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1.
  • Locke, Adam E, et al. (författare)
  • Genetic studies of body mass index yield new insights for obesity biology.
  • 2015
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
  • Tidskriftsartikel (refereegranskat)abstract
    • Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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2.
  • Roswall, Pernilla, et al. (författare)
  • Microenvironmental control of breast cancer subtype elicited through paracrine platelet-derived growth factor-CC signaling
  • 2018
  • Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 24, s. 463-473
  • Tidskriftsartikel (refereegranskat)abstract
    • Breast tumors of the basal-like, hormone receptor-negative subtype remain an unmet clinical challenge, as there is high rate of recurrence and poor survival in patients following treatment. Coevolution of the malignant mammary epithelium and its underlying stroma instigates cancer-associated fibroblasts (CAFs) to support most, if not all, hallmarks of cancer progression. Here we delineate a previously unappreciated role for CAFs as determinants of the molecular subtype of breast cancer. We identified paracrine crosstalk between cancer cells expressing platelet-derived growth factor (PDGF)-CC and CAFs expressing the cognate receptors in human basal-like mammary carcinomas. Genetic or pharmacological intervention of PDGF-CC activity in mouse models of cancer resulted in conversion of basal-like breast cancers into a hormone receptor-positive state that enhanced sensitivity to endocrine therapy in previously resistant tumors. We conclude that specification of breast cancer to the basal-like subtype is under microenvironmental control and is therapeutically actionable.
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3.
  • Anand, Kanwlajeet J. S., et al. (författare)
  • Assessment of continuous pain in newborns admitted to NICUs in 18 European countries
  • 2017
  • Ingår i: Acta Paediatrica. - : John Wiley & Sons. - 0803-5253 .- 1651-2227. ; 106:8, s. 1248-1259
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: Continuous pain occurs routinely, even after invasive procedures, or inflammation and surgery, but clinical practices associated with assessments of continuous pain remain unknown.Methods: A prospective cohort study in 243 Neonatal Intensive Care Units (NICUs) from 18 European countries recorded frequency of pain assessments, use of mechanical ventilation, sedation, analgesia, or neuromuscular blockade for each neonate upto 28 days after NICU admission.Results: Only 2113/6648 (31·8%) of neonates received assessments of continuous pain, occurring variably among tracheal ventilation (TrV, 46·0%), noninvasive ventilation (NiV, 35·0%), and no ventilation (NoV, 20·1%) groups (p<0·001). Daily assessments for continuous pain occurred in only 10·4% of all neonates (TrV: 14·0%, NiV: 10·7%, NoV: 7·6%; p<0·001). More frequent assessments of continuous pain occurred in NICUs with pain guidelines, nursing champions, and surgical admissions prompted (all p<0·01), and for newborns <32 weeks gestational age, those requiring ventilation, or opioids, sedatives-hypnotics, general anesthetics (O-SH-GA) (all p<0·001), or surgery (p=0·028). Use of O-SH-GA drugs increased the odds for pain assessment in the TrV (OR:1·60, p<0·001) and NiV groups (OR:1·40, p<0·001).Conclusion: Assessments of continuous pain occurred in less than one-third of NICU admissions, and daily in only 10% of neonates. NICU clinical practices should consider including routine assessments of continuous pain in newborns.
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4.
  • Andersen, Christina, et al. (författare)
  • Inhalation and dermal uptake of particle and gas phase phthalates - A human chamber exposure study
  • 2018
  • Ingår i: 15th Conference of the International Society of Indoor Air Quality and Climate, INDOOR AIR 2018. - 9781713826514
  • Konferensbidrag (refereegranskat)abstract
    • We have exposed sixteen test subjects to particle and gas phase phthalates in the controlled chamber exposure study. Deuterium labelled phthalates were used to generate particle D4-DEHP (di(2-ethylhexyl) phthalate) and gas phase D4-DEP (diethyl phthalate) for exposures scenarios allowed studying the dermal only and combined inhalational and dermal uptake. Metabolites were measured in urine samples before and after three hours of exposure. The inhalation was the dominant route of uptake for both DEHP and DEP in this study design and exposure settings. Larger uptake of DEP compared to DEHP both via inhalation and dermal uptake was observed. Dermal uptake of DEHP was not observed in this study. Inhalational urinary excretion factors of the metabolites were found to be 0.73 for DEHP and 0.53 for DEP. This study also highlights the importance of taking into consideration the deposited dose of inhaled particles in studies of uptake of particles.
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5.
  • Andersen, Christina, et al. (författare)
  • Inhalation and Dermal Uptake of Particle and Gas-phase Phthalates - A Human Exposure Study
  • 2018
  • Ingår i: Environmental Science & Technology. - : American Chemical Society (ACS). - 1520-5851 .- 0013-936X. ; 52:21, s. 12792-12800
  • Tidskriftsartikel (refereegranskat)abstract
    • Phthalates are ubiquitous in indoor environments, which raises concern about their endocrine disrupting properties. However, studies of human uptake from airborne exposure are limited. We studied the inhalation uptake and dermal uptake by air-to-skin transfer with clean clothing as a barrier of two deuterium-labelled airborne phthalates: particle-phase D4-DEHP (di-(2-ethylhexyl)phthalate) and gas-phase D4-DEP (diethyl phthalate). Sixteen participants, wearing trousers and long-sleeved shirts, were under controlled conditions exposed to airborne phthalates in four exposure scenarios: dermal uptake alone, and combined inhalation+dermal uptake of both phthalates. The results showed an average uptake of D4-DEHP by inhalation of 0.0014±0.00088 (µg kg-1 bw)/(µg m-3)/h. No dermal uptake of D4-DEHP was observed during the 3 hour exposure with clean clothing. The deposited dose of D4-DEHP accounted for 26% of the total inhaled D4-DEHP mass. For D4-DEP, the average uptake by inhalation+dermal was 0.0067±0.0045 and 0.00073±0.00051 (µg kg-1 bw)/(µg m-3)/h for dermal uptake. Urinary excretion factors of metabolites after inhalation were estimated to 0.69 for D4-DEHP and 0.50 for D4-DEP. Under the described settings, the main uptake of both phthalates was through inhalation. The results demonstrate the differences in uptake of gas and particles, and highlights the importance of considering the deposited dose in particle uptake studies.
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6.
  • Bamia, Christina, et al. (författare)
  • Self-rated health and all-cause and cause-specific mortality of older adults : Individual data meta-analysis of prospective cohort studies in the CHANCES Consortium
  • 2017
  • Ingår i: Maturitas. - : Elsevier BV. - 0378-5122 .- 1873-4111. ; 103, s. 37-44
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: To evaluate, among the elderly, the association of self-rated health (SRH) with mortality, and to identify determinants of self-rating health as “at-least-good”.Study design: Individual data on SRH and important covariates were obtained for 424,791 European and United States residents, ≥60 years at recruitment (1982–2008), in eight prospective studies in the Consortium on Health and Ageing: Network of Cohorts in Europe and the United States (CHANCES). In each study, adjusted mortality ratios (hazard ratios, HRs) in relation to SRH were calculated and subsequently combined with random-effect meta-analyses.Main outcome measures: All-cause, cardiovascular and cancer mortality.Results: Within the median 12.5 years of follow-up, 93,014 (22%) deaths occurred. SRH “fair” or “poor” vs. “at-least-good” was associated with increased mortality: HRs 1.46 (95% CI 1·23–1.74) and 2.31 (1.79–2.99), respectively. These associations were evident: for cardiovascular and, to a lesser extent, cancer mortality, and within-study, within-subgroup analyses. Accounting for lifestyle, sociodemographic, somatometric factors and, subsequently, for medical history explained only a modest amount of the unadjusted associations. Factors favourably associated with SRH were: sex (males), age (younger-old), education (high), marital status (married/cohabiting), physical activity (active), body mass index (non-obese), alcohol consumption (low to moderate) and previous morbidity (absence).Conclusion: SRH provides a quick and simple tool for assessing health and identifying groups of elders at risk of early mortality that may be useful also in clinical settings. Modifying determinants of favourably rating health, e.g. by increasing physical activity and/or by eliminating obesity, may be important for older adults to “feel healthy” and “be healthy”.
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7.
  • Chang, Ya-Ting, et al. (författare)
  • Versican accumulates in vascular lesions in pulmonary arterial hypertension
  • 2016
  • Ingår i: PULMONARY CIRCULATION. - : Wiley. - 2045-8932 .- 2045-8940. ; 6:3, s. 347-359
  • Tidskriftsartikel (refereegranskat)abstract
    • Pulmonary arterial hypertension (PAH) is a lethal condition for which there is no effective curative pharmacotherapy. PAH is characterized by vasoconstriction, wall thickening of pulmonary arteries, and increased vascular resistance. Versican is a chondroitin sulfate proteoglycan in the vascular extracellular matrix that accumulates following vascular injury and promotes smooth-muscle cell proliferation in systemic arteries. Here, we investigated whether versican may play a similar role in PAH. Paraffin-embedded lung sections from patients who underwent lung transplantation to treat PAH were used for immunohistochemistry. The etiologies of PAH in the subjects involved in this study were idiopathic PAH, scleroderma, and congenital heart disease (atrial septal defect) with left-to-right shunt. Independent of the underlying etiology, increased versican immunostaining was observed in areas of medial thickening, in neointima, and in plexiform lesions. Western blot of lung tissue lysates confirmed accumulation of versican in patients with PAH. Double staining for versican and CD45 showed only occasional colocalization in neointima of high-grade lesions and plexiform lesions. In vitro, metabolic labeling with [S-35] sulfate showed that human pulmonary artery smooth-muscle cells (hPASMCs) produce mainly chondroitin sulfate glycosaminoglycans. In addition, hypoxia, but not cyclic stretch, was demonstrated to increase both versican messenger RNA expression and protein synthesis by hPASMCs. Versican accumulates in vascular lesions of PAH, and the amount of versican correlates more with lesion severity than with underlying etiology or inflammation. Hypoxia is a possible regulator of versican accumulation, which may promote proliferation of pulmonary smooth-muscle cells and vascular remodeling in PAH.
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8.
  • Chapellier, Marion, et al. (författare)
  • Arrayed molecular barcoding identifies TNFSF13 as a positive regulator of acute myeloid leukemia-initiating cells
  • 2019
  • Ingår i: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 1592-8721 .- 0390-6078. ; 104:10, s. 2006-2016
  • Tidskriftsartikel (refereegranskat)abstract
    • Dysregulation of cytokines in the bone marrow microenvironment promotes acute myeloid leukemia cell growth. Due to the complexity and low throughput of in vivo stem-cell based assays, studying the role of cytokines in the bone marrow niche in a screening setting is challenging. Herein, we developed an ex vivo cytokine screen using 11 arrayed molecular barcodes, allowing for a competitive in vivo readout of leukemia-initiating capacity. With this approach, we assessed the effect of 114 murine cytokines on MLL-AF9 acute myeloid leukemia mouse cells and identified the tumor necrosis factor ligand superfamily member 13 (TNFSF13) as a positive regulator of leukemia-initiating cells. By using Tnfsf13-/- recipient mice, we confirmed that TNFSF13 supports leukemia-initiation also under physiological conditions. TNFSF13 was secreted by normal myeloid cells but not by leukemia mouse cells, suggesting that mature myeloid bone marrow cells support leukemia cells by secreting TNFSF13. TNFSF13 supported leukemia cell proliferation in an NF-κB-dependent manner by binding TNFRSF17 and suppressed apoptosis. Moreover, TNFSF13 supported the growth and survival of several human myeloid leukemia cell lines, demonstrating that our findings translate to human disease. Taken together, using arrayed molecular barcoding, we identified a previously unrecognized role of TNFSF13 as a positive regulator of acute myeloid leukemia-initiating cells. The arrayed barcoded screening methodology is not limited to cytokines and leukemia, but can be extended to other types of ex vivo screens, where a multiplexed in vivo read-out of stem cell functionality is needed.
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9.
  • Drevinge, Christina, 1983, et al. (författare)
  • Perilipin 5 is protective in the ischemic heart
  • 2016
  • Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 219, s. 446-454
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Myocardial ischemia is associated with alterations in cardiac metabolism, resulting in decreased fatty acid oxidation and increased lipid accumulation. Here we investigate how myocardial lipid content and dynamics affect the function of the ischemic heart, and focus on the role of the lipid droplet protein perilipin 5 (Plin5) in the pathophysiology of myocardial ischemia. Methods and results: We generated Plin5(-/-) mice and found that Plin5 deficiency dramatically reduced the triglyceride content in the heart. Under normal conditions, Plin5(-/-) mice maintained a close to normal heart function by decreasing fatty acid uptake and increasing glucose uptake, thus preserving the energy balance. However, during stress or myocardial ischemia, Plin5 deficiency resulted in myocardial reduced substrate availability, severely reduced heart function and increased mortality. Importantly, analysis of a human cohort with suspected coronary artery disease showed that a common noncoding polymorphism, rs884164, decreases the cardiac expression of PLIN5 and is associated with reduced heart function following myocardial ischemia, indicating a role for Plin5 in cardiac dysfunction. Conclusion: Our findings indicate that Plin5 deficiency alters cardiac lipid metabolism and associates with reduced survival following myocardial ischemia, suggesting that Plin5 plays a beneficial role in the heart following ischemia. (C) 2016 The Authors. Published by Elsevier Ireland Ltd.
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10.
  • Eriksson, Axel C., et al. (författare)
  • The role of organic fraction of aerosol particles in uptake of indoor SVOC investigated with real time aerosol mass spectrometry
  • 2018
  • Ingår i: 15th Conference of the International Society of Indoor Air Quality and Climate, INDOOR AIR 2018. - 9781713826514
  • Konferensbidrag (refereegranskat)abstract
    • We investigate the uptake of the Di(2-ethylhexyl) phthalate (DEHP) by laboratory generated and ambient aerosol particles passing through a 1.2 liter chamber covered with vinyl flooring on its internal surfaces. We found approximately five times more efficient DEHP uptake on a mass basis by organic particles (ambient particles) compared to laboratory generated salt particles. The increased uptake is likely due to increased adsorption by pre-existing organic aerosol, which is abundant in the ambient aerosol particles. This implies that compounds with adverse health outcomes are added to particles in indoor air after infiltration into buildings via gas-to-particle conversion of indoor generated SVOCs. We show that aerosol mass spectrometry is a suitable tool for highly time-resolved investigations of this process.
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12.
  • Eriksson, Christina Nilsdotter (författare)
  • The process of occupational therapists implementing client-centred ADL intervention in clinical practice
  • 2016
  • Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The overall aim: The overall aim of the thesis was to identify and describe the characteristics of the implementation process and what hinders and contributes to the implementation of complex interventions when occupational therapists interact with researchers. The long-term goal of the thesis is to contribute to the development of strategies for the implementation of complex interventions in health care. Methods: The two studies in the thesis are based on occupational therapists’ (OTs) experience of implementing a client-centred ADL intervention (CADL) in collaboration with researchers within a randomized control study (RCT). In Study I, 33 OTs participated in focus group interviews two, six and 12 months after completing a workshop before implementing the CADL intervention to persons with stroke. By using a grounded theory approach, it was possible to describe the OTs’ implementation process according to their experiences of being involved in a research project. In Study II, two questionnaires with both closed- and open-ended questions were sent out one year after participating in the workshops and five years after the project was ended. Thirty-one of the 41 OTs responded to the first questionnaire and 19 of 39 responded to the second. This study was a cross-sectional study, and a convergent parallel design of mixed methods was used in order to get a broader understanding of the OTs’ attitudes and experiences of being involved in a research project. Findings: In the analysis of the interviews in Study I, one core category emerged: ‘The implementation of a client-centred intervention enabled the fusion of science and practice’ and three sub-categories followed: 1) Including in the scientific world, 2) Involving as an actor of science, and 3) Integrating in a partnership. The OTs’ attitudes towards engaging in research were changed by support from the researchers, while the OTs acquired more and more experience in using the CADL intervention. The process comprised of being an outsider to the scientific world to being included and then becoming a part of the research as an implementer of science. The findings in Study II explored the OTs’ experience after they ended the participation in the research project. Hindrances like access to clients limited the ability to feel safe in using the CADL in meeting with the client or when the OTs had to update the knowledge given in the workshop. Experience of the team’s limited support was another factor. The majority of the OTs considered support from the researchers during the time that the projected continued to be a factor that facilitated during the implementation of the intervention revealed both one year after participating in the workshop and five years after the project ended. The opportunity to discuss and reflect on the role and experience as implementers to participate in a research project contributed to changes in the meeting with the client. The OTs felt more professional with the support of the CADL. The availability of research-based knowledge, as relayed by the researchers, was a further factor when the CADL intervention became a bridge between practice and science. Conclusions: To create a context built on a collaborative partnership between practitioners and researchers enabled the fusion of practice and science. Support from the organizations and teams, a sufficient interaction with the researchers, a satisfying self-image, and an accessible context were important and sustainable factors.
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13.
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14.
  • Eriksson, Gerd, et al. (författare)
  • The need for palliative care education, support and reflection among rural nurses and other staff – A quantitative study
  • 2015
  • Ingår i: Palliative & Supportive Care. - 1478-9515 .- 1478-9523. ; 13:2, s. 265-274
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Many people now die in community care, and, considering the aging population, all healthcare staff members must be prepared to provide palliative care. Our objectives were to describe the total staff working in different care organizations in a rural community in Sweden and to explore palliative care competence, to describe educational gaps and the need for support and reflection, and to determine whether there are differences in care organizations, professions, age, and gender.Method: A 4-section 20-item questionnaire was distributed to 1686 staff (65% response rate): in nursing homes (n = 395), home care (n = 240), and group residential settings (n = 365). Registered nurses (n = 70), assistant nurses (n = 916), managers (n = 43), and paramedics (n = 33) participated. Descriptive and correlational statistics were employed.Results: Significant differences were found, and 40% (53% among men) lacked palliative care education, Fewer than 50% lacked education in the spiritual/existential areas, and 75% of those aged 20–66 (75% women, 55% men) needed further education. More women than men and staff aged 50–59 had an increased need to reflect.Significance of Results: Our study may provide guidance for managers in rural communities when planning educational interventions in palliative care for healthcare staff and may support direct education with content for specific professions.
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15.
  • Eriksson, Linda, 1972- (författare)
  • Elevinflytande i gränslandet mellan didaktik och makt – en studie av undervisningspraktiken i tre grundskolor
  • 2019
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • This thesis focuses on student influence in the borderland between didactics and power. Student influence is ambiguous and the mission of student influence can be interpreted in different ways in Swedish compulsory schools. In the school reforms of the 1990s, the intentions of student influence, based on both moral and political as well as theoretical positions were stated. Student influence was seen as a right, as being important for education in democracy, and as a prerequisite for learning. Democracy, knowledge and learning are essentially contested concepts. As a didactic practice student influence cannot be understood as general impact through learning, nor as fully-fledged democracy. The question of the limitations of student influence is described and analysed in the thesis. The aim is to describe and critically analyse student influence as didactic practice. The research questions that have directed the study are: How is student influence expressed in three different schools, where there has been a particular ambition to implement student influence? What prerequisites are given for student influence in the way teaching is organised and carried out?What possibilities and constraints (conditions) appear, from the perspective of didactics and power? A fourth question links together the empirical study with the problem of the limits of student influence: Can a didactic model be designed for student influence as didactic practice, and if so, how? The study was conducted using an abductive approach and strategy, and with a point of departure in critical realism as scientific approach. Three primary schools, with the particular ambition of implementing the mission of student influence, were studied through a multiple case study design. The empirical material was produced using ethnographic methods. The a didactic framework is used for description, whilst a sociological concept of power has contributed to the construction of analytical tools. Using ‘order’ and ‘renegotiation’ as analytic tools, the conditions for student influence on how teaching is organised and carried out, are described. Responsibility and transparency are tested as conditions, in order to answer the question of possibilities and constraints from the perspective of didactics and power. The analysis of teaching practice in the three schools shows that student influence is complex, and that it has to be understood as local bound and situationally. This impacts on the possibility of understanding its limitations. The results show that experiences and interests of students can concern motivating them to work, adapting teaching to different learning styles, or that the teachers pay attention to their expressions to fostering more generally. Furthermore, all models of democracy, and of different approaches to learning and knowledge are visible in the schools. The importance of classroom discussion for student influence needs to be illuminated, and the distinction between didactic considerations, and what could be understood as unwarranted power. The results are discussed in relation to issues of learning theory and curriculum theory, as well as to ideals of democratic education, to understand the limits of student influence. A didactic model, with three conceptual tools that enable repeated questioning of the limits of student influence, is proposed.
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16.
  • Eriksson, Mia, et al. (författare)
  • Agonistic targeting of TLR1/TLR2 induces p38 MAPK-dependent apoptosis and NFκB-dependent differentiation of AML cells
  • 2017
  • Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 1:23, s. 2046-2057
  • Tidskriftsartikel (refereegranskat)abstract
    • Acute myeloid leukemia (AML) is associated with poor survival, and there is a strong need to identify disease vulnerabilities that might reveal new treatment opportunities. Here, we found that Toll-like receptor 1 (TLR1) and TLR2 are upregulated on primary AML CD34+CD38-cells relative to corresponding normal bone marrow cells. Activating the TLR1/TLR2 complex by the agonist Pam3CSK4 inMLL-AF9-driven human AML resulted in induction of apoptosis by p38 MAPK-dependent activation of Caspase 3 and myeloid differentiation in a NFκB-dependent manner. By using murineTrp53 -/- MLL-AF9AML cells, we demonstrate that p53 is dispensable for Pam3CSK4-induced apoptosis and differentiation. Moreover, murineAML1-ETO9a-driven AML cells also were forced into apoptosis and differentiation on TLR1/TLR2 activation, demonstrating that the antileukemic effects observed were not confined toMLL-rearranged AML. We further evaluated whether Pam3CSK4 would exhibit selective antileukemic effects. Ex vivo Pam3CSK4 treatment inhibited murine and human leukemia-initiating cells, whereas murine normal hematopoietic stem and progenitor cells (HSPCs) were relatively less affected. Consistent with these findings, primary human AML cells across several genetic subtypes of AML were more vulnerable for TLR1/TLR2 activation relative to normal human HSPCs. In theMLL-AF9AML mouse model, treatment with Pam3CSK4 provided proof of concept for in vivo therapeutic efficacy. Our results demonstrate that TLR1 and TLR2 are upregulated on primitive AML cells and that agonistic targeting of TLR1/TLR2 forces AML cells into apoptosis by p38 MAPK-dependent activation of Caspase 3, and differentiation by activating NFκB, thus revealing a new putative strategy for therapeutically targeting AML cells.
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17.
  • Eriksson, Maria Christina, 1981, et al. (författare)
  • Long-term effects of Internet-delivered cognitive behavioral therapy for depression in primary care - the PRIM-NET controlled trial.
  • 2017
  • Ingår i: Scandinavian journal of primary health care. - : Informa UK Limited. - 1502-7724 .- 0281-3432. ; 35:2, s. 126-136
  • Tidskriftsartikel (refereegranskat)abstract
    • Internet-delivered cognitive behavioral therapy (ICBT) is recommended as an efficient treatment alternative for depression in primary care. However, only few previous studies have been conducted at primary care centers (PCCs). We evaluated long-term effects of ICBT treatment for depression compared to treatment as usual (TAU) in primary care settings.Randomized controlled trial.Patients were enrolled at16 PCCs in south-west Sweden.Patients attending PCCs and diagnosed with depression (n=90).Patients were assessed by a primary care psychologist/psychotherapist and randomized to ICBT or TAU. The ICBT included an ICBT program consisting of seven modules and weekly therapist e-mail or telephone support during the 3-month treatment period.Questionnaires on depressive symptoms (BDI-II), quality of life (EQ-5D) and psychological distress (GHQ-12) were administered at baseline, with follow-ups at 3, 6 and 12 months. Antidepressants and sedatives use, sick leave and PCC contacts were registered.Intra-individual change in depressive symptoms did not differ between the ICBT group and the TAU group during the treatment period or across the follow-up periods. At 3-month follow-up, significantly fewer patients in ICBT were on antidepressants. However, the difference leveled out at later follow-ups. There were no differences between the groups concerning psychological distress, sick leave or quality of life, except for a larger improvement in quality of life in the TAU group during the 0- to 6-month period.ICBT with weekly minimal therapist support in primary care can be equally effective as TAU among depressed patients also over a 12-month period.The trial was registered in the Swedish Registry, researchweb.org, ID number 30511.
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18.
  • Fransson, Sara, et al. (författare)
  • The Swedish Mathematics Case : Learning to See Fractions as Numbers on the Number Line
  • 2018
  • Ingår i: School Development Through Teacher Research. - Dar es Salaam, Tanzania : Mkuki na Nyota Publishers Ltd.. - 9789987083411 ; , s. 154-163
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
    • With inspiration from national exams, we tested locally constructed and standardised diagnosis material in Mathematics and, by taking advantage of the local experience, we analysed what effects teaching had on student performance. The analysis showed that the students, among other problems, experienced difficulty in comparing the size offractions. Furthermore, the analysis indicated that most students could easily use fractions if they were asked to divide a whole into smaller parts, for instance when they were asked to divide a pizza or an amount of money into equal parts. In the previous curriculum, before the 2011 reform, fractions have not been part of the content in lower grades mathematics teaching. The common way of teaching fractions was to show a picture representing the whole, for example a pizza, a cake or an apple. The teachers realized that the students needed to have more representations in order to be able to understand the value of fractions, for example, when arranging portions according to size (Eriksson & Eriksson, 2016).The purpose and the object of learning of the Swedish mathematics case was initially to find out what the students needed in order to be able to arrange fractions in size order. The teachers wanted to identify which aspects students needed to discern in order to understand that a fraction has a precise value. During the work the teachers readjusted the object of learning to focus on the development of the students’ ability to use fractions as numbers on the number line.
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19.
  • Grotenfelt, Nora E., et al. (författare)
  • Interaction between rs10830963 polymorphism in MTNR1B and lifestyle intervention on occurrence of gestational diabetes
  • 2016
  • Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 59:8, s. 1655-1658
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims/hypothesis: The aim of this study was to assess the interaction between melatonin receptor 1B gene (MTNR1B) rs10830963 polymorphism and lifestyle intervention during pregnancy on occurrence of gestational diabetes mellitus (GDM) in high-risk women. Methods: This is a secondary analysis of the randomised controlled gestational diabetes prevention trial ‘RADIEL’, conducted between 2008 and 2014 in four maternity hospitals in southern Finland. A total of 226 women with a history of GDM and/or a pre-pregnancy BMI ≥ 30 kg/m2 were enrolled at
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20.
  • Hange, Dominique, 1963, et al. (författare)
  • Experiences of staff members participating in primary care research activities: a qualitative study
  • 2015
  • Ingår i: International Journal of General Medicine. - 1178-7074. ; 8, s. 143-8
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The aim of this paper was to study primary care staff members' experiences and perceptions of participating in a randomized controlled trial concerning Internet therapy. METHODS: Data were collected via five focus groups, each containing four to eight nurses or general practitioners. The systematic text condensation method described by Malterud was used for thematic analysis of meaning and content of data across cases. RESULTS: The informants believed it was important to conduct research within the primary care setting, but it was difficult to combine clinical work and research. They stressed also that there was a need for continuous information and communication between primary care centers and researchers as well as internally at each primary care center. CONCLUSION: Staff members' experiences of participating in a research study were positive, although associated with various difficulties. It is important to include staff members when designing clinical studies; information should be given continuously during the study and communication facilitated between different occupational groups working at the primary care center.
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21.
  • Hange, Dominique, 1963, et al. (författare)
  • The impact of internet-based cognitive behavior therapy on work ability in patients with depression - a randomized controlled study.
  • 2017
  • Ingår i: International Journal of General Medicine. - 1178-7074. ; 10, s. 151-159
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this randomized controlled trial (RCT) was to investigate the effects of internet-based cognitive behavior therapy (ICBT) treatment for depression compared to treatment-as-usual (TAU) on improving work ability and quality of life in patients with mild-to-moderate depression. We also examined whether patients treated with ICBT returned to work more rapidly, that is, had fewer days of sick leave, than patients treated with TAU.This study is based on material from the PRIM-NET RCT that took place between 2010 and 2013.Primary care centers in Region Vastra Gotaland, Sweden, population about 1.6 million.A total of 77 patients with depression randomized to either ICBT (46 patients) or TAU (31 patients). Mean age of participants was 35.8 years, and 67.5% were women.Work ability was measured with the Work Ability Index, depressive symptoms with Montgomery Asberg Depression Rating Scale - self-rating version (MADRS-S), quality of life with EuroQoL-5D (EQ-5D), and number of sick leave days.Both groups showed an association between improved work ability and reduction of depressive symptoms and between improved work ability and better quality of life. ICBT could not be shown to improve work ability more than TAU among patients with mild-to-moderate depression. There were no differences between the groups concerning number of patients with sick leave or number of sick leave days.Our study indicates that a high level of work ability has an association with high health-related quality of life in patients with mild-to-moderate depression, whether they are treated with ICBT or TAU. ICBT has previously been found to be cost-effective and can be seen as a good alternative to TAU. In addition to the ICBT, an intervention oriented toward the work place might improve work ability and reduce the number of sick leave days among patients with depression.
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22.
  • Holst, Anna, et al. (författare)
  • Cost-effectiveness analysis of internet-mediated cognitive behavioural therapy for depression in the primary care setting : results based on a controlled trial
  • 2018
  • Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 8:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective To perform a cost-effectiveness analysis of a randomised controlled trial of internet-mediated cognitive behavioural therapy (ICBT) compared with treatment as usual (Tall) for patients with mild to moderate depression in the Swedish primary care setting. In particular, the objective was to assess from a healthcare and societal perspective the incremental cost-effectiveness ratio (ICER) of ICBT versus TaU at 12 months follow-up. Design A cost-effectiveness analysis alongside a pragmatic effectiveness trial. Setting Sixteen primary care centres (PCCs) in south-west Sweden. Participants Ninety patients diagnosed with mild to moderate depression at the PCCs. Main outcome measure ICERs calculated as (Cost(ICBT)-Cost(TaU))/(Health outcome(ICBT)-Health outcome(TaU))=Delta Cost/Delta Health outcomes, the health outcomes being changes in the Beck Depression Inventory-II (BDI-II) score and quality-adjusted life-years (QALYs). Results The total cost per patient for ICBT was 4044 Swedish kronor (SEK) ((sic)426) (healthcare perspective) and SEK47679 ((sic)5028) (societal perspective). The total cost per patient for TaU was SEK4434 ((sic)468) and SEK50 343 ((sic)5308). In both groups, the largest cost was associated with productivity loss. The differences in cost per patient were not statistically significant. The mean reduction in BDI-ll score was 13.4 and 13.8 units in the ICBT and Tall groups, respectively. The mean QALYs per patient was 0.74 and 0.79 in the ICBT and TaU groups, respectively. The differences in BDI-11 score reduction and mean QALYs were not statistically significant. The uncertainty of the study estimates when assessed by bootstrapping indicated that no firm conclusion could be drawn as to whether ICBT treatment compared with Tall was the most cost-effective use of resources. Conclusions ICBT was regarded to be as cost-effective as TaU as costs, health outcomes and cost-effectiveness were similar for ICBT and TaU, both from a healthcare and societal perspective.
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23.
  • Holst, Anna, et al. (författare)
  • Patients' experiences of a computerised self-help program for treating depression - a qualitative study of Internet mediated cognitive behavioural therapy in primary care.
  • 2017
  • Ingår i: Scandinavian journal of primary health care. - : Informa UK Limited. - 0281-3432 .- 1502-7724. ; 35:1, s. 46-53
  • Tidskriftsartikel (refereegranskat)abstract
    • The objective of this study was to explore primary care patients' experiences of Internet mediated cognitive behavioural therapy (iCBT) depression treatment.Qualitative study. Data were collected from focus group discussions and individual interviews.Primary care.Data were analysed by systematic text condensation by Malterud.Thirteen patients having received iCBT for depression within the PRIM-NET study.Analysis presented different aspects of patients' experiences of iCBT.The informants described a need for face-to-face meetings with a therapist. A therapist who performed check-ups and supported the iCBT process seemed important. iCBT implies that a responsibility for the treatment is taken by the patient, and some patients felt left alone, while others felt well and secure. This was a way to work in privacy and freedom with a smoothly working technology although there was a lack of confidence and a feeling of risk regarding iCBT.iCBT is an attractive alternative to some patients with depression in primary care, but not to all. An individual treatment design seems to be preferred, and elements of iCBT could be included as a complement when treating depression in primary care. Such a procedure could relieve the overall treatment burden of depression. Key points Internet mediated cognitive behavioural therapy (iCBT) can be effective in treating depression in primary care, but patients' experiences of iCBT are rarely studied •Most patients express a need for human contact, real-time interaction, dialogue and guidance when treated for depression. •The patient's opportunity to influence the practical circumstances about iCBT is a success factor, though this freedom brings a large responsibility upon the receiver. •An individual treatment design seems to be crucial, and elements of iCBT could be included as a complement to face-to-face meetings.
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24.
  • Horikoshi, Momoko, et al. (författare)
  • Discovery and Fine-Mapping of Glycaemic and Obesity-Related Trait Loci Using High-Density Imputation.
  • 2015
  • Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 11:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Reference panels from the 1000 Genomes (1000G) Project Consortium provide near complete coverage of common and low-frequency genetic variation with minor allele frequency ≥0.5% across European ancestry populations. Within the European Network for Genetic and Genomic Epidemiology (ENGAGE) Consortium, we have undertaken the first large-scale meta-analysis of genome-wide association studies (GWAS), supplemented by 1000G imputation, for four quantitative glycaemic and obesity-related traits, in up to 87,048 individuals of European ancestry. We identified two loci for body mass index (BMI) at genome-wide significance, and two for fasting glucose (FG), none of which has been previously reported in larger meta-analysis efforts to combine GWAS of European ancestry. Through conditional analysis, we also detected multiple distinct signals of association mapping to established loci for waist-hip ratio adjusted for BMI (RSPO3) and FG (GCK and G6PC2). The index variant for one association signal at the G6PC2 locus is a low-frequency coding allele, H177Y, which has recently been demonstrated to have a functional role in glucose regulation. Fine-mapping analyses revealed that the non-coding variants most likely to drive association signals at established and novel loci were enriched for overlap with enhancer elements, which for FG mapped to promoter and transcription factor binding sites in pancreatic islets, in particular. Our study demonstrates that 1000G imputation and genetic fine-mapping of common and low-frequency variant association signals at GWAS loci, integrated with genomic annotation in relevant tissues, can provide insight into the functional and regulatory mechanisms through which their effects on glycaemic and obesity-related traits are mediated.
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25.
  • Karakatsanis, Andreas, et al. (författare)
  • The Nordic SentiMag trial : a comparison of super paramagnetic iron oxide (SPIO) nanoparticles versus Tc(99) and patent blue in the detection of sentinel node (SN) in patients with breast cancer and a meta-analysis of earlier studies.
  • 2016
  • Ingår i: Breast Cancer Research and Treatment. - New York : Springer-Verlag New York. - 0167-6806 .- 1573-7217. ; 157:2, s. 281-294
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of the study is to compare the efficacy of SPIO as a tracer in sentinel node biopsy (SNB) in breast cancer with Tc and patent blue in a multicentre prospective study and perform a meta-analysis of all published studies. It also aims to follow skin discoloration after SPIO injection and describe when and how it resolves. Totally 206 patients with early breast cancer were recruited. Tc and patent blue were administered in standard fashion. Patients were injected with SPIO (Sienna+) preoperatively. SNB was performed and detection rates were recorded for both methods. Skin discoloration was followed and documented postoperatively. Data extraction and subsequent meta-analysis of all previous studies were also performed. SN detection rates were similar between standard technique succeeded and SPIO both per patient (97.1 vs. 97.6 %, p = 0.76) as well as per node (91.3 vs. 93.3 %, p = 0.34), something which was not affected by the presence of malignancy. Concordance rates were also consistently high (98.0 % per patient and 95.9 % per node). Discoloring was present in 35.5 % of patients postoperatively, almost exclusively in breast conservation. It fades slowly and is still detectable in 8.6 % of patients after 15 months. Meta-analysis depicted similar detection rates (p = 0.71) and concordance rates (p = 0.82) per patient. However, it seems that SPIO is characterized by higher nodal retrieval (p < 0.001). SPIO is an effective method for the detection of SN in patients with breast cancer. It is comparable to the standard technique and seems to simplify logistics. Potential skin discoloration is something of consideration in patients planned for breast conservation.
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26.
  • Karmin, Monika, et al. (författare)
  • A recent bottleneck of Y chromosome diversity coincides with a global change in culture.
  • 2015
  • Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 25:4
  • Tidskriftsartikel (refereegranskat)abstract
    • It is commonly thought that human genetic diversity in non-African populations was shaped primarily by an out-of-Africa dispersal 50-100 thousand yr ago (kya). Here, we present a study of 456 geographically diverse high-coverage Y chromosome sequences, including 299 newly reported samples. Applying ancient DNA calibration, we date the Y-chromosomal most recent common ancestor (MRCA) in Africa at 254 (95% CI 192-307) kya and detect a cluster of major non-African founder haplogroups in a narrow time interval at 47-52 kya, consistent with a rapid initial colonization model of Eurasia and Oceania after the out-of-Africa bottleneck. In contrast to demographic reconstructions based on mtDNA, we infer a second strong bottleneck in Y-chromosome lineages dating to the last 10 ky. We hypothesize that this bottleneck is caused by cultural changes affecting variance of reproductive success among males.
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27.
  • Kivi, Marie, et al. (författare)
  • Experiences and attitudes of primary care therapists in the implementation and use of internet-based treatment in Swedish primary care settings
  • 2015
  • Ingår i: Internet Interventions. - : Elsevier BV. - 2214-7829. ; 2:3, s. 248-256
  • Tidskriftsartikel (refereegranskat)abstract
    • © 2015 The Authors. Published by Elsevier B.V. Background: The current knowledge of internet-based cognitive behavior therapy (ICBT) implemented in primary care settings is sparse. Our objective was to explore primary care therapists' experiences and attitudes of ICBT, the opportunities and conditions for research in primary care, and to identify potential barriers to the implementation of ICBT treatment in primary care. Methods: Eleven therapists (of 14) participating in the research and implementation project PRIM-NET completed a survey. Four of them were selected also for a detailed semi-structured interview. Data from the interviews were analyzed qualitatively and according to methods used in implementation science. Results: Six general themes were identified in which the therapists considered ICBT as a good treatment that ought to be introduced in primary care. To optimize procedure in primary care settings, several adaptations of ICBT were suggested. Integrating and blending ICBT and face-to-face therapies, for example, would render primary care psychology more efficient. The PRIM-NET study and research within primary care was seen as rewarding and necessary, but challenging. To a large extent primary care still revolves around the general practitioner, with a focus on production, finances, and a somatic aspect of the patients. Five possible barriers to implementation of ICBT were identified which perhaps explains why psychological procedures are not fully integrated into primary care. Conclusions: Although the implementation of new methods and routines is typically accompanied by challenges, the overall experience of the therapists supports the implementation of ICBT as an additional treatment in primary care.
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28.
  • Krais, Annette M., et al. (författare)
  • Excretion of Urinary Metabolites of the Phthalate Esters DEP and DEHP in 16 Volunteers after Inhalation and Dermal Exposure
  • 2018
  • Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1660-4601. ; 15:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Phthalate esters are suspected endocrine disruptors that are found in a wide range of applications. The aim of this study was to determine the excretion of urinary metabolites in 16 individuals after inhalation and/or dermal exposure to 100⁻300 µg/m³ of deuterium-labelled diethyl phthalate (D₄-DEP) and bis(2-ethylhexyl) phthalate (D₄-DEHP). Dermal exposure in this study represents a case with clean clothing acting as a barrier. After inhalation, D₄-DEP and D₄-DEHP metabolites were excreted rapidly, though inter-individual variation was high. D₄-DEP excretion peaked 3.3 h (T½ of 2.1 h) after combined inhalation and dermal exposure, with total excreted metabolite levels ranging from 0.055 to 2.351 nmol/nmol/m³ (nmol of urinary metabolites per phthalates air concentration in (nmol/m³)). After dermal exposure to D₄-DEP, metabolite excretion peaked 4.6 h (T½ of 2.7 h) after exposure, with excreted metabolite levels in between 0.017 and 0.223 nmol/nmol/m³. After combined inhalation and dermal exposure to D₄-DEHP, the excretion of all five analysed metabolites peaked after 4.7 h on average (T½ of 4.8 h), and metabolite levels ranged from 0.072 to 1.105 nmol/nmol/m³ between participants. No dermal uptake of particle phase D₄-DEHP was observed. In conclusion, the average excreted levels of metabolites after combined inhalation and dermal exposure to D₄-DEP was three times higher than after combined exposure to D₄-DEHP; and nine times higher than after dermal exposure of D₄-DEP. This study was made possible due to the use of novel approaches, i.e., the use of labelled phthalate esters to avoid the background concentration, and innovative technique of phthalate generation, both in the particle and the gas phase.
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29.
  • Lawrence, Maggie, et al. (författare)
  • Stroke secondary prevention, a non-surgical and non-pharmacological consensus definition: results of a Delphi study
  • 2019
  • Ingår i: BMC Research Notes. - : Springer Science and Business Media LLC. - 1756-0500. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Evidence supporting lifestyle modification in vascular risk reduction is limited, drawn largely from primary prevention studies. To advance the evidence base for non-pharmacological and non-surgical stroke secondary prevention (SSP), empirical research is needed, informed by a consensus-derived definition of SSP. To date, no such definition has been published. We used Delphi methods to generate an evidence-based definition of non-pharmacological and non-surgical SSP. RESULTS: The 16 participants were members of INSsPiRE (International Network of Stroke Secondary Prevention Researchers), a multidisciplinary group of trialists, academics and clinicians. The Elicitation stage identified 49 key elements, grouped into 3 overarching domains: Risk factors, Education, and Theory before being subjected to iterative stages of elicitation, ranking, discussion, and anonymous voting. In the Action stage, following an experience-based engagement with key stakeholders, a consensus-derived definition, complementing current pharmacological and surgical SSP pathways, was finalised: Non-pharmacological and non-surgical stroke secondary prevention supports and improves long-term health and well-being in everyday life and reduces the risk of another stroke, by drawing from a spectrum of theoretically informed interventions and educational strategies. Interventions to self-manage modifiable lifestyle risk factors are contextualized and individualized to the capacities, needs, and personally meaningful priorities of individuals with stroke and their families.
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30.
  • Mandalenakis, Zacharias, 1979, et al. (författare)
  • Risk of Cancer Among Children and Young Adults With Congenital Heart Disease Compared With Healthy Controls
  • 2019
  • Ingår i: Jama Network Open. - : American Medical Association (AMA). - 2574-3805. ; 2:7
  • Tidskriftsartikel (refereegranskat)abstract
    • IMPORTANCE Adult patients with congenital heart disease (CHD) have an increased incidence of cancer, presumably owing to repeated radiation exposure, genetic predisposition, or repeated stress factors during heart interventions. However, there are limited data on the risk of cancer in children and young adults with CHD compared with the general population. OBJECTIVE To determine the risk of developing cancer from birth to age 41 years among patients with CHD compared with healthy matched controls. DESIGN, SETTING, AND PARTICIPANTS This registry-based, matched, prospective cohort study in Sweden used data from the Patient and Cause of Death Registers. Successive cohorts of patients with CHD born from 1970 to 1979, 1980 to 1989, and 1990 to 1993 were identified. Each patient (n = 21 982) was matched for birth year, sex, and county with 10 controls without CHD from the general population (n = 219 816). Follow-up and comorbidity data were collected from 1970 until 2011. Data analysis began in September 2018 and concluded in February 2019. MAIN OUTCOMES AND MEASURES Risk of cancer among children and young adults with CHD and among healthy controls. RESULTS Among 21 982 individuals with CHD and 219 816 healthy matched controls, 428 patients with CHD (2.0%) and 2072 controls (0.9%) developed cancer. Among patients with CHD, the mean (SD) age at follow-up was 26.6 (8.4) years, and 11332 participants (51.6%) were men. Among healthy controls, the mean (SD) age at follow-up was 28.5 (9.1) years, and 113 319 participants (51.6%) were men. By the age of 41 years, 1 of 50 patients with CHD developed cancer. The overall hazard ratio (HR) for cancer was 2.24 (95% CI, 2.01-2.48) in children and young adults with CHD compared with controls. Risk increased by each successive birth cohort to an HR of 3.37 (95% CI, 2.60-4.35) among those born from 1990 to 1993. The risk of cancer was similar in men and women with CHD (men: HR, 2.41; 95% CI, 2.08-2.79; women: HR, 2.08; 95% CI, 1.80-2.41). The HR for cancer among patients with CHD who underwent surgery was 1.95 (95% CI, 1.58-2.33) compared with controls; for patients with CHD who had not undergone surgery, the HR was 2.43 (95% CI, 2.12-2.76). According to a hierarchical classification, a significantly increased risk of cancer was found among patients with complex heart lesions, such as conotruncal defects (HR, 2.29; 95% CI, 1.62-3.25), compared with healthy controls. CONCLUSIONS AND RELEVANCE Children and young adult patients with CHD had an increased risk of developing cancer compared with healthy matched controls, and the risk was significantly higher among patients with CHD from the most recent birth cohort. An increased risk of cancer in all CHD lesion groups was found, and a systematic screening for cancer could be considered for this at-risk group of patients.
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31.
  • Mariathasan, Sanjeev, et al. (författare)
  • TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells
  • 2018
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 554:7693, s. 544-548
  • Tidskriftsartikel (refereegranskat)abstract
    • Therapeutic antibodies that block the programmed death-1 (PD-1)-programmed death-ligand 1 (PD-L1) pathway can induce robust and durable responses in patients with various cancers, including metastatic urothelial cancer. However, these responses only occur in a subset of patients. Elucidating the determinants of response and resistance is key to improving outcomes and developing new treatment strategies. Here we examined tumours from a large cohort of patients with metastatic urothelial cancer who were treated with an anti-PD-L1 agent (atezolizumab) and identified major determinants of clinical outcome. Response to treatment was associated with CD8 + T-effector cell phenotype and, to an even greater extent, high neoantigen or tumour mutation burden. Lack of response was associated with a signature of transforming growth factor β (TGFβ) signalling in fibroblasts. This occurred particularly in patients with tumours, which showed exclusion of CD8 + T cells from the tumour parenchyma that were instead found in the fibroblast-and collagen-rich peritumoural stroma; a common phenotype among patients with metastatic urothelial cancer. Using a mouse model that recapitulates this immune-excluded phenotype, we found that therapeutic co-Administration of TGFβ-blocking and anti-PD-L1 antibodies reduced TGFβ signalling in stromal cells, facilitated T-cell penetration into the centre of tumours, and provoked vigorous anti-Tumour immunity and tumour regression. Integration of these three independent biological features provides the best basis for understanding patient outcome in this setting and suggests that TGFβ shapes the tumour microenvironment to restrain anti-Tumour immunity by restricting T-cell infiltration.
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32.
  • Martinsson, Johan, et al. (författare)
  • Impacts of Combustion Conditions and Photochemical Processing on the Light Absorption of Biomass Combustion Aerosol
  • 2015
  • Ingår i: Environmental Science and Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 49:24, s. 14663-14671
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim was to identify relationships between combustion conditions, particle characteristics, and optical properties of fresh and photochemically processed emissions from biomass combustion. The combustion conditions included nominal and high burn rate operation and individual combustion phases from a conventional wood stove. Low temperature pyrolysis upon fuel addition resulted in "tar-ball" type particles dominated by organic aerosol with an absorption Angstrom exponent (AAE) of 2.5-2.7 and estimated Brown Carbon contributions of 50-70% to absorption at the climate relevant aethalometer-wavelength (520 nm). High temperature combustion during the intermediate (flaming) phase was dominated by soot agglomerates with AAE 1.0-1.2 and 85-100% of absorption at 520 nm attributed to Black Carbon. Intense photochemical processing of high burn rate flaming combustion emissions in an oxidation flow reactor led to strong formation of Secondary Organic Aerosol, with no or weak absorption. PM1 mass emission factors (mg/kg) of fresh emissions were about an order of magnitude higher for low temperature pyrolysis compared to high temperature combustion. However, emission factors describing the absorption cross section emitted per kg of fuel consumed (m(2)/kg) were of similar magnitude at 520 nm for the diverse combustion conditions investigated in this study. These results provide a link between biomass combustion conditions, emitted particle types, and their optical properties in fresh and processed plumes which can be of value for source apportionment and balanced mitigation of biomass combustion emissions from a climate and health perspective.
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33.
  • Mohammad, Aladdin J, et al. (författare)
  • Incidence and disease severity of anti-neutrophil cytoplasmic antibody-associated nephritis are higher than in lupus nephritis in Sweden.
  • 2015
  • Ingår i: Nephrology, Dialysis and Transplantation. - : Oxford University Press. - 0931-0509 .- 1460-2385. ; 30, s. i23-i30
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives :The objectives of this study were to compare incidence rates, renal and patient survival between lupus nephritis (LN) and anti-neutrophil cytoplasmic antibody-associated nephritis (AAN) during a 12-year period in two geographically defined populations in Sweden.METHODS: In the health care districts surrounding the Skåne University Hospital in Lund [mean population ≥18 years (1997-2008), 188 400] and the University Hospital in Linköping [mean population ≥18 years (1997-2008), 328 900] all patients with biopsy-proven LN and AAN during the period 1997-2008 were included in the study if they (i) were residing within the study areas at the time of onset of nephritis, (ii) had a clinical diagnosis of either SLE or ANCA-associated vasculitis (AAV) and (iii) experienced a first flare of biopsy-proven nephritis during the study period.RESULTS: Eighty-two patients (Lund 44 + Linköping 38) with biopsy-proven AAN were identified and 27 patients with LN (Lund 13 + Linköping 14). The annual incidence rate per million inhabitants aged ≥18 years in both study areas was estimated to be 13.2 (95% CI 10.4-16.1) for AAN and 4.3 (95% CI 2.7-6.0) for LN, P < 0.001. The patients were followed until January 2013. During the follow-up time 38 patients died (AAN 36, LN 2; P = 0.001), and 20 patients went into end-stage renal disease (AAN 19 and LN 1), P = 0.020.CONCLUSIONS: In Sweden, AAN was three times more common than LN, and the outcome was considerably worse. SLE is often diagnosed before the onset of nephritis leading to earlier treatment, while AAN is still often diagnosed at a later stage.
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34.
  • Ortiz-Catalan, Max, et al. (författare)
  • Phantom motor execution facilitated by machine learning and augmented reality as treatment for phantom limb pain : a single group, clinical trial in patients with chronic intractable phantom limb pain
  • 2016
  • Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 388:10062, s. 2885-2894
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Phantom limb pain is a debilitating condition for which no eff ective treatment has been found. We hypothesised that re-engagement of central and peripheral circuitry involved in motor execution could reduce phantom limb pain via competitive plasticity and reversal of cortical reorganisation.Methods: Patients with upper limb amputation and known chronic intractable phantom limb pain were recruited at three clinics in Sweden and one in Slovenia. Patients received 12 sessions of phantom motor execution using machine learning, augmented and virtual reality, and serious gaming. Changes in intensity, frequency, duration, quality, and intrusion of phantom limb pain were assessed by the use of the numeric rating scale, the pain rating index, the weighted pain distribution scale, and a study-specifi c frequency scale before each session and at follow-up interviews 1, 3, and 6 months after the last session. Changes in medication and prostheses were also monitored. Results are reported using descriptive statistics and analysed by non-parametric tests. The trial is registered at ClinicalTrials. gov, number NCT02281539.Findings: Between Sept 15, 2014, and April 10, 2015, 14 patients with intractable chronic phantom limb pain, for whom conventional treatments failed, were enrolled. After 12 sessions, patients showed statistically and clinically signifi cant improvements in all metrics of phantom limb pain. Phantom limb pain decreased from pre-treatment to the last treatment session by 47% (SD 39; absolute mean change 1 . 0 [0 . 8]; p= 0 . 001) for weighted pain distribution, 32% (38; absolute mean change 1 . 6 [1 . 8]; p= 0 . 007) for the numeric rating scale, and 51% (33; absolute mean change 9 . 6 [8 . 1]; p= 0 . 0001) for the pain rating index. The numeric rating scale score for intrusion of phantom limb pain in activities of daily living and sleep was reduced by 43% (SD 37; absolute mean change 2 . 4 [2 . 3]; p= 0 . 004) and 61% (39; absolute mean change 2 . 3 [1 . 8]; p= 0 . 001), respectively. Two of four patients who were on medication reduced their intake by 81% (absolute reduction 1300 mg, gabapentin) and 33% (absolute reduction 75 mg, pregabalin). Improvements remained 6 months after the last treatment.Interpretation: Our fi ndings suggest potential value in motor execution of the phantom limb as a treatment for phantom limb pain. Promotion of phantom motor execution aided by machine learning, augmented and virtual reality, and gaming is a non-invasive, non-pharmacological, and engaging treatment with no identifi ed side-eff ects at present.
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35.
  • Patomella, Ann-Helen, et al. (författare)
  • Primary prevention of stroke : randomised controlled pilot trial protocol on engaging everyday activities promoting health
  • 2019
  • Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 9:11
  • Tidskriftsartikel (refereegranskat)abstract
    • IntroductionStroke is a globally common disease that has detrimental effects on the individual and, more broadly, on society. Lifestyle change can contribute to reducing risk factors for stroke. Although a healthy lifestyle has direct benefits, sustaining and incorporating healthy activities into everyday life is a challenge. Engaging everyday activities have the potential to support lifestyle change and to promote sustainable activity patterns. Current healthcare is failing to reduce modifiable risk factors in people at risk, and in addition to current practice, there is a need for systematic and efficient non-pharmacological and non-surgical stroke-prevention strategies. The aim of the pilot study was to increase knowledge about the effects of a prevention programme and its feasibility to promote sustainable and healthy activity patterns among persons at risk of stroke.Methods and analysisThe proposed pilot study will be a two-armed randomised, assessor-blinded, parallel pilot trial. The study will include feasibility data, investigating acceptability and delivery of the intervention. Persons at risk of stroke (n=60) will be included in a mobile phone-supported prevention programme. The 10-week programme will be conducted at primary healthcare clinics, combining group meetings and online resources to support self-management of lifestyle change. Main outcomes are stroke risk, lifestyle habits and healthy activity patterns. Assessments will be performed at baseline and at follow-up (immediately following the end of the programme and at 6 and 12 months). Effects of the programme will be analysed using inferential statistics. Feasibility will be analysed using both qualitative and quantitative methods.Ethics and disseminationThe study has been approved by the Regional Ethical Review Board in Stockholm, Sweden, being granted reference numbers 2015/834-31, 2016/2203-32 and 2019/01444. Study results will be disseminated through peer-review journals and presentations to mixed audiences at regional and international conferences. Trial registration number NCT03730701.
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36.
  • Sezgin, Ibrahim Can, 1992, et al. (författare)
  • A Low-Complexity Distributed-MIMO Testbed Based on High-Speed Sigma-Delta-Over-Fiber
  • 2019
  • Ingår i: IEEE Transactions on Microwave Theory and Techniques. - 0018-9480 .- 1557-9670. ; 67:7, s. 2861-2872
  • Tidskriftsartikel (refereegranskat)abstract
    • Distributed multiple-input-multiple-output (D-MIMO) is a very promising technique to improve capacity and quality of service for emerging 5G systems. In this paper, we propose a flexible and low-cost testbed for D-MIMO systems, where a sigma-delta over fiber (SDoF) solution is proposed to address the fundamental challenge of phase-coherent transmission between multiple distributed access points (APs) from a central unit (CU). Employing low-cost standardized optical data interconnects, SDoF, brings a very flexible and software controlled transmission of RF signals over optical fiber. An SDoF-based D-MIMO testbed with a CU feeding 12 distributed APs has been realized and experimentally evaluated. Initial experiments of D-MIMO and conventional colocated MIMO systems at 2.365 GHz have been performed to demonstrate the flexibility and potential of the proposed testbed as a new powerful tool in the design and analysis of emerging communication system concepts.
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37.
  • Sluik, Diewertje, et al. (författare)
  • Alcoholic Beverage Preference and Dietary Habits in Elderly across Europe : Analyses within the Consortium on Health and Ageing: Network of Cohorts in Europe and the United States (CHANCES) Project
  • 2016
  • Ingår i: PLOS ONE. - : Public library science. - 1932-6203. ; 11:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: The differential associations of beer, wine, and spirit consumption on cardiovascular risk found in observational studies may be confounded by diet. We described and compared dietary intake and diet quality according to alcoholic beverage preference in European elderly. Methods: From the Consortium on Health and Ageing: Network of Cohorts in Europe and the United States (CHANCES), seven European cohorts were included, i.e. four sub-cohorts from EPIC-Elderly, the SENECA Study, the Zutphen Elderly Study, and the Rotterdam Study. Harmonized data of 29,423 elderly participants from 14 European countries were analyzed. Baseline data on consumption of beer, wine, and spirits, and dietary intake were collected with questionnaires. Diet quality was assessed using the Healthy Diet Indicator (HDI). Intakes and scores across categories of alcoholic beverage preference (beer, wine, spirit, no preference, non-consumers) were adjusted for age, sex, socio-economic status, self-reported prevalent diseases, and lifestyle factors. Cohort-specific mean intakes and scores were calculated as well as weighted means combining all cohorts. Results: In 5 of 7 cohorts, persons with a wine preference formed the largest group. After multivariate adjustment, persons with a wine preference tended to have a higher HDI score and intake of healthy foods in most cohorts, but differences were small. The weighted estimates of all cohorts combined revealed that non-consumers had the highest fruit and vegetable intake, followed by wine consumers. Non-consumers and persons with no specific preference had a higher HDI score, spirit consumers the lowest. However, overall diet quality as measured by HDI did not differ greatly across alcoholic beverage preference categories. Discussion: This study using harmonized data from ~30,000 elderly from 14 European countries showed that, after multivariate adjustment, dietary habits and diet quality did not differ greatly according to alcoholic beverage preference.
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38.
  • Surakka, Ida, et al. (författare)
  • The impact of low-frequency and rare variants on lipid levels.
  • 2015
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:6, s. 589-597
  • Tidskriftsartikel (refereegranskat)abstract
    • Using a genome-wide screen of 9.6 million genetic variants achieved through 1000 Genomes Project imputation in 62,166 samples, we identify association to lipid traits in 93 loci, including 79 previously identified loci with new lead SNPs and 10 new loci, 15 loci with a low-frequency lead SNP and 10 loci with a missense lead SNP, and 2 loci with an accumulation of rare variants. In six loci, SNPs with established function in lipid genetics (CELSR2, GCKR, LIPC and APOE) or candidate missense mutations with predicted damaging function (CD300LG and TM6SF2) explained the locus associations. The low-frequency variants increased the proportion of variance explained, particularly for low-density lipoprotein cholesterol and total cholesterol. Altogether, our results highlight the impact of low-frequency variants in complex traits and show that imputation offers a cost-effective alternative to resequencing.
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39.
  • Tarp, Julie Bjerre, et al. (författare)
  • Subclinical atherosclerosis in patients with cyanotic congenital heart disease
  • 2019
  • Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 277, s. 97-103
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Survival in patients with cyanotic congenital heart disease (CCHD) has improved dramatically. The result is an ageing population with risk of acquired heart disease. Previous small uncontrolled studies suggested that these patients are protected against the development of atherosclerosis. To test this hypothesis, we sought to determine the prevalence of subclinical atherosclerosis in a larger population of patients with CCHD. Method: We compared the prevalence of subclinical atherosclerosis in adult CCHD patients from Denmark, Sweden, Norway and Australia, with that in age-, sex-, smoking status-, and body mass index matched controls. Coronary artery atherosclerosis was assessed on computed tomography with coronary artery calcification (CAC) score. Subclinical atherosclerosis was defined by CAC-score > 0. Carotid artery atherosclerosis was evaluated using ultrasound by measuring carotid plaque thickness (cPT-max) and carotid intima media thickness (CIMT). Lipid status was evaluated as an important atherosclerotic risk factor. Results: Seventy-four patients with CCHD (57% women, median age 49.5 years) and 74 matched controls (57% women, median age 50.0 years) were included. There were no differences between the groups in: CAC-score > 0 (21% vs. 19%, respectively; p = 0.8), carotid plaques (19% vs. 9%, respectively; p = 0.1), cPT-max (2.3 mm vs. 2.8 mm, respectively; p = 0.1) or CIMT (0.61 mm vs. 0.61 mm, respectively; p = 0.98). And further no significant differences in lipoprotein concentrations measured by ultracentrifugation. Conclusion: Young adults with CCHD have similar cardiovascular risk factor profiles and measures of subclinical atherosclerosis, compared with controls. Given their increasing life expectancies, athero-preventive strategies should be an important part of their clinical management.
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40.
  • Therkildsen, Christina, et al. (författare)
  • Molecular subtype classification of urothelial carcinoma in Lynch syndrome
  • 2018
  • Ingår i: Molecular Oncology. - : Wiley. - 1574-7891 .- 1878-0261. ; 12:8, s. 1286-1295
  • Tidskriftsartikel (refereegranskat)abstract
    • Lynch syndrome confers an increased risk for urothelial carcinoma (UC). Molecular subtypes may be relevant to prognosis and therapeutic possibilities, but have to date not been defined in Lynch syndrome-associated urothelial cancer. We aimed to provide a molecular description of Lynch syndrome-associated UC. Thus, Lynch syndrome-associated UCs of the upper urinary tract and the urinary bladder were identified in the Danish hereditary nonpolyposis colorectal cancer (HNPCC) register and were transcriptionally and immunohistochemically profiled and further related to data from 307 sporadic urothelial carcinomas. Whole-genome mRNA expression profiles of 41 tumors and immunohistochemical stainings against FGFR3, KRT5, CCNB1, RB1, and CDKN2A (p16) of 37 tumors from patients with Lynch syndrome were generated. Pathological data, microsatellite instability, anatomic location, and overall survival data were analyzed and compared with sporadic bladder cancer. The 41 Lynch syndrome-associated UC developed at a mean age of 61 years with 59% women. mRNA expression profiling and immunostaining classified the majority of the Lynch syndrome-associated UC as urothelial-like tumors with only 20% being genomically unstable, basal/SCC-like, or other subtypes. The subtypes were associated with stage, grade, and microsatellite instability. Comparison to larger datasets revealed that Lynch syndrome-associated UC shares molecular similarities with sporadic UC. In conclusion, transcriptomic and immunohistochemical profiling identifies a predominance of the urothelial-like molecular subtype in Lynch syndrome and reveals that the molecular subtypes of sporadic bladder cancer are relevant also within this hereditary, mismatch-repair defective subset.
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41.
  • Thorsten, Anja (författare)
  • Berättelseskrivande i skolan : Att studera, beskriva och utveckla ett kunnande
  • 2018
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Syftet med avhandlingen är att bidra med kunskap om hur kunnandet att skriva berättelser kan bli undervisningsbart. Detta belyses ur två infallsvinklar, svenskdidaktiskt och metodologiskt. Avhandlingens empiriska underlag består av elevintervjuer, filmade lektioner, elevtexter, fältanteckningar, mötesprotokoll och reflektionsanteckningar som samlades in under genomförandet av en Learning study om berättelseskrivande i årskurs 3 och 4. I en Learning study undersöker en forskargrupp, med forskande lärare, iterativt hur undervisningen kan läggas upp för att eleverna ska utveckla ett avsett kunnande.Med hjälp av narratologi, fenomenografi och variationsteori analyserades elevers kunnande, elevers lärande och undervisningen. Resultatet visar att när kunnandet att skriva berättelser ska göras undervisningsbart, behöver eleverna få möjlighet att urskilja (a) vad ett läsarperspektiv innebär samt (b) hur berättelsers struktur kan byggas upp med problem och lösning. Dessa båda aspekter specificeras i några andra aspekter, till exempel det utrymme olika delar i berättelsen får samt övergångarna mellan berättelsens ingående delar. I den här avhandlingen analyseras också hur lärares erfarenhetsbaserade kunskap samverkar med variationsteori i en Learning study, med utgångspunkt i Polanyis begrepp tyst kunskap och teoretiska resonemang om hur erfarenhet påverkar hantering, tolkning och bedömning av yrkesspecifika situationer. Resultatet visar att när lärares erfarenhet och variationsteorin kombineras i en iterativ modell finns förutsättningar för en kunskapsgenererande forskningsprocess. Lärarnas erfarenhetsbaserade kunskap påverkar valet av forskningsområde och gör att fokus riktas mot relevanta delar i analysprocessen. Variationsteorin bidrar med teoretiska redskap i analysen och leder till att lärandeobjektets innebörd och synliggörande är i fokus i hela processen.
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42.
  • Tsilidis, Konstantinos K, et al. (författare)
  • Burden of Cancer in a Large Consortium of Prospective Cohorts in Europe
  • 2016
  • Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 108:10
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Disability-adjusted life-years (DALYs) are an indicator of mortality, morbidity, and disability. We calculated DALYs for cancer in middle-aged and older adults participating in the Consortium on Health and Ageing Network of Cohorts in Europe and the United States (CHANCES) consortium.METHODS: A total of 90 199 participants from five European cohorts with 10 455 incident cancers and 4399 deaths were included in this study. DALYs were calculated as the sum of the years of life lost because of premature mortality (YLLs) and the years lost because of disability (YLDs). Population-attributable fractions (PAFs) were also estimated for five cancer risk factors, ie, smoking, adiposity, physical inactivity, alcohol intake, and type II diabetes.RESULTS: After a median follow-up of 12 years, the total number of DALYs lost from cancer was 34 474 (382 per 1000 individuals) with a similar distribution by sex. Lung cancer was responsible for the largest number of lost DALYs (22.9%), followed by colorectal (15.3%), prostate (10.2%), and breast cancer (8.7%). Mortality (81.6% of DALYs) predominated over disability. Ever cigarette smoking was the risk factor responsible for the greatest total cancer burden (24.0%, 95% confidence interval [CI] = 22.2% to 26.0%), followed by physical inactivity (4.9%, 95% CI = 0.8% to 8.1%) and adiposity (1.8%, 95% CI = 0.2% to 2.8%).CONCLUSIONS: DALYs lost from cancer were substantial in this large European sample of middle-aged and older adults. Even if the burden of disease because of cancer is predominantly caused by mortality, some cancers have sizeable consequences for disability. Smoking remained the predominant risk factor for total cancer burden.
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43.
  • Varga, Tibor V., et al. (författare)
  • Novel genetic loci associated with long-term deterioration in blood lipid concentrations and coronary artery disease in European adults
  • 2017
  • Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 46:4, s. 1211-1222
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Cross-sectional genome-wide association studies have identified hundreds of loci associated with blood lipids and related cardiovascular traits, but few genetic association studies have focused on long-term changes in blood lipids.Methods: Participants from the GLACIER Study (N-max = 3492) were genotyped with the MetaboChip array, from which 29 387 SNPs (single nucleotide polymorphisms;replication, fine-mapping regions and wildcard SNPs for lipid traits) were extracted for association tests with 10-year change in total cholesterol (Delta TC) and triglycerides (Delta TG). Four additional prospective cohort studies (MDC, PIVUS, ULSAM, MRC Ely; N-max = 8263 participants) were used for replication. We conducted an in silico look-up for association with coronary artery disease (CAD) in the Coronary ARtery DIsease Genome-wide Replication and Meta-analysis (CARDIoGRAMplusC4D) Consortium (N similar to 190 000) and functional annotation for the top ranking variants.Results: In total, 956 variants were associated (P < 0.01) with either Delta TC or Delta TG in GLACIER. In GLACIER, chr19:50121999 at APOE was associated with Delta TG and multiple SNPs in the APOA1/A4/C3/A5 region at genome-wide significance (P < 5 x 10(-8)), whereas variants in four loci, DOCK7, BRE, SYNE1 and KCNIP1, reached study-wide significance (P < 1.7 x 10(-6)). The rs7412 variant at APOE was associated with DTC in GLACIER (P < 1.7 x 10(-6)). In pooled analyses of all cohorts, 139 SNPs at six and five loci were associated with Delta TC and for Delta TG, respectively (P < 10(-3)). Of these, a variant at CAPN3 (P = 1.2 x 10(-4)), multiple variants at HPR (P-min = 1.5 x 10(-6)) and a variant at SIX5 (P = 1.9 x 10(-4)) showed evidence for association with CAD.Conclusions: We identified seven novel genomic regions associated with long-term changes in blood lipids, of which three also raise CAD risk.
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44.
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45.
  • Westerlund, Kristina, et al. (författare)
  • Radionuclide Therapy of HER2-Expressing Human Xenografts Using Affibody-Based Peptide Nucleic Acid-Mediated Pretargeting : In Vivo Proof of Principle
  • 2018
  • Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 59:7, s. 1092-1098
  • Tidskriftsartikel (refereegranskat)abstract
    • Affibody molecules are small proteins engineered using a nonanti-body scaffold. Radiolabeled Affibody molecules are excellent imaging probes, but their application to radionuclide therapy has been prevented by high renal reabsorption. The aim of this study was to test the hypothesis that Affibody-based peptide nucleic acid (PNA)-mediated pretargeted therapy of human epidermal growth factor receptor 2 (HER2)-expressing cancer extends survival without accompanying renal toxicity.Methods: A HER2-targeting Affibody molecule ligated with an AGTCGTGATGTAGTC PNA hybridization probe (Z(HER2:342)-SR-HP1) was used as the primary pretargeting agent. A complementary AGTCGTGATGTAGTC PNA conjugated to the chelator DOTA and labeled with the radionuclide Lu-177 (Lu-177-HP2) was used as the secondary agent. The influence of different factors on pretargeting was investigated. Experimental radionuclide therapy in mice bearing SKOV-3 xenografts was performed in 6 cycles separated by 7 d.Results: Optimal tumor targeting was achieved when 16 MBq/3.5 mu g (0.65 nmol) of Lu-177-HP2 was injected 16 h after injection of 100 mu g (7.7 nmol) of Z(HER2:342)-SR-HP1. The calculated absorbed dose to tumors was 1,075 mGy/MBq, whereas the absorbed dose to kidneys was 206 mGy/MBq and the absorbed dose to blood (surrogate of bone marrow) was 4 mGy/MBq. Survival of mice was significantly longer (P < 0.05) in the treatment group (66 d) than in the control groups treated with the same amount of Z(HER2:342)-SR-HP1 only (37 d), the same amount and activity of Lu-177-HP2 only (32 d), or phosphate-buffered saline (37 d).Conclusion: The studied pretargeting system can deliver an absorbed dose to tumors appreciably exceeding absorbed doses to critical organs, making Affibody-based PNA-mediated pretargeted radionuclide therapy highly attractive.
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46.
  • Wikberg, Carl, et al. (författare)
  • Comparison Between the Montgomery-Asberg Depression Rating Scale–Self and the Beck Depression Inventory II in Primary Care
  • 2015
  • Ingår i: The Primary Care Companion for CNS Disorders. - 0160-6689 .- 1555-2101 .- 2155-7772. ; 17:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The Montgomery-Asberg Depression Rating Scale–Self (MADRS-S) and the Beck Depression Inventory II (BDI-II) are commonly used self-assessment instruments for screening and diagnosis of depression. The BDI-II has 21 items and the MADRS-S has 9 items. These instruments have been tested with psychiatric inpatients but not in outpatient primary care, where most patients with symptoms of depression initially seek treatment. The purpose of this study was to compare these 2 instruments in the primary care setting. Method: Data were collected from 2 primary care randomized controlled trials that were performed from 2010 to 2013 in Sweden: the Primary Care Self-Assessment MADRS-S Study and Primary Care Internet-Based Cognitive Behavioral Therapy Study. There were 146 patients (73 patients each from both trials) who had newly diagnosed mild or moderate depression (per DSM-IV recommendations) and who had assessment with both the MADRS-S and BDI-II at primary care centers. Comparability and reliability of the instruments were estimated by Pearson product moment correlation and Cronbach α. Results: A good correlation was observed between the 2 instruments: 0.66 and 0.62 in the 2 study cohorts. The reliability within the 2 study cohorts was good for both MADRS-S (Cronbach α: 0.76 for both cohorts) and BDI-II items (Cronbach α: 0.88 and 0.85). Conclusions: The 2 instruments showed good comparability and reliability for low, middle, and high total depression scores. The MADRS-S may be used as a rapid, easily administered, and inexpensive tool in primary care and has results comparable to the BDI-II in all domains.
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47.
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48.
  • Zachrisson, Helene, et al. (författare)
  • An extended high-frequency ultrasound protocol for detection of vessel wall inflammation.
  • 2018
  • Ingår i: Clinical Physiology and Functional Imaging. - : John Wiley & Sons. - 1475-0961 .- 1475-097X. ; 38:4, s. 586-594
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: The aim of this study was to evaluate an extended protocol of the large vessels using high-frequency duplex ultrasound (DUS) for detection of vessel wall inflammation.METHODS: Fifty-eight patients performed a DUS examination where arteritis could not be excluded. All DUS examinations were performed using ACUSON S2000 TM ultrasound system (Siemens Medical Solutions USA, Inc.). High-frequency linear transducers were used (18L6 MHz, 9L4MHz) or curve linear for the aortic arch (6C2 MHz). Carotid, vertebral, central neck arteries (subclavian, axillary, innominate) arteries, aortic arch and femoral arteries were studied. Circumferential, homogenous wall thickening, with or without a hyperechogenic stripe lining the innermost layer, were regarded as typical signs of arteritis. Intima-media thickness (IMT) was measured in the patients and a normal control group. The latest clinical updated diagnosis was assessed at least 6 months after DUS.RESULTS: The DUS findings showed normal vessels (n = 14), arteritis and atherosclerosis (n = 13), atherosclerosis (n = 15) and arteritis (n = 16). The latter group had a significant increased IMT in the common femoral artery and the common carotid artery (mean 1·0 ±  SD 0·3 mm versus 0·6 ± 0·2 mm in the normal group (n = 37), P<0·00001, 1·2 ± 0·5 mm versus 0·8 ± 0·2 mm in the normal group (n = 40), P<0·00001). In the groups with sonographic signs implying arteritis (n = 29), 20 patients had a clinical diagnosis of arteritis, whereas eight patients had another main diagnosis such as malignancy/other inflammatory or infectious disease complicated by inflammation of the vessel wall. One patient had multiple diagnoses and was not possible to classify.CONCLUSION: An extended ultrasound protocol for central neck and leg arteries could be of value for diagnosis of arteritis. In case of atypical vessel wall inflammation, other main diagnoses should be considered.
  •  
49.
  • Åkerlind, Christina, et al. (författare)
  • Optical polarization - Background and Camouflage
  • 2017
  • Ingår i: TARGET AND BACKGROUND SIGNATURES III. - : SPIE-INT SOC OPTICAL ENGINEERING. - 9781510613294 - 9781510613287
  • Konferensbidrag (refereegranskat)abstract
    • Polarimetric imaging sensors in the electro-optical region, already military and commercially available in both the visual and infrared, show enhanced capabilities for advanced target detection and recognition. The capabilities arise due to the ability to discriminate between man-made and natural background surfaces using the polarization information of light. In the development of materials for signature management in the visible and infrared wavelength regions, different criteria need to be met to fulfil the requirements for a good camouflage against modern sensors. In conventional camouflage design, the aimed design of the surface properties of an object is to spectrally match or adapt it to a background and thereby minimizing the contrast given by a specific threat sensor. Examples will be shown from measurements of some relevant materials and how they in different ways affect the polarimetric signature. Dimensioning properties relevant in an optical camouflage from a polarimetric perspective, such as degree of polarization, the viewing or incident angle, and amount of diffuse reflection, mainly in the infrared region, will be discussed.
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50.
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