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Background:Gastro-intestinal tract (GIT) symptoms is highly prevalent in patients with systemic sclerosis (SSc). The GIT-symptoms impact on the quality of life is significant, and available treatment alternatives are limited. Recently published articles show associations between gut microbiota changes and GIT-symptoms in SSc. We, therefore, performed a successful feasibility trial on faecal microbiota transplantation (FMT) in SSc patients using the single-donor bacterial culture “Anaerobic Cultivated Human Intestinal Microbiome (ACHIM)”. Based on the promising results from the feasibility trial, we aim to evaluate the safety and efficacy of FMT by ACHIM in SSc patients. (NCT04300426)Objectives:To design a clinical trial that explores the safety and efficacy of FMT in SSc patients.Methods:The ReSScue trial is a phase II, placebo-controlled, randomised 20-week, multicentre trial. The trial comprises three parts. In the induction phase (A1) lasting from week 0 to week 12, participants are randomised 1:1 to repeat infusions of 30 ml ACHIM or placebo at week 0 and 2 by gastro-duodenoscopy. In the maintenance phase (A2), all study participants will receive 30 ml ACHIM at week 12 and are followed continued blinded until week 20.For longer-term data on intervention effects and safety, the participant will be followed for a maximum extended monitoring period of 16 weeks (part B).The primary endpoint is change from baseline to week 12 in UCLA GIT scores on bloating or diarrhoea, depending on the worst symptom at baseline evaluated separately for each patient. Secondary endpoints are changes in UCLA GIT scores (bloating, diarrhoea and total) and safety measures.Results:We aim to enrol 70 SSc patients based on the power calculations for the primary endpoint “change in worst symptom from baseline to week 12”, with a considered drop out rate of 10%. This number of patients is expected to give a power of 80% of detecting a change in mean (p=0.05, two-sided) of -5.0 (or higher) if the relating standard deviation is 0.70 or lower. The patient screening started in September 2020, and we expect the study to be completed in May 2022.Conclusion:The ReSScue-study is to our knowledge the first FMT-study in SSc. This trial will assess the safety and efficacy of FMT in SSc patients with lower GI-symptoms, possibly leading to a novel treatment approach in SSc patients.Disclosure of Interests:Håvard Fretheim Grant/research support from: Received travel bursaries from Actelion, and remuneration from Bayer., Imon Barua: None declared, Vikas Sarna: None declared, Maylen N Carstens: None declared, Oliver Distler Speakers bureau: Below, Consultant of: Below, Grant/research support from: OD has/had consultancy relationship and/or has received research funding in the area of potential treatments for systemic sclerosis and its complications from (last three years): Abbvie, Acceleron Pharma, Amgen, AnaMar, Arxx, Baecon Discovery, Blade, Bayer, Boehringer Ingelheim, ChemomAb, Corbus, CSL Behring, Galapagos NV, Glenmark, GSK, Horizon (Curzion), Inventiva, iQvia, Italfarmaco, iQone, Kymera, Lilly, Medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Novartis, Pfizer, Roche, Sanofi, Serodapharm, Topadur, Target Bioscience and UCB. Patent issued “mir-29 for the treatment of systemic sclerosis” (US8247389, EP2331143)., Dinesh Khanna Consultant of: Abbvie, Actelion/Janssen, Acceleron Pharma, Amgen, Bayer, Boehringer Ingelheim, CSL Behring, GSK, Horizon Pharmaceuticals, Mitsubishi Tanabe Pharma, Pfizer, Roche, Sanofi, United Therapeutics. DK is chief medical officer of Eicos Sciences, Inc., Grant/research support from: Abbvie, Actelion/Janssen, Acceleron Pharma, Amgen, Bayer, Boehringer Ingelheim, CSL Behring, GSK, Horizon Pharmaceuticals, Mitsubishi Tanabe Pharma, Pfizer, Roche, Sanofi, United Therapeutics. DK is chief medical officer of Eicos Sciences, Inc., Elizabeth Volkmann Consultant of: Boehringer Ingelheim, Grant/research support from: Corbus, Forbius, Boehringer Ingelheim, Øyvind Midtvedt Shareholder of: Son of owner of ACHIM., Henriette Didriksen Speakers bureau: Travel bursary - GSK, Alvilde Dhainaut: None declared, Anna-Kristine H Halse: None declared, Gunnstein Bakland: None declared, Inge Christoffer Olsen: None declared, Maiju E Pesonen: None declared, Øyvind Molberg: None declared, Anna-Maria Hoffmann-Vold Consultant of: Actelion, ARXX, Bayer, Boehringer Ingelheim, Medscape, Merck Sharp & Dohme, Lilly and Roche., Grant/research support from: Actelion, ARXX, Bayer, Boehringer Ingelheim, Medscape, Merck Sharp & Dohme, Lilly and Roche.

There is growing appreciation of the importance of understanding thestudent perspective in Higher Education (HE) at both institutional andinternational levels. This is particularly important in Sci ...

In this paper, we investigate which aspects are overriding in the concept images of monotonicity of Finnish tertiary mathematics students, i.e., on which aspects of monotonicity they base their argument in different types of exercises related to that concept. Further, we examine the relationship between the quality of principal aspects and the success in solving monotonicity exercises and a few other standard problems in calculus. Our findings indicate that a mathematics student's conception about monotone functions is often restricted to continuous or differentiable functions and the algebraic aspect – the nearest one to the formal definition of monotonicity – is rare.

Radial and longitudinal strain assessment in the carotid artery wall using speckle tracking

Aim: To evaluate the efficacy of various echocardiographic markers in predicting a patent ductus arteriosus (PDA) in need of treatment. Methods: Forty-five preterm infants with a mean (SD) gestational age of 27.7 (1.9) weeks underwent echocardiography at a postnatal age of 24 +/- 6 and 72 +/- 6 h. Four echocardiographic markers were studied: ductus diameter, ductal flow Doppler curves, the left atrial to aortic root (LA/Ao) ratio and Doppler pixels representing ductal shunting. Results: Twenty-eight infants had a PDA with a detectable left-to-right shunt. Of these, 12 (43%) were treated for a shunt through the PDA. Ductal diameter was the most accurate echocardiographic marker when it came to predicting a significant shunt, with a sensitivity of 89%, a specificity of 70%, a positive likelihood ratio of 2.97 and a negative likelihood ratio of 0.16 at the age of 72 h. The efficacy of the method at 72 h of age was 84%. The corresponding efficacy of the pulsatile Doppler curve was 72%, percentage of green colour pixels 63% and the LA/Ao ratio 53%. Conclusion: Ductus diameter appears to be the most important variable in determining the need for therapeutic intervention for PDA in preterm infants. (Less)

The effects of maternal smoking on the fetal coronary arteries were studied in 50 babies who died during the first month of life. The intimal layers of the coronary arteries of babies whose mothers smoked during pregnancy were smaller than those of babies of non-smoking mothers. The difference was independent of sex, birthweight, heartweight and infection. Tobacco smoking seems to prevent normal development of the intimal layer of fetal coronary arteries.

The main branch of the left coronary artery of 14 autopsied newborn babies was studied both in light and electron microscopy. Intimal and medial changes of varying severity were found in most cases. The lesions show edema and suggest insudation of the blood solutes into the vessel wall. The edematic phase is followed by proliferation of smooth-muscle and undifferentiated cells, leading to a thickening of the arterial wall. The structure of the lesions resembles the so-called preatherosclerotic changes found frequently in adults. The relationship of the neonatal coronary changes to arteriosclerosis is discussed.

Detection of adenosine triphosphate (ATP) by bioluminescence is used, for instance, in the food industry and in hospitals to assess the hygiene status of surfaces. The aim of this laboratory study was to investigate the feasibility of the ATP method for estimating the cleanability of resilient floor coverings from biological soil. The surfaces were worn using a Soiling and Wearing Drum Tester, and soiled and cleaned with an Erichsen Washability and Scrubbing Resistance Tester. In the laboratory test carried out with the bioluminescence method, most of the new and worn floor coverings that were biologically soiled were cleaned efficiently. According to this study, the semiquantitative ATP screening method can be used for hygiene monitoring of flooring materials. No correlation was found between cleanability and contact angles or surface topography measured using a profilometer. However, by revealing local irregularities and damage on surfaces, scanning electron micrographs appeared useful in explaining differences in cleanability.

Diamond-like, tetrahedrally bonded amorphous carbon (ta-C) coating was used to enhance the wear resistance of laboratory-made microstructured poly(vinyl chloride) (PVC) surfaces. Formulation of PVC samples was kept simple; they contained only stabilizer and plasticizer added to PVC. Two sizes of microstructures were imprinted on PVC. Both smooth and microstructured PVC surfaces were coated with amorphous diamond and the surfaces were characterized by spectroscopic ellipsometry, AFM and contact profilometry. In addition, water contact angles were measured. The plasticizer, plasticizer concentration and amorphous carbon coating affected the topography of the microstructure and the water contact angles on surfaces. The ta-C-coated microstructured surfaces were worn with a soiling and wearing drum tester to study their wearing behavior. Surface topographies were measured with a profilometer after wearing studies.

A quantitative radiochemical measuring procedure was used to investigate soil adhesion on laboratory-made polyvinyl chloride (PVC) surfaces. The materials contained different plasticizers and microstructures. Both the quality and amount of plasticizers and the microstructure affected the cleanability of the PVC samples. The surface topography and structures were examined with a contact angle meter, atomic force microscopy (AFM) and a contact profilometer.

UNLABELLED Although clinical manifestations of atherosclerotic coronary heart disease occur in adult life, the initial stages of its development commence in childhood. Therefore, elucidating the pathogenesis of early atherosclerosis and identifying the network of risk factors have become fundamental priorities for both cardiovascular healthcare providers and scientists. There is mounting evidence from both human studies and animal experiments that infectious pathogens could be implicated in atherosclerosis development. The vulnerability of the arterial wall to the adverse effects of infection is probably augmented when additional risk factors and/or certain proatherogenic genetic profiles are also present. The precise mechanisms whereby infection, alone or in synergy with conventional cardiovascular risk factors, could contribute to atherosclerosis are not fully understood. CONCLUSION Injury to the vascular endothelium, which could be elicited by infection through inflammatory, metabolic, autoimmune, and pathogen-related mechanisms, might be a central link between infection and early atherosclerosis.

The aim of this investigation was to examine the effect of surface topography of different compositions and surface coatings of glazed ceramic tiles on their cleanability. The cleanability was estimated with color measurements. Contact angle measurements were used to describe the surface properties and profilometry and electron microscopy to describe the topography. The effect of additional coatings on the surface properties was compared by applying experimental zirconia and titania coatings as well as a commercial fluoropolymer coating on one of the experimental and all reference glazes. The results show that there were clear differences between the soiling tendencies of the glazes. Generally the topography measurements show that the rougher was ceramic glaze, the more soil adhered on its surface.

The soiling and cleanability of eleven worn commercial plastic floor coverings were examined. The new and worn floor coverings appeared very similar in both visual and stereo microscopic inspection. However, wear had caused changes to both topography and cleanability parameters. Profilometer measurements provided information on the topography of new and worn floor coverings. According to the results new surfaces did not always clean better or become soiled more easily than worn coverings. Therefore, we cannot derive a general rule of relationship between wear, soiling and cleanability. The general premise that a rough surface will yield poor cleanability was not confirmed here for all materials.

Adhesion of soil on glazed surfaces and their cleanability depends on chemical composition, phase composition, and roughness of the surface. The surface can be glossy consisting mainly of a smooth glassy phase. A matt and rough surface consists of a glassy phase and one or more crystalline phases. The origin and composition of the crystalline phases affect the chemical resistance and the cleanability of the surface. Fifteen experimental glossy and matt glazes were soaked in a slightly alkaline cleaning agent solution. The surfaces were spin-coated with sebum, i.e. a soil component typical for sanitary facilities. After wiping out the soil film in a controlled manner, the surface conditions and the soil left were evaluated with colour measurements, SEM/EDXA and COM. The results show that wollastonite-type crystals in the glaze surfaces were attacked in aqueous solutions containing typical cleaning agents. This corrosion led to significant decrease in the cleanability of the surface. The other crystal types observed, i.e. diopside and quartz crystals were not corroded, and the cleanability of glazes containing only these crystals was not changed in the cleaning agent exposures. Also the glassy phase was found to be attacked in some formulations leading to a somewhat decreased cleanability. The repeated soiling and cleaning procedures indicated that soil is accumulated on rough surfaces and surfaces which were clearly corroded by the cleaning agent.

The tendency to soil and cleanability of ten commercial plastic floor coverings: eight vinyl (PVC) floor coverings, one vinyl composite tile and one plastic composite tile, were examined. Floor coverings were soiled with inorganic, organic and biological soil. The cleanability was measured both by bioluminescence of ATP (adenosine triphosphate) and colorimetrically. The surface topography was studied by AFM, SEM and with a profilometer. From the 2D- and 3D-profilometric measurements several characteristic parameters of the surface profiles were extracted. The tendency to soil and cleanability were compared with the characteristics of the surface. A weak correlation was found between roughness and soilability but no correlation between roughness and cleanability. Roughness had no correlation with contact angle.

The purpose of this study was to test the feasibility of contact angle measurement in evaluating soilability and cleanability of 11 different surfaces of flooring materials. The surface properties were examined using an expanding contact angle technique and the cleanability was evaluated colorimetrically. The values of advancing contact angles θA were related to the soil residues on particle-soiled surfaces and oil-soiled surfaces. The results indicate the potential of contact angle measurements to evaluate cleanability of flooring materials.

Appendicectomy is an operation that is often performed without certainty of diagnosis. This study aimed to construct and to validate a prognostic score for the diagnosis of acute appendicitis in children.Data for 35 symptoms and signs were prospectively recorded for 131 consecutive children with suspected appendicitis. Logistic regression analysis of the variables yielded a diagnostic score: gender (male 2 points, female 0) + intensity of abdominal pain (severe 2, mild or moderate 0) + relocation of pain (yes 4, no 0) + vomiting (yes 2, no 0) + pain in the right lower abdominal quadrant (yes 4, no 0) + fever (yes 3, no 0) + guarding (yes 4, no 0) + bowel sounds (abnormal 4, normal 0) + rebound tenderness (yes 7, no 0). The cut-off level for recommendation of appendicectomy wasor =21, and the cut-off level for non-appendicitis wasor =15. The score was prospectively validated on 109 children.In the validation sample, based on clinical judgment, unnecessary appendicectomy was performed in ten (27%) children, and one (4%) child was misdiagnosed as not having appendicitis. By application of the score, unnecessary appendicectomies would have been reduced to four (13%), and three children (11%) with appendicitis would have been discharged.The use of a predictive mathematical model may facilitate the diagnosis of appendicitis to avoid unnecessary operations.

A new method to study the wear of floor coverings is presented. Surfaces were worn in a drum based on a new standard proposal. A test device called a “hexapod” walks along the floor coverings, which are placed on the wall of the drum containing sand. This walking mimics the real situation better than the current European standard EN 660-2 abrasive wear test for floor coverings. The proposed method was applied to testing the durability of 15 commercial floor coverings. The results were compared with the standard abrasive test EN 660-2. No correlation between the two methods was obtained, showing convincingly that the two tests represent different kinds of wearing mechanisms. Profilometry measurements were performed to obtain information about wearing. Mean waviness did not correlate with wearing.

The paper describes the changes that are being made in the mathematics teachers' subject studies in the Department of Mathematics at the University of Joensuu, in order to provide our mathematics students both with a sufficiently deep knowledge of mathematics and science, and with present-day expertise in their profession as teachers. While the formal structure of the mathematics curriculum remains structured and taught as courses with mostly traditional names like algebra, analysis, and linear algebra, there are also totally new ‘professionally oriented’ courses. Some of the old courses—with rather traditional and rigorous contents—have been changed in a more student-driven direction. In these ‘pedagogically oriented’ courses students are encouraged, and even forced, to study co-operatively in social interaction, for example to negotiate how to solve a problem decently, or how to build a formal definition for a concept with certain wanted attributes. As an ultimate example of a pedagogical experiment we ...

In this study different substitution methods for the replacement of missing data values were inspected for the use of these cases in a neural network based decision support system for acute appendicitis. The leucocyte count had the greatest number of missing values and was used in the analyses. Four different methods were compared: substituting means, random values, nearest neighbour and a neural network. There were great differences in the substituted leucocyte count values between different methods and only nearest neighbour and neural network agreed about most of the cases. The importance of the substitution method for the final diagnostic classification of the patients by the neural network based decision support system was found to be small.

The use of an artificial neural network system was studied in the diagnosis of acute abdominal pain, especially acute appendicitis, with patients from Finland and Germany. Separate Learning Vector Quantization (LVQ) neural networks were trained with a training set from each database and also with a combined database. Each neural network was evaluated separately with a test set of cases from each database. With the combined database different neighborhood methods were compared to find the optimal choice for this decision-making problem. The acute appendicitis cases of the Finnish test data set were classified well with all the networks, but the cases of the German test set were difficult to classify for the Finnish network. The use of larger neighborhoods increased the sensitivity of the classification by nearly 10%. The differences in the results of the Finnish and German databases suggest that there are differences in the data collection or patient populations between centers. Therefore, care must be taken when using decision-support systems which have been developed in other centers. Neural networks offer a method to evaluate differences between databases. With the use of larger neighborhoods, the effects of the differences on the accuracy of the classification can be partly diminished.

This paper reports an ongoing study on CS freshmen at two universities in Finland. The goal of this report is to describe what kind of students decide to study computer science; what are students' programming background, expectations and perceptions regarding their studies and future work life. We collected data from 190 students from two universities at the beginning of the first study year. The results draw a picture of students' who have mainly positive and trusting perceptions of the IT field and who have high expectations of their success at their studies. We will discuss the results, especially the students' heterogeneous programming background and some gender differences, in more detail and consider how we could and should take those into consideration in our curriculum and teaching.

Four different neural network algorithms, binary adaptive resonance theory (ART1), self-organizing map, learning vector quantization and back-propagation, were compared in the diagnosis of acute appendicitis with different parameter groups. The results show that supervised learning algorithms learning vector quantization and back-propagation were better than unsupervised algorithms in this medical decision making problem. The best results were obtained with the learning vector quantization. The self-organizing map algorithm showed good specificity, but this was in conjunction with lower sensitivity. The best parameter group was found to be the clinical signs. It seems beneficial to design a decision support system which uses these methods in the decision making process.

Free radical-mediated oxidation of proteins may impair their function and cause cellular damage. We studied pulmonary protein oxidation and its association with the development of chronic lung disease in 61 newborn infants (mean gestational age 31.1 +/- 4.0, range 24-41 weeks) requiring intensive care with oxygen therapy. Protein oxidation was quantified as protein carbonylation in tracheal aspirates recovered daily during the first week of life. Mean carbonyl concentration was 3.5 +/- 1.6 mumol/mg protein. Negative correlations existed between protein carbonylation during days 2-4 and gestational age (day 2: r = -0.37, p = 0.01; day 3: r = -0.48, p = 0.001; and day 4: r = -0.33, p = 0.03). Patients who developed bronchopulmonary dysplasia showed significantly higher protein carbonylation on days 1-6 (all p < 0.05). In multiple regression analysis explaining bronchopulmonary dysplasia, using gestational age, inspired oxygen on days 1-3 and protein carbonylation on day 3 as independent variables, only protein carbonylation remained significant. We conclude that immaturity is the most important factor explaining free radical-mediated pulmonary protein oxidation in newborn infants and that oxidation of proteins is related to the development of chronic lung disease.

Right-atrial isomerism (RAI) is a heterotaxy syndrome with disturbances of left-right axis development resulting in complex heart malformations and anomalies of the thoracic and abdominal organs. To study the outcome of RAI, all data from patients diagnosed with this syndrome at Helsinki University Hospital between January 1976 and December of 2010 were reviewed. The outcomes were studied for 32 patients (38 % girls). The overall survival was 22 % at a median follow-up time of 13.8 years (range 0.1-33). Extracardiac malformations, mostly asplenic, occurred in 91 % of patients. Cardiac defects included dextrocardia in 44 % and common atrioventricular valve in 100 % of patients. Ventriculoarterial discordance or double-outlet ventricle was seen in 56 and 44 % of patients, respectively. Total anomalous pulmonary venous drainage occurred in 75 % and partially anomalous venous drainage in 13 % of patients. Pulmonary outflow-tract obstruction was identified in 91 % of patients. Cardiac arrhythmias were noted in nine patients (28 %), two of them with atrioventricular block. Cardiovascular surgery was performed in 71 % patients (N = 25), seven patients were inoperable. Biventricular repair was not possible in any of the patients. During long-term follow-up there was no significant difference between the patients with total, normal, or partially anomalous pulmonary venous drainage (P = 0.5). In conclusion, RAI is one of the most severe forms of congenital cardiac diseases. The prognosis remains poor despite modern surgical techniques. When RAI is identified during pregnancy, prenatal counseling, termination, or planning for prompt cardiac treatment after the birth is necessary.

Smart/precision farming systems are expected to play an important role in improving farming activities. During the past years, sophisticated farm management systems have emerged to replace outdated complex and monolithic farm systems and software tools. The latest trend is to enable these management systems to operate over the Internet. However, the Internet, in its current operation form, faces a number of shortcomings especially in handling vast numbers of networked devices (i.e., Internet of Things) or allowing a simplified integration of systems and services developed by different players. Currently, a number of research initiatives aim at addressing these shortcomings. Such an example is the " Future Internet" program launched by the European Commission. In the context of our work, we have specified a farm management system that takes advantage of the new characteristics that " Future Internet" offers. These come in terms of generic software modules that can be used to build farming related specialized modules. We present the functional architecture of this farm management system and provide an operational example. We also analyze the technological enablers that will make this architecture a reality. © 2012 Elsevier B.V.

Post-mortem examination in children may reveal narrowing of coronary artery diameter by up to 60% due to intimal thickening. This is statistically associated with recent or intercurrent infection. Endothelial injury is known to be caused by septicaemia, for example, and endothelial injury initiates atherogenesis. Elevation of tumour necrosis factor alpha (TNF alpha) levels is a feature of both septicaemia and atheroma, and TNF alpha can damage endothelium, stimulate platelet-derived-growth-factor (PDGF) secretion and thereby promote vascular smooth muscle cell proliferation. Episodes of infection-related endothelial damage, leading to intimal thickening followed by partial regression, may start in infancy and contribute cumulatively to the development of coronary atheroma.

The aim of this randomized study was to compare the neonatal outcome in infants who have been exposed in utero to indomethacin with that in infants exposed to a β -adrenergic agonist, nylidrin hydrochloride. Eighty pregnant women threatened with preterm labor between 24 and 34 weeks of gestation were enrolled in the study. An intravenous infusion of nylidrin or enterally administered indomethacin was given for a maximum of 72 hours. If preterm labor recurred, all parturient patients were treated with nylidrin. Indomethacin prolonged gestation significantly more than the β-adrenergic agonist (6.6 weeks vs 4.5 weeks; p = 0.04). Ten of the forty-two infants exposed to indomethacin and 2 of the 45 infants exposed to nylidrin had bronchopulmonary dysplasia (24% vs 5%; p = 0.02). Among the 28 infants delivered within 120 hours after the start of treatment, the incidences of respiratory distress syndrome (82% vs 29%; p = 0.02), bronchopulmonary dysplasia (73% vs 6%; p = 0.0006), and necrotizing enterocolitis or focal intestinal perforation (27% vs 0%; p = 0.03) were higher among those exposed to indomethacin than among those exposed to nylidrin. We infer that administration of indomethacin to pregnant women threatened with premature labor is associated with an increased risk of bronchopulmonary dysplasia in their infants if delivery occurs early. (J P EDIATR 1994;124:782-8)

Acute appendicitis is the most common cause of acute abdomen requiring surgical intervention. The clinical diagnosis of acute appendicitis is not always easy due to variable symptomatology, particularly at the onset. The contributions of history-taking and physical examination in the diagnosis of acute appendicitis was studied in connection with the Research Committee of the World Organization of Gastroenterology (OMGE) survey of acute abdominal pain. Especially the suitability of diagnostic parameters in the construction of an expert system for automatic decision making was studied. The results clearly show that it is possible to construct an expert system for automatic decision making in the diagnosis of acute appendicitis.

BACKGROUND Intimal thickenings of the coronary arteries of newborn children are composed mainly of smooth muscle cell proliferations. To investigate whether thickening of the intima in infants is associated with a family history of coronary artery disease (CAD), we studied the relation of coronary death of grandparents to intimal thickening of 136 infants. METHODS AND RESULTS The length of internal elastic lamina of the artery and the areas of arterial layers in cross section were measured, and the arteries were transformed to idealized round circles. Intimal thickening was assessed as the degree of luminal narrowing (ratio of intimal area to the area on the luminal side of the arterial media). Among 136 infants, luminal narrowing varied between 0% and 58%. CAD deaths accounted for 108 of the total 281 deaths among the grandparents of the infants. Family history of CAD (defined as at least one CAD death among the four grandparents) was positive for 77 infants. Family history of CAD was significantly more common in the infants with luminal narrowing of both the left and right coronary arteries compared with the infants with no narrowing in at least one artery (odds ratio adjusted for sex, infection status, and age of infant, 5.69; 95% confidence interval, 1.46-22.2). After adjustment for sex and age, infants with both a positive family history and presence of infection had an increased degree of luminal narrowing compared with infants with a negative family history and no infection. CONCLUSIONS The association of coronary artery intimal thickening in infancy with family history of CAD suggests that intimal thickening is a morphological manifestation of predisposition to CAD.

To evaluate the efficacy of various echocardiographic markers in predicting a patent ductus arteriosus (PDA) in need of treatment.Forty-five preterm infants with a mean (SD) gestational age of 27.7 (1.9) weeks underwent echocardiography at a postnatal age of 24 ± 6 and 72 ± 6 h. Four echocardiographic markers were studied: ductus diameter, ductal flow Doppler curves, the left atrial to aortic root (LA/Ao) ratio and Doppler pixels representing ductal shunting.Twenty-eight infants had a PDA with a detectable left-to-right shunt. Of these, 12 (43%) were treated for a shunt through the PDA. Ductal diameter was the most accurate echocardiographic marker when it came to predicting a significant shunt, with a sensitivity of 89%, a specificity of 70%, a positive likelihood ratio of 2.97 and a negative likelihood ratio of 0.16 at the age of 72 h. The efficacy of the method at 72 h of age was 84%. The corresponding efficacy of the pulsatile Doppler curve was 72%, percentage of green colour pixels 63% and the LA/Ao ratio 53%.Ductus diameter appears to be the most important variable in determining the need for therapeutic intervention for PDA in preterm infants.

A multicentre study on atherosclerosis precursors in young Finns aged three to 18 years was started in 1980 (3596 subjects) serum lipid concentrations (cholesterol, HDL (high density lipoprotein) cholesterol and triglycerides) were determined (n = 3554) and the apolipoproteins A-I and B measured (n = 1355). Two follow-up studies were carried out in 1983 (n = 2851) and 1986 (n = 2489), when HDL-subfractions (HDL-2-cholesterol and HDL-3-cholesterol) were also determined. Apolipoproteins A-I and B were measured again in 1986 (n = 1202). Serum total cholesterol concentration has fallen by about 1% annually during the 1980's from 5.07 mmol/l (1980) to 4.79 mmol/l (1986) in 9- to 18-year old children and adolescents. Mean values of serum triglycerides have slightly increased during the follow-up from 0.79 mmol/l to 0.84 mmol/l, respectively. In children and young adults (3-24 years) the mean cholesterol concentration was highest at the age of six and lowest during puberty. Concentrations of serum cholesterol, LDL (low density lipoprotein) cholesterol apoprotein B and triglycerides were higher in eastern than in western Finland in 1980 and 1983, but these differences were smaller in 1986, with the exception of serum triglycerides. Both in 1983 and in 1986 HDL-2-cholesterol was lower in the west than in the east, whereas HDL-3-cholesterol was higher in the former. The favourable changes in lipid levels should be reflected in future morbidity and mortality rates from coronary heart disease in Finland.

Two mitotic activity indices, volume fraction of neoplastic epithelium, nuclear area, nuclear perimeter, and shortest nuclear axis were estimated in 46 ovarian tumors by three observers in two independent laboratories. The mitotic activity index, the volume corrected mitotic index (M/V index) and subjective volume fraction estimates showed a very good correlation from the same fields by two observers in the same laboratory (r = .999, .995, .950). Repeat estimates from different fields by the same observer showed coefficient values of .949, .939, and .813, and estimates by two different observers within one laboratory values of .949, .936, and .789, respectively. The correlation between two independent observers in different laboratories was also good (r = .894, .834, .834, respectively). Grading based on morphometric measurements was uniformly performed in 90-100% of cases in an interfield interobserver intralaboratory situation, and in 79-97% (M/V index) or 76-93% (mitotic activity index) in an interlaboratory situation. Because the cases near the grade limits were more often differently graded than other cases, the methods allowed the pathologist to locate the probably incorrectly graded cases. Morphometry of ovarian tumors was shown to be easy, which makes morphometric malignancy grading systems potentially able to support diagnostic and therapeutic decisions in practice.

Coronary arteries of 93 clinically healthy Finnish children of both sexes were collected from successive, medicolegal autopsies of victims of violent death. In the histological and histochemical study, local, cushion-type thickenings of the coronary walls were demonstrable in 47, i.e. 50 per cent, of the children, the occurrence increasing with age. The most prominent change was the splitting of the internal elastic membrane and the accumulation of smooth muscle cells, forming a new, musculo-elastic layer. Glycosaminoglycans appeared in the luminal parts of the thickenings. There was an average decrease in the succinate dehydrogenase reaction in the cushion area, implying a degenerative process. The increase in the reaction of "injury markers", acid phosphatase and esterase based on the increase of cells rich in these enzymes, indicated pathologic process. It was concluded that change of this kind, demonstrable early in childhood, may dispose coronary arteries to atherosclerosis.

The nuclear DNA content of archival paraffin-embedded bladder cancer samples (70 patients) of WHO grades I-III has been measured by flow cytometry. The female/male ratio was 15/55. The mean follow-up time was 13 years (range 9.6-22.0 years). 37 of 70 (53%) patients had DNA index 1.0 (diploid DNA content), and the remaining 33 (47%) patients had an aneuploid tumor. There was no significant difference in the age (mean +/- SD) of the patients having a diploid (66 +/- 9 years) or an aneuploid tumor (68 +/- 11 years) at the time of diagnosis. 47 deaths occurred during the follow-up period; 24 (51%) of these were due to bladder cancer (12 diploid, 12 aneuploid tumors). No significant difference was found after radical treatment during the disease-free interval (mean +/- SD) between diploid (48 +/- 45 months) and aneuploid (35.5 +/- 35 months) groups of patients. Recurrences during the follow-up period were equally common among aneuploid and diploid tumors. A statistically significant relation between histological grade and survival could be demonstrated, but DNA ploidy and S phase fraction had little prognostic value in this respect. There was no statistically significant difference in survival between aneuploid (30%) and diploid (35%) groups of tumors during the follow-up period. The study suggests that flow cytometric determination of nuclear DNA ploidy from paraffin-embedded samples in bladder tumors does not add to the prognostic power of subjective histological grading.

A retrospective follow-up (range 9.4-22 years, mean 13 years) study of 83 patients with grade I-III (WHO) bladder carcinomas was performed. Nuclear area (mean +/- SD 59.7 +/- 18.7 microns2) and the SD of nuclear area (mean +/- SD 19.7 +/- 13.4 microns2) were determined by using morphometric methods. The SD of nuclear area and histopathological grade exhibited a clearly significant relation, the relation between grade and nuclear area was weaker. The number of recurrences in the bladder and the recurrence-free period were not significantly related to histopathological grade, mean nuclear area or SD of nuclear area. The progress in nodal or metastatic stage could be predicted by histopathological grade, mean nuclear area and SD of the nuclear area. Prediction of crude survival, however, was not efficient. When only bladder cancer deaths were included in the analysis, histopathological grade (p less than 0.001), mean nuclear area (p = 0.011) and SD of the nuclear area (p = 0.001) showed a significant relation to survival. Grade II tumors could be divided into two prognostically different groups using nuclear area and SD of the nuclear area as classifiers. The results suggest that morphometric parameters are as good as histopathological grade in predicting long-term prognosis of bladder carcinomas, and better than the histopathological grade in predicting progress in nodal (N) or metastatic (M) stage.

The prognostic value of subjective histological and morphometric grading was studied in 75 primary ovarian carcinomas. Histological grading methods recommended by Czernobilsky and by Russell and the morphometric method of Baak and co-workers were compared in a two-observer system. The 5-year survival could be correctly predicted in about two-thirds of the patients with all three methods. When mitotic counting (volume corrected mitotic index, M/V-index) was compared with the above grading methods by using a receiver operating characteristic curve) the M/V-index was generally superior in its prognostic power regardless of the sensitivity/specificity level chosen. The morphometric grading method and the grading method based on the M/V index were also shown to be readily reproducible.

A quantitative radiochemical test procedure was developed for investigating soil adhesion on polyvinyl chloride (PVC) model materials containing different plasticizers (DOP and Hexamoll) and commercial flooring materials. A repeatable test procedure was developed, including soiling and cleaning with a Mini Cleanability Tester. Three soils all containing 51Cr emitting gamma radiation were used. The materials were subjected to successive soiling and cleaning cycles in order to generate soil accumulation. The type and amount of plasticizer appeared to affect soil adhesion on plastic model materials.

The effects of fetal asphyxia on cerebral function and development, involve the transition from fetal to neonatal life. Changes in cerebral glucose metabolism may be an early postnatal indicator of fetal asphyxia. The objective is to develop an experimental lamb model involving the transition from fetal to neonatal life and to examine the effect of fetal asphyxia with cerebral hypoxic ischemia on early postnatal cerebral glucose metabolism. Fetal asphyxia was induced by total umbilical cord occlusion in eight near-term fetal lambs (134-138 days) with the ewe under isoflurane-opiate anesthesia. The mean occlusion time until cardiac arrest was 14.5 (4.2) min (SD). Lambs were immediately delivered and standardized resuscitation was instituted after 2 min asystole. At 4 hr postnatal age, [18-F]Fluoro-2-deoxy-glucose (18-FDG) was injected intravenously in eight asphyxiated lambs and in eight controls. Cerebral glucose metabolism was examined by positron emission tomography (PET). As a result the mean arterial blood pressure, acid-base values, blood glucose and serum lactate at 4 hr postnatal age did not differ significantly between lambs subjected to umbilical cord occlusion and controls. EEG was abnormal in all lambs subjected to cord occlusion and normal in the controls at 4 hr postnatal age. Global cerebral metabolic rate (CMRgl) as determined by PET was significantly lower in lambs subjected to cord occlusion mean/median (SD) 22.2/19.6 (8.4) micromol/min/100 g) than in controls mean/median (SD) 37.8/35.9 (6.1); P0.01). Global CMRgl is significantly reduced in newborn lambs 4 hr after fetal asphyxia induced by umbilical cord occlusion. A reduction in CMRgl is an early indicator of global hypoxic cerebral ischemia.

High-frequency components in ECG during global ischaemia were studied in isolated guinea-pig hearts perfused ad modum Langendorf. Electrocardiograph recordings were carried out from the epicardial surface both in normo- and low-flow perfusion. After bandpass filtering (5-500 Hz), signal-averaging, was undertaken. The high-frequency components either increased or decreased after low-flow perfusion was instituted. Root-mean-square voltage (RMS) of the depolarization signal correlated poorly with the signal amplitude, but highly with the first and second derivative, i.e. the velocity and the acceleration of the signal. It is concluded that high-frequency components are not pathological phenomena per se, but reflect the shape of the original electrocardiographic signal.

To assess possible interactions between inflammation and activation of the anticoagulant protein C system during post-ischemic reperfusion protein C, APC, neutrophil L-selectin expression and myocardial myeloperoxidase activity (MPO) were measured in 19 patients undergoing cardiopulmonary bypass. After reperfusion for 10 min, APC to protein C ratio (APC/PC) increased from pre-reperfusion value 1.43 +/- 0.12 (mean +/- SEM) to 2.25 +/- 0.29, p = 0.015. Negative correlations were observed between APC/PC and MPO activity (Spearman r -0.64, p = 0.007) and APC/PC and neutrophil L-selectin expression (r = -0.7, p = 0.007, demonstrating that post-ishemic protein C activation was associated with decreased neutrophil tissue sequestration. Thus, physiological protein C activation may be involved in regulation of the inflammatory injury during reperfusion of human ischemic coronary circulation.

Therapy with inhaled nitric oxide is usually given with high concentrations of oxygen. As nitric oxide (NO) is a free radical and hyperoxia increases oxygen radical production, we examined the effect of short exposure to NO or oxygen (O2) or both, on free radical-mediated changes in macromolecules, i.e. lipids and proteins, in vivo. Wistar rats were exposed to95% O2 or 40 ppm NO, or both, for 6 h. Rats in 21% O2 served as controls. Lipid peroxidation was quantified as expired pentane, oxidative protein modification as carbonyl concentration, and pulmonary neutrophil accumulation as myeloperoxidase activity in the lungs. Hyperoxia for 6 h caused higher expired pentane (4.83 +/- 1.39 pmol/min/100 g) and protein carbonylation (15.91 +/- 2.49 nmol/mg) compared to controls (2.26 +/- 1.00 pmol/min/100 g, and 7.40 +/- 1.12 nmol/mg, respectively; both p0.05). After exposure to NO in air, protein carbonylation (14.50 +/- 5.44 nmol/mg) and myeloperoxidase activity (4.85 +/- 1.52 mU/mg) were higher than in controls (myeloperoxidase 2.49 +/- 0.56 mU/mg; both p0.05). NO with hyperoxia decreased pentane (2.56 +/- 1.51 pmol/min/ 100 g) and protein carbonylation (11.38 +/- 3.58 nmol/mg) compared to hyperoxia (both p0.05).In vivo, 6 h exposure to hyperoxia or to 40 ppm NO induces free radical-mediated lung injury. The combination of hyperoxia and 40 ppm NO significantly attenuates free radical-mediated effects in the lungs compared to hyperoxia or 40 ppm NO in air.

We compared the performance of multivariate models based on mitotic activity index, lymph node status, and tumor size in the prognostication of breast cancer.Cox and discriminant models for survival were created for two patient groups: a) 120 breast cancer patients, and b) 86 patients with ductal infiltrating carcinoma. The models were compared with the model of Baak et al (1985).The models distinguished between dying and surviving patients with an efficiency of 70.9-77.9% in mutual tests. With a single cutoff the model of Baak et al was less efficient (50.8-65.8%). If a region of uncertainty was allowed between two cutpoints, the efficiencies below and above the cutpoints increased. When the uncertain region included a third of the patients, the efficiency varied between 73.8 and 84.7%.Multivariate models seem to need a region of uncertainty between two discriminating cutpoints. These models resulted in the correct prediction of prognosis in about 75% and more of patients. With different materials the models differed in efficiency. With a region of uncertainty the model of Baak et al performed well with completely independent material.