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1.
  • Groundstroem, Henrik, et al. (author)
  • A systematic mapping of Nordic youth surveys
  • 2020
  • Conference paper (peer-reviewed)abstract
    • Aim: The aim of this study was to map the existing Nordic youth surveys and to answer the following research questions: how many youth surveys are conducted in the Nordic countries?, what major youth surveys are being conducted in all Nordic countries?, and what themes do the existing questionnaires deal with in the various countries?Method: Data was collected from January to April 2018 through a systematic mapping technique and the surveys were analyzed according to quality criteria.Results: The results showed a total of 143 surveys and after exclusion due to poor survey quality, 82 fit the inclusion criteria. In the Nordic countries, six surveys were identified that covered all Nordic countries. The themes that youth surveys usually focus on are criminality, school, physical and mental health, addiction, societal participation and family relationships.Conclusion: Many similar youth surveys exist both nationally and on a Nordic level. During the last forty years, there has also been an exponential increase in surveys aimed at young people. A larger coordination of these surveys would be beneficial and increase their quality as well as limit the number of surveys that young people are exposed to. This study identifies the need for a coordinated Nordic youth survey and the potential benefits on a regional, national and Nordic level.
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2.
  • Baumann, Pia, et al. (author)
  • Factors important for efficacy of stereotactic body radiotherapy of medically inoperable stage I lung cancer. A retrospective analysis of patients treated in the Nordic countries.
  • 2006
  • In: Acta oncologica (Stockholm, Sweden). - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 45:7, s. 787-95
  • Journal article (peer-reviewed)abstract
    • We reviewed results of SBRT treatment of 138 patients with medically inoperable stage I NSCLC treated during 1996-2003 at five different centres in Sweden and Denmark. Mean age was 74 years (range 56-90) with 69 men and 72 women. SBRT was delivered using a 3D conformal multifield technique and a stereotactic body frame. Doses delivered were 30-48 Gy (65% isodose at the periphery of planning target volume, PTV) in 2-4 fractions. Equivalent dose in 2 Gy fractions (EQD2) was in the range of 50-100 Gy. Mean gross tumour volume (GTV) was 39 cm3 (2-436), and planning target volume was 101 cm3 (11-719). Overall response rate (CR, PR) was 61% (84/138). SD was noted in 36% (50/138). During a median follow-up period of 33 months (1-107), 16 (12%) local failures occurred, ten of which also included distant metastases. Local failure was associated with tumour size, target definition and central or pleura proximity. Distant metastases occurred in 25% (35/138) of the patients. Ninety-one (65%) patients died during follow-up of which 55 patients (60%) died of other causes than lung cancer. Three- and 5-year overall survival was 52 and 26% respectively. Lung cancer specific 3- and 5-year overall survival was 66 and 40% respectively. Fifty nine percent (83/138) of the patients had no side effects. Fourteen patients experienced grade 3-4 toxicity according to radiation therapy oncology group (RTOG). EQD2 (> v.s.<55.6 Gy) showed a statistically significant benefit survival for the higher doses. SBRT for stage I NSCLC results in favourable local control not inferior to fractionated RT and with acceptable toxicity.
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3.
  • Baumann, Pia, et al. (author)
  • Outcome in a prospective phase II trial of medically inoperable stage I non-small-cell lung cancer patients treated with stereotactic body radiotherapy.
  • 2009
  • In: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. - 1527-7755 .- 0732-183X. ; 27:20, s. 3290-6
  • Journal article (peer-reviewed)abstract
    • PURPOSE: The impact of stereotactic body radiotherapy (SBRT) on 3-year progression-free survival of medically inoperable patients with stage I non-small-cell lung cancer (NSCLC) was analyzed in a prospective phase II study. PATIENTS AND METHODS: Fifty-seven patients with T1NOMO (70%) and T2N0M0 (30%) were included between August 2003 and September 2005 at seven different centers in Sweden, Norway, and Denmark and observed up to 36 months. SBRT was delivered with 15 Gy times three at the 67% isodose of the planning target volume. RESULTS: Progression-free survival at 3 years was 52%. Overall- and cancer-specific survival at 1, 2, and 3 years was 86%, 65%, 60%, and 93%, 88%, 88%, respectively. There was no statistically significant difference in survival between patients with T1 or T2 tumors. At a median follow-up of 35 months (range, 4 to 47 months), 27 patients (47%) were deceased, seven as a result of lung cancer and 20 as a result of concurrent disease. Kaplan-Meier estimated local control at 3 years was 92%. Local relapse was observed in four patients (7%). Regional relapse was observed in three patients (5%). Nine patients (16%) developed distant metastases. The estimated risk of all failure (local, regional, or distant metastases) was increased in patients with T2 (41%) compared with those with T1 (18%) tumors (P = .027). CONCLUSION: With a 3-year local tumor control rate higher than 90% with limited toxicity, SBRT emerges as state-of-the-art treatment for medically inoperable stage I NSCLC and may even challenge surgery in operable instances.
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4.
  • Baumann, Pia, et al. (author)
  • Stereotactic body radiotherapy for medically inoperable patients with stage I non-small cell lung cancer - a first report of toxicity related to COPD/CVD in a non-randomized prospective phase II study.
  • 2008
  • In: Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology. - : Elsevier BV. - 0167-8140 .- 1879-0887. ; 88:3, s. 359-67
  • Journal article (peer-reviewed)abstract
    • BACKGROUND AND AIMS: In a retrospective study using stereotactic body radiotherapy (SBRT) in medically inoperable patients with stage I NSCLC we previously reported a local control rate of 88% utilizing a median dose of 15Gyx3. This report records the toxicity encountered in a prospective phase II trial, and its relation to coexisting chronic obstructive pulmonary disease (COPD) and cardio vascular disease (CVD). MATERIAL AND METHODS: Sixty patients were entered in the study between August 2003 and September 2005. Fifty-seven patients (T1 65%, T2 35%) with a median age of 75 years (59-87 years) were evaluable. The baseline mean FEV1% was 64% and median Karnofsky index was 80. A total dose of 45Gy was delivered in three fractions at the 67% isodose of the PTV. Clinical, pulmonary and radiological evaluations were made at 6 weeks, 3, 6, 9, 12, 18, and 36 months post-SBRT. Toxicity was graded according to CTC v2.0 and performance status was graded according to the Karnofsky scale. RESULTS: At a median follow-up of 23 months, 2 patients had relapsed locally. No grade 4 or 5 toxicity was reported. Grade 3 toxicity was seen in 12 patients (21%). There was no significant decline of FEV1% during follow-up. Low grade pneumonitis developed to the same extent in the CVD 3/17 (18%) and COPD 7/40 (18%) groups. The incidence of fibrosis was 9/17 (53%) and pleural effusions was 8/17 (47%) in the CVD group compared with 13/40 (33%) and 5/40 (13%) in the COPD group. CONCLUSION: SBRT for stage I NSCLC patients who are medically inoperable because of COPD and CVD results in a favourable local control rate with a low incidence of grade 3 and no grade 4 or 5 toxicity.
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5.
  • Carlströmer Berthén, Nellie, et al. (author)
  • The AxBioTick Study: Borrelia Species and Tick-Borne Encephalitis Virus in Ticks, and Clinical Responses in Tick-Bitten Individuals on the Aland Islands, Finland
  • 2023
  • In: Microorganisms. - : MDPI. - 2076-2607. ; 11:5
  • Journal article (peer-reviewed)abstract
    • The AxBioTick Study: Borrelia Species and Tick-Borne Encephalitis Virus in Ticks, and Clinical Responses in Tick-Bitten Individuals on the Aland Islands, Finlandby  Nellie Carlströmer Berthén 1,2,*,† , Eszter Tompa 3,† , Susanne Olausson 1,2, Clara Nyberg 1, Dag Nyman 1,2, Malin Ringbom 1,4, Linda Perander 1,4, Joel Svärd 3, Per-Eric Lindgren 3,5, Pia Forsberg 3, Peter Wilhelmsson 3,5,‡, Johanna Sjöwall 3,6,‡  and Marika Nordberg 1,4,‡  1Borrelia Research Group of the Aland Islands, 22100 Mariehamn, The Aland Islands, Finland2Bimelix AB, 22100 Mariehamn, The Aland Islands, Finland3Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection, Linkoping University, 581 83 Linkoping, Sweden4The Aland Islands Healthcare Services, 22100 Mariehamn, The Aland Islands, Finland5Clinical Microbiology, Laboratory Medicine, County Hospital Ryhov, 551 85 Jonkoping, Sweden6Department of Infectious Diseases, Vrinnevi Hospital, 603 79 Norrkoping, Sweden*Author to whom correspondence should be addressed.†These authors contributed equally to the study.‡These authors contributed equally to the study.Microorganisms 2023, 11(5), 1100; https://doi.org/10.3390/microorganisms11051100Received: 30 March 2023 / Revised: 17 April 2023 / Accepted: 19 April 2023 / Published: 22 April 2023(This article belongs to the Special Issue Research on Ticks and Tick-Borne Pathogens)Download Browse Figures Versions NotesArticle Views585 AbstractThe AxBioTick study was initiated to investigate the prevalence of ticks and tick-borne pathogens and their impact on antibody and clinical responses in tick-bitten individuals on the Aland Islands. This geographical area is hyperendemic for both Lyme borreliosis (LB) and Tick-borne encephalitis (TBE). Blood samples and ticks were collected from 100 tick-bitten volunteers. A total of 425 ticks was collected, all determined to Ixodes ricinus using molecular tools. Of them 20% contained Borrelia species, of which B. garinii and B. afzelii were most common. None contained the TBE virus (TBEV). Blood samples were drawn in conjunction with the tick bite, and eight weeks later. Sera were analyzed for Borrelia- and TBEV-specific antibodies using an ELISA and a semiquantitative antibody assay. In total 14% seroconverted in Borrelia C6IgG1, 3% in TBEV IgG, and 2% in TBEV IgM. Five participants developed clinical manifestations of LB. The high seroprevalence of both Borrelia (57%) and TBEV (52%) antibodies are likely attributed to the endemic status of the corresponding infections as well as the TBE vaccination program. Despite the similar prevalence of Borrelia spp. detected in ticks in other parts of Europe, the infection rate in this population is high. The AxBioTick study is continuing to investigate more participants and ticks for co-infections, and to characterize the dermal immune response following a tick bite.
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6.
  • Dessau, Ram B, et al. (author)
  • Study of a Cohort of 1,886 Persons To Determine Changes in Antibody Reactivity to Borrelia burgdorferi 3 Months after a Tick Bite
  • 2015
  • In: Clinical and Vaccine Immunology. - 1556-6811 .- 1556-679X. ; 22:7, s. 823-827
  • Journal article (peer-reviewed)abstract
    • Lyme borreliosis is a tick-borne disease caused by the bacterium Borrelia burgdorferi. The most frequent clinical manifestation is a rash called erythema migrans. Changes in antibody reactivity to B. burgdorferi 3 months after a tick bite are measured using enzyme-linked immunosorbent assays (ELISAs). One assay is based on native purified flagellum antigen (IgG), and the other assay is based on a recombinant antigen called C6 (IgG or IgM). Paired samples were taken at the time of a tick bite and 3 months later from 1,886 persons in Sweden and the Åland Islands, Finland. The seroconversion or relative change is defined by dividing the measurement units from the second sample by those from the first sample. The threshold for the minimum level of significant change was defined at the 2.5% level to represent the random error level. The thresholds were a 2.7-fold rise for the flagellar IgG assay and a 1.8-fold rise for the C6 assay. Of 1,886 persons, 102/101 (5.4%) had a significant rise in antibody reactivity in the flagellar assay or the C6 assay. Among 40 cases with a diagnosis of Lyme borreliosis, the sensitivities corresponding to a rise in antibodies were 33% and 50% for the flagellar antigen and the C6 antigen, respectively. Graphical methods to display the antibody response and to choose thresholds for a rise in relative antibody reactivity are shown and discussed. In conclusion, 5.4% of people with tick bites showed a rise in Borrelia-specific antibodies above the 2.5% threshold in either ELISA but only 40 (2.1%) developed clinical Lyme borreliosis.
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  • Djärv, Emma, et al. (author)
  • Dummy run for a phase II study of stereotactic body radiotherapy of T1-T2 N0M0 medical inoperable non-small cell lung cancer.
  • 2006
  • In: Acta oncologica (Stockholm, Sweden). - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 45:7, s. 973-7
  • Journal article (peer-reviewed)abstract
    • In forthcoming multicentre studies on stereotactic body radiotherapy (SBRT) compliance with volume and dose prescriptions will be mandatory to avoid unnecessary heterogeneity bias. To evaluate compliance in a multicentre setting we used two cases from an ongoing phase II study of SBRT of T1-T2N0M0 inoperable NSCLC in a dummy run oriented on volumes and doses. Six Scandinavian centres participated. Each centre received CT-scans covering the whole lung volumes of two patients with instructions to follow the study protocol when outlining tumour and target volumes, prescribing doses and creating dose plans. Volumes and doses of the 12 dose plans were evaluated according to the study protocol. For the two patients the GTV volume range was 24 to 39 cm3 and 26 to 41 cm3, respectively. The PTV volume range was 90 to 116 cm3, and 112 to 155 cm3, respectively. For all plans the margin between CTV and PTV in all directions followed in detail the protocol. The prescribed dose was for all centres 45 Gy/3 fractions (isocentre dose about 66 Gy). The mean GTV doses ranged from 63 to 67 Gy and from 63 to 68 Gy, respectively. The minimum doses for GTV were between 50-64 Gy and between 55-65 Gy, respectively. The dose distribution was conformed to PTV for 10 of 12 plans and 2 of 12 plans from one centre had sub-optimal dose distribution. Most of the volume and dose parameters for the participating centres showed fully acceptable compliance with the study protocol.
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  • Fryland, Linda, et al. (author)
  • Biomarkers in blood a few days after a bite by a Borrelia burgdorferi infected tick: : Asymptomatic Borrelia burgdorferi-infected subjects show higher Th1-associated response compared with subjects who later develop Lyme borreliosis
  • 2012
  • Other publication (other academic/artistic)abstract
    • The clinical outcome following infection with Borrelia (B.) burgdorferi sensu lato (s.l.) differs between individuals, ranging from asymptomatic infection to Lyme borreliosis (LB) with persistent symptoms post-treatment. Previous studies in mice and humans have generated the hypothesis that a successful outcome of B. burgdorferi s.l. infection is associated with an early strong pro-inflammatory T helper (Th)1-like immune response. The aim of this study was to assess the early course of events in B. burgdorferi s.l.-associated inflammation by screening for possible early immune biomarkers in peripheral blood from newly tick-bitten persons. The study subjects bitten by B. burgdorferi s.l.-infected ticks were divided into (1) those later developing clinical LB, (2) those who developed anti-B. burgdorferi s.l. antibodies but not clinical LB, (3) those who neither developed antibodies nor clinical LB. A fourth group consisted of bitten study subjects without development of antibodies or clinical LB. Two sets of samples, both comprising all four groups, were collected in order to repeat the analyses and confirm the data. Sera or plasma collected a few days after the tick bite were analysed for 18 biomarkers (IL-1β, IL-6, CXCL8/IL-8, IL-12p70, IL-17A, IL-27, TNF, CCL18, CCL20, CCL22, CXCL1, CXCL9, CXCL10, CXCL11, calprotectin, MMP-3, MMP-8, MMP-9) by multiplex bead assay and ELISA. In the first set of samples, the neutrophil activation marker calprotectin was increased in subjects who developed clinical LB compared with subjects who developed antibodies against B. burgdorferi s.l. but did not develop LB. However, the finding could not be confirmed in the second set of samples, thus the study failed to identify an early prognostic marker for development of clinical LB. Interestingly, both sets of samples showed increases in two different Th1-associated markers, CXCL10 and IL-12p70, respectively, in subjects who following a bite by a B. burgdorferi s.l.-infected tick developed antibodies against B. burgdorferi s.l. but did not develop LB compared with subjects who developed clinical LB, thus supporting the hypothesis of an early strong Th1-response being important for optimal resolution of B. burgdorferi s.l. infection.
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10.
  • Fryland, Linda, et al. (author)
  • Low risk of developing Borrelia burgdorferi infection in the south-east of Sweden after being bitten by a Borrelia burgdorferi-infected tick
  • 2011
  • In: INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES. - : Elsevier Science B. V., Amsterdam. - 1201-9712. ; 15:3, s. E174-E181
  • Journal article (peer-reviewed)abstract
    • Objectives: The risk of developing Lyme borreliosis (LB) from Borrelia burgdorferi sensu lato (Bb)-infected ticks in Sweden is largely unknown. In the current study, we investigated the prevalence of Bb in ticks that had bitten humans and the risk of developing LB from Bb-infected ticks. Methods: Health questionnaires, blood samples, and ticks were collected from 394 tick-bitten study subjects in the County of Ostergotland, Sweden, at the time of the tick bite. Questionnaires and blood samples were also collected 3 months later. Ticks were screened for Bb DNA with PCR, while sera were analyzed for antibodies against Bb using two ELISA assays. Seroconversion, i.e., an at least two-fold increase in anti-Bb antibodies after 3 months, was confirmed using a Strip-Immunoassay. Results: Seventy-five of 397 ticks collected from the study subjects were determined to be Bb-positive. Sixty-four of the tick-bitten subjects had been bitten by Bb-infected ticks. Four of them showed seroconversion and were therefore considered to have an active Bb infection. None of these four subjects had sought health care due to symptoms, but one reported symptoms. Conclusions: Our data suggest that the risk of developing LB after being bitten by a Bb-infected tick is low, and asymptomatic Bb infections appear to be more frequent than symptomatic infections.
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  • Grubb, Tamara, et al. (author)
  • Effects of pulse-delivered inhaled nitric oxide administration on pulmonary perfusion and arterial oxygenation in dorsally recumbent isoflurane-anesthetized horses
  • 2014
  • In: American Journal of Veterinary Research. - : American Veterinary Medical Association (AVMA). - 0002-9645. ; 75, s. 949-955
  • Journal article (peer-reviewed)abstract
    • Objective-To image the spatial distribution of pulmonary blood flow by means of scintigraphy, evaluate ventilation-perfusion (V-A/Q) matching and pulmonary blood shunting (Qs/Qt) by means of the multiple inert gas elimination technique (MIGET), and measure arterial oxygenation and plasma endothelin-1 concentrations before, during, and after pulse-delivered inhaled nitric oxide (PiNO) administration to isoflurane-anesthetized horses in dorsal recumbency.Animals-3 healthy adult Standardbreds.Procedures-Nitric oxide was pulsed into the inspired gases in dorsally recumbent isoflurane-anesthetized horses. Assessment of V-A/Q matching, Qs/Qt, and PaO2 content was performed by use of the MIGET, and spatial distribution of pulmonary blood flow was measured by perfusion scintigraphy following IV injection of technetium Tc 99m-labeled macroaggregated human albumin before, during, and 30 minutes after cessation of PiNO administration.Results-During PiNO administration, significant redistribution of blood flow from the dependent regions to the nondependent regions of the lungs was found and was reflected by improvements in V-A/Q matching, decreases in Qs/Qt, and increases in PaO2 content, all of which reverted to baseline values at 30 minutes after PiNO administration.Conclusions and Clinical Relevance-Administration of PiNO in anesthetized dorsally recumbent horses resulted in redistribution of pulmonary blood flow from dependent atelectatic lung regions to nondependent aerated lung regions. Because hypoxemia is commonly the result of atelectasis in anesthetized dorsally recumbent horses, the addition of nitric oxide to inhaled gases could be used clinically to alleviate hypoxemia in horses during anesthesia.
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  • Grubb, Tamara, et al. (author)
  • The effects of pulse-delivered inhaled nitric oxide on arterial oxygenation, ventilation-perfusion distribution and plasma endothelin-1 concentration in laterally recumbent isoflurane-anaesthetized horses
  • 2013
  • In: Veterinary Anaesthesia and Analgesia. - : Elsevier BV. - 1467-2987 .- 1467-2995. ; 40:6, s. E19-E30
  • Journal article (peer-reviewed)abstract
    • Objectives Anaesthetized horses commonly become hypoxaemic due to ventilation/perfusion ((V) over dot(A)/(Q) over dot) mismatch and increased pulmonary shunt fraction ((Q) over dots/(Q) over dott). Pulse-delivered inhaled nitric oxide may improve oxygenation but may increase plasma concentration of the potent vasoconstrictor, endothelin-1 (ET-1). Objectives: Study 1) compare arterial oxygen concentration (PaO2) and saturation (SaO(2)), calculated ((Q) over dots/(Q) over dott) and ET-1 concentration; and Study 2) assess ((V) over dot(A)/(Q) over dot) matching and measured ((Q) over dots/(Q) over dott) in isoflurane-anaesthetized horses in left lateral recumbency receiving pulse-delivered inhaled nitric oxide (PiNO group) or inhalant gas only (C group). Study design Prospective research trial. Animals Ten Healthy adult Standardbred horses. Two horses were anaesthestized in both groups in a random cross-over design with >4 weeks between studies. Methods Study 1) Cardiopulmonary data including PaO2, SaO(2), ((Q) over dots/(Q) over dott) and ET-1 concentration were measured or calculated prior to and at various points during PiNO administration in 6PiNO and 6C horses. Two-way repeated measures ANOVA with Bonferroni significant difference test was used for data analysis with p < 0.05 considered significant. Study 2) ((V) over dot(A)/(Q) over dot) matching and ((Q) over dots/(Q) over dott) were determined using the multiple inert gas elimination technique in 3 horses. Data were collected after 60 minutes of anaesthesia without PiNO (baseline) and 15 minutes after PiNO was pulsed during the first 30%, and then the first 60%, of inspiration. Data were descriptive only. Results Study 1) PaO2 and SaO2 were higher and calculated ((Q) over dots/(Q) over dott) was lower in the PiNO group than the C group at most time points. ET-1 was not different over time or between groups. Study 2) ((V) over dot(A)/(Q) over dot) matching and measured ((Q) over dots/(Q) over dott) were improved from baseline in all horses but PiNO60% provided no improvement when compared to PiNO30%. Conclusions and Clinical Relevance PiNO delivered in the initial portion of the inspiration effectively relieves hypoxaemia in anaesthetized horses by improving ((V) over dot(A)/(Q) over dot) matching and decreasing ((Q) over dots/(Q) over dott) without affecting ET-1.
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  • Hemberg, Jessica, et al. (author)
  • Loneliness as experienced by adolescents and young adults : an explorative qualitative study
  • 2022
  • In: International Journal of Adolescence and Youth. - : Routledge. - 0267-3843 .- 2164-4527. ; 27:1, s. 362-384
  • Journal article (peer-reviewed)abstract
    • Mental health problems among adolescents and young adults are increasing worldwide together with loneliness, which is considered a global public health problem. The aim of this study was to explore loneliness through adolescents´ and young adults´ own descriptions and experiences. The research questions were: (1) How do adolescents and young adults describe and experience loneliness?, (2) What types of loneliness do adolescents and young adults describe? Data were collected through interviews with fifteen Swedish-speaking Finns aged 17-30. Content analysis was used for data analysis. Loneliness was linked to earlier negative experiences, mental illness or physical disorders, self-centred society, social norms and social media. Three different types of loneliness were identified: social loneliness, emotional loneliness and existential loneliness. It is important that adults and professionals are able to identify, interpret and understand signs that adolescents and young adults are experiencing negative feelings, which may indicate underlying loneliness.
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  • Hemberg, Jessica, et al. (author)
  • Loneliness - two sides to the story : adolescents´ lived experiences
  • 2021
  • In: International Journal of Adolescence and Youth. - : Routledge. - 0267-3843 .- 2164-4527. ; 26:1, s. 41-56
  • Journal article (peer-reviewed)abstract
    • Loneliness in adolescents is related to common mental health issues, and as a major global concern it is important to investigate loneliness from their own perspectives. The aim of this study was to explore how adolescents experience and describe negative and positive sides of loneliness. Data was collected through interviews with fifteen young Swedish-speaking Finns. Two main themes and seven subthemes were found. Negative experiences of involuntary loneliness were stressful and paralyzing giving rise to physical symptoms, emptiness, anxiety, fear and invisibility. Other negative experiences resulting from involuntary loneliness were shame, self-blame and self-contempt, as well as meaninglessness, hopelessness and exclusion. Positive experiences from self-chosen solitude were freedom, calmness and recovery, creativity and meaningfulness as well as reflection, recharging and personal growth. 
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  • Henningsson, Anna J., et al. (author)
  • Complement activation in Lyme neuroborreliosis : increased levels of C1q and C3a in cerebrospinal fluid indicate complement activation in the CNS
  • 2007
  • In: Journal of Neuroimmunology. - : Elsevier BV. - 0165-5728 .- 1872-8421. ; 183:1-2, s. 200-207
  • Journal article (peer-reviewed)abstract
    • A strong initial inflammatory response is important in neuroborreliosis. Since complement is a main player in early inflammation, we monitored the concentration and activation of complement in plasma and cerebrospinal fluid from 298 patients, of whom 23 were diagnosed with neuroborreliosis. Using sandwich ELISAs, we found significantly elevated levels of C1q, C4, C3, and C3a in cerebrospinal fluid, but not in plasma, in patients with neuroborreliosis. This finding indicates that complement plays a role in the human immune response in neuroborreliosis, that the immunologic process is compartmentalized to the CNS, and that complement activation may occur via the classical pathway.
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  • Henningsson, Anna, et al. (author)
  • Low risk of seroconversion or clinical disease in humans after a bite by an Anaplasma phagocytophilum-infected tick
  • 2015
  • In: Ticks and Tick-borne Diseases. - : Elsevier. - 1877-959X .- 1877-9603. ; 6:6, s. 787-792
  • Journal article (peer-reviewed)abstract
    • The risk of contracting human granulocytic anaplasmosis (HGA) after a tick bite is mainly unknown. In this study we investigated the clinical and serological response in 30 humans bitten by ticks positive for Anaplasma phagocytophilum (Group A), 30 humans bitten by Borrelia burgdorferi sensu lato (s.l.)-positive ticks (Group B), and 30 humans bitten by ticks negative for both A. phagocytophilum and B. burgdorferi s.l. (Group C). Ticks, blood samples and questionnaires were collected from tick-bitten humans at 34 primary healthcare centres in Sweden and in the Åland Islands, Finland, at the time of the tick bite and after three months. A total of 2553 ticks detached from humans in 2007-2009 were analyzed by polymerase chain reaction, and 31 (1.2%) were positive for A. phagocytophilum, 556 (21.8%) were positive for B. burgdorferi s.l., and eight (0.3%) were co-infected by A. phagocytophilum and B. burgdorferi s.l. The overall prevalence of Anaplasma IgG antibodies in the included participants (n=90) was 17%, and there was no significant difference between the groups A-C. Only one of the participants (in Group C) showed a four-fold increase of IgG antibodies against A. phagocytophilum at the three-month follow-up, but reported no symptoms. The frequency of reported symptoms did not differ between groups A-C, and was unrelated to the findings of A. phagocytophilum and B. burgdorferi s.l. in the detached ticks. We conclude that the risk for HGA or asymptomatic seroconversion after a tick bite in Sweden or in the Åland Islands is low, even if the tick is infected by A. phagocytophilum.
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  • Jonsson Henningsson, Anna, et al. (author)
  • Laboratory Methods for Detection of Infectious Agents and Serological Response in Humans With Tick-Borne Infections : A Systematic Review of Evaluations Based on Clinical Patient Samples
  • 2021
  • In: Frontiers In Public Health. - : Frontiers Media S.A.. - 2296-2565. ; 9
  • Research review (peer-reviewed)abstract
    • Background: For the most important and well-known infections spread by Ixodes ticks, Lyme borreliosis (LB) and tick-borne encephalitis (TBE), there are recommendations for diagnosis and management available from several health authorities and professional medical networks. However, other tick-borne microorganisms with potential to cause human disease are less known and clear recommendations on diagnosis and management are scarce. Therefore, we performed a systematic review of published studies and reviews focusing on evaluation of laboratory methods for clinical diagnosis of human tick-borne diseases (TBDs), other than acute LB and TBE. The specific aim was to evaluate the scientific support for laboratory diagnosis of human granulocytic anaplasmosis, rickettsiosis, neoehrlichiosis, babesiosis, hard tick relapsing fever, tularemia and bartonellosis, as well as tick-borne co-infections and persistent LB in spite of recommended standard antibiotic treatment.Methods: We performed a systematic literature search in 11 databases for research published from 2007 through 2017, and categorized potentially relevant references according to the predefined infections and study design. An expert group assessed the relevance and eligibility and reviewed the articles according to the QUADAS (diagnostic studies) or AMSTAR (systematic reviews) protocols, respectively. Clinical evaluations of one or several diagnostic tests and systematic reviews were included. Case reports, non-human studies and articles published in other languages than English were excluded.Results: A total of 48 studies fulfilled the inclusion criteria for evaluation. The majority of these studies were based on small sample sizes. There were no eligible studies for evaluation of tick-borne co-infections or for persistent LB after antibiotic treatment.Conclusions: Our findings highlight the need for larger evaluations of laboratory tests using clinical samples from well-defined cases taken at different time-points during the course of the diseases. Since the diseases occur at a relatively low frequency, single-center cross-sectional studies are practically not feasible, but multi-center case control studies could be a way forward.
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  • Karlsson, Kristin, et al. (author)
  • Retrospective Cohort Study of Bronchial Doses and Radiation-Induced Atelectasis After Stereotactic Body Radiation Therapy of Lung Tumors Located Close to the Bronchial Tree
  • 2013
  • In: International Journal of Radiation Oncology, Biology, Physics. - : Elsevier BV. - 0360-3016 .- 1879-355X. ; 87:3, s. 590-595
  • Journal article (peer-reviewed)abstract
    • Purpose: To evaluate the dose-response relationship between radiation-induced atelectasis after stereotactic body radiation therapy (SBRT) and bronchial dose. Methods and Materials: Seventy-four patients treated with SBRT for tumors close to main, lobar, or segmental bronchi were selected. The association between incidence of atelectasis and bronchial dose parameters (maximum point-dose and minimum dose to the high-dose bronchial volume [ranging from 0.1 cm(3) up to 2.0 cm(3)]) was statistically evaluated with survival analysis models. Results: Prescribed doses varied between 4 and 20 Gy per fraction in 2-5 fractions. Eighteen patients (24.3%) developed atelectasis considered to be radiation-induced. Statistical analysis showed a significant correlation between the incidence of radiation-induced atelectasis and minimum dose to the high-dose bronchial volumes, of which 0.1 cm(3) (D-0.1cm3) was used for further analysis. The median value of D-0.1cm3 (alpha/beta = 3 Gy) was EQD(2,LQ) = 147 Gy(3) (range, 20-293 Gy(3)). For patients who developed atelectasis the median value was EQD(2,LQ) = 210 Gy(3), and for patients who did not develop atelectasis, EQD(2,LQ) = 105 Gy(3). Median time from treatment to development of atelectasis was 8.0 months (range, 1.1-30.1 months). Conclusion: In this retrospective study a significant dose-response relationship between the incidence of atelectasis and the dose to the high-dose volume of the bronchi is shown.
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24.
  • Kurkiala, Jacob, et al. (author)
  • Youth, Citizenship and Democracy : Findings from a youth survey in two Nordic regions
  • 2015
  • In: Differences, Inequalities and Sociological Imagination. - : European Sociological Association (ESA). - 9788073302726 ; , s. 1283-1284
  • Conference paper (peer-reviewed)abstract
    • There are significant differences between young people regarding political interest and engagement because of different social and economic conditions. Further, an active citizenship may be impeded by a societal development where life conditions deteriorate more for some groups than for others. At the same time, the reluctance among economically marginalized groups to participate in the procedures of democracy remains when the meaning of an active democratic citizenship is perceived as limited. Research shows that there is a need for further research in the field, in particular more qualitative studies to complement the various national and international longitudinal quantitative studies such as IEA: Cived and ICCS.Every third year in the Nordic countries, a comprehensive longitudinal youth survey is conducted which follows up national youth policy. The target groups for the study are young people aged 13-16. The survey focuses on young people’s views on questions concerning democracy and participation, citizenship, health, enjoyment of school, leisure activities, work, and future plans.This study focuses on young people’s democratic and civic competence in two Nordic regions: Gävleborg (Sweden) and Ostrobothnia (Finland). Based on the longitudinal youth surveys studying young people’s skills, capacities, and opportunities for active democratic citizenship, in order to further assure the quality of education and youth policy work in the surveyed regions, the research study’s overall objectives are to:a) Compare youth survey results from two regions in Sweden and Finland as well as make comparisons over time, focusing on the importance of social sustainability, particularly gender, age, and diversity aspects; and b) Deepen understanding of young people’s opportunities, circumstances, and knowledge of active democratic citizenship. The samples are 2,207 students (14-15 years old) from Sweden and 1,718 students (15-16 years old) from Finland.One example from the initial analysis is: if the students want to have a say in what they learn in school. They answered 70% (SWE) and 46% (FIN) want it, but only 37% (SWE) and 7% (FIN) answered that they get it. The result is interesting in terms of PISA results, but also for how the pupils enjoy school.
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25.
  • Lindblom, Pontus, et al. (author)
  • Determining factors for successful vaccination against tick-borne encephalitis virus in older individuals
  • 2014
  • Other publication (other academic/artistic)abstract
    • We performed a cross-sectional study including 533 persons (median age 61) from the highly TBE endemic Åland Islands in the archipelago between Sweden and Finland. Blood samples, questionnaires and vaccination records were obtained from all study participants. The aim was to investigate if there was any association between TBEV antibody titer and 14 healthrelated factors: [age, gender, number of vaccine doses (0-5), time since last vaccine dose, previous TBE disease, vaccination against other flaviviruses, ≥2 tick-bites during the previous 3 months, pet-ownership, asthma, smoking, allergy, diabetes, medication, and previous tumor]. Measurement of TBEV IgG antibodies was performed using two commercial ELISA assays (Enzygnost and Immunozym), and a third in-house rapid fluorescent focus inhibition test was used to measure TBEV neutralizing antibodies. The age of the person and the number of vaccine doses were the two most important factors determining successful vaccination. The response to each vaccine dose declined linearly with increased age. A 35 year age difference corresponds to a vaccine dose increment from 3 to 4 to achieve the same response. Participants receiving medication and participants previously vaccinated against other flaviviruses had lower TBEV antibody titers on average, while those with self-reported asthma had higher titers. By comparing the 3 serological assays we show that the Enzygnost and Immunozym assay differ due to choice of cutoffs, but not in overall accuracy.
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26.
  • Lindblom, Pontus, et al. (author)
  • Factors Determining Immunological Response to Vaccination against Tick-Borne Encephalitis Virus in Older Individuals
  • 2014
  • In: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 9:6, s. e0100860-
  • Journal article (peer-reviewed)abstract
    • We performed a cross-sectional study including 533 individuals (median age 61) from the highly TBE endemic A land Islands in the archipelago between Sweden and Finland. Blood samples, questionnaires and vaccination records were obtained from all study participants. The aim was to investigate if there was any association between TBEV antibody titer and 12 health-related factors. Measurement of TBEV IgG antibodies was performed using two commercial ELISA assays (Enzygnost and Immunozym), and a third in-house rapid fluorescent focus inhibition test was used to measure TBEV neutralizing antibodies. The age of the individual and the number of vaccine doses were the two most important factors determining the immunological response to vaccination. The response to each vaccine dose declined linearly with increased age. A 35 year age difference corresponds to a vaccine dose increment from 3 to 4 to achieve the same immunological response. Participants previously vaccinated against other flaviviruses had lower odds of being seropositive for neutralizing TBEV antibodies on average, while participants with self-reported asthma had higher odds of being seropositive. By comparing the 3 serological assays we show that the Enzygnost and Immunozym assay differ due to choice of cutoffs, but not in overall accuracy.
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27.
  • Lindblom, Pontus, et al. (author)
  • Tick-borne encephalitis virus in ticks detached from humans and follow-up of serological and clinical response.
  • 2014
  • In: Ticks and Tick Borne Diseases. - Jena, Germany : Elsevier. - 1877-959X. ; 5:1, s. 21-28
  • Journal article (peer-reviewed)abstract
    • The risk of tick-borne encephalitis virus (TBEV) infection after a tick bite remains largely unknown. To address this, we investigated the presence of TBEV in ticks detached from humans in an attempt to relate viral copy number, TBEV subtype, and tick feeding time with the serological and clinical response of the tick-bitten participants. Ticks, blood samples, and questionnaires were collected from tick-bitten humans at 34 primary health care centers in Sweden and in the Aland Islands (Finland). A total of 2167 ticks was received from 1886 persons in 2008-2009. Using a multiplex quantitative real-time PCR, 5 TBEV-infected ticks were found (overall prevalence 0.23%, copy range <4 X 10(2)-7.7 X 10(6) per tick). One unvaccinated person bitten by a tick containing 7.7 x 10(6) TBEV copies experienced symptoms. Another unvaccinated person bitten by a tick containing 1.8 x 10(3) TBEV copies developed neither symptoms nor TBEV antibodies. The remaining 3 persons were protected by vaccination. In contrast, despite lack of TBEV in the detached ticks, 2 persons developed antibodies against TBEV, one of whom reported symptoms. Overall, a low risk of TBEV infection was observed, and too few persons got bitten by TBEV-infected ticks to draw certain conclusions regarding the clinical outcome in relation to the duration of the blood meal and virus copy number. However, this study indicates that an antibody response may develop without clinical symptoms, that a bite by an infected tick not always leads to an antibody response or clinical symptoms, and a possible correlation between virus load and tick feeding time. (C) 2013 Elsevier GmbH. All rights reserved.
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28.
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29.
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30.
  • Nordberg, Marika, et al. (author)
  • Can ELISPOT Be Applied to A Clinical Setting as A Diagnostic Utility for Neuroborreliosis?
  • 2012
  • In: Cells. - Basel, Switzerland : MDPI AG. - 2073-4409. ; 13:48, s. 153-167
  • Journal article (peer-reviewed)abstract
    • The aim of this prospective study was to investigate the diagnostic performance of Borrelia (Bb)-induced interferon (IFN)-γ secretion detected by ELISPOT modified to be feasible for clinical laboratories as a supplementary test to the laboratory diagnosis of Lyme neuroborreliosis (LNB) in an endemic setting. Between 2002 and 2004, patients with symptoms of suspected clinical LNB were included in a study conducted on the Åland islands in the Finnish archipelago, which is a hyper-endemic area for Lyme borreliosis (LB). Fourteen patients with confirmed LNB and 103 patients with non-LNB were included, and the numbers of spontaneous and Bb-induced IFN-γ-secreting cells were assayed by the ELISPOT test. The ELISPOT assay showed a weak diagnostic performance with a sensitivity of 36% and a specificity of 82%. The findings in this study show that this ELISPOT-assay modified to be feasible in clinical routine laboratories is not useful as a supplementary diagnostic tool in the laboratory diagnosis of patients with clinically suspected LNB.
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31.
  • Nordberg, Marika, et al. (author)
  • Cytotoxic mechanisms may play a role in the local immune response in the central nervous system in neuroborreliosis
  • 2011
  • In: Journal of Neuroimmunology. - : Elsevier Science B.V., Amsterdam.. - 0165-5728 .- 1872-8421. ; 232:1-2, s. 186-193
  • Journal article (peer-reviewed)abstract
    • Aiming to investigate the role of cytotoxic mechanisms in neuroborreliosis (NB), the cytokines IL-2, IL-7, IL-10, IL-12p70, IL-15, GM-CSF and the Th17-cytokine IL-17 were analyzed in cerebrospinal fluid (CSF) and plasma from NB-patients. NB-patients showed increased levels in CSF compared to controls of all analyzed cytokines except IL-15 but not in plasma. Blood lymphocytes from three NB-patients showed functional cytotoxicity in response to autologous Borrelia-infected macrophages. The findings support a role for cytotoxic mechanisms in the local immune response in NB and in addition suggest an increase of IL-17.
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32.
  • Nyman, Görel, et al. (author)
  • Effect of sedation with detomidine and butorphanol on pulmonary gas exchange in the horse
  • 2009
  • In: Acta Veterinaria Scandinavica. - : Springer Science and Business Media LLC. - 0044-605X .- 1751-0147. ; 51:1, s. 22-
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Sedation with alpha2-agonists in the horse is reported to be accompanied by impairment of arterial oxygenation. The present study was undertaken to investigate pulmonary gas exchange using the Multiple Inert Gas Elimination Technique (MIGET), during sedation with the alpha2-agonist detomidine alone and in combination with the opioid butorphanol. METHODS: Seven Standardbred trotter horses aged 3-7 years and weighing 380-520 kg, were studied. The protocol consisted of three consecutive measurements; in the unsedated horse, after intravenous administration of detomidine (0.02 mg/kg) and after subsequent butorphanol administration (0.025 mg/kg). Pulmonary function and haemodynamic effects were investigated. The distribution of ventilation-perfusion ratios (VA/Q) was estimated with MIGET. RESULTS: During detomidine sedation, arterial oxygen tension (PaO2) decreased (12.8 +/- 0.7 to 10.8 +/- 1.2 kPa) and arterial carbon dioxide tension (PaCO2) increased (5.9 +/- 0.3 to 6.1 +/- 0.2 kPa) compared to measurements in the unsedated horse. Mismatch between ventilation and perfusion in the lungs was evident, but no increase in intrapulmonary shunt could be detected. Respiratory rate and minute ventilation did not change. Heart rate and cardiac output decreased, while pulmonary and systemic blood pressure and vascular resistance increased. Addition of butorphanol resulted in a significant decrease in ventilation and increase in PaCO2. Alveolar-arterial oxygen content difference P(A-a)O2 remained impaired after butorphanol administration, the VA/Q distribution improved as the decreased ventilation and persistent low blood flow was well matched. Also after subsequent butorphanol no increase in intrapulmonary shunt was evident. CONCLUSION: The results of the present study suggest that both pulmonary and cardiovascular factors contribute to the impaired pulmonary gas exchange during detomidine and butorphanol sedation in the horse.
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33.
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34.
  • Nyman, Pia, et al. (author)
  • Youth and sustainable co-creative citizenship
  • 2016
  • Conference paper (peer-reviewed)abstract
    • This research focuses on youths’ terms, possibilities and knowledge for active democratic citizenship. In Lindberg & Persson’s (2013) report on Youths’ relationship to democracy a need for further research in the eld emerges. The report calls for more qualitative studies as a complement to various national and international longitudinal, quantitative studies. The aim of the present study is to fill this gap in the field through qualitative interview data collected during spring 2014. The respondents are from the region of Gävleborg in Sweden and from Östrobothnia in Finland. One of the purposes of this study is also to discern similarities and differences in the youths’ views on active democratic citizenship in the two Nordic neighbouring countries Sweden and Finland. The research group presents the first preliminary results at the conference in Lund. 
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35.
  • Sandholm, Kerstin, et al. (author)
  • Early Immune Responses to Borrelia garinii and Borrelia afzeliiin Lyme Borreliosis : Local Complement Activation in Erythema Migrans and in vitro Studies ofComplement Activation, Phagocytosis and Cytokine Profile
  • Other publication (other academic/artistic)abstract
    • An optimal eradication of spirochetes in Lyme borreliosis depends on the early immune response, including the potent actions of the complement system. We here assessed possible differences between two Borrelia burgdorferi genospecies in their ability to activate complement, and the consequences of complement activation in terms of phagocytosis and induction of cytokines.Early local complement activation was assessed immunohistochemically in skin biopsies from patients with erythema migrans (EM) caused by B. afzelii or B. garinii. Complement activation, phagocytosis and early cytokine and chemokine release were studied in vitro by incubating clinical isolates of B. afzelii (K78 from a human skin biopsy) and B. garinii (LU59 from human cerebrospinal fluid) in human whole blood.B. afzelii and B. garinii were detected in skin biopsies from EM and deposition of C3-fragments and IgG was found adjacent to the spirochetes. In vitro, B. garinii LU59 induced higher complement activation (measured as the generation of C3a and C5b-9), while B. afzelii K78 recruited more factor H. Phagocytosis by granulocytes and monocytes was demonstrated to be largely dependent on complement activation since phagocytosis was substantially reduced by addition of the C3 inhibitor compstatin or a C5a receptor antagonist. The early cytokine and chemokine release in human blood in response to live spirochetes revealed a rapid and pronounced pro-inflammatory response, mainly associated with the Th1- and Th17-types.We conclude that complement is activated locally in the skin in EM, and that B. garinii LU59 activates complement more than B. afzelii K78. Complement activation is pivotal for efficient phagocytosis of Borrelia spirochetes, especially in early infection before specific antibodies are produced. Both B. garinii LU59 and B. afzelii K78 induce proinflammatory cytokines rapidly, but no clear differences were seen between the two genospecies in this respect.
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36.
  • Sjöwall, Johanna, et al. (author)
  • Decreased Th1-Type Inflammatory Cytokine Expression in the Skin Is Associated with Persisting Symptoms after Treatment of Erythema Migrans
  • 2011
  • In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:3, s. 0018220-
  • Journal article (peer-reviewed)abstract
    • Background: Despite the good prognosis of erythema migrans (EM), some patients have persisting symptoms of various character and duration post-treatment. Several factors may affect the clinical outcome of EM, e. g. the early interaction between Borrelia (B.) burgdorferi and the host immune response, the B. burgdorferi genotype, antibiotic treatment as well as other clinical circumstances. Our study was designed to determine whether early cytokine expression in the skin and in peripheral blood in patients with EM is associated with the clinical outcome. Methods: A prospective follow-up study of 109 patients with EM was conducted at the A land Islands, Finland. Symptoms were evaluated at 3, 6, 12 and 24 months post-treatment. Skin biopsies from the EM and healthy skin were immunohistochemically analysed for expression of interleukin (IL)-4, IL-10, IL-12p70 and interferon (IFN)-gamma, as well as for B. burgdorferi DNA. Blood samples were analysed for B. burgdorferi antibodies, allergic predisposition and levels of systemic cytokines. Findings: None of the patients developed late manifestations of Lyme borreliosis. However, at the 6-month follow-up, 7 of 88 patients reported persisting symptoms of diverse character. Compared to asymptomatic patients, these 7 patients showed decreased expression of the Th1-associated cytokine IFN-gamma in the EM biopsies (p = 0.003). B. afzelii DNA was found in 48%, B. garinii in 15% and B. burgdorferi sensu stricto in 1% of the EM biopsies, and species distribution was the same in patients with and without post-treatment symptoms. The two groups did not differ regarding baseline patient characteristics, B. burgdorferi antibodies, allergic predisposition or systemic cytokine levels. Conclusion: Patients with persisting symptoms following an EM show a decreased Th1-type inflammatory response in infected skin early during the infection, which might reflect a dysregulation of the early immune response. This finding supports the importance of an early, local Th1-type response for optimal resolution of LB.
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37.
  • 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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38.
  • 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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39.
  • Wallin, Stina, et al. (author)
  • Occupational self-efficacy and work engagement associated with work ability among an ageing work force : A cross-sectional study
  • 2021
  • In: Work. - : IOS Press. - 1051-9815 .- 1875-9270. ; 70:2, s. 591-602
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Occupational self-efficacy (OSE) is an appropriate adaption capability to react to continuous changes in work life today. While self-efficacy is an important component in work context, there is less knowledge regarding older workers' OSE.OBJECTIVE: This study examined the relationship between work ability, OSE and work engagement among a middle-aged workforce, and whether there were any differences between age groups and between professionals in different work context.METHODS: Data were collected by questionnaire, which included Work Ability Index (WAI), Occupational Self-Efficacy Scale, and Utrecht Work Engagement Scale.RESULTS: A total of 359 home care workers and engineers (response rate 43%) participated. The average age was 54 (SD±5.3) years, 69%were women. The results of logistic regression analyses revealed an association between WAI, OSE (OR 0.66; 95%CI 0.52 to 0.86) and work engagement (OR 0.61; 95%CI 0.47 to 0.78). Higher OSE and work engagement were related to higher work ability. No difference in OSE (5.9; ±0.8) between professional groups was seen, but the home care workers scored considerably higher work engagement (5.1; ±0.9) than the engineers (4.5; ±1.3).CONCLUSIONS: Improving OSE could be worthwhile to support work ability among middle-aged workers, despite dissimilarities in work context and educational level.
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40.
  • Wennberg, Berit M., et al. (author)
  • NTCP modelling of lung toxicity after SBRT comparing the universal survival curve and the linear quadratic model for fractionation correction
  • 2011
  • In: Acta Oncologica. - : Informa Healthcare. - 0284-186X .- 1651-226X. ; 50:4, s. 518-527
  • Journal article (peer-reviewed)abstract
    • Background. In SBRT of lung tumours no established relationship between dose-volume parameters and the incidence of lung toxicity is found. The aim of this study is to compare the LQ model and the universal survival curve (USC) to calculate biologically equivalent doses in SBRT to see if this will improve knowledge on this relationship. Material and methods. Toxicity data on radiation pneumonitis grade 2 or more (RP2+) from 57 patients were used, 10.5% were diagnosed with RP2+. The lung DVHs were corrected for fractionation (LQ and USC) and analysed with the Lyman-Kutcher-Burman (LKB) model. In the LQ-correction alpha/beta = 3 Gy was used and the USC parameters used were: alpha/beta = 3 Gy, D-0 = 1.0 Gy, (n) over bar = 10, alpha = 0.206 Gy(-1) and d(T) = 5.8 Gy. In order to understand the relative contribution of different dose levels to the calculated NTCP the concept of fractional NTCP was used. This might give an insight to the questions of whether "high doses to small volumes" or "low doses to large volumes" are most important for lung toxicity. Results and Discussion. NTCP analysis with the LKB-model using parameters m = 0.4, D-50 = 30 Gy resulted for the volume dependence parameter (n) with LQ correction n = 0.87 and with USC correction n = 0.71. Using parameters m = 0.3, D-50 = 20 Gy n = 0.93 with LQ correction and n = 0.83 with USC correction. In SBRT of lung tumours, NTCP modelling of lung toxicity comparing models (LQ, USC) for fractionation correction, shows that low dose contribute less and high dose more to the NTCP when using the USC-model. Comparing NTCP modelling of SBRT data and data from breast cancer, lung cancer and whole lung irradiation implies that the response of the lung is treatment specific. More data are however needed in order to have a more reliable modelling.
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41.
  • Wilhelmsson, Peter, et al. (author)
  • A prospective study on the incidence of Borrelia burgdorferi sensu lato infection after a tick bite in Sweden and On the Åland Islands, Finland (2008-2009)
  • 2016
  • In: Ticks and Tick-borne Diseases. - : Elsevier. - 1877-959X .- 1877-9603. ; 7:1, s. 71-79
  • Journal article (peer-reviewed)abstract
    • Lyme borreliosis (LB) is a common and increasing tick-borne disease in Europe. The risk of acquiring a Borrelia infection after a tick bite is not fully known. Therefore, we investigated the incidence of Borrelia infection after a bite by a Borrelia-infected tick and if the Borrelia load and/or the duration of tick-feeding influenced the risk of infection. During 2008-2009, ticks and blood samples were collected from 1546 tick-bitten persons from Sweden and the Åland Islands, Finland. Follow-up blood samples were taken 3 months after the tick bite. The duration of tick feeding was microscopically estimated and Borrelia was detected and quantified in ticks by real-time PCR. Anti-Borrelia antibodies were detected in sera using ELISA tests and immunoblot. Five percent (78/1546) of the study participants developed Borrelia infection (LB diagnosis and/or seroconversion) after a tick bite (45% bitten by Borrelia-infected ticks and 55% bitten by uninfected ticks). Of these, 33 developed LB (whereof 9 also seroconverted) while 45 participants seroconverted only. Experience of non-specific symptoms was more frequently reported by Borrelia-infected participants compared to uninfected participants. All who seroconverted removed "their" ticks significantly later than those who did not. The Borrelia load in the ticks did not explain the risk of seroconversion. Regional and sex differences in the Borrelia seroprevalence were found. The risk of developing a Borrelia infection after a bite by a Borrelia-infected tick is small but increases with the duration of tick feeding.
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42.
  • Wilhelmsson, Peter, et al. (author)
  • A prospective study on the incidence of Borrelia infection after a tick bite in Sweden and on the Åland Islands, Finland (2008-2009)
  • 2016
  • In: Ticks and Tick-borne Diseases. - : Elsevier. - 1877-959X .- 1877-9603. ; 7:1, s. 71-79
  • Journal article (peer-reviewed)abstract
    • Lyme borreliosis (LB) is a common and increasing tick-borne disease in Europe. The risk of acquiring a Borrelia infection after a tick bite is not fully known. Therefore, we investigated the incidence of Borrelia infection after a tick bite and if the Borrelia load and/or the duration of tick-feeding influenced the risk of infection. During 2008-2009, ticks and blood samples were collected from 1546 tick-bitten persons from Sweden and the Åland Islands, Finland. Follow-up blood samples were taken three months after the tick bite. The duration of tick feeding was microscopically estimated and Borrelia was detected and quantified in ticks by real-time PCR. Anti-Borrelia antibodies were detected in sera using ELISA assays and immunoblot.Even though 28 % of the participants were bitten by a Borrelia-positive tick, only 7.5% (32/428) of them developed a Borrelia infection, half of them LB. All who seroconverted removed “their” ticks significantly later than those who did not. The Borrelia load in the ticks did not explain the risk of seroconversion. Regional as well as gender differences in the Borrelia seroprevalence were found. The risk of developing a Borrelia infection after a bite by a Borrelia-infected tick is small but increases with the duration of tick feeding.
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43.
  • Wilhelmsson, Peter, et al. (author)
  • Ixodes ricinus ticks removed from humans in Northern Europe : seasonal pattern of infestation, attachment sites and duration of feeding
  • 2013
  • In: Parasites & Vectors. - : Springer Science and Business Media LLC. - 1756-3305. ; 6, s. 362-
  • Journal article (peer-reviewed)abstract
    • BackgroundThe common tick Ixodes ricinus is the main vector in Europe of the tick-borne encephalitis virus and of several species of the Borrelia burgdorferi sensu lato complex, which are the etiological agents of Lyme borreliosis. The risk to contract bites of I. ricinus is dependent on many factors including the behaviour of both ticks and people. The tick’s site of attachment on the human body and the duration of tick attachment may be of clinical importance. Data on I. ricinus ticks, which were found attached to the skin of people, were analysed regarding potentially stage-specific differences in location of attachment sites, duration of tick attachment (= feeding duration), seasonal and geographical distribution of tick infestation in relation to age and gender of the tick-infested hosts.MethodsDuring 2008–2009, 1770 tick-bitten persons from Sweden and the Åland Islands removed 2110 I. ricinus ticks. Participants provided information about the date of tick detection and location on their body of each attached tick. Ticks were identified to species and developmental stage. The feeding duration of each nymph and adult female tick was microscopically estimated based on the scutal and the coxal index.ResultsIn 2008, participants were tick-bitten from mid-May to mid-October and in 2009 from early April to early November. The infestation pattern of the nymphs was bimodal whereas that of the adult female ticks was unimodal with a peak in late summer. Tick attachment site on the human body was associated with stage of the tick and gender of the human host. Site of attachment seemed to influence the duration of tick feeding. Overall, 63% of nymphs and adult female ticks were detected and removed more than 24 hours after attachment. Older persons, compared to younger ones, and men, compared to women, removed “their” ticks after a longer period of tick attachment.ConclusionsThe infestation behaviour of the different tick stages concerning where on the host’s body the ticks generally will attach and when such ticks generally will be detected and removed in relation to host age and gender, should be of value for the development of prophylactic methods against tick infestation and to provide relevant advice to people on how to avoid or reduce the risk of tick infestation.
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44.
  • Yáñez-Mó, María, et al. (author)
  • Biological properties of extracellular vesicles and their physiological functions.
  • 2015
  • In: Journal of extracellular vesicles. - : Wiley. - 2001-3078. ; 4
  • Research review (peer-reviewed)abstract
    • In the past decade, extracellular vesicles (EVs) have been recognized as potent vehicles of intercellular communication, both in prokaryotes and eukaryotes. This is due to their capacity to transfer proteins, lipids and nucleic acids, thereby influencing various physiological and pathological functions of both recipient and parent cells. While intensive investigation has targeted the role of EVs in different pathological processes, for example, in cancer and autoimmune diseases, the EV-mediated maintenance of homeostasis and the regulation of physiological functions have remained less explored. Here, we provide a comprehensive overview of the current understanding of the physiological roles of EVs, which has been written by crowd-sourcing, drawing on the unique EV expertise of academia-based scientists, clinicians and industry based in 27 European countries, the United States and Australia. This review is intended to be of relevance to both researchers already working on EV biology and to newcomers who will encounter this universal cell biological system. Therefore, here we address the molecular contents and functions of EVs in various tissues and body fluids from cell systems to organs. We also review the physiological mechanisms of EVs in bacteria, lower eukaryotes and plants to highlight the functional uniformity of this emerging communication system.
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