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This work presents a numerical model to analyse the hygro-thermal behaviour of wooden bridge members. A multi-Fickian hygro-thermal model, previously implemented by some of the authors, is extended by including the dependency of wood sorption on temperature above and below zero degrees Celsius to predict moisture, temperature and relative humidity in wood under Northern European climates. The performance of the model in the presence of protective paints is particularly investigated. The finite element analysis based on the proposed model simulates the hygro-thermal behaviour of a glue-laminated beam of Älsvbacka Bridge located in Skellefteå (North of Sweden). The beam, coated by paints and claddings, was monitored by using wireless sensors in a previous research. Comparisons with the available measurements reveal that the numerical model is able to predict the moisture content in locations sheltered from rain and sun with moisture levels below the fibre saturation point. A study of the influence of different protective paints shows that the maximum and minimum moisture content at various depths along horizontal paths of the beam cross section, as well as the moisture gradients in different seasonal periods, are strongly affected by the type of paint. The proposed numerical approach is a promising tool to facilitate sensor-based monitoring techniques and to optimize the choice of protective paints for improved performance of timber bridges and other wooden structures under variable climates.

Identifying design variations that strike the balance between environmental, energy and cost can be aided using multi-objective optimization. From the resulting Pareto-solutions, selecting a single optimal solution remains a challenge. Thus, research is still needed to increase the practical use of optimization for architectural, engineering and construction (AEC) practitioners. This paper presents the use of an optimization approach where the results and an environmental assessment are discussed with AEC practitioners. The method was tested in two case studies: a prestige tourist cottage and a multifamily residential building. Different superstructures, insulation materials and windows were varied for the cottage’s envelope whilst evaluating life-cycle energy and cost. In addition, the environmental impact in terms of CO2 emissions was evaluated for the initial and optimal design suggestions for the two different superstructures. For the residential building, the insulation material thickness and the windows were varied for its evaluation of life-cycle energy and cost. For the cottage, a report was written and then read by the practitioners and used as a base for future decisions. For the residential building, the results were presented orally for the practitioners. In both cases, it was possible to communicate the overarching results of the optimizations through visual plots, although future research should find ways to also explain the detailed results. Godkänd;2020;Nivå 0;2020-05-05 (alebob);Konferensartikel i tidskrift

Objectives Amelogenesis imperfecta (AI) is a rare, genetically determined defect in enamel mineralization. Several problems are associated with AI: hypersensitivity, wear, restorations requiring replacement, gingivitis, aesthetic problems, and social avoidance. We conducted a randomized controlled trial of crown therapy in young individuals with AI showing excellent results. This study reports results from a long-term-follow-up with focus on quality, longevity and adverse events. Methods The RCT included 27 patients (aged 11–22 years) with severe AI in need of crown therapy and used a split-mouth technique. After placing 119 Procera® crowns and 108 IPS e.max Press crowns following randomization, we assessed longevity, quality, adverse events, and tooth sensitivity and calculated survival rates and success rates. Results We followed the original 227 crowns for 4.3–7.4 years (mean 5.5 ± 0.8). In all, 79% (193) crowns were followed for at least 5 years. The survival rate was 99.6% and the success rate, 94.7%; 95% of the crowns had excellent or acceptable quality. Due to suboptimal marginal integrity, 4% of the crowns required adjustment. Sensitivity problems decreased after crown therapy (p Conclusions Ceramic crown therapy in adolescents and young adults with severe forms of AI show excellent survival and success rates and longevity with few adverse events. Clinical significance Ceramic crown therapy can be recommended for adolescents and young adults with severe forms of amelogenesis imperfecta.

Research on patient safety has indicated that focusing on technologies, routines, control systems, and individual caregiver attributes is not sufficient. The aim of this critical-incident interview study was to identify organizational and social-psychological conditions and processes that Swedish physicians and nurses (n = 36) perceived as important for patient and/or staff safety, and participative safety behavior. Injury due to psychological overload was the most salient type of healthcare worker hazard. Patient and healthcare worker safety went hand in hand. Good patient safety was present when caregivers had good access to their psychological and social capacities. These functions were jeopardized by stress. Our results indicated that quantitative overload, excessive cognitive and emotional complexity, lack of social support and good teamwork, organizational instability, and distrust for and frustration with the way healthcare organizations were managed, caused stress related function impairment in staff, which lead to mistakes and near misses. These aspects also in themselves contributed to risks. Good safety was associated with adequate resources and routines, workplace learning, and supportive unit level managers and colleagues. Features of professional cultures related to ethical norms to offer best possible care for the patient, in spite of insufficient resources, contributed to acceptance of working conditions that could lead to stress and overload.

The longevity of dental restorations in patients with amelogenesis imperfecta (AI) is limited. The aim of this paper is to compare oral health and longevity of dental restorations in a group of young patients with AI compared to a control group.Patients included were 82 patients with AI, 40 boys and 42 girls, 6 to 25 years old (mean age 14.5±4.3 years) and a control group matched in age, gender and residential area. All patients received an examination recording dental caries, gingivitis, previous therapy, replaced restorations, tooth sensitivity, and number of dental visits. Patient dental records, extending from 6 to 10 years before the study, provided data on previous care.Annual mean number of dental visits in the AI group was 2.9±1.7 compared to 1.9±1.2 in the control group (p0.001). DMFS was 8.1±15.6 in the AI group compared to 1.0±2.0 in the control group (p0.001). The longevity of dental restorations was significantly lower in the patients with AI, with 24.7±35.1% of the AI group requiring replacement of fillings during the observation period compared to 9.23±23.7% in the control group (p=0.001). Patients with hypomineralized/hypomaturized AI have restorations of shorter longevity than those with hypoplastic AI (p0.01). Porcelain crowns had significantly longer survival than composite resin materials in the AI group (p0.001). Clinical Significance This study shows the need for long-lasting restorative solutions for patients with AI. It also shows the importance of establishing an early permanent therapy plan for these patients to avoid frequent dental visits.

We investigated the effects of LMX in leader and member ratings on leader and member creative performance among 137 leader–member dyads in academic and commercial R&D groups. By using the sub-dimensions of LMX-MDM (affect, loyalty, contribution, and professional respect) we wanted to show which dimensions of the leader–member relationship that is beneficial to creative performance. Analyses were conducted with consideration to nesting and dependencies occurring in the data. Findings indicated that certain sub-dimensions of exchanges between leaders and followers are substantive for creative performance in either positive or negative ways, depending on academic and commercial setting. LMX sub-dimensions were also differently related to creative performance depending on leaders' or members' perspective. The mixed results of this study indicate that LMX theory needs further analysis from a multidimensional, multitarget, and multilevel perspective.

Although there is a plethora of questionnaire instruments for measuring safety climate or culture, very few have proven able to present a factor structure that is consistent in different contexts, and many have a vague theoretical grounding. The Nordic Safety Climate Questionnaire (NOSACQ-50) was developed by a team of Nordic occupational safety researchers based on organizational and safety climate theory, psychological theory, previous empirical research, empirical results acquired through international studies, and a continuous development process. Safety climate is defined as workgroup members’ shared perceptions of management and workgroup safety related policies, procedures and practices. NOSACQ50 consists of 50 items across seven dimensions, i.e. shared perceptions of: 1) management safety priority, commitment and competence; 2) management safety empowerment; and 3) management safety justice; as well as shared perceptions of 4) workers’ safety commitment; 5) workers’ safety priority and risk non-acceptance; 6) safety communication, learning, and trust in co-workers’ safety competence; and 7) workers’ trust in the efficacy of safety systems. Initial versions of the instrument were tested for validity and reliability in four separate Nordic studies using native language versions in each respective Nordic country. NOSACQ-50 was found to be a reliable instrument for measuring safety climate, and valid for predicting safety motivation, perceived safety level, and self-rated safety behavior. The validity of NOSACQ-50 was further confirmed by its ability to distinguish between organizational units through detecting significant differences in safety climate. Relevance to industry: NOSACQ-50 will enable comparative studies of safety climate between and within companies, industries and countries. It is suitable for research purposes as well as for practical use in evaluating safety climate status, as a diagnostic tool, and in evaluating the effect of safety climate interventions.

Psychological climate has shown reliable relations to work outcomes. In the present study focus was placed on the significance of psychological climate for occupational safety. To gain further understanding of how to improve safety in organisations, mechanisms by which psychological climate may influence safety behaviour were investigated. A questionnaire survey was conducted among blue-collar construction workers (n = 189). Data were analysed using structural equation modelling (SEM). The results showed that psychological climate has direct and indirect relations to safety behaviour, and safety motivation and safety knowledge were found to be key mediators in explaining these relations.

The present paper investigates the dimensionality of safety climate, tests a hypothesis of sharedness among members in a social unit as a characteristic of safety climate and tests the predictive validity of safety climate with regard to safety behaviour. The dimensionality of safety climate reported by [Cheyne, A., Cox, S., Oliver, A., Tomas, J.M., 1998. Modelling safety climate in the prediction of levels of safety activity. Work and Stress, 12 (3), 255-271.] was successfully replicated in three different samples (N1 = 242, N2 = 275, N3 = 284) in Swedish construction industry. Support was found for a hypothesis of a second order safety climate factor. A theoretically suggested distinction between safety climate and individual safety attitudes was supported. Safety climate was found to significantly predict self-reported safety behaviour 7 months later. This was true also with previous safety behaviour under control, supporting a causal relationship between safety climate and how workers behave with regard to safety.

Ezrin is a key signaling molecule that regulates cell survival, adhesion migration, and invasion. We have previously shown that ezrin is regulated by androgen in rat prostate and that its expression is increased in prostate cancer and in prostate intraepithelial neoplasia. We have used the androgen-sensitive cell line LNCaP-FGC to investigate the role of ezrin in androgen-induced cell invasion. We found that androgen treatment of LNCaP-FGC cells induces ezrin expression, an effect that is inhibited by the androgen receptor antagonist, bicalutamide. In addition, androgen treatment induces the phosphorylation of ezrin in Thr-567 and Tyr-353 in a sequential manner. This is mediated through protein kinase C alpha and Src tyrosine kinase, respectively. Androgen treatment induces the translocation of both protein kinase C alpha and ezrin to the cell membrane and their association. Inhibition of ezrin function using short interference RNA or the overexpression of T567A and Y353F-ezrin mutants significantly reduces androgen-induced Matrigel invasion but does not affect cell proliferation or cell adhesion. Matrigel invasion of the androgen-insensitive prostate cancer cell lines PC-3 and LNCaP-R is also dependent on ezrin. In summary, we have shown that androgens regulate ezrin at transcriptional and posttranscriptional levels. Hormonal regulation of ezrin phosphorylation is required for androgen-induced cell invasion.

Objectives To study the protein expression and gene copy number of ezrin in a set of high-grade prostatic intraepithelial neoplasia (HGPIN) samples with concomitant prostate cancer. Ezrin is a cytoskeleton linker protein that is actively involved in regulating the growth and metastatic capacity of cancer cells. Methods Nineteen HGPIN samples obtained from radical prostatectomy specimens were used for the study. Among them, 13 samples also contained invasive prostate cancer. The expression of ezrin was studied by immunohistochemistry. The same samples were also used for fluorescence in situ hybridization to study the gene copy number of ezrin. Results Immunoreactivity for ezrin was absent or weak in benign prostatic epithelial cells. Weak or moderate immunostaining was detected in 11 of 13 prostate cancer specimens. However, the immunostaining was moderate or strong in all HGPIN samples. In addition, whenever HGPIN and prostate cancer were found in the same sample, the staining was always more intense in the HGPIN cells than in the cancer cells. No alteration was found in the gene copy number detected by fluorescence in situ hybridization. Conclusions We have shown that ezrin is overexpressed in HGPIN and prostate cancer compared with adjacent benign prostatic epithelium. In addition, HGPIN has a greater expression level of ezrin compared with that of prostate cancer. Our results indicate that aberrant expression of ezrin might be involved in the pathogenesis of prostate cancer, and ezrin expression may be useful for the diagnosis of HGPIN.

Objective: To study effects of estrogens on endothelin-1 (ET-1) mRNA expression in the androgen-sensitive LNCaP-FGC cell line and its androgen-resistant derivative LNCaP-r. Further, if effects of estrone sulfate (E1S) are mediated via conversion to estradiol-17β (E2). Estrogens have been shown to down-regulate ET-1, a mediator of the osteoblastic response of bone to metastatic prostate cancer. Methods: Cells were grown in steroid-depleted medium and incubated for 2–4 and 48 hours with 0, 1, 10, and 100nM of either E1S or E2. mRNA levels were measured with an RT-PCR technique. Estrogen metabolism by LNCaP-FGC cells was studied by incubation with estrone (E1) and E1S at the same conditions, followed by determination of E1 and E2. Results: ET-1 mRNA expression in LNCaP-FGC cells was significantly suppressed by E2 and E1S following incubation for 2–4h but after 48h only by E2 at 1 and 10nM and in LNCaP-r cells only by E2 at 100nM following 2–4h of incubation. ET-1 mRNA expression was significantly higher in untreated LNCaP-r than in untreated LNCaP-FGC cells. E1 was efficiently transformed into E2 by LNCaP-FGC cells but very little to E1 and no E2 was formed from E1S. Conclusion: ET-1 mRNA expression in LNCaP-FGC can be inhibited by E2, but also by its prehormone E1S. The lack of formation of E2 from E1S suggests a mode of action not related to classical steroid receptors. The higher level of ET-1 mRNA expression found in LNCaP-r cells may reflect the capability of a hormone refractory tumor to maintain activity on its own, independently of known regulatory mechanisms such as sex steroids.

A human pancreas-specific protein (PASP), previously characterized as a serum marker for acute pancreatitis and pancreatic graft rejection, has been identified as pancreatic procarboxypeptidase B (PCPB). cDNAs encoding PASP/PCPB were isolated from a human pancreas cDNA library using a combination of nucleic acid hybridization screening and immunoscreening with antisera raised against native PASP. The deduced amino acid sequence of PASP/PCPB cDNA predicts the translation of a 416-amino acid preproenzyme with a 15-amino acid signal/leader peptide and a 95-amino acid activation peptide. The proenzyme portion of this protein has 76% identity with rat PCPB and 84% identity with bovine carboxypeptidase B. DNA and RNA blot analyses indicate that human PCPB mRNA (1,400 nucleotides) is transcribed from a single locus in the human genome in a tissue-specific fashion. N-terminal sequencing of native PASP and the specific immunoreactivity of bacterially expressed PASP/PCPB with native PASP antibodies confirm the identification of PASP as human pancreatic PCPB.

Serum concentrations of dehydroepiandrosterone sulphate (DHAS) were determined in 590 healthy women aged 20-87 yr. Simultaneous assays of dehydroepiandrosterone (DHA) were performed in 417 of the women. DHA and DHAS levels correlated negatively with age while the DHA/DHAS ratio proved to be unrelated to age. When values for 60 healthy men in the age range 20-84 yr were compared with those obtained in 60 randomly-selected healthy women who were exactly age-matched, the DHAS levels were found to be significantly lower and the DHA/DHAS ratios significantly higher in the women. These results might be of use in establishing normal clinical ranges for serum DHA, DHAS and the DHA/DHAS ratio in women.

The steroid binding properties of the human pancreatic estrogen binding protein (hEBP) in cytosol were studied by equilibrium dialysis. A high ligand specificity of the protein was revealed. hEBP in cytosol binds unconjugated steroid estrogens with a medium affinity (Kd = 10−7M) but does not bind conjugated estrogens or unconjugated androgens, gestagens, glucocorticoids or cholesterol. Quantitation of hEBP by radioimmunoassay in subcellular fractions of human pancreatic tissue indicated that the protein is translocated into different subcellular compartments. Duodenal juice taken from patients following stimulation of pancreatic secretion by food ingestion (Lund's test) showed high hEBP concentrations, and the levels of hEBP changed concomitantly with the levels of pancreatic isoamylase, indicating that hEBP secretion was stimulated by food ingestion. The levels of hEBP in peripheral serum from healthy subjects showed no sex difference, but were positively correlated to age. Highly elevated (10–20-fold) hEBP levels were found in serum from patients wih acute pancreatitis, while normal serum hEBP values were found in other abdominal diseases. It is speculated that hEBP might have a specific role in the transport of estrogens from the peripheral circulation via the pancreas to the duodenum. The elevated hEBP levels in patients with acute pancreatitis indicate that this protein may be used as a marker of cellular damage in the pancreas.

A radioimmunoassay for quantitation of the human pancreatic estrogen binding protein (hEBP) was developed using polyclonal rabbit hEBP antiserum and iodinated purified hEBP. Parallel dose-response curves were obtained when serial dilutions of human serum and of cytosols obtained from human pancreas, prostate and colon were analyzed simultaneously with serial dilutions of purified hEBP standard. Very high levels of hEBP (500–1000 mg/kg wet weight) were found in normal pancreas. High as well as medium levels were found in pancreatic carcinoma tissue and medium values (0.1–1 mg/kg wet weight) in prostate, colon and ovarian tissue. Other tissues and serum from healthy volunteers showed low values, usually below 0.1 mg/kg. When serial dilutions of rat pancreatic cytosol were analyzed in the hEBP assay, [ 125 I]hEBP was displaced by the rat preparation, but the dose-response curves were not parallel to the standard curves, indicating similarity but non-identity between the estrogen binding proteins in human and in rat pancreas.

Steroid metabolizing enzyme activities in rat liver may be classified according to their regulation. One group consists of enzymes, the activities of which are irreversibly determined at birth by androgens, a second group encompasses enzymes that are reversibly affected by androgens and a third group is made up of enzymes essentially independent of androgens. The mechanisms by which androgens influence hepatic enzyme activities are still not clear but the hypophysis seems to be essential for the sexual differentiation of liver metabolism in the rat. Possibly this control is exerted by a hypophyseal feminizing factor that feminizes a basal masculine enzyme pattern in rat liver. Some kind of direct androgen action on the liver cell may also be postulated since a radioactively labelled complex between 4-androstene-3,17-dione and a high affinity protein can be extracted from liver cytosol and nuclei after intrapertitoneal administration of [1,2,6,7- 3 H]-testosterone to castrated male and female rats. This androgen “receptor” moves as a 10 S protein when analysed by sucrose density gradient centrifugation, has a pI of about H5 when analysed by isoelectric focusing and is selectively concentrated in unlabelled liver nuclei when these are incubated with liver cytosol containing labelled androgen-protein complex.

3 H-labelled R 1881 (methyltrienolone) was bound with high affinity ( K d , 2 · 10 −9 M) and low capacity (11–15 fmol/mg protein) in prostate cytosol from rats castrated 18 h earlier. The binding was inhibited by 5α-dihydrotosterone, testosterone, cyproterone acetate and LEO 1727, but not by estradiol-17β, R 5020 or corticosterone. The 3 H-labelled R 1881-receptor complex was excluded from a Sephadex G-200 column, had a sedimentation coefficient of 3.5 S, was eluted from a DEAE-cellulose column at 0.2 M KCl concentration and precipitated between 20–40% of saturation of ammonium sulfate. 20% of specifically bound 3 H-labelled R 1881 was retained by DNA-cellulose at low ionic strength. The fraction which was not bound to DNA-cellulose did not bind either, after rechromatography, not even following heating at 20°C for 20 min or following fractionation with ammonium sulphate. In summary, the results indicate that the 3 H-labelled R 1881-receptor complex in rat prostate cytosol has characteristics similar to those of the 5μ-[ 3 H]-dihydrotestosterone-receptor complex.

The metabolism and binding of [1, 2, 6, 7-3H] testosterone in male and female rat brain has been studied in an attempt to find an explanation for the relative androgen unresponsiveness characterizing the female hypothalamo-pituitary axis involved in regulation of hepatic steroid metabolism. The most significant sex differences in the pattern of [3H] testosterone metabolites recovered from several brain regions (including pituitary, pineal gland, and hypothalamus) after intraperitoneal administration of [3H] testosterone were the predominance of testosterone and androstenedione in male brain compared to the quantitative importance of 5alpha-androstane-3alpha, 17beta-diol, 5alpha-androstane-3beta, 17beta-diol, epitestosterone, and dihydroepitestosterone in female brain. One possible explanation for the androgen unresponsiveness of female rats is, therefore, the faster metabolism of testosterone to inactive compounds in female brain. Experiments both in vivo and in vitro showed the presence of high affinity, low capacity binding sites for [3H] testosterone in male pituitary, pineal gland, and hypothalamus (Kd values in the region of 1 X 10(-10) to 1 X 10(-9) M and number of binding sites 1.0 to 1.4 X 10(-14) mol per mg of protein). The steroid - macromolecular complexes generally had a pI of 5.1, were excluded from Sephadex G-200, were heat-labile, and were sensitive to protease. Competition experiments indicated the following order of ligand affinities: testosterone is greater than 5alpha-dihydrotestosterone and estradiol is greater than androstenedione is greater than corticosterone. No steroid-binding proteins of similar nature were found in pituitary, pineal gland, or hypothalamus from female rats. On the basis of these results it is suggested that the androgen unresponsiveness of female rats referred to above relates to the absence of receptor protein for androgens in female rat brain. In support of this hypothesis, 28-day-old female rats, which are known to be affected by androgens with regard to liver enzyme activities, were shown to contain receptor proteins for androgen in the brain. In conclusion, the relative androgen unresponsiveness of the female hypothalamo-pituitary axis is probably explained by the absence of receptor proteins for androgen in female hypothalamus and pituitary. The fast metabolism of testosterone in female rat brain also serves to decrease the availability of active androgen to potential receptor sites. It may be speculated that the presence of androgen receptors in male brain is the result of neonatal programming ("imprinting") by testicular androgen.

At birth testicular androgens irreversibly programme hypothalamic centres involved in hypothalamopituitary control of hepatic sex-dependent steroid and drug metabolism. This imprinting process results in activation of a hypothalamic ‘feminostatin’—secreting centre that is turned on just before puberty. Feminostatin inhibits pituitary secretion of ‘feminotropin’, a novel pituitary hormone that feminizes the basal type of metabolism characterizing the autonomous liver, i.e. the liver of hypophysectomized and gonadectomized rats. Consequently, female rats that are devoid of feminostatin will secrete feminotropin from the pituitary, leading to a feminine type of hepatic metabolism. Male rats, on the other hand, have an active feminostatin-secreting centre and the inhibition of pituitary feminotropin release results in an autonomous type of liver metabolism. Full ‘masculinity’ of hepatic metabolism in male rats is induced by testicular androgens that act on the hypothalamo-pituitary axis to stimulate release of a pituitary ‘masculinizing factor’. Female rats show a relative androgen unresponsiveness and seem incapable of releasing masculinizing factor after treatment with androgens. A possible explanation for this is the absence of androgen receptor proteins in female brain as contrasted to the presence of androgen receptors in male pituitary, hypothalamus and pineal gland. It seems reasonable to assume on the basis of present knowledge that the level of androgen receptors in the central nervous system is programmed at the time of birth by testicular androgens. The hypothesis presented above has been based on results obtained from experiments involving hypophysectomy, pituitary transplants under the kidney capsule, electrothermic lesions in the hypothalamus, neonatal and postpubertal castrations, treatment with androgens and estrogens at various times during development and transplantations with different lines of pituitary tumour cells. The novel pituitary hormone, feminotropin, has also been studied in vitro using hepatoma (HTC) cells or isolated hepatocytes in tissue culture. Feminotropin increases the apparent 5α-reductase activity in HTC cells at subsaturation concentrations of substrate (androstenedione) by decreasing the K m value of the enzyme. Furthermore, feminotropin increases the apparent 5α/16α ratio in isolated hepatocytes, i.e. the ratio between total 5α-reduced and 16α-hydroxylated metabolites formed from androstenedione. Feminotropin has been shown to be different from any of the known pituitary hormones. It is stored in pituitary granules with a density of 1.13–1.17 g/cm 3 and has a molecular weight of about 20,000 daltons. Feminotropin is produced by isolated pituitary cells in primary culture and by certain lines of pituitary tumour cells, e.g. C 8 11RAP cells. Tissue culture medium from cultures of this cell line serves as source in our purification programme for feminotropin.

Recent advances in the field of steroid hormone receptors have opened up new possibilities to individualize the treatment of patients with malignancies in hormone-dependent tissues. Examples of tumours where steroid receptor assays have been shown to be or may be of value for planning of therapy are breast, prostatic and endometrial carcinoma and leukaemia. This article focuses on the first two cancer forms.