Showing papers by "University of Turku published in 2001"

Effect of the Tyrosine Kinase Inhibitor STI571 in a Patient with a Metastatic Gastrointestinal Stromal Tumor

Abstract: Gastrointestinal stromal tumors are a group of mesenchymal neoplasms that arise from precursors of the connective-tissue cells of the gastrointestinal tract.1 They occur predominantly in middle-aged and older persons, and approximately 70 percent of the tumors are found in the stomach, 20 to 30 percent are found in the small intestine, and less than 10 percent are found elsewhere in the gastrointestinal tract.1 Recent studies have shown that cells in gastrointestinal stromal tumors express a growth factor receptor with tyrosine kinase activity termed c-kit. This receptor, the product of the proto-oncogene c-kit, can be detected by immunohistochemical staining for . . .

Distinct patterns of neonatal gut microflora in infants in whom atopy was and was not developing.

Abstract: Background: Improved hygiene has altered early microbial exposure by reducing childhood infections, which has been suggested as a cause for the continuously rising prevalence of atopic diseases. On the basis of both intensity and timing of stimulus, it has been hypothesized that exposure to commensal microflora may represent another key protective modulator of immunity against atopy and subsequent atopic diseases. Objective: We sought to investigate whether differences in early gut microflora precede the later development of atopic sensitization. Methods: Intestinal microflora from 76 infants at high risk of atopic diseases were analyzed at 3 weeks and 3 months of age by using conventional bacterial cultivation and 2 culture-independent methods, gas-liquid chromatography of bacterial cellular fatty acids and quantitative fluorescence in situ hybridization of bacterial cells. Infants evincing at least one positive skin prick reaction at 12 months were grouped as atopic subjects, and those without positive reactions were grouped as nonatopic subjects. Results: Atopic sensitization was observed in 22 (29%) of 76 children. At 3 weeks, the bacterial cellular fatty acid profile in fecal samples differed significantly between infants in whom atopy was and was not developing ( P = .005). By using fluorescence in situ hydridization, atopic subjects had more clostridia (geometric mean [95% confidence interval]: 9.3 × 10 7 [3.8-22.9 × 10 7 ] vs 3.3 × 10 7 [1.8-6.1 × 10 7 ], P = .04) and tended to have fewer bifidobacteria (1.8 × 10 9 [0.4-7.6 × 10 9 ] vs 6.1 × 10 9 [2.5-14.6 × 10 9 ], P = .11) in their stools than nonatopic subjects, resulting in a reduced ratio of bifidobacteria to clostridia ( P = .03). The differences were not detected by bacterial cultivation. Conclusion: Differences in the neonatal gut microflora precede the development of atopy, suggesting a crucial role of the balance of indigenous intestinal bacteria for the maturation of human immunity to a nonatopic mode. (J Allergy Clin Immunol 2001;107:129-34.)

Normal prenatal but arrested postnatal sexual development of luteinizing hormone receptor knockout (LuRKO) mice.

Abstract: To study further the role of gonadotropins in reproductive functions, we generated mice with LH receptor (LHR) knockout (LuRKO) by inactivating, through homologous recombination, exon 11 on the LHR gene. LuRKO males and females were born phenotypically normal, with testes, ovaries, and genital structures indistinguishable from their wild-type (WT) littermates. Postnatally, testicular growth and descent, and external genital and accessory sex organ maturation, were blocked in LuRKO males, and their spermatogenesis was arrested at the round spermatid stage. The number and size of Leydig cells were dramatically reduced. LuRKO females also displayed underdeveloped external genitalia and uteri postnatally, and their age of vaginal opening was delayed by 5–7 days. The (−/−) ovaries were smaller, and histological analysis revealed follicles up to the early antral stage, but no preovulatory follicles or corpora lutea. Reduced gonadal sex hormone production was found in each sex, as was also reflected by the suppr...

Non-response and related factors in a nation-wide health survey

Abstract: Objective: To analyse selective factors associated with an unexpectedly low response rate. Subjects and methods: The baseline questionnaire survey of a large prospective follow-up study on the psychosocial health of the Finnish working-aged randomly chosen population resulted in 21,101 responses (40.0%) in 1998. The non-respondent analysis used demographic and health-related population characteristics from the official statistics and behavioural, physical and mental health-related outcome differences between early and late respondents to predict possible non-response bias. Reasons for non-response, indicated by missing responses of late respondents, and factors affecting the giving of consent were also analysed. Results: The probability of not responding was greater for men, older age groups, those with less education, divorced and widowed respondents, and respondents on disability pension. The physical health-related differences between the respondents and the general population were small and could be explained by differences in definitions. The late respondents smoked and used more psychopharmaceutical drugs than the early ones, suggesting similar features in non-respondents. The sensitive issues had a small effect on the response rate. The consent to use a medical register-based follow-up was obtained from 94.5% of the early and 90.9% of the late respondents (odds ratio: 1.70; 95% confidence interval: 1.49–1.93). Consent was more likely among respondents reporting current smoking, heavy alcohol use, panic disorder or use of tranquillisers. Conclusions: The main reasons for non-response may be the predisposing sociodemographic and behavioural factors, the length and sensitive nature of the questionnaire to some extent, and a suspicion of written consent and a connection being made between the individual and the registers mentioned on the consent form.

SMAA-2: Stochastic Multicriteria Acceptability Analysis for Group Decision Making

Abstract: Stochastic multicriteria acceptability analysis (SMAA) is a multicriteria decision support method for multiple decision makers in discrete problems. In SMAA, the decision makers need not express their preferences explicitly or implicitly. Instead, the method is based on exploring the weight space in order to describe the valuations that would make each alternative the preferred one. Inaccurate or uncertain criteria values are represented by probability distributions from which the method computes confidence factors describing the reliability of the analysis. In this paper we introduce the SMAA-2 method, which extends the original SMAA by considering all ranks in the analysis. In situations where the "elitistic" SMAA may assess large acceptability only for extreme alternatives without sufficient majority support, the more holistic SMAA-2 analysis can be used to identify good compromise candidates. The results are presented graphically. We consider also situations where partial preference information is available. We demonstrate the new method using a real-life decision problem.

Surface binding of aflatoxin B(1) by lactic acid bacteria.

Abstract: Specific lactic acid bacterial strains remove toxins from liquid media by physical binding. The stability of the aflatoxin B1 complexes formed with 12 bacterial strains in both viable and nonviable (heat- or acid-treated) forms was assessed by repetitive aqueous extraction. By the fifth extraction, up to 71% of the total aflatoxin B1 remained bound. Nonviable bacteria retained the highest amount of aflatoxin B1. Lactobacillus rhamnosus strain GG (ATCC 53103) and L. rhamnosus strain LC-705 (DSM 7061) removed aflatoxin B1 from solution most efficiently and were selected for further study. The accessibility of bound aflatoxin B1 to an antibody in an indirect competitive inhibition enzyme-linked immunosorbent assay suggests that surface components of these bacteria are involved in binding. Further evidence is the recovery of around 90% of the bound aflatoxin from the bacteria by solvent extraction. Autoclaving and sonication did not release any detectable aflatoxin B1. Variation in temperature (4 to 37°C) and pH (2 to 10) did not have any significant effect on the amount of aflatoxin B1 released. Binding of aflatoxin B1 appears to be predominantly extracellular for viable and heat-treated bacteria. Acid treatment may permit intracellular binding. In all cases, binding is of a reversible nature, but the stability of the complexes formed depends on strain, treatment, and environmental conditions. Food contaminants entering the body through the oral route are directly exposed to the action of gut microflora. Normal healthy intestinal microflora contains many strains of lactic acid bacteria (LAB), some of which have been isolated, ascribed health benefits, and termed probiotic strains (22). The protective effect of LAB against food mutagens such as heterocyclic amines, N-nitroso compounds, and aflatoxins has been reported (8, 12, 19, 24, 27). Many of these studies have involved Lactobacillus strains, and physical binding has been proposed as one mechanism of mutagen removal. This study focuses on the nature of the binding of aflatoxin B1 (AFB1) by 12 LAB strains. The potent mycotoxin AFB1 is a secondary metabolite of Aspergillus fungi that grow on a variety of food and feed commodities at any stage during growth, harvest, storage, and transportation. The occurrence of aflatoxin contamination is global, with severe problems especially prevalent in developing countries (11). Aflatoxins are of great concern because of their detrimental effects on the health of humans and animals, including carcinogenic, mutagenic, teratogenic, and immunosuppressive effects (3). Aflatoxins are also of industrial importance due to the economic losses resulting from condemnation of contaminated crops, cheese defects, and impaired growth and feed efficiency of animals fed contaminated feeds. Consequently there is a great demand for

Time domain, geometrical and frequency domain analysis of cardiac vagal outflow: effects of various respiratory patterns.

Abstract: The purpose of this study was to compare the applicability of four different measures of heart rate variability (HRV) in the assessment of cardiac vagal outflow, with special reference to the effect of breathing pattern. The anticholinergic effects of an intravenous glycopyrrolate infusion (5 microg x kg(-1) x h(-1) for 2 h) during spontaneous and controlled (15 min(-1)) breathing rate were investigated in eight volunteers, and the effects of different fixed breathing rates (6-15-24 min(-1)) and hyperventilation in 12 subjects. Cardiac vagal activity was assessed by ECG recordings in which the following measures of HRV were computed: the high-frequency (HF) spectral component, the instantaneous RR interval (RRI) variability (SD1) analysed from the Poincare plots, the percentage of differences between successive RRIs greater than 50 ms (pNN50), and the square root of the mean squared differences of successive RRIs (RMSSD). On average, glycopyrrolate reduced the HF spectral component by 99.8%, SD1 by 91.3%, pNN50 by 100% and RMSSD by 97.0%. The change of breathing pattern from controlled to spontaneous decreased significantly the HF component and pNN50, but did not affect SD1 or RMSSD. Rapid breathing rate (24 min(-1)) decreased the HF component, but had no effects on the other measures. A controlled breathing rate is needed for a reliable assessment of cardiac vagal outflow by the spectral analysis technique. The quantitative geometrical analysis of short-term RRI variability from the Poincare plots and the time domain measure RMSSD were not significantly affected by changes in the breathing rate, suggesting that these indices are more suitable for the measurement of cardiac vagal outflow during the 'free-running' ambulatory conditions.

Small‐rodent dynamics and predation

Abstract: The hypothesis that the regular multiannual population oscillations of boreal and arctic small rodents (voles and lemmings) are driven by predation is as old as the scientific study of rodent cycles itself Subsequently, for several decades, the predation hypothesis fell into disrepute, possibly because the views about predation and rodent dy- namics were too simplistic Here we review the work that has been done on the predation hypothesis primarily in Fennoscandia over the past decade Models of predator-prey interaction have been constructed for the least weasel (Mustela nivalis) and the field vole (Microtus agrestis), which are considered to be the key specialist predator and the key prey species in the multispecies communities in the boreal forest region in Fennoscandia The basic model has been parameterized with independent field data, and it predicts well the main features of the observed dynamics An extension of the model also including generalist and nomadic avian predators predicts correctly the well- documented and striking geographic gradient in rodent oscillations in Fennoscandia, with the amplitude and cycle period decreasing from north to south These geographic changes are attributed to the observed latitudinal change in the density of generalist and nomadic predators, which are expected to have a stabilizing effect on rodent dynamics We review the other observational, modeling, and experimental results bearing on the predation hypothesis and conclude that it accounts well for the broad patterns in rodent oscillations in Fennoscandia We discuss the application of the predation hypothesis to other regions in the northern hemisphere The predation hypothesis does not make predictions about multiannual and latitudinal changes in body size, behavior, and demography of ro- dents, which may have some population-dynamic consequences With the current evidence, however, we consider it unlikely that the phenotypic and genotypic composition of pop- ulations would be instrumental for generating the broad patterns in rodent oscillations

A role for estrogen receptor β in the regulation of growth of the ventral prostate

Abstract: In normal rats and mice, immunostaining with specific antibodies revealed that nuclei of most prostatic epithelial cells harbor estrogen receptor beta (ERbeta). In rat ventral prostate, 530- and 549-aa isoforms of the receptor were identified. These sediment in the 4S region of low-salt sucrose gradients, indicating that prostatic ERbeta does not contain the same protein chaperones that are associated with ERalpha. Estradiol (E(2)) binding and ERbeta immunoreactivity coincide on the gradient, with no indication of ERalpha. In prostates from mice in which the ERbeta gene has been inactivated (BERKO), androgen receptor (AR) levels are elevated, and the tissue contains multiple hyperplastic foci. Most epithelial cells express the proliferation antigen Ki-67. In contrast, prostatic epithelium from wild-type littermates is single layered with no hyperplasia, and very few cells express Ki-67. Rat ventral prostate contains an estrogenic component, which comigrates on HPLC with the testosterone metabolite 5alpha-androstane-3beta,17beta-diol (3betaAdiol). This compound, which competes with E(2) for binding to ERbeta and elicits an estrogenic response in the aorta but not in the pituitary, decreases the AR content in prostates of wild-type mice but does not affect the elevated levels seen in ERbeta knockout (BERKO) mice. Thus ERbeta, probably as a complex with 3betaAdiol, is involved in regulating the AR content of the rodent prostate and in restraining epithelial growth. These findings suggest that ligands specific for ERbeta may be useful in the prevention and/or clinical management of prostatic hyperplasia and neoplasia.

Pore diameter of more than 100 microm is not requisite for bone ingrowth in rabbits.

Abstract: The optimal pore size for bone ingrowth is claimed to be 100-400 microm. With the use of a highly standardized experimental model, the present study reevaluated whether a pore size of 100 microm is the threshold value for bone ingrowth into porous structures under non-load-bearing conditions. Titanium triangle-shaped plates 250 or 500 microm thick were perforated with the use of a laser in order to create standard-sized holes ( 50, 75, 100, and 125 microm) in multiple rows. The amount of bone ingrowth through the implant holes was studied in the cancellous bone of the distal rabbit femur. Twelve weeks after implantation, detailed analysis of bone ingrowth was performed with computerized image analysis of backscattered electron imaging techniques of scanning electron microscopy. The results showed that the amount of ingrown new bone was independent of the pore size and implant thickness. The median value for bone ingrowth varied between 64 and 78%. A striking feature was the formation of secondary osteonal structures even in the smallest holes. Based on these results, there is no threshold value for new bone ingrowth in pore sizes ranging from 50 to 125 microm under non-load-bearing conditions.

Phosphorylation of serine 230 promotes inducible transcriptional activity of heat shock factor 1

Abstract: Heat shock factor 1 (HSF1) is a serine-rich constitutively phosphorylated mediator of the stress response. Upon stress, HSF1 forms DNA-binding trimers, relocalizes to nuclear granules, undergoes inducible phosphorylation and acquires the properties of a transactivator. HSF1 is phosphorylated on multiple sites, but the sites and their function have remained an enigma. Here, we have analyzed sites of endogenous phosphorylation on human HSF1 and developed a phosphopeptide antibody to identify Ser230 as a novel in vivo phosphorylation site. Ser230 is located in the regulatory domain of HSF1, and promotes the magnitude of the inducible transcriptional activity. Ser230 lies within a consensus site for calcium/calmodulin-dependent protein kinase II (CaMKII), and CaMKII overexpression enhances both the level of in vivo Ser230 phosphorylation and transactivation of HSF1. The importance of Ser230 was further established by the S230A HSF1 mutant showing markedly reduced activity relative to wild-type HSF1 when expressed in hsf1(-/-) cells. Our study provides the first evidence that phosphorylation is essential for the transcriptional activity of HSF1, and hence for induction of the heat shock response.

Feasibility of genetic and immunological prediction of Type I diabetes in a population-based birth cohort

Abstract: Aims/hypothesis. Population-wide genetic screening of susceptibility to multifactorial diseases will become relevant as knowledge of the pathogenesis of these diseases increases and preventive interventions are identified. Methods. Feasibility and acceptance of neonatal genetic screening for Type I (insulin-dependent) diabetes mellitus susceptibility and adherence of the at-risk children to frequent autoantibody follow-up were studied. Screening was offered to all families. The infants with HLA-DQB1 genotypes *02/*0302 and *0302/x (x?*02, *0301, *0602) were invited to autoantibody follow-up. The children who developed signs of β-cell autoimmunity were invited to a separate prevention trial. Results. The parents of 31 526 babies born between November 1994 and April 1999 (94.4 % of those eligible) agreed to genetic screening. We found that 4651 infants (14.8 %) had increased genetic risk (2.5 to 15 times that of the general population) for Type I (insulin-dependent) diabetes mellitus, and 80 % of them joined the autoantibody surveillance. At the age of 1, 2, 3 and 4 years, 74, 69, 68 and 76 % of the at-risk children, respectively, attended the follow-up. A total of 17 of the 22 children (77 %) who were born during the study period and have developed diabetes carry the risk genotypes we currently use for screening. Conclusions/interpretation. Population-based screening of genetic susceptibility for Type I diabetes, linked with a possibility to participate later in a prevention trial, is highly accepted in Finland and identifies about 75 % of those developing diabetes at an early age. Families adhere well to the frequent measurement of signs of β-cell autoimmunity in the children at-risk. [Diabetologia (2001) 44: 290–297]

A Signal, from Human mtDNA, of Postglacial Recolonization in Europe

Abstract: Mitochondrial HVS-I sequences from 10,365 subjects belonging to 56 populations/geographical regions of western Eurasia and northern Africa were first surveyed for the presence of the T→C transition at nucleotide position 16298, a mutation which has previously been shown to characterize haplogroup V mtDNAs. All mtDNAs with this mutation were then screened for a number of diagnostic RFLP sites, revealing two major subsets of mtDNAs. One is haplogroup V proper, and the other has been termed “pre*V,” since it predates V phylogenetically. The rather uncommon pre*V tends to be scattered throughout Europe (and northwestern Africa), whereas V attains two peaks of frequency: one situated in southwestern Europe and one in the Saami of northern Scandinavia. Geographical distributions and ages support the scenario that pre*V originated in Europe before the Last Glacial Maximum (LGM), whereas the more recently derived haplogroup V arose in a southwestern European refugium soon after the LGM. The arrival of V in eastern/central Europe, however, occurred much later, possibly with (post-)Neolithic contacts. The distribution of haplogroup V mtDNAs in modern European populations would thus, at least in part, reflect the pattern of postglacial human recolonization from that refugium, affecting even the Saami. Overall, the present study shows that the dissection of mtDNA variation into small and well-defined evolutionary units is an essential step in the identification of spatial frequency patterns. Mass screening of a few markers identified using complete mtDNA sequences promises to be an efficient strategy for inferring features of human prehistory.

The Tec family of cytoplasmic tyrosine kinases: mammalian Btk, Bmx, Itk, Tec, Txk and homologs in other species

Abstract: Cytoplasmic protein-tyrosine kinases (PTKs) are enzymes involved in transducing a vast number of signals in metazoans, The importance of the Tec family of kinases was immediately recognized when, i ...

Cardiomyocyte apoptosis and ventricular remodeling after myocardial infarction in rats.

Abstract: We investigated the role of cardiomyocyte apoptosis in the remodeling of the left ventricle from 24 h to 12 wk after myocardial infarction in the rat. Infarct size planimetry, quantification of cardiomyocyte apoptosis, terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL) methodology, and echocardiography (left ventricular diastolic diameter and ejection fraction) were performed. Sham-operated animals showed low rates of cardiomyocyte apoptosis (0.03%) and no change in diastolic diameter or ejection fraction during the study. Twenty-four hours after infarction, TUNEL positivity was high in the infarct areas (1.4%) and border zones (4.9%). It declined to 0.34% (P 50%) to the apoptotic cell loss by 4 wk.

Fatty acid composition of lipids in sea buckthorn (Hippophaë rhamnoides L.) berries of different origins.

Abstract: The oil content and fatty acid composition of berries from two subspecies of sea buckthorn (Hippophae rhamnoides L.) were investigated. The berries of subsp. rhamnoides contained a higher proportio...

Europium Nanoparticles and Time-resolved Fluorescence for Ultrasensitive Detection of Prostate-specific Antigen

Abstract: Background: Nanoparticle-based detection technologies have the potential to improve detection sensitivity in miniature as well as in conventional biochemical assays. We introduce a detection technology that relies on the use of europium(III) nanoparticles and time-resolved fluorometry to improve the detection limit of biochemical assays and to visualize individual molecules in a microtiter plate format. Methods: Streptavidin was covalently coated on 107-nm nanoparticles containing >30 000 europium molecules entrapped with β-diketones. In a model assay system, these nanoparticles were used to trace biotinylated prostate-specific antigen (PSA) in a microtiter plate format. Results: The detection limit (mean + 3 SD of the zero calibrator) of biotinylated PSA was 0.38 ng/L, corresponding to 10 fmol/L or 60 zeptomoles (60 × 10−21 moles) of PSA. Moreover, single nanoparticles, representing individual PSA molecules, were visualized in the same microtiter wells with a time-resolved fluorescence microscope using a ×10 objective. Single nanoparticles, possessing high specific activity, were also detected in solution by a standard time-resolved plate fluorometer. Conclusions: The universal streptavidin-coated europium(III) nanoparticle label is suitable for detection of any biotinylated molecule either in solution or on a solid phase. The europium(III) nanoparticle labeling technology is applicable to many areas of modern biochemical analysis, such as immunochemical and multianalyte DNA-chip assays as well as histo- and cytochemistry to improve detection sensitivities.

Regional differences in semen quality in Europe

Abstract: Recent reports have indicated a decrease in semen quality of men in some countries, and suggested regional differences. A study was undertaken of semen samples from 1082 fertile men from four European cities (Copenhagen, Denmark; Paris, France; Edinburgh, Scotland; and Turku, Finland). Semen analysis was standardized, interlaboratory differences in assessment of sperm concentration were evaluated, and morphology assessment centralized. Lowest sperm concentrations and total counts were detected for Danish men, followed by French and Scottish men. Finnish men had the highest sperm counts. Men from Edinburgh had the highest proportion of motile spermatozoa, followed by men from Turku, Copenhagen and Paris. Only the differences between Paris/Edinburgh and Paris/ Turku were statistically significant (P < 0.003 and P < 0.002 respectively). No significant differences in morphology were detected. A general seasonal variation in sperm concentration (summer 70% of winter) and total sperm count (summer 72% of winter) was detected. Semen quality of a 'standardized' man (30 years old, fertile, ejaculation abstinence of 96 h) were estimated. Typically, sperm concentrations (× 10 6 /ml) for winter/summer were: Turku 132/93; Edinburgh 119/84; Paris 103/73; and Copenhagen 98/69. These differences in semen quality may indicate different environmental exposures or lifestyle changes in the four populations. However, it remains to be seen whether such changes can account for these differences. These data may also serve as a reference point for future studies on time trends in semen quality in Europe.

Characterization of the properties of human- and dairy-derived probiotics for prevention of infectious diseases in fish.

Abstract: The present study aimed to investigate the potential probiotic properties of six lactic acid bacteria (LAB) intended for human use, Lactobacillus rhamnosus ATCC 53103, Lactobacillus casei Shirota, Lactobacillus bulgaricus, L. rhamnosus LC 705, Bifidobacterium lactis Bb12, and Lactobacillus johnsonii La1, and one for animal use, Enterococcus faecium Tehobak, for use as a fish probiotic. The strains for human use were specifically chosen since they are known to be safe for human use, which is of major importance because the fish are meant for human consumption. The selection was carried out by five different methods: mucosal adhesion, mucosal penetration, inhibition of pathogen growth and adhesion, and resistance to fish bile. The adhesion abilities of the seven LAB and three fish pathogens, Vibrio anguillarum, Aeromonas salmonicida, and Flavobacterium psychrophilum, were determined to mucus from five different sites on the surface or in the gut of rainbow trout. Five of the tested LAB strains showed considerable adhesion to different fish mucus types (14 to 26% of the added bacteria). Despite their adhesive character, the LAB strains were not able to inhibit the mucus binding of A. salmonicida. Coculture experiments showed significant inhibition of growth of A. salmonicida, which was mediated by competition for nutrients rather than secretion of inhibitory substances by the probiotic bacteria as measured in spent culture liquid. All LAB except L. casei Shirota showed tolerance against fish bile. L. rhamnosus ATCC 53103 and L. bulgaricus were found to penetrate fish mucus better than other probiotic bacteria. Based on bile resistance, mucus adhesion, mucus penetration, and suppression of fish pathogen growth, L. rhamnosus ATCC 53103 and L. bulgaricus can be considered for future in vivo challenge studies in fish as a novel and safe treatment in aquaculture.

Trends in the incidence of cryptorchidism and hypospadias, and methodological limitations of registry-based data

Abstract: Cryptorchidism and hypospadias share possible risk factors, such as intrauterine growth retardation. According to the data collected by the International Clearinghouse for Birth Defects Monitoring Systems (ICBDMS), apparently increasing trends in the incidence of hypospadias were found in Sweden during the 1960s, and in Norway, Denmark, England and Hungary during the 1970s. In Norway and Denmark, the increase continued in the 1980s, while in the USA it has continued from the 1970s to the 1990s. Finland has shown a lower reported rate of hypospadias than other Nordic countries. However, it is difficult to make comparisons between countries because of variable inclusion criteria. Furthermore, the reliability of the data depends on correct ascertainment and reporting of the cases. The ICBDMS has also collected data on cryptorchidism, but these appear to be unreliable because of a discrepancy with the data from cohort studies. According to two comparable English studies, the incidence of cryptorchidism in full-term boys approximately doubled between the 1950s and the 1980s. Regionally there are large differences: e.g. in Finland the incidence of cryptorchidism is clearly lower than in Denmark. Regional and temporal trends may help to identify environmental factors that might be associated with these disorders.

Critical Aspects of Organizational Learning Research and Proposals for Its Measurement

Abstract: Based on an extensive literature review, this paper reveals several gaps in organizational learning (OL) research that need filling before we can really talk about a theory of organizational learning or verify the traits and very existence of learning organizations (LO) as a phenomenon. The critique, however, is not targeted at any single model or theory of organizational learning, but at theory building, which constantly drifts away with new definitions and approaches that break up rather than construct a theory. Despite the fact that numerous consultation tools for turning organizations into learning models have been developed and applied, the concept of organizational learning itself still remains vague and there is an urgent need for a holistic model of OL. Too much emphasis is put on studying the learning of individuals instead of concentrating on the learning of organizations. Since the theory is highly dispersed and does not really build on earlier findings, rich empirical studies are needed in order to validate measures of organizational learning. Modelling of the organizational learning process and clarification of how learning of individuals is turned into learning of organizations is needed. This paper introduces one set of OL measures developed to study whether organizational learning occurred during the operational and business culture change process of a single case company. Suggestions for further OL research are made on the basis of experiences gained when empirically testing this model.