Cerebrospinal fluid biomarkers in twins with schizophrenia and bipolar disorder

Previously identified cerebrospinal fluid (CSF) biomarkers were studied in 37 twins with schizophrenia or bipolar disorder to determine their genetic and environmental properties. Further, comorbidities and sibling risks were investigated in patients with schizophrenia (n=22,781), bipolar disorder (n=30,761) and depression (n=172,479) in relation to multiple sclerosis (MS) (n=16,467) in a nationwide cohort. In Study I, CSF was analyzed using scanning electron microscopy in twins with schizophrenia and bipolar disorder to identify microscopic structures that had previously been established in patients with schizophrenia and bipolar disorder. Microscopic structures were found not only in the patients but also in the non-affected twin siblings to a higher degree than in healthy controls. The results indicate that genetic and shared environmental mechanisms might be involved in the development of CSF structures. Study II was a case series in which microparticles were studied in the CSF of healthy controls and in patients with schizophrenia. Microparticles may be indicative of stressinduced cell activation. In the patients with schizophrenia microparticles that originated from leukocyte and endothelial cells were accumulated in higher levels as compared with the healthy controls. In Study III, immune and amyloid biomarkers previously associated with psychotic disorders were analyzed in the CSF of twins. Soluble cluster of differentiation 14 (sCD14), a protein expressed by microglia in the central nervous system, was found to highly correlate within monozygotic twins. In the co-twin control analysis higher levels were observed in patients with schizophrenia and bipolar disorder compared with the nonaffected co-twins. sCD14 was also associated with negative psychotic symptoms and schizotypal and paranoid personality traits. The results strengthen previous findings of microglia activation in psychotic disorders. In Study IV, tryptophan metabolites and cytokines were analyzed in twins with schizophrenia and bipolar disorder. None of the substances correlated within the monozygotic twin pairs, which indicates the influence of environmental factors. Kynurenic and quinolinic acid were shown to be associated with schizotypal personality traits, strengthening previous results of an association between the tryptophan metabolites and psychosis. In Study V, comorbidity between the neuroinflammatory disorder MS and schizophrenia, bipolar disorder and depression was analyzed in a nationwide cohort. Consistent with previous studies an increased MS risk was noted in patients with bipolar disorder and depression. An increased MS risk was also found in males with a diagnosis of bipolar disorder and previous manic episodes. Decreased MS risk was seen in patients with schizophrenia. No change in MS risk was detected in the siblings to patients with schizophrenia, bipolar disorder and depression. Possible inflammatory mechanisms may account for the comorbidity between affective disorders and MS, whereas the protective effect of schizophrenia on MS risk remains to be further investigated. Biomarker analysis in CSF using twin methodology revealed some promising findings for future biomarker studies. However, larger twin cohorts are desirable for conclusive confirmation. The potential mechanisms underlying the associations between MS and psychiatric disorders require further study

BIM in construction production: Gains and hinders for firms, projects and industry

The construction industry strives to implement digitalization and Building Information Modelling (BIM). Studies of BIM in construction claim that a pronounced BIM strategy, knowledge of the subject and a willingness to change are important factors to succeed, but even when such conditions are in place, BIM implementation in construction production is scant and has limited impact. So how should the construction industry go from grand digital visions to practical application in reality? By identifying gains, obstacles and success factors on company, project and sector levels the paper aims to set out a road map for successful BIM implementation in construction production. Data sets, both qualitative and quantitative from eleven studies of using BIM in construction production, show that although the industry is making progresses in implementing BIM and digitalization, the full potential is far from realised. Specifically, the research presents an analysis of factors in relation to (1) strategy and innovation, (2) technology, (3) organizing, and (4) ecosystem. Conclusively, all these levels are strongly interdependent and need to be considered by adopting a holistic approach to reach an enhanced implementation

Multiple sclerosis and psychiatric disorders : comorbidity and sibling risk in a nationwide Swedish cohort

Background: Psychiatric disorders are known to be prevalent in Multiple Sclerosis (MS). Objective: To study comorbidity between MS and bipolar disorder, schizophrenia and depression in a nation-wide cohort and to determine whether shared genetic liability underlies the putative association. Methods: We identified ICD-diagnosed patients with MS (n=16,467), bipolar disorder (n=30,761), schizophrenia (n= 22,781) and depression (n=172,479) in the Swedish National Patient Register and identified their siblings in the Multi-Generation Register. The risk of MS was compared in psychiatric patients and in matched unexposed individuals. Shared familial risk between MS and psychiatric disorders was estimated by sibling comparison. Results: The risk of MS was increased in patients with bipolar disorder (hazard ratio [HR] 1.8, 95% confidence interval [CI] 1.6-2.2, p<0.0001) and depression (HR 1.9, 95% CI 1.7-2.0, p<0.0001). MS risk in schizophrenia was decreased (HR 0.6, 95% CI 0.4-0.9, p=0.005). The association between having a sibling with a psychiatric disorder and developing MS was not significant. Conclusion: We found a strong positive association between MS and bipolar disorder and depression that could not be explained by genetic liability. The unexpected negative association between MS and schizophrenia might be spurious or indicate possible protective mechanisms that warrant further exploration.Stockholm County CouncilThe Swedish Research CouncilKarolinska InstitutetAccepte

TOTAL BIM PROJECT: THE FUTURE OF A DIGITAL CONSTRUCTION PROCESS

Although the construction industry strives to implement Building Information Modeling (BIM) toimprove efficiency and quality, adoption in the actual construction phase is still limited. However, in Scandinavia,recent years have seen the rise of an idea known as Total BIM - An approach where the BIM is the legally bindingconstruction document and no traditional 2D-drawings are used on-site. In this paper we present a case study of asuccessful Total BIM project. We investigate the prerequisites for – and outcomes of – implementing the Total BIMconcept, where commonly found individual and isolated BIM uses is turned into an all-inclusive approach toachieve a more efficient design and construction process. Our analysis shows that the success was contingent onfactors from within several different areas, including strategy and innovation, organizing, and technology, but alsoon the commitment shown by the construction management company responsible for the project. In addition, threekey elements were identified; BIM as the legally binding construction document, cloud-based model management,and user-friendly on-site mobile BIM software

TOTAL BIM PROJECT: THE FUTURE OF A DIGITAL CONSTRUCTION PROCESS

Although the construction industry strives to implement Building Information Modeling (BIM) to improve efficiency and quality, adoption in the actual construction phase is still limited. However, in Scandinavia, recent years have seen the rise of an idea known as Total BIM - An approach where the BIM is the legally binding construction document and no traditional 2D drawings are used on-site. In this paper we present a case study of a successful Total BIM project. We investigate the prerequisites for – and outcomes of – implementing the Total BIM concept, where commonly found individual and isolated BIM uses is turned into an all-inclusive approach to achieve a more efficient design and construction process. Our analysis shows that the success was contingent on factors from within several different areas, including strategy and innovation, organizing, and technology, but also on the commitment shown by the construction management company responsible for the project. In addition, three key elements were identified; BIM as the legally binding construction document, cloud-based model management, and user-friendly on-site mobile BIM software

Cerebrospinal fluid microglia and neurodegenerative markers in twins concordant and discordant for psychotic disorders

International audienceThe jacket type offshore wind turbine transfers efficiently the horizontal load applied on the wind turbine to an axial load on the four piles of its foundation. The axial behaviour of one single pile of the foundation is investigated in a geotechnical centrifuge. The model pile, tested under a 100 g centrifuge acceleration, is designed to represent a cast-in-place pile with a 1.8 m diameter and a 40 m embedded length. The pile, installed in dense Fontainebleau sand, is instrumented with a load sensor at its end to measure the tip resistance. By subtracting the total load applied on the pile, its shaft capacity is also calculated. Different axial loading paths are applied: i) monotonic loadings in compression and tension to obtain ultimate capacities and ii) cyclic loadings which represent a more realistic loading path applied by the jacket during its life time in order to observe the tip and shaft capacities reductions

Growth hormone and somatolactin function during sexual maturation of female Atlantic salmon

Background and aims: The growth hormone-insulin-like growth factor I (GH-IGF-I) system is known to act during sexual maturation of female salmonids, but the specific roles are not known. Somatolactin (SL) is a pituitary hormone closely related to GH and is only found in fish. In some species, including salmonids, there are two forms, SLa and SLß. The SL receptor (SLR) has recently been cloned and phylogenetic analysis shows that it is similar to previously cloned GH receptors (GHRs) of non-salmonids. The ligand-specificity of the GHR/SLR is unclear. Little is known about the role of the SLs in sexual maturation of fish. The aim of this thesis has been to increase our knowledge about the regulatory role(s) of both the GH-IGF-I system and of SLs during sexual maturation in female Atlantic salmon. Methods: The cDNA sequences of Atlantic salmon GHRs (two isoforms), SLR, as well as SLa and SLß were obtained with the goals of carrying out a phylogenetic analysis, and of developing molecular tools for analysis of mRNA levels using real time quantitative PCR (RTqPCR). The roles of GH, IGF-I and SL were examined in a 17-month long study on one sea winter Atlantic salmon females. mRNA expression levels of ovarian components of the GH-IGF-I system and SLR and pituitary GH, SLa and SLß were studied by RTqPCR. Levels of GH and IGF-I in plasma, and of GH in the pituitary were measured by radio-immunoassay. Results and Conclusions: The phylogenetic analysis (Paper I and II) of the cloned sequences reveals the placement of Atlantic salmon GHR in the GHR type II clade and SLR in the controversial GHR type I clade (putative SLRs). Concurrent analyses of pituitary GH mRNA levels, GH protein and plasma GH in the same individual fish demonstrates the complex dynamics of the GH system, which is inhibited by a continuous light. Papers III and IV confirm that there is an active GH-IGF-I-gonad axis in the female Atlantic salmon that appears to be functional at the start of exogenous vitellogenesis, final oocyte growth, spawning and possibly during postovulatory events. Evidence has been found for a photoperiod-driven GH-system activation which is initiated in January with stimulation of GH secretion from pituitary somatotropes. The role of this activation of the GH system in late winter/early spring appears to be the reversal of a prior plasma IGF-I and ovarian IGF-I mRNA downregulation driven by an unknown factor(s). This downregulation in IGF-I is thought to inhibit somatic cell proliferation. The activation of the GH-IGF-I-gonadal system also appears to limit energy allocation to gonadal growth. This series of events involving the GH-IGF-I system appears to take place during the so-called spring window of opportunity and it is the first time this has been described. The GH-IGF-I system also appears to have an important role during final oocyte growth, spawning and post-spawning events. SLa and SLß are both actively regulated during sexual maturation and could have several roles, such as signaling the status of visceral fat reserves during the spring window of opportunity, signaling lipid metabolic status before the onset of anorexia, involvement in Ca mobilization during vitellogenesis and/or control of lipid metabolism in lieu of GH during the final stages of oocyte growth

Intake estimation of total and individual flavan-3-ols, proanthocyanidins and theaflavins, their food sources and determinants in the European Prospective Investigation into Cancer and Nutrition (EPIC) study

Epidemiological studies suggest health-protective effects of flavan-3-ols and their derived compounds on chronic diseases. The present study aimed to estimate dietary flavan-3-ol, proanthocyanidin (PA) and theaflavin intakes, their food sources and potential determinants in the European Prospective Investigation into Cancer and Nutrition (EPIC) calibration cohort. Dietary data were collected using a standardised 24 h dietary recall software administered to 36 037 subjects aged 35-74 years. Dietary data were linked with a flavanoid food composition database compiled from the latest US Department of Agriculture and Phenol-Explorer databases and expanded to include recipes, estimations and retention factors. Total flavan-3-ol intake was the highest in UK Health-conscious men (453·6 mg/d) and women of UK General population (377·6 mg/d), while the intake was the lowest in Greece (men: 160·5 mg/d; women: 124·8 mg/d). Monomer intake was the highest in UK General population (men: 213·5 mg/d; women: 178·6 mg/d) and the lowest in Greece (men: 26·6 mg/d in men; women: 20·7 mg/d). Theaflavin intake was the highest in UK General population (men: 29·3 mg/d; women: 25·3 mg/d) and close to zero in Greece and Spain. PA intake was the highest in Asturias (men: 455·2 mg/d) and San Sebastian (women: 253 mg/d), while being the lowest in Greece (men: 134·6 mg/d; women: 101·0 mg/d). Except for the UK, non-citrus fruits (apples/pears) were the highest contributors to the total flavan-3-ol intake. Tea was the main contributor of total flavan-3-ols in the UK. Flavan-3-ol, PA and theaflavin intakes were significantly different among all assessed groups. This study showed heterogeneity in flavan-3-ol, PA and theaflavin intake throughout the EPIC countries

Estimation of the intake of anthocyanidins and their food sources in the European prospective investigation into cancer and nutrition (EPIC) study

Anthocyanidins are bioactive flavonoids with potential health-promoting effects. These may vary among single anthocyanidins considering differences in their bioavailability and some of the mechanisms involved. The aim of the present study was to estimate the dietary intake of anthocyanidins, their food sources and the lifestyle factors (sex, age, BMI, smoking status, educational level and physisical activity) involved among twenty-seven centres in ten European countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Anthocyanidin intake and their food sources for 36 037 subjects, aged between 35 and 74 years, in twenty-seven redefined centres were obtained using standardised 24 h dietary recall software (EPIC-SOFT). An ad hoc food composition database on anthocyanidins (cyanidin, delphinidin, malvidin, pelargonidin, peonidin, petunidin) was compiled using data from the US Department of Agriculture and Phenol-Explorer databases and was expanded by adding recipes, estimated values and cooking factors. For men, the total anthocyanidin mean intake ranged from 19·83 (se 1·53) mg/d (Bilthoven, The Netherlands) to 64·88 (se 1·86) mg/d (Turin, Italy), whereas for women the range was 18·73 (se 2·80) mg/d (Granada, Spain) to 44·08 (se 2·45) mg/d (Turin, Italy). A clear south to north gradient intake was observed. Cyanidins and malvidins were the main anthocynidin contributors depending on the region and sex. Anthocyanidin intake was higher in non-obese older females, non-smokers, and increased with educational level and physical activity. The major food sources were fruits, wine, non-alcoholic beverages and some vegetables. The present study shows differences in both total and individual anthocyanidin intakes and various lifestyle factors throughout Europe, with some geographical variability in their food sources