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1.
  • Ademuyiwa, Adesoji O., et al. (författare)
  • Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
  • 2016
  • Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
  • Tidskriftsartikel (refereegranskat)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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2.
  • Andersson, Cecilia, et al. (författare)
  • "Vad förväntas av en?" : Upplevelser av "idealstudenten" och mötet med universitetet
  • 2024
  • Ingår i: Lifelong Learning and Higher Education: New (and Old) Perspectives : Proceedings from the 2022 Lund University Conference on Teaching and Learning - Proceedings from the 2022 Lund University Conference on Teaching and Learning. - 9789172674844 - 9789172674851 ; , s. 35-53
  • Konferensbidrag (refereegranskat)abstract
    • Swedish institutions of higher education must promote widening participation. This goal is also expressed in policy documents at Lund University. To accomplish this, teachers at Lund University formed a group to strategically work towards student inclusion. This article reports on an interview study conducted by this group investigating students’ experiences and perceptions of entering education at two different programs. The theory of “the ideal student” was used to analyze the interview material. The result indicates the need for clarity and predictability in course layout and teaching.
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  • Gerhardt, Karin, et al. (författare)
  • Nog nu, politiker – ta klimatkrisen på allvar
  • 2022
  • Ingår i: Aftonbladet Debatt. - 1103-9000. ; -:-
  • Tidskriftsartikel (populärvet., debatt m.m.)abstract
    • 1944 svenska forskare och anställda i forskarvärlden: Vad är det ni inte förstår?
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6.
  • Hober, Sophia, Professor, 1965-, et al. (författare)
  • Systematic evaluation of SARS-CoV-2 antigens enables a highly specific and sensitive multiplex serological COVID-19 assay
  • 2021
  • Ingår i: Clinical & Translational Immunology. - : Wiley. - 2050-0068. ; 10:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. The COVID-19 pandemic poses an immense need for accurate, sensitive and high-throughput clinical tests, and serological assays are needed for both overarching epidemiological studies and evaluating vaccines. Here, we present the development and validation of a high-throughput multiplex bead-based serological assay. Methods. More than 100 representations of SARS-CoV-2 proteins were included for initial evaluation, including antigens produced in bacterial and mammalian hosts as well as synthetic peptides. The five best-performing antigens, three representing the spike glycoprotein and two representing the nucleocapsid protein, were further evaluated for detection of IgG antibodies in samples from 331 COVID-19 patients and convalescents, and in 2090 negative controls sampled before 2020. Results. Three antigens were finally selected, represented by a soluble trimeric form and the S1-domain of the spike glycoprotein as well as by the C-terminal domain of the nucleocapsid. The sensitivity for these three antigens individually was found to be 99.7%, 99.1% and 99.7%, and the specificity was found to be 98.1%, 98.7% and 95.7%. The best assay performance was although achieved when utilising two antigens in combination, enabling a sensitivity of up to 99.7% combined with a specificity of 100%. Requiring any two of the three antigens resulted in a sensitivity of 99.7% and a specificity of 99.4%. Conclusion. These observations demonstrate that a serological test based on a combination of several SARS-CoV-2 antigens enables a highly specific and sensitive multiplex serological COVID-19 assay.
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7.
  • Wang, Zhaoming, et al. (författare)
  • Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
  • 2014
  • Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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9.
  • Ahlryd, Sara, et al. (författare)
  • Stärkta skolbibliotek kräver stora satsningar på att utbilda bibliotekarier
  • 2024
  • Annan publikation (populärvet., debatt m.m.)abstract
    • Debatt: Äntligen kom den: regeringens lagrådsremiss som ska stärka elevers rätt till skolbibliotek. Vi som utbildar blivande bibliotekarier gläds över remissen som i linje med forskning visar skolbibliotekets och skolbibliotekariers betydelse för elevers lärande. Samtidigt konstaterar vi att en lagändring också måste följas av riktade satsningar på landets bibliotekarieutbildningar för att förverkligas, skriver 16 biblioteksforskare.
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11.
  • Andersson, Jens A, et al. (författare)
  • Hybrid Data Communication Lab – a Case Study
  • 2023
  • Ingår i: Proceedings från LTHs 12:e Pedagogiska inspirationskonferensen. ; , s. 80-82
  • Konferensbidrag (refereegranskat)abstract
    • Due to restrictions following the Covid-19 pandemic,major changes regarding teaching have been called for. Sincestudents’ presence in lab classrooms has been very restricted alsophysical labs have had to be transformed into e.g. simulationsperformed at home or via remote connections. After lifting of therestrictions, hybrid learning where both physical and simulatedlab environment are combined have been introduced. This reportdescribes such a case regarding a lab in data communication forelectrical engineering students on bachelor level. The result showsadded value to the learning outcome of the lab.
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12.
  • Andersson, Sara-Linnea, et al. (författare)
  • Plug-in Hybrid Electric Vehicles as Regulating Power Providers - Case Studies of Sweden and Germany
  • 2010
  • Ingår i: Energy Policy. - : Elsevier BV. - 0301-4215. ; 38:6, s. 2751-2762
  • Tidskriftsartikel (refereegranskat)abstract
    • This study investigates plug-in hybrid electric vehicles (PHEVs) as providers of regulating power in the form of primary, secondary and tertiary frequency control. Previous studies have shown that PHEVs could generate substantial profits while providing ancillary services. This study investigates under what conditions PHEVs can generate revenues using actual market data, i.e. prices and activations of regulating power, from Sweden and Germany from four months in 2008. PHEV market participation is modelled for individual vehicles in a fleet subject to a simulated movement pattern. Costs for infrastructure and vehicle-to-grid equipment are not included in the analysis. The simulation results indicate that maximum average profits generated on the German markets are in the range 30–80 h per vehicle and month whereas the Swedish regulating power markets give no profit.In addition, an analysis is performed to identify strengths, weaknesses, opportunities, and threats (SWOT) of PHEVs as regulating power providers. Based on the simulation results and the SWOT analysis, characteristics for an ideal regulating power market for PHEVs are presented.
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  • Ansari, Daniel, et al. (författare)
  • Artificial neural networks predict survival from pancreatic cancer after radical surgery.
  • 2013
  • Ingår i: The American Journal of Surgery. - : Elsevier BV. - 1879-1883 .- 0002-9610. ; 205:1, s. 1-7
  • Tidskriftsartikel (refereegranskat)abstract
    • Artificial neural networks (ANNs) are nonlinear pattern recognition techniques that can be used as a tool in medical decision making. The objective of this study was to develop an ANN model for predicting survival in patients with pancreatic ductal adenocarcinoma (PDAC).
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15.
  • Bergqvist Rydén, Johanna, et al. (författare)
  • Frågan om anonymiserade examinationer ur ett pedagogiskt perspektiv
  • 2024
  • Ingår i: Lifelong Learning and Higher Education: New (and Old) Perspectives : Proceedings from the 2022 Lund University Conference on Teaching and Learning - Proceedings from the 2022 Lund University Conference on Teaching and Learning. - 9789172674844 ; , s. 153-170
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Anonymisation of assessments has been discussed for decades. It stems from a concern about unduly bias in assessment and grading. In Sweden, anonymised assessments were introduced in many universities a decade ago. It was rarely preceded by discussions on potential pedagogical consequences. Recent research on the effects of anonymisation does not confirm the hypothesis of reduced bias in grading. Research have also indicated that assessment and feedback designs affect student learning, and that anonymised assessment designs might obstruct the intentions of learning-oriented designs. I advocate a certain degree of caution and call for a nuanced discussion with students’ learning in focus.
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16.
  • Bombarda, F., et al. (författare)
  • Runaway electron beam control
  • 2019
  • Ingår i: Plasma Physics and Controlled Fusion. - : IOP Publishing. - 1361-6587 .- 0741-3335. ; 61:1
  • Tidskriftsartikel (refereegranskat)
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17.
  • Cejvan, Olivia, et al. (författare)
  • The Writing Group : A Community of Practice and Collegiality
  • 2024
  • Ingår i: Lifelong learning and Higher Education: New (and Old) Perspectives : Proceedings from the 2022 Lund University Conference on Teaching and Learning - Proceedings from the 2022 Lund University Conference on Teaching and Learning. - 9789172674851 - 9789172674844 ; , s. 109-118
  • Konferensbidrag (refereegranskat)abstract
    • In a seminar room at LUX, one of the buildings of the Joint Faculties of Humanities and Theology, a group of PhD students and senior scholars are in deep concentration in front of their computers. It is pin-drop silent in the room until the alarm goes off and everyone starts moving and talking. This is the writing group, an informal and voluntary way of working together in time slots with 45 minutes of writing and a 15-minute break each hour. This collegial way of structuring the day and working together is gaining interest and the group is growing. This article describes the experiences of group participants and, with the aid of theoretical perspectives on collegiality and social learning, explains the benefits of this group for individual scholars as well as for their working environment.
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18.
  • Chew, Michelle S., et al. (författare)
  • Identification of myocardial injury using perioperative troponin surveillance in major noncardiac surgery and net benefit over the Revised Cardiac Risk Index
  • 2022
  • Ingår i: British Journal of Anaesthesia. - : Elsevier. - 0007-0912 .- 1471-6771. ; 128:1, s. 26-36
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Patients with perioperative myocardial injury are at risk of death and major adverse cardiovascular and cerebrovascular events (MACCE). The primary aim of this study was to determine optimal thresholds of preoperative and perioperative changes in high-sensitivity cardiac troponin T (hs-cTnT) to predict MACCE and mortality.METHODS: Prospective, observational, cohort study in patients ≥50 yr of age undergoing elective major noncardiac surgery at seven hospitals in Sweden. The exposures were hs-cTnT measured before and days 0-3 after surgery. Two previously published thresholds for myocardial injury and two thresholds identified using receiver operating characteristic analyses were evaluated using multivariable logistic regression models and externally validated. The weighted comparison net benefit method was applied to determine the additional value of hs-cTnT thresholds when compared with the Revised Cardiac Risk Index (RCRI). The primary outcome was a composite of 30-day all-cause mortality and MACCE.RESULTS: We included 1291 patients between April 2017 and December 2020. The primary outcome occurred in 124 patients (9.6%). Perioperative increase in hs-cTnT ≥14 ng L-1 above preoperative values provided statistically optimal model performance and was associated with the highest risk for the primary outcome (adjusted odds ratio 2.9, 95% confidence interval 1.8-4.7). Validation in an independent, external cohort confirmed these findings. A net benefit over RCRI was demonstrated across a range of clinical thresholds.CONCLUSIONS: Perioperative increases in hsTnT ≥14 ng L-1 above baseline values identifies acute perioperative myocardial injury and provides a net prognostic benefit when added to RCRI for the identification of patients at high risk of death and MACCE.CLINICAL TRIAL REGISTRATION: NCT03436238.
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19.
  • Dillner, Joakim, et al. (författare)
  • Antibodies to SARS-CoV-2 and risk of past or future sick leave
  • 2021
  • Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The extent that antibodies to SARS-CoV-2 may protect against future virus-associated disease is unknown. We invited all employees (n=15,300) at work at the Karolinska University Hospital, Stockholm, Sweden to participate in a study examining SARS-Cov-2 antibodies in relation to registered sick leave. For consenting 12,928 healthy hospital employees antibodies to SARS-CoV-2 could be determined and compared to participant sick leave records. Subjects with viral serum antibodies were not at excess risk for future sick leave (adjusted odds ratio (OR) controlling for age and sex: 0.85 [95% confidence interval (CI) (0.85 (0.43-1.68)]. By contrast, subjects with antibodies had an excess risk for sick leave in the weeks prior to testing [adjusted OR in multivariate analysis: 3.34 (2.98-3.74)]. Thus, presence of viral antibodies marks past disease and protection against excess risk of future disease. Knowledge of whether exposed subjects have had disease in the past or are at risk for future disease is essential for planning of control measures.Trial registration: First registered on 02/06/20, ClinicalTrials.gov NCT04411576.
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20.
  • Eriksson, Kimmo, et al. (författare)
  • Perceptions of the appropriate response to norm violation in 57 societies
  • 2021
  • Ingår i: Nature Communications. - : Nature Research. - 2041-1723. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Norm enforcement may be important for resolving conflicts and promoting cooperation. However, little is known about how preferred responses to norm violations vary across cultures and across domains. In a preregistered study of 57 countries (using convenience samples of 22,863 students and non-students), we measured perceptions of the appropriateness of various responses to a violation of a cooperative norm and to atypical social behaviors. Our findings highlight both cultural universals and cultural variation. We find a universal negative relation between appropriateness ratings of norm violations and appropriateness ratings of responses in the form of confrontation, social ostracism and gossip. Moreover, we find the country variation in the appropriateness of sanctions to be consistent across different norm violations but not across different sanctions. Specifically, in those countries where use of physical confrontation and social ostracism is rated as less appropriate, gossip is rated as more appropriate. Little is known about peoples preferred responses to norm violations across countries. Here, in a study of 57 countries, the authors highlight cultural similarities and differences in peoples perception of the appropriateness of norm violations.
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21.
  • Freerks, Per, et al. (författare)
  • Att utveckla gymnasieelevers förmåga att formulera, värdera och precisera naturvetenskapligt undersökningsbara frågor
  • 2018
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Tidigare forskning visar att elevers deltagande i laborationer inte självklart utvecklar förmågan till systematiskt undersökande arbete. I studien som presenteras utforskas därför hur undervisning kan bidra till att utveckla elevers förmåga att formulera naturvetenskapligt undersökningsbara frågor. Lärare från tre olika gymnasieskolor och fem ämnesdidaktiska forskare har i tre cykler tillsammans designat, implementerat och analyserat lektioner där elever engagerats i att formulera naturvetenskapligt undersökningsbara frågor. Det preliminära resultatet visar att gymnasieelever kan urskilja och diskutera flera aspekter av vad som kan känneteckna en naturvetenskapligt undersökningsbar fråga. Vidare synliggörs betydelsen av att sätta formuleringen av naturvetenskapliga frågor i relation till att också planera och genomföra en undersökning.
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22.
  • Granvik, Christoffer, et al. (författare)
  • Olfactory dysfunction as an early predictor for post-COVID condition at 1-year follow-up
  • 2024
  • Ingår i: Brain and Behavior. - : John Wiley & Sons. - 2162-3279. ; 14:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Olfactory dysfunction together with neurological and cognitive symptoms are common after COVID-19. We aimed to study whether performance on olfactory and neuropsychological tests following infection predict post-COVID condition (PCC), persisting symptoms, and reduced health-related quality of life.Methods: Both hospitalized (N = 10) and non-hospitalized individuals (N = 56) were enrolled in this prospective cohort study. Participants were evaluated 1–3 months after infection with an olfactory threshold test and neuropsychological tests, which was used as predictors of PCC. A questionnaire outlining persisting symptoms and the validated instrument EuroQol five-dimension five-level for health-related quality of life assessment were used as outcome data 1 year after infection (N = 59). Principal component analysis was used to identify relevant predictors for PCC at 1 year.Results: Objectively assessed olfactory dysfunction at 1–3 months post infection, but not subjective olfactory symptoms, predicted post-COVID condition with reduced health-related quality of life (PCC+) at 1 year. The PCC+ group scored more often below the cut off for mild cognitive impairment on the Montreal Cognitive Assessment (61.5% vs. 21.7%) and higher on the Multidimensional Fatigue Inventory-20, compared to the group without PCC+.Conclusion: Our results indicate that objectively assessed, olfactory dysfunction is a predictor for PCC+. These findings underscore the importance of objective olfactory testing. We propose that olfactory screening in the early post-acute phase of COVID-19 infection might identify individuals that are at higher risk of developing long-term health sequalae.
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23.
  • Haghighi, Mona, et al. (författare)
  • A Comparison of Rule-based Analysis with Regression Methods in Understanding the Risk Factors for Study Withdrawal in a Pediatric Study
  • 2016
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
  • Tidskriftsartikel (refereegranskat)abstract
    • Regression models are extensively used in many epidemiological studies to understand the linkage between specific outcomes of interest and their risk factors. However, regression models in general examine the average effects of the risk factors and ignore subgroups with different risk profiles. As a result, interventions are often geared towards the average member of the population, without consideration of the special health needs of different subgroups within the population. This paper demonstrates the value of using rule-based analysis methods that can identify subgroups with heterogeneous risk profiles in a population without imposing assumptions on the subgroups or method. The rules define the risk pattern of subsets of individuals by not only considering the interactions between the risk factors but also their ranges. We compared the rule-based analysis results with the results from a logistic regression model in The Environmental Determinants of Diabetes in the Young (TEDDY) study. Both methods detected a similar suite of risk factors, but the rule-based analysis was superior at detecting multiple interactions between the risk factors that characterize the subgroups. A further investigation of the particular characteristics of each subgroup may detect the special health needs of the subgroup and lead to tailored interventions.
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24.
  • Hanzén, Sarah, et al. (författare)
  • Lifespan Control by Redox-Dependent Recruitment of Chaperones to Misfolded Proteins
  • 2016
  • Ingår i: Cell. - : Elsevier BV. - 0092-8674. ; 166:1, s. 140-151
  • Tidskriftsartikel (refereegranskat)abstract
    • Caloric restriction (CR) extends the lifespan of flies, worms, and yeast by counteracting age-related oxidation of H2O2-scavenging peroxiredoxins (Prxs). Here, we show that increased dosage of the major cytosolic Prx in yeast, Tsa1, extends lifespan in an Hsp70 chaperone-dependent and CR-independent manner without increasing H2O2 scavenging or genome stability. We found that Tsa1 and Hsp70 physically interact and that hyperoxidation of Tsa1 by H2O2 is required for the recruitment of the Hsp70 chaperones and the Hsp104 disaggregase to misfolded and aggregated proteins during aging, but not heat stress. Tsa1 counteracted the accumulation of ubiquitinated aggregates during aging and the reduction of hyperoxidized Tsa1 by sulfiredoxin facilitated clearance of H2O2-generated aggregates. The data reveal a conceptually new role for H2O2 signaling in proteostasis and lifespan control and shed new light on the selective benefits endowed to eukaryotic peroxiredoxins by their reversible hyperoxidation.
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26.
  • Johansson, Torbjörn, et al. (författare)
  • Underwater noise from fairways – policies, incentives and measures to reduce the environmental impact
  • 2023
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • Undervattensbuller och dess negativa inverkan på det marina livet är ett växande miljöproblem där den vetenskapliga kunskapen ökar men effektiva åtgärder saknas.Denna rapport är resultatet av en gemensam insats av IVL Svenska Miljöinstitutet och Sjöfartsverket som adresserar denna utmaning. Motiverade av miljöhänsyn och kommande EU-lagstiftning är vår vision att Sverige ska bli det första landet som genomför nationella incitament för att minska undervattensbuller. De tekniska aspekterna av fartygsbuller under vatten är relativt välkända. I marschfart är kavitation vid propellern vanligtvis den dominerande källan till undervattensbuller, men detta gäller inte för alla fartyg. Standardiserade mätmetoder finns men är kostsamma att genomföra.Prediktionsmodeller är användbara för bullerkartläggning och uppskattningar över en hel flotta, men inte tillräckligt exakta för enskilda fartyg. Miljöpåverkan av undervattensbuller från fartyg har fått ökad vetenskaplig uppmärksamhet de senaste åren. Många studier har gjorts men dos-respons samband och trösklar för olika effekter är i stort sett okända. Beteendeeffekter, inklusive flyktreaktioner, svårigheter att undvika rovdjur och maskering av viktig kommunikation, har observerats hos ett stort antal arter vid exponering för fartygsbuller.Det finns inga nationella eller internationella bindande regler för undervattensbuller från fartyg. FN:s internationella sjöfartsorgan IMO håller för närvarande på att uppdatera sina frivilliga riktlinjer om fartygsbuller under vatten. EU inför lagstiftning om tillåtna nivåer av undervattensbuller från fartyg i miljön, som förväntas träda i kraft i medlemsländerna inom några år.Tekniska metoder för att minska undervattensbuller är kända men inte vetenskapligt validerade. Hastighetssänkningar kan minska undervattensbuller men kan medföra ökade driftskostnader för fartygsägarna. Intressenter inom reduktion av fartygs undervattensbuller finns hos fartygsägare, fartygsdesigners och teknikindustri, forskningsorgan och myndigheter.Genom intervjuer och workshops har ett nätverk av relevanta intressenter i Sverige etablerats. En intressentanalys visar att det finns ett behov av mer kunskap om fartygs undervattensbuller och dess miljöpåverkan samt dess begränsning. Farledsutformning för minskad transmission av undervattensbuller till miljön undersöks genom långtidsmätningar vid olika delar av farleden som leder till Västerås i Mälaren. Varken djup eller gir kunde påvisas ha någon effekt på det utstrålade bruset.Ett mer detaljerat försök skulle krävas för att klargöra om farledsdesign är ett genomförbart alternativ för bullerdämpning. Sex olika sätt att utforma ett ekonomiskt incitament för att minska fartygs undervattensbuller beskrivs. Det är möjligt att belöna hastighetssänkningar eller tekniska åtgärder för bullerdämpning, men det är inte utrett hur effektivt detta skulle vara.Ett incitament kan baseras på en tyst fartygsnotation från ett klassificeringssällskap, men dessa utfärdas relativt sällan. En bullerutredning kan utföras, men det kan vara svårt att identifiera de mest relevanta åtgärderna utan mätning av undervattensbuller.Skräddarsydda mätstationer vid eller nära hamninlopp kan vara ett kostnadseffektivt sätt att samla in mätdata, men noggrannheten i sådana opportunistiska mätningar skulle behöva förbättras om data ska kunna användas för ett ekonomiskt incitament.
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27.
  • Kjellström, Sofia, 1970-, et al. (författare)
  • Exploring, measuring and enhancing the coproduction of health and well-being at the national, regional and local levels through comparative case studies in Sweden and England : the 'Samskapa' research programme protocol
  • 2019
  • Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 9:7
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION:Cocreation, coproduction and codesign are advocated as effective ways of involving citizens in the design, management, provision and evaluation of health and social care services. Although numerous case studies describe the nature and level of coproduction in individual projects, there remain three significant gaps in the evidence base: (1) measures of coproduction processes and their outcomes, (2) mechanisms that enable inclusivity and reciprocity and (3) management systems and styles. By focusing on these issues, we aim to explore, enhance and measure the value of coproduction for improving the health and well-being of citizens.METHODS AND ANALYSIS:Nine ongoing coproduction projects form the core of an interactive research programme ('Samskapa') during a 6-year period (2019-2024). Six of these will take place in Sweden and three will be undertaken in England to enable knowledge exchange and cross-cultural comparison. The programme has a longitudinal case study design using both qualitative and quantitative methods. Cross-case analysis and a sensemaking process will generate relevant lessons both for those participating in the projects and researchers. Based on the findings, we will develop explanatory models and other outputs to increase the sustained value (and values) of future coproduction initiatives in these sectors.ETHICS AND DISSEMINATION:All necessary ethical approvals will be obtained from the regional Ethical Board in Sweden and from relevant authorities in England. All data and personal data will be handled in accordance with General Data Protection Regulations. Given the interactive nature of the research programme, knowledge dissemination to participants and stakeholders in the nine projects will be ongoing throughout the 6 years. External workshops-facilitated in collaboration with participating case studies and citizens-both during and at the end of the programme will provide an additional dissemination mechanism and involve health and social care practitioners, policymakers and third-sector organisations. 
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28.
  • Kurland, Sara, et al. (författare)
  • Exploring a Pool-seq-only approach for gaining population genomic insights in nonmodel species
  • 2019
  • Ingår i: Ecology and Evolution. - : Wiley. - 2045-7758. ; 9, s. 11448-11463
  • Tidskriftsartikel (refereegranskat)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.
  •  
29.
  • Liljander, Maria, et al. (författare)
  • Identification of collagen-induced arthritis loci in aged multiparous female mice.
  • 2006
  • Ingår i: Arthritis Research and Therapy. - : Springer Science and Business Media LLC. - 1478-6362 .- 1478-6354. ; 8:2, s. 45-45
  • Tidskriftsartikel (refereegranskat)abstract
    • Collagen-induced arthritis in mice is one of the most commonly used autoimmune experimental models, with many similarities to rheumatoid arthritis. Since collagen-induced arthritis is a complex polygenic disease there is a need for identification of several major disease-controlling genes. Because rheumatoid arthritis particularly affects aged women, we have in the present study identified new genetic regions critical for collagen-induced arthritis by studying aged female mice of a cross between NFR/N and B10.Q (H-2q haplotype). The mice in the present study had different reproductive histories, which did not significantly affect the onset, incidence or severity of the disease. A total of 200 female mice were used in a total genome-wide screening with 125 microsatellite markers. We found one new significant quantitative trait locus affecting the arthritis incidence, severity and day of onset on chromosome 11 (denoted Cia40), which colocalizes with a locus controlling pregnancy failure. Furthermore, a quantitative trait locus of suggestive significance associated with the incidence, severity and day of onset was identified on chromosome 1. Finally, a suggestively significant quantitative trait locus associated with collagen type II antibody titers was identified on chromosome 13. This study indicates that several gene loci control arthritis in aged multiparous females, and that at least one of these loci coincides with pregnancy failure.
  •  
30.
  • Liljander, Maria, et al. (författare)
  • Identification of Genetic Regions of Importance for Reproductive Performance in Female Mice.
  • 2006
  • Ingår i: Genetics. - : Oxford University Press (OUP). - 0016-6731 .- 1943-2631. ; 173:2, s. 901-909
  • Tidskriftsartikel (refereegranskat)abstract
    • Both environmental and genetic factors can dramatically affect reproductive performance in mice. In this study we have focused on the identification of genetic regions, quantitative trait loci (QTL), which affect the breeding capacity of female mice. We have identified polymorphic microsatellite markers for the mouse strains used and performed a genomewide scan on 237 females from a gene-segregating backcross between a high breeder and a relatively poor breeder. The high-breeder mouse strain we used is the inbred NFR/N mouse (MHC haplotype H-2q), which has extraordinary good breeding properties. The moderate breeder chosen for F(1) and N2 progeny was B10.Q, which is a genetically well-characterized MHC-congenic mouse of the H-2q haplotype. Each of the 237 females of the N2 generation was allowed to mate twice with MHC-congenic B10.RIII (H-2r) males and twice with B10.Q males. A predetermined number of phenotypes related to reproductive performance were recorded, and these included litter size, neonatal growth, and pregnancy rate. Loci controlling litter size were detected on chromosomes 1 (Fecq3) and 9 (Fecq4). The neonatal growth phenotype was affected by Fecq3 and a locus on chromosome 9 (Neogq1). On chromosome 11 two loci affecting the pregnancy rate (Pregq1 and Pregq2) were identified. Furthermore, on chromosomes 13 and 17 we found loci (Pregq3 and Pregq4) influencing the outcome of allogeneic pregnancy (allogeneic by means of MHC disparity between mother and fetuses). A locus on chromosome 1 affecting maternal body weight was also identified and has been denoted Bwq7. It is well known that reproductive performance is polygenically controlled, and the identification of the major loci in this complex process opens the possibility of investigating the natural genetic control of reproduction.
  •  
31.
  • Lindberg, Marie K, 1975, et al. (författare)
  • Estrogen receptor alpha, but not estrogen receptor beta, is involved in the regulation of the OPG/RANKL (osteoprotegerin/receptor activator of NF-kappa B ligand) ratio and serum interleukin-6 in male mice.
  • 2001
  • Ingår i: The Journal of endocrinology. - : Bioscientifica. - 0022-0795 .- 1479-6805. ; 171:3, s. 425-33
  • Tidskriftsartikel (refereegranskat)abstract
    • Estrogens are important for the male skeleton. Osteoprotegerin (OPG), receptor activator of NF-kappa B ligand (RANKL), interleukin-6 (IL-6), IL-1 and tumor necrosis factor alpha (TNFalpha) have been suggested to be involved in the skeletal effects of estrogen. We treated orchidectomized mice with estradiol for 2 weeks and observed a 143% increase in the trabecular bone mineral density of the distal metaphysis of femur that was associated with a decreased OPG/RANKL mRNA ratio in vertebral bone. A similar decreased OPG/RANKL ratio was also seen after estrogen treatment of ovariectomized female mice. The effect of estrogen receptor (ER) inactivation on the OPG/RANKL ratio was dissected by using intact male mice lacking ER alpha (ERKO), ER beta (BERKO) or both receptors (DERKO). The expression of OPG was increased in ERKO and DERKO but not in BERKO male mice, resulting in an increased OPG/RANKL ratio. Furthermore, serum levels of IL-6 and tartrate-resistant acid phosphatase 5b (TRAP 5b) were decreased in ERKO and DERKO, but not in BERKO male mice. These results demonstrate that ER alpha, but not ER beta, is involved in the regulation of the vertebral OPG/RANKL ratio, serum levels of IL-6 and TRAP 5b in male mice.
  •  
32.
  • Lindberg, Marie K, 1975, et al. (författare)
  • Estrogen receptor specificity for the effects of estrogen in ovariectomized mice.
  • 2002
  • Ingår i: The Journal of endocrinology. - : Bioscientifica. - 0022-0795 .- 1479-6805. ; 174:2, s. 167-78
  • Tidskriftsartikel (refereegranskat)abstract
    • Estrogen exerts a variety of important physiological effects, which have been suggested to be mediated via the two known estrogen receptors (ERs), alpha and beta. Three-month-old ovariectomized mice, lacking one or both of the two estrogen receptors, were given estrogen subcutaneously (2.3 micro g/mouse per day) and the effects on different estrogen-responsive parameters, including skeletal effects, were studied. We found that estrogen increased the cortical bone dimensions in both wild-type (WT) and double ER knockout (DERKO) mice. DNA microarray analysis was performed to characterize this effect on cortical bone and it identified four genes that were regulated by estrogen in both WT and DERKO mice. The effect of estrogen on cortical bone in DERKO mice might either be due to remaining ERalpha activity or represent an ERalpha/ERbeta-independent effect. Other effects of estrogen, such as increased trabecular bone mineral density, thymic atrophy, fat reduction and increased uterine weight, were mainly ERalpha mediated.
  •  
33.
  • Ljotsson, Brjann, et al. (författare)
  • Internet-Delivered Exposure-Based Treatment vs. Stress Management for Irritable Bowel Syndrome : A Randomized Trial
  • 2011
  • Ingår i: American Journal of Gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 0002-9270 .- 1572-0241. ; 106:8, s. 1481-1491
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: Our research group has developed an internet-delivered cognitive behavioral treatment (ICBT) for irritable bowel syndrome (IBS). We compared ICBT with internet-delivered stress management (ISM) for IBS to assess whether the effects of ICBT are specific. METHODS: This was a randomized controlled trial, including 195 self-referred participants diagnosed with IBS. The treatment interventions lasted for 10 weeks and included an online therapist contact. The ICBT emphasized acceptance of symptoms through exposure to IBS symptoms and related negative feelings. The ICBT also included mindfulness training. The ISM emphasized symptom control through relaxation techniques, dietary adjustments, and problem-solving skills. Severity of IBS symptoms was measured with the gastrointestinal symptom rating scale-IBS version (GSRS-IBS). Credibility of the treatments and expectancy of improvement were assessed with the treatment credibility scale. The participants' perceived therapeutic alliance with their online therapist was measured with the working alliance inventory. RESULTS: At post-treatment and 6-month follow-up, 192 (99%) and 169 (87%) participants returned data, respectively. At post-treatment and 6-month follow-up, we found significant differences on the GSRS-IBS, favoring ICBT. The difference on GSRS-IBS scores was 4.8 (95% confidence interval (CI): 1.2-8.4) at post-treatment and 5.9 (95% CI: 1.9-9.9) at 6-month follow-up. There were no significant differences on the treatment credibility scale or the working alliance inventory between the groups. CONCLUSIONS: Internet-delivered CBT has specific effects that cannot be attributed only to treatment credibility, expectancy of improvement, therapeutic alliance, or attention. Furthermore, a treatment based on exposure exercises specifically tailored for IBS may be a better treatment option than general stress and symptom management for IBS patients. ICBT is a promising treatment modality for IBS as it can be offered to IBS patients in much larger scale than conventional psychological treatments.
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34.
  • Malyshev, Dmitry, et al. (författare)
  • Mode of action of Disinfection chemicals  on the bacterial spore structure and their Raman spectra
  • 2021
  • Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 93:6, s. 3146-3153
  • Tidskriftsartikel (refereegranskat)abstract
    • Contamination of toxic spore-forming bacteria is problematic since spores can survive a plethora of disinfection chemicals and it is hard to rapidly detect if the disinfection chemical has inactivated the spores. Thus, robust decontamination strategies and reliable detection methods to identify dead from viable spores are critical. In this work, we investigate the chemical changes of Bacillus thuringiensis spores treated with sporicidal agents such as chlorine dioxide, peracetic acid, and sodium hypochlorite using laser tweezers Raman spectroscopy. We also image treated spores using SEM and TEM to verify if we can correlate structural changes in the spores with changes to their Raman spectra. We found that over 30 min, chlorine dioxide did not change the Raman spectrum or the spore structure, peracetic acid showed a time-dependent decrease in the characteristic DNA/DPA peaks and ∼20% of the spores were degraded and collapsed, and spores treated with sodium hypochlorite showed an abrupt drop in DNA and DPA peaks within 20 min and some structural damage to the exosporium. Structural changes appeared in spores after 10 min, compared to the inactivation time of the spores, which is less than a minute. We conclude that vibrational spectroscopy provides powerful means to detect changes in spores but it might be problematic to identify if spores are live or dead after a decontamination procedure.
  •  
35.
  • Markljung, Ellen, et al. (författare)
  • ZBED6, a novel transcription factor derived from a domesticated DNA transposon regulates IGF2 expression and muscle growth
  • 2009
  • Ingår i: PLoS biology. - : Public Library of Science (PLoS). - 1544-9173 .- 1545-7885. ; 7:12, s. e1000256-
  • Tidskriftsartikel (refereegranskat)abstract
    • A single nucleotide substitution in intron 3 of IGF2 in pigs abrogates a binding site for a repressor and leads to a 3-fold up-regulation of IGF2 in skeletal muscle. The mutation has major effects on muscle growth, size of the heart, and fat deposition. Here, we have identified the repressor and find that the protein, named ZBED6, is previously unknown, specific for placental mammals, and derived from an exapted DNA transposon. Silencing of Zbed6 in mouse C2C12 myoblasts affected Igf2 expression, cell proliferation, wound healing, and myotube formation. Chromatin immunoprecipitation (ChIP) sequencing using C2C12 cells identified about 2,500 ZBED6 binding sites in the genome, and the deduced consensus motif gave a perfect match with the established binding site in Igf2. Genes associated with ZBED6 binding sites showed a highly significant enrichment for certain Gene Ontology classifications, including development and transcriptional regulation. The phenotypic effects in mutant pigs and ZBED6-silenced C2C12 myoblasts, the extreme sequence conservation, its nucleolar localization, the broad tissue distribution, and the many target genes with essential biological functions suggest that ZBED6 is an important transcription factor in placental mammals, affecting development, cell proliferation, and growth.
  •  
36.
  • Napoleone, Antonino, et al. (författare)
  • Fed-batch production assessment of a tetravalent bispecific antibody : A case study on piggyBac stably transfected HEK293 cells
  • 2021
  • Ingår i: New Biotechnology. - : Elsevier BV. - 1871-6784 .- 1876-4347. ; 65, s. 9-19
  • Tidskriftsartikel (refereegranskat)abstract
    • The transition from preclinical biological drug development into clinical trials requires an efficient upscaling process. In this context, bispecific antibody drugs are particularly challenging due to their propensity to form aggregates and generally produce low titers. Here, the upscaling process for a tetravalent bispecific antibody expressed by a piggyBac transposon-mediated stable HEK293 cell pool has been evaluated. The project was performed as a case study at Testa Center, a non-GMP facility for scale-up testing of biologics in Sweden, and encompassed media adaptation strategies, fed-batch optimization and a novel antibody purification technology. The cell pool was adapted to different culture media for evaluation in terms of cell viability and titers compared to its original Expi293 Expression Medium. These parameters were assessed in both sequential stepwise adaption and direct media exchanges. By this, a more affordable medium was identified that did not require stepwise adaptation and with similar titers and viability as in the Expi293 Expression Medium. Fed-batch optimizations resulted in culture densities reaching up to 20 x 106 viable cells/mL with over 90 % viability 12 days postinoculum, and antibody titers three times higher than corresponding batch cultures. By implementing a novel high-speed protein A fiber technology (Fibro PrismA) with a capture residence time of only 7.5 s, 8 L of supernatant could be purified in 4.5 h without compromising the purity, structural integrity and function of the bispecific antibody. Results from this study related to medium adaptation and design of fed-batch protocols will be highly beneficial during the forthcoming scale-up of this therapeutic antibody.
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37.
  • Nestor, David, 1992-, et al. (författare)
  • Early prediction of blood stream infection in a prospectively collected cohort
  • 2021
  • Ingår i: BMC Infectious Diseases. - : BioMed Central (BMC). - 1471-2334. ; 21:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Blood stream infection (BSI) and sepsis are serious clinical conditions and identification of the disease-causing pathogen is important for patient management. The RISE (Rapid Identification of SEpsis) study was carried out to collect a cohort allowing high-quality studies on different aspects of BSI and sepsis. The aim of this study was to identify patients at high risk for BSI who might benefit most from new, faster, etiological testing using neutrophil to lymphocyte count ratio (NLCR) and Shapiro score.METHODS: Adult patients (≥ 18 years) presenting at the emergency department (ED) with suspected BSI were prospectively included between 2014 and 2016 at Örebro University Hospital. Besides extra blood sampling, all study patients were treated according to ED routines. Electronic patient charts were retrospectively reviewed. A modified Shapiro score (MSS) and NLCR were extracted and compiled. Continuous score variables were analysed with area under receiver operator characteristics curves (AUC) to evaluate the ability of BSI prediction.RESULTS: The final cohort consisted of 484 patients where 84 (17%) had positive blood culture judged clinically significant. At optimal cut-offs, MSS (≥3 points) and NLCR (> 12) showed equal ability to predict BSI in the whole cohort (AUC 0.71/0.74; sensitivity 69%/67%; specificity 64%/68% respectively) and in a subgroup of 155 patients fulfilling Sepsis-3 criteria (AUC 0.71/0.66; sensitivity 81%/65%; specificity 46%/57% respectively). In BSI cases only predicted by NLCR> 12 the abundance of Gram-negative to Gram-positive pathogens (n = 13 to n = 4) differed significantly from those only predicted by MSS ≥3 p (n = 7 to n = 12 respectively) (p < 0.05).CONCLUSIONS: MSS and NLCR predicted BSI in the RISE cohort with similar cut-offs as shown in previous studies. Combining the MSS and NLCR did not increase the predictive performance. Differences in BSI prediction between MSS and NLCR regarding etiology need further evaluation.
  •  
38.
  • Niles, Andrea N., et al. (författare)
  • Internet-based cognitive behavior therapy for depression, social anxiety disorder, and panic disorder : Effectiveness and predictors of response in a teaching clinic
  • 2021
  • Ingår i: Behaviour Research and Therapy. - : Elsevier BV. - 0005-7967 .- 1873-622X. ; 136
  • Tidskriftsartikel (refereegranskat)abstract
    • Though therapist-guided Internet-based cognitive behavior therapy (ICBT) appears to be efficacious for depression, social anxiety disorder, and panic disorder, relatively little is known about real-world settings and predictors of treatment effects derived from cognitive-behavioral theory. We examined treatment effectiveness and predictors of improvement in a prospective cohort study where patients took part in 10 weeks of ICBT for depression (n = 114), social anxiety disorder (n = 150), or panic disorder (n = 106) at a teaching clinic. Patients self-reported symptoms before, during, and after treatment. Effect sizes were large for improvement in the primary symptom domain of each treatment group: depression (d = 1.48), social anxiety disorder (d = 1.01), and panic disorder (d = 1.15). In ICBT for depression, having no previous experience of psychological treatment (r = 0.21), and more frequent baseline negative automatic thoughts (r = 0.20) predicted larger improvement. In ICBT for panic disorder, having more baseline safety behaviors (r = 0.25) predicted larger improvement. Predictors remained significant when baseline symptoms were included in the statistical models. We conclude that ICBT can be effective in a real-world teaching clinic, and that patients with greater deficits at baseline benefit the most.
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39.
  • Nordin, Steven, et al. (författare)
  • Impact of Health-Risk Perception on Odor Perception and Cognitive Performance
  • 2013
  • Ingår i: Chemosensory Perception. - : Springer Science and Business Media LLC. - 1936-5802 .- 1936-5810. ; 6:4, s. 190-197
  • Tidskriftsartikel (refereegranskat)abstract
    • Indications of adverse effects of nontoxic malodorous chemical exposure on work performance and safety and the role of health-risk perception on odor perception motivated the present study of the impact of health-risk perception on odor perception and cognitive performance. Healthy young adults were informed that they were to be exposed to an odorous substance that is either potentially health-enhancing (positive information bias, n = 24) or hazardous (negative information bias, n = 25). The two groups, screened for loss in odor-detection sensitivity, were matched for age, sex, chemical intolerance, and negative affectivity. During each of 14 trials of exposure to 433 mg/m(3) of n-butanol, the participants rated the intensity and valence of odor perception and performed a cognitive task that taxed working memory and attention. The results showed that the negative-bias group rated the odor perception as more unpleasant than did the positive-bias group during the entire session, but significantly more unpleasant only during the first half of the session. The negative-bias group was also found to perform significantly poorer on the cognitive task during both halves of the session. No effect of information bias was found on perceived odor intensity. The results provide experimental support for the hypotheses that belief that exposure to an odorous chemical is hazardous contributes to the odor perception being more unpleasant and to poorer cognitive performance.
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40.
  • Padra, Médea, 1986, et al. (författare)
  • Increased MUC1 plus a larger quantity and complex size for MUC5AC in the peripheral airway lumen of long-term tobacco smokers
  • 2020
  • Ingår i: Clinical Science. - : Portland Press Ltd.. - 0143-5221 .- 1470-8736. ; 134:10, s. 1107-1125
  • Tidskriftsartikel (refereegranskat)abstract
    • There is little information on mucins versus potential regulatory factors in the peripheral airway lumen of long-term smokers with (LTS+) and without (LTS-) chronic obstructive pulmonary disease (COPD). We explored these matters in bronchoalveolar lavage (BAL) samples from two study materials, both including LTS+ and LTS- with a very similar historic exposure to tobacco smoke, and healthy non-smokers (HNSs; n=4-20/group). Utilizing slot blot and immunodetection of processed (filtered and centrifuged), as well as unprocessed BAL samples from one of the materials, we compared the quantity and fraction of large complexes of mucins. All LTS displayed an enhanced (median) level of MUC5AC compared with HNS. LTS- displayed a higher level of large MUC5AC complexes than HNS while LTS+ displayed a similar trend. In all LTS, total MUC5AC correlated with blood leukocytes, BAL neutrophil elastase and net gelatinase activity. Large mucin complexes accounted for most MUC5B, without clear group differences. In all LTS, total MUC5B correlated with total MUC5AC and local bacteria. In the same groups, large MUC5B complexes correlated with serum cotinine. MUC1 was increased and correlated with BAL leukocytes in all LTS whereas MUC2 was very low and without clear group differences. Thus, the main part of MUC5AC and MUC5B is present as large complexes in the peripheral airway lumen and historic as well as current exposure to tobacco smoke emerge as potential regulatory factors, regardless of COPD per se. Bacteria, leukocytes and proteinases also constitute potential regulatory factors, of interest for future therapeutic strategies.
  •  
41.
  • Padra, Médea, 1986, et al. (författare)
  • Mucin Binding to Moraxella catarrhalis During Airway Inflammation is Dependent on Sialic Acid.
  • 2021
  • Ingår i: American journal of respiratory cell and molecular biology. - 1535-4989. ; 65:6, s. 593-602
  • Tidskriftsartikel (refereegranskat)abstract
    • Chronic obstructive pulmonary disease (COPD) is associated with colonization by bacterial pathogens and repeated airway infections, leading to exacerbations and impaired lung function. The highly glycosylated mucins in the mucus lining the airways are an important part of the host defense against pathogens. However, mucus accumulation can contribute to COPD pathology. Here, we examined whether inflammation is associated with glycosylation changes that affect interactions between airway mucins and pathogens. We isolated mucins from lower airway samples (LAS, n=4-9) from long-term smokers with and without COPD and from never-smokers. The most abundant terminal glycan moiety was N-acetylneuraminic acid (Neu5Ac) among smokers with and without COPD and N-acetyl-hexoseamine among never-smokers. Moraxella catarrhalis bound to MUC5 mucins from smokers with and without COPD. M. catarrhalis binding correlated with inflammatory parameters and Neu5Ac content. M. catarrhalis binding was abolished by enzymatic removal of Neu5Ac. Furthermore, M. catarrhalis bound to α2-6 sialyl-lactose suggesting that α2-6 sialic acid contributes to M. catarrhalis binding to mucins. Further, we detected more M. catarrhalis binding to mucins from patients with pneumonia than to those from control subjects (n=8-13) and this binding correlated with C-reactive protein and Neu5Ac levels. These results suggest a key role of inflammation induced Neu5Ac in adhesion of M. catarrhalis to airway mucins. Inflammation induced ability of MUC5 mucins to bind M. catarrhalis is likely a host defense mechanism in the healthy lung, although it cannot be excluded that impaired mucociliary clearance limits the effectiveness of this defense in COPD patients.
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42.
  • Persson, Josefine, 1980, et al. (författare)
  • Stratification of COVID-19 patients based on quantitative immune-related gene expression in whole blood.
  • 2022
  • Ingår i: Molecular immunology. - : Elsevier BV. - 1872-9142 .- 0161-5890. ; 145, s. 17-26
  • Tidskriftsartikel (refereegranskat)abstract
    • The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes mild symptoms in the majority of infected individuals, yet in some cases it leads to a life-threatening condition. Determination of early predictive biomarkers enabling risk stratification for coronavirus disease 2019 (COVID-19) patients can inform treatment and intervention strategies. Herein, we analyzed whole blood samples obtained from individuals infected with SARS-CoV-2, varying from mild to critical symptoms, approximately one week after symptom onset. In order to identify blood-specific markers of disease severity status, a targeted expression analysis of 143 immune-related genes was carried out by dual-color reverse transcriptase multiplex ligation-dependent probe amplification (dcRT-MLPA). The clinically well-defined subgroups of COVID-19 patients were compared with healthy controls. The transcriptional profile of the critically ill patients clearly separated from that of healthy individuals. Moreover, the number of differentially expressed genes increased by severity of COVID-19. It was also found that critically ill patients can be distinguished by reduced peripheral blood expression of several genes, which most likely reflects the lower lymphocyte counts. There was a notable predominance of IFN-associated gene expression in all subgroups of COVID-19, which was most profound in critically ill patients. Interestingly, the gene encoding one of the main TNF-receptors, TNFRS1A, had selectively lower expression in mild COVID-19 cases. This report provides added value in understanding COVID-19 disease, and shows potential of determining early immune transcript signatures in the blood of patients with different disease severity. These results can guide further explorations to uncover mechanisms underlying immunity and immunopathology in COVID-19.
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43.
  •  
44.
  • Sampson, Joshua N., et al. (författare)
  • Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
  • 2015
  • Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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45.
  • Sjögren, Erik, et al. (författare)
  • Assessment of Free Drug Concentration in Cyclodextrin Formulations Is Essential to Determine Drug Potency in Functional In Vitro Assays
  • 2016
  • Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549 .- 1520-6017. ; 105:9, s. 2913-2920
  • Tidskriftsartikel (refereegranskat)abstract
    • Cyclodextrins (CD) have the ability to form inclusion complexes with drugs and can be used as excipients to enhance solubility of poorly soluble drugs. To make accurate estimations of the potency of the drug, knowledge of the free drug concentration is important. The aim of this study was to evaluate the applicability of calculated free drug concentrations toward response measurements in a transient receptor potential vanilloid receptor-1 cell-based in vitro assay. This included accounting for potential competitive CD binding of 2 transient receptor potential vanilloid receptor-1 active entities: 1 antagonist, and 1 agonist (capsaicin). Solubility of the CD-drug complexes was measured, and the ligand to substrate affinity in CD formulations was determined according to the phase-solubility technique. The total concentration of antagonist, agonist, CD, and the binding constants between ligands and CD were used to calculate the free concentration of CD ligands. For capsaicin and 2 of the 3 investigated model drugs, the calculated free drug concentration was consistent with the experimental in vitro data while it was overestimated for one of the compounds. In conclusion, the suggested approach can be used to calculate free drug concentration and competitive binding in CD formulations for the application of cell-based drug functionality assays. (C) 2016 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.
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46.
  • Thorsson, Sofia, 1972, et al. (författare)
  • Adapting cities to climate induced risks - a coordinated approach
  • 2011
  • Ingår i: Climate and Construction. ; , s. 173-180
  • Konferensbidrag (refereegranskat)abstract
    • In an era of changing climate there is a growing interest to create resilient cities, which can absorb and manage climate induce risks, such as heat waves and natural hazards (flooding, landslides etc). The increased frequencies and magnitudes of these climate hazards are expected to have a major impact on society. In order to maintain risks to society at acceptable levels, measures to reduce the vulnerability need to be taken. Such measures may, however, have significant non-expected and non-wanted impacts elsewhere on society. The need of holistic planning strategies becomes apparent. The overall aim of this new transdisciplinary research project is to develop knowledge and methods that enable an integrated assessment of the impact of climate induced risks on society. The free-port area in Gothenburg, Sweden, will has been selected for a case study that will sharpen both the individual scientific methods and the interdisciplinary and intersectoral cooperation and integration. The project brings together experts in urban climate, atmospheric science, natural risk assessment, stratified vulnerability and multi-criteria analyses with local city planners in an integrated research effort. Strategic plans for climate adaptation will be developed and proposed. The stakeholder involvement will promote transfer of knowledge and applicability of results.
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47.
  • Westlund, Malin, et al. (författare)
  • Rätt att bo kvar : en handbok i organisering mot hyreshöjningar och gentrifiering
  • 2016
  • Bok (övrigt vetenskapligt/konstnärligt)abstract
    • Det här är en handbok som skrivits för att användas praktiskt i kampen om hyresrättens framtid. Boken har växt fram ur gemensamma erfarenheter av att ta strid mot renoveringar med höga hyreshöjningar som följd. Det har gett oss både kunskaper om lokal organisering och en övertygelse om vikten av att hyresgäster ska ha rätt till att påverka framtiden i de bostadsområden de bor i. De senaste åren har vi kunnat se hur hyreslägenheter renoveras med omfattande hyreshöjningar som följd. Konsekvenserna har blivit att många hyresgäster har tvingats flytta, ibland från bostadsområden de bott i under lång tid, då de inte längre har råd att betala hyran. Om inte hyresgäster går samman och kräver sina rättigheter kommer inget förändras och flera tusentals människor tvingas flytta. Den här handboken ska användas som ett praktiskt verktyg för lokal organisering. Vi som har gjort den här boken är engagerade i olika rörelser, några av oss är också forskare med inriktning mot bostad- spolitik och stadsutveckling. Boken har tillkommit genom en kollektiv process, där många varit inblandade för att bidra med sina erfarenheter och perspektiv. En lista med alla medverkande inklusive de rörelser som står bakom den här boken finns lägst bak.
  •  
48.
  • Wibom, Carl, et al. (författare)
  • DNA-repair gene variants are associated with glioblastoma survival
  • 2012
  • Ingår i: Acta Oncologica. - : Informa Healthcare. - 0284-186X .- 1651-226X. ; 51:3, s. 325-332
  • Tidskriftsartikel (refereegranskat)abstract
    • Patient outcome from glioma may be influenced by germline variation. Considering the importance of DNA repair in cancer biology as well as in response to treatment, we studied the relationship between 1458 SNPs, which captured the majority of the common genetic variation in 136 DNA repair genes, in 138 glioblastoma samples from Sweden and Denmark. We confirmed our findings in an independent cohort of 121 glioblastoma patients from the UK. Our analysis revealed nine SNPs annotating MSH2, RAD51L1 and RECQL4 that were significantly (p < 0.05) associated with glioblastoma survival.
  •  
49.
  •  
50.
  • 2018
  • Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 58:9
  • Tidskriftsartikel (refereegranskat)
  •  
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