| 1. |
- Allard, Christina, et al.
(författare)
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Rasbiologiskt språkbruk i statens rättsprocess mot sameby : DN Debatt 2015-06-11
- 2015
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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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| 2. |
- Belfrage, Anna Karin, et al.
(författare)
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Discovery of pyrazinone based compounds that potently inhibit the drug resistant enzyme variant R155K of the hepatitis C virus NS3 protease
- 2016
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Ingår i: Bioorganic & Medicinal Chemistry. - : Elsevier BV. - 0968-0896 .- 1464-3391. ; 24:12, s. 2603-2620
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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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| 3. |
- Ahlbeck Bergendahl, Ida, et al.
(författare)
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Fisk- och skaldjursbestånd i hav och sötvatten 2016 : Resursöversikt
- 2016
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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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| 4. |
- Allard, Christina, et al.
(författare)
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Rasbiologiskt språkbruk i statens rättsprocess mot sameby
- 2015
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Ingår i: Dagens Nyheter. - 1101-2447.
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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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| 5. |
- Bjärstig, Therese, 1978-, et al.
(författare)
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Between protocol and reality : Swedish municipal comprehensive planning
- 2018
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Ingår i: European Planning Studies. - : Informa UK Limited. - 0965-4313 .- 1469-5944. ; 26:1, s. 35-54
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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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| 6. |
- Gaillard, Marie-José, et al.
(författare)
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Causes of Regional Change : Land Cover
- 2015
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Ingår i: Second Assessment of Climate Change for the Baltic Sea Basin. - Cham : Springer. - 9783319160054 - 9783319160061 ; , s. 453-477
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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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| 7. |
- Granfors, Michaela, et al.
(författare)
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Placental location and pregnancy outcomes in nulliparous women : A population-based cohort study
- 2019
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : WILEY. - 0001-6349 .- 1600-0412. ; 98:8, s. 988-996
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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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| 8. |
- Jonsson, Anna, 1981-, et al.
(författare)
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Small constrained SP1-7 analogues bind to a unique site and promote anti-allodynic effects following systemic injection in mice
- 2015
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Ingår i: Neuroscience. - : Elsevier BV. - 0306-4522 .- 1873-7544. ; 298, s. 112-119
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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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| 9. |
- Klocker Larsen, Rasmus, et al.
(författare)
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Kumulativa effekter av exploateringar på renskötseln : Vad behöver göras inom tillståndsprocesser
- 2016
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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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| 10. |
- Sandström, Anna, et al.
(författare)
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Clinical risk assessment in early pregnancy for preeclampsia in nulliparous women : a population-based cohort study
- 2019
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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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| 11. |
- Sandström Gerdtsson, Anna, et al.
(författare)
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A Multicenter Trial Defining a Serum Protein Signature Associated with Pancreatic Ductal Adenocarcinoma.
- 2015
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Ingår i: International Journal of Proteomics. - : Hindawi Limited. - 2090-2174 .- 2090-2166. ; 2015
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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.
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| 12. |
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| 13. |
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| 14. |
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| 15. |
- Skogh, Anna, et al.
(författare)
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Impact of N-methylation of the substance P 1-7 amide on anti-allodynic effect in mice after peripheral administration
- 2017
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Ingår i: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 109, s. 533-540
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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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| 16. |
- Skogh, Anna, et al.
(författare)
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Importance of N-and C-terminal residues of substance P 1-7 for alleviating allodynia in mice after peripheral administration
- 2017
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Ingår i: European Journal of Pharmaceutical Sciences. - : Elsevier. - 0928-0987 .- 1879-0720. ; 106, s. 345-351
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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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| 17. |
- Webb, Charlotta, et al.
(författare)
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Celiac disease can be predicted by high levels of anti-tissue transglutaminase antibodies in population-based screening
- 2015
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Ingår i: Journal of Pediatric Gastroenterology and Nutrition - JPGN. - : Lippincott Williams & Wilkins. - 0277-2116 .- 1536-4801. ; 60:6, s. 787-791
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To evaluate any potential correlation between anti-tissue transglutaminase antibodies of type immunoglobulin A (tTG-IgA) and the degree of gluten induced enteropathy in children participating in a screening study for celiac disease (CD) and to assess to what extent the revised ESPGHAN (European Society for Paediatric Gastroenterology, Hepatology and Nutrition) guidelines cover this group of patients.METHODS: This is a sub-study of a cross-sectional CD screening study, ETICS (Exploring the Iceberg of Celiacs in Sweden), a two-phased study performed during 2005-2006 and 2009-2010. The 13,279 participating children had a blood test obtained and those with positive tTG-IgA were recommended a small intestinal biopsy. The tTG-IgA levels at the time of biopsy were compared with the assessment of the biopsy.RESULTS: There were 267 children included, of whom 230 were diagnosed with CD. Out of all children, 67 children had low tTG-IgA levels (<5 U/mL), whereof 55% had Marsh 3 lesions. All children with tTG-IgA levels exceeding 10 times the upper limit of normal values of 5 U/mL, i.e. 50 U/mL, were diagnosed with CD. Lowering the cut-off to 3 U/mL, all but one child with 30 U/mL got CD diagnosis.CONCLUSION: By adapting the revised ESPGHAN criteria, biopsies could have been omitted in a fourth of all cases. Our results indicate, that the criteria might be useful even on screened children. Further studies are needed to confirm whether the 2012 ESPGHAN guidelines should be revised to also apply to the populations being screened.
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| 18. |
- Webb, Charlotta, et al.
(författare)
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High adherence to a gluten-free diet in adolescents with screening-detected celiac disease
- 2015
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Ingår i: Journal of Pediatric Gastroenterology and Nutrition - JPGN. - : Lippincott Williams & Wilkins. - 0277-2116 .- 1536-4801. ; 60:1, s. 54-59
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To evaluate the gluten-free diet (GFD) adherenceafter one year of follow-up in children with screening-detected celiac disease (CD) in a general population. METHODS: A total of 18,325 12 year olds were invited to participate in apopulation-based CD screening (ETICS- Exploring the Iceberg of Celiacs in Sweden), of whom 13,279 participated. In 240 children, CD was detected through elevated anti-tissue transglutaminase antibodies 2 (TG2-IgA) and verified by a small-intestinal biopsy. This sub-study included the 210 children with TG2-IgAevaluated both at the initialbiopsy occasion and at the one-year follow-up. GFD adherence was evaluated by a combination of TG2-IgA measurements and self-reported adherence (n = 193). RESULTS: After one year, 83% (179/210) had normalizedTG2-IgA levels (<5U/mL). Among those who had >50 U/mL at diagnosis,25% (16/63) still had elevated TG2-IgA but for the majority their initial values were more than halved. Most reported a high level ofGFD adherence ('always' 75%(158/193) and 'often' 14%(30/193)), and 75% (145/193) reported always adhereingcombined with normalized TG2-IgA. Although reporting that they were always adherent, 13 (6.7%) had not yet normalized their TG2-IgA levels completely, however, a majority of these initially had the highestTG2-IgA levels. CONCLUSIONS: GFD adherence is high in adolescents with CD detected by screening of the general population of Swedish 12yearolds. Almost all had normalized serology and reported GFD adherenceat the one-year follow-up. However, a few adolescents whoreported GFD adherence still had elevated TG2-IgA levelssuggesting more severe disease and/or non-adherence.
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| 19. |
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| 20. |
- Abrahamsson, Johanna, 1990, et al.
(författare)
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A Raman spectroscopic approach to investigate the production of biodiesel from soybean oil using 1-alkyl-3-methylimidazolium ionic liquids with intermediate chain length
- 2015
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Ingår i: Applied Energy. - : Elsevier BV. - 1872-9118 .- 0306-2619. ; 154, s. 763-770
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Tidskriftsartikel (refereegranskat)abstract
- We present a Raman spectroscopic study of the conversion of soybean oil into biodiesel by methanol using the lipase B enzyme pseudomonas cepacia as the bio-catalyst and 1-alkyl-3-methylimidazolium ionic liquids (CnC1Im) as co-solvents, where the alkyl chain length is varied from ethyl (n=2) to decyl (n=10). We have limited this study to a low reaction temperature, 40°C, and a low enzyme concentration to investigate the possibility of producing biodiesel with low energy and cost demands. We also demonstrate that Raman spectroscopy is a powerful and straightforward method to estimate the yield of the transesterification reaction, by analysis of the characteristic CO stretching mode found in the range ~1730-1750cm-1. Our results indicate that both reaction yield and reaction rate increase with the chain length, but also that for chains longer than decyl further improvements are marginal. We discuss these results from the viewpoint of local interactions and local structure of the investigated ionic liquids.
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| 21. |
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| 22. |
- Ahlbeck Bergendahl, Ida, et al.
(författare)
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Fisk- och skaldjursbestånd i hav och sötvatten 2017 : Resursöversikt
- 2017
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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 och sju skaldjursarter.Nytt för i år är att vi även beskriver fritidsfisket mer utförligt. Det fisket får allt större betydelse för utvecklingen av många av Sveriges bestånd av fisk- och skaldjur, till exempel sötvattens- och kustlevande arter som abborre, gädda, gös, lax, röding och öring, liksom marina arter som torsk och hummerÖversikten är utarbetad av SLU Aqua på uppdrag av Havs- och vattenmyndigheten.
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| 23. |
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| 24. |
- Altman, Maria, et al.
(författare)
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Prolonged second stage of labor is associated with low Apgar score
- 2015
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Ingår i: European Journal of Epidemiology. - Stockholm : Karolinska Institutet, Dept of Medicine, Solna. - 0393-2990 .- 1573-7284.
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Tidskriftsartikel (refereegranskat)abstract
- There is no consensus on the effects of a prolonged second stage of labor on neonatal outcomes. In this large Swedish population-based cohort study, our objective was to investigate prolonged second stage and risk of low Apgar score at 5 minutes. All nulliparous women (n= 32 796) delivering a live born singleton infant in cephalic presentation at ≥37 completed weeks after spontaneous onset of labor between 2008 and 2012 in the counties of Stockholm and Gotland were included. Data were obtained from computerized records. Exposure was time from fully retracted cervix until delivery. Logistic regression analyses were used to estimate crude and adjusted odds ratios (OR) with 95% confidence intervals (CI). Adjustments were made for maternal age, height, BMI, smoking, sex, gestational age, sex-specific birth weight for gestational age and head circumference. Epidural analgesia was included in a second model. The primary outcome measure was Apgar score at 5 minutes <7 and <4. We found that the overall rates of 5 minute Apgar score <7 and <4 were 7.0 and 1.3 per 1000 births, respectively. Compared to women with <1 hour from retracted cervix to birth, adjusted ORs of Apgar score <7 at 5 minutes generally increased with length of second stage of labor: 1-<2 hours: OR 1.78 (95% CI 1.19-2.66); 2- <3 hours: OR 1.66 (1.05-2.62); 3-<4 hours: OR 2.08 (1.29-3.35); and ≥4 hours: OR 2.71 (1.67-4.40). We conclude that prolonged second stage of labor is associated with an increased risk of low 5 minute Apgar score.
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| 25. |
- Andersson, Jan, et al.
(författare)
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Fisk- och skaldjursbestånd i hav och sötvatten 2015 : Resursöversikt
- 2015
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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 (SLU Aqua) vid Sveriges lantbruksuniversitet (SLU) samt yrkesfiskets rapportering.Rapporten omfattar 40 fiskarter uppdelade i olika bestånd, samt sex skal-och blötdjursarter.Nytt för årets upplaga är en beskrivning av hur de provfisken som ligger till grund för analys och rådgivning utförs.Översikten är utarbetad av Sveriges lantbruksuniversitet (SLU), Institutionen för akvatiska resurser (SLU Aqua), på uppdrag av Havs- och vattenmyndigheten.
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| 26. |
- Andersson, Ken G, et al.
(författare)
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Comparative evaluation of 111In-labeled NOTA‑conjugated affibody molecules for visualization of HER3 expression in malignant tumors
- 2015
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Ingår i: Oncology Reports. - : Spandidos Publications. - 1021-335X .- 1791-2431. ; 34:2, s. 1042-8
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Tidskriftsartikel (refereegranskat)abstract
- Expression of human epidermal growth factor receptor type 3 (HER3) in malignant tumors has been associated with resistance to a variety of anticancer therapies. Several anti-HER3 monoclonal antibodies are currently under pre-clinical and clinical development aiming to overcome HER3-mediated resistance. Radionuclide molecular imaging of HER3 expression may improve treatment by allowing the selection of suitable patients for HER3-targeted therapy. Affibody molecules are a class of small (7kDa) high-affinity targeting proteins with appreciable potential as molecular imaging probes. In a recent study, we selected affibody molecules with affinity to HER3 at a low picomolar range. The aim of the present study was to develop an anti-HER3 affibody molecule suitable for labeling with radiometals. The HEHEHE-Z08698-NOTA and HEHEHE-Z08699-NOTA HER3-specific affibody molecules were labeled with indium‑111 (111In) and assessed invitro and invivo for imaging properties using single photon emission computed tomography (SPECT). Labeling of HEHEHE-Z08698-NOTA and HEHEHE-Z08699-NOTA with 111In provided stable conjugates. Invitro cell tests demonstrated specific binding of the two conjugates to HER3-expressing BT‑474 breast carcinoma cells. In mice bearing BT‑474 xenografts, the tumor uptake of the two conjugates was receptor‑specific. Direct invivo comparison of 111In-HEHEHE-Z08698-NOTA and 111In-HEHEHE-Z08699‑NOTA demonstrated that the two conjugates provided equal radioactivity uptake in tumors, although the tumor-to-blood ratio was improved for 111In-HEHEHE-Z08698-NOTA [12±3 vs. 8±1, 4h post injection (p.i.)] due to more efficient blood clearance. 111In-HEHEHE-Z08698-NOTA is a promising candidate for imaging of HER3-expression in malignant tumors using SPECT. Results of the present study indicate that this conjugate could be used for patient stratification for anti-HER3 therapy.
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| 27. |
- Belfrage, Anna Karin, 1977-
(författare)
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Design and Synthesis of Hepatitis C Virus NS3 Protease Inhibitors : Targeting Different Genotypes and Drug-Resistant Variants
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Since the first approved hepatitis C virus (HCV) NS3 protease inhibitors in 2011, numerous direct acting antivirals (DAAs) have reached late stages of clinical trials. Today, several combination therapies, based on different DAAs, with or without the need of pegylated interferon-α injection, are available for chronic HCV infections. The chemical foundation of the approved and late-stage HCV NS3 protease inhibitors is markedly similar. This could partly explain the cross-resistance that have emerged under the pressure of NS3 protease inhibitors. The first-generation NS3 protease inhibitors were developed to efficiently inhibit genotype 1 of the virus and were less potent against other genotypes.The main focus in this thesis was to design and synthesize a new class of 2(1H)-pyrazinone based HCV NS3 protease inhibitors, structurally dissimilar to the inhibitors evaluated in clinical trials or approved, potentially with a unique resistance profile and with a broad genotypic coverage. Successive modifications were performed around the pyrazinone core structure to clarify the structure-activity relationship; a P3 urea capping group was found valuable for inhibitory potency, as were elongated R6 residues possibly directed towards the S2 pocket. Dissimilar to previously developed inhibitors, the P1’ aryl acyl sulfonamide was not essential for inhibition as shown by equally good inhibitory potency for P1’ truncated inhibitors. In vitro pharmacokinetic (PK) evaluations disclosed a marked influence from the R6 moiety on the overall drug-properties and biochemical evaluation of the inhibitors against drug resistant enzyme variants showed retained inhibitory potency as compared to the wild-type enzyme. Initial evaluation against genotype 3a displayed micro-molar potencies. Lead optimization, with respect to improved PK properties, were also performed on an advanced class of HCV NS3 protease inhibitors, containing a P2 quinazoline substituent in combination with a macro-cyclic proline urea scaffold with nano-molar cell based activities.Moreover, an efficient Pd-catalyzed C-N urea arylation protocol, enabling high yielding introductions of advanced urea substituents to the C3 position of the pyrazinone, and a Pd-catalyzed carbonylation procedure, to obtain acyl sulfinamides, were developed. These methods can be generally applicable in the synthesis of bioactive compounds containing peptidomimetic scaffolds and carboxylic acid bioisosteres.
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| 28. |
- Belfrage, Anna Karin, 1977-, et al.
(författare)
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Efficient and Selective Palladium-Catalysed C-3 Urea Couplings to 3,5-Dichloro-2(1H)-pyrazinones
- 2015
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Ingår i: European Journal of Organic Chemistry. - : Wiley. - 1434-193X .- 1099-0690. ; :5, s. 978-986
-
Tidskriftsartikel (refereegranskat)abstract
- The development of a robust palladium-catalysed urea N-arylation protocol to install various ureas at the 3-position of the 2(1H)-pyrazinone scaffold is described. The method involves Pd(OAc)2 in combination with bidentate ligands, xantphos [4,5-bis(diphenylphosphino)-9,9-dimethylxanthene] in particular, and resulted in good to excellent coupling yields of aliphatic, aromatic, and sterically hindered ureas. Furthermore, the C-3 chlorine was shown to be selectively displaced in the presence of aryl halide ureas, and this finding was supported by density functional theory (DFT) calculations. This allows further diversification of the scaffold for the production of compound libraries. Overall, the protocol facilitates further exploitation of pyrazinones as beta-sheet-inducing scaffolds in the development of sophisticated peptidomimetics/protease inhibitors. This is exemplified here by the synthesis of a new pyrazinone-based hepatitis C virus (HCV) NS3 protease inhibitor.
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| 29. |
- Belfrage, Anna Karin, 1977-, et al.
(författare)
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Palladium-Catalyzed Carbonylation of Aryl Iodides with Sulfinamides
- 2015
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Ingår i: European Journal of Organic Chemistry. - : Wiley. - 1434-193X .- 1099-0690. ; :32, s. 7069-7074
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Tidskriftsartikel (refereegranskat)abstract
- A facile palladium(0)-catalyzed carbonylative protocol for the generation of new acyl-sulfinamides in moderate to good yields is described. Aliphatic and aromatic sulfinamides were exploited as hitherto unexplored nucleophiles in carbonylation chemistry, with use of CO gas generated ex situ from Mo(CO)6 in a sealed two-chamber system. Both electron-poor and electron-rich (hetero)aryl iodides were employed as electrophiles. The two-chamber system and the use of an inorganic base were essential for efficacious synthesis of acyl-sulfinamide products. Finally, it was demonstrated that a one-pot (or single-vial) synthesis of acyl-sulfinamides was feasible under CO at balloon pressure in the presence of Cs2CO3 as base.
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| 30. |
- Björnsson, Bergthor, et al.
(författare)
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Laparoscopic versus open distal pancreatectomy (LAPOP) : Study protocol for a single center, nonblinded, randomized controlled trial
- 2019
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Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 20:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Earlier nonrandomized studies have suggested that laparoscopic distal pancreatectomy (LDP) is advantageous compared with open distal pancreatectomy (ODP) regarding hospital stay, blood loss, and recovery. Only one randomized study has been conducted showing reduced time to functional recovery after LDP compared with ODP. Methods: LAPOP is a prospective randomized, nonblinded, parallel-group, single-center superiority trial. Sixty patients with lesions in the pancreatic body or tail that are found by a multidisciplinary tumor board to need surgical resection will be randomized to receive LDP or ODP. The primary outcome variable is postoperative hospital stay, and secondary outcomes include functional recovery (defined as no need for intravenous medications or fluids and as the ability of an ambulatory patient to perform activities of daily life), perioperative bleeding, complications, need for pain medication, and quality of life comparison. Discussion: The LAPOP trial will test the hypothesis that LDP reduces postoperative hospital stay compared with ODP.
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| 31. |
- Brodin, Yngve, et al.
(författare)
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Tvåvingar Diptera
- 2015
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Ingår i: Rödlistade arter i Sverige 2015. - 9789187853104 ; , s. 113-118
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 32. |
- Chinthakindi, Praveen K., et al.
(författare)
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Synthesis of Sulfonimidamide-Based Amino Acid Building Blocks with Orthogonal Protecting Groups
- 2019
-
Ingår i: European Journal of Organic Chemistry. - : WILEY-V C H VERLAG GMBH. - 1434-193X .- 1099-0690. ; :5, s. 1045-1057
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Tidskriftsartikel (refereegranskat)abstract
- Herein, we report the synthesis of novel sulfonimidamides (SIAs) based on amino acid building blocks using a one-pot method from tert-butyldiphenylsilyl-protected (TBDPS) sulfonamides, as well as exploration of orthogonal deprotection strategies. Among the several protecting groups investigated, TBDPS showed higher conversion, allowed UV detection and simple diastereomeric separation; in particular in combination with amino acid tert-butyl esters. Moreover, we applied the present method to synthesize cyclic five-membered acyl sulfonimidamides in two steps. The described synthesis of SIA-based amino acid building blocks in combination with the orthogonal protection groups provide access to unnatural amino acid building blocks useful for further incorporation into larger molecules, such as peptide-based transition-state analogues and peptidomimetics. The chirality of the SIA group, as well as its additional point of diversity provided by the extra NH group, creates opportunities for the development of unique compound libraries that explore new chemical space, which is of considerable importance for the pharmaceutical and agrochemical industry.
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| 33. |
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| 34. |
- El-Schich, Zahra, et al.
(författare)
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Interfacing antibody-based microarrays and digital holography enables label-free detection for loss of cell volume
- 2015
-
Ingår i: Future Science OA. - : Future Science Group. - 2056-5623. ; 1:3
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Tidskriftsartikel (refereegranskat)abstract
- Background: We introduce the combination of digital holographic microscopy (DHM) and antibody microarrays as a powerful tool to measure morphological changes in specifically antibody-captured cells. The aim of the study was to develop DHM for analysis of cell death of etoposide-treated suspension cells. Result/Methodology: We demonstrate that the cell number, mean area, thickness, and volume were non-invasively measured by using DHM. The cell number was stable over time, but the two cell lines showed changes of cell area and cell irregularity after treatment. The cell volume in etoposide-treated cells was decreased, whereas untreated cells showed stable volume. Conclusions: Our results provide proof of concept for using DHM combined with antibody-based microarray technology for detecting morphological changes in captured cells.
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| 35. |
- Garousi, Javad, et al.
(författare)
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ADAPT, a Novel Scaffold Protein-Based Probe for Radionuclide Imaging of Molecular Targets That Are Expressed in Disseminated Cancers
- 2015
-
Ingår i: Cancer Research. - : American Association for Cancer Research Inc.. - 0008-5472 .- 1538-7445. ; 75:20, s. 4364-4371
-
Tidskriftsartikel (refereegranskat)abstract
- Small engineered scaffold proteins have attracted attention as probes for radionuclide-based molecular imaging. One class of these imaging probes, termed ABD-Derived Affinity Proteins (ADAPT), has been created using the albumin-binding domain (ABD) of streptococcal protein G as a stable protein scaffold. In this study, we report the development of a clinical lead probe termed ADAPT6 that binds HER2, an oncoprotein overexpressed in many breast cancers that serves as a theranostic biomarker for several approved targeting therapies. Surface-exposed amino acids of ABD were randomized to create a combinatorial library enabling selection of high-affinity binders to various proteins. Furthermore, ABD was engineered to enable rapid purification, to eradicate its binding to albumin, and to enable rapid blood clearance. Incorporation of a unique cysteine allowed site-specific conjugation to a maleimido derivative of a DOTA chelator, enabling radionuclide labeling, In-111 for SPECT imaging and Ga-68 for PET imaging. Pharmacologic studies in mice demonstrated that the fully engineered molecule In-111/Ga-68-DOTA(HE) 3-ADAPT6 was specifically bound and taken up by HER2-expressing tumors, with a high tumor-to-normal tissue ratio in xenograft models of human cancer. Unbound tracer underwent rapid renal clearance followed by high renal reabsorption. HER2-expressing xenografts were visualized by gamma-camera or PET at 1 hour after infusion. PET experiments demonstrated feasibility for discrimination of xenografts with high or low HER2 expression. Our results offer a preclinical proof of concept for the use of ADAPT probes for noninvasive in vivo imaging.
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| 36. |
- Gerdtsson, Anna Sandström, et al.
(författare)
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Plasma protein profiling in a stage defined pancreatic cancer cohort – Implications for early diagnosis
- 2016
-
Ingår i: Molecular Oncology. - : Wiley. - 1574-7891. ; 10:8, s. 1305-1316
-
Tidskriftsartikel (refereegranskat)abstract
- Pancreatic ductal adenocarcinoma (PDAC) is a disease where detection preceding clinical symptoms significantly increases the life expectancy of patients. In this study, a recombinant antibody microarray platform was used to analyze 213 Chinese plasma samples from PDAC patients and normal control (NC) individuals. The cohort was stratified according to disease stage, i.e. resectable disease (stage I/II), locally advanced (stage III) and metastatic disease (stage IV). Support vector machine analysis showed that all PDAC stages could be discriminated from controls and that the accuracy increased with disease progression, from stage I to IV. Patients with stage I/II PDAC could be discriminated from NC with high accuracy based on a plasma protein signature, indicating a possibility for early diagnosis and increased detection rate of surgically resectable tumors.
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| 37. |
- Hasselgren, Kristina, 1976-, et al.
(författare)
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Future Liver Remnant (FLR) Increase in Patients with Colorectal Liver Metastases Is Highest the First Week After Portal Vein Occlusion: FLR Increase in Patients with CRLM Is Highest the First Week After PVO
- 2019
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Ingår i: Journal of Gastrointestinal Surgery. - : Springer Science and Business Media LLC. - 1091-255X .- 1873-4626. ; 23:3, s. 556-562
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundPortal vein occlusion (PVO) is an established method to increase the volume of the future liver remnant (FLR). The main reasons for not proceeding to radical hepatectomy are lack of volume increase and tumor progression due to a wait-time interval of up to 8weeks. The hypothesis was that the increase in FLR volume is not linear and is largest during the first weeks.MethodsPatients with colorectal liver metastases (CRLM) and standardized future liver remnant (sFLR) <30% treated with PVO were prospectively included. All patients had at least one CT evaluation before radical hepatectomy.ResultsForty-eight patients were included. During the first week after PVO, the kinetic growth rate (KGR) was 5.4 (4), compared to 1.5 (+/- 2) between the first and second CT (p<0.05). For patients reaching adequate FLR and therefore treated with radical hepatectomy, the KGR was 7 (+/- 4) the first week, compared to 4.3 (+/- 2) for patients who failed to reach a sufficient volume (p=0.4). During the interval between the first and second CT, the KGR was 2.2 (+/- 2), respectively (+/- 0.1) (p=0.017).Discussion p id=Par4 The increase in liver volume after PVO is largest during the first week. As KGR decreases over time, it is important to shorten the interval between PVO and the first volume evaluation; this may aid in decision-making and reduce unnecessary waiting time.
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| 38. |
- Holm, Anna, et al.
(författare)
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Mapping of Human Papilloma Virus, p16, and Epstein-Barr Virusin Non-Malignant Tonsillar Disease
- 2019
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Ingår i: Laryngoscope Investigative Otolaryngology (LIO). - : Wiley-Blackwell. - 2378-8038. ; 4:3, s. 285-291
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: Due to their location in the entrance of the aero‐digestive tract, tonsils are steadily exposed to viruses. Human papilloma virus (HPV) and Epstein‐Barr virus (EBV) are two potentially oncogenic viruses that tonsils encounter. The incidence of HPV positive tonsillar cancer is on the rise and it is unknown when infection with HPV occurs.Aim: To investigate if tonsils are infected with HPV and EBV, to study the co‐expression of HPV and its surrogate marker p16, and to evaluate the number of EBV positive cells in benign tonsillar disease.Materials and Methods: Tonsils from 40 patients in a university hospital were removed due to hypertrophy, chronic or recurrent infection. These were analyzed for presence of HPV, its surrogate marker p16, and EBV. HPV was studied using PapilloCheck (a PCR method), while p16 was identified in epithelial and lymphoid tissue with immunohistochemistry and EBV using EBER‐ISH (Epstein‐Barr encoding region–in situ hybridization).Results: HPV was not detected, and p16 was present at low numbers in all epithelial samples as well as in 92.5% of the lymphoid tonsillar samples. At least one EBER‐positive cell was seen in 65% of cases. Larger numbers of EBER‐expressing cells were only seen in two cases.Conclusion: These findings demonstrate that EBV and HPV infect tonsils independently, but further studies are warranted to confirm their infectious relationship.Level of Evidence: Cross‐sectional study
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| 39. |
- Holmgren, Lina, et al.
(författare)
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Protected area governance in Sweden : new modes of governance or business as usual?
- 2017
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Ingår i: Local Environment. - : Taylor & Francis. - 1354-9839 .- 1469-6711. ; 22:1, s. 22-37
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Tidskriftsartikel (refereegranskat)abstract
- This paper explores whether ambitions to open up the traditional Swedish model of top-down conservation methods to local influences are indicative of an actual transition in governance of Swedish national park policy (NPP), and examines whether such a shift entails an increase in local influence over local interests and needs. Methodologically, we analyse a combination of governance types and incorporate theoretical definitions of power and accountability. The establishment of new governance arrangements – where power is shared, interactions promoted and accountability is directed downwards – indicates that Sweden's NPP is undergoing a change in its mode of governance. This change also seems to include ceding some influence to local interests, and the possibility of combining conservation with the utilisation of certain natural resources. The results of our research also provide valuable insights into when the establishment of shared-governance arrangements are likely to succeed; in short, this seems more likely when there are established sectors sited in a robust legal framework and where strong international commitments potentially play a role. In conclusion, we contend that when seeking diversified governance arrangements it is not enough simply to take local practices and customs into consideration – they have to be strengthened.
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| 40. |
- Honarvar, Hadis, et al.
(författare)
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Feasibility of Affibody Molecule-Based PNA-Mediated Radionuclide Pretargeting of Malignant Tumors
- 2016
-
Ingår i: Theranostics. - : Ivyspring International Publisher. - 1838-7640. ; 6:1, s. 93-103
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Tidskriftsartikel (refereegranskat)abstract
- Affibody molecules are small (7 kDa), non-immunoglobulin scaffold proteins with a potential as targeting agents for radionuclide imaging of cancer. However, high renal re-absorption of Affibody molecules prevents their use for radionuclide therapy with residualizing radiometals. We hypothesized that the use of Affibody-based peptide nucleic acid (PNA)-mediated pretargeting would enable higher accumulation of radiometals in tumors than in kidneys. To test this hypothesis, we designed an Affibody-PNA chimera Z(HER2:342)-SR-HP1 containing a 15-mer HP1 PNA recognition tag and a complementary HP2 hybridization probe permitting labeling with both I-125 and In-111. In-111-Z(HER2:342)-SR-HP1 bound specifically to HER2-expressing BT474 and SKOV-3 cancer cells in vitro, with a K-D of 6+/-2 pM for binding to SKOV-3 cells. Specific high affinity binding of the radiolabeled complementary PNA probe In-111-/I-125-HP2 to Z(HER2:342)-SR-HP1 pre-treated cells was demonstrated. In-111-Z(HER2:342)-SR-HP1 demonstrated specific accumulation in SKOV-3 xenografts in BALB/C nu/nu mice and rapid clearance from blood. Pre-saturation of SKOV-3 with non-labeled anti-HER2 Affibody or the use of HER2-negative Ramos xenografts resulted in significantly lower tumor uptake of In-111-Z(HER2:342)-SR-HP1. The complementary PNA probe In-111/I-125-HP2 accumulated in SKOV-3 xenografts when Z(HER2:342)-SR-HP1 was injected 4 h earlier. The tumor accumulation of In-111/I-125-HP2 was negligible without Z(HER2:342)-SR-HP1 pre-injection. The uptake of In-111-HP2 in SKOV-3 xenografts was 19+/-2 % ID/g at 1 h after injection. The uptake in blood and kidneys was approximately 50- and 2-fold lower, respectively. In conclusion, we have shown that the use of Affibody-based PNA-mediated pretargeting enables specific delivery of radiometals to tumors and provides higher radiometal concentration in tumors than in kidneys.
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| 41. |
- Ibrahim, Farzana, et al.
(författare)
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'I want to know why and need to be involved in my own care…' : a qualitative interview study with liver, bile duct or pancreatic cancer patients about their experiences with involvement in care.
- 2019
-
Ingår i: Supportive Care in Cancer. - : Springer. - 0941-4355 .- 1433-7339. ; 27:7, s. 2561-2567
-
Tidskriftsartikel (refereegranskat)abstract
- PurposePatients’ involvement in their own care is important for those with upper abdominal tumours. Care is often conducted according to standardized fast-track care programs (FTCP), and a shorter hospital stay is one of the goals. However, there is no research providing an in-depth perspective on patients’ experiences of involvement in care. In this qualitative study, we explored experiences of involvement among patients who had surgery for upper abdominal tumours and were cared for according to an FTCP.MethodsQualitative in-depth face-to-face interviews about patient involvement in care were conducted with 20 patients who had surgery for the liver, bile duct, or pancreatic cancer using an open-interview guide.ResultsThe most important findings are that customized information and active dialogue about care decisions stimulate patient involvement. We identified three themes from the analysed data: involvement depended on the quality of information, communication and involvement during the care period, and safety at discharge.ConclusionsIndividualized care and continuous information about treatment and care goals in the FTCP during the care process create trust between patients and healthcare professionals and increase patient experiences of involvement.
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| 42. |
- Jin, Y. K., et al.
(författare)
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A Dual-Promoter Gene Orchestrates the Sucrose-Coordinated Synthesis of Starch and Fructan in Barley
- 2017
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Ingår i: Molecular Plant. - : Elsevier BV. - 1674-2052 .- 1752-9867. ; 10:12, s. 1556-1570
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Tidskriftsartikel (refereegranskat)abstract
- Sequential carbohydrate synthesis is important for plant survival because it guarantees energy supplies for growth and development during plant ontogeny and reproduction. Starch and fructan are two important carbohydrates in many flowering plants and in human diets. Understanding this coordinated starch and fructan synthesis and unraveling how plants allocate photosynthates and prioritize different carbohydrate synthesis for survival could lead to improvements to cereals in agriculture for the purposes of greater food security and production quality. Here, we report a system from a single gene in barley employing two alternative promoters, one intronic/exonic, to generate two sequence-overlapping but functionally opposing transcription factors, in sensing sucrose, potentially via sucrose/glucose/fructose/trehalose 6-phosphate signaling. The system employs an autoregulatory mechanism in perceiving a sucrose-controlled trans activity on one promoter and orchestrating the coordinated starch and fructan synthesis by competitive transcription factor binding on the other promoter. As a case in point for the physiological roles of the system, we have demonstrated that this multitasking system can be exploited in breeding barley with tailored amounts of fructan to produce healthy food ingredients. The identification of an intron/exon-spanning promoter in a hosting gene, resulting in proteins with distinct functions, adds to the complexity of plant genomes. ERYSTWYTH, WALES, V123, P453
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| 43. |
- Larnebratt, Anton, et al.
(författare)
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Information is the key to successful participation for patients receiving surgery for upper gastrointestinal cancer
- 2019
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Ingår i: European Journal of Cancer Care. - : John Wiley & Sons. - 0961-5423 .- 1365-2354. ; :2
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Tidskriftsartikel (refereegranskat)abstract
- Fast-track programmes are aimed at improving perioperative care. The purpose of this study was to identify and explore patient participation among patients who had surgery for liver, bile duct or pancreatic cancer and followed a fast-track programme. A total of 116 questionnaires to investigate patient participation were analysed. Information was important for the patients, as was having the opportunity to ask questions and express personal views. The results showed differences by sex; men responded to a greater extent that they did not want to make decisions as a patient (p = 0.044) and that they had been motivated to take more responsibility for their future health (p = 0.011). Patients with pancreatic cancer discussed treatment goals with doctors to a greater extent than did patients with liver cancer (p = 0.041). Half of the patients perceived that they had not been involved in their care planning after discharge but had a desired to be involved. This seems to be an important point to improve in future care, and also that professionals should be aware of patients' needs for information and participation, especially at discharge.
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| 44. |
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| 45. |
- Lindahl, Karin Beland, et al.
(författare)
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The Swedish forestry model : more of everything?
- 2017
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Ingår i: Forest Policy and Economics. - : Elsevier. - 1389-9341 .- 1872-7050. ; 77, s. 44-55
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Tidskriftsartikel (refereegranskat)abstract
- "The Swedish forestry model" refers to the forest regime that evolved following the 1993 revision of the Swedish Forestry Act. It is key to Swedish forest politics and used to capture the essence of a sustainable way of managing forests. However, the ideas, institutions and practices comprising the model have not been comprehensively analyzed previously. Addressing this knowledge gap, we use frame analysis and a Pathways approach to investigate the underlying governance model, focusing on the way policy problems are addressed, goals, implementation procedures, outcomes and the resulting pathways to sustainability. We suggest that the institutionally embedded response to pressing sustainability challenges and increasing demands is expansion, inclusion and integration: more of everything. The more-of-everything pathway is influenced by ideas of ecological modernization and the optimistic view that existing resources can be increased. Our findings suggest that in effect it prioritizes the economic dimension of sustainability. While broadening out policy formulation it closes down the range of alternative outputs, a shortcoming that hampers its capacity to respond to current sustainability challenges. Consequently, there is a need for a broad public debate regarding not only the role of forests in future society, but also the operationalization of sustainable development.
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| 46. |
- Lindblom, Anna, et al.
(författare)
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Interspecies plasmid transfer appears rare in sequential infections with extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae
- 2019
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Ingår i: Diagnostic Microbiology and Infectious Disease. - : Elsevier BV. - 0732-8893 .- 1879-0070. ; 93:4, s. 380-385
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Tidskriftsartikel (refereegranskat)abstract
- From a cohort of 1836 Swedish patients infected with ESBL-producing Enterobacteriaceae (EPE) during 2004-2014, 513 patients with recurrent EPE infection were identified. Only in 14 of the 513 patients was a change of species (ESBL-E. coli to ESBL-K. pneumoniae or vice versa) found between the index and subsequent infection. Eleven sequential urine isolates from 5 of the 14 patients were available for further analysis of possible transfer of ESBL-carrying plasmids. The plasmid content was studied using optical DNA mapping (ODM), PCR-based replicon typing, and ESBL gene sequencing. ODM allowed us to directly compare whole plasmids between isolates and found similar ESBL-carrying plasmids in 3 out of the 5 patients. The ODM results and the rarity in shift of species between ESBL-E. coli and ESBL-K. pneumoniae imply that in recurrent EPE infections interspecies plasmid transfer is uncommon. (C) 2018 Elsevier Inc. All rights reserved.
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| 47. |
- Mitran, Bogdan, et al.
(författare)
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Evaluation of Tc-99m-Z(IGF1R:4551)-GGGC affibody molecule, a new probe for imaging of insulin-like growth factor type 1 receptor expression
- 2015
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Ingår i: Amino Acids. - : Springer Science and Business Media LLC. - 0939-4451 .- 1438-2199. ; 47:2, s. 303-315
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Tidskriftsartikel (refereegranskat)abstract
- Overexpression of insulin-like growth factor-1 receptor (IGF-1R) in several cancers is associated with resistance to therapy. Radionuclide molecular imaging of IGF-1R expression in tumors may help in selecting the patients that will potentially respond to IGF-1R-targeted therapy. Affibody molecules are small (7 kDa) non-immunoglobulin-based scaffold proteins that are well-suited probes for radionuclide imaging. The aim of this study was the evaluation of an anti-IGF-1R affibody molecule labeled with technetium-99m using cysteine-containing peptide-based chelator GGGC at C-terminus. Z(IGF1R:4551)-GGGC was efficiently and stably labeled with technetium-99m (radiochemical yield 97 +/- A 3 %). Tc-99m-Z(IGF1R:4551)-GGGC demonstrated specific binding to IGF-1R-expressing DU-145 (prostate cancer) and MCF-7 (breast cancer) cell lines and slow internalization in vitro. The tumor-targeting properties were studied in BALB/c nu/nu mice bearing DU-145 and MCF-7 xenografts. [Tc-99m(CO)(3)](+)-(HE)(3)-Z(IGF1R:4551) was used for comparison. The biodistribution study demonstrated high tumor-to-blood ratios (6.2 +/- A 0.9 and 6.9 +/- A 1.0, for DU-145 and MCF-7, respectively, at 4 h after injection). Renal radioactivity concentration was 16-fold lower for Tc-99m-Z(IGF1R:4551)-GGGC than for [Tc-99m(CO)(3)](+)-(HE)(3)-Z(IGF1R:4551) at 4 h after injection. However, the liver uptake of Tc-99m-Z(IGF1R:4551)-GGGC was 1.2- to 2-fold higher in comparison with [Tc-99m(CO)(3)](+)-(HE)(3)-Z(IGF1R:4551). A possible reason for the elevated hepatic uptake of Tc-99m-Z(IGF1R:4551)-GGGC is a high lipophilicity of amino acids in the binding site of Z(IGF1R:4551), which is not compensated in Tc-99m-Z(IGF1R:4551)-GGGC. In conclusion, Tc-99m-Z(IGF1R:4551)-GGGC can visualize the IGF-1R expression in human tumor xenografts and provides low retention of radioactivity in kidneys. Further development of this imaging agent should include molecular design aimed at reducing the hepatic uptake.
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| 48. |
- Molander, Marcus, et al.
(författare)
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Development of condition monitoring methods for polymeric com-ponents including low dose rate radiation exposure
- 2018
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Konferensbidrag (refereegranskat)abstract
- Different plastics, rubber and other polymer based materials are widely used in various applications in nuclear power plants and inside containments, e.g. cable jacketing/insulators, sealants, paint coatings, lubricants and greases. As any other material or component, polymers are susceptible to ageing. Ele-vated temperature, ionizing radiation and moisture are considered to be the most important ageing stressors and they tend to interact with the polymer structure in different ways. In addition to these ageing stressors, properties of polymer composition, e.g. crystallinity degree, amount of fillers and antioxidants, has an effect to the ageing behavior. Thus, the degradation mechanism can be quite complex.Proper ageing management procedures are based on knowledge on the ageing behavior and how to set correct requirements for the polymer components in use that they will endure their designed life-time. The ageing behavior needs to be known when polymer components are qualified. Accelerated ageing is used as part of the artificial ageing of the qualified polymer and the ageing mechanism should be the same as in the real service environment in order to yield in identical ageing conditions. Thus, the effects of dose rate and temperature to the ageing mechanism must be known as well as the synergistic effects rising from the simultaneous and/or sequential exposure to ionizing radiation and excess heat.In a previous feasibility study [2015:157]1 the acceptance criteria for functional properties for different polymers in system components was studied. The components were selected based on interviews with the five Nordic nuclear power plants. A need to study the polymer degradation, using low dose rates (20-50 Gy/h to total dose of 14 kGy) was identified since previous work described in literature often focused on using a high dose rate to achieve the life time dose during a short period of time to achieve a life time dose2. This may cause different degradation, compared to that obtained with a long exposure at a low dose rate, which is the case for many O-rings inside a Nuclear Power plant (NPP). Like the previous feasibility study this research project is performed in collaboration with the Nordic nuclear industry for in a longer perspective implementing the results.Rubber materials were tested for different properties such as compression set, stress relaxation, elon-gation at break, Oxidation Induction Temperature (Tox) and hardness after heat ageing and gamma irradiation. These properties were then correlated to the function of the O-ring i.e. tightness verified by a leakage test in a specially designed test rig. To be able to better compare the degradation effect caused by the irradiation, a parallel test on samples aged in heat only was performed. By testing the correlation between material data and tightness of an O-ring an understanding of the function (tight-ness) based on a material property (compression set) can be made. The aim was to be able to use this to set acceptance criteria for an O-ring using compression set as a property. A model using Finite Elements (FE) based on the relaxation data and compression set data from the experiment was also done but is only described briefly in this paper.
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| 49. |
- Mukaida, Saori, et al.
(författare)
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BRL37344 stimulates GLUT4 translocation and glucose uptake in skeletal muscle via beta(2)-adrenoceptors without causing classical receptor desensitization
- 2019
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Ingår i: American Journal of Physiology. Regulatory Integrative and Comparative Physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 316:5, s. R666-R677
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Tidskriftsartikel (refereegranskat)abstract
- The type 2 diabetes epidemic makes it important to find insulinin-dependent ways to improve glucose homeostasis. This study examines the mechanisms activated by a dual beta(2)-/beta(3)-adrenoceptor agonist, BRL37344, to increase glucose uptake in skeletal muscle and its effects on glucose homeostasis in vivo. We measured the effect of BRL37344 on glucose uptake, glucose transporter 4 (GLUT4) translocation, cAMP levels, beta(2)-adrenoceptor desensitization, beta-arrestin recruitment, Akt, AMPK, and mammalian target of rapamycin (mTOR) phosphorylation using L6 skeletal muscle cells as a model. We further tested the ability of BRL37344 to modulate skeletal muscle glucose metabolism in animal models (glucose tolerance tests and in vivo and ex vivo skeletal muscle glucose uptake). In L6 cells, BRL37344 increased GLUT4 translocation and glucose uptake only by activation of beta(2)-adrenoceptors, with a similar potency and efficacy to that of the nonselective beta-adrenoceptor agonist isoprenaline, despite being a partial agonist with respect to cAMP generation. GLUT4 translocation occurred independently of Akt and AMPK phosphorylation but was dependent on mTORC2. Furthermore, in contrast to isoprenaline, BRL37344 did not promote agonist-mediated desensitization and failed to recruit beta-arrestin1/2 to the beta(2)-adrenoceptor. In conclusion, BRL37344 improved glucose tolerance and increased glucose uptake into skeletal muscle in vivo and ex vivo through a beta(2)-adrenoceptor-mediated mechanism independently of Akt. BRL37344 was a partial agonist with respect to cAMP, but a full agonist for glucose uptake, and importantly did not cause classical receptor desensitization or internalization of the receptor.
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| 50. |
- Myléus, Anna, MD PhD, et al.
(författare)
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Questionnaire showed that Swedish paediatric clinics complied well with the revised European guidelines for diagnosing coeliac disease
- 2019
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Ingår i: Acta Paediatrica. - : John Wiley & Sons. - 0803-5253 .- 1651-2227. ; 108:6, s. 1140-1143
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Tidskriftsartikel (refereegranskat)abstract
- Aim: In 2012, revised criteria for diagnosing childhood coeliac disease were published by the European Society for Paediatric Gastroenterology, Hepatology and Nutrition and incorporated into the revised Swedish guidelines the same year. These made it possible, in certain cases, to diagnose coeliac disease without taking small bowel biopsies. This survey assessed the extent to which the new guidelines were implemented by Swedish paediatric clinics two years after their introduction.Methods: In October 2014, we distributed a paper questionnaire including five questions on diagnostic routines to the 40 paediatric clinics in university or regional hospitals in Sweden that perform small bowel biopsies.Results: All 36 (90%) clinics that responded used anti-tissue transglutaminase antibodies as the initial diagnostic test and some also used serological markers. Most clinics (81%) used endoscopy and took multiple duodenal biopsies, whereas only a few (19%) occasionally employed a suction capsule. Almost all clinics (86%) omitted taking small bowel biopsies in symptomatic children with repeatedly high coeliac serology and positive genotyping, thereby avoiding the need for invasive endoscopy under anaesthesia.Conclusion: The 2012 Swedish Paediatric Coeliac Disease Diagnostic Guidelines had been widely accepted and implemented in routine health care two years after their introduction.
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