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2.
  • Persson, Gustav, et al. (author)
  • Splenic contraction and cardiovascular responses are augmented during apnea compared to rebreathing in humans
  • 2023
  • In: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 14
  • Journal article (peer-reviewed)abstract
    • The spleen contracts during apnea, releasing stored erythrocytes, thereby increasing systemic hemoglobin concentration (Hb). We compared apnea and rebreathing periods, of equal sub-maximal duration (mean 137 s; SD 30), in eighteen subjects to evaluate whether respiratory arrest or hypoxic and hypercapnic chemoreceptor stimulation is the primary elicitor of splenic contraction and cardiovascular responses during apnea. Spleen volume, Hb, cardiovascular variables, arterial (SaO2), cerebral (ScO2), and deltoid muscle oxygen saturations (SmO2) were recorded during the trials and end-tidal partial pressure of oxygen (PETO2) and carbon dioxide (PETCO2) were measured before and after maneuvers. The spleen volume was smaller after apnea, 213 (89) mL, than after rebreathing, 239 (95) mL, corresponding to relative reductions from control by 20.8 (17.8) % and 11.6 (8.0) %, respectively. The Hb increased 2.4 (2.0) % during apnea, while there was no significant change with rebreathing. The cardiovascular responses, including bradycardia, decrease in cardiac output, and increase in total peripheral resistance, were augmented during apnea compared to during rebreathing. The PETO2 was higher, and the PETCO2 was lower, after apnea compared to after rebreathing. The ScO2 was maintained during maneuvers. The SaO2 decreased 3.8 (3.1) % during apnea, and even more, 5.4 (4.4) %, during rebreathing, while the SmO2 decreased less during rebreathing, 2.2 (2.8) %, than during apnea, 8.3 (6.2) %. We conclude that respiratory arrest per se is an important stimulus for splenic contraction and Hb increase during apnea, as well as an important initiating factor for the apnea-associated cardiovascular responses and their oxygen-conserving effects. 
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3.
  • Zar, Gustav, et al. (author)
  • Whole-genome sequencing based on formalin-fixed paraffin-embedded endomyocardial biopsies for genetic studies on outcomes after heart transplantation
  • 2019
  • In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 14:6
  • Journal article (peer-reviewed)abstract
    • Background Whole-genome sequencing (WGS) of heart transplant recipient- and donor-derived cardiac biopsies may facilitate organ matching, graft failure prediction, and immunotolerance research. The objective of this study was to determine the feasibility of WGS based on formalin-fixed paraffin-embedded endomyocardial biopsies. Methods and results The study included serial donor- and recipient samples from patients who had undergone heart transplantation at Skane University Hospital, Lund, Sweden, between 1988 and 2009. DNA extraction and WGS were conducted. Additional WGS sequencing quality metrics and coverage were obtained with the Genome Analysis Toolkit (GATK). 455 endomyocardial samples from 37 heart transplant recipients were acquired from routine rejection monitoring and stored as formalin-fixed paraffin-embedded samples. They were analyzed after 3–26 years of storage. DNA was extracted from 114 samples and WGS was run on 85 samples. DNA extraction yielded 313 ng (IQR 96–601) for all samples. A coverage of 11.3x (IQR 9.0–15.9) was recorded for all WGS samples. Three samples stored for > 25 years yielded a coverage of > 25x. Data were generated for 1.7 billion reads per sample (IQR 1.4–2.7). A Transition/Transversion (TiTv) ratio of 2.09 ± 0.05 was calculated for all WGS samples. No associations were found among storage time, DNA yield, or sequencing quality metrics. Conclusions The present study demonstrated the feasibility of whole-genome sequencing based on endomyocardial biopsies. This process could enable large-scale retrospective genomic studies using stored histopathological samples.
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4.
  • Zhao, Xue, et al. (author)
  • Amylose starch with no detectable branching developed through DNA-free CRISPR-Cas9 mediated mutagenesis of two starch branching enzymes in potato
  • 2021
  • In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11
  • Journal article (peer-reviewed)abstract
    • DNA-free genome editing was used to induce mutations in one or two branching enzyme genes (Sbe) in tetraploid potato to develop starch with an increased amylose ratio and elongated amylopectin chains. By using ribonucleoprotein (RNP) transfection of potato protoplasts, a mutation frequency up to 72% was achieved. The large variation of mutations was grouped as follows: Group 1 lines with all alleles of Sbe1 mutated, Group 2 lines with all alleles of Sbe1 as well as two to three alleles of Sbe2 mutated and Group 3 lines having all alleles of both genes mutated. Starch from lines in Group 3 was found to be essentially free of amylopectin with no detectable branching and a chain length (CL) distribution where not only the major amylopectin fraction but also the shortest amylose chains were lost. Surprisingly, the starch still formed granules in a low-ordered crystalline structure. Starch from lines of Group 2 had an increased CL with a higher proportion of intermediate-sized chains, an altered granule phenotype but a crystalline structure in the granules similar to wild-type starch. Minor changes in CL could also be detected for the Group 1 starches when studied at a higher resolution.
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5.
  • Acevedo, Nathalie, et al. (author)
  • Epigenetic alterations in skin homing CD4(+)CLA(+) T cells of atopic dermatitis patients
  • 2020
  • In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
  • Journal article (peer-reviewed)abstract
    • T cells expressing the cutaneous lymphocyte antigen (CLA) mediate pathogenic inflammation in atopic dermatitis (AD). The molecular alterations contributing to their dysregulation remain unclear. With the aim to elucidate putative altered pathways in AD we profiled DNA methylation levels and miRNA expression in sorted T cell populations -(CD4(+), -CD4(+)CD45RA(+) naive, -CD4(+)CLA(+), and -CD8(+)) from adult AD patients and healthy controls (HC). Skin homing -CD4(+)CLA(+) T cells from AD patients showed significant differences in DNA methylation in 40 genes compared to HC (p < 0.05). Reduced DNA methylation levels in the upstream region of the interleukin-13 gene (IL13) in -CD4(+)CLA(+) T cells from AD patients correlated with increased IL13 mRNA expression in these cells. Sixteen miRNAs showed differential expression in -CD4(+)CLA(+) T cells from AD patients targeting genes in 202 biological processes (p < 0.05). An integrated network analysis of miRNAs and CpG sites identified two communities of strongly interconnected regulatory elements with strong antagonistic behaviours that recapitulated the differences between AD patients and HC. Functional analysis of the genes linked to these communities revealed their association with key cytokine signaling pathways, MAP kinase signaling and protein ubiquitination. Our findings support that epigenetic mechanisms play a role in the pathogenesis of AD by affecting inflammatory signaling molecules in skin homing -CD4(+)CLA(+) T cells and uncover putative molecules participating in AD pathways.
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6.
  • Alim, Abdul, 1983- (author)
  • Mechanisms in Tendon Healing : Pain, Biomarkers and the Role of Mast Cells
  • 2019
  • Doctoral thesis (other academic/artistic)abstract
    • Tendon injuries and tendinopathy are common disorders, but the underlying mechanisms are not well understood. The overall aim of this thesis was to better understand the mechanisms underlying tendon healing, pain, and inflammation.The aim of the first study was to assess biomarkers of tendon healing, including procollagen type I (PINP) and type III (PIIINP) in relation to patient outcome in 65 patients with Achilles tendon rupture (ATR). At two weeks post-ATR, PINP and PIIINP-levels were quantified using microdialysis followed by ELISA. At one-year post-ATR patient outcome was assessed using the validated Achilles tendon Total Rupture Score. We found that higher ratio of PINP and PIIINP to total protein were significantly associated with less pain but more fatigue in the affected limb.In the second study, we applied Intermittent Pneumatic Compression (IPC) therapy for two weeks to stimulate tendon healing. The patients received either adjuvant IPC treatment or treatment-as-usual in a plaster cast without IPC. We observed that IPC therapy significantly increased PINP levels in the injured tendon, suggesting enhanced healing response.In our third study, we investigated healing response and the role of mast cells (MCs) in-vivo using an ATR rat model. Three weeks postoperatively, we demonstrated an increased number of MCs and a higher proportion of degranulated MCs in the injured tendon compared to the control. We further established that MCs in the injured tendon were positive for the glutamate receptor NMDAR1.In our final study, we assessed the effect of glutamate stimulation on in-vitro-derived mouse bone marrow MCs. Mast cell degranulation was quantified through β-hexosaminidase release, immunofluorescence was used to quantify NMDARs at the protein level, and RT-qPCR/microarray was used to study the expression of NMDARs and associated genes. Glutamate induced a robust upregulation of glutamate receptors of both ionotropic and metabotropic type, both at the mRNA and at protein level. NMDAR1 co-localized with glutamate in the membrane of MCs, thereby confirming an interaction between glutamate and its receptor. Glutamate also induced expression of pro-inflammatory compounds such as IL-6 and CCL2 and transcription factors such as Egr2, Egr3 and FosB. Moreover, the NMDA-channel blocker MK-801 completely abrogated the response of MCs to glutamate, supporting a functional glutamate–glutamate receptor axis in MCs.Together, findings presented in this dissertation reveal possible mechanisms of tendon healing in relation to pain and function, and establish a novel principle for how immune cells can communicate with nerve cells after ATR.
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  • Almqvist, Gustav, et al. (author)
  • Carrots, sticks, sermons, and nudges during the pandemic: There are many ways to change public behaviour, but not all are equally popular.
  • 2020
  • In: Sweden through the crisis. - Stockholm : Stockholm School of Economics Institute for Research. - 9789186797386 ; , s. 83-90
  • Book chapter (other academic/artistic)abstract
    • In this article, Gustav Almqvist and Patric Andersson discuss policy implications of nudging during COVID-19. Conducting a survey with 596 individuals in Sweden, the authors show that individuals are fine with nudges but that they prefer traditional methods of governmental interventions such as economic incentives (carrots), mandates (sticks) and information (sermons). A conclusion is therefore that policy makers should use nudging with caution when potentially better alternatives exist.
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8.
  • Almqvist, Gustav, et al. (author)
  • Low support for nudging among Swedes in a population-representative sample
  • 2024
  • In: Behavioural Public Policy. - : Cambridge University Press. - 2398-0648 .- 2398-063X. ; 8:2, s. 382-394
  • Journal article (peer-reviewed)abstract
    • Recent surveys in China, South Korea, Brazil, South Africa, Russia, Australia, Italy, the UK, Canada, France, Germany, the USA, Japan, Hungary, and Denmark indicate that citizens generally are positive toward state nudging. However, less is known about differences in the support for nudging across socio-demographics and political party preferences, a research gap recently identified in the literature. This article investigates the relationship between the support for nudging and trust in public institutions through a population representative survey in Sweden. It also analyzes differences in the support for nudging across political party preferences in two ideological dimensions: the economic left-right and cultural GAL-TAN spectra. Data were collected in December 2017 through a custom web survey, using Reisch and Sunstein’s (2016) questionnaire. The respondents (N = 1032) were representative of the adult population with regard to gender, age, education, job sector, household income, living region, and political party preference. Sweden was found to belong to the cautiously pronudge nations (along with Japan, Hungary, and Denmark), contrary to hypotheses in previous research. Differences in the support for nudging were found along the economic left-right and GAL-TAN spectra. Individual nudges’ variation in support, polarization, and politicization are analyzed and discussed.
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  • Andell, Pontus, et al. (author)
  • Epidemiology of valvular heart disease in a Swedish nationwide hospital-based register study
  • 2017
  • In: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 103:21, s. 1696-1703
  • Journal article (peer-reviewed)abstract
    • Objective: Transitions in the spectrum of valvular heart diseases (VHDs) in developed countries over the 20th century have been reported from clinical case series, but large, contemporary population-based studies are lacking.Methods: We used nationwide registers to identify all patients with a first diagnosis of VHD at Swedish hospitals between 2003 and 2010. Age-stratified and sex-stratified incidence of each VHD and adjusted comorbidity profiles were assessed.Results: In the Swedish population (n=10 164 211), the incidence of VHD was 63.9 per 100 000 person-years, with aortic stenosis (AS; 47.2%), mitral regurgitation (MR; 24.2%) and aortic regurgitation (AR; 18.0%) contributing most of the VHD diagnoses. The majority of VHDs were diagnosed in the elderly (68.9% in subjects aged ≥65 years), but pulmonary valve disease incidence peaked in newborns. Incidences of AR, AS and MR were higher in men who were also more frequently diagnosed at an earlier age. Mitral stenosis (MS) incidence was higher in women. Rheumatic fever was rare. Half of AS cases had concomitant atherosclerotic vascular disease (48.4%), whereas concomitant heart failure and atrial fibrillation were common in mitral valve disease and tricuspid regurgitation. Other common comorbidities were thoracic aortic aneurysms in AR (10.3%), autoimmune disorders in MS (24.5%) and abdominal hernias or prolapse in MR (10.7%) and TR (10.3%).Conclusions: Clinically diagnosed VHD was primarily a disease of the elderly. Rheumatic fever was rare in Sweden, but specific VHDs showed a range of different comorbidity profiles . Pronounced sex-specific patterns were observed for AR and MS, for which the mechanisms remain incompletely understood.
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  • Andersson, Anton, et al. (author)
  • Design of a Foiling Optimist
  • 2018
  • In: Journal of Sailboat Technology. ; 2018, s. 1-24
  • Journal article (peer-reviewed)abstract
    • Because of the successful application of hydrofoils on the America's Cup catamarans in the past two campaigns the interest in foiling sailing craft has boosted. Foils have been fitted to a large number of yachts with great success, ranging from dinghies to ocean racers. An interesting question is whether one of the slowest racing boats in the world, the Optimist dinghy, can foil, and if so, at what minimum wind speed. The present paper presents a comprehensive design campaign to answer the two questions. The campaign includes a newly developed Velocity Prediction Program (VPP) for foiling/non-foiling conditions, a wind tunnel test of sail aerodynamics, a towing tank test of hull hydrodynamics and a large number of numerical predictions of foil characteristics. An optimum foil configuration is developed and towing tank tested with satisfactory results. The final proof of the concept is a successful on the water test with stable foiling at a speed of 12 knots.
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  • Andersson, Charlotte, et al. (author)
  • A risk score for predicting 30-day mortality in heart failure patients undergoing non-cardiac surgery
  • 2014
  • In: European Journal of Heart Failure. - : Wiley. - 1879-0844 .- 1388-9842. ; 16:12, s. 1310-1316
  • Journal article (peer-reviewed)abstract
    • BackgroundHeart failure is an established risk factor for poor outcomes in patients undergoing non-cardiac surgery, yet risk stratification remains a clinical challenge. We developed an index for 30-day mortality risk prediction in this particular group. Methods and resultsAll individuals with heart failure undergoing non-cardiac surgery between October 23 2004 and October 31 2011 were included from Danish administrative registers (n=16827). In total, 1787 (10.6%) died within 30days. In a simple risk score based on the variables from the revised cardiac risk index, plus age, gender, acute surgery, and body mass index category the following variables predicted mortality (points): male gender (1), age 56-65years (2), age 66-75years (4), age 76-85years (5), or age >85years (7), being underweight (4), normal weight (3), or overweight (1), undergoing acute surgery (5), undergoing high-risk procedures (intra-thoracic, intra-abdominal, or suprainguinal aortic) (3), having renal disease (1), cerebrovascular disease (1), and use of insulin (1). The c-statistic was 0.79 and calibration was good. Mortality risk ranged from <2% for a score <5 to >50% for a score 20. Internal validation by bootstrapping (1000 re-samples) provided c-statistic of 0.79. A more complex risk score based on stepwise logistic regression including 24 variables at P<0.05 performed only slightly better, c-statistic=0.81, but was limited in use by its complexity. ConclusionsFor patients with heart failure, this simple index can accurately identify those at low risk for perioperative mortality.
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  • Andersson, Charlotte, et al. (author)
  • Enhanced Ribosome and tRNA Contents in Escherichia coli Expressing a Truncated Vitreoscilla Hemoglobin Mutant Analyzed by Flow Field-Flow Fractionation
  • 2003
  • In: Biotechnology Letters. - 1573-6776. ; 25:18, s. 1499-1504
  • Journal article (peer-reviewed)abstract
    • The ribosome and tRNA levels of Escherichia coli cells, transformed with a native or mutated Vitreoscilla hemoglobin genes (vhb), were investigated using asymmetrical flow field-flow fractionation (AFFFF). Mutagenesis of vhb by error-prone PCR was carried out to alter the growth behavior of microaerobically cultivated native VHb-expressing E. coli. A VHb mutant, pVMT1, was identified, which was able to reach a remarkably high final A600 of 15, the value of which being 160% higher than that of a VHb control carrying pVHb8 (A600 5.8). AFFFF revealed that cells expressing mutant vhbs showed up to a doubling in the number of active 70S ribosomes cell-1, an almost 3-fold increase in the number of tRNAs cell-1, and up to a 26% increase in the mass fraction of active 70S ribosomes.
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14.
  • Andersson, Claes-Henrik, et al. (author)
  • Synthesis and IR Spectroelectrochemical Studies of a [60]Fulleropyrrolidine-(tricarbonyl)chromium Complex : Probing C-60 Redox States by IR Spectroscopy
  • 2011
  • In: European Journal of Inorganic Chemistry. - : John Wiley & Sons. - 1434-1948 .- 1099-1948 .- 1099-0682. ; :11, s. 1744-1749
  • Journal article (peer-reviewed)abstract
    • The synthesis of a new fulleropyrrolidine-(tricarbonyl)chromium complex: 1-methyl-2-(4-methoxyphenyl)-3,4-[60]fulleropyrrolidine-(tricarbonyl)chromium is described together with its characterization by IR, NMR and cyclic voltammetry. IR spectro-electrochemistry has been used to probe the redox level of the fullerene derivative via the relative position of the vibrational bands of the CO ligands, which are sensitive to the electronic state of the complex. Other strategies to incorporate a tricarbonylchromium moiety to fullerene C60 are also briefly discussed and evaluated.
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  • Andersson, Charlotte, et al. (author)
  • Noncardiac Surgery in Patients With Aortic Stenosis: A Contemporary Study on Outcomes in a Matched Sample From the Danish Health Care System
  • 2014
  • In: Clinical Cardiology. - : Wiley. - 1932-8737 .- 0160-9289. ; 37:11, s. 680-686
  • Journal article (peer-reviewed)abstract
    • BackgroundPast research has identified aortic stenosis (AS) as a major risk factor for adverse outcomes in noncardiac surgery; however, more contemporary studies have questioned the grave prognosis. To further our understanding of this, the risks of a 30-day major adverse cardiovascular event (MACE) and all-cause mortality were investigated in a contemporary Danish cohort. HypothesisAS is not an independent risk factor for adverse outcomes in noncardiac surgery. MethodsAll patients with and without diagnosed AS who underwent noncardiac surgery in 2005 to 2011 were identified through nationwide administrative registers. AS patients (n=2823; mean age, 75.5years, 53% female) were matched with patients without AS (n=2823) on propensity score for AS and surgery type. ResultsIn elective surgery, MACE (ie, nonfatal myocardial infarction, ischemic stroke, or cardiovascular death) occurred in 66/1772 (3.7%) of patients with AS and 52/1772 (2.9%) of controls (P=0.19), whereas mortality occurred in 67/1772 (3.8%) AS patients and 51/1772 (2.9%) controls (P=0.13). In emergency surgery, 163/1051 (15.5%) AS patients and 120/1051 (11.4%) controls had a MACE (P=0.006), whereas 225/1051 (21.4%) vs 179/1051 (17.0%) AS patients and controls died, respectively (P=0.01). Event rates were higher for those with symptoms (defined as use of nitrates, congestive heart failure, or use of loop diuretics), compared with those without symptoms (P<0.0001). ConclusionsAS is associated with high perioperative rates of MACE and mortality, but perhaps prognosis is, in practice, not much worse for patients with AS than for matched controls. Symptomatic patients and patients undergoing emergency surgery are at considerable risks of a MACE and mortality.
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  • Andersson, David (author)
  • Deciding Fast and Slow : How Intuitive and Reflective Thinking Influence Decision Making
  • 2016
  • Doctoral thesis (other academic/artistic)abstract
    • Paper I “Intuition and cooperation reconsidered”: Does intuition make people more cooperative? Rand et al. (Rand, Greene, & Nowak, 2012) reported increased cooperation in social dilemmas after forcing individuals to decide quickly. We test the robustness of this finding in a series of five experiments involving about 2,500 subjects in three countries. None of the experiments confirms the Rand et al. (2012) finding, indicating that their result was an artefact of excluding about 50% of the subjects who failed to respond on time.Paper II “Intuition and moral decision-making – the effect of time pressure and cognitive load on moral judgment and altruistic behavior”: Do individuals intuitively favor certain moral actions over others? This study explores the role of intuitive thinking — induced by time pressure and cognitive load — in moral judgment and behavior. Overall we find converging evidence that intuitive states do not influence moral decisions. Across all samples and decision tasks men were more likely to make utilitarian moral judgments and act selfishly compared to women, providing further evidence that there are robust gender differences in moral decision-making.Paper III “Public views on policies involving nudges”: When should nudging be deemed as permissible and when should it be deemed as intrusive to individuals’ freedom of choice? The main objective of this study is to elicit public views on the use of nudges in policy. In particular we investigate attitudes toward two broad categories of nudges that we label pro-self (i.e. focusing on private welfare) and pro-social (i.e. focusing on social welfare) nudges. Results show that the level of acceptance toward nudge-policies was generally high. Nudge polices classified as pro-social had a significantly lower acceptance rate compared to pro-self nudges.Paper IV “The effect of fast and slow decisions on financial risk-taking”: Are individuals financial risk taking influenced by time available? We experimentally compare fast and slow decisions in a series of experiments on financial risk taking in three countries involving over 1,700 subjects. We find that time pressure increases risk aversion for gains and risk taking for losses compared to time delay; implying that time pressure increase the reflection effect of Prospect Theory.Paper V “Incidental effect and financial risk-taking – a neural investigation: This study builds on the results from Paper IV. Here I explore the influence of incidental negative emotions on financial risk-taking in an fMRI environment in order to assess underlying neural mechanisms. I experimentally compare neutral and unpleasant valence framing on gambles involving pure monetary gain and pure monetary loss. I find a significantly increased BOLD response in left amygdala and bilateral visual cortex when contrasting when showing unpleasant pictures, a neural effect which is in line with previous neuroimaging studies on negative emotions. However the neural effect of showing unpleasant pictures did not affect choices in the risk tasks. Consequently, I did not find any support for the hypothesis that the reflection effect of Prospect theory should be more pronounced when making risky choices influenced by incidental negative emotions.
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  • Andersson, Daniel P., et al. (author)
  • Relation among hypertriglyceridaemia, cardiometabolic disease, and hereditary factors : design and rationale of the Stockholm hyperTRIglyceridaemia REGister study
  • 2024
  • In: European Heart Journal Open. - : Oxford University Press. - 2752-4191. ; 4:2
  • Journal article (peer-reviewed)abstract
    • AimsHypertriglyceridaemia (hTG) is associated with atherosclerotic cardiovascular disease, pancreatitis, and non-alcoholic fatty liver disease (NAFLD) in large population-based studies. The understanding of the impact of hereditary hTG and cardiometabolic disease status on the development of hTG and its associated cardiometabolic outcomes is more limited. We aimed to establish a multigenerational cohort to enable studies of the relationship between hTG, cardiometabolic disease and hereditary factors.Methods and resultsThe population-based observational Stockholm hyperTRIglyceridaemia REGister (STRIREG) study includes 1 460 184 index individuals who have measured plasma triglycerides in the clinical routine in Region Stockholm, Sweden, between 1 January 2000 and 31 December 2021. The laboratory measurements also included basic haematology, blood lipid panel, liver function tests, and HbA1c. Using the Swedish Multi-Generation register, 2 147 635 parents and siblings to the indexes were identified to form the complete study cohort. Laboratory data from participants were combined with data from several national registers that provided information on the cause of death, medical diagnoses, dispensed medicines, and socioeconomic factors including country of birth, education level, and marital status.ConclusionThe multi-generational longitudinal STRIREG cohort provides a unique opportunity to investigate different aspects of hTG as well as heredity for other metabolic diseases. Important outcome measures include mortality, cardiovascular mortality, major cardiovascular events, development of incident diabetes, and NAFLD. The STRIREG study will provide a deeper understanding of the impact of hereditary factors and associated cardiometabolic complications.
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20.
  • Andersson, Gustav, 1990, et al. (author)
  • Acoustic spectral hole-burning in a two-level system ensemble
  • 2021
  • In: npj Quantum Information. - : Springer Science and Business Media LLC. - 2056-6387. ; 7:1
  • Journal article (peer-reviewed)abstract
    • Microscopic two-level system (TLS) defects at dielectric surfaces and interfaces are among the dominant sources of loss in superconducting quantum circuits, and their properties have been extensively probed using superconducting resonators and qubits. We report on spectroscopy of TLSs coupling to the strain field in a surface acoustic wave (SAW) resonator. The narrow free spectral range of the resonator allows for two-tone spectroscopy where a strong pump is applied at one resonance, while a weak signal is used to probe a different mode. We map the spectral hole burnt by the pump tone as a function of frequency and extract parameters of the TLS ensemble. Our results suggest that detuned acoustic pumping can be used to enhance the coherence of superconducting devices by saturating TLSs.
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21.
  • Andersson, Gustav, et al. (author)
  • Arteries in the area targeted with successful sclerosing injections for Achilles tendinosis are under distinct neural control
  • 2006
  • Conference paper (peer-reviewed)abstract
    • It has been scientifically demonstrated that there are blood vessels with pathologically high blood flow inside and outside the ventral part of the Achilles tendon in chronic painful tendinosis, but not in pain-free normal Achilles tendons. Injections of local anaesthesia on the outside of the ventral part of the tendon have been found to temporarily abolish the tendon pain, and this has been an inspiration in the development of a new approach in the treatment of tendinosis: Based on ultrasound- (US) and colour Doppler- (CD) guidance, the sclerosing substance polidocanol, for many years used in treatment of varicose veins, was injected targeting the area of high-flow blood vessels just outside the ventral part of the Achilles tendon. The treatment has in pilot studies and a randomized controlled clinical study been shown to cure the pain in about 70-80 % of the patients. Also, follow up examinations, using US and CD, have shown a possible remodeling potential of the tendon. There is some previous information available on the innervation patterns of the human Achilles tendon itself. However, the innervation patterns of the area just outside the ventral part of the tendon, i.e. the area that is targeted by the sclerosing injections (target area), are unknown. This includes a lack of information concerning the nerve-related characteristics of the blood vessels in the area. In this study, therefore, tissue specimens from this target area, obtained during surgical treatment of patients with chronic painful mid-portion Achilles tendinosis, were examined. Histological and immunohistochemical examinations were performed. In the tissue of the target area, in which loose connective tissue and fat cells were frequent constituents, there was a presence of arteries and nerve fascicles. The arteries were of varying dimensions, some being very large. The nerve fascicles were distinguished in sections processed for the pan-neural marker protein gene-product 9.5 (PGP 9.5).  Some of the arteries were supplied by an extensive perivascular innervation, as seen via PGP 9.5 staining. As seen via processing for the rate limiting enzyme in catecholamine synthesis, tyrosine hydroxylase (TH), sympathetic innervation was found to be a constituent of this innervation. There was furthermore a marked occurrence of immunoreactions for the α1-adrenoreceptor in arterial walls. Also, there was a presence of immunoreactions for the substance P (SP)-preferred receptor, the neurokinin-1 (NK-1) receptor in arterial walls. This receptor was particularly detected in the endothelial parts. The study shows that the arteries in the target area are accompanied by nerve fascicles and that there is a presence of a perivascular innervation, as well as a presence of adrenergic and NK-1 receptors in arterial walls, in this region. Thus, arteries in this area are under distinct neural control. The nerve-related characteristics of the area targeted in the successful polidicanol injection treatment for Achilles tendinosis are here for the first time shown.
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  • Andersson, Gustav, et al. (author)
  • Clinical significance of stromal ER and PR expression in periampullary adenocarcinoma
  • 2019
  • In: Biomarker research. - : Springer Science and Business Media LLC. - 2050-7771. ; 7:1
  • Journal article (peer-reviewed)abstract
    • Background: Tamoxifen treatment has previously been reported to confer life-prolonging effects in patients with advanced pancreatic cancer, and most evidently so in women. None of these trials did however include biomarkers, and the relevance of female hormone signaling in pancreatic or other periampullary adenocarcinoma remains largely unexplored. The aim of this study was to examine the extent and potential clinical significance of estrogen receptor-α (ER) and progesterone receptor (PR) expression in pancreatic and other periampullary cancers. Methods: ER and PR expression was examined using immunohistochemistry on tissue microarrays with primary tumors from a retrospective consecutive cohort of 175 patients with resected periampullary adenocarcinoma, with long-term clinical follow-up. Non-parametric and Chi square tests were applied to examine the associations of stromal ER and PR expression with patient and tumor characteristics. Kaplan-Meier analysis and log rank test were applied to illustrate survival differences in relation to ER and PR expression. Cox regression proportional hazards models were applied to examine the associations between investigative factors and risk of death and recurrence, and to test for interactions between KRAS mutation status and hormone receptor expression in relation to survival. Results: Expression of both ER and PR was more frequent in the tumor-associated stroma than in the epithelium. A significant prognostic interaction, independent of tumor morphology, was found between stromal PR expression and KRAS mutation status in relation to both overall and recurrence-free survival (pinteraction = 0.026 and pinteraction = 0.005), in particular in women (pinteraction = 0.002 and pinteraction = 0.005). Specifically, stromal PR expression was associated with a prolonged survival in patients with KRAS-mutated tumors, whereas the opposite was seen for KRAS wild-type tumors. The prognostic value of ER positivity was limited to the subgroup of women with tumors of pancreatic origin. Conclusions: These results demonstrate that stromal PR rather than ER expression, together with KRAS mutation status, provides long-term prognostic information in patients with periampullary adenocarcinoma. Further study into the mechanistic basis for these observations may unveil important clues to the pathogenesis of these cancers and open up for the discovery of novel treatment options.
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23.
  • Andersson, Gustav, 1990, et al. (author)
  • Electromagnetically Induced Acoustic Transparency with a Superconducting Circuit
  • 2020
  • In: Physical Review Letters. - 1079-7114 .- 0031-9007. ; 124:24
  • Journal article (peer-reviewed)abstract
    • We report the observation of electromagnetically induced transparency (EIT) of a mechanical field, where a superconducting artificial atom is coupled to a 1D-transmission line for surface acoustic waves. An electromagnetic microwave drive is used as the control field, rendering the superconducting transmon qubit transparent to the acoustic probe beam. The strong frequency dependence of the acoustic coupling enables EIT in a ladder configuration due to the suppressed relaxation of the upper level. Our results show that superconducting circuits can be engineered to interact with acoustic fields in parameter regimes not readily accessible to purely electromagnetic systems.
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24.
  • Andersson, Gustav, et al. (author)
  • Hormonal factors and pancreatic cancer risk in women : The Malmö Diet and Cancer Study
  • 2018
  • In: International Journal of Cancer. - : Wiley. - 0020-7136. ; 143:1, s. 52-62
  • Journal article (peer-reviewed)abstract
    • The incidence of pancreatic cancer is leveling between sexes. Smoking, high age and heredity are established risk factors, but evidence regarding the influence of hormonal factors is unclear. In this study, we investigated the associations of reproductive factors, use of oral contraceptives (OC) and hormone replacement therapy (HRT) with pancreatic cancer risk in the Malmö Diet and Cancer Study, a prospective, population-based cohort encompassing 17,035 women. Up until 31 December 2015, 110 women were identified with incident pancreatic cancer through the Swedish Cancer Registry. Higher age at menarche was significantly associated with pancreatic cancer risk (age-adjusted [hazard ratio] HR = 1.17; 95% confidence interval [CI] 1.04–1.32, and fully adjusted HR = 1.17; 95% CI 1.04–1.32). Ever use of OC was not significantly associated with pancreatic cancer risk but ever use of HRT was significantly associated with a decreased risk of pancreatic cancer (age-adjusted HR = 0.47, 95% CI 0.23–0.97, and fully adjusted HR = 0.48, 95% CI 0.23–1.00), in particular use of estrogen-only regimen (age-adjusted HR = 0.21; 95% CI 0.05–0.87 and fully adjusted HR = 0.22; 95% CI 0.05–0.90). Age at menopause or first childbirth, parity and breastfeeding history were not significantly associated with pancreatic cancer risk. Collectively, these findings suggest a protective role of female hormones against pancreatic cancer. Further studies are needed, and potential modifying genetic factors and indirect hazardous effects of smoking should also be considered.
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25.
  • Andersson, Gustav, et al. (author)
  • In vivo Diffusion Tensor Imaging, Diffusion Kurtosis Imaging, and Tractography of a Sciatic Nerve Injury Model in Rat at 9.4T
  • 2018
  • In: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 8
  • Journal article (peer-reviewed)abstract
    • Peripheral nerve injuries result in severe loss of sensory and motor functions in the afflicted limb. There is a lack of standardised models to non-invasively study degeneration, regeneration, and normalisation of neuronal microstructure in peripheral nerves. This study aimed to develop a non-invasive evaluation of peripheral nerve injuries, using diffusion tensor imaging (DTI), diffusion kurtosis imaging (DKI), and tractography on a rat model of sciatic nerve injury. 10 female Sprague Dawley rats were exposed to sciatic nerve neurotmesis and studied using a 9.4 T magnet, by performing DTI and DKI of the sciatic nerve before and 4 weeks after injury. The distal nerve stump showed a decrease in fractional anisotropy (FA), mean kurtosis (MK), axonal water fraction (AWF), and radial and axonal kurtosis (RK, AK) after injury. The proximal stump showed a significant decrease in axial diffusivity (AD) and increase of MK and AK as compared with the uninjured nerve. Both mean diffusivity (MD) and radial diffusivity (RD) increased in the distal stump after injury. Tractography visualised the sciatic nerve and the site of injury, as well as local variations of the diffusion parameters following injury. In summary, the described method detects changes both proximal and distal to the nerve injury.
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26.
  • Andersson, Gustav, 1983- (author)
  • Influences of paratendinous innervation and non-neuronal substance P in tendinopathy : studies on human tendon tissue and an experimental model of Achilles tendinopathy
  • 2010
  • Doctoral thesis (other academic/artistic)abstract
    • Pain of the musculoskeletal system is one of the most common reasons for people seeking medical attention, and is also one of the major factors that prevent patients from working. Chronic tendon pain, tendinopathy, affects millions of workers world-wide, and the Achilles tendon is an important structure often afflicted by this condition. The pathogenesis of tendinopathy is poorly understood, but it is thought to be of multifactoral aetiology. It is known that tendon pain is often accompanied not only by impaired function but also by structural tissue changes, like vascular proliferation, irregular collagen organisation, and hypercellularity, whereby the condition is called tendinosis. In light of the poor knowledge of tendinosis pathophysiology and recent findings of a non-neuronal signalling system in tendon tissue, the contributory role of neuropeptides such as substance P (SP) has gained increased interest. SP, known for afferent pain signalling in the nervous system, also has multiple efferent functions and has been described to be expressed by non-neuronal cells. As pain is the most prominent symptom of tendinopathy, the focus of the studies in this thesis was the innervation patterns of the tissue ventral to the Achilles tendon (i.e. the tissue targeted in many contemporary treatment methods) as well as the distribution of SP and its preferred receptor, the neurokinin-1 receptor (NK-1R), in the tendon tissue itself. It was hereby hypothesised that the source of SP affecting the Achilles tendon might be the main cells of the tendon tissue (the tenocytes) as well as paratendinous nerves, and that SP might be involved in tendinosis- development. The studies were conducted, via morphological staining methods including immunohistochemistry and in situ hybridisation, on tendon biopsies from patients suffering from Achilles tendinosis and on those from healthy volunteers. The hypothesis of the thesis was furthermore tested using an experimental animal model (rabbit) of Achilles tendinopathy, which was first validated. The model was based on a previously established overuse protocol of repetitive exercise. In the human biopsies of the tissue ventral to the Achilles tendon, there was a marked occurrence of sympathetic innervation, but also sensory, SP-containing, nerve fibres. NK-1R was expressed on blood vessels and nerve fascicles of the paratendinous tissue, but also on the tenocytes of the tendon tissue proper itself, and notably more so in patients suffering from tendinosis. Furthermore, the human tenocytes displayed not only NK-1R mRNA but also mRNA for SP. The animal model was shown to produce objectively verified tendinosis-like changes, such as hypercellularity and increased vascularity, in the rabbit Achilles tendons, after a minimum of three weeks of the exercise protocol. The contralateral leg of the animals in the model was found to be an unreliable control, as bilateral changes occured. The model furthermore demonstrated that exogenously administered SP triggers an inflammatory response in the paratendinous tissue and accelerates the intratendinous tendinosis-like changes such that they now occur after only one week of the protocol. Injections of saline as a control showed similar results as SP concerning hypercellularity, but did not lead to vascular changes or pronounced paratendinous inflammation. In summary, this thesis concludes that interactions between the peripheral sympathetic and sensory nervous systems may occur in Achilles tendinosis at the level of the ventral paratendinous tissue, a region thought to be of great importance in chronic tendon pain since many successful treatments are directed toward it. Furthermore, the distribution of NK-1R:s in the Achilles tendon described in these studies gives a basis for SP, whether produced by nerves mainly outside the tendon or by tenocytes within the tendon, to affect blood vessels, nerve structures, and/or tendon cells, especially in tendinosis patients. In light of this and of previously known SP-effects, such as stimulation of angiogenesis, pain signalling, and cell proliferation, the proposed involvement of SP in tendinosis development seems likely. Indeed, the animal model of Achilles tendon overuse confirms that SP does induce vascular proliferation and hypercellularity in tendon tissue, thus strengthening theories of SP playing a role in tendinosis pathology.
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27.
  • Andersson, Gustav, et al. (author)
  • Nerve distributions in insertional Achilles tendinopathy - a comparison of bone, bursae and tendon
  • 2017
  • In: Histology and Histopathology. - 0213-3911 .- 1699-5848. ; 32:3, s. 263-270
  • Journal article (peer-reviewed)abstract
    • Background/Aim. In a condition of pain in the Achilles tendon insertion there are multiple structures involved, such as the Achilles tendon itself, the retrocalcaneal bursa and a bony protrusion at the calcaneal tuberosity called Haglund's deformity. The innervation patterns of these structures are scarcely described, and the subcutaneous calcaneal bursa is traditionally not considered to be involved in the pathology. This study aimed at describing the innervation patterns of the four structures described above to provide a better understanding of possible origins of pain at the Achilles tendon insertion.Methods. Biopsies were taken from 10 patients with insertional Achilles tendinopathy, which had pathological changes in the subcutaneous and retrocalcaneal bursae, a Haglund deformity and Achilles tendon tendinopathy as verified by ultrasound. The biopsies were stained using immunohistochemistry in order to delineate the innervation patterns in the structures involved in insertional Achilles tendinopathy.Results. Immunohistochemical examinations found that the subcutaneous bursa scored the highest using a semi-quantitative evaluation of the degree of innervation when compared to the retrocalcaneal bursa, the Achilles tendon, and the calcaneal bone.Conclusions. These findings suggest that the subcutaneous bursa, which is traditionally not included in surgical treatment, may be a clinically important factor in insertional Achilles tendinopathy.
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28.
  • Andersson, Gustav, 1983-, et al. (author)
  • Nerve-related characteristics of ventral paratendinous tissue in chronic Achilles tendinosis
  • 2007
  • In: Knee Surgery, Sports Traumatology, Arthroscopy. - : Springer Science and Business Media LLC. - 0942-2056 .- 1433-7347. ; 15:10, s. 1272-1279
  • Journal article (peer-reviewed)abstract
    • Ultrasound and Doppler examination has shown high blood flow-neovascularisation inside and outside the ventral Achilles tendon in chronic painful tendinosis, but not in pain-free normal Achilles tendons. In patients with Achilles tendinosis, injections with the sclerosing substance polidocanol, targeting the areas with increased blood flow, have been demonstrated to give pain relief. A drawback when interpreting these findings is the fact that the pattern of nerve supply in the target area, i.e. the ventral area of the tendon, is so far unknown. In this study, therefore, tissue specimens from this area, obtained during surgical treatment of patients with chronic painful midportion Achilles tendinosis, were examined. In the examined area, containing loose connective tissue, the general finding was a presence of large and small arteries and nerve fascicles. The nerve fascicles were distinguished in sections processed for the pan-neural marker protein gene-product 9.5. The nerve fascicles contain sensory nerve fibers, as shown via staining for the sensory markers substance P (SP) and calcitonin gene-related peptide, and sympathetic nerve fibers as seen via processing for tyrosine hydroxylase. In addition, there were immunoreactions for the SP-preferred receptor, the neurokinin-1 receptor, in blood vessel walls and nerve fascicles. Some of the blood vessels were supplied by an extensive peri-vascular innervation, sympathetic nerve fibers being a distinct component of this innervation. There was also a marked occurrence of immunoreactions for the alpha1-adrenoreceptor in arterial walls as well as in the nerve fascicles. Altogether, these findings suggest that the area investigated is under marked influence by the nervous system, including sympathetic and sensory components. Thus, sympathetic/sensory influences may be involved in the pain mechanisms from this area. In conclusion, the nerve-related characteristics of the area targeted by the polidicanol injection treatment for Achilles tendinosis, are shown here for the first time.
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29.
  • Andersson, Gustav, 1990, et al. (author)
  • Non-exponential decay of a giant artificial atom
  • 2019
  • In: Nature Physics. - : Springer Science and Business Media LLC. - 1745-2481 .- 1745-2473. ; 15:11, s. 1123-1127
  • Journal article (other academic/artistic)abstract
    • In quantum optics, light–matter interaction has conventionally been studied using small atoms interacting with electromagnetic fields with wavelength several orders of magnitude larger than the atomic dimensions1,2. In contrast, here we experimentally demonstrate the vastly different ‘giant atom’ regime, where an artificial atom interacts with acoustic fields with wavelength several orders of magnitude smaller than the atomic dimensions. This is achieved by coupling a superconducting qubit3 to surface acoustic waves at two points with separation on the order of 100 wavelengths. This approach is comparable to controlling the radiation of an atom by attaching it to an antenna. The slow velocity of sound leads to a significant internal time-delay for the field to propagate across the giant atom, giving rise to non-Markovian dynamics4. We demonstrate the non-Markovian character of the giant atom in the frequency spectrum as well as non-exponential relaxation in the time domain.
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30.
  • Andersson, Gustav, et al. (author)
  • Pancreatic cancer risk in relation to sex, lifestyle factors, and pre-diagnostic anthropometry in the Malmö Diet and Cancer Study
  • 2016
  • In: Biology of Sex Differences. - : Springer Science and Business Media LLC. - 2042-6410. ; 7:1
  • Journal article (peer-reviewed)abstract
    • Background: Lifestyle factors may influence the risk of developing pancreatic cancer. Whereas cigarette smoking is an established risk factor, the effects of high alcohol intake and obesity are more uncertain. The aim of the present study was to examine the associations of pre-diagnostic anthropometry, alcohol consumption, and smoking habits with pancreatic cancer risk in a Swedish prospective, population-based cohort, with particular reference to potential sex differences. Methods: The studied cohort consists of 28,098 participants, including all incident cases of pancreatic cancer, in the Malmö Diet and Cancer Study up until December 31, 2013 (n = 163). Non-parametric and chi-squared tests were applied to compare the distribution of risk factors between cases and non-cases. Cox regression proportional hazards models were used to estimate the relationship between investigative factors and pancreatic cancer risk. Anthropometric factors included height, weight, body mass index (BMI), waist and hip circumference, waist-hip ratio (WHR), and body fat percentage. Results: BMI was not a significant risk factor for pancreatic cancer, but a higher WHR was significantly associated with an increased risk in the entire cohort (hazard ratio (HR) 2.36, 95% confidence interval (CI) 1.28-4.35, p for trend = 0.009). Regular smoking was a significant risk factor among both women (HR 2.62, 95% CI 1.61-4.27) and men (HR 3.57, 95% CI 1.70-7.47), whereas occasional smoking was a significant risk factor only in women (HR 3.29, 95% CI 1.50-7.19). Passive smoking at work for >20 years was significantly associated with an increased risk in the entire cohort (HR 1.73, 95% CI 1.15-2.58) and in women selectively (HR 2.01, 95% CI 1.21-3.31). Alcohol consumption was not a significant risk factor. A significant interaction was found between female sex and age (p = 0.045), but no other factor, in relation to pancreatic cancer risk. Conclusions: WHR was the only pre-diagnostic anthropometric factor associated with pancreatic cancer risk, with no sex-related differences. Regular smoking was confirmed as a significant risk factor in both sexes, whereas occasional and passive smoking were significant risk factors only in women. Despite the lack of a significant interaction between smoking and sex in relation with pancreatic cancer risk, potential sex differences should be considered in future epidemiological studies.
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31.
  • Andersson, Gustav, 1983-, et al. (author)
  • Presence of substance P and the neurokinin-1 receptor in tenocytes of the human Achilles tendon
  • 2008
  • In: Regulatory Peptides. - : Elsevier BV. - 0167-0115 .- 1873-1686. ; 150:1-3, s. 81-87
  • Journal article (peer-reviewed)abstract
    • Nerve signal substances, such as the tachykinin substance P (SP), may be involved in the changes that occur in response to tendinopathy (tendinosis). It is previously known that the level of SP innervation within tendon tissue is limited, but results of experimental studies have suggested that SP may have stimulatory, angiogenetic and healing effects in injured tendons. Therefore, it would be of interest to know if there is a local SP-supply in tendon tissue. In the present study, the patterns of expression of SP and its preferred receptor, the neurokinin-1 receptor (NK-1 R), in normal and tendinosis human Achilles tendons were analyzed by use of both immunohistochemistry and in situ hybridization. We found that there was expression of SP mRNA in tenocytes, and that tenocytes showed expression of NK-1 R at protein as well as mRNA levels. The observations concerning both SP and NK-1 R were most evident for tenocytes in tendinosis tendons. Our findings suggest that SP is produced in tendinosis tendons, and furthermore that SP has marked effects on the tenocytes via the NK-1 R. It cannot be excluded that the SP effects are of importance concerning the processes of reorganization and healing that occur for tendon tissue in tendinosis. In conclusion, it appears as if SPergic autocrine/paracrine effects occur in tendon tissue during the processes of tendinosis, hitherto unknown effects for human tendons.
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32.
  • Andersson, Gustav, 1990 (author)
  • Quantum acoustics with superconducting circuits
  • 2020
  • Doctoral thesis (other academic/artistic)abstract
    • The past 20 years has seen rapid developments in circuit quantum electrodynamics, where superconducting qubits and resonators are used to control and study quantum light-matter interaction at a fundamental level. The development of this field is strongly influenced by quantum information science and the prospect of realizing quantum computation, but also opens up opportunities for combinations of different physical systems and research areas. Superconducting circuits in the microwave domain offer a versatile platform for interfacing with other quantum systems thanks to strong nonlinearities and zero-point fluctuations, as well as flexibility in design and fabrication. Hybrid quantum systems based on circuit quantum electrodynamics could enable novel functionalities by exploiting the strengths of the individual components. This thesis covers experiments coupling superconducting circuits to surface acoustic waves (SAWs), mechanical waves propagating along the surface of a solid. Strong coupling can be engineered using the piezoelectric properties of GaAs substrates, and our experiments exploit this to investigate phenomena in quantum field-matter interaction. A key property of surface acoustic waves is the slow propagation speed, typically five orders of magnitude slower than light in vacuum, and the associated short wavelength. This enables the giant atom regime where the artificial atom in the form of a superconducting circuit is large compared to the wavelength of interacting SAW radiation, a condition which is difficult to realize in other systems. Experiments described in this thesis use these properties to demonstrate electromagnetically induced transparency for a mechanical mode, as well as non-Markovian interactions between an artificial giant atom and the SAW field. When the SAW field is confined to a resonant cavity, the short wavelength allows multimode spectra suitable for interacting with a frequency comb. We use a multimode SAW resonator to characterize the ensemble of microscopic two-level system defects with a two-tone spectroscopy approach. Finally, we introduce a hybrid superconducting-SAW resonator with applications in quantum information processing in mind. Experiments with this device demonstrate entanglement of SAW modes, and show promising results on the way to engineer cluster states for quantum computation in continuous variables.
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33.
  • Andersson, Gustav, et al. (author)
  • Reduced expression of ezrin in urothelial bladder cancer signifies more advanced tumours and an impaired survival : validatory study of two independent patient cohorts
  • 2014
  • In: BMC Urology. - : BioMed Central (BMC). - 1471-2490. ; 14:1, s. 36-
  • Journal article (peer-reviewed)abstract
    • Background: Reduced membranous expression of the cytoskeleton-associated protein ezrin has previously been demonstrated to correlate with tumour progression and poor prognosis in patients with T1G3 urothelial cell carcinoma of the bladder treated with non-maintenance Bacillus Calmette-Guerin (n = 92), and the associations with adverse clinicopathological factors have been validated in another, unselected, cohort (n = 104). In the present study, we examined the prognostic significance of ezrin expression in urothelial bladder cancer in a total number of 442 tumours from two independent patient cohorts. Methods: Immunohistochemical expression of ezrin was evaluated in tissue microarrays with tumours from one retrospective cohort of bladder cancer (n = 110; cohort I) and one population-based cohort (n = 342; cohort II). Classification regression tree analysis was applied for selection of prognostic cutoff. Kaplan-Meier analysis, log rank test and Cox regression proportional hazards' modeling were used to evaluate the impact of ezrin on 5-year overall survival (OS), disease-specific survival (DSS) and progression-free survival (PFS). Results: Ezrin expression could be evaluated in tumours from 100 and 342 cases, respectively. In both cohorts, reduced membranous ezrin expression was significantly associated with more advanced T-stage (p < 0.001), high grade tumours (p < 0.001), female sex (p = 0.040 and p = 0.013), and membranous expression of podocalyxin-like protein (p < 0.001 and p = 0.009). Moreover, reduced ezrin expression was associated with a significantly reduced 5-year OS in both cohorts (HR = 3.09 95% CI 1.71-5.58 and HR = 2.15(1.51-3.06), and with DSS in cohort II (HR = 2.77, 95% CI 1.78-4.31). This association also remained significant in adjusted analysis in Cohort I (HR1.99, 95% CI 1.05-3.77) but not in Cohort II. In pTa and pT1 tumours in cohort II, there was no significant association between ezrin expression and time to progression. Conclusions: The results from this study validate previous findings of reduced membranous ezrin expression in urothelial bladder cancer being associated with unfavourable clinicopathological characteristics and an impaired survival. The utility of ezrin as a prognostic biomarker in transurethral resection specimens merits further investigation.
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34.
  • Andersson, Gustav (author)
  • Sex, hormonal factors and pancreatic cancer
  • 2019
  • Doctoral thesis (other academic/artistic)abstract
    • Pancreatic cancer represents three percent of all incident cancer cases in developed countries, but stands the 7th most common cause of cancer related death. Worldwide, pancreatic cancer is more common among men, however in Sweden, the incidence ratio between sexes is levelling. Despite extensive research to map underlying risk factors, results are still largely inconclusive. Furthermore, there is a lack of knowledge regarding the influence of hormonal factors on risk and clinical outcome. A few studies have investigated the expression of female hormone receptors in pancreatic cancer, and others have reported beneficial effects of tamoxifen treatment in advanced pancreatic cancer, particularly in elderly women. The primary aim of this thesis was to investigate potential risk factors for pancreatic cancer, with particular reference to sex differences, and furthermore, to evaluate the presence and prognostic significance of hormone receptors in pancreatic and other periampullary cancers. Finally, based on the third paper, we composed a protocol for a clinical trial investigating the impact of tamoxifen treatment in women with advanced pancreatic cancer.The thesis is based on the Malmö Diet and Cancer Study (MDCS), a prospective population-based cohort with 28 098 participants, as well as a retrospective cohort with 175 consecutive cases of resected pancreatic and other periampullary adenocarcinoma. Cox proportional hazards regression models were applied to study the potential associations between investigative baseline factors and risk of pancreatic cancer in the MDCS. Immunohistochemical expression of estrogen and progesterone receptors (ER, PR) was analysed on tumour tissue microarrays from the retrospective cohort.Paper I confirms smoking as one of the most significant risk factors for pancreatic cancer, also proposing a greater risk increase among women.Paper II demonstrates an increased risk of pancreatic cancer among women with high age at menarche and a lower risk among postmenopausal women with a history of ever using hormonal replacement therapy.Paper III provides evidence of a prognostic interaction between stromal PR expression and KRAS mutation status in periampullary cancer, being particularly evident in women. More specifically, stromal PR positivity signified a prolonged survival in patients with KRAS-mutated tumours, and shorter survival in patients with KRAS wild-type tumours.Paper IV is a protocol for a single-centre, randomized, double-blind, placebo-controlled, two-arm, phase II clinical trial, investigating the effects of tamoxifen treatment on survival and quality of life in women with advanced pancreatic cancer.In summary, the thesis provides further evidence of tobacco smoking as one of the strongest risk factors for pancreatic cancer, with women being potentially more susceptible to these hazardous effects. Moreover, exogenous female hormones appear to have a protective effect, which is also in line with findings from some previous studies. The presence of ER and PR in the tumour-associated stroma in pancreatic and other periampullary adenocarcinoma, and the prognostic interaction between PR expression and KRAS status further supports that hormonal factors drive the pathogenesis and progression of these cancers. Based on the observations in Paper III, we will launch a randomized trial with tamoxifen treatment and control in women with advanced pancreatic cancer, that will also include relevant biomarker analyses.
  •  
35.
  • Andersson, Gustav, 1990, et al. (author)
  • Squeezing and Multimode Entanglement of Surface Acoustic Wave Phonons
  • 2022
  • In: PRX Quantum. - 2691-3399. ; 3:1
  • Journal article (peer-reviewed)abstract
    • Exploiting multiple modes in a quantum acoustic device could enable applications in quantum information in a hardware-efficient setup, including quantum simulation in a synthetic dimension and continuous-variable quantum computing with cluster states. We develop a multimode surface acoustic wave (SAW) resonator with a superconducting quantum interference device (SQUID) integrated in one of the Bragg reflectors. The interaction with the SQUID-shunted mirror gives rise to coupling between the more than 20 accessible resonator modes. We exploit this coupling to demonstrate two-mode squeezing of SAW phonons, as well as four-mode multipartite entanglement. Our results open avenues for continuous-variable quantum computing in a compact hybrid quantum system.
  •  
36.
  • Andersson, Gustav, et al. (author)
  • Squeezing and Multimode Entanglement of Surface Acoustic Wave Phonons
  • 2022
  • In: PRX Quantum. - : American Physical Society (APS). - 2691-3399. ; 3:1
  • Journal article (peer-reviewed)abstract
    • Exploiting multiple modes in a quantum acoustic device could enable applications in quantum information in a hardware-efficient setup, including quantum simulation in a synthetic dimension and continuous-variable quantum computing with cluster states. We develop a multimode surface acoustic wave (SAW) resonator with a superconducting quantum interference device (SQUID) integrated in one of the Bragg reflectors. The interaction with the SQUID-shunted mirror gives rise to coupling between the more than 20 accessible resonator modes. We exploit this coupling to demonstrate two-mode squeezing of SAW phonons, as well as four-mode multipartite entanglement. Our results open avenues for continuous-variable quantum computing in a compact hybrid quantum system.
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37.
  • Andersson, Gustav, et al. (author)
  • Substance P accelerates hypercellularity and angiogenesis in tendon tissue and enhances paratendinitis in response to Achilles tendon overuse in a tendinopathy model
  • 2011
  • In: British Journal of Sports Medicine. - Loughborough : British Assoc. of Sport and Medicine. - 0306-3674 .- 1473-0480. ; 45:13, s. 1017-1022
  • Journal article (peer-reviewed)abstract
    • Background Tenocytes produce substance P (SP) and its receptor (neurokinin-1 receptor (NK-1R) is expressed throughout the tendon tissue, expecially in patients with tendinopathy and tissue changes (tendinosis) including hypercellularity and vascular proliferation. Considering the known effects of SP, one might ask whether SP contributes to these canges.Objectives To test whether development of tendinosislike changes (hypercellularity and angiogenesis) is accelerated during a 1-week course of ecercise with local administration of SP in an establish Achilles tendinopathy model.Methods Rabbits were subjected to a protocol of Achilles tendon overuse for 1 week, in conjunction with SP injections in the paratenon. Exercised control animals received NaCl injections or no injections, and unexercised, uninjected controls were also used. Tenocyte number and vascular density, as well as paratendinous inflammation, were evaluated. Immunohistochemistry and in sity hybridisation to detect NK-1R were conducted.Results There was a significant increase in tenocyte number in the SP-injected and NaCl-injected groups compared with both unexercised and exercised, uninjected controls. Tendon blood vessels increased in number in the SP-injected group compared with unexercised controls, a finding not seen in NaCl-injected controls or in uninjected, exercised animals. Paratendinous inflammation was more pronounced in the SP-injected group than in the NaCl controls. NK-1R was detected in blood vessel walls, nerves, inflammatory cells and tenocytes.Conclusions SP accelerated the development of tendinosis-like changes in the rabbit. Achilles tendon, which supports theories of a potential role of SP in tendinosis development; a fact of clinical interest since SP effects can be effectively blocked. The angiogenic response to SP injections seems related to parateninitis.
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38.
  • Andersson, Gustav, 1983-, et al. (author)
  • Substance P induces tendinosis-like changes in a rabbit model of Achilles tendon overuse
  • Other publication (other academic/artistic)abstract
    • BACKGROUND: In previous studies we found evidence favouring that human Achilles tendon cells (tenocytes) are capable of producing the neuropeptide substance P (SP). Furthermore, the preferred receptor for SP (the neurokinin-1 receptor, NK-1 R) was widely expressed throughout the tendon, especially in patients suffering from chronic tendon pain (tendinopathy) with tissue changes (tendinosis) including hypercellularity and vascular proliferation. Considering known effects of SP, one might ask whether SP contributes to tendon cell proliferation and neovascularisation in tendinosis. We have an established animal (rabbit) model of Achilles tendinopathy based on overuse in the form of repetitive exercise. Recent studies with this model have shown that tendinosis-like changes are present after 3 weeks of exercise, but not after only 1 week. The current study aimed to test whether the development of tendinosis-like changes would be accelerated during a 1 week course of exercise with repetitive local administration of SP. MATERIAL AND METHODS: Four groups of animals (5-6 New Zealand white rabbits per group) were used. Three groups were subjected to the previously established protocol of Achilles tendon overuse for 1 week. One of these groups was given repetitive SP injections in the paratendinous tissue of the Achilles tendon, whereas one group (‘NaCl controls’) was given an equivalent schedule of saline injections. Two additional control groups existed: One in which the animals were neither subjected to the overuse protocol nor to any injections (‘untrained controls’), and one in which the animals trained for 1 week but were not given any injections (‘1 week controls’). Tenocyte number, vascular density, and the possible occurrence of paratendinous inflammation were evaluated. Immunohistochemistry and in situ hybridisation to detect NK-1 R were also conducted. RESULTS: There was a significant increase in tenocyte number in the SP-injected group compared to both untrained controls and 1 week controls. However, the same phenomenon was noticed for NaCl controls, i.e. tenocyte number was significantly increased in response to NaCl injections compared to untrained controls. There was an increase in the number of tendon blood vessels in the SP-injected group as compared to untrained controls, and this increase in vascularity was not seen for the NaCl controls or the 1 week controls. Paratendinous inflammation, as evidenced by invasion of inflammatory cells in the paratenon, was clearly more pronounced in the SP-injected group than in the NaCl controls. NK-1 R was detected in blood vessel walls, on nerves, on inflammatory cells, and on tenocytes. DISCUSSION AND CONCLUSIONS: The observations suggest that SP induces tenocyte proliferation and angiogenesis in the rabbit Achilles tendon, thus supporting a potential role of this neuropeptide in the processes that occur in tendinosis. The study corroborates findings on the human Achilles tendon in that NK-1 R was expressed on tenocytes and tendon blood vessel walls, thereby providing a potential anatomic basis for the observed effects of SP on the development of tendinosis. The hypercellularity observed in response to NaCl injections might be due increased tissue pressure or to stimulation of endogenous SPproduction, a phenomenon not unheard of. The angiogenic effect of SP injections, on the other hand, appeared to be more specifically related to an induction of inflammation in the paratendon.
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39.
  • Andersson, Gustav, 1983-, et al. (author)
  • Tenocyte hypercellularity and vascular proliferation in a rabbit model of tendinopathy : contralateral effects suggest the involvement of central neuronal mechanisms
  • 2011
  • In: British Journal of Sports Medicine. - : BMJ. - 0306-3674 .- 1473-0480. ; 45:5, s. 399-406
  • Journal article (peer-reviewed)abstract
    • Objective To determine whether there are objective findings of tendinosis in a rabbit tendinopathy model on exercised and contralateral (non-exercised) Achilles tendons. Design Four groups of six New Zealand white rabbits per group were used. The animals of one (control) group were not subjected to exercise/stimulation. Interventions Animals were subjected to a protocol of electrical stimulation and passive flexion-extension of the right triceps surae muscle every second day for 1, 3 or 6 weeks. Main Outcome Measures Tenocyte number and vascular density were calculated. Morphological evaluations were also performed as well as in-situ hybridisation for vascular endothelial growth factor (VEGF) messenger RNA. Results There was a significant increase in the tenocyte number after 3 and 6 weeks of exercise, but not after 1 week, in comparison with the control group. This was seen in the Achilles tendons of both legs in experimental animals, including the unexercised limb. The pattern of vascularity showed an increase in the number of tendon blood vessels in rabbits that had exercised for 3 weeks or more, compared with those who had exercised for 1 week or not at all. VEGF-mRNA was detected in the investigated tissue, with the reactions being more clearly detected in the tendon tissue with tendinosis-like changes (6-week rabbits) than in the normal tendon tissue (control rabbits). Conclusions There were bilateral tendinosis-like changes in the Achilles tendons of rabbits in the current model after 3 weeks of training, suggesting that central neuronal mechanisms may be involved and that the contralateral side is not appropriate as a control.
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40.
  • Andersson, John, 1993, et al. (author)
  • Control of Polymer Brush Morphology, Rheology, and Protein Repulsion by Hydrogen Bond Complexation
  • 2021
  • In: Langmuir. - : American Chemical Society (ACS). - 1520-5827 .- 0743-7463. ; 37:16, s. 4943-4952
  • Journal article (peer-reviewed)abstract
    • Polymer brushes are widely used to alter the properties of interfaces. In particular, poly(ethylene glycol) (PEG) and similar polymers can make surfaces inert toward biomolecular adsorption. Neutral hydrophilic brushes are normally considered to have static properties at a given temperature. As an example, PEG is not responsive to pH or ionic strength. Here we show that, by simply introducing a polymeric acid such as poly(methacrylic acid) (PMAA), the highly hydrated brush barrier can change its properties entirely. This is caused by multivalent hydrogen bonds in an extremely pH-sensitive process. Remarkably, it is sufficient to reduce the pH to 5 for complexation to occur at the interface, which is two units higher than in the corresponding bulk systems. Below this critical pH, PMAA starts to bind to PEG in large amounts (comparable to the PEG amount), causing the brush to gradually compact and dehydrate. The brush also undergoes major rheology changes, from viscoelastic to rigid. Furthermore, the protein repelling ability of PEG is lost after reaching a threshold in the amount of PMAA bound. The changes in brush properties are tunable and become more pronounced when more PMAA is bound. The initial brush state is fully recovered when releasing PMAA by returning to physiological pH. Our findings are relevant for many applications involving functional interfaces, such as capture-release of biomolecules.
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41.
  • Andersson, Jakob, 1974-, et al. (author)
  • Geomapping Landscapes of Writing (GLoW) : Large-Scale Spatial Analysis of the Cuneiform Corpus (c. 3400 BCE to 100 CE)
  • 2021
  • Conference paper (other academic/artistic)abstract
    • The cuneiform record ranks among the largest preserved bodies of historical documentation from the ancient world (Streck 2010). Conveyed on omnipresent and extremely durable types of material, cuneiform texts are preserved in immense, extending over all of the Middle East and a historical period of more than three millennia of early human history. Drawing on recent advances in digital humanities and geospatial data mapping, GLoW aims to survey, analyse, and investigate broader, macrohistorical patterns in the formation and preservation of this unique historical record. As a first quantifiable, comprehensive study of the cuneiform corpus, GLoW will provide a benchmark example of the application of digital and spatial computing tools to the study of writing in early human history. This poster offers an introduction to key research foci and the project research programme, including an introduction to data infrastructure, dissemination, and key collaborators.
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42.
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43.
  • Andersson, John, 1993, et al. (author)
  • Surface plasmon resonance sensing with thin films of palladium and platinum - quantitative and real-time analysis
  • 2022
  • In: Physical Chemistry Chemical Physics. - : Royal Society of Chemistry (RSC). - 1463-9084 .- 1463-9076. ; 24:7, s. 4588-4594
  • Journal article (peer-reviewed)abstract
    • Surface plasmon resonance (SPR) is a highly useful technique in biology and is gradually becoming useful also for materials science. However, measurements to date have been performed almost exclusively on gold, which limits the possibility to probe chemical modifications of other metals. In this work we show that 20 nm Pd and Pt films work "fairly well" for quantitative SPR sensing of organic films despite the high light absorption. In the interval between total reflection and the SPR angle, high intensity changes occur when a film is formed on the surface. Fresnel models accurately describe the full angular spectra and our data analysis provides good resolution of surface coverage in air (a few ng cm(-2)). Overall, the Pd sensors behave quite similarly to 50 nm gold in terms of sensitivity and field extension, although the noise level in real-time measurements is similar to 5 times higher. The Pt sensors exhibit a longer extension of the evanescent field and similar to 10 times higher noise compared to gold. Yet, formation of organic layers a few nm in thickness can still be monitored in real-time. As a model system, we use thiolated poly(ethylene glycol) to make Pd and Pt protein repelling. Our findings show how SPR can be used for studying chemical modifications of two metals that are important in several contexts, for instance within heterogeneous catalysis. We emphasize the advantages of simple sample preparation and accurate quantitative analysis in the planar geometry by Fresnel models.
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44.
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45.
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46.
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47.
  • Andersson, M, et al. (author)
  • Accuracy in multiangle light scattering measurements for molar mass and radius estimations. Model calculations and experiments.
  • 2003
  • In: Analytical Chemistry. - : American Chemical Society (ACS). - 1520-6882 .- 0003-2700. ; 75:16, s. 4279-4291
  • Journal article (peer-reviewed)abstract
    • Multiangle light scattering (MALS) is a well-established technique used to determine the size of macromolecules and particles. In this study, different extrapolation procedures used in MALS were investigated with regard to accuracy and robustness in the obtained molar mass and rms radius. Three different mathematical transformations of the light scattering function referred to as the Debye, Zimm, and Berry methods for constructing the Debye plot were investigated for two idealized polymer shapes, homogeneous spheres and random coils, with radii from 25 to 250 nm. The effect of the angular interval used for the extrapolation was investigated, as was the robustness of the different transformations toward errors in the measured light scattering intensity at low angles. For an rms radius less than 50 nm, the relative error in molar mass due to extrapolation was less than 1% independent of the method used. For larger radii, the error increased and the extrapolation procedure became more critical. For random coil polymers, the Berry method was superior in terms of accuracy and robustness. For spheres, the Debye method was superior. The Zimm method was inferior to the others. The different extrapolation methods were evaluated and compared on experimental data from a size exclusion chromatography-MALS analysis of an ultrahigh molar mass poly(ethylene oxide) (PEO). The PEO data qualitatively verified the calculations and stressed the importance of optimizing the extrapolation procedure after careful evaluation of the experimental data. A discussion of how to detect erroneous data in an experimental Debye plot is given.
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48.
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49.
  • Andersson, Martin, et al. (author)
  • Indoor 5G Positioning using Multipath Measurements
  • 2023
  • In: 2023 IEEE/ION POSITION, LOCATION AND NAVIGATION SYMPOSIUM, PLANS. - : IEEE. - 9781665417723 - 9781665417730 ; , s. 1092-1098
  • Conference paper (peer-reviewed)abstract
    • Positioning with high precision and reliability can be provided by 5G cellular networks in environments where satellite positioning is not available or reliable. The accuracy that can be achieved by classical methods like triangulation and trilateration however degrades significantly under non line of sight (NLOS) conditions. The problem can be mitigated with increasingly dense deployments of network transmission and reception points (TRPs), but that is both impractical and costly. As an alternative, this study investigates if multipath propagation of radio signals can be exploited to improve positioning accuracy and reduce the necessary deployment density. With 3GPP Rel. 17 new signaling support has been introduced to report the propagation delay, corresponding to the length, of multiple paths between the user equipment (UE) and a network TRP. The length of a multipath can, in combination with a partially known map of the environment, give additional information about the UE position. In this study we develop multipath-assisted tracking algorithms and evaluate their performances in realistic simulations using 3GPP standardized positioning reference signals and measurements in an indoor factory environment. Our evaluations show that multipath-assisted algorithms can achieve an accuracy below 0.9 m in 90% of the cases, which is more than tenfold better than a conventional LOS based algorithm. Moreover, one algorithm variant also shows an ability to track a UE using very few TRPs.
  •  
50.
  • Andersson, M, et al. (author)
  • NIR spectroscopy on moving solids using a scanning grating spectrometer - impact on multivariate process analysis
  • 2005
  • In: Chemometrics and Intelligent Laboratory Systems. - : Elsevier BV. - 0169-7439. ; 75:1, s. 1-11
  • Journal article (peer-reviewed)abstract
    • The effect of sample movement on spectral response during fiber probe diffuse reflectance near-infrared spectrometry (NIR) sampling was characterized. This is of central importance in Process Analytical Chemistry (PAC) and Process Analytical Technology (PAT). The incitement to this study was the observation of spectral artifacts during measurements of powder samples in process streams when using a mechanically scanning spectrometer. Artifacts appeared as momentary changes in the spectral response during acquisition of a scan. These transitions emanate from continuous replacement of the sample subfraction seen by the probe and are typical for turbid media where sample properties may vary locally with respect to scattering and/or absorption. The impact on qualitative and quantitative analysis using chemometric methods such as principal component analysis (PCA) and partial least squares (PLS) regression was evaluated through experimental and theoretical simulations. It was generally found that spectra with the smallest residuals after projection onto the models came from non-moving samples or samples moving only slowly. It is shown that the magnitude of the spectral residuals is directly connected to the effective sample size, which relates both to sample speed as well as to the sample area presented to the probe. Implications for in-line/on-line process analysis of solids are discussed. (C) 2004 Elsevier B.V. All rights reserved.
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