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2.
  • Marklund, Emelie, et al. (author)
  • Serum-IgG responses to SARS-CoV-2 after mild and severe COVID-19 infection and analysis of IgG non-responders.
  • 2020
  • In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 15:10
  • Journal article (peer-reviewed)abstract
    • To accurately interpret COVID-19 seroprevalence surveys, knowledge of serum-IgG responses to SARS-CoV-2 with a better understanding of patients who do not seroconvert, is imperative. This study aimed to describe serum-IgG responses to SARS-CoV-2 in a cohort of patients with both severe and mild COVID-19, including extended studies of patients who remained seronegative more than 90 days post symptom onset.SARS-CoV-2-specific IgG antibody levels were quantified using two clinically validated and widely used commercial serological assays (Architect, Abbott Laboratories and iFlash 1800, YHLO), detecting antibodies against the spike and nucleocapsid proteins.Forty-seven patients (mean age 49 years, 38% female) were included. All (15/15) patients with severe symptoms and 29/32 (90.6%) patients with mild symptoms of COVID-19 developed SARS-CoV-2-specific IgG antibodies in serum. Time to seroconversion was significantly shorter (median 11 vs. 22 days, P = 0.04) in patients with severe compared to mild symptoms. Of the three patients without detectable IgG-responses after >90 days, all had detectable virus-neutralizing antibodies and in two, spike-protein receptor binding domain-specific IgG was detected with an in-house assay. Antibody titers were preserved during follow-up and all patients who seroconverted, irrespective of the severity of symptoms, still had detectable IgG levels >75 days post symptom onset.Patients with severe COVID-19 both seroconvert earlier and develop higher concentrations of SARS-CoV-2-specific IgG than patients with mild symptoms. Of those patients who not develop detectable IgG antibodies, all have detectable virus-neutralizing antibodies, suggesting immunity. Our results showing that not all COVID-19 patients develop detectable IgG using two validated commercial clinical methods, even over time, are vital for the interpretation of COVID-19 seroprevalence surveys.
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4.
  • Beck-Friis, Thomas, et al. (author)
  • Comparison of SARS-CoV-2 spike RNA sequences in feces and nasopharynx indicates intestinal replication
  • 2022
  • In: Gut Pathogens. - : Springer Science and Business Media LLC. - 1757-4749. ; 14:1
  • Journal article (peer-reviewed)abstract
    • Background Little is known of possible selection and replication of SARS-CoV-2 in the intestines and if viral load in feces is associated with severity of disease. Therefore, sequence variations of the spike region in strains collected from feces and nasopharynx (NPH) from the same patients were compared. It was also investigated whether viral load in feces related to severity of COVID-19 in hospitalized patients. Results SARS-CoV-2 RNA was found in 88 (79%) fecal samples from 112 patients. The complete spike region could be sequenced in 15 fecal and 14 NPH samples. Fourteen Alpha-variants and one Beta-variant of SARS-CoV-2 were identified. The majority of the viral genetic variants (viral populations) in two fecal samples, but none in NPH, had a reversion of the H69/V70 amino acid deletion normally seen in the Alpha variants. Nine fecal samples contained up to nine minority variants, each which may constitute a separate viral population. Five NPH samples had one genetic variant each, and one NPH sample contained nine minority populations of SARS-CoV-2 spike genes. Conclusions The higher genomic diversity of SARS-CoV-2 in feces compared to NPH, and the reversion of the H69/V70 deletion in Alpha variants from feces indicate a selection of viral strains and replication of SARS-CoV-2 in the gastrointestinal tract.
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5.
  • Borssén, Magnus, et al. (author)
  • DNA Methylation Adds Prognostic Value to Minimal Residual Disease Status in Pediatric T-Cell Acute Lymphoblastic Leukemia
  • 2016
  • In: Pediatric Blood & Cancer. - : Wiley. - 1545-5009 .- 1545-5017. ; 63:7, s. 1185-1192
  • Journal article (peer-reviewed)abstract
    • Background. Despite increased knowledge about genetic aberrations in pediatric T-cell acute lymphoblastic leukemia (T-ALL), no clinically feasible treatment-stratifying marker exists at diagnosis. Instead patients are enrolled in intensive induction therapies with substantial side effects. In modern protocols, therapy response is monitored by minimal residual disease (MRD) analysis and used for postinduction risk group stratification. DNA methylation profiling is a candidate for subtype discrimination at diagnosis and we investigated its role as a prognostic marker in pediatric T-ALL. Procedure. Sixty-five diagnostic T-ALL samples from Nordic pediatric patients treated according to the Nordic Society of Pediatric Hematology and Oncology ALL 2008 (NOPHO ALL 2008) protocol were analyzed by HumMeth450K genome wide DNA methylation arrays. Methylation status was analyzed in relation to clinical data and early T-cell precursor (ETP) phenotype. Results. Two distinct CpG island methylator phenotype (CIMP) groups were identified. Patients with a CIMP-negative profile had an inferior response to treatment compared to CIMP-positive patients (3-year cumulative incidence of relapse (CIR3y) rate: 29% vs. 6%, P = 0.01). Most importantly, CIMP classification at diagnosis allowed subgrouping of high-risk T-ALL patients (MRD >= 0.1% at day 29) into two groups with significant differences in outcome (CIR3y rates: CIMP negative 50% vs. CIMP positive 12%; P = 0.02). These groups did not differ regarding ETP phenotype, but the CIMP-negative group was younger (P = 0.02) and had higher white blood cell count at diagnosis (P = 0.004) compared with the CIMP-positive group. Conclusions. CIMP classification at diagnosis in combination with MRD during induction therapy is a strong candidate for further risk classification and could confer important information in treatment decision making.
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6.
  • Lundgren, Anna, 1974, et al. (author)
  • Plasmablasts in previously immunologically naive COVID-19 patients express markers indicating mucosal homing and secrete antibodies cross-reacting with SARS-CoV-2 variants and other beta-coronaviruses
  • 2023
  • In: Clinical and Experimental Immunology. - 0009-9104 .- 1365-2249. ; 213:2, s. 173-89
  • Journal article (peer-reviewed)abstract
    • Antigen-specific class-switched antibodies are detected at the same time or even before IgM in serum of non-vaccinated individuals infected with SARS-CoV-2. These derive from the first wave of plasmablasts formed. Hence, the phenotype and specificity of plasmablasts can reveal information about early B-cell activation. Here we have analyzed B cells and plasmablasts circulating in blood of COVID-19 patients not previously exposed to SARS-CoV-2 during and after disease. We find that during infection with the original Wuhan strain, plasmablasts in blood produce IgA1, IgG1, and IgM, and that most express CCR10 and integrin beta 1, only some integrin beta 7, while the majority lack CCR9. Plasmablast-secreted antibodies are reactive to the spike (S) and nucleocapsid (N) proteins of the Wuhan strain as well as later variants of concern, but also bind S proteins from endemic and non-circulating betacoronaviruses. In contrast, after recovery, antibodies produced from memory B cells target variants of SARS-CoV-2 and SARS-CoV-1 but compared to previously non-infected individuals do not show increased binding to endemic coronaviruses. This suggests that the early antibody response to a large extent stems from pre-existing cross-reactive class-switched memory B cells, and that although newly formed memory cells target the novel SARS-CoV-2 virus the numbers of broadly cross-reactive memory B cells do not increase extensively. The observations give insight into the role of pre-existing memory B cells in early antibody responses to novel pathogens and may explain why class-switched antibodies are detected early in the serum of COVID-19 patients. During an infection, plasmablasts circulating in blood represent ongoing formation of antibody-producing cells from activated B cells. Here we study the early plasmablasts in previously naive COVID-19 patients arriving at hospital. We find extensive cross-reactivity to circulating and non-circulating beta-coronaviruses, that IgA1 responses dominate, and that the cells express markers suggesting mucosal homing.
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7.
  • Marklund, Emelie, et al. (author)
  • Longitudinal Follow Up of Immune Responses to SARS-CoV-2 in Health Care Workers in Sweden With Several Different Commercial IgG-Assays, Measurement of Neutralizing Antibodies and CD4+ T-Cell Responses.
  • 2021
  • In: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 12
  • Journal article (peer-reviewed)abstract
    • The risk of SARS-CoV-2 infection among health care workers (HCWs) is a concern, but studies that conclusively determine whether HCWs are over-represented remain limited. Furthermore, methods used to confirm past infection vary and the immunological response after mild COVID-19 is still not well defined.314 HCWs were recruited from a Swedish Infectious Diseases clinic caring for COVID-19 patients. IgG antibodies were measured using two commercial assays (Abbot Architect nucleocapsid (N)-assay and YHLO iFlash-1800 N and spike (S)-assays) at five time-points, from March 2020 to January 2021, covering two pandemic waves. Seroprevalence was assessed in matched blood donors at three time-points. More extensive analyses were performed in 190 HCWs in September/October 2020, including two additional IgG-assays (DiaSorin LiaisonXL S1/S2 and Abbot Architect receptor-binding domain (RBD)-assays), neutralizing antibodies (NAbs), and CD4+ T-cell reactivity using an in-house developed in vitro whole-blood assay based on flow cytometric detection of activated cells after stimulation with Spike S1-subunit or Spike, Membrane and Nucleocapsid (SMN) overlapping peptide pools.Seroprevalence was higher among HCWs compared to sex and age-matched blood donors at all time-points. Seropositivity increased from 6.4% to 16.3% among HCWs between May 2020 and January 2021, compared to 3.6% to 11.9% among blood donors. We found significant correlations and high levels of agreement between NAbs and all four commercial IgG-assays. At 200-300 days post PCR-verified infection, there was a wide variation in sensitivity between the commercial IgG-assays, ranging from <30% in the N-assay to >90% in the RBD-assay. There was only moderate agreement between NAbs and CD4+ T-cell reactivity to S1 or SMN. Pre-existing CD4+ T-cell reactivity was present in similar proportions among HCW who subsequently became infected and those that did not.HCWs in COVID-19 patient care in Sweden have been infected with SARS-CoV-2 at a higher rate compared to blood donors. We demonstrate substantial variation between different IgG-assays and propose that multiple serological targets should be used to verify past infection. Our data suggest that CD4+ T-cell reactivity is not a suitable measure of past infection and does not reliably indicate protection from infection in naive individuals.
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8.
  • Nyström, Thomas, et al. (author)
  • Evaluation of Effects of Continuous Glucose Monitoring on Physical Activity Habits and Blood Lipid Levels in Persons With Type 1 Diabetes Managed With MDI: An Analysis Based on the GOLD Randomized Trial (GOLD 8)
  • 2024
  • In: Journal of diabetes science and technology. - : SAGE Publications. - 1932-2968. ; 18:1, s. 89-98
  • Journal article (peer-reviewed)abstract
    • Background: People with type 1 diabetes generally view it easier to exercise when having continuous information of the glucose levels. We evaluated whether patients with type 1 diabetes managed with multiple daily insulin injections (MDI) exercised more after initiating continuous glucose monitoring (CGM) and whether the improved glycemic control and well-being associated with CGM translates into improved blood lipids and markers of inflammation. Method: The GOLD trial was a randomized cross-over trial over 16 months where patients used either CGM or capillary self-monitoring of blood glucose (SMBG) over six months, with a four-month wash-out period between the two treatment periods. We compared grade of physical activity, blood lipids, apolipoproteins, and high-sensitivity C-reactive protein (hsCRP) levels during CGM and SMBG. Results: There were 116 patients with information of physical activity estimated by the International Physical Activity Questionnaire (IPAQ) during both CGM and SMBG. No changes were found during CGM or SMBG, IPAQ scores 3305 versus 3878 (P =.16). In 136 participants with information of blood lipid levels with no change in lipid-lowering medication during the two treatment periods, HbA1c differed by 4.2 mmol/mol (NGSP 0.39%) between SMBG and CGM treatment (P <.001). No significant changes existed in low-density lipoprotein, high-density lipoprotein, triglycerides, total cholesterol, apolipoprotein A1, apolipoprotein B1, or hsCRP, during CGM and SMBG. Conclusion: Although many patients experience it easier to perform physical activity when monitoring glucose levels with CGM, it does not influence the amount of physical activity in persons with type 1 diabetes. Blood lipids, apolipoprotein, and hsCRP levels were similar during CGM and SMBG.
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9.
  • Saguti, Fredy, et al. (author)
  • Surveillance of wastewater revealed peaks of SARS-CoV-2 preceding those of hospitalized patients with COVID-19.
  • 2021
  • In: Water research. - : Elsevier BV. - 1879-2448 .- 0043-1354. ; 189
  • Journal article (peer-reviewed)abstract
    • SARS-CoV-2 was discovered among humans in Wuhan, China in late 2019, and then spread rapidly, causing a global pandemic. The virus was found to be transmitted mainly by respiratory droplets from infected persons or by direct contact. It was also shown to be excreted in feces, why we investigated whether the virus could be detected in wastewater and if so, to which extent its levels reflects its spread in society. Samples of wastewater from the city of Gothenburg, and surrounding municipalities in Sweden were collected daily from mid-February until June 2020 at the Rya wastewater treatment plant. Flow proportional samples of wastewater were collected to ensure that comparable amounts were obtained for analysis. Daily samples were pooled into weekly samples. Virus was concentrated on a filter and analyzed by RT-qPCR. The amount of SARS-CoV-2 varied with peaks approximately every four week, preceding variations in number of newly hospitalized patients by 19-21 days. At that time virus testing for COVID-19 was limited to patients with severe symptoms. Local differences in viral spread was shown by analyzing weekly composite samples of wastewater from five sampling sites for four weeks. The highest amount of virus was found from the central, eastern, and northern parts of the city. SARS-CoV-2 was also found in the treated effluent wastewater from the WWTP discharged into the recipient, the Göta River, although with a reduction of 4-log10. The viral peaks with regular temporal intervals indicated that SARS-CoV-2 may have a cluster spread, probably reflecting that the majority of infected persons only spread the disease during a few days. Our results are important for both the planning of hospital care and to rapidly identify and intervene against local spread of the virus.
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10.
  • Saguti, Fredy, et al. (author)
  • Surveillance of wastewater revealed peaks of SARS-CoV-2 preceding those of hospitalized patients with COVID-19
  • 2021
  • In: Water Research. - : Elsevier BV. - 0043-1354 .- 1879-2448. ; 189
  • Journal article (peer-reviewed)abstract
    • SARS-CoV-2 was discovered among humans in Wuhan, China in late 2019, and then spread rapidly, causing a global pandemic. The virus was found to be transmitted mainly by respiratory droplets from infected persons or by direct contact. It was also shown to be excreted in feces, why we investigated whether the virus could be detected in wastewater and if so, to which extent its levels reflects its spread in society. Samples of wastewater from the city of Gothenburg, and surrounding municipalities in Sweden were collected daily from mid-February until June 2020 at the Rya wastewater treatment plant. Flow proportional samples of wastewater were collected to ensure that comparable amounts were obtained for analysis. Daily samples were pooled into weekly samples. Virus was concentrated on a filter and analyzed by RT-qPCR. The amount of SARS-CoV-2 varied with peaks approximately every four week, preceding variations in number of newly hospitalized patients by 19-21 days. At that time virus testing for COVID-19 was limited to patients with severe symptoms. Local differences in viral spread was shown by analyzing weekly composite samples of wastewater from five sampling sites for four weeks. The highest amount of virus was found from the central, eastern, and northern parts of the city. SARS-CoV-2 was also found in the treated effluent wastewater from the WWTP discharged into the recipient, the Göta River, although with a reduction of 4-log10. The viral peaks with regular temporal intervals indicated that SARS-CoV-2 may have a cluster spread, probably reflecting that the majority of infected persons only spread the disease during a few days. Our results are important for both the planning of hospital care and to rapidly identify and intervene against local spread of the virus.
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11.
  • Tesi, Bianca, et al. (author)
  • Diagnostic yield and clinical impact of germline sequencing in children with CNS and extracranial solid tumors : a nationwide, prospective Swedish study
  • 2024
  • In: The Lancet Regional Health. - : Elsevier. - 2666-7762. ; 39
  • Journal article (peer-reviewed)abstract
    • BackgroundChildhood cancer predisposition (ChiCaP) syndromes are increasingly recognized as contributing factors to childhood cancer development. Yet, due to variable availability of germline testing, many children with ChiCaP might go undetected today. We report results from the nationwide and prospective ChiCaP study that investigated diagnostic yield and clinical impact of integrating germline whole-genome sequencing (gWGS) with tumor sequencing and systematic phenotyping in children with solid tumors.MethodsgWGS was performed in 309 children at diagnosis of CNS (n = 123, 40%) or extracranial (n = 186, 60%) solid tumors and analyzed for disease-causing variants in 189 known cancer predisposing genes. Tumor sequencing data were available for 74% (227/309) of patients. In addition, a standardized clinical assessment for underlying predisposition was performed in 95% (293/309) of patients.FindingsThe prevalence of ChiCaP diagnoses was 11% (35/309), of which 69% (24/35) were unknown at inclusion (diagnostic yield 8%, 24/298). A second-hit and/or relevant mutational signature was observed in 19/21 (90%) tumors with informative data. ChiCaP diagnoses were more prevalent among patients with retinoblastomas (50%, 6/12) and high-grade astrocytomas (37%, 6/16), and in those with non-cancer related features (23%, 20/88), and ≥2 positive ChiCaP criteria (28%, 22/79). ChiCaP diagnoses were autosomal dominant in 80% (28/35) of patients, yet confirmed de novo in 64% (18/28). The 35 ChiCaP findings resulted in tailored surveillance (86%, 30/35) and treatment recommendations (31%, 11/35).InterpretationOverall, our results demonstrate that systematic phenotyping, combined with genomics-based diagnostics of ChiCaP in children with solid tumors is feasible in large-scale clinical practice and critically guides personalized care in a sizable proportion of patients.
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12.
  • Tesi, Bianca, et al. (author)
  • Diagnostic yield and clinical impact of germline sequencing in children with CNS and extracranial solid tumors : a nationwide, prospective Swedish study
  • 2024
  • In: The Lancet Regional Health. - : Elsevier. - 2666-7762. ; 39
  • Journal article (peer-reviewed)abstract
    • Background: Childhood cancer predisposition (ChiCaP) syndromes are increasingly recognized as contributing factors to childhood cancer development. Yet, due to variable availability of germline testing, many children with ChiCaP might go undetected today. We report results from the nationwide and prospective ChiCaP study that investigated diagnostic yield and clinical impact of integrating germline whole-genome sequencing (gWGS) with tumor sequencing and systematic phenotyping in children with solid tumors.Methods: gWGS was performed in 309 children at diagnosis of CNS (n = 123, 40%) or extracranial (n = 186, 60%) solid tumors and analyzed for disease-causing variants in 189 known cancer predisposing genes. Tumor sequencing data were available for 74% (227/309) of patients. In addition, a standardized clinical assessment for underlying predisposition was performed in 95% (293/309) of patients.Findings: The prevalence of ChiCaP diagnoses was 11% (35/309), of which 69% (24/35) were unknown at inclusion (diagnostic yield 8%, 24/298). A second-hit and/or relevant mutational signature was observed in 19/21 (90%) tumors with informative data. ChiCaP diagnoses were more prevalent among patients with retinoblastomas (50%, 6/12) and high-grade astrocytomas (37%, 6/16), and in those with non-cancer related features (23%, 20/88), and ≥2 positive ChiCaP criteria (28%, 22/79). ChiCaP diagnoses were autosomal dominant in 80% (28/35) of patients, yet confirmed de novo in 64% (18/28). The 35 ChiCaP findings resulted in tailored surveillance (86%, 30/35) and treatment recommendations (31%, 11/35).Interpretation: Overall, our results demonstrate that systematic phenotyping, combined with genomics-based diagnostics of ChiCaP in children with solid tumors is feasible in large-scale clinical practice and critically guides personalized care in a sizable proportion of patients.Funding: The study was supported by the Swedish Childhood Cancer Fund and the Ministry of Health and Social Affairs.
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13.
  • Vesterbacka, Jan, et al. (author)
  • Kinetics of microbial translocation markers in patients on efavirenz or lopinavir/r based antiretroviral therapy
  • 2013
  • In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 8:1, s. e55038-
  • Journal article (peer-reviewed)abstract
    • OBJECTIVES: We investigated whether there are differences in the effects on microbial translocation (MT) and enterocyte damage by different antiretroviral therapy (ART) regimens after 1.5 years and whether antibiotic use has impact on MT. In a randomized clinical trial (NCT01445223) on first line ART, patients started either lopinavir/r (LPV/r) (n = 34) or efavirenz (EFV) containing ART (n = 37). Lipopolysaccharide (LPS), sCD14, anti-flagellin antibodies and intestinal fatty acid binding protein (I-FABP) levels were determined in plasma at baseline (BL) and week 72 (w72).RESULTS: The levels of LPS and sCD14 were reduced from BL to w72 (157.5 pg/ml vs. 140.0 pg/ml, p = 0.0003; 3.13 ug/ml vs. 2.85 ug/ml, p = 0.005, respectively). The levels of anti-flagellin antibodies had decreased at w72 (0.35 vs 0.31 [OD]; p<0.0004), although significantly only in the LPV/r arm. I-FABP levels increased at w72 (2.26 ng/ml vs 3.13 ng/ml; p<0.0001), although significantly in EFV treated patients only. Patients given antibiotics at BL had lower sCD14 levels at w72 as revealed by ANCOVA compared to those who did not receive (Δ = -0.47 µg/ml; p = 0.015).CONCLUSIONS: Markers of MT and enterocyte damage are elevated in untreated HIV-1 infected patients. Long-term ART reduces the levels, except for I-FABP which role as a marker of MT is questionable in ART-experienced patients. Why the enterocyte damage seems to persist remains to be established. Also antibiotic usage may influence the kinetics of the markers of MT.TRIAL REGISTRATION: ClinicalTrials.gov NCT01445223.
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15.
  • Agebratt, Christian, et al. (author)
  • A Randomized Study of the Effects of Additional Fruit and Nuts Consumption on Hepatic Fat Content, Cardiovascular Risk Factors and Basal Metabolic Rate
  • 2016
  • In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:1, s. e0147149-
  • Journal article (peer-reviewed)abstract
    • BackgroundFruit has since long been advocated as a healthy source of many nutrients, however, the high content of sugars in fruit might be a concern.ObjectivesTo study effects of an increased fruit intake compared with similar amount of extra calories from nuts in humans.MethodsThirty healthy non-obese participants were randomized to either supplement the diet with fruits or nuts, each at +7 kcal/kg bodyweight/day for two months. Major endpoints were change of hepatic fat content (HFC, by magnetic resonance imaging, MRI), basal metabolic rate (BMR, with indirect calorimetry) and cardiovascular risk markers.ResultsWeight gain was numerically similar in both groups although only statistically significant in the group randomized to nuts (fruit: from 22.15±1.61 kg/m2 to 22.30±1.7 kg/m2, p = 0.24 nuts: from 22.54±2.26 kg/m2 to 22.73±2.28 kg/m2, p = 0.045). On the other hand BMR increased in the nut group only (p = 0.028). Only the nut group reported a net increase of calories (from 2519±721 kcal/day to 2763±595 kcal/day, p = 0.035) according to 3-day food registrations. Despite an almost three-fold reported increased fructose-intake in the fruit group (from 9.1±6.0 gram/day to 25.6±9.6 gram/day, p<0.0001, nuts: from 12.4±5.7 gram/day to 6.5±5.3 gram/day, p = 0.007) there was no change of HFC. The numerical increase in fasting insulin was statistical significant only in the fruit group (from 7.73±3.1 pmol/l to 8.81±2.9 pmol/l, p = 0.018, nuts: from 7.29±2.9 pmol/l to 8.62±3.0 pmol/l, p = 0.14). Levels of vitamin C increased in both groups while α-tocopherol/cholesterol-ratio increased only in the fruit group.ConclusionsAlthough BMR increased in the nut-group only this was not linked with differences in weight gain between groups which potentially could be explained by the lack of reported net caloric increase in the fruit group. In healthy non-obese individuals an increased fruit intake seems safe from cardiovascular risk perspective, including measurement of HFC by MRI.
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16.
  • Al-Karkhi, Isam, et al. (author)
  • Comparisons of automated blood pressures in a primary health care setting with self-measurements at the office and at home using the Omron i-C10 device
  • 2015
  • In: Blood Pressure Monitoring. - : Lippincott Williams & Wilkins. - 1359-5237 .- 1473-5725. ; 20:2, s. 98-103
  • Journal article (peer-reviewed)abstract
    • OBJECTIVE: We aimed to compare blood pressure (BP) levels recorded using the semiautomatic oscillometric Omron i-C10 BP device in patients with or without hypertension in three different settings: (a) when used by a doctor or a nurse at the office (OBP); (b) when used for self-measurement by the patient at the office (SMOBP); and (c) when used for 7 consecutive days at home (HBP).MATERIALS AND METHODS: A total of 247 individuals were invited to participate, but 78 of these individuals declined and a further seven were excluded, leaving a final cohort of 162 participants.RESULTS: The mean OBP was higher than HBP (difference 8.1±14/3.1±8.8 mmHg, P<0.0001) and so was SMOBP compared with HBP (difference 7.0±13/4.2±7.3 mmHg, P<0.0001). Sixteen participants (9.9%) had at least 10 mmHg higher systolic SMOBP than OBP and 28 (17%) participants had at least 10 mmHg lower systolic SMOBP than OBP. Participants who were current smokers had a larger mean difference between systolic OBP and SMOBP than nonsmokers (OBP-SMOBP in smokers: 6.6±9.4 mmHg, OBP-SMOBP in nonsmokers: 0.5±9.2 mmHg, P=0.011 between groups).CONCLUSION: Self-measurement of BP in the office does not preclude an increase in BP when levels in the individual patients are compared with HBP using the same equipment. Thus, SMOBP with a semiautomatic device does not lead to a reduction in the white-coat effect in the same manner as fully automatic devices.This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially. http://creativecommons.org/licenses/by-nc-nd/3.0.
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17.
  • Ammar, Yosr, et al. (author)
  • Exploring future ecosystem novelty and resilience using the adaptive cycle
  • Other publication (other academic/artistic)abstract
    • Marine ecosystems worldwide are under unprecedented pressure from the impacts of climate change and human activities. Such pressure increased novelty in species assemblages, i.e., assemblages increasingly outside their historical range of variation. It may further rise in the future, and whether it will unfold and influence resilience remains unclear. Using the adaptive cycle, we explore the relationship between resilience and novelty under the compound effect of climate, nutrient load, and fishing management scenarios in the Finnish Archipelago Sea (FAS) future food web model. Novelty was measured as the minimum dissimilarity over time relative to a specific baseline. Ecological Network Analysis indices associated to the model: ascendancy, capacity, and overhead flow, were used as indicators of connectedness, potential, and resilience axes of the adaptive cycle. A model-based clustering method distinguished four regimes determined by the impact of the nutrient load and climate on the bottom-up dynamic of the FAS food web. Resilience decreased in regimes where higher and faster novelty emerged in response to warmer climate pathways. The number of reorganization phases of the adaptive cycle, characterized by the generation of novelty, was greater in regimes under low nutrient load management scenarios. We highlight the importance of understanding ecosystem reorganization and resilience in a growing Anthropogenic novelty to inform future management. 
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18.
  • Ammar, Yosr, 1992- (author)
  • Novelty in social-ecological systems: understanding the past to plan the future
  • 2020
  • Licentiate thesis (other academic/artistic)abstract
    • Human activities are shaping the Earth system and creating novel properties in the intertwined Social-Ecological Systems (SES). Although novelty is acknowledged in SES theories, the concept of novelty is not well understood, and little mathematical formalization and empirical foundations have been made. Building on the theoretical frameworks of Complex Adaptive Systems (CAS) and concepts of novelty in ecology, this licentiate thesis suggests a first attempt to quantify novelty in a marine ecosystem, in a SES context. Here, I focus on the past emergence of novelty in a marine SES to better understand when and where novelty has emerged and which drivers affect this emergence. Novelty emerges in a CAS when it has moved beyond its historical range of variation. The historical state depends on the temporal and spatial scale as well as the context of the study. Building on the characteristics of CAS, novelty is multidimensional, emerges on a continuum, can be nonlinear, and follows baseline specific trajectories. It has been quantified as the degree of dissimilarity of a system relative to a specific baseline. I used the case of the Baltic Sea SES, where long-term data exists, and many ecological, political, and economic changes have been recorded. Here, I focus on structural changes of the system rather than interactions and feedbacks. Paper 1 focuses on the ecological novelty in the Baltic Sea and contributes as the first study that quantifies novelty in marine ecosystems and across different trophic levels. Results reveal that over the 35-year study-period (1980-2015), novelty has emerged following the pattern of change, but at a slower pace. It has emerged in complex temporal and spatial pattern of the tested abiotic and biotic components. Both abiotic and biotic novelty showed a higher rate of novelty in confined northern basins than in the Central Baltic Sea, which indicated that some areas are more susceptible to the rise of novelty than others. Temperature and salinity were identified as the main abiotic drivers of biotic novelty in the Baltic Sea. Paper 2 contributes as the first study to quantify socio-economic novelty in a marine SES. Socio-economic novelty in the Baltic Sea showed a change in the contribution to novelty from factors linked to local and regional management levels, i.e., fishing gears and commercial groups, to trades which are linked to international level. A high increase in imports and exports in recent years marked the fastest increase in novelty over the period studied. In the latter, novelty in terms of economic value of fishery products was higher than their novelty in quantity. Sweden, Denmark, and Poland have been the countries contributing most to the emergence of novelty in the studied period. This paper illustrates that understanding socio-economic novelty together with ecological novelty, may provide a better understanding of the complexity of marine SES. Although not all the characteristics of CAS could be captured by the methodological approach used in Paper 1 and 2, many have been identified and considered. However, this highlights the need for more methods that can capture different characteristics of CAS, such as interactions and feedbacks, and more knowledge on the emergence of novelty in SES. Understanding how novelty emerges, its processes in different SES components and across-scales, may reduce the risk of missing opportunities for biodiversity conservation, and of unintended management outcomes for long-term sustainability.
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19.
  • Andersson, Peter, et al. (author)
  • Low symptomatic load in Crohn's disease with surgery and medicine as complementary treatments
  • 1998
  • In: Scandinavian Journal of Gastroenterology. - : Informa Healthcare. - 0036-5521 .- 1502-7708. ; 33:4, s. 423-429
  • Journal article (peer-reviewed)abstract
    • Background: The treatment of Crohn's disease has changed owing to the recognition of its chronicity. Medical maintenance treatment and limited resections have evolved as major concepts of management, regarded as complementary, and both aim at reducing the symptoms.Methods: We investigated the symptomatic load in Crohn's disease as reflected in a cross-sectional study of the symptom index, physicians' assessment, and the patients' perception of health. A cohort of 212 patients from the primary catchment area and 125 referred patients were studied.Results: Of catchment area patients, 83% were receiving medication, and the annual rate of abdominal surgery was 5.7%. Corresponding figures for the referred patients were 82% and 10.3%. According to the symptom index, 87% of catchment area patients were in remission or had only mild symptoms; according to the physicians' assessment, 90% were. The patients' median perception of health was 90% of perfect health according to the visual analogue scale. The figures were similar for referred patients, except that referrals were considered more diseased by the physician.Conclusion: The great majority of patients with Crohn's disease are able to live in remission or experience only mild symptoms.
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20.
  • Angeler, David, et al. (author)
  • Management applications of discontinuity theory
  • 2016
  • In: Journal of Applied Ecology. - : Wiley. - 0021-8901 .- 1365-2664. ; 53:3, s. 688-698
  • Research review (peer-reviewed)abstract
    • 1. Human impacts on the environment are multifaceted and can occur across distinct spatiotemporal scales. Ecological responses to environmental change are therefore difficult to predict, and entail large degrees of uncertainty. Such uncertainty requires robust tools for management to sustain ecosystem goods and services and maintain resilient ecosystems. 2. We propose an approach based on discontinuity theory that accounts for patterns and processes at distinct spatial and temporal scales, an inherent property of ecological systems. Discontinuity theory has not been applied in natural resource management and could therefore improve ecosystem management because it explicitly accounts for ecological complexity. 3. Synthesis and applications. We highlight the application of discontinuity approaches for meeting management goals. Specifically, discontinuity approaches have significant potential to measure and thus understand the resilience of ecosystems, to objectively identify critical scales of space and time in ecological systems at which human impact might be most severe, to provide warning indicators of regime change, to help predict and understand biological invasions and extinctions and to focus monitoring efforts. Discontinuity theory can complement current approaches, providing a broader paradigm for ecological management and conservation.
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21.
  • Anthony, Kenneth R. N., et al. (author)
  • Operationalizing resilience for adaptive coral reef management under global environmental change
  • 2015
  • In: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 21:1, s. 48-61
  • Research review (peer-reviewed)abstract
    • Cumulative pressures from global climate and ocean change combined with multiple regional and local-scale stressors pose fundamental challenges to coral reef managers worldwide. Understanding how cumulative stressors affect coral reef vulnerability is critical for successful reef conservation now and in the future. In this review, we present the case that strategically managing for increased ecological resilience (capacity for stress resistance and recovery) can reduce coral reef vulnerability (risk of net decline) up to a point. Specifically, we propose an operational framework for identifying effective management levers to enhance resilience and support management decisions that reduce reef vulnerability. Building on a system understanding of biological and ecological processes that drive resilience of coral reefs in different environmental and socio-economic settings, we present an Adaptive Resilience-Based management (ARBM) framework and suggest a set of guidelines for how and where resilience can be enhanced via management interventions. We argue that press-type stressors (pollution, sedimentation, overfishing, ocean warming and acidification) are key threats to coral reef resilience by affecting processes underpinning resistance and recovery, while pulse-type (acute) stressors (e.g. storms, bleaching events, crown-of-thorns starfish outbreaks) increase the demand for resilience. We apply the framework to a set of example problems for Caribbean and Indo-Pacific reefs. A combined strategy of active risk reduction and resilience support is needed, informed by key management objectives, knowledge of reef ecosystem processes and consideration of environmental and social drivers. As climate change and ocean acidification erode the resilience and increase the vulnerability of coral reefs globally, successful adaptive management of coral reefs will become increasingly difficult. Given limited resources, on-the-ground solutions are likely to focus increasingly on actions that support resilience at finer spatial scales, and that are tightly linked to ecosystem goods and services.
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22.
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23.
  • Belitsky, Victor, 1955, et al. (author)
  • Design and performance of ALMA band 5 receiver cartridge
  • 2010
  • In: 35th International Conference on Infrared Millimeter and Terahertz Waves (IRMMW-THz), 2010. - 9781424466559 ; , s. 1-2
  • Conference paper (peer-reviewed)abstract
    • ALMA, Atacama Large Millimetre Array, covers the frequency band from 30 GHz to 960 GHz in ten separate frequency bands. We present here the design and performance of the ALMA Band 5 receiver cartridge that covers 163–211 GHz. The Band 5 receiver shows the state-of-the-art performance with the noise temperature below 65K (SSB) and sideband rejection above 12 dB over 80% of the RF band.
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24.
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25.
  • Belitsky, Victor, 1955, et al. (author)
  • Prototype ALMA Band 5 Cartridge:Design and Performance
  • 2009
  • In: Proceedings of the 20TH INTERNATIONAL SYMPOSIUM ON SPACE TERAHERTZ TECHNOLOGY, Charlottesville, VA, USA, April 20-22, 2009, s. 2-5.
  • Conference paper (peer-reviewed)abstract
    • The Atacama Large Millimeter/submillimeterArray (ALMA), an international astronomy facility, is apartnership of East Asia, Europe and North America incooperation with the Republic of Chile and aims to build aninterferometer radio telescope consisting of more than 60antennas. The instrument is under construction at the Llano deChajnantor, about 50 km east of San Pedro de Atacama, Chile.This work presents a part of ALMA frontend, the development,design and performance of one of the frequency channels of theALMA receiver, the Band 5 prototype cartridge for 163 – 211GHz frequency band.
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