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2.
  • Holmqvist, Lina, et al. (author)
  • Drug adherence in treatment resistant and in controlled hypertension - Results from the Swedish Primary Care Cardiovascular Database (SPCCD)
  • 2018
  • In: Pharmacoepidemiology and Drug Safety. - : Wiley. - 1053-8569 .- 1099-1557. ; 27:3, s. 315-321
  • Journal article (peer-reviewed)abstract
    • Purpose To assess drug adherence in patients treated with 3 antihypertensive drug classes, with both controlled and uncontrolled blood pressure and describe associated factors for nonadherence. Methods Patients with hypertension, without cardiovascular comorbidity, aged >30years treated with 3 antihypertensive drug classes were followed for 2years. Both patients with treatment resistant hypertension (TRH) and patients with controlled hypertension were included. Clinical data were derived from a primary care database. Pharmacy refill data from the Swedish Prescribed drug registry was used to calculate proportion of days covered (PDC). Patients with a PDC level80% were included. Results We found 5846 patients treated 3 antihypertensive drug classes, 3508 with TRH (blood pressure140/90), and 2338 with controlled blood pressure (<140/90mmHg). TRH patients were older (69.1 vs 65.8years, P<.0001) but had less diabetes (28.5 vs 31.7%, P<.009) compared with patients with controlled blood pressure. The proportion of patients with PDC80% declined with 11% during the first year in both groups. Having diabetes was associated with staying adherent at 1year (RR 0.82; 95% CI, 0.68-0.98) whilst being born outside Europe was associated with nonadherence at one and (RR 2.05; 95% CI, 1.49-2.82). ConclusionsPatients with multiple antihypertensive drug therapy had similar decline in adherence over time regardless of initial blood pressure control. Diabetes was associated with better adherence, which may imply that the structured caregiving of these patients enhances antihypertensive drug treatment.
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  • Meeths, M, et al. (author)
  • Familial hemophagocytic lymphohistiocytosis type 3 (FHL3) caused by deep intronic mutation and inversion in UNC13D
  • 2011
  • In: Blood. - Washington : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 118:22, s. 5783-5793
  • Journal article (peer-reviewed)abstract
    • Familial hemophagocytic lymphohistiocytosis (FHL) is an autosomal recessive, often-fatal hyperinflammatory disorder. Mutations in PRF1, UNC13D, STX11, and STXBP2 are causative of FHL2, 3, 4, and 5, respectively. In a majority of suspected FHL patients from Northern Europe, sequencing of exons and splice sites of such genes required for lymphocyte cytotoxicity revealed no or only monoallelic UNC13D mutations. Here, in 21 patients, we describe 2 pathogenic, noncoding aberrations of UNC13D. The first is a point mutation localized in an evolutionarily conserved region of intron 1. This mutation selectively impairs UNC13D transcription in lymphocytes, abolishing Munc13-4 expression. The second is a 253-kb inversion straddling UNC13D, affecting the 3'-end of the transcript and likewise abolishing Munc13-4 expression. Carriership of the intron 1 mutation was found in patients across Europe, whereas carriership of the inversion was limited to Northern Europe. Notably, the latter aberration represents the first description of an autosomal recessive human disease caused by an inversion. These findings implicate an intronic sequence in cell-type specific expression of Munc13-4 and signify variations outside exons and splice sites as a common cause of FHL3. Based on these data, we propose a strategy for targeted sequencing of evolutionary conserved noncoding regions for the diagnosis of primary immunodeficiencies.
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  • Romantsik, Olga, et al. (author)
  • Severe intraventricular hemorrhage causes long-lasting structural damage in a preterm rabbit pup model
  • 2022
  • In: Pediatric Research. - : Springer Science and Business Media LLC. - 0031-3998 .- 1530-0447. ; 92:2, s. 403-414
  • Journal article (peer-reviewed)abstract
    • Background Intraventricular hemorrhage causes significant lifelong mortality and morbidity, especially in preterm born infants. Progress in finding an effective therapy is stymied by a lack of preterm animal models with long-term follow-up. This study addresses this unmet need, using an established model of preterm rabbit IVH and analyzing outcomes out to 1 month of age. Methods Rabbit pups were delivered preterm and administered intraperitoneal injection of glycerol at 3 h of life and approximately 58% developed IVH. Neurobehavioral assessment was performed at 1 month of age followed by immunohistochemical labeling of epitopes for neurons, synapses, myelination, and interneurons, analyzed by means of digital quantitation and assessed via two-way ANOVA or Student's t test. Results IVH pups had globally reduced myelin content, an aberrant cortical myelination microstructure, and thinner upper cortical layers (I-III). We also observed a lower number of parvalbumin (PV)-positive interneurons in deeper cortical layers (IV-VI) in IVH animals and reduced numbers of neurons, synapses, and microglia. However, there were no discernable changes in behaviors. Conclusions We have established in this preterm pup model that long-term changes after IVH include significant wide-ranging alterations to cortical organization and microstructure. Further work to improve the sensitivity of neurocognitive testing in this species at this age may be required. Impact This study uses an established animal model of preterm birth, in which the rabbit pups are truly born preterm, with reduced organ maturation and deprivation of maternally supplied trophic factors. This is the first study in preterm rabbits that explores the impacts of severe intraventricular hemorrhage beyond 14 days, out to 1 month of age. Our finding of persisting but subtle global changes including brain white and gray matter will have impact on our understanding of the best path for therapy design and interventions.
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  • Schleiermacher, G., et al. (author)
  • Emergence of New ALK Mutations at Relapse of Neuroblastoma
  • 2014
  • In: Journal of Clinical Oncology. - : American Society of Clinical Oncology (ASCO). - 0732-183X .- 1527-7755. ; 32:25, s. 2727-2734
  • Journal article (peer-reviewed)abstract
    • Purpose In neuroblastoma, the ALK receptor tyrosine kinase is activated by point mutations. We investigated the potential role of ALK mutations in neuroblastoma clonal evolution. We analyzed ALK mutations in 54 paired diagnosis-relapse neuroblastoma samples using Sanger sequencing. When an ALK mutation was observed in one paired sample, a minor mutated component in the other sample was searched for by more than 100,000 x deep sequencing of the relevant hotspot, with a sensitivity of 0.17%. All nine ALK-mutated cases at diagnosis demonstrated the same mutation at relapse, in one case in only one of several relapse nodules. In five additional cases, the mutation seemed to be relapse specific, four of which were investigated by deep sequencing. In two cases, no mutation evidence was observed at diagnosis. In one case, the mutation was present at a subclonal level (0.798%) at diagnosis, whereas in another case, two different mutations resulting in identical amino acid changes were detected, one only at diagnosis and the other only at relapse. Further evidence of clonal evolution of ALK-mutated cells was provided by establishment of a fully ALK-mutated cell line from a primary sample with an ALK-mutated cell population at subclonal level (6.6%). In neuroblastoma, subclonal ALK mutations can be present at diagnosis with subsequent clonal expansion at relapse. Given the potential of ALK-targeted therapy, the significant spatiotemporal variation of ALK mutations is of utmost importance, highlighting the potential of deep sequencing for detection of subclonal mutations with a sensitivity 100-fold that of Sanger sequencing and the importance of serial samplings for therapeutic decisions.
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  • Seifert, Mariam B., et al. (author)
  • Genetic variants on chromosomes 7p31 and 12p12 are associated with abnormal atrial electrical activation in patients with early-onset lone atrial fibrillation
  • 2019
  • In: Annals of Noninvasive Electrocardiology. - : Wiley. - 1082-720X .- 1542-474X. ; 24:6
  • Journal article (peer-reviewed)abstract
    • Background: Abnormal P-wave morphology (PWM) has been associated with a history of atrial fibrillation (AF) in earlier studies. Although lone AF is believed to have substantial genetic basis, studies on associations between single nucleotide polymorphisms (SNP) linked to lone AF and PWM have not been reported. We aimed to assess whether SNPs previously associated with lone AF (rs2200733, rs13376333, rs3807989, and rs11047543) are also linked to P-wave abnormalities. Methods: Four SNPs were studied in 176 unrelated individuals with early-onset lone AF (age at onset <50 years), median age 38 years (19–63 years), 149 men. Using sinus rhythm ECG, orthogonal PWM was classified as Type 1—positive in leads X and Y and negative in lead Z, Type 2—positive in leads X and Y and biphasic (−/+) in lead Z, Type 3—positive in lead X and biphasic in lead Y (+/−), and the remaining as atypical. Results: Two SNPs were found to be significantly associated with altered P-wave morphology distribution: rs3807989 near the gene CAV1/CAV2 and rs11047543 near the gene SOX5. Both SNPs were associated with a higher risk of non-Type 1 P-wave morphology (rs3807989: OR = 4.8, 95% CI = 2.3–10.2, p < 0.001; rs11047543: OR = 4.7, 95% CI = 1.1–20.5, p = 0.04). No association was observed for rs2200733 and rs13376333. Conclusion: In this study, the two variants rs3807989 and rs11047543, previously associated with PR interval and lone AF, were associated with altered P-wave morphology distribution in patients with early-onset lone AF. These findings suggest that common genetic variants may modify atrial conduction properties.
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  • Wang, Dong, et al. (author)
  • A study of artificial eyes for the measurement of precision in eye-trackers
  • 2017
  • In: Behavior Research Methods. - : Springer Science and Business Media LLC. - 1554-3528. ; 49:3, s. 947-959
  • Journal article (peer-reviewed)abstract
    • The precision of an eye-tracker is critical to the correct identification of eye movements and their properties. To measure a system’s precision, artificial eyes (AEs) are often used, to exclude eye movements influencing the measurements. A possible issue, however, is that it is virtually impossible to construct AEs with sufficient complexity to fully represent the human eye. To examine the consequences of this limitation, we tested currently used AEs from three manufacturers of eye-trackers and compared them to a more complex model, using 12 commercial eye-trackers. Because precision can be measured in various ways, we compared different metrics in the spatial domain and analyzed the power-spectral densities in the frequency domain. To assess how precision measurements compare in artificial and human eyes, we also measured precision using human recordings on the same eye-trackers. Our results show that the modified eye model presented can cope with all eye-trackers tested and acts as a promising candidate for further development of a set of AEs with varying pupil size and pupil–iris contrast. The spectral analysis of both the AE and human data revealed that human eye data have different frequencies that likely reflect the physiological characteristics of human eye movements. We also report the effects of sample selection methods for precision calculations. This study is part of the EMRA/COGAIN Eye Data Quality Standardization Project.
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  • Agyemang, Alex Adusei, et al. (author)
  • Cerebellar Exposure to Cell-Free Hemoglobin Following Preterm Intraventricular Hemorrhage: Causal in Cerebellar Damage?
  • 2017
  • In: Translational Stroke Research. - : Springer Science and Business Media LLC. - 1868-4483 .- 1868-601X. ; 8:5, s. 461-473
  • Journal article (peer-reviewed)abstract
    • Decreased cerebellar volume is associated with intraventricular hemorrhage (IVH) in very preterm infants and may be a principal component in neurodevelopmental impairment. Cerebellar deposition of blood products from the subarachnoid space has been suggested as a causal mechanism in cerebellar underdevelopment following IVH. Using the preterm rabbit pup IVH model, we evaluated the effects of IVH induced at E29 (3 days prior to term) on cerebellar development at term-equivalent postnatal day 0 (P0), term-equivalent postnatal day 2 (P2), and term-equivalent postnatal day 5 (P5). Furthermore, the presence of cell-free hemoglobin (Hb) in cerebellar tissue was characterized, and cell-free Hb was evaluated as a causal factor in the development of cerebellar damage following preterm IVH. IVH was associated with a decreased proliferative (Ki67-positive) portion of the external granular layer (EGL), delayed Purkinje cell maturation, and activated microglia in the cerebellar white matter. In pups with IVH, immunolabeling of the cerebellum at P0 demonstrated a widespread presence of cell-free Hb, primarily distributed in the white matter and the molecular layer. Intraventricular injection of the Hb scavenger haptoglobin (Hp) resulted in a corresponding distribution of immunolabeled Hp in the cerebellum and a partial reversal of the damaging effects observed following IVH. The results suggest that cell-free Hb is causally involved in cerebellar damage following IVH and that blocking cell-free Hb may have protective effects.
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  • Ahlen, K., et al. (author)
  • Platelet-derived growth factor-BB modulates membrane mobility of ß1 integrins
  • 2004
  • In: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 314:1, s. 89-96
  • Journal article (peer-reviewed)abstract
    • Platelet-derived growth factor (PDGF)-BB elicits a migratory response including reorganization of the actin cytoskeleton in different cell types. Here we have investigated the effects of PDGF-BB stimulation on ß 1 integrin containing focal adhesions in human diploid fibroblasts adhered to collagen type I. Stimulation with PDGF-BB dissociated focal adhesions and relocated ß1 integrins from focal adhesions to the periphery of the cells. These changes were rapid and transient in character. Relocation of ß1 integrins was prevented by inhibitors of phosphoinositide-3-kinase and protein kinase C. PDGF-BB stimulated fibroblasts exhibited an increased diffusion coefficient of cell surface ß1 integrins as determined by fluorescence recovery of photobleaching. The cell surface expression of ß1 integrins was not changed after stimulation with PDGF-BB. Our data suggest that PDGF-BB increases the dynamic properties of cell-surface ß1 integrins, which most likely are important for the migratory response elicited by PDGF-BB. © 2003 Elsevier Inc. All rights reserved.
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  • Ammoun, Sylwia, et al. (author)
  • Distinct Recognition of OX1 and OX2 Receptors by Orexin Peptides
  • 2003
  • In: Journal of Pharmacology and Experimental Therapeutics. - : American Society for Pharmacology & Experimental Therapeutics (ASPET). - 0022-3565 .- 1521-0103. ; 305:2, s. 507-514
  • Journal article (peer-reviewed)abstract
    • In this study, we have compared the abilities of orexin-A and orexin-B and variants of orexin-A to activate different Ca(2+) responses (influx and release) in human OX(1) and OX(2) receptor- expressing Chinese hamster ovary cells. Responses mediated by activation of both receptor subtypes with either orexin-A or -B were primarily dependent on extracellular Ca(2+), suggesting similar activation of Ca(2+) influx as we have previously shown for orexin-A and OX(1) receptors. Amino acid-wise truncation of orexin-A reduced its ability to activate OX(1) and OX(2) receptors, but the response mediated by the OX(2) receptor was more resistant to truncation than the response mediated by the OX(1) receptor. We also performed a sequential replacement of amino acids 14 to 26 with alanine in the truncated orexin-A variant orexin-A(14-33). Replacement of the same amino acids produced a fall in the potency for each receptor subtype, but the reduction was less prominent for the OX(2) receptor. The most marked reduction was produced by the replacement of Leu20, Asp25, and His26 with alanine. Interestingly, extracellular Ca(2+) dependence of responses to some of the mutated peptides was different from those of orexin-A and -B. The mutagenesis also suggests that although the determinants required from orexin-A for binding to and activation of the receptor are highly conserved between the orexin receptor subtypes, the OX(2) receptor requires fewer determinants. This might in part explain why orexin-B has the affinity and potency equal to orexin-A for this subtype, although it has 10- to 100-fold lower affinity and potency for the OX(1) receptor.
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  • Choudhary, Mariam B, et al. (author)
  • Low atrial fibrillatory rate is associated with spontaneous conversion of recent-onset atrial fibrillation.
  • 2013
  • In: Europace. - : Oxford University Press (OUP). - 1532-2092. ; 15:10, s. 1445-1452
  • Journal article (peer-reviewed)abstract
    • AIMS: Atrial fibrillatory rate (AFR) is considered a non-invasive index of atrial remodelling. Low AFR has been associated with favourable outcome of interventions in patients with persistent atrial fibrillation (AF). However, AFR has never been studied in unselected patients with short duration of AF, prone to regain sinus rhythm (SR) spontaneously. The aim of the study was to assess if AFR can predict spontaneous conversion in patients with recent-onset AF.METHODS AND RESULTS: Files of consecutive patients with AF < 48 h seeking emergency room care during a 12-month period were screened (n = 225). Patients with thyroid illness, acute ischaemic heart disease (IHD) or acute congestive heart failure, significant valvular heart disease, congenital heart disease, history of cardiac surgery or catheter ablation, or on class I/III antiarrhythmics were excluded. Atrial fibrillatory rate was obtained by QRST cancellation and time frequency analysis of electrocardiogram at admission. The study population comprised 148 patients (age 64 ± 13 years, 52 men), of whom 48 converted to SR within 18 h. Those converting spontaneously comprised more women, had a higher prevalence of first-ever AF episode, IHD, and a lower AFR. The multivariate analysis revealed: AFR < 350 fibrillations per minute [odds ratio (OR) 3.7, 95% confidence interval (CI) 1.3-10.5, P = 0.016], IHD (OR 5.7, 95% CI 1.5-22.4, P = 0.012) and first-ever AF episode (OR 4.1, 95% CI 1.3-13.0, P = 0.015) as independent predictors of spontaneous conversion.CONCLUSION: A low AFR was predictive of spontaneous conversion in patients with recent-onset AF. Along with first-ever AF episode and IHD, AFR can be used in assessing likelihood of spontaneous conversion, if proven in prospective studies.
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  • Elmståhl, S., et al. (author)
  • Dietary patterns in high and low consumers of meat in a Swedish cohort study
  • 1999
  • In: Appetite. - : Elsevier BV. - 0195-6663. ; 32:2, s. 191-206
  • Journal article (peer-reviewed)abstract
    • The objective was to examine relationships between meat and other food items which have been associated with higher risk of cancer in the colon and prostate in some epidemiological studies. The study was conducted as a population-based cohort study comprising 11648 subjects (4816 male and 6742 female) born between 1926 and 1945 and living in the city of Malmo, Sweden. Data on mean daily intake of foods and nutrients were assessed with a diet history method combining a 7-day menu book and a food frequency questionnaire. Increasing meat intake, expressed in quintiles and adjusted for energy, was associated with decreasing intakes of poultry, fish, fruits, bread, cereals and cheese in both sexes. Low negative correlations between meat intake and ascorbic acid (r = -0.11) and fiber (r = -0.16 to -0.20) were noted. The average intake of fat from meat out of total fat intake was 13.6% in men and 11.9% in women. No major associations were noted between meat and the cholesterol raising fatty acids C:12:0, C:14:0, C:160 nor for C:20:4 or its precursor C:18:2. In conclusion, our findings indicate that meat consumption is negatively associated with food groups rich in antioxidants and fiber and the positive covariance reported between meat and cancer and coronary heart disease might, therefore, not be directly linked to components in meat.
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  • Gao, Jingfang, et al. (author)
  • Clinical and biological significance of angiogenesis and lymphangiogenesis in colorectal cancer
  • 2009
  • In: DIGESTIVE AND LIVER DISEASE. - : Elsevier BV. - 1590-8658. ; 41:2, s. 116-122
  • Journal article (peer-reviewed)abstract
    • Purpose. The aim of this study was to get a deeper understanding into how adults with cerebral palsy (CP) experience physiotherapy and physical activity in a perspective from childhood to adulthood; and how personal and environmental factors influence possibilities for physiotherapy and physical activity. Method. Data was collected through interviews with 22 community-living adults (35-68 years) with CP, from five counties in Sweden. The questions were open-ended and the interviews were taped and transcribed to written language. The material was analysed through qualitative content analysis, a classification process resulting in different themes. Results. The narratives from the 22 informants, based on experiences from childhood to adulthood, resulted in a description of prerequisites for carrying out physiotherapy and physical activity. Five different themes were identified: (i) Being enjoyable, (ii) Giving effects, (iii) Being comprehensible, (iv) Being integrated in daily life, and (v) Supportive healthcare with competent professionals. Conclusion. The information from the interviews elucidates the importance of a lifelong support from healthcare professionals. Physiotherapists with attentiveness to different life situations in combination with good understanding and knowledge in CP could facilitate continuous physical activity in people growing up and ageing with CP.
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  • Gloris, M, et al. (author)
  • Proton-induced production of residual radionuclides in lead at intermediate energies
  • 2001
  • In: NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION A-ACCELERATORS SPECTROMETERS DETECTORS AND ASSOCIATED EQUIPMENT. - : ELSEVIER SCIENCE BV. ; 463:3, s. 593-633
  • Review (other academic/artistic)abstract
    • Integral excitation functions for the production of residual nuclides are basic quantities for the calculation of radioactive inventories of spallation targets in spallation neutron sources and in accelerator-driven devices for energy amplification or for
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  • Gram, Magnus, et al. (author)
  • Insulin-Like Growth Factor 1 in the Preterm Rabbit Pup: Characterization of Cerebrovascular Maturation following Administration of Recombinant Human Insulin-Like Growth Factor 1/Insulin-Like Growth Factor 1-Binding Protein 3
  • 2021
  • In: Developmental Neuroscience. - : S. Karger AG. - 0378-5866 .- 1421-9859. ; 43:5, s. 281-295
  • Journal article (peer-reviewed)abstract
    • Following preterm birth, serum levels of insulin-like growth factor 1 (IGF-1) decrease compared to corresponding in utero levels. A recent clinical trial indicated that supplementation with recombinant human (rh) IGF-1/rhIGF-binding protein 3 (rhIGF-1/rhIGFBP-3) prevents severe intraventricular hemorrhage (IVH) in extremely preterm infants. In a preterm rabbit pup model, we characterized endogenous serum and hepatic IGF-1, along with brain distribution of IGF-1 and IGF-1 receptor (IGF1R). We then evaluated the effects of rhIGF-1/rhIGFBP-3 on gene expression of regulators of cerebrovascular maturation and structure. Similar to preterm infants, serum IGF-1 concentrations decreased rapidly after preterm birth in the rabbit pup. Administration of rhIGF-1/rhIGFBP-3 restored in utero serum levels but was rapidly eliminated. Immunolabeled IGF1R was widely distributed in multiple brain regions, displaying an abundant density in the choroid plexus and sub-ependymal germinal zones. Increased IGF-1 immunoreactivity, distributed as IGF1R, was detected 4 h after rhIGF-1/rhIGFBP-3 administration. The rhIGF-1/rhIGFBP-3 treatment led to upregulation of choroid plexus genes involved in vascular maturation and structure, with corresponding protein translation for most of these genes. The preterm rabbit pup model is well suited for evaluation of IGF-1-based prevention of IVH. Administration of rhIGF-1/rhIGFBP-3 affects cerebrovascular maturation, suggesting a role for it in preventing preterm IVH.
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  • Granqvist, Svante, et al. (author)
  • Resonance tube phonation in water : High-speed imaging, electroglottographic and oral pressure observations of vocal fold vibrations - A pilot study
  • 2015
  • In: Logopedics, Phoniatrics, Vocology. - : Taylor & Francis. - 1401-5439 .- 1651-2022. ; 40:3, s. 113-121
  • Journal article (peer-reviewed)abstract
    • Phonation into glass tubes (resonance tubes), keeping the free end of the tube in water, has been a frequently used voice therapy method in Finland and more recently also in other countries. The purpose of this exploratory study was to investigate what effects tube phonation with and without water has on the larynx. Two participants were included in the study. The methods used were high-speed imaging, electroglottographic observations of vocal fold vibrations, and measurements of oral pressure during tube phonation. Results showed that the fluctuation in the back pressure during tube phonation in water altered the vocal fold vibrations. In the high-speed imaging, effects were found in the open quotient and amplitude variation of the glottal opening. The open quotient increased with increasing water depth (from 2 cm to 6 cm). A modulation effect by the water bubbles on the vocal fold vibrations was seen both in the high-speed glottal area tracings and in the electroglottography signal. A second experiment revealed that the increased average oral pressure was largely determined by the water depth. The increased open quotient can possibly be explained by an increased abduction of the vocal folds and/or a reduced transglottal pressure. The back pressure of the bubbles also modulates glottal vibrations with a possible massage effect on the vocal folds. This effect and the well-defined average pressure increase due to the known water depth are different from those of other methods using a semi-occluded vocal tract.
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  • Halmin, Märit, et al. (author)
  • Length of Storage of Red Blood Cells and Patient Survival After Blood Transfusion : A Binational Cohort Study
  • 2017
  • In: Annals of Internal Medicine. - 0003-4819 .- 1539-3704. ; 166:4, s. 248-256
  • Journal article (peer-reviewed)abstract
    • Background: Possible negative effects, including increased mortality, among persons who receive stored red blood cells (RBCs) have recently garnered considerable attention. Despite many studies, including 4 randomized trials, no consensus exists.Objective: To study the association between the length of RBC storage and mortality in a large population-based cohort of patients who received transfusions, allowing detection of small yet clinically significant effects.Design: Binational cohort study.Setting: All transfusion recipients in Sweden and Denmark. Patients: 854 862 adult patients who received transfusions from 2003 to 2012.Measurements: Patients were followed from first blood transfusion. Relative and absolute risks for death in 30 days or 1 year in relation to length of RBC storage were assessed by using 3 independent analytic approaches. All analyses were conducted by using Cox proportional hazards regression.Results: Regardless of the analytic approach, no association was found between the length of RBC storage and mortality. The difference in 30-day cumulative mortality between patients receiving blood stored for 30 to 42 days and those receiving blood stored for 10 to 19 days was -0.2% (95% CI, -0.5% to 0.1%). Even among patients who received more than 6 units of RBCs stored for 30 days or longer, the hazard ratio of death was 1.00 (CI, 0.96 to 1.05) compared with those who received no such units.Limitation: Observational study; risk of confounding by indication.Conclusion: Consistent with previous randomized trials, this study found no association between the length of storage of transfused RBCs and patient mortality. Results were homogeneous, with differences in absolute mortality consistently less than 1% among the most extreme exposure categories. These findings suggest that the current practice of storing RBCs for up to 42 days does not need to be changed.
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  • Holmqvist, Bo, et al. (author)
  • The early ontogeny of neuronal nitric oxide synthase systems in the zebrafish.
  • 2004
  • In: Journal of Experimental Biology. - : The Company of Biologists. - 1477-9145 .- 0022-0949. ; 207:Pt 6, s. 923-935
  • Journal article (peer-reviewed)abstract
    • To examine a putative role for neuronal nitric oxide synthase (nNOS) in early vertebrate development we investigated nNOS mRNA expression and cGMP production during development of the zebrafish Danio rerio. The nNOS mRNA expression in the central nervous system (CNS) and periphery showed a distinct spatio-temporal pattern in developing zebrafish embryo and young larvae. nNOS mRNA expression was first detected at 19 h postfertilisation (h.p.f.), in a bilateral subpopulation of the embryonic ventrorostral cell cluster in the forebrain. The number of nNOS mRNA-expressing cells in the brain slowly increased, also appearing in the ventrocaudal cell cluster from about 26 h.p.f., and in the dorsorostral and hindbrain cell cluster and in the medulla at 30 h.p.f. A major increase in nNOS mRNA expression started at about 40 h.p.f., and by 55 h.p.f. the expression constituted cell populations in differentiated central nuclei and in association with the proliferation zones of the brain, and in the medulla and retina. In parts of the skin, nNOS mRNA expression started at 20 h.p.f. and ended at 55 h.p.f. Between 40 and 55 h.p.f., nNOS mRNA expression started in peripheral organs, forming distinct populations after hatching within or in the vicinity of the presumptive swim bladder, enteric ganglia, and along the alimentary tract and nephritic ducts. Expression of nNOS mRNA correlated with the neuronal differentiation pattern and with the timing and degree of cGMP production. These studies indicate spatio-temporal actions by NO during embryogenesis in the formation of the central and peripheral nervous system, with possible involvement in processes such as neurogenesis, organogenesis and early physiology.
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  • Holmqvist, F., et al. (author)
  • Pacemaker programming in patients with first-degree AV-block : Programming pattern and possible consequences
  • 2018
  • In: Health Science Reports. - : Wiley. - 2398-8835. ; 1:6
  • Journal article (peer-reviewed)abstract
    • Background: The optimal way of pacing in patients with an indication for pacing and concomitant first-degree atrioventricular (AV)–block is not known, and consequently, firm guidelines on this topic are lacking. This study explored the current pacemaker programming pattern in patients with first-degree AV-block who have a dual chamber pacemaker without cardiac resynchronization. Methods: The study was a retrospective chart review conducted at Duke University Hospital. Patients receiving a pacemaker due to sinus node dysfunction with coexistent first-degree AV-block were studied. Baseline demographics and characteristics, as well as pacemaker programming parameters and follow-up data, were collected through chart review. Preimplantation and postimplantation electrocardiograms were analyzed. Results: A total of 74 patients were included (mean age, 75 ± 11 y; 53% men). The mean ± SD preimplant PR interval and QRS duration was 243 ± 46 and 110 ± 30 milliseconds, respectively. A history of atrial fibrillation was present in 49% of the patients, and 77% had a normal left ventricular ejection fraction. The majority of patients (65%) had their pacemakers programmed to atrial pacing (AAI/DDD +/−R), whereas 32% and 2.7% of the pacemakers were programmed to AV-sequential pacing (DDD) and ventricular pacing (VVI), respectively. There were no significant differences in baseline characteristics or electrocardiogram measures between patients programmed to the 3 pacing modes. Patients with pacemakers programmed to AAI had a lower ventricular pacing percentage at follow-up (8 vs 55, and 46% [DDD and VVI, respectively]; P <.001). Conclusions: There was no evident association between baseline characteristics and programmed pacing mode in patients with first-degree AV-block. The choice of pacing mode affects long-term pacing burden, which in turn has been shown to influence outcome.
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  • Holmqvist, Jacob, et al. (author)
  • No evidence of transfusion transmitted sporadic Creutzfeldt-Jakob disease: results from a bi-national cohort study
  • 2020
  • In: Transfusion. - : Wiley. - 0041-1132 .- 1537-2995. ; 60:4, s. 694-697
  • Journal article (peer-reviewed)abstract
    • BACKGROUND Creutzfeldt-Jakob disease (CJD) is an uncommon, invariably fatal, neurodegenerative disorder that presents as progressive dementia with concurrent motor symptoms and myoclonia. The pathophysiology involves prion protein misfolding and spreading in a self-catalyzed manner. It has been shown to be transmissible through tissue transplants. Variant CJD (vCJD), a subtype of the disease is also transmissible through transfusion of blood products. This study aims to corroborate the scarce data that suggest that sporadic CJD (sCJD) is not transmitted via blood transfusion. METHODS AND STUDY DESIGN A retrospective cohort study was performed, using data from the bi-national Scandinavian Donations and Transfusions (SCANDAT2) database containing data on blood donors, donations, transfusions, and transfused patients in Sweden and Denmark since 1968 and 1982, respectively. Mortality and medical data were collected from nationwide health care and population registries. Donors with subsequent CJD were identified, as well as recipients of blood products from these donors. A second analysis was performed, screening for clustering of CJD cases from donors without a CJD diagnosis. RESULTS We identified 39 donors with a subsequent diagnosis of sCJD. No cases of CJD occurred among the 883 recipients of blood products from these donors. A total of 89 CJD cases were identified among recipients of transfusions. No clustering of cases from the same donor occurred. DISCUSSION Using data from a large, bi-national database of transfused patients, we find no evidence of sCJD transmission. Our data adds to the growing body of evidence indicating that sCJD is not transfusion transmitted.
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31.
  • Holmqvist-Jämsén, S., et al. (author)
  • Investigating the role of salivary cortisol on vocal symptoms
  • 2017
  • In: Journal of Speech, Language, and Hearing Research. - 1092-4388. ; 60:10, s. 2781-2791
  • Journal article (peer-reviewed)abstract
    • Purpose: We investigated whether participants who reported more often occurring vocal symptoms showed higher salivary cortisol levels and if such possible associations were different for men and women. Method: The participants (N = 170; men n = 49, women n = 121) consisted of a population-based sample of Finnish twins born between 1961 and 1989. The participants submitted saliva samples for hormone analysis and completed a web questionnaire including questions regarding the occurrence of 6 vocal symptoms during the past 12 months. The data were analyzed using the generalized estimated equations method. Results: A composite variable of the vocal symptoms showed a significant positive association with salivary cortisol levels (p <.001). Three of the 6 vocal symptoms were significantly associated with the level of cortisol when analyzed separately (p values less than.05). The results showed no gender difference regarding the effect of salivary cortisol on vocal symptoms. Conclusions: There was a positive association between the occurrence of vocal symptoms and salivary cortisol levels. Participants with higher cortisol levels reported more often occurring vocal symptoms. This could have a connection to the influence of stress on vocal symptoms because stress is a known risk factor of vocal symptoms and salivary cortisol can be seen as a biomarker for stress. © 2017 American Speech-Language-Hearing Association.
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32.
  • Holmqvist, Kenneth, et al. (author)
  • Eye tracking : empirical foundations for a minimal reporting guideline
  • 2023
  • In: Behavior Research Methods. - : Springer Science and Business Media LLC. - 1554-3528. ; 55:1, s. 364-416
  • Journal article (peer-reviewed)abstract
    • In this paper, we present a review of how the various aspects of any study using an eye tracker (such as the instrument, methodology, environment, participant, etc.) affect the quality of the recorded eye-tracking data and the obtained eye-movement and gaze measures. We take this review to represent the empirical foundation for reporting guidelines of any study involving an eye tracker. We compare this empirical foundation to five existing reporting guidelines and to a database of 207 published eye-tracking studies. We find that reporting guidelines vary substantially and do not match with actual reporting practices. We end by deriving a minimal, flexible reporting guideline based on empirical research (Section "An empirically based minimal reporting guideline").
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33.
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34.
  • Holmqvist, Lina, et al. (author)
  • Cardiovascular outcome in treatment-resistant hypertension: results from the Swedish Primary Care Cardiovascular Database (SPCCD).
  • 2018
  • In: Journal of hypertension. - 1473-5598. ; 36:2, s. 402-409
  • Journal article (peer-reviewed)abstract
    • To assess cardiovascular outcome in patients with treatment-resistant hypertension (TRH) compared with patients with nontreatment-resistant hypertension (HTN).Cohort study with data from 2006 to 2012 derived from the Swedish Primary Care Cardiovascular Database with hypertensive patients aged at least 30 years. TRH was defined as blood pressure at least 140/90mmHg despite medication adherence to three or more dispensed antihypertensive drug classes. Patients with cardiovascular comorbidity were excluded. The association between TRH and cardiovascular events with adjustment for important confounders was analyzed.We included 4317 TRH patients and 32282 HTN patients. TRH patients (61% women) were older (70 vs. 66 years), had higher SBP (152 vs. 141mmHg) and more diabetes (30 vs. 20%) (P<0.001 for all) compared with HTN patients. Mean follow-up time was 4.3 years. In the adjusted analysis, TRH patients had an increased risk for total mortality [hazard ratio 1.12; 95% confidence interval (CI), 1.03-1.23], cardiovascular mortality (hazard ratio 1.20; 95% CI, 1.03-1.40) and incident heart failure (hazard ratio 1.34; 95% CI, 1.17-1.54) but not for incident stroke (hazard ratio 1.03; 95% CI, 0.90-1.19) or transitoric ischemic attack (hazard ratio 1.12; 95% CI, 0.86-1.46) compared with HTN patients.Patients with TRH have a poor prognosis beyond blood pressure level, compared with hypertensive patients without TRH. In particular, the high risk for heart failure is of clinical importance and merits further investigation.
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35.
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36.
  • Holmqvist, Rolf, 1948-, et al. (author)
  • Sources of therapists' countertransference feelings
  • 1996
  • In: Psychotherapy research : official journal of the Society for Psychotherapy Research. - New York : Guilford Publications. - 1050-3307. ; 6, s. 70-78
  • Journal article (peer-reviewed)
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37.
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38.
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39.
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40.
  • Issa, Shams A. M., et al. (author)
  • Proton-induced production of residual radionuclides in Re-nat up to 2590 MeV
  • 2013
  • In: Nuclear Instruments and Methods in Physics Research Section B. - : Elsevier BV. - 0168-583X .- 1872-9584. ; 298, s. 19-32
  • Journal article (peer-reviewed)abstract
    • The excitation functions for residual nuclide production by proton reactions on rhenium was investigated using activated targets from irradiation experiments at the cyclotron of the Svedberg Laboratory at Uppsala up to 180 MeV and the higher energies were used at the Laboratoire Saturne at Saclay. The measured experimental results were compared with previous published and theoretical models calculations by the codes TALYS, INCL4 + ABLA and Bertini/Dresner. A total of 5252 cross-section was determined covering 54 residual nuclides in the energy range from 78.2 to 2590 MeV.
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41.
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42.
  • Johansson, Margareta, et al. (author)
  • Family life starts at home : Fathers' experiences of a newly implemented Swedish home-based postnatal care model - an interview study
  • 2021
  • In: Midwifery. - : Elsevier. - 0266-6138 .- 1532-3099. ; 105
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: To explore and describe fathers' experiences of a newly implemented Swedish home-based postnatal care model.DESIGN: A descriptive cross-sectional qualitative study was conducted as a part of a larger study.SETTING: Families who qualified to be discharged early were offered to participate in a postnatal home-based model of midwifery care by a hospital in Stockholm, Sweden.PARTICIPANTS AND MEASUREMENTS: In total, 16 fathers participated in a semi-structured telephone interview, averaging 43 min. Data were analyzed using systematic text condensation.FINDINGS: Three major themes emerged: To decide on home- or hospital-based postnatal care - a matter of safety, To be offered professional midwifery postnatal support at home, and To be at home helped fathers to navigate parenthood. Fathers appreciated the home-based postnatal care and felt safe because of the received professional support from midwives.KEY CONCLUSIONS: Home-based postnatal care was valued by fathers whose partner had a non-complicated vaginal birth because they felt safe in their home environment and supported by midwives. The home environment aided fathers in supporting their partners and developing a father-infant bond.IMPLICATIONS FOR PRACTICE: Home-based postnatal care was valued by fathers and should be considered an option for new families. To offer home-based postnatal care may result in less overcrowded postnatal wards. Midwives need to enable fathers' participation and support their parental role regardless of where the care takes place.
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43.
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44.
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45.
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46.
  • Macher, M.-B., et al. (author)
  • Hydrogenation of palm oil in near-critical and supercritical propane
  • 2001
  • In: European Journal of Lipid Science and Technology. - 1438-7697 .- 1438-9312. ; 103:2, s. 81-84
  • Journal article (peer-reviewed)abstract
    • Palm oil was hydrogenated in a single-phase mixture with propane and hydrogen. This was done in a small (0.5 ml), continuous fixed-bed reactor, using a 1% Pd/C catalyst. Temperature (65-135 °C), H2/TG ratio (4-50 mol/mol) and residence time (0.2-2.0 s) were varied systematically to assess the iodine value (IV) as a function of these three variables. The substrate concentration was 1 wt-%. The IV was dependent mainly on temperature and residence time. At 120 °C and a residence time of 2.0 s, full hydrogenation was achieved. The trends observed indicate that this is possible even at lower temperatures, if the residence time is increased further. Unexpectedly, the hydrogen concentration (i.e. the H2/TG ratio) was of minor importance, which can be a sign of either H2-saturation of the catalyst or a phase-split of the reaction mixture with resulting mass transport limitations for the hydrogen. Unfortunately, the catalyst showed strong signs of deactivation very early in the experiments, possibly due to impurities in the feedstock and/or to coke formation.
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47.
  • Macher, M.-B., et al. (author)
  • Triacylglycerol analysis of partially hydrogenated vegetable oils by silver ion HPLC
  • 2001
  • In: Journal of Separation Science. - 1615-9306 .- 1615-9314. ; 24:3, s. 179-185
  • Journal article (peer-reviewed)abstract
    • A fast and reliable method was developed for the analysis of positional and geometrical triacylglycerol isomers in partially hydrogenated vegetable oils. A binary gradient of heptane/acetonitrile was employed in silver ion HPLC with evaporative light scattering detection. Good resolution of native and partially hardened oils was achieved within 22 min for palm oil and within 60 min for rapeseed oil. Initial stability problems were found to be caused by decreasing acetonitrile concentration in the solvent mixture, due to selective evaporation of acetonitrile. By tightening the bottle caps and plugging the usual ventilation inlets, this could be prevented; the system then became very stable. A complementary system (heptane/acetone) was used to confirm the absence of 1,2-elaidin-3-palmitin in the hydrogenated samples. This system shows better resolution in the more saturated region (up to three double bonds). However, for less saturated species, peak-split problems occurred (e.g. for triolein), and the elution strength of acetone was not sufficient for the elution of the most polyunsaturated triacylglycerols of rapeseed oil. This would have required a ternary gradient with an additional, stronger solvent, e.g. acetonitrile. Hence, the original heptane/acetonitrile system was retained as the method of choice. It is sufficiently fast and accurate over a wide range of unsaturation to make it suitable for hydrogenation process control, especially of continuous processes with rapidly changing product composition.
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48.
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49.
  • Nissen-Lie, Helene A., et al. (author)
  • Are Therapists Uniformly Effective Across Patient Outcome Domains? A Study on Therapist Effectiveness in Two Different Treatment Contexts
  • 2016
  • In: Journal of counseling psychology. - : AMER PSYCHOLOGICAL ASSOC. - 0022-0167 .- 1939-2168. ; 63:4, s. 367-378
  • Journal article (peer-reviewed)abstract
    • As established in several studies, therapists differ in effectiveness. A vital research task now is to understand what characterizes more or less effective therapists, and investigate whether this differential effectiveness systematically depends on client factors, such as the type of mental health problem. The purpose of the current study was to examine whether therapists are universally effective across patient outcome domains reflecting different areas of mental health functioning. Data were obtained from 2 sites: the Research Consortium of Counseling and Psychological Services in Higher Education (N = 5,828) in the United States and from primary and secondary care units (N = 616) in Sweden. Outcome domains were assessed via the Outcome Questionnaire-45 (Lambert et al., 2004) and the CORE-OM (Evans et al., 2002). Multilevel models with observations nested within patients were used to derive a reliable estimate for each patients change (which we call a multilevel growth d) based on all reported assessment points. Next, 2 multilevel confirmatory factor analytic models were fit in which these effect sizes (multilevel ds) for the 3 subscales of the OQ-45 (Study 1) and 6 subscales of CORE-OM (Study 2) were indicators of 1 common latent factor at the therapist level. In both data sets, such a model, reflecting a global therapist effectiveness factor, yielded large factor loadings and excellent model fit. Results suggest that therapists effective (or ineffective) within one outcome domain are also effective within another outcome domain. Tentatively, therapist effectiveness can thus be conceived of as a global construct.
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50.
  • Ny, Lars, 1967, et al. (author)
  • A magnetic resonance imaging study of intestinal dilation in Trypanosoma cruzi-infected mice deficient in nitric oxide synthase.
  • 2008
  • In: The American journal of tropical medicine and hygiene. - 1476-1645. ; 79:5, s. 760-7
  • Journal article (peer-reviewed)abstract
    • Infection with Trypanosoma cruzi causes megasyndromes of the gastrointestinal (GI) tract. We used magnetic resonance imaging (MRI) to monitor alterations in the GI tract of T. cruzi-infected mice, and to assess the role of nitric oxide (NO) in the development of intestinal dilation. Brazil strain-infected C57BL/6 wild-type (WT) mice exhibited dilatation of the intestines by 30 days post-infection. Average intestine lumen diameter increased by 72%. Levels of intestinal NO synthase (NOS) isoforms, NOS2 and NOS3, were elevated in infected WT mice. Inflammation and ganglionitis were observed in all infected mice. Intestinal dilation was observed in infected WT, NOS1, NOS2, and NOS3 null mice. This study demonstrates that MRI is a useful tool to monitor intestinal dilation in living mice and that these alterations may begin during acute infection. Furthermore, our data strongly suggests that NO may not be the sole contributor to intestinal dysfunction resulting from this infection.
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