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1.
  • Jauhiainen, Alexandra, 1981, et al. (author)
  • Distinct cytoplasmic and nuclear functions of the stress induced protein DDIT3/CHOP/GADD153
  • 2012
  • In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:4
  • Journal article (peer-reviewed)abstract
    • DDIT3, also known as GADD153 or CHOP, encodes a basic leucine zipper transcription factor of the dimer forming C/EBP family. DDIT3 is known as a key regulator of cellular stress response, but its target genes and functions are not well characterized. Here, we applied a genome wide microarray based expression analysis to identify DDIT3 target genes and functions. By analyzing cells carrying tamoxifen inducible DDIT3 expression constructs we show distinct gene expression profiles for cells with cytoplasmic and nuclear localized DDIT3. Of 175 target genes identified only 3 were regulated by DDIT3 in both cellular localizations. More than two thirds of the genes were downregulated, supporting a role for DDIT3 as a dominant negative factor that could act by either cytoplasmic or nuclear sequestration of dimer forming transcription factor partners. Functional annotation of target genes showed cell migration, proliferation and apoptosis/survival as the most affected categories. Cytoplasmic DDIT3 affected more migration associated genes, while nuclear DDIT3 regulated more cell cycle controlling genes. Cell culture experiments confirmed that cytoplasmic DDIT3 inhibited migration, while nuclear DDIT3 caused a G1 cell cycle arrest. Promoters of target genes showed no common sequence motifs, reflecting that DDIT3 forms heterodimers with several alternative transcription factors that bind to different motifs. We conclude that expression of cytoplasmic DDIT3 regulated 94 genes. Nuclear translocation of DDIT3 regulated 81 additional genes linked to functions already affected by cytoplasmic DDIT3. Characterization of DDIT3 regulated functions helps understanding its role in stress response and involvement in cancer and degenerative disorders.
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  • Ademuyiwa, Adesoji O., et al. (author)
  • Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
  • 2016
  • In: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
  • Journal article (peer-reviewed)abstract
    • Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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  • Andersson, Elin, et al. (author)
  • Prehospital Identification of Patients with a Final Hospital Diagnosis of Stroke.
  • 2018
  • In: Prehospital and Disaster Medicine. - 1049-023X .- 1945-1938. ; , s. 63-70
  • Journal article (peer-reviewed)abstract
    • Introduction the early phase of stroke, minutes are critical. Since the majority of patients with stroke are transported by the Emergency Medical Service (EMS), the early handling and decision making by the EMS clinician is important. Problem The study aim was to evaluate the frequency of a documented suspicion of stroke by the EMS nurse, and to investigate differences in the clinical signs of stroke and clinical assessment in the prehospital setting among patients with regard to if there was a documented suspicion of stroke on EMS arrival or not, in patients with a final hospital diagnosis of stroke.METHODS: The study had a retrospective observational design. Data were collected from reports on patients who were transported by the EMS and had a final diagnosis of stroke at a single hospital in western Sweden (630 beds) in 2015. The data sources were hospital and prehospital medical journals.RESULTS: In total, 454 patients were included. Among them, the EMS clinician suspected stroke in 52%. The findings and documentation on patients with a suspected stroke differed from the remaining patients as follows: a) More frequently documented symptoms from the face, legs/arms, and speech; b) More frequently assessments of neurology, face, arms/legs, speech, and eyes; c) More frequently addressed the major complaint with regard to time and place of onset, duration, localization, and radiation; d) Less frequently documented symptoms of headache, vertigo, and nausea; and e) More frequently had an electrocardiogram (ECG) recorded and plasma glucose sampled. In addition to the 52% of patients who had a documented initial suspicion of stroke, seven percent of the patients had an initial suspicion of transitory ischemic attack (TIA) by the EMS clinician, and a neurologist was approached in another 10%.CONCLUSION: Among 454 patients with a final diagnosis of stroke who were transported by the EMS, an initial suspicion of stroke was not documented in one-half of the cases. These patients differed from those in whom a suspicion of stroke was documented in terms of limited clinical signs of stroke, a less extensive clinical assessment, and fewer clinical investigations. Andersson E , Bohlin L , Herlitz J , Sundler AJ , Fekete Z , Andersson Hagiwara M . Prehospital identification of patients with a final hospital diagnosis of stroke.
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6.
  • Andersson-Engels, Stefan, et al. (author)
  • In vivo luminescence imaging and tomography using upconverting nanoparticles as contrast agents
  • 2012
  • In: 2012 Asia Communications and Photonics Conference. - 2162-108X. ; , s. 2-3
  • Conference paper (peer-reviewed)abstract
    • Upconverting nanoparticles have recently drawn increasingly attention as contrast agents for optical bioimaging. They enable autofluorescence-free imaging within the tissue optical window, and improved spatial resolution as compared to conventional fluorescence-based contrast agents. (C) 2012 Optical Society of America
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7.
  • Andersson, Henrik, et al. (author)
  • T A microarray analysis of the murine macrophage response to infection with Francisella tularensis LVS
  • 2006
  • In: Journal of Medical Microbiology. - : Microbiology Society. - 0022-2615 .- 1473-5644. ; 55:8, s. 1023-1033
  • Journal article (peer-reviewed)abstract
    • The response of cells of the mouse macrophage cell line J774 to infection with Francisella tularensis LVS was analysed by means of a DNA microarray representing approximately 18 500 genes (20 600 clones). The adaptive response was modest at all time points, and at most, 81 clones were differentially regulated from the time point of uptake of bacteria (0 min) up to 240 min later. For all five time points, 229 clones fulfilled the criteria of being differentially regulated, i.e. the ratio between infected versus non-infected cells was at least 1.7-fold up- or down-regulated and P <0.05. It was found that many of the differentially regulated genes are known to respond to stress in general and to oxidative stress specifically. However, at 120 min it was observed that genes that lead to depletion of glutathione were upregulated. Possibly, this was a result of mechanisms induced by F. tularensis. Generally, there was a conspicuous lack of inflammatory responses and, for example, although tumour necrosis factor alpha (TNF-α) was upregulated at 0 min, a significant down-regulation was noted at all subsequent time points. When cells were treated with an inhibitor of inducible nitric oxide synthase (iNOS) or the antioxidant N-acetylcysteine (NAC), the infection-induced cytopathogenic effect was significantly inhibited. Together, the results suggest that F. tularensis LVS infection confers an oxidative stress upon the target cells and that many of the host-defence mechanisms appear to be intended to counteract this stress. The infection is characterized by a very modest inflammatory response.
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8.
  • Andersson, Jan, et al. (author)
  • Trafiksäkerhetspåverkan vid omkörning av 30-metersfordon
  • 2011
  • Reports (other academic/artistic)abstract
    • Trafikverket överväger att tillåta längre och tyngre fordon på vägarna förutsatt att de inte påverkar trafiksäkerheten negativt. Syftet med studien var att undersöka säkerhetseffekten av fordonslängd, speciellt med avseende på olycksrisken vid omkörningar. Intervjuade förare av en 30-meters timmerbil hade inte upplevt de farhågor som förare av normallånga lastbilar uttryckt i samband med trånga rondeller och korsningar, men de nämner betydelsen av stödjande åkeri, arbetsmiljö och fordonsutrustning. En simulatorstudie studerade bilförares omkörningar av ett 30- och ett 18,75-metersfordon på en 2+1-väg i situationen då två körfält går ihop till ett. Tidluckan till ett återstående körfält var i genomsnitt 0,2 s (sign.) kortare efter omkörningar av 30-metersfordonet i situationer då bakänden var i samma relativa position som för 18,75-metersfordonet vid början av omkörningen. En fältstudie analyserade videoinspelade omkörningar av en 30- och en 24-meters timmerbil på en 2+1-väg och en tvåfältig väg. Ingen signifikant skillnad i tidluckor kunde påvisas mellan omkörningar av de två fordonen för någon av vägtyperna. Det senare resultatet ska dock tolkas med försiktighet på grund av ojämnt distribuerad data som insamlats under specifika förhållanden. Slutsatserna är att det finns en liten tendens till negativ säkerhetseffekt vid omkörningar av längre fordon, och att fler fältstudier är nödvändiga.
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11.
  • Andersson, Linda, et al. (author)
  • Transition towards sustainable transportation : What determines fuel choice?
  • 2020
  • In: Transport Policy. - : Elsevier. - 0967-070X .- 1879-310X. ; 90, s. 31-38
  • Journal article (peer-reviewed)abstract
    • For the transport sector to become more sustainable, substantial technological and behavioural changes are required. Increased understanding about household choices related to more green alternatives in transportation is needed in order for policy makers to make efficient policies in the future. The main purpose of this paper is to analyze which factors that determines the fuel choice between ethanol and gasoline for owners of flex-fuel vehicles (FFVs). We evaluate how the self-reported fuel choice is influenced by the relative price, as well as individual differences in norms and perceptions about environmental and quality attributes of ethanol. Data was collected through a survey sent to Swedish FFV owners and is analyzed in a binary choice and a LCM framework. Results show that price, perceptions about quality, age and environmental attitudes influence the self-reported willingness to choose ethanol. Furthermore, results show that preferences are not homogenous, three groups are identified; price conscious respondents, ethanol skeptical respondents and respondents with pronounced environmental concern. However, although the motive for introducing and subsidizing ethanol was to reduce climate and environmental impacts, the group that chooses ethanol based on climate and environmental motives is small. The results further reveal that the debate about motor damages from ethanol have had a long lasting effect on the willingness to choose ethanol. Thus, it is necessary to try to prevent or mitigate concerns regarding e.g. potential technical or ethical issues when promoting future technologies or fuels aimed at a sustainable transportation sector.
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12.
  • Andersson, Linda, et al. (author)
  • Why flex-fuel failed? : A household perspective
  • 2016
  • In: Meeting Sweden's current and future energy challenges, Luleå: Luleå tekniska universitet, 2016. - Luleå : Luleå tekniska universitet.
  • Conference paper (other academic/artistic)
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13.
  • Andersson, Sandra Andersson, et al. (author)
  • Undersökning av kalciumkarbonatförekomsten i Vombfältet
  • 2015
  • In: Vatten: tidskrift för vattenvård /Journal of Water Management and research. - 0042-2886. ; 71, s. 17-26
  • Journal article (pop. science, debate, etc.)abstract
    • In a study of the neutralization capacity and limestone content the artificial recharge area of the Sydvatten waterworks Vombverket in Vomb, Skåne, five samples from different locations in the area was collected, sieved and acidified with hydrochloric acid. The neutralization capacity measured as calcium carbonate content was found to vary in the different sandy soil samples but was generally high (about 2–14 % by weight). The total mass of calcium carbonate in the infiltration area was determined taking into account the volume and density, i.e. possible porosity of the soil. There is at least equal to 4.3 million tons of calcium carbonate present in the infiltration area. This corresponds to a neutralization capacity of 88 x 109 moles in the study area. The annual limestone dissolution in the area is about 750 tons. The limestone content in the area is generally high and has a good ability to buffer also more acidic water than water from Vombsjön. At present limestone consumption, the neutralization capacity lasts for at least 5700 years.
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  • Ek, Kristina, et al. (author)
  • Motives for walking and cycling when commuting - differences in local contexts and attitudes
  • 2021
  • In: European Transport Research Review. - : Springer. - 1867-0717 .- 1866-8887. ; 13:1
  • Journal article (peer-reviewed)abstract
    • Background The purpose of this study is to analyse what factors that explain individual differences in walking and cycling when commuting in different parts of Sweden. Walking and cycling is potentially accessible all over the country, while well developed public transport is mainly a viable option in densely populated areas. Methodology The importance of differences in local characteristics for the choice of transport mode will be scrutinised, together with individual differences in attitudes andpreferences. Data is collected through a survey sent to people living in five Swedish municipalities with different demographic, socio-economic ,infrastructural and geographical characteristics. Results The results for the pooled sample indicate that the choice to walk/cycle when commuting is related to health considerations and environmental concerns. Distance to work/school is also an important factor. Men tend to be more prone to choose active transport, and so do respondents with lower income. The results further reveal that availability of safe routes for walking and cycling are important for the choice to walk/cycle when commuting. As health considerations are important, we suggest policy makers to stress health motives when they promote walking and cycling in the future. Our results further suggest that it is important to consider availability and accessibility in community planning, and to prioritize safety and comfort of walking and cycling, not least in parts of the country where public transport is not an economically viable option.
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  • Kurland, Sara, et al. (author)
  • Exploring a Pool-seq-only approach for gaining population genomic insights in nonmodel species
  • 2019
  • In: Ecology and Evolution. - : Wiley. - 2045-7758. ; 9, s. 11448-11463
  • Journal article (peer-reviewed)abstract
    • Developing genomic insights is challenging in nonmodel species for which resources are often scarce and prohibitively costly. Here, we explore the potential of a recently established approach using Pool-seq data to generate a de novo genome assembly for mining exons, upon which Pool-seq data are used to estimate population divergence and diversity. We do this for two pairs of sympatric populations of brown trout (Salmo trutta): one naturally sympatric set of populations and another pair of populations introduced to a common environment. We validate our approach by comparing the results to those from markers previously used to describe the populations (allozymes and individual-based single nucleotide polymorphisms [SNPs]) and from mapping the Pool-seq data to a reference genome of the closely related Atlantic salmon (Salmo salar). We find that genomic differentiation (F-ST) between the two introduced populations exceeds that of the naturally sympatric populations (F-ST = 0.13 and 0.03 between the introduced and the naturally sympatric populations, respectively), in concordance with estimates from the previously used SNPs. The same level of population divergence is found for the two genome assemblies, but estimates of average nucleotide diversity differ (pi over bar approximate to 0.002 and pi over bar approximate to 0.001 when mapping to S. trutta and S. salar, respectively), although the relationships between population values are largely consistent. This discrepancy might be attributed to biases when mapping to a haploid condensed assembly made of highly fragmented read data compared to using a high-quality reference assembly from a divergent species. We conclude that the Pool-seq-only approach can be suitable for detecting and quantifying genome-wide population differentiation, and for comparing genomic diversity in populations of nonmodel species where reference genomes are lacking.
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17.
  • Lindfors, Lina, et al. (author)
  • Is GPR146 really the receptor for proinsulin C-peptide?
  • 2020
  • In: Bioorganic & Medicinal Chemistry Letters. - : Elsevier. - 0960-894X .- 1464-3405. ; 30:13
  • Journal article (peer-reviewed)abstract
    • Proinsulin C-peptide has previously been proposed to interact with a G-protein coupled receptor (GPCR), specifically the orphan receptor GPR146. To investigate the potential of C-peptide in treating complications of diabetes, such as kidney damage, it is necessary to understand its mode of action. We used CHO-K1 cells expressing human GPR146 to study human and murine C-peptide in dynamic mass redistribution and GPCR beta-arrestin assays, as well as with fluorescence confocal microscopy. Neither assay revealed any significant intracellular response to C-peptide at concentrations of up to 33 mu M. We observed no internalisation of C-peptide by fluorescence microscopy. Our results do not support GPR146 as the receptor for C-peptide, but suggest that further investigations of the mode of action of C-peptide should be undertaken.
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  • Muszynska, Carolina, et al. (author)
  • A risk score model to predict incidental gallbladder cancer in patients scheduled for cholecystectomy
  • 2020
  • In: American Journal of Surgery. - : Elsevier BV. - 0002-9610 .- 1879-1883. ; 220:3, s. 741-744
  • Journal article (peer-reviewed)abstract
    • Background: Gallbladder cancer (GBC) has a poor prognosis. The aim was to develop and validate a preoperative risk score for incidental gallbladder cancer (IGBC) in patients scheduled for cholecystectomy. Methods: Data registered in the nationwide Swedish Registry for Gallstone Surgery (GallRiks) was analyzed, including the derivation cohort (n = 28915, 2007–2014) and the validation cohort (n = 7851, 2014–2016). An additive risk score model based on odds ratio was created. Results: The scoring model to predict IGBC includes age, female gender, previous cholecystitis, and either jaundice or acute cholecystitis. The calibration by HL test and discrimination by AUROC was 8.27 (P = 0.291) and 0.76 in the derivation cohort (214 IGBC) and 14.28 (P = 0.027) and 0.79 in the validation cohort (35 IGBC). The scoring system was applied to three risk-groups, based on the risk of having IGBC, eg. the high-risk group (>8 points) included 7878 patients, with 154 observed and 148 expected IGBC cases. Conclusion: We present the first risk score model to predict IGBC. The model estimates the expected risk for the individual patient and may help to optimize treatment strategies.
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  • Muszynska, Carolina, et al. (author)
  • Incidental metastases and lymphoma of the gallbladder–an analysis of ten rare cases identified from a large national database
  • 2019
  • In: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 54, s. 350-358
  • Journal article (peer-reviewed)abstract
    • Background: The aim was to identify and characterize rare malignancies of the gallbladder, incidentally found at cholecystectomy, and describe the diagnostic work-up, treatment and outcome. Methods: Data from cholecystectomies during 2007–2014 registered in the Swedish Register for Gallstone Surgery (GallRiks) were analyzed for incidental cancer. For completion of the pathology report, data were linked with the Swedish Registry for Cancer in the liver and biliary tract (SweLiv) and/or the Swedish Cancer Registry. Results: From 36,355 patients that underwent cholecystectomy on a benign indication 215 cases of incidental gallbladder cancer (IGBC) were identified. In total seven patients with metastases to the gallbladder from different primary tumors (breast cancer, malignant melanoma, gastric cancer, renal cell carcinoma, upper gastrointestinal cancer, colon cancer and pancreatic cancer) and three patients with lymphoma involvement of the gallbladder were found. Most patients were female with no difference between the groups (8/10 versus 171/215). The median age for the metastasis and lymphoma (MOL) group was equal to the IGBC group, 70 (64–72) years versus 70 (63–78) years. All patients in the MOL group underwent preoperative imaging with ultrasound or computed tomography, on which no metastases were identified. In only two patients a tumor was seen by the surgeon during the perioperative examination of the gallbladder. The median survival was 5.8 months for MOL patients and 23 months for IGBC patients. Conclusion: Metastases and lymphoma of the gallbladder are rare. Traditional imaging methods prior to cholecystectomy may miss gallbladder malignancies. A liberal approach of histopathological analysis of the gallbladder should be applied.
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20.
  • Muszynska, Carolina, et al. (author)
  • Predictors of incidental gallbladder cancer in patients undergoing cholecystectomy for benign gallbladder disease : Results from a population-based gallstone surgery registry
  • 2017
  • In: Surgery. - : Elsevier BV. - 0039-6060 .- 1532-7361. ; 162:2, s. 256-263
  • Journal article (peer-reviewed)abstract
    • Background: Gallbladder cancer is a rare neoplasm with a poor prognosis. Early diagnosis and correct treatment strategy is important. The aim of this study was to identify predictors for incidental gallbladder cancer. Methods: Data from cholecystectomies registered in the nationwide Swedish Register for Gallstone Surgery between 2007 and 2014 were analyzed for incidental gallbladder cancer. Exclusion criteria were patients with a gallbladder not sent for histopathology, preoperative suspicion of polyps/gallbladder cancer, and indication for operation for other reasons than gallstone disease. Predictive factors for incidental gallbladder cancer were identified using multivariable logistic regression. Results: A total of 86,154 procedures were registered in the Swedish Register for Gallstone Surgery. Of these, 36,355 patients were included in the analysis, and 215 of the included patients had incidental gallbladder cancer (0.59%). Mean age was 70 ± 11 years for index cases and 54 ± 16 years for the control group, and 80% of cases and 60% of controls were female. Predictors for incidental gallbladder cancer were older age (odds ratio = 1.08; P < .001), female sex (odds ratio = 3.58; P < .001), previous cholecystitis (odds ratio = 1.37; P = .045), and the combination of acute cholecystitis without jaundice (odds ratio = 1.39; P = .041) and jaundice without acute cholecystitis (odds ratio = 2.02; P = .009). A preoperative risk model including these factors gave an area under receiver operating characteristic curve of 0.82. By adding macroscopic evaluation of the gallbladder by the surgeon, the area under receiver operating characteristic curve increased to 0.87. Intraoperatively suspected gallbladder cancer was confirmed as cancer in 31% of the cases. Conclusion: Incidental gallbladder cancer is more likely to be diagnosed in older patients, women, and after previous cholecystitis. Jaundice and acute cholecystitis were also shown to be important risk factors. Intraoperative inspection of the gallbladder improved the risk model.
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21.
  • Persson, Linda, et al. (author)
  • Approach to optical interference fringes reduction in diode laser absorption spectroscopy
  • 2007
  • In: Applied Physics B. - : Springer Science and Business Media LLC. - 0946-2171 .- 1432-0649. ; 87:3, s. 523-530
  • Journal article (peer-reviewed)abstract
    • The advantage of a new scheme for balanced detection has been investigated to reduce the influence of optical interference fringes when performing diode laser gas absorption spectroscopy employing lock-in amplifiers and pigtailed lasers. The influence of the fringes has been reduced by comparing the lock-in 2 f signal due to the gas sample with that of a reference beam. The frequency regions outside the absorption feature have been used to obtain information on the interference fringe impact on the signal of interest. We have demonstrated an efficient way to reduce the influence of such fringes by employing this technique combined with non-linear signal processing methods. The different steps of the algorithm are presented. In the experimental arrangement presented, a reduction of the optical interference fringes by about 10 times is achieved, as demonstrated in measurements on molecular oxygen around 761 nm. The new technique is compared with an analog technique for balanced detection and certain advantages of the computer algorithm are pointed out. In particular, the emerging field of gas spectroscopy in scattering solid media strongly benefits from the technique presented.
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  • Silfvernagel, Kristin, et al. (author)
  • Individually tailored internet-based cognitive behaviour therapy for older adults with anxiety and depression : a randomised controlled trial
  • 2018
  • In: Cognitive Behaviour Therapy. - : Taylor & Francis Group. - 1650-6073 .- 1651-2316. ; 47:4, s. 286-300
  • Journal article (peer-reviewed)abstract
    • Mixed anxiety and depression is common among older adults. The aim of the study was to compare the effects of an eight-week-long tailored internet-supported cognitive behaviour therapy (ICBT) programme and to compare against the provision of weekly general support. A second aim was to investigate if pre-treatment cognitive flexibility and self-reported cognitive problems would predict outcome. We included 66 older adults (aged over 60 years) with mixed anxiety/depression following media recruitment and randomised them into treatment and control groups. We also included a one-year follow-up. As a measure of executive function, we used the Wisconsin Card Sorting Test (perseverative errors) and the Cognitive Failures Questionnaire during the pre-treatment phase. Results showed a moderate between-group effect on the main outcome measure, the Beck Anxiety Inventory (BAI) (d= .50), favouring the treatment group. Nearly half (45.5%) of that group were classified as responders. One person (3%) in the treatment group deteriorated. There were significant correlations between perseverative errors and outcome (on the BAI r = -.45), but not among self-reported cognitive function. We conclude that guided, tailored ICBT may be effective for some older adults and that the role of cognitive function needs to be investigated further.
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  • Tancred, Linda, 1974-, et al. (author)
  • Administration of a donor of nitric oxide inhibits mglA expression of intracellular Francisella tularensis and counteracts phagosomal escape and subversion of TNF-α secretion
  • 2011
  • In: Journal of Medical Microbiology. - : Microbiology Society. - 0022-2615 .- 1473-5644. ; 30:11, s. 1570-1583
  • Journal article (peer-reviewed)abstract
    • Francisella tularensis is a highly virulent intracellular bacterium capable of rapid multiplication in phagocytic cells. Previous studies have revealed that activation of F. tularensis-infected macrophages leads to control of infection and reactive nitrogen and oxygen species make important contributions to the bacterial killing. We investigated the effects of adding S-nitroso-acetyl-penicillamine (SNAP), which generates nitric oxide or 3-morpholinosydnonimine hydrochloride (SIN-1), which indirectly leads to formation of peroxynitrite, to J774 murine macrophage-like cell cultures infected with F. tularensis LVS. Addition of SNAP led to significantly increased colocalization between LAMP-1 and bacteria, indicating containment of F. tularensis in the phagosome within 2 h, although no killing occurred within 4 h. A specific inhibitory effect on bacterial transcription was observed since the gene encoding the global regulator MglA was inhibited 50- to 100-fold. F. tularensis-infected J774 cells are incapable of secreting TNF-alpha in response to Escherichia coli LPS but addition of SNAP almost completely reversed the suppression. Similarly, infection with an MglA mutant did not inhibit LPS-induced TNF-alpha secretion of J774 cells. Strong staining for nitrotyrosine was observed in SNAP-treated bacteria and mass spectrometry identified nitration of two ribosomal 50S proteins, a CBS domain pair protein, and bacterioferritin. The results demonstrate that addition of SNAP initially did not affect the viability of intracellular F. tularensis LVS but led to containment of the bacteria in the phagosome. Moreover, the treatment resulted in nitration of several F. tularensis proteins.
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25.
  • Zlabinger, Markus, et al. (author)
  • Medical Entity Corpus with PICO Elements and Sentiment Analysis
  • 2018
  • In: Proceedings of the Eleventh International Conference on Language Resources and Evaluation (LREC 2018). - 9791095546009 ; , s. 292-296
  • Conference paper (peer-reviewed)abstract
    • In this paper, we present our process to establish a PICO and a sentiment annotated corpus of clinical trial publications. PICO stands for Population, Intervention, Comparison and Outcome - these four classes can be used for more advanced and specific search queries. For example, a physician can determine how well a drug works only in the subgroup of children. Additionally to the PICO extraction, we conducted a sentiment annotation, where the sentiment refers to whether the conclusion of a trial was positive, negative or neutral. We created both corpora with the help of medical experts and non-experts as annotators.
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Matikainen, N. (7)
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Levin, Max, 1969 (7)
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