Associations of interleukin-1 (IL-1) gene variation and IL-1 receptor antagonist phenotypes with immunological responses, metabolic dysregulation and type 2 diabetes

The upstream proinflammatory interleukin-1 (IL-1) cytokines, together with a naturally occurring IL-1 receptor antagonist (IL-1Ra), play a significant role in several diseases and physiologic conditions. The IL-1 proteins affect glucose homeostasis at multiple levels contributing to vascular injuries and metabolic dysregulations that precede diabetes. An association between IL-1 gene variations and IL-1Ra levels has been suggested, and genetic studies have reported associations with metabolic dysregulation and altered inflammatory responses. The principal aims of this study were to: 1) examine the associations of IL-1 gene variation and IL-1Ra expression in the development and persistence of thyroid antibodies in subacute thyroiditis; 2) investigate the associations of common variants in the IL-1 gene family with plasma glucose and insulin concentrations, glucose homeostasis measures and prevalent diabetes in a representative population sample; 3) investigate genetic and non-genetic determinants of IL-1Ra phenotypes in a cross-sectional setting in three independent study populations; 4) investigate in a prospective setting (a) whether variants of the IL-1 gene family are predictors for clinically incident diabetes in two population-based observational cohort studies; and (b) whether the IL-1Ra levels predict the progression of metabolic syndrome to overt diabetes during the median follow-up of 10.8 and 7.1 years. Results from on patients with subacte thyroiditis showed that the systemic IL-1Ra levels are elevated during a specific proinflammatory response and they correlated with C-reactive protein (CRP) levels. Genetic variation in the IL-1 family seemed to have an association with the appearance of thyroid peroxidase antibodies and persisting local autoimmune responses during the follow-up. Analysis of patients suffering from diabetes and metabolic traits suggested that genetic IL-1 variation and IL-1Ra play a role in glucose homeostasis and in the development of type 2 diabetes. The coding IL-1 beta SNP rs1143634 was associated with traits related to insulin resistance in cross-sectional analyses. Two haplotype variants of the IL-1 beta gene were associated with prevalent diabetes or incident diabetes in a prospective setting and both of these haplotypes were tagged by rs1143634. Three variants of the IL-1Ra gene and one of the IL-1 beta gene were consistently identified as significant, independent determinants of the IL-1Ra phenotype in two or three populations. The proportion of the phenotypic variation explained by the genetic factors was modest however, while obesity and other metabolic traits explained a larger part. Body mass index was the strongest predictor of systemic IL-1Ra concentration overall. Furthermore, the age-adjusted IL-1Ra concentrations were elevated in individuals with metabolic syndrome or diabetes when compared to those free of metabolic dysregulation. In prospective analyses the systemic IL-1Ra levels were found as independent predictors for the development of diabetes in people with metabolic syndrome even after adjustment for multiple other factors, including plasma glucose and CRP levels. The predictive power of IL-1Ra was better than that of CRP. The prospective results also provided some evidence for a role of common IL-1 alpha promoter SNP rs1800587 in the development of type 2 diabetes among men and suggested that the role may be gender specific. Likewise, common variations in the IL-1 beta coding region may have a gender specific association with diabetes development. Further research on the potential benefits of IL-1Ra measurements in identifying individuals at high risk for diabetes, who then could be targeted for specific treatment interventions, is warranted. It has been reported in the recent literature that IL-1Ra secreted from adipose tissue has beneficial effects on glucose homeostasis. Furthermore, treatment with recombinant human IL-1Ra has been shown to have a substantial therapeutic potential. The genetic results from the prospective analyses performed in this study remain inconclusive, but together with the cross-sectional analyses they suggest gender-specific effects of the IL-1 variants on the risk of diabetes. Larger studies with more extensive genotyping and resequencing may help to pinpoint the exact variants responsible and to further elucidate the biological mechanisms for the observed associations. This would improve our understanding of the pathways linking inflammation and obesity with glucose and insulin metabolism.

Puunoston kehittäminen Stora Enso Metsän Helsingin palvelupisteessä

The operation environment in the roundwood trade in Finland in the 1990’s include several changes. They are changes in the structure of non-industrial private forest (NIPF) ownership, forest taxation, in forest legislation, in price recommendation agreement, diminishing resources of forestry extension services, etc. At the same time, the roundwood demand has been rising. All these developments cause uncertainty in wood procurement organisations, and call for research to find out how to adapt into the changing environment. The objective of this study is to produce information for roundwood purchasing planning and cus-tomer satisfaction management to be used by Stora Enso Metsä Customer Service, Helsinki. For this pur-pose, data needs to be gathered about the urban NIPFs and their forest estates, behaviour related to forestry and timber-selling, customer satisfaction in their latest timber selling transaction, and their opinions about Enso’s new customer service office and its service concept. To fulfil the objective of the study, a NIPF -owner -survey (N=1064, response rate 39,7%) was con-ducted in October 1998-January 1999. The sample was made on the basis of the marketing database of Stora Enso Oyj Forest Customer Service in Helsinki. In planning the frame of reference of the empirical study, the model of service quality by Grönroos was applied. The following aspects were included in the 7-page questionnaire: demographic, sosio-economic and forest estate background, relation to the forest service supply, behaviour related to forestry, timber-selling motives and behaviour, last contact organisation and its image in forestry business, expectations and percep-tions in the latest timber-selling transactions, and behavioural intentions. The results revealed that the share of women, pensioners and academically educated people among forest owners was quite high. The majority of the forest estates of the metropolitan forest owners were situ-ated in the provinces of South Finland and East Finland. The average forest estate area was considerably smaller than in a previous study. Economic and recreational objectives were most important in the use of forests. Forest Associations were involved in half of the roundwood sales transactions of the respondents in the metropolitan area. The wood quantity of transactions was considerably higher than the average in the whole country. Bank-organised forest-related activities, taxation infos and trips to the forest were the most popular activities. Among the services, silvicultural advices were needed mostly and stub treatment least. Brochure material related to stumpage timber sales and taxation were considered most important compared to material related to delivery sales. The service expectations were at highest for women and they were less satisfied with the service than men. 2nd and 3rd generation residents of the metropolitan area thought about the new customer service concept more positively than the 1st generation residents. Internet users under 60 years thought more positively about new satellite picture-based woodlot search concept. Cross-tabulation of factor scores against background variables indicated that women with relatively low education level a greater need to sell roundwood than entrepreneurs, white-collar workers and directors, and Internet users. Suspiciousness towards timber procurement organisations was relatively strong among women and those whose forest income share of the total income was either null or over 20 %. The average customer satisfaction score was negative in all nine questions. Statistical differences be-tween different companies did not exist in the average satisfaction scores. Stora Enso’s Helsinki forest cus-tomer service could choose the ability to purchase all timber grades as its competitive advantage. Out of nine service dimension included in the questionnaire, in this particular service dimension, Enso’s Helsinki forest customer service’s score exceeded most all organisations’ average customer satisfaction score. On the basis of importance – performance matrix, advice and quidance could have been provided more to the forest owners in their latest timber–selling transaction.

A Hub System for Cloud-Computing Based Business-Collaboration: Automating Ontology-Enabled Electronic Business-Service Discovery

The management and coordination of business-process collaboration experiences changes because of globalization, specialization, and innovation. Service-oriented computing (SOC) is a means towards businessprocess automation and recently, many industry standards emerged to become part of the service-oriented architecture (SOA) stack. In a globalized world, organizations face new challenges for setting up and carrying out collaborations in semi-automating ecosystems for business services. For being efficient and effective, many companies express their services electronically in what we term business-process as a service (BPaaS). Companies then source BPaaS on the fly from third parties if they are not able to create all service-value inhouse because of reasons such as lack of reasoures, lack of know-how, cost- and time-reduction needs. Thus, a need emerges for BPaaS-HUBs that not only store service offers and requests together with information about their issuing organizations and assigned owners, but that also allow an evaluation of trust and reputation in an anonymized electronic service marketplace. In this paper, we analyze the requirements, design architecture and system behavior of such a BPaaS-HUB to enable a fast setup and enactment of business-process collaboration. Moving into a cloud-computing setting, the results of this paper allow system designers to quickly evaluate which services they need for instantiationg the BPaaS-HUB architecture. Furthermore, the results also show what the protocol of a backbone service bus is that allows a communication between services that implement the BPaaS-HUB. Finally, the paper analyzes where an instantiation must assign additional computing resources vor the avoidance of performance bottlenecks.

A Reference Architecture for Electronic Business-to-Business Collaboration Setup and Enactment Systems

The question what a business-to-business (B2B) collaboration setup and enactment application-system should look like remains open. An important element of such collaboration constitutes the inter-organizational disclosure of business-process details so that the opposing parties may protect their business secrets. For that purpose, eSourcing [37] has been developed as a general businessprocess collaboration concept in the framework of the EU research project Cross- Work. The eSourcing characteristics are guiding for the design and evaluation of an eSourcing Reference Architecture (eSRA) that serves as a starting point for software developers of B2B-collaboration systems. In this paper we present the results of a scenario-based evaluation method conducted with the earlier specified eSourcing Architecture (eSA) that generates as results risks, sensitivity, and tradeoff points that must be paid attention to if eSA is implemented. Additionally, the evaluation method detects shortcomings of eSA in terms of integrated components that are required for electronic B2B-collaboration. The evaluation results are used for the specification of eSRA, which comprises all extensions for incorporating the results of the scenario-based evaluation, on three refinement levels.

Exploring a framework for advanced electronic business transactions

With the emergence of service-oriented computing technology, companies embrace new ways of carrying out business transactions electronically. Since the parties involved in an electronic business transaction (eBT) manage a heterogeneous information-systems infrastructure within their organizational domains, the collaboration complexity is considerable and safeguarding an interorganizational collaboration with an eBT is difficult, but of high significance. This paper describes a conceptual framework that pays attention to the complexities of an eBT and its differentiating characteristics that go further than traditional database transactions. Since the eBT is a framework that comprises separate levels, pre-existing transaction concepts are explored for populating the respective levels. To show the feasibility of the described eBT framework, industry initiatives that are aspiring to become business-transaction standards, are checked for eBT compatible characteristics. Since realizing an eBT framework raises many tricky issues, the paper maps out important research areas that require scientific attention. Essentially, it is required to investigate how the business semantics influences the nature of an eBT throughout its lifecycle.

Hostility: A prospective study of the genetic and environmental background and associations with cardiovascular risk

Hostility is a multidimensional construct having wide effects on society. In its different forms, hostility is related to a large array of social and health problems, such as criminality, substance abuse, depression, and cardiovascular risks. Identifying and tackling early-life factors that contribute to hostility may have public health significance. Although the variance in hostility is estimated to be 18-50 percent heritable, there are significant gaps in knowledge regarding the molecular genetics of hostility. It is known that a cold and unsupportive home atmosphere in childhood predicts a child s later hostility. However, the long-term effects of care-giving quality on hostility in adulthood and the role of genes in this association are unclear. The present dissertation is part of the ongoing population-based prospective Young Finns study, which commenced in 1980 with 3596 3-18-year-old boys and girls who were followed for 27 years. The specific aims of the dissertation were first to study the antecedents of hostility by looking at 1) the genetic background, 2) the early environmental predictors, and 3) the gene environment interplay behind hostility. As a second aim, the thesis endeavored to examine 4) the association between hostility and cardiovascular risks, and 5) the moderating effect of demographic factors, such as gender and socioeconomic status, on this association. The study found potential gene polymorphisms from chromosomes 7, 14, 17, and 22 suggestively associated with hostility. Of early environmental influences, breastfeeding and early care-giving were found to predict hostility in adulthood. In addition, a serotonin receptor 2A polymorphism rs6313 moderated the effect of early care-giving on later hostile attitudes. Furthermore, hostility was shown to predict cardiovascular risks, such as metabolic syndrome and inflammation. Finally, parental socioeconomic status was found to moderate the association between anger and early atherosclerosis. The new genetic and early environmental antecedents of hostility identified in this research may help in understanding the development of hostility and its health risks, and in planning appropriate prevention. The significance of early influences on this development is stressed. Although the markers studied are individual- and family-related factors, these may be influenced at the societal level by giving accurate information to all individuals concerned and by improving the societal circumstances.

Strategic Sales Process Adaptation: Relationship Orientation of the Sales Process in a Business-to-Business Context

Although previous research has recognised adaptation as a central aspect in relationships, the adaptation of the sales process to the buying process has not been studied. Furthermore, the linking of relationship orientation as mindset with adaptation as a strategy and forming the means has not been elaborated upon in previous research. Adaptation in the context of relationships has mostly been studied in relationship marketing. In sales and sales management research, adaptation has been studied with reference to personal selling. This study focuses on adaptation of the sales process to strategically match it to the buyer’s mindset and buying process. The purpose of this study is to develop a framework for strategic adaptation of the seller’s sales process to match the buyer’s buying process in a business-to-business context to make sales processes more relationship oriented. In order to arrive at a holistic view of adaptation of the sales process during relationship initiation, both the seller and buyer are included in an extensive case analysed in the study. However, the selected perspective is primarily that of the seller, and the level focused on is that of the sales process. The epistemological perspective adopted is constructivism. The study is a qualitative one applying a retrospective case study, where the main sources of information are in-depth semi-structured interviews with key informants representing the counterparts at the seller and the buyer in the software development and telecommunications industries. The main theoretical contributions of this research involve targeting a new area in the crossroads of relationship marketing, sales and sales management, and buying and purchasing by studying adaptation in a business-to-business context from a new perspective. Primarily, this study contributes to research in sales and sales management with reference to relationship orientation and strategic sales process adaptation. This research fills three research gaps. Firstly, linking the relationship orientation mindset with adaptation as strategy. Secondly, extending adaptation in sales from adaptation in selling to strategic adaptation of the sales process. Thirdly, extending adaptation to include facilitation of adaptation. The approach applied in the study, systematic combining, is characterised by continuously moving back and forth between theory and empirical data. The framework that emerges, in which linking mindset with strategy with mindset and means forms a central aspect, includes three layers: purchasing portfolio, seller-buyer relationship orientation, and strategic sales process adaptation. Linking the three layers enables an analysis of where sales process adaptation can make a contribution. Furthermore, implications for managerial use are demonstrated, for example how sellers can avoid the ‘trap’ of ad-hoc adaptation. This includes involving the company, embracing the buyer’s purchasing portfolio, understanding the current position that the seller has in this portfolio, and possibly educating the buyer about advantages of adopting a relationship-oriented approach.

Emerging bioenergy business at Finnish independent industrial sawmills

Finnish forest industry is in the middle of a radical change. Deepening recession and the falling demand of woodworking industry´s traditional products have forced also sawmilling industry to find new and more fertile solutions to improve their operational preconditions. In recent years, the role of bioenergy production has often been highlighted as a part of sawmills´ business repertoire. Sawmilling produces naturally a lot of by-products (e.g. bark, sawdust, chips) which could be exploited more effectively in energy production, and this would bring more incomes or maybe even create new business opportunities for sawmills. Production of bioenergy is also supported by government´s climate and energy policies favouring renewable energy sources, public financial subsidies, and soaring prices of fossil fuels. Also the decreasing production of domestic pulp and paper industry releases a fair amount of sawmills´ by-products for other uses. However, bioenergy production as a part of sawmills´ by-product utilization has been so far researched very little from a managerial point of view. The purpose of this study was to explore the relative significance of the main bioenergy-related processes, resources and factors at Finnish independent industrial sawmills including partnerships, cooperation, customers relationships and investments, and also the future perspectives of bioenergy business at these sawmills with the help of two resource-based approaches (resource-based view, natural-resource-based view). Data of the study comprised of secondary data (e.g. literature), and primary data which was attracted from interviews directed to sawmill managers (or equivalent persons in charge of decisions regarding bioenergy production at sawmill). While a literature review and the Delphi method with two questionnaires were utilized as the methods of the study. According to the results of the study, the most significant processes related to the value chain of bioenergy business are connected to raw material availability and procurement, and customer relationships management. In addition to raw material and services, the most significant resources included factory and machinery, personnel, collaboration, and geographic location. Long-term cooperation deals were clearly valued as the most significant form of collaboration, and especially in processes connected to raw material procurement. Study results also revealed that factors related to demand, subsidies and prices had highest importance in connection with sawmills´ future bioenergy business. However, majority of the respondents required that certain preconditions connected to the above-mentioned factors should be fulfilled before they will continue their bioenergy-related investments. Generally, the answers showed a wide divergence of opinions among the respondents which may refer to sawmills´ different emphases and expectations concerning bioenergy. In other words, bioenergy is still perceived as a quite novel and risky area of business at Finnish independent industrial sawmills. These results indicate that the massive expansion of bioenergy business at private sawmills in Finland is not a self-evident truth. The blocking barriers seem to be connected mainly to demand of bioenergy and money. Respondents´ answers disseminated a growing dissatisfaction towards the policies of authorities, which don´t treat equally sawmill-based bioenergy compared to other forms of bioenergy. This proposition was boiled down in a sawmill manager´s comment: “There is a lot of bioenergy available, if they just want to make use of it.” It seems that the positive effects of government´s policies favouring the renewables are not taking effect at private sawmills. However, as there anyway seems to be a lot of potential connected to emerging bioenergy business at Finnish independent industrial sawmills, there is also a clear need for more profound future studies over this topic.