umu.sePublications
Change search
Refine search result
1 - 26 of 26
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 1.
    Brink, Mikael
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Hansson, Monika
    Mathsson, Linda
    Jakobsson, Per-Johan
    Holmdahl, Rikard
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Rönnelid, Johan
    Klareskog, Lars
    Rantapää-Dahlqvist, Solbritt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Rheumatology.
    Multiplex analyses of antibodies against citrullinated peptides in individuals prior to development of rheumatoid arthritis2013In: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 65, no 4, p. 899-910Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: The presence of antibodies against cyclic citrullinated peptides has been demonstrated to precede the symptom onset of rheumatoid arthritis (RA) by several years. Antibodies against 10 citrullinated autoantigen-derived peptides were analysed for reactivity before onset of symptoms. METHODS: In the Medical Biobank of Northern Sweden 409 individuals were identified, of whom 386 provided 717 samples, obtained before onset of symptoms of RA (median time 7.4 (IQR 9.3) years); 1305 population based controls were also identified. Antibodies to 10 citrullinated peptides; fibrinogen (Fib) Fibα573, Fibα591, Fibß36-52, Fibß72, Fibß74, α-enolase (CEP-1), Type II Collagen citC1(III) , filaggrin, vimentin (Vim)2-17, and Vim60-75 were analysed using a microarray system. RESULTS: The antibody fluorescence intensity of Fibß36-52, Fibß74, CEP-1, citC1(III) , and filaggrin was significantly increased in pre-disease individuals compared with controls (p<0.001). The levels of the earliest detectable antibodies (Fibα591 and Vim60-75) fluctuated over time, with only a slight increase after onset of disease. Antibodies against Fibß36-52, CEP-1 and filaggrin increased gradually reaching the highest levels of all antibodies before symptom onset. A cluster of antibodies, citC1(III) , Fibα573 and Fibß74 increased only slightly before onset of symptoms but prominently after disease onset. The odds ratio for development of RA with a combination of CEP-1 and Fibß36-52 antibodies (<3.35 years pre-dating) was 38.8 (CI95%14.5-103.5) compared with having either. CONCLUSION: Development of an immune response towards citrullinated peptides is initially restricted but expands with time to induce a more specific response with increasing levels towards onset of symptoms, particularly invoving antibodies against CEP-1, Fibß36-52 and filaggrin.

  • 2. Caminade, Cyril
    et al.
    Kovats, Sari
    Rocklöv, Joacim
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Tompkins, Adrian M
    Morse, Andrew P
    Colón-González, Felipe J
    Stenlund, Hans
    Martens, Pim
    Lloyd, Simon J
    Impact of climate change on global malaria distribution2014In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 111, no 9, p. 3286-3291Article in journal (Refereed)
    Abstract [en]

    Malaria is an important disease that has a global distribution and significant health burden. The spatial limits of its distribution and seasonal activity are sensitive to climate factors, as well as the local capacity to control the disease. Malaria is also one of the few health outcomes that has been modeled by more than one research group and can therefore facilitate the first model intercomparison for health impacts under a future with climate change. We used bias-corrected temperature and rainfall simulations from the Coupled Model Intercomparison Project Phase 5 climate models to compare the metrics of five statistical and dynamical malaria impact models for three future time periods (2030s, 2050s, and 2080s). We evaluated three malaria outcome metrics at global and regional levels: climate suitability, additional population at risk and additional person-months at risk across the model outputs. The malaria projections were based on five different global climate models, each run under four emission scenarios (Representative Concentration Pathways, RCPs) and a single population projection. We also investigated the modeling uncertainty associated with future projections of populations at risk for malaria owing to climate change. Our findings show an overall global net increase in climate suitability and a net increase in the population at risk, but with large uncertainties. The model outputs indicate a net increase in the annual person-months at risk when comparing from RCP2.6 to RCP8.5 from the 2050s to the 2080s. The malaria outcome metrics were highly sensitive to the choice of malaria impact model, especially over the epidemic fringes of the malaria distribution.

  • 3. Diab, Joseph
    et al.
    Hansen, Terkel
    Goll, Rasmus
    Stenlund, Hans
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Jensen, Einar
    Moritz, Thomas
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). The Novo Nordisk Foundation Center for Basic Metabolic Research, Copenhagen, Denmark.
    Florholmen, Jon
    Forsdahl, Guro
    Mucosal Metabolomic Profiling and Pathway Analysis Reveal the Metabolic Signature of Ulcerative Colitis2019In: Metabolites, ISSN 2218-1989, E-ISSN 2218-1989, Vol. 9, no 12, article id 291Article in journal (Refereed)
    Abstract [en]

    The onset of ulcerative colitis (UC) is characterized by a dysregulated mucosal immune response triggered by several genetic and environmental factors in the context of host–microbe interaction. This complexity makes UC ideal for metabolomic studies to unravel the disease pathobiology and to improve the patient stratification strategies. This study aims to explore the mucosal metabolomic profile in UC patients, and to define the UC metabolic signature. Treatment- naïve UC patients (n = 18), UC patients in deep remission (n = 10), and healthy volunteers (n = 14) were recruited. Mucosa biopsies were collected during colonoscopies. Metabolomic analysis was performed by combined gas chromatography coupled to time-of-flight mass spectrometry (GC-TOF-MS) and ultra-high performance liquid chromatography coupled with mass spectrometry (UHPLC-MS). In total, 177 metabolites from 50 metabolic pathways were identified. The most prominent metabolome changes among the study groups were in lysophosphatidylcholine, acyl carnitine, and amino acid profiles. Several pathways were found perturbed according to the integrated pathway analysis. These pathways ranged from amino acid metabolism (such as tryptophan metabolism) to fatty acid metabolism, namely linoleic and butyrate. These metabolic changes during UC reflect the homeostatic disturbance in the gut, and highlight the importance of system biology approaches to identify key drivers of pathogenesis which prerequisite personalized medicine.

  • 4.
    Gorzsás, András
    et al.
    Swedish University of Agricultural Sciences (SLU), Sweden.
    Stenlund, Hans
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Persson, Per
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Trygg, Johan
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Sundberg, Björn
    Umeå Plant Science Centre, Department of Forest Genetics and Plant Physiology, Swedish University of Agricultural Sciences (SLU), Sweden.
    Cell specific chemotyping and multivariate imaging by combined FT-IR microspectroscopy and OPLS analysis reveals the chemical landscape of secondary xylem2011In: The Plant Journal, ISSN 0960-7412, E-ISSN 1365-313X, Vol. 66, no 5, p. 903-914Article in journal (Refereed)
    Abstract [en]

    Fourier-transform infrared (FT-IR) spectroscopy combined with microscopy enables acquiring chemical information from native plant cell walls with high spatial resolution. Combined with a 64 x 64 focal plane array (FPA) detector 4096 spectra from a 0.3 x 0.3 mm image can be simultaneously obtained, where each spectrum represents a compositional and structural "fingerprint" of all cell wall components. For optimal use and analysis of such large amount of information, multivariate approaches are preferred. Here, FT-IR microspectroscopy with FPA detection is combined with orthogonal projections to latent structures discriminant analysis (OPLS-DA). This allows for 1) the extraction of spectra from specific cell types, 2) identification and characterization of different chemotypes using the full spectral information, and 3) further visualising the pattern of identified chemotypes by multivariate imaging. As proof of concept, the chemotypes of Populus tremula xylem cell types are described. The approach revealed unknown features about chemical plasticity and patterns of lignin composition in wood fibers that would have remained hidden in the dataset with traditional data analysis. The applicability of the method on Arabidopsis xylem, and its usefulness in mutant chemotyping is also demonstrated. The methodological approach is not limited to xylem tissues but can be applied to any plant organ/tissue also using other microspectroscopy techniques such as Raman- and UV-microspectroscopy.

  • 5.
    Jiye, A
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Granström, Micael
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Marklund, Stefan
    Johansson, Annika
    Stenlund, Hans
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Moritz, Thomas
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Antti, Henrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Jonsson, Pär
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Trygg, Johan
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Jiye, A
    Guangji, Wang
    Dynamic modification of blood erythrocytes metabolism based on GC/TOF-MS analysis2006Other (Other (popular science, discussion, etc.))
  • 6.
    Jonsson, Pär
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Stenlund, Hans
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Moritz, Thomas
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Trygg, Johan
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Sjöström, Michael
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Verheij, Elwin R
    Lindberg, Johan
    Schuppe-Koistinen, Ina
    Antti, Henrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    A strategy for modelling dynamic responses in metabolic samples characterized by GC/MS2006In: Metabolomics, Vol. 2, no 3, p. 135-143Article in journal (Refereed)
    Abstract [sv]

    A multivariate strategy for studying the metabolic response over time in urinary GC/MS data is presented and exemplified by a study of drug-induced liver toxicity in the rat. The strategy includes the generation of representative data through hierarchical multivariate curve resolution (H-MCR), highlighting the importance of obtaining resolved metabolite profiles for quantification and identification of exogenous (drug related) and endogenous compounds (potential biomarkers) and for allowing reliable comparisons of multiple samples through multivariate projections. Batch modelling was used to monitor and characterize the normal (control) metabolic variation over time as well as to map the dynamic response of the drug treated animals in relation to the control. In this way treatment related metabolic responses over time could be detected and classified as being drug related or being potential biomarkers. In summary the proposed strategy uses the relatively high sensitivity and reproducibility of GC/MS in combination with efficient multivariate curve resolution and data analysis to discover individual markers of drug metabolism and drug toxicity. The presented results imply that the strategy can be of great value in drug toxicity studies for classifying metabolic markers in relation to their dynamic responses as well as for biomarker identification.

  • 7. Kuhl, Jeanette
    et al.
    Moritz, Thomas
    Wagner, Henrik
    Stenlund, Hans
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Lundgren, Krister
    Båvenholm, Peter
    Efendic, Suad
    Norstedt, Gunnar
    Tollet-Egnell, Petra
    Metabolomics as a tool to evaluate exercise-induced improvements in insulin sensitivity2008In: Metabolomics, Vol. 4, no 3, p. 273-82Article in journal (Refereed)
    Abstract [en]

    Exercise affects substrate utilisation and insulin sensitivity, which in turn improve blood glucose and lipid levels in subjects with type 2 diabetes (T2D). However, making long-lasting lifestyle-changes might be more realistic if the results were easier to record. Screening for biomarkers reflecting metabolic fitness could thus serve as a tool for maintained motivation. The aim of this study was to test the possibility that metabolomics can be used to identify individuals with improved insulin sensitivity as a result of increased physical activity. Healthy and diabetic subjects were investigated before and after 3 months of exercise to determine various metabolic parameters. Insulin sensitivity was determined by hyperinsulinemic euglycemic clamps and found to be improved in the diabetic men. Plasma was collected during the clamp and analyzed through GC/TOFMS. Healthy subjects could be distinguished from diabetics by means of low molecular-weight compounds (LMC) in plasma independently of gender or exercise, and exercise induced differences in LMC patterns both for healthy and T2D subjects. Forty-four significant metabolites were found to explain differences between LMC patterns obtained from trained and non-trained diabetics. Among these compounds, 17 could be annotated and 5 classified. Inositol-1-phosphate showed the highest correlation to insulin sensitivity in diabetic men, whereas an as yet unknown fatty acid correlated best with insulin sensitivity in women. Both metabolites were better correlated to insulin sensitivity than glucose. Finally, the finding that inostitol-1-phosphate negatively correlates with insulin sensitivity in diabetic men, was validated using samples obtained from a similar training study on diabetic men. 

  • 8. Lindén, Pernilla
    et al.
    Keech, Olivier
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Stenlund, Hans
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Gardeström, Per
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Moritz, Thomas
    Reduced mitochondrial malate dehydrogenase activity has a strong effect on photorespiratory metabolism as revealed by 13C labelling2016In: Journal of Experimental Botany, ISSN 0022-0957, E-ISSN 1460-2431, Vol. 67, no 10, p. 3123-3135Article in journal (Refereed)
    Abstract [en]

    Mitochondrial malate dehydrogenase (mMDH) catalyses the interconversion of malate and oxaloacetate (OAA) in the tricarboxylic acid (TCA) cycle. Its activity is important for redox control of the mitochondrial matrix, through which it may participate in regulation of TCA cycle turnover. In Arabidopsis, there are two isoforms of mMDH. Here, we investigated to which extent the lack of the major isoform, mMDH1 accounting for about 60% of the activity, affected leaf metabolism. In air, rosettes of mmdh1 plants were only slightly smaller than wild type plants although the fresh weight was decreased by about 50%. In low CO2 the difference was much bigger, with mutant plants accumulating only 14% of fresh weight as compared to wild type. To investigate the metabolic background to the differences in growth, we developed a 13CO2 labelling method, using a custom-built chamber that enabled simultaneous treatment of sets of plants under controlled conditions. The metabolic profiles were analysed by gas- and liquid- chromatography coupled to mass spectrometry to investigate the metabolic adjustments between wild type and mmdh1. The genotypes responded similarly to high CO2 treatment both with respect to metabolite pools and 13C incorporation during a 2-h treatment. However, under low CO2 several metabolites differed between the two genotypes and, interestingly most of these were closely associated with photorespiration. We found that while the glycine/serine ratio increased, a concomitant altered glutamine/glutamate/α-ketoglutarate relation occurred. Taken together, our results indicate that adequate mMDH activity is essential to shuttle reductants out from the mitochondria to support the photorespiratory flux, and strengthen the idea that photorespiration is tightly intertwined with peripheral metabolic reactions.

  • 9.
    Liu-Helmersson, Jing
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Quam, Mikkel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Stenlund, Hans
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Wilder-Smith, Annelies
    Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.
    Ebi, K
    Massad, E
    Rocklöv, Joacim
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Seasonality of dengue epidemic potential in Europe - based on vectorial capacity for Aedes mosquitoes2015In: Tropical medicine & international health, ISSN 1360-2276, E-ISSN 1365-3156, Vol. 20, no Suppl. 1, p. 113-113Article in journal (Other academic)
    Abstract [en]

    Introduction: Dengue is a mosquito-borne viral infection that has become a major public health concern. About 390 million people are infected yearly. Increased global connectivity and population movement as well as climate change affect the global distribution of both dengue vectors and the virus, facilitating the spread of dengue to new geographic areas. Weather is an important factor determining mosquito behaviour and effectiveness of dengue virus transmission. Dengue epidemic potential depends on vectorial capacity of Aedes mosquitoes, which depend on climate, such as, temperature and diurnal temperature range. This study aims at identifying high-risk areas and high-risk time windows in Europe based on temperature, in order for timely vector surveillance and control.

    Methods: Relative vectorial capacity (rVc) was used to estimate dengue epidemic potential. Using historical and projected temperature data over two centuries (1901–2099) and temperature dependent vector parameters for Aedes vectors, rVc was calculated for 10 selected European cities from Stockholm in the North to Malaga in the South.

    Results: Compared to dengue endemic areas, rVc in Europe was lower and showed more prominent seasonality. The peak and width of the seasonal windows in rVc were generally higher in the South than the North. Currently, only South and Central-East Europe and the summer season corresponds to rVc that is over the threshold for possible dengue transmission. By the end of this century, in the best case scenario, all the Central and Southern European cities would be at risk for dengue transmission during the warmer months; in the worst case scenario, this risk would extend to Northern European to include Stockholm if dengue vectors were established and virus introduced.

    Conclusion: As travel and globalization become more frequent channels for dengue vector and virus introduction, Europe may face the reality of more frequent dengue outbreaks in their warmer months. Madeira's outbreak in 2012 underlines this concern. The future's high risk area and time window depend sensitively on climate scenarios. Therefore, it is important to emphasize climate change mitigation and enhance vector surveillance and control in Europe.

    Acknowledgement: This research was funded by the European Union 7th Framework Programme through 'DengueTools' (www.denguetools.net).

    Disclosure: Nothing to disclose.

  • 10.
    Liu-Helmersson, Jing
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Quam, Mikkel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Wilder-Smith, Annelies
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health. Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Ebi, Kristie
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health. University of Washington, Seattle, Washington, USA.
    Massad, Eduardo
    School of Medicine, University of Sao Paulo, Brazil.
    Rocklöv, Joacim
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Climate change and Aedes vectors: 21st century projections for dengue transmission in Europe2016In: EBioMedicine, ISSN 0360-0637, E-ISSN 2352-3964, Vol. 7, p. 267-277Article in journal (Refereed)
    Abstract [en]

    Warming temperatures may increase the geographic spread of vector-borne diseases into temperate areas. Although a tropical mosquito-borne viral disease, a dengue outbreak occurred in Madeira, Portugal, in 2012; the first in Europe since 1920s. This outbreak emphasizes the potential for dengue re-emergence in Europe given changing climates. We present estimates of dengue epidemic potential using vectorial capacity (VC) based on historic and projected temperature (1901–2099). VC indicates the vectors' ability to spread disease among humans. We calculated temperature-dependent VC for Europe, highlighting 10 European cities and three non-European reference cities. Compared with the tropics, Europe shows pronounced seasonality and geographical heterogeneity. Although low, VC during summer is currently sufficient for dengue outbreaks in Southern Europe to commence–if sufficient vector populations (either Ae. aegypti and Ae. albopictus) were active and virus were introduced. Under various climate change scenarios, the seasonal peak and time window for dengue epidemic potential increases during the 21st century. Our study maps dengue epidemic potential in Europe and identifies seasonal time windows when major cities are most conducive for dengue transmission from 1901 to 2099. Our findings illustrate, that besides vector control, mitigating greenhouse gas emissions crucially reduces the future epidemic potential of dengue in Europe.

  • 11.
    Liu-Helmersson, Jing
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Wilder-Smith, Annelies
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health. Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.
    Rocklöv, Joacim
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Vectorial capacity of Aedes aegypti: Effects of temperature and implications for global dengue epidemic potential2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 3, article id e89783Article in journal (Refereed)
    Abstract [en]

    Dengue is a mosquito-borne viral disease that occurs mainly in the tropics and subtropics but has a high potential to spread to new areas. Dengue infections are climate sensitive, so it is important to better understand how changing climate factors affect the potential for geographic spread and future dengue epidemics. Vectorial capacity (VC) describes a vector's propensity to transmit dengue taking into account human, virus, and vector interactions. VC is highly temperature dependent, but most dengue models only take mean temperature values into account. Recent evidence shows that diurnal temperature range (DTR) plays an important role in influencing the behavior of the primary dengue vector Aedes aegypti. In this study, we used relative VC to estimate dengue epidemic potential (DEP) based on the temperature and DTR dependence of the parameters of A. aegypti. We found a strong temperature dependence of DEP; it peaked at a mean temperature of 29.3°C when DTR was 0°C and at 20°C when DTR was 20°C. Increasing average temperatures up to 29°C led to an increased DEP, but temperatures above 29°C reduced DEP. In tropical areas where the mean temperatures are close to 29°C, a small DTR increased DEP while a large DTR reduced it. In cold to temperate or extremely hot climates where the mean temperatures are far from 29°C, increasing DTR was associated with increasing DEP. Incorporating these findings using historical and predicted temperature and DTR over a two hundred year period (1901–2099), we found an increasing trend of global DEP in temperate regions. Small increases in DEP were observed over the last 100 years and large increases are expected by the end of this century in temperate Northern Hemisphere regions using climate change projections. These findings illustrate the importance of including DTR when mapping DEP based on VC.

  • 12. Peolsson, Michael
    et al.
    Löfstedt, Tommy
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Vogt, Susanna
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Stenlund, Hans
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Arndt, Anton
    Trygg, Johan
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Modelling human musculoskeletal functional movements using ultrasound imaging2010In: BMC Medical Imaging, ISSN 1471-2342, E-ISSN 1471-2342, Vol. 10, no 9Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: A widespread and fundamental assumption in the health sciences is that muscle functions are related to a wide variety of conditions, for example pain, ischemic and neurological disorder, exercise and injury. It is therefore highly desirable to study musculoskeletal contributions in clinical applications such as the treatment of muscle injuries, post-surgery evaluations, monitoring of progressive degeneration in neuromuscular disorders, and so on.The spatial image resolution in ultrasound systems has improved tremendously in the last few years and nowadays provides detailed information about tissue characteristics. It is now possible to study skeletal muscles in real-time during activity.

    METHODS: The ultrasound images are transformed to be congruent and are effectively compressed and stacked in order to be analysed with multivariate techniques. The method is applied to a relevant clinical orthopaedic research field, namely to describe the dynamics in the Achilles tendon and the calf during real-time movements.

    RESULTS: This study introduces a novel method to medical applications that can be used to examine ultrasound image sequences and to detect, visualise and quantify skeletal muscle dynamics and functions.

    CONCLUSIONS: This new objective method is a powerful tool to use when visualising tissue activity and dynamics of musculoskeletal ultrasound registrations.

  • 13. Redestig, Henning
    et al.
    Fukushima, Atsushi
    Stenlund, Hans
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Moritz, Thomas
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Masanori, Arita
    Saito, Kazuki
    Kusano, Miyako
    Compensation for systematic cross-contribution improves normalization of mass spectrometry based metabolomics data2009In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 81, no 19, p. 7974-7980Article in journal (Refereed)
    Abstract [en]

    Most mass spectrometry based metabolomics studies are semiquantitative and depend on efficient normalization techniques to suppress systematic error. A common approach is to include isotope-labeled internal standards (ISs) and then express the estimated metabolite abundances relative to the IS. Because of problems such as insufficient chromatographic resolution, however, the analytes may directly influence estimates of the IS, a phenomenon known as cross-contribution (CC). Normalization using ISs that suffer from CC effects will cause significant loss of information if the interfering analytes are associated with the studied factors. We present a novel normalization algorithm, which compensates for systematic CC effects that can be traced back to a linear association with the experimental design. The proposed method was found to be superior at purifying the signal of interest compared to current normalization methods when applied to two biological data sets and a multicomponent dilution mixture. Our method is applicable to data from randomized and designed experiments that use ISs to monitor the systematic error.

  • 14. Regnell, Simon E.
    et al.
    Hessner, Martin J.
    Åkesson, Lina
    Stenlund, Hans
    Swedish Metabolomics Centre, Swedish University of Agricultural Sciences, Umeå, Sweden.
    Moritz, Thomas
    La Torre, Daria
    Lernmark, Åke
    Longitudinal analysis of hepatic transcriptome and serum metabolome demonstrates altered lipid metabolism following the onset of hyperglycemia in spontaneously diabetic biobreeding rats2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 2, article id e0171372Article in journal (Refereed)
    Abstract [en]

    Type 1 diabetes is associated with abberations of fat metabolism before and after the clinical onset of disease. It has been hypothesized that the absence of the effect of insulin in the liver contributes to reduced hepatic fat synthesis. We measured hepatic gene expression and serum metabolites before and after the onset of hyperglycemia in a BioBreeding rat model of type 1 diabetes. Functional pathway annotation identified that lipid metabolism was differentially expressed in hyperglycemic rats and that these pathways significantly overlapped with genes regulated by insulin. 17 serum metabolites significantly changed in concentration. All but 2 of the identified metabolites had previously been reported in type 1 diabetes, and carbohydrates were overall the most upregulated class of metabolites. We conclude that lack of insulin in the liver contributes to the changes in fat metabolism observed in type 1 diabetes. Further studies are needed to understand the clinical consequences of a lack of insulin in the liver in patients with type 1 diabetes.

  • 15.
    Renberg, Linda
    et al.
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Johansson, Annika I.
    Shutova, Tatiana
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Stenlund, Hans
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Aksmann, Anna
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Raven, John A.
    Gardeström, Per
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Moritz, Thomas
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Samuelsson, Göran
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    A metabolomic approach to study major metabolite changes during acclimation to limiting CO2 in chlamydomonas reinhardtii2010In: Plant Physiology, ISSN 0032-0889, E-ISSN 1532-2548, Vol. 154, no 1, p. 187-196Article in journal (Refereed)
    Abstract [en]

    Using a gas chromatography-mass spectrometry-time of flight technique, we determined major metabolite changes during induction of the carbon-concentrating mechanism in the unicellular green alga Chlamydomonas reinhardtii. In total, 128 metabolites with significant differences between high-and low-CO2-grown cells were detected, of which 82 were wholly or partially identified, including amino acids, lipids, and carbohydrates. In a 24-h time course experiment, we show that the amino acids serine and phenylalanine increase transiently while aspartate and glutamate decrease after transfer to low CO2. The biggest differences were typically observed 3 h after transfer to low-CO2 conditions. Therefore, we made a careful metabolomic examination at the 3-h time point, comparing low-CO2 treatment to high-CO2 control. Five metabolites involved in photorespiration, 11 amino acids, and one lipid were increased, while six amino acids and, interestingly, 21 lipids were significantly lower. Our conclusion is that the metabolic pattern during early induction of the carbon-concentrating mechanism fit a model where photorespiration is increasing.

  • 16.
    Rui Climaco, Pinto
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Stenlund, Hans
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Hertzberg, Magnus
    Lundstedt, Torbjörn
    Johansson, Erik
    Trygg, Johan
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Design of experiments on 135 cloned poplar trees to map environmental influence in greenhouse2011In: Analytica Chimica Acta, ISSN 0003-2670, E-ISSN 1873-4324, Vol. 685, no 2, p. 127-131Article in journal (Refereed)
    Abstract [en]

    To find and ascertain phenotypic differences, minimal variation between biological replicates is always desired. Variation between the replicates can originate from genetic transformation but also from environmental effects in the greenhouse. Design of experiments (DoE) has been used in field trials for many years and proven its value but is underused within functional genomics including greenhouse experiments. We propose a strategy to estimate the effect of environmental factors with the ultimate goal of minimizing variation between biological replicates, based on DoE. DoE can be analyzed in many ways. We present a graphical solution together with solutions based on classical statistics as well as the newly developed OPLS methodology.In this study, we used DoE to evaluate the influence of plant specific factors (plant size, shoot type, plant quality, amount of fertilizer) and rotation of plant positions on height and section area of 135 cloned wild type poplar trees grown in the greenhouse. Statistical analysis revealed that plant position was the main contributor to variability among biological replicates and applying a plant rotation scheme could reduce this variation.

  • 17.
    Salzer, Jonatan
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Nyström, Maria
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Smoking as a risk factor for multiple sclerosis2013In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 19, no 8, p. 1022-1027Article in journal (Refereed)
    Abstract [en]

    Background: Smoking has been associated with an increased risk for multiple sclerosis, but no studies have measured levels of the nicotine metabolite cotinine in prospectively collected samples to assess exposure.

    Objective: To investigate the effects of laboratory defined tobacco use on the risk for multiple sclerosis using prospectively collected biobank blood samples.

    Methods: Levels of cotinine were measured in n=192 cases, and n=384 matched controls, using an immunoassay. The risk for multiple sclerosis was estimated using matched logistic regression.

    Results: Elevated cotinine levels (≥10 ng/ml) were associated with a significantly increased risk for multiple sclerosis, (odds ratio, OR 1.5, 95% confidence interval, CI 1.0–2.1). This association was only present in young individuals (below median age at blood sampling, <26.4 years), (OR 2.2, 95% CI 1.3–3.8).

    Conclusions: This study confirms that smoking is a risk factor for multiple sclerosis. It has the advantage of using analyses of cotinine levels in samples that were collected several years before disease onset, thus excluding any risk for recall bias and minimising the risk for reversed causation. Our results also suggest that the smoking related immunological events that contribute to the development of multiple sclerosis occur early in life.

  • 18.
    Salzer, Jonatan
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Nyström, Maria
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Vitamin A and systemic inflammation as protective factors in multiple sclerosis2013In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 19, no 8, p. 1046-1051Article in journal (Refereed)
    Abstract [en]

    Background: Vitamin A is important for the immune system, and might suppress inflammatory activity in multiple sclerosis (MS).

    Objectives: We aimed to examine if vitamin A levels were associated with MS risk in samples collected prospectively and during gestation.

    Methods: We measured Retinol Binding Protein (RBP – a surrogate marker for vitamin A) and high-sensitivity C-reactive protein (hs-CRP) levels, in (1) prospectively collected biobank blood samples from MS cases and controls, and (2) gestational samples where the offspring had later developed MS, and gestational control samples. The risk of MS was calculated using matched multivariable logistic regression adjusted for confounders.

    Results: In prospective samples, RBP levels within the second quintile (vs. the first) were associated with a lower MS risk (OR = 0.38, 95% CI 0.19–0.74). No effect on MS risk in the offspring by gestational RBP levels was found. In young subjects hs-CRP levels ≥10 mg/l in prospective samples were associated with a lower MS risk (OR = 0.36, 95% CI 0.14–0.95).

    Conclusions: Our results suggest that sub-optimal vitamin A levels may be associated with MS risk. The association between hs-CRP levels and MS risk in young subjects may support the role of the hygiene hypothesis in MS aetiology. 

  • 19.
    Salzer, Jonatan
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Nyström, Maria
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Vitamin D as a protective factor in multiple sclerosis2012In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 79, no 21, p. 2140-2145Article in journal (Refereed)
    Abstract [en]

    Objective: To examine the association between 25-hydroxyvitamin D (25[OH]D) levels and the risk of multiple sclerosis (MS) in blood samples collected prospectively and during gestation.

    Methods: In this nested case-control study, 2 population-based biobanks with 291,500 samples from164,000 persons collected since 1975 in the northern half of Sweden were used. We identified prospectively collected blood samples from MS cases (n = 192, controls matched 2:1) and gestational samples from pregnant mothers where the offspring had later developed MS (n = 37, control mothers matched 5:1). 25(OH)D levels were measured using an ELISA, and the risk of MS was analyzed using matched logistic regression.

    Results: Levels of 25(OH)D ≥75 (vs <75) nmol/L in prospectively collected blood samples were associated with a decreased risk of MS (odds ratio [OR] 0.39, 95% confidence interval [CI] 0.16- 0.98). No decrease in MS risk was found in the offspring exposed to gestational 25(OH)D levels ≥75 (vs <75) nmol/L (OR 1.8, 95%CI 0.53-5.8). The prevalence of 25(OH)D levels ≥75 nmol/L in female controls decreased gradually during 1976-2005 (p trend = 0.005).

    Conclusion: This study supports the presence of an association between high 25(OH)D levels during the years preceding disease onset and a decreased risk of MS. In the very limited material with samples drawn in early pregnancy, where month-of-birth effects were controlled for, we found no association between gestational 25(OH)D levels and MS risk in the offspring. Decreasing 25(OH) D levels in the population may contribute to explain the increasing MS incidence that is suggested from epidemiologic studies.

  • 20.
    Salzer, Jonatan
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Nyström, Maria
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Stenlund, Hans
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Wadell, Göran
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Epstein-Barr virus antibodies and vitamin D in prospective multiple sclerosis biobank sampels2013In: Multiple Sclerosis Journal, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 19, no 12, p. 1587-1591Article in journal (Refereed)
    Abstract [en]

    Background: Increased antibody reactivity against Epstein-Barr Nuclear Antigen-1 (EBNA-1) has been associated with an increased risk for MS, and high levels of 25-Hydroxyvitamin D (25[OH]D) have been associated with a lower risk for MS. Interaction between these two factors has been proposed.

    Objectives: To examine the association between antibody reactivity against EBNA-1 and five EBNA-1 domains, and the risk for multiple sclerosis (MS), and to examine if these antibodies and 25(OH)D status interact regarding MS risk in prospectively collected blood samples.

    Methods: Antibody reactivity (as specified above) and 25(OH)D levels were measured using ELISAs in n=192 MS cases and n=384 matched controls. The risk for MS was analysed using matched logistic regression.

    Results: The risk for MS increased across tertiles of antibody reactivity against EBNA-1, domain EBNA-1402–502, and domain EBNA-1385–420; p trend <0.001. The risk increase was most pronounced for EBNA-1385–420. In young individuals (below median age at sampling, <26.4 years) these associations were stronger, and 25(OH)D levels correlated inversely to antibody reactivity against EBNA-1 and the EBNA-1 domains.

    Conclusions: We confirm that increased antibody reactivity against EBNA-1 is a risk factor for MS. Our findings in young individuals suggest that 25(OH)D status might influence the immune response towards Epstein-Barr virus, and thereby modulate MS risk.

  • 21.
    Salzer, Jonatan
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Stenlund, Hans
    Sundström, Peter
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    The interaction between smoking and Epstein-Barr virus as multiple sclerosis risk factors may depend on age2014In: Multiple Sclerosis, ISSN 1352-4585, E-ISSN 1477-0970, Vol. 20, no 6, p. 747-750Article in journal (Refereed)
    Abstract [en]

    The multiple sclerosis (MS) risk factors smoking and remote Epstein-Barr virus (EBV) infection have been suggested to interact statistically, but the results are conflicting. In a prospective study on 192 MS cases and 384 matched controls, we analysed levels of cotinine as a marker of smoke exposure, and Epstein-Barr Nuclear Antigen-1 antibody reactivity. We assessed interaction on the additive and multiplicative scales, and estimated the effects of the risk factors across strata of each other. The results suggest that a negative interaction may be present in samples drawn at a young age, and a positive interaction among older subjects.

  • 22.
    Stenlund, Hans
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Improving interpretation by orthogonal variation: Multivariate analysis of spectroscopic data2011Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The desire to use the tools and concepts of chemometrics when studying problems in the life sciences, especially biology and medicine, has prompted chemometricians to shift their focus away from their field‘s traditional emphasis on model predictivity and towards the more contemporary objective of optimizing information exchange via model interpretation. The complex data structures that are captured by modern advanced analytical instruments open up new possibilities for extracting information from complex data sets. This in turn imposes higher demands on the quality of data and the modeling techniques used.

    The introduction of the concept of orthogonal variation in the late 1990‘s led to a shift of focus within chemometrics; the information gained from analysis of orthogonal structures complements that obtained from the predictive structures that were the discipline‘s previous focus. OPLS, which was introduced in the beginning of 2000‘s, refined this view by formalizing the model structure and the separation of orthogonal variations. Orthogonal variation stems from experimental/analytical issues such as time trends, process drift, storage, sample handling, and instrumental differences, or from inherent properties of the sample such as age, gender, genetics, and environmental influence.

    The usefulness and versatility of OPLS has been demonstrated in over 500 citations, mainly in the fields of metabolomics and transcriptomics but also in NIR, UV and FTIR spectroscopy. In all cases, the predictive precision of OPLS is identical to that of PLS, but OPLS is superior when it comes to the interpretation of both predictive and orthogonal variation. Thus, OPLS models the same data structures but provides increased scope for interpretation, making it more suitable for contemporary applications in the life sciences.

    This thesis discusses four different research projects, including analyses of NIR, FTIR and NMR spectroscopic data. The discussion includes comparisons of OPLS and PLS models of complex datasets in which experimental variation conceals and confounds relevant information. The PLS and OPLS methods are discussed in detail. In addition, the thesis describes new OPLS-based methods developed to accommodate hyperspectral images for supervised modeling. Proper handling of orthogonal structures revealed the weaknesses in the analytical chains examined. In all of the studies described, the orthogonal structures were used to validate the quality of the generated models as well as gaining new knowledge. These aspects are crucial in order to enhance the information exchange from both past and future studies.

  • 23.
    Stenlund, Hans
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Gorzsás, András
    Swedish Agricultural University.
    Persson, Per
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Sundberg, Björn
    Trygg, Johan
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Orthogonal Projections to Latent Structures Discriminant Analysis Modeling on in Situ FT-IR Spectral Imaging of Liver Tissue for Identifying Sources of Variability.2008In: Analytical Chemistry, ISSN 1520-6882, Vol. 80, no 18, p. 6898-906Article in journal (Refereed)
    Abstract [en]

    In this study, the orthogonal projections to latent structures discriminant analysis (OPLS-DA) method was used to assess the in situ chemical composition of two different cell types in mouse liver samples, hepatocytes and erythrocytes. High spatial resolution FT-IR microspectroscopy equipped with a focal plan array (FPA) detector is capable of simultaneously recording over 4000 spectra from 64 x 64 pixels with a maximum spatial resolution of about 5 mum x 5 mum, which allows for the differentiation of individual cells. The main benefit with OPLS-DA lies in the ability to separate predictive variation (between cell type) from variation that is uncorrelated to cell type in order to facilitate understanding of different sources of variation. OPLS-DA was able to differentiate between chemical properties and physical properties (e.g., edge effects). OPLS-DA model interpretation of the chemical features that separated the two cell types clearly highlighted proteins and lipids/bile acids. The modeled variation that was uncorrelated to cell type made up a larger portion of the total variation and displayed strong variability in the amide I region. This could be traced back to a gradient in the high intensity (high-density) areas vs the low intensity areas (close to empty areas) that as a result of normalization had an adverse effect on FT-IR spectral profiles. This highlights that OPLS-DA provides an effective solution to identify different sources of variability, both predictive and uncorrelated, and also facilitates understanding of any sampling, experimental, or preprocessing issues.

  • 24.
    Stenlund, Hans
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Johansson, Erik
    Gottfries, Johan
    Trygg, Johan
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Unlocking Interpretation in Near Infrared Multivariate Calibrations by Orthogonal Partial Least Squares2009In: Analytical Chemistry, Vol. 81, no 1, p. 203-9Article in journal (Refereed)
    Abstract [en]

    Near infrared spectroscopy (NIR) was developed primarily for applications such as the quantitative determination of nutrients in the agricultural and food industries. Examples include the determination of water, protein, and fat within complex samples such as grain and milk. Because of its useful properties, NIR analysis has spread to other areas such as chemistry and pharmaceutical production. NIR spectra consist of infrared overtones and combinations thereof, making interpretation of the results complicated. It can be very difficult to assign peaks to known constituents in the sample. Thus, multivariate analysis (MVA) has been crucial in translating spectral data into information, mainly for predictive purposes. Orthogonal partial least squares (OPLS), a new MVA method, has prediction and modeling properties similar to those of other MVA techniques, e.g., partial least squares (PLS), a method with a long history of use for the analysis of NIR data. OPLS provides an intrinsic algorithmic improvement for the interpretation of NIR data. In this report, four sets of NIR data were analyzed to demonstrate the improved interpretation provided by OPLS. The first two sets included simulated data to demonstrate the overall principles; the third set comprised a statistically replicated design of experiments (DoE), to demonstrate how instrumental difference could be accurately visualized and correctly attributed to Wood’s anomaly phenomena; the fourth set was chosen to challenge the MVA by using data relating to powder mixing, a crucial step in the pharmaceutical industry prior to tabletting. Improved interpretation by OPLS was demonstrated for all four examples, as compared to alternative MVA approaches. It is expected that OPLS will be used mostly in applications where improved interpretation is crucial; one such area is process analytical technology (PAT). PAT involves fewer independent samples, i.e., batches, than would be associated with agricultural applications; in addition, the Food and Drug Administration (FDA) demands “process understanding” in PAT. Both these issues make OPLS the ideal tool for a multitude of NIR calibrations. In conclusion, OPLS leads to better interpretation of spectrometry data (e.g., NIR) and improved understanding facilitates cross-scientific communication. Such improved knowledge will decrease risk, with respect to both accuracy and precision, when using NIR for PAT applications.

  • 25.
    Stenlund, Hans
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Madsen, Rasmus
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Vivi, Antonio
    Nuclear Magnetic Resonance Centre of Siena University, Siena, Italy.
    Calderisi, Marco
    Nuclear Magnetic Resonance Centre of Siena University, Siena, Italy.
    Lundstedt, Torbjörn
    AcureOmics AB, Umeå, Sweden.
    Tassini, Maria
    Nuclear Magnetic Resonance Centre of Siena University, Siena, Italy.
    Carmellini, Mario
    Department of Surgery and Bioengineering, University of Siena, Siena, Italy.
    Trygg, Johan
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Monitoring kidney-transplant patients using metabolomics and dynamic modeling2009In: Chemometrics and Intelligent Laboratory Systems, ISSN 0169-7439, E-ISSN 1873-3239, Vol. 98, no 1, p. 45-50Article in journal (Refereed)
    Abstract [en]

    A kidney transplant provides the only hope for a normal life for patients with end-stage renal disease, i.e., kidney failure. Unfortunately, the lack of available organs leaves some patients on the waiting list for years. In addition, the post-transplant treatment is extremely important for the final outcome of the surgery, since immune responses, drug toxicity and other complications pose a real and present threat to the patient. In this article, we describe a novel strategy for monitoring kidney transplanted patients for immune responses and adverse drug effects in their early recovery. Nineteen patients were followed for two weeks after renal transplantation, two of them experienced problems related to kidney function, both of whom were correctly identified by means of nuclear magnetic resonance spectroscopic analysis of urine samples and multivariate data analysis.

  • 26.
    Åkesson, Lina
    et al.
    Department of Clinical Sciences, Diabetes and Celiac Disease Unit, Lund University, Malmö, Sweden.
    Trygg, Johan
    Umeå University.
    Fuller, Jessica M
    Department of Medicine, University of Washington, Seattle, WA, USA.
    Madsen, Rasmus
    Umeå University.
    Gabrielsson, Jon
    AcureOmics AB, Umeå, Sweden.
    Bruce, Stephen
    Nestle´ Research Center–Lausanne, Nestec Ltd, CH-1000 Lausanne 26, Vers-chez-les-Blanc, Switzerland.
    Stenlund, Hans
    Tupling, Terry
    Department of Medicine, University of Washington, Seattle, WA, USA.
    Pefley, Ranae
    Department of Medicine, University of Washington, Seattle, WA, USA.
    Lundstedt, Torbjörn
    AcurePharma AB, Uppsala, Sweden.
    Lernmark, Åke
    Department of Clinical Sciences, Diabetes and Celiac Disease Unit, Lund University, Malmö, Sweden.
    Moritz, Thomas
    Umeå Plant Science Centre, Department of Forest Genetics and Plant Physiology, Swedish University of Agricultural Sciences, Umeå, Sweden.
    Serum metabolite signature predicts the acute onset of diabetes in spontaneously diabetic congenic BB rats2011In: Metabolomics, ISSN 1573-3882, Vol. 7, no 4, p. 593-603Article in journal (Refereed)
    Abstract [en]

    The clinical presentation of type 1 diabetes is preceded by a prodrome of beta cell autoimmunity. We probed the short period of subtle metabolic abnormalities, which precede the acute onset of diabetes in the spontaneously diabetic BB rat, by analyzing the serum metabolite profile detected with combined gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS). We found that the metabolite pattern prior to diabetes included 17 metabolites, which differed between individual diabetes prone (DP) BB rats and their age and sex matched diabetes resistant (DR) littermates. As the metabolite signature at the 40 days of age baseline failed to distinguish DP from DR, there was a brief 10-day period after which the diabetes prediction pattern was observed, that includes fatty acids (e.g. oleamide), phospholipids (e.g. phosphocholines) and amino acids (e.g. isoleucine). It is concluded that distinct changes in the serum metabolite pattern predict type 1 diabetes and precede the appearance of insulitis in spontaneously diabetic BB DP rats. This observation should prove useful to dissect mechanisms of type 1 diabetes.

1 - 26 of 26
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf