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3.
  • Almung, Magnus, et al. (författare)
  • I solitärens skugga : Nyttobyggnadens kreativa restaurering
  • 2015
  • Rapport (populärvet., debatt m.m.)abstract
    • Ekonomibyggnader har alltid behövts för de huvudbyggnader som finns inom våra bevarade kulturmiljöer. Några nyttobyggnader uppskattas och används fortfarande, andra betraktas som problematiska överloppsbyggnader, många rivs. Alltför få har dokumenterats eller fått sin historia klarlagd vilket undanhållit viktig kunskap om samhällets framväxt. Vi vill synliggöra och betona vikten av att bevara och utveckla hela bebyggelsemiljöer, ofta med ett antal hus utöver huvudbyggnaden och tillhörande yttre miljö i staden eller på landet. Denna rapport visar kursdeltagarnas projektarbeten om nyttobyggnader. De har dokumenterat med traditionella och nya arbetsmetoder, inventerat och intervjuat, läst och besökt arkiv, värderat, analyserat och därefter föreslagit hur man ska ta hand om och utveckla nyttobyggnaderna i sina kulturmiljöer.
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4.
  • Arver, Brita, et al. (författare)
  • Bilateral Prophylactic Mastectomy in Swedish Women at High Risk of Breast Cancer: A National Survey.
  • 2011
  • Ingår i: Annals of surgery. - : Lippincott Williams and Wilkins; 1999. - 1528-1140 .- 0003-4932. ; 253:6, s. 1147-1154
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND/OBJECTIVE:: This study attempted a national inventory of all bilateral prophylactic mastectomies performed in Sweden between 1995 and 2005 in high-risk women without a previous breast malignancy. The primary aim was to investigate the breast cancer incidence after surgery. Secondary aims were to describe the preoperative risk assessment, operation techniques, complications, histopathological findings, and regional differences. METHODS:: Geneticists, oncologists and surgeons performing prophylactic breast surgery were asked to identify all women eligible for inclusion in their region. The medical records were reviewed in each region and the data were analyzed centrally. The BOADICEA risk assessment model was used to calculate the number of expected/prevented breast cancers during the follow-up period. RESULTS:: A total of 223 women operated on in 8 hospitals were identified. During a mean follow-up of 6.6 years, no primary breast cancer was observed compared with 12 expected cases. However, 1 woman succumbed 9 years post mastectomy to widespread adenocarcinoma of uncertain origin. Median age at operation was 40 years. A total of 58% were BRCA1/2 mutation carriers. All but 3 women underwent breast reconstruction, 208 with implants and 12 with autologous tissue. Four small, unifocal, invasive cancers and 4 ductal carcinoma in situ were found in the mastectomy specimens. The incidence of nonbreast related complications was low (3%). Implant loss due to infection/necrosis occurred in 21 women (10%) but a majority received a new implant later. In total, 64% of the women underwent at least 1unanticipated secondary operation. CONCLUSIONS:: Bilateral prophylactic mastectomy is safe and efficacious in reducing future breast cancer in asymptomatic women at high risk. Unanticipated reoperations are common. Given the small number of patients centralization seems justified.
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5.
  • Asklund, Thomas, et al. (författare)
  • Brain tumors in Sweden : Data from a population-based registry 1999-2012
  • 2015
  • Ingår i: Acta Oncologica. - : Informa Healthcare. - 0284-186X .- 1651-226X. ; 54:3, s. 377-384
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. The Swedish brain tumor registry has, since it was launched in 1999, provided significant amounts of data on histopathological diagnoses and on important aspects of surgical and medical management of these patients. The purpose is mainly quality control, but also as a resource for research.Methods. Three Swedish healthcare regions, constituting 40% of the Swedish population, have had an almost complete registration. The following parameters are registered: diagnosis according to SNOMED/WHO classification, symptoms, performance status, pre- and postoperative radiology, tumor size and localization, extent of surgery and occurrence of postoperative complications, postoperative treatment, such as radiotherapy and/or chemotherapy, other treatments, complications and toxicity, occurrence of reoperation/s, participation in clinical trials, multidisciplinary conferences and availability of a contact nurse.Results. Surgical radicality has been essentially constant, whereas the use of early (within 72 hours) postoperative CT and MRI has increased, especially for high-grade glioma, which is a reflection of quality of surgery. Survival of patients with high-grade glioma has increased, especially in the age group 60-69. Patients aged 18-39 years had a five-year survival of 40%. Waiting times for the pathological report has been slightly prolonged. Geographical differences do exist for some of the variables.Conclusion. Population-based registration is valuable for assessment of clinical management, which could have impact on patient care. As a result of short survival and/or the propensity to affect cognitive functions this patient group has considerable difficulties to make their voices heard in society. We therefore believe that a report like the present one can contribute to the spread of knowledge and increase the awareness for this patient group among caregivers and policy makers.
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8.
  • Asklund, Thomas, et al. (författare)
  • Överlevnanden vid maligna gliom har ökat senaste tio åren. Analys av kvalitetsregisterdata.
  • 2012
  • Ingår i: Läkartidningen. - : Läkartidningen Förlag AB. - 0023-7205 .- 1652-7518. ; 109:17-18, s. 875-878
  • Tidskriftsartikel (refereegranskat)abstract
    • The annual incidence rate of high grade malignant glioma (WHO grade III-IV) in Sweden is approximately 400 patients. The objective for the Swedish National CNS-tumor Group is to lay a foundation for research efforts and facilitate implementation and assessment of therapeutic strategies and health care for this patient group. In the analyses the diagnoses of high grade malignant gliomas are compared for the years 1999-2003, 2004-2006 and 2007-2009 for the Northern Region, the Uppsala Region and the South-east Region of Sweden, a population of 1844 patients. Survival was estimated from Kaplan-Meier survival curves, and a log-rank test was performed to assess whether the survival curves differed. The crude hazard ratio between years of diagnosis was estimated from a Cox regression model. Median survival for all patients 2004-2006 was 10.0 months (95 % confidence interval (CI) 8.9-10.9) compared to 8.1 months 1999-2003 (95 % CI 7.3-8.8). For patients 60-69 years of age almost a doubling of the survival rate has occurred during the last decade. Medan survival has increased from 5.8 months (95 % CI 5.1-7.5) 1999-2003 to 8.5 months (95 % CI 7.0-10.3) for 2004-2006 and to 10.5 months (95 % CI 9.0-12.6) for 2007-2009. Concomitant radiochemotherapy, but also the development of neurosurgical and radiotheraputic techniques and a more active therapeutic attitude, including the older patient groups, have probably contributed to the improved survival rate. A national population based registry, with a close to 100% registration compliance for important diagnostic and outcome parameters is probably an efficient instrument for evaluation of quality measures and implementation of new therapeutic strategies.
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9.
  • Berglund, U. W., et al. (författare)
  • Validation and development of MTH1 inhibitors for treatment of cancer
  • 2016
  • Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534 .- 1569-8041. ; 27:12, s. 2275-2283
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Previously, we showed cancer cells rely on the MTH1 protein to prevent incorporation of otherwise deadly oxidised nucleotides into DNA and we developed MTH1 inhibitors which selectively kill cancer cells. Recently, several new and potent inhibitors of MTH1 were demonstrated to be non-toxic to cancer cells, challenging the utility of MTH1 inhibition as a target for cancer treatment. Material and methods: Human cancer cell lines were exposed in vitro to MTH1 inhibitors or depleted of MTH1 by siRNA or shRNA. 8-oxodG was measured by immunostaining and modified comet assay. Thermal Proteome profiling, proteomics, cellular thermal shift assays, kinase and CEREP panel were used for target engagement, mode of action and selectivity investigations of MTH1 inhibitors. Effect of MTH1 inhibition on tumour growth was explored in BRAF V600E-mutated malignant melanoma patient derived xenograft and human colon cancer SW480 and HCT116 xenograft models. Results: Here, we demonstrate that recently described MTH1 inhibitors, which fail to kill cancer cells, also fail to introduce the toxic oxidized nucleotides into DNA. We also describe a new MTH1 inhibitor TH1579, (Karonudib), an analogue of TH588, which is a potent, selective MTH1 inhibitor with good oral availability and demonstrates excellent pharmacokinetic and anti-cancer properties in vivo. Conclusion: We demonstrate that in order to kill cancer cells MTH1 inhibitors must also introduce oxidized nucleotides into DNA. Furthermore, we describe TH1579 as a best-in-class MTH1 inhibitor, which we expect to be useful in order to further validate the MTH1 inhibitor concept.
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10.
  • Björk, Anna, et al. (författare)
  • High prevalence of neurodevelopmental problems in adolescents eligible for bariatric surgery for severe obesity
  • 2021
  • Ingår i: Acta Paediatrica, International Journal of Paediatrics. - : Wiley. - 0803-5253 .- 1651-2227. ; 110:5, s. 1534-1540
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: To assess the prevalence of neurodevelopmental problems in adolescents with severe obesity and their associations with binge eating and depression. Methods: Data were collected at inclusion in a randomised study of bariatric surgery in 48 adolescents (73% girls; mean age 15.7 ± 1.0 years; mean body mass index 42.6 ± 5.2 kg/m2). Parents completed questionnaires assessing their adolescents’ symptoms of attention-deficit/hyperactivity disorder and autism spectrum disorder and reported earlier diagnoses. Patients answered self-report questionnaires on binge eating and depressive symptoms. Results: The parents of 26/48 adolescents (54%) reported scores above cut-off for symptoms of the targeted disorders in their adolescents, but only 15% reported a diagnosis, 32% of adolescents reported binge eating, and 20% reported symptoms of clinical depression. No significant associations were found between neurodevelopmental problems and binge eating or depressive symptoms. Only a third of the adolescents reported no problems in either area. Conclusion: Two thirds of adolescents seeking surgical weight loss presented with substantial mental health problems (reported by themselves or their parents). This illustrates the importance of a multi-professional approach and the need to screen for and treat mental health disorders in adolescents with obesity.
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11.
  • Brechensbauer Brandin, Madeleine, et al. (författare)
  • Centralen : Studier i området kring Stockholms Centralstation
  • 1989
  • Rapport (populärvet., debatt m.m.)abstract
    • Denna skrift handlar om Centralen i Stockholm och dess närmaste omgivningar, Centralplan, T-centralen, Vasagatan och Klarabergsg­atan. Den är resultatet av Arkitekturskolans arbete läsåret 1983- 84 och innehåller förutom en rad projekt också historiska ut­blickar och samtidskritiska resonemang. En stor del av innehållet redovisades redan våren 1984 - det skedde genom en utställning på Arkitekturmuseet och en preliminär publikation. Materialet har se­dan svällt ut med innehållsrika uppsatser om Centralen, om äldre och nyare insatser för att förena konst och arkitektur och om den föga kända, ännu obebyggda Blekholmen.
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12.
  • Brendle, Annika, et al. (författare)
  • Polymorphisms in predicted microRNA-binding sites in integrin genes and breast cancer ITGB4 as prognostic marker.
  • 2008
  • Ingår i: Carcinogenesis. - : Oxford University Press. - 0143-3334 .- 1460-2180. ; 29:7, s. 1394-1399
  • Tidskriftsartikel (refereegranskat)abstract
    • Integrins control the cell attachment to the extracellular matrix and play an important role in mediating cell proliferation, migration and survival. A number of important cancer-associated integrin genes can be regulated by microRNAs (miRNAs) that bind to their target sites in the 3' untranslated regions. We examined the effect of single-nucleotide polymorphisms (SNPs) in predicted miRNA target sites of six integrin genes (ITGA3, ITGA6, ITGAv, ITGB3, ITGB4 and ITGB5) on breast cancer (BC) risk and clinical outcome. Six SNPs were genotyped in 749 Swedish incident BC cases with detailed clinical data and up to 15 years of follow-up together with 1493 matched controls. We evaluated associations between genotypes and BC risk and clinical tumour characteristics. Survival probabilities were compared between different subgroups. As a novel finding, several SNPs seemed to associate with the hormone receptor status. The strongest association was observed between the A allele of the SNP rs743554 in the ITGB4 gene and oestrogen receptor-negative tumours [odds ratio 2.09, 95% confidence intervals (CIs) 1.19-3.67]. The same SNP was associated with survival. The A allele carriers had a worse survival compared with the wild-type genotype carriers (hazard ratio 2.11, 95% CIs 1.21-3.68). The poor survival was significantly associated with the aggressive tumour characteristics: high grade, lymph node metastasis and high stage. None of the SNPs was significantly associated with BC risk. As the ITGB4 SNP seems to influence tumour aggressiveness and survival, it may have prognostic value in the clinic.
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  • Bruhn, Helena, et al. (författare)
  • Initial cognitive impairment predicts shorter survival of patients with glioblastoma
  • 2022
  • Ingår i: Acta Neurologica Scandinavica. - : Wiley. - 0001-6314 .- 1600-0404. ; 145:1, s. 94-101
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives Seizures as presenting symptom of glioblastoma (GBM) are known to predict prolonged survival, whereas the clinical impact of other initial symptoms is less known. Our main objective was to evaluate the influence of different presenting symptoms on survival in a clinical setting. We also assessed lead times, tumour size and localization. Methods Medical records of 189 GBM patients were reviewed regarding the first medical appointment, presenting symptom/s, date of diagnostic radiology and survival. Tumour size, localization and treatment data were retrieved. Overall survival was calculated using Kaplan-Meier and Mann-Whitney U test. Cox regression was used for risk estimation. Results Cognitive impairment as the initial symptom was often misinterpreted in primary health care leading to a delayed diagnosis. Initial global symptoms (66% of all patients) were associated with reduced survival compared to no global symptoms (median 8.4 months vs. 12.6 months). Those with the most common cognitive dysfunctions: change of behaviour, memory impairment and/or disorientation had a reduced median survival to 6.4 months. In contrast, seizures (32%) were associated with longer survival (median 11.2 months vs. 8.3 months). Global symptoms were associated with larger tumours than seizures, but tumour size had no linear association with survival. The setting of the first medical appointment was evenly distributed between primary health care and emergency units. Conclusion Patients with GBM presenting with cognitive symptoms are challenging to identify, have larger tumours and reduced survival. In contrast, epileptic seizures as the first symptom are associated with longer survival and smaller tumours.
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14.
  • Bäckström, Sebastian, et al. (författare)
  • Klimatsmarta lägen - Beräkning av minskade utsläpp av växthusgaser genom förtätning av stationsnära lägen
  • 2013
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • ”Hur skiljer sig koldioxidutsläppen åt för resor till och från verksamheter som ligger i byggnader nära respektive långt ifrån spårbunden kollektivtrafik och reseknutpunkter?” Svaret på denna fråga är viktig när för- och nackdelar med en förtätning av stationsnära delar av städer bedöms. Att närhet till en järnvägsstation med högfrekvent lokal och regional tågtrafik skapar goda förutsättningar för ett resmönster med minskat inslag av bilåkande är uppenbart. Att tillgången till annan kollektivtrafik vid stationen ytterligare stimulerar val av kollektiva färdmedel förvånar ingen. Att det tillsammans i sin tur leder till fördelar för miljön i form av minskade utsläpp av klimatpåverkande och luftförorenade avgaser är också självklart. Men hur stora är de kvantitativa vinsterna mätt som minskade utsläpp om man bygger vid en knutpunkt för kollektiva transportslag jämfört med lägen sämre försörjda med kollektivtrafik? Och hur påverkar olika verksamheter i byggnaden resmönstret i den geografiska jämförelsen? Detta försöker vi klarlägga genom att utveckla ett kalkylverktyg med vilket det totala antalet resor till och från varje typ av verksamhet i en byggnad beräknas. Därefter inhämtar vi uppgifter om brukarnas olika resmönster, som används för att beräkna det totala transportarbetet, mätt som person-kilometer kopplat till byggnaden. Till sist kombineras dessa uppgifter med de olika trafikslagens utsläpp av koldioxid för att få fram en total siffra för byggnadens reserelaterade emissioner. Genom att ange möjliga alternativa lägen för de ingående verksamheterna i den analyserade byggnaden räknas den potentiella minskningen i koldioxidemissioner ut om etablering sker i det valda, stationsnära läget. Underlagsdata till kalkylverktyget planerades ursprungligen att hämtas från litteraturen och från annan forskning. Inga användbara data fanns dock tillgängliga vad gäller personers resmönster (det vill säga reslängd och val av färdmedel) nedbrutet på målpunkter, varför ett datainsamlingsprojekt initierades. Därför användes webbenkäter, frågeformulär till besökare, som direkta intervjuer i butik för att kunna beskriva hur resmönstret skiljer sig åt till för exempelvis en kund till detaljhandel på Stockholms Centralstation, Södermalm (innerstadsmiljö) och Nacka Forum (extern storhandel). I det typfall som vi har undersökt beräknas utsläppen för en möjlig etablering av en byggnad i Västra city i Stockholm, i direkt anslutning till Centralstationen. Byggnaden är tänkt att innehålla såväl trafikantutrymmen som handel, kontor, service och bostäder. Som jämförelse har vi beräknat resornas emissioner om motsvarande byggnadsytor etableras på alternativa adresser med sämre tillgång till effektiva kollektiva transportsystem. Kalkylen visar på tre till fem gånger högre reserelaterade emissioner i ett externt läge jämfört med det stationsnära i Västra city. Vi ger ett intervall därför att det speglar effekten av om vi antar att besöksfrekvensen till verksamheter med olika geografisk lokalisering är lika (högre siffran) eller olika (lägre siffran). Rent diskussionsmässigt tror vi att sanningen ligger mer åt den högre siffran som en följd av att verksamheter centralt belägna i staden tenderar att använda sig av mindre yta per verksamhet vilket balanserar en skillnad i besöksfrekvens. Kort sagt, det är förmodligen mer riktigt att jämföra en mindre byggnad i den centrala staden med en större i ett mer externt läge, givet att de både innehåller kvantitativt lika mängd verksamheter som utgör målpunkter för ett resande. En etablering av nya kontorsplatser i ett centralt, stationsnära läge indikerar också att 10 procent av de nyanställda kommer att pendla regionalt med tåg. I det externa läget verkar den regionala pendlingen uteslutande ske med bil. Skillnaden i utsläpp från det tillkommande regionala pendlandet är 78 procent till det centrala lägets fördel.
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15.
  • Dahlrot, R. H., et al. (författare)
  • Prognostic value of O-6-methylguanine-DNA methyltransferase (MGMT) protein expression in glioblastoma excluding nontumour cells from the analysis
  • 2018
  • Ingår i: Neuropathology and Applied Neurobiology. - : Wiley. - 0305-1846 .- 1365-2990. ; 44:2, s. 172-184
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: It is important to predict response to treatment with temozolomide (TMZ) in glioblastoma (GBM) patients. Both MGMT protein expression and MGMT promoter methylation status have been reported to predict the response to TMZ. We investigated the prognostic value of quantified MGMT protein levels in tumour cells and the prognostic importance of combining information of MGMT protein level and MGMT promoter methylation status.Methods: MGMT protein expression was quantified in tumour cells in 171 GBMs from the population‐based Region of Southern Denmark (RSD)‐cohort using a double immunofluorescence approach. Pyrosequencing was performed in 157 patients. For validation we used GBM‐patients from a Nordic Study (NS) investigating the effect of radiotherapy and different TMZ schedules.Results: When divided at the median, patients with low expression of MGMT protein (AF‐low) had the best prognosis (HR = 1.5, P = 0.01). Similar results were observed in the subgroup of patients receiving the Stupp regimen (HR = 2.0, P = 0.001). In the NS‐cohort a trend towards superior survival (HR = 1.6, P = 0.08) was seen in patients with AF‐low. Including MGMT promoter methylation status, we found for both cohorts that patients with methylated MGMT promoter and AF‐low had the best outcome; median OS 23.1 and 20.0 months, respectively.Conclusion: Our data indicate that MGMT protein expression in tumour cells has an independent prognostic significance. Exclusion of nontumour cells contributed to a more exact analysis of tumour‐specific MGMT protein expression. This should be incorporated in future studies evaluating MGMT status before potential integration into clinical practice.
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16.
  • Eriksson, Jenny, 1975-, et al. (författare)
  • Intressent- och behovsanalys för resvaneundersökningar : resultat från intervjuer och enkätundersökning
  • 2017
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • I Sverige genomförs en nationell resvaneundersökning med viss regelbundenhet med Trafikanalys som ansvarig myndighet. Undersökningen har problem med bortfall, täckning, kostnader och uppgiftslämnarbörda. Ett projekt pågår som syftar till att utveckla nya metoder för att samla in data om personers mobilitet. Projektet är indelat i fem arbetspaket, varav detta arbete är ett. Syftet är att utföra en intressent- och behovsanalys avseende framtida resvaneundersökningar. I detta ingår att identifiera syften och frågeställningar som resvaneundersökningar ska kunna hantera och besvara.Det genomfördes 20 telefonintervjuer och utskick av webbenkät till 142 personer (svar från 81 personer, svarsfrekvens 57 procent). Intressenterna delades in i tre olika grupper: offentlig sektor, forskningsorganisation och övriga aktörer. Tillsammans med egna erfarenheter har en analys gjorts av vad som efterfrågas från den nationella resvaneundersökningen. Frågeställningar som centrala för användare av resvaneundersökningar är val av färdsätt, resans ärende samt mått på hur resvanorna förändras över tid och hur olika grupper reser. För detta behövs både uppgifter om individen och resorna. Utöver detta önskar man bra data på kommunal nivå eller lägre. Dock kan Trafikanalys i nuläget inte erbjuda den möjligheten, men här finns det möjlighet för kommuner, regioner och andra aktörer att välja ett extraurval från den befintliga nationella resvaneundersökningen.
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17.
  • Eriksson, Jenny, 1975-, et al. (författare)
  • New ways of collecting individual travel information : Evaluation of data collection and recruitment methods
  • 2018
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • The overall purpose of the project is to conduct a demonstration study that shows how two data collection methods that have been developed to collect travel survey data perform in the field, and how they perform compared with traditional TS (i.e., postal questionnaires and/or telephone interviews). The project is also intended to provide a better understanding of the ways in which different recruitment methods of respondents can be used so that future TS can be more cost effective.The two collection methods tested consist of a mobile app and an online questionnaire with a map to assist the respondents to identify travel destinations. Three recruitment methods were used, i.e., recruitment via random sampling, a web panel, and crowdsourcing. The portion of the random sample that received an online questionnaire was divided into two groups. Half the group was given no incentive, while the other half received a gift card worth SEK 100 after answering the questioner. Those who were recruited via a web panel and were to use the mobile app were rewarded in the form of a gift card worth SEK 100 if, at minimum, they made corrections to trips made on one day registered in the mobile app. A nonresponse analysis was performed of the random sample for both the online questionnaire and the mobile app. Cost estimates for each collection method and recruitment method were also performed, as were uncertainty estimates.Overall, the study shows that the mobile app registered significantly more trips per respondent than did the online questionnaire, while the distances travelled were comparable. There are several possible interpretations of this. One is that people who responded to the online questionnaire either forget about and/or combined short trips (particularly trips made for the purposes of leisure or shopping, and using the travel modes walking and car). One presumable explanation for this is that it is easier to confirm/correct the trips that the mobile app suggests than it is to recall and enter all trips in an online questionnaire. Another possible interpretation is that people responding to different data collection methods have different travel patterns. Yet another explanation is connected to technique issues regarding the different data collection methods.
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18.
  • Eriksson, Jenny, 1975-, et al. (författare)
  • Nya sätt att samla in individuell resvaneinformation : Utvärdering av insamlings- och rekryteringsmetoder
  • 2018
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • Inom samverkansprogrammet Nästa generations resor och transporter, som Trafikanalys är huvudansvarig för, har man identifierat ett behov av att finna och utveckla nya lösningar för resvaneundersökningar (RVU:er). Bakgrunden till detta är bland annat sjunkande svarsfrekvenser med dagens metoder, vilket skulle kunna ge problem med representativiteten. Det anses som mycket angeläget att utveckla nya metoder för datainsamling för framtidens RVU:er, både på kort och lång sikt.Det övergripande syftet med projektet är att göra en demonstrationsstudie som visar hur två datainsamlingsmetoder som har utvecklats för att samla in resevaneundersökningsdata presterar i fält, samt hur de presterar jämfört med ”traditionell” RVU (postal enkät och/eller telefonintervjuer). Projektet syftar också till att få bättre förståelse för hur olika rekryteringsmetoder kan användas för att framtida RVU:er ska kunna bli mer kostnadseffektiva. De två insamlingsmetoder som testats är webbenkät med karta och mobilapp. Tre rekryteringsmetoder har använts och dessa är rekrytering via slumpmässigt urval, webbpanel och crowdsourcing.
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19.
  • Gad, Helge, et al. (författare)
  • MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool
  • 2014
  • Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 508:7495, s. 215-221
  • Tidskriftsartikel (refereegranskat)abstract
    • Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bindin the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.
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20.
  • Green, Alanna C., et al. (författare)
  • Formate overflow drives toxic folate trapping in MTHFD1 inhibited cancer cells
  • 2023
  • Ingår i: Nature Metabolism. - : Springer Nature. - 2522-5812. ; 5:4, s. 642-659
  • Tidskriftsartikel (refereegranskat)abstract
    • Cancer cells fuel their increased need for nucleotide supply by upregulating one-carbon (1C) metabolism, including the enzymes methylenetetrahydrofolate dehydrogenase–cyclohydrolase 1 and 2 (MTHFD1 and MTHFD2). TH9619 is a potent inhibitor of dehydrogenase and cyclohydrolase activities in both MTHFD1 and MTHFD2, and selectively kills cancer cells. Here, we reveal that, in cells, TH9619 targets nuclear MTHFD2 but does not inhibit mitochondrial MTHFD2. Hence, overflow of formate from mitochondria continues in the presence of TH9619. TH9619 inhibits the activity of MTHFD1 occurring downstream of mitochondrial formate release, leading to the accumulation of 10-formyl-tetrahydrofolate, which we term a ‘folate trap’. This results in thymidylate depletion and death of MTHFD2-expressing cancer cells. This previously uncharacterized folate trapping mechanism is exacerbated by physiological hypoxanthine levels that block the de novo purine synthesis pathway, and additionally prevent 10-formyl-tetrahydrofolate consumption for purine synthesis. The folate trapping mechanism described here for TH9619 differs from other MTHFD1/2 inhibitors and antifolates. Thus, our findings uncover an approach to attack cancer and reveal a regulatory mechanism in 1C metabolism.
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21.
  • Hedman, Håkan, et al. (författare)
  • LRIG2 in contrast to LRIG1 predicts poor survival in early-stage squamous cell carcinoma of the uterine cervix
  • 2010
  • Ingår i: Acta Oncologica. - : Informa Healthcare. - 0284-186X .- 1651-226X. ; 49:6, s. 812-815
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The human leucine-rich repeats and immunoglobulin-like domains (LRIG) protein family comprises LRIG1, 2, and 3. LRIG1 negatively regulates growth factor signaling and is a proposed tumor suppressor. In early stage uterine cervical carcinoma, expression of LRIG1 is associated with good survival. Less is known about the function and expression of LRIG2; it has not been studied in cervical carcinoma, previously. MATERIALS AND METHODS: LRIG2 expression was studied by immunohistochemistry in 129 uterine cervical squamous cell carcinomas and 36 uterine cervical adenocarcinomas. Possible associations between LRIG2 immunoreactivity and patient survival were evaluated. RESULTS: In early-stage squamous cell carcinoma (stages IB-IIB), high expression of LRIG2 was associated with poor survival (Kaplan-Meier, log-rank, p=0.02). The 10-year survival rate for patients with high expression of LRIG2 was 60%, compared to 87% in patients with low expression (odds ratio 0.22, 95% CI 0.07-0.64). In multivariate analysis including the previously studied tumor suppressor LRIG1 and clinical stage, LRIG2 emerged as an independent prognostic factor (odds ratio 0.22, 95% CI 0.09-0.50). For patients with both high expression of LRIG2 and low expression of LRIG1, the 10-year survival rate was only 26% compared to 66% for the remaining study population. There was no correlation between LRIG2 expression and prognosis in the limited adenocarcinoma series. DISCUSSION AND CONCLUSION: LRIG2 appears to be a significant predictor of poor prognosis in early-stage squamous cell carcinoma of the uterine cervix. A combination of high LRIG2 expression and low LRIG1 expression identified women with a very poor prognosis.
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22.
  • Henriksson, Andreas, 1980- (författare)
  • Organising Intimacy : Exploring Heterosexual Singledoms at Swedish Singles Activities
  • 2014
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Single activities have long been places where single people can come to meet friends, build community or look for partners. The activities have relevance for studies of heterosexuality, intimacy, personal life and space. This dissertation discusses a conference, a cruise, an online site and an association for heterosexual singles in contemporary Sweden. It shows how these activities, analysed as organising people and spaces, offer participants different versions of intimacy, relationships, personal life and ultimately singledom itself.  The concept non-relationality is coined to describe how people understand and enact what it means to lack a certain kind of relationship.Multi-sited ethnographic observations are combined with interviews and a survey (n=416). The chosen methods allow insight into both the heterogeneous character of the contemporary single activity scene, as well as existing tendencies to form communities. The group whose single activities are examined is deemed fairly typical of the single population at large. Nevertheless, most conclusions centre on the specific set of activities described in the book and relate them to historical examples and theory.The single activities examined can be interpreted to enact different practices entailed in a relationship without necessarily demanding commitment to a whole relationship or a specific person. In that way, the activities accommodate the inflexible personal lives that some singles report having. This challenges strict boundaries between coupledom and singledom. Such transgressive or “hetero-doxical” potential in single activities is nevertheless circumscribed by organisers’ notion that the activities provide therapeutic community in a phase before singles take the step (back) into coupledom.
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23.
  • Henriksson, Catrin, et al. (författare)
  • Patients’ experiences of clinical trial participation involving a product remotely assessing study drug adherence
  • 2024
  • Ingår i: Contemporary Clinical Trials Communications. - 2451-8654. ; 40
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The participation of patients in clinical trials is crucial for the development of healthcare. There are several challenges in the recruitment of trial participants with acute medical conditions. The registry-based randomized DAPA-MI clinical trial recruited patients during hospitalization for myocardial infarction and provided study drugs in bottles with smart caps that used wireless technology to transmit monitoring data. This interview study aimed to investigate patients’ experience of participation in a clinical trial and their attitude to the new bottle cap technology. Methods: A subset of patients participating in the DAPA-MI trial were recruited from four hospitals in Sweden. Semi-structured interviews were conducted and analysed using manifest content analysis. Results: Video interviews were performed including 21 patients (four women and 17 men). The median age was 59 years (range 44–80). Four categories of patients' experiences were identified. A willingness to contribute consisted of patients’ positive attitudes to participation and to be a part of development and research. The perception of information emphasized the value of the oral information as well as the importance of time for reflection. Be in a vulnerable condition highlighted the impaired ability to perceive and remember in the acute medical condition. Adaptation to a new technology described the overall positive experiences of the smart bottle cap to evaluate adherence. Conclusions: Patients’ experiences of trial participation were in general positive but some challenges in the acute setting of a myocardial infarction were revealed. The smart bottle cap was well accepted, despite some handling difficulties.
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24.
  • Henriksson, Roger, et al. (författare)
  • Boron neutron capture therapy (BNCT) for glioblastoma multiforme : a phase II study evaluating a prolonged high-dose of boronophenylalanine (BPA)
  • 2008
  • Ingår i: Radiotherapy and Oncology. - : Elsevier BV. - 0167-8140 .- 1879-0887. ; 88:2, s. 183-91
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND AND PURPOSE: To evaluate the efficacy and safety of boron neutron capture therapy (BNCT) for glioblastoma multiforme (GBM) using a novel protocol for the boronophenylalanine-fructose (BPA-F) infusion. PATIENT AND METHODS: This phase II study included 30 patients, 26-69 years old, with a good performance status of which 27 have undergone debulking surgery. BPA-F (900 mg BPA/kg body weight) was given i.v. over 6h. Neutron irradiation started 2h after the completion of the infusion. Follow-up reports were monitored by an independent clinical research institute. RESULTS: The boron-blood concentration during irradiation was 15.2-33.7 microg/g. The average weighted absorbed dose to normal brain was 3.2-6.1 Gy (W). The minimum dose to the tumour volume ranged from 15.4 to 54.3 Gy (W). Seven patients suffered from seizures, 8 from skin/mucous problem, 5 patients were stricken by thromboembolism and 4 from abdominal disturbances in close relation to BNCT. Four patients displayed 9 episodes of grade 3-4 events (WHO). At the time for follow-up, minimum ten months, 23 out of the 29 evaluable patients were dead. The median time from BNCT treatment to tumour progression was 5.8 months and the median survival time after BNCT was 14.2 months. Following progression, 13 patients were given temozolomide, two patients were re-irradiated, and two were re-operated. Patients treated with temozolomide lived considerably longer (17.7 vs. 11.6 months). The quality of life analysis demonstrated a progressive deterioration after BNCT. CONCLUSION: Although, the efficacy of BNCT in the present protocol seems to be comparable with conventional radiotherapy and the treatment time is shorter, the observed side effects and the requirement of complex infrastructure and higher resources emphasize the need of further phase I and II studies, especially directed to improve the accumulation of (10)B in tumour cells.
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25.
  • Henriksson, Roger, et al. (författare)
  • High-grade astrocytoma treated concomitantly with estramustine and radiotherapy.
  • 2006
  • Ingår i: Journal of neuro-oncology. - : Springer Science and Business Media LLC. - 0167-594X .- 1573-7373. ; 78:3, s. 321-6
  • Tidskriftsartikel (refereegranskat)abstract
    • Experimental and early clinical investigations have demonstrated encouraging results for estramustine in the treatment of malignant glioma. The present study is an open randomized clinical trial comparing estramustine phosphate (Estracyt) in addition to radiotherapy with radiotherapy alone as first line treatment of astrocytoma grade III and IV. The 140 patients included were in a good clinical condition with a median age of 55 years (range 22-87). Estramustine was given orally, 280 mg twice daily, as soon as the diagnosis was established, during and after the radiotherapy for a period of in total 3 months. Radiotherapy was delivered on weekdays 2 Gy daily up to 56 Gy. Eighteen patients were excluded due to misclassification, leaving 122 patients eligible for evaluation. Overall the treatment was well tolerated. Mild or moderate nausea was the most common side effect of estramustine. The minimum follow-up time was 5.2 years for the surviving patients. For astrocytoma grade III the median survival time was 10.6 (1.3-92.7) months for the radiotherapy only group and 17.3 (0.4-96.9+) months for the estramustine + radiotherapy group. In grade IV the corresponding median survival time was 12.3 (2.1-89.2) and 10.3 (0.3-91.7+) months, respectively. Median time to progress for radiotherapy only and radiotherapy and estramustin group in grade III tumours was 6.5 and 10.1 months, respectively. In grade IV tumours the corresponding figures were 5.1 and 3.3 months, respectively. Although there was a tendency for improved survival in grade III, no statistical significant differences were found between the treatment groups. No differences between the two treatment groups were evident with respect to quality of life according to the EORTC QLQ-protocol. In conclusion, this first randomized study did not demonstrate any significant improvement of using estramustine in addition to conventional radiotherapy, however, a trend for a positive response for the estramustine group was found in patients with grade III glioma.
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26.
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27.
  • Johansson, Annika, 1967- (författare)
  • Är det alltid rätt person som vinner? : bedömningarnas reliabilitet och validitet inom bedömningssporterna acroski och rytmisk gymnastik
  • 2001
  • Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Did the right person win? In competitive sports the difference between winning and loosing can be very marginal but still the result will have a big impact. To finish second, even if it is an Olympic Game, can be felt like a failure for the athlete. In the light of this the quality of the measurements and the judgements in sports are an extremely important issue. In this dissertation, consisting of two separate reports and one summary report, the freestyle discipline, acroski, and the gymnastic discipline, rhythmic gymnastics (RG) where studied with a focus on the rules and judgements in the sports. The reliability and validity of the rule and judging systems were analysed together with changes in the rule and judging systems. The reliability, as the judges ability to interpret the rules and judge in a consistent way, and validity in the sense that the judgements, and the rules for the judgements, where in accordance with the idea of the sport. Information was gathered from rulebooks, judging manuals, meeting protocols, and historical documents. For information on how the rules and judgements where perceived among people involved in the two sports, interviews where carried out with two coaches, two judges and four athletes from each of the sports. In the summary report the results from the two reports where discussed and a comparison of the rule systems and judgements was made together with a discussion about reliability and validity problems in sports measured by time, length and height. The results showed that the rule and judging systems in acroski and RG in a short time have gone through major changes to increase the reliability and validity in the judgements. The quick evolution of these sports seems to be the main reason for these changes but also other factors where of vital importance. Finding the balance between making the judgements as objective as possible, without loosing the idea of the sport, together with the quick evolution of the sports, seemed to be the main challenges in the rule and judging systems of acroski and RG.
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28.
  • Karimi, Masoud, et al. (författare)
  • A retrospective study of extracolonic, non-endometrial cancer in Swedish Lynch syndrome families
  • 2018
  • Ingår i: Hereditary Cancer in Clinical Practice. - : BMC. - 1731-2302 .- 1897-4287. ; 16
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundLynch Syndrome is an autosomal dominant cancer syndrome caused by pathogenic germ-line variants in one of the DNA-mismatch-repair (MMR) genes MLH1, MSH2, MSH6 or PMS2. Carriers are predisposed to colorectal and endometrial cancer, but also other cancer types. The purpose of this retrospective study was to characterize the tumour spectrum of the Swedish Lynch syndrome families.MethodsData were obtained from genetically verified 235 Lynch families from five of the six health care regions in Sweden. The material was stratified for gender, primary cancer, age and mutated gene and the relative proportions of specific cancer types were compared to those in the general population.ResultsA total of 1053 family members had 1493 cancer diagnoses of which 1011 were colorectal or endometrial cancer. Individuals with pathogenic variants in MLH1 and MSH2 comprised 78% of the cohort. Among the 482 non-colorectal/non-endometrial cancer diagnoses, MSH2 carriers demonstrated a significantly increased proportion of urinary tract, gastric, small bowel, ovarian and non-melanoma skin cancer compared to the normal population. MLH1 carriers had an elevated proportion of gastrointestinal cancers (gastric, small bowel, pancreas), while MSH6 carriers had more ovarian cancer than expected. Gastric cancer was predominantly noted in older generations.ConclusionLynch syndrome confers an increased risk for multiple cancers other than colorectal and endometrial cancer. The proportions of other cancers vary between different MMR genes, with highest frequency in MSH2-carriers. Gender and age also affect the tumour spectrum, demonstrating the importance of additional environmental and constitutional parameters in determining the predisposition for different cancer types.
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29.
  • Karimi, Masoud, et al. (författare)
  • A retrospective study of extracolonic, non-endometrial cancer in Swedish Lynch syndrome families 11 Medical and Health Sciences 1112 Oncology and Carcinogenesis 11 Medical and Health Sciences 1117 Public Health and Health Services
  • 2018
  • Ingår i: Hereditary Cancer in Clinical Practice. - : Springer Science and Business Media LLC. - 1731-2302 .- 1897-4287. ; 16:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Lynch Syndrome is an autosomal dominant cancer syndrome caused by pathogenic germ-line variants in one of the DNA-mismatch-repair (MMR) genes MLH1, MSH2, MSH6 or PMS2. Carriers are predisposed to colorectal and endometrial cancer, but also other cancer types. The purpose of this retrospective study was to characterize the tumour spectrum of the Swedish Lynch syndrome families. Methods: Data were obtained from genetically verified 235 Lynch families from five of the six health care regions in Sweden. The material was stratified for gender, primary cancer, age and mutated gene and the relative proportions of specific cancer types were compared to those in the general population. Results: A total of 1053 family members had 1493 cancer diagnoses of which 1011 were colorectal or endometrial cancer. Individuals with pathogenic variants in MLH1 and MSH2 comprised 78% of the cohort. Among the 482 non-colorectal/non-endometrial cancer diagnoses, MSH2 carriers demonstrated a significantly increased proportion of urinary tract, gastric, small bowel, ovarian and non-melanoma skin cancer compared to the normal population. MLH1 carriers had an elevated proportion of gastrointestinal cancers (gastric, small bowel, pancreas), while MSH6 carriers had more ovarian cancer than expected. Gastric cancer was predominantly noted in older generations. Conclusion: Lynch syndrome confers an increased risk for multiple cancers other than colorectal and endometrial cancer. The proportions of other cancers vary between different MMR genes, with highest frequency in MSH2-carriers. Gender and age also affect the tumour spectrum, demonstrating the importance of additional environmental and constitutional parameters in determining the predisposition for different cancer types.
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30.
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31.
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32.
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33.
  • Lindström, Annika, 1953-, et al. (författare)
  • LRIG1 and squamous epithelial uterine cervical cancer : correlation to prognosis, other tumor markers, sex steroid hormones, and smoking
  • 2008
  • Ingår i: International Journal of Gynecological Cancer. - : BMJ. - 1048-891X .- 1525-1438. ; 18:2, s. 312-317
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim is to evaluate LRIG1 as a prognosis predictor and correlations to cofactors in squamous cell cervical cancer. LRIG1 expression was studied in 128 cervical carcinomas and was compared with expression of nine other tumor markers. Smoking history was registered and pretreatment serum estradiol and progesterone levels were evaluated in 79 women. At clinical stage IB, 58% of the tumors showed LRIG1 expression, but there was a decline by increasing stage (33% in stage IV). Ninety percent of women with stage IB cancer and LRIG1 positivity survived, as compared to 64% without expression (P = 0.02). LRIG1 expression did not predict prognosis in advanced stages, but in stage IIA there was a marked relative difference, with 75% survival in tumors expressing LRIG1, as compared to 43% in those without. No correlation was found between LRIG1 and the other nine tumor markers studied. A high serum progesterone and smoking correlated to absent LRIG1 expression. We conclude that LRIG1 appears to be a significant prognosis predictor in early-stage cervical cancer, independent of the other tumor markers that were studied. Diminished expression in advanced stages and the inverse correlation to serum progesterone and smoking indicates that LRIG1 is a tumor suppressor in cervix.
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34.
  • Lindström, Annika, 1953- (författare)
  • Prognostic factors for squamous cell cervical cancer : tumor markers, hormones, smoking, and S-phase fraction
  • 2010
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Cervical cancer is the second most common malignancy in women worldwide and one of the leading causes of cancer mortality globally. In patients with invasive cervical cancer prognostic factors are of value for the choice of treatment, monitoring of treatment and follow-up. The most important clinical prognostic factors are stage, tumor volume, parametrial infiltration, vascular invasion, lymph node metastases, and distant metastases. An improved estimation of the prognosis of cervical cancer is desirable, especially in early cancer stages.The aim of this research was to study possible associations between tumor markers, female sex steroids, smoking, S-phase fraction (SPF), and prognosis in invasive squamous cell cervical cancer (SCC). The study comprised 190 patients with SCC, stages IB-IV, admitted to the Department of Gynecologic Oncology at Norrland University Hospital in Umeå between September 1984 and October1990. Ten year mortality was estimated.In study I, of a total of 103 patients, it was found that increased tumor growth, measured by the DNA SPF, was associated with elevated serum progesterone and smoking in the premenopasual patients and with aneuploidy in the whole group.In study II, comprising 128 patients, survival length related to hormone levels and SPF was evaluated in women who died of cervical cancer. In both pre- and postmenopausal women, who died of cervical cancer, SPF at or above 12% was correlated with reduced survival. There was significant positive correlation between a low serum estradiol/progesterone ratio and short survival in those premenopausal women who died of cancer (p=0.02).In study III, ten-year follow-up results in 128 women were compared with the expression of ten relevant tumor markers, assessed by immunohistochemistry. The overall ten-year survival rate in patients with low COX-2 and high CD4+ expression was 76%, versus 53% in the remaining women. The survival rate with absent p53 and high COX-2 expression in the tumors was 42%, versus 71%, while the corresponding figure for the combination of high COX-2 intensity and expression of c-myc was 27%, versus 62%. None of the single markers correlated significantly with outcome in the final Cox regression analyses, while five combinations did.Study IV addressed possible associations between selected tumor markers and cofactors in SCC. Ten tumor markers were examined in 128 patients. Smoking habits and previous oral contraceptive use were recorded. Serum estradiol and progesterone levels were evaluated in 80 women. Highly significant associations were found between strong c-myc staining and increased progesterone, low EGFR staining and high serum estradiol, and absence of p53 staining and smoking. There was an association between absence of p53 and high serum progesterone.In study V, LRIG1 expression was studied in 128 patients and was compared with expression of nine other tumor markers, smoking history, hormone levels, and prognosis. LRIG1 appears to be a significant prognostic predictor in early stage SCC, independent of the other tumor markers that were studied.  Diminished expression in advanced cancer stages and the inverse correlation to serum progesterone and smoking indicate that LRIG1 is a tumor suppressor in squamous cell cervical cancer.Conclusion: The results of these studies support a role of progesterone as a promoter of cervical cancer and indicate that smoking is associated with tumor progression. A combination of tumor markers might be of help in prognostic prediction. LRIG1 acts as a tumor suppressor. These findings might contribute towards greater understanding of prognostic prediction of squamous cell cervical cancer.
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35.
  • Lundström, Annika, et al. (författare)
  • Prognostic Value of Circulating Microvesicle Subpopulations in Ischemic Stroke and TIA
  • 2020
  • Ingår i: Translational Stroke Research. - : Springer Science and Business Media LLC. - 1868-4483 .- 1868-601X. ; 11:4, s. 708-719
  • Tidskriftsartikel (refereegranskat)abstract
    • Platelet microvesicles (PMV) have previously been found elevated in acute ischemic stroke (IS) and could be biomarkers for risk of recurrence. PMV surface antigens such as P-selectin and phosphatidylserine (PS) reflect platelet activation and procoagulance. Tissue factor-positive microvesicles (TF+MV) are considered procoagulant, in particular if co-expressing PS. We enumerated MV subpopulations with these surface antigens in a cohort of 211 patients with primarily non-cardioembolic IS or transient ischemic attack (TIA) and investigated their association with long-term outcome. MV concentrations were determined by flow cytometry in the acute and convalescent phase. Primary outcome was a composite of fatal and non-fatal recurrent IS or myocardial infarction. Secondary outcomes were recurrent IS and all-cause mortality. Outcome events were obtained from Swedish registers during a follow-up of 1100 patient years. Concentrations of PS-positive and PS-negative MV populations were elevated in patients compared with healthy controls in both the acute and convalescent phase. PS+TF+PMV displayed pronounced elevations, median fold change 77 in the acute phase (p < 0.0001) but were not associated with outcome, neither were PS+P-selectin(+)PMV. The only subpopulation positively associated with primary outcome was PS-TF+PMV, with adjusted hazard ratio of 1.86 (1.04-3.31,p = 0.036) by Cox regression. Unexpectedly, several MV subpopulations tended to be associated with reduced risk of poor long-term outcome. Our results suggest that PS+TF+PMV may be a promising marker for cerebral ischemia, and that the in vivo generation of PS-MV after IS/TIA warrants further study. Future MV studies should ideally enumerate PS(+)and PS-MV subpopulations separately.
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36.
  • Lutter, Reimo, et al. (författare)
  • Belowground resource utilization in monocultures and mixtures of Scots pine and Norway spruce
  • 2021
  • Ingår i: Forest Ecology and Management. - : Elsevier BV. - 0378-1127 .- 1872-7042. ; 500
  • Tidskriftsartikel (refereegranskat)abstract
    • Mixed forests have been recommended to replace monocultures, often being more productive and resilient ecosystems. Those benefits of species mixing have been suggested to be attributed to lower competition (aboveand belowground) due to potential separation of resource acquisition strategies, yet a mechanistic understanding of belowground processes has largely been missing. We applied an isotopic-labelling technique using N-15 and H-2 at similar to 5 cm soil depth to study acquisition of two important resources, nitrogen (N) and water, in a replicated field experiment including mature Scots pine and Norway spruce monocultures and their mixture in boreal Sweden. Based on the isotopic data, we modelled distance-dependent N and water uptake and described the horizontal reach of active rooting areas around trees. The active root area for both N and water uptake in monocultures of both species was approximately 6-10 m(2). Substantially wider areas were observed inside the mixture for N acquisition (27 m(2) for pine and 21 m(2) for spruce). Water was mainly acquired from within a 12-15 m(2) area in mixture. The mixture and the pine monocultures exhibited similar recovery of the added N-15 (3.8-4.5%) and its uptake per unit of foliage mass. The recovery of N-15 for the spruce monocultures was generally lower (2.1%) but no difference was noted in the uptake per unit of foliage mass between spruce monoculture and mixture. No differences were found for recovery of H-2 between the stand types. Mixing pine and spruce did not improve the resource uptake in comparison with the estimated theoretical mixture (according to the normalized basal area in monocultures). However, the mixing revealed significant differences between tree species whereas pines inside the mixture recovered 11.3-fold more N-15 than accompanying spruce. Root overlap of 3-11 trees on 1 m(2) was observed in all stand types, far exceeding the degree of canopy overlap. We discuss this overlap in terms of competition between individual trees. Spruces have proportionally larger horizontal rooting area relative to their aboveground size than pines. Scots pine and Norway spruce mixing in this type of boreal forest does not significantly enhance resource acquisition but leads to compensatory partitioning of growth, suggesting fierce interspecific competition, rather than niche separation.
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37.
  • Malmström, Annika, 1957-, et al. (författare)
  • Do we really know who has an MGMT methylated glioma? : results of an international survey regarding use of MGMT analyses for glioma
  • 2020
  • Ingår i: Neuro-Oncology Practice. - Oxford : Oxford University Press. - 2054-2577 .- 2054-2585. ; 7:1, s. 68-76
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Glioma O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status informs clinical decision making. Worldwide different methods and cutoff levels are used, which can lead to discordant methylation results.Methods: We conducted an international survey to clarify which methods are regularly used and why. We also explored opinions regarding international consensus on methods and cutoff.Results: The survey had 152 respondents from 25 countries. MGMT methylation status is determined for all glioblastomas in 37% of laboratories. The most common methods are methylation-specific polymerase chain reaction (msPCR) (37%) and pyrosequencing (34%). A method is selected for simplicity (56%), cost-effectiveness (50%), and reproducibility of results (52%). For sequencing, the number of CpG sites analyzed varies from 1–3 up to more than 16. For 50% of laboratories, the company producing the kit determines which CpG sites are examined, whereas 33% select the sites themselves. Selection of cutoff is equally distributed among a cutoff defined in the literature, by the local laboratory, or by the outside laboratory performing the analysis. This cutoff varies, reported from 1% to 30%, and in 1 laboratory tumor is determined as methylated in case of 1 methylated CpG site of 17 analyzed. Some report tumors as unmethylated or weakly vs highly methylated. An international consensus on MGMT methylation method and cutoff is warranted by 66% and 76% of respondents, respectively. The method preferred would be msPCR (45%) or pyrosequencing (42%), whereas 18% suggest next-generation sequencing.Conclusion: Although analysis of MGMT methylation status is routine, there is controversy regarding laboratory methods and cutoff level. Most respondents favor development of international consensus guidelines.
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38.
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39.
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40.
  • Malmström, Annika, et al. (författare)
  • Postoperative neoadjuvant temozolomide before radiotherapy versus standard radiotherapy in patients 60 years or younger with anaplastic astrocytoma or glioblastoma: a randomized trial
  • 2017
  • Ingår i: Acta Oncologica. - : TAYLOR & FRANCIS LTD. - 0284-186X .- 1651-226X. ; 56:12, s. 1776-1785
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: A pilot study of temozolomide (TMZ) given before radiotherapy (RT) for anaplastic astrocytoma (AA) and glioblastoma (GBM) resulted in prolonged survival compared to historical controls receiving RT alone. We therefore investigated neoadjuvant TMZ (NeoTMZ) in a randomized trial. During enrollment, concomitant and adjuvant radio-chemotherapy with TMZ became standard treatment. The trial was amended to include concurrent TMZ.Patients and methods: Patients, after surgery for GBM or AA, age 60 years and performance status (PS) 0-2, were randomized to either 2-3 cycles of TMZ, 200mg/m(2) days 1-5 every 28 days, followed by RT 60Gy in 30 fractions or RT only. Patients without progressive disease after two TMZ cycles, received the third cycle. From March 2005, TMZ 75mg/m(2) was administered daily concomitant with RT. TMZ was recommended first-line treatment at progression. Primary endpoint was overall survival and secondary safety.Results: The study closed prematurely after enrolling 144 patients, 103 with GBM and 41 with AA. Median age was 53 years (range 24-60) and 89 (62%) were male. PS was 0-1 for 133 (92%) patients, 53 (37%) had complete surgical resection and 18 (12%) biopsy. Ninety-two (64%) received TMZ concomitant with RT. Seventy-two (50%) were randomized to neoadjuvant treatment. For the overall study population survival was 20.3 months for RT and 17.7 months for NeoTMZ (p=.76), this not reaching the primary objective. For the preplanned subgroup analysis, we found that NeoTMZ AA patients had a median survival of 95.1 months compared to 35.2 months for RT (p=.022). For patients with GBM, no difference in survival was observed (p=.10). MGMT and IDH status affected outcome.Conclusions: No advantage of NeoTMZ was noted for the overall study population or subgroup of GBM, while NeoTMZ resulted in 5 years longer median survival for patients diagnosed as AA.
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41.
  • Malmström, Annika, 1957- (författare)
  • Studies for Better Treatment of Patients with Glioma
  • 2019
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • In Sweden annually over 500 people will be diagnosed with the malignant brain tumor glioma. They are graded from I-IV. The majority are glioblastoma (grade IV) (GBM), these being the most aggressive type. Median survival for those treated with standard of care is expected to be around 15 months. This tumor will mainly affect those 60 years or older.The studies in this thesis focus on treatment of patients with malignant gliomas grade III and IV. The aim of the studies is to improve the care of glioma patients. Papers I and II explored different therapeutic options in randomized trials, to facilitate individualized treatment recommendations. Findings from studies I and II, together with additional trials, demonstrated the importance of analyzing the tumor marker O6-methylguanine DNA methyltransferase (MGMT) methylation status for survival of GBM patients treated with Temozolomide (TMZ). The third paper investigated how the analysis of this marker is implemented internationally.The first study (paper I, Nordic trial) investigated treatment options for patients 60 years or older with GBM. The trial compared standard radiotherapy (SRT) over 6 weeks versus hypofractionated radiotherapy (HRT) over 2 weeks versus single agent TMZ administered in up to six 4 weekly cycles. In all, 342 patients were included in the trial. This study demonstrated that those randomized to TMZ had superior survival as compared to SRT. In addition, quality of life (QoL) data also suggested a better QoL for TMZ treatment than for radiotherapy. The benefit of TMZ treatment seemed to be limited to those with the tumor molecular marker MGMT methylated (inactivated).The second trial (paper II, Neoadjuvant trial) studied whether integrating TMZ treatment with SRT for patients younger than 60 years with GBM (grade IV) and astrocytoma grade III would confer a survival benefit, if administered postoperatively, before the start of SRT (neoadjuvant). TMZ was provided for 2-3 four weekly cycles followed by SRT to patients randomized to neoadjuvant treatment and was compared to postoperative SRT alone. Although this trial could not illustrate any advantage of delaying the start of SRT while administering TMZ for the study cohort in general, for those included as astrocytoma grade III the median survival was found to be superior by 5 years when randomized to neoadjuvant TMZ. This trial also confirmed the importance of MGMT promoter methylation for the efficacy of TMZ.The third study (paper III) investigated international practices for analyzing tumor MGMT promoter methylation status. MGMT analysis can be conducted by various laboratory methods, which in some cases can provide opposing results regarding the MGMT methylation status of the patient´s tumor. This can lead to incorrect treatment recommendations. To establish which methods and cut-offs that are regularly used to determine tumor MGMT status in the clinic, an international survey was provided to those working in the field. We also inquired about opinions regarding an international consensus on how MGMT should be tested. The 152 respondents reported several methodologies and different cut-off levels also for the same method. A majority of respondents warrant international guidelines.In conclusion, the results of the 2 randomized trials contribute to individualized treatment recommendations for patients affected by GBM or astrocytoma grade III. The results of the survey regarding analyses of MGMT clarify the current problematic situation. The request of the respondents regarding international guidelines might contribute to their future development, so that personalized treatment recommendations can be improved.
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42.
  • Malmström, Annika, et al. (författare)
  • Temozolomide versus standard 6-week radiotherapy versus hypofractionated radiotherapy in patients older than 60 years with glioblastoma: the Nordic randomised, phase 3 trial
  • 2012
  • Ingår i: The Lancet Oncology. - : Elsevier. - 1470-2045 .- 1474-5488. ; 13:9, s. 916-926
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Most patients with glioblastoma are older than 60 years, but treatment guidelines are based on trials in patients aged only up to 70 years. We did a randomised trial to assess the optimum palliative treatment in patients aged 60 years and older with glioblastoma. less thanbrgreater than less thanbrgreater thanMethods Patients with newly diagnosed glioblastoma were recruited from Austria, Denmark, France, Norway, Sweden, Switzerland, and Turkey. They were assigned by a computer-generated randomisation schedule, stratified by centre, to receive temozolomide (200 mg/m(2) on days 1-5 of every 28 days for up to six cycles), hypofractionated radiotherapy (34.0 Gy administered in 3.4 Gy fractions over 2 weeks), or standard radiotherapy (60.0 Gy administered in 2.0 Gy fractions over 6 weeks). Patients and study staff were aware of treatment assignment. The primary endpoint was overall survival. Analyses were done by intention to treat. This trial is registered, number ISRCTN81470623. less thanbrgreater than less thanbrgreater thanFindings 342 patients were enrolled, of whom 291 were randomised across three treatment groups (temozolomide n=93, hypofractionated radiotherapy n=98, standard radiotherapy n=100) and 51 of whom were randomised across only two groups (temozolomide n=26, hypofractionated radiotherapy n=25). In the three-group randomisation, in comparison with standard radiotherapy, median overall survival was significantly longer with temozolomide (8.3 months [95% CI 7.1-9.5; n=93] vs 6.0 months [95% CI 5.1-6.8; n=100], hazard ratio [HR] 0.70; 95% CI 0.52-0.93, p=0.01), but not with hypofractionated radiotherapy (7.5 months [6.5-8.6; n=98], HR 0.85 [0.64-1.12], p=0.24). For all patients who received temozolomide or hypofractionated radiotherapy (n=242) overall survival was similar (8.4 months [7.3-9.4; n=119] vs 7.4 months [6.4-8.4; n=123]; HR 0.82, 95% CI 0.63-1.06; p=0.12). For age older than 70 years, survival was better with temozolomide and with hypofractionated radiotherapy than with standard radiotherapy (HR for temozolomide vs standard radiotherapy 0.35 [0.21-0.56], pandlt;0.0001; HR for hypofractionated vs standard radiotherapy 0.59 [95% CI 0.37-0.93], p=0.02). Patients treated with temozolomide who had tumour MGMT promoter methylation had significantly longer survival than those without MGMT promoter methylation (9.7 months [95% CI 8.0-11.4] vs 6.8 months [5.9-7.7]; HR 0.56 [95% CI 0.34-0.93], p=0.02), but no difference was noted between those with methylated and unmethylated MGMT promoter treated with radiotherapy (HR 0.97 [95% CI 0.69-1.38]; p=0.81). As expected, the most common grade 3-4 adverse events in the temozolomide group were neutropenia (n=12) and thrombocytopenia (n=18). Grade 3-5 infections in all randomisation groups were reported in 18 patients. Two patients had fatal infections (one in the temozolomide group and one in the standard radiotherapy group) and one in the temozolomide group with grade 2 thrombocytopenia died from complications after surgery for a gastrointestinal bleed. less thanbrgreater than less thanbrgreater thanInterpretation Standard radiotherapy was associated with poor outcomes, especially in patients older than 70 years. Both temozolomide and hypofractionated radiotherapy should be considered as standard treatment options in elderly patients with glioblastoma. MGMT promoter methylation status might be a useful predictive marker for benefit from temozolomide.
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43.
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44.
  • Nilsson, Anders K., 1982, et al. (författare)
  • The proteome signature of cord blood plasma with high hematopoietic stem and progenitor cell count
  • 2022
  • Ingår i: Stem Cell Research. - : Elsevier BV. - 1873-5061. ; 61
  • Tidskriftsartikel (refereegranskat)abstract
    • Hematopoietic stem and progenitor cells (HSPC) from umbilical cord blood (UCB) are used for transplantation to treat blood disorders. Methods to estimate the HSPC count in umbilical cord blood, and thereby identify high-value blood units, are time-consuming and costly. Recent studies indicate that the UCB plasma protein composition relates to the HSPC count. We compared the plasma proteome of UCB with high vs low HSPC cell count (> 115 x 10(6) vs < 51 x 10(6) CD34(+) cells l(-1)) by using a combination of global untargeted MS quantitative proteomics and targeted proximity extension assay (PEA) proteomics. For the MS platform, 96 proteins differed significantly between the CD34(+) groups, and out of these, 44 proteins showed more than a two-fold difference. Seven pathways were enriched in high CD34(+) samples, including pathways relating to platelets, coagulation, and lipid transport. For the PEA platform, 61 proteins were differentially abundant, and among these 7 proteins showed more than a two-fold difference between groups. In the PEA data, a high CD34(+) cell count was associated with a protein hub with functions in platelet degranulation. We conclude that the HSPC count is related to the UCB plasma proteome, but that further studies are needed to discern if these findings reflect causal relationships.
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45.
  • Nordborg, Maria, 1985, et al. (författare)
  • Energy analysis of poplar production for bioenergy in Sweden
  • 2018
  • Ingår i: Biomass and Bioenergy. - : Elsevier BV. - 1873-2909 .- 0961-9534. ; 112, s. 110-120
  • Tidskriftsartikel (refereegranskat)abstract
    • Poplar (Populus spp.) species are currently not widely grown in Sweden but offer interesting options for future large-scale biomass production for bioenergy. This study assesses the average annual net energy yield and the ratio between the gross energy yield and the total primary energy input for well-managed current commercial poplar production systems in Sweden, with and without fertilization with mineral nitrogen (N). The two systems perform similarly, mainly because the yield response to fertilization is estimated to be small. The average annual net energy yields with and without fertilization are estimated at 190 and 179 GJ ha−1 yr−1, respectively. The corresponding energy ratios are 32 and 34, i.e., the total primary energy inputs correspond to only ca. 3% of the gross energy yield, in both cases. Therefore, improving the net energy yield by increasing the harvest level may be considered the most important objective from an energy performance point of view. To do this, more research is needed in order to develop poplar clones that are better adapted to the Swedish climate and identify in which situations poplar responds well to fertilization. At the same time, by reducing the energy inputs associated with the most fuel-intensive activities (wood-chip transportation, chipping, harvesting, forwarding, and stump lifting), greenhouse gas emissions can be reduced. The results should be interpreted with caution since several parameters, especially the yield response to fertilization and fuel consumption rates, are associated with considerable uncertainties.
  •  
46.
  • Nordborg, Maria, 1985, et al. (författare)
  • Energy analysis of willow production for bioenergy in Sweden
  • 2018
  • Ingår i: Renewable and Sustainable Energy Reviews. - : Elsevier BV. - 1879-0690 .- 1364-0321. ; 93, s. 473-482
  • Forskningsöversikt (refereegranskat)abstract
    • Energy from biomass, including lignocellulosic crops such as willow (Salix spp.), is expected to increase in importance in Sweden. This study assesses the average annual net energy yield and the ratio between gross energy yield and total primary energy input for well-managed current commercial willow production systems in Sweden subject to three levels of fertilization with mineral nitrogen (N): N-high, N-medium, and N-zero. The average annual net energy yields are estimated at 175, 133, and 86 GJ ha −1 yr −1 , and the (dimensionless) energy ratios are estimated at 19, 32, and 47, for N-high, N-medium, and N-zero, respectively. Thus, there is a trade-off between achieving a high net energy yield and achieving a high energy ratio. Since the total primary energy input amounts to ≤ 5% of the gross energy yield in all cases, and the amount of arable land is limited, productivity increases may be considered more important than energy efficiency improvements. Substantial improvements in energy performance can be achieved by increasing harvest levels and improving energy efficiency in ammonia production and biomass transportation. The results should be interpreted with caution since several input parameters, especially energy use in ammonia production, fuel consumption rates, and the yield response to fertilization, are associated with considerable uncertainties.
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47.
  • Nyberg, Jenny, 1976, et al. (författare)
  • Cardiovascular fitness in late adolescent males and later risk of serious non-affective mental disorders: a prospective, population-based study.
  • 2018
  • Ingår i: Psychological medicine. - 1469-8978. ; 48:3, s. 416-425
  • Tidskriftsartikel (refereegranskat)abstract
    • Cardiovascular fitness in late adolescence is associated with future risk of depression. Relationships with other mental disorders need elucidation. This study investigated whether fitness in late adolescence is associated with future risk of serious non-affective mental disorders. Further, we examined how having an affected brother might impact the relationship.Prospective, population-based cohort study of 1 109 786 Swedish male conscripts with no history of mental illness, who underwent conscription examinations at age 18 between 1968 and 2005. Cardiovascular fitness was objectively measured at conscription using a bicycle ergometer test. During the follow-up (3-42 years), incident cases of serious non-affective mental disorders (schizophrenia and schizophrenia-like disorders, other psychotic disorders and neurotic, stress-related and somatoform disorders) were identified through the Swedish National Hospital Discharge Register. Cox proportional hazards models were used to assess the influence of cardiovascular fitness at conscription and risk of serious non-affective mental disorders later in life.Low fitness was associated with increased risk for schizophrenia and schizophrenia-like disorders [hazard ratio (HR) 1.44, 95% confidence interval (CI) 1.29-1.61], other psychotic disorders (HR 1.41, 95% CI 1.27-1.56), and neurotic or stress-related and somatoform disorders (HR 1.45, 95% CI 1.37-1.54). Relationships persisted in models that included illness in brothers.Lower fitness in late adolescent males is associated with increased risk of serious non-affective mental disorders in adulthood.
  •  
48.
  • Parra-López, Carlos, et al. (författare)
  • Strengthening the development of the short-rotation plantations bioenergy sector : Policy insights from six European countries
  • 2017
  • Ingår i: Renewable energy. - : Elsevier BV. - 0960-1481 .- 1879-0682. ; 114, s. 781-793
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper, based on a participatory methodological framework involving expert stakeholders and researchers from six European countries (Germany, Ireland, Poland, Spain, Sweden and UK), analyses the priority issues for the development of short-rotation plantations (SRP), and proposes a series of policy strategies to strengthen this development. The results indicate that there is a lack of awareness of the multifaceted benefits of SRP at the level of farmers, policy makers and public authorities. More research is required to put a value on the multifunctionality of SRP and justify its public support. Small-scale projects using established technologies are also required with energy crops introduced in a phased manner. The simultaneous dissemination of this knowledge upwards to policy makers and downwards to producers and farmers is critical in the success of SRP. Also, greater financial support on both the supply and demand side is highlighted as being necessary: on the supply side linking multifunctional benefits of SRP and targeted payments, along with increased long-term contractual arrangements between farmers and energy plant operators; demand side incentives should overcome any difference in price between fossil fuels and energy crops. Groups to lobby for the uptake and support of SRP and bioenergy are also of necessary.
  •  
49.
  • Roodakker, Kenney R., et al. (författare)
  • PROX1 is a novel pathway-specific prognostic biomarker for high-grade astrocytomas; results from independent glioblastoma cohorts stratified by age and IDH mutation status
  • 2016
  • Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:45, s. 72431-72442
  • Tidskriftsartikel (refereegranskat)abstract
    • PROX1 is a transcription factor with an essential role in embryonic development and determination of cell fate. In addition, PROX1 has been ascribed suppressive as well as oncogenic roles in several human cancers, including brain tumors. In this study we explored the correlation between PROX1 expression and patient survival in high-grade astrocytomas. For this purpose, we analyzed protein expression in tissue microarrays of tumor samples stratified by patient age and IDH mutation status. We initially screened 86 unselected high-grade astrocytomas, followed by 174 IDH1-R132H1 immunonegative glioblastomas derived from patients aged 60 years and older enrolled in the Nordic phase III trial of elderly patients with newly diagnosed glioblastoma. Representing the younger population of glioblastomas, we studied 80 IDH-wildtype glioblastomas from patients aged 18-60 years. There was no correlation between PROX1 protein and survival for patients with primary glioblastomas included in these cohorts. In contrast, high expression of PROX1 protein predicted shorter survival in the group of patients with IDH-mutant anaplastic astrocytomas and secondary glioblastomas. The prognostic impact of PROX1 in IDH-mutant 1p19q non-codeleted high-grade astrocytomas, as well as the negative findings in primary glioblastomas, was corroborated by gene expression data extracted from the Cancer Genome Atlas. We conclude that PROX1 is a new prognostic biomarker for 1p19q non-codeleted high-grade astrocytomas that have progressed from pre-existing lowgrade tumors and harbor IDH mutations.
  •  
50.
  • Stacey, Simon N, et al. (författare)
  • Ancestry-shift refinement mapping of the C6orf97-ESR1 breast cancer susceptibility locus.
  • 2010
  • Ingår i: PLoS genetics. - : Public Library of Science. - 1553-7404. ; 6:7, s. e1001029-
  • Tidskriftsartikel (refereegranskat)abstract
    • We used an approach that we term ancestry-shift refinement mapping to investigate an association, originally discovered in a GWAS of a Chinese population, between rs2046210[T] and breast cancer susceptibility. The locus is on 6q25.1 in proximity to the C6orf97 and estrogen receptor alpha (ESR1) genes. We identified a panel of SNPs that are correlated with rs2046210 in Chinese, but not necessarily so in other ancestral populations, and genotyped them in breast cancer case:control samples of Asian, European, and African origin, a total of 10,176 cases and 13,286 controls. We found that rs2046210[T] does not confer substantial risk of breast cancer in Europeans and Africans (OR = 1.04, P = 0.099, and OR = 0.98, P = 0.77, respectively). Rather, in those ancestries, an association signal arises from a group of less common SNPs typified by rs9397435. The rs9397435[G] allele was found to confer risk of breast cancer in European (OR = 1.15, P = 1.2 x 10(-3)), African (OR = 1.35, P = 0.014), and Asian (OR = 1.23, P = 2.9 x 10(-4)) population samples. Combined over all ancestries, the OR was 1.19 (P = 3.9 x 10(-7)), was without significant heterogeneity between ancestries (P(het) = 0.36) and the SNP fully accounted for the association signal in each ancestry. Haplotypes bearing rs9397435[G] are well tagged by rs2046210[T] only in Asians. The rs9397435[G] allele showed associations with both estrogen receptor positive and estrogen receptor negative breast cancer. Using early-draft data from the 1,000 Genomes project, we found that the risk allele of a novel SNP (rs77275268), which is closely correlated with rs9397435, disrupts a partially methylated CpG sequence within a known CTCF binding site. These studies demonstrate that shifting the analysis among ancestral populations can provide valuable resolution in association mapping.
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