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  • 201.
    Larsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Carlsson, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Axelsson, John
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Low diurnal variability of apolipoprotein A1, apolipoprotein B and apolipoprotein B/apolipoprotein A1 ratio during normal sleep and after an acute shift of sleep2008In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 41, no 10-11, p. 859-862Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The aim of this study was to study the diurnal variation of the cardiovascular risk markers apolipoprotein A1 and B and apo B/apo A1 ratio. DESIGN AND METHODS: We have studied the diurnal variation of apolipoprotein A1, apolipoprotein B and apo B/apo A1 ratio during night sleep and the day sleep conditions in seven healthy volunteers (age 22-32 yr). Samples were collected every hour to evaluate the effect of different sampling times on the test results. RESULTS: The lowest diurnal coefficient of variation (CV) was observed for the apo B/apo A1 ratio, which usually was below 2% but also apolipoprotein A1, apolipoprotein B showed low CV. There were no significant differences between nightsleep and daysleep for any of the studied markers. CONCLUSION: Even if there was a diurnal variation for these markers, the variation was very low. Thus, sampling does not have to be restricted to certain times of the day.

  • 202.
    Larsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Carlsson, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Gordh, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lind, Anne-Li
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Thulin, Måns
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Statistics.
    Kamali-Moghaddam, Masood
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    The effects of age and gender on plasma levels of 63 cytokines2015In: JIM - Journal of Immunological Methods, ISSN 0022-1759, E-ISSN 1872-7905, Vol. 425, p. 58-61Article in journal (Refereed)
    Abstract [en]

    Cytokines play important roles as regulators of cell functions, and over the last decades a number of cytokine assays have been developed. The aim of the present study was to investigate the effects of age and gender on a large number of cytokines. Plasma samples were collected from 33 healthy blood donors. The samples were analyzed using the multiplex proximity extension assay (PEA) allowing simultaneous measurement of 92 cytokines and four technical controls. Biomarkers with less than 80% quantitative results were excluded leaving 63 cytokines that were analyzed for the effects of gender and age. The plasma level of three of the investigated biomarkers (DNER, MCP-4 and MMP-10) were found to be significantly different for the two genders (adjusted p-value <0.05), and 15 of the biomarkers (CCL11, CCL25, CDCP1, CSF-1, CXCL11, CXCL9, FGF-23, Flt3L, HGF, IL-10RB, MCP-3, MCP-4, MMP-10, OPG, VEGF-A) were significantly associated with age. This study reveals the effects of age and gender on a large number of cytokine assays. CXCL5 and TNFB were significantly higher in females, while the other markers with significant gender-dependent differences were higher in males. For the markers that were significantly associated with age, only CXCL6 was found to decrease with age, while the other biomarkers increased with age.

  • 203.
    Larsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Carlsson, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Karlsson, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Rapid testing of red blood cell parameters in primary care patients using HemoScreen™ point of care instrument2019In: BMC Family Practice, ISSN 1471-2296, E-ISSN 1471-2296, Vol. 20, no 1, article id 77Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Patients with anemia are frequently encountered in primary care. Once anemia is detected, it is essential to define the type and identify the underlying cause prior to initiation of treatment. In most cases, the cause can be determined using information from the patient history, physical exam, and complete blood counts (CBC). Point of care testing of blood cell counts would speed up the work up of anemia patients. The aim of the present study was to evaluate if the HemoScreen™ instrument (PixCell Medical, Yokneam Ilit, Israel) could be used for primary care samples. It is a POCT instrument that utilizes single sample cuvettes and image analysis of full blood count including RBC, Hemoglobin, MCV, MCH, platelets, WBC, and WBC 5-part differential.

    METHODS: We compared the HemoScreen™ and the Sysmex XN instrument results of 100 primary care patient samples focusing on the total white blood cells, red blood cell parameters RBC, Hemoglobin, MCH, MCV and platelets.

    RESULTS: Deming correlations between the HemoScreen™ and the Sysmex XN instruments for the CBC were WBCHemoScreen™ = 1.016* WBCSysmex + 0.34; r = 0.981, RBCHemoScreen™ = 0.988* RBCSysmex + 0.015; r = 0.974, HemoglobinHemoScreen™ = 1.081* HemoglobinSysmex - 11.25; r = 0.964, MCHHemoScreen™ = 0.978* MCHSysmex + 0.78; r = 0.939, MCVHemoScreen™ = 0.963* MCVSysmex + 8.68; r = 0.946, PlateletsHemoScreen™ = 0.964* PlateletsSysmex + 25.7; r = 0.953.

    CONCLUSION: The HemoScreen™ instrument could provide rapid and accurate test results for evaluation of the red blood cell parameters in primary care. This new technology is interesting as it allows the analysis red blood cell parameters also at small primary care centers.

  • 204.
    Larsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Carlsson, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lind, Anne-Li
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Gordh, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Bodolea, Constantin
    Kamali-Moghaddam, Masood
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Thulin, Måns
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Statistics.
    The body mass index (BMI) is significantly correlated with levels of cytokines and chemokines in cerebrospinal fluid2015In: Cytokine, ISSN 1043-4666, E-ISSN 1096-0023, Vol. 76, no 2, p. 514-518Article in journal (Refereed)
    Abstract [en]

    Cytokines and chemokines regulate many functions in the body including the brain. The interactions between adipose tissue and the central nervous system (CNS) are important for the regulation of energy balance. CNS function is also influenced by age. The aim of the present study was to investigate the effects of body mass index (BMI) and age on cytokine and chemokine levels in cerebrospinal fluid. Cerebrospinal fluid samples (n=89) were collected from patients undergoing routine surgical procedures. The samples were analyzed using the multiplex proximity extension assay (PEA) in which 92 different cytokines are measured simultaneously using minute sample volume. We found no significant correlations between age and cytokine levels for any of the studied markers. In contrast, at a false discovery rate of 10%, 19 markers were significantly associated with BMI (in decreasing significance: FGF-5, ADA, Beta-NGF, CD40, IL-10RB, CCL19, TGF-alpha, SIRT2, TWEAK, SCF, CSF-1, 4E-BP1, DNER, LIF-R, STAMPB, CXCL10, CXCL6, VEGF-A and CX3CL1). This study reveals a clear effect of BMI on cytokine and chemokine levels in cerebrospinal fluid.

  • 205.
    Larsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Flodin, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Hansson, Lars-Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Carlsson, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Patient selection has a strong impact on cystatin C and Modification of Diet in Renal Disease (MDRD) estimated glomerular filtration rate2008In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 41, no 16-17, p. 1355-1361Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Estimation of the glomerular filtration rate (GFR) is essential for the evaluation of patients with kidney disease, and for correct dosage of drugs that are eliminated from the circulation by the kidneys. In most cases GFR is estimated based on serum creatinine and the Modification of Diet in Renal Disease (MDRD) formula. As both cystatin C and creatinine are used for the determination of GFR it is important to investigate if estimated GFR by the two methods differ in various patient groups. DESIGN AND METHODS: We have compared cystatin C and MDRD estimated GFR calculated from the same request from primary care units (n=488), a cardiology ward (n=826), the cardiointensive care unit (n=1026), two oncology wards (n=919 and 1021), and the neurosurgical intensive care unit (n=1515) in an observational cross-sectional study. RESULTS: We found better agreement between the two GFR estimates in samples from primary care patients and patients in the cardiology wards, than in samples from oncology wards or the neurosurgical intensive care unit. In the latter settings there was a pronounced difference between the two GFR estimates. CONCLUSION: The comparisons show that differences in patient selections have a strong impact on the agreement between cystatin C and MDRD estimated glomerular filtration rate.

  • 206.
    Larsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Greig-Pylypczuk, Roman
    Huisman, Albert
    The state of point-of-care testing: a european perspective2015In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 120, no 1, p. 1-10Article, review/survey (Refereed)
    Abstract [en]

    Abstract Point-of-care testing (POCT) refers to any diagnostic test administered outside the central laboratory at or near the location of the patient. By performing the sample collection and data analysis steps in the same location POCT cuts down on transport and processing delays, resulting in the rapid feedback of test results to medical decision-makers. Over the past decades the availability and use of POCT have steadily increased in Europe and throughout the international community. However, concerns about overall utility and the reliability of benefits to patient care have impeded the growth of POCT in some areas. While there is no agreed-upon standard for how success should be judged, the increases in speed and mobility provided by POCT can lead to substantial advantages over traditional laboratory testing. When properly utilized, POCT has been shown to yield measurable improvements in patient care, workflow efficiency, and even provide significant financial benefits. However, important organizational and quality assurance challenges must be addressed with the implementation of POCT in any health care environment. To ensure maximal benefits it may be necessary to evaluate critically and restructure existing clinical pathways to capitalize better on the rapid test turnaround times provided by POCT.

  • 207.
    Larsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Nilsson, Lennart
    Department of Medical and Health Sciences , Linkoping University , Linkoping , Sweden..
    Svensson, Maria K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Treatment target re-classification of subjects comparing estimation of low-density lipoprotein cholesterol by the Friedewald equation and direct measurement of LDL-cholesterol2018In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 123, no 2, p. 94-99Article in journal (Refereed)
    Abstract [en]

    AIMS: To compare low-density lipoprotein cholesterol (LDL-C) values calculated by the Friedewald equation with direct LDL-C in patient samples and assess the possible impact on re-classification of LDL-C target values for primary prevention or high cardiovascular disease (CVD) risk (<2.5 mmol/L) and secondary prevention or very high CVD risk (<1.8 mmol/L). LDL-C is an important CVD risk factor. Over the last decade, there has been a change in laboratory methodology from indirectly calculated LDL-C with the Friedewald equation to direct LDL-C measurements (dLDL-C).

    METHODS: Reported results for plasma triglycerides, total cholesterol, high-density lipoprotein-cholesterol, and dLDL-C from 34,981 samples analyzed in year 2014 were extracted from the laboratory information system, Uppsala University Hospital, Uppsala, Sweden.

    RESULTS: dLDL-C was approximately 10% lower than the corresponding LDL-C results calculated by the Friedewald equation in both men and women. In subjects with triglyceride concentrations above 4 mmol/L (n = 1250) the same discordant pattern was seen as for the entire study population. Altogether 5469 out of 18,051 men (30.3%) and 4604 out of 16,928 women (27.2%) were down-classified at least one CVD risk category. A very small number of subject was up-classified, in total 37 out of 18,051 men (0.2%) and 28 out of 16,928 women (0.2%).

    CONCLUSIONS: The two LDL-C methods had a high concordance, but the direct LDL-C measurement consistently gave approx. 10% lower values, and this caused one-third of subjects to be re-classified as having a lower cardiovascular disease risk in relation to recommended LDL-C target values and decision limits.

  • 208.
    Larsson, Anders
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. klinisk kemi.
    Hansson, Lars-Olof
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. klinisk kemi.
    Analysis of inflammatory response in human plasma samples by an automated multicapillary electrophoresis system.2004In: clin chem lab med, Vol. 42, no 12, p. 1396-1400Article in journal (Refereed)
  • 209.
    Larsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Hansson, Lars-Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Comparison between a second generation automated multicapillary electrophoresis system with an automated agarose gel electrophoresis system for the detection of M-components2008In: Upsala Journal of Medical Sciences, Supplement, ISSN 0300-9726, Vol. 113, no 1, p. 65-72Article in journal (Refereed)
    Abstract [en]

    During the last decade, capillary electrophoresis (CE) has emerged as an interesting alternative to traditional analysis of serum, plasma and urine proteins by agarose gel electrophoresis. Initially there was a considerable difference in resolution between the two methods but the quality of CE has improved significantly. We thus wanted to evaluate a second generation of automated multicapillary instruments (Capillarys, Sebia, Paris, France) and the high resolution (HR) buffer for serum or plasma protein analysis with an automated agarose gel electrophoresis system for the detection of M-components. The comparison between the two systems was performed with patients samples with and without M-components. The comparison included 76 serum samples with M-components > 1 g/L. There was a total agreement between the two methods for detection of these M-components. When studying samples containing oligoclonal bands/small M-components, there were differences between the two systems. The capillary electrophoresis system detected a slightly higher number of samples with oligoclonal bands but the two systems found oligoclonal bands in different samples. When looking at resolution, the agarose gel electrophoresis system yielded a slightly better resolution in the alpha and beta regions, but it required an experienced interpreter to be able to benefit from the increased resolution. The capillary electrophoresis has shorter turn-around times and bar-code reader that allows positive sample identification. The Capillarys in combination with HR buffer gives better resolution of the alpha and beta regions than the same instrument with the beta1-beta2+ buffer or the Paragon CZE2000 (Beckman) which was the first generation of capillary electrophoresis systems.

  • 210.
    Larsson, Anders
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. klinisk kemi.
    Hansson, Lars-Olof
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. klinisk kemi.
    Inflammatory activity: capillary electrophoresis provides more information than erythrocyte sedimentation rate.2005In: Ups J Med Sci, ISSN 0300-9734, Vol. 110, no 2, p. 151-8Article in journal (Other scientific)
  • 211.
    Larsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Hansson, Lars-Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Plasma protein fractions in healthy blood donors quantitated by an automated multicapillary electrophoresis system2006In: Journal of Chromatographic Science, ISSN 0021-9665, E-ISSN 1945-239X, Vol. 44, no 8, p. 479-483Article in journal (Refereed)
    Abstract [en]

    During the last decade, capillary electrophoresis (CE) has emerged as an important alternative to traditional analysis of serum and plasma proteins by agarose or celluloseacetate electrophoresis. CE analysis of plasma proteins can now be fully automated and also includes bar-code identification of samples, preseparation steps, and direct post-separation quantitation of individual peaks, which permits short assay times and high throughput. For laboratory work, it is important to have reference values from healthy individuals. Therefore, plasma samples from 156 healthy blood donors (79 females and 77 males) have been analyzed with the Capillarys instrument and the new high resolution buffer, which yields higher resolution than the b1-b2+ buffer. Albumin concentrations in samples are measured using nephelometry in order to assign protein concentrations to each peak. The 2.5 and 97.5 percentiles for both the percentages of different peaks and the protein concentrations in the peaks are calculated according to the recommendations of the International Federation of Clinical Chemistry on the statistical treatment of reference values. The Capillarys instrument is a reliable system for plasma protein analysis, combining advantages of full automation with high analytical performances and throughput.

  • 212.
    Larsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Hansson, Lars-Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Flodin, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Katz, Ronit
    Shlipak, Michael G.
    Calibration of the Siemens Cystatin C Immunoassay Has Changed over Time2011In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 57, no 5, p. 777-778Article in journal (Refereed)
  • 213.
    Larsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Hansson, Lars-Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Åkerfeldt, Torbjörn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Weight reduction is associated with decreased CRP levels2013In: Clinical Laboratory, ISSN 1433-6510, Vol. 59, no 9-10, p. 1135-1138Article in journal (Refereed)
    Abstract [en]

    Background:

    Obesity is very costly for society and weight reduction is important to reduce obesity related dis-eases. We have evaluated the effect of weight reduction on CRP values to see if high sensitivity CRP could be used to provide persons on life style intervention programs with positive feedback.

    Methods:

    Study subjects (n = 26) were recruited to a life style intervention program aiming for weight loss among the laboratory staff at Uppsala University Hospital, Sweden. Blood samples for high sensitivity CRP were collect-ed at inclusion and after 4 weeks. Body composition was estimated by measurements performed on an inexpensive bioimpedance analyzer.

    Results:

    CRP reduction was significantly associated with weight reduction after four weeks (p = 0.00005) and eight weeks (p = 0.0002). Data from the bioimpedance analyzer were not useful on an individual level.

    Conclusions:

    High sensitivity CRP could be used to provide positive feedback in workplace weight reduction pro-grams.

  • 214.
    Larsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Helmersson, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Hansson, Lars-Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Increased serum cyststin C is associated with increased mortality in elderly men2005In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 65, no 4, p. 301-305Article in journal (Refereed)
    Abstract [en]

    Renal dysfunction measured by serum creatinine is associated with increased cardiovascular morbidity and mortality. Plasma cystatin C has been shown in several studies to be superior to plasma creatinine for the estimation of glomerular filtration rate (GFR). The aim of the present study was to investigate the relationship between cystatin C and mortality in elderly men. Serum cystatin C was analyzed by nephelometry in a group of 77-year-old men (n=792) and correlated cystatin C levels with mortality during a follow-up period of 1-4 years. The cystatin C values were significantly correlated with overall mortality (p=0.013). Mortality was three times higher in the highest cystatin C quintile in relation to the lowest quintile.

  • 215.
    Larsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Helmersson, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Hansson, Lars-Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Serum cystatin C is associated with other cardiovascular risk markers and cardiovascular disease in elderly men2008In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 125, no 2, p. 263-264Article in journal (Refereed)
    Abstract [en]

    Renal dysfunction is associated with increased cardiovascular morbidity and mortality. The aim of this cross-sectional study was to investigate the relationship between the glomerular filtration marker cystatin C and other cardiovascular risk markers and morbidity in elderly males. Cystatin C was measured in a group of 77-year-old males (n=792) and compared cystatin C with other known risk markers for cardiovascular disease. Cystatin C values were significantly increased in individuals with diabetes (p=0.05) and cardiovascular diseases (p<0.0001). There were significant correlations between cystatin C values and body mass index, HbA1c, insulin, triglycerides and hsCRP.

  • 216.
    Larsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Lindqvist, A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Hillered, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurosurgery.
    Pseudoparaproteinemia Detected by CE due to Omnipaque™ Infusion: A Case Report2007In: Chromatographia, ISSN 0009-5893, E-ISSN 1612-1112, Vol. 65, no 11-12, p. 775-777Article in journal (Refereed)
    Abstract [en]

    Serum or plasma protein electrophoresis is often performed in clinical laboratories to detect and monitor M-components. During the last decade, capillary electrophoresis (CE) has emerged as an interesting alternative to traditional analysis of serum, plasma and urine proteins by agarose gel electrophoresis. We here report a case of pseudoparaproteinemia detected by capillary electrophoresis after Omnipaque™ (iohexol) infusion in a patient with normal kidney function. It is important for the laboratories to be aware of this source of erroneous results and not misclassify it as monoclonal gammopathies.

  • 217.
    Larsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Klinisk kemi.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Infektion.
    Hansson, Lars-Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Klinisk kemi.
    Eriksson, Mats B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Slight Increase of Serum S-100B During Porcine Endotoxemic Shock May Indicate Blood-Brain Barrier Damage.2005In: Anesth Analg, ISSN 0003-2999, Vol. 101, no 5, p. 1465-9Article in journal (Refereed)
    Abstract [en]

    Septic shock is a condition that affects many organs, but little is known about the effects on the central nervous system. S-100B, an acidic low molecular weight protein, has attracted considerable interest as a marker for brain damage and disintegration of the blood-brain barrier. It is released into the cerebrospinal fluid and blood from brain tissue after brain damage. We studied S-100B in a porcine model of endotoxemic shock that resembles human Gram-negative septic shock. Ten piglets received IV endotoxin, and plasma samples were collected before the endotoxin infusion and each hour (1-6 h) during the endotoxin infusion. S-100B was measured by sandwich enzyme-linked immunosorbent assay. Low levels of plasma S-100B were detected, but there was a significant increase in S-100B during Hours 1-5 in comparison with the 0 values. We determined that endotoxemia causes a very small but significant increase in the levels of the widely used brain damage marker serum S-100B. However, it cannot be excluded that the increase in S-100B could be caused by release from organs other than the brain.

  • 218.
    Larsson, Anders
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. klinisk kemi.
    Malm, Johan
    Grubb, Anders
    Hansson, Lars-Olof
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. klinisk kemi.
    Calculation of glomerular filtration rate expressed in mL/min from plasma cystatin C values in mg/L2004In: Scand J Clin Lab Invest, Vol. 64, p. 9-16Article in journal (Refereed)
  • 219.
    Larsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Nordin, Gunnar
    För kort ”bäst före-datum” ett hot mot patientsäkerheten2014In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 111, article id C9A6Article in journal (Other (popular science, discussion, etc.))
  • 220.
    Larsson, Anders O
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Specificity of B-type natriuretic peptide assays: Knockin’ on the assay door2017In: Journal of Laboratory and Precision Medicine, ISSN 2519-9005, Vol. 2, article id 4Article in journal (Refereed)
  • 221.
    Larsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Palm, M
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Hansson, L-O
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Axelsson, O
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Reference values for clinical chemistry tests during normal pregnancy2008In: British Journal of Obstetrics and Gynecology, ISSN 1470-0328, E-ISSN 1471-0528, Vol. 115, no 7, p. 874-881Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Reference values are usually defined based on blood samples from healthy men or nonpregnant women. This is not optimal as many biological markers changes during pregnancy and adequate reference values are of importance for correct clinical decisions. There are only few studies on the variations of laboratory tests during normal pregnancies, especially during the first two trimesters. It is thus a need to establish such reference values. DESIGN: Longitudinal study of laboratory markers in normal pregnancies. SETTING: Uppsala University Hospital, Sweden. POPULATION: Healthy pregnant females. METHODS: We have studied 25 frequently used laboratory tests during 52 normal pregnancies. Each woman was sampled up to nine times and the samples were divided according to collection time into the following groups: gestational week 7-17; week 17-24; week 24- 28; week 28-31; week 31-34; week 34-38; predelivery (0-2 weeks before delivery) and postpartum (> 6 weeks after delivery). The 2.5 and 97.5 percentiles for these markers were calculated according to the recommendations of the International Federation of Clinical Chemistry on the statistical treatment of reference values. RESULTS: Reference intervals are reported for plasma alanine aminotransferase, albumin, alkaline phosphatase, pancreas amylase, apolipoprotein A1, apolipoprotein B, aspartate aminotransferase, bilirubin, calcium, chloride, creatinine, cystatin C, ferritin, gamma-glutamyltransferase, iron, lactate dehydrogenase, magnesium, phosphate, potassium, sodium, transferrin, triglycerides, thyroid-stimulating hormone, urate and urea during these pregnancy periods. CONCLUSIONS: Most of the analytes change during normal pregnancy. It is thus of importance to use special reference values during pregnancy.

  • 222.
    Larsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Palm, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Axelsson, Ove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Insulin-like growth factor binding protein-1 (IGFBP-1) during normal pregnancy2013In: Gynecological Endocrinology, ISSN 0951-3590, E-ISSN 1473-0766, Vol. 29, no 2, p. 129-132Article in journal (Refereed)
    Abstract [en]

    Background:

    Insulin-like growth factor (IGF) binding protein-1 (IGFBP-1) is the main binder of IGFs in secretory endometrium and decidualized stromal endometrial cells and IGFBP-1 has been shown to modulate IGF bioactivities and influence fetal growth. To be able to evaluate IGFBP-1 values during pregnancy it is important to establish normal values in pregnant women.

    Materials & Methods:

    We have studied IGFBP-1 concentrations in maternal plasma from 52 healthy women with normal singleton pregnancies. Several plasma samples were collected from each woman and the samples were grouped according to gestational age into the following periods: week 7-17; week 17-24; week 24-28; week 28-31; week 31-34; week 34-38; -2 to 0 weeks prior to delivery and postpartum (>6 weeks after delivery).

    Results:

    The 2.5 and 97.5 percentiles for IGFBP-1 were calculated according to the recommendations of the International Federation of Clinical Chemistry on the statistical treatment of reference values.

    Conclusions:

    IGFBP-1 is increased during pregnancy compared to postpartum. Two peaks, at week 17-24 and just before delivery, were observed.

  • 223.
    Larsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Palm, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Helmersson, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Axelsson, Ove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Pentraxin 3 Values During Normal Pregnancy2011In: Inflammation, ISSN 0360-3997, E-ISSN 1573-2576, Vol. 34, no 5, p. 448-451Article in journal (Refereed)
    Abstract [en]

    Pentraxin 3 (PTX3) is an inflammatory molecule that has been reported to be a promising early biomarker for subsequent preeclampsia. The levels of PTX3 vary during pregnancy and it is thus a need to establish reference intervals during normal pregnancy. Repeated blood samples were collected from 52 healthy pregnant females. The samples were divided according to collection time into the following groups: week 7-17, week 17-24, week 24-28, week 28-31, week 31-34, week 34-38, before delivery and after delivery. The samples were analyzed for PTX3 with a sandwich ELISA and the 2.5 and 97.5 percentiles for each sample period was calculated. There was a continuous increase of serum PTX3 as pregnancy progressed. The increase was most evident after week 31 with the highest levels just before delivery.

  • 224.
    Larsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Ridefelt, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Pediatric reference intervals for liver markers derived from healthy community-based subjects will improve diagnostic interpretation in children and adolescents2018In: Journal of Laboratory and Precision Medicine, ISSN 2519-9005, Vol. 3, p. 2-Article in journal (Refereed)
  • 225.
    Larsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Ridefelt, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Reference intervals for parathyroid hormone for 70-year-old males and females: exclusion of individuals from the reference interval based on sex, calcium, diabetes, cardiovascular diseases or reduced kidney function has limited effects on the interval2015In: Annals of Clinical Biochemistry, ISSN 0004-5632, E-ISSN 1758-1001, Vol. 52, no 1, p. 39-43Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: A problem when producing reference intervals for elderly individuals is that they often suffer from a number of diseases and they are most often on medication. If all such persons are excluded, there is a risk that the residual subgroup may not be representative of the population, we therefore wanted to compare the effects different exclusion criteria has on the reference intervals.

    METHODS: We measured parathyroid hormone (PTH), calcium, albumin and cystatin C in a cohort of 70-year-old males and females (n = 1003). Reference intervals for PTH for males and females were calculated for the entire population and after exclusion of persons with calcium >2.60 mmol/L, calcium >2.51 mmol/L, diabetes, reduced glomerular filtration rate (GFR), and cardiovascular diseases.

    RESULTS: The calculated PTH reference interval 16 (CI 14-17) to 94 (CI 87-101) ng/L. Exclusion of study subjects resulted in smaller reference sample groups, but the reference limits remained within the 90% confidence intervals of the original reference limits. The selections thus had a very limited effect on the calculated reference interval for PTH.

    CONCLUSIONS: Exclusion of elderly individuals with high calcium concentrations, diabetes, reduced GFR or cardiovascular disease has little effect on the reference interval for PTH. It is better not to exclude these individuals, as it will provide a broader base for the reference interval.

  • 226.
    Larsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Ronquist, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Wülfing, Christian
    Eltze, Elke
    Bettendorf, Olaf
    Carlsson, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Nilsson, B. Ove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Semjonow, Axel
    Antiprostasome antibodies: possible serum markers for prostate cancer metastasizing liability2006In: Urologic Oncology, ISSN 1078-1439, E-ISSN 1873-2496, Vol. 24, no 3, p. 195-200Article in journal (Refereed)
    Abstract [en]

    Prostasomes are secretory granules synthesized, stored, and secreted by normal and neoplastic human prostate epithelial cells. In prostate cancer, they are anticipated to be released into the blood circulation where they may be immunogenic. The aim of our study was to examine whether prostasome antibody presence in serum bears any prognostic significance for men with prostate cancer. We developed a sensitive and specific immunoassay (enzyme-linked immunosorbent assay) to establish the presence of antiprostasome antibodies in serum. The antiprostasome antibody titer in serum, sampled before any kind of therapy for prostate cancer, was examined together with clinicopathologic variables and outcome over a median follow-up of 350 days in 218 patients with verified prostate cancer. We detected these antibodies in 191 (88%) of these patients. This antibody titer did not correlate to serum values of prostate-specific antigen. Significant, inverse relationships were registered for antiprostasome antibody titer, and metastases to bone and/or lymph nodes (P = 0.035) and pT (P = 0.025). These results indicate that the antiprostasome antibody titer in serum may be a novel marker for prostate cancer liability to metastasize.

  • 227.
    Larsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Ronquist, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Åkerfeldt, Torbjörn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Lifestyle intervention is associated with decreased concentrations of circulating pentraxin 3 independent of CRP decrease2013In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 118, no 3, p. 165-168Article in journal (Refereed)
    Abstract [en]

    Objectives. Pentraxin 3 (PTX3) is an acute phase marker, which is produced at the site of infection or inflammation in contrast to CRP that is mainly synthesized by the liver. The aim of the present study was to see if lifestyle interventions/weight loss would lead to decreased blood plasma concentrations of PTX3. Methods. Study subjects (n = 31) were recruited to a lifestyle intervention program aiming at increased physical activity, improved eating habits, and weight loss. High-sensitivity C-reactive protein (CRP) and PTX3 methods were used for analysis of CRP and PTX3 in plasma samples collected at inclusion and after 4 and 8 weeks of treatment. Results. Wilcoxon paired samples test showed a significant decrease in PTX3 concentrations from 2068 pg/mL at start to 2007 pg/mL at 4 weeks (P = 0.002) and 1748 pg/mL at 8 weeks (P = 0.003). The PTX3 decrease was not significantly correlated with a corresponding decrease in CRP or weight reduction. Conclusions. The lifestyle intervention program resulted in a significant reduction of circulating concentrations of pentraxin 3 already after 4 and 8 weeks of treatment.

  • 228.
    Larsson, Anders
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. klinisk kemi.
    Schneider, Karin
    Department of Oncology, Radiology and Clinical Immunology.
    Hansson, Lars-Olof
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. klinisk kemi.
    Knutsson, Folke
    Department of Oncology, Radiology and Clinical Immunology.
    Capillary electrophoresis for monitoring the effects of plasmapheresis: a feasibility study.2005In: Transfus Apher Sci, ISSN 1473-0502, Vol. 33, no 1, p. 19-23Article in journal (Refereed)
  • 229.
    Larsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Smekal, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Rapid testing of red blood cells, white blood cells and platelets in intensive care patients using the HemoScreen™ point-of-care analyzer2018In: Platelets, ISSN 0953-7104, E-ISSN 1369-1635, p. 1-4Article in journal (Refereed)
    Abstract [en]

    Acute major bleeding is a condition that can be encountered in critically ill patients and may require rapid transfusions. To evaluate the need for packed red blood cells (RBCs) and platelets (PLTs), it is important to have rapid test results for RBC/hemoglobin and PLTs. Recently, PixCell Medical (Yokneam Ilit, Israel) introduced the HemoScreen™, an automated hematology analyzer. It is a point-of-care device that uses single sample cuvettes and image analysis of RBCs, PLTs and white blood cells (WBCs), performing a five-part differential count. The HemoScreen™ is the first portable differential count instrument that uses image analysis. We compared the RBC, PLT, and WBC test results of the HemoScreen™ with the Sysmex XN device. In the study we analyzed 104 samples from the cardiothoracic, neuro and general intensive care units. The HemoScreen™ technique showed good precision, with total coefficient of variation of 1-2% for RBCs and 3-5% for PLTs. Deming correlations between the HemoScreen and the Sysmex XN instrument analyzer: (WBCHemoScreen™ = 1.061* WBCSysmex - 0.644; r = 0.995), RBC (RBCHemoScreen™ = 0.998* RBCSysmex + 0.049; r = 0.993) for WBC and (PlateletsHemoScreen™ = 1.087* PlateletsSysmex - 14.80; r = 0.994) for PLT. The HemoScreen™ device provided rapid and accurate test results to evaluate the need for RBC and PLT transfusion. This new technology is promising given that it allows the analysis of WBCs, RBCs, and PLTs further out in the healthcare organization compared with laboratory infrastructure based on traditional cell counters.

  • 230.
    Larsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Reference values for fasting insulin in 75 year old females and males2013In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 46, no 12, p. 1125-1127Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES:

    Reference intervals for insulin are often based on fairly small study groups with unknown body mass index (BMI). They are also much younger than most patients seeking care. These values are not optimal for elderly patients, as many biological markers change over time and adequate reference intervals are important for correct clinical decisions.

    DESIGN AND METHODS:

    We studied fasting insulin (f-insulin) values in a cohort of 698 75-year old non-diabetic males and females. The 2.5th and 97.5th percentiles for all individuals, males and females were calculated according to the recommendations of the International Federation of Clinical Chemistry on the statistical treatment of reference intervals.

    RESULTS:

    There was a strong positive correlation between BMI and f-insulin, which led to the calculation of separate reference intervals for individuals with BMI ≤30.

    CONCLUSIONS:

    The reference interval for f-insulin for all study subjects was 1.74-18.27mIU/L and for individuals with BMI ≤30 (n=574) the reference interval was 1.66-15.05mIU/L.

  • 231.
    Larsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Svensson, Michael B
    Ronquist, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Åkerfeldt, Torbjörn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Life style intervention in moderately overweight individuals is associated with decreased levels of cathepsins L and S in plasma2014In: Annals of Clinical and Laboratory Science, ISSN 0091-7370, E-ISSN 1550-8080, Vol. 44, no 3, p. 283-285Article in journal (Refereed)
    Abstract [en]

    Background Adipose tissue cells produce cathepsins L and S, which have proatherogenic effects. Obesity is strongly linked to atherogenesis, cardiovascular morbidity, and mortality.

    Objective The aim of the present study was to see if life style interventions/weight reduction could decrease cathepsin L and S levels in blood plasma.

    Method Study subjects (n=31) were recruited to a life style intervention program aiming at increased physical activity, more healthy eating habits, and weight reduction for most of the participants. Blood samples were collected at inclusion and after 4 and 8 weeks.

    Results Cathepsin L was significantly reduced at 4 weeks (p<0.0001) and 8 weeks (p=0.0004). A similar reduction was also seen for cathepsin S at 4 weeks (p=0.03) and 8 weeks (p=0.008). No significant change in fractalkine values was observed at 4 weeks (p=0.58), but a significant increase was apparent at 8 weeks (p=0.0002).

    Conclusion The intervention program resulted in significant reductions of cathepsin L and S levels in plasma after 4 and 8 weeks of intervention.

  • 232.
    Larsson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Åkerstedt, Torbjörn
    Hansson, Lars-Olof
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Axelsson, John
    Circadian Variability of Cystatin C, Creatinine, and Glomerular Filtration Rate (GFR) in Healthy Men during Normal Sleep and after an Acute Shift of Sleep2008In: Chronobiology International, ISSN 0742-0528, E-ISSN 1525-6073, Vol. 25, no 6, p. 1047-61Article in journal (Refereed)
    Abstract [en]

    The estimation of the glomerular filtration rate (GFR) is essential for the evaluation of patients with kidney disease and for the treatment of patients with medications that are eliminated by the kidneys. Plasma cystatin C has been shown in several studies to be superior to plasma creatinine for the estimation of GFR. However, there is limited information on the circadian variation of cystatin C and estimated GFR using cystatin C (eGFR(CystC)) or "The Modification of Diet in Renal Disease Study" (MDRD) (eGFR(MDRD)) equations. We studied the circadian variation of cystatin C and creatinine during night- and day-sleep conditions in seven healthy volunteers. Serum samples were collected every hour (48 samples per individual) to evaluate the effect of different sampling times on the test results. The median intra-individual coefficients of variations for the studied markers were 4.2% for creatinine, 4.7% for eGFR(MDRD), 5.5% for cystatin C, and 7.7% for eGFR(CystC). Neither cystatin C nor creatinine differed significantly between the night- and day-sleep conditions. Cystatin C differed significantly with time of day (p=.0003), but this was not the case for creatinine (p=.11). The circadian variation of cystatin C was minor. Small but significant increases in creatinine values and a decrease of eGFR(MDRD) were observed after food intake. Thus, cystatin C and creatinine sampling does not have to be restricted to specific times of the day.

  • 233. Larsson, E
    et al.
    Erlandsson Harris, H
    Lorentzen, Johnny
    Larsson, Anders
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. klinisk kemi.
    Klareskog, lars
    Corticosteroid treatment of experimental arthritis retards cartilage destruction as determined by histology and serum COMP2004In: Reumatology, Vol. 43, no 4, p. 428-434Article in journal (Refereed)
  • 234.
    Larsson, Torsten
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Strandberg, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Eriksson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Bondesson, Ulf
    National Veterinary Institute (SVA), Department of Chemistry, Environment and Feed Hygiene, Uppsala, Sweden.
    Lipcsey, Miklós
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Intraosseous samples can be used for opioid measurements: An experimental study in the anaesthetized pig2013In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 73, no 2, p. 102-106Article in journal (Refereed)
    Abstract [en]

    Aim.

    The intraosseous route provides access to the systemic circulation in an emergency situation when other forms of vascular access are unavailable and there is an urgent need for fluid or drug therapy. The intraosseous access has also been used for collecting samples for laboratory testing. A question that may arise in an unconscious or severely exhausted patient is whether this condition is caused by an unknown drug. We aimed to evaluate whether intraosseous samples could be used to measure opioids and to study the accuracy and precision of such measurements.

    Methods.

    Five healthy, anaesthetized pigs were treated with a continuous morphine infusion as part of the anaesthesia procedure. Samples for morphine testing were collected hourly for 6 h from two tibial intraosseous cannulae and a central venous catheter.

    Results.

    The differences in morphine concentrations between the two tibial intraosseous cannulae were less than 10% in 32/33 times. The values were also relatively stable over time.

    Conclusion.

    Our findings suggest that intraosseous samples can be used for the analysis of opioids if an IV route is not available.

  • 235. Leion, Felicia
    et al.
    Hegbrant, Josefine
    den Bakker, Emil
    Jonsson, Magnus
    Abrahamson, Magnus
    Nyman, Ulf
    Björk, Jonas
    Lindström, Veronica
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Bökenkamp, Arend
    Grubb, Anders
    Estimating glomerular filtration rate (GFR) in children. The average between a cystatin C- and a creatinine-based equation improves estimation of GFR in both children and adults and enables diagnosing Shrunken Pore Syndrome.2017In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 77, no 5, p. 338-344Article in journal (Refereed)
    Abstract [en]

    Estimating glomerular filtration rate (GFR) in adults by using the average of values obtained by a cystatin C- (eGFRcystatin C) and a creatinine-based (eGFRcreatinine) equation shows at least the same diagnostic performance as GFR estimates obtained by equations using only one of these analytes or by complex equations using both analytes. Comparison of eGFRcystatin C and eGFRcreatinine plays a pivotal role in the diagnosis of Shrunken Pore Syndrome, where low eGFRcystatin C compared to eGFRcreatinine has been associated with higher mortality in adults. The present study was undertaken to elucidate if this concept can also be applied in children. Using iohexol and inulin clearance as gold standard in 702 children, we studied the diagnostic performance of 10 creatinine-based, 5 cystatin C-based and 3 combined cystatin C-creatinine eGFR equations and compared them to the result of the average of 9 pairs of a eGFRcystatin C and a eGFRcreatinine estimate. While creatinine-based GFR estimations are unsuitable in children unless calibrated in a pediatric or mixed pediatric-adult population, cystatin C-based estimations in general performed well in children. The average of a suitable creatinine-based and a cystatin C-based equation generally displayed a better diagnostic performance than estimates obtained by equations using only one of these analytes or by complex equations using both analytes. Comparing eGFRcystatin and eGFRcreatinine may help identify pediatric patients with Shrunken Pore Syndrome.

  • 236. Ligthart, Symen
    et al.
    Vaez, Ahmad
    Võsa, Urmo
    Stathopoulou, Maria G
    de Vries, Paul S
    Prins, Bram P
    Van der Most, Peter J
    Tanaka, Toshiko
    Naderi, Elnaz
    Rose, Lynda M
    Wu, Ying
    Karlsson, Robert
    Barbalic, Maja
    Lin, Honghuang
    Pool, René
    Zhu, Gu
    Macé, Aurélien
    Sidore, Carlo
    Trompet, Stella
    Mangino, Massimo
    Sabater-Lleal, Maria
    Kemp, John P
    Abbasi, Ali
    Kacprowski, Tim
    Verweij, Niek
    Smith, Albert V
    Huang, Tao
    Marzi, Carola
    Feitosa, Mary F
    Lohman, Kurt K
    Kleber, Marcus E
    Milaneschi, Yuri
    Mueller, Christian
    Huq, Mahmudul
    Vlachopoulou, Efthymia
    Lyytikäinen, Leo-Pekka
    Oldmeadow, Christopher
    Deelen, Joris
    Perola, Markus
    Zhao, Jing Hua
    Feenstra, Bjarke
    Amini, Marzyeh
    Lahti, Jari
    Schraut, Katharina E
    Fornage, Myriam
    Suktitipat, Bhoom
    Chen, Wei-Min
    Li, Xiaohui
    Nutile, Teresa
    Malerba, Giovanni
    Luan, Jian'an
    Bak, Tom
    Schork, Nicholas
    Del Greco M, Fabiola
    Thiering, Elisabeth
    Mahajan, Anubha
    Marioni, Riccardo E
    Mihailov, Evelin
    Eriksson, Joel
    Ozel, Ayse Bilge
    Zhang, Weihua
    Nethander, Maria
    Cheng, Yu-Ching
    Aslibekyan, Stella
    Ang, Wei
    Gandin, Ilaria
    Yengo, Loïc
    Portas, Laura
    Kooperberg, Charles
    Hofer, Edith
    Rajan, Kumar B
    Schurmann, Claudia
    den Hollander, Wouter
    Ahluwalia, Tarunveer S
    Zhao, Jing
    Draisma, Harmen H M
    Ford, Ian
    Timpson, Nicholas
    Teumer, Alexander
    Huang, Hongyan
    Wahl, Simone
    Liu, YongMei
    Huang, Jie
    Uh, Hae-Won
    Geller, Frank
    Joshi, Peter K
    Yanek, Lisa R
    Trabetti, Elisabetta
    Lehne, Benjamin
    Vozzi, Diego
    Verbanck, Marie
    Biino, Ginevra
    Saba, Yasaman
    Meulenbelt, Ingrid
    O'Connell, Jeff R
    Laakso, Markku
    Giulianini, Franco
    Magnusson, Patrik K E
    Ballantyne, Christie M
    Hottenga, Jouke Jan
    Montgomery, Grant W
    Rivadineira, Fernando
    Rueedi, Rico
    Steri, Maristella
    Herzig, Karl-Heinz
    Stott, David J
    Menni, Cristina
    Frånberg, Mattias
    St Pourcain, Beate
    Felix, Stephan B
    Pers, Tune H
    Bakker, Stephan J L
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    Peters, Annette
    Vaidya, Dhananjay
    Delgado, Graciela
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    Großmann, Vera
    Sinisalo, Juha
    Seppälä, Ilkka
    Williams, Stephen R
    Holliday, Elizabeth G
    Moed, Matthijs
    Langenberg, Claudia
    Räikkönen, Katri
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    Campbell, Harry
    Sale, Michele M
    Chen, Yii-Der I
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    Smith, Erin N
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    Hernandez, Dena
    Tiesler, Carla M T
    Giedraitis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Liewald, David
    Fischer, Krista
    Mellström, Dan
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Wang, Yunmei
    Scott, William R
    Lorentzon, Matthias
    Beilby, John
    Ryan, Kathleen A
    Pennell, Craig E
    Vuckovic, Dragana
    Balkau, Beverly
    Concas, Maria Pina
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    Kutalik, Zoltán
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    Karhunen, Ville
    Kritchevsky, Stephen B
    Sattar, Naveed
    Lachance, Genevieve
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    Attia, John R
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    Kajantie, Eero
    Sorice, Rossella
    Gambaro, Giovanni
    Scott, Robert A
    Hicks, Andrew A
    Ferrucci, Luigi
    Standl, Marie
    Lindgren, Cecilia M
    Starr, John M
    Karlsson, Magnus
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Li, Jun Z
    Chambers, John C
    Mori, Trevor A
    de Geus, Eco J C N
    Heath, Andrew C
    Martin, Nicholas G
    Auvinen, Juha
    Buckley, Brendan M
    de Craen, Anton J M
    Waldenberger, Melanie
    Strauch, Konstantin
    Meitinger, Thomas
    Scott, Rodney J
    McEvoy, Mark
    Beekman, Marian
    Bombieri, Cristina
    Ridker, Paul M
    Mohlke, Karen L
    Pedersen, Nancy L
    Morrison, Alanna C
    Boomsma, Dorret I
    Whitfield, John B
    Strachan, David P
    Hofman, Albert
    Vollenweider, Peter
    Cucca, Francesco
    Jarvelin, Marjo-Riitta
    Jukema, J Wouter
    Spector, Tim D
    Hamsten, Anders
    Zeller, Tanja
    Uitterlinden, André G
    Nauck, Matthias
    Gudnason, Vilmundur
    Qi, Lu
    Grallert, Harald
    Borecki, Ingrid B
    Rotter, Jerome I
    März, Winfried
    Wild, Philipp S
    Lokki, Marja-Liisa
    Boyle, Michael
    Salomaa, Veikko
    Melbye, Mads
    Eriksson, Johan G
    Wilson, James F
    Penninx, Brenda W J H
    Becker, Diane M
    Worrall, Bradford B
    Gibson, Greg
    Krauss, Ronald M
    Ciullo, Marina
    Zaza, Gianluigi
    Wareham, Nicholas J
    Oldehinkel, Albertine J
    Palmer, Lyle J
    Murray, Sarah S
    Pramstaller, Peter P
    Bandinelli, Stefania
    Heinrich, Joachim
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Stanford Univ, Sch Med, Div Cardiovasc Med, Dept Med, Stanford, CA USA; Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA USA.
    Deary, Ian J
    Mägi, Reedik
    Vandenput, Liesbeth
    van der Harst, Pim
    Desch, Karl C
    Kooner, Jaspal S
    Ohlsson, Claes
    Hayward, Caroline
    Lehtimäki, Terho
    Shuldiner, Alan R
    Arnett, Donna K
    Beilin, Lawrence J
    Robino, Antonietta
    Froguel, Philippe
    Pirastu, Mario
    Jess, Tine
    Koenig, Wolfgang
    Loos, Ruth J F
    Evans, Denis A
    Schmidt, Helena
    Smith, George Davey
    Slagboom, P Eline
    Eiriksdottir, Gudny
    Morris, Andrew P
    Psaty, Bruce M
    Tracy, Russell P
    Nolte, Ilja M
    Boerwinkle, Eric
    Visvikis-Siest, Sophie
    Reiner, Alex P
    Gross, Myron
    Bis, Joshua C
    Franke, Lude
    Franco, Oscar H
    Benjamin, Emelia J
    Chasman, Daniel I
    Dupuis, Josée
    Snieder, Harold
    Dehghan, Abbas
    Alizadeh, Behrooz Z
    Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders2018In: American Journal of Human Genetics, ISSN 0002-9297, E-ISSN 1537-6605, Vol. 103, no 5, p. 691-706, article id S0002-9297(18)30320-3Article in journal (Refereed)
    Abstract [en]

    C-reactive protein (CRP) is a sensitive biomarker of chronic low-grade inflammation and is associated with multiple complex diseases. The genetic determinants of chronic inflammation remain largely unknown, and the causal role of CRP in several clinical outcomes is debated. We performed two genome-wide association studies (GWASs), on HapMap and 1000 Genomes imputed data, of circulating amounts of CRP by using data from 88 studies comprising 204,402 European individuals. Additionally, we performed in silico functional analyses and Mendelian randomization analyses with several clinical outcomes. The GWAS meta-analyses of CRP revealed 58 distinct genetic loci (p < 5 × 10-8). After adjustment for body mass index in the regression analysis, the associations at all except three loci remained. The lead variants at the distinct loci explained up to 7.0% of the variance in circulating amounts of CRP. We identified 66 gene sets that were organized in two substantially correlated clusters, one mainly composed of immune pathways and the other characterized by metabolic pathways in the liver. Mendelian randomization analyses revealed a causal protective effect of CRP on schizophrenia and a risk-increasing effect on bipolar disorder. Our findings provide further insights into the biology of inflammation and could lead to interventions for treating inflammation and its clinical consequences.

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    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
    Bhutta, Zulficiar A.
    Aga Khan Univ, Ctr Excellence Women & Child Hlth, Karachi, Pakistan.;Hosp Sick Children, Ctr Global Child Hlth, Toronto, ON, Canada..
    Dandona, Lalit
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA.;Publ Hlth Fdn India, New Delhi, India..
    Forouzanfar, Mohammad H.
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
    Fullman, Nancy
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
    Gething, Peter W.
    Univ Oxford, Dept Zool, Oxford, England..
    Goldberg, Ellen M.
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
    Hay, Simon I.
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
    Holmberg, Mollie
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
    Kinfu, Yohannes
    Univ Canberra, Fac Hlth, Ctr Res & Act Publ Hlth, Canberra, ACT, Australia..
    Kutz, Michael J.
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
    Larson, Heidi J.
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA.;London Sch Hyg & Trop Med, Dept Infect Dis Epidemiol, London, England..
    Liang, Xiaofeng
    Chinese Ctr Dis Control & Prevent, Beijing, Peoples R China..
    Lopez, Alan D.
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA.;Univ Melbourne, Melbourne Sch Populat & Global Hlth, Melbourne, Vic, Australia..
    Lozano, Rafael
    Natl Inst Publ Hlth, Cuernavaca, Morelos, Mexico..
    McNellan, Claire R.
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
    Mokdad, Ali H.
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
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    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
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    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
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    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
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    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
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    Harvard Univ, Dept Global Hlth & Populat, Harvard TH Chan Sch Publ Hlth, Boston, MA 02115 USA..
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    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
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    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
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    Univ Queensland, Sch Publ Hlth, Brisbane, Qld, Australia..
    Abate, Kalkidan Hassen
    Jimma Univ, Jimma, Ethiopia..
    Abbafati, Cristiana
    Univ Roma La Sapienza, Rome, Italy..
    Abbas, Kaja M.
    Virginia Tech, Blacksburg, VA USA..
    Abd-Allah, Foad
    Cairo Univ, Dept Neurol, Cairo, Egypt..
    Abdulle, Abdishakur M.
    New York Univ Abu Dhabi, Abu Dhabi, U Arab Emirates..
    Abraham, Biju
    NMSM Govt Coll Kalpetta, Kalpetta, Kerala, India..
    Abubakar, Ibrahim
    UCL, Inst Global Hlth, London, England..
    Abu-Raddad, Laith J.
    Weill Cornell Med Coll Qatar, Infect Dis Epidemiol Grp, Doha, Qatar..
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    Birzeit Univ, Inst Community & Publ Hlth, Ramallah, Israel..
    Abyu, Gebre Yitayih
    Mekelle Univ, Mekelle, Ethiopia..
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    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
    Adebiyi, Akindele Olupelumi
    Univ Ibadan, Coll Med, Ibadan, Nigeria.;Univ Coll Hosp, Ibadan, Nigeria..
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    Olabisi Onabanjo Univ, Ago Iwoye, Nigeria..
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    Direct Dist Sanitaire Haho, Notse, Togo.;Univ Lome, Fac Sci Sante, Lome, Togo..
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    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA.;Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA..
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    McMaster Univ, Hamilton, ON, Canada..
    Agrawal, Anurag
    CSIR Inst Genom & Integrat Biol, Delhi, India.;Baylor Coll Med, Dept Internal Med, Houston, TX 77030 USA..
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    Ahmadieh, Hamid
    Ahmed, Kedir Yimam
    Debre Markos Univ, Debre Markos, Ethiopia..
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    Univ Rhode Isl, Kingston, RI 02881 USA..
    Akinyemi, Rufus Olusola
    Univ Ibadan, Ibadan, Nigeria.;Newcastle Univ, Newcastle Upon Tyne, Tyne & Wear, England..
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    Akseer, Nadia
    Hosp Sick Children, Ctr Global Child Hlth, Toronto, ON, Canada..
    Al-Aly, Ziyad
    Washington Univ, St Louis, MO USA..
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    Univ Melbourne, Murdoch Childrens Res Inst, Melbourne, Vic, Australia.;Univ Melbourne, Melbourne, Vic, Australia..
    Alam, Uzma
    Int Ctr Humanitarian Affairs, Nairobi, Kenya..
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    AlBuhairan, Fadia S.
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    King Saud Univ, Riyadh, Saudi Arabia..
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    UCL, Inst Global Hlth, London, England.;UCL, Ctr Publ Hlth Data Sci, Inst Hlth Informat, London, England.;UCL, Farr Inst Hlth Informat Res, London, England..
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    Debre Markos Univ, Debre Markos, Ethiopia..
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    Univ Oxford, Oxford, England..
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    Luxembourg Inst Hlth, Strassen, Luxembourg..
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    King Saud Univ, King Khalid Univ Hosp, Riyadh, Saudi Arabia..
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    Univ Lorraine, Sch Publ Hlth, Nancy, France..
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    Allen, Christine
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
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    Minist Hlth, Jeddah, Saudi Arabia..
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    King Saud Univ, Riyadh, Saudi Arabia..
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    Govt Madrid, Madrid, Spain..
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    Univ Cartagena, Cartagena, Colombia..
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    Univ Adelaide, Sch Med, Adelaide, SA, Australia.;Bahir Dar Univ, Coll Med & Hlth Sci, Bahir Dar, Ethiopia..
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    Dignitas Int, Zomba, Malawi..
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    Univ Cape Coast, Cape Coast, Ghana..
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    Kurdistan Univ Med Sci, Environm Hlth Res Ctr, Sanandaj, Iran.;Swiss Trop & Publ Hlth Inst, Dept Epidemiol & Publ Hlth, Basel, Switzerland..
    Ammar, Walid
    Amrock, Stephen Marc
    Oregon Hlth & Sci Univ, Portland, OR 97201 USA..
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    Aalborg Univ, Fac Med, Dept Hlth Sci & Technol, Ctr Sensory Motor Interact, Aalborg, Denmark..
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    Univ Washington, Seattle, WA 98121 USA..
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    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
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    Univ Philippines Manila, Coll Publ Hlth, Dept Hlth Policy & Adm, Manila, Philippines..
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    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Dalarna Univ, Falun, Sweden..
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    Univ Manitoba, Winnipeg, MB, Canada..
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    Qom Univ Med Sci, Sch Paramed, Dept Emergency Med, Qom, Iran..
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    South Asian Publ Hlth Forum, Islamabad, Pakistan..
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    Taipei Med Univ, Grad Inst Biomed Informat, Taipei, Taiwan..
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    Inst Rech Clin Benin, Cotonou, Benin.;LERAS Afrique, Parakou, Benin..
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    Sanjay Gandhi Postgrad Inst Med Sci, Lucknow, Uttar Pradesh, India..
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    La Trobe Univ, Judith Lumley Ctr Mother Infant & Family Hlth Res, Melbourne, Vic, Australia.;Peruvian Natl Inst Hlth, Lima, Peru..
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    Univ Melbourne, Dept Paediat, Melbourne, Vic, Australia.;Univ Melbourne, Murdoch Childrens Res Inst, Melbourne, Vic, Australia.;South Australian Hlth & Med Res Inst, Wardliparingga Aboriginal Res Unit, Adelaide, SA, Australia.;Burnet Inst, Ctr Int Hlth, Melbourne, Vic, Australia..
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    Univ Management & Technol, Sch Hlth Sci, Lahore, Pakistan..
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    Publ Hlth Agcy Canada, Toronto, ON, Canada..
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    Sri Ramachandra Univ, Dept Environm Hlth Engn, Chennai, Tamil Nadu, India..
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    UCL, Farr Inst Hlth Informat Res, London, England..
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    Univ Belgrade, Fac Med, Belgrade, Serbia..
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    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
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    Univ Auckland, Sch Psychol, Auckland, New Zealand..
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    Harvard Univ, Harvard TH Chan Sch Publ Hlth, Boston, MA 02115 USA.;Africa Hlth Res Inst, Mtubatuba, South Africa.;Heidelberg Univ, Inst Publ Hlth, Heidelberg, Germany..
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    Pontificia Univ Javeriana, Sch Engn, Dept Ind Engn, Bogota, Colombia..
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    Natl Inst Publ Hlth, Cuernavaca, Morelos, Mexico..
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    Stanford Univ, Stanford, CA 94305 USA..
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    Mekelle Univ, Mekelle, Ethiopia..
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    Charles R Drew Univ Med & Sci, Coll Med, 1621 E 120th St, Los Angeles, CA 90059 USA.;Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.;Kermanshah Univ Med Sci, Kermanshah, Iran..
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    Univ Oxford, Ho Chi Minh City, Vietnam..
    Bedi, Neeraj
    Coll Publ Hlth & Trop Med, Jazan, Saudi Arabia..
    Beghi, Ettore
    IRCCS Ist Ric Farmacol Mario Negri, Milan, Italy..
    Bejot, Yannick
    Univ Burgundy, Univ Hosp & Med Sch Dijon, Dijon, France..
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    Yale Univ, Sch Med, New Haven, CT USA..
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    Univ Alberta, Edmonton, AB, Canada..
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    Univ Oxford, Oxford, England..
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    Univ Sao Paulo, Sao Paulo, Brazil..
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    UCL, Dept Epidemiol & Publ Hlth, London, England.;NYU, Coll Dent, Dept Epidemiol & Hlth Promot, New York, NY USA..
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    Debre Berhane Univ, Debre Berhan, Ethiopia..
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    Kings Coll London, London, England..
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    Univ Andes, Bogota, Colombia. Haramaya Univ, Coll Hlth & Med Sci, Harar, Ethiopia..
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    Mekelle Univ, Mekelle, Ethiopia..
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    Haramaya Univ, Harar, Ethiopia..
    Bhala, Neeraj
    Queen Elizabeth Hosp Birmingham, Birmingham, W Midlands, England.;Univ Otago, Sch Med, Wellington, New Zealand..
    Bhatt, Samir
    Imperial Coll, London, England..
    Biadgilign, Sibhatu
    Bienhoff, Kelly A.
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
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    Academician VI Shumakov Fed Res Ctr Transplantol, Issues Transplanted Kidney, Dept Nephrol, Moscow, Russia..
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    Harvard Univ, Harvard Med Sch, Dept Global Hlth & Social Med, Boston, MA 02115 USA.;Dartmouth Coll, Dept Pediat, Hanover, NH 03755 USA.;Dartmouth Coll, Dartmouth Inst Hlth Policy & Clin Practice, Geisel Sch Med, Hanover, NH 03755 USA.;Univ Global Hlth Equ, Kigali, Rwanda..
    Bisanzio, Donal
    Univ Oxford, Nuffield Dept Med, Oxford, England..
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    Univ Oslo, Dept Community Med, Oslo, Norway..
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    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
    Bourne, Rupert R. A.
    Anglia Ruskin Univ, Vis Eye Res Unit, Cambridge, England..
    Brainin, Michael
    Danube Univ Krems, Krems, Austria..
    Brauer, Michael
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA.;Univ British Columbia, Vancouver, BC, Canada..
    Brazinova, Alexandra
    Trnava Univ, Dept Publ Hlth, Fac Hlth Sci & Social Work, Trnava, Slovakia.;Int Neurotrauma Res Org, Vienna, Austria..
    Breitborde, Nicholas J. K.
    Ohio State Univ, Coll Med, Columbus, OH 43210 USA..
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    Technion, Haifa, Israel..
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    Univ Leicester, Leicester, Leics, England..
    Buchbinder, Rachelle
    Cabrini Inst, Monash Dept Clin Epidemiol, Melbourne, Vic, Australia.;Monash Univ, Dept Epidemiol & Prevent Med, Melbourne, Vic, Australia..
    Butt, Zahid A.
    Al Shifa Trust Eye Hosp, Rawalpindi, Pakistan..
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    Harvard Univ, Harvard TH Chan Sch Publ Hlth, Boston, MA 02115 USA.;Dalhousie Univ, Halifax, NS, Canada..
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    Natl Inst Publ Hlth, Cuernavaca, Morelos, Mexico.;Harvard Univ, Harvard TH Chan Sch Publ Hlth, Boston, MA 02115 USA..
    Campuzano, Julio Cesar
    Natl Inst Publ Hlth, Cuernavaca, Morelos, Mexico..
    Carabin, Helene
    Univ Oklahoma, Hlth Sci Ctr, Dept Biostat & Epidemiol, Oklahoma City, OK USA..
    Cardenas, Rosario
    Metropolitan Autonomous Univ, Mexico City, DF, Mexico..
    Carrero, Juan Jesus
    Carter, Austin
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
    Casey, Daniel
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
    Caso, Valeria
    Univ Perugia, Stroke Unit, Perugia, Italy..
    Castaneda-Orjuela, Carlos A.
    Inst Nacl Salud, Colombian Natl Hlth Observ, Bogota, Colombia.;Univ Nacl Colombia, Dept Publ Hlth, Epidemiol & Publ Hlth Evaluat Grp, Bogota, Colombia..
    Rivas, Jacqueline Castillo
    Caja Costarricense Seguro Social, San Jose, Costa Rica.;Univ Costa Rica, San Pedro, Montes De Oca, Costa Rica..
    Catala-Lopez, Ferran
    Cavalleri, Fiorella
    Cecilio, Pedro
    Chang, Hsing-Yi
    Chang, Jung-Chen
    Charlson, Fiona J.
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA.;Univ Queensland, Sch Publ Hlth, Brisbane, Qld, Australia..
    Che, Xuan
    Chen, Alan Zian
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
    Chiang, Peggy Pei-Chia
    Chibalabala, Mirriam
    Chisumpa, Vesper Hichilombwe
    Choi, Jee-Young Jasmine
    Chowdhury, Rajiv
    Christensen, Hanne
    Ciobanu, Liliana G.
    Univ Adelaide, Adelaide, SA, Australia..
    Cirillo, Massimo
    Coates, Matthew M.
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
    Coggeshall, Megan
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
    Cohen, Aaron J.
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
    Cooke, Graham S.
    Cooper, Cyrus
    Univ Oxford, NIHR Musculoskeletal Biomed Res Ctr, Oxford, England..
    Cooper, Leslie Trumbull
    Cowie, Benjamin C.
    Univ Melbourne, Peter Doherty Inst Infect & Immun, Melbourne, Vic, Australia..
    Crump, John A.
    Damtew, Solomon Abrha
    Dandona, Rakhi
    Publ Hlth Fdn India, New Delhi, India..
    Dargan, Paul I.
    das Neves, Jose
    Davis, Adrian C.
    Davletov, Kairat
    de Castro, E. Filipa
    De Leo, Diego
    Degenhardt, Louisa
    Del Gobbo, Liana C.
    Stanford Univ, Stanford, CA 94305 USA..
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    Derrett, Sarah
    Jarlais, Don C. Des
    Deshpande, Aniruddha
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
    deVeber, Gabrielle A.
    Hosp Sick Children, Ctr Global Child Hlth, Toronto, ON, Canada..
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    Dharmaratne, Samath D.
    Dhillon, Preet K.
    Ding, Eric L.
    Harvard Univ, Harvard TH Chan Sch Publ Hlth, Boston, MA 02115 USA..
    Dorsey, E. Ray
    Doyle, Kerrie E.
    Driscoll, Tim R.
    Duan, Leilei
    Chinese Ctr Dis Control & Prevent, Natl Ctr Chron & Noncommun Dis Control & Prevent, Beijing, Peoples R China..
    Dubey, Manisha
    Duncan, Bruce Bartholow
    Ebrahimi, Hedyeh
    Endries, Aman Yesuf
    Ermakov, Sergey Petrovich
    Erskine, Holly E.
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA.;Univ Queensland, Sch Publ Hlth, Brisbane, Qld, Australia..
    Eshrati, Babak
    Esteghamati, Alireza
    Fahimi, Saman
    Farid, Talha A.
    Farinha, Carla Sofia e Sa
    Faro, Andre
    Farvid, Maryam S.
    Harvard Univ, Harvard TH Chan Sch Publ Hlth, Boston, MA 02115 USA..
    Farzadfar, Farshad
    Feigin, Valery L.
    Felicio, Manuela Mendonca
    Fereshtehnejad, Seyed-Mohammad
    Fernandes, Jefferson G.
    Fernandes, Joao C.
    Ferrari, Alize J.
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA.;Univ Queensland, Sch Publ Hlth, Brisbane, Qld, Australia..
    Fischer, Florian
    Fitchett, Joseph R. A.
    Harvard Univ, Boston, MA 02115 USA..
    Fitzmaurice, Christina
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
    Foigt, Nataliya
    Foreman, Kyle
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
    Fowkes, F. Gerry R.
    Franca, Elisabeth Barboza
    Franklin, Richard C.
    Fraser, Maya
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
    Friedman, Joseph
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
    Frostad, Joseph
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
    Furst, Thomas
    Swiss Trop & Publ Hlth Inst, Dept Epidemiol & Publ Hlth, Basel, Switzerland..
    Gabbe, Belinda
    Monash Univ, Sch Publ Hlth & Prevent Med, Melbourne, Vic, Australia..
    Garcia-Basteiro, Alberto L.
    Gebre, Teshome
    Gebrehiwot, Tsegaye Tewelde
    Jimma Univ, Jimma, Ethiopia..
    Gebremedhin, Amanuel Tesfay
    Jimma Univ, Jimma, Ethiopia..
    Gebru, Alemseged Aregay
    Mekelle Univ, Mekelle, Ethiopia..
    Gessner, Bradford D.
    Gillum, Richard F.
    Ginawi, Ibrahim Abdelmageem Mohamed
    Giref, Ababi Zergaw
    Giroud, Maurice
    Gishu, Melkamu Dedefo
    Godwin, William
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
    Gona, Philimon
    Goodridge, Amador
    Gopalani, Sameer Vali
    Gotay, Carolyn C.
    Univ British Columbia, Vancouver, BC, Canada..
    Goto, Atsushi
    Gouda, Hebe N.
    Univ Queensland, Brisbane, Qld, Australia..
    Graetz, Nicholas
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
    Greenwell, Karen Fern
    Griswold, Max
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
    Guo, Yuming
    Univ Queensland, Brisbane, Qld, Australia..
    Gupta, Rahul
    Gupta, Rajeev
    Gupta, Vipin
    Gutierrez, Reyna A.
    Gyawali, Bishal
    Haagsma, Juanita A.
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
    Haakenstad, Annie
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA.;Harvard Univ, Harvard TH Chan Sch Publ Hlth, Boston, MA 02115 USA..
    Hafezi-Nejad, Nima
    Haile, Demewoz
    Hailu, Gessessew Bugssa
    Mekelle Univ, Mekelle, Ethiopia..
    Halasa, Yara A.
    Hamadeh, Randah Ribhi
    Hamidi, Samer
    Hammami, Mouhanad
    Hankey, Graeme J.
    Harb, Hilda L.
    Minist Publ Hlth, Beirut, Lebanon..
    Haro, Josep Maria
    Hassanvand, Mohammad Sadegh
    Havmoeller, Rasmus
    Heredia-Pi, Ileana Beatriz
    Natl Inst Publ Hlth, Cuernavaca, Morelos, Mexico..
    Hoek, Hans W.
    Horino, Masako
    Horita, Nobuyuki
    Hosgood, H. Dean
    Hoy, Damian G.
    Htet, Aung Soe
    Univ Oslo, Oslo, Norway..
    Hu, Guoqing
    Huang, Hsiang
    Iburg, Kim Moesgaard
    Idrisov, Bulat T.
    Inoue, Manami
    Islami, Farhad
    Jacobs, Troy A.
    Jacobsen, Kathryn H.
    Jahanmehr, Nader
    Jakovljevic, Mihajlo B.
    James, Peter
    Harvard Univ, Dept Epidemiol, Boston, MA 02115 USA.;Harvard Univ, Channing Div Network Med, Brigham & Womens Hosp, Harvard Med Sch, Boston, MA 02115 USA..
    Jansen, Henrica A. F. M.
    Javanbakht, Mehdi
    Jayatilleke, Achala Upendra
    Jee, Sun Ha
    Jeemon, Panniyammakal
    Publ Hlth Fdn India, Ctr Control Chron Condit, New Delhi, India..
    Jha, Vivekanand
    Univ Oxford, Oxford, England..
    Jiang, Ying
    Jibat, Tariku
    Jin, Ye
    Chinese Ctr Dis Control & Prevent, Natl Ctr Chron & Noncommun Dis Control & Prevent, Beijing, Peoples R China..
    Jonas, Jost B.
    Kabir, Zubair
    Kalkonde, Yogeshwar
    Kamal, Ritul
    Kan, Haidong
    Kandel, Amit
    Karch, Andre
    Karema, Corine Kakizi
    Swiss Trop & Publ Hlth Inst, Basel, Switzerland..
    KarimIchani, Chante
    Karunapema, Palitha
    Kasaeian, Amir
    Kassebaum, Nicholas J.
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
    Kaul, Anil
    Kawakami, Norito
    Kayibanda, Jeanne Francoise
    Keiyoro, Peter Njenga
    Kemmer, Laura
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
    Kemp, Andrew Haddon
    Kengne, Andre Pascal
    Keren, Andre
    Kesavachandran, Chandrasekharan Nair
    Khader, Yousef Saleh
    Khan, Abdur Rahman
    Khan, Ejaz Ahmad
    Khan, Gulfaraz
    Khang, Young-Ho
    Khoja, Tawfik Ahmed Muthafer
    Khosravi, Ardeshir
    Khubchandani, Jagdish
    Kieling, Christian
    Kim, Cho-il
    Kim, Daniel
    Kim, Sungroul
    Kim, Yun Jin
    Kimokoti, Ruth W.
    Kissoon, Niranjan
    Univ British Columbia, Vancouver, BC, Canada..
    Kivipelto, Miia
    Knibbs, Luke D.
    Univ Queensland, Sch Publ Hlth, Brisbane, Qld, Australia..
    Kokubo, Yoshihiro
    Kolte, Dhaval
    Kosen, Soewarta
    Kotsakis, Georgios A.
    Univ Washington, Sch Dent, Seattle, WA 98121 USA..
    Koul, Parvaiz A.
    Koyanagi, Ai
    Kravchenko, Michael
    Krueger, Hans
    Univ British Columbia, Sch Populat & Publ Hlth, Vancouver, BC, Canada..
    Defo, Barthelemy Kuate
    Kuchenbecker, Ricardo S.
    Kuipers, Ernst J.
    Kulikoff, Xie Rachel
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
    Kulkarni, Veena S.
    Kumar, G. Anil
    Publ Hlth Fdn India, New Delhi, India..
    Kwan, Gene F.
    Kyu, Hmwe H.
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
    Lal, Aparna
    Lal, Dharmesh Kumar
    Lalloo, Ratilal
    Univ Queensland, Sch Dent, Brisbane, Qld, Australia..
    Lam, Hilton
    Lan, Qing
    Langan, Sinead M.
    London Sch Hyg & Trop Med, London, England..
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Laryea, Dennis Odai
    Latif, Asma Abdul
    Leasher, Janet L.
    Leigh, James
    Leinsalu, Mall
    Leung, Janni
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA.;Univ Queensland, Sch Publ Hlth, Brisbane, Qld, Australia..
    Leung, Ricky
    Levi, Miriam
    Li, Yichong
    Li, Yongmei
    Lind, Margaret
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
    Linn, Shai
    Lipshultz, Steven E.
    Liu, Patrick Y.
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
    Liu, Shiwei
    Chinese Ctr Dis Control & Prevent, Natl Ctr Chron & Noncommun Dis Control & Prevent, Beijing, Peoples R China..
    Liu, Yang
    Chinese Ctr Dis Control & Prevent, Natl Ctr Chron & Noncommun Dis Control & Prevent, Beijing, Peoples R China..
    Lloyd, Belinda K.
    Lo, Loon-Tzian
    Logroscino, Giancarlo
    Lotufo, Paulo A.
    Univ Sao Paulo, Sao Paulo, Brazil..
    Lucas, Robyn M.
    Lunevicius, Raimundas
    Abd El Razek, Mohammed Magdy
    Magis-Rodriguez, Carlos
    Mandavi, Mandi
    Majdan, Marek
    Trnava Univ, Dept Publ Hlth, Fac Hlth Sci & Social Work, Trnava, Slovakia..
    Majeed, Azeem
    Malekzadeh, Reza
    Malta, Deborah Carvalho
    Mapoma, Chabila C.
    Margolis, David Joel
    Martin, Randall V.
    Dalhousie Univ, Halifax, NS, Canada..
    Martinez-Raga, Jose
    Masiye, Felix
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
    Mason-Jones, Amanda J.
    Massano, Joao
    Matzopoulos, Richard
    Mayosi, Bongani M.
    McGrath, John J.
    Univ Queensland, Brisbane, Qld, Australia..
    McKee, Martin
    London Sch Hyg & Trop Med, London, England..
    Meaney, Peter A.
    Mehari, Alem
    Mekonnen, Alemayehu B.
    Melaku, Yohannes Adama
    Mekelle Univ, Sch Publ Hlth, Mekelle, Ethiopia.;Univ Adelaide, Sch Med, Adelaide, SA, Australia..
    Memiah, Peter
    Memish, Ziad A.
    Mendoza, Walter
    Mensink, Gert B. M.
    Meretoja, Atte
    Univ Melbourne, Dept Med, Melbourne, Vic, Australia..
    Meretoja, Tuomo J.
    Mesfin, Yonatan Moges
    Haramaya Univ, Harar, Ethiopia..
    Mhimbira, Francis Apolinary
    Micha, Renata
    Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA..
    Miller, Ted R.
    Mills, Edward J.
    Mirarefin, Mojde
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
    Misganaw, Awoke
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
    Mitchell, Philip B.
    Mock, Charles N.
    Univ Washington, Harborview Injury Prevent & Res Ctr, Seattle, WA 98121 USA..
    Mohammadi, Alireza
    Mohammed, Shafiu
    Heidelberg Univ, Inst Publ Hlth, Heidelberg, Germany..
    Monasta, Lorenzo
    Monis, Jonathan de la Cruz
    Hernandez, Julio Cesar Montanez
    Natl Inst Publ Hlth, Cuernavaca, Morelos, Mexico..
    Montico, Marcella
    Moradi-Lakeh, Maziar
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
    Morawska, Lidia
    Mori, Rintaro
    Mueller, Ulrich O.
    Murdoch, Michele E.
    Murimira, Brighton
    Murray, Joseph
    Murthy, Gudlavalleti Venkata Satyanarayana
    London Sch Hyg & Trop Med, London, England..
    Murthy, Srinivas
    Univ British Columbia, Vancouver, BC, Canada..
    Musa, Kamarul Imran
    Nachega, Jean B.
    Nagel, Gabriele
    Naidoo, Kovin S.
    Naldi, Luigi
    Nangia, Vinay
    Neal, Bruce
    Nejjari, Chakib
    Newton, Charles R.
    Newton, John N.
    Ngalesoni, Frida Namnyak
    Nguhiu, Peter
    Nguyen, Grant
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
    Nguyen, Quyen Le
    Nisar, Muhammad Imran
    Aga Khan Univ, Karachi, Pakistan..
    Pete, Patrick Martial Nkamedjie
    Nolte, Sandra
    Nomura, Marika
    Norheim, Ole F.
    Norrving, Bo
    Obermeyer, Carla Makhlouf
    Ogbo, Felix Akpojene
    Oh, In-Hwan
    Oladimeji, Olanrewaju
    Olivares, Pedro R.
    Olusanya, Bolajoko Olubukunola
    Olusanya, Jacob Olusegun
    Opio, John Nelson
    Oren, Eyal
    Ortiz, Alberto
    Osborne, Richard H.
    Ota, Erika
    Owolabi, Mayowa O.
    Univ Ibadan, Dept Med, Ibadan, Nigeria..
    Mahesh, P. A.
    Park, Eun-Kee
    Park, Hye-Youn
    Parry, Charles D.
    Parsaeian, Mahboubeh
    Patel, Tejas
    Patel, Vikram
    London Sch Hyg & Trop Med, Ctr Global Mental Hlth, London, England..
    Caicedo, Angel J. Paternina
    Univ Cartagena, Cartagena, Colombia..
    Patil, Snehal T.
    Patten, Scott B.
    Patton, George C.
    Univ Melbourne, Murdoch Childrens Res Inst, Melbourne, Vic, Australia..
    Paudel, Deepak
    Pedro, Joao Mario
    Pereira, David M.
    Perico, Norberto
    Pesudovs, Konrad
    Petzold, Max
    Phillips, Michael Robert
    Piel, Frederic B.
    Pillay, Julian David
    Pinho, Christine
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
    Pishgar, Farhad
    Polinder, Suzanne
    Poulton, Richie G.
    Pourmalek, Farshad
    Univ British Columbia, Vancouver, BC, Canada..
    Qorbani, Mostafa
    Rabiee, Rynaz H. S.
    Radfar, Amir
    Rahimi-Movaghar, Vafa
    Rahman, Mahfuzar
    Rahman, Mohammad Hifz Ur
    Rahman, Sajjad Ur
    Rai, Rajesh Kumar
    Rajsic, Sasa
    Raju, Murugesan
    Ram, Usha
    Rana, Saleem M.
    Ranabhat, Chhabi Lal
    Ranganathan, Kavitha
    Rao, Puja C.
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
    Refaat, Amany H.
    Reitsma, Marissa B.
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
    Remuzzi, Giuseppe
    Resnikoff, Serge
    Ribeiro, Antonio L.
    Blancas, Maria Jesus Rios
    Natl Inst Publ Hlth, Cuernavaca, Morelos, Mexico..
    Rolm, Hirbo Shore
    Roberts, Bayard
    London Sch Hyg & Trop Med, London, England..
    Rodriguez, Mina
    Rojas-Rueda, David
    Ronfani, Luca
    Roshandel, Gholamreza
    Roth, Gregory A.
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
    Rothenbacher, Dietrich
    Roy, Ambuj
    Roy, Nobhojit
    Sackey, Ben Benasco
    Sagar, Rajesh
    Saleh, Muhammad Muhammad
    Sanabria, Juan R.
    Santomauro, Damian F.
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA.;Univ Queensland, Sch Publ Hlth, Brisbane, Qld, Australia..
    Santos, Itamar S.
    Univ Sao Paulo, Dept Internal Med, Sao Paulo, Brazil..
    Sarmiento-Suarez, Rodrigo
    Sartorius, Benn
    Satpathy, Maheswar
    Savic, Miloje
    Sawhney, Monika
    Sawyer, Susan M.
    Univ Melbourne, Dept Pediat, Melbourne, Vic, Australia..
    Schmidhuber, Josef
    Schmidt, Maria Ines
    Schneider, Ione J. C.
    Schutte, Aletta E.
    Schwebel, David C.
    Seedat, Soraya
    Sepanlou, Sadaf G.
    Servan-Mori, Edson E.
    Natl Inst Publ Hlth, Cuernavaca, Morelos, Mexico..
    Shackelford, Katya
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
    Shaheen, Amira
    Shaikh, Masood Ali
    Levy, Teresa Shamah
    Natl Inst Publ Hlth, Cuernavaca, Morelos, Mexico..
    Sharma, Rajesh
    She, Jun
    Sheikhbahaei, Sara
    Shen, Jiabin
    Sheth, Kevin N.
    Shey, Muki
    Shi, Peilin
    Tufts Univ, Boston, MA 02111 USA..
    Shibuya, Kenji
    Shigematsu, Mika
    Shin, Min-Jeong
    Shiri, Rahman
    Shishani, Kawkab
    Shiue, Ivy
    Sigfusdottir, Inga Dora
    Silpakit, Naris
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
    Silva, Diego Augusto Santos
    Silverberg, Jonathan I.
    Simard, Edgar P.
    Sindi, Shireen
    Singh, Abhishek
    Singh, Gitanjali M.
    Tufts Univ, Boston, MA 02111 USA..
    Singh, Jasvinder A.
    Singh, Om Prakash
    Singh, Prashant Kumar
    Skirbekk, Vegard
    Sligar, Amber
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
    Soneji, Samir
    Dartmouth Coll, Hanover, NH 03755 USA..
    Soreide, Kjetil
    Sorensen, Reed J. D.
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
    Soriano, Joan B.
    Soshnikov, Sergey
    Sposato, Luciano A.
    Sreeramareddy, Chandrashekhar T.
    Stahl, Hans-Christian
    Stanaway, Jeffrey D.
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
    Stathopoulou, Vasiliki
    Steckling, Nadine
    Steel, Nicholas
    Stein, Dan J.
    Steiner, Caitlyn
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
    Stockl, Heidi
    London Sch Hyg & Trop Med, London, England..
    Stranges, Saverio
    Strong, Mark
    Sun, Jiandong
    Sunguya, Bruno F.
    Sur, Patrick
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
    Swaminathan, Soumya
    Sykes, Bryan L.
    Szoeke, Cassandra E. I.
    Univ Melbourne, Inst Hlth & Ageing, Melbourne, Vic, Australia..
    Tabares-Seisdedos, Rafael
    Tabb, Karen M.
    Talongwa, Roberto Tchio
    Tarawneh, Mohammed Rasoul
    Tavakkoli, Mohammad
    Taye, Bineyam
    Taylor, Hugh R.
    Univ Melbourne, Melbourne, Vic, Australia..
    Tedla, Bemnet Amare
    Tefera, Worku
    Tegegne, Teketo Kassaw
    Debre Markos Univ, Debre Markos, Ethiopia..
    Tekle, Dejen Yemane
    Mekelle Univ, Mekelle, Ethiopia..
    Shifa, Girma Temam
    Terkawi, Abdullah Sulieman
    Tessema, Gizachew Assefa
    Univ Adelaide, Adelaide, SA, Australia..
    Thakur, J. S.
    Thomson, Alan J.
    Thorne-Lyman, Andrew L.
    Harvard Univ, Dept Nutr, Harvard TH Chan Sch Publ Hlth, Boston, MA 02115 USA..
    Thrift, Amanda G.
    Monash Univ, Dept Med, Sch Clin Sci, Monash Hlth, Melbourne, Vic, Australia..
    Thurston, George D.
    Tillmann, Taavi
    UCL, Dept Epidemiol & Publ Hlth, London, England..
    Tobe-Gai, Ruoyan
    Tonelli, Marcelo
    Topor-Madry, Roman
    Topouzis, Fotis
    Tran, Bach Xuan
    Dimbuene, Zacharie Tsala
    Tura, Abera Kenay
    Tuzcu, Emin Murat
    Tyrovolas, Stefanos
    Ukwaja, Kingsley Nnanna
    Undurraga, Eduardo A.
    Uneke, Chigozie Jesse
    Uthman, Olalekan A.
    van Donkelaar, Aaron
    Dalhousie Univ, Dept Phys & Atmospher Sci, Halifax, NS, Canada..
    Varakin, Yuri Y.
    Vasankari, Tommi
    Vasconcelos, Ana Maria Nogales
    Veerman, J. Lennert
    Univ Queensland, Sch Publ Hlth, Brisbane, Qld, Australia..
    Venketasubramanian, Narayanaswamy
    Verma, Raj Kumar
    Violante, Francesco S.
    Vlassov, Vasiliy Victorovich
    Volkow, Patricia
    Vollset, Stein Emil
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
    Wagner, Gregory R.
    Harvard Univ, Harvard TH Chan Sch Publ Hlth, Boston, MA 02115 USA..
    Wallin, Mitchell T.
    Wang, Linhong
    Chinese Ctr Dis Control & Prevent, Natl Ctr Chron & Noncommun Dis Control & Prevent, Beijing, Peoples R China..
    Wanga, Valentine
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
    Watkins, David A.
    Univ Washington, Seattle, WA 98121 USA..
    Weichenthal, Scott
    Weiderpass, Elisabete
    Weintraub, Robert G.
    Univ Melbourne, Murdoch Childrens Res Inst, Melbourne, Vic, Australia.;Univ Melbourne, Melbourne, Vic, Australia..
    Weiss, Daniel J.
    Univ Oxford, Oxford, England..
    Werdecker, Andrea
    Westerman, Ronny
    Whiteford, Harvey A.
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA.;Univ Queensland, Sch Publ Hlth, Brisbane, Qld, Australia..
    Wilkinson, James D.
    Wiysonge, Charles Shey
    Wolfe, Charles D. A.
    Kings Coll London, Div Hlth & Social Care Res, London, England..
    Wolfe, Ingrid
    Kings Coll London, London, England..
    Won, Sungho
    Woolf, Anthony D.
    Workie, Shimelash Bitew
    Wubshet, Mamo
    Xu, Gelin
    Yadav, Ajit Kumar
    Yakob, Bereket
    Yalew, Ayalnesh Zemene
    Mekelle Univ, Mekelle, Ethiopia..
    Yan, Lijing L.
    Yano, Yuichiro
    Yaseri, Mehdi
    Ye, Pengpeng
    Chinese Ctr Dis Control & Prevent, Natl Ctr Chron & Noncommun Dis Control & Prevent, Beijing, Peoples R China..
    Yip, Paul
    Univ Hong Kong, Social Work & Social Adm Dept, Hong Kong, Hong Kong, Peoples R China.;Univ Hong Kong, Hong Kong Jockey Club Ctr Suicide Res & Prevent, Hong Kong, Hong Kong, Peoples R China..
    Yonemoto, Naohiro
    Kyoto Univ, Sch Publ Hlth, Dept Biostat, Kyoto, Japan..
    Yoon, Seok-Jun
    Younis, Mustafa Z.
    Jackson State Univ, Jackson, MS USA..
    Yu, Chuanhua
    Zaidi, Zoubida
    Zaki, Maysaa El Sayed
    Zambrana-Torrelio, Carlos
    Zapata, Tomas
    Zegeye, Elias Asfaw
    Ethiopian Publ Hlth Inst, Addis Ababa, Ethiopia..
    Zhao, Yi
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
    Zhou, Maigeng
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA.;Chinese Ctr Dis Control & Prevent, Natl Ctr Chron & Noncommun Dis Control & Prevent, Beijing, Peoples R China..
    Zodpey, Sanjay
    Zonies, David
    Oregon Hlth & Sci Univ, Portland, OR 97201 USA..
    Murray, Christopher J. L.
    Univ Washington, Inst Hlth Metr & Evaluat, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA..
    Measuring the health-related Sustainable Development Goals in 188 countries: a baseline analysis from the Global Burden of Disease Study 20152016In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 388, no 10053, p. 1813-1850Article in journal (Refereed)
    Abstract [en]

    Background In September, 2015, the UN General Assembly established the Sustainable Development Goals (SDGs). The SDGs specify 17 universal goals, 169 targets, and 230 indicators leading up to 2030. We provide an analysis of 33 health-related SDG indicators based on the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015). Methods We applied statistical methods to systematically compiled data to estimate the performance of 33 health-related SDG indicators for 188 countries from 1990 to 2015. We rescaled each indicator on a scale from 0 (worst observed value between 1990 and 2015) to 100 (best observed). Indices representing all 33 health-related SDG indicators (health-related SDG index), health-related SDG indicators included in the Millennium Development Goals (MDG index), and health-related indicators not included in the MDGs (non-MDG index) were computed as the geometric mean of the rescaled indicators by SDG target. We used spline regressions to examine the relations between the Socio-demographic Index (SDI, a summary measure based on average income per person, educational attainment, and total fertility rate) and each of the health-related SDG indicators and indices. Findings In 2015, the median health-related SDG index was 59.3 (95% uncertainty interval 56.8-61.8) and varied widely by country, ranging from 85.5 (84.2-86.5) in Iceland to 20.4 (15.4-24.9) in Central African Republic. SDI was a good predictor of the health-related SDG index (r(2) = 0.88) and the MDG index (r(2) = 0.2), whereas the non-MDG index had a weaker relation with SDI (r(2) = 0.79). Between 2000 and 2015, the health-related SDG index improved by a median of 7.9 (IQR 5.0-10.4), and gains on the MDG index (a median change of 10.0 [6.7-13.1]) exceeded that of the non-MDG index (a median change of 5.5 [2.1-8.9]). Since 2000, pronounced progress occurred for indicators such as met need with modern contraception, under-5 mortality, and neonatal mortality, as well as the indicator for universal health coverage tracer interventions. Moderate improvements were found for indicators such as HIV and tuberculosis incidence, minimal changes for hepatitis B incidence took place, and childhood overweight considerably worsened. Interpretation GBD provides an independent, comparable avenue for monitoring progress towards the health-related SDGs. Our analysis not only highlights the importance of income, education, and fertility as drivers of health improvement but also emphasises that investments in these areas alone will not be sufficient. Although considerable progress on the health-related MDG indicators has been made, these gains will need to be sustained and, in many cases, accelerated to achieve the ambitious SDG targets. The minimal improvement in or worsening of health-related indicators beyond the MDGs highlight the need for additional resources to effectively address the expanded scope of the health-related SDGs.

  • 238.
    Lind, Anne-Li
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Yu, Di
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Freyhult, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
    Bodolea, Constantin
    Department of Anaesthesia and Intensive Care, University of Medicine and Pharmacy, Cluj, Napoca, Romania..
    Ekegren, Titti
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Gustafsson, Mats G
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
    Katila, Lenka
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry.
    Gordh, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Landegren, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Kamali-Moghaddam, Masood
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    A Multiplex Protein Panel Applied to Cerebrospinal Fluid Reveals Three New Biomarker Candidates in ALS but None in Neuropathic Pain Patients2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 2, article id e0149821Article in journal (Refereed)
    Abstract [en]

    The objective of this study was to develop and apply a novel multiplex panel of solid-phase proximity ligation assays (SP-PLA) requiring only 20 μL of samples, as a tool for discovering protein biomarkers for neurological disease and treatment thereof in cerebrospinal fluid (CSF). We applied the SP-PLA to samples from two sets of patients with poorly understood nervous system pathologies amyotrophic lateral sclerosis (ALS) and neuropathic pain, where patients were treated with spinal cord stimulation (SCS). Forty-seven inflammatory and neurotrophic proteins were measured in samples from 20 ALS patients and 15 neuropathic pain patients, and compared to normal concentrations in CSF from control individuals. Nineteen of the 47 proteins were detectable in more than 95% of the 72 controls. None of the 21 proteins detectable in CSF from neuropathic pain patients were significantly altered by SCS. The levels of the three proteins, follistatin, interleukin-1 alpha, and kallikrein-5 were all significantly reduced in the ALS group compared to age-matched controls. These results demonstrate the utility of purpose designed multiplex SP-PLA panels in CSF biomarker research for understanding neuropathological and neurotherapeutic mechanisms. The protein changes found in the CSF of ALS patients may be of diagnostic interest.

  • 239.
    Lind, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Andersson, Jessika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Sandhagen, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Shear stress in the common carotid artery is related to both intima-media thickness and echogenecity: the prospective investigation of the vasculature in Uppsala seniors study2009In: Clinical hemorheology and microcirculation, ISSN 1386-0291, E-ISSN 1875-8622, Vol. 43, no 4, p. 299-308Article in journal (Refereed)
    Abstract [en]

    It has previously been shown that the degree of shear stress (SS) in the carotid artery is related to both plaque occurrence and intima-media thickness (IMT). Since the echogenecity also is an important feature of plaques, we investigated if a reduced shear stress also is related to the echolucency of plaque and the intima-media complex. In the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study, a population-based study of 1016 subjects aged 70, left common carotid artery diameter, IMT, the grey scale median (GSM) of the intima-media complex (IM-GSM) and the blood flow velocity were measured by ultrasound. Occurrence of plaque was noted, and the echogenecity of the plaques was visually estimated by the Gray-Weale classification. Shear stress was inversely related to both IMT and IM-GSM (p=0.0084 and p=0.003, respectively), independently of gender and coronary risk, estimated by the Framingham risk score. Shear stress was lower in subjects with carotid plaque (44% of the sample) than in those without (p=0.0013), and was inversely related to the echogenecity in the subjects with plaque (p=0.0092), independently of gender and coronary risk. A low shear stress in the common carotid artery was associated with both a thick IMT and an echolucent intima-media complex. A similar picture was seen when overt plaques were evaluated, suggesting that shear stress is of importance for both the extent and composition of atherosclerosis.

  • 240.
    Lind, Lars
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Carlstedt, F
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Rastad, J
    Department of Surgical Sciences.
    Stiernström, H
    Department of Surgical Sciences. Anaesthesiology and Intensive Care.
    Stridsberg, M
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Clinical Chemistry.
    Ljunggren, Ö
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Wide, L
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Clinical Chemistry.
    Larsson, A
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences. Clinical Chemistry.
    Hellman, P
    Department of Surgical Sciences.
    Ljunghall, S
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Sciences.
    Hypocalcemia and parathyroid hormone secretion in critically ill patients2000In: Crit Care Med, Vol. 28, p. 93-99Article in journal (Refereed)
  • 241.
    Lind, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Axelsson, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Lundmark, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Hagg, S.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Variation in genes in the endothelin pathway and endothelium-dependent and endothelium-independent vasodilation in an elderly population2013In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 208, no 1, p. 88-94Article in journal (Refereed)
    Abstract [en]

    Aim Indirect evidences by blockade of the endothelin receptors have suggested a role of endothelin in endothelium-dependent vasodilation. This study aimed to investigate whether circulating levels of endotehlin-1 or genetic variations in genes in the endothelin pathway were related to endothelium-dependent vasodilation. Methods In 1016 seventy-year-old participants of the population-based Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study (52% women), we measured endothelium-dependent vasodilation using the invasive forearm technique with acetylcholine given in the brachial artery (EDV) and the brachial artery ultrasound technique with measurement of flow-mediated dilatation (FMD). Plasma endothelin-1 levels were measured and 60 SNPs in genes in the endothelin pathway (ECE1, EDN1, EDNRA, EDNRB) were genotyped. Results No significant associations were found between circulating endothelin levels and EDV or FMD. No single genotype was related to EDV or FMD following adjustment for multiple testing, but a genotype score for 3 SNPs (rs11618266 in EDNRB, rs17675063 in EDNRA, rs3026868 in ECE1) was significantly related to EDV (beta coefficient 0.070, 95% CI 0.0250.12, P=0.002) when adjusting for gender, systolic blood pressure, HDL and LDL cholesterol, serum triglycerides, BMI, diabetes, smoking, antihypertensive medication or statins and CRP. This score was also related to nitroprusside-induced vasodilation in the forearm. Conclusion A combination of genotypes in the endothelin pathway was related to both endothelium-dependent and endothelium-independent vasodilation in forearm resistance vessels, but not in the brachial artery in an elderly population, giving evidence for a role of the endothelin system in resistance vessel reactivity independent of major cardiovascular risk factors.

  • 242.
    Lind, Monica
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Salihovic, Samira
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Univ Orebro, MTM Res Ctr, Sch Sci & Technol, SE-70182 Orebro, Sweden..
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    van Bavel, B.
    Univ Orebro, MTM Res Ctr, Sch Sci & Technol, SE-70182 Orebro, Sweden..
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Circulating levels of perfluoroalkyl substances and biomarkers of liver function in a large population based sample of elderly men and women from Sweden2015In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 238, no 2, p. S91-S91Article in journal (Other academic)
  • 243.
    Lindholm, Åsa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Bixo, Marie
    Björn, Inger
    Wölner-Hanssen, Pål
    Eliasson, Mats
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Johnson, Owe
    Sundström Poromaa, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Effect of sibutramine on weight reduction in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial2008In: Fertility and Sterility, ISSN 0015-0282, E-ISSN 1556-5653, Vol. 89, no 5, p. 1221-1228Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To examine the efficacy of sibutramine together with brief lifestyle modification for weight reduction in obese women with polycystic ovary syndrome (PCOS). DESIGN: Investigator-initiated, multicenter, double-blind, randomized, parallel-group clinical trial. SETTING: Departments of Obstetrics and Gynecology in primary care, referral centers, and private practice. PATIENT(S): Forty-two patients with confirmed PCOS were included in the study, and 34 patients completed the study. INTERVENTION: Sibutramine 15 mg once daily together with brief lifestyle modification was compare with placebo together with brief lifestyle modification. MAIN OUTCOME MEASURE(S): The primary endpoint was to assess weight loss. Secondary endpoints included the efficacy of sibutramine for treatment of menstrual pattern and cardiovascular risk factors. RESULT(S): After 6 months the sibutramine group had lost 7.8 +/- 5.1 kg compared with a weight loss of 2.8 +/- 6.2 kg in the placebo group. Sibutramine treatment resulted in significant decreases in apolipoprotein B, apolipoprotein B/apolipoprotein A ratio, triglycerides, and cystatin C levels. CONCLUSION(S): Sibutramine in combination with lifestyle intervention results in significant weight reduction in obese patients with PCOS. In addition to the weight loss, sibutramine seems to have beneficial effects on metabolic and cardiovascular risk factors.

  • 244.
    Lipcsey, Miklos
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Olovsson, Matts
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Larsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Einarsson, Roland
    Abdul Qadhr, Goran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    The brain is a source of S100B increase during endotoxemia in the pig2010In: Anesthesia and Analgesia, ISSN 0003-2999, E-ISSN 1526-7598, Vol. 110, no 1, p. 174-180Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Cerebral dysfunction frequently complicates septic shock. A marker of cerebral dysfunction could be of significant value in managing sedated septic patients. Plasma S100 (S100B) proteins increase in sepsis. S100B is present not only in the brain but also in other tissues. The source of this protein has not been investigated in sepsis. Our aim in this study was to determine whether the brain is an important source of S100B in an experimental sepsis model.

    METHODS:

    Twenty-seven pigs were anesthetized and randomized to either infusion of endotoxin at the rate of 1 µg · kg-1 · h-1 (n = 19) or saline (n = 8). Catheters were inserted into a cervical artery and the superior sagittal sinus. Blood samples were collected from both sites and physiologic data were registered before the start of the endotoxin infusion and hourly during the experiment. After 6 h, the animals were killed and brain tissue samples were taken from the left hemisphere. S100B in plasma was measured by enzyme-linked immunosorbent assay. Brain tissue samples were stained with biotinylated S100B antibodies.

    RESULTS:

    In the endotoxemic animals, the arterial S100B concentration increased to 442 ± 33 and 421 ± 24 ng/L at 1 and 2 h, respectively, vs 306 ± 28 and 261 ± 25 ng/L in controls (P = 0.018 and 0.00053, respectively). Mean superior sagittal sinus S100B concentrations were higher than mean arterial concentrations at all time points in the endotoxemic animals; however, significance was only reached at 2 h (P = 0.033). The focal glial S100B expression was more intense in the endotoxemic pigs than in controls (P = 0.0047).

    CONCLUSIONS:

    Our results support the hypothesis that the brain is an important source of S100B in endotoxemia even though there may be other sources. These findings make S100B a candidate as a marker of cerebral dysfunction in septic shock.

  • 245.
    Lipcsey, Miklós
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Aronsson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Renlund, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Gedeborg, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Multivariable models using administrative data and biomarkers to adjust for case mix in the ICU2019In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 63, no 6, p. 751-760Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Routinely collected laboratory biomarkers could improve control of confounding from disease severity in non-interventional studies of general intensive care unit (ICU) patients. Their ability to predict both short- and long-term mortality was evaluated.

    METHODS: The performance of age, sex, Charlson co-morbidity index, and baseline values of ten predefined blood biomarkers as predictors of 30-day and 1-year mortality was evaluated in 5505 general ICU stays.

    RESULTS: Regression models based on age, sex, Charlson index, and biomarkers were somewhat less accurate in predicting 30-day mortality (c-index 0.83, Brier score 0.27) compared to the SAPS II score (c-index = 0.88, Brier score = 0.09) and in predicting 1-year mortality (c-index = 0.82, Brier score = 0.31) compared to the SAPS II score (c-index = 0.85, Brier score = 0.13). Cystatin C improved predictive ability slightly compared to creatinine, but age and Charlson comorbidity index were more important predictors. Using multiple imputation to replace missing biomarker values notably improved predictive ability of the models.

    CONCLUSIONS: Automatically collected baseline variables are almost as predictive of both short- and long-term mortality in general ICU patients, as the SAPS II score. This can facilitate internal control of confounding in non-interventional studies of mortality using administrative data.

  • 246.
    Lipcsey, Miklós
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Carlsson, Markus
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Algotsson, Lars
    Eriksson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Lukinius, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Effect of a single dose of tobramycin on systemic inflammatory response-induced acute kidney injury in a 6-hour porcine model2009In: Critical Care Medicine, ISSN 0090-3493, E-ISSN 1530-0293, Vol. 37, no 10, p. 2782-2790Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    To evaluate whether the addition of tobramycin further compromises renal function in inflammatory response-induced acute kidney injury. Effective antibiotic treatment in septic shock is crucial for the outcome. The combination of aminoglycosides with different beta-lactam antibiotics offers a broad antimicrobial coverage, rapid bacterial killing, synergistic effects, and low antibiotic-induced endotoxin release. However, aminoglycosides have nephrotoxic effects that may aggravate sepsis-induced acute kidney injury.

    DESIGN:

    Prospective, randomized, placebo-controlled experimental study.

    SETTING:

    University research unit.

    SUBJECTS:

    Twenty-four healthy pigs.

    INTERVENTIONS:

    The animals were anesthetized and randomized to four groups. Groups I (n = 8) and II (n = 8) received endotoxin infusion for 6 hrs, whereas groups III (n = 4) and IV (n = 4) received saline. Groups I and III received 7 mg/kg of tobramycin 20 mins after the initiation of the protocol, whereas groups II and IV received saline.

    MEASUREMENTS AND MAIN RESULTS:

    The renal elimination rate of a bolus dose of cefuroxime was chosen as the primary end point. Renal function was also evaluated by urine output, creatinine clearance, plasma cystatin C, plasma urea, and urine NAG (N-acetyl-beta-D-glucoaminidase). After 3 hrs, there were significantly lower cefuroxime elimination rates in the two endotoxin groups than in the nonendotoxin groups. No difference in cefuroxime elimination rates between groups I and II could be detected at any time point. Similarly, there were changes indicating acute kidney injury in urine output, creatinine clearance, and plasma cystatin C in the endotoxin groups with no differences between groups I and II. Plasma urea and urine NAG did not differ between any of the groups.

    CONCLUSIONS:

    The result of this study does not lend any support to the hypothesis that a single dose of tobramycin enhances the risk of acute renal failure in cases with systemic inflammatory response-induced acute kidney injury.

  • 247.
    Lipcsey, Miklós
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Hanslin, Katja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infection medicine.
    Stålberg, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Smekal, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    The time course of calprotectin liberation from human neutrophil granulocytes after Escherichia coli and endotoxin challenge2019In: Innate Immunity, ISSN 1753-4259, E-ISSN 1753-4267, Vol. 25, no 6, p. 369-373Article in journal (Refereed)
    Abstract [en]

    Plasma calprotectin has previously been reported as a biomarker for sepsis. The aim of the present study was to elucidate the kinetics of calprotectin release from neutrophils exposed to Escherichia coli and endotoxin. Whole blood samples were exposed to E. coli bacteria or endotoxin in vitro. Blood samples were collected after 0, 1, 2, 3 and 4 h and plasma calprotectin was analysed by particle enhanced turbidimetric immunoassay while TNF-α, IL-6, neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) were analyzed by ELISA. When neutrophils were exposed to either E. coli or endotoxin, calprotectin levels began to increase within a couple of hours after the challenge. Calprotectin increases early in response to bacterial challenge. Given the logistic advantages of the calprotectin analysis, this may be of interest for early diagnosis of bacterial infections.

  • 248.
    Lipcsey, Miklós
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Eriksson, Mats B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Inflammatory, coagulatory and circulatory responses to logarithmic increases in the endotoxin dose in the anaesthetised pig2006In: Journal of Endotoxin Research, ISSN 0968-0519, E-ISSN 1743-2839, Vol. 12, no 2, p. 99-112Article in journal (Other academic)
    Abstract [en]

    Although porcine intravenous endotoxin shock models are widely employed in experimental sepsis, endotoxin dose-effect studies are scarce. Our primary aim was to establish the dose response to increasing endotoxin doses in inflammatory, coagulatory and haemodynamic effect variables, as well as to determine the optimal time point for assessment in a pig model. A secondary aim was to study pathophysiological covariations between the different responses. Twenty anaesthetised piglets received endotoxin intravenously in doses of 0.063 (n = 3), 0.25 (n = 3), 1.0 (n = 3), 4.0 (n = 3), 8 (n = 3) and 16 microg/kg/h (n = 2). In addition, non-endotoxin piglets constituted a control group (n = 3). Physiological variables were registered and blood samples analysed for TNF-alpha, IL-6, leukocyte, platelet and haemoglobin concentrations hourly for 6 h. Increases in the endotoxin dose induced significant log-log cytokine responses as well as log-linear leukocyte and platelet responses. Significant log-linear responses were observed for circulatory parameters, plasma leakage, hypoperfusion and pulmonary compliance. Significant covariations in the responses were noted. In conclusion, there were log-log or log-linear responses to endotoxin suggesting a greater effect of a given dose at lower pre-existing endotoxin concentrations and lower doses of < or = 1 microg/kg/h may be of advantage in experiments designed to study potential anti-endotoxin effects of experimental drugs or measures.

  • 249.
    Lipcsey, Miklós
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Eriksson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Effect of the Administration Rate on the Biological Responses To A Fixed Dose of Endotoxin in the Anesthetized Pig2008In: Shock, ISSN 1073-2322, E-ISSN 1540-0514, Vol. 29, no 2, p. 173-180Article in journal (Refereed)
    Abstract [en]

    There have been difficulties to demonstrate a relationship between endotoxin concentration and clinical response. One hypothesis for this difficulty might be that a fast increase in endotoxin concentration elicits a stronger biological response than a more gradual one of the same dose. The aim of the present study was to investigate the existence of such a response. Eighteen randomized pigs were given the same amount of endotoxin either with an initial infusion rate of 4 μg kg-1 h-1, which after 1 h was tapered to 0.5 μg kg-1 h-1, and after 2 h to 0.063 μg kg-1 h-1 (group I), or with a reverse escalating order with the lowest infusion rate given first (group II). After 3 h, the endotoxin infusion was stopped, and the pigs were observed for another 3 h. The responses in TNF-α, core temperature, leukocytes, platelets, MAP, left ventricular stroke work index, mixed venous saturation, base excess, pH, and pulmonary compliance were greater in group I than in group II, whereas the IL-6 response did not differ between groups. The biological responses of inflammation, hypotension, hypoperfusion, and organ dysfunction are increased if the organism is exposed to a fixed amount of endotoxin more quickly.

    Abbreviations - BE-Base excess; CI-Cardiac index; DO2-Oxygen delivery; Fio2-fraction of oxygen; Hb-Hemoglobin; LVSWI-Left ventricular stroke work index; MPAP-Mean pulmonary arterial pressure; Paco2-Arterial partial pressure of carbon dioxide; Pao2-Arterial partial pressure of oxygen; pH-Potentia Hydrogenii; SEM-Standard error of the mean; Svo2-Venous oxygen saturation

  • 250.
    Lipcsey, Miklós
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Olovsson, Matts
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Sjölin, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Infectious Diseases.
    Eriksson, Mats B
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Early endotoxin-mediated haemostatic and inflammatory responses in the clopidogrel-treated pig2005In: Platelets, ISSN 0953-7104, E-ISSN 1369-1635, Vol. 16, no 7, p. 408-414Article in journal (Refereed)
    Abstract [en]

    We have previously shown that the thrombin inhibiting agent melagatran markedly prolongs aPTT and counteracts creatinine increase in endotoxemic pigs. Against this background the effects of the platelet-inhibiting agent, clopidogrel on basic haemostatic, inflammatory and physiological variables were evaluated during porcine endotoxemia. Clopidogrel (10 mg/kg) or saline was randomly injected i.v. 30 min before start of a 6-h continuous infusion of endotoxin in 12 anaesthetised pigs. Another three pigs were given clopidogrel but not endotoxin. Clopidogrel did not affect physiological variables, formation of activated platelet microparticles, PK, aPTT, platelet count, plasma fibrinogen, TNF-alpha, or IL-6 during porcine endotoxemia. Although renal function, as evaluated by creatinine clearance (CLcr) deteriorated significantly (P = 0.01) in the saline-endotoxin, but not in the clopidogrel-endotoxin group, there was no significant difference between the saline-endotoxin and the clopidogrel-endotoxin groups. Renal biopsies were marked with a FITC-labelled chicken anti-fibrinogen antibody detecting fibrinogen and platelet bound fibrinogen, as a marker of porcine platelet activation, and examined by light microscopy. Evaluation of these immunohistochemical slides did not indicate that clopidogrel, significantly reduced the amount of intrarenal fibrin or fibrinogen depositions. Besides a trend to preserve renal function, clopidogrel did not affect haemodynamics or the coagulatory and inflammatory responses in porcine endotoxemia.

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