughout the last 15 years it has become increasingly popular for Finnish listed firms to use this type of managerial compensation. The empirical work in the thesis is conducted using data from Finland, in contrast to most previous studies that predominantly use U.S. data. Using Finnish data provides insight of how market conditions affect compensation and managerial action and provides an opportunity to explore what parts of the U.S. evidence can be generalized to other markets. The thesis consists of four essays. The first essay investigates the exercise policy of the executive stock option holders in Finland. In summary, Essay 1 contributes to our understanding of the exercise policies by examining both the determinants of the exercise decision and the markets reaction to the actual exercises. The second essay analyzes the factors driving stock option grants using data for Finnish publicly listed firms. Several agency theory based variables are found to have have explanatory power on the likelihood of a stock option grant. Essay 2 also contributes to our understanding of behavioral factors, such as prior stock return, as determinants of stock option compensation. The third essay investigates the tax and stock option motives for share repurchases and dividend distributions. We document strong support for the tax motive for share repurchases. Furthermore, we also analyze the dividend distribution decision in companies with stock options and find a significant difference between companies with and without dividend protected options. We thus document that the cutting of dividends found in previous U.S. studies can be avoided by dividend protection. In the fourth essay we approach the puzzle of negative skewness in stock returns from an altogether different angle than in previous studies. We suggest that negative skewness in stock returns is generated by management disclosure practices and find proof for this. More specifically, we find that negative skewness in daily returns is induced by returns for days when non-scheduled firm specific news is disclosed.