Nutrimetabolomics fingerprinting to identify biomarkers of bread exposure in a free-living population from the PREDIMED study cohort

Bread is one of the most widely consumed foods. Its impact on human health is currently of special interest for researchers. We aimed to identify biomarkers of bread consumption by applying a nutrimetabolomic approach to a free-living population. An untargeted HPLC q-TOF-MS and multivariate analysis was applied to human urine from 155 subjects stratified by habitual bread consumption in three groups: non-consumers of bread (n = 56), white-bread consumers (n = 48) and whole-grain bread consumers (n = 51). The most differential metabolites (variable importance for projection ≥1.5) included compounds originating from cereal plant phytochemicals such as benzoxazinoids and alkylresorcinol metabolites, and compounds produced by gut microbiota (such as enterolactones, hydroxybenzoic and dihydroferulic acid metabolites). Pyrraline, riboflavin, 3-indolecarboxylic acid glucuronide, 2,8-dihydroxyquinoline glucuronide and N-α-acetylcitrulline were also tentatively identified. In order to combine multiple metabolites in a model to predict bread consumption, a stepwise logistic regression analysis was used. Receiver operating curves were constructed to evaluate the global performance of individual metabolites and their combination. The area under the curve values [AUC (95 % CI)] of combined models ranged from 77.8 % (69.1 86.4 %) to 93.7 % (89.4 98.1 %), whereas the AUC for the metabolites included in the models had weak values when they were evaluated individually: from 58.1 % (46.6 69.7 %) to 78.4 % (69.8 87.1 %). Our study showed that a daily bread intake significantly impacted on the urinary metabolome, despite being examined under uncontrolled free-living conditions. We further concluded that a combination of several biomarkers of exposure is better than a single biomarker for the predictive ability of discriminative analysis.

Avaliação de risco ambiental de ambientes aquáticos afetados pelo uso de agrotóxicos

Ecological risk assessment is a process evaluating the likelihood that adverse ecological effects may occur or are occurring as a result of exposure to one or more substances. Relevant information needed to predict risks from pesticides includes their physical chemical properties, mobility in soil, persistence in the environment, and bioaccumulation and toxicity in relevant organisms. Although currently a requirement for pesticide registration in Brazil, this process is not yet fully implemented in the country. This review aims to outline the principles of environmental risk assessment for pesticides, focusing on aquatic organisms, and to discuss the studies and efforts conducted in Brazil in this area.

Managing regulatory risks when outsourcing network-related services in the electricity distribution sector

Deregulation of the electricity sector liberated the electricity sale and production for competitive forces while in the network business, electricity transmission and distribution, natural monopoly positions were recognised. Deregulation was accompanied by efficiencyoriented thinking on the whole electricity supply industry. For electricity distribution this meant a transition from a public service towards profit-driven business guided by economic regulation. Regulation is the primary means to enforce societal and other goals in the regulated monopoly sector. The design of economic regulation is concerned with two main attributes; end-customer price and quality of electricity distribution services. Regulation limits the costs of the regulated company but also defines the desired quality of monopoly services. The characteristics of the regulatory framework and the incentives it provides are therefore decisive for the electricity distribution sector. Regulation is not a static factor; changes in the regulatory practices cause discontinuity points, which in turn generate risks. A variety of social and environmental concerns together with technological advancements have emphasised the relevance of quality regulation, which is expected to lead to the large-scale replacement of overhead lines with underground cables. The electricity network construction activity is therefore currently witnessing revolutionary changes in its competitive landscape. In a business characterised by high statutory involvement and a high level of sunk costs, recognising and understanding the regulatory risks becomes a key success factor. As a response, electricity distribution companies have turned into outsourcing to attain efficiency and quality goals. This doctoral thesis addresses the impacts of regulatory risks on electricity network construction, which is a commonly outsourced activity in the electricity distribution network sector. The chosen research approach is characterised as an action analytical research on account of the fact that regulatory risks are greatly dependent on the individual nature of the regulatory regime applied in the electricity distribution sector. The main contribution of this doctoral thesis is to develop a concept for recognising and managing the business risks stemming from economic regulation. The degree of outsourcing in the sector is expected to increase in years to come. The results of the research provide new knowledge to manage the regulatory risks when outsourcing services.

Investment risks in Russia: A Finnish perspective

Purpose of this study is to analyze the effect of Russia's economic environment changes in the total return indexes of Finnish companies. The research data consisted of Finnish publicly listed companies, which have made physical investments to Russia, and operating in the area. The study used six different variables to model the Russian operating environment. The data consists of total return indexes of Finnish companies. From those we calculated the monthly mean interval between timeline of 1 January 2000 to 31 December 2009. Sample period is divided into two different parts. Variables impact on companies' total return indices is tested by regression analysis. By F-test we tested significance of model and squared coefficient correlation told us how much model explains from changes. Goodness of the β-coefficient is tested in the model by t-test. The research results shows that the Russian operating environment, or changes in which the active Finnish companies in total return indices. On partial sample periods results were not so significant.

The analysis and mitigation of risks in FMCG supply chain: the case of British American Tobacco Eastern Europe

This work investigates the Bullwhip Effect, which is one of the most important phenomena in contemporary supply chain management. The author uses most recent theoretical apparatus to analyze operational activities of a leading FMCG company British American Tobacco Eastern Europe. This paper investigates and describes the process in BAT supply chain management and considers the impact of the Bullwhip Effect together with the potential risks threatening company's operations. Emergence of the Bullwhip Effect leads to supply chain inefficiency. This paper contains methodological supply chain risk mitigation recommendations, description of a real case study and an analytical study of internal and external supply chain processes

Evaluation of roof slope and exposure with different roofing materials in reduced models of animal production facilities in spring and summer

The present study was conducted at the Department of Rural Engineering and the Department of Animal Morphology and Physiology of FCAV/Unesp, Jaboticabal, SP, Brazil. The objective was to verify the influence of roof slope, exposure and roofing material on the internal temperature of reduced models of animal production facilities. For the development of the research, 48 reduced and dissemble models with dimensions 1.00 × 1.00 × 0.50 m were used. The roof was shed-type, and the models faced to the North or South directions, with 24 models for each side of exposure. Ceramic, galvanized-steel and fibro tiles were used to build the roofs. Slopes varied between 20, 30, 40 and 50% for the ceramic tile and 10, 30, 40 and 50% for the other two. Inside the models, temperature readings were performed at every hour, for 12 months. The results were evaluated in a general linear model in a nested 3 × 4 × 2 factorial arrangement, in which the effects of roofing material and exposure were nested on the factor Slope. Means were compared by the Tukey test at 5% of probability. After analyzing the data, we observed that with the increase in the slope and exposure to the South, there was a drop in the internal temperature within the model at the geographic coordinates of Jaboticabal city (SP/Brazil).

Management of commercial property derived risks in the market context of the Russian Federation

The objective of the thesis is to examine the current state of risk management and to determine an appropriate risk management policy for commercial property derived risks in the Russian branch of a Finnish retail trade company. The employed research methodologies are comparative in-depth interviews and empirical value at risk analysis, including portfolio risk decomposition to determine the inter-currency characteristics. For a multinational retail trade company, the commercial property derived risks open up as a diverse combination of financial and non-financial risks with four distinctive interest groups. The research results indicate that geographical diversification across currency regimes provides diversification benefits. The Russian ruble is the most significant single risk component when considering the net investments outside the euro-zone. Decreasing the Russian ruble and Swedish krona exposures are the most effective methods to reduce translation derived risk. Exchange rate volatility varies over time according to idiosyncratic currency regime characteristics, and cost-effective risk management requires comprehensive analysis of the business environment. Profound and proactive risk management methods are found to be pivotal for companies with cross-border operations in order to succeed among international competitors.

Work-related crisis exposure : psychological trauma and PTSD in news journalists

I avhandlingen undersöktes hur journalister själva reagerar efter att ha arbetat med en plötslig krissituation, samt vilka faktorer som kan bidra till en förhöjd risk för allvarliga långsiktiga stressymptom. Temat undersöktes (1) genom att se på hur journalisters tidigare erfarenheter av krisuppdrag och traumatiska upplevelser i privatlivet var relaterade till stressymptom (posttraumatiskt stressyndrom, sekundär traumatisk stress, depression och utmattningssyndrom), och (2) genom att studera riskfaktorer i en identifierad typ av kris, de finländska skolskjutningarna 2007-08. Avhandlingens resultat baserades på enkätsvar från finländska nyhetsjournalister (N = 503) och intervjuer med personer som jobbat på plats vid skolskjutningar (N = 28). En klar majoritet av journalisterna hade inte allvarliga långsiktiga stressymptom vid tiden för undersökningen. De som varit på ett tidigare krisuppdrag där man bevittnat många obehagliga detaljer hade fler allvarliga stressymptom. En annan riskfaktor var att ha ett förflutet med fler traumatiska händelser i privatlivet. Bland de som arbetat med skolskjutningar var starka kortsiktiga reaktioner, t.ex. hjälplöshet och chock, relativt vanliga. Reaktionerna hörde ändå oftast till den normala återhämtningsprocessen, och ledde inte till en långsiktig försämring av måendet. Journalister som i hög grad identifierade sig med krisen, t.ex. personer med egna barn, hade större risk för att drabbas av allvarliga symptom på lång sikt. Detsamma gällde de som på plats upplevt journalistiska etiska dilemman, t.ex. att beordras av överordnade till uppdrag som gick emot egna principer. För att förebygga psykisk stress bland journalister är det viktigt att inom branschen sprida kunskap om stressreaktioner och utveckla rekommendationer för etisk krisjournalistik. Därmed kan journalister få bättre verktyg för att minimera risken att via sitt yrkesutövande orsaka ytterligare skada åt krisdrabbade.

Enterprise applications migration to the cloud: risks and opportunities

Millions of enterprises move their applications to a cloud every year. According to Forrester Research “the global cloud computing market will grow from a $40.7 billion in 2011 to $241 billion in 2020”. Due to increased interests and demand broad range of providers and solutions have appeared in the market. It is vital to be able to predict possible problems correctly and to classify and mitigate risks associated with the migration process. The study will show the main criteria that should be taken into consideration while making decision of moving enterprise applications to the cloud and choosing appropriate vendor. The main goal of the research is to identify main problems during the migration to a cloud and propose a solution for their prevention and mitigation of consequences in case of occurrence. The research provides an overview of existing cloud solutions and deployment models for enterprise applications. It identifies decision drivers of an applications migration to a cloud and potential risks and benefits associated with this. Finally, the best practices for the successful enterprise-to-cloud migration based on the case studies analysis are formulated.

Fetal alcohol spectrum disorders in Finnish children and adolescents : diagnosis, cognition, behavior, adaptation and brain metabolic alterations

Alcohol consumption during pregnancy can potentially affect the developing fetus in devastating ways, leading to a range of physical, neurological, and behavioral alterations most accurately termed Fetal Alcohol Spectrum Disorders (FASD). Despite the fact that it is a preventable disorder, prenatal alcohol exposure today constitutes a leading cause of intellectual disability in the Western world. In Western countries where prevalence studies have been performed the rates of FASD exceed, for example, autism spectrum disorders, Down’s syndrome and cerebral palsy. In addition to the direct effects of alcohol, children and adolescents with FASD are often exposed to a double burden in life, as their neurological sequelae are accompanied by adverse living surroundings exposing them to further environmental risk. However, children with FASD today remain remarkably underdiagnosed by the health care system. This thesis forms part of a larger multinational research project, The Collaborative Initiative on Fetal Alcohol Spectrum Disorders (the CIFASD), initiated by the National Institute of Alcohol Abuse and Alcoholism (NIAAA) in the U.S.A. The general aim of the present thesis was to examine a cohort of children and adolescents growing up with fetal alcohol-related damage in Finland. The thesis consists of five studies with a broad focus on diagnosis, cognition, behavior, adaptation and brain metabolic alterations in children and adolescents with FASD. The participants consisted of four different groups: one group with histories of prenatal exposure to alcohol, the FASD group; one IQ matched contrast group mostly consisting of children with specific learning disorder (SLD); and two typically-developing control groups (CON1 and CON2). Participants were identified through medical records, random sampling from the Finnish national population registry and email alerts to students. Importantly, the participants in the present studies comprise a group of very carefully clinically characterized children with FASD as the studies were performed in close collaboration with leading experts in the field (Prof. Edward Riley and Prof. Sarah Mattson, Center for Behavioral Teratology, San Diego State University, U.S.A; Prof. Eugene Hoyme, Sanford School of Medicine, University of South Dakota, U.S.A.). In the present thesis, the revised Institute of Medicine diagnostic criteria for FASD were tested on a Finnish population and found to be a reliable tool for differentiating among the subgroups of FASD. A weighted dysmorphology scoring system proved to be a valuable additional adjunct in quantification of growth deficits and dysmorphic features in children with FASD (Study 1). The purpose of Study 2 was to clarify the relationship between alcohol-related dysmorphic features and general cognitive capacity. Results showed a significant correlation between dysmorphic features and cognitive capacity, suggesting that children with more severe growth deficiency and dysmorphic features have more cognitive limitations. This association was, however, only moderate, indicating that physical markers and cognitive capacity not always go hand in hand in individuals with FASD. Behavioral problems in the FASD group proved substantial compared to the typically developing control group. In Study 3 risk and protective factors associated with behavioral problems in the FASD group were explored further focusing on diagnostic and environmental factors. Two groups with elevated risks for behavioral problems emerged: length of time spent in residential care and a low dysmorphology score proved to be the most pervasive risk factor for behavioral problems. The results underscore the clinical importance of appropriate services and care for less visibly alcohol affected children and highlight the need to attend to children with FASD being raised in institutions. With their background of early biological and psychological impairment compounded with less opportunity for a close and continuous caregiver relationship, such children seem to run an especially great risk of adverse life outcomes. Study 4 focused on adaptive abilities such as communication, daily living skills and social skills, in other words skills that are important for gradually enabling an independent life, maintain social relationships and allow the individual to become integrated into society. The results showed that adaptive abilities of children and adolescents growing up with FASD were significantly compromised compared to both typically-developing peers and IQ-matched children with SLD. Clearly different adaptive profiles were revealed where the FASD group performed worse than the SLD group, who in turn performed worse than the CON1 group. Importantly, the SLD group outperformed the FASD group on adaptive behavior in spite of comparable cognitive levels. This is the first study to compare adaptive abilities in a group of children and adolescents with FASD relative to both a contrast group of IQ-matched children with SLD and to a group of typically-developing peers. Finally, in Study 5, through magnetic resonance spectroscopic imaging (MRS) evidence of longstanding neurochemical alterations were observed in adolescents and young adults with FASD related to alcohol exposure in utero 14-20 years earlier. Neurochemical alterations were seen in several brain areas: in frontal and parietal cortices, corpus callosum, thalamus and frontal white matter areas as well as in the cerebellar dentate nucleus. The findings are compatible with neuropsychological findings in FASD. Glial cells seemed to be more affected than neurons. In conclusion, more societal efforts and resources should be focused on recognizing and diagnosing FASD, and supporting subgroups with elevated risk of poor outcome. Without adequate intervention children and adolescents with FASD run a great risk of marginalization and social maladjustment, costly not only to society but also to the lives of the many young people with FASD.

Identification and application of bile metabolites to assess the exposure of fish to pharmaceuticals in the environment

Thousands of tons of pharmaceuticals are consumed yearly worldwide. Due to the continuous and increasing consumption and their incomplete elimination in wastewater treatment plants (WWTP), pharmaceuticals and their metabolites can be detected in receiving waters, although at low concentrations (ng to low μg/L). As bioactive molecules the presence of pharmaceuticals in the aquatic environment must be considered potentially hazardous for the aquatic organisms. In this thesis, the biotransformation and excretion of pharmaceuticals in fish was studied. The main biotransformation pathways of three anti‐inflammatory drugs, diclofenac, naproxen and ibuprofen, in rainbow trout were glucuronidation and taurine conjugation of the parent compounds and their phase I metabolites. The same metabolites were present in fish bile in aquatic exposures as in fish dosed with intraperitoneal injection. Higher bioconcentration factor in bile (BCFbile) was found for ibuprofen when compared to diclofenac and naproxen. Laboratory exposure studies were followed by a study of uptake of pharmaceuticals in a wild fish population living in lake contaminated with WWTP effluents. Of the analyzed 17 pharmaceuticals and six phase I metabolites, only diclofenac, naproxen and ibuprofen was present in bream and roach bile. It was shown, that diclofenac, naproxen and ibuprofen excreted by the liver can be found in rainbow trout and in two native fish species living in the receiving waters. In the bream and roach bile, the concentrations of diclofenac, naproxen and ibuprofen were roughly 1000 times higher than those found in the lake water, while in the laboratory exposures, the bioconcentration of the compounds and their metabolites in rainbow trout bile were at the same level as in wild fish or an order of magnitude higher. Thus, the parent compounds and their metabolites in fish bile can be used as a reliable biomarker to monitor the exposure of fish to environmental pharmaceuticals present in water receiving discharges from WWTPs.

Effect of exposure to sublethal concentrations of sodium cyanide on the carbohydrate metabolism of the Indian Major Carp Labeo rohita (Hamilton, 1822)

Experiments were designed to study in-vivo effects of sodium cyanide on biochemical endpoints in the freshwater fish Labeo rohita. Fish were exposed to two sublethal concentrations (0.106 and 0.064mg/L) for a period of 15 days. Levels of glycogen, pyruvate, lactate and the enzymatic activities of lactate dehydrogenase (LDH), succinate dehydrogenase (SDH), glucose-6-phosphate dehydrogenase (G6PDH), phosphorylase, alkaline phosphatase (ALP), acid phosphatase (AcP) were assessed in different tissues (liver, muscle and gills). Result indicated a steady decrease in glycogen, pyruvate, SDH, ALP and AcP activity with a concomitant increase in the lactate, phosphorylase, LDH and G6PD activity in all selected tissues. The alterations in all the above biochemical parameters were significantly (p<0.05) time and dose dependent. In all the above parameters, liver pointing out the intensity of cyanide intoxication compare to muscle and gills. Study revealed change in the metabolic energy by means of altered metabolic profile of the fish. Further, these observations indicated that even sublethal concentrations of sodium cyanide might not be fully devoid of deleterious influence on metabolism in L. rohita.

Metformin in gestational diabetes mellitus

METFORMIININ KÄYTTÖ RASKAUSDIABETEKSESSA Raskausdiabeteksella tarkoitetaan sokeriaineenvaihdunnan häiriötä, joka todetaan ensimmäisen kerran raskauden aikana. Hoidolla voidaan vähentää raskausdiabetekseen liittyviä äidin ja vastasyntyneen haittoja. Lääkitystä tarvitaan, jos ruokavaliohoidolla ei saavuteta hyvää sokeritasapainoa. Perinteisesti lääkityksenä on käytetty insuliinia, mutta metformii¬nin käyttöä insuliinin vaihtoehtona on ehdotettu. Metformiini läpäisee istukan, mutta sen läpäisymekanismi ei ole selvillä. Tämän tutkimuskokonaisuuden pääasiallisin tarkoitus oli verrata metformiinin tehokkuutta ja turvallisuutta insuliiniin raskausdiabeteksen hoidossa selvittämällä lääkkeen vaiku¬tusta äitiin ja vastasyntyneeseen. Lisäksi haluttiin tutkia, mitkä tekijät ennustavat insulii¬nin tarvetta metformiinin lisänä, jotta saavutettaisiin hyvä sokeritasapaino. Metformiinin annoksen vaikutus äitiin ja vastasyntyneeseen arvioitiin mittaamalla metformiinin pitoisuus äidistä, ja sikiön puolelta napanuoran veressä. Tässä tutkimuksessa selvitettiin myös aktiivisen kuljetusproteiinin (OCT) merkitystä metformiinin kulkeutumiseen istukan läpi perfusiomalla istukkaa ex vivo . Ex vivo istukkaperfuusiotutkimuksen tulokset viittasivat siihen, että OCT-kuljetusproteiinilla ei ollut todennäköisesti merkittävää osuutta metformiinin kulkeutumisessa istukan läpi. Metformiinin pitoisuusmittaukset synnytyksen yhteydessä osoittivat metformiinin siirtyvän sikiöön istukan läpi suuressa määrin (96 %) kertymättä kuitenkaan sikiön verenkiertoon. Metformiinin pitoisuudella ei ollut vaikutusta vastasyntyneen hyvinvointiin. Maksi¬maalisella metformiinin annostuksella ja korkealla metformiinipitoisuudella todettiin olevan suotuisa vaikutus äidin painon nousuun raskauden aikana. Insuliiniin verrattuna metformiini ei lisännyt äidin, sikiön tai vastasyntyneen haittatapahtumia, eikä sillä ollut vaikutusta synnytystapaan. Sokeritasapaino insuliini- ja metformiinilääkityksen aikana oli yhtäläinen arvioitaessa sitä HbA1c- ja fruktosamiinimittauksilla, mutta 21 % metformiinin käyttäjistä tarvitsi lisäksi insuliinia hyvän sokeritasapainon saavuttamiseksi. Tutkimuksesssa todettiin, että mitä iäkkäämpi äiti oli, mitä varhaisemmassa raskauden vaiheessa sokerirasitus oli tehty ja lääkitys aloitettu, ja mitä korkeammat HbA1c ja fruktosamiinipitoisuudet olivat, sitä suuremmalla todennäköisyydellä metformiinin lisänä tarvittiin insuliinia.