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1.
  • Allard, Christina, et al. (författare)
  • Rasbiologiskt språkbruk i statens rättsprocess mot sameby : DN Debatt 2015-06-11
  • 2015
  • Annan publikation (populärvet., debatt m.m.)abstract
    • Statens hantering av forskningsresultat i rättsprocessen med Girjas sameby utgör ett hot mot Sverige som rättsstat och kunskapsnation. Åratal av svensk och internationell forskning underkänns och man använder ett språkbruk som skulle kunna vara hämtat från rasbiologins tid. Nu måste staten ta sitt ansvar och börja agera som en demokratisk rättsstat, skriver 59 forskare.
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3.
  • Belfrage, Anna Karin, et al. (författare)
  • Discovery of pyrazinone based compounds that potently inhibit the drug resistant enzyme variant R155K of the hepatitis C virus NS3 protease
  • 2016
  • Ingår i: Bioorganic & Medicinal Chemistry. - : Elsevier BV. - 0968-0896 .- 1464-3391. ; 24:12, s. 2603-2620
  • Tidskriftsartikel (refereegranskat)abstract
    • Herein, we present the design and synthesis of 2(1H)-pyrazinone based HCV NS3 protease inhibitors with variations in the C-terminus. Biochemical evaluation was performed using genotype 1a, both the wildtype and the drug resistant enzyme variant, R155K. Surprisingly, compounds without an acidic sulfonamide retained good inhibition, challenging our previous molecular docking model. Moreover, selected compounds in this series showed nanomolar potency against R155K NS3 protease; which generally confer resistance to all HCV NS3 protease inhibitors approved or in clinical trials. These results further strengthen the potential of this novel substance class, being very different to the approved drugs and clinical candidates, in the development of inhibitors less sensitive to drug resistance.
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4.
  • Bergman, Lina, et al. (författare)
  • Multi-Fetal Pregnancy, Preeclampsia, and Long-Term Cardiovascular Disease
  • 2020
  • Ingår i: Hypertension. - 0194-911X .- 1524-4563. ; 76:1, s. 167-175
  • Tidskriftsartikel (refereegranskat)abstract
    • This Swedish register-based cohort study determined the separate and joint contribution of preeclampsia and multi-fetal pregnancy on a woman's risk of cardiovascular disease (CVD) later in life. The study included 892 425 first deliveries between 1973 and 2010 of women born 1950 until 1971, identified in the Swedish Medical Birth Register. A composite outcome of CVD was retrieved through linkage with the National Patient and Cause of Death Registers. Cox proportional hazard regression was used to assess the risk of CVD in women who had preeclampsia in a singleton or multi-fetal pregnancy, adjusting for potential confounders, and presented as adjusted hazard ratios. Compared with women who had a singleton pregnancy without preeclampsia (the referent group), women with preeclampsia in a singleton pregnancy had an increased risk of CVD (adjusted hazard ratio 1.75 [95% CI, 1.64-1.86]). Women who had a multi-fetal pregnancy without or with preeclampsia did not have an increased risk of future CVD (adjusted hazard ratios 0.94 [95% CI, 0.79-1.10] and 1.25 [95% CI, 0.83-1.86], respectively). As opposed to preeclampsia in a first singleton pregnancy, preeclampsia in a first multi-fetal pregnancy was not associated with increased risk of future CVD. This may support the theory that preeclampsia in multi-fetal pregnancies more often occurs as a result of the larger pregnancy-related burden on the maternal cardiovascular system and excessive placenta-shed inflammatory factors, rather than the woman's underlying cardiovascular phenotype.
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5.
  • Sederholm Lawesson, Sofia, 1973-, et al. (författare)
  • Association Between History of Adverse Pregnancy Outcomes and Coronary Artery Disease Assessed by Coronary Computed Tomography Angiography.
  • 2023
  • Ingår i: JAMA. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 329:5, s. 393-404
  • Tidskriftsartikel (refereegranskat)abstract
    • Adverse pregnancy outcomes are recognized risk enhancers for cardiovascular disease, but the prevalence of subclinical coronary atherosclerosis after these conditions is unknown.To assess associations between history of adverse pregnancy outcomes and coronary artery disease assessed by coronary computed tomography angiography screening.Cross-sectional study of a population-based cohort of women in Sweden (n=10528) with 1 or more deliveries in 1973 or later, ascertained via the Swedish National Medical Birth Register, who subsequently participated in the Swedish Cardiopulmonary Bioimage Study at age 50 to 65 (median, 57.3) years in 2013-2018. Delivery data were prospectively collected.Adverse pregnancy outcomes, including preeclampsia, gestational hypertension, preterm delivery, small-for-gestational-age infant, and gestational diabetes. The reference category included women with no history of these exposures.Coronary computed tomography angiography indexes, including any coronary atherosclerosis, significant stenosis, noncalcified plaque, segment involvement score of 4 or greater, and coronary artery calcium score greater than 100.A median 29.6 (IQR, 25.0-34.9) years after first registered delivery, 18.9% of women had a history of adverse pregnancy outcomes, with specific pregnancy histories ranging from 1.4% (gestational diabetes) to 9.5% (preterm delivery). The prevalence of any coronary atherosclerosis in women with a history of any adverse pregnancy outcome was 32.1% (95% CI, 30.0%-34.2%), which was significantly higher (prevalence difference, 3.8% [95% CI, 1.6%-6.1%]; prevalence ratio, 1.14 [95% CI, 1.06-1.22]) compared with reference women. History of gestational hypertension and preeclampsia were both significantly associated with higher and similar prevalence of all outcome indexes. For preeclampsia, the highest prevalence difference was observed for any coronary atherosclerosis (prevalence difference, 8.0% [95% CI, 3.7%-12.3%]; prevalence ratio, 1.28 [95% CI, 1.14-1.45]), and the highest prevalence ratio was observed for significant stenosis (prevalence difference, 3.1% [95% CI, 1.1%-5.1%]; prevalence ratio, 2.46 [95% CI, 1.65-3.67]). In adjusted models, odds ratios for preeclampsia ranged from 1.31 (95% CI, 1.07-1.61) for any coronary atherosclerosis to 2.21 (95% CI, 1.42-3.44) for significant stenosis. Similar associations were observed for history of preeclampsia or gestational hypertension among women with low predicted cardiovascular risk.Among Swedish women undergoing coronary computed tomography angiography screening, there was a statistically significant association between history of adverse pregnancy outcomes and image-identified coronary artery disease, including among women estimated to be at low cardiovascular disease risk. Further research is needed to understand the clinical importance of these associations.
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6.
  • Ahlbeck Bergendahl, Ida, et al. (författare)
  • Fisk- och skaldjursbestånd i hav och sötvatten 2016 : Resursöversikt
  • 2016
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • I rapporten kan du ta del av bedömningen som görs av situationen för bestånd som regleras inom ramen för EU:s gemensamma fiskeripolitik (GFP). Bedömningarna baseras på det forskningssamarbete och den rådgivning som sker inom det Internationella Havsforskningsrådet (ICES).De bestånd som förvaltas nationellt baseras på de biologiska underlagen, och rådgivningen i huvudsak på den forskning och övervakning samt analys som bedrivs av Institutionen för akvatiska resurser vid Sveriges lantbruksuniversitet (SLU Aqua) samt yrkesfiskets rapportering.Rapporten omfattar 41 fiskarter uppdelade i olika bestånd, samt sju skal- och blötdjursarter.Nytt för årets upplaga är kapitlet om ekosystemtjänster. Avsnittet beskriver de fördelar människan får genom ekosystemen, till exempel hur fisk och skaldjur kommer till nytta för människan genom föda, rekreation och biologisk mångfald. Nytt för i år är också att rapportens diagram och figurer anpassats för läsare med defekt färgseende.Översikten är utarbetad av SLU Aqua på uppdrag av Havs- och vattenmyndigheten.
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7.
  • Ahlgren, Sara, et al. (författare)
  • Evaluation of maleimide derivative of DOTA for site-specific labeling of recombinant affibody molecules
  • 2008
  • Ingår i: Bioconjugate chemistry. - : American Chemical Society (ACS). - 1043-1802 .- 1520-4812. ; 19:1, s. 235-243
  • Tidskriftsartikel (refereegranskat)abstract
    • Affibody molecules are a new class of small (7 kDa) scaffold affinity proteins, which demonstrate promising properties as agents for in vivo radionuclide targeting. The Affibody scaffold is cysteine-free and therefore independent of disulfide bonds. Thus, a single thiol group can be engineered into the protein by introduction of one cysteine. Coupling of thiol-reactive bifunctional chelators can enable site-specific labeling of recombinantly produced Affibody molecules. In this study, the use of 1,4,7,10-tetraazacyclododecane-1,4,7-tris-acetic acid-10-maleimidoethylacetamide (MMA-DOTA) for 111 In-labeling of anti-HER2 Affibody molecules His 6-Z HER2:342-Cys and Z HER2:2395-Cys has been evaluated. The introduction of a cysteine residue did not affect the affinity of the proteins, which was 29 pM for His 6-Z HER2:342-Cys and 27 pM for Z HER2:2395-Cys, comparable with 22 pM for the parental Z HER2:342. MMA-DOTA was conjugated to DTT-reduced Affibody molecules with a coupling efficiency of 93% using a 1:1 molar ratio of chelator to protein. The conjugates were labeled with 111 In to a specific radioactivity of up to 7 GBq/mmol, with preserved binding for the target HER2. In vivo, the non-His-tagged variant 111 In-[MMA-DOTA-Cys61]-Z HER2:2395-Cys demonstrated appreciably lower liver uptake than its His-tag-containing counterpart. In mice bearing HER2-expressing LS174T xenografts, 111 In-[MMA-DOTA-Cys61]-Z HER2:2395-Cys showed specific and rapid tumor localization, and rapid clearance from blood and nonspecific compartments, leading to a tumor-to-blood-ratio of 18 +/- 8 already 1 h p.i. Four hours p.i., the tumor-to-blood ratio was 138 +/- 8. Xenografts were clearly visualized already 1 h p.i.
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8.
  • Allard, Christina, et al. (författare)
  • Rasbiologiskt språkbruk i statens rättsprocess mot sameby
  • 2015
  • Ingår i: Dagens Nyheter. - 1101-2447.
  • Tidskriftsartikel (populärvet., debatt m.m.)abstract
    • Statens hantering av forskningsresultat i rättsprocessen med Girjas sameby utgör ett hot mot Sverige som rättsstat och kunskapsnation. Åratal av svensk och internationell forskning underkänns och man använder ett språkbruk som skulle kunna vara hämtat från rasbiologins tid. Nu måste staten ta sitt ansvar och börja agera som en demokratisk rättsstat, skriver 59 forskare.
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9.
  • Alsterholm, Mikael, 1977, et al. (författare)
  • Establishment and utility of SwedAD : a nationwide Swedish registry for patients with atopic dermatitis receiving systemic pharmacotherapy
  • 2023
  • Ingår i: Acta Dermato-Venereologica. - : Medical Journals Sweden AB. - 0001-5555 .- 1651-2057. ; 103
  • Tidskriftsartikel (refereegranskat)abstract
    • SwedAD, a Swedish nationwide registry for patients with atopic dermatitis receiving systemic pharmacotherapy, was launched on 1 September 2019. We describe here the establishment of a user-friendly registry to the benefit of patients with atopic dermatitis. By 5 November 2022, 38 clinics had recorded 931 treatment episodes in 850 patients with an approximate national coverage rate of 40%. Characteristics at enrolment included median Eczema Area and Severity Index (EASI) 10.2 (interquartile range 4.0, 19.4), Patient-Oriented Eczema Measure (POEM) 18.0 (10.0, 24.0), Dermatology Life Quality Index (DLQI) 11.0 (5.0, 19.0) and Peak Itch Numerical Rating Scale-11 (NRS-11) 6.0 (3.0, 8.0). At 3 months, median EASI was 3.2 (1.0, 7.3) and POEM, DLQI, and NRS-11 were improved. Regional coverage varied, reflecting the distribution of dermatologists, the ratio of public to private healthcare, and difficulties in recruiting certain clinics. This study highlights the importance of a nationwide registry when managing systemic pharmacotherapy of atopic dermatitis.
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10.
  • Altai, Mohamed, et al. (författare)
  • Preclinical evaluation of anti-HER2 Affibody molecules site-specifically labeled with In-111 using a maleimido derivative of NODAGA
  • 2012
  • Ingår i: Nuclear Medicine and Biology. - : Elsevier BV. - 0969-8051 .- 1872-9614. ; 39:4, s. 518-529
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Affibody molecules have demonstrated potential for radionuclide molecular imaging. The aim of this study was to synthesize and evaluate a maleimido derivative of the 1,4,7-triazacyclononane-l-glutaric acid-4,7-diacetic acid (NODAGA) for site-specific labeling of anti-HER2 Affibody molecule. Methods: The maleimidoethylmonoamide NODAGA (MMA-NODAGA) was synthesized and conjugated to Z(HER2:2395) Affibody molecule having a C-terminal cysteine. Labeling efficiency, binding specificity to and cell internalization by HER2-expressing cells of [In-111-MMA-NODAGA-Cys(61)]-Z(HER2:2395) were studied. Biodistribution of [In-111-MMA-NODAGA-Cys(61)]-Z(HER2:2395) and [In-111-MMA-DOTA-Cys(61)]-Z(HER2:2395) was compared in mice. Results: The affinity of [MMA-NODAGA-Cys(61)]-Z(HER2:2395) binding to HER2 was 67 pM. The In-1111-labeling yield was 99.6%+/- 0.5% after 30 min at 60 degrees C. [In-111-MMA-NODAGA-Cys(61)]-Z(HER2:2395) bound specifically to HER2-expressing cells in vitro and in vivo. Tumor uptake of [In-111-MMA-NODAGA-Cys(61)]-ZHER(2:2395) in mice bearing DU-145 xenografts (4.7%+/- 0.8% ID/g) was lower than uptake of [In-111-MMA-DOTA-Cys(61)]-Z(HER2:2395) (7.5%+/- 1.6% ID/g). However, tumor-to-organ ratios were higher for [In-111-MMA-NODAGA-Cys(61)]-Z(HER2:2395) due to higher clearance rate from normal tissues. Conclusions: MMA-NODAGA is a promising chelator for site-specific labeling of targeting proteins containing unpaired cysteine. Appreciable influence of chelators on targeting properties of Affibody molecules was demonstrated.
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11.
  • Andersson, Magnus, et al. (författare)
  • Fiskbestånd och miljö i hav och sötvatten : Resurs- och miljööversikt 2012
  • 2012
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • Detta är den nionde utgåvan av den samlade översikten över fisk- och kräftdjursbeståndens status i våra vatten. Kunskap om fiskbestånden och miljön är en förutsättning för att utnyttjandet av fiskresurserna skall bli bärkraftigt. För svenska vattenområden beskrivs miljöutvecklingen i ett ekosystemsperspektiv, dels för att tydliggöra fiskens ekologiska roll och beskriva yttre miljöfaktorer som påverkar fiskbestånden, dels för att belysa fiskets effekter på miljön.Fiskbestånd och miljö i hav och sötvatten är utarbetad av Sveriges lantbruksuniversitet (SLU), Institutionen för akvatiska resurser (SLU Aqua), på uppdrag av Havs- och vattenmyndigheten. Rapporten sammanfattar utveckling och beståndsstatus för de kommersiellt viktigaste fisk- och kräftdjursarterna i våra vatten. Bedömningar och förvaltningsråd är baserade på Internationella Havsforskningsrådets (ICES) rådgivning, SLU Aquas nationella och regionala provfiskedata, samt yrkesfiskets rapportering.
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12.
  • Axelsson Linkowski, Weronika, et al. (författare)
  • Shifting Strategies between Generations in Sami Reindeer Husbandry : the Challenges of Maintaining Traditions while Adapting to a Changing Context
  • 2020
  • Ingår i: Human Ecology. - : Springer Science and Business Media LLC. - 0300-7839 .- 1572-9915. ; 48, s. 481-490
  • Tidskriftsartikel (refereegranskat)abstract
    • Many traditional pastoralist systems are greatly impacted by cumulative encroachments of other land users and by climate change. Understanding land degradation and the adaptive capacity of people who are dependent on the rangelands is an urgent priority for many areas in the world. In this research we explore how changing environmental conditions affect herding strategies on winter pastures and the role of indigenous and local traditional knowledge (ILK) in Sami reindeer husbandry. Our results indicate that traditional Sami reindeer herding strategies are still practiced, but that rapidly changing environmental circumstances are forcing herders into uncharted territories where these traditional strategies and the transmission of knowledge between generations may be of limited use. For example, rotational grazing is no longer possible as all pastures are being used, and changes in climate result in unpredictable weather patterns unknown to earlier generations.
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13.
  • Bergman, Lina, 1982, et al. (författare)
  • Study for Improving Maternal Pregnancy And Child ouTcomes (IMPACT): a study protocol for a Swedish prospective multicentre cohort study
  • 2020
  • Ingår i: BMJ Open. - : BMJ. - 2044-6055 .- 2044-6055. ; 10:9, s. e033851-e033851
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction First-trimester pregnancy risk evaluation facilitates individualised antenatal care, as well as application of preventive strategies for pre-eclampsia or birth of a small for gestational age infant. A range of early intervention strategies in pregnancies identified as high risk at the end of the first trimester has been shown to decrease the risk of preterm pre-eclampsia (<37 gestational weeks). The aim of this project is to create the Improving Maternal Pregnancy And Child ouTcomes (IMPACT) database; a nationwide database with individual patient data, including predictors recorded at the end of the first trimester and later pregnancy outcomes, to identify women at high risk of pre-eclampsia. A second aim is to link the IMPACT database to a biobank with first-trimester blood samples. Methods and analysis This is a Swedish prospective multicentre cohort study. Women are included between the 11th and 14th weeks of pregnancy. At inclusion, pre-identified predictors are retrieved by interviews and medical examinations. Blood samples are collected and stored in a biobank. Additional predictors and pregnancy outcomes are retrieved from the Swedish Pregnancy Register. Inclusion in the study began in November 2018 with a targeted sample size of 45 000 pregnancies by end of 2021. Creation of a new risk prediction model will then be developed, validated and implemented. The database and biobank will enable future research on prediction of various pregnancy-related complications. Ethics and dissemination Confidentiality aspects such as data encryption and storage comply with the General Data Protection Regulation and with ethical committee requirements. This study has been granted national ethical approval by the Swedish Ethical Review Authority (Uppsala 2018-231) and national biobank approval at Uppsala Biobank (18237 2 2018 231). Results from the current as well as future studies using information from the IMPACT database will be published in peer-reviewed journals.
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14.
  • Bjärstig, Therese, 1978-, et al. (författare)
  • Between protocol and reality : Swedish municipal comprehensive planning
  • 2018
  • Ingår i: European Planning Studies. - : Informa UK Limited. - 0965-4313 .- 1469-5944. ; 26:1, s. 35-54
  • Tidskriftsartikel (refereegranskat)abstract
    • Spatial planning using a landscape approach has been recognized as being essential for reconciling ecological, cultural and socioeconomic dimensions in sustainable development (SuD). Although embraced as a concept, there is a lack of planning tools capable of incorporating multi-level, multifunctional and multi-sectoral perspectives, especially in a rural context. The departure point in this paper is the legal requirements for municipal comprehensive planning (MCP) in Sweden and an e-mail survey about incentives, stakeholder involvement, policy integration and implementation in MCP in all 15 Swedish mountain municipalities. The purpose of this explorative study is to examine whether MCP could be a tool in planning for SuD. Results indicate a general lack of resources and a low status of MCP that affect, and even limit, stakeholder involvement, policy integration and implementation. However, legal requirements for MCP are targeted at SuD, and municipal personnel responsible for planning appreciate the potential of MCP. Therefore, there is potential to develop the MCP into an effective landscape planning tool. To accomplish this, the status of an active planning process has to be raised, the mandate of the local planning agency has to be secured, and residents and land users have to be involved throughout the planning process.
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15.
  • Bragina, Olga, et al. (författare)
  • Phase I study of 99mTc-ADAPT6, a scaffold protein-based probe for visualization of HER2 expression in breast cancer
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Radionuclide molecular imaging of human epidermal growth factor (HER2) expression may be helpful to stratify breast and gastroesophageal cancer patients for HER2-targeting therapies. ADAPTs (albumin-binding domain derived affinity proteins) are a new type of small (46-59 amino acids) proteins useful as probes for molecular imaging. The aim of this first in-human study was to evaluate biodistribution, dosimetry, and safety of HER2-specific 99mTc-ADAPT6.METHODS. Twenty-two patients with HER2-positive (n=11) or HER2-negative (n=11) primary breast cancer were intravenously injected with 385125 MBq. The injected amount of protein was either 500 μg (n=11) or 1000 μg (n=11). Planar scintigraphy followed by SPECT imaging was performed after 2, 4, 6 and 24 h. An additional cohort received a dose of 250 μg, and the planar scintigraphy followed by SPECT imaging was performed after 2 h only.RESULTS. Injection of 99mTc-ADAPT6 was well tolerated for all doses evaluated in the study, and was not associated with any adverse effects. 99mTc-ADAPT6 cleared rapidly from the blood and the majority of tissues. The normal organs with the highest accumulation were kidney, liver and lung. The effective doses were determined to 0.0090.002 and 0.0100.003 mSv/MBq when injecting protein amounts of 500 and 1000 μg, respectively. Injection of 500 μg resulted in excellent discrimination between HER2-positive and HER2-negative tumors already 2 h after injection (tumor-to-contralateral breast ratio was 3719 vs 52, p < 0.01). The tumor-to-contralateral breast ratios for HER2-positive tumors were significantly (p < 0.5) higher for the injected  mass of 500 μg than for both 250 and 1000 μg. In one patient, the imaging using 99mTc-ADAPT6 revealed three bone metastases, which were not found at the time of diagnosis by CT or 99mTcpyrophosphate bone scan. MRI imaging confirmed this finding.CONCLUSION. Injections of 99mTc-ADAPT6 are safe and associated with low absorbed and effective doses. A protein dose of 500 μg is preferable for discrimination between tumors with high and low expression of HER2. 99mTc-ADAPT6 is a promising imaging probe for the stratification of patients for HER2-targeting therapy.
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16.
  • Bragina, Olga, et al. (författare)
  • Phase I study of 99mTc-ADAPT6, a scaffold protein-based probe for visualization of HER2 expression in breast cancer
  • 2021
  • Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 62:4, s. 493-499
  • Tidskriftsartikel (refereegranskat)abstract
    • Radionuclide molecular imaging of human epidermal growth factor (HER2) expression may be helpful to stratify breast and gastroesophageal cancer patients for HER2-targeting therapies. ADAPTs (albumin-binding domain derived affinity proteins) are a new type of small (46-59 amino acids) proteins useful as probes for molecular imaging. The aim of this first-in-human study was to evaluate biodistribution, dosimetry, and safety of the HER2-specific 99mTc-ADAPT6.METHODS: Twenty-nine patients with primary breast cancerwere included. In 22 patients with HER2-positive (n = 11) or HER2-negative (n = 11) histopathology an intravenous injection with 385±125 MBq 99mTc-ADAPT6 was performed, randomized to an injected protein mass of either 500 µg (n = 11) or 1000 µg (n = 11). Planar scintigraphy followed by SPECT imaging was performed after 2, 4, 6 and 24 h. An additional cohort (n = 7) was injected with 165±29 MBq (injected protein mass 250 µg) and imaging was performed after 2 h only.RESULTS: Injections of 99mTc-ADAPT6 at all injected mass levels were well tolerated and not associated with adverse effects. 99mTc-ADAPT6 cleared rapidly from blood and most other tissues. The normal organs with the highest accumulation were kidney, liver and lung. Effective doses were 0.009±0.002 and 0.010±0.003 mSv/MBq for injected protein masses of 500 and 1000 µg, respectively. Injection of 500 µg resulted in excellent discrimination between HER2-positive and HER2-negative tumors already 2 h after injection (tumor-to-contralateral breast ratio was 37±19 vs 5±2, p<0.01). The tumor-to-contralateral breast ratios for HER2-positive tumors were significantly (p<0.05) higher for injected mass of 500 µg than for both 250 and 1000 µg.CONCLUSION: Injections of 99mTc-ADAPT6 are safe and associated with low absorbed and effective doses. Protein dose of 500 µg is preferable for discrimination between tumors with high and low expression of HER2. Further studies are justified to evaluate if 99mTc-ADAPT6 can be used as an imaging probe for stratification of patients for HER2-targeting therapy in the areas where PET imaging is not readily available.
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17.
  • Carlsson, Ylva, 1975, et al. (författare)
  • Comparing the results from a Swedish pregnancy cohort using data from three automated placental growth factor immunoassay platforms intended for first-trimester preeclampsia prediction.
  • 2023
  • Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; :8, s. 1084-1091
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: Risk evaluation for preeclampsia in early pregnancy allows identification of women at high risk. Prediction models for preeclampsia often include circulating concentrations of placental growth factor (PlGF); however, the models are usually limited to a specific PlGF method of analysis. The aim of this study was to compare three different PlGF methods of analysis in a Swedish cohort to assess their convergent validity and appropriateness for use in preeclampsia risk prediction models in the first trimester of pregnancy.MATERIAL AND METHODS: First-trimester blood samples were collected in gestational week 11+0 to 13+6 from 150 pregnant women at Uppsala University Hospital during November 2018 until November 2020. These samples were analyzed using the different PlGF methods from Perkin Elmer, Roche Diagnostics, and Thermo Fisher Scientific.RESULTS: There were strong correlations between the PlGF results obtained with the three methods, but the slopes of the correlations clearly differed from 1.0: PlGFPerkinElmer  = 0.553 (95% confidence interval [CI] 0.518-0.588) * PlGFRoche -1.112 (95% CI -2.773 to 0.550); r = 0.966, mean difference -24.6 (95% CI -26.4 to -22.8). PlGFPerkinElmer  = 0.673 (95% CI 0.618-0.729) * PlGFThermoFisher -0.199 (95% CI -2.292 to 1.894); r = 0.945, mean difference -13.8 (95% CI -15.1 to -12.6). PlGFRoche  = 1.809 (95% CI 1.694-1.923) * PlGFPerkinElmer +2.010 (95% CI -0.877 to 4.897); r = 0.966, mean difference 24.6 (95% CI 22.8-26.4). PlGFRoche  = 1.237 (95% CI 1.113-1.361) * PlGFThermoFisher +0.840 (95% CI -3.684 to 5.363); r = 0.937, mean difference 10.8 (95% CI 9.4-12.1). PlGFThermoFisher  = 1.485 (95% CI 1.363-1.607) * PlGFPerkinElmer +0.296 (95% CI -2.784 to 3.375); r = 0.945, mean difference 13.8 (95% CI 12.6-15.1). PlGFThermoFisher  = 0.808 (95% CI 0.726-0.891) * PlGFRoche -0.679 (95% CI -4.456 to 3.099); r = 0.937, mean difference -10.8 (95% CI -12.1 to -9.4).CONCLUSION: The three PlGF methods have different calibrations. This is most likely due to the lack of an internationally accepted reference material for PlGF. Despite different calibrations, the Deming regression analysis indicated good agreement between the three methods, which suggests that results from one method may be converted to the others and hence used in first-trimester prediction models for preeclampsia.
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18.
  • Carlsson, Ylva, 1975, et al. (författare)
  • COVID-19 in Pregnancy and Early Childhood (COPE): study protocol for a prospective, multicentre biobank, survey and database cohort study.
  • 2021
  • Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:9
  • Tidskriftsartikel (refereegranskat)abstract
    • There is limited knowledge on how the SARS-CoV-2 affects pregnancy outcomes. Studies investigating the impact of COVID-19 in early pregnancy are scarce and information on long-term follow-up is lacking.The purpose of this project is to study the impact of COVID-19 on pregnancy outcomes and long-term maternal and child health by: (1) establishing a database and biobank from pregnant women with COVID-19 and presumably non-infected women and their infants and (2) examining how women and their partners experience pregnancy, childbirth and early parenthood in the COVID-19 pandemic.This is a national, multicentre, prospective cohort study involving 27 Swedish maternity units accounting for over 86000 deliveries/year. Pregnant women are included when they: (1) test positive for SARS-CoV-2 (COVID-19 group) or (2) are non-infected and seek healthcare at one of their routine antenatal visits (screening group). Blood, as well as other biological samples, are collected at different time points during and after pregnancy. Child health up to 4years of age and parent experience of pregnancy, delivery, early parenthood, healthcare and society in general will be examined using web-based questionnaires based on validated instruments. Short- and long-term health outcomes will be collected from Swedish health registers and the parents' experiences will be studied by performing qualitative interviews.Confidentiality aspects such as data encryption and storage comply with the General Data Protection Regulation and with ethical committee requirements. This study has been granted national ethical approval by the Swedish Ethical Review Authority (dnr 2020-02189 and amendments 2020-02848, 2020-05016, 2020-06696 and 2021-00870) and national biobank approval by the Biobank Väst (dnr B2000526:970). Results from the project will be published in peer-reviewed journals.NCT04433364.
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19.
  • Claeson, Anna-Sara, 1974-, et al. (författare)
  • Volatile organic compounds (VOCs) emitted from materials collected from buildings affected by microorganisms
  • 2007
  • Ingår i: Journal of Environmental Monitoring. - : Royal Society of Chemistry. - 1464-0325 .- 1464-0333. ; 9:3, s. 240-245
  • Tidskriftsartikel (refereegranskat)abstract
    • In this study mould damaged materials, including carpet, concrete, gypsum board, insulation, plastic, sand and wood, from 20 different buildings with moisture problems were collected. To study emissions from these materials both conventional methods for sampling, such as collection on Tenax TA, were used as well as complementary methods for sampling a wider spectrum of compounds, such as more volatile VOCs, amines and aldehydes. Analysis was carried out using gas chromatography and high-performance liquid chromatography. Mass spectrometry was used for identification of compounds. Alcohols and ketones were almost exclusively emitted from the materials after they had been wet for a week. Acids were also emitted in large quantities from wet gypsum board and plastic. No primary or secondary amines could be identified, but two tertiary amines, trimethylamine and triethylamine, were emitted from sand contaminated by Bacillus. The most common moulds found were Penicillium and Aspergillus. A multivariate method (partial least squares, PLS) was used to investigate the emission patterns from the materials. Materials with bacterial growth had a different VOC profile to those with only mould growth.
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20.
  • Gaillard, Marie-José, et al. (författare)
  • Causes of Regional Change : Land Cover
  • 2015
  • Ingår i: Second Assessment of Climate Change for the Baltic Sea Basin. - Cham : Springer. - 9783319160054 - 9783319160061 ; , s. 453-477
  • Bokkapitel (refereegranskat)abstract
    • Anthropogenic land-cover change (ALCC) is one of the few climate forcings for which the net direction of the climate response over the last two centuries is still not known. The uncertainty is due to the often counteracting temperature responses to the many biogeophysical effects and to the biogeochemical versus biogeophysical effects. Palaeoecological studies show that the major transformation of the landscape by anthropogenic activities in the southern zone of the Baltic Sea basin occurred between 6000 and 3000/2500 cal year BP. The only modelling study of the biogeophysical effects of past ALCCs on regional climate in north-western Europe suggests that deforestation between 6000 and 200 cal year BP may have caused significant change in winter and summer temperature. There is no indication that deforestation in the Baltic Sea area since AD 1850 would have been a major cause of the recent climate warming in the region through a positive biogeochemical feedback. Several model studies suggest that boreal reforestation might not be an effective climate warming mitigation tool as it might lead to increased warming through biogeophysical processes.
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21.
  • Granfors, Michaela, et al. (författare)
  • Placental location and pregnancy outcomes in nulliparous women : A population-based cohort study
  • 2019
  • Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : WILEY. - 0001-6349 .- 1600-0412. ; 98:8, s. 988-996
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: The impact of placenta previa on pregnancy, delivery and infant outcomes has been extensively studied. However, less is known about the possible association of placental location other than previa with pregnancy outcomes. The aim of this study was to investigate if placental location other than previa is associated with adverse pregnancy, delivery and infant outcomes.Material and methods: This is a population-based cohort study, with data from the regional population-based Stockholm-Gotland Obstetric Cohort, Sweden, from 2008 to 2014. The study population included 74 087 nulliparous women with singleton pregnancies resulting in live-born infants, with information about placental location from the second-trimester ultrasound screening. The association between placental location (fundal, lateral, anterior or posterior) and pregnancy outcomes was estimated using logistic regression analysis. Odds ratios (OR) with 95% confidence intervals (95% CI) were calculated, and adjustments were made for maternal age, height, country of birth, smoking in early pregnancy, sex of the infant and in vitro fertilization. Main outcome measures were pregnancy, delivery and infant outcomes.Results: Compared with posterior placental location, fundal and lateral placental locations were associated with a number of adverse pregnancy outcomes, the most important being: very preterm birth (<32 weeks of gestation) (adjusted OR [aOR] 1.78, 95% CI 1.18-2.63 and aOR 2.12, 95% CI 1.39-2.25, respectively), moderate preterm birth (32-36 weeks of gestation) (aOR 1.23, 95% CI 1.001-1.51 and aOR 1.62, 95% CI 1.32-2.00, respectively), small-for-gestational-age birth (aOR 1.67, 95% CI 1.34-2.07 and aOR 1.77, 95% CI 1.39-2.25, respectively) and manual removal of the placenta in vaginal births (aOR 3.27, 95% CI 2.68-3.99 and aOR 3.27, 95% CI 2.60-4.10, respectively). Additionally, lateral placental location was associated with preeclampsia (aOR 1.30, 95% CI 1.03-1.65) and severe postpartum hemorrhage (aOR 1.42, 95% CI 1.27-1.82).Conclusions: Compared with posterior placental location, fundal and lateral placental locations are associated with a number of adverse pregnancy, delivery and infant outcomes.
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22.
  • Granfors, Michaela, et al. (författare)
  • Placental location and risk of retained placenta in women with a previous cesarean section : A population-based cohort study.
  • 2020
  • Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 99:12, s. 1666-1673
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: Some studies have shown that women with a previous cesarean section, compared with women with a previous vaginal delivery, have an increased risk of retained placenta during a subsequent vaginal delivery. It is unknown whether this is mediated by anterior placental location, when the placenta might cover the uterine scar. The aim of this study was to evaluate whether the increased risk of retained placenta in women with a previous cesarean section is mediated by anterior placental location.MATERIAL AND METHODS: This is a population-based cohort study, with data from the regional population-based Stockholm-Gotland Obstetric Cohort, Sweden, from 2008 to 2014. The overall study population included 49 598 women with a vaginal second delivery, where adequate information about placental location from the second-trimester ultrasound scan was available. For the main analysis, including the 3921 women with a previous cesarean section, we calculated the relative risk of retained placenta in women with an anterior placental location, using women with non-anterior placental locations as reference. Relative risks were calculated as odds ratios (OR) with 95% CI. In a second model, adjustments were made for maternal age, height, country of birth, smoking in early pregnancy, infant sex, and in vitro fertilization.RESULTS: In the overall study population, the rate of retained placenta at the second delivery was 2.0%. The proportion of women with a retained placenta was higher among women with a previous cesarean compared with those with a previous vaginal delivery (3.4% vs 1.9%; P < .0001). In the main analysis, including women with a previous cesarean section, the risk for retained placenta was not increased with anterior compared with non-anterior placental location (OR 0.84, 95% CI 0.60-1.20). Adjustments did not affect the estimates in a significant way.CONCLUSIONS: The increased risk of retained placenta in women with a previous cesarean section is not mediated by anterior placental location.
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23.
  • Hastie, Roxanne, et al. (författare)
  • Aspirin use during pregnancy and the risk of bleeding complications : a Swedish population-based cohort study
  • 2021
  • Ingår i: American Journal of Obstetrics and Gynecology. - : Elsevier. - 0002-9378 .- 1097-6868. ; 224:1, s. 95.e1-95.e12
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Aspirin is offered to pregnant women to prevent preeclampsia, a severe obstetrical complication. Large studies of nonpregnant populations have consistently shown that aspirin prophylaxis increases the risk of hemorrhagic complications. However, there have not been any population-based studies investigating this in a pregnant population.OBJECTIVE: This study aimed to investigate whether aspirin use during pregnancy is associated with an increased risk of bleeding complications.STUDY DESIGN: We performed a register-based cohort study using the Swedish Pregnancy Register wherein we examined 313,624 women giving birth between January 2013 and July 2017. Logistic regression was used to assess the risk of antepartum, intrapartum, and postpartum hemorrhage. A propensity score and inverse probability treatment weighting was used to generate an odds ratio that corrects for differences in baseline characteristics.RESULTS: Aspirin use was registered in 4088 (1.3%) women during pregnancy. Compared with women who did not take aspirin, aspirin use was not associated with bleeding complications during the antepartum period (adjusted odds ratio, 1.22; 95% confidence interval, 0.97-1.54). However, aspirin users had a higher incidence of intrapartum bleeding (2.9% aspirin users vs 1.5% nonusers; adjusted odds ratio, 1.63; 95% confidence interval, 1.30-2.05), postpartum hemorrhage (10.2% vs 7.8%; adjusted odds ratio, 1.23; 95% confidence interval, 1.08-1.39), and postpartum hematoma (0.4% vs 0.1%; adjusted odds ratio, 2.21; 95% confidence interval, 1.13-4.34). The risk of a neonatal intracranial hemorrhage was also increased (0.07% vs 0.01%; adjusted odds ratio, 9.66; 95% confidence interval, 1.88-49.48). After stratifying by mode of birth, a higher incidence of bleeding among aspirin users was present for those who had a vaginal birth but not those who had a cesarean delivery.CONCLUSION: Using aspirin during pregnancy is associated with increased postpartum bleeding and postpartum hematoma. It may also be associated with neonatal intracranial hemorrhage. When offering aspirin during pregnancy, these risks need to be weighed against the potential benefits.
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24.
  • Hastie, R., et al. (författare)
  • Duration of labor among women with hypertensive disorders of pregnancy; A Swedish register cohort study
  • 2020
  • Ingår i: European Journal of Obstetrics and Gynecology and Reproductive Biology. - : Elsevier BV. - 0301-2115 .- 1872-7654. ; 251, s. 114-118
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Preeclampsia is a severe obstetric complication affecting 2–8% of pregnancies. There is a common belief that women with preeclampsia experience a shorter duration of labor, where it is thought that increased inflammation that occurs with the disease facilitates labor. However, little evidence exists to support or refute this. Thus, we undertook a register-based cohort study investigating the association between hypertensive disorders of pregnancy and labor duration. Study design: This was a Swedish register-based cohort study of nulliparous women with spontaneous or induced onset of labor at >34 weeks of gestation with a singleton fetus in cephalic presentation. Information of duration of labor was retrieved from electronic birth records and compared between women with hypertensive disorders and normotensives pregnancies. Data was represented as mean adjusted difference in hours (adjusted for pre-gestational disorders, maternal characteristics and mode of delivery) and adjusted hazard ratios (aHR), with an event defined as vaginal birth and women with intrapartum caesarean section censored. An aHR >1 indicated shorter duration of labor. Results: Among 101,531 women, 5548 (5.5%) developed a hypertensive disorder of pregnancy. The overall mean duration of labor was 9.43 (SD 5.32) hours. Women with hypertensive disorders experienced a shorter duration of labor compared to normotensive women, with an adjusted mean difference of -0.68 h (95% CI −0.90, −0.47) for gestational hypertension and -1.53 h (95% CI −1.72, −1.35) for preeclampsia. This corresponded to an aHR of 1.05 (95% CI 1.01, 1.10) and 1.12 (95% CI 1.08, 1.17), respectively. However, when we confined the analysis to those who labored spontaneously, the presence of hypertensive disorders did not alter duration of labor (aHR 0.98, 95% CI 0.95,1.01). Only women who were induced and also had hypertensive disorders experienced a shorter duration of labor (aHR 1.07, 95% CI 1.04,1.09). Conclusions: Hypertensive disorders did not alter labor duration among women with spontaneous onset of labor, however an association was observed among women who were induced. © 2020 Elsevier B.V.
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25.
  • Hesselman, Susanne, 1973-, et al. (författare)
  • Duration of labor among women with thromboembolic events: A Swedish register study
  • 2021
  • Ingår i: European Journal of Obstetrics and Gynecology and Reproductive Biology: X. - : Elsevier BV. - 2590-1613. ; 11
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Inflammation is central to initiation of labor and coagulation is closely interlinked with inflammation. Low-molecular-weight-heparin (LMWH) promotes inflammatory cervical remodeling, myometrium contractility and has been associated with shorter duration of labor. Material and methods: This was a cohort study of 136,661 deliveries 2013–2017, identified in the Swedish Pregnancy Register with prospectively collected pregnancy and labor characteristics. Information of duration of labor was retrieved from the electronic birth records and analyzed with Cox proportional hazard regressions according to previous or current thromboembolic disease (overall) with or without LMWH treatment with non-exposed as reference. Results: The crude hazard ratio for vaginal delivery was not different between women with thromboembolic disease and women without thromboembolic disease (HR 0.99, 95 % CI 0.91–1.09). A lower hazard ratio for vaginal delivery was observed among women with venous thromboembolism (VTE) with concomitant LMWH use/treatment (adjusted HR 0.86, 95 % CI 0.76−0.98) compared to non-exposed, implying a longer duration of labor in these cases. Conclusion: Thromboembolic disease was not associated with shorter duration of labor and in presence of LMWH these women experienced longer duration of labor. © 2021 The Authors
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26.
  • Horstkotte, Tim, 1981-, et al. (författare)
  • Pastures under pressure : Effects of other land users and the environment
  • 2022
  • Ingår i: Reindeer Husbandry and Global Environmental Change. - London : Routledge. - 9781000593402 - 9780367632670 ; , s. 76-98
  • Bokkapitel (refereegranskat)abstract
    • Reindeer husbandry has a long history of sharing landscapes with a multitude of other forms of land use. By competing for space, industrial resource developments from the early 20th century onwards have affected where, when and how the landscape can be used for reindeer grazing. Extending from the local to the landscape level, these impacts can reduce pastures either directly or indirectly as a result of increasing landscape fragmentation or changing reindeer behaviour. Furthermore, environmental drivers influence the dynamics of forage availability or accessibility for reindeer. The observed trend of shrinking pastures in the three countries is caused by these cumulative impacts. As a consequence, grazing pressure on the remaining pastures increases, and it curtails reindeer herders’ options to respond to the challenges of climate change. Reversing the continuing decrease in pastures requires the restoration of grazing resources and increasing landscape connectivity to facilitate movement and grazing rotation. However, socio-political incentives are also required to sustain reindeer pastures in the future. This includes an increase in the influence of reindeer herders on land use decisions and the inclusion of their traditional ecological knowledge of pasture management to identify alternative approaches to natural resource management.
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27.
  • Ivarsson, Anneli, et al. (författare)
  • Prevalence of Childhood Celiac Disease and Changes in Infant Feeding
  • 2013
  • Ingår i: Pediatrics. - : American Academy of Pediatrics. - 0031-4005 .- 1098-4275. ; 131:3, s. E687-E694
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: Between 1984 and 1996, Sweden experienced an "epidemic" of clinical celiac disease in children andlt;2 years of age, attributed partly to changes in infant feeding. Whether infant feeding affects disease occurrence and/or the clinical presentation remains unknown. We investigated and compared the total prevalence of celiac disease in 2 birth cohorts of 12-year-olds and related the findings to each cohorts ascertained infant feeding. less thanbrgreater than less thanbrgreater thanMETHODS: A 2-phase cross-sectional screening study was performed in which 13 279 children from 2 birth cohorts participated: children born during the epidemic (1993) and children born after the epidemic (1997). Previously diagnosed cases were reported and confirmed. Blood samples were analyzed for serological markers and children with positive values were referred for small intestinal biopsy. Infant feeding practices in the cohorts were ascertained via questionnaires. Prevalence comparisons were expressed as prevalence ratios. less thanbrgreater than less thanbrgreater thanRESULTS: The total prevalence of celiac disease was 29 in 1000 and 22 in 1000 for the 1993 and 1997 cohorts, respectively. Children born in 1997 had a significantly lower risk of having celiac disease compared with those born in 1993 (prevalence ratio: 0.75; 95% confidence interval: 0.60-0.93; P = .01). The cohorts differed in infant feeding (specifically, in the proportion of infants introduced to dietary gluten in small amounts during ongoing breastfeeding). less thanbrgreater than less thanbrgreater thanCONCLUSIONS: A significantly reduced prevalence of celiac disease in 12-year-olds indicates an option for disease prevention. Our findings suggest that the present infant feeding recommendation to gradually introduce gluten-containing foods from 4 months of age, preferably during ongoing breastfeeding, is favorable. Pediatrics 2013;131:e687-e694
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28.
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29.
  • Johansson, Anna, 1982-, et al. (författare)
  • Patient-reported recovery in upper abdominal cancer surgery care : A prospective study
  • 2021
  • Ingår i: Science Progress. - : Sage Publications. - 0036-8504 .- 2047-7163. ; 104:2
  • Tidskriftsartikel (refereegranskat)abstract
    • The study aimed to describe and analyse patient-reported recovery in patients after upper abdominal cancer surgery. This study had a quantitative design and patients were consecutively included in a university hospital in southern Sweden. Twenty-four patients answered the Postoperative Recovery Profile (PRP) questionnaire at three measurement points. All five dimensions were affected. In the physical symptoms dimension, the majority of patients reported a lack of energy upon discharge. High levels of anxiety were reported. Over 50% of patients reported some degree of depressed mood at all three measurement points. In the social dimension, the majority of patients reported some degree of being dependent on help from others in everyday life at 4?weeks after discharge. Few patients are fully recovered at 4?weeks after discharge. Individual patient-reported recovery estimates may be valuable in identifying and planning interventions tailored to each patients needs throughout the care process.
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30.
  • Jonsson, Anna, 1981-, et al. (författare)
  • Small constrained SP1-7 analogues bind to a unique site and promote anti-allodynic effects following systemic injection in mice
  • 2015
  • Ingår i: Neuroscience. - : Elsevier BV. - 0306-4522 .- 1873-7544. ; 298, s. 112-119
  • Tidskriftsartikel (refereegranskat)abstract
    • Previous results have shown that the substance P (SP) N-terminal fragment SP1–7 may attenuate hyperalgesia and produce anti-allodynia in animals using various experimental models for neuropathic pain. The heptapeptide was found to induce its effects through binding to and activating specific sites apart from any known neurokinin or opioid receptor. Furthermore, we have applied a medicinal chemistry program to develop lead compounds mimicking the effect of SP1–7. The present study was designed to evaluate the pharmacological effect of these compounds using the mouse spared nerve injury (SNI) model of chronic neuropathic pain. Also, as no comprehensive screen with the aim to identify the SP1–7 target has yet been performed we screened our lead compound H-Phe-Phe-NH2 toward a panel of drug targets. The extensive target screen, including 111 targets, did not reveal any hit for the binding site among a number of known receptors or enzymes involved in pain modulation. Our animal studies confirmed that SP1–7, but also synthetic analogs thereof, possesses anti-allodynic effects in the mouse SNI model of neuropathic pain. One of the lead compounds, a constrained H-Phe-Phe-NH2 analog, was shown to exhibit a significant anti-allodynic effect.
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31.
  • Klocker Larsen, Rasmus, et al. (författare)
  • Kumulativa effekter av exploateringar på renskötseln : Vad behöver göras inom tillståndsprocesser
  • 2016
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • En av de största utmaningarna i dagens landskapsplanering rör de många och ofta konkurrerande anspråken på mark och naturresurser. Denna rapport redovisar resultaten från ett projekt som syftade till att utveckla kunskap och metodik för att beskriva och ta hänsyn till kumulativa effekter av exploateringar på den samiska renskötseln.Projektet sökte svar på följande frågor:1. Kartläggning av kumulativa effektera. Hur stora arealer upptar de kumulativa effekterna av exploateringar på renskötseln?b. Vilka metoder kan utvecklas för att dokumentera och kommunicera omfattning och effekter av olika former av exploateringar på renskötseln i ett landskap?2. Beaktandet av kumulativa effekter i tillståndsprocessera. Vilka möjligheter och svårigheter har svenska myndigheter inom dagens regelverk och myndighetspraxis att beakta kumulativa effekter och hantera konflikter mellan olika anspråk?b. Vilka ansatser kan utvecklas för att förbättra hänsynen till kumulativa effekter i tillståndsprövning?Metod Kartläggningen av kumulativa effekter gjordes för Vilhelmina norra sameby genom att beräkna det totala störningsområdet utifrån information om historiska, befintliga och potentiella framtida exploateringar samt forskning kring störningszoner. Vi har använt kartlagd information för all infrastruktur och mänsklig aktivitet, och applicerat störningszoner för respektive störningskälla för att beräkna hur stor yta som berörs av de olika störningskällorna. Detta är första gången en metod presenteras för att uppskatta det totala störningsområdet som mått för de kumulativa effekterna av exploateringar på renskötseln.Studien av hänsyn till kumulativa effekter i tillståndsprocesserna gjordes i en deltagande policyanalys med bidrag från tjänstemän på de berörda tillståndsmyndigheterna som fick belysa hur de ser på regelverket och sin praxis och hur dessa kan förbättras. Detta är också första gången i Sverige som berörda tjänstemän från olika myndigheter tillsammans medverkat vid analys av regelverket och sin egen praxis rörande kumulativa effekter. Huvudmomentet i arbetet var en tvådagars workshop som hölls den 7–8 maj 2015.Resultat Vilhelmina norra sameby har sett en omfattande kumulativ förlust av sitt betesområde, mätt i det samlade störningsområdet. Det totala störningsområdet sedan förra sekelskiftet och fram till i dag i Vilhelmina norra sameby uppgick till 30 % (4679 km2) av samebyns 15 709 km2. Beräknat för vinterbeteslandet är störningsområdet 54 % (4111 km2) av samebyns 7656 km2 vinterbetesmark. I scenariot för år 2050 beräknas det totala störningsområdet till 39 % (6131 km2) av hela samebyn och 50 % (3815 km2) av vinterbeteslandet. Scenarioberäkningen visar att är det möjligt att faktiskt öka den tillgängliga betesarealen i ett framtida renbeteslandskap genom ett antal strategiska åtgärder i landskapet.Erfarenheterna från tjänstemännen som deltog i denna studie visar på avsevärda hinder i det befintliga regelverket och myndighetspraxis för att beakta de kumulativa effekterna. Följande hinder för att beakta kumulativa effekter i tillståndsprocesserna identifierades:Isolerade stuprör och fragmenterade tillståndsprocesser;Bristande underlag vid tillståndsprövning;Hög arbetsbörda och orealistiska förväntningar på samebyarna;Spänningar mellan politisk styrning och myndighetsutövning;Olika tolkningar av regelverk och underlag.Följande åtgärder som kan anammas för att förbättra beaktandet av kumulativa effekter i tillståndsprocesserna framkom:Minska fragmentering i prövningen;Säkerställa en oberoende MKB-process;Etablera en gemensam databas och en regional landskapsplanering;Införa en toleransnivå för vad samebyar förväntas tåla;Förse renskötseln med tillräckliga resurserSlutsatser Denna studie initierades i syfte att sätta igång en strukturerad diskussion kring hur myndigheter kan ta hänsyn till och motverka kumulativa effekter av andra markanvändningar på renskötseln. Detta kommer att kräva fortsatt engagemang från de involverade aktörerna. Vi skulle gärna se att dialogen utökas till att innefatta också bolag och deras konsulter, då denna pilotstudie fokuserade på myndigheternas erfarenhet.I brist på tydliga riktlinjer och praxis kring hur kumulativa effekter ska beaktas får enskilda tjänstemän för närvarande en svår sits när de förväntas medla mellan samebyar och bolag. Omfattande osäkerhet präglar vad som kan betraktas som ”relevanta” effekter, vilka metoder som är legitima för att beakta dessa effekter, och hur evidensen bör inkluderas i beslutsfattandet. När regelverk och procedur är otydliga, lämnar staten i praktiken över ansvaret till samebyarna och bolagen att, på eget initiativ, förhandla kring vad som är relevanta effekter att ta hänsyn till. Det finns starka argument för att skapa en tydligare ansats inom lagstiftning och förvaltningspraxis så att hänsyn kan tas till de kumulativa effekterna.
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32.
  • Kløcker Larsen, Rasmus, et al. (författare)
  • Omtvistade landskap : Navigering mellan konkurrerande markanvändning och kumulativa effekter
  • 2020
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • Rapporten presenterar ny kunskap om hur staten, exploatörer och samebyar kan förbättra hanteringen av exploateringars kumulativa effekter på renskötseln och samisk markanvändning.Rapporten bygger på ett forskningsprojekt som genomförts i partnerskap mellan samiska organisationer knutna till renskötseln, och forskningsinstitutionerna. Sex delstudier ingår i rapporten.•Hänsynen till kumulativa effekter i gruvbolags miljökonsekvensbeskrivningar, •samiskt inflytande i samband med miljöbedömningar, •vindkraftens påverkan under driftsfas på renskötseln i kalvningsområde, •metodik för att beräkna störningszoner, •konsekvenserna för renskötseln av vattenkraftutbyggnaden i Porjus och Vojmån samt möjliga skadelindrande åtgärder, samt •hur myndigheter kan efterleva sina skyldigheter mot samebyar i samband med tillståndsprocesser för konkurrerande markanvändning.Forskningen har finansierats av Naturvårdsverkets miljöforskningsanslag till stöd för Naturvårdsverket och Havs- och vattenmyndighetens verksamhet.
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33.
  • Malmberg, Jennie, et al. (författare)
  • Comparative evaluation of synthetic anti-HER2 Affibody molecules site-specifically labelled with 111In using N-terminal DOTA, NOTA and NODAGA chelators in mice bearing prostate cancer xenografts.
  • 2012
  • Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 39:3, s. 481-492
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: In disseminated prostate cancer, expression of human epidermal growth factor receptor type 2 (HER2) is one of the pathways to androgen independence. Radionuclide molecular imaging of HER2 expression in disseminated prostate cancer might identify patients for HER2-targeted therapy. Affibody molecules are small (7 kDa) targeting proteins with high potential as tracers for radionuclide imaging. The goal of this study was to develop an optimal Affibody-based tracer for visualization of HER2 expression in prostate cancer. METHODS: A synthetic variant of the anti-HER2 Z(HER2:342) Affibody molecule, Z(HER2:S1), was N-terminally conjugated with the chelators DOTA, NOTA and NODAGA. The conjugated proteins were biophysically characterized by electrospray ionization mass spectroscopy (ESI-MS), circular dichroism (CD) spectroscopy and surface plasmon resonance (SPR)-based biosensor analysis. After labelling with (111)In, the biodistribution was assessed in normal mice and the two most promising conjugates were further evaluated for tumour targeting in mice bearing DU-145 prostate cancer xenografts. RESULTS: The HER2-binding equilibrium dissociation constants were 130, 140 and 90 pM for DOTA-Z(HER2:S1), NOTA-Z(HER2:S1) and NODAGA-Z(HER2:S1), respectively. A comparative study of (111)In-labelled DOTA-Z(HER2:S1), NOTA-Z(HER2:S1) and NODAGA-Z(HER2:S1) in normal mice demonstrated a substantial influence of the chelators on the biodistribution properties of the conjugates. (111)In-NODAGA-Z(HER2:S1) had the most rapid clearance from blood and healthy tissues. (111)In-NOTA-Z(HER2:S1) showed high hepatic uptake and was excluded from further evaluation. (111)In-DOTA-Z(HER2:S1) and (111)In-NODAGA-Z(HER2:S1) demonstrated specific uptake in DU-145 prostate cancer xenografts in nude mice. The tumour uptake of (111)In-NODAGA-Z(HER2:S1), 5.6 ± 0.4%ID/g, was significantly lower than the uptake of (111)In-DOTA-Z(HER2:S1), 7.4 ± 0.5%ID/g, presumably because of lower bioavailability due to more rapid clearance. (111)In-NODAGA-Z(HER2:S1) provided higher tumour-to-blood ratio, but somewhat lower tumour-to-liver, tumour-to-spleen and tumour-to-bone ratios. CONCLUSION: Since distant prostate cancer metastases are situated in bone or bone marrow, the higher tumour-to-bone ratio is the most important. This renders (111)In-DOTA-Z(HER2:S1) a preferable agent for imaging of HER2 expression in disseminated prostate cancer.
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34.
  • Malmberg, Jennie, et al. (författare)
  • Comparative evaluation of synthetic anti-HER2 Affibody molecules site-specifically labelled with In-111 using N-terminal DOTA, NOTA and NODAGA chelators in mice bearing prostate cancer xenografts
  • 2012
  • Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 39:3, s. 481-492
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose In disseminated prostate cancer, expression of human epidermal growth factor receptor type 2 (HER2) is one of the pathways to androgen independence. Radionuclide molecular imaging of HER2 expression in disseminated prostate cancer might identify patients for HER2-targeted therapy. Affibody molecules are small (7 kDa) targeting proteins with high potential as tracers for radionuclide imaging. The goal of this study was to develop an optimal Affibody-based tracer for visualization of HER2 expression in prostate cancer. Methods A synthetic variant of the anti-HER2 Z(HER2:342) Affibody molecule, Z(HER2:S1), was N-terminally conjugated with the chelators DOTA, NOTA and NODAGA. The conjugated proteins were biophysically characterized by electrospray ionization mass spectroscopy (ESI-MS), circular dichroism (CD) spectroscopy and surface plasmon resonance (SPR)-based biosensor analysis. After labelling with In-111, the biodistribution was assessed in normal mice and the two most promising conjugates were further evaluated for tumour targeting in mice bearing DU-145 prostate cancer xenografts. Results The HER2-binding equilibrium dissociation constants were 130, 140 and 90 pM for DOTA-Z(HER2:S1), NOTA-Z(HER2:S1) and NODAGA-Z(HER2:S1), respectively. A comparative study of In-111-labelled DOTA-Z(HER2:S1), NOTA-Z(HER2:S1) and NODAGA-Z(HER2:S1) in normal mice demonstrated a substantial influence of the chelators on the biodistribution properties of the conjugates. In-111-NODAGA-Z(HER2:S1) had the most rapid clearance from blood and healthy tissues. In-111-NOTA-Z(HER2:S1) showed high hepatic uptake and was excluded from further evaluation. In-111-DOTA-Z(HER2:S1) and In-111-NODAGAZHER2: S1 demonstrated specific uptake in DU-145 prostate cancer xenografts in nude mice. The tumour uptake of In-111-NODAGA-Z(HER2:S1), 5.6 +/- 0.4% ID/g, was significantly lower than the uptake of In-111-DOTA-Z(HER2:S1), 7.4 +/- 0.5% ID/g, presumably because of lower bioavailability due to more rapid clearance. In-111-NODAGA-Z(HER2:S1) provided higher tumour-to-blood ratio, but somewhat lower tumour-to-liver, tumour-to-spleen and tumour-to-bone ratios. Conclusion Since distant prostate cancer metastases are situated in bone or bone marrow, the higher tumour-to-bone ratio is the most important. This renders In-111-DOTA-Z(HER2:S1) a preferable agent for imaging of HER2 expression in disseminated prostate cancer.
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35.
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36.
  • Myléus, Anna, 1978-, et al. (författare)
  • Celiac disease revealed in 3% of Swedish 12-year-olds born during an epidemic
  • 2009
  • Ingår i: Journal of Pediatric Gastroenterology and Nutrition - JPGN. - New York : Raven P. - 0277-2116 .- 1536-4801. ; 49:2, s. 170-176
  • Tidskriftsartikel (refereegranskat)abstract
    • Objetive: Sweden experienced a marked epidemic of celiac disease between 1984 and 1996 in children younger than 2 years of age, partly explained by changes in infant feeding. The objective of this study was to determine the prevalence of celiac disease in 12-year-olds born during the epidemic (1993), including both symptomatic and screening detected cases.Patients and methods: All sixth-grade children in participating schools were invited (n = 10,041). Symptomatic and, therefore, previously diagnosed celiac disease cases were ascertained through the National Swedish Childhood Celiac Disease Register and/or medical records. All serum samples were analyzed for antihuman tissue transglutaminase (tTG)-IgA (Celikey), and serum-IgA, and some for tTG-IgG and endomysial antibodies. A small intestinal biopsy was recommended for all children with suspected undiagnosed celiac disease.Results: Participation was accepted by 7567 families (75%). Previously diagnosed celiac disease was found in 67 children; 8.9/1000 (95% confidence interval [CI] 6.7-11). In another 192 children, a small intestinal biopsy was recommended and was performed in 180. Celiac disease was verified in 145 children, 20/1000 (95% CI 17-23). The total prevalence was 29/1000 (95% CI 25-33).Conclusions: The celiac disease prevalence of 29/1000 (3%)-with two thirds of cases undiagnosed before screening-is 3-fold higher than the usually suggested prevalence of 1%. When these 12-year-olds were infants, the prevailing feeding practice was to introduce gluten abruptly, often without ongoing breast-feeding, which might have contributed to this unexpectedly high prevalence.
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37.
  • Människan i skogen, skogen i människan : Miun Research Exhibition
  • 2021
  • Konstnärligt arbeteabstract
    • Med utställningen Människan i skogen, skogen i människan vill projektet belysa ett antal aktuella och viktiga frågor för vår region och samtid, samlade under ett tema: skog och hållbar utveckling. I utställningen får besökaren möta kunskap och perspektiv från fem forskare och forskargrupper vid Mittuniversitetet. Forskarna är verksamma inom biologi, ekoteknik, historia, litteraturvetenskap respektive turismvetenskap. Forskningens olika perspektiv länkas i utställningen samman genom sina förhållningssätt till tid, såsom avgörande för förståelse, kunskap och handling. De olika forskningsinriktningarna visar också fram spänningar mellan olika synsätt på skog och kan tillsammans ge flera svar och berättelser om skogens värden. En arbetsgrupp vid Universitetsbiblioteket står för gestaltning och produktion av utställningen.
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38.
  • Newby-Kew, Abigail, et al. (författare)
  • Severe Perineal Lacerations in First Delivery : Association with Subsequent Reproductive Outcomes
  • 2024
  • Ingår i: Journal of Women's Health. - : Mary Ann Liebert. - 1540-9996 .- 1931-843X. ; 33:4, s. 542-550
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Severe perineal lacerations (SPLs), common worldwide, are associated with short- and long-term complications: pelvic floor disorders, fecal incontinence, fistula, and profound psychological impacts. Limited research suggests that experiencing SPL may influence future reproductive intentions, but research on outcomes is lacking.Methods: We analyzed the effect of experiencing SPL during a first delivery among a large cohort of Swedish births between 1992 and 2013. We used linear and multinomial logistic regression to estimate the associations between SPL and four reproductive outcomes: subsequent total birth number, probability of a second birth, interpregnancy interval (IPI), and subsequent scheduled cesarean birth.Results: Among 947,035 singleton live-born first-births, we found that experiencing SPL was associated with slightly fewer overall births in fully adjusted models (a decrease of -0.020 births; 95% confidence interval [CI]: -0.028 to -0.012), but no difference in the probability of a second birth (risk ratio [RR]: 1.00; 95% CI: 0.99 to 1.00) or IPI. Scheduled cesarean was increased in births after SPL (adjusted RR: 4.57; 95% CI: 4.42 to 4.73). A secondary comparison of SPL to severe postpartum hemorrhage suggests that some of these observed differences may be related to experiencing any severe outcome, and some specifically to perineum disruption.Conclusion: This study provides a deeper understanding of the long-term impacts of SPL, which may be useful in informing best clinical practices for supporting women who have experienced SPL.
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39.
  • Olin, Anna-Carin, 1960, et al. (författare)
  • Nitric oxide (NO) in exhaled air after experimental ozone exposure in humans.
  • 2001
  • Ingår i: Respiratory medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 95:6, s. 491-5
  • Tidskriftsartikel (refereegranskat)abstract
    • We hypothesized that ozone, a common air pollutant, potent in producing airway inflammation, would increase the production of exhaled nitric oxide (NO). If so, measurement of exhaled NO could potentially be a valuable tool in population studies of air pollution effects. Eleven healthy non-smoking volunteers were exposed to 0.2 ppm ozone (O3) and filtered air for 2h on two separate occasions. Exhaled NO and nasal NO were measured before and on five occasions following the exposures. Changes in exhaled and nasal NO after ozone exposure were adjusted for changes after air exposure. There was a slight decrease in exhaled NO (-0.6; -3.1-1.2 ppb) (median and 95% confidence interval) and of nasal NO (-57; -173-75 ppb) directly after the ozone exposure. No significant changes in exhaled or nasal NO were however found 6 or 24 h after the exposure. Within the examined group, an O3 exposure level proven to induce an airway inflammation caused no significant changes in exhaled or nasal NO levels. Hence, the current study did not yield support for exhaled NO as a useful marker of ozone-induced oxidative stress and airway inflammation after a single exposure. This contrasts with data for workers exposed to repeated high peaks of ozone. The potential for exhaled NO as a marker of oxidative stress therefore deserves to be further elucidated.
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40.
  • Sandström, Anna, et al. (författare)
  • Clinical risk assessment in early pregnancy for preeclampsia in nulliparous women : a population-based cohort study
  • 2019
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 14:11
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectiveTo evaluate the capacity of multivariable prediction of preeclampsia during pregnancy, based on detailed routinely collected early pregnancy data in nulliparous women.Design and settingA population-based cohort study of 62 562 pregnancies of nulliparous women with deliveries 2008–13 in the Stockholm-Gotland Counties in Sweden.MethodsMaternal social, reproductive and medical history and medical examinations (including mean arterial pressure, proteinuria, hemoglobin and capillary glucose levels) routinely collected at the first visit in antenatal care, constitute the predictive variables. Predictive models for preeclampsia were created by three methods; logistic regression models using 1) pre-specified variables (similar to the Fetal Medicine Foundation model including maternal factors and mean arterial pressure), 2) backward selection starting from the full suite of variables, and 3) a Random forest model using the same candidate variables. The performance of the British National Institute for Health and Care Excellence (NICE) binary risk classification guidelines for preeclampsia was also evaluated. The outcome measures were diagnosis of preeclampsia with delivery <34, <37, and ≥37 weeks’ gestation.ResultsA total of 2 773 (4.4%) nulliparous women subsequently developed preeclampsia. The pre-specified variables model was superior the other two models, regarding prediction of preeclampsia with delivery <34 and <37 weeks, both with areas under the curve of 0.68, and sensitivity of 30.6% (95% CI 24.5–37.2) and 29.2% (95% CI 25.2–33.4) at a 10% false positive rate, respectively. The performance of these customizable multivariable models at the chosen false positive rate, was significantly better than the binary NICE-guidelines for preeclampsia with delivery <37 and ≥37 weeks’ gestation.ConclusionMultivariable models in early pregnancy had a modest performance, although providing advantages over the NICE-guidelines, in predicting preeclampsia in nulliparous women. Use of a machine learning algorithm (Random forest) did not result in superior prediction.
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41.
  • Sandström, Anna, et al. (författare)
  • Routinely collected antenatal data for longitudinal prediction of preeclampsia in nulliparous women: a population-based study
  • 2021
  • Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1, s. 17973-
  • Tidskriftsartikel (refereegranskat)abstract
    • The objective was to evaluate the sequentially updated predictive capacity for preeclampsia during pregnancy, using multivariable longitudinal models including data from antenatal care. This population-based cohort study in the Stockholm-Gotland Counties, Sweden, included 58,899 pregnancies of nulliparous women 2008–2013. Prospectively collected data from each antenatal care visit was used, including maternal characteristics, reproductive and medical history, and repeated measurements of blood pressure, weight, symphysis-fundal height, proteinuria, hemoglobin and blood glucose levels. We used a shared-effects joint longitudinal model including all available information up until a given gestational length (week 24, 28, 32, 34 and 36), to update preeclampsia prediction sequentially. Outcome measures were prediction of preeclampsia, preeclampsia with delivery < 37, and preeclampsia with delivery ≥ 37 weeks’ gestation. The area under the curve (AUC) increased with gestational length. AUC for preeclampsia with delivery < 37 weeks’ gestation was 0.73 (95% CI 0.68–0.79) at week 24, and increased to 0.87 (95% CI 0.84–0.90) in week 34. For preeclampsia with delivery ≥ 37 weeks’ gestation, the AUC in week 24 was 0.65 (95% CI 0.63–0.68), but increased to 0.79 (95% CI 0.78–0.80) in week 36. The addition of routinely collected clinical measurements throughout pregnancy improve preeclampsia prediction and may be useful to individualize antenatal care.
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42.
  • Sandström Gerdtsson, Anna, et al. (författare)
  • A Multicenter Trial Defining a Serum Protein Signature Associated with Pancreatic Ductal Adenocarcinoma.
  • 2015
  • Ingår i: International Journal of Proteomics. - : Hindawi Limited. - 2090-2174 .- 2090-2166. ; 2015
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with rapid tumor progression and poor prognosis. This study was motivated by the lack of sensitive and specific PDAC biomarkers and aimed to identify a diagnostic, serum protein signature for PDAC. Methods. To mimic a real life test situation, a multicenter trial comprising a serum sample cohort, including 338 patients with either PDAC or other pancreatic diseases (OPD) and controls with nonpancreatic conditions (NPC), was analyzed on 293-plex recombinant antibody microarrays targeting immunoregulatory and cancer-associated antigens. Results. Serum samples collected from different hospitals were analyzed and showed that (i) sampling from five different hospitals could not be identified as a preanalytical variable and (ii) a multiplexed biomarker signature could be identified, utilizing up to 10 serum markers that could discriminate PDAC from controls, with sensitivities and specificities in the 91-100% range. The first protein profiles associated with the location of the primary tumor in the pancreas could also be identified. Conclusions. The results demonstrate that robust enough serum signatures could be identified in a multicenter trial, potentially contributing to the development of a multiplexed biomarker immunoassay for improved PDAC diagnosis.
  •  
43.
  • Sandström Gerdtsson, Anna, et al. (författare)
  • Overexpression of the key metabolic protein CPT1A defines mantle cell lymphoma patients with poor response to standard high dose chemotherapy independent of MIPI and complement established high-risk factors
  • 2023
  • Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 108:4, s. 1092-1104
  • Tidskriftsartikel (refereegranskat)abstract
    • The variable outcome to standard immunochemotherapy for mantle cell lymphoma (MCL) patients is a clinical challenge. Established risk factors, including high MCL international prognostic index (MIPI), high proliferation (Ki-67), non-classic (blastoid/pleomorphic) morphology, and mutated TP53, only partly identify patients in need of alternative treatment. Deepened understanding of biological factors that influence time to progression and relapse would allow for an improved stratification, and identification of novel targets for high-risk patients. We performed gene expression analyses to identify pathways and genes associated with outcome in a cohort of homogeneously treated patients. In addition to deregulated proliferation, we show that thermogenesis, fatty acid degradation and oxidative phosphorylation are altered in patients with poor survival, and that high expression of carnitine palmitoyltransferase 1A (CPT1A), an enzyme involved in fatty acid degradation, can specifically identify high-risk patients independent of the established high-risk factors. We suggest that complementary investigations of metabolism may increase the accuracy of patient stratification and that immunohistochemistry-based assessment of CPT1A can contribute to defining high-risk MCL.
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44.
  • Sandström, Olof, et al. (författare)
  • Transglutaminase IgA antibodies in a celiac disease mass screening and the role of HLA-DQ genotyping and endomysial antibodies in a sequential testing
  • 2013
  • Ingår i: Journal of Pediatric Gastroenterology and Nutrition - JPGN. - : Lippincott Williams & Wilkins. - 0277-2116 .- 1536-4801. ; 57:4, s. 472-476
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: The aim of this study was to evaluate hypothetical screening strategies in a Swedish celiac disease (CD) mass screening.Methods: Of 10,041 Swedish sixth graders born in 1993 invited to a population-based CD mass screening, 7208 participated. Anti-tissue transglutaminase (tTG) immunoglobulin (Ig) A were analyzed in all children and total serum IgA (s-IgA) in 7161 children. Additional analyses of tTG-IgG, endomysial antibodies (EMA) IgA and IgG, and human leukocyte antigen (HLA) alleles were performed according to a standardized protocol. Children with elevated levels of serological markers were recommended to undergo a small intestinal biopsy to verify diagnosis, and 153 children with CD were thus identified. Sensitivity, specificity, positive predictive values (PPVs) and negative predictive values (NPVs) were calculated and receiver operating characteristic curves were plotted.Results: By lowering the cutoff for tTG-IgA, 17 additional cases of CD were identified at the cost of 32 biopsies. All children with tTG-IgA >50 U/mL (10 times the recommended upper limit of normal) had gluten enteropathy. Area under the receiver operating characteristic curve for tTG-IgA was 0.988. All cases carried HLA-DQ2 or HLA-DQ8, as did 53% of the controls. For different hypothetical screening strategies, sensitivity, specificity, PPV, and NPV ranged between 87.6% and 100%, 99.5% and 99.9%, 79.7% and 89.7%, and 99.7% and 100%, respectively. Efforts to increase sensitivity by lowering tTG-IgA cutoff would result in increased number of small intestinal biopsies and lower PPV. Sequential testing for both EMA and HLA-DQ genotyping would reduce the number of negative small intestinal biopsies.Conclusions: tTG-IgA is a robust marker when used in CD mass screening and its performance can be enhanced by sequential testing for EMA or HLA-DQ genotyping.
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45.
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46.
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47.
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48.
  • Schepke, Elizabeth, et al. (författare)
  • DNA methylation profiling improves routine diagnosis of paediatric central nervous system tumours: A prospective population-based study
  • 2022
  • Ingår i: Neuropathology and Applied Neurobiology. - : Wiley. - 0305-1846 .- 1365-2990. ; 48:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: Paediatric brain tumours are rare, and establishing a precise diagnosis can be challenging. Analysis of DNA methylation profiles has been shown to be a reliable method to classify central nervous system (CNS) tumours with high accuracy. We aimed to prospectively analyse CNS tumours diagnosed in Sweden, to assess the clinical impact of adding DNA methylation-based classification to standard paediatric brain tumour diagnostics in an unselected cohort. Methods: All CNS tumours diagnosed in children (0-18 years) during 2017-2020 were eligible for inclusion provided sufficient tumour material was available. Tumours were analysed using genome-wide DNA methylation profiling and classified by the MNP brain tumour classifier. The initial histopathological diagnosis was compared with the DNA methylation-based classification. For incongruent results, a blinded re-evaluation was performed by an experienced neuropathologist. Results: Two hundred forty tumours with a histopathology-based diagnosis were profiled. A high-confidence methylation score of 0.84 or more was reached in 78% of the cases. In 69%, the histopathological diagnosis was confirmed, and for some of these also refined, 6% were incongruent, and the re-evaluation favoured the methylation-based classification. In the remaining 3% of cases, the methylation class was non-contributory. The change in diagnosis would have had a direct impact on the clinical management in 5% of all patients. Conclusions: Integrating DNA methylation-based tumour classification into routine clinical analysis improves diagnostics and provides molecular information that is important for treatment decisions. The results from methylation profiling should be interpreted in the context of clinical and histopathological information.
  •  
49.
  • Skogh, Anna, et al. (författare)
  • Impact of N-methylation of the substance P 1-7 amide on anti-allodynic effect in mice after peripheral administration
  • 2017
  • Ingår i: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 109, s. 533-540
  • Tidskriftsartikel (refereegranskat)abstract
    • Substance P 1-7 (SP1-7, Arg1-Pro2-Lys3-Pro4-Gln5-Gln6-Phe7) is the major bioactive metabolite formed after proteolytic degradation of the tachykinin substance P (SP). This heptapeptide often opposes the effects of the mother peptide. Hence, SP1-7 is having anti-inflammatory, anti-nociceptive and anti-hyperalgesic effects in experimental models. Despite all encouraging properties of SP1-7 its exact mode of action has not yet been elucidated which has hampered further development of this heptapeptide in drug discovery. Contrary to SP that mediates its biological activity via the NK-1 receptor, the N-terminal fragment SP1-7 acts through an unknown target that is distinct from all known opioid and tachykinin receptors. The SP1-7 amide 1 (Arg1-Pro2-Lys3-Pro4-Gln5-Gln6-Phe7-NH2) was previously shown to be superior to the endogenous SP1-7 in all experimental pain models where the two compounds were compared. Herein, we report that N-methylation scan of the backbone of the SP1-7 amide (1) results in peptides that are significantly less prone to undergo proteolysis in plasma from both mouse and human. However, with the two exceptions of the [MeLys3]SP1-7 amide (3) and the [MeGln5]SP1-7 amide (4), the peptides with a methyl group attached to the backbone are devoid of significant anti-allodynic effects after peripheral administration in the spared nerve injury (SNI) mouse model of neuropathic pain. It is suggested that the N-methylation does not allow these peptides to form the accurate bioactive conformations or interactions required for efficient binding to the macromolecular target. The importance of intact N-terminal Arg1 and C-terminal Phe7, anticipated to serve as address and message residues, respectively, for achieving the anti-allodynic effect is emphasized. Notably, the three heptapeptides: the SP1-7 amide (1), the [MeLys3]SP1-7 amide (3) amide and the [MeGln5]SP1-7 amide (4) are all considerably more effective in the SNI mouse model than gabapentin that is widely used in the clinic for treatment of neuropathic pain.
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50.
  • Skogh, Anna, et al. (författare)
  • Importance of N-and C-terminal residues of substance P 1-7 for alleviating allodynia in mice after peripheral administration
  • 2017
  • Ingår i: European Journal of Pharmaceutical Sciences. - : Elsevier. - 0928-0987 .- 1879-0720. ; 106, s. 345-351
  • Tidskriftsartikel (refereegranskat)abstract
    • The heptapeptide SP1-7 (1, Arg(1)-Pro(2)-Lys(3)-Pro(4)-Gln(5)-Gln(6)-Phe(7)) is the major bioactive metabolite formed after proteolytic processing of the neuropeptide substance P (SP, Arg(1)-Pro(2)-Lys(3)-Pro(4)-GIn(5)-Gln(6)-Phe(7)-Phe(8)-Gly(9)-Leu(10)-Meti(11)-NH2). The heptapeptide 1 frequently exhibits opposite effects to those induced by SP, such as exerting antinociception, or attenuating thermal hyperalgesia and mechanical allodynia. The heptapeptide SP1-7 amide (2, Arg(1)-Pro(2)-Lys(3)-Pro(4)-Gln(5)-Gln(6)-Phe(7)-NH2 ) is often more efficacious than 1 in experimental pain models. We have now assessed the anti-allodynic outcome after systemic administration of 2 and a series of Ala substituted and truncated analogues of 2, in the spared nerve injury (SNI) mice model and the results obtained were correlated with in vitro plasma stability and permeability measurements. It is herein demonstrated that an intact Arg(1) in SP1-7 amide analogues is fundamental for retaining a potent in vivo effect, while Lys(3) of 2 is less important. A displacement with Ala(1) or truncation rendered the peptide analogues either inactive or with a significantly attenuated in vivo activity. Thus, the pentapeptide SP3-7 amide (7, t(1/2) = 11.1 min) proven to be the major metabolite of 2, demonstrated an in vivo effect itself although considerably less significant than 2 in the SNI model. Intraperitoneal administration of 2 in a low dose furnished the most powerful anti-allodynic effect in the SNI model of all the analogous evaluated, despite a fast proteolysis of 2 in plasma (t(1/2) = 6.4 min). It is concluded that not only the C-terminal residue, that we previously demonstrated, but also the N-terminal with its basic side chain, are important for achieving effective pain relief. This information is of value for the further design process aimed at identifying more drug-like SP1-7 amide related peptidomimetics with pronounced antiallodynic effects.
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