Mesenchymal heterogeneity in the adult human lung

The human lung is a complex tissue consisting of a heterogeneous mix of different structures and cells, each which a specific role that together contribute to the primary function of the organ: the gas exchange. Different mesenchymal cells populate the interstitial areas around airways and blood vessels and form the connective tissue together with the extracellular matrix. Fibroblasts constitute one group of mesenchymal cells which are potent producers of extracellular matrix, an important part of the tissue niche which is heavily altered during remodeling in fibrotic lung diseases. In addition to providing structure and support, the extracellular matrix is also a part of the dynamic microenvironment that interacts and communicates with the cells. Yet, the different functions of fibroblasts and other mesenchymal cells in the lung under homeostatic and pathophysiological conditions remain elusive. Furthermore, the extensive heterogeneity displayed by fibroblasts and other mesenchymal cells in terms of phenotype and function, which in part can be related to their spatial localization, is not fully understood. Deciphering this heterogeneity is important to better understand specific functions of specialized mesenchymal cells.The aim of this thesis was to investigate the heterogeneity of fibroblastic mesenchymal cells that reside in the human lungs and to explore how different cellular phenotypes can contribute to mesenchymal-associated functions such as tissue remodeling. The studies included in the thesis are based on experimental work on primary cells derived from human lung tissue. Mass-spectrometry and RNA-sequencing technologies were used to perform comprehensive analysis of the proteome and transcriptome of targeted cell populations. To study mesenchymal cells in heterogeneous tissue material, we also utilized techniques with single-cell resolution, including flow cytometry, single-cell RNA-sequencing and histology, together with distinct anatomical tissue sampling (proximal vs distal airways).Based on these approaches we could confirm the existence of heterogeneity within the mesenchymal cell compartment, with a specific phenotypical pattern associated with fibroblasts in the peribronchovascular compartment emerging. In paper I, we characterize the proteome of fibroblast from proximal and distal airways and confirm specific protein expression in the bronchvascular regions. In paper II, we explore the functional attribute of colony formation (reflecting proliferative capacity) that has been connected to a mesenchymal progenitor population, and describe a link between this property and an adventitial localization and an adventitial fibroblasts phenotype. In paper III, we describe the existence of a CD26+ adventitial fibroblast phenotype in human lung and show that it is not associated to an actived profibrotic phenotype in idiopathic pulmonary fibrosis, contrary to what other studies have suggested. Finally, in paper IV, we applied our bioinformatical approach to characterize non-fibroblastic cells, alveolar epithelial cell, with a focus on their contribution to ECM remodeling, and revealed an overlooked complexity in their matrix producing capacity that include interstitial matrix proteins commonly associated with mesenchymal cells.Taken together, the results presented in the thesis describe a phenotypic heterogeneity among mesenchymal cells that appear to be intricately connected to their local environment, highlighting the importance of the extracellular context for cell function. The generated information could contribute to reduce the inconsistency and confusion regarding different terminology used and provide information regarding potential functions of these elusive cells in lung tissue

Implementing relational contracting in a public client organization: the influence of policy clashes, resources and project autonomy

Relational contracting models are increasingly being used for large and complex public infrastructure construction projects, but both practices and outcomes still widely vary. When analyzing the causes of failures and successes, most studies have focused on practices at the project level. In this paper, we add to the current understanding of relational contracting in public construction by examining the influence of factors at the organizational and institutional levels. We develop a framework based on theories of policy implementation and analyze two projects piloting a new Early Contractor Involvement model in a large public infrastructure client organization. In this case, a previous marketization policy, prescribing low client involvement in project processes, interfered with the relational contracting policy. This policy clash was not openly acknowledged from the start, despite causing significant confusion and frustration at the project level, but became recognizable largely through its consequences for resource allocation and managerial attention. We conclude that policy ambiguities, combined with a project-based implementation context, produce local interpretations and variations in relational contracting models. When project autonomy is high, industry-level agreements, standards and resources are important to align practices also between projects within the same client organization

Employers’ Attitudes Toward Older Workers and Obstacles and Opportunities for the Older Unemployed to Reenter Working Life

The present study aimed at identifying the attitude-related barriers that older unemployed, jobseeking workers (50+) face when they endeavor to reenter the labor market and to investigate employers’ attitudes and perceptions of older workers. Two studies were conducted. In study 1, interviews were undertaken with 26 unemployed persons and 24 representatives of other stakeholders, including social partners and officials representing the Social Insurance Agency (FK) and the Public Employment Service (AF). In study 2, the attitudes among private sector employers were studied by carrying out a questionnaire survey (N = 147). The interview results showed that many unemployed job seekers had experienced negative age-related attitudes among employers. This observation was supported by other stakeholders. Perceived attitudes to older workers and lack of updated competence were considered crucial. The questionnaire study showed a mixed picture concerning employer attitudes. There was a statistical difference between older (>50 years) and younger employers; older employers believed that older women wanted competence development to a greater extent. There was also a significant difference between female and male employers’ opinions; female employers, in particular the older ones, assessed that older women wished competence development to a greater extent. These differences were not found with respect to views on older men. About half (52%) of the employers had the opinion that there was no difference between older and younger employees with respect to the ability to cope with changes or learning new things. However, younger female employers (but not older female employers) considered that older employees had greater difficulties with changes or learning new things. It is concluded that negative attitudes to older workers with respect to competence development tend to be most common among younger employers

Meaningfulness and Coherence? Experiences Among Young Soldiers in the Swedish Armed Forces

The twofold aim of the present study was to try to understand why young recruits to the Swedish Armed Forces chose a military career rather than a civilian one, and how their expectations were met when confronted with the realities of life as a soldier or marine. The study material consisted of 57 interviews with 37 young recruits; the interviews were carried out at units representing different branches of the Armed Forces. The interviews were semi-structured, transcribed, and categorized. It was found that the desire to remain employed as a soldier or marine in the Swedish Armed Forces is based on a set of individual and organizational factors: the selection process, the sense of meaningfulness and organizational coherence, the safety offered, and the salutogenic nature of military working life. The recruits are part of a system that offers good work conditions in return for taxing and stressful work assignments

Samverkan och kunskapsintegration i vårdbyggande - en studie av Tehuset

I byggprojekt där det finns ett behov av ett närmare samarbete mellan olika kompetenser hos beställare, projektörer och entreprenörer blir det allt vanligare att använda uttalad partnering. Då ingår ofta särskilda åtgärders för att bygga relationer, nya mötesformer och system för att kontinuerligt utvärdera och förbättra samarbetet. Man talar ofta om betydelsen av förtroende mellan olika parter för att lyckas, men det är heller inte självklart hur ett samarbete som involverar många olika deltagare från olika företag rent praktiskt skall organiseras. I den här rapporten beskrivs och analyseras samarbetsformerna i Tehusprojektet, en vårdbyggnad vid Södra Älvsborgs sjukhus i Borås. Två frågor behandlas i rapporten: 1. På vilket sätt har partneringprocesserna påverkat projektgenomförande och resultat i Tehuset? 2. Vilka aspekter behöver man fokusera i utvecklingen av bredare partneringsamarbeten som involverar även konsulter och entreprenörer? Studien baseras på intervjuer med representanter för sjukhuset, beställaren, arkitekten, VVS-projektören, byggentreprenören och ventilationsentreprenören. Bakgrunden till att välja ett partneringkoncept för Tehuset var att sjukhuset ville ha en byggnad som var modern och verksamhetsanpassad vid inflyttningen, optimerad för att uppnå lägsta livscykelkostnad för vårdverksamheten och byggnadsdriften samt uppfyllde höga krav på energihushållning. Med partnering kunde man uppnå både en ökad integration av olika kompetenser och möjlighet att anpassa lösningar till utvecklingen inom sjukhusteknik och SÄS organisation långt fram i byggprocessen. Sjukhuset och beställaren Västfastigheter är mycket nöjda med resultatet: man tycker att man har fått en fått en mer anpassad byggnad med betydligt högre kvalitet. Alla intervjuade uppfattar samarbetet som mycket bra, och de relationsbyggande åtgärderna i form av bland annat workshops, partneringdeklaration och tillhörande bonussystem har haft stor betydelse, liksom det faktum att man haft öppna böcker. När det gäller utvecklingsbehov är en övergripande slutsats att när antalet medverkande ökar så blir det också en större utmaning att förena relationsutveckling med effektiva processer. I studien finns flera exempel på att det uppstår en balansproblematik där det gäller att hitta en rimlig avvägning mellan olika mål. En lösning kan vara att arbeta mer medvetet med att integrera relationsutveckling i projektets kärnprocesser. Exempelvis har även andra möten än workshops en relationsbyggande roll, och en bred delaktighet i planering och utvärdering av processupplägg kan utnyttjas för att minska behovet av direkt deltagande i själva processerna. Centralt är att planera de tidiga skedena med projekteringssamverkan noga, så att inte viktiga och komplexa beslut hämmas av att relationerna i gruppen inte kommit så långt att de klarar konflikter. Det finns också anledning att utveckla samarbetet mellan partneringledare och projektledning

Trust, control and knowledge integration in a rock tunnel project

Rock tunnel projects that experience geological uncertainties tend to be both lengthier and more costly than planned. Traditional contract arrangements have proved to be less suitable when uncertainty is high; problem-solving being further hampered by contract-related distrust, communication failures and disputes. To efficiently respond to uncertainty and control risks of time and cost overruns, the knowledge of specialists in different firms needs to be mobilized. Findings from a case study of a railway tunnel project in Sweden aim to describe knowledge integration, communication and decision making related to geological conditions, comprising both formal and informal aspects. Findings show that formal and informal aspects are often complementary, also when they are contradictory, but that knowledge integration may suffer from a more formalized communication. Further, it is also relationships and structures extending beyond the individual project

Attitudes Among Male and Female University Professors, and other Categories of University Employees, to Working up to and Beyond Normal retirement age

A study was undertaken in order to identify variables predicting the willingness of male and female university professors, and other employment categories, to work up to and beyond normal retirement age (65 years). Employees were asked by means of a questionnaire about their willingness to continue working to age 67, or to age 70, if they were given the chance. Hierarchical multiple regression analysis was carried out (N = 3,019; 59.8% women and 40.2% men). The interest to continue working into old age was significantly higher in men than in women (p<0.01). Among independent variables, age, position, and work satisfaction predicted women’s as well as men’s interest to work to age 67 and 70, whereas among women perceived health predicted the willingness to work to age 67. Professors and lecturers were the categories showing the highest interest to work to age 70, compared to administrative and technical personnel; men showed significantly higher interest than women among lecturers and administrative personnel. The study emphasizes the effects of position and gender on willingness to continue working into old age, but identifies in addition also work satisfaction and age as significant predictors

Client-Contractor Relationships in Building Projects: Co-Operation, Conflict and Social Influence

The division of responsibility in the client-contractor relationship and the formal contractual arrangements has long been a question of considerable debate and concern, in the Swedish construction industry as well as in construction management research.<p /> Due to uncertainty and incomplete contractual documents, many negotia-tions continue between the parties during the contract period. These negotia-tions are often performed by the client's and contractor's repre-sentatives on the construction site. The aim of this thesis is to gain an increased understanding of informal aspects of the client-contractor relation-ship and of the role of the client during the contract period. The discussion is based on two case studies of the interaction between the parties during the production phase of building projects. The focus is on the individuals who participate in the decision making, and an ethnographic, interpretative approach is used. Theories of human decision making and social influence form the basis of the analysis.<p /> As there is a great need for joint problem-solving during the execution of the work, it is important to the parties that the relations between the interacting individuals are kept co-operative, and that perceptions of unfair-ness are avoided. A main finding is that the contractor has a naturally strong informal position. In part, this is due to intuitive norms of justice, according to which it is considered unfair that a seller makes a loss. Also, the contractor's organization involves many people, while the client's representative often works autonomously in close contact with the contractors. This can explain why contractors often prefer informal decision making and communication.<p /> Clients tend to improve their position by organizing the interaction so that the contractors' informal power is neutralized.<p /> Conceptions formed on the industry level are important determinants of informal power relations. This is because perceptions of fairness are social constructs, and are influenced by explanations as well as by expectations. Publicly expressed conflicts and antagonistic attitudes should, therefore, be viewed as ways of promoting interests without harming relations on the project level. An improved understanding of informal aspects of client-contractor relationships, thus, suggests novel explanations of general cultural aspects of the construction industry

Supply-chain collective action towards zero CO2 emissions in infrastructure construction: Mapping barriers and opportunities

Successful decarbonisation of the supply chains for buildings and infrastructure, including the production of basic materials, will involve the pursuit - in parallel - of measures to ensure circularity of material flows, measures to improve material efficiency, and to radically reduce CO2 emissions from basic materials production. Emphasis in this work has been on how “intangible” factors such as implicit or explicit constraints within organisations, inadequate communication between actors in the supply chain, overly conservative norms or lack of information, hinder the realisation of the current carbon mitigation potential. Although this work draw primarily from experiences in Sweden and other developed economies we believe the focus on innovations in the policy arena and efforts to develop new ways of co-operating, coordinating and sharing information between actors (SDG17) and on practices and processes that could enable more sustainable resource use in infrastructure construction may be of relevance also elsewhere. Not the least, since there are still many regions of the world where much of the infrastructure to provide basic services remains to be built (SDG6-7, SDG9, SDG11) a challenge that must be handled in parallel with efforts to reduce/erase the climate impact from infrastructure construction (in line with the Paris Agreement and SDG13)

Public procurement for carbon reduction in infrastructure projects - An international overview

Carbon emissions emanating from infrastructure construction projects are substantial and stem primarily from production of construction materials and use of energy for construction transport and site activities. In recent years, public infrastructure clients world-wide have begun to include carbon reduction goals in their procurement requirements. This is however a new and complex field where practices vary and are still developing. In this paper, we compare models for carbon reduction requirements in infrastructure construction projects based on case studies of large projects in Australia, USA, the Netherlands, Sweden and UK. We found that open, functional carbon reduction requirements were considered innovative but entailed costs for calculating baselines and risks for speculation. Also, high time pressure in projects limits contractors\u27 opportunities to explore reduction opportunities. Thus, specific, prescriptive requirements may play an important role in client-led, long-term innovation processes. Organizational competence and resources on the buyer side are essential, and policies for carbon reduction should aim to increase client capacity. Further, procurement practices are developed in mutual interaction between clients and suppliers over longer periods of time, which limits possibilities to transfer procurement policies and requirements between contexts