Change search
Refine search result
72737475767778 3701 - 3750 of 4176
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 3701. Uhlén, Mathias
    et al.
    Fagerberg, Linn
    Hallström, Bjoern M.
    Lindskog, Cecilia
    Oksvold, Per
    Mardinoglu, Adil
    Sivertsson, Asa
    Kampf, Caroline
    Sjöstedt, Evelina
    Asplund, Anna
    Olsson, IngMarie
    Edlund, Karolina
    Lundberg, Emma
    Navani, Sanjay
    Szigyarto, Cristina Al-Khalili
    Odeberg, Jacob
    Djureinovic, Dijana
    Ottosson Takanen, Jenny
    Hober, Sophia
    Alm, Tove
    Edqvist, Per-Henrik
    Berling, Holger
    Tegel, Hanna
    Mulder, Jan
    Rockberg, Johan
    Nilsson, Peter
    Schwenk, Jochen M.
    Hamsten, Marica
    von Feilitzen, Kalle
    Forsberg, Mattias
    Persson, Lukas
    Johansson, Fredric
    Zwahlen, Martin
    von Heijne, Gunnar
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Nielsen, Jens
    Pontén, Fredrik
    Tissue-based map of the human proteome2015In: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 347, no 6220, article id 1260419Article in journal (Refereed)
    Abstract [en]

    Resolving the molecular details of proteome variation in the different tissues and organs of the human body will greatly increase our knowledge of human biology and disease. Here, we present a map of the human tissue proteome based on an integrated omics approach that involves quantitative transcriptomics at the tissue and organ level, combined with tissue microarray-based immunohistochemistry, to achieve spatial localization of proteins down to the single-cell level. Our tissue-based analysis detected more than 90% of the putative protein-coding genes. We used this approach to explore the human secretome, the membrane proteome, the druggable proteome, the cancer proteome, and the metabolic functions in 32 different tissues and organs. All the data are integrated in an interactive Web-based database that allows exploration of individual proteins, as well as navigation of global expression patterns, in all major tissues and organs in the human body.

  • 3702. Ulfvarson, Johanna
    et al.
    Rahmner, Pia Bastholm
    Fastbom, Johan
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Sjöviker, Susanne
    Karlsson, Eva Andersén
    Medication reviews with computerised expert support: evaluation of a method to improve the quality of drug utilisation in the elderly2010In: International Journal of Health Care Quality Assurance, ISSN 0952-6862, E-ISSN 1758-6542, Vol. 23, no 6, p. 571-82Article in journal (Refereed)
    Abstract [en]

    PURPOSE: This paper aims to examine whether a computerised system for medication reviews can support physicians' decisions and improve the quality of drug treatment in the elderly.

    DESIGN/METHODOLOGY/APPROACH: This is a descriptive intervention study. The study included 275 patients living in community settings and nursing homes in Stockholm, Sweden. Patient data were analysed using computer software and scrutinised by a clinical pharmacologist. Pharmaco-therapeutic advice was sent to the physician responsible for each patient. The main outcome measures were initiation and discontinuation of drugs, changes of doses and rates of identified drug-related problems.

    FINDINGS: Expert opinions were given by the clinical pharmacologist, for 275 patients, mean age 85 years; 70 per cent female. An average of 3.3 remarks was given concerning unsuitable drugs, unclear indication, dosing when the kidney function was decreased, drug-drug interactions and quality indicators. On average 1.5 drug-related problems (DRP) per patient were attended to by the responsible physician at each unit. The most common action taken was withdrawal of a drug (n = 208). On average the drug use decreased from 10.4 to 9.5 drugs per patient, and several quality indicators were met. The drug costs decreased, and resulted in a more cost-effective drug therapy.

    ORIGINALITY/VALUE: The paper develops and tests a method for intervention in the care of elderly patients. The method is based on a computerised expert support system for medication reviews at a distance and on education of the staff. A safer drug therapy with improved quality and cost-effectiveness is thus provided.

  • 3703. Ulhaq, Mazhar
    et al.
    Sundström, Maria
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Larsson, Pia
    Gabrielsson, Johan
    Bergman, Åke
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Norrgren, Leif
    Örn, Stefan
    Tissue uptake, distribution and elimination of C-14-PFOA in zebrafish (Danio rerio)2015In: Aquatic Toxicology, ISSN 0166-445X, E-ISSN 1879-1514, Vol. 163, p. 148-157Article in journal (Refereed)
    Abstract [en]

    Perfluorooctanoic acid (PFOA) is a long-chain perfluorinated chemical that has been shown to be non-degradable and persistent in the environment. Laboratory studies on bioconcentration and compound-specific tissue distribution in fish can be valuable for prediction of the persistence and environmental effects of the chemicals. In the present study male and female zebrafish (Danio redo) were continuously exposed to 10 mu g/L of radiolabeled perfluorooctanoic acid (C-14-PFOA) for 40 days, after which the exposed fish were transferred to fresh clean water for another 80 days wash-out period. At defined periodic intervals during the uptake and wash-out, fish were sampled for liquid scintillation counting and whole body autoradiography to profile the bioconcentration and tissue distribution of PFOA. The steady-state concentration of C-14-PFOA in the zebrafish was reached within 20-30 days of exposure. The concentration-time course of C-14-PFOA displayed a bi-exponential decline during washout, with a terminal half-life of approximately 13-14 days. At steady-state the bioconcentration of C-14-PFOA into whole-body fish was approximately 20-30 times greater than that of the exposure concentration, with no differences between females and males. The bioconcentration factors for liver and intestine were approximately 100-fold of the exposure medium, while in brain, ovary and gall bladder the accumulation factors were in the range 15-20. Whole-body autoradiograms confirmed the highest labeling of PFOA in bile and intestines, which implies enterohepatic circulation of PFOA. The C-14-PFOA was also observed in maturing vitellogenic oocytes, suggesting chemical accumulation via yolk proteins into oocytes with plausible risk for adverse effects on early embryonic development and offspring health. The bioconcentration at several C-14-PFOA exposure concentrations were also investigated (0.3-30 mu g/L). This showed that bioconcentration increased linearly with tank exposure in the present in vivo model under steady-state conditions. From this model tissue concentrations of PFOA can be predicted when the external exposure level is known. The present study has generated experimental data on PFOA kinetics in zebrafish that can be valuable for aquatic environmental risk assessment.

  • 3704. Ulhassan, W.
    et al.
    Sandahl, C.
    Westerlund, Hugo
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    von Thiele Schwarz, U.
    Thor, J.
    Lean and teamwork: A longitudinal study of how Lean isrelated to teamwork in a hospital2013Conference paper (Refereed)
  • 3705. Ulhassan, Waqar
    et al.
    Sandahl, Christer
    Westerlund, Hugo
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Henriksson, Peter
    Bennermo, Marie
    von Thiele Schwarz, Ulrica
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Thor, Johan
    Antecedents and Characteristics of Lean Thinking Implementation in a Swedish Hospital: A Case Study2013In: Quality Management in Health Care, ISSN 1063-8628, E-ISSN 1550-5154, Vol. 22, no 1, p. 48-61Article in journal (Refereed)
    Abstract [en]

    Despite the reported success of Lean in health care settings, it is unclear why and how organizations adopt Lean and how Lean transforms work design and, in turn, affects employees' work. This study investigated a cardiology department's journey to adopt and adapt Lean. The investigation was focused on the rationale and evolution of the Lean adoption to illuminate how a department with a long quality improvement history arrived at the decision to introduce Lean, and how Lean influenced employees' daily work. This is an explanatory single case study based on semistructured interviews, nonparticipant observations, and document studies. Guided by a Lean model, we undertook manifest content analysis of the data. We found that previous improvement efforts may facilitate the introduction of Lean but may be less important when forecasting whether Lean will be sustained over time. Contextual factors seemed to influence both what Lean tools were implemented and how well the changes were sustained. For example, adoption of Lean varied with the degree to which staff saw a need for change. Work redesign and teamwork were found helpful to improve patient care whereas problem solving was found helpful in keeping the staff engaged and sustaining the results over time.

  • 3706. Ulhassan, Waqar
    et al.
    von Thiele Schwarz, Ulrica
    Thor, Johan
    Sandahl, Christer
    Westerlund, Hugo
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Interactions between Lean and Psychosocial Work Environment in a Hospital Setting: A Multiple Method Study2013Conference paper (Refereed)
  • 3707. Ulhassan, Waqar
    et al.
    von Thiele Schwarz, Ulrica
    Stockholm University, Faculty of Social Sciences, Department of Psychology. Karolinska Institutet, Sweden.
    Thor, Johan
    Westerlund, Hugo
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Interactions between lean management and the psychosocial work environment in a hospital setting - a multi-method study2014In: BMC Health Services Research, ISSN 1472-6963, E-ISSN 1472-6963, Vol. 14, p. 480-Article in journal (Refereed)
    Abstract [en]

    Background: As health care struggles to meet increasing demands with limited resources, Lean has become a popular management approach. It has mainly been studied in relation to health care performance. The empirical evidence as to how Lean affects the psychosocial work environment has been contradictory. This study aims to study the interaction between Lean and the psychosocial work environment using a comprehensive model that takes Lean implementation information, as well as Lean theory and the particular context into consideration. Methods: The psychosocial work environment was measured twice with the Copenhagen Psychosocial Questionnaire (COPSOQ) employee survey during Lean implementations on May-June 2010 (T1) (n = 129) and November-December 2011 (T2) (n = 131) at three units (an Emergency Department (ED), Ward-I and Ward-II). Information based on qualitative data analysis of the Lean implementations and context from a previous paper was used to predict expected change patterns in the psychosocial work environment from T1 to T2 and subsequently compared with COPSOQ-data through linear regression analysis. Results: Between T1 and T2, qualitative information showed a well-organized and steady Lean implementation on Ward-I with active employee participation, a partial Lean implementation on Ward-II with employees not seeing a clear need for such an intervention, and deterioration in already implemented Lean activities at ED, due to the declining interest of top management. Quantitative data analysis showed a significant relation between the expected and actual results regarding changes in the psychosocial work environment. Ward-I showed major improvements especially related to job control and social support, ED showed a major decline with some exceptions while Ward-II also showed improvements similar to Ward-I. Conclusions: The results suggest that Lean may have a positive impact on the psychosocial work environment given that it is properly implemented. Also, the psychosocial work environment may even deteriorate if Lean work deteriorates after implementation. Employee managers and researchers should note the importance of employee involvement in the change process. Employee involvement may minimize the intervention's harmful effects on psychosocial work factors. We also found that a multi-method may be suitable for investigating relations between Lean and the psychosocial work environment.

  • 3708. Ulhassan, Waqar
    et al.
    von Thiele Schwarz, Ulrica
    Stockholm University, Faculty of Social Sciences, Department of Psychology. Karolinska Institutet, Sweden.
    Westerlund, Hugo
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Sandahl, Christer
    Thor, Johan
    How Visual Management for Continuous Improvement Might Guide and Affect Hospital Staff: A Case Study2015In: Quality Management in Health Care, ISSN 1063-8628, E-ISSN 1550-5154, Vol. 24, no 4, p. 222-228Article in journal (Refereed)
    Abstract [en]

    Visual management (VM) tools such as whiteboards, often employed in Lean thinking applications, are intended to be helpful in improving work processes in different industries including health care. It remains unclear, however, how VM is actually applied in health care Lean interventions and how it might influence the clinical staff. We therefore examined how Lean-inspired VM using whiteboards for continuous improvement efforts related to the hospital staff's work and collaboration. Within a case study design, we combined semistructured interviews, nonparticipant observations, and photography on 2 cardiology wards. The fate of VM differed between the 2 wards; in one, it was well received by the staff and enhanced continuous improvement efforts, whereas in the other ward, it was not perceived to fit in the work flow or to make enough sense in order to be sustained. Visual management may enable the staff and managers to allow communication across time and facilitate teamwork by enabling the inclusion of team members who are not present simultaneously; however, its adoption and value seem contingent on finding a good fit with the local context. A combination of continuous improvement and VM may be helpful in keeping the staff engaged in the change process in the long run.

  • 3709. Ulhassan, Waqar
    et al.
    Westerlund, Hugo
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Thor, Johan
    Sandahl, Christer
    von Thiele Schwarz, Ulrica
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Does lean implementation interact with group functioning?2014In: Journal of Health Organisation & Management, ISSN 1477-7266, E-ISSN 1758-7247, Vol. 28, no 2, p. 196-213Article in journal (Refereed)
    Abstract [en]

    PURPOSE: As healthcare often is studied in relation to operational rather than socio-technical aspects of Lean such as teamwork, the purpose of this paper is to explore how a Swedish hospital Lean intervention was related to changes in teamwork over time.

    DESIGN/METHODOLOGY/APPROACH: Teamwork was measured with the Group Development Questionnaire (GDQ) employee survey during Lean implementation at three units, in 2010 (n = 133) and 2011 (n = 130). Qualitative data including interviews, observations and document analysis were used to characterize the Lean implementation and context. The expected teamwork change patterns were compared with GDQ data through linear regression analysis.

    FINDINGS: At Ward-I, Lean implementation was successful and teamwork improved. At Ward-II, Lean was partially implemented and teamwork improved slightly, while both Lean and teamwork deteriorated at the emergency department (ED). The regression analysis was significant at ED (p = 0.02) and the Ward-II (p = 0.04), but not at Ward-I (p = 0.11).

    RESEARCH LIMITATIONS/IMPLICATIONS: Expected changes in teamwork informed by theory and qualitative data may make it possible to detect the results of a complex change.

    PRACTICAL IMPLICATIONS: Overall, Lean may have some impact on teamwork, if properly implemented. However, this impact may be more prominent in relation to structural and productivity issues of teamwork than group members' relational issues. Practitioners should note that, with groups struggling with initial stages of group functioning, Lean may be very challenging.

    ORIGINALITY/VALUE: This study focussed specifically on implications of Lean for nurse teamwork in a hospital setting using both qualitative and quantitative data. Importantly, the group functioning at the time when Lean is initiated may affect the implementation of Lean.

  • 3710. Ulhoa, M. A.
    et al.
    Marqueze, E. C.
    Burgos, L. G. A.
    Moreno, C. R. C.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Universidade de Sao Paulo, Brazil.
    Shift Work and Endocrine Disorders2015In: International Journal of Endocrinology, ISSN 1687-8337, E-ISSN 1687-8345, article id 826249Article, review/survey (Refereed)
    Abstract [en]

    The objective of this review was to investigate the impact of shift and night work on metabolic processes and the role of alterations in the sleep-wake cycle and feeding times and environmental changes in the occurrence of metabolic disorders. The literature review was performed by searching three electronic databases for relevant studies published in the last 10 years. The methodological quality of each study was assessed, and best-evidence synthesis was applied to draw conclusions. The literature has shown changes in concentrations of melatonin, cortisol, ghrelin, and leptin among shift workers. Melatonin has been implicated for its role in the synthesis and action of insulin. The action of this hormone also regulates the expression of transporter glucose type 4 or triggers phosphorylation of the insulin receptor. Therefore, a reduction in melatonin can be associated with an increase in insulin resistance and a propensity for the development of diabetes. Moreover, shift work can negatively affect sleep and contribute to sedentarism, unhealthy eating habits, and stress. Recent studies on metabolic processes have increasingly revealed their complexity. Physiological changes induced in workers who invert their activity-rest cycle to fulfill work hours include disruptions in metabolic processes.

  • 3711. Ullén, Fredrik
    et al.
    de Manzano, Örjan
    Theorell, Töres
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Harmat, Lazlo
    The physiology of Effortless Attention: Correlates of State Flow and Flow Proneness.2010In: Effortless Attention: A New Perspective in the Cognitive Science of Attention and Action / [ed] Bruya Brian, Bradford Books , 2010, 1, p. 205-218Chapter in book (Other academic)
  • 3712. Ulvestad, Bente
    et al.
    Randem, Britt Grethe
    Skare, Oivind
    Aalokken, Trond Mogens
    Myranek, Georg Karl
    Elihn, Karine
    Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.
    Lund, May Brit
    Lung function in asphalt pavers: a longitudinal study2017In: International Archives of Occupational and Environmental Health, ISSN 0340-0131, E-ISSN 1432-1246, Vol. 90, no 1, p. 63-71Article in journal (Refereed)
    Abstract [en]

    To study longitudinal changes in lung function in asphalt pavers and a reference group of road maintenance workers, and to detect possible signs of lung disease by high-resolution computed tomography (HRCT) scans. Seventy-five asphalt pavers and 71 road maintenance workers were followed up with questionnaires and measurements of lung function. Not every worker was tested every year, but most of them had four or more measurement points. The 75 asphalt pavers were also invited to have HRCT scans of the lungs at the end of the follow-up period. Mean annual decline in forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) of the asphalt pavers was 58 and 35 ml, respectively. Adjusted for age at baseline, packyears of smoking and BMI, the asphalt pavers had a significant excess annual decline in FVC and FEV1 compared to the references. The screedmen, the most exposed group of the asphalt pavers, showed a significantly larger decline in FVC than the other asphalt pavers (P = 0.029). Fine intralobular fibrosis without evident cysts was identified with HRCT in three subjects (4 %). We conclude that our findings may indicate an excess annual decline in FVC and FEV1 related to exposure to asphalt fumes. The screedmen, who carry out their work behind and close to the paving machine, had the largest decline in lung function. The finding of adverse pulmonary effects in asphalt pavers calls for better technological solutions to prevent exposure.

  • 3713. Underwood, Nora
    et al.
    Inouye, Brian D.
    Hambäck, Peter A.
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences.
    A CONCEPTUAL FRAMEWORK FOR ASSOCIATIONAL EFFECTS: WHEN DO NEIGHBORS MATTER AND HOW WOULD WE KNOW?2014In: The Quarterly review of biology, ISSN 0033-5770, E-ISSN 1539-7718, Vol. 89, no 1, p. 1-19Article, review/survey (Refereed)
    Abstract [en]

    Interactions between individual consumer and resource organisms can be modified by neighbors, e.g., when herbivory depends on the identity or diversity of neighboring plants. Effects of neighbors on consumer-resource interactions (associational effects) occur in many systems, including plant-herbivore interactions, predator-prey interactions (mimicry), and plant-pollinator interactions. Unfortunately, we know little about how ecologically or evolutionarily important these effects are because we lack appropriate models and data to determine how neighbor effects on individuals contribute to net interactions at population and community levels. Here we supply a general definition of associational effects, review relevant theory, and suggest strategies for future theoretical and empirical work. We find that mathematical models from a variety of fields suggest that individual-level associational effects will influence population and community dynamics when associational effects create local frequency dependence. However, there is little data on how local frequency dependence in associational effects is generated, or on the form or spatial scale of that frequency dependence. Similarly, existing theory lacks consideration of nonlinear and spatially explicit frequency dependence. We outline an experimental approach for producing data that can be related to models to advance our understanding of how associational effects contribute to population and community processes.

  • 3714. Undén, Anna-Lena
    et al.
    Elofsson, Stig
    Stockholm University, Faculty of Social Sciences, Department of Social Work.
    Andréasson, Anna
    Hillered, Eva
    Eriksson, Ingeborg
    Brismar, Kerstin
    Gender Differences in Self-Rated Health, Quality of Life, Quality of Care, and Matebolic Control in Patients with Diabetes2008In: Gender Medicine, ISSN 1550-8579, E-ISSN 1878-7398, Vol. 5, no 2, p. 162-180Article in journal (Refereed)
    Abstract [en]

    Background: Because the projected increase in the number of diabetic patients is expected to strain the capabilities of health care providers worldwide, we are challenged to find ways of reducing the burden of diabetes. Maintaining and improving health-related quality of life (QoL) for diabetic patients may be viewed as public health goals.

    Objective: The aim of this cross-sectional study was to compare different aspects of health, QoL, and quality of care (QoC) between men and women with diabetes as a basis for planning and managing diabees care.

    Methods: All patients in 2 age groups (aged 20–30 years [younger age group] and aged 50–60 years [middle-aged group]) who were registered with the Department of Endocrinology, Metabolism, and Diabetes at Karolinska University Hospital, Stockholm, Sweden, in October 2004, were recruited for a survey. Questions were included about self-rated health (SRH), QoL, QoC, diabetes-related worries, occupational status, physical activity level, living arrangements, and educational background. Glycosylated hemoglobin (HbA1c) values were obtained from medical records.

    Results: Of the 223 eligible patients (109 men, 114 women) in the younger age group, 49 men and 74 women responded to the questionnaire; of the 300 eligible patients (170 men, 130 women) in the middle-aged group, 120 men and 93 women responded. Middle-aged women rated their mental well-being and QoL as worse compared with men (P < 0.001 and P < 0.05, respectively). In both age groups, women reported more diabetes-related worries and less ability to cope (P < 0.05 for the younger age group and P < 0.001 for the middle-aged group for both variables), thus the differences were more marked for middleaged women. Although there were no gender differences in metabolic control, middle-aged women reported less satisfaction with diabetes care (P < 0.001). Higher HbA1c was related to worse SRH in both men and women when analyzing the age groups together (P < 0.05). This association was most prominent in young women, in whom having more diabetes-related worries was also related to higher HbA1c (P < 0.01).

    Conclusion: In this study, women with diabetes appeared to have worse QoL and mental well-being compared with men with diabetes. Therefore, identifying strategies to improve SRH and QoL among diabetic patients, especially among women, is of great importance.

  • 3715.
    Unge, Annika
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Marker genes: molecular tools for in situ monitoring of bacterial distribution and activity in environmental samples2000Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Many different microorganisms carry out environmental functions, such as nutrient cycling, plant growth enhancement, or biodegradation. Some microorganisms also negatively affect their environment by causing disease. In order to gain a better understanding of the fate and behavior of specific microorganisms in nature, specific monitoring methods are required.

    This work focuses on the development of marker genes to monitor bacteria in environmental samples. The gfp gene, encoding the Green Fluorescent Protein (GFP), and the luxAB genes, encoding bacterial luciferase, were developed and applied as tools to track specific bacteria. To enable a strong expression of the eukaryotic gfp gene in bacteria, an expression cassette was assembled by fusing gfp to a ribosome binding site under control of a constitutive promoter. A variant cassette containing two copies of gfp was also constructed for higher expression of GFP. The gfp cassettes were inserted into Tn5 based transposon vectors for stable integration of gfp into the chromosomes of different bacterial strains. The Tn5-gfp cassettes were used to tag both Gram- and Gram+ strains with gfp. The intensity of fluorescence was dependent on the copy number of gfp. However, one copy of gfp was enough for visualisation of single bacterial cells by epifluorescence microscopy and confocal laser microscopy as well as for quantification by flow cytometry. GFP-fluorescent cells could also easily be distinguished from the indigenous bacterial population in soil samples and on plant surfaces by their fluorescence phenotype.

    In order to simultaneously quantify bacterial numbers and activity, a dual marker cassette containing both gfp and luxAB genes was constructed. Expression of the luminescence phenotype conferred by the luxAB genes is dependent on cellular energy reserves. The luciferase activity was highly correlated to the cell number when cells were actively growing, but decreased relative to cell number under starvation conditions. On the other hand, the GFP phenotype was insensitive to starvation conditions allowing gfp-tagged cells to be monitored independently of nutrient availability. Also, cells were detected by their GFP fluorescence when they were viable but nonculturable. The GFP fluorescence phenotype was found to be dependent on cell membrane integrity, as GFP was lost from dead cells with permeabilised membranes.

    The dual gfp-luxAB marker was useful for in situ studies of the plant growth promoting bacterium, Pseudomonas fluorescens SBW25, during colonisation of wheat plants starting from seed inoculum. The highest bacterial concentrations were found on the wheat seed, compared to the roots and leaves. By stereomicroscopy the in situ distribution of P. fluorescens SBW25 cells and the regions where they were metabolically active, were simultaneously monitored on the same wheat seeds. The P. fluorescens SBW25 cells showed a preference for specific regions on the wheat seed, such as the groove formed between the scutellum and the coleoptile. Interestingly, the P. fluorescens SBW25 cells were metabolically active on all plant parts where they were localised.

    In conclusion, the methods developed in this study are optimal tools for detection and quantification of bacteria and have wide applications for monitoring specific bacterial populations of interest in environmental samples.

  • 3716.
    Unger, Maria
    et al.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK). Stockholm University, Faculty of Science, Department of Applied Environmental Science (ITM).
    Asplund, Lillemor
    Stockholm University, Faculty of Science, Department of Applied Environmental Science (ITM).
    Marsh, Göran
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Environmental Chemistry.
    Gustafsson, Örjan
    Stockholm University, Faculty of Science, Department of Applied Environmental Science (ITM).
    Characaterization of an abundant and novel methyl- and methoxy-substituted brominated diphenyl ether isolated from whale blubber2010In: Chemosphere, ISSN 0045-6535, E-ISSN 1879-1298, Vol. 79, no 4, p. 408-413Article in journal (Refereed)
    Abstract [en]

    A previously unidentified yet abundant substituted polybrominated diphenyl ether (PBDE) was isolated from a northern bottlenose whale (Hyperoodon ampullatus) found dead in the Skagerrak, North Sea. A combination of gas chromatography, high and low resolution mass spectrometry and nuclear magnetic resonance spectroscopy (NMR) (1H, 1H–1H and 1H–13C) after isolation with preparative capillary gas chromatography (PCGC) lead to the identification of the unknown substance as 6-MeO-5-Me-2,2′,3,4′-tetrabromo diphenyl ether (6-MeO-5-Me-BDE42). To our knowledge this is only the second time PCGC has been used to isolate individual organohalogen compounds present in trace amounts for identification with NMR. The concentration of this novel bioaccumulated compound was estimated to be about 100 ng g−1 lipid, which was 2.5 times higher compared with the most abundant MeO-PBDE congeners.

  • 3717. Urgard, Egon
    et al.
    Lorents, Annely
    Klaas, Mariliis
    Padari, Kart
    Viil, Janeli
    Runnel, Toomas
    Langel, Kent
    Kingo, Kulli
    Tkaczyk, Eric
    Langel, Ülo
    Stockholm University, Faculty of Science, Department of Neurochemistry. University of Tartu, Estonia.
    Maimets, Toivo
    Jaks, Viljar
    Pooga, Margus
    Rebane, Ana
    Pre-administration of PepFect6-microRNA-146a nanocomplexes inhibits inflammatory responses in keratinocytes and in a mouse model of irritant contact dermatitis2016In: Journal of Controlled Release, ISSN 0168-3659, E-ISSN 1873-4995, Vol. 235, p. 195-204Article in journal (Refereed)
    Abstract [en]

    The skin is a difficult to access tissue for efficient delivery of large and/or chargedmacromolecules, including therapeutic DNA and RNA oligonucleotides. Cell-penetrating peptide PepFect6 (PF6) has been shown to be suitable transport vehicle for siRNAs in cell culture and systemically in vivo in mice. MiR-146a is known as anti-inflammatory miRNA that inhibits multiple factors fromthe nuclear factor (NF)-kappa B pathway in various cell types, including keratinocytes. In this study, PF6 was shown to form unimodal nanocomplexes with miR-146a mimic that entered into human primary keratinocytes, where miR-146a inhibited the expression of its direct targets fromthe NF-kappa B pathway and the genes known to be activated by NF-kappa B, C-C motif ligand (CCL)5 and interleukin (IL)-8. The transfection of miR-146a mimic with PF6 was more efficient in sub-confluent keratinocyte cultures, affected keratinocyte proliferation less and had similar effect on cell viability when compared with a lipid based agent. Subcutaneous pre-administration of PF6-miR-146a nanocomplexes attenuated ear-swelling and reduced the expression of pro-inflammatory cytokines and chemokines IL-6, CCL11, CCL24 and C-X-C motif ligand 1 (CXCL1) in a mouse model of irritant contact dermatitis. Our data demonstrates that PF6-miR-146a nanoparticles might have potential in the development of therapeutics to target inflammatory skin diseases.

  • 3718. Urquia, Marcelo L
    et al.
    Qiao, Yao
    Ray, Joel G
    Liu, Can
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS).
    Hjern, Anders
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS).
    Birth Outcomes of Foreign-Born, Native-Born, and Mixed Couples in Sweden.2015In: Paediatric and Perinatal Epidemiology, ISSN 0269-5022, E-ISSN 1365-3016, Vol. 29, no 2, p. 123-130Article in journal (Refereed)
    Abstract [en]

    Background: Many births in industrialised countries are to immigrant parents, or to one immigrant and one domestically born parent. Their newborn outcomes have not been well studied. 

    Methods: We conducted a study of 1690423 singleton infants born in Sweden between 1987 and 2008, including those of immigrants from East Asia, South Asia, Sub-Saharan Africa, and East Africa. Preterm delivery and small for gestational age (SGA) were assessed among infants of (i) immigrant parents from the same world region, (ii) an immigrant mother and a Swedish-born father, and (iii) a Swedish-born mother and an immigrant father; each compared to (iv) two Swedish-born parents. Log binomial regression analysis generated adjusted risk ratios (ARRs) and 95% confidence intervals (CIs) for preterm delivery and SGA.

    Results: Compared with infants of two Swedish-born parents, infants born to immigrant mothers from East Asia, South Asia, and Sub-Saharan African were at higher risk of preterm delivery (ARR ranging from 1.2 to 1.9), irrespective of whether the father was from the same world region or Swedish-born, with the only exception of East African women, who had lower risk. Infants born to two foreign-born parents had the highest risks of SGA, particularly South Asians (ARR 4.69; 95% CI 4.29, 5.12). Mixed couples exhibited intermediate risks of SGA. 

    Conclusions: Adverse birth outcomes differ according to a couple's ethnic composition. Having a Swedish-born partner is associated with lower risk of SGA among immigrant mothers and fathers, and with lower risk of preterm delivery among immigrant fathers but not mothers.

  • 3719. Urquia, ML
    et al.
    Glazier, RH
    Gagnon, AJ
    Mortensen, LH
    Nybo Andersen, A-M
    Janevic, T
    Guendelman, S
    Thornton, D
    Bolumar, F
    Sanchez, I
    Small, J
    Davey, M-A
    Hjern, Anders
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS).
    Disparities in pre-eclampsia and eclampsia among immigrant women giving birth in six industrialised countries2014In: Obstetrics and Gynecology, ISSN 0029-7844, E-ISSN 1873-233X, Vol. 121, no 12, p. 1492-1500Article in journal (Refereed)
  • 3720. Uusküla, Anneli
    et al.
    Rajaleid, Kristiina
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS).
    Talu, Ave
    Abel-Ollo, Katri
    Des Jarlais, Don C.
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS).
    A decline in the prevalence of injecting drug users in Estonia, 2005–20092013In: International Journal of Drug Policy, ISSN 0955-3959, Vol. 24, no 4, p. 312-318Article in journal (Refereed)
    Abstract [en]

    Aims: Here we report a study aimed at estimating trends in the prevalence of injection drug use between 2005 and 2009 in Estonia. Background: Descriptions of behavioural epidemics have received little attention compared with infectious disease epidemics in Eastern Europe. Methods: The number of injection drug users (IDUs) aged 15–44 each year between 2005 and 2009 was estimated using capture–recapture methodology based on 4 data sources (2 treatment data bases: drug use and non-fatal overdose treatment; criminal justice (drug related offences) and mortality (injection drug use related deaths) data). Poisson log-linear regression models were applied to the matched data, with interactions between data sources fitted to replicate the dependencies between the data sources. Linear regression was used to estimate average change over time. Results: There were 24305, 12,292, 238, 545 records and 8100, 1655, 155, 545 individual IDUs identified in the four capture sources (police, drug treatment, overdose, and death registry, accordingly) over the period 2005–2009. The estimated prevalence of IDUs among the population aged 15–44 declined from 2.7% (1.8–7.9%) in 2005 to 2.0% (1.4–5.0%) in 2008, and 0.9% (0.7–1.7%) in 2009. Regression analysis indicated an average reduction of about 1600 injectors per year. Conclusion: While the capture–recapture method has known limitations, the results are consistent with other data from Estonia. Identifying the drivers of change in the prevalence of injection drug use warrants further research.

  • 3721. Vaag, Jonas
    et al.
    Saksvik, Per Oystein
    Theorell, Töres
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institute, Sweden.
    Skillingstad, Trond
    Bjerkeset, Ottar
    Sound of well-being - choir singing as an intervention to improve well-being among employees in two Norwegian county hospitals2013In: Arts and Health, ISSN 1753-3015, E-ISSN 1753-3023, Vol. 5, no 2, p. 93-102Article in journal (Refereed)
    Abstract [en]

    Objective: Interventions promoting a healthy psychosocial work environment are common, yet little is known about participation and effectiveness of such measures. The aim of this study was to describe differences between participants and nonparticipants in the Sound of Wellbeing (SOW) initiative, including a variety of demographic characteristics, perceived work environment, psychological factors and self-perceived health. The study also compared the participants' and non-participants' retrospective perception of change in the psychosocial work environment and their health during the project period.

    Methods: In this cultural organizational-level intervention, employees in two county hospitals participated as singers with different hospital departments forming their own choir. The majority of employees (1431 employees; 57.4%) completed a survey questionnaire after the intervention, of which 426 (29.8%) had participated.

    Results: We analysed the differences between participants and non-participants on several descriptive characteristics, personality, engagement, commitment, general health and demand-control-support, as well as their self-perceived change in some of these variables. Lower participation was found among men, employees above 62 and below 38 years of age, part-time employees, university-educated workers and health care workers. Furthermore, we found more engagement, organizational commitment and self-reported positive change with regard to psychosocial work environment and global health in participants compared to non-participants.

    Conclusions: The intervention showed promising results for incorporating cultural activities in the work environment, but further investigation of the effectiveness of organizational-level interventions using a pre-post design is needed.

  • 3722. Vaag, Jonas
    et al.
    Saksvik, Per Öystein
    Milch, Vibeke
    Theorell, Töres
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Bjerkeset, Ottar
    "Sound of well-being" revisited - choir singing and well-being among Norwegian municipal employees2014In: Journal of Applied Arts & Health, ISSN 2040-2457, E-ISSN 2040-2465, Vol. 5, no 1, p. 51-63Article in journal (Refereed)
    Abstract [en]

    A recent cross-sectional study investigating an organizational choir-singing intervention called ‘Sound of Well-being’ (SOW) indicated health and organizational benefits, and a gender-specific pattern of participation and outcomes. In this study we investigate participation and effects in a short version of SOW. A total of 1100 employees of a Norwegian municipality were invited to participate in SOW. At baseline, 472 (42.9 per cent) employees filled in a questionnaire concerning demographics, personality, health, engagement, commitment and psychosocial work environment. A total of 312 (66.1 per cent) of these completed the same survey one to three weeks after SOW was finished. We found that female gender and extroversion were linked to participation in SOW. Women reported significant changes in engagement, self-perceived health and control, while men reported changes in job demands. Overall, participants reported an increase, while non-participants reported decrease on aforementioned variables. In terms of participation and effects of SOW, findings differed between professions, personality types and gender. In order to provide desirable alternatives to a wider group of employees, future interventions should include a variety of both receptive and creative activities.

  • 3723. Vadeby, Anna
    et al.
    Forsman, Asa
    Kecklund, Göran
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Åkerstedt, Torbjörn
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Sandberg, David
    Anund, Anna
    Sleepiness and prediction of driver impairment in simulator studies using a Cox proportional hazard approach2010In: Accident Analysis and Prevention, ISSN 0001-4575, E-ISSN 1879-2057, Vol. 42, no 3, p. 835-41Article in journal (Refereed)
    Abstract [en]

    Cox proportional hazard models were used to study relationships between the event that a driver is leaving the lane caused by sleepiness and different indicators of sleepiness. In order to elucidate different indicators' performance, five different models developed by Cox proportional hazard on a data set from a simulator study were used. The models consisted of physiological indicators and indicators from driving data both as stand alone and in combination. The different models were compared on two different data sets by means of sensitivity and specificity and the models' ability to predict lane departure was studied. In conclusion, a combination of blink indicators based on the ratio between blink amplitude and peak closing velocity of eyelid (A/PCV) (or blink amplitude and peak opening velocity of eyelid (A/POV)), standard deviation of lateral position and standard deviation of lateral acceleration relative road (ddy) was the most sensitive approach with sensitivity 0.80. This is also supported by the fact that driving data only shows the impairment of driving performance while blink data have a closer relation to sleepiness. Thus, an effective sleepiness warning system may be based on a combination of lane variability measures and variables related to eye movements (particularly slow eye closure) in order to have both high sensitivity (many correct warnings) and acceptable specificity (few false alarms).

  • 3724. Vadimovna Permyakova, Natalia
    et al.
    Billingsley, Sunnee
    Stockholm University, Faculty of Social Sciences, Department of Sociology.
    Men's health and co-residence with older generations in Russia: better or worse?2018In: Journal of Epidemiology and Community Health, ISSN 0143-005X, E-ISSN 1470-2738, Vol. 72, no 3, p. 179-184Article in journal (Refereed)
    Abstract [en]

    Background Previous studies show contradictory findings on the relationship between health and intergenerational living arrangements (ILAs), which may be due to variation in who selects themselves into and out of ILA. Addressing the selectivity into ILA and the health of the older generation, we assess whether there is a health-protective or health-damaging effect of ILA. We locate our study in the Russian context, where ILA is prevalent and men's health has become a public health issue.

    Methods We apply a fixed-effects logistic regression to self-rated health status of 11546 men aged 25 years or older who participated in at least two waves in the Russian Longitudinal Monitoring Survey from 1994 to 2015. To further isolate the health effect of ILA, we observe only associations after transitioning into or out of ILA.

    Results A transition into co-residence with an unhealthy older generation increases men's odds of reporting poor health (OR=0.64, CI 0.44 to 0.93). A transition out of co-residence with a healthy older generation decreases men's odds of reporting fine health by 63% (OR=0.37, CI 0.28 to 0.50), whereas continuing to live with an unhealthy older generation decreases the odds by half (OR=0.49, CI 0.38 to 0.63).

    Conclusions We reveal a health interlinkage between co-residing generations by finding a detrimental health effect of co-residence with an unhealthy older generation. No longer living with an older generation who was in fine health also negatively affects men's health. Future studies should address heterogeneity related to the health of older generations, unobserved time-constant characteristics of younger generations and selectivity into/out of ILA.

  • 3725. Vahtera, Jussi
    et al.
    Westerlund, Hugo
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Ferrie, Jane E
    Head, Jenny
    Melchior, Maria
    Singh-Manoux, Archana
    Zins, Marie
    Goldberg, Marcel
    Alexanderson, Kristina
    Kivimäki, Mika
    All-cause and diagnosis-specific sickness absence as a predictor of sustained suboptimal health: a 14-year follow-up in the GAZEL cohort2010In: Journal of Epidemiology and Community Health, ISSN 0143-005X, E-ISSN 1470-2738, Vol. 64, no 4, p. 311-7Article in journal (Refereed)
    Abstract [en]

    background: Previous studies show that sickness absence predicts health, but it is unclear whether this association is persistent over time and whether specific diseases underlie long-term associations. The aim of this study was to investigate overall and diagnosis-specific sickness absences as predictors of sustained suboptimal health. METHODS: Prospective occupational cohort study of 15 320 employees (73% men) aged 37-51. Sickness absence records in 1990-1992, including 13 diagnostic categories, were examined in relation to self-rated health measured annually for the years 1993-2006. RESULTS: 3385 employees (22%) had >30 days of sickness absence and 5564 (36%) 1-30 days during the 3-year exposure window. Repeated-measures logistic regression analysis adjusted for age, sex, occupational status and chronic diseases show that employees with >30 absence days, compared with those with no absences, had 2.14 (95% CI 2.00 to 2.29) times higher odds for suboptimal health over the 14 years of follow-up. Retirement did not dilute this association. Nine sickness absence diagnostic categories, such as diseases of the nervous, circulatory, metabolic, musculoskeletal, sensory and gastrointestinal systems, cancer, mental disorders and external causes, independently predicted increased risk of sustained suboptimal health. CONCLUSIONS: There is a remarkably persistent association between sickness absence and future long-term self-rated health status for the majority of diagnostic categories for sickness absence. This suggests that the association between sickness absence and health is ubiquitous and not driven by a limited number of rare and severe diseases.

  • 3726. Vahtera, Jussi
    et al.
    Westerlund, Hugo
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Hall, Martica
    Sjösten, Noora
    Kivimäki, Mika
    SalO, Paula
    Ferrie, Jane E
    Jokela, Markus
    Pentti, Jaana
    Singh-Manoux, Archana
    Goldberg, Marcel
    Zins, Marie
    Effect of retirement on sleep disturbances: the GAZEL prospective cohort study.2009In: Sleep, ISSN 0161-8105, E-ISSN 1550-9109, Vol. 32, no 11, p. 1459-66Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Changes in health following retirement are poorly understood. We used serial measurements to assess the effect of retirement on sleep disturbances. DESIGN: Prospective cohort study. SETTING: The French national gas and electricity company. PARTICIPANTS: Fourteen thousand seven hundred fourteen retired employees (79% men). MEASUREMENTS AND RESULTS: Annual survey measurements of sleep disturbances ranging from 7 years before to 7 years after retirement (a mean of 12 measurements). Before retirement 22.2% to 24.6% of participants reported having disturbed sleep. According to repeated-measures logistic-regression analysis with generalized estimating equations estimation, the odds ratio (OR) for having a sleep disturbance in the postretirement period was 0.74 (95% confidence interval 0.71-0.77), compared with having a sleep disturbance in the preretirement period. The postretirement improvement in sleep was more pronounced in men (OR 0.66 [0.63-0.69]) than in women (OR 0.89 [0.84-0.95]) and in higher-grade workers than lower-grade workers. Postretirement sleep improvement was explained by the combination of preretirement risk factors suggesting removal of work-related exposures as a mechanism. The only exception to the general improvement in sleep after retirement was related to retirement on health grounds. In this group of participants, there was an increase in sleep disturbances following retirement. CONCLUSIONS: Repeated measurements provide strong evidence for a substantial and sustained decrease in sleep disturbances following retirement. The possibility that the health and well-being of individuals are significantly worse when in employment than following retirement presents a great challenge to improve the quality of work life in Western societies in which the cost of the aging population can only be met through an increase in average retirement age.

  • 3727. Valanne, Susanna
    et al.
    Myllymäki, Henna
    Kallio, Jenni
    Schmid, Martin Rudolf
    Kleino, Anni
    Murumägi, Astrid
    Airaksinen, Laura
    Kotipelto, Tapio
    Kaustio, Meri
    Ulvila, Johanna
    Esfahani, Shiva Seyedoleslami
    Stockholm University, Faculty of Science, Department of Molecular Biology and Functional Genomics.
    Engström, Ylva
    Stockholm University, Faculty of Science, Department of Molecular Biology and Functional Genomics.
    Silvennoinen, Olli
    Hultmark, Dan
    Parikka, Mataleena
    Rämet, Mika
    Genome-Wide RNA Interference in Drosophila Cells Identifies G Protein-Coupled Receptor Kinase 2 as a Conserved Regulator of NF-kappa B Signaling2010In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 184, no 11, p. 6188-6198Article in journal (Refereed)
    Abstract [en]

    Because NF-kappa B signaling pathways are highly conserved in evolution, the fruit fly Drosophila melanogaster provides a good model to study these cascades. We carried out an RNA interference (RNAi)-based genome-wide in vitro reporter assay screen in Drosophila for components of NF-kappa B pathways. We analyzed 16,025 dsRNA-treatments and identified 10 novel NF-kappa B regulators. Of these, nine dsRNA-treatments affect primarily the Toll pathway. G protein-coupled receptor kinase (Gprk) 2, CG15737/Toll pathway activation mediating protein, and u-shaped were required for normal Drosomycin response in vivo. Interaction studies revealed that Gprk2 interacts with the Drosophila I kappa B homolog Cactus, but is not required in Cactus degradation, indicating a novel mechanism for NF-kappa B regulation. Morpholino silencing of the zebrafish ortholog of Gprk2 in fish embryos caused impaired cytokine expression after Escherichia coli infection, indicating a conserved role in NF-kappa B signaling. Moreover, small interfering RNA silencing of the human ortholog GRK5 in HeLa cells impaired NF-kappa B reporter activity. Gprk2 RNAi flies are susceptible to infection with Enterococcus faecalis and Gprk2 RNAi rescues Toll(10b)-induced blood cell activation in Drosophila larvae in vivo. We conclude that Gprk2/GRK5 has an evolutionarily conserved role in regulating NF-kappa B signaling. The Journal of Immunology, 2010, 184: 6188-6198.

  • 3728. Valerie, Nicholas C. K.
    et al.
    Hagenkort, Anna
    Page, Brent D. G.
    Masuyer, Geoffrey
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Rehling, Daniel
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Carter, Megan
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Bevc, Luka
    Herr, Patrick
    Homan, Evert
    Sheppard, Nina G.
    Stenmark, Pål
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Jemth, Ann-Sofie
    Helleday, Thomas
    NUDT15 Hydrolyzes 6-Thio-DeoxyGTP to Mediate the Anticancer Efficacy of 6-Thioguanine2016In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 76, no 18, p. 5501-5511Article in journal (Refereed)
    Abstract [en]

    Thiopurines are a standard treatment for childhood leukemia, but like all chemotherapeutics, their use is limited by inherent or acquired resistance in patients. Recently, the nucleoside diphosphate hydrolase NUDT15 has received attention on the basis of its ability to hydrolyze the thiopurine effector metabolites 6-thio-deoxyGTP (6-thio-dGTP) and 6-thio-GTP, thereby limiting the efficacy of thiopurines. In particular, increasing evidence suggests an association between the NUDT15 missense variant, R139C, and thiopurine sensitivity. In this study, we elucidated the role of NUDT15 and NUDT15 R139C in thiopurine metabolism. In vitro and cellular results argued that 6-thio-dGTP and 6-thio-GTP are favored substrates for NUDT15, a finding supported by a crystallographic determination of NUDT15 in complex with 6-thio-GMP. We found that NUDT15 R139C mutation did not affect enzymatic activity but instead negatively influenced protein stability, likely due to a loss of supportive intramolecular bonds that caused rapid proteasomal degradation in cells. Mechanistic investigations in cells indicated that NUDT15 ablation potentiated induction of the DNA damage checkpoint and cancer cell death by 6-thioguanine. Taken together, our results defined how NUDT15 limits thiopurine efficacy and how genetic ablation via the R139C missense mutation confers sensitivity to thiopurine treatment in patients.

  • 3729. van de Ven, Hardy A
    et al.
    Brouwer, Sandra
    Koolhaas, Wendy
    Goudswaard, Anneke
    de Looze, Michiel P
    Kecklund, Göran
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Radboud University, The Netherlands.
    Almansa, Josue
    Bültmann, Ute
    van der Klink, Jac J. L.
    Associations between shift schedule characteristics with sleep, need for recovery, health and performance measures for regular (semi-)continuous 3-shift systems.2016In: Applied Ergonomics, ISSN 0003-6870, E-ISSN 1872-9126, Vol. 56, p. 203-212Article in journal (Refereed)
    Abstract [en]

    In this cross-sectional study associations were examined between eight shift schedule characteristics with shift-specific sleep complaints and need for recovery and generic health and performance measures. It was hypothesized that shift schedule characteristics meeting ergonomic recommendations are associated with better sleep, need for recovery, health and performance. Questionnaire data were collected from 491 shift workers of 18 companies with 9 regular (semi)-continuous shift schedules. The shift schedule characteristics were analyzed separately and combined using multilevel linear regression models. The hypothesis was largely not confirmed. Relatively few associations were found, of which the majority was in the direction as expected. In particular early starts of morning shifts and many consecutive shifts seem to be avoided. The healthy worker effect, limited variation between included schedules and the cross-sectional design might explain the paucity of significant results.

  • 3730. Van den Berg, Gerard J.
    et al.
    Modin, Bitte
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS).
    Economic Conditions at Birth, Birth Weight, Ability, and the Causal Path to Cardiovascular Mortality2013Report (Other academic)
  • 3731.
    Van der Velde, Lode
    Stockholm University, Faculty of Social Sciences, Department of Human Geography.
    Missing links in the genesis of type 1 diabetes: A geographical approach to the case of enteroviruses in the Nordic region2018Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Type 1 diabetes (T1D) is an autoimmune disease that destroys the bodies’ insulin producing beta-cells. The disease is understood to be triggered in genetically susceptible individuals by environmental factors. While the genetic side of the etiological model has to some degree been uncovered, there is no clear understanding of which environmental factors play a role in the disease process. Several hypotheses claim to explain the development of T1D, of which enteroviral infections show the most promise. According to this hypothesis high prevalence of enteroviral infections would also mean high incidence rates of T1D. This study focused on four Nordic countries (Denmark, Finland, Norway and Sweden) that as late as 2017 were found in the top 10 countries for incidence rate of childhood-onset T1D in the world. Incidence rates of T1D and prevalence of enteroviruses were mapped and geographically analyzed according to the principles of spatial epidemiology, after which correlation coefficients were calculated. In doing so the study tried to answer to which extent the prevalence of enteroviruses could explain the regional variations in T1D. For all countries no significant correlation was found, but increasing sample size, by grouping countries, showed considerably different outcomes with a small positive correlation in the case of Norway and Finland.

  • 3732.
    van Diepen, Cornelia
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS).
    Work-life conflict and self-rated health of Brazilian civil servants: Findings from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)2014Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Abstract

    Objectives

    The relationship between work-life conflict and self-rated health is widely researched but whether the association differs according to educational level has received less attention. This study investigated the association of work-life conflict with self-rated health taking gender, education, working conditions and socio-demographic characteristics into account.

    Methods

    The cross-sectional data came from the ELSA-Brasil (2008-2010), a cohort study of civil servants 35-74 years old from six states of Brazil. Complete information was available for 12121 individuals (48% men). Work-life conflict was measured by four indicators representing different aspects, i.e. work-to-family time-based, work-to-family strain-based, family-to-work and lack of leisure time. Multiple logistic regression analyses stratified by gender and educational level were performed.

    Results

    More frequent work-life conflict was associated with poor self-rated health in all the indicators. The magnitude of association was greater for women and the same occurred with the higher educated respondents. An exception is in the family-to-work indicators where it affected lower educated women more than higher educated.

    Conclusions

    There is an association between work-life conflict and self-rated health and it differs according to work-life conflict indicator. Stratifying by gender and educational level presents an important addition to research in the field of work-life conflict.

  • 3733. van Hedel, Karen
    et al.
    Avendano, Mauricio
    Berkman, Lisa F
    Bopp, Matthias
    Deboosere, Patrick
    Lundberg, Olle
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS).
    Martikainen, Pekka
    Menvielle, Gwenn
    van Lenthe, Frank J
    Mackenbach, Johan P
    The contribution of national disparities to international differences in mortality between the United States and 7 European countries.2015In: American Journal of Public Health, ISSN 0090-0036, E-ISSN 1541-0048, Vol. 105, no 4, p. e112-e119Article in journal (Refereed)
  • 3734. van Hedel, Karen
    et al.
    Martikainen, Pekka
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS). Max Planck Institute for Demographic Research, Germany; University of Helsinki, Finland.
    Moustgaard, Heta
    Myrskylä, Mikko
    Cohabitation and mental health: Is psychotropic medication use more common in cohabitation than marriage?2018In: SSM - Population Health, ISSN 2352-8273, Vol. 4, p. 244-253Article in journal (Refereed)
    Abstract [en]

    Marriage is associated with better mental health. While research on the mental health of cohabiting individuals has increased in recent years, it has yielded mixed results thus far. We assessed whether the mental health of cohabiters is comparable to that of married individuals or those living alone using longitudinal data on psychotropic medication purchases. Panel data from an 11% random sample of the population residing in Finland for the years 1995 to 2007, with annual measurements of all covariates, were used. Ordinary least squares (OLS) models were applied to disentangle the relation between cohabitation and psychotropic medication purchases while controlling for relevant time-varying factors (age, education, economic activity, and number of children), and individual fixed effects (FE) models to further account for unobserved time-invariant individual factors. Our sample consisted of 63,077 men and 61,101 women aged 25 to 39 years in 1995. Descriptive results and the OLS model indicated that the likelihood of purchasing psychotropic medication was lowest for married individuals, higher for cohabiters, and highest for individuals living alone. This difference between cohabiting and married individuals disappeared after controlling for time-varying covariates (percent difference [% diff] for men: 0.3, 95% confidence interval [CI]: -0.0, 0.6; % diff for women: -0.2, 95% CI: -0.6, 0.2). Further controlling for unobserved confounders in the FE models did not change this non-significant difference between cohabiting and married individuals. The excess purchases of psychotropic medication among individuals living alone compared to those cohabiting decreased to 1.2 (95% CI: 1.0, 1.4) and 1.4 (95% CI: 1.1, 1.6) percentage-points in the fully-adjusted FE model for men and women, respectively. Similar results were found for all subcategories of psychotropic medication. In summary, these findings suggested that the mental health difference between cohabiting and married individuals, but not the difference between cohabiting individuals and those living alone, was largely due to selection.

  • 3735. Van Laethem, Michelle
    et al.
    Beckers, Debby G. J.
    Geurts, Sabine A. E.
    Garefelt, Johanna
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Magnusson Hanson, Linda
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Leineweber, Constanze
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Perseverative Cognition as an Explanatory Mechanism in the Relation Between Job Demands and Sleep Quality2018In: International Journal of Behavioral Medicine, ISSN 1070-5503, E-ISSN 1532-7558, Vol. 25, no 2, p. 231-242Article in journal (Refereed)
    Abstract [en]

    Purpose The aim of this longitudinal three-wave study was to examine (i) reciprocal associations among job demands, work-related perseverative cognition (PC), and sleep quality; (ii) PC as a mediator in-between job demands and sleep quality; and (iii) continuous high job demands in relation to sleep quality and work-related PC over time.

    Method A representative sample of the Swedish working population was approached in 2010, 2012, and 2014, and 2316 respondents were included in this longitudinal full-panel survey study. Structural equation modelling was performed to analyse the temporal relations between job demands, work-related PC, and sleep quality. Additionally, a subsample (N = 1149) consisting of individuals who reported the same level of exposure to job demands during all three waves (i.e. stable high, stable moderate, or stable low job demands) was examined in relation to PC and sleep quality over time.

    Results Analyses showed that job demands, PC, and poor sleep quality were positively and reciprocally related. Work-related PC mediated the normal and reversed, direct across-wave relations between job demands and sleep quality. Individuals with continuous high job demands reported significantly lower sleep quality and higher work-related PC, compared to individuals with continuous moderate/low job demands.

    Conclusion This study substantiated reciprocal relations between job demands, work-related PC, and sleep quality and supported work-related PC as an underlying mechanism of the reciprocal job demands-sleep relationship. Moreover, this study showed that chronically high job demands are a risk factor for low sleep quality.

  • 3736. Van Laethem, Michelle
    et al.
    Beckers, Debby G. J.
    Kompier, Michiel A. J.
    Kecklund, Göran
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    van den Bossche, Seth N. J.
    Geurts, Sabine A. E.
    Bidirectional relations between work-related stress, sleep quality and perseverative cognition2015In: Journal of Psychosomatic Research, ISSN 0022-3999, E-ISSN 1879-1360, Vol. 79, no 5, p. 391-398Article in journal (Refereed)
    Abstract [en]

    Objective

    In this longitudinal two-wave study, bidirectional relations between work-related stress and sleep quality were examined. Moreover, it was investigated whether perseverative cognition is a potential underlying mechanism in this association, related to both work-related stress and sleep quality.

    Methods

    A randomly selected sample of Dutch employees received an online survey in 2012 and 2013. Of all invited employees, 877 participated in both waves. Structural equation modeling was performed to analyze the data.

    Results

    We found evidence for reversed relations between work-related stress and sleep quality. Specifically, when controlling for perseverative cognition, work-related stress was not directly related to subsequent sleep quality, but low sleep quality was associated with an increase in work-related stress over time. Moreover, negative bidirectional associations over time were found between perseverative cognition and sleep quality, and positive bidirectional associations were found between work-related stress and perseverative cognition. Lastly, a mediation analysis showed that perseverative cognition fully mediated the relationship between work-related stress and sleep quality.

    Conclusion

    The study findings suggest that perseverative cognition could be an important underlying mechanism in the association between work-related stress and sleep quality. The bidirectionality of the studied relationships could be an indication of a vicious cycle, in which work-related stress, perseverative cognition, and sleep quality mutually influence each other over time.

  • 3737.
    van Leeuwen, Wessel M A
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Barnett, M
    Peksan, C
    Kecklund, Göran
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Åkerstedt, Torbjörn
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Long term sleep and fatigue at sea: a field study2014In: Journal of sleep research, Special issue: 22nd Congress of the European Sleep Research Society, 16-20 September 2014, Tallinn, Estonia, 2014Conference paper (Other academic)
  • 3738.
    van Leeuwen, Wessel M A
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Kircher, Albert
    Dahlgren, Anna
    Lützhöft, Margareta
    Barnett, Mike
    Kecklund, Göran
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Åkerstedt, Torbjörn
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Sleep, Sleepiness, and Neurobehavioral Performance While on Watch in a Simulated 4 Hours on/8 Hours off Maritime Watch System2013In: Chronobiology International, ISSN 0742-0528, E-ISSN 1525-6073, Vol. 30, no 9, p. 1108-1115Article in journal (Refereed)
    Abstract [en]

    Seafarer sleepiness jeopardizes safety at sea and has been documented as a direct or contributing factor in many maritime accidents. This study investigates sleep, sleepiness, and neurobehavioral performance in a simulated 4 h on/8 h off watch system as well as the effects of a single free watch disturbance, simulating a condition of overtime work, resulting in 16 h of work in a row and a missed sleep opportunity. Thirty bridge officers (age 30 ± 6 yrs; 29 men) participated in bridge simulator trials on an identical 1-wk voyage in the North Sea and English Channel. The three watch teams started respectively with the 00-04, the 04-08, and the 08-12 watches. Participants rated their sleepiness every hour (Karolinska Sleepiness Scale [KSS]) and carried out a 5-min psychomotor vigilance test (PVT) test at the start and end of every watch. Polysomnography (PSG) was recorded during 6 watches in the first and the second half of the week. KSS was higher during the first (mean ± SD: 4.0 ± 0.2) compared with the second (3.3 ± 0.2) watch of the day (p < 0.001). In addition, it increased with hours on watch (p < 0.001), peaking at the end of watch (4.1 ± 0.2). The free watch disturbance increased KSS profoundly (p < 0.001): from 4.2 ± 0.2 to 6.5 ± 0.3. PVT reaction times were slower during the first (290 ± 6 ms) compared with the second (280 ± 6 ms) watch of the day (p < 0.001) as well as at the end of the watch (289 ± 6 ms) compared with the start (281 ± 6 ms; p = 0.001). The free watch disturbance increased reaction times (p < 0.001) from 283 ± 5 to 306 ± 7 ms. Similar effects were observed for PVT lapses. One third of all participants slept during at least one of the PSG watches. Sleep on watch was most abundant in the team working 00-04 and it increased following the free watch disturbance. This study reveals that-within a 4 h on/8 h off shift system-subjective and objective sleepiness peak during the night and early morning watches, coinciding with a time frame in which relatively many maritime accidents occur. In addition, we showed that overtime work strongly increases sleepiness. Finally, a striking amount of participants fell asleep while on duty.

  • 3739.
    van Leeuwen, Wessel M A
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Porkka-Heiskanen, T.
    Sallinen, M.
    Härmä, M.
    Sleep and sleepiness during cumulative sleep restriction and subsequent recovery sleep2014Conference paper (Other academic)
  • 3740. van Raalte, A.
    et al.
    Kunst, A. E.
    Deboosere, P.
    Leinsalu, M.
    Lundberg, Olle
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS).
    Martikainen, P.
    Strand, P. H.
    Artnik, B.
    Wojtyniak, B.
    Mackenbach, J. P.
    More variation in lifespan in lower educated groups: evidence from 10 European countries2011In: International Journal of Epidemiology, ISSN 0300-5771, E-ISSN 1464-3685, Vol. 40, no 6, p. 1703-1714Article in journal (Refereed)
    Abstract [en]

    Background Whereas it is well established that people with a lower socio-economic position have a shorter average lifespan, it is less clear what the variability surrounding these averages is. We set out to examine whether lower educated groups face greater variation in lifespans in addition to having a shorter life expectancy, in order to identify entry points for policies to reduce the impact of socio-economic position on mortality.

    Methods We used harmonized, census-based mortality data from 10 European countries to construct life tables by sex and educational level (low, medium, high). Variation in lifespan was measured by the standard deviation conditional upon survival to age 35 years. We also decomposed differences between educational groups in lifespan variation by age and cause of death.

    Results Lifespan variation was higher among the lower educated in every country, but more so among men and in Eastern Europe. Although there was an inverse relationship between average life expectancy and its standard deviation, the first did not completely predict the latter. Greater lifespan variation in lower educated groups was largely driven by conditions causing death at younger ages, such as injuries and neoplasms.

    Conclusions Lower educated individuals not only have shorter life expectancies, but also face greater uncertainty about the age at which they will die. More priority should be given to efforts to reduce the risk of an early death among the lower educated, e.g. by strengthening protective policies within and outside the health-care system.

  • 3741.
    van Raalte, Alyson A.
    et al.
    Max Planck Inst Demog Res, Rostock, Germany .
    Kunst, Anton E.
    Univ Amsterdam, Acad MC, Dept Publ Hlth, Amsterdam, Netherlands.
    Lundberg, Olle
    Stockholm University, Faculty of Social Sciences, Centre for Health Equity Studies (CHESS).
    Leinsalu, Mall
    Sodertorn Univ, Stockholm Ctr Hlth Soc Transit, Sodertorn, Sweden .
    Martikainen, Pekka
    Univ Helsinki, Dept Sociol, Helsinki, Finland .
    Artnik, Barbara
    Univ Ljubljana, Fac Med, Dept Publ Hlth, Ljubljana, Slovenia .
    Deboosere, Patrick
    Vrije Univ Brussel, Dept Social Res, Brussels, Belgium .
    Stirbu, Irina
    Erasmus MC, Dept Publ Hlth, Rotterdam, Netherlands .
    Wojtyniak, Bogdan
    Natl Inst Hyg, Natl Inst Publ Hlth, Dept Monitoring & Anal Populat Hlth, PL-00791 Warsaw, Poland .
    Mackenbach, Johan P.
    Erasmus MC, Dept Publ Hlth, Rotterdam, Netherlands .
    The contribution of educational inequalities to lifespan variation2012In: Population Health Metrics, ISSN 1478-7954, E-ISSN 1478-7954, Vol. 10, no 3Article in journal (Refereed)
    Abstract [en]

    Background

    Studies of socioeconomic inequalities in mortality consistently point to higher death rates in lower socioeconomic groups. Yet how these between-group differences relate to the total variation in mortality risk between individuals is unknown.

    Methods

    We used data assembled and harmonized as part of the Eurothine project, which includes census-based mortality data from 11 European countries. We matched this to national data from the Human Mortality Database and constructed life tables by gender and educational level. We measured variation in age at death using Theil's entropy index, and decomposed this measure into its between- and within-group components.

    Results

    The least-educated groups lived between three and 15 years fewer than the highest-educated groups, the latter having a more similar age at death in all countries. Differences between educational groups contributed between 0.6% and 2.7% to total variation in age at death between individuals in Western European countries and between 1.2% and 10.9% in Central and Eastern European countries. Variation in age at death is larger and differs more between countries among the least-educated groups.

    Conclusions

    At the individual level, many known and unknown factors are causing enormous variation in age at death, socioeconomic position being only one of them. Reducing variations in age at death among less-educated people by providing protection to the vulnerable may help to reduce inequalities in mortality between socioeconomic groups.

  • 3742. Van Rooij, Antonius J.
    et al.
    Ferguson, Christopher J.
    Colder Carras, Michelle
    Kardefelt-Winther, Daniel
    Shi, Jing
    Aarseth, Espen
    Bean, Anthony M.
    Helmersson Bergmark, Karin
    Stockholm University, Faculty of Social Sciences, Department of Sociology.
    Brus, Anne
    Coulson, Mark
    Deleuze, Jory
    Dullur, Pravin
    Dunkels, Elza
    Edman, Johan
    Stockholm University, Faculty of Social Sciences, Department of Criminology.
    Elson, Malte
    Etchells, Peter J.
    Fiskaali, Anne
    Granic, Isabela
    Jansz, Jeroen
    Karlsen, Faltin
    Kaye, Linda K.
    Kirsh, Bonnie
    Lieberoth, Andreas
    Markey, Patrick
    Mills, Kathryn L.
    Lundedal Nielsen, Rune Kristian
    Orben, Amy
    Poulsen, Arne
    Prause, Nicole
    Prax, Patrick
    Quandt, Thorsten
    Schimmenti, Adriano
    Starcevic, Vladan
    Stutman, Gabrielle
    Turner, Nigel E.
    Van Looy, Jan
    Przybylski, Andrew K.
    A weak scientific basis for gaming disorder: Let us err on the side of caution2018In: Journal of Behavioral Addictions, ISSN 2062-5871, E-ISSN 2063-5303, Vol. 7, no 1, p. 1-9Article in journal (Refereed)
    Abstract [en]

    We greatly appreciate the care and thought that is evident in the 10 commentaries that discuss our debate paper, the majority of which argued in favor of a formalized ICD-11 gaming disorder. We agree that there are some people whose play of video games is related to life problems. We believe that understanding this population and the nature and severity of the problems they experience should be a focus area for future research. However, moving from research construct to formal disorder requires a much stronger evidence base than we currently have. The burden of evidence and the clinical utility should be extremely high, because there is a genuine risk of abuse of diagnoses. We provide suggestions about the level of evidence that might be required: transparent and preregistered studies, a better demarcation of the subject area that includes a rationale for focusing on gaming particularly versus a more general behavioral addictions concept, the exploration of non-addiction approaches, and the unbiased exploration of clinical approaches that treat potentially underlying issues, such as depressive mood or social anxiety first. We acknowledge there could be benefits to formalizing gaming disorder, many of which were highlighted by colleagues in their commentaries, but we think they do not yet outweigh the wider societal and public health risks involved. Given the gravity of diagnostic classification and its wider societal impact, we urge our colleagues at the WHO to err on the side of caution for now and postpone the formalization.

  • 3743. Van Zalk, Nejra
    et al.
    Tillfors, Maria
    Trost, Kari
    Stockholm University, Faculty of Social Sciences, Department of Child and Youth Studies.
    Mothers' and Fathers' Worry and Over-Control: One Step Closer to Understanding Early Adolescent Social Anxiety2018In: Child Psychiatry and Human Development, ISSN 0009-398X, E-ISSN 1573-3327, Vol. 49, no 6, p. 917-927Article in journal (Refereed)
    Abstract [en]

    This study investigated the links between parental worry, parental over-control and adolescent social anxiety in parent-adolescent dyads. Using a longitudinal sample of adolescents (M-age=14.28) and their parents (224 mother-daughter, 234 mother-son, 51 father-daughter, and 47 father-son dyads), comparisons were conducted using cross-lagged path models across two time points. We used adolescent reports of social anxiety and feelings of being overly controlled by parents, and mother and father self-reports of worries. Our results show that boys' social anxiety predicted higher perceived parental overcontrol, whereas girls' social anxiety predicted higher paternal worry over time. In addition, girls' reports of feeling overly controlled by parents predicted higher maternal worry but lower paternal worry over time. For boys, feeling overly controlled predicted less social anxiety instead. The study illustrates how mothers and fathers might differ in their behaviors and concerns regarding their children's social anxiety and feelings of overcontrol.

  • 3744. Vandenberg, Laura N.
    et al.
    Ågerstrand, Marlene
    Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.
    Beronius, Anna
    Beausoleil, Claire
    Bergman, Åke
    Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry. Swedish Toxicology Sciences Research Center, Sweden.
    Bero, Lisa A.
    Bornehag, Carl-Gustaf
    Boyer, C. Scott
    Cooper, Glinda S.
    Cotgreave, Ian
    Gee, David
    Grandjean, Philippe
    Guyton, Kathryn Z.
    Hass, Ulla
    Heindel, Jerrold J.
    Jobling, Susan
    Kidd, Karen A.
    Kortenkamp, Andreas
    Macleod, Malcolm R.
    Martin, Olwenn V.
    Norinder, Ulf
    Scheringer, Martin
    Thayer, Kristina A.
    Toppari, Jorma
    Whaley, Paul
    Woodruff, Tracey J.
    Rudén, Christina
    Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.
    A proposed framework for the systematic review and integrated assessment (SYRINA) of endocrine disrupting chemicals2016In: Environmental health, ISSN 1476-069X, E-ISSN 1476-069X, Vol. 15, article id 74Article in journal (Refereed)
    Abstract [en]

    Background: The issue of endocrine disrupting chemicals (EDCs) is receiving wide attention from both the scientific and regulatory communities. Recent analyses of the EDC literature have been criticized for failing to use transparent and objective approaches to draw conclusions about the strength of evidence linking EDC exposures to adverse health or environmental outcomes. Systematic review methodologies are ideal for addressing this issue as they provide transparent and consistent approaches to study selection and evaluation. Objective methods are needed for integrating the multiple streams of evidence (epidemiology, wildlife, laboratory animal, in vitro, and in silico data) that are relevant in assessing EDCs.

    Methods: We have developed a framework for the systematic review and integrated assessment (SYRINA) of EDC studies. The framework was designed for use with the International Program on Chemical Safety (IPCS) and World Health Organization (WHO) definition of an EDC, which requires appraisal of evidence regarding 1) association between exposure and an adverse effect, 2) association between exposure and endocrine disrupting activity, and 3) a plausible link between the adverse effect and the endocrine disrupting activity.

    Results: Building from existing methodologies for evaluating and synthesizing evidence, the SYRINA framework includes seven steps: 1) Formulate the problem; 2) Develop the review protocol; 3) Identify relevant evidence; 4) Evaluate evidence from individual studies; 5) Summarize and evaluate each stream of evidence; 6) Integrate evidence across all streams; 7) Draw conclusions, make recommendations, and evaluate uncertainties. The proposed method is tailored to the IPCS/WHO definition of an EDC but offers flexibility for use in the context of other definitions of EDCs.

    Conclusions: When using the SYRINA framework, the overall objective is to provide the evidence base needed to support decision making, including any action to avoid/minimise potential adverse effects of exposures. This framework allows for the evaluation and synthesis of evidence from multiple evidence streams. Finally, a decision regarding regulatory action is not only dependent on the strength of evidence, but also the consequences of action/inaction, e.g. limited or weak evidence may be sufficient to justify action if consequences are serious or irreversible.

  • 3745. Vander Elst, Tinne
    et al.
    Näswall, Katharina
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Work and organizational psychology. University of Canterbury, Christchurch, New Zealand.
    Bernhard-Oettel, Claudia
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Work and organizational psychology.
    De Witte, Hans
    Sverke, Magnus
    Stockholm University, Faculty of Social Sciences, Department of Psychology, Work and organizational psychology. North West University, Potchefstroom, South Africa.
    The effect of job insecurity on employee health complaints: A within-person analysis of the explanatory role of threats to the manifest and latent benefits of work2016In: Journal of Occupational Health Psychology, ISSN 1076-8998, E-ISSN 1939-1307, Vol. 21, no 1, p. 65-76Article in journal (Refereed)
    Abstract [en]

    The current study contributes to the literature on job insecurity by highlighting threat to the benefits of work as an explanation of the effect of job insecurity on health complaints. Building on the latent deprivation model, we predicted that threats to both manifest (i.e., financial income) and latent benefits of work (i.e., collective purpose, social contacts, status, time structure, activity) mediate the relationships from job insecurity to subsequent mental and physical health complaints. In addition, in line with the conservation of resources theory, we proposed that financial resources buffer the indirect effect of job insecurity on health complaints through threat to the manifest benefit. Hypotheses were tested using a multilevel design, in which 3 measurements (time lag of 6 months between subsequent measurements) were clustered within 1,994 employees (in Flanders, Belgium). This allowed for the investigation of within-person processes, while controlling for variance at the between-person level. The results demonstrate that job insecurity was related to subsequent threats to both manifest and latent benefits, and that these threats in turn were related to subsequent health complaints (with an exception for threat to the manifest benefit that did not predict mental health complaints). Three significant indirect effects were found: threat to the latent benefits mediated the relationships between job insecurity and both mental and physical health complaints, and threat to the manifest benefit mediated the relationship between job insecurity and physical health complaints. Unexpectedly, the latter indirect effect was exacerbated by financial resources.

  • 3746. Vannini, Patrizia
    et al.
    Almkvist, Ove
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Dierks, Thomas
    Lehmann, Christoph
    Wahlund, Lars-Olof
    Reduced neuronal efficacy in progressive mild cognitive impairment: A prospective fMRI study on visuospatial processing2007In: Psychiatry Research: Neuroimaging, ISSN 0925-4927, E-ISSN 1872-7506, Vol. 156, no 1, p. 43-57Article in journal (Refereed)
    Abstract [en]

    Mild cognitive impairment (MCI) often refers to the preclinical stage of dementia, where the majority develop Alzheimer's disease (AD). Given that neurodegenerative burden and compensatory mechanisms might exist before accepted clinical symptoms of AD are noticeable, the current prospective study aimed to investigate the functioning of brain regions in the visuospatial networks responsible for preclinical symptoms in AD using event-related functional magnetic resonance imaging (fMRI). Eighteen MCI patients were evaluated and clinically followed for approximately 3 years. Five progressed to AD (PMCI) and eight remained stable (SMCI). Thirteen age-, gender- and education-matched controls also participated. An angle discrimination task with varying task demands was used. Brain activation patterns as well as task demand-dependent and -independent signal changes between the groups were investigated by using an extended general linear model including individual performance (reaction time [RT]) of each single trial. Similar behavioral (RT and accuracy) responses were observed between MCI patients and controls. A network of bilateral activations, e.g. dorsal pathway, which increased linearly with increasing task demand, was engaged in all subjects. Compared with SMCI patients and controls, PMCI patients showed a stronger relation between task demand and brain activity in left superior parietal lobules (SPL) as well as a general task demand-independent increased activation in left precuneus. Altered brain function can be detected at a group level in individuals that progress to AD before changes occur at the behavioral level. Increased parictal activation in PMCI could reflect a reduced neuronal efficacy due to accumulating AD pathology and might predict future clinical decline in patients with MCI.

  • 3747.
    Vare, Daniel
    et al.
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Groth, Petra
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Carlsson, Rickard
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Johansson, Fredrik
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Erixon, Klaus
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Jenssen, Dag
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    DNA interstrand crosslinks induce a potent replication block followed by formation and repair of double strand breaks in intact mammalian cells2012In: DNA Repair, ISSN 1568-7864, E-ISSN 1568-7856, Vol. 11, no 12, p. 976-985Article in journal (Refereed)
    Abstract [en]

    DNA interstrand crosslinks (ICLs) are highly toxic lesions that covalently link both strands of DNA and distort the DNA helix. Crosslinking agents have been shown to stall DNA replication and failure to repair ICL lesions before encountered by replication forks may induce severe DNA damage. Most knowledge of the ICL repair process has been revealed from studies in bacteria and cell extracts. However, for mammalian cells the process of ICL repair is still unclear and conflicting data exist. In this study we have explored the fate of psoralen-induced ICLs during replication, by employing intact mammalian cells and novel techniques. By comparative studies distinguishing between effects by monoadducts versus ICLs, we have been able to link the block of replication to the ICLs induction. We found that the replication fork was equally blocked by ICLs in wild-type cells as in cells deficient in ERCC1/XPF and XRCC3. The formation of ICL induced double strand breaks (DSBs), detected by formation of 53PB1 foci, was equally induced in the three cell lines suggesting that these proteins are involved at a later step of the repair process. Furthermore, we found that forks blocked by ICLs were neither bypassed, restarted nor restored for several hours. We propose that this process is different from that taking place following monoadduct induction by UV-light treatment where replication bypass is taking place as an early step. Altogether our findings suggest that restoration of an ICL blocked replication fork, likely initiated by a DSB occurs relatively rapidly at a stalled fork, is followed by restoration, which seems to be a rather slow process in intact mammalian cells.

  • 3748.
    Vare, Daniel
    et al.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Johansson, Fredrik
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Persson, Jan-Olov
    Stockholm University, Faculty of Science, Department of Mathematics.
    Erixon, Klaus
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Jenssen, Dag
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Quantification and repair of psoralen-induced interstrand crosslinks in human cells2014In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 226, no 3, p. 343-350Article in journal (Refereed)
    Abstract [en]

    Bi-functional alkylating agents that cause crosslinks are commonly used in chemotherapy. However, there is no conclusive knowledge for human cells regarding the number of induced interstrand crosslinks (ICLs) and the unhooking rate when the lesion is removed from one of the DNA strand. Using a newly developed method, we quantified the number of induced ICLs for the five furocoumarins; psoralen, 5-methoxypsoralen, 8-methoxypsoralen, tri-methoxypsoralen and angelicin. In quantitative terms, the results were in agreement with the values found by others. In kinetic studies using mammalian cells, we found that half of the psoralen-induced ICLs were unhooked within 2.5 h. The rate in normal human diploid fibroblasts was found to be 20,000 ICLs/h/cell. In comparison to survival, 2500 ICLs per cell led to 50% toxicity, indicating that the unhooking of the ICLs is not the crucial step for ICL tolerance. Surprisingly, only 3500 ICLs per cell corresponded to a significant delay in the replication fork elongation. The results indicate involvements of additional pathway(s) for the delay since the effect on replication elongation could be monitored when only 10% of the replication forks encounter an ICL.

  • 3749. Vargas-Uribe, Mauricio
    et al.
    Rodnin, Mykola V.
    Öjemalm, Karin
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Holgado, Aurora
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Kyrychenko, Alexander
    Nilsson, IngMarie
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Posokhov, Yevgen O.
    Makhatadze, George
    von Heijne, Gunnar
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Ladokhin, Alexey S.
    Thermodynamics of Membrane Insertion and Refolding of the Diphtheria Toxin T-Domain2015In: Journal of Membrane Biology, ISSN 0022-2631, E-ISSN 1432-1424, Vol. 248, no 3, p. 383-394Article in journal (Refereed)
    Abstract [en]

    The diphtheria toxin translocation (T) domain inserts into the endosomal membrane in response to the endosomal acidification and enables the delivery of the catalytic domain into the cell. The insertion pathway consists of a series of conformational changes that occur in solution and in the membrane and leads to the conversion of a water-soluble state into a transmembrane state. In this work, we utilize various biophysical techniques to characterize the insertion pathway from the thermodynamic perspective. Thermal and chemical unfolding measured by differential scanning calorimetry, circular dichroism, and tryptophan fluorescence reveal that the free energy of unfolding of the T-domain at neutral and mildly acidic pH differ by 3-5 kcal/mol, depending on the experimental conditions. Fluorescence correlation spectroscopy measurements show that the free energy change from the membrane-competent state to the interfacial state is approximately -8 kcal/mol and is pH-independent, while that from the membrane-competent state to the transmembrane state ranges between -9.5 and -12 kcal/mol, depending on the membrane lipid composition and pH. Finally, the thermodynamics of transmembrane insertion of individual helices was tested using an in vitro assay that measures the translocon-assisted integration of test sequences into the microsomal membrane. These experiments suggest that even the most hydrophobic helix TH8 has only a small favorable free energy of insertion. The free energy for the insertion of the consensus insertion unit TH8-TH9 is slightly more favorable, yet less favorable than that measured for the entire protein, suggesting a cooperative effect for the membrane insertion of the helices of the T-domain.

  • 3750. Varrone, Andrea
    et al.
    Svenningsson, Per
    Forsberg, Anton
    Varnäs, Katarina
    Tiger, Mikael
    Nakao, Ryuji
    Halldin, Christer
    Nilsson, Lars-Göran
    Stockholm University, Faculty of Social Sciences, Department of Psychology. Stockholm Brain Institute, Sweden.
    Farde, Lars
    Positron emission tomography imaging of 5-hydroxytryptamine(1B) receptors in Parkinson's disease2014In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 35, no 4, p. 867-875Article in journal (Refereed)
    Abstract [en]

    Impairment of the central serotonin system in Parkinson's disease (PD) has been shown postmortem and in vivo with positron emission tomography (PET). The aim of this PET study was to examine and compare the availability of the 5-hydroxytryptamine (5-HT)(1B)-receptor subtype in patients with PD and age-matched control subjects. Twelve control subjects and 12 PD patients were examined with PET using the 5-HT1B-radioligand [C-11]AZ10419369. In PD patients, 5-HT1B-receptor availability in the right orbitofrontal cortex was lower than in control subjects. A statistically significant negative correlation between 5-HT1B-receptor availability and age was obtained for the right temporal cortex in control subjects and for the right midbrain and left parahippocampal gyrus in PD patients. The lower regional 5-HT1B-receptor availability is in line with previous studies showing a decrease of serotonin imaging markers in PD and corroborates a role of the serotonin system in the pathophysiology of PD. The demonstrated age effect on 5-HT1B receptors suggest a physiologic and PD-related decline of serotonin function, indicating the importance of controlling for age in clinical studies.

72737475767778 3701 - 3750 of 4176
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf