Elements of Volatility at High Frequency

Volatility is central in options pricing and risk management. It reflects the uncertainty of investors and the inherent instability of the economy. Time series methods are among the most widely applied scientific methods to analyze and predict volatility. Very frequently sampled data contain much valuable information about the different elements of volatility and may ultimately reveal the reasons for time varying volatility. The use of such ultra-high-frequency data is common to all three essays of the dissertation. The dissertation belongs to the field of financial econometrics. The first essay uses wavelet methods to study the time-varying behavior of scaling laws and long-memory in the five-minute volatility series of Nokia on the Helsinki Stock Exchange around the burst of the IT-bubble. The essay is motivated by earlier findings which suggest that different scaling laws may apply to intraday time-scales and to larger time-scales, implying that the so-called annualized volatility depends on the data sampling frequency. The empirical results confirm the appearance of time varying long-memory and different scaling laws that, for a significant part, can be attributed to investor irrationality and to an intraday volatility periodicity called the New York effect. The findings have potentially important consequences for options pricing and risk management that commonly assume constant memory and scaling. The second essay investigates modelling the duration between trades in stock markets. Durations convoy information about investor intentions and provide an alternative view at volatility. Generalizations of standard autoregressive conditional duration (ACD) models are developed to meet needs observed in previous applications of the standard models. According to the empirical results based on data of actively traded stocks on the New York Stock Exchange and the Helsinki Stock Exchange the proposed generalization clearly outperforms the standard models and also performs well in comparison to another recently proposed alternative to the standard models. The distribution used to derive the generalization may also prove valuable in other areas of risk management. The third essay studies empirically the effect of decimalization on volatility and market microstructure noise. Decimalization refers to the change from fractional pricing to decimal pricing and it was carried out on the New York Stock Exchange in January, 2001. The methods used here are more accurate than in the earlier studies and put more weight on market microstructure. The main result is that decimalization decreased observed volatility by reducing noise variance especially for the highly active stocks. The results help risk management and market mechanism designing.

Kognitiva system i namngivningen av finländska handelsfartyg 1838-1938

This dissertation is an onomastic study of Finland s stock of ship names (nautonomasticon) recorded over the period 1838 1938. The primary material investigated consists of 2 066 examples of ship names from the fleets of coastal towns, distributed over five sample years. The material is supplemented with two bodies of comparative data; one that consists of 2 535 examples of boat names from the archipelago area at the corresponding time, and another that comprises 482 examples of eighteenth century Finnish ship names. This study clarifies the categories of names that appear the frequency of the names, formation, morphology, linguistic origin, functions, and semantic qualities. By comparing the material with boat names from previous centuries, and from other countries, the characteristics of Finnish vessel names are further highlighted. Additional clarification is brought to the chronological, regional, and social variations, and to the emergence of various forms of systematic naming. This dissertation builds on older research from other countries, and uses traditional onomastic methods alongside a more modern methodology. The approach is interdisciplinary, meaning that the names are explored using facts not only from nautical history, but also from a range of other historical disciplines such as economics, culture, art, and literature. In addition, the approach is socio-onomastic, i.e. that the variations in names are studied in a societal context. Using a synchronised perspective, cognitive linguistic theories have provided the tools for this exploration into the metaphorical and the prototypical meaning of the names, and the semantic domains that the names create. The quantitative analysis has revealed the overall picture of Finnish boat names. Personal names, names from mythology, and place names, emerge as significant categories, alongside nonproprial names in Swedish and Finnish. The interdisciplinary perspective has made it possible to explain certain trends in the stock of boat names, for example, the predisposition towards names from classical mythology, the breakthrough of names taken from the national epos Kalevala, names in the Finnish language from around the middle of the nineteenth century, and the continuing rise of place names during the latter part of the period 1838 1938. The socio-onomastic perspective has also identified clear differences between those ship names used in towns, and those ship names used in the archipelago, and it has clarified how naming conventions tend to spread from town centres to peripheral areas. The cognitive linguistic methods have revealed that the greater part of the vessel names can be interpreted as metaphors, in particular personifications, and that many names are related in their content and also form semantic networks and cognitive systems. The results indicate that there is a mental nautonomasticon that consists of a standard set of traditional ship names, but they also reveal the existence of conscious or unconscious cognitive systems (rules and conventions) that guide the naming of boats.

Nonverbal predication in Erzya : Studies on morphosyntactic variation and part of speech distinctions

This dissertation consists of four articles and an introduction. The five parts address the same topic, nonverbal predication in Erzya, from different perspectives. The work is at the same time linguistic typology and Uralic studies. The findings based on a large corpus of empirical Erzya data, which was collected using several different methods and included recordings of the spoken language, made it possible for the present study to apply, then test and finally discuss the previous theories based on cross-linguistic data. Erzya makes use of multiple predication patterns which vary from totally analytic to the morphologically very complex. Nonverbal predicate clause types are classified on the basis of propositional acts in clauses denoting class-membership, identity, property and location. The predicates of these clauses are nouns, adjectives and locational expressions, respectively. The following three predication strategies in Erzya nonverbal predication can be identified: i. the zero-copula construction, ii. the predicative suffix construction and iii. the copula construction. It has been suggested that verbs and nouns cannot be clearly distinguished on morphological grounds when functioning as predicates in Erzya. This study shows that even though predicativity must not be considered a sufficient tool for defining parts of speech in any language, the Erzya lexical classes of adjective, noun and verb can be distinguished from each other also in predicate position. The relative frequency and degree of obligation for using the predicative suffix construction decreases when moving left to right on the scale verb adjective/locative noun ( identificational statement). The predicative suffix is the main pattern in the present tense over the whole domain of nonverbal predication in Standard Erzya, but if it is replaced it is most likely to be with a zero-copula construction in a nominal predication. This study exploits the theory of (a)symmetry for the first time in order to describe verbal vs. nonverbal predication. It is shown that the asymmetry of paradigms and constructions differentiates the lexical classes. Asymmetrical structures are motivated by functional level asymmetry. Variation in predication as such adds to the complexity of the grammar. When symmetric structures are employed, the functional complexity of grammar decreases, even though morphological complexity increases. The genre affects the employment of predication strategies in Erzya. There are differences in the relative frequency of the patterns, and some patterns are totally lacking from some of the data. The clearest difference is that the past tense predicative suffix construction occurs relatively frequently in Standard Erzya, while it occurs infrequently in the other data. Also, the predicative suffixes of the present tense are used more regularly in written Standard Erzya than in any other genre. The genre also affects the incidence of the translative in uľ(ń)ems copula constructions. In translations from Russian to Erzya the translative case is employed relatively frequently in comparison to other data. This study reveals differences between the two Mordvinic languages Erzya and Moksha. The predicative suffixes (bound person markers) of the present tense are used more regularly in Moksha in all kinds of nonverbal predicate clauses compared to Erzya. It should further be observed that identificational statements are encoded with a predicative suffix in Moksha, but seldom in Erzya. Erzya clauses are more frequently encoded using zero-constructions, displaying agreement in number only.

Neuronal oscillations in gamma- and alpha-frequency bands: from object representations to sensory awareness

The synchronization of neuronal activity, especially in the beta- (14-30 Hz) /gamma- (30 80 Hz) frequency bands, is thought to provide a means for the integration of anatomically distributed processing and for the formation of transient neuronal assemblies. Thus non-stimulus locked (i.e. induced) gamma-band oscillations are believed to underlie feature binding and the formation of neuronal object representations. On the other hand, the functional roles of neuronal oscillations in slower theta- (4 8 Hz) and alpha- (8 14 Hz) frequency bands remain controversial. In addition, early stimulus-locked activity has been largely ignored, as it is believed to reflect merely the physical properties of sensory stimuli. With human neuromagnetic recordings, both the functional roles of gamma- and alpha-band oscillations and the significance of early stimulus-locked activity in neuronal processing were examined in this thesis. Study I of this thesis shows that even the stimulus-locked (evoked) gamma oscillations were sensitive to high-level stimulus features for speech and non-speech sounds, suggesting that they may underlie the formation of early neuronal object representations for stimuli with a behavioural relevance. Study II shows that neuronal processing for consciously perceived and unperceived stimuli differed as early as 30 ms after stimulus onset. This study also showed that the alpha band oscillations selectively correlated with conscious perception. Study III, in turn, shows that prestimulus alpha-band oscillations influence the subsequent detection and processing of sensory stimuli. Further, in Study IV, we asked whether phase synchronization between distinct frequency bands is present in cortical circuits. This study revealed prominent task-sensitive phase synchrony between alpha and beta/gamma oscillations. Finally, the implications of Studies II, III, and IV to the broader scientific context are analysed in the last study of this thesis (V). I suggest, in this thesis that neuronal processing may be extremely fast and that the evoked response is important for cognitive processes. I also propose that alpha oscillations define the global neuronal workspace of perception, action, and consciousness and, further, that cross-frequency synchronization is required for the integration of neuronal object representations into global neuronal workspace.

Cognitive deficits and the Paced Auditory Serial Addition Test performance among patients with multiple sclerosis

Multiple sclerosis (MS) is a chronic, inflammatory disease of the central nervous system, characterized especially by myelin and axon damage. Cognitive impairment in MS is common but difficult to detect without a neuropsychological examination. Valid and reliable methods are needed in clinical practice and research to detect deficits, follow their natural evolution, and verify treatment effects. The Paced Auditory Serial Addition Test (PASAT) is a measure of sustained and divided attention, working memory, and information processing speed, and it is widely used in MS patients neuropsychological evaluation. Additionally, the PASAT is the sole cognitive measure in an assessment tool primarly designed for MS clinical trials, the Multiple Sclerosis Functional Composite (MSFC). The aims of the present study were to determine a) the frequency, characteristics, and evolution of cognitive impairment among relapsing-remitting MS patients, and b) the validity and reliability of the PASAT in measuring cognitive performance in MS patients. The subjects were 45 relapsing-remitting MS patients from Seinäjoki Central Hospital, Department of Neurology and 48 healthy controls. Both groups underwent comprehensive neuropsychological assessments, including the PASAT, twice in a one-year follow-up, and additionally a sample of 10 patients and controls were evaluated with the PASAT in serial assessments five times in one month. The frequency of cognitive dysfunction among relapsing-remitting MS patients in the present study was 42%. Impairments were characterized especially by slowed information processing speed and memory deficits. During the one-year follow-up, the cognitive performance was relatively stable among MS patients on a group level. However, the practice effects in cognitive tests were less pronounced among MS patients than healthy controls. At an individual level the spectrum of MS patients cognitive deficits was wide in regards to their characteristics, severity, and evolution. The PASAT was moderately accurate in detecting MS-associated cognitive impairment, and 69% of patients were correctly classified as cognitively impaired or unimpaired when comprehensive neuropsychological assessment was used as a "gold standard". Self-reported nervousness and poor arithmetical skills seemed to explain misclassifications. MS-related fatigue was objectively demonstrated as fading performance towards the end of the test. Despite the observed practice effect, the reliability of the PASAT was excellent, and it was sensitive to the cognitive decline taking place during the follow-up in a subgroup of patients. The PASAT can be recommended for use in the neuropsychological assessment of MS patients. The test is fairly sensitive, but less specific; consequently, the reasons for low scores have to be carefully identified before interpreting them as clinically significant.

Processing of Stimulus Repetition and Change in the Somatosensory System: Recordings of Electrical and Magnetic Brain Responses

In the present work, effects of stimulus repetition and change in a continuous stimulus stream on the processing of somatosensory information in the human brain were studied. Human scalp-recorded somatosensory event-related potentials (ERPs) and magnetoencephalographic (MEG) responses rapidly diminished with stimulus repetition when mechanical or electric stimuli were applied to fingers. On the contrary, when the ERPs and multi-unit a ctivity (MUA) were directly recorded from the primary (SI) and secondary (SII) somatosensory cortices in a monkey, there was no marked decrement in the somatosensory responses as a function of stimulus repetition. These results suggest that this rate effect is not due to the response diminution in the SI and SII cortices. Obviously the responses to the first stimulus after a long "silent" period are nhanced due to unspecific initial orientation, originating in more broadly distributed and/or deeper neural structures, perhaps in the prefrontal cortices. With fast repetition rates not only the late unspecific but also some early specific somatosensory ERPs were diminished in amplitude. The fast decrease of the ERPs as a function of stimulus repetition is mainly due to the disappearance of the orientation effect and with faster repetition rates additively due to stimulus specific refractoriness. A sudden infrequent change in the continuous stimulus stream also enhanced somatosensory MEG responses to electric stimuli applied to different fingers. These responses were quite similar to those elicited by the deviant stimuli alone when the frequent standard stimuli were omitted. This enhancement was obviously due to the release from refractoriness because the neural structures generating the responses to the infrequent deviants had more time to recover from the refractoriness than the respective structures for the standards. Infrequent deviant mechanical stimuli among frequent standard stimuli also enhanced somatosensory ERPs and, in addition, they elicited a new negative wave which did not occur in the deviants-alone condition. This extra negativity could be recorded to deviations in the stimulation site and in the frequency of the vibratory stimuli. This response is probably a somatosensory analogue of the auditory mismatch negativity (MMN) which has been suggested to reflect a neural mismatch process between the sensory input and the sensory memory trace.

Aivojen jännitevasteiden rekisteröinti useaan äänen piirteeseen yhdellä mittauskerralla terveillä musiikkileikkikoulua käyvillä kaksivuotiailla

The early detection of hearing deficits is important to a child's development. However, examining small children with behavioural methods is often difficult. Research with ERPs (event-related potentials), recorded with EEG (electroencephalography), does not require attention or action from the child. Especially in children's ERP research, it is essential that the duration of a recording session is not too long. A new, faster optimum paradigm has been developed to record MMN (mismatch negativity), where ERPs to several sound features can be recorded in one recording session. This substantially shortens the time required for the experiment. So far, the new paradigm has been used in adult and school-aged children research. This study examines if MMN, LDN (late discriminative negativity) and P3a components can be recorded in two-year-olds with the new paradigm. The standard stimulus (p=0.50) was an 80 dB harmonic tone consisting of three harmonic frequencies (500 Hz, 1000 Hz and 1500 Hz) with a duration of 200 ms. The loudness deviants (p=0.067) were at a level of +6 dB or -6 dB compared to the standards. The frequency deviants (p=0.112) had a fundamental frequency of 550 or 454.4 Hz (small deviation), 625 or 400 Hz (medium deviation) or 750 or 333.3 Hz (large deviation). The duration deviants (p=0.112) had a duration of 175 ms (small deviation), 150 ms (medium deviation) or 100 ms (large deviation). The direction deviants (p=0.067) were presented from the left or right loudspeaker only. The gap deviant (p=0.067) included a 5-ms silent gap in the middle of the sound. Altogether 17 children participated in the experiment, of whom the data of 12 children was used in the analysis. ERP components were observed for all deviant types. The MMN was significant for duration and gap deviants. The LDN was significant for the large duration deviant and all other deviant types. No significant P3a was observed. These results indicate that the optimum paradigm can be used with two-year-olds. With this paradigm, data on several sound features can be recorded in a shorter time than with the previous paradigms used in ERP research.

Ravintoa keholle, ruokaa mielelle : vertailututkimus pohjoismaisten nuorten ruokatottumuksista kotona ja koulussa

Aims. The main meals that youngsters have during the day are eaten at home and at school. In the Nordic countries breakfast and supper are often eaten with other members of the family. The way that Nordic countries arrange the school lunch and the frequency of family meals differ between countries. However, the challenges related to eating habits of the young are surprisingly similar. The aim of this study is to discuss how the Nordic countries could support youngsters’ healthy eating habits. This study was carried out as a part of a Nordic research project and it completed the work done by Kauppinen (2009) and Niemi (2009) in their Master’s Theses. The research questions are: 1. How do the youngsters evaluate their own eating habits and those of their family? 2. How do the youngsters evaluate the influence of home, family and school on their own eating habits? 3. What kind of relationship exists between eating at home and at school according to the data? Data and methods. A quantitative internet-based survey was used to collect data (N=1539) on the 9th graders conceptions and understandings. The survey consisted of respondents from Finland (N=586), Sweden (N=427), Denmark (N=295) and Norway (N=246). In this study the whole data to the appropriate extent was analyzed. The analysis was done with the SPSS-software and included examination of means, standard deviations, cross-tabulations, Pearson´s correlations, Chi-squared -tests, t-tests and one-way analysis of variance (ANOVA). The results were compaired between the countries and between sexes. Results and discussion. The studied youngsters evaluated their own eating habits positively. There were statistically signifigant differences (p< .05) between countries concerning the people who influence the youngsters’ healthy eating habits. Youngsters from Finland and Sweden considered making healthy choices at school easier than those from Denmark and Norway. Also eating a so called healthy lunch at school was more common in Finland and in Sweden. Eating breakfast and eating a healthy meal at school had a statistically significant interconnection (p< .001). The differences between sexes were not equal between the countries. The results supported those from previous studies, but also raised ideas for further study. Youngsters’ near environments should support their possibilities to make healthy choices and to participate to the decicion making process. Co-operation between the Nordic countries and between the home and the school is important. Listening to the youngsters’ own voice is a challence and a possibility for developing both home economics education and research in this area. Key words: Nordic countries, youngsters, healthy eating habits, eating at home, school meals

Urban energy fluxes in Helsinki and their high frequency spectral corrections

Inadvertent climate modification has led to an increase in urban temperatures compared to the surrounding rural area. The main reason for the temperature rise is the altered energy portioning of input net radiation to heat storage and sensible and latent heat fluxes in addition to the anthropogenic heat flux. The heat storage flux and anthropogenic heat flux have not yet been determined for Helsinki and they are not directly measurable. To the contrary, turbulent fluxes of sensible and latent heat in addition to net radiation can be measured, and the anthropogenic heat flux together with the heat storage flux can be solved as a residual. As a result, all inaccuracies in the determination of the energy balance components propagate to the residual term and special attention must be paid to the accurate determination of the components. One cause of error in the turbulent fluxes is the fluctuation attenuation at high frequencies which can be accounted for by high frequency spectral corrections. The aim of this study is twofold: to assess the relevance of high frequency corrections to water vapor fluxes and to assess the temporal variation of the energy fluxes. Turbulent fluxes of sensible and latent heat have been measured at SMEAR III station, Helsinki, since December 2005 using the eddy covariance technique. In addition, net radiation measurements have been ongoing since July 2007. The used calculation methods in this study consist of widely accepted eddy covariance data post processing methods in addition to Fourier and wavelet analysis. The high frequency spectral correction using the traditional transfer function method is highly dependent on relative humidity and has an 11% effect on the latent heat flux. This method is based on an assumption of spectral similarity which is shown not to be valid. A new correction method using wavelet analysis is thus initialized and it seems to account for the high frequency variation deficit. Anyhow, the resulting wavelet correction remains minimal in contrast to the traditional transfer function correction. The energy fluxes exhibit a behavior characteristic for urban environments: the energy input is channeled to sensible heat as latent heat flux is restricted by water availability. The monthly mean residual of the energy balance ranges from 30 Wm-2 in summer to -35 Wm-2 in winter meaning a heat storage to the ground during summer. Furthermore, the anthropogenic heat flux is approximated to be 50 Wm-2 during winter when residential heating is important.

Cavity-enhanced laser spectroscopic studies of vibrational overtones of acetylene

This thesis contains five experimental spectroscopic studies that probe the vibration-rotation energy level structure of acetylene and some of its isotopologues. The emphasis is on the development of laser spectroscopic methods for high-resolution molecular spectroscopy. Three of the experiments use cavity ringdown spectroscopy. One is a standard setup that employs a non-frequency stabilised continuous wave laser as a source. In the other two experiments, the same laser is actively frequency stabilised to the ringdown cavity. This development allows for increased repetition rate of the experimental signal and thus the spectroscopic sensitivity of the method is improved. These setups are applied to the recording of several vibration-rotation overtone bands of both H(12)C(12)CH and H(13)C(13)CH. An intra-cavity laser absorption spectroscopy setup that uses a commercial continuous wave ring laser and a Fourier transform interferometer is presented. The configuration of the laser is found to be sub-optimal for high-sensitivity work but the spectroscopic results are good and show the viability of this type of approach. Several ro-vibrational bands of carbon-13 substituted acetylenes are recorded and analysed. Compared with earlier work, the signal-to-noise ratio of a laser-induced dispersed infrared fluorescence experiment is enhanced by more than one order of magnitude by exploiting the geometric characteristics of the setup. The higher sensitivity of the spectrometer leads to the observation of two new symmetric vibrational states of H(12)C(12)CH. The precision of the spectroscopic parameters of some previously published symmetric states is also improved. An interesting collisional energy transfer process is observed for the excited vibrational states and this phenomenon is explained by a simple step-down model.

The Effect of Intrauterine Growth Restriction on Long-Term Outcome in Very or Extremely Low Birth Weight Infants

The project consisted of two long-term follow-up studies of preterm children addressing the question whether intrauterine growth restriction affects the outcome. Assessment at 5 years of age of 203 children with a birth weight less than 1000 g born in Finland in 1996-1997 showed that 9% of the children had cognitive impairment, 14% cerebral palsy, and 4% needed a hearing aid. The intelligence quotient was lower (p<0.05) than the reference value. Thus, 20% exhibited major, 19% minor disabilities, and 61% had no functional abnormalities. Being small for gestational age (SGA) was associated with sub-optimal growth later. In children born before 27 gestational weeks, the SGA had more neuropsychological disabilities than those appropriate for gestational age (AGA). In another cohort with birth weight less than 1500 g assessed at 5 years of age, echocardiography showed a thickened interventricular septum and a decreased left ventricular end-diastolic diameter in both SGA and AGA born children. They also had a higher systolic blood pressure than the reference. Laser-Doppler flowmetry showed different endothelium-dependent and -independent vasodilation responses in the AGA children compared to those of the controls. SGA was not associated with cardio-vascular abnormalities. Auditory event-related potentials (AERPs) were recorded using an oddball paradigm with frequency deviants (standard tone 500 Hz and deviant 750-Hz with 10% probability). At term, the P350 was smaller in SGA and AGA infants than in controls. At 12 months, the automatic change detection peak (mismatch negativity, MMN) was observed in the controls. However, the pre-term infants had a difference positivity that correlated with their neurodevelopment scores. At 5 years of age, the P1-deflection, which reflects primary auditory processing, was smaller, and the MMN larger in the preterm than in the control children. Even with a challenging paradigm or a distraction paradigm, P1 was smaller in the preterm than in the control children. The SGA and AGA children showed similar AERP responses. Prematurity is a major risk factor for abnormal brain development. Preterm children showed signs of cardiovascular abnormality suggesting that prematurity per se may carry a risk for later morbidity. The small positive amplitudes in AERPs suggest persisting altered auditory processing in the preterm in-fants.

Epidemiology, treatment and outcome of Staphylococcus aureus bacteremia and endocarditis

Staphylococcus aureus is the second most common bloodstream isolate both in community- and hospital-acquired bacteremias. The clinical course of S. aureus bacteremia (SAB) is determined by its complications, particularly by the development of deep infections and thromboembolic events. Despite the progress of antimicrobial therapy, SAB is still associated with high mortality. However, injection drug users (IDUs) tend to have fewer complications and better prognosis than nonaddicts, especially in endocarditis. The present study was undertaken to investigate epidemiology, treatment and outcome of S. aureus bacteremia and endocarditis in Finland. In particular, differences in bacterial strains and their virulence factors, and host immune responses were compared between IDUs and nonaddicts. In Finland, 5045 SAB cases during 1995-2001 were included using the National Infectious Disease Register maintained by National Public Health Institute. The annual incidence of SAB increased, especially in elderly. While the increase in incidence may partly be explained by better reporting, it most likely reflects a growing population at risk, affected by such factors as age and/or severe comorbidity. Nosocomial infections accounted for 51% of cases, with no change in their proportion during the study period. The 28-day mortality was 17% and remained unchanged over time. A total of 381 patients with SAB were randomized to receive either standard antibiotic treatment or levofloxacin added to standard treatment. Levofloxacin combination therapy did not decrease the mortality, lower the incidence of deep infections, nor did it speed up the recovery during 3 months follow-up. However, patients with a deep infection appeared to benefit from combination therapy with rifampicin, as suggested also by experimental data. Deep infections were found in 84% of SAB patients within one week after randomization, and they appeared to be more common than previously reported. Endocarditis was observed in 74 of 430 patients (17%) with SAB, of whom 20 were IDUs and 54 nonaddicts. Right-sided involvement was diagnosed in 60% of addicts whereas 93% of nonaddicts had left-sided endocarditis. Unexpectedly, IDUs showed extracardiac deep infections, thromboembolic events and severe sepsis with the same frequency as nonaddicts. The prognosis of endocarditis was better among addicts due to their younger age and lack of underlying diseases in agreement with earlier reports. In total, all 44 IDUs with SAB were included and 20 of them had endocarditis. An equal number of nonaddicts with SAB were chosen as group matched controls. Serological tests were not helpful in identifying patients with a deep infection. No individual S. aureus strain dominated in endocarditis among addicts. Characterization of the virulence factors of bacterial strains did not reveal any significant differences in IDUs and nonaddicts.

Cyclosporine A in the treatment of Interstitial Cystitis

Painful bladder syndrome/interstitial cystitis (PBS/IC) is a chronic urinary bladder disorder of unknown etiology characterized by symptoms of bladder pain and urinary frequency. PBS/IC is a chronic disease in which drug therapy has not led to significant success over the course of time. If the symptoms of PBS/IC are refractory to standard treatments, a possible cure might demand surgical intervention involving cystectomy. The eventual autoimmune etiology in mind, immunosuppressive drug therapy with cyclosporine A (CyA) was started to patients with refractory PBS/IC. CyA is a potent anti-inflammatory drug, a calcineurin inhibitor which inhibits T lymphocyte IL-2 produc-tion. T cells are present in abundance in inflammation of the bladder in PBS/IC. On the basis of a pilot, short-term study with CyA on PBS/IC, use of CyA was continued empirically over the long term. We conducted a prospective, randomized, six-month study in 64 patients comparing the effect of CyA with the FDA approved treatment, pentosan polysulfate sodium (PPS). We measured the drug effect on patient s symptoms, the potassium sensitivity test, and on urinary biomarkers. We further tested the impact of CyA, PPS, DMSO and BCG therapy on a health-related quality of life questionnaire and evaluated the response rate to treatment with these therapies. Long-term use of CyA was safe and effective in PBS/IC patients. The good clinical effect matured individually during the years in which CyA was continued. Cessation of medication led to the reappearance of symptoms, and restarting CyA to renewed alleviation, so that CyA was administered as continuous medication. The response rate to CyA increased during the study period, comprising 75% of CyA patients at six months. 19% of patients responded to PPS therapy. Adverse effects were more common in the CyA group, underlining the importance of monitoring the drug safety and appropriate titration of the dose. The potassium sensitivity test is positive in the majority of PBS/IC patients. Successful therapy of PBS/IC can alter nerve sensitivity to external potassium. This effect was seen more often after CyA therapy. Successful treatment of PBS/IC with CyA resulted to decreasing urinary levels of EGF. IL-6 levels in urine were higher among older patient with a longer history of PBS/IC. In these patients, reduced levels of urinary IL-6 were measured after CyA therapy. Patients who experience the best treatment response have improved quality of life according to the post-treatment health-related quality of life (HRQOL) questionnaire. CyA had more impact on the ma-jority of the aspects of QoL than PPS. Despite DMSO therapy being more successful than BCG in the count of responders, DMSO and BCG had equal effects on the HRQOL questionnaire.

Gastric motility: Measurement, symptoms and therapy

Gastric motility disorders, including delayed gastric emptying (gastroparesis), impaired postprandial fundic relaxation, and gastric myoelectrical disorders, can occur in type 1 diabetes, chronic renal failure, and functional dyspepsia (FD). Symptoms like upper abdominal pain, early satiation, bloating, nausea and vomiting may be related to gastroparesis. Diabetic gastroparesis is related to autonomic neuropathy. Scintigraphy is the gold standard in measuring gastric emptying, but it is expensive, requires specific equipment, and exposes patients to radiation. It also gives information about the intragastric distribution of the test meal. The 13C-octanoic acid breath test (OBT) is an alternative, indirect method of measuring gastric emptying with a stable isotope. Electrogastrography (EGG) registers the slow wave originating in the pacemaker area of the stomach and regulating the peristaltic contractions of the antrum. This study compares these three methods of measuring gastric motility in patients with type 1 diabetes, functional dyspepsia, and chronic renal failure. Currently no effective drugs for treating gastric motility disorders are available. We studied the effect of nizatidine on gastric emptying, because in preliminary studies this drug has proven to have a prokinetic effect due to its cholinergic properties. Of the type 1 patients, 26% had delayed gastric emptying of solids as measured by scintigraphy. Abnormal intragastric distribution of the test meal occurred in 37% of the patients, indicating impaired fundic relaxation. The autonomic neuropathy score correlated positively with the gastric emptying rate of solids (P = 0.006), but HbA1C, plasma glucose levels, or abdominal symptoms were unrelated to gastric emptying or intragastric distribution of the test meal. Gastric emptying of both solids and liquids was normal in all FD patients but abnormal intragastric distribution occurred in 38% of the patients. Nizatidine improved symptom scores and quality of life in FD patients, but not significantly. Instead of enhancing, nizatidine slowed gastric emptying in FD patients (P < 0.05). No significant difference appeared in the frequency of the gastric slow waves measured by EGG in the patients and controls. The correlation between gastric half-emptying times of solids measured by scintigraphy and OBT was poor both in type 1 diabetes and FD patients. According to this study, dynamic dual-tracer scintigraphy is more accurate than OBT or EGG in measuring gastric emptying of solids. Additionally it provides information about gastric emptying of liquids and the intragastric distribution of the ingested test meal.