| 1. |
- Lundgren, Markus, et al.
(författare)
-
Analgesic antipyretic use among young children in the TEDDY study : No association with islet autoimmunity
- 2017
-
Ingår i: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 17:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The use of analgesic antipyretics (ANAP) in children have long been a matter of controversy. Data on their practical use on an individual level has, however, been scarce. There are indications of possible effects on glucose homeostasis and immune function related to the use of ANAP. The aim of this study was to analyze patterns of analgesic antipyretic use across the clinical centers of The Environmental Determinants of Diabetes in the Young (TEDDY) prospective cohort study and test if ANAP use was a risk factor for islet autoimmunity. Methods: Data were collected for 8542 children in the first 2.5 years of life. Incidence was analyzed using logistic regression with country and first child status as independent variables. Holm's procedure was used to adjust for multiplicity of intercountry comparisons. Time to autoantibody seroconversion was analyzed using a Cox proportional hazards model with cumulative analgesic use as primary time dependent covariate of interest. For each categorization, a generalized estimating equation (GEE) approach was used. Results: Higher prevalence of ANAP use was found in the U.S. (95.7%) and Sweden (94.8%) compared to Finland (78.1%) and Germany (80.2%). First-born children were more commonly given acetaminophen (OR 1.26; 95% CI 1.07, 1.49; p = 0.007) but less commonly Non-Steroidal Anti-inflammatory Drugs (NSAID) (OR 0.86; 95% CI 0.78, 0.95; p = 0.002). Acetaminophen and NSAID use in the absence of fever and infection was more prevalent in the U.S. (40.4%; 26.3% of doses) compared to Sweden, Finland and Germany (p < 0.001). Acetaminophen or NSAID use before age 2.5 years did not predict development of islet autoimmunity by age 6 years (HR 1.02, 95% CI 0.99-1.09; p = 0.27). In a sub-analysis, acetaminophen use in children with fever weakly predicted development of islet autoimmunity by age 3 years (HR 1.05; 95% CI 1.01-1.09; p = 0.024). Conclusions: ANAP use in young children is not a risk factor for seroconversion by age 6 years. Use of ANAP is widespread in young children, and significantly higher in the U.S. compared to other study sites, where use is common also in absence of fever and infection.
|
|
| 2. |
- Falck, Eva, et al.
(författare)
-
Loss of Glutathione peroxidase 3 expression is correlated with epigenetic mechanisms in endometrial adenocarcinoma
- 2010
-
Ingår i: Cancer Cell International. - : BioMed Central (BMC). - 1475-2867. ; 10
-
Tidskriftsartikel (refereegranskat)abstract
- Glutathione peroxidase 3 (GPX3) is one of the key enzymes in the cellular defense against oxidative stress and the hepatocyte growth factor receptor, (MET) has been suggested to be influenced by the GPX3 gene expression. In a previous microarray study performed by our group, Gpx3 was identified as a potential biomarker for rat endometrial adenocarcinoma (EAC), since the expression was highly downregulated in rat EAC tumors. Herein, we have investigated the mRNA expression and Gpx3 and Met in rat EAC by real time quantitative PCR (qPCR), and the methylation status of Gpx3. In addition we have examined the expression of GPX3 and MET in 30 human EACs of different FIGO grades and 20 benign endometrial tissues. We found that the expression of GPX3 was uniformly down regulated in both rat and human EAC, regardless of tumor grade or histopathological subtype, implying that the down-regulation is an early event in EAC. The rate of Gpx3 promoter methylation reaches 91%, where biallelic methylation was present in 90% of the methylated tumors. The expression of the Met oncogene was slightly upregulated in EACs that showed loss of expression of Gpx3, but no tumor suppressor activity of Gpx3/GPX3 was detected. Preliminary results also suggest that the production of H2O2 is higher in rat endometrial tumors with down-regulated Gpx3 expression. A likely consequence of loss of GPX3 protein function would be a higher amount of ROS in the cancer cell environment. Thus, the results suggest important clinical implications of the GPX3 expression in EAC, both as a molecular biomarker for EAC and as a potential target for therapeutic interventions.
|
|
| 3. |
- Nordlander, Carola, 1969, et al.
(författare)
-
Analysis of chromosome 10 aberrations in rat endometrial cancer-evidence for a tumor suppressor locus distal to Tp53.
- 2007
-
Ingår i: International journal of cancer. Journal international du cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 120:7, s. 1472-81
-
Tidskriftsartikel (refereegranskat)abstract
- We have recently shown in the BDII rat model of human endometrial adenocarcinoma (EAC), rat chromosome 10 (RNO10) is frequently involved in chromosomal aberrations. In the present study, we investigated the association between RNO10 deletions, allelic imbalance (AI) at RNO10q24 and Tp53 mutation in 27 rat EAC tumors. We detected chromosomal breakage accompanied by loss of proximal and/or gain of distal parts of RNO10 in approximately 2/3 of the tumors. This finding is suggestive of a tumor suppressor activity encoded from the proximal RNO10. Given the fact that Tp53 is located at RNO10q24-q25, we then performed Tp53 mutation analysis. However, we could not find a strong correlation between AI/deletions at RNO10q24 and Tp53 mutation. Instead, the observed patterns for AI, chromosomal breaks and deletions suggest that major selection was directed against a region located close to, but distal of Tp53. In different human malignancies a similar situation of AI at chromosome band 17p13.3 (HSA17p13.3) unassociated with TP53 mutation has been observed. Although RNO10 is largely homologous to HSA17, the conservation with respect to gene order among them is not extensive. We utilized publicly available draft DNA sequences to study intrachromosomal rearrangement during the divergence between HSA17 and RNO10. By using reciprocal comparison of rat and human genome data, we could substantially narrow down the candidate tumor suppressor region in rat from 3 Mb to a chromosomal segment of about 0.5 Mb in size. These results provide scientific groundwork for identification of the putative tumor suppressor gene(s) at 17p13.3 in human tumors.
|
|
| 4. |
|
|
| 5. |
- Pennbrant, Sandra, 1967-, et al.
(författare)
-
Unlicensed Personnel’s Experience of Digital Signing for Medication Administration in Municipal Healthcare
- 2020
-
Ingår i: Open Journal of Nursing. - Wuhan, Hubei Province, China : Scientific Research Publishing (SCIRP). - 2162-5336 .- 2162-5344. ; 10:12, s. 1163-1177
-
Tidskriftsartikel (refereegranskat)abstract
- Aim: To describe unlicensed personnel’s experience of digital signing lists via a smartphone application for the distribution of medication in municipal healthcare in Western Sweden. Design: A qualitative and quantitative design was used.Methods: The study included 48 unlicensed personnel, 28 of whom answered an open-ended questionnaire, while an additional 20 volunteered for individual interviews. The material was analysed by qualitative content analysis.Results: The results indicate that digital signing lists via a smartphone application are feasible, and efficient and facilitate the work. However, some aspects negatively affected the sense of security, meetings with patients and quality of care, such as an insufficient internet signal in some rural areas, difficulty remembering the password, as well as the change of focus from patient to smartphone. To improve quality of care and the meeting with the patient, it is crucial that the technology works and that unlicensed personnel develop technical skills.
|
|
| 6. |
- Sylvan, Sandra Eketorp, et al.
(författare)
-
First-line therapy in chronic lymphocytic leukemia : a Swedish nation-wide real-world study on 1053 consecutive patients treated between 2007 and 2013
- 2019
-
Ingår i: Haematologica. - : FERRATA STORTI FOUNDATION. - 0390-6078 .- 1592-8721. ; 104:4, s. 797-805
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate long-term outcome following first-line therapy in consecutive chronic lymphocytic leukemia (CLL) patients in a well-defined geographic area: Sweden. All patients diagnosed with CLL (2007-2013) (n=3672) were identified from national registries, screening of patient files identified all (100%) treated first line (n=1053) and for those, an in-depth analysis was performed. End points were overall response rate, progression-free survival (PFS), overall survival (OS), and safety. Median age was 71 years; 53% had Rai stage III-IV and 97% had performance status grade 0-2. Fluorescence in situ hybridization (FISH) was performed in 57% of patients: 15% had del(17p). Chlorambucil + prednisone was used in 39% (5% also received rituximab). Fludarabine+cyclophosphamide+rituximab or fludarabine+cyclophosphamide was used in 43% and bendamustine + rituximab in 6%. Overall response rate was 64%; chlorambucil 43%, fludarabine+cyclophosphamide+rituximab 84%, fludarabine+cyclophosphamide 75% and bendamustine + rituximab 75%. Median PFS and OS was 24 and 58 months, respectively, both were significantly associated (multivariate analysis) with type of treatment, del(17p), performance status, gender, age and geographical region (OS only). Chlorambucil-treated patients had a median PFS and OS of only 9 and 33 months, respectively. Chlorambucil usage declined gradually throughout the study period, but one-third of patients still received chlorambucil + rituximab in 2013. Infections >= grade III were significantly associated with treatment; chlorambucil 19% versus fludarabine+cyclophosphamide+rituximab 30%. Richter transformation occurred in 5.5% of the patients, equally distributed across therapies. This is the largest retrospective, real-world cohort of consecutive first-line treated CLL patients with a complete follow up. In elderly patients, an unmet need for more effective, well-tolerated therapies was identified.
|
|
| 7. |
|
|
| 8. |
- Allwood, Carl Martin, 1952, et al.
(författare)
-
Does consulting with others affect answerability judgments of difficult questions?
- 2016
-
Ingår i: Social Influence. - : Informa UK Limited. - 1553-4510 .- 1553-4529. ; 11:1, s. 40-53
-
Tidskriftsartikel (refereegranskat)abstract
- People's judgments of the answerability of questions relating to how things are in the world can have important consequences for society and people's lives. Thirty-one individuals and 30 pairs made answerability judgments of 20 general knowledge questions, many with less known, or unknown, answers. Four questions had high expected consensus regarding their answerability (consensus questions) and the rest had less expected consensus with respect to their answerability (non-consensus questions). The pairs showed two polarization effects: pairs gave higher answerability ratings for questions with answerability ratings over 80% and lower ratings than individuals for questions with the lower answerability ratings. Stronger consensus-seeking tendencies and a more active memory environment in the pairs may have contributed to these results.
|
|
| 9. |
- Andersson, Martin O., et al.
(författare)
-
Co-infection with Babesia divergens and Anaplasma phagocytophilum in cattle (Bos taurus), Sweden
- 2017
-
Ingår i: Ticks and Tick-borne Diseases. - : Elsevier. - 1877-959X .- 1877-9603. ; 8:6, s. 933-935
-
Tidskriftsartikel (refereegranskat)abstract
- Babesiosis is a severe disease in cattle worldwide. In Europe, the main causative agent of bovine babesiosis is Babesia divergens. In some areas, this species is reported to have declined or even disappeared, and its etiological role overtaken by other piroplasmid species. Moreover, co-infection with other tick-transmitted pathogens can be expected to complicate diagnosis in cattle. Hence, molecular identification of the causative agent of babesiosis should be a priority. Therefore, samples from 71 domestic cattle, 39 with clinical signs of babesiosis and 32 without, from southern Sweden were screened for Babesia spp. and Anaplasma spp. using molecular methods Babesia divergens was detected in 38 of the samples, and Anaplasma phagocytophilum in 17. Co-infections with both pathogens were frequent, occurring in 18% of the animals with a B. divergens infection. The possibility of co-infection should be considered in diagnosis and treatment of bovine babesiosis.
|
|
| 10. |
- Andersson, Marie, 1974-, et al.
(författare)
-
Transfer of developmental neurotoxin beta-N-methylamino-L-alanine (BMAA) via milk to nursed offspring : Studies by mass spectrometry and image analysis
- 2016
-
Ingår i: Toxicology Letters. - : Elsevier BV. - 0378-4274 .- 1879-3169. ; 258, s. 108-114
-
Tidskriftsartikel (refereegranskat)abstract
- The cyanobacterial non-proteinogenic amino acid beta-N-methylamino-L-alanine (BMAA) is proposed to be involved in the etiology of amyotrophic lateral sclerosis/parkinsonism dementia complex. When administered as single doses to neonatal rats, BMAA gives rise to cognitive and neurodegenerative impairments in the adult animal. Here, we employed mass spectrometry (LC-MS/MS) and autoradiographic imaging to examine the mother-to-pup transfer of BMAA in rats. The results show that unchanged BMAA was secreted into the milk and distributed to the suckling pups. The concentration of BMAA in pup stomach milk and the neonatal liver peaked after 8 h, while the concentration in the pup brain increased throughout the study period. About 1 and 6% of the BMAA recovered from adult liver and brain were released following hydrolysis, suggesting that this fraction was associated with protein. No association to milk protein was observed. Injection of rat pups with [methyl-C-14]-L-BMAA or [carboxyl-C-14]-L-BMAA resulted in highly similar distribution patterns, indicating no or low metabolic elimination of the methylamino- or carboxyl groups. In conclusion, BMAA is transported as a free amino acid to rat milk and suckling pups. The results strengthen the proposal that mothers' milk could be a source of exposure for BMAA in human infants. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
|
|
| 11. |
|
|
| 12. |
- Axberg Pålsson, Sandra, 1991-
(författare)
-
The role of non-coding single-stranded oligonucleotides on Respiratory syncytial virus infection
- 2022
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Respiratory syncytial virus (RSV) is an enveloped RNA virus of the Pneumoviridae family. RSV is reported to infect host cells by receptor-mediated endocytosis, also called clathrin-dependent endocytosis. Many reports indicate that the virus utilizes the host receptor nucleolin for entry. RSV is one of the leading causes of acute lower respiratory tract infection in children, the elderly and immunocompromised individuals. It is therefore important to find viable treatments against RSV infections. To this date, the development of an RSV vaccine has unfortunately been unsuccessful. Therefore, a lot of research is instead focusing on developing entry or replication inhibitors against RSV.We have previously discovered that a 35 bases long single-stranded oligonucleotide (ssON) can inhibit certain endocytic pathways, such as clathrin- and caveolin-dependent endocytosis. Based on this, the overall aim of the projects in this thesis is to investigate if ssON can work as an entry inhibitor against RSV and to study the overall effect that ssON has on RSV infection in vivo in a murine RSV challenge model. Furthermore, we aim to study the effect that proteins present in the surrounding extracellular environment of the virus have on the viral infectivity and pathogenesis.In Paper I we show that single-stranded oligonucleotides can inhibit RSV infection in vitro and in vivo. We demonstrate that ssON shields nucleolin in vitro. Nucleolin is a receptor involved in RSV entry and by shielding nucleolin present in the cell membrane, ssON prevents RSV from binding to the cells. Furthermore, we show that ssON inhibits RSV infection in vivo. ssON treatment of RSV infection was associated with enhanced expression of RSV-induced Interferon-stimulated genes (ISGs), suggesting that interferon responses likely contributed to reduced RSV infection. As a continuation to Paper I, in Paper II we investigate if small non-coding RNAs (sncRNAs) exhibit the same antiviral capacity as ssON. We demonstrate that sncRNAs, of similar size as ssON, can inhibit RSV infection in vitro and similarly to ssON, they bind to the entry co-receptor nucleolin. In Paper III we study the pathogenesis of RSV. We show that proteins from the extracellular environment of the virus can bind to the virus and affect the viral infectivity as well as the interaction of the virus with host cells. We determine that RSV accumulates a rich and distinctive protein corona in different biological fluids including human plasma (HP), human bronchoalveolar lavage fluid (BALF), non-human primate plasma (MP) and fetal bovine serum (FBS). We show that RSV incubated with BALF has an increased viral infectivity in epithelial HEp-2 and monocyte-derived dendritic cells (moDCs). Moreover, RSV surrounded by a BALF-derived corona induce the activation of moDCs as assessed by increased expression of co-stimulatory molecules.In summary, the projects in this thesis aim to assess the hypothesis that single-stranded oligonucleotides of DNA or RNA origin can be used to inhibit RSV infection. Furthermore, we aim to determine the effects, in terms of viral infectivity and pathogenesis, of the differential protein compositions present in biological fluids surrounding viruses.
|
|
| 13. |
- Backlund, Sandra, et al.
(författare)
-
A regional method for increased resource-efficiency in industrial energy systems
- 2014
-
Ingår i: eceee Industrial Summer Study Proceedings. - 9789198048254 - 9789198048247
-
Konferensbidrag (refereegranskat)abstract
- The impact of global climate change as a result of greenhouse gas emissions (GHG), primarily from the use of fossil fuels, is demanding actions from all sectors of society. The industry sector is one of the world’s largest energy using sectors and GHG emitters. Improved energy efficiency in industry is one of the foremost means of improving energy efficiency and reducing GHG emissions. Research shows that despite large untapped potentials for improved energy efficiency in industry, cost-efficient energy efficiency measures are not always implemented, explained by the existence of barriers to energy efficiency, e.g. information imperfections and asymmetries. Moreover, research shows that a major energy efficiency potential lies in the energy system and the way it is governed. For regional governments, the industrial energy use is difficult to affect as they only have indirect power to influence the decisions in those organizations. This underlies the importance of developing methods on how a region can support and effectively contribute to energy efficiency improvements in the local industry. So far, methods are limited related to regional governance of industrial energy systems. The aim of this paper is to present a structured methodology for improved regional resource efficiency in the local industry from a regional perspective, inspired by the Triple Helix Model. Results display the county administrative board of administration’s current method how to target industry, and ends with a proposal for how the methods could be improved.
|
|
| 14. |
- Bayati, Zahra, 1958, et al.
(författare)
-
Nytt centrum mot rasism får fel vetenskaplig inriktning
- 2015
-
Ingår i: Göteborgs Posten. - 1103-9345. ; :2015-06-14
-
Tidskriftsartikel (populärvet., debatt m.m.)abstract
- När rasism ska förstås som något som kan lösas genom att lära ut tolerans undergrävs förtroendet för regeringens satsning. Dessutom saknas det etnisk/rasifierad mångfald bland forskargruppen.
|
|
| 15. |
|
|
| 16. |
- Benazzi, Elisabetta, et al.
(författare)
-
Acid-triggering of light-induced charge-separation in hybrid organic/inorganic molecular photoactive dyads for harnessing solar energy
- 2021
-
Ingår i: Inorganic Chemistry Frontiers. - : Royal Society of Chemistry (RSC). - 2052-1553. ; 8:6, s. 1610-1618
-
Tidskriftsartikel (refereegranskat)abstract
- H+ modulated charge-transfer in photoexcited covalent polyoxometalate-bodipy conjugates is described. The hybrid organic/inorganic molecular photoactive dyads are based on Keggin-type polyoxometalates (POMs, where KM = [PM11O39] and M = Mo or W) covalently grafted via an organotin linker to a bodipy (BOD) photosensitizer. The relative potentials of the photosensitizer and POM are aligned such that light-induced electron transfer from BOD to POM is permitted for the polyoxomolybdate KMoSn[BOD] but not effective for the polyoxotungstate analogue KWSn[BOD]. In both cases, the addition of acid shifts the redox potential of the POM only, to increase the driving force for electron transfer. This leads to charge-separation being switched on for KWSn[BOD] in the presence of acid. The addition of acid to KMoSn[BOD] accelerates charge-separation by an order of magnitude (from 2 ns to 200 ps) and is accompanied by a deceleration of charge recombination, leading to a charge-separated state lifetime of up to 1.3 μs. This behaviour is consistent with proton coupled electron transfer, which has previously been observed electrochemically for POMs, but this study shows, for the first time, the impact of protonation on photoinduced electron transfer. This journal is
|
|
| 17. |
- Bergstrand, Martin, 1977-, et al.
(författare)
-
Semi-mechanistic PK/PD modeling of Paracetamol and Sulfapyridine to characterize pharmacological effects on gastric emptying and small intestinal transit.
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The paracetamol (PCM) and sulfapyridine (SP) double marker technique is based on combined gastric administration of PCM and sulfasalazine followed by plasma concentration measurements for PCM and SP. PCM is rapidly absorbed from the duodenum and can be regarded as a marker for gastric emptying (GE). Sulfasalazine is poorly absorbed from the small intestine but is extensively metabolized in the colon by bacteria into SP. As SP is only absorbed from the colon it serves as a marker for small intestinal transit time (SITT). The double marker method is used to identify and characterize effects on GE and SITT. The aim of the present investigation was to demonstrate how semi-mechanistic modeling of PCM and SP could facilitate characterization and the understanding of pharmacologically induced changes in GI transit under fed and fasting conditions. Two double marker validation studies were performed in dogs with erythromycin (1 mg/kg) and atropine (0.06 mg/kg), both of which have been described to affect GE and SITT. A semi-mechanistic nonlinear mixed-effects model was applied for simultaneous analysis of PCM and SP plasma concentrations. The model featured a compartment representing the stomach linked to a colon compartment via a series of four transit compartments representing the small intestine. Disposition of PCM and SP was described with standard 2- and 1-compartment models respectively. An essential part of the model was the inclusion of saturable first pass metabolism of PCM. This has been described before, but never taken into account when using PCM as a marker for GE. The effect of concomitant food intake on GE and SITT was found to be time dependent. Atropine and erythromycin were found to have time/concentration dependent effects on GE and SITT. As expected, erythromycin stimulated and atropine inhibited GE in the fasting state. Given the saturable first pass metabolism this resulted in almost twice as high bioavailability for PCM in erythromycin treated dogs (90%) as in atropine treated dogs (50%). Atropine treatment was primarily found to counteract the stimulatory effect of food intake on SITT, whereas erythromycin prolonged SITT under both fed and fasting conditions. Simultaneous modeling of PCM and SP was found to increase mechanistic understanding and result in plausible estimates of GE and SITT.
|
|
| 18. |
- Bestas, Burcu, et al.
(författare)
-
A Type II-B Cas9 nuclease with minimized off-targets and reduced chromosomal translocations in vivo
- 2023
-
Ingår i: NATURE COMMUNICATIONS. - 2041-1723. ; 14:1
-
Tidskriftsartikel (refereegranskat)abstract
- Streptococcus pyogenes Cas9 (SpCas9) and derived enzymes are widely used as genome editors, but their promiscuous nuclease activity often induces undesired mutations and chromosomal rearrangements. Several strategies for mapping off-target effects have emerged, but they suffer from limited sensitivity. To increase the detection sensitivity, we develop an off-target assessment workflow that uses Duplex Sequencing. The strategy increases sensitivity by one order of magnitude, identifying previously unknown SpCas9's off-target mutations in the humanized PCSK9 mouse model. To reduce off-target risks, we perform a bioinformatic search and identify a high-fidelity Cas9 variant of the II-B subfamily from Parasutterella secunda (PsCas9). PsCas9 shows improved specificity as compared to SpCas9 across multiple tested sites, both in vitro and in vivo, including the PCSK9 site. In the future, while PsCas9 will offer an alternative to SpCas9 for research and clinical use, the Duplex Sequencing workflow will enable a more sensitive assessment of Cas9 editing outcomes. SpCas9 unintended editing is a major concern. Here the authors report an off-target method using Duplex Sequencing with increased sensitivity for Cas9 mutation detection; they also identify a Cas9 variant of the II-B subfamily with intrinsic high fidelity (PsCas9) and see improved specificity.
|
|
| 19. |
- Bjerkne Wenneberg, Sandra, et al.
(författare)
-
Association between inflammatory response and outcome after subarachnoid haemorrhage.
- 2021
-
Ingår i: Acta neurologica Scandinavica. - : Hindawi Limited. - 1600-0404 .- 0001-6314. ; 143:2, s. 195-205
-
Tidskriftsartikel (refereegranskat)abstract
- Recent reports suggest an association between the inflammatory response after aneurysmal subarachnoid haemorrhage (aSAH) and patients' outcome. The primary aim of this study was to identify a potential association between the inflammatory response after aSAH and 1-year outcome. The secondary aim was to investigate whether the inflammatory response after aSAH could predict the development of delayed cerebral ischaemia (DCI).This prospective observational pilot study included patients with an aSAH admitted to Sahlgrenska University Hospital, Gothenburg, Sweden, between May 2015 and October 2016. The patients were stratified according to the extended Glasgow Outcome Scale (GOSE) as having an unfavourable (score: 1-4) or favourable outcome (score: 5-8). Furthermore, patients were stratified depending on development of DCI or not. Patient data and blood samples were collected and analysed at admission and after 10days.Elevated serum concentrations of inflammatory markers such as tumour necrosis factor-α and interleukin (IL)-6, IL-1Ra, C-reactive protein and intercellular adhesion molecule-1 were detected in patients with unfavourable outcome. When adjustments for Glasgow coma scale were made, only IL-1Ra remained significantly associated with poor outcome (p=0.012). The inflammatory response after aSAH was not predictive of the development of DCI.Elevated serum concentrations of inflammatory markers were associated with poor neurological outcome 1-year after aSAH. However, inflammatory markers are affected by many clinical events, and when adjustments were made, only IL-1Ra remained significantly associated with poor outcome. The robustness of these results needs to be tested in a larger trial.
|
|
| 20. |
|
|
| 21. |
- Brembeck, Helene, 1952, et al.
(författare)
-
Exploring Children’s foodscapes
- 2010
-
Ingår i: Proceedings from the 4th International Conference on Multidisciplinary Perspectives on Child and Teen Consumption. June 21-23 2010, Campus Norrköping, Sweden.
-
Konferensbidrag (refereegranskat)
|
|
| 22. |
- Brembeck, Helene, 1952, et al.
(författare)
-
Exploring children's foodscapes
- 2013
-
Ingår i: Children's Geographies. - : Informa UK Limited. - 1473-3285 .- 1473-3277. ; 11:1, s. 74-88
-
Tidskriftsartikel (refereegranskat)abstract
- In this article, we discuss children’s becoming as food consumers in the intersection of various foodscapes. We draw from a project, Children as co-researchers of foodscapes, where we have been working with children as co-researchers, using basically ethnographic methods, and as co-designers in a collaborative design effort. This article focuses on the findings from a theoretically inspired perspective, using the concept of foodscapes. These are food-related structures of different kinds, which evolve as the child explores them and where children as food consumers are generated. In this article, we highlight the scapes of taste, routines, people, things, commerce, child (as opposed to adult) and health and give brief accounts of the way the children related to them. Finally, we turn to the benefits of working with foodscapes for a better understanding of children’s becoming as food consumers in the intersection of various foodscapes. This article is based on data gathered by the children, but also on our fieldwork notes and observations following the children in their foodscapes.
|
|
| 23. |
- Broberg, Sarah, et al.
(författare)
-
Industrial excess heat deliveries to Swedish district heating networks : drop it like it's hot
- 2012
-
Ingår i: Energy Policy. - : Elsevier BV. - 0301-4215 .- 1873-6777. ; 51, s. 332-339
-
Tidskriftsartikel (refereegranskat)abstract
- Using industrial excess heat in District Heating (DH) networks reduces the need for primary energy and is considered efficient resource use. The conditions of Swedish DH markets are under political discussion in the Third Party Access (TPA) proposal, which would facilitate the delivery of firms' industrial excess heat to DH networks. This paper estimates and discusses the untapped potential for excess heat deliveries to DH networks and considers whether the realization of this potential would be affected by altered DH market conditions. The results identify untapped potential for industrial excess heat deliveries, and calculations based on estimated investment costs and revenues indicate that realizing the TPA proposal could enable profitable excess heat investments.
|
|
| 24. |
|
|
| 25. |
|
|
| 26. |
- Buratti, Sandra, 1983, et al.
(författare)
-
Who knows? Knowledge activation, belief in certainty of knowledge, maximization tendencies and need for cognition in answerability judgments.
- 2017
-
Ingår i: The Journal of general psychology. - : Informa UK Limited. - 0022-1309 .- 1940-0888. ; 144:1, s. 35-58
-
Tidskriftsartikel (refereegranskat)abstract
- In this study, investigating answerability judgments, 123 participants judged whether each of 46 general knowledge questions could currently be answered by themselves, by someone else, or by no one. There were 26 consensus questions (high expected consensus about their answerability) and 20 non-consensus questions. Before each question, half of the participants rated the extent of their knowledge related to the question. Results showed that answering consensus questions compared with non-consensus led to a lower proportion of “No one knows” answers. Moreover, in the knowledge rating condition compared with the control condition, participants choose " No one knows" proportionally less. Participants’ ratings of belief in certainty of knowledge were associated with more “Someone else knows” for the non-consensus questions. Moreover, tendency to maximization led to a higher proportion of “Someone else knows” options for the non-consensus questions. Finally, high need for cognition was associated with fewer choices of “Someone else knows.”
|
|
| 27. |
- Burden, Håkan, et al.
(författare)
-
Accelerating Acquisition in an Open Innovation Ecosystem
- 2019
-
Ingår i: Proc of Twenty-fifth Americas Conference on Information Systems.
-
Konferensbidrag (refereegranskat)abstract
- Maritime transports are to be regarded as a self-organized ecosystem (Kay et al., 1999) characterized by sub-optimization where historically each actor to has optimized its own operations, often giving rise to inefficiencies as a whole. In recent years however, digital transformation has challenged this by providing means for enhanced transparency in data sharing and situational awareness, enabling better coordination and improved efficiency on the whole (Lind et al. 2018a). Digital transformation drives the possibilities of creating new value by enabling higher degrees of connectivity between actors, digitally twin physical objects, drawing patterns of behaviour based on extensive sets of historical data, as well as harmonizing data sharing through standardized interfaces and communication protocols (e.g. Almirall and Casadesus-Masanell 2010; Gassman et al. 2010; Lakhani et al. 2006). To break existing patterns of behaviour and to avoid the creation of proprietary solutions that feed sub-optimization, there is a need for new inspiration and perspectives that capitalize on the opportunities that digital transformation provides. From an open innovation point of view, this means that innovators both having experience from the sector as well as from other sectors would come together, come up with, and provide new applications not previously possible or never thought about before. A core capability that the ecosystem needs to develop and ensure is data streams made accessible for those that can provide new applications aimed for the single actor and/or clusters of actors, within or outside the maritime sector (Lind et al. 2018).This has also been one of the objectives for Port Collaborative Decision Making (PortCDM), which is a concept that provides guidelines and standards for the data exchange within and between ports, between ships and ports, and between ports and hinterland operators (Lind et al 2018). Such data exchange is necessary if enhanced efficiency during port call operations is to be achieved but also facilitates open innovation within the maritime sector. In order to realise that potential, a purposive transfer of knowledge between the established actors and potential new service providers has to be established (Chesbrough 2006). We therefore set out to explore How can open innovation intermediaries accelerate acquisition in an ecosystem through the management and throughput of knowledge transfer?We address the question through a longitudinal study by applying an action research approach involving actors from the local port and students from three bachelor programs. Before we describe the specifics of the research methodology, we outline our theoretical framework in terms of how knowledge transfer can be framed within an open innovation ecosystem. After the research methodology we detail the five iterations and then discuss the effect on knowledge transfer within the ecosystem. Finally, we conclude and give directions on future research.
|
|
| 28. |
- Capellera-Garcia, Sandra, et al.
(författare)
-
Defining the Minimal Factors Required for Erythropoiesis through Direct Lineage Conversion
- 2016
-
Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 15:11, s. 2550-2562
-
Tidskriftsartikel (refereegranskat)abstract
- Erythroid cell commitment and differentiation proceed through activation of a lineage-restricted transcriptional network orchestrated by a group of well characterized genes. However, the minimal set of factors necessary for instructing red blood cell (RBC) development remains undefined. We employed a screen for transcription factors allowing direct lineage reprograming from fibroblasts to induced erythroid progenitors/precursors (iEPs). We show that Gata1, Tal1, Lmo2, and c-Myc (GTLM) can rapidly convert murine and human fibroblasts directly to iEPs. The transcriptional signature of murine iEPs resembled mainly that of primitive erythroid progenitors in the yolk sac, whereas addition of Klf1 or Myb to the GTLM cocktail resulted in iEPs with a more adult-type globin expression pattern. Our results demonstrate that direct lineage conversion is a suitable platform for defining and studying the core factors inducing the different waves of erythroid development.
|
|
| 29. |
- Carnrot, Cecilia, et al.
(författare)
-
Marginal zone B cells are naturally reactive to collagen type II and are involved in the initiation of the immune response in collagen-induced arthritis
- 2011
-
Ingår i: Cellular & Molecular Immunology. - : Springer Science and Business Media LLC. - 1672-7681 .- 2042-0226. ; 8:4, s. 296-304
-
Tidskriftsartikel (refereegranskat)abstract
- Antibodies against type II collagen (CII) are essential for development of collagen-induced arthritis (CIA), but how and where the B-cell response to CII is initiated is not fully known. We show here that naive DBA/1 mice display naturally reactive IgM and IgG anti-CII producing B cells prior to immunization. The CII-reactive B cells were observed in the spleen and recognized as marginal zone (MZ) B cells. After CII immunization, CII-specific B cells expanded rapidly in the spleen, in contrast to the lymph nodes, with the initial response derived from MZ B cells and later by follicular (FO) B cells. This was evident despite that the MZ B cells were subject to stringent tolerance mechanisms by having a greater Fc gamma receptor IIb expression than the FO B cells. Further, the MZ B cells migrated to the FO areas upon immunization, possibly providing antigen and activating FO T cells and subsequently FO B cells. Thus, around CIA onset increased numbers of IgG anti-CII producing FO B cells was seen in the spleen, which was dominated by IgG2a- and IgG2b-positive cells. These data demonstrate that CII-reactive MZ B cells are present before and expand after CII immunization, suggesting an initiating role of MZ B cells in the development of CIA.
|
|
| 30. |
- Castro Dopico, Xaquin, et al.
(författare)
-
Probabilistic classification of anti-SARS-CoV-2 antibody responses improves seroprevalence estimates
- 2022
-
Ingår i: Clinical & Translational Immunology (CTI). - : John Wiley & Sons. - 2050-0068. ; 11:3
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: Population-level measures of seropositivity are critical for understanding the epidemiology of an emerging pathogen, yet most antibody tests apply a strict cutoff for seropositivity that is not learnt in a data-driven manner, leading to uncertainty when classifying low-titer responses. To improve upon this, we evaluated cutoff-independent methods for their ability to assign likelihood of SARS-CoV-2 seropositivity to individual samples. Methods: Using robust ELISAs based on SARS-CoV-2 spike (S) and the receptor-binding domain (RBD), we profiled antibody responses in a group of SARS-CoV-2 PCR+ individuals (n = 138). Using these data, we trained probabilistic learners to assign likelihood of seropositivity to test samples of unknown serostatus (n = 5100), identifying a support vector machines-linear discriminant analysis learner (SVM-LDA) suited for this purpose. Results: In the training data from confirmed ancestral SARS-CoV-2 infections, 99% of participants had detectable anti-S and -RBD IgG in the circulation, with titers differing > 1000-fold between persons. In data of otherwise healthy individuals, 7.2% (n = 367) of samples were of uncertain serostatus, with values in the range of 3-6SD from the mean of pre-pandemic negative controls (n = 595). In contrast, SVM-LDA classified 6.4% (n = 328) of test samples as having a high likelihood (> 99% chance) of past infection, 4.5% (n = 230) to have a 50–99% likelihood, and 4.0% (n = 203) to have a 10–49% likelihood. As different probabilistic approaches were more consistent with each other than conventional SD-based methods, such tools allow for more statistically-sound seropositivity estimates in large cohorts. Conclusion: Probabilistic antibody testing frameworks can improve seropositivity estimates in populations with large titer variability.
|
|
| 31. |
|
|
| 32. |
- Diaz Cruz, Maria Araceli, et al.
(författare)
-
Characterization of methylation patterns associated with lifestyle factors and vitamin D supplementation in a healthy elderly cohort from Southwest Sweden
- 2022
-
Ingår i: Scientific Reports. - : Nature Portfolio. - 2045-2322. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- Numerous studies have shown that lifestyle factors, such as regular physical activity and vitamin D intake, may remarkably improve overall health and mental wellbeing. This is especially important in older adults whose vitamin D deficiency occurs with a high prevalence. This study aimed to examine the influence of lifestyle and vitamin D on global DNA methylation patterns in an elderly cohort in Southwest of Sweden. We also sought to examine the methylation levels of specific genes involved in vitamin D's molecular and metabolic activated pathways. We performed a genome wide methylation analysis, using Illumina Infinium DNA Methylation EPIC 850kBeadChip array, on 277 healthy individuals from Southwest Sweden at the age of 70-95. The study participants also answered queries on lifestyle, vitamin intake, heart medication, and estimated health. Vitamin D intake did not in general affect methylation patterns, which is in concert with other studies. However, when comparing the group of individuals taking vitamin supplements, including vitamin D, with those not taking supplements, a difference in methylation in the solute carrier family 25 (SCL25A24) gene was found. This confirms a previous finding, where changes in expression of SLC25A24 were associated with vitamin D treatment in human monocytes. The combination of vitamin D intake and high physical activity increased methylation of genes linked to regulation of vitamin D receptor pathway, the Wnt pathway and general cancer processes. To our knowledge, this is the first study detecting epigenetic markers associated with the combined effects of vitamin D supplementation and high physical activity. These results deserve to be further investigated in an extended, interventional study cohort, where also the levels of 25(OH)D3 can be monitored.
|
|
| 33. |
- Diaz Cruz, Maria Araceli, et al.
(författare)
-
Cis-regulatory elements in conserved non-coding sequences of nuclear receptor genes indicate for crosstalk between endocrine systems
- 2021
-
Ingår i: Open Medicine (Poland). - : De Gruyter Open. - 2391-5463. ; 16:1, s. 640-650
-
Tidskriftsartikel (refereegranskat)abstract
- Nuclear receptors (NRs) are ligand-activated transcription factors that regulate gene expression when bound to specific DNA sequences. Crosstalk between steroid NR systems has been studied for understanding the development of hormone-driven cancers but not to an extent at a genetic level. This study aimed to investigate crosstalk between steroid NRs in conserved intron and exon sequences, with a focus on steroid NRs involved in prostate cancer etiology. For this purpose, we evaluated conserved intron and exon sequences among all 49 members of the NR Superfamily (NRS) and their relevance as regulatory sequences and NR-binding sequences. Sequence conservation was found to be higher in the first intron (35%), when compared with downstream introns. Seventy-nine percent of the conserved regions in the NRS contained putative transcription factor binding sites (TFBS) and a large fraction of these sequences contained splicing sites (SS). Analysis of transcription factors binding to putative intronic and exonic TFBS revealed that 5 and 16%, respectively, were NRs. The present study suggests crosstalk between steroid NRs, e.g., vitamin D, estrogen, progesterone, and retinoic acid endocrine systems, through cis-regulatory elements in conserved sequences of introns and exons. This investigation gives evidence for crosstalk between steroid hormones and contributes to novel targets for steroid NR regulation.
|
|
| 34. |
- Diaz Cruz, Maria Araceli, et al.
(författare)
-
Differential expression of protein disulfide-isomerase A3 isoforms, PDIA3 and PDIA3N, in human prostate cancer cell lines representing different stages of prostate cancer
- 2021
-
Ingår i: Molecular Biology Reports. - : Springer. - 0301-4851 .- 1573-4978. ; 48:3, s. 2429-2436
-
Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer (PCa) is a highly heterogeneous and unpredictable progressive disease. Sensitivity of PCa cells to androgens play a central role in tumor aggressiveness but biomarkers with high sensitivity and specificity that follow the progression of the disease has not yet been verified. The vitamin D endocrine system and its receptors, the Vitamin D Receptor (VDR) and the Protein Disulfide-Isomerase A3 (PDIA3), are related to anti-tumoral effects as well as carcinogenesis and have therefore been suggested as potential candidates for the prevention and therapy of several cancer forms, including PCa. In this study, we evaluated the mRNA expression of VDR and PDIA3 involved in vitamin D signaling in cell lines representing different stages of PCa (PNT2, P4E6, LNCaP, DU145 and PC3). This study further aimed to evaluate vitamin D receptors and their isoforms as potential markers for clinical diagnosis of PCa. A novel transcript isoform of PDIA3 (PDIA3N) was identified and found to be expressed in all PCa cell lines analyzed. Androgen-independent cell lines showed a higher mRNA expression ratio between PDIA3N/PDIA3 contrary to androgen-dependent cell lines that showed a lower mRNA expression ratio between PDIA3N/PDIA3. The structure of PDIA3N differed from PDIA3. PDIA3N was found to be a N-truncated isoform of PDIA3 and differences in protein structure suggests an altered protein function i.e. cell location, thioredoxin activity and affinity for 1,25(OH)2D3. Collectively, PDIA3 transcript isoforms, the ratio between PDIA3N/PDIA3 and especially PDIA3N, are proposed as candidate markers for future studies with different stages of PCa progression.
|
|
| 35. |
|
|
| 36. |
- Einarsson, Sandra, 1981-, et al.
(författare)
-
Mapping impact factors leading to the GLIM diagnosis of malnutrition in patients with head and neck cancer
- 2020
-
Ingår i: Clinical Nutrition ESPEN. - : Elsevier BV. - 2405-4577. ; 40, s. 149-155
-
Tidskriftsartikel (refereegranskat)abstract
- Background & aims: In head and neck cancer, the combination of weight loss and elevated C-reactive protein levels means that patients have malnutrition as defined by the Global Leadership Initiative on Malnutrition (GLIM). This study aimed to identify impact factors for malnutrition as defined by the GLIM criteria among patients with head and neck cancer at the start of treatment and up to 12 months posttreatment.Methods: In a prospective, observational study, patient, tumour, treatment, and nutritional data from 229 patients with head and neck cancer were collected at the start of treatment and at three follow-ups (7 weeks after the start of treatment and at 3 and 12 months after the termination of treatment). These clinical variables were statistically analysed in relation to malnutrition at each follow-up using univariate and multivariate analyses. Malnutrition was defined according to the two GLIM criteria of >5% body weight loss during the last 6 months and C-reactive protein >5 mg/L.Results: The following factors were predictive for malnutrition in the multivariate analysis performed 7 weeks after the start of treatment: moderate or severe mucositis, chemoradiotherapy +/- surgery, and the need for nutritional support (total or partial use of tube feeding/parenteral nutrition). Advanced tumour stage (III-IV) was significant for malnutrition at the start of treatment and at the 7 week and 3 month follow-ups, but not at 12 months.Conclusions: Severe mucositis, chemoradiotherapy +/- surgery, and advanced tumour stage were found to be impact factors for the diagnosis of malnutrition using GLIM at different follow-up times from the start of treatment up to 12 months after the end of treatment. Few patients with head and neck cancer are diagnosed with malnutrition according to the GLIM criteria in a long-term perspective after the termination of treatment. Research on the validity of the GLIM criteria is needed to build a comprehensive evidence base of impact factors for malnutrition in head and neck cancer.
|
|
| 37. |
- Eliasson, Ingegärd, 1961, et al.
(författare)
-
Kulturella ekosystemtjänster i fjällen
- 2016
-
Ingår i: Podcastserien Storslagen fjällmiljö. - Östersund : Storslagen fjällmiljö. ; :5
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- För att vårt storslagna fjällandskap ska kunna vårdas varsamt och hållbart, krävs att politiker och beslutsfattare skaffar sig större kunskap om vad fjällen verkligen betyder för de som bor och verkar där. För att bidra till just det – det vill säga en tydligare helhetsbild och ett bra planeringsunderlag för de som bestämmer – uppstod forskningsprojektet ”Fjällandskap – betydelsen av kulturella ekosystemtjänster”. Forskningssatsningen Storslagen fjällmiljö har som slutprodukt gjort en podcastserie om de tio ingående projekt som ingår i satsningen. I avsnitt 5 pratar Ingegärd Eliasson, som är professor vid Göteborgs universitet, Eva Karlsson som är antikvarie på Länsstyrelsen och Sandra Landén som är företagare inom naturturism, bland annat om fjällen som ett kulturlandskap och platsens betydelse för människors identitetsskapande och välbefinnande. Programledare Tomas Hagström.
|
|
| 38. |
- Fagerlind, Magnus, et al.
(författare)
-
Modeling the effect of acylated homoserine lactone antagonists in Pseudomonas aeruginosa
- 2005
-
Ingår i: Biosystems (Amsterdam. Print). - : Elsevier. - 0303-2647 .- 1872-8324. ; 80:2, s. 201-213
-
Tidskriftsartikel (refereegranskat)abstract
- Pseudomonas aeruginosa is a gram-negative bacterium that causes serious illnesses, particularly in immunocompromised individuals, often with a fatal outcome. The finding that the acylated homoserine lactone quorum sensing (QS) system controls the production of virulence factors in P. aeruginosa makes this system a possible target for antimicrobial therapy. It has been suggested that an N-(3-oxododecanoyl)-homoserine lactone (3O-C12-HSL) antagonist, a QS blocker (QSB), would interfere efficiently with the quorum sensing system in P. aeruginosa and thus reduce the virulence of this pathogen. In this work, a mathematical model of the QS system in P. aeruginosa has been developed. The model was used to virtually add 3O-C12-HSL antagonists that differed in their affinity for the receptor protein and for their ability to mediate degradation of the receptor. The model suggests that very small differences in these parameters for different 3O-C12-HSL antagonists can greatly affect the success of QSB based inhibition of the QS system in P. aeruginosa. Most importantly, it is proposed that the ability of the 3O-C12-HSL antagonist to mediate degradation of LasR is the core parameter for successful QSB based inhibition of the QS system in P. aeruginosa. Finally, this study demonstrates that QSBs can shift the system to a low steady state, corresponding to an uninduced state and thus, suggests that the use of 3O-C12-HSL antagonists may constitute a promising therapeutic approach against P. aeruginosa involved infections.
|
|
| 39. |
- Falck, Ann-Christine, 1949, et al.
(författare)
-
A comparison of two methods for assembly complexity- What are they good for?
- 2015
-
Ingår i: NES, Nordic Ergonomics society, 47th Annual Conference, 02-04 November 2015, Lillehammer, Norway. ; , s. 1-5
-
Konferensbidrag (refereegranskat)abstract
- This study aimed at comparing two methods for assessing manual assembly complexity, the CXB considering basic assembly complexity from product design perspective and the CXI, which assesses complexity as perceived by operators in production. The objective was to see if and how the two methods overlap. The results showed that they had some assessment criteria in common but that other criteria differed and covered different areas of interest. Both method approaches are important for a manufacturer to manage in order to create sustainable assembly conditions, good working conditions and reduce errors in manual assembly.
|
|
| 40. |
- Falås, Per, et al.
(författare)
-
Microbial bromate reduction following ozonation of bromide-rich wastewater in coastal areas
- 2022
-
Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697. ; 841
-
Tidskriftsartikel (refereegranskat)abstract
- Ozonation of wastewater can reduce the release of organic micropollutants, but may result in the formation of undesirable by-products, such as bromate from bromide. Bromide is one of the most abundant ions in seawater, the primary precursor of bromate during ozonation, and the end product in microbial bromate reduction. Investigations were carried out to compare the concentration of bromide in wastewater in coastal and non-coastal catchment areas, to monitor bromate formation during ozonation, and to assess the potential for subsequent bromate reduction with denitrifying carriers. Higher bromide concentrations were systematically observed in wastewater from coastal catchment areas (0.2–2 mg Br−/L) than in wastewater from non-coastal areas (0.06–0.2 mg Br−/L), resulting in elevated formation of bromate during ozonation. Subsequent investigations of bromate reduction in contact with denitrifying carriers from two full-scale moving bed biofilm reactors (MBBRs) showed that 80 % of the bromate formed during ozonation could be reduced to bromide in 60 min with first-order rate constants of 0.3–0.8 L/(gbiomass·h). Flow-through experiments with denitrifying carriers also showed that combined reduction of bromate and nitrate could be achieved below a concentration of 2 mg NOx−-N/L. These findings indicate that bromide-rich wastewater is more likely to be of concern when using ozonation in coastal than in non-coastal areas, and that bromate and nitrate reduction can be combined in a single biofilm reactor.
|
|
| 41. |
|
|
| 42. |
- Fransson, Kristin, et al.
(författare)
-
Miljöhandbokför upphandlare
- 2015
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Hållbar utveckling innefattar såväl social, ekonomisk som miljömässig hållbar utveckling.I Miljöhandboken kommer dessa tre aspekter av hållbar utveckling att behandlas,dock ligger störst fokus på miljöaspekterna.Miljöhandboken ska hjälpa upphandlare att ställa relevanta miljökrav vid upphandlingoch är ett komplement till exempelvis Konkurrensverkets (f.d. Miljöstyrningsrådets)upphandlingskriterier och ska bidra med fakta kring hur miljökrav kan ställas.Miljökrav vid upphandling kan innefatta bl. a. energianvändning, livslängd, skadligaämnen, strålning, återvinning och miljöledningssystem. Kravens betydelse påverkasbl. a. av upphandlingens omfattning och miljömognaden inom produktsegmentet. Imiljöhandboken presenteras inga specifika kriterier eller gränsvärden för olika miljöaspekter,i stället ges länkar till exempelvis lagstiftning, myndigheter och miljömärkningar.Detta för att kriterier och gränsvärden uppdateras kontinuerligt som en följdav teknikutveckling men också för att den samlade kunskapen om vad som är miljöproblemständigt växer och kan ge upphov till nya kriterier och gränsvärden. Tyngdpunkteni denna handbok ligger på miljöpåverkan ur ett livscykelperspektiv, vilket innebäratt hänsyn tas till miljöpåverkan från utvinning av råmaterial till resthantering aven produkt.
|
|
| 43. |
- Fredricsson, Malin, et al.
(författare)
-
Nationell luftövervakning – Sakrapport med data från övervakning inom Programområde Luft t.o.m. 2017
- 2018
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Naturvårdsverket, Luftenheten, ansvarar för den nationella luftövervakningen i bakgrundsmiljö i Sverige. I rapporten redovisas resultat från verksamheten inom Programområde Luft avseende mätningar (genomförda av IVL, SU, SLU och SMHI) till och med 2017 och regionala modellberäkningar (utförda av SMHI) till och med 2016.För flertalet av de luftföroreningskomponenter som övervakas inom den nationella miljöövervakningen har det, sedan mätningarna startade för mellan 15 och 35 år sedan, generellt sett skett en avsevärd förbättring avseende såväl halter i luft som deposition i bakgrundsmiljö. Utvecklingen har dock varierat i något olika utsträckning beroende på komponenter och lokalisering i landet. Föroreningsbelastningen är oftast lägre ju längre norrut i landet man kommer.För de flesta ämnen som det finns miljökvalitetsnormer (MKN) respektive miljömål för ligger halterna i regional bakgrund avsevärt lägre än angivna gräns- och målvärden. Halterna av ozon överskrider dock i dagsläget MKN för hälsa.
|
|
| 44. |
- Fredricsson, Malin, et al.
(författare)
-
Nationell luftövervakning Sakrapport med data från övervakning inom Programområde Luft t.o.m 2019
- 2021
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Naturvårdsverket ansvarar för den nationella luftövervakningen i bakgrundsmiljö i Sverige. I rapporten redovisas resultat från verksamheten inom Programområde Luft avseende mätningar (genomförda av IVL, SU, SLU och SMHI) till och med 2019 och regionala modellberäkningar (utförda av SMHI) till och med 2018.För flertalet av de luftföroreningskomponenter som övervakas inom den nationella miljöövervakningen har det, sedan mätningarna startade för mellan 20 och 40 år sedan, generellt sett skett en avsevärd förbättring avseende såväl halter i luft som deposition i bakgrundsmiljö. Utvecklingen har dock varierat i något olika utsträckning beroende på komponenter och lokalisering i landet. Föroreningsbelastningen är oftast lägre ju längre norrut i landet man kommer.För de flesta ämnen som det finns miljökvalitetsnormer (MKN) respektive miljömål för ligger halterna i regional bakgrund avsevärt lägre än angivna gräns- och målvärden. Halterna av ozon överskrider dock i dagsläget (2019) MKN för hälsa.
|
|
| 45. |
- Gawel, Danuta, et al.
(författare)
-
A validated single-cell-based strategy to identify diagnostic and therapeutic targets in complex diseases
- 2019
-
Ingår i: Genome Medicine. - : Springer Science and Business Media LLC. - 1756-994X. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Genomic medicine has paved the way for identifying biomarkers and therapeutically actionable targets for complex diseases, but is complicated by the involvement of thousands of variably expressed genes across multiple cell types. Single-cell RNA-sequencing study (scRNA-seq) allows the characterization of such complex changes in whole organs. Methods: The study is based on applying network tools to organize and analyze scRNA-seq data from a mouse model of arthritis and human rheumatoid arthritis, in order to find diagnostic biomarkers and therapeutic targets. Diagnostic validation studies were performed using expression profiling data and potential protein biomarkers from prospective clinical studies of 13 diseases. A candidate drug was examined by a treatment study of a mouse model of arthritis, using phenotypic, immunohistochemical, and cellular analyses as read-outs. Results: We performed the first systematic analysis of pathways, potential biomarkers, and drug targets in scRNA-seq data from a complex disease, starting with inflamed joints and lymph nodes from a mouse model of arthritis. We found the involvement of hundreds of pathways, biomarkers, and drug targets that differed greatly between cell types. Analyses of scRNA-seq and GWAS data from human rheumatoid arthritis (RA) supported a similar dispersion of pathogenic mechanisms in different cell types. Thus, systems-level approaches to prioritize biomarkers and drugs are needed. Here, we present a prioritization strategy that is based on constructing network models of disease-associated cell types and interactions using scRNA-seq data from our mouse model of arthritis, as well as human RA, which we term multicellular disease models (MCDMs). We find that the network centrality of MCDM cell types correlates with the enrichment of genes harboring genetic variants associated with RA and thus could potentially be used to prioritize cell types and genes for diagnostics and therapeutics. We validated this hypothesis in a large-scale study of patients with 13 different autoimmune, allergic, infectious, malignant, endocrine, metabolic, and cardiovascular diseases, as well as a therapeutic study of the mouse arthritis model. Conclusions: Overall, our results support that our strategy has the potential to help prioritize diagnostic and therapeutic targets in human disease.
|
|
| 46. |
|
|
| 47. |
- Ghadzi, Siti Maisharah Sheikh
(författare)
-
Pharmacometrics Modelling in Type 2 Diabetes Mellitus : Implications on Study Design and Diabetes Disease Progression
- 2017
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Pharmacometric modelling is widely used in many aspects related to type 2 diabetes mellitus (T2DM), for instance in the anti-diabetes drug development, and in quantifying the disease progression of T2DM.The aim of this thesis were to improve the design of early phase anti-diabetes drug development studies with the focus on the power to identify mechanism of drug action (MoA), and to characterize and quantify the progression from prediabetes to overt diabetes, both the natural progression and the progression with diet and exercise interventions, using pharmacometrics modelling.The appropriateness of a study design depends on the MoAs of the anti-hyperglycaemic drug. Depending on if the focus is power to identify drug effect or accuracy and precision of drug effect, the best design will be different. Using insulin measurements on top of glucose has increase the power to identify a correct drug effect, distinguish a correct MoA from the incorrect, and to identify a secondary MoA in most cases. The accuracy and precision of drug parameter estimates, however, was not affected by insulin. A natural diabetes disease progression model was successfully added in a previously developed model to describe parameter changes of glucose and insulin regulation among impaired glucose tolerance (IGT) subjects, with the quantification of the lifestyle intervention. In this model, the assessment of multiple short-term provocations was combined to predict the long-term disease progression, and offers apart from the assessment of the onset of T2DM also the framework for how to perform similar analysis. Another previously published model was further developed to characterize the weight change in driving the changes in glucose homeostasis in subjects with IGT. This model includes the complex relationship between dropout from study and weight and glucose changes.This thesis has provided a first written guidance in designing a study for pharmacometrics analysis when characterizing drug effects, for early phase anti-diabetes drug development. The characterisation of the progression from prediabetes to overt diabetes using pharmacometrics modelling was successfully performed. Both the natural progression and the progression with diet and exercise interventions were quantified in this thesis.
|
|
| 48. |
- Gillsjö, Catharina, Senior Lecturer, 1963-, et al.
(författare)
-
Lifestyle's influence on community-dwelling older adults' health : A mixed-methods study design
- 2021
-
Ingår i: Contemporary Clinical Trials Communications. - Amsterdam : Elsevier. - 2451-8654. ; 21
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Aging often involves health problems and difficulties, such as physical and psychological impairments, isolation, and loneliness, causing social and existential consequences. Studies have explored aging from different perspectives. However, few studies have examined healthy older adults’ genetic backgrounds, lifestyles, and meaning in life separately or in combination. This study aims to describe how healthy older adults experience aging, health, lifestyles, and meaning in life and explore potential genetic correlations.Methods and Design: The project will comprise three main parts: a quantitative section featuring the development and testing of a lifestyle questionnaire, a quantitative genetic analysis, and a qualitative interview study. Participants will be community-dwelling, healthy, older adults between 70 and 95 years of age. A sample size of 800 older adults will be invited to participate in seminars in collaboration with the national Swedish association Active Seniors. Data will be collected through lifestyle questionnaire, DNA extracted from saliva samples, and interviews. Based on questionnaire responses, profile groups will be created and compared statistically with variations in genetic backgrounds, providing the basis for recruiting participants to the qualitative interviews.Discussion: This study's expected outcome will be to gain knowledge about variations in genetic backgrounds correlated with individual experiences regarding aging, health, and meaning in life. This knowledge can improve the understanding of motivations for healthy lifestyle changes. The results can reveal potential implications for individual prerequisites to healthy aging and how health-promoting aging and lifestyle counseling can be adjusted to meet individual needs.
|
|
| 49. |
- Gliga, Anda R., et al.
(författare)
-
Cerium oxide nanoparticles inhibit differentiation of neural stem cells
- 2017
-
Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- Cerium oxide nanoparticles (nanoceria) display antioxidant properties and have shown cytoprotective effects both in vitro and in vivo. Here, we explored the effects of nanoceria on neural progenitor cells using the C17.2 murine cell line as a model. First, we assessed the effects of nanoceria versus samarium (Sm) doped nanoceria on cell viability in the presence of the prooxidant, DMNQ. Both particles were taken up by cells and nanoceria, but not Sm-doped nanoceria, elicited a temporary cytoprotective effect upon exposure to DMNQ. Next, we employed RNA sequencing to explore the transcriptional responses induced by nanoceria or Sm-doped nanoceria during neuronal differentiation. Detailed computational analyses showed that nanoceria altered pathways and networks relevant for neuronal development, leading us to hypothesize that nanoceria inhibits neuronal differentiation, and that nanoceria and Sm-doped nanoceria both interfere with cytoskeletal organization. We confirmed that nanoceria reduced neuron specific beta 3-tubulin expression, a marker of neuronal differentiation, and GFAP, a neuroglial marker. Furthermore, using super-resolution microscopy approaches, we could show that both particles interfered with cytoskeletal organization and altered the structure of neural growth cones. Taken together, these results reveal that nanoceria may impact on neuronal differentiation, suggesting that nanoceria could pose a developmental neurotoxicity hazard.
|
|
| 50. |
- Gouveia-Figueira, Sandra, et al.
(författare)
-
Characterisation of (R)-2-(2-Fluorobiphenyl-4-yl)-N-(3-Methylpyridin-2-yl)Propanamide as a Dual Fatty Acid Amide Hydrolase : Cyclooxygenase Inhibitor
- 2015
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:9
-
Tidskriftsartikel (refereegranskat)abstract
- Background Increased endocannabinoid tonus by dual-action fatty acid amide hydrolase (FAAH) and substrate selective cyclooxygenase (COX-2) inhibitors is a promising approach for pain-relief. One such compound with this profile is 2-(2-fluorobiphenyl-4-yl)-N-(3-methylpyridin-2-yl)propanamide (Flu-AM1). These activities are shown by Flu-AM1 racemate, but it is not known whether its two single enantiomers behave differently, as is the case towards COX-2 for the parent flurbiprofen enantiomers. Further, the effects of the compound upon COX-2-derived lipids in intact cells are not known. Methodology/Principal Findings COX inhibition was determined using an oxygraphic method with arachidonic acid and 2-arachidonoylglycerol (2-AG) as substrates. FAAH was assayed in mouse brain homogenates using anandamide (AEA) as substrate. Lipidomic analysis was conducted in unstimulated and lipopolysaccharide + interferon gamma-stimulated RAW 264.7 macrophage cells. Both enantiomers inhibited COX-2 in a substrate-selective and time-dependent manner, with IC50 values in the absence of a preincubation phase of: (R)-Flu-AM1, COX-1 (arachidonic acid) 6 mu M; COX-2 (arachidonic acid) 20 mu M; COX-2 (2-AG) 1 mu M; (S)-Flu-AM1, COX-1 (arachidonic acid) 3 mu M; COX-2 (arachidonic acid) 10 mu M; COX-2 (2-AG) 0.7 mu M. The compounds showed no enantiomeric selectivity in their FAAH inhibitory properties. (R)-Flu-AM1 (10 mu M) greatly inhibited the production of prostaglandin D2 and E2 in both unstimulated and lipopolysaccharide + interferon.-stimulated RAW 264.7 macrophage cells. Levels of 2-AG were not affected either by (R)-Flu-AM1 or by 10 mu M flurbiprofen, either alone or in combination with the FAAH inhibitor URB597 (1 mu M). Conclusions/Significance Both enantiomers of Flu-AM1 are more potent inhibitors of 2-AG compared to arachidonic acid oxygenation by COX-2. Inhibition of COX in lipopolysaccharide + interferon.-stimulated RAW 264.7 cells is insufficient to affect 2-AG levels despite the large induction of COX-2 produced by this treatment.
|
|
