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Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): Helsinki and Uusimaa Hospital District TYH2019309 and The Finnish Foundation for Cardiovascular Research Background/Introduction Acute myocardial infarction (AMI) and atrial fibrillation (AF) are commonly seen in a same patient. It is not unusual that patients are diagnosed with new-onset AF as a complication of AMI. Nevertheless, little is known about the temporal relations of these two diagnoses. Purpose We evaluated the temporal relations of AMI and new-onset AF in the Nationwide Finnish Anticoagulation in Atrial Fibrillation (FinACAF) comprising all patients with AF during 2004-2018 in Finland. Methods Patients with AF and AMI in Finland during 2010 to 2017 were analyzed, and individual patient data from the different registries were merged. Results Of the 157,658 patients with new-onset AF, a total of 16,971 (10.8%) patients were diagnosed with AMI at any point. The mean-age was 77.5 years (SD 10.6) and 72.3 years (SD 13.2), and the proportion of females 7,864 (46.3%) and 70,873 (50.4%) in AF patients with and without AMI, respectively. Altogether 8,889 (52.4%) of the AMI-AF patients had a history of established AMI diagnosis; whereas 4,278 (25.2%) were diagnosed with AMI during the same hospitalization period as new-onset AF or within 30 days; and 3,804 (22.4%) over 30 days after new-onset AF. A total of 6,928 (40.83%) of all AMI diagnoses were diagnosed within 1 year from new-onset AF. The temporal relation between new-onset AF and AMI are described in the Figure. Conclusions AMI-AF patients are older than AF patients without AMI at the time of new-onset AF. The diagnoses of AMI and AF tend to accumulate close to one another. One fourth of all AMI-AF patients were diagnosed with both diseases occurring same hospitalization period or within 30 days from new-onset AF.

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Sigrid Juselius foundation Finnish Foundation for Cardiovascular Research Background Atrial flutter (AFL) is often encountered in atrial fibrillation (AF) patients. There are many similarities in the etiology and treatment of these arrhythmias, including the need for anticoagulation for the majority, but there are also significant differences in their management. In many population-based studies AFL and AF are combined; thus, data are lacking on their individual prevalence in the general population. Purpose To investigate how common are isolated AF and AFL in the population and how often these two arrhythmias coexist in a patient. Methods All adult patients with an ICD-10 code I48 (including AF and AFL) in Finland 2004-2017 were identified from comprehensive national registries including primary and specialist care, reimbursement registries and hospitalization records. A subset of the cohort living in a region using an electronical ECG storage system had their ECG reports produced by the ECG analysis program retrieved for the analysis. ECGs with poor quality and paced or unspecified rhythm were excluded. Results Altogether, 1,248,851 ECGs from 85,690 patients (14.6 ECGs per patient) with the ICD-10 code I48 were included. Mean age was 70.7 ± 13.1 and 53.4% were men. ECGs documenting AF/AFL were available for 67,529 patients (78.8% of the entire ECG-cohort). 51,105 of them had ECG documentation of AF only (AF-only; 53.7% male), and 13,195 (20.5%) of patients with AF had also AFL documented in the ECG (AF+AFL; 47.6% male). 3,229 (4.8% of those with AF/AFL) presented with isolated AFL (AFL-only, 63.1% male). Of the total of 16,424 patients with documented AFL, 80.3% also had AF. The rest of the subjects did not have a 12-lead ECG in the retrieved electronic records documenting atrial arrhythmia. Conclusions One-fifth of the AF patients had also atrial flutter documented with a 12-lead ECG. Moreover, 80% of the atrial flutter patients experiences atrial fibrillation as well. These findings may have implications for the treatment and follow-up of these patients.

Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): The Finnish Foundation for Cardiovascular Research, and Helsinki and Uusimaa Hospital District research fund. Background and aims Direct oral anticoagulants (DOACs) have largely replaced warfarin in patients with atrial fibrillation (AF) to reduce risk of stroke. However, it is not known whether DOACs are more efficacious in preventing stroke or safer than good-quality warfarin treatment with high time in therapeutic range (TTR). Methods The Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) is a nationwide study of AF patients that combines data from several Finnish health care registers. We analyzed all new-onset AF patients in Finland from January 2011 to December 2018 with laboratory data available. Comorbidities, concomitant medications and CHA2DS2-VASc -scores were recorded until date of AF diagnosis. OAC purchases from diagnosis of AF to the end of study were analyzed. ICD-10 diagnoses for stroke (ischemic or hemorrhagic) or transient ischemic attack during OAC use were analyzed until maximum follow-up of 730 days. Confounding factors by baseline characteristics as well as medications were taken in account by use of an inverse probability of treatment weighted analysis. For warfarin users, time in therapeutic range (TTR) was calculated and patient quartiles by TTR were assigned. Rate of stroke in different TTR quartiles for warfarin users were compared to standard dose dabigatran (150 mg bd.), apixaban (5mg bd.) and rivaroxaban (20mg od.). Results Altogether, 74 008 new-onset AF patients with OAC therapy (50.4 % male, mean age 73.0 years, 43 549 on warfarin, with mean TTR 66% and median TTR 72%) were followed for 109 143 patient years (py). Rate of stroke among patients with standard dose direct oral anticoagulants was 6.0/100 py for dabigatran (n=4545), 6.2/100 py for apixaban (n=12 426) and 4.0/100 py for rivaroxaban (n=12 950). In the TTR quartiles of patients on warfarin, rates of stroke were 9.3, 7.2, 5.5 and 4.3/100 py from the lowest (mean TTR 32%) to the highest quartile (mean TTR 90%), respectively. The weighted rates of stroke were 6.3, 6.1 and 4.5/100 py for dabigatran, apixaban and rivaroxaban, respectively, and for warfarin from the lowest to the highest quartile: 8.8, 7.0, 5.5 and 4.2/100 py, respectively. The Figure provides survival probabilities (crude rates) of stroke with confidence intervals of the analysed OAC groups. Conclusion Rates of stroke were evidently the highest among patients on warfarin in the two lowest TTR quartiles, while the differences between high TTR groups and standard dose DOACs were only modest.

Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): Helsinki and Uusimaa Hospital District (TYH2019309) and The Finnish Foundation for Cardiovascular Research Background and aims Elderly patients with atrial fibrillation (AF) and patients with renal failure – for example – are recommended to use reduced doses of direct oral anticoagulants (DOACs) to minimize risk of ischemic stroke and hemorrhagic complications. However, it is not known whether DOACs used with reduced doses are better than warfarin when the quality of warfarin treatment is available by means of time in therapeutic range (TTR). Methods The Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) is a nationwide study of AF patients that combines data from several Finnish health care registers. Here all new-onset AF patients from 2011 to 2018 on reduced dose DOAC in Finland and patients on warfarin with TTR data were analyzed. Comorbidities, concomitant medications and CHA2DS2-VASc -scores were recorded until date of AF diagnosis. OAC purchases from diagnosis of AF to the end of study were analyzed. ICD-10 diagnoses for stroke (ischemic or hemorrhagic) or transient ischemic attack during OAC-use were analyzed until maximum follow-up of 730 days. Crude rates of stroke as well as weighted rates are provided. To avoid confounding by baseline characteristics as well as medications, an inverse probability of treatment weighted analysis was made. For warfarin users with sufficient laboratory data, time in therapeutic range (TTR) was calculated and patient quartiles by TTR were assigned. Results Altogether, 52 204 new-onset AF patients with OAC therapy (46.1 % male, mean age 75.7 years, 43 549 on warfarin - with mean TTR 66%, median TTR 72%) were followed for 91 549 patient-years (py). Rate of stroke among patients on lower dose DOACs was 5.2/100 patient years (py) for dabigatran (n=2 672), 4.3/100 py for apixaban (n=3 936), 3.9 /100 py for rivaroxaban (n=1 866). In the TTR-quartiles of patients on warfarin, the rates of stroke were 9.3, 7.2, 5.5 and 4.3 /100 py from the lowest (mean TTR 32%) to the highest quartile (mean TTR 90%), respectively. The weighted rates of stroke were 5.1, 3.5 and 3.1/100 py for dabigatran, apixaban and rivaroxaban, respectively and for warfarin from the lowest to the highest quartile: 8.7, 7.0, 5.4 and 4.1/100 py. Figure provides survival probabilities of the OAC groups with confidence limits. Conclusion In AF patients treated with OAC, the rates of stroke were highest among patients on warfarin at the lowest TTR quartiles, while the differences between high TTR groups and lower dose DOACs were only modest.

Introduction Atrial fibrillation (AF) is the most common, complex, and clinically relevant arrhythmia [1]. It is a growing medical condition associated with significant morbidity and mortality, but its pathophysiology has remained widely unknown [2]. Aims We aim to unravel the complex pathophysiological mechanisms of AF and identify clinically relevant AF-related metabolites. We aim to identify targets for therapeutical interventions and biomarkers for AF diagnostics. Our study material is unique as we can safely study human heart and pericardial fluid in addition to blood, that has been mainly examined in previous studies. Material and methods Patients recruited were undergoing cardiac surgery due to valve defects at the University Hospital. For our research, we collected preoperative blood samples and intraoperative right atrial appendage biopsy and pericardial fluid. For our metabolomics study on AF patients, we selected 16 patients with permanent AF and 17 age, gender and underlying disease matched control patients (Fig. 1). Liquid chromatography mass spectrometry (LC-MS) was used to identify molecules and metabolites related to AF. We integrated targeted assays for absolute quantification of specific metabolites with untargeted metabolomics to discover novel compounds and metabolites. Results Untargeted mass spectrometry (MS) metabolite analysis identified altogether 15751 molecular features and metabolites divided unequally between the sample types (Fig. 2). Altogether, we found 1041 (p Conclusions We identified totally new pathophysiological processes and novel potential metabolites related to permanent AF to be used as AF biomarkers. Permanent AF is associated with dysreculation of multiple biologically relevant metabolic pathways. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Academy of FinlandThe Finnish Foundation for Cardiovascular Research

Background Catheter based ASD closure has been a mainstay therapy for secundum type ASD for over 20 years and up to 80–90% of defects are deemed eligible for catheter closure. We are starting to get long term results for the outcome of the procedure. Numerous studies have reported excellent prognosis and low complication rates in patients with TC closed defects. However, little is known about the disease burden in the long run after the closure. Objectives This nationwide cohort aimed to evaluate long-term outcome of transcatheter closed atrial septal defects (ASD) by evaluating 1) hospitalisations and disease burden, 2) complications and 3) echocardiographic changes. Material and methods We gathered every transcatheter ASD closure done in Finland during 1999–2019. Mean follow-up time was 6.8 years (SD 5.1). We used hospital discharge register to study the incidence of new onset atrial fibrillation, stoke and migraine after the closure. Closure complications and echocardiographic changes were gathered from the electronic health records. Results Overall transcatheter ASD closure was performed for 1000 patients (68.5% females) during the study period. ASD patients had increased risk for new-onset atrial fibrillation (RR 2.55, 95% CI: 1.94–3.36), migraine (RR 3.41, 95% CI: 2.40–4.84) and heart failure. Stroke risk was not increased during the follow-up (p=0.19). Hospitalisations were more common in the ASD group in the following 12 months after the closure (RR 2.52, 95% CI: 2.14–2.98). Adverse events occurred in 6.9% (n=69) of the patients, including 4 erosions and 10 device embolisations. Right heart size was enlarged in 83.9% of the patients before the closure and in 24.4% after the closure. Rate of mild mitral regurgitation increased 21.2% vs. 27.6%, p=0.005) and rate of sever to moderate tricuspid regurgitation decreased (9.4% vs. 5.6%, p=0.009) during the follow-up. Conclusion Catheter based Atrial septal defect closure is a safe procedure with low complication rates. TC closed ASD patients had more new-onset atrial fibrillation, heart failure and migraine during the follow-up. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): The Emil Aaltonen Foundation, Tampere, Finland

Background Cardioversion is routinely used to restore sinus rhythm in patients with atrial fibrillation (AF). Elective cardioversion (ECV) is associated with an increased risk of thromboembolic complications even during adequate oral anticoagulation (OAC). Purpose The aim was to analyze the incidence of ischemic stroke and transient ischemic attack (TIA) after first-ever ECV of AF in patients using guideline-recommended OAC. Methods This nationwide register-based study includes all (N=9625) AF patients undergoing their first-ever ECV between 2012 and 2018 in Finland. Data was obtained from the Finnish health care registers, including both primary and special health care. The risk of stroke and TIA within 30 days after ECV were estimated in patients using OAC. Results The mean age of patients was 68 (±9.9) years, 61.2% were men, and the mean CHA2DS2-VASc score was 2.6 (±1.6, range 0–9). Warfarin was used in 6245 (64.9%) and non-vitamin K oral anticoagulants in 3380 (35.1%) cardioversions, of which 1453 (15.1%) was rivaroxaban, 1246 (12.9%) apixaban, 635 (6.6%) dabigatran, and 46 (0.5%) edoxaban. Twenty-nine (0.3%; 95% confidence interval [CI] 0.2–0.4%) ischemic strokes or TIAs occurred within 30 days after ECV (median 3 days, interquartile range 2.0–8.5) (Figure 1 and Table 1). In warfarin-treated patients experiencing stroke or TIA, the mean INR value before ECV and at the time of stroke or TIA were 2.5 (±0.5) and 2.5 (±0.5), respectively. One of the patients had INR-value Conclusion In our nationwide study, the rate of stroke and TIA after first-ever ECV was low (0.3%) in all OAC groups. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Helsinki and Uusimaa Hospital District

Introduction Prevalence of atrial fibrillation (AF) is strongly associated with age, and with longer life-time expectancy number of AF patients is worldwide strongly increasing. However, nationwide prevalence of AF is not known when primary care data as well is accessible. Purpose The FinACAF-study is a nationwide registry study including of all AF patients searched from all available national health care registers. To our knowledge, this is the first nationwide AF study including both primary, secondary, and tertiary health care register data. The aim of this study was to assess the prevalence of AF in unselected nationwide population in Finland. Methods In the FinACAF study we gathered data of all AF patients (hospitalizations and outpatient specialist visits and primary health care, and National Reimbursement Register) from all national health care registers from 01st January 2004 to 31st December 2018. The annual prevalence on December 31st of each year 2007–2018 was calculated as the cumulative number of patients alive with AF divided by the number of Finnish population on the last day of that year. The prevalence is presented for population ≥20 years, and with the entire population as the background population, as well as for populations ≥65 years, and ≥75 years. Results In total, 411,387 patients with the diagnosis of AF were documented during 2004–2018 in Finland. The number of adult patients with AF at the end of the study period in 2018 was 226,847, corresponding to an AF prevalence of 5.2% in the age group ≥20 years. The prevalence in the total Finnish population was 4.1%. The prevalence rates increased remarkably with increasing age and were higher in men compared to women (5.9% vs. 4.6%, p Conclusions Based on comprehensive, nationwide data – also including the primary care – we observed extremely increasing prevalence of AF in the older population, as well as remarkably increasing prevalence of AF over time. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Helsinki and Uusimaa Hospital District

Introduction Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, with a current prevalence of 4.1% in Finland. Many of the comorbidities associated with AF are known risk factors for the arrhythmia and vice versa, as well as contributors to the risk of stroke and other AF related adverse events. A generally used evaluation method for the risk of stroke is the clinical risk factor -based CHA2DS2-VASc score, but other thromboembolic risk factors also exist. Purpose To better understand current AF population, this study describes characteristics, comorbidities, medication, and laboratory values of Finnish AF patients at the time of first AF diagnosis. Methods The Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) study is a nationwide register-based cohort study in which AF patient data has been linked from several Finnish health care- and national registers, with information from primary-, secondary-, and tertiary care. This substudy consists of patients over 20 years old with available laboratory data and an incident AF diagnosis (ICD-10 I48) between 1/1/2010–31/12/2018 in any of the used registers. Results Within the study period 143,455 patients with a new AF were registered. The mean age at time of diagnosis was 69.1 years for men and 76.3 years for women. The mean CHA2DS2-VASc score when entering the cohort was 3.48 (SD 1.88), and 84.9% of the cohort had at least one of the comorbidities included in the CHA2DS2-VASc score. The most prevalent comorbidities and medications of the cohort are shown in the figure, and a more comprehensive look is presented in the table. The medications listed have been in use during the year before cohort entry. Conclusion Atrial fibrillation does not come alone. Almost all patients diagnosed with AF have previous comorbidities and medications. Future analysis will provide information on how these evolve after AF diagnosis and elucidate their association with different endpoints. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Helsinki and Uusimaa Hospital District

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Sigrid Juselius Foundation Introduction Atrial fibrillation (AF) is the most common sustained arrhythmia worldwide, and its prevalence is increasing with aging population. AF is associated with increased cardiovascular morbidity and mortality, but the prognosis of newly detected AF in the general population is not well established. Purpose Using data from the large FinACAF-study, a comprehensive nationwide retrospective cohort study including all diagnosed Finnish AF patients, we studied one-year mortality after new-onset AF in the general population and determined the causes of death of deceased AF patients. Methods All patients with new-onset AF in Finland 2007-17 were identified from nationwide primary care and reimbursements registries and hospitalization records. Baseline characteristics of these patients were determined, and their survival was followed from registries for one year. Principal cause of death was determined from death certificate’s International Classification of Diseases (ICD-10) Codes. Results A total of 229 321 patients with first-diagnosed AF were identified (50.0% female). Mean age of men and women with new-onset AF was 69.4 ± 13.4 and 77.1 ± 11.8 years, respectively (p During the one-year follow-up, 11.6% of men and 13.7% of women died (Figure). Most common cause of death in these patients was ischaemic heart disease (26.2% of all deaths), followed by malignancies (17.4%) and dementia (12.4%). Cerebrovascular diseases were responsible for 10.8% of mortality. Conclusion In this population-based nationwide study, we demonstrated that one-eight of patients with new AF died within one year of the diagnosis. Ischaemic heart disease was most frequent cause of death.

Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): Helsinki and Uusimaa Hospital District Funding The Finnish Foundation of Cardiovascular Research Introduction Initiation of oral anticoagulation (OAC) in case of a new-onset atrial fibrillation (AF) requires assessment of bleeding history. Gastrointestinal (GI) bleedings are among the most common bleeding events. Purpose We aimed to assess clinical characteristics and initiation of OAC in patients with new-onset AF and a history of previous GI bleeding. Methods The Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) study is a nationwide study among AF patients conducted as a retrospective register-based linkage study combining data from several Finnish health care registers. The study population consists of all patients diagnosed with AF between the years 2010-2018 and with laboratory data available. Patients were identified from nationwide primary care and reimbursement registries and hospitalization records. OAC purchases at 90 days from cohort entry were obtained from the National Prescription Register upheld by the Social Insurance Institution of Finland. Results 134 242 patients from the initial FinACAF cohort were included in this substudy. Of these, 6543 (4.9%) patients had a history of GI bleeding. Those with GI bleeding were more often male (52.6%), older (mean age 76.6 ± 11.4 vs 72.4 ± 13.1 years), and had more comorbidities. They also had lower blood hemoglobin (mean 124.9 ± 21.3 vs 135.8 ± 18.4 g/l) and higher serum creatinine (mean 99.7 ± 75.8 vs 87.5 ± 52.7 µmol/l) levels than patiens without preceding GI bleeding. Furthermore, initiation of OAC medication was less frequent in the GI bleeding group (46.9% vs 58.6%). Patient characteristics of the study population including age, sex, comorbidities, OAC medication and laboratory findings are shown in Figures 1 and 2. Conclusions Patients with AF and preceding GI bleeding are vulnerable to rebleeding events. This may affect decision-making of clinicians, leading to more infrequent initiation of OAC medications.

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Sigrid Juselius Foundation Background Atrial fibrillation (AF) is recognized as a major public health problem due to increased mortality, morbidity and risk of stroke. Advanced age and burden of other comorbidities are potential contributors to AF development and adverse outcomes. Clinical risk factor based CHA2DS2-VASc score is widely used to assess thromboembolic risk in AF, but mortality risk associated with different CHA2DS2-VASc scores is not established. Purpose Using data from a nationwide AF registry study including comorbidities and outcomes of unselected AF patients, we wanted to study whether CHA2DS2-VASc score could be useful in estimating prognosis in newly diagnosed AF patients. Methods New-onset AF patients in Finland 2007-2017 were identified from comprehensive national registries. Comorbidities were gathered from individualized registry data on drug reimbursements and from ICD-10 diagnoses during hospitalizations and outpatient visits in primary and specialist care. These were used to create CHA2DS2-VASc risk score for each AF patient at cohort entry, including data on heart failure, hypertension, age, diabetes, stroke, vascular disease and sex. Patients were followed until the end of 2018 from the causes of death registry, which records every death in the country. All-cause mortality in each CHA2DS2-VASc category per 1000 person-years was determined, and relative risk (RR) of death according to the CHA2DS2-VASc category was calculated. Results A total of 229 357 patients with new-onset AF (mean age 73.2 ± 13.2 years, 50.0% female) were identified. Distribution of CHA2DS2-VASc score among these individuals is shown in Table. Mortality increased significantly with rising CHA2DS2-VASc risk score points, as demonstrated in Table. Compared to CHA2DS2-VASc 0, those with 2 points had a RR 2.9 (95%CI 2.7-3.1), 3 points RR 5.0 (4.7-5.3), 4 points RR 8.0 (7.5-8.4), 5 points RR 11.0 (10.4-11.7) and >5 points RR 14.8 (14.0-15.7) for all-cause mortality. Conclusions In new-onset AF, mortality increased drastically with increasing age and comorbidities as depicted in the CHA2DS2-VASc score. Besides assessing thromboembolic risk, CHA2DS2-VASc score seems to be useful in estimating survival of AF patients.

We studied 263 eyes of 141 normal subjects, 33 men and 108 women, including 129 Finns and 12 Ibero-Americans, with the age ranging between 12 and 89 (mean 43.0 +/- 20.4) years using the Kowa FC-1000 laser flare cell meter. The mean photon count/ms was 4.5, it was 3.1 in the age groups of 10-19 years and 11.5 in the age group of 80 years or over; the increase with age was statistically significant (p = 0.0001). There were no significant differences in the photon count/ms between right and left eyes (p = 0.75), between sexes (p = 0.61), or between Ibero-Americans and age-matched Finns (p = 0.62). The mean cell count was 1.1 and there were no significant changes between the right and left eyes (p = 0.56) or between different age (p = 0.38), sex (p = 0.32) and race (p = 0.64) groups. There were no significant differences in the mean photon count/ms (p = 0.97) and cell counts (p = 0.35) between the first and second measurements 5 min later. There was no subject-within variability after 24 h and 7 days in the flare (p = 0.95) and cell counts (p = 0.89).

We studied the correlation between laser flare cell meter photon count/ms and actual protein concentration both in vitro and in vivo. Laser flare cell meter measurement of human albumin concentrations of 0 to 10 g/l showed photon counts/ms from 0.3 +/- 0.3 to 78.9 +/- 3.9. There was a statistically highly significant linear correlation between photon count/ms and human albumin concentration (r = 0.98, p = 0.0001). Laser flare cell meter measurements were done on 39 cataract patients with the mean age of 77.9 +/- 6.7 years. Aqueous humour obtained by peroperative paracentesis was analysed for total protein. The mean photon count/ms before pupillary dilatation was 11.93 +/- 6.03. There was a significant linear correlation (r = 0.4, p = 0.019) between the photon count/ms after pupillary dilatation (mean 14.73 +/- 12.9, range 2.6-62.4) and anterior chamber protein concentration (mean 0.62 +/- 0.27, range 0.23-1.3 g/l) with the linear regression formula being y = 0.231 x -1.105 where y = log protein concentration (g/l) and x = log of photon count/ms. Laser flare cell meter photon counts/ms may be converted into an equivalent anterior chamber total protein concentration using this formula.

Structure and fracture behaviour of long glass fibre (LGF) reinforced polypropylene (LGF PP) composites including calcium carbonate (CaCO 3 ) as a filler were studied. Fibre orientation, fibre length distribution and mechanical properties of LGF PP/CaCO 3 hybrid composites, as well as the crystallinity changes of polypropylene upon filler addition are reported. Furthermore, an acoustic emission (AE) analysis was applied to the fracture mechanical test, in order to get information about the fracture modes during the loading. It was found out that the filler addition had little effect on the fibre orientation and crystallisation behaviour of LGF PP, but the average fibre length decreased. AE analysis showed that the addition of filler caused early stage debonding of the LGFs, when the samples were subjected to low speed tensile loading (1 mm/min). These observations may explain the changes of the mechanical properties of LGF PP upon filler addition.

The mechanical behaviour of long discontinuous glass fibre (LGF) reinforced polypropylene (PP) composites filled with talc or calcium carbonate fillers was studied. Sample specimens were processed by injection moulding, after which tensile and impact properties were analysed. In addition, scanning electron microscopy was used to analyse the morphology of the fracture surfaces. The results showed that the use of talc as a hybrid filler in LGF reinforced PP leads to a better tensile strength and toughness than in a corresponding hybrid composite based on calcium carbonate. Furthermore, it was observed that the matrix had a dominant role at low fibre content, whereas at high fibre loading, the effect of fibres was more evident.

In order to determine the content of group II phospholipase A2 in the aqueous humour we studied 41 cataract patients including 8 men and 33 women with age ranging between 65 and 92 (mean +/- SD being 77.0 +/- 6.7) years. In all patients preoperative biomicroscopy showed neither aqueous flare nor cells. Eleven patients (26.8%) had pseudoexfoliation syndrome. Aqueous humour tap was done at the beginning of cataract surgery before perforating the corneoscleral wound. We used time-resolved fluoroimmunoassay for the detection of group II phospholipase A2 in the aqueous humour. The group II phospholipase A2 content in the aqueous humor varied between less than measurable (in 23 patients) and 3.3 ng/ml, with an interquartile range from less than measurable to 1.4 ng/ml. There was no significant difference in the group II phospholipase A2 content of the aqueous humour whether or not the patient had pseudoexfoliation syndrome. The results show that the aqueous humour of cataract patients contains only minute amounts of group II phospholipase A2.

Three experimental holes the size of deposition holes in a KBS-3 type repository (depth 7.5 m and diameter 1.5 m) were bored in hard granitic rock in the Research Tunnel at Olkiluoto to study, among other things, the properties of the rock in the excavation-disturbed zone. In the analysis described in this report, the porosities, effective diffusivities and permeabilities of disturbed and intact rock were determined by using two novel methods: the 14 C -polymethylmethacrylate method and the He-gas method. In addition, the structure of the rock in the excavation-disturbed zone was assessed using both scanning electron and optical microscopy.

The matrix diffusion of non-sorbing tracers was studied in rocks from the Syyry area, Central Finland (SY1). The effect of alteration and weathering on rock matrix porosity and on the available pore space, which affects diffusivity, are discussed. The main rock type in the crystalline bedrock of Syyry is a slightly foliated, gray tonalite with mica gneiss inclusions as well as minor, more mafic inclusions. The total porosity and the spatial porosity distribution and microstructure of the rocks were investigated using infiltration of carbon- 14-methylmethacrylate, electron microscopy and Hg-porosimetry. The laboratory-scale diffusion experiments were performed using (1) the out-leaching technique of methylmethacrylate (MMA), (2) the through-diffusion of tritiated water (HTO) and chloride in the liquid phase and (3) the through-diffusion of helium in the gas phase. The results of structure investigations indicate that alteration and weathering create micrometric-scale pore apertures, visible as fissures and cracks. These migration pathways dominate in laboratory-scale diffusion experiments and result in high effective porosities and effective diffusivities. Alteration also creates spherical pores, smaller than 1 μm, especially in heavily altered biotite and plagioclase minerals. The altered mineral phases act as quasi dead-end pores hindering the diffusion of non-sorbing tracers. The heterogeneity of the matrix is increased. The heterogeneous spatial pore structure of altered and weathered rock samples causes uncertainty in the diffusion coefficients owing to an assumed homogeneous matrix in Fickian diffusion models.

A thermal nondestructive testing method based on an infrared line scanner for cylindrical specimens is presented. A seven-layered carbon-glass fibre tube with an artificial delamination was used as a test sample. A finite difference computational model of the heating of the tube was constructed in order to simulate the measurement and evaluate the capability of detecting delaminations. The numerical results show the temperature difference caused by the delamination to be well above the practical detection limit, which was verified by the actual measurements.

The main purpose of this work is to investigate the working range of a new travel time test method for use in low amplitude shear modulus determination. The equipment used consists of an enlarged triaxial cell equipped with an oscillator at the top of the cell and a pair of piezoceramic bender elements mounted in both the top cap and the bottom cap. Piezocrystals are used to represent the coarse grained soil. The results are compared with those obtained using resonant column tests. The validity of the equations used is also examined and discussed.

In a closed inpatient unit, valproate and lithium were initially combined in the treatment of 12 severely manic patients (ICD-10 F30, F31, F25). Onset of response and the use of additional neuroleptic medication were analyzed. For 5 patients a comparision was performed between the index episode and a pre-treatment period during which lithium therapy was administered without valproate. Outcome criteria for the analysis were the latency of response and remission, as well as the dose of neuroleptic medication necessary for additional sedation. The mean severity of mania syndrome (AMDP-System) in the study patients was comparable to the mean mania score of the total manic patient population of the inpatient unit. All patients responded to the combination of valproate and lithium, and the mean total-remission time was 30 days for the whole group. Mean serum levels were 0.8 mmol/L for lithium and 73.8 mg/L for valproate. The mean remission time for the 5 readmitted patients was 22.8 days under combination treatment compared to 35.6 days in the pre-treatment episode without additional valproate (p = 0.06). It was possible to markedly reduce the use of neuroleptic medication in these patients from 18 601.6 mg CPZ equivalents to 3927.6 mg (p < 0.025). Initially combining valproate and lithium thus appears to be an effective therapeutic option for the inpatient management of severe manic syndromes.

The aim of the study was to investigate the frequency and severity of adverse events (AEs) and laboratory abnormalities of interest over 96 weeks of treatment with etravirine or placebo in the pooled TMC125 DUET (Demonstrate Undetectable viral load in patients Experienced with ARV Therapy) trials.Treatment-experienced, HIV-1-infected patients randomly received etravirine 200 mg twice a day (bid) or placebo, plus a background regimen. The frequency and severity of neuropsychiatric, rash, hepatic and lipid AEs were analysed; frequencies were also adjusted for total patient-years of exposure (PYE).A total of 599 and 604 patients received etravirine and placebo, respectively (median treatment duration 96.0 and 69.6 weeks, respectively). There was no significant difference between the treatment groups in the frequency of neuropsychiatric AEs. However, a significant difference in the frequency of rash was observed (20.5% vs. 11.8%, respectively; P0.0001); rash was generally mild to moderate in severity; the rate of discontinuation because of rash was low (2.2% vs. 0% in the etravirine and placebo groups, respectively). The frequency of hepatic AEs was low and similar between the treatment groups (8.7% vs. 7.1%, respectively; P = 0.3370); hepatic enzyme levels did not increase over time. Lipid-related laboratory abnormalities and changes over time in lipid levels were generally comparable between treatment groups. Adjusting for treatment exposure, the frequency of AEs remained similar between treatment groups, with the exception of rash [13.7 vs. 9.3 per 100 PYE; relative risk (95% confidence interval) 1.48 (1.02-1.95)].The frequency of AEs of interest was generally similar between the treatment groups, both overall and when adjusted for treatment exposure, with the exception of rash which was more frequent in the etravirine group.

In this paper we describe the use of thermal microscopes in measuring the lengths of vertical cracks in silicon nitride. Results of theoretical calculations for temperature profiles in samples near the end of the cracks are demonstrated. These calculations showed that the effect of the crack decreases to a non-measurable level at distances of about 10 μm from the end of the crack. Experimental measurements showed that thermally obtained crack lengths were at least 34% longer than those that were optically measured. The obtained crack length was independent of the heat modulation frequency used.

A finite element scheme is presented for the numerical solution of soil freezing problem. It is based on the space-time finite element concept and on the appropriate choice of weighting functions.

Heart rate variability (HRV) has been used for assessment of depth of anesthesia. Alterations in respiratory rate and tidal volume modulate the sympatovagal neural drive to the heart. The changes in PaCO2 that accompany changes in breathing pattern may, through chemoreceptors in the brainstem, independently influence the autonomic control of the heart and modulate HRV.We measured the effects of PaCO2, tidal volume and respiratory rate on HRV during spontaneous and mechanical ventilation in 22 healthy volunteers and in 25 mechanically ventilated anesthetized patients.Adding CO2 to the inspiratory gas increased high frequency (HF) and low frequency (LF) components of HRV in awake volunteers both during spontaneous and mechanical ventilation, while this effect of CO2 was abolished in patients during anesthesia. Increase of tidal volume increased HF component of HRV only in volunteers during spontaneous ventilation. On the other hand, when respiratory rate was reduced, the balance of HF and LF power moved toward LF power in all study groups. Breathing frequency altered HRV independent on PaCO2, tidal volume and the level of consciousness. In contrast, the effect of PaCO2 appeared to be related to normal level of consciousness, suggesting that a cortical modulation of the autonomic nervous activity contributes to the effects of PaCO2 on HRV.PaCO2, tidal volume and respiratory rate should be controlled when HRV power spectrum is measured in conscious patients or volunteers, while in anesthetized patients small changes in end-tidal CO2 or tidal volume do not modulate HRV if respiratory rate remains unchanged.

The quality of matching layers suitable for air-coupled transducers was studied with an air-coupled photoacoustic microscope. The matching layers studied were silica aerogel and balsa wood. Ultrasonic pulses were used to determine the ultrasound absorption profiles of aerogel-glass and balsa-wood-glass interfaces. The results show a need for developing bonding techniques. The main advantages of the method considered are its noncontacting character and the good control of the bandwidth, the power, and the geometry of the sound beam. The drawback of the method is a fairly long measurement time, because of which the main use of the measurement method would be the development of transducer-manufacturing techniques. >

The authors describe the use of thermal waves to detect delaminations or poor adhesion of coatings on various substrate materials. The thermal waves are generated by an argon laser and the total wave on the surface of the sample is picked up with an IR (infrared) detector. The phase and amplitude of the wave are analyzed for properties that characterize adhesion. Results are presented for a Cr/sub 2/O/sub 3/ coating on a steel substrate. The authors also describe a fast synchronous IR scanning method. >

The application of induction heating as a selective heat source in a thermal nondestructive evaluation system is described. The conductive parts of the sample are heated with a scanning induction coil. Defects such as broken fibers or delaminations affect the heat flow in the sample and thus can be detected by monitoring the infrared radiation from the sample surface. In addition to thermal irregularities, the altered electrical characteristics of the flaws also contribute to the signal. Therefore, the detectability of the defects can be enhanced compared to that of defects investigated using the traditional nonselective heating methods. The functionality of the system is demonstrated with carbon fiber reinforced composites.

How cardiac autonomic nervous control is related to the severity of essential hypertension in patients receiving long-term antihypertensive therapy is not well known. The aim of this study was to examine heart rate variability (HRV), a non-invasive measure of cardiac autonomic function, in patients with long-term and medically treated mild and severe essential hypertension and healthy control subjects, and to assess the clinical determinants of HRV in these patients. Thirty-four patients with severe essential hypertension (SEHT) and 29 with mild essential hypertension (MEHT) as well as healthy age- and sex-matched control subjects were studied. HRV was assessed from 10 min ECG-recordings during paced (0.2 Hz) breathing at rest and expressed as time and frequency domain measures. In the SEHT group time (SDNN, RMSSD) and frequency domain measures (total power, low-frequency (LF) power and high-frequency (HF) power of HRV in absolute units, and LF and HF power of HRV in normalized units) of HRV were significantly lower when compared with those of the control group. The MEHT and control groups did not differ from each other with respect to time or frequency domain measures of HRV. Comparison between the hypertensive groups showed that SDNN, total power, LF power and HF power were lower in the SEHT group compared with the MEHT group (P0.05 for all). Among hypertensive patients RR-interval, age, gender, systolic finger blood pressure and diastolic office blood pressure as well as 24-h blood pressure were significant determinants of HRV. In conclusion, we found that the severity of chronic essential hypertension seems to be related to the severity of impairment of cardiac autonomic control.

Cardiotoxicity of anthracyclines is a clinical challenge in cancer chemotherapy. Limited data is available on the physiological mechanisms responsible for anthracycline-induced heart failure or its recovery. We studied four patients with a history of severe anthracycline-induced heart failure manifested 2-116 months earlier by using radionuclide ventriculography for the measurement of left ventricular function, indium-111-antimyosin scintigraphy for the detection of myocardial cell injury and iodine-123-metaiodobenzylguanidine (MIBG) scintigraphy for the assessment of cardiac adrenergic innervation. Myocardial perfusion and fatty acid utilization were assessed with iodine-123-paraphenyl pentadecanoid acid (pPPA) and single photon emission computed tomography (SPECT). Symptoms of congestive heart failure (CHF) were still present in two patients whereas the others were asymptomatic at the time of the study. The patients who showed complete clinical recovery had normal or near normal left ventricular ejection fraction (LVEF) (47 and 52%), whereas the patients with symptoms of heart failure had low ejection fractions (21 and 31%). All patients presented with abnormal antimyosin uptake and decreased myocardial MIBG uptake. Patients with low ejection fraction tended to have higher antimyosin uptake suggesting more severe, persistent myocyte injury. All but one patient showed normal fatty acid utilization. These data suggest that patients with a history of severe anthracycline-induced cardiomyopathy have persistent myocardial cell injury and adrenergic dysfunction up to 10 years after the development of heart failure. These findings seem to be present regardless of recovery of left ventricular function.

It is widely accepted that myocardial infarction results in adrenergic denervation of the infarcted and peri-infarcted myocardium. On the contrary, the concept of re-innervation of adrenergic nerve fibres is less well established. Although there is evidence of partial re-innervation occuring several months after myocardial infarction, the extent and time scale of re-innervation are only poorly known. In this study we investigated changes in cardiac adrenergic innervation and myocardial perfusion during the early convalescence period (the first 3 months) after an acute myocardial infarction. Single-photon emission computed tomographic imaging was conducted in 15 men 1 week and 3 months after an acute myocardial infarction with I123-metaiodobentzylguanidine (MIBG) and Tc99m-sestamibi (MIBI) to determine the extent of adrenergic denervation and impaired perfusion, respectively. A MIBG and MIBI defect was determined as regional uptake/=30% of maximal myocardial activity. The size of the MIBG defect calculated as a percentage of left ventricular mass remained unchanged between 1 week and 3 months after myocardial infarction (31.1 +/- 17.3% vs. 30. 5 +/- 16.8%, respectively). Accordingly, MIBG activity of the infarct and peri-infarct zones (expressed as a percentage of MIBG activity of the myocardium with normal perfusion) showed no significant change (23.7 +/- 10.0% vs. 25.3 +/- 11.0% and 39.0 +/- 11.3% vs. 40.8 +/- 12.8%, respectively) during the follow-up. On the other hand, the size of MIBI defect decreased significantly during the follow-up (14.2 +/- 11.5% vs. 11.4 +/- 9.7%, P0.05, respectively) indicating improved myocardial perfusion. The results demonstrate that cardiac adrenergic re-innervation is a slow process; despite a significant increase in myocardial perfusion we found no evidence of adrenergic re-innervation during the first 3 months after acute myocardial infarction.

The aim of this study was to examine the effect of a very low-calorie diet (VLCD)-induced weight loss on the severity of obstructive sleep apnoea (OSA), blood pressure and cardiac autonomic regulation in obese patients with obstructive sleep apnoea syndrome (OSAS). A total of 15 overweight patients (14 men and one woman, body weight 114 +/- 20 kg, age 52 +/- 9 years, range 39-67 years) with OSAS were studied prospectively. They were advised to follow a 2.51-3.35 MJ (600-800 kcal) diet daily for a 3-month period. In the beginning of the study, the patients underwent nocturnal sleep studies, autonomic function tests and 24-h electrocardiograph (ECG) recording. In addition, 15 age-matched, normal-weight subjects were studied. They underwent the Valsalva test, the deep-breathing test and assessment of heart rate variability at rest. The sleep studies and autonomic function tests were repeated after the weight loss period. There was a significant reduction in weight (114 +/- 20 kg to 105 +/- 21 kg, P0.001), the weight loss being 9.2 +/- 4.0 kg (range 2.3-19.5 kg). This was associated with a significant improvement in the oxygen desaturation index (ODI4) during sleep (31 +/- 20-19 +/- 18, P0.001). Before the weight loss the OSAS patients had significantly higher blood pressure (150 +/- 18 vs. 134 +/- 20, P0.05, for systolic blood pressure, 98 +/- 10 vs. 85 +/- 13, P0.05, for diastolic blood pressure) and heart rate (67 +/- 10 beats min-1 vs. 60 +/- 13, P0.05) at rest than the control group. They had also lower baroreflex sensitivity (4.7 +/- 2.8 ms mmHg-1 vs. 10.8 +/- 7.1 ms mmHg-1, P0.01). During the weight reduction, the blood pressure declined significantly, and the baroreflex sensitivity increased by 49%. In conclusion, our experience shows that weight loss with VLCD is an effective treatment for OSAS. Weight loss improved significantly sleep apnoea and had favourable effects on blood pressure and baroreflex sensitivity that may have prognostic implications.

AIMS—To determine the current bacteriology of lacrimal duct obstruction (LDO) and to relate the bacteriological findings to the type of symptoms. METHODS—127 samples were obtained from the lacrimal sac in 118 consecutive adult patients with LDO, including nine bilateral cases. RESULTS—Altogether, 156 isolates were recovered from the 127 samples cultured. Cultures were positive from 84% of the samples. Gram positive bacteria were isolated in 79 (62%) samples. The most frequently cultured bacterial species was Staphylococcus epidermidis, representing 27% of the isolates. Gram negative bacteria were recovered from 26 (20%) samples, and these bacteria were statistically significantly more common in cases with copious discharge than in cases with minor discharge (p=0.000). Cases with simple stenosis of the lacrimal duct (SSLD) showed significantly less Streptococcus sp (p=0.004) and Gram negative organisms (p=0.004) than those with chronic dacryocystitis. CONCLUSION—The bacteriology of SSLD resembles that of normal conjunctival flora. Chronic dacryocystitis in adults is associated with an increased proportion of Gram negative bacteria which may be a reservoir for postoperative intraocular infection. They should also be taken into account in selecting antimicrobial prophylaxis in lacrimal drainage surgery.

The association between myocardial sympathetic innervation and heart rate variability after myocardial infarction was studied in a group of 12 men (aged 30-65 yr) 3 mo after their first myocardial infarction.Viable myocardium was imaged using 123I-phenylpentadecanoic acid (pPPA). Functioning myocardial sympathetic nervous tissue was imaged using [123I]-metaiodobenzylguanidine (MIBG). Heart rate variability was measured as the ratio of maximum-to-minimum RR intervals in ECG during deep breathing.The patients were divided into normal (n = 6) and low (n = 6) heart rate variability groups. Myocardial infarction size (pPPA defect) was comparable in the normal and low heart rate variability groups. Even the MIBG defect size was not significantly different in the normal and low groups, the portion of viable myocardium with impaired sympathetic innervation (MIBG defect minus pPPA defect) was significantly greater in the low heart rate variability group than in the normal group.The extent of viable myocardium with disturbed sympathetic innervation was greater in patients with low heart rate variability as compared to those with normal heart rate variability 3 mo after myocardial infarction.

Chest pain is a common reason for consulting a physician. Although the underlying cause of the chest pain varies, the most frequent cause is coronary disease. In many cases the diagnosis emerges from the case history, the clinical picture or non-invasive examination procedures. In cases of severe symptoms or unclear diagnosis, coronary angiography is performed which often shows the coronary arteries to be patent. In a large proportion of these patients the chest pain is of non-cardiac origin. In addition to coronary disease, other heart-related conditions may give rise to chest pain.

Earlier we have described the various uses of infrared line scanner based thermal nondestructive testing equipment [1]. Time constants of measurements made with these kind of equipment are very suitable for testing carbon fiber composites. Scanning a line heat source over a sample surface causes a nonuniform temperature distribution in the sample. In addition to the heat flow normal to the surface, lateral heat flow exists in the surface plane. In the case of carbon fiber composites with a specific oriented structure, the surface temperature distributions depend on the direction where the line source moves. Generally, this is true of any sample having anisotropic thermal conductivity. In oriented carbon fiber composites the bulk thermal conductivity can be considered anisotropic, because the heat transfer in the composite is different in the direction of the fibers compared to perpendicular directions [2,3]. Varis et al. have discussed these phenomenon briefly with the testing of carbon fiber tubes using numerical methods [4]. Here, we represent a more detailed numerical analysis of the effects of line heating on a sample having anisotropic thermal conductivity.