Det ökade behovet av distansarbete utmanar tidigare organisatoriska förutsättningar. Detta påverkar ansvariga chefers orientering i att utvärdera och följa upp anställda. Uppsatsen ämnar att undersöka huruvida chefers användning av utvärdering och uppföljning förändrats i samband med ökat distansarbete. Undersökningen ska förhoppningsvis kunna bidra till en ökad förståelse för huruvida chefer i framtiden kan använda sig av utvärdering och uppföljning då de anställda inte befinner sig på en fysisk gemensam plats. Utgångspunkten för undersökningen är att kombinera tidigare teorier gällande informationsteknologi med en utvecklad utformning av utvärdering och uppföljning genom Tight- och Loose Control. Fördjupad kunskap samlades genom intervjuer av fem chefer från olika företag och avdelningar. Resultatet visar på en ökad frekvenstäthet och detaljnivå av kortsiktiga mål samt en ökad flerdimensionell utvärdering och uppföljning vilket indikerar på en utvecklad teoretisk kombination av Tight- och Loose Control i samband med ökat distansarbete.

The direct endothelial contact with adjacent astrocytic end-feet is believed to establish blood-brain barrier (BBB) typical characteristics in endothelial cells of the central nervous system (CNS). However, this contact is only present in capillary vessels of the brain parenchyma and absent in larger veins, arteries and vessels within the meninges. To investigate a potential impact of direct endothelial interactions with adjacent astrocytic end-feet on the molecular tight junction (TJ) composition and ultrastructure, we performed a systematic analysis of endothelial cell contacts within the vascular tree of parenchymal and leptomeningeal vessels. Immunofluorescence labeling for claudin-3, claudin-5, zonula occludens-1 and occludin was used to compare the molecular composition, without showing significant differences in their distribution along the vascular tree of parenchymal and leptomeningeal vessels. Furthermore, electron microscopy in combination with quantitative analyses was performed to investigate the endothelial ultrastructure revealing significant differences within the length of endothelial overlaps between the different vessel types. Here, parenchymal arteries exhibit noticeably longer cell contacts compared to capillaries, which could not be observed in leptomeningeal vessels. It was also observed that arterial vessels regularly contain a higher density of endothelial vesicles throughout the parenchyma and meninges as a sign for transendothelial traffic. Hence, endothelial expression of blood-brain barrier typical TJs is not limited to capillary vessels with an intimate contact to surrounding astrocytes, but is also observed in arteries and veins of the brain parenchyma as well as the meninges, the latter of which are lacking a direct astrocyte-endothelial interaction. These vessel-specific characteristics can now be used to address and compare alterations of the BBB in different settings of CNS pathologies.:Table of Content 1. INTRODUCTION 4 1.1 THE BLOOD-BRAIN BARRIER 4 1.2 HISTORY 5 1.3 STRUCTURE AND COMPOSITION 6 1.4 THE ROLE OF THE MICROENVIRONMENT 8 1.4.1 ASTROCYTES 8 1.4.2 PERICYTES 9 1.5 BLOOD BRAIN BARRIER FUNCTION 10 1.5.1 PHYSIOLOGIC CONDITIONS 10 1. 5.2 PATHOLOGIC CONDITIONS 11 2. OPEN QUESTIONS AND SCIENTIFIC APPROACH 12 3. PUBLICATIONS 13 3.1 DIFFERENT SEGMENTS OF THE CEREBRAL VASCULATURE REVEAL SPECIFIC ENDOTHELIAL SPECIFICATIONS, WHILE TIGHT JUNCTION PROTEINS APPEAR EQUALLY DISTRIBUTED 13 3.2 THE BLOOD-BRAIN BARRIER 28 4. SUMMARY 40 5. REFERENCES 43 6. PROOF OF SIGNIFICANT CONTRIBUTION 48 7. DECLARATION OF ACADEMIC HONESTY 49 8. ACKNOWLEDGMENT 50 9. CURRICULUM VITAE 51

Background and Aim: Bacterial infections are a well described complication of cirrhosis and occur in 37% of hospitalized patients. Culture positive infections in addition to the presence of bacterial products and DNA lead to loss of liver function and decompensation in cirrhosis. The mechanisms and molecular pathways associated with Bacterial Translocation (BT) are unknown. The aims of this study were to determine: i. macrophage phenotype and molecular pathways associated with bacterial translocation ii. if intestinal macrophages in liver cirrhosis are capable of modulating intestinal permeability.iii. structural integrity of the epithelial barrier. Methods: Duodenal biopsies and serum samples were collected from 29 patients with decompensated cirrhosis, 15 patients with compensated and 19 controls. Duodenal macrophages were characterized by means of flow cytometry and IHC. Gene expression analysis was performed to determine molecular pathways involved in BT. Inflammatory cytokine determination was done in serum and culture supernatant by means of customized cytometric bead arrays. Results: Patients with decompensated cirrhosis demonstrated: increased frequency of CD33+/CD14+/TREM-1+ and iNOS+ macrophages in their duodenum, elevated mRNA levels of nitric oxide synthase 2 (NOS2), chemokine ligand 2 (CCL2), chemokine ligand 13 (CCL13) and interleukin 8 (IL8) and increased serum levels of interleukin 6 (IL6), IL8 and lipopolysaccharides (LPS). Additionally, patients with decompensated cirrhosis showed an increase in NO, IL6, IL8 and CCL2 levels in culture supernatant after short term duodenal biopsy culture. Although the epithelial barrier on EM seemed intact, significantly increased expression of the “pore” forming tight junction claudin 2 was observed. Conclusion: This study showed the presence of activated CD14+Trem- 1+iNOS+ intestinal macrophages and increased levels of NO, IL-6 and claudin-2 levels in the duodenum of patients with decompensated liver cirrhosis, suggesting that these factors enhance intestinal permeability to bacterial products. / Afrikaans: Inleiding: Bakteriele infeksie is ‘n beskryfde komplikasie van lewersirrose wat in 37% van gehospitaliseerde pasiente voorkom. Kultuur positiewe infeksies asook die teenwoordigheid van bakteriele produkte en DNA lei tot verlies van lewerfunksie en dekompensasie. Die molekulere meganismes wat verband hou met bakteriele translokasie is nog onbekend. Die doel van hierdie studie was om: i. Makrofaag fenotipe en molekulere meganismes geassosieerd met bakteriele translokasie te beskryf, ii. te bepaal of intestinale makrofage dermdeurlaatbaarheid beinvloed, asook iii. om die struktruele integriteit van die dermwand te bepaal. Methods: Serum en dunderm biopsies was verkry van 29 pasiente met gedekompenseerde lewer sirrose, 15 pasiente met gekompenseerde sirrose en 19 kontroles. Dunderm makrofage was gekarakteriseer met behulp van vloeisitometrie en immunohistochemie. Molekulere meganisms belangrik tydens bakteriele translokasie was bepaal met behulp van geneekspressie. Serum en selkultuur supernatant sitokien bepalings was met Bioplex assays gedoen. Resultate: Pasiente met gedekompenseerde sirrose demonstreer: ‘n verhoogde frekwensie van CD33+/CD14+/TREM-1+ en iNOS+ makrofage in hul dunderm, verhoogde mRNA vlakke van NOS2, CCL2, CCL13 en IL8 asook verhoogde serum vlakke van IL6, IL8, LPS. Addisioneel het pasiente met gedekompenseerde sirrose vehoogde supernatant vlakke van NO, IL6, IL8 and CCL2 na kort termyn dunderm biopsie kulture. Alhoewel elekronmikroskopie gewys het dat die dundermwand intak is, was daar statisties-beduidend verhoogde ekspressie van die “porie” vormende vasteaansluitings- proteien, claudin 2 sigbaar. Gevolgtrekking: Gesamentlik het die studie gewys dat geaktiveerde CD14+/Trem-1+/iNOS+ intestinale makrofage asook verhoogde vlakke van NO, IL-6 en claudin-2 teenwoordig is in die dunderm van pasiente met gedekompenseerde sirrose. Dit dui daarop dat diè faktore derm deurlaatbaarheid vir bakteriele produkte kan verhoog. / Dissertation (MSc)--University of Pretoria, 2011. / Immunology / MSc / Unrestricted

This study aims to examine how the shift from analog to remote work, as a result of digitalization, has affected performance monitoring in organizations and impacted management control systems. Earlier studies within the subject show that a shift results in a reduction in performance monitoring or that classical performance monitoring are replaced with electronic performance monitoring (EPM). In order to examine how performance monitoring changes as a result of the shift and if management control has gotten tighter or looser, this thesis has been based on four semi-structured interviews that were held with managers from three different Swedish organizations. The shift to remote work shows tendencies of a loosening of control in the organizations and to compensate for the loss, managers have implemented different Electronic Performance Monitoring (EPM) systems. The most common EPM systems implemented were video meetings, but other EPM systems were also implemented such as online monitoring. But managers still experience an overall loosening of control as a result of the shift to remote work. Trust seems to be a factor that becomes more important as a result of the shift and seems to have a mitigating effect on the degree of EPM systems the managers choose to implement.

No description available.

Purpose. These experiments were designed to characterize tight junction formation by retinal pigment epithelial (RPE) cells in vitro and to compare the effects on this process of hormonally defined medium (HDM) and serum- containing medium. Methods. Formation of RPE tight junctions was analyzed in freshly isolated rat RPE cells maintained either in HDM or serum-containing medium. Junctions were evaluated functionally by measuring transepithelial electrical resistance (TER) and permeability and structurally by immunolocalization of the junction-associated actin microfilaments. Calcium dependency of the junction was determined by reducing media calcium concentration. Results. RPE cells cultured in serum-free HDM developed calcium-dependent tight junctions, which exhibited TER levels > 150 Ω · cm 2 and low paracellular permeability. Serum-containing media inhibited tight junction formation as indicated by significant reductions in TER and increases in permeability. Junction-associated actin microfilaments and cell density were unchanged. Conclusions. Tight junction formation by RPE cells is inhibited by serum. This activity may play an important role in responses of the RPE layer to injury, contributing to the pathologic progression of blood- retinal barrier dysfunction.

Purpose. In the genetically defective Royal College of Surgeons (RCS) rat model for retinal degeneration, a breakdown occurs in the retinal pigment epithelial (RPE) cell tight junctions just as the photoreceptors begin to degenerate. These experiments sought to determine the impact of the RPE genetic defect on this alteration in the RPE cell tight junctions. Methods. Retinal pigment epithelial cell cultures prepared from RCS and control rats were treated with hormonally defined medium (HDM), base medium conditioned by RCS or control retinas, or unconditioned base medium. The tight junctions formed by these cultures were assayed functionally by measuring transepithelial electrical resistance and permeability. Junction structure was evaluated by immunolocalization of the tight junction protein zonula occludens I and of the junction-associated actin microfilaments. Results. Retinal pigment epithelial cultures from dystrophic rats formed structurally and functionally normal tight junctions when maintained in hormonally defined medium. The junctions remained stable when the medium bathing the apical surface was switched to base medium preconditioned by normal retinas. In contrast, cultures treated with medium preconditioned by degenerating dystrophic retinas or with unconditioned medium exhibited a breakdown in their tight junctions. Conclusions. Retinal pigment epithelial cells isolated from dystrophic RCS rats can form tight junctions normally in vitro. Normal, but not dystrophic, retinas release factors that support RPE tight junctions. Therefore, the junctional abnormality seen in dystrophic rat RPE cells in vivo is probably caused by the loss of trophic factors normally provided by the healthy neural retina rather than by a direct effect of the genetic defect on the tight junctions.

[pt] O campo de pesquisa que busca entender a relação entre cultura e as preferências ao risco e tempo tem se desenvolvido nos últimos dez anos. No entanto, o número de trabalhos que utilizam uma amostra significativa de países, tornando possível a comparação através das nações, ainda é pequeno. Ademais, os trabalhos existentes utilizam o mesmo construto de cultura, o de Hofstede (2001). Sendo assim, este estudo teve o objetivo de identificar, através de uma análise cross-country de 24 nações, se o construto de cultura de Gelfand et al (2001) se relaciona com as preferências ao risco e tempo. Além disso, foram investigadas as relações entre cultura, risco e paciência com indicadores econômicos, demográficos e de saúde. Para atingir a finalidade proposta foram utilizados os dados sobre risco e paciência de Falk et al (2018), o construto de culturas rígidas e tolerantes proposto por Gelfand et al (2011) e indicadores coletados nos sites do World Bank e Transparency International. Após a análise dos resultados não foi encontrada relação entre o construto de cultura de Gelfand com os índices de risco e paciência. No entanto, foram detectadas associações entre o tipo de cultura, rígida ou tolerante, com taxa de mortalidade geral, taxa de mortalidade infantil e índice de gravidez na adolescência. Ao examinar a paciência observa-se que este índice se associa com o PIB per capita, conforme os resultados de Falk et al (2018) e Wang et al (2016), e com a taxa de mortalidade geral. / [en] The field of research that seeks to understand the relationship between culture and preferences for risk and time has developed over the past ten years. However, the number of studies using a significant sample of countries, making it possible to compare across nations, is still small. Furthermore, the existing works use the same culture construct, that of Hofstede (2001). Thus, this study aimed to identify, through a cross-country analysis of 24 nations, whether the culture construct of Gelfand et al (2001) is related to risk and time preferences. In addition, the relationship between culture, risk and patience with economic, demographic and health indicators were investigated. In order to achieve the goal, the data on risk and patience from Falk et al (2018), the construct of tight and loose cultures proposed by Gelfand et al (2011) and indicators collected on the World Bank and Transparency International websites were used. After analyzing the results no relationship was found between the Gelfand culture construct and patience or risk taking. However, associations were detected between the type of culture, tight or loose, with general mortality rate, infant mortality rate and teenage pregnancy rate. When examining patience, it is observed that this index is associated with GDP per capita, according to the results of Falk et al (2018) and Wang et al (2016), and with the overall mortality rate.

Active and passive transport of substances between the microcirculation in the brain and the central nervous system is regulated by the Blood-Brain Barrier (BBB). This barrier allows for chronic and acute modulation of the CNS microenvironment, and protects the brain from potentially noxious compounds carried in the circulatory system. In-vitro modeling of the BBB has become the target of much research over the past decade, as there are many unanswered questions regarding modulations in the permeability of this barrier. Additionally, the development of a practical and inexpensive model of the BBB would facilitate a much more efficient drug development process. The goal of this project is to investigate the formation of the BBB through assessment of tight junction formation and endothelial cell monolayer permeability. Accomplishment of this goal will include completion of the two primary aims of this thesis, which are 1) development of an immunohistochemical staining protocol for the labeling of tight junctional proteins, and 2) characterization of permeability across a porous membrane co-cultured with bovine aortic endothelial cells (BAECs) and C6 glioma cells. Both of these aims were met, as a reliable IF protocol for tight junctional staining was developed, and permeability values across a permeable membrane seeded with BAECs and C6s were collected. The completion of these aims has helped to accomplish the goal of investigating the formation of tight junctions in an in-vitro model of the BBB. The IF protocol that has been developed, along with the collected permeability data will aid the development of a more dynamic in-vitro model of the BBB to aid in research surrounding acute modulation of the BBB, along with facilitating a timelier drug development process.

<p>In sum, these studies described in this dissertation showed that both mycotoxin deoxynivalenol exposure and nutrient starvation can increase endocytosis and degradation of tight junction proteins in the lysosome. Therefore, manipulation of endocytic pathway as well as the signaling pathway involved in this process can be used to prevent intestinal barrier dysfunction in animals.</p> <p><br></p>