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1.	Palmqvist, Charlotta L, et al. (författare) Monitoring and evaluating surgical care: defining perioperative mortality rate and standardising data collection. 2015 Ingår i: The Lancet. - 1474-547X. ; 385 Suppl 2, s. 27-27 Tidskriftsartikel (refereegranskat)abstract Case volume per 100 000 population and perioperative mortality rate (POMR) are key indicators to monitor and strengthen surgical services. However, comparisons of POMR have been restricted by absence of standardised approaches to when it is measured, the ideal denominator, need for risk adjustment, and whether data are available. We aimed to address these issues and recommend a minimum dataset by analysing four large mixed surgical datasets, two from well-resourced settings with sophisticated electronic patient information systems and two from resource-limited settings where clinicians maintain locally developed databases.
2.	Ariyaratnam, Roshan, et al. (författare) Toward a standard approach to measurement and reporting of perioperative mortality rate as a global indicator for surgery. 2015 Ingår i: Surgery. - : Elsevier BV. - 1532-7361 .- 0039-6060. ; 158:1, s. 17-26 Tidskriftsartikel (refereegranskat)abstract The proportion of patients who die during or after surgery, otherwise known as the perioperative mortality rate (POMR), is a credible indicator of the safety and quality of operative care. Its accuracy and usefulness as a metric, however, particularly one that enables valid comparisons over time or between jurisdictions, has been limited by lack of a standardized approach to measurement and calculation, poor understanding of when in relation to surgery it is best measured, and whether risk-adjustment is needed. Our aim was to evaluate the value of POMR as a global surgery metric by addressing these issues using 4, large, mixed, surgical datasets that represent high-, middle-, and low-income countries.
3.	Fioretos, Thoas, et al. (författare) Implementing precision medicine in a regionally organized healthcare system in Sweden 2022 Ingår i: Nature Medicine. - : Springer Nature. - 1078-8956 .- 1546-170X. ; 28:10, s. 1980-1982 Tidskriftsartikel (refereegranskat)
4.	Ng-Kamstra, J. S., et al. (författare) Perioperative mortality rates in low-income and middle-income countries: a systematic review and meta-analysis 2018 Ingår i: Bmj Global Health. - : BMJ. - 2059-7908. ; 3:3 Tidskriftsartikel (refereegranskat)abstract Introduction The Lancet Commission on Global Surgery proposed the perioperative mortality rate (POMR) as one of the six key indicators of the strength of a country's surgical system. Despite its widespread use in high-income settings, few studies have described procedure-specific POMR across low-income and middle-income countries (LMICs). We aimed to estimate POMR across a wide range of surgical procedures in LMICs. We also describe how POMR is defined and reported in the LMIC literature to provide recommendations for future monitoring in resource-constrained settings. Methods We did a systematic review of studies from LMICs published from 2009 to 2014 reporting POMR for any surgical procedure. We extracted select variables in duplicate from each included study and pooled estimates of POMR by type of procedure using random-effects meta-analysis of proportions and the Freeman-Tukey double arcsine transformation to stabilise variances. Results We included 985 studies conducted across 83 LMICs, covering 191 types of surgical procedures performed on 1 020 869 patients. Pooled POMR ranged from less than 0.1% for appendectomy, cholecystectomy and caesarean delivery to 20%-27% for typhoid intestinal perforation, intracranial haemorrhage and operative head injury. We found no consistent associations between procedure-specific POMR and Human Development Index (HDI) or income-group apart from emergency peripartum hysterectomy POMR, which appeared higher in low-income countries. Inpatient mortality was the most commonly used definition, though only 46.2% of studies explicitly defined the time frame during which deaths accrued. Conclusions Efforts to improve access to surgical care in LMICs should be accompanied by investment in improving the quality and safety of care. To improve the usefulness of POMR as a safety benchmark, standard reporting items should be included with any POMR estimate. Choosing a basket of procedures for which POMR is tracked may offer institutions and countries the standardisation required to meaningfully compare surgical outcomes across contexts and improve population health outcomes.
5.	Ng-Kamstra, Joshua S, et al. (författare) Use and definitions of perioperative mortality rates in low-income and middle-income countries : a systematic review 2015 Ingår i: The Lancet. - 1474-547X. ; 385:Suppl 2, s. 29-29 Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract BACKGROUND: Aggregate and risk-stratified perioperative mortality rates (POMR) are well-documented in high-income countries where surgical databases are common. In many low-income and middle-income country (LMIC) settings, such data are unavailable, compromising efforts to understand and improve surgical outcomes. We undertook a systematic review to determine how POMR is used and defined in LMICs and to inform baseline rates.METHODS: We searched PubMed for all articles published between Jan 1, 2009, and Sept 1, 2014, reporting surgical mortality in LMICs. Search criteria, inclusion and exclusion criteria, and study assessment methodology are reported in the appendix. Titles and abstracts were screened independently by two reviewers. Full-text review and data extraction were completed by four trained clinician coders with regular validation for consistency. We extracted the definition of POMR used, clinical risk scores reported, and strategies for risk adjustment in addition to reported mortality rates.FINDINGS: We screened 2657 abstracts and included 373 full-text articles. 493 409 patients in 68 countries and 12 surgical specialties were represented. The most common definition for the numerator of POMR was in-hospital deaths following surgery (55·3%) and for the denominator it was the number of operative patients (96·2%). Few studies reported preoperative comorbidities (41·8%), ASA status (11·3%), and HIV status (7·8%), with a smaller proportion stratifying on or adjusting mortality for these factors. Studies reporting on planned procedures recorded a median mortality of 1·2% (n=121 [IQR 0·0-4·7]). Median mortality was 10·1% (n=182 [IQR 2·5-16·2) for emergent procedures.INTERPRETATION: POMR is frequently reported in LMICs, but a standardised approach for reporting and risk stratification is absent from the literature. There was wide variation in POMR across procedures and specialties. A quality assessment checklist for surgical mortality studies could improve mortality reporting and facilitate benchmarking across sites and countries.FUNDING: None.
6.	Ossenkoppele, Rik, et al. (författare) Accuracy of Tau Positron Emission Tomography as a Prognostic Marker in Preclinical and Prodromal Alzheimer Disease : A Head-to-Head Comparison against Amyloid Positron Emission Tomography and Magnetic Resonance Imaging 2021 Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149. ; 78:8, s. 961-971 Tidskriftsartikel (refereegranskat)abstract Importance: Tau positron emission tomography (PET) tracers have proven useful for the differential diagnosis of dementia, but their utility for predicting cognitive change is unclear. Objective: To examine the prognostic accuracy of baseline fluorine 18 (18F)-flortaucipir and [18F]RO948 (tau) PET in individuals across the Alzheimer disease (AD) clinical spectrum and to perform a head-to-head comparison against established magnetic resonance imaging (MRI) and amyloid PET markers. Design, Setting, and Participants: This prognostic study collected data from 8 cohorts in South Korea, Sweden, and the US from June 1, 2014, to February 28, 2021, with a mean (SD) follow-up of 1.9 (0.8) years. A total of 1431 participants were recruited from memory clinics, clinical trials, or cohort studies; 673 were cognitively unimpaired (CU group; 253 [37.6%] positive for amyloid-β [Aβ]), 443 had mild cognitive impairment (MCI group; 271 [61.2%] positive for Aβ), and 315 had a clinical diagnosis of AD dementia (315 [100%] positive for Aβ). Exposures: [18F]Flortaucipir PET in the discovery cohort (n = 1135) or [18F]RO948 PET in the replication cohort (n = 296), T1-weighted MRI (n = 1431), and amyloid PET (n = 1329) at baseline and repeated Mini-Mental State Examination (MMSE) evaluation. Main Outcomes and Measures: Baseline [18F]flortaucipir/[18F]RO948 PET retention within a temporal region of interest, MRI-based AD-signature cortical thickness, and amyloid PET Centiloids were used to predict changes in MMSE using linear mixed-effects models adjusted for age, sex, education, and cohort. Mediation/interaction analyses tested whether associations between baseline tau PET and cognitive change were mediated by baseline MRI measures and whether age, sex, and APOE genotype modified these associations. Results: Among 1431 participants, the mean (SD) age was 71.2 (8.8) years; 751 (52.5%) were male. Findings for [18F]flortaucipir PET predicted longitudinal changes in MMSE, and effect sizes were stronger than for AD-signature cortical thickness and amyloid PET across all participants (R2, 0.35 [tau PET] vs 0.24 [MRI] vs 0.17 [amyloid PET]; P <.001, bootstrapped for difference) in the Aβ-positive MCI group (R2, 0.25 [tau PET] vs 0.15 [MRI] vs 0.07 [amyloid PET]; P <.001, bootstrapped for difference) and in the Aβ-positive CU group (R2, 0.16 [tau PET] vs 0.08 [MRI] vs 0.08 [amyloid PET]; P <.001, bootstrapped for difference). These findings were replicated in the [18F]RO948 PET cohort. MRI mediated the association between [18F]flortaucipir PET and MMSE in the groups with AD dementia (33.4% [95% CI, 15.5%-60.0%] of the total effect) and Aβ-positive MCI (13.6% [95% CI, 0.0%-28.0%] of the total effect), but not the Aβ-positive CU group (3.7% [95% CI, -17.5% to 39.0%]; P =.71). Age (t = -2.28; P =.02), but not sex (t = 0.92; P =.36) or APOE genotype (t = 1.06; P =.29) modified the association between baseline [18F]flortaucipir PET and cognitive change, such that older individuals showed faster cognitive decline at similar tau PET levels. Conclusions and Relevance: The findings of this prognostic study suggest that tau PET is a promising tool for predicting cognitive change that is superior to amyloid PET and MRI and may support the prognostic process in preclinical and prodromal stages of AD.
7.	Ossenkoppele, Rik, et al. (författare) Assessment of Demographic, Genetic, and Imaging Variables Associated with Brain Resilience and Cognitive Resilience to Pathological Tau in Patients with Alzheimer Disease 2020 Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149. ; 77:5, s. 632-642 Tidskriftsartikel (refereegranskat)abstract Importance: Better understanding is needed of the degree to which individuals tolerate Alzheimer disease (AD)-like pathological tau with respect to brain structure (brain resilience) and cognition (cognitive resilience). Objective: To examine the demographic (age, sex, and educational level), genetic (APOE-ϵ4 status), and neuroimaging (white matter hyperintensities and cortical thickness) factors associated with interindividual differences in brain and cognitive resilience to tau positron emission tomography (PET) load and to changes in global cognition over time. Design, Setting, an Participants: In this cross-sectional, longitudinal study, tau PET was performed from June 1, 2014, to November 30, 2017, and global cognition monitored for a mean [SD] interval of 2.0 [1.8] years at 3 dementia centers in South Korea, Sweden, and the United States. The study included amyloid-β-positive participants with mild cognitive impairment or AD dementia. Data analysis was performed from October 26, 2018, to December 11, 2019. Exposures: Standard dementia screening, cognitive testing, brain magnetic resonance imaging, amyloid-β PET and cerebrospinal fluid analysis, and flortaucipir (tau) labeled with fluor-18 (18F) PET. Main Outcomes and Measures: Separate linear regression models were performed between whole cortex [18F]flortaucipir uptake and cortical thickness, and standardized residuals were used to obtain a measure of brain resilience. The same procedure was performed for whole cortex [18F]flortaucipir uptake vs Mini-Mental State Examination (MMSE) as a measure of cognitive resilience. Bivariate and multivariable linear regression models were conducted with age, sex, educational level, APOE-ϵ4 status, white matter hyperintensity volumes, and cortical thickness as independent variables and brain and cognitive resilience measures as dependent variables. Linear mixed models were performed to examine whether changes in MMSE scores over time differed as a function of a combined brain and cognitive resilience variable. Results: A total of 260 participants (145 [55.8%] female; mean [SD] age, 69.2 [9.5] years; mean [SD] MMSE score, 21.9 [5.5]) were included in the study. In multivariable models, women (standardized β =-0.15, P =.02) and young patients (standardized β =-0.20, P =.006) had greater brain resilience to pathological tau. Higher educational level (standardized β = 0.23, P <.001) and global cortical thickness (standardized β = 0.23, P <.001) were associated with greater cognitive resilience to pathological tau. Linear mixed models indicated a significant interaction of brain resilience × cognitive resilience × time on MMSE (β [SE] =-0.235 [0.111], P =.03), with steepest slopes for individuals with both low brain and cognitive resilience. Conclusions and Relevance: Results of this study suggest that women and young patients with AD have relative preservation of brain structure when exposed to neocortical pathological tau. Interindividual differences in resilience to pathological tau may be important to disease progression because participants with both low brain and cognitive resilience had the most rapid cognitive decline over time.
8.	Ossenkoppele, Rik, et al. (författare) Discriminative Accuracy of F-18 flortaucipir Positron Emission Tomography for Alzheimer Disease vs Other Neurodegenerative Disorders 2018 Ingår i: Jama-Journal of the American Medical Association. - : American Medical Association (AMA). - 0098-7484. ; 320:11, s. 1151-1162 Tidskriftsartikel (refereegranskat)abstract IMPORTANCE The positron emission tomography (PET) tracer [F-18]flortaucipir allows in vivo quantification of paired helical filament tau, a core neuropathological feature of Alzheimer disease (AD), but its diagnostic utility is unclear. OBJECTIVE To examine the discriminative accuracy of [F-18]flortaucipir for AD vs non-AD neurodegenerative disorders. DESIGN, SETTING, AND PARTICIPANTS In this cross-sectional study, 719 participants were recruited from 3 dementia centers in South Korea, Sweden, and the United States between June 2014 and November 2017 (160 cognitively normal controls, 126 patients with mild cognitive impairment [MCI], of whom 65.9% were amyloid-beta [A beta]positive [ie, MCI due to AD], 179 patients with AD dementia, and 254 patients with various non-AD neurodegenerative disorders). EXPOSURES The index testwas the [F-18]flortaucipir PET standardized uptake value ratio (SUVR) in 5 predefined regions of interest (ROIs). Cut points for tau positivity were determined using the mean +2 SDs observed in controls and Youden Index for the contrast AD dementia vs controls. MAIN OUTCOMES AND MEASURES The reference standard was the clinical diagnosis determined at the specialized memory centers. In the primary analysis, the discriminative accuracy (ie, sensitivity and specificity) of [F-18]flortaucipir was examined for AD dementia vs all non-AD neurodegenerative disorders. In secondary analyses, the area under the curve (AUC) of [F-18]flortaucipir SUVR was compared with 3 established magnetic resonance imaging measures (hippocampal volumes and AD signature and whole-brain cortical thickness), and sensitivity and specificity of [F-18]flortaucipir in MCI due to AD vs non-AD neurodegenerative disorders were determined. RESULTS Among 719 participants, the overall mean (SD) age was 68.8 (9.2) years and 48.4% were male. The proportions of patients who were amyloid-beta positive were 26.3%, 65.9%, 100%, and 23.8% among cognitively normal controls, patients with MCI, patients with AD dementia, and patients with non-AD neurodegenerative disorders, respectively. [F-18]flortaucipir uptake in the medial-basal and lateral temporal cortex showed 89.9% (95% CI, 84.6%-93.9%) sensitivity and 90.6%(95% CI, 86.3%-93.9%) specificity using the threshold based on controls (SUVR, 1.34), and 96.8%(95% CI, 92.0%-99.1%) sensitivity and 87.9%(95% CI, 81.9%-92.4%) specificity using the Youden Index-derived cutoff (SUVR, 1.27) for distinguishing AD dementia from all non-AD neurodegenerative disorders. The AUCs for all 5 [F-18]flortaucipir ROIs were higher (AUC range, 0.92-0.95) compared with the 3 volumetric MRI measures (AUC range, 0.63-0.75; all ROIs P<.001). Diagnostic performance of the 5 [F-18]flortaucipir ROIs were lower in MCI due to AD (AUC range, 0.75-0.84). CONCLUSIONS AND RELEVANCE Among patients with established diagnoses at a memory disorder clinic, [F-18]flortaucipir PET was able to discriminate AD from other neurodegenerative diseases. The accuracy and potential utility of this test in patient care require further research in clinically more representative populations.
9.	Ossenkoppele, Rik, et al. (författare) Distinct tau PET patterns in atrophy-defined subtypes of Alzheimer's disease 2020 Ingår i: Alzheimer's and Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 16:2, s. 335-344 Tidskriftsartikel (refereegranskat)abstract Introduction: Differential patterns of brain atrophy on structural magnetic resonance imaging (MRI) revealed four reproducible subtypes of Alzheimer's disease (AD): (1) “typical”, (2) “limbic-predominant”, (3) “hippocampal-sparing”, and (4) “mild atrophy”. We examined the neurobiological characteristics and clinical progression of these atrophy-defined subtypes. Methods: The four subtypes were replicated using a clustering method on MRI data in 260 amyloid-β–positive patients with mild cognitive impairment or AD dementia, and we subsequently tested whether the subtypes differed on [18F]flortaucipir (tau) positron emission tomography, white matter hyperintensity burden, and rate of global cognitive decline. Results: Voxel-wise and region-of-interest analyses revealed the greatest neocortical tau load in hippocampal-sparing (frontoparietal-predominant) and typical (temporal-predominant) patients, while limbic-predominant patients showed particularly high entorhinal tau. Typical patients with AD had the most pronounced white matter hyperintensity load, and hippocampal-sparing patients showed the most rapid global cognitive decline. Discussion: Our data suggest that structural MRI can be used to identify biologically and clinically meaningful subtypes of AD.
10.	Ossenkoppele, Rik, et al. (författare) The impact of demographic, clinical, genetic, and imaging variables on tau PET status 2021 Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 48:7, s. 2245-2258 Tidskriftsartikel (refereegranskat)abstract Purpose: A substantial proportion of amyloid-β (Aβ)+ patients with clinically diagnosed Alzheimer’s disease (AD) dementia and mild cognitive impairment (MCI) are tau PET–negative, while some clinically diagnosed non-AD neurodegenerative disorder (non-AD) patients or cognitively unimpaired (CU) subjects are tau PET–positive. We investigated which demographic, clinical, genetic, and imaging variables contributed to tau PET status. Methods: We included 2338 participants (430 Aβ+ AD dementia, 381 Aβ+ MCI, 370 non-AD, and 1157 CU) who underwent [18F]flortaucipir (n = 1944) or [18F]RO948 (n = 719) PET. Tau PET positivity was determined in the entorhinal cortex, temporal meta-ROI, and Braak V-VI regions using previously established cutoffs. We performed bivariate binary logistic regression models with tau PET status (positive/negative) as dependent variable and age, sex, APOEε4, Aβ status (only in CU and non-AD analyses), MMSE, global white matter hyperintensities (WMH), and AD-signature cortical thickness as predictors. Additionally, we performed multivariable binary logistic regression models to account for all other predictors in the same model. Results: Tau PET positivity in the temporal meta-ROI was 88.6% for AD dementia, 46.5% for MCI, 9.5% for non-AD, and 6.1% for CU. Among Aβ+ participants with AD dementia and MCI, lower age, MMSE score, and AD-signature cortical thickness showed the strongest associations with tau PET positivity. In non-AD and CU participants, presence of Aβ was the strongest predictor of a positive tau PET scan. Conclusion: We identified several demographic, clinical, and neurobiological factors that are important to explain the variance in tau PET retention observed across the AD pathological continuum, non-AD neurodegenerative disorders, and cognitively unimpaired persons.
11.	Rezayee, F, et al. (författare) Whole genome sequencing as the sole method to characterize genetically pediatric B-cell precursor acute lymphoblastic leukemia in a diagnostic setting 2024 Ingår i: EUROPEAN JOURNAL OF HUMAN GENETICS. - 1018-4813. ; 32, s. 641-641 Konferensbidrag (övrigt vetenskapligt/konstnärligt)
12.	Barthélemy, Nicolas R, et al. (författare) Highly Accurate Blood Test for Alzheimer's Disease Comparable or Superior to Clinical CSF Tests Ingår i: Nature Medicine. - 1546-170X. Tidskriftsartikel (refereegranskat)abstract With the emergence of Alzheimer's disease (AD) disease-modifying therapies, identifying patients who could benefit from these treatments becomes critical. We evaluated whether a precise blood test could perform as well as established cerebrospinal fluid (CSF) tests in detecting amyloid-β (Aβ) plaques and tau tangles. Plasma %p-tau217 (ratio of phosporylated-tau217 to non-phosphorylated tau) was analyzed by mass spectrometry in the Swedish BioFINDER-2 cohort (n=1,422) and the US Knight ADRC cohort (n=337). Matched CSF samples were analyzed with clinically used and FDA-approved automated immunoassays for Aβ42/40 and p-tau181/Aβ42. The primary and secondary outcomes were detection of brain Aβ or tau pathology, respectively, using PET imaging as the reference standard. Main analyses were focused on individuals with cognitive impairment (mild cognitive impairment and mild dementia), which is the target population for available disease-modifying treatments. Plasma %p-tau217 was clinically equivalent to FDA-approved CSF tests in classifying Aβ PET status, with an area-under-the-curve (AUC) for both between 0.95-0.97. Plasma %p-tau217 was generally superior to CSF tests in classification of tau-PET with AUCs of 0.95-0.98. In cognitively impaired sub-cohorts (BioFINDER-2: n=720; Knight ADRC: n=50), plasma %p-tau217 had an accuracy, positive predictive value and negative predictive value of 89-90% for Aβ PET and 87-88% for tau-PET status, which was clinically equivalent to CSF tests, further improving to 95% using a two cut-off approach. Blood plasma %p-tau217 demonstrated performance clinically equivalent or superior to clinically used FDA-approved CSF tests in the detection of AD pathology. Use of high performance blood tests in clinical practice can improve access to accurate AD diagnosis and AD-specific treatments.
13.	Cullen, Nicholas C., et al. (författare) Plasma biomarkers of Alzheimer’s disease improve prediction of cognitive decline in cognitively unimpaired elderly populations 2021 Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1 Tidskriftsartikel (refereegranskat)abstract Plasma biomarkers of amyloid, tau, and neurodegeneration (ATN) need to be characterized in cognitively unimpaired (CU) elderly individuals. We therefore tested if plasma measurements of amyloid-β (Aβ)42/40, phospho-tau217 (P-tau217), and neurofilament light (NfL) together predict clinical deterioration in 435 CU individuals followed for an average of 4.8 ± 1.7 years in the BioFINDER study. A combination of all three plasma biomarkers and basic demographics best predicted change in cognition (Pre-Alzheimer’s Clinical Composite; R2 = 0.14, 95% CI [0.12–0.17]; P < 0.0001) and subsequent AD dementia (AUC = 0.82, 95% CI [0.77–0.91], P < 0.0001). In a simulated clinical trial, a screening algorithm combining all three plasma biomarkers would reduce the required sample size by 70% (95% CI [54–81]; P < 0.001) with cognition as trial endpoint, and by 63% (95% CI [53–70], P < 0.001) with subsequent AD dementia as trial endpoint. Plasma ATN biomarkers show usefulness in cognitively unimpaired populations and could make large clinical trials more feasible and cost-effective.
14.	DAWODY, JAZAER, 1959, et al. (författare) E4-Mistra, a research program for the development of an energy efficient low emission exhaust aftertreatment system for heavy duty vehicles 2012 Ingår i: World Renewable Energy Forum, WREF 2012, Including World Renewable Energy Congress XII and Colorado Renewable Energy Society (CRES) Annual Conference. - : American Solar Energy Society. - 9781622760923 ; , s. 4530-4536 Konferensbidrag (refereegranskat)abstract This paper presents a unique system approach applied in a joint academic - industrial research program, E4 Mistra, to reach the goals of energy efficiency and low emissions exhaust aftertreatment system for heavy duty vehicles. The high energy efficiency is achieved by heat recuperation, on-board hydrogen production for use in both an auxiliary power unit and for NOx reduction and by finding new solutions for making the after-treatment system active at low exhaust temperatures. To reach low particulate emissions a mechanical filter using a sintered metal filter is developed. Low NOx emissions are achieved by an efficient NOx reduction catalyst. The system is based on four technological advances: Thermoelectric material s for heat recuperation, catalytic reduction of NOx over innovative catalyst substrates using hydrocarbons from the fuel and H2 from a high efficiency fuel reformer, and particulate filtration over a porous metal filter.
15.	Gauslaa, Y., et al. (författare) Growth of epiphytic old forest lichens across climatic and successional gradients 2007 Ingår i: Canadian Journal of Forest Research. - 0045-5067 .- 1208-6037. ; 37:10, s. 1832-1845 Tidskriftsartikel (refereegranskat)abstract This paper aims to assess the influence of canopy cover on lichen growth in boreal forests along a regional forest gradient. Biomass and area gain, and some acclimation traits, were assessed in the old-forest lichens Lobaria pulmonaria (L.) Hoffm., Pseudocyphellaria crocata (L.) Vain., and Usnea longissima Ach. transplanted 110days in three successional Norway spruce (Picea abies (L.) Karst.) forest stands (clearcut, young, and old forest) repeated along a rainfall gradient (continental, suboceanic, and Atlantic zones) in Scandinavia. Lichen growth peaked in Atlantic rainforests with mean dry matter (DM) gain up to 36%-38%. The alectorioid lichen U. longissima showed the widest range of growth responses and no signs of chlorophyll degradation. Its highest DM gain consistently occurred in clearcuts, whereas the DM gain was close to zero in the shadiest young forest. The two foliose lichens L. pulmonaria and P. crocata exhibited maximal growth rates in old forests, but apparently growth was limited by low light even in old forests. Their DM gain was reduced in the most sun-exposed clearcuts due to chlorophyll degradation and was relatively high under closed young canopies, suggesting a better adaptation to shade. The lichen responses show that a high frequency and dominance of young and dense fast-growing forest stands at a landscape level are not compatible with large populations of these old-forest lichens and that a lack of lichens under an industrial forestry regime may not necessarily be determined by low dispersal efficiency only. Cet article a pour but d'évaluer l'influence du couvert de la canopée sur la croissance des lichens dans les forêts boréales le long d'un gradient forestier régional. Le gain en biomasse et en superficie ainsi que certains caractères d'acclimatation ont été évalués chez les lichens des forêts âgées, Lobaria pulmonaria (L.) Hoffm., Pseudocyphellaria crocata (L.) Vain. et Usnea longissima Ach., qui ont été transplantés pendant 110 jours dans trois peuplements d'épicéa commun (Picea abies (L.) Karst.) rendus à différents stades de succession (forêt coupée à blanc, jeune et vieille forêts). L'expérience a été répétée le long d'un gradient pluvial (zones continentale, subocéanique et atlantique) en Scandinavie. La croissance des lichens a culminé dans les forêts pluviales atlantiques avec un gain moyen en matière anhydre allant jusqu'à 36%-38%. Le lichen alectorioïde U. longissima a montré la plus vaste gamme de réponses en croissance végétative et aucun signe de dégradation de la chlorophylle. Son gain maximal en matière anhydre est survenu essentiellement dans les coupes à blanc alors qu'il était presque nul dans la jeune forêt la plus ombragée. Les deux lichens foliacés, L. pulmonaria et P. crocata, montraient des taux maximum de croissance dans les vieilles forêts, mais la croissance était apparemment limitée par la faible luminosité, même dans les forêts âgées. Leur gain en matière anhydre était réduit dans la plupart des coupes à blanc exposées au soleil à cause de la dégradation de la chlorophylle alors qu'il était relativement élevé sous les jeunes canopées fermées, ce qui indique une meilleure adaptation à l'ombre. La réponse des lichens montre qu'une fréquence élevée et une forte dominance de jeunes peuplements forestiers à croissance rapide à l'échelle du paysage ne sont pas compatibles avec de grandes populations de ces lichens, typiques des forêts matures, et que le manque de lichens sous un régime forestier industriel pourrait ne pas nécessairement être dû seulement à la faible efficacité de dispersion des lichens.
16.	Janelidze, Shorena, et al. (författare) Detecting amyloid positivity in early Alzheimer's disease using combinations of plasma A beta 42/A beta 40 and p-tau 2022 Ingår i: Alzheimers & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 18:2, s. 283-293 Tidskriftsartikel (refereegranskat)abstract Introduction: We studied usefulness of combining blood amyloid beta A(beta)42/A beta 40, phosphorylated tau (p-tau)217, and neurofilament light (NfL) to detect abnormal brain A beta deposition in different stages of early Alzheimer's disease (AD). Methods: Plasma biomarkers were measured using mass spectrometry (A beta 42/A beta 40) and immunoassays (p-tau217 and NfL) in cognitively unimpaired individuals (CU, N = 591) and patients with mild cognitive impairment (MCI, N = 304) from two independent cohorts (BioFINDER-1, BioFINDER-2). Results: In CU, a combination of plasma A beta 42/A beta 40 and p-tau217 detected abnormal brain A beta status with area under the curve (AUC) of 0.83 to 0.86. In MCI, the models including p-tau217 alone or A beta 42/A beta 40 and p-tau217 had similar AUCs (0.86-0.88); however, the latter showed improved model fit. The models were implemented in an online application providing individualized risk assessments (https://brainapps.shinyappas.io/PredictAAbplasma/). Discussion:A combination of plasma A beta 42/A beta 40 and p-tau217 discriminated A beta status with relatively high accuracy, whereas p-tau217 showed strongest associations with A beta pathology in MCI but not in CU.
17.	Krowiorz, K, et al. (författare) MiR-139-5p is a potent tumor suppressor in adult acute myeloid leukemia. 2016 Ingår i: Blood cancer journal. - : Springer Science and Business Media LLC. - 2044-5385. ; 6:12 Tidskriftsartikel (refereegranskat)
18.	Lindgren, M., et al. (författare) Influence of IL-28B and IL-6 Genetic Polymorphism on IFN-ALFA Treatment Outcome in Patients with Polycythemia Vera and Essential Trombocythemia 2014 Ingår i: Haematologica. - 0390-6078 .- 1592-8721. ; 99:S1, s. 130-131 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
19.	Mattke, S., et al. (författare) Estimates of Current Capacity for Diagnosing Alzheimer's Disease in Sweden and the Need to Expand Specialist Numbers 2024 Ingår i: JPAD-JOURNAL OF PREVENTION OF ALZHEIMERS DISEASE. - 2274-5807 .- 2426-0266. ; 11:1, s. 155-161 Tidskriftsartikel (refereegranskat)abstract BackgroundThe emergence of disease-modifying Alzheimer's (AD) treatments provides new hope to patients and families but concerns have been raised about the preparedness of healthcare systems to provide timely access to such treatments because of a combination of a complex diagnostic process and a large prevalent pool.ObjectivesWe assess the preparedness of Sweden, a high-income country known for its dementia-friendly policies, to diagnose AD patients eligible for treatment within a six-month window, given current capacity for specialist evaluations and biomarker testing. We calculate the investment requirements for Sweden to achieve this target over a timeframe of 20 years.DesignDesk research to identify data for population, mortality, disease burden, cost of services and current capacity, expert consultation to inform assumptions about patient journey, and use of a Markov model to predict waiting times. The model simulates the patients' journey through different evaluation stages: initial evaluation by a primary care specialist, neurocognitive testing by an AD specialist, and confirmatory biomarker testing with PET scanning or cerebrospinal fluid (CSF) testing. The model assumes specialist appointments and PET scans are capacity constrained, and patients progress from cognitively normal to MCI and from MCI to dementia in the resulting waiting times.MeasurementsProjected waiting times for diagnosis of eligibility for disease-modifying Alzheimer's treatment from 2023 to 2042 assuming current capacity, assuming 20% of Swedish residents aged 60 years and above would seek an evaluation for cognitive decline. Investments required to scale capacity up to reach target of providing diagnosis within six months on average.ResultsInitial average waiting times for AD specialist appointments would be around 21 months in 2023 and remain around 55 months through 2042, as demand would continue to outstrip supply throughout the 20-year model horizon. Waiting times for biomarker testing would be stable at less than four weeks, as patients would be held up in the queue for their first specialist consultations, and use of CSF testing is widely accepted in Sweden. An additional 25% of AD specialists would have to be added above the current growth trend to reduce waiting times to less than 6 months at an average annual cost of approximately 805 million SEK. The increased cost of volume of biomarker testing would amount to about 106 million SEK per year.ConclusionsAt current capacity, the Swedish healthcare system is unable to provide timely diagnosis of patients eligible for disease-modifying AD treatment. Although future diagnostic technologies, such as digital cognitive assessments and blood tests for the AD pathology, might decrease demand for capacity-constrained services, substantial investments will be required to meet a target of less than six months of waiting time for a diagnosis.
20.	Mattsson-Carlgren, Niklas, et al. (författare) Longitudinal plasma p-tau217 is increased in early stages of Alzheimer's disease 2020 Ingår i: Brain : a journal of neurology. - : Oxford University Press (OUP). - 1460-2156. ; 143:11, s. 3234-3241 Tidskriftsartikel (refereegranskat)abstract Plasma levels of tau phosphorylated at threonine-217 (p-tau217) is a candidate tool to monitor Alzheimer's disease. We studied 150 cognitively unimpaired participants and 100 patients with mild cognitive impairment in the Swedish BioFINDER study. P-tau217 was measured repeatedly for up to 6 years (median three samples per person, median time from first to last sample, 4.3 years). Preclinical (amyloid-β-positive cognitively unimpaired, n = 62) and prodromal (amyloid-β-positive mild cognitive impairment, n = 49) Alzheimer's disease had accelerated p-tau217 compared to amyloid-β-negative cognitively unimpaired (β = 0.56, P < 0.001, using linear mixed effects models) and amyloid-β-negative mild cognitive impairment patients (β = 0.67, P < 0.001), respectively. Mild cognitive impairment patients who later converted to Alzheimer's disease dementia (n = 40) had accelerated p-tau217 compared to other mild cognitive impairment patients (β = 0.79, P < 0.001). P-tau217 did not change in amyloid-β-negative participants, or in patients with mild cognitive impairment who did not convert to Alzheimer's disease dementia. For 80% power, 109 participants per arm were required to observe a slope reduction in amyloid-β-positive cognitively unimpaired (71 participants per arm in amyloid-β-positive mild cognitive impairment). Longitudinal increases in p-tau217 correlated with longitudinal worsening of cognition and brain atrophy. In summary, plasma p-tau217 increases during early Alzheimer's disease and can be used to monitor disease progression.
21.	Rezayee, F., et al. (författare) Feasibility to use whole-genome sequencing as a sole diagnostic method to detect genomic aberrations in pediatric B-cell acute lymphoblastic leukemia 2023 Ingår i: FRONTIERS IN ONCOLOGY. - : Frontiers Media SA. - 2234-943X. ; 13 Tidskriftsartikel (refereegranskat)abstract Introduction The suitability of whole-genome sequencing (WGS) as the sole method to detect clinically relevant genomic aberrations in B-cell acute lymphoblastic leukemia (ALL) was investigated with the aim of replacing current diagnostic methods.Methods For this purpose, we assessed the analytical performance of 150 bp paired-end WGS (90x leukemia/30x germline). A set of 88 retrospective B-cell ALL samples were selected to represent established ALL subgroups as well as ALL lacking stratifying markers by standard-of-care (SoC), so-called B-other ALL.Results Both the analysis of paired leukemia/germline (L/N)(n=64) as well as leukemia-only (L-only)(n=88) detected all types of aberrations mandatory in the current ALLTogether trial protocol, i.e., aneuploidies, structural variants, and focal copy-number aberrations. Moreover, comparison to SoC revealed 100% concordance and that all patients had been assigned to the correct genetic subgroup using both approaches. Notably, WGS could allocate 35 out of 39 B-other ALL samples to one of the emerging genetic subgroups considered in the most recent classifications of ALL. We further investigated the impact of high (90x; n=58) vs low (30x; n=30) coverage on the diagnostic yield and observed an equally perfect concordance with SoC; low coverage detected all relevant lesions.Discussion The filtration of the WGS findings with a short list of genes recurrently rearranged in ALL was instrumental to extract the clinically relevant information efficiently. Nonetheless, the detection of DUX4 rearrangements required an additional customized analysis, due to multiple copies of this gene embedded in the highly repetitive D4Z4 region. We conclude that the diagnostic performance of WGS as the standalone method was remarkable and allowed detection of all clinically relevant genomic events in the diagnostic setting of B-cell ALL.
22.	Waraky, A, et al. (författare) MNX1 INDUCES LEUKEMIA TRANSFORMATION THROUGH INTERACTION WITH THE METHIONINE CYCLE IN A MODEL OF PEDIATRIC T(7;12) ACUTE MYELOID LEUKEMIA 2021 Ingår i: EXPERIMENTAL HEMATOLOGY. - 0301-472X. ; 100, s. S110-S110 Konferensbidrag (övrigt vetenskapligt/konstnärligt)
23.	Westerlind, H, et al. (författare) Is tea consumption associated with reduction of risk of rheumatoid arthritis? A Swedish case-control study 2021 Ingår i: Arthritis research & therapy. - : Springer Science and Business Media LLC. - 1478-6362. ; 23:1, s. 209- Tidskriftsartikel (refereegranskat)abstract BackgroundTea is a popular beverage around the world and has properties that can affect the immune system. The association between tea consumption and the risk of rheumatoid arthritis (RA), a chronic autoimmune disease primarily affecting the joints, is not well studied and results are conflicting.MethodsWe collected data on tea consumption for 2237 incident RA cases diagnosed 2005–2018 and 4661 controls matched on age, sex, and residential area. Tea consumption was classified into no (0 cups/day), irregular (< 1 cup/day), regular (1–2 cups/day), and high (≥ 2 cups/day) consumption, and irregular consumption was used as the reference category. Missing data on tea consumption was classified as no consumers, and sensitivity analyses were performed to test this assumption. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression, adjusting for smoking, coffee, alcohol, educational level, and body mass index. We also performed stratified analysis on sex, anti-citrullinated autoantibody (ACPA) status, and smoking habits.ResultsAmong the cases, we found 57.3% to be ever consumers of tea with 19.7 having a high tea consumption. Corresponding figures for the controls were 58.4% ever drinkers with 22.1% high tea consumers. High tea consumption had an inverse association to the risk of RA compared to irregular consumption [OR = 0.78 (95% CI 0.66–0.92)], but the association lost statistical significance in the adjusted model [adjusted OR (adjOR) = 0.85 (95% CI 0.71–1.01)]. Among non-tea consumers, a protective effect was also observed compared to irregular consumers [adjOR = 0.82 (95% CI 0.70–0.88)], but this association did not withstand sensitivity analysis, possibly due to bias. In the ACPA-positive group and among current smokers, a protective effect of tea consumption was observed among the high tea consumers [adjOR = 0.76 (95% CI 0.62–0.94) and adjOR = 0.60 (95% CI 0.38–0.95), respectively].ConclusionsThis study suggests a protective effect of high consumption of tea, among smokers and for ACPA-positive RA.Trial registrationNot applicable
24.	Westerlind, H, et al. (författare) IS TEA CONSUMPTION ASSOCIATED WITH RISK OF RHEUMATOID ARTHRITIS? 2021 Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 80, s. 1059-1060 Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract Only few studies have looked at the association between tea consumption and risk of rheumatoid arthritis (RA) with inconclusive results.Objectives:To estimate the association between tea consumption and risk of RA in a large population-based case-control study.Methods:We used data from the Swedish Epidemiological Investigation of RA (EIRA), a population-based case-control study including incident RA cases with 2 controls randomly matched from the general population, based on age, sex and residential area at the date of diagnosis. All participants filled in a comprehensive questionnaire on lifestyle factors, including a 124-item food frequency questionnaire (FFQ). Data from October 2005 - May 2018 was used.Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using conditional logistic regression, overall and stratified by anti-citrullinated protein antibody (ACPA) and smoking status. We adjusted for smoking status, coffee and alcohol consumption, educational level and BMI. The dose-response trend of the association between tea consumption and risk of rheumatoid arthritis was estimated using restricted cubic spline with knots at 0, 0.29, and 2.29 cups per day. Missing tea values (44.8%) were imputed based on the zero-consumption assumption. A sensitivity analysis was performed to evaluate the influence of the assumption on the main result, with 70% of the missing randomly imputed as no consumption, and the remaining 30% randomly assigned to the other categories (10% per category).Results:We included 2237 cases and 4661 controls. Controls were more likely to drink ≥2 tea cups/day compared to RA cases (22.1% vs. 19.7%).The crude odds of developing RA was 22% lower (OR=0.78, 95% CI: 0.66-0.92) among those who consumed ≥2 tea cups/day compared to those who drank <1 cup/day (irregular drinkers). After adjustment for covariates, the inverse association was less pronounced and only borderline significant (OR=0.85, 95% CI: 0.71-1.01). A similar OR was observed among non-tea consumer (OR=0.82, 95% CI: 0.70-0.95). The odds of developing ACPA positive RA (but not ACPA negative) was statistically significant lower among participants drinking >=2 cups/day compared to irregular tea drinkers (OR=0.76, 95% CI: 0.62-0.94). In analyses stratified by smoking, an inverse association between tea intake and RA was found only among current smokers (OR=0.58, 95% CI: 0.37-0.92), while no association was found in never smoker. The sensitivity analysis showed results similar to the main analysis, although the OR in the no consumption category was not significant (OR=0.88, 95% CI: 0.76-1.02) while the OR in the highest category was statistically significant (OR=0.85, 95% CI: 0.73-0.99).Overall tea consumption0 cups/day<1 cup/day1-2 cups/day>=2 cups/dayOverall Number955/1941453/847388/845441/1028 OR crude*0.89 (0.77-1.03)Ref0.84 (0.71-1.00)0.78 (0.66-0.92) OR adjusted±0.82 (0.70-0.95)Ref0.87 (0.73-1.04)0.85 (0.71-1.01)ACPA positive Number637/1156321/527268/501277/630 OR adjusted0.81 (0.67-0.97)Ref0.88 (0.71-1.09)0.76 (0.62-0.94)ACPA negative Number312/571129/221119/251162/288 OR adjusted0.87 (0.66-1.14)Ref0.87 (0.63-1.19)1.07 (0.78-1.46)Never smokers Number290/859164/436142/433213/563 OR adjusted0.90 (0.72-1.14)Ref0.88 (0.68-1.15)1.04 (0.81-1.33)Current smokers Number296/37189/9659/7859/99 OR adjusted0.81 (0.57-1.14)Ref0.83 (0.52-1.31)0.58 (0.37-0.92)Figure 1.Dose-response odds ratio for risk of rheumatoid arthritis (RA) by tea consumption.Conclusion:In this large population-based case-control study, high tea consumption, as well as no consumption, was associated with a decreased risk to develop ACPA positive, but not negative, RA, when compared to irregular tea drinking (<1 cup/day). The inverse association between high tea consumption and RA was lowest in analyses restricted to current smokers.Disclosure of Interests:Helga Westerlind: None declared, Ida Palmqvist: None declared, Saedis Saevarsdottir Employee of: part-time employee of deCODE genetics, Lars Alfredsson: None declared, Lars Klareskog: None declared, Daniela Di Giuseppe: None declared
25.	Aleksandrova, Krasimira, et al. (författare) Adiposity, mediating biomarkers and risk of colon cancer in the European prospective investigation into cancer and nutrition study 2014 Ingår i: International Journal of Cancer. - : Wiley-Blackwell. - 0020-7136 .- 1097-0215. ; 134:3, s. 612-621 Tidskriftsartikel (refereegranskat)abstract Adiposity is a risk factor for colon cancer, but underlying mechanisms are not well understood. We evaluated the extent to which 11 biomarkers with inflammatory and metabolic actions mediate the association of adiposity measures, waist circumference (WC) and body mass index (BMI), with colon cancer in men and women. We analyzed data from a prospective nested case-control study among 662 incident colon cancer cases matched within risk sets to 662 controls. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. The percent effect change and corresponding CIs were estimated after adjusting for biomarkers shown to be associated with colon cancer risk. After multivariable adjustment, WC was associated with colon cancer risk in men (top vs. bottom tertile RR 1.68, 95% CI 1.06-2.65; ptrend = 0.02) and in women (RR 1.67, 95% CI 1.09-2.56; ptrend = 0.03). BMI was associated with risk only in men. The association of WC with colon cancer was accounted mostly for by three biomarkers, high-density lipoprotein cholesterol, non-high-molecular-weight adiponectin and soluble leptin receptor, which in combination explained 46% (95% CI 37-57%) of the association in men and 50% (95% CI 40-65%) of the association in women. Similar results were observed for the associations with BMI in men. These data suggest that alterations in levels of these metabolic biomarkers may represent a primary mechanism of action in the relation of adiposity with colon cancer. Further studies are warranted to determine whether altering their concentrations may reduce colon cancer risk.
26.	Aleksandrova, Krasimira, et al. (författare) Leptin and soluble leptin receptor in risk of colorectal cancer in the European prospective investigation into Cancer and nutrition cohort 2012 Ingår i: Cancer Research. - Philadelphia, USA : American Association for Cancer Research. - 0008-5472 .- 1538-7445. ; 72:20, s. 5328-5337 Tidskriftsartikel (refereegranskat)abstract Leptin, a peptide hormone produced primarily by the adipocytes, is hypothesized to play a role in the pathogenesis of colorectal cancer (CRC). Soluble leptin receptor (sOB-R) may regulate leptin's physiologic functions; however its relation to CRC risk is unknown. This study explored the association of leptin and sOB-R with risk of CRC in a prospective nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A total of 1,129 incident CRC cases (713 colon, 416 rectal) were matched within risk sets to 1,129 controls. Conditional logistic regression was used to calculate relative risks (RR) and 95% confidence intervals (CI). After multivariable adjustment including body mass index (BMI), waist circumference, and baseline leptin concentrations, sOB-R was strongly inversely associated with CRC (RR comparing the highest quintile vs. the lowest, 0.55; 95% CI, 0.40-0.76; P-trend = 0.0004) and colon cancer (RR, 0.42; 95% CI, 0.28-0.63, P-trend = 0.0001); whereas no association was seen for rectal cancer (RR adjusted for BMI and waist circumference, 0.83; 95% CI, 0.48-1.44, P-trend = 0.38). In contrast, leptin was not associated with risk of CRC (RR adjusted for BMI and waist circumference, 0.85; 95% CI, 0.56-1.29, P-trend = 0.23). Additional adjustments for circulating metabolic biomarkers did not attenuate these results. These novel findings suggest a strong inverse association between circulating sOB-R and CRC risk, independent of obesity measures, leptin concentrations, and other metabolic biomarkers. Further research is needed to confirm the potentially important role of sOB-R in CRC pathogenesis. Cancer Res; 72(20); 5328-37. (C) 2012 AACR.
27.	Aleksandrova, Krasimira, et al. (författare) Total and high-molecular-weight adiponectin and risk of colorectal cancer : the European prospective investigation into cancer and nutrition study 2012 Ingår i: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 33:6, s. 1211-1218 Tidskriftsartikel (refereegranskat)abstract Adiponectin - an adipose-tissue-derived protein may provide a molecular link between obesity and colorectal cancer (CRC), but evidence from large prospective studies is limited. In particular, no epidemiological study explored high-molecular-weight (HMW) and non-HMW adiponectin fractions in relation to CRC risk, despite they were hypothesised to have differential biological activities, i.e. regulating insulin sensitivity (HMW-adiponectin) versus inflammatory response (non-HMW-adiponectin). In a prospective nested case-control study we investigated whether pre-diagnostic serum concentrations of total, HMW and non-HMW-adiponectin are associated with risk of CRC, independent of obesity and other known CRC risk factors. A total of 1206 incident cases (755 colon, 451 rectal) were matched to 1206 controls using incidence density sampling. In conditional logistic regression, adjusted for dietary and lifestyle factors, total adiponectin and non-HMW-adiponectin concentrations were inversely associated with risk of CRC [relative risk (RR) comparing highest versus lowest quintile = 0.71, 95% confidence interval (CI) = 0.53-0.95, P (trend)=0.03 for total adiponectin and 0.45, 95%CI=0.34-0.61, P (trend)<0.0001 for non-HMW-adiponectin]. HMW-adiponectin concentrations were not associated with CRC risk (RR=0.91, 95%CI=0.68-1.22, P (trend)=0.55). Non-HMW-adiponectin was associated with CRC risk even after adjustment for body mass index and waist circumference (RR=0.39, 95%CI=0.26-0.60, P (trend)<0.0001); whereas the association with total adiponectin was no longer significant (RR=0.81, 95%CI=0.60-1.09, P (trend)=0.23). When stratified by cancer site, non-HMW-adiponectin was inversely associated with both colon and rectal cancer. These findings suggest an important role of the relative proportion of non-HMW-adiponectin in CRC pathogenesis. Future studies are warranted to confirm these results and to elucidate the underlying mechanisms.
28.	Araghi, Marzieh, et al. (författare) Smokeless tobacco (snus) use and colorectal cancer incidence and survival : Results from nine pooled cohorts 2017 Ingår i: Scandinavian Journal of Public Health. - : SAGE Publications. - 1403-4948 .- 1651-1905. ; 45:8, s. 741-748 Tidskriftsartikel (refereegranskat)abstract AIMS: Although smoking is considered to be an established risk factor for colorectal cancer, the current evidence on the association between smokeless tobacco and colorectal cancer is scant and inconclusive. We used pooled individual data from the Swedish Collaboration on Health Effects of Snus Use to assess this association.METHODS: A total of 417,872 male participants from nine cohort studies across Sweden were followed up for incidence of colorectal cancer and death. Outcomes were ascertained through linkage to health registers. We used shared frailty models with random effects at the study level to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).RESULTS: During 7,135,504 person-years of observation, 4170 men developed colorectal cancer. There was no clear association between snus use and colorectal cancer overall. Exclusive current snus users, however, had an increased risk of rectal cancer (HR 1.40: 95% CI 1.09, 1.79). There were no statistically significant associations between snus use and either all-cause or colorectal cancer-specific mortality after colorectal cancer diagnosis.CONCLUSIONS: Our findings, from a large sample, do not support any strong relationships between snus use and colorectal cancer risk and survival among men. However, the observed increased risk of rectal cancer is noteworthy, and in merit of further attention.
29.	Argiropoulos, B, et al. (författare) Meis1 disrupts the genomic imprint of Dlk1 in a NUP98-HOXD13 leukemia model. 2010 Ingår i: Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. - : Springer Science and Business Media LLC. - 1476-5551. ; 24:10, s. 1788-91 Tidskriftsartikel (refereegranskat)
30.	Ashton, Nicholas J., et al. (författare) A multicentre validation study of the diagnostic value of plasma neurofilament light 2021 Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12, s. 1-12 Tidskriftsartikel (refereegranskat)abstract Increased cerebrospinal fluid neurofilament light (NfL) is a recognized biomarker for neurodegeneration that can also be assessed in blood. Here, we investigate plasma NfL as a marker of neurodegeneration in 13 neurodegenerative disorders, Down syndrome, depression and cognitively unimpaired controls from two multicenter cohorts: King's College London (n = 805) and the Swedish BioFINDER study (n = 1,464). Plasma NfL was significantly increased in all cortical neurodegenerative disorders, amyotrophic lateral sclerosis and atypical parkinsonian disorders. We demonstrate that plasma NfL is clinically useful in identifying atypical parkinsonian disorders in patients with parkinsonism, dementia in individuals with Down syndrome, dementia among psychiatric disorders, and frontotemporal dementia in patients with cognitive impairment. Data-driven cut-offs highlighted the fundamental importance of age-related clinical cut-offs for disorders with a younger age of onset. Finally, plasma NfL performs best when applied to indicate no underlying neurodegeneration, with low false positives, in all age-related cut-offs.
31.	Caldwell, Jessica Z.K., et al. (författare) Cognitively normal women with Alzheimer's disease proteinopathy show relative preservation of memory but not of hippocampal volume 2019 Ingår i: Alzheimer's Research & Therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 11:1 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: We examined interactive effects of sex, diagnosis, and cerebrospinal fluid (CSF) amyloid beta/phosphorylated tau ratio (Aβ/P-tau) on verbal memory and hippocampal volumes. METHODS: We assessed 682 participants (350 women) from BioFINDER (250 cognitively normal [CN]; and 432 symptomatic: 186 subjective cognitive decline [SCD], 246 mild cognitive impairment [MCI]). General linear models evaluated effects of Alzheimer's disease (AD) proteinopathy (CSF Aß/p-tau ratio), diagnosis, and sex on verbal memory (ADAS-cog 10-word recall), semantic fluency (animal naming fluency), visuospatial skills (cube copy), processing speed/attention functions (Symbol Digit Modalities Test and Trail Making Part A), and hippocampal volumes. RESULTS: Amyloid-positive (Aβ/P-tau+) CN women (women with preclinical AD) showed memory equivalent to amyloid-negative (Aβ/P-tau-) CN women. In contrast, Aβ/P-tau+ CN men (men with preclinical AD) showed poorer memory than Aβ/P-tau- CN men. Symptomatic groups showed no sex differences in effect of AD proteinopathy on memory. There was no interactive effect of sex, diagnosis, and Aβ/P-tau on other measures of cognition or on hippocampal volume. CONCLUSIONS: CN women show relatively preserved verbal memory, but not general cognitive reserve or preserved hippocampal volume in the presence of Aβ/P-tau+. Results have implications for diagnosing AD in women, and for clinical trials.
32.	Cullen, Nicholas C., et al. (författare) Individualized prognosis of cognitive decline and dementia in mild cognitive impairment based on plasma biomarker combinations 2021 Ingår i: Nature Aging. - : Springer Science and Business Media LLC. - 2662-8465. ; 1, s. 114-123 Tidskriftsartikel (refereegranskat)abstract We developed models for individualized risk prediction of cognitive decline in mild cognitive impairment (MCI) using plasma biomarkers of β-amyloid (Aβ), tau and neurodegeneration. A total of 573 patients with MCI from the Swedish BioFINDER study and the Alzheimer’s Disease Neuroimaging Initiative (ADNI) were included in the study. The primary outcomes were longitudinal cognition and conversion to Alzheimer’s disease (AD) dementia. A model combining tau phosphorylated at threonine 181 (P-tau181) and neurofilament light (NfL), but not Aβ42/Aβ40, had the best prognosis performance of all models (area under the curve = 0.88 for 4-year conversion to AD in BioFINDER, validated in ADNI), was stronger than a basic model of age, sex, education and baseline cognition, and performed similarly to cerebrospinal fluid biomarkers. A publicly available online tool for individualized prognosis in MCI based on our combined plasma biomarker models is introduced. Combination of plasma biomarkers may be of high value to identify individuals with MCI who will progress to AD dementia in clinical trials and in clinical practice.
33.	Dahlin, Anna M, 1979-, et al. (författare) Colorectal cancer prognosis depends on T-cell infiltration and molecular characteristics of the tumor 2011 Ingår i: Modern Pathology. - : Elsevier BV. - 0893-3952 .- 1530-0285. ; 24, s. 671-682 Tidskriftsartikel (refereegranskat)abstract The aim of this study was to relate the density of tumor infiltrating T cells to cancer-specific survival in colorectal cancer, taking into consideration the CpG island methylator phenotype (CIMP) and microsatellite instability (MSI) screening status. The T-cell marker CD3 was stained by immunohistochemistry in 484 archival tumor tissue samples. T-cell density was semiquantitatively estimated and scored 1-4 in the tumor front and center (T cells in stroma), and intraepithelially (T cells infiltrating tumor cell nests). Total CD3 score was calculated as the sum of the three CD3 scores (range 3-12). MSI screening status was assessed by immunohistochemistry. CIMP status was determined by quantitative real-time PCR (MethyLight) using an eight-gene panel. We found that patients whose tumors were highly infiltrated by T cells (total CD3 score ≥7) had longer survival compared with patients with poorly infiltrated tumors (total CD3 score ≤4). This finding was statistically significant in multivariate analyses (multivariate hazard ratio, 0.57; 95% confidence interval, 0.31-1.00). Importantly, the finding was consistent in rectal cancer patients treated with preoperative radiotherapy. Although microsatellite unstable tumor patients are generally considered to have better prognosis, we found no difference in survival between microsatellite unstable and microsatellite stable (MSS) colorectal cancer patients with similar total CD3 scores. Patients with MSS tumors highly infiltrated by T cells had better prognosis compared with intermediately or poorly infiltrated microsatellite unstable tumors (log rank P=0.013). Regarding CIMP status, CIMP-low was associated with particularly poor prognosis in patients with poorly infiltrated tumors (multivariate hazard ratio for CIMP-low versus CIMP-negative, 3.07; 95% confidence interval, 1.53-6.15). However, some subset analyses suffered from low power and are in need of confirmation by independent studies. In conclusion, patients whose tumors are highly infiltrated by T cells have a beneficial prognosis, regardless of MSI, whereas the role of CIMP status in this context is less clear.
34.	Dahlin, Anna M, 1979-, et al. (författare) The role of the CpG island methylator phenotype in colorectal cancer prognosis depends on microsatellite instability screening status 2010 Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 16:6, s. 1845-1855 Tidskriftsartikel (refereegranskat)abstract PURPOSE: The aim of this study was to relate the CpG island methylator phenotype (CIMP; characterized by extensive promoter hypermethylation) to cancer-specific survival in colorectal cancer, taking into consideration relevant clinicopathologic factors, such as microsatellite instability (MSI) screening status and the BRAF V600E mutation. EXPERIMENTAL DESIGN: Archival tumor samples from 190 patients from the Northern Sweden Health and Disease Study (NSHDS) and 414 patients from the Colorectal Cancer in Umeå Study (CRUMS), including 574 with cancer-specific survival data, were analyzed for an eight-gene CIMP panel using quantitative real-time PCR (MethyLight). MSI screening status was assessed by immunohistochemistry. RESULTS: CIMP-low patients had a shorter cancer-specific survival compared with CIMP-negative patients (multivariate hazard ratio in NSHDS, 2.01; 95% confidence interval, 1.20-3.37; multivariate hazard ratio in CRUMS, 1.48; 95% confidence interval, 1.00-2.22). This result was similar in subgroups based on MSI screening status and was statistically significant in microsatellite stable (MSS) tumors in NSHDS. For CIMP-high patients, a shorter cancer-specific survival compared with CIMP-negative patients was observed in the MSS subgroup. Statistical significance was lost after adjusting for the BRAF mutation, but the main findings were generally unaffected. CONCLUSIONS: In this study, we found a poor prognosis in CIMP-low patients regardless of MSI screening status, and in CIMP-high patients with MSS. Although not consistently statistically significant, these results were consistent in two separate patient groups and emphasize the potential importance of CIMP and MSI status in colorectal cancer research.
35.	Dahlman, L, et al. (författare) Carbon and nitrogen distribution in the green algal lichens Hypogymnia physodes and and Platismatia glauca in relation to nutrient supply. 2003 Ingår i: Planta. - 0032-0935. ; 217:1, s. 41-48 Tidskriftsartikel (refereegranskat)
36.	Dahlman, L, et al. (författare) Growth, nitrogen uptake, and resource allocation in the two tripartite lichens Nephroma arcticum and Peltigera aphthosa during nitrogen stress 2002 Ingår i: New Phytologist. - 0028-646X. ; 153:2, s. 307-315 Tidskriftsartikel (refereegranskat)abstract The lichens were irrigated with different N forms, enriched in 15N to assess N uptake, during 3 months in the field, with a total N dosage of 500 mg m−2. Nitrogen deprivation was induced by removing the nitrogen-fixing cephalodia. The lichens took up 11–134 mg N m−2 of the added N, corresponding to 1–4% of their total thallus N. Uptake was 4 times higher for NH4+ than for NO3−, and the highest 15N concentrations were found in newly synthesized tissue. Both forms of N stress affected thallus expansion rates in both species. It is concluded that the two lichens were able to maintain a balanced tissue N concentration despite large variations in N supply, and that assimilated N might be transported to growing apices. Alternatively, N assimilation from external sources might be greater in the margins than in the mature thallus. Thallus expansion was sensitive to N stress, apparently being tightly coupled to N assimilation.
37.	Edin, Sofia, et al. (författare) Macrophages : Good guys in colorectal cancer 2013 Ingår i: Oncoimmunology. - : Informa UK Limited. - 2162-4011 .- 2162-402X. ; 2:2, s. e23038- Tidskriftsartikel (refereegranskat)abstract Macrophages play a complex role in tumor progression since they can exert both tumor-preventing (M1 macrophages) and tumor-promoting (M2 macrophages) activities. In colorectal carcinoma (CRC), at odds to many other cancers, macrophage infiltration has been correlated with an improved patient survival. In a recent study, we have evaluated the distribution of M1 and M2 macrophage subtypes in CRC and their impact on patient prognosis.
38.	Edin, Sofia, et al. (författare) Phenotypic skewing of macrophages in vitro by secreted factors from colorectal cancer cells 2013 Ingår i: PLOS ONE. - : PLoS, Public Library of Science. - 1932-6203. ; 8:9, s. e74982- Tidskriftsartikel (refereegranskat)abstract Macrophages are cells with many important functions in both innate and adaptive immune responses and have been shown to play a complex role in tumor progression since they harbour both tumor preventing (M1 macrophages) and tumor promoting (M2 macrophages) activities. In many human cancers, infiltrating macrophages have been associated with a poor patient prognosis, and therefore suggested to be mainly of an M2 phenotype. However, we and others have previously shown that increased macrophage density in colorectal cancer (CRC) instead is correlated with an improved prognosis. It is an intriguing question if the different roles played by macrophages in various cancers could be explained by variations in the balance between M1 and M2 macrophage attributes, driven by tumor- or organ-specific factors in the tumor microenvironment of individual cancers. Here, we utilized an in vitro cell culture system of macrophage differentiation to compare differences and similarities in the phenotype (morphology, antigen-presentation, migration, endocytosis, and expression of cytokine and chemokine genes) between M1/M2 and tumor activated macrophages (TAMs), that could explain the positive role of macrophages in CRC. We found that secreted factors from CRC cells induced TAMs of a "mixed" M1/M2 phenotype, which in turn could contribute to a "good inflammatory response". This suggests that re-education of macrophages might allow for important therapeutic advances in the treatment of human cancer.
39.	Edin, Sofia, et al. (författare) The Distribution of Macrophages with a M1 or M2 Phenotype in Relation to Prognosis and the Molecular Characteristics of Colorectal Cancer 2012 Ingår i: PLOS ONE. - : PLoS One. - 1932-6203. ; 7:10, s. e47045- Tidskriftsartikel (refereegranskat)abstract High macrophage infiltration has been correlated to improved survival in colorectal cancer (CRC). Tumor associated macrophages (TAMs) play complex roles in tumorigenesis since they are believed to hold both tumor preventing (M1 macrophages) and tumor promoting (M2 macrophages) activities. Here we have applied an immunohistochemical approach to determine the degree of infiltrating macrophages with a M1 or M2 phenotype in clinical specimens of CRC in relation to prognosis, both in CRC in general but also in subgroups of CRC defined by microsatellite instability (MSI) screening status and the CpG island methylator phenotype (CIMP). A total of 485 consecutive CRC specimens were stained for nitric oxide synthase 2 (NOS2) (also denoted iNOS) as a marker for the M1 macrophage phenotype and the scavenger receptor CD163 as a marker for the M2 macrophage phenotype. The average infiltration of NOS2 and CD163 expressing macrophages along the invasive tumor front was semi-quantitatively evaluated using a four-graded scale. Two subtypes of macrophages, displaying M1 (NOS2(+)) or M2 (CD163(+)) phenotypes, were recognized. We observed a significant correlation between the amount of NOS2(+) and CD163(+) cells (P<0.0001). A strong inverse correlation to tumor stage was found for both NOS2 (P<0.0001) and CD163 (P<0.0001) infiltration. Furthermore, patients harbouring tumors highly infiltrated by NOS2+ cells had a significantly better prognosis than those infiltrated by few NOS2+ cells, and this was found to be independent of MSI screening status and CIMP status. No significant difference was found on cancer-specific survival in groups of CRC with different NOS2/CD163 ratios. In conclusion, an increased infiltration of macrophages with a M1 phenotype at the tumor front is accompanied by a concomitant increase in macrophages with a M2 phenotype, and in a stage dependent manner correlated to a better prognosis in patients with CRC.
40.	Ekblom, Kim, et al. (författare) Iron Biomarkers in Plasma, HFE Genotypes, and the Risk for Colorectal Cancer in a Prospective Setting 2012 Ingår i: Diseases of the Colon & Rectum. - 0012-3706 .- 1530-0358. ; 55:3, s. 337-344 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: High iron levels can increase the formation of noxious oxygen radicals, which are thought to promote carcinogenesis. OBJECTIVE: The aim of this prospective study was to determine whether iron biomarkers and HFE genotypes, which influence iron regulation, constitute risk factors for colorectal cancer. DESIGN: This is a prospective nested case-referent study. SETTINGS: The study was performed within the population-based Northern Sweden Health and Disease Study. PATIENTS: The study included 226 cases of colorectal cancer and 437 matched referents. MAIN OUTCOME MEASURES: Conditional regression analysis was performed. Adjustments for smoking, smoking and BMI, and HFE C282Y and H63D were performed. RESULTS: The highest quintile of total iron-binding capacity showed significantly higher risk for colorectal cancer, unadjusted OR 2.35 (95% CI 1.38-4.02). When stratified by sex, the findings were only present in women (OR 3.34 (95% CI 1.59-7.02)). Ferritin was associated with reduced risk throughout quintiles 2 to 5 both in univariate and multivariate models. LIMITATIONS: Colorectal cancer may influence iron markers because of occult bleeding. Homozygotes for HFE C282Y were too few to make conclusions for this group. The relatively short follow-up time might be insufficient to detect risk of iron biomarkers. CONCLUSIONS: High iron levels do not increase the risk of colorectal cancer. HFE genotypes influencing iron uptake had no effect on colorectal cancer risk.
41.	Eklöf, Vincy, 1984-, et al. (författare) Cancer-associated fecal microbial markers in colorectal cancer detection 2017 Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 141:12, s. 2528-2536 Tidskriftsartikel (refereegranskat)abstract Colorectal cancer (CRC) is the second most common cause of cancer death in the western world. An effective screening program leading to early detection of disease would severely reduce the mortality of CRC. Alterations in the gut microbiota have been linked to CRC, but the potential of microbial markers for use in CRC screening has been largely unstudied. We used a nested case-control study of 238 study subjects to explore the use of microbial markers for clbA+ bacteria harboring the pks pathogenicity island, afa-C+ diffusely adherent Escherichia coli harboring the afa-1 operon, and Fusobacterium nucleatum in stool as potential screening markers for CRC. We found that individual markers for clbA+ bacteria and F. nucleatum were more abundant in stool of patients with CRC, and could predict cancer with a relatively high specificity (81.5% and 76.9%, respectively) and with a sensitivity of 56.4% and 69.2%, respectively. In a combined test of clbA+ bacteria and F. nucleatum, CRC was detected with a specificity of 63.1% and a sensitivity of 84.6%. Our findings support a potential value of microbial factors in stool as putative noninvasive biomarkers for CRC detection. We propose that microbial markers may represent an important future screening strategy for CRC, selecting patients with a "high-risk" microbial pattern to other further diagnostic procedures such as colonoscopy.
42.	Eklöf, Vincy, 1984-, et al. (författare) The combined diagnostic value of faecal haemoglobin and calprotectin in colorectal cancer Annan publikation (övrigt vetenskapligt/konstnärligt)
43.	Eklöf, Vincy, 1984-, et al. (författare) The Combined Value of Faecal Haemoglobin andCalprotectin in Diagnosis of Colorectal Cancer inSymptomatic Patients Referred to Colonoscopy 2019 Ingår i: Academic Journal of Gastroenterology & Hepatology (AJGH). - San Fransisco : Iris Publishers. ; 1:3, s. 1-7 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract Aim: To investigate the diagnostic value of a combined analyses of faecal immunological haemoglobin (FIT) and faecal calprotectin (FC) in detection of colorectal cancer (CRC).Methods: Out-patients (n=1440) referred to the endoscopy unit were analysed for FIT and FC in stool samples collected before the colonoscopy bowel preparation. The samples were collected from one defecation by the patients at home. Patients with IBD were excluded leaving stool samples from 1133 patients for further analyses. FIT was analysed using the immunological Analyse F.O.B Test and FC was analysed using the CALPRO® Calprotectin Elisa Test. Sensitivity and specificity to detect CRC was calculated for the individual tests, as well as for combined FIT/FC tests.Results: Out of the included patients, 38 were diagnosed with CRC, 9 with high grade dysplasia (HGD), and 133 with low grade dysplasia (LGD). FIT was analysed in 673 (59.4%), FC in 1021 (90.1%) and both FIT and FC in 561 (49.5%) patients. A ROC curve analysis showed that the most accurate cut-off level for FC in detecting CRC in our study was 105.5 µg/g. The sensitivity for CRC when using FIT, FC (cut-off > 100 µg/g) and the combination of FIT and FC (at least one positive test) was 65.5%, 74.1% and 94.4%, respectively. The corresponding specificity was 84.8%, 74.9% and 68.3%, respectively.Conclusion: Combined analyses of FIT and FC improved sensitivity for detection of CRC. Further studies in larger cohorts are required to find the optimal cut-off levels for different combinations of tests.
44.	Eklöf, Vincy, 1984-, et al. (författare) The prognostic role of KRAS, BRAF, PIK3CA and PTEN in colorectal cancer 2013 Ingår i: British Journal of Cancer. - : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 108:10, s. 2153-2163 Tidskriftsartikel (refereegranskat)abstract Background Mutations in KRAS, BRAF, PIK3CA and PTEN expression have been in focus to predict the effect of epidermal growth factor receptor-blocking therapy in colorectal cancer (CRC). Here, information on these four aberrations was collected and combined to a Quadruple index and used to evaluate the prognostic role of these factors in CRC. Patients We analysed the mutation status in KRAS, BRAF and PIK3CA and PTEN expression in two separate CRC cohorts, Northern Sweden Health Disease Study (NSHDS; n = 197) and Colorectal Cancer in Umea Study (CRUMS; n = 414). A Quadruple index was created, where Quadruple index positivity specifies cases with any aberration in KRAS, BRAF, PIK3CA or PTEN expression. Results Quadruple index positive tumours had a worse prognosis, significant in the NSHDS but not in the CRUMS cohort (NSHDS; P = 0.003 and CRUMS; P = 0.230) in univariate analyses but significance was lost in multivariate analyses. When analysing each gene separately, only BRAF was of prognostic significance in the NSHDS cohort (multivariate HR 2.00, 95% CI: 1.16-3.43) and KRAS was of prognostic significance in the CRUMS cohort (multivariate HR 1.48, 95% CI: 1.02-2.16). Aberrations in PIK3CA and PTEN did not add significant prognostic information. Conclusions Our results suggest that establishment of molecular subgroups based on KRAS and BRAF mutation status is important and should be considered in future prognostic studies in CRC.
45.	Espersen, A. D. L., et al. (författare) Acute myeloid leukemia (AML) with t(7;12)(q36;p13) is associated with infancy and trisomy 19: Data from Nordic Society for Pediatric Hematology and Oncology (NOPHO-AML) and review of the literature 2018 Ingår i: Genes Chromosomes & Cancer. - : Wiley. - 1045-2257 .- 1098-2264. ; 57:7, s. 359-365 Tidskriftsartikel (refereegranskat)abstract The t(7;12)(q36;p13) (MNX1/ETV6) is not included in the WHO classification but has been described in up to 30% of acute myeloid leukemia (AML) in children <2 years and associated with a poor prognosis. We present the clinical and cytogenetics characteristics of AML cases with t(7;12)(p36;p13). A literature review identified 35 patients with this translocation, published between 2000 and 2015. Outcome data were available in 22 cases. The NOPHO-AML (Nordic Society for Pediatric Hematology and Oncology) database contained 651 patients with AML from 1993 to 2014 and seven (1.1%) had the translocation. The t(7;12) was only present in patients <2 years of age (median age 6 months) but none was diagnosed as newborn. These patients constituted 4.3% of the patients <2 years of age. There was a strong association with trisomy 19 (literature: 86%, NOPHO: 100%) and +8 (literature: 19%, NOPHO: 14%). Seventeen of 22 patients from the literature with t(7;12) and four of seven patients from the NOPHO database suffered from relapse. The patients with t(7;12) had a 3-year event free survival of 24% (literature) vs. 43% (NOPHO) and a 3-year overall survival of 42% (literature) vs. 100% (NOPHO). None of the NOPHO patients was treated with hematopoietic stem cell transplantation (HSCT) in first complete remission. Relapse was frequent but the salvage rate using HSCT was high. We conclude that t(7;12)(q36;13) is a unique subgroup of childhood AML with presentation before 2 years of age with most cases being associated with +19.
46.	Faria, Vanda, et al. (författare) Pretreatment Anterior Cingulate Activity Predicts Amygdala Attenuation in Social Phobic Placebo Responders 2010 Ingår i: Biol. Psychiatry 67, 34S-34S. ; , s. 34S-34S 109 Konferensbidrag (refereegranskat)
47.	Ferrari, P, et al. (författare) Alcohol dehydrogenase and aldehyde dehydrogenase gene polymorphisms, alcohol intake and the risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition study 2012 Ingår i: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 0954-3007 .- 1476-5640. ; 66:12, s. 1303-1308 Tidskriftsartikel (refereegranskat)abstract BACKGROUND/OBJECTIVES: Heavy alcohol drinking is a risk factor of colorectal cancer (CRC), but little is known on the effect of polymorphisms in the alcohol-metabolizing enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) on the alcohol-related risk of CRC in Caucasian populations.SUBJECTS/METHODS: A nested case-control study (1269 cases matched to 2107controls by sex, age, study centre and date of blood collection) was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC) to evaluate the impact of rs1229984 (ADH1B), rs1573496 (ADH7) and rs441 (ALDH2) polymorphisms on CRC risk. Using the wild-type variant of each polymorphism as reference category, CRC risk estimates were calculated using conditional logistic regression, with adjustment for matching factors.RESULTS: Individuals carrying one copy of the rs1229984(A) (ADH1B) allele (fast metabolizers) showed an average daily alcohol intake of 4.3 g per day lower than subjects with two copies of the rs1229984(G) allele (slow metabolizers) (P-diff<0.01). None of the polymorphisms was associated with risk of CRC or cancers of the colon or rectum. Heavy alcohol intake was more strongly associated with CRC risk among carriers of the rs1573496(C) allele, with odds ratio equal to 2.13 (95% confidence interval: 1.26-3.59) compared with wild-type subjects with low alcohol consumption P-((interaction)=0.07).CONCLUSIONS: The rs1229984(A) (ADH1B) allele was associated with a reduction in alcohol consumption. The rs1229984 (ADH1B), rs1573496 (ADH7) and rs441 (ALDH2) polymorphisms were not associated with CRC risk overall in Western-European populations. However, the relationship between alcohol and CRC risk might be modulated by the rs1573496 (ADH7) polymorphism. European Journal of Clinical Nutrition (2012) 66, 1303-1308; doi: 10.1038/ejcn.2012.173; published online 14 November 2012
48.	Forssell, Johan, et al. (författare) High macrophage infiltration along the tumor front correlates with improved survival in colon cancer. 2007 Ingår i: Clin Cancer Res. - 1078-0432. ; 13:5, s. 1472-1479 Tidskriftsartikel (refereegranskat)
49.	Gaio-Oliveira, G, et al. (författare) Ammonium uptake in the nitrophytic lichen Xanthoria parietina (L.) Th. Fr. and its effects on vitality and balance between symbionts 2004 Ingår i: Lichenologist. ; 36, s. 75-86 Tidskriftsartikel (refereegranskat)
50.	Gaio-Oliveira, G, et al. (författare) Growth in relation to microclimatic conditions and physiological characteristics of four Lobaria pulmonaria populations in two contrasting habitats 2004 Ingår i: Ecography. ; 27, s. 75-86 Tidskriftsartikel (refereegranskat)

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