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2.
  • Johansson, Pernilla, et al. (author)
  • Utveckling och validering av modeller för att prediktera mögelväxt i byggnader
  • 2018
  • Reports (other academic/artistic)abstract
    • In this project we have tested a mould model originally developed by Skanska (the m-model) and a method developed by RISE in Sweden (the GLC-method) on data from both laboratory and field measurements. The laboratory measurements had durations of a few months and were made in climate chambers at RISE; the field measurements were made in 12 buildings during 30 months. In both cases, temperature, relative humidity and mould growth was assessed on six different materials. The results were used to investigate if the m-model or the GLC-method could predict when there was mould growth. Both methods could differentiate between the (dry) cases without mould and the (moist) cases with mould. However, we could not find mould resistance parameters for the tested materials to be used with the m-model. This could be because the m-model cannot predict mould growth well enough, but it can also be because the types of measurements that we have made have relative large uncertainties in relative humidity. Isotheral calorimetry was also investigated as an interesting method to study how drying affects the activity of mould fungi.
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3.
  • Johansson, Roger, et al. (author)
  • Om forskningscirkeln
  • 2019
  • In: Tjänstelogik i välfärden. En modell för samskapande mellan professionella med barnet i fokus. - 9789144120577 ; , s. 153-160
  • Book chapter (other academic/artistic)
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4.
  • Kindstedt, Elin, et al. (author)
  • Association between marginal jawbone loss and the onset of rheumatoid arhtritis and relationship to plasma levels of RANKL
  • 2018
  • In: Arthritis & Rheumatology. - : Wiley-Blackwell. - 2326-5191 .- 2326-5205. ; 70:4, s. 508-515
  • Journal article (peer-reviewed)abstract
    • Objective: To investigate whether periodontitis, characterized by marginal jawbone loss, precedes the onset of symptoms of rheumatoid arthritis (RA), and to analyze plasma levels of RANKL (a cytokine that is crucial for bone resorption) and anti–citrullinated peptide antibodies (ACPAs) in presymptomatic individuals compared with matched referent controls.Methods: Marginal jawbone loss was measured on dental radiographs of the premolar/molar regions in the jaws in 176 subjects, 93 of whom subsequently developed RA. Among these participating subjects, 46 had documented radiographs predating symptom onset, and 45 cases could be matched to controls, according to sex, age, and smoking status. Plasma RANKL concentrations were analyzed using enzyme‐linked immunosorbent assay. A receiver operating characteristic curve was used to define the cutoff value for RANKL positivity.Results: Bone loss was significantly greater in presymptomatic subjects classified as never smokers compared with that in controls, and increasing levels of bone loss were associated with a higher risk of the subsequent development of RA (hazard ratio 1.03, 95% confidence interval 1.01–1.05). No association between jawbone loss and RA was observed in smokers. A significantly greater extent of marginal jawbone loss was detected in RANKL‐positive presymptomatic subjects, and even more pronounced jawbone loss was observed in those who were positive for both RANKL and ACPA.Conclusion: Marginal jawbone loss preceded the clinical onset of RA symptoms, but this was observed only in nonsmokers. Moreover, marginal jawbone loss was significantly greater in RANKL‐positive presymptomatic subjects compared with RANKL‐negative presymptomatic subjects and was highest in presymptomatic subjects positive for both ACPA and RANKL.
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5.
  • Kindstedt, Elin, et al. (author)
  • Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL) and Marginal Jawbone Loss Predates the Onset of Rheumatoid Arthritis
  • 2017
  • In: Arthritis & Rheumatology. - : Wiley-Blackwell. - 2326-5191 .- 2326-5205. ; 69
  • Journal article (other academic/artistic)abstract
    • Background/Purpose: Previous studies have shown a higher incidence of alveolar bone loss in patients with rheumatoid arthritis (RA) and that patients with periodontitis are at a greater risk for developing RA. Periodontitis, displayed as marginal jawbone loss was analysed in individuals prior to symptom onset of RA and related to plasma levels of receptor activator of nuclear factor kappa-B (RANKL), a cytokine crucial for bone resorption. Methods: A case-control study performed within the Medical Biobank of Northern Sweden included 232 pre-symptomatic individuals with blood samples donated before symptom onset and 194 controls. A questionnaire on self-assed dental status and smoking status was retrieved. Dental radiographs to evaluate marginal jawbone levels were available from 93 pre-symptomatic individuals (mean age; 56.8 95%CI55.9, 57.7 years and pre-dating time; -5.3 95%CI -12.2, -0.2, 74.2% females) and 83 controls (mean age; 55.5 95%CI54.6, 56.5, 73.5% females) . Of these individuals 45 had radiograph documentations prior to development of RA symptoms and to whom sex, age and smoking status could be matched among the controls. Plasma were analysed for RANKL (BioVendor, Karasek, Czech Republic), and anti-citrullinated peptide antibodies (ACPA) (anti-CCP2 test, Eurodiagnostics, Sweden) from similar time points. Results: Compared to matched controls, total bone loss was significantly higher in never-smokers who developed RA but not in smokers and increasing levels on total jawbone loss was associated with a significantly higher odds to be diagnosed with RA later (OR=1.06, 95%CI 1.01, 1.11). Regardless of smoking status, the number of unaffected teeth did not differ significantly between those who were subsequently diagnosed with RA and their matched controls. In the pre-symptomatic individuals RANKL positive individuals had significantly higher extent of marginal jawbone loss, which was further increased in ACPA positive individuals. Previously documented association between smoking and ageing and marginal jawbone loss was verified. Conclusion: Marginal jawbone loss preceded onset of symptoms of RA but the difference was only manifested in non-smokers. Moreover, marginal jawbone loss and plasma RANKL levels were related in the pre-symptomatic individuals particularly in ACPA positive individuals.
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6.
  • Westrup, Ulrika, et al. (author)
  • Att förstå varandra och tänka om
  • 2019
  • In: Tjänstelogik i välfärden : En modell för samskapande mellan professionella med barnet i fokus - En modell för samskapande mellan professionella med barnet i fokus. - 9789144120577 ; 1:1, s. 107-119
  • Book chapter (other academic/artistic)abstract
    • En modell för samskapande mellan professionella med barnet i fokusDenna bok handlar om hur välfärdsorganisationer kan samskapa värde tillsammans med den som de är till för. Boken belyser betydelsen av att förstå olika verksamheters perspektiv – socialtjänsten, barn- och ungdomspsykiatrin och skolan – genom yrkesgruppernas egna röster för att effektivt kunna ta tillvara varandras kompetenser. I boken föreslås en modell för samskapande i välfärdstjänster som bygger på ett tjänsteperspektiv, ibland kallat tjänstelogik.Boken vänder sig till studenter vid lärarutbildningar, socionomutbildningar och beteendevetenskapliga utbildningar samt inom området hälsa.
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7.
  • Abrahamsson, Pernilla, et al. (author)
  • Outcome of microdialysis sampling on liver surface and parenchyma
  • 2016
  • In: Journal of Surgical Research. - : Elsevier BV. - 0022-4804 .- 1095-8673. ; 200:2, s. 480-487
  • Journal article (peer-reviewed)abstract
    • Background: To investigate whether surface microdialysis (μD) sampling in probes covered by a plastic film, as compared to noncovered and to intraparenchymatous probes, would increase the technique's sensitivity for pathophysiologic events occurring in a liver ischemia-reperfusion model. Placement of μD probes in the parenchyma of an organ, as is conventionally done, may cause adverse effects, e.g., bleeding, possibly influencing outcome.Methods: A transient ischemia-reperfusion model of the liver was used in six anesthetized normoventilated pigs. μD probes were placed in the parenchyma and on the liver surface. Surface probes were either left uncovered or were covered by plastic film.Results: Lactate and glucose levels were significantly higher in plastic film covered probes than in uncovered surface probes throughout the ischemic period. Glycerol levels were significantly higher in plastic film covered probes than in uncovered surface probes at 30 and 45 min into ischemia.Conclusions: Covering the μD probe increases the sensibility of the μD–technique in monitoring an ischemic insult and reperfusion in the liver. These findings confirm that the principle of surface μD works, possibly replacing need of intraparenchymatous placement of μD probes. Surface μD seemingly allows, noninvasively from an organ's surface, via the extracellular compartment, assessment of intracellular metabolic events. The finding that covered surface μD probes allows detection of local metabolic changes earlier than do intraparenchymatous probes, merit further investigation focusing on μD probe design.
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8.
  • Alskär, Linda C., et al. (author)
  • Effect of lipids on absorption of carvedilol in dogs : Is coadministration of lipids as efficient as a lipid-based formulation?
  • 2019
  • In: Journal of Controlled Release. - : Elsevier BV. - 0168-3659 .- 1873-4995. ; 304, s. 90-100
  • Journal article (peer-reviewed)abstract
    • Lipid-based formulations (LBFs) is a formulation strategy for enabling oral delivery of poorly water-soluble drugs. However, current use of this strategy is limited to a few percent of the marketed products. Reasons for that are linked to the complexity of LBFs, chemical instability of pre-dissolved drug and a limited understanding of the influence of LBF intestinal digestion on drug absorption. The aim of this study was to explore intestinal drug solubilization from a long-chain LBF, and evaluate whether coadministration of LBF is as efficient as a lipidbased drug formulation containing the pre-dissolved model drug carvedilol. Thus, solubility studies of this weak base were performed in simulated intestinal fluid (SIF) and aspirated dog intestinal fluid (DIF). DIF was collected from duodenal stomas after dosing of water and two levels (1 g and 2 g) of LBF. Similarly, the in vitro SIF solubility studies were conducted prior to, and after addition of, undigested or digested LBF. The DIF fluid was further characterized for lipid digestion products (free fatty acids) and bile salts. Subsequently, carvedilol was orally administered to dogs in a lipid-based drug formulation and coadministered with LBF, and drug plasma exposure was assessed. In addition to these studies, in vitro drug absorption from the different formulation approaches were evaluated in a lipolysis-permeation device, and the obtained data was used to evaluate the in vitro in vivo correlation. The results showed elevated concentrations of free fatty acids and bile salts in the DIF when 2 g of LBF was administered, compared to only water. As expected, the SIF and DIF solubility data revealed that carvedilol solubilization increased by the presence of lipids and lipid digestion products. Moreover, coadministration of LBF and drug demonstrated equal plasma exposure to the lipid-based drug formulation. Furthermore, evaluation of in vitro absorption resulted in the same rank order for the LBFs as in the in vivo dog study. In conclusion, this study demonstrated increased intestinal solubilization from a small amount of LBF, caused by lipid digestion products and bile secretion. The outcomes also support the use of coadministration of LBF as a potential dosing regimen in cases where it is beneficial to have the drug in the solid form, e.g. due to chemical instability in the lipid vehicle. LBFs.
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10.
  • Andersson, Camilla (author)
  • PET/CT in oncology : Patient experience, image quality and the value of information
  • 2018
  • Doctoral thesis (other academic/artistic)abstract
    • The overall aim was to investigate patients’ experiences with a PET/CT examination, satisfaction with care provided in connection to the examination and whether web-based information can improve satisfaction with care and image quality, compared to standard care. An additional aim was to explore how satisfaction with care and image quality is associated with health-related quality of life (HRQoL) and perceived stress. Methods: Study I and IV included patients with known or suspected malignancy scheduled for an 18F-FDG PET/CT examination. Study II included prostate cancer patients with known or suspected bone metastases scheduled for an 18F-fluoride PET/CT examination, and study III included head and neck cancer patients scheduled for an 18F-FDG PET/CT examination in a fixation mask. Study I and II had cross-sectional designs, study III used a phenomenological methodology according to Max van Manen, and study IV was a randomized controlled trial. Results: Study I and II found that many patients did not know before what a PET/CT examination was but were satisfied with care provided by the nursing staff. In study II the image quality was high and there was no difference in image quality between those patients that experienced pain or discomfort during the PET/CT and those that did not. Study III showed that the patient’s lifeworld was changed during the PET/CT examination and the use of coping strategies helped the patient to endure the examination procedure. In study IV the overall satisfaction, satisfaction single-variables and image quality was high in the intervention group and standard care group. There was no statistically significant difference between patients the intervention group and standard care group. However, there was slightly higher number of detected image quality defects in the standard care group. In study I and IV there were some statistically significant correlations between patient satisfaction and HRQoL (p<0.01-0.05). Conclusion: The results of this thesis may be used to improve patient information and care in connection to PET/CT examinations and thereby help optimize PET/CT imaging procedure. However, the results need to be investigated in larger populations.
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12.
  • Bok, Gunilla, et al. (author)
  • Mikroorganismer bakom keramiskaplattor i badrum
  • 2015
  • Reports (other academic/artistic)abstract
    • Microorganisms behind ceramic tiles in bathroomsIn this study the interface between the backside of ceramic tiles and the waterproof membrane was investigated for microbial growth in 13 bathrooms. This interface is made up of the backside of the ceramic tile, tile adhesive and the waterproof membrane. In every day used bathrooms water will accumulate in this particular environment. It is calculated that a tiled wall exposed to water in 15 minutes needs approximately six months to dry out since water is sucked, by capillary actions, through the grout joints between the ceramic tiles. The wall dries through diffusion forces and diffusion force is a weaker than capillary force and therefore the drying need longer time than the wetting of the wall with a water accumulation in the interface as a result.Samples were taken from areas where the wall and floor had been exposed to free water regularly, due to showering.Mould and/or bacterial growth was found on 69 % of the analysed specimens from the most water exposed places in the bathrooms. No such growth was found on the samples from the dryer areas. The results shows that although the environment behind the tiles may seem to disadvantaged for microbial growth, due to a limited amount of organic substances and due to pH values not favourable for microbial growth, such growth is possible when the moisture conditions are high.To our knowledge the microbial occurrence in this particular environment has not been investigated before.
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13.
  • Bok, Gunilla, et al. (author)
  • Nya möjligheter att minska mängden deponerat gipsavfall från bygg- och ombyggnadsprojekt
  • 2018
  • Reports (other academic/artistic)abstract
    • Plasterboard is a common building material used in several parts of a building. In the case of retrofitting and demolition a part of the waste consists of components combined with the plasterboards, for example, frame work timber.In the case of new construction and retrofitting, construction waste is produced from clean plasterboard boards, either as cut off pieces or as unused whole boards. This waste can be used as raw material to produce new plasterboards. Manufacturers want to use gypsum from wasted boards to decrease the use of primary gypsum from mining and the quality requirements are relatively easy to achieve.In this project it has been found that the major construction companies already handle gypsum from new construction separately. This waste fraction could already be used in the production of new boards. Gypsum from retrofitting is usually assembled with other building materials and require more extensive efforts to achieve necessary purity to be used in the productions of new boards. Today, plasterboard waste is deposited or used to improve soil and/or sludge. In order to increase the recycling of plasterboards new inventory routines of rebuilding and demolition projects need to be elaborated. New tools and methods for dismantling plasterboard need to be development to achieve safe working environment and environmentally and economically sustainable recycling.Preparation plants producing raw material from plasterboard waste are already in operation. Today the waste mainly is wastage from the production stage. In order to increase the recycling of plasterboards from the construction- and demolition branch new logistic systems need to be developed, for example by creating collection points for gypsum board waste and / or developing new transport vehicles and systems. Prerequisites of changing the system of piece work in the construction industry need to be investigated with the intension to create a more sustainable building industry.
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14.
  • Bostrom, E. A., et al. (author)
  • Increased Eotaxin and MCP-1 Levels in Serum from Individuals with Periodontitis and in Human Gingival Fibroblasts Exposed to Pro-Inflammatory Cytokines
  • 2015
  • In: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 10:8
  • Journal article (peer-reviewed)abstract
    • Periodontitis is a chronic inflammatory disease of tooth supporting tissues resulting in periodontal tissue destruction, which may ultimately lead to tooth loss. The disease is characterized by continuous leukocyte infiltration, likely mediated by local chemokine production but the pathogenic mechanisms are not fully elucidated. There are no reliable serologic biomarkers for the diagnosis of periodontitis, which is today based solely on the degree of local tissue destruction, and there is no available biological treatment tool. Prompted by the increasing interest in periodontitis and systemic inflammatory mediators we mapped serum cytokine and chemokine levels from periodontitis subjects and healthy controls. We used multivariate partial least squares (PLS) modeling and identified monocyte chemoattractant protein-1 (MCP-1) and eotaxin as clearly associated with periodontitis along with C-reactive protein (CRP), years of smoking and age, whereas the number of remaining teeth was associated with being healthy. Moreover, body mass index correlated significantly with serum MCP-1 and CRP, but not with eotaxin. We detected higher MCP-1 protein levels in inflamed gingival connective tissue compared to healthy but the eotaxin levels were undetectable. Primary human gingival fibroblasts displayed strongly increased expression of MCP-1 and eotaxin mRNA and protein when challenged with tumor necrosis factor-alpha (TNF-alpha and interleukin-1 beta (IL-1 beta), key mediators of periodontal inflammation. We also demonstrated that the upregulated chemokine expression was dependent on the NF-kappa B pathway. In summary, we identify higher levels of CRP, eotaxin and MCP-1 in serum of periodontitis patients. This, together with our finding that both CRP and MCP-1 correlates with BMI points towards an increased systemic inflammatory load in patients with periodontitis and high BMI. Targeting eotaxin and MCP-1 in periodontitis may result in reduced leukocyte infiltration and inflammation in periodontitis and maybe prevent tooth loss.
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15.
  • Bäckström, Ingela, 1963-, et al. (author)
  • Communicative Leadership development conduction to impact on   Quality culture and co-worker health
  • 2019
  • In: 22nd QMOD conference on Quality and Service Sciences ICQSS 2019, 13-15 October. - Lund. - 9789176230862
  • Conference paper (peer-reviewed)abstract
    • Purpose – The purpose of this paper explore effects of a communicative leadership development program in an organization and to present and discuss results from assessing Quality Culture and co-worker health in the same organization. Methodology/approach –  In a company conducted a communicative leadership developing program, a questionnaire measuring QM values and co-worker health has been handed out to leaders and co-workers. Leaders conducted a communicative leadership developing program have been interviewed and observation studies have been conducted.  Findings – The interviewed and observed leaders are working with communicative leadership in a structured way, The measured factors, assessing quality culture and co-worker health showed rather high mean values. Practical implications – The communicative leadership developing program seams to help leaders to communicate in a structured way.
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16.
  • Bäckström, Ingela, et al. (author)
  • How Communicative Leadership influences co-workers’ health : A Quality Management perspective
  • 2016
  • In: International Journal of Quality and Service Sciences. - 1756-669X .- 1756-6703. ; 8:2, s. 143-158
  • Journal article (peer-reviewed)abstract
    • Purpose - The purpose of this paper is to describe leaders’ views on how Communicative Leadership influences co-worker health by comparing their opinions with the health-related values within Quality Management.Design/methodology/approach - A multinational manufacturing organization that has been working with Communicative Leadership for several years was investigated. 21 managers trained in Communicative Leadership were interviewed and asked about their views on how their communication influences both the well-being of their co-workers and the working environment. Various communication behaviors and communication methodologies emerged from the interviews and were then analyzed versus the health-related Quality Management dimensions.Findings - The result shows concrete communication behavior and methodologies that influence co-worker well-being and the working environment positively and negatively. Another result is a description of the prerequisites for managers to be able to communicate in a way that influences co-worker well-being and the working environment. The analysis of the communication behaviors and communication methodologies versus the health-related Quality Management values shows that several of the health-related Quality Management dimensions were present.Research limitations/implications – A limitation of this research is that it is just managers’ view that has been investigated and analyzed.Practical implications – Managers acting and behaving in accordance with the communicative behaviors and methodologies described in the results can influence co-worker health and the working environment in a positive way. The level of awareness of the prerequisites could help managers to influence co-worker well-being and create a good working environment.Originality/value – The connection between Communicative Leadership and health-related Quality Management values is rarely made. This research can contribute to greater understanding in both areas. Keywords Health-related Quality Management, co-worker health, Communicative Leadership, well-being, working environment.Paper type Research paper. 
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17.
  • Dahlgren, David, et al. (author)
  • Regional Intestinal Permeability in Dogs : Biopharmaceutical Aspects for Development of Oral Modified-Release Dosage Forms
  • 2016
  • In: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 13:9, s. 3022-3033
  • Journal article (peer-reviewed)abstract
    • The development of oral modified-release (MR) dosage forms requires an active pharmaceutical ingredient (API) with a sufficiently high absorption rate in both the small and large intestine. Dogs are commonly used in preclinical evaluation of regional intestinal absorption and in the development of novel MR dosage forms. This study determined regional intestinal effective permeability (P-eff) in dogs with the aim to improve regional Peff prediction in humans. Four model drugs, atenolol, enalaprilat, metoprolol, and ketoprofen, were intravenously and regionally dosed twice as a solution into the proximal small intestine (P-SI) and large intestine (LI) of three dogs with intestinal stomas. Based on plasma data from two separate study occasions for each dog, regional Peff values were calculated using a validated intestinal deconvolution method. The determined mean P-eff values were 0.62, 0.14, 1.06, and 3.66 X 10(-4) cm/s in the P-SI, and 0.13, 0.02, 1.03, and 2.20 X 10(-4) cm/s in the LI, for atenolol, enalaprilat, metoprolol, and ketoprofen, respectively. The determined P-SI Peff values in dog were highly correlated (R-2 = 0.98) to the historically directly determined human jejunal P-eff after a single-pass perfusion. The determined dog P-SI P-eff values were also successfully implemented in GI-Sim to predict the risk for overestimation of LI absorption of low permeability drugs. We conclude that the dog intestinal stoma model is a useful preclinical tool for determination of regional intestinal permeability. Still, further studies are recommended to evaluate additional APIs, sources of variability, and formulation types, for more accurate determination of the dog model in the drug development process.
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18.
  • Darwich, Adam S., et al. (author)
  • IMI - Oral biopharmaceutics tools project - Evaluation of bottom-up PBPK prediction success part 3 : Identifying gaps in system parameters by analysing In Silico performance across different compound classes
  • 2017
  • In: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 96, s. 626-642
  • Journal article (peer-reviewed)abstract
    • Three Physiologically Based Pharmacokinetic software packages (GI-Sim, Simcyp (R) Simulator, and GastroPlus (TM)) were evaluated as part of the Innovative Medicine Initiative Oral Biopharmaceutics Tools project (OrBiTo) during a blinded "bottom-up" anticipation of human pharmacokinetics. After data analysis of the predicted vs. measured pharmacokinetics parameters, it was found that oral bioavailability (F-oral) was underpredicted for compounds with low permeability, suggesting improper estimates of intestinal surface area, colonic absorption and/or lack of intestinal transporter information. Foralwas also underpredicted for acidic compounds, suggesting overestimation of impact of ionisation on permeation, lack of information on intestinal transporters, or underestimation of solubilisation of weak acids due to less than optimal intestinal model pH settings or underestimation of bile micelle contribution. F-oral was overpredicted for weak bases, suggesting inadequate models for precipitation or lack of in vitro precipitation information to build informed models. Relative bioavailability was underpredicted for both high logP compounds as well as poorly water-soluble compounds, suggesting inadequate models for solubility/dissolution, underperforming bile enhancement models and/or lack of biorelevant solubility measurements. These results indicate areas for improvement in model software, modelling approaches, and generation of applicable input data. However, caution is required when interpreting the impact of drug-specific properties in this exercise, as the availability of input parameters was heterogeneous and highly variable, and the modellers generally used the data "as is" in this blinded bottom-up prediction approach.
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19.
  • Eriksson, Linda, et al. (author)
  • Allelic Variation in Taste Genes Is Associated with Taste and Diet Preferences and Dental Caries
  • 2019
  • In: Nutrients. - : MDPI. - 2072-6643. ; 11:7
  • Journal article (peer-reviewed)abstract
    • Taste and diet preferences are complex and influenced by both environmental and host traits while affecting both food selection and associated health outcomes. The present study genotyped 94 single nucleotide polymorphisms (SNPs) in previously reported taste and food intake related genes and assessed associations with taste threshold (TT) and preferred intensity (PT) of sweet, sour and bitter, food preferences, habitual diet intake, and caries status in healthy young Swedish men and women (n = 127). Polymorphisms in the GNAT3, SLC2A4, TAS1R1 and TAS1R2 genes were associated with variation in TT and PT for sweet taste as well as sweet food intake. Increasing PT for sweet was associated with increasing preference and intake of sugary foods. Similarly, increasing TT for sour was associated with increasing intake of sour foods, whereas the associations between food preference/intake and TT/PT for bitter was weak in this study group. Finally, allelic variation in the GNAT3, SLC2A2, SLC2A4, TAS1R1 and TAS1R2 genes was associated with caries status, whereas TT, PT and food preferences were not. It was concluded that variations in taste receptor, glucose transporter and gustducin encoding genes are related to taste perception, food preference and intake as well as the sugar-dependent caries disease.
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20.
  • Eriksson, Linda, et al. (author)
  • Microbial complexes and caries in 17-year-olds with and without Streptococcus mutans
  • 2018
  • In: Journal of Dental Research. - Thousand oaks : Sage Publications. - 0022-0345 .- 1544-0591. ; 97:3, s. 275-282
  • Journal article (peer-reviewed)abstract
    • Streptococcus mutans is a key bacterial species in the caries process, which affects >90% of the population worldwide. However, other acidogenic and aciduric/acidophilic species may contribute to disease development. In Sweden, a country with low prevalences of caries and S. mutans, a significant portion of caries-affected adolescents lack detectable levels of S. mutans. The objectives of the present study were 1) to characterize the tooth biofilm and saliva microbiota of adolescents with caries disease, with or without detectable S. mutans, from tooth biofilm and saliva samples and 2) to assess taxa clustering in the tooth biofilm and saliva samples and relate this information to caries status. For 17-y-old participants ( N = 154), enamel and dentin caries (the total number of present carious surfaces in the enamel and dentin) and caries experience (the number of decayed and filled tooth surfaces) were recorded, dental biofilm and saliva samples obtained, and information on medical and lifestyle habits collected. Multiplex 16S rDNA (V3-V4) sequencing of bacterial DNA was performed with the Illumina MiSeq platform. The Human Oral Microbiome Database and the ProbeSeq pipeline were used in the HOMI NGS procedure. In subjects with caries experience, high levels of S. mutans were associated with a few species and low levels with a panel of saccharolytic species. Present caries was similarly associated with a panel of saccharolytic species in subjects without S. mutans. Furthermore, tooth biofilm microbiota could be used to establish 4 clusters of subjects with different caries experiences. In particular, high levels of S. mutans were associated with the presence of a few influential species in multivariate modeling, including Scardovia wiggsiae. By contrast, a panel of less avid lactic acid-producing species was influential in patients with undetectable or low S. mutans levels in such modeling. These findings support a prominent role of S. mutans in infected adolescents but also the ecologic concept, especially in S. mutans-free subjects.
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21.
  • Eriksson, Linda, et al. (author)
  • Saliva and tooth biofilm bacterial microbiota in adolescents in a low caries community
  • 2017
  • In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
  • Journal article (peer-reviewed)abstract
    • The oral cavity harbours a complex microbiome that is linked to dental diseases and serves as a route to other parts of the body. Here, the aims were to characterize the oral microbiota by deep sequencing in a low-caries population with regular dental care since childhood and search for association with caries prevalence and incidence. Saliva and tooth biofilm from 17-year-olds and mock bacteria communities were analysed using 16S rDNA Illumina MiSeq (v3-v4) and PacBio SMRT (v1-v8) sequencing including validity and reliability estimates. Caries was scored at 17 and 19 years of age. Both sequencing platforms revealed that Firmicutes dominated in the saliva, whereas Firmicutes and Actinobacteria abundances were similar in tooth biofilm. Saliva microbiota discriminated caries-affected from caries-free adolescents, with enumeration of Scardovia wiggsiae, Streptococcus mutans, Bifidobacterium longum, Leptotrichia sp. HOT498, and Selenomonas spp. in caries-affected participants. Adolescents with B. longum in saliva had significantly higher 2-year caries increment. PacBio SMRT revealed Corynebacterium matruchotii as the most prevalent species in tooth biofilm. In conclusion, both sequencing methods were reliable and valid for oral samples, and saliva microbiota was associated with cross-sectional caries prevalence, especially S. wiggsiae, S. mutans, and B. longum; the latter also with the 2-year caries incidence.
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22.
  • Esberg, Anders, et al. (author)
  • Carbonic Anhydrase 6 Gene Variation influences Oral Microbiota Composition and Caries Risk in Swedish adolescents
  • 2019
  • In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322 .- 2045-2322. ; 9:1
  • Journal article (peer-reviewed)abstract
    • Carbonic anhydrase VI (CA6) catalyses the reversible hydration of carbon dioxide in saliva with possible pH regulation, taste perception, and tooth formation effects. This study assessed effects of variation in the CA6 gene on oral microbiota and specifically the acidophilic and caries-associated Streptococcus mutans in 17-year old Swedish adolescents (n = 154). Associations with caries status and secreted CA6 protein were also evaluated. Single Nucleotide Polymorphisms (27 SNPs in 5 haploblocks) and saliva and tooth biofilm microbiota from Illumina MiSeq 16S rDNA (V3-V4) sequencing and culturing were analysed. Haploblock 4 (rs10864376, rs3737665, rs12138897) CCC associated with low prevalence of S. mutans (OR (95% CI): 0.5 (0.3, 0.8)), and caries (OR 0.6 (0.3, 0.9)), whereas haploblock 4 TTG associated with high prevalence of S. mutans (OR: 2.7 (1.2, 5.9)) and caries (OR: 2.3 (1.2, 4.4)). The TTG-haploblock 4 (represented by rs12138897(G)) was characterized by S. mutans, Scardovia wiggsiae, Treponema sp. HOT268, Tannerella sp. HOT286, Veillonella gp.1 compared with the CCC-haploblock 4 (represented by rs12138897(C)). Secreted CA6 in saliva was weakly linked to CA6 gene variation. In conclusion, the results indicate that CA6 gene polymorphisms influence S. mutans colonization, tooth biofilm microbiota composition and risk of dental caries in Swedish adolescents.
  •  
23.
  • Good, James A. D., 1985-, et al. (author)
  • Attenuating Listeria monocytogenes virulence by targeting the regulatory protein PrfA
  • 2016
  • In: Cell chemical biology. - : Elsevier BV. - 2451-9448 .- 2451-9456. ; 23:3, s. 404-414
  • Journal article (peer-reviewed)abstract
    • The transcriptional activator PrfA, a member of the Crp/Fnr family, controls the expression of some key virulence factors necessary for infection by the human bacterial pathogen Listeria monocytogenes. Phenotypic screening identified ring-fused 2-pyridone molecules that at low micromolar concentrations attenuate L. monocytogenes infectivity by reducing the expression of virulence genes, without compromising bacterial growth. These inhibitors bind the transcriptional regulator PrfA and decrease its affinity for the consensus DNA binding site. Structural characterization of this interaction revealed that one of the ring-fused 2-pyridones, compound 1, binds within a hydrophobic pocket, located between the C- and N-terminal domains of PrfA, and interacts with residues important for PrfA activation. This indicates that these inhibitors maintain the DNA-binding helix-turn-helix motif of PrfA in a disordered state, thereby preventing a PrfA:DNA interaction. Ring-fused 2-pyridones represent a new class of chemical probes for studying virulence in L. monocytogenes.
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24.
  • Gyll, Johanna, et al. (author)
  • Vitamin D status and dental caries in healthy Swedish children
  • 2018
  • In: Nutrition Journal. - London : BioMed Central. - 1475-2891. ; 17
  • Journal article (peer-reviewed)abstract
    • Background: Vitamin D is crucial for mineralized tissue formation and immunological functions. The purpose of this study was to evaluate the association between vitamin D status and dental status in healthy children with vitamin D supplementation in infancy and at 6 years of age.Method: Eight-year-old children who had participated, in a vitamin D intervention project when they were 6 years old were invited to participate in a dental follow-up study. They had fair or darker skin complexion and represented two geographically distant parts of Sweden. 25-hydroxy vitamin D in serum had been measured at 6 years of age and after a 3-month intervention with 25, 10 or 2 (placebo) mu g of vitamin D-3 per day. Two years later, caries and enamel defects were scored, self-reported information on e.g., oral behavior, dietary habits and intake of vitamin D supplements was collected, and innate immunity peptide LL37 levels in saliva and cariogenic mutant streptococci in tooth biofilm were analyzed. The outcome variables were caries and tooth enamel defects.Results: Dental status was evaluated in 85 of the 206 children in the basic intervention study. Low vitamin D levels were found in 28% at baseline compared to 11% after the intervention, and 34% reported continued intake of vitamin D supplements. Logistic regression supported a weak inverse association between vitamin D status at 6 years of age and caries 2 years later (odds ratio 0.96; p = 0.024) with minor attenuation after an adjustment for potential confounders. Multivariate projection regression confirmed that insufficient vitamin D levels correlated with caries and higher vitamin D levels correlated with being caries-free. Vitamin D status at 6 years of age was unrelated to enamel defects but was positively associated with saliva LL37 levels.Conclusion: An association between vitamin D status and caries was supported, but it was not completely consistent. Vitamin D status at 6 years of age was unrelated to enamel defects but was positively associated with LL37 expression.
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25.
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26.
  • Hallqvist, Andreas, 1973, et al. (author)
  • Intraperitoneal alpha-Emitting Radioimmunotherapy with At-211 in Relapsed Ovarian Cancer: Long-Term Follow-up with Individual Absorbed Dose Estimations
  • 2019
  • In: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 2159-662X. ; 60:8, s. 1073-1079
  • Journal article (peer-reviewed)abstract
    • Eliminating microscopic residual disease with alpha-particle radiation is theoretically appealing. After extensive preclinical work with alpha-particle-emitting At-211, we performed a phase I trial with intraperitoneal alpha-particle therapy in epithelial ovarian cancer using At-211 conjugated to MX35, the antigen-binding fragments-F(ab')(2)-of a mouse monoclonal antibody. We now present clinical outcome data and toxicity in a long-term follow-up with individual absorbed dose estimations. Methods: Twelve patients with relapsed epithelial ovarian cancer, achieving a second complete or nearly complete response with chemotherapy, received intraperitoneal treatment with escalating (20-215 MBq/L) activity concentrations of At-211-MX35 F(ab')(2). Results: The activity concentration was escalated to 215 MBq/L without any dose-limiting toxicities. Most toxicities were low-grade and likely related to the treatment procedure, not clearly linked to the alpha-particle irradiation, with no observed hematologic toxicity. One grade 3 fatigue and 1 grade 4 intestinal perforation during catheter implantation were observed. Four patients had a survival of more than 6 y, one of whom did not relapse. At progression, chemotherapy was given without signs of reduced tolerability. Overall median survival was 35 mo, with a 1-, 2-, 5-, and 10-y survival of 100%, 83%, 50%, and 25%, respectively. Calculations of the absorbed doses showed that a lower specific activity is associated with a lower single-cell dose, whereas a high specific activity may result in a lower central dose in microtumors. Individual differences in absorbed dose to possible microtumors were due to variations in administered activity and the specific activity. Conclusion: No apparent signs of radiation-induced toxicity or decreased tolerance to relapse therapy were observed. The dosimetric calculations show that further optimization is advisable to increase the efficacy and reduce possible long-term toxicity.
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27.
  • Haworth, Simon, et al. (author)
  • Inference and visualization of phenome-wide causal relationships using genetic data : an application to dental caries and periodontitis
  • 2019
  • Other publication (other academic/artistic)abstract
    • Background: Hypothesis-free Mendelian randomization studies provide a way to assess the causal relevance of a trait across the human phenome but can be limited by statistical power or complicated by horizontal pleiotropy. The recently described latent causal variable (LCV) approach provides an alternative method for casual inference which might be useful in hypothesis-free experiments.Methods: We developed an automated pipeline for phenome-wide tests using the LCV approach including steps to estimate partial genetic causality, filter to a meaningful set of estimates, apply correction for multiple testing and then present the findings in a graphical summary termed a causal architecture plot. We apply this process to body mass index and lipid traits as exemplars of traits where there is strong prior expectation for causal effects and dental caries and periodontitis as exemplars of traits where there is a need for causal inference.Results: The results for lipids and BMI suggest that these traits are best viewed as creating consequences on a multitude of traits and conditions, thus providing additional evidence that supports viewing these traits as targets for interventions to improve health. On the other hand, caries and periodontitis are best viewed as a downstream consequence of other traits and diseases rather than a cause of ill health.Conclusions: The automated process is available as part of the MASSIVE pipeline from the Complex-Traits Genetics Virtual Lab (https://vl.genoma.io) and results are available in (https://view.genoma.io). We propose causal architecture plots based on phenome-wide partial genetic causality estimates as a way visualizing the overall causal map of the human phenome.
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28.
  • Isehed, Catrine, et al. (author)
  • Effectiveness of enamel matrix derivative on the clinical and microbiological outcomes following surgical regenerative treatment of peri-implantitis : A randomized controlled trial
  • 2016
  • In: Journal of Clinical Periodontology. - Hoboken, USA : Wiley-Blackwell Publishing Inc.. - 0303-6979 .- 1600-051X. ; 43:10, s. 863-873
  • Journal article (peer-reviewed)abstract
    • Objective: This randomized clinical trial aimed at comparing radiological, clinical and microbial effects of surgical treatment of peri-implantitis alone or in combination with enamel matrix derivative (EMD).Methods: Twenty-six subjects were treated with open flap debridement and decontamination of the implant surfaces with gauze and saline preceding adjunctive EMD or no EMD. Bone level (BL) change was primary outcome and secondary outcomes were changes in pocket depth (PD), plaque, pus, bleeding and the microbiota of the peri-implant biofilm analyzed by the Human Oral Microbe Identification Microarray over a time period of 12 months.Results: In multivariate modelling, increased marginal BL at implant site was significantly associated with EMD, the number of osseous walls in the peri-implant bone defect and a Gram+/aerobic microbial flora, whereas reduced BL was associated with a Gram-/anaerobic microbial flora and presence of bleeding and pus, with a cross-validated predictive capacity (Q(2) ) of 36.4%. Similar, but statistically non-significant, trends were seen for BL, PD, plaque, pus and bleeding in univariate analysis.Conclusion: Adjunctive EMD to surgical treatment of peri-implantitis was associated with prevalence of Gram+/aerobic bacteria during the follow-up period and increased marginal BL 12 months after treatment.
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29.
  • Johansson, Ingegerd, et al. (author)
  • Self-reported bovine milk intake is associated with oral microbiota composition
  • 2018
  • In: PLOS ONE. - San Fransisco : Public Library of Science (PLoS). - 1932-6203. ; 13:3
  • Journal article (peer-reviewed)abstract
    • Bovine milk intake has been associated with various disease outcomes, with modulation of the gastro-intestinal microbiome being suggested as one potential mechanism. The aim of the present study was to explore the oral microbiota in relation to variation in self-reported milk intake. Saliva and tooth biofilm microbiota was characterized by 16S rDNA sequencing, PCR and cultivation in 154 Swedish adolescents, and information on diet and other lifestyle markers were obtained from a questionnaire, and dental caries from clinical examination. A replication cohort of 31,571 adults with similar information on diet intake, other lifestyle markers and caries was also studied. Multivariate partial least squares (PLS) modelling separated adolescents with low milk intake (lowest tertile with <0.4 servings/day) apart from those with high intake of milk (≥3.7 servings/day) based on saliva and tooth biofilm, respectively. Taxa in several genera contributed to this separation, and milk intake was inversely associated with the caries causing Streptococcus mutans in saliva and tooth biofilm samples by sequencing, PCR and cultivation. Despite the difference in S. mutans colonization, caries prevalence did not differ between milk consumption groups in the adolescents or the adults in the replication cohort, which may reflect that a significant positive association between intake of milk and sweet products was present in both the study and replication group. It was concluded that high milk intake correlates with different oral microbiota and it is hypothesized that milk may confer similar effects in the gut. The study also illustrated that reduction of one single disease associated bacterial species, such as S. mutans by milk intake, may modulate but not prevent development of complex diseases, such as caries, due to adverse effects from other causal factors, such as sugar intake in the present study.
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30.
  • Johansson, Ingegerd, et al. (author)
  • The Microbiome in Populations with a Low and High Prevalence of Caries
  • 2016
  • In: Journal of Dental Research. - : Sage Publications. - 0022-0345 .- 1544-0591. ; 95:1, s. 80-86
  • Journal article (peer-reviewed)abstract
    • The oral microbiota was compared between Romanian adolescents with a high prevalence of caries and no dental care and Swedish caries-active and caries-free adolescents in caries prevention programs and with a low prevalence of caries. Biofilm samples were analyzed by FLX+ pyrosequencing of the V1 to V4 hypervariable regions of the 16S rRNA gene and polymerase chain reaction (PCR)/quantitative PCR (qPCR) for Streptococcus mutans and Streptococcus sobrinus. Sequences obtained blasted to 9 phyla, 66 genera, and 401 human oral taxa (HOT) in the 16S rRNA Human Oral Microbiome Database, of which 295 were represented by >= 20 sequences. The Romanian adolescents had more sequences in Firmicutes and fewer in Actinobacteria phyla and more sequences in the genera Bacteroidetes [G-3], Porphyromonas, Abiotrophia, Filifactor, Peptostreptococcaceae [11][G-4], Pseudoramibacter, Streptococcus, and Neisseria and fewer in Actinomyces, Selenomonas, Veillonella, Campylobacter, and TM7 [G-1] than the Swedish groups. Multivariate modeling employing HOT, S. sobrinus and S. mutans (PCR/qPCR), and sugar snacks separated Romanian from Swedish adolescents. The Romanian adolescents' microbiota was characterized by a panel of streptococci, including S. mutans, S. sobrinus, and Streptococcus australis, and Alloprevotella, Leptotrichia, Neisseria, Porphyromonas, and Prevotella. The Swedish adolescents were characterized by sweet snacks, and those with caries activity were also characterized by Prevotella, Actinomyces, and Capnocytophaga species and those free of caries by Actinomyces, Prevotella, Selenomonas, Streptococcus, and Mycoplasma. Eight species including Streptococcus mitis and Streptococcus species HOT070 were prevalent in Romanian and Swedish caries-active subjects but not caries-free subjects. In conclusion, S. mutans and S. sobrinus correlated with Romanian adolescents with caries and with limited access to dental care, whereas S. mutans and S. sobrinus were detected infrequently in Swedish adolescents in dental care programs. Swedish caries-active adolescents were typically colonized by Actinomyces, Selenomonas, Prevotella, and Capnocytophaga. Hence, the role of mutans streptococci as a primary caries pathogen appears less pronounced in populations with prevention programs compared to populations lacking caries treatment and prevention strategies.
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31.
  • Johansson, Krister, et al. (author)
  • Effects of Bacterial Contamination on Dental Implants During Surgery : A Systematic Review
  • 2017
  • In: Implant Dentistry. - : Lippincott Williams & Wilkins. - 1056-6163 .- 1538-2982. ; 26:5, s. 778-789
  • Research review (peer-reviewed)abstract
    • INTRODUCTION: Contamination during surgery negatively influences the prognosis of orthopaedic implants; however, it has not been proven whether contamination influences the success of dental implant treatment. The aim of the systematic review was to investigate if there exists evidence in the literature whether contamination of dental implants during surgery affects osseointegration and clinical success. MATERIALS AND METHODS: Four data bases were used for the literature search. Primary studies and reviews regarding both clinical and preclinical research were eligible. Rating of the summarized quality of the evidence was performed. RESULTS: Five preclinical studies were included. Because of the estimated high risk of bias in all included studies and extensive differences in study design between the included studies, meta-analysis was not performed and no reliable aggregated data could be extracted. CONCLUSIONS: It is suggested that the scientific evidence with regard to the current topic is insufficient. Further controlled studies are warranted.
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32.
  • Johansson, Pernilla, et al. (author)
  • Environmental impact of recycling digested food waste as a fertilizer in agriculture : A case study
  • 2015
  • In: Resources, Conservation and Recycling. - : Elsevier BV. - 0921-3449 .- 1879-0658. ; 95, s. 1-14
  • Journal article (peer-reviewed)abstract
    • This study assessed the environmental impacts of recycling the plant nutrients in anaerobically digested food waste as fertilizer in agriculture. This was compared with the impacts of using chemical fertilizer, where the food waste was incinerated, producing heat. The study site was a biogas plant in central Sweden and life cycle assessment methodology was used. The impacts studied were primary energy use, global warming potential (GWP), potential acidification, potential eutrophication, cadmium flow to farmland and use of phosphate rock. Use of digested food waste as fertilizer proved to have larger negative results than use of chemical fertilizer in all categories assessed except use of non-renewable phosphate rock. Sensitivity analyses showed that the scenarios were comparable in terms of primary energy use and better for GWP if some improvements in the anaerobic digestion system were made. However, acidification and eutrophication caused by digestate handling and the cadmium content of digestate should still be considered.
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33.
  • Johansson, Pernilla, et al. (author)
  • Examples of characteristics of wood that affect mould growth : a meta-analysis
  • 2017
  • In: European Journal of Wood and Wood Products. - : Springer Science and Business Media LLC. - 0018-3768 .- 1436-736X. ; 75:4, s. 603-613
  • Journal article (peer-reviewed)abstract
    • Building materials differ in their susceptibility to mould growth. Wood is a material often considered to have a low mould resistance. However, wood is not a homogenous material and different characteristics of the material are expected to have an impact on mould growth. In this paper, it was shown that wood species (pine or spruce), sawing pattern (centre-board or side-board) and surface structure (planed or sawn) affected mould growth. In addition, it was indicated that the susceptibility cannot be described by one single parameter, but also depends on other parameters. It is therefore difficult to estimate the susceptibility of wood in general. These conclusions were drawn from a meta-analysis, using data from five separate, previously performed laboratory studies conducted at 90% relative humidity and 22 °C, and from a laboratory study performed at 95% RH and 22 °C. © 2016 Springer-Verlag Berlin Heidelberg
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34.
  • Johansson, Pernilla, et al. (author)
  • Kvalitet hos byggnadsmaterial i cirkulära flöden
  • 2017
  • Reports (other academic/artistic)abstract
    • Denna rapport är en del av ett projekt med det övergripande målet att bygg- och rivningsavfall i högre utsträckning skall återvinnas eller återanvändas. Detta utan att kvaliteten på materialet, och därmed framtida byggnader, försämras.Syftet med projektet har varit att kartlägga och sammanställa de kunskaper och erfarenheter som finns kring de tekniska aspekterna vid cirkulära flöden av byggmaterial, med fokus på kvalitetsfrågor, att identifiera nya projekt som kan minska mängden bygg- och rivningsavfall som deponeras eller förbränns samt att skapa nya nätverk. Det finns spridd kunskap i byggbranschen om dessa frågor och dessutom finns en mängd forskningsresultat inom olika områden. I projektet har kunskaper och erfarenheter inom området samlats in genom litteraturstudier, workshops och seminarier, studiebesök och intervjuer.I första delen av rapporten diskuteras generella tekniska erfarenheter och utmaningar i olika delar av byggkedjan, medan utmaningar för specifika materialgrupper diskuteras i den andra delen av rapporten. Dessa materialgrupper är polymera material, planglas, stenull, glasull, gipsskivor, krossad betong samt trä och träbaserade material. I rapporten redovisas en enkätundersökning som genomförts av Optimera hos deras proffskunder, i syfte att samla in dessas erfarenheter och synpunkter kring hållbart byggande.Generellt kan vi konstatera att det finns stora utmaningar med att öka återvinningsgraden för rivnings- och ombyggnadsavfall. För installationsspill och byggavfall är de tekniska utmaningarna inte lika stora. Utmaningar och förutsättningar för ökad återvinning med bibehållen god kvalitet varierar mellan olika materialslag/produkter, typ av byggprojekt samt avsedd användning.I rapporten föreslås ett antal konkreta förslag på områden där arbetet kan drivas vidare. Dessa inkluderar bland annat förbättrad/utökad inventering inför rivning och ombyggnad, rutiner och metoder för provtagning, korrekt sortering, hantering och lagring för att få rätt och jämn kvalitet, ge möjlighet för separering av sammansatta material, logistikfrågor, produktionstekniska lösningar samt kvalitetssäkring. Resultaten visar också på vikten av utbildning, nätverk och mötesplatser samt att forskningsprojekt genomförs tvärvetenskapligt. Det finns goda möjligheter för ökad återvinning genom samarbete genom hela byggkedjan.
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35.
  • Johansson, Pernilla, et al. (author)
  • Missfärgade fasader på svenska flerbostadshus
  • 2017
  • Reports (other academic/artistic)abstract
    • The study contains a field study in which several facades of buildings were studied, as well as a survey where real estate managers have shared their experiences.On 28% of the total of 268 facades studied in the field study, discoloration was found to such an extent that it was judged to affect the aesthetic impression. Both mould fungi and algae could be identified in the samples taken on discoloured facades. Most of the facade materials studied consisted of rendering or sheet metal. On buildings with façade of sheet metal, the north side was more susceptible to discoloration than other parts of the buildings. No impact on the point of the compass could be observed on buildings with other facade materials. No regional difference in the extent of discoloration could be found in the study. The survey confirms these observations.The survey shows that many property managers consider that discolouration generally constitutes a problem in their property portfolio, due to costs for maintenance or cleaning, complaints from residents or a reduced general impression of the property portfolio. Although some managers did not consider it to be a general problem, some specific façade types in the property stock may be discoloured and cause problems. Most property managers considered that a façade should not receive an unacceptable discoloration until after at least 10 years. Their experience was that several buildings received such growth already within 10 years after construction of the building.Respondents of the survey were asked to evaluate discolouration of some example facades, by looking at pictures. It was found that the extent of a discolouration to be regarded as unacceptable varies between different people and different types of buildings. In the survey, real estate owners' experiences of different remediation methods of discoloured facades were surveyed, and it was found that the experiences differ. The property managers believe that a cleaned facade should last at least 5 years before the extent of discoloration becomes unacceptable.Results from the study will be used as questions and hypotheses in future studies, e.g. to investigate the effectiveness of remediation agents and to develop tools and guidelines for preventing new discoloration.
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36.
  • Johansson, Pernilla, et al. (author)
  • Missfärgning av byggnaders fasader : En kunskapsöversikt
  • 2015
  • Reports (other academic/artistic)abstract
    • Discolouration of building facades. A knowledge surveyMicroorganisms that grow on facades can cause extensive discoloration, which often poses a problem for home owners as it can provide an aesthetically unfavourable impression of the building. Fouling occurs as a result of a complex process that involves several parameters, including biological factors, climatic factors and factors related to the building. This report describes and discusses these factors and their implications for the incidence of fouling, based on scientifically published research. One chapter of the report deals with cleaning and maintenance of facades. Based on the knowledge available in the literature suggestions are given for further research that can contribute to decreased problems with discoloured facades. Finally, the report provides references to a number of scientific articles categorized by keywords in order to make it easier for those who want to read more on the topic.
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37.
  • Johansson-Pajala, Rose-Marie (author)
  • Pharmacovigilance in municipal elderly care : From a nursing perspective
  • 2017
  • Doctoral thesis (other academic/artistic)abstract
    • Medication management constitutes a large part of registered nurses' (RNs) daily work in municipal elderly care. They are responsible for monitoring multimorbid older persons with extensive treatments, and they often work alone, without daily access to physicians. RNs’ drug monitoring is, in this thesis, based on the concept of pharmacovigilance. Pharmacovigilance is about the science and the activities that aim to improve patient care and safety in drug use, that is, to detect, assess, understand and prevent drug-related problems.The overall aim was to explore conditions for pharmacovigilance from a nursing perspective, focusing on implications of RNs’ competence and use of a computerized decision support system (CDSS). Both quantitative and qualitative research methods were used, including a questionnaire (I), focus group discussions (II), individual interviews (III) and an intervention study (IV). In total 216 RNs and 54 older persons participated from 13 special accommodations, located in three different regions.RNs who had completed further training in pharmacovigilance rated their medication competence higher than those who had not. However, there was no difference between groups in the number of pharmacovigilant activities they performed in clinical practice (I). The RNs appeared to act as “vigilant intermediaries” in drug treatment. They depended on the nursing staff's observations of drug-related problems. The RNs continuously controlled the work of staff and physicians, and attempted to compensate for shortcomings in competence, accessibility and continuity (II). RNs’ use of a CDSS was found to affect drug monitoring, including aspects of time, responsibility, standardization of the work, as well as access to knowledge and opportunities for evidence-based care (III). The CDSS detected significantly more drug-related problems when conducting medication reviews, than the RNs did. Nevertheless, this did not result in any significant improvement in the quality of drug use in the follow up, three and six months later (IV).This thesis contributes to the recognition of pharmacovigilance from a nursing perspective. Increased medication competence seems to be insufficient to generate pharmacovigilant activities. RNs depend on other health care professionals and organizational conditions in order to perform their work. A CDSS has the potential to support RNs, both in structured medication reviews and in daily clinical practice. Inter-professional collaboration is crucial, with or without a CDSS, and the entire team needs to be aware of and take responsibility. Other important conditions is the existence of well-functioning communication channels, competence across the team, and established procedures based on current guidelines.
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38.
  • Kallberg, Pernilla, 1971- (author)
  • Två lärarkategoriers arbete med sociala relationer i övergången från förskoleklass till årskurs 1
  • 2018
  • Doctoral thesis (other academic/artistic)abstract
    • Denna studie undersöker två lärarkategoriers, i studien benämnda som förskoleklass-lärare och grundskol-lärares, allmändidaktiska arbete med sociala relationer i övergången mellan förskoleklass och årskurs 1. Detta är ett relationellt arbete som sker över tid och handlar om att samordna vuxnas och barns handlingar och uppfattningar i en utbildningsmiljö. Samordnandet syftar till att möjliggöra en undervisningsmiljö och utgör i övergången en viktig del av hur barn upplever sammanhang och mening. Med utgångspunkt i ett deltagande i de två lärarkategoriernas pedagogiska praktiker syftar studien till att få en fördjupad förståelse av den mening lärare i förskoleklass respektive grundskolans år 1 ger sitt didaktiska arbete med sociala relationer i övergången. Med en tolkande ansats och med hjälp av begrepp, inspirerade av teorin om professionella representationer, fördjupas förståelsen av lärares handlingar som uttryck för den mening som ges arbetet.Den mening lärare ger sitt arbete med sociala relationer handlar övergripande om att underlätta för barn och vuxna att möta skilda kulturella och sociala undervisningssammanhang. I resultatet framkommer att lärares arbete med sociala relationer ges en något skild framtoning i respektive skolform. Förskoleklassen beskrivs som en mer socialt inriktad praktik där grupprocesser och normer blir ett tydligt undervisningsinnehåll till skillnad mot årskurs 1 där sociala relationer succesivt sammantvinnas med hela undervisningssammanhanget, främst i form av klassrumsregler. I lärares handlingar framträder hur normer och värden, relationer och samverkan tillsammans med strukturer och organisation utgör delar av lärares arbete med sociala relationer. Det är ett arbete som till stor del är erfarenhetsbaserad. Analyserna visar hur de två lärarkategoriernas handlingar tar form och ges mening utifrån gränsdragande processer som klargör skillnaderna mellan de båda utbildningspraktikerna förskoleklass och årskurs 1. Samverkan mellan förskoleklass och årskurs 1 bidrar till ett upprätthållande av skillnader i synen på barn, verksamheternas innehåll och hur respektive yrkesroll gestaltas. Mening för arbetet med sociala relationer ges därmed olika innebörd för olika lärarkategorier.Studien bidrar till att belysa hur lärares målmedvetna handlingar för att skapa en fungerande undervisningsmiljö i övergången blir särskilt värdefulla ur utbildningssynpunkt, i form av uppmärksammade socialisationsprocesser.
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39.
  • Kjellsdotter Ivert, Linea, et al. (author)
  • Effektivitet i insamlingen av byggavfall
  • 2019
  • In: PLAN's Forsknings- och Utvecklingskonferens 2019.
  • Conference paper (peer-reviewed)abstract
    • Syftet med denna artikel är att öka kunskapen om vad en ökad sorteringsgrad av byggavfall får för konsekvenser på fyllnadsgrader vid transporter och insamlingskostnader. Denna kunskap är av stor vikt för att kunna effektivisera insamlingen av bygg- och rivningsavfall, dvs sortering, lagring och transporter. Endast hälften av det 9,8 miljoner ton bygg- och rivningsavfall som genereras årligen återvinns idag och tidigare studier visar att det finns förbättringspotential avseende ökade fyllnadsgrader och samordning av transporter. I artikeln har vi för 22 byggprojekt räknat fram sorteringsgrader i termer av andel utsorterat material från materialkategorierna brännbara material, inerta material, och metaller, samt beräknat logistikeffektivitet i termer av fyllnadsgrad i de fordon som används för att transportera avfall från byggarbetsplats till förbehandlingsanläggningen. Andel utsorterat material och fyllnadsgrader har satts i relation till insamlingskostnader, det vill säga lagrings- och hanteringskostnader, transportkostnader och behandlingskostnader.   Resultat visar att det finns en stor förbättringspotential avseende sorteringsgrader och fyllnadsgrader i projekten. Sorteringsgrader för samtliga projekt ligger i medeltal på 52 % för brännbara material, 52 % för inerta material och 3% för metaller. Fyllnadsgrader i projekten i materialkategorierna blandat avfall för eftersortering, brännbara material, sorterade brännbara material, inerta material, sorterade inerta material, metaller samt sorterade metaller ligger mellan 24 % och 48 %. Intressant att notera är att fyllnadsgraden för de sorterade materialen i snitt är högre än för de blandade fraktionerna. Gällande förhållandet mellan sorteringsgrad och fyllnadsgrad så finns inget samband för de projekt som studerats. Byggföretaget har sparat drygt tre miljoner kronor i behandlingskostnader genom att sortera på det sätt man gör i jämförelse med att inte sortera alls. Dock tillkommer lagrings- och hanteringskostnader samt eventuella transportkostnader som kan öka eller minska besparingen något. Huruvida man tjänar på källsortering eller inte är beroende på vilket material det handlar om. Om man endast tittar på behandlingskostnaderna så har man sparat mer på att sortera brännbara material än inerta material. Rekommendationen är att lägga fokus på att sortera ut material med låga behandlingskostnader relativt behandlingskostnaden för blandat material. Det finns även kostnadsbesparingar att göra genom att ta fram smarta sätt att sortera ut skrymmande delar av blandade material till icke skrymmande sorterade material.
  •  
40.
  • Lif Holgerson, Pernilla, et al. (author)
  • Maturation of oral microbiota in children with or without dental caries
  • 2015
  • In: PLOS ONE. - : Public Library Science. - 1932-6203. ; 10:5
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: The aim of this longitudinal study was to evaluate the oral microbiota in children from age 3 months to 3 years, and to determine the association of the presence of caries at 3 years of age.METHODS AND FINDINGS: Oral biofilms and saliva were sampled from children at 3 months (n = 207) and 3 years (n = 155) of age, and dental caries was scored at 3 years of age. Oral microbiota was assessed by culturing of total lactobacilli and mutans streptococci, PCR detection of Streptococcus mutans and Streptococcus sobrinus, 454 pyrosequencing and HOMIM (Human Oral Microbe Identification Microarray) microarray detection of more then 300 species/ phylotypes. Species richness and taxa diversity significantly increased from 3 months to 3 years. Three bacterial genera, present in all the 3-month-old infants, persisted at 3 years of age, whereas three other genera had disappeared by this age. A large number of new taxa were also observed in the 3-year-olds. The microbiota at 3 months of age, except for lactobacilli, was unrelated to caries development at a later age. In contrast, several taxa in the oral biofilms of the 3-year-olds were linked with the presence or absence of caries. The main species/phylotypes associated with caries in 3-year-olds belonged to the Actinobaculum, Atopobium, Aggregatibacter, and Streptococcus genera, whereas those influencing the absence of caries belonged to the Actinomyces, Bergeyella, Campylobacter, Granulicatella, Kingella, Leptotrichia, and Streptococcus genera.CONCLUSIONS: Thus, during the first years of life, species richness and taxa diversity in the mouth increase significantly. Besides the more prevalent colonization of lactobacilli, the composition of the overall microbiota at 3 months of age was unrelated to caries development at a later age. Several taxa within the oral biofilms of the 3-year-olds could be linked to the presence or absence of caries.
  •  
41.
  • Margolskee, Alison, et al. (author)
  • IMI - Oral biopharmaceutics tools project - Evaluation of bottom-up PBPK prediction success part 2 : An introduction to the simulation exercise and overview of results
  • 2017
  • In: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 96, s. 610-625
  • Journal article (peer-reviewed)abstract
    • Orally administered drugs are subject to a number of barriers impacting bioavailability (F-oral), causing challenges during drug and formulation development. Physiologically-based pharmacokinetic (PBPK) modelling can help during drug and formulation development by providing quantitative predictions through a systems approach. The performance of three available PBPK software packages (GI-Sim, Simcyp (R), and GastroPlus (TM)) were evaluated by comparing simulated and observed pharmacokinetic (PK) parameters. Since the availability of input parameters was heterogeneous and highly variable, caution is required when interpreting the results of this exercise. Additionally, this prospective simulation exercise may not be representative of prospective modelling in industry, as API information was limited to sparse details. 43 active pharmaceutical ingredients (APIs) from the OrBiTo database were selected for the exercise. Over 4000 simulation output files were generated, representing over 2550 study arm-institution-software combinations and approximately 600 human clinical study arms simulated with overlap. 84% of the simulated study arms represented administration of immediate release formulations, 11% prolonged or delayed release, and 5% intravenous (i.v.). Higher percentages of i.v. predicted area under the curve (AUC) were within two-fold of observed (52.9%) compared to per oral (p.o.) (37.2%), however, F-oral and relative AUC (F-rel) between p.o. formulations and solutions were generally well predicted (64.7% and 75.0%). Predictive performance declined progressing from i.v. to solution and immediate release tablet, indicating the compounding error with each layer of complexity. Overall performance was comparable to previous large-scale evaluations. A general overprediction of AUC was observed with average fold error (AFE) of 1.56 over all simulations. AFE ranged from 0.0361 to 64.0 across the 43 APIs, with 25 showing overpredictions. Discrepancies between software packages were observed for a few APIs, the largest being 606, 171, and 81.7-fold differences in AFE between SimCYP and GI-Sim, however average performance was relatively consistent across the three software platforms.
  •  
42.
  • Romani Vestman, Nelly, 1978-, et al. (author)
  • Oral Microbiota Shift after 12-Week Supplementation with Lactobacillus reuteri DSM 17938 and PTA 5289 : A Randomized Control Trial
  • 2015
  • In: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 10:5
  • Journal article (peer-reviewed)abstract
    • Background: Lactobacillus spp. potentially contribute to health by modulating bacterial biofilm formation, but their effects on the overall oral microbiota remain unclear.Methods and Findings: Oral microbiota was characterized via 454-pyrosequencing of the 16S rDNA hypervariable region V3-V4 after 12 weeks of daily Lactobacillus reuteri DSM 17938 and PTA 5289 consumption. Forty-four adults were assigned to a test group (n = 22) that received lactobacilli lozenges (108 CFU of each strain/lozenge) or a control group that received placebo (n = 22). Presence of L. reuteri was confirmed by cultivation and species specific PCR. Tooth biofilm samples from 16 adults before, during, and after exposure were analyzed by pyrosequencing. A total of 1,310,292 sequences were quality filtered. After removing single reads, 257 species or phylotypes were identified at 98.5% identity in the Human Oral Microbiome Database. Firmicutes, Bacteroidetes, Fusobacteria, Proteobacteria, and Actinobacteria were the most abundant phyla. Streptococcus was the most common genus and the S. oralis/S. mitis/S. mitis bv2/S. infantis group comprised the dominant species. The number of observed species was unaffected by L. reuteri exposure. However, subjects who had consumed L. reuteri were clustered in a principal coordinates analysis relative to scattering at baseline, and multivariate modeling of pyrosequencing microbiota, and culture and PCR detected L. reuteri separated baseline from 12-week samples in test subjects. L. reuteri intake correlated with increased S. oralis/S. mitis/S. mitis bv2/S. infantis group and Campylobacter concisus, Granulicatella adiacens, Bergeyella sp. HOT322, Neisseria subflava, and SR1 [G-1] sp. HOT874 detection and reduced S. mutans, S. anginosus, N. mucosa, Fusobacterium periodicum, F. nucleatum ss vincentii, and Prevotella maculosa detection. This effect had disappeared 1 month after exposure was terminated.Conclusions: L. reuteri consumption did not affect species richness but induced a shift in the oral microbiota composition. The biological relevance of this remains to be elucidated.Trial Registration: ClinicalTrials.gov NCT02311218
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43.
  • Shungin, Dmitry, et al. (author)
  • Using genetics to test the causal relationship of total adiposity and periodontitis : Mendelian randomization analyses in the Gene-Lifestyle Interactions and Dental Endpoints (GLIDE) Consortium
  • 2015
  • In: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 44:2, s. 638-650
  • Journal article (peer-reviewed)abstract
    • Background: The observational relationship between obesity and periodontitis is widely known, yet causal evidence is lacking. Our objective was to investigate causal associations between periodontitis and body mass index (BMI). Methods: We performed Mendelian randomization analyses with BMI-associated loci combined in a genetic risk score (GRS) as the instrument for BMI. All analyses were conducted within the Gene-Lifestyle Interactions and Dental Endpoints (GLIDE) Consortium in 13 studies from Europe and the USA, including 49 066 participants with clinically assessed (seven studies, 42.1% of participants) and self-reported (six studies, 57.9% of participants) periodontitis and genotype data (17 672/31 394 with/without periodontitis); 68 761 participants with BMI and genotype data; and 57 871 participants (18 881/38 990 with/without periodontitis) with data on BMI and periodontitis. Results: In the observational meta-analysis of all participants, the pooled crude observational odds ratio (OR) for periodontitis was 1.13 [95% confidence interval (CI): 1.03, 1.24] per standard deviation increase of BMI. Controlling for potential confounders attenuated this estimate (OR = 1.08; 95% CI: 1.03, 1.12). For clinically assessed periodontitis, corresponding ORs were 1.25 (95% CI: 1.10, 1.42) and 1.13 (95% CI: 1.10, 1.17), respectively. In the genetic association meta-analysis, the OR for periodontitis was 1.01 (95% CI: 0.99, 1.03) per GRS unit (per one effect allele) in all participants and 1.00 (95% CI: 0.97, 1.03) in participants with clinically assessed periodontitis. The instrumental variable meta-analysis of all participants yielded an OR of 1.05 (95% CI: 0.80, 1.38) per BMI standard deviation, and 0.90 (95% CI: 0.56, 1.46) in participants with clinical data. Conclusions: Our study does not support total adiposity as a causal risk factor for periodontitis, as the point estimate is very close to the null in the causal inference analysis, with wide confidence intervals.
  •  
44.
  • Steimberger, Cerafino, et al. (author)
  • Wear Analysis of PM Compacts with Bainitic Microstructures, Under Unlubricated Sliding Conditions
  • 2015
  • In: Procedia Materials Science. - : Elsevier BV. - 2211-8128. ; 9, s. 578-589
  • Journal article (peer-reviewed)abstract
    • Ferrous and non-ferrous alloys can be processed by PM. Complex shapes and good surface finishes can be achieved, leading to promising applications, if mechanical properties are demonstrated to be high enough. At the same time, both bainitic and carbide free bainitic microstructures have proved to be excellent candidates for wear applications. Therefore, the aims of this project were steered towards analysing wear behaviour of PM compacts, in relation to their bainitic microstructures.Three materials were employed and two conditions were taken into account: materials before and after austempering. A reference material was considered, corresponding to Distaloy DC with Mo and Ni. Microstructure was analysed in all the cases by means of optical and scanning electron microscope and it was related to the behaviour observed. Pin on plate reciprocating sliding test without lubricant was utilised in order to measure friction coefficient and specific wear rate in the pins. Effects of alloying elements were also examined.It was found that austempering decreased impact resistance, but enhanced hardness in Distaloy DC. In contrast, the other two materials presented the opposite behaviour. However, the presence of additional alloying elements in the initial composition fulfilled to increase wear resistance, compared to the reference material. A possible interaction between pores and oxides that may influence wear behaviour was observed. Si allowed carbide free bainitic microstructure to form but heterogeneity could not be prevented. Therefore, the advantage of this microstructure could not be fully used. Results obtained in the present work can lead to new wear applications for PM products, containing bainitic microstructures.
  •  
45.
  • Strell, Carina, et al. (author)
  • Impact of Epithelial-Stromal Interactions on Peritumoral Fibroblasts in Ductal Carcinoma in Situ
  • 2019
  • In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 111:9, s. 983-995
  • Journal article (peer-reviewed)abstract
    • Background: A better definition of biomarkers and biological processes related to local recurrence and disease progression is highly warranted for ductal breast carcinoma in situ (DCIS). Stromal-epithelial interactions are likely of major importance for the biological, clinical, and pathological distinctions between high- and low-risk DCIS cases. Methods: Stromal platelet derived growth factor receptor (PDGFR) was immunohistochemically assessed in two DCIS patient cohorts (n = 458 and n = 80). Cox proportional hazards models were used to calculate the hazard ratios of recurrence. The molecular mechanisms regulating stromal PDGFR expression were investigated in experimental in vitro co-culture systems of DCIS cells and fibroblasts and analyzed using immunoblot and quantitative real-time PCR. Knock-out of JAG1 in DCIS cells and NOTCH2 in fibroblasts was obtained through CRISPR/Cas9. Experimental data were validated by mammary fat pad injection of DCIS and DCIS-JAG1 knock-out cells (10 mice per group). All statistical tests were two-sided. Results: PDGFR alpha((low))/PDGFR beta((high)) fibroblasts were associated with increased risk for recurrence in DCIS (univariate hazard ratio = 1.59, 95% confidence interval [CI] = 1.02 to 2.46; P = .04 Wald test; multivariable hazard ratio = 1.78, 95% CI = 1.07 to 2.97; P = .03). Tissue culture and mouse model studies indicated that this fibroblast phenotype is induced by DCIS cells in a cell contact-dependent manner. Epithelial Jagged1 and fibroblast Notch2 were identified through loss-of-function studies as key juxtacrine signaling components driving the formation of the poor prognosis-associated fibroblast phenotype. Conclusions: A PDGFR alpha((low))/PDGFR beta((high)) fibroblast subset was identified as a marker for high-risk DCIS. The Jagged-1/Notch2/PDGFR stroma-epithelial pathway was described as a novel signaling mechanism regulating this poor prognosis-associated fibroblast subset. In general terms, the study highlights epithelial-stromal crosstalk in DCIS and contributes to ongoing efforts to define clinically relevant fibroblast subsets and their etiology.
  •  
46.
  • Timby, Niklas, et al. (author)
  • Oral Microbiota in Infants Fed a Formula Supplemented with Bovine Milk Fat Globule Membranes : A Randomized Controlled Trial
  • 2017
  • In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:1
  • Journal article (peer-reviewed)abstract
    • Background In a recent study, supplementation of infant formula with milk fat globule membranes (MFGM) decreased the incidence of otitis media in infants <6 months of age. Objectives The aim of the present study was to characterize the oral microbiota in infants fed MFGM-supplemented formula and compare it to that of infants fed standard formula or breast milk.Methods In a prospective double-blinded randomized controlled trial, exclusively formula-fed infants <2 months of age were randomized to be fed experimental formula (EF, n = 80) with reduced energy and protein and supplemented with a bovine MFGM concentrate, or standard formula (SF, n = 80) until 6 months of age. A breast-fed reference (BFR, n = 80) group was also recruited. The oral microbiota was analyzed at 4 (n = 124) and 12 (n = 166) months of age using Illumina MiSeq multiplex sequencing and taxonomic resolution against the HOMD 16S rDNA database of oral bacteria.Results Species richness in the oral samples did not differ between the EF and SF groups, but partial least square modeling identified a few taxa that were significantly associated with being in either group, e.g. lower level of Moraxella catarrhalis in the EF group. Infants in the BFR group had significantly lower species richness at 4 months of age and their microbiota pattern differed markedly from the formula-fed groups.Conclusions Supplementation of infant formula with MFGM yielded moderate effects on the oral micro biome. Moraxella catarrhalis was less prevalent in infants fed EF than in those fed SF and may be associated with the decrease in otitis media seen in the same group.
  •  
47.
  • Tjänstelogik i välfärden : En modell för samskapande mellan professionella med barnet i fokus
  • 2019
  • Editorial collection (other academic/artistic)abstract
    • Denna bok handlar om hur välfärdsorganisationer kan samskapa värde tillsammans med den som de är till för. Boken belyser betydelsen av att förstå olika verksamheters perspektiv – socialtjänsten, barn- och ungdomspsykiatrin och skolan – genom yrkesgruppernas egna röster för att effektivt kunna ta tillvara varandras kompetenser. I boken föreslås en modell för samskapande i välfärdstjänster som bygger på ett tjänsteperspektiv, ibland kallat tjänstelogik.Boken vänder sig till studenter vid lärarutbildningar, socionomutbildningar och beteendevetenskapliga utbildningar samt inom området hälsa.
  •  
48.
  • Winsö, Ola, et al. (author)
  • Thoracic epidural anaesthesia reduces insulin resistance and inflammatory response in experimental acute pancreatitis
  • 2018
  • In: Upsala Journal of Medical Sciences. - Abingdon : Taylor & Francis. - 0300-9734 .- 2000-1967. ; 123:4, s. 207-215
  • Journal article (peer-reviewed)abstract
    • AIMS: The activity of the sympathetic nervous system (SNS) is crucial at an early stage in the development of an inflammatory reaction. A study of metabolic events globally and locally in the early phase of acute pancreatitis (AP), implying hampered SNS activity, is lacking. We hypothesized that thoracic epidural anaesthesia (TEA) modulates the inflammatory response and alleviates the severity of AP in pigs.MATERIAL AND METHODS: The taurocholate (TC) group (n = 8) had only TC AP. The TC + TEA group (n = 8) had AP and TEA. A control group (n = 8) underwent all the preparations, without having AP or TEA. Metabolic changes in the pancreas were evaluated by microdialysis and by histopathological examination.RESULTS: The relative increase in serum lipase concentrations was more pronounced in the TC group than in TC + TEA and control groups. A decrease in relative tissue oxygen tension (PtiO2) levels occurred one hour later in the TC + TEA group than in the TC group. The maintenance of normoglycaemia in the TC group required a higher glucose infusion rate than in the TC + TEA group. The relative decrease in serum insulin concentrations was most pronounced in the TC + TEA group.CONCLUSION: TEA attenuates the development of AP, as indicated by changes observed in haemodynamic parameters and by the easier maintenance of glucose homeostasis. Further, TEA was associated with attenuated insulin resistance and fewer local pathophysiological events.
  •  
49.
  • Wiseman, J., et al. (author)
  • Generation of a functional humanized Delta-like ligand 4 transgenic mouse model
  • 2017
  • In: Transgenic Research. - : Springer Science and Business Media LLC. - 0962-8819 .- 1573-9368. ; 26:6, s. 791-798
  • Journal article (peer-reviewed)abstract
    • Humanized mouse models are important tools in many areas of biological drug development including, within oncology research, the development of antagonistic antibodies that have the potential to block tumor growth by controlling vascularization and are key to the generation of in vivo proof-of-concept efficacy data. However, due to cross reactivity between human antibodies and mouse target such studies regularly require mouse models expressing only the human version of the target molecule. Such humanized knock-in/knock-out, KIKO, models are dependent upon the generation of homozygous mice expressing only the human molecule, compensating for loss of the mouse form. However, KIKO strategies can fail to generate homozygous mice, even though the human form is expressed and the endogenous mouse locus is correctly targeted. A typical strategy for generating KIKO mice is by ATG fusion where the human cDNA is inserted downstream of the endogenous mouse promoter elements. However, when adopting this strategy it is possible that the mouse promoter fails to express the human form in a manner compensating for loss of the mouse form or alternatively the human protein is incompatible in the context of the mouse pathway being investigated. So to understand more around the biology of KIKO models, and to overcome our failure with a number of ATG fusion strategies, we developed a range of humanized models focused on Delta-like 4 (Dll4), a target where we initially failed to generate a humanized model. By adopting a broader biologic strategy, we successfully generated a humanized DLL4 KIKO which led to a greater understanding of critical biological aspects for consideration when developing humanized models.
  •  
50.
  • ÅKESSON, OSCAR, et al. (author)
  • Surface microdialysis on small bowel serosa in monitoring of ischemia
  • 2016
  • In: Journal of Surgical Research. - : Elsevier BV. - 0022-4804 .- 1095-8673. ; 204:1, s. 39-46
  • Journal article (peer-reviewed)abstract
    • Background: Ischemic injury of an organ causes metabolic change from aerobic to anaerobic metabolism. It has been shown in experimental studies on the heart and liver that such conversion may be detected by conventional microdialysis probes placed intraparenchymatously, as well as on organ surfaces, by assaying lactate, pyruvate, glucose, and glycerol in dialysate. We developed a microdialysis probe (S-mu D) intended for use solely on organ surfaces. The aim of this study was to assess whether the newly developed S-mu D probe could be used for detection and monitoring of small bowel ischemia. Methods: In anesthetized normoventilated pigs, a control S-mu D probe was applied on the jejunal serosa 50 cm downstream from the duodenojejunal junction (DJJ). Starting 100 cm from DJJ, a 100-cm long ischemic segment was created by division of all mesenteric vessels. S-mu Ds were applied at 2.5, 5, 20, and 50 cm from the starting point of ischemia by serosal sutures. A standard mu D probe was placed in the abdominal cavity as a further control. Dialysate was harvested before inducing ischemia and subsequently every 20 min for 4 h. Central venous blood was drawn every hour to monitor systemic lactate, C-reactive protein, and white blood cell count. Results: Microdialysis lactate levels were significantly higher than baseline from 20 min on into protocol time in the ischemic segment and in the control S-mu D probe. The peritoneal cavity probe showed no significant elevation. Lactate levels from the ischemic segment reached a plateau at 60 min. Courses of pyruvate, glucose, and glycerol levels were in accordance with transition from an aerobic to anaerobic metabolism in the bowel wall. No statistically significant changes in hemoglobin, white blood cell count, or lactate values in central venous blood were recorded. Conclusions: Assaying the aforementioned compounds in dialysate, harvested by the newly developed S-mu D probe, allowed detection and monitoring of small bowel ischemia from 20 min on following its onset.
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