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1.
  • Kulmala, M., et al. (författare)
  • General overview: European Integrated project on Aerosol Cloud Climate and Air Quality interactions (EUCAARI) - integrating aerosol research from nano to global scales
  • 2011
  • Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 11:24, s. 13061-13143
  • Tidskriftsartikel (refereegranskat)abstract
    • In this paper we describe and summarize the main achievements of the European Aerosol Cloud Climate and Air Quality Interactions project (EUCAARI). EUCAARI started on 1 January 2007 and ended on 31 December 2010 leaving a rich legacy including: (a) a comprehensive database with a year of observations of the physical, chemical and optical properties of aerosol particles over Europe, (b) comprehensive aerosol measurements in four developing countries, (c) a database of airborne measurements of aerosols and clouds over Europe during May 2008, (d) comprehensive modeling tools to study aerosol processes fron nano to global scale and their effects on climate and air quality. In addition a new Pan-European aerosol emissions inventory was developed and evaluated, a new cluster spectrometer was built and tested in the field and several new aerosol parameterizations and computations modules for chemical transport and global climate models were developed and evaluated. These achievements and related studies have substantially improved our understanding and reduced the uncertainties of aerosol radiative forcing and air quality-climate interactions. The EUCAARI results can be utilized in European and global environmental policy to assess the aerosol impacts and the corresponding abatement strategies.
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  • Kim, J., et al. (författare)
  • Hygroscopicity of nanoparticles produced from homogeneous nucleation in the CLOUD experiments
  • 2016
  • Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 16:1, s. 293-304
  • Tidskriftsartikel (refereegranskat)abstract
    • Sulfuric acid, amines and oxidized organics have been found to be important compounds in the nucleation and initial growth of atmospheric particles. Because of the challenges involved in determining the chemical composition of objects with very small mass, however, the properties of the freshly nucleated particles and the detailed pathways of their formation processes are still not clear. In this study,we focus on a challenging size range, i.e., particles that have grown to diameters of 10 and 15 nm following nucleation, and measure their water uptake. Water uptake is useful information for indirectly obtaining chemical composition of aerosol particles. We use a nanometer-hygroscopicity tandem differential mobility analyzer (nano-HTDMA) at sub-saturated conditions (ca. 90% relative humidity at 293 K) to measure the hygroscopicity of particles during the seventh Cosmics Leaving OUtdoor Droplets (CLOUD7) campaign performed at CERN in 2012. In CLOUD7, the hygroscopicity of nucleated nanoparticles was measured in the presence of sulfuric acid, sulfuric acid-dimethylamine, and sulfuric acid-organics derived from alpha-pinene oxidation. The hygroscopicity parameter kappa decreased with increasing particle size, indicating decreasing acidity of particles. No clear effect of the sulfuric acid concentration on the hygroscopicity of 10 nm particles produced from sulfuric acid and dimethylamine was observed, whereas the hygroscopicity of 15 nm particles sharply decreased with decreasing sulfuric acid concentrations. In particular, when the concentration of sulfuric acid was 5.1 x 10(6) molecules cm(-3) in the gas phase, and the dimethylamine mixing ratio was 11.8 ppt, the measured kappa of 15 nm particles was 0.31 +/- 0.01: close to the value reported for dimethylaminium sulfate (DMAS) (kappa(DMAS) similar to 0.28). Furthermore, the difference in kappa between sulfuric acid and sulfuric acid-dimethylamine experiments increased with increasing particle size. The kappa values of particles in the presence of sulfuric acid and organics were much smaller than those of particles in the presence of sulfuric acid and dimethylamine. This suggests that the organics produced from alpha-pinene ozonolysis play a significant role in particle growth even at 10 nm sizes.
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  • Kellokumpu-Lehtinen, PLI, et al. (författare)
  • Triweekly docetaxel versus biweekly docetaxel as a treatment for advanced castration resistant prostate cancer: Quality of life analysis
  • 2014
  • Ingår i: JOURNAL OF CLINICAL ONCOLOGY. - : American Society of Clinical Oncology (ASCO). - 0732-183X .- 1527-7755. ; 32:4
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • 23 Background: Bi-weekly docetaxel (T) with prednisone improved progression free survival and overall survival when compared with the standard tri-weekly T as first-line treatment for advanced castration resistant prostate cancer (CRPC) (Lancet Oncol. 2013;14:117-124). We report here the quality of life (QoL) results of this prospective randomized trial. Methods: Three hundred and forty-six patients were randomly allocated centrally to receive intravenous therapy T of either 75 mg/m² d1 q3 wks (the triweekly arm) or 50 mg/m² d1 and d 14, q4 wks (the biweekly arm) (identifier NCT00255606). Prednisone (10 mg/d) was administered orally in both groups. The baseline patients characteristics were well balanced between the groups with respect to the performance status, mean age (69, range 45 to 87 vs. 68, range 46 to 85), and median serum prostate-specific antigen (PSA) content (109 µg/L, range 11 to 1,230 vs. 116 µg/L, range 12 to 1,870). Quality of life (QoL), the frequency and severity of symptoms including pain were assessed using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) version 4.0 questionnaire. Results: The baseline (QoL) of both treatment groups was compared to QoL after six months of the treatment within each treatment group and between groups. Changes in fatigue, symptoms of pain and nausea, and the overall performance status did not differ between the groups. There were statistically significant differences in overall quality of life values (p=0.010) and discomforting pain values (p=0.028) favoring the bi-weekly treatment arm. Conclusions: Bi-weekly T is better tolerated than the tri-weekly standard T. Following the results from the clinical outcome and the QoL outcome in the PROSTY trial we would recommend the use of bi-weekly docetaxel as first line treatment of CRPC Clinical trial information: NCT00255606.
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  • Viviani, M., et al. (författare)
  • Transition from axi- to nonaxisymmetric dynamo modes in spherical convection models of solar-like stars
  • 2018
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 616
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. Both dynamo theory and observations of stellar large-scale magnetic fields suggest a change from nearly axisymmetric configurations at solar rotation rates to nonaxisymmetric configurations for rapid rotation. Aims. We seek to understand this transition using numerical simulations. Methods. We use three-dimensional simulations of turbulent magnetohydrodynamic convection in spherical shell wedges and considered rotation rates between 1 and 31 times the solar value. Results. We find a transition from axi- to nonaxisymmetric solutions at around 1.8 times the solar rotation rate. This transition coincides with a change in the rotation profile from antisolar- to solar-like differential rotation with a faster equator and slow poles. In the solar-like rotation regime, the field configuration consists of an axisymmetric oscillatory field accompanied by an m = 1 azimuthal mode (two active longitudes), which also shows temporal variability. At slow (rapid) rotation, the axisymmetric (nonaxisymmetric) mode dominates. The axisymmetric mode produces latitudinal dynamo waves with polarity reversals, while the nonaxisymmetric mode often exhibits a slow drift in the rotating reference frame and the strength of the active longitudes changes cyclically over time between the different hemispheres. In the majority of cases we find retrograde waves, while prograde waves are more often found from observations. Most of the obtained dynamo solutions exhibit cyclic variability either caused by latitudinal or azimuthal dynamo waves. In an activity-period diagram, the cycle lengths normalized by the rotation period form two different populations as a function of rotation rate or magnetic activity level. The slowly rotating axisymmetric population lies close to what in observations is called the inactive branch, where the stars are believed to have solar-like differential rotation, while the rapidly rotating models are close to the superactive branch with a declining cycle to rotation frequency ratio and an increasing rotation rate. Conclusions. We can successfully reproduce the transition from axi- to nonaxisymmetric dynamo solutions for high rotation rates, but high-resolution simulations are required to limit the effect of rotational quenching of convection at rotation rates above 20 times the solar value.
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11.
  • Andersen, JH, et al. (författare)
  • Getting the measure of eutrophication in the Baltic Sea: towards improved assessment principles and methods
  • 2011
  • Ingår i: Biogeochemistry. - 0168-2563. ; 106:2, s. 137-156
  • Tidskriftsartikel (refereegranskat)abstract
    • The eutrophication status of the entire Baltic Sea is classified using a multi-metric indicator-based assessment tool. A total of 189 areas are assessed using indicators where information on reference conditions (RefCon), and acceptable deviation (AcDev) from reference condition could be combined with national monitoring data from the period 2001–2006. Most areas (176) are classified as ‘affected by eutrophication’ and only two open water areas and 11 coastal areas are classified as ‘unaffected by eutrophication’. The classification is made by application of the recently developed HELCOM Eutrophication Assessment Tool (HEAT), which is described in this paper. The use of harmonized assessment principles and the HEAT tool allows for direct comparisons between different parts of the Baltic Sea despite variations in monitoring activities. The impaired status of 176 areas is directly related to nutrient enrichment and elevated loads from upstream catchments. Baltic Sea States have implemented nutrient management strategies since years which have reduced nutrient inputs. However, eutrophication is still a major problem for large parts of the Baltic Sea. The 2007 Baltic Sea Action Plan is projected to further reduce nutrient inputs aiming for a Baltic Sea unaffected by eutrophication by 2021.
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  • Gardberg, M., et al. (författare)
  • FHOD1, a Formin Upregulated in Epithelial-Mesenchymal Transition, Participates in Cancer Cell Migration and Invasion
  • 2013
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:9, s. e74923-
  • Tidskriftsartikel (refereegranskat)abstract
    • Cancer cells can obtain their ability to invade and metastasise by undergoing epithelial-to-mesenchymal transition (EMT). Exploiting this mechanism of cellular plasticity, malignant cells can remodel their actin cytoskeleton and down-regulate proteins needed for cell-cell contacts. The mechanisms of cytoskeletal reorganisation resulting in mesenchymal morphology and increased invasive potential are poorly understood. Actin nucleating formins have been implicated as key players in EMT. Here, we analysed which formins are altered in squamous cell carcinoma related EMT. FHOD1, a poorly studied formin, appeared to be markedly upregulated upon EMT. In human tissues FHOD1 was primarily expressed in mesenchymal cells, with little expression in epithelia. However, specimens from oral squamous cell cancers demonstrated consistent FHOD1 upregulation in mesenchymally transformed cells at the invasive edge. This upregulation was confirmed in an oral squamous carcinoma model, where FHOD1 expression was markedly increased upon EMT in a PI3K signalling dependent manner. In the EMT cells FHOD1 contributed to the spindle-shaped morphology and mesenchymal F-actin organization. Furthermore, functional assays demonstrated that FHOD1 contributes to cell migration and invasion. Finally, FHOD1 depletion reduced the ability of EMT cancer cells to form invadopodia and to degrade extracellular matrix. Our results indicate that FHOD1 participates in cytoskeletal changes in EMT. In addition, we show that FHOD1 upregulation occurs during cancer cell EMT in vivo, which indicates that FHOD1 may contribute to tumour progression.
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  • Grankvist, R., et al. (författare)
  • Superselective endovascular tissue access using trans-vessel wall technique : feasibility study for treatment applications in heart, pancreas and kidney in swine
  • 2019
  • Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 285:4, s. 398-406
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives. With the emergence of targeted cell transplantation and gene therapy, there is a need for minimally invasive tissue access to facilitate delivery of therapeutic substrate. The objective of this study was to demonstrate the suitability of an endovascular device which is able to directly access tissue and deliver therapeutic agent to the heart, kidney and pancreas without need to seal the penetration site. Methods. In vivo experiments were performed in 30 swine, including subgroups with follow-up to evaluate complications. The previously described trans-vessel wall (VW) device was modified to be sharper and not require tip detachment to seal the VW. Injections into targets in the heart (n = 13, 24-h follow-up n = 5, 72-h follow-up n = 3), kidney (n = 8, 14-day follow-up n = 3) and pancreas (n = 5) were performed. Some animals were used for multiple organ injections. Follow-up consisted of clinical monitoring, angiography and necropsy. Transvenous (in heart) and transarterial approaches (in heart, kidney and pancreas) were used. Injections were targeted towards the subepicardium, endomyocardium, pancreas head and tail, and kidney subcapsular space and cortex. Results. Injections were successful in target organs, visualized by intraparenchymal contrast on fluoroscopy and by necropsy. No serious complications (defined as heart failure or persistent arrhythmia, haemorrhage requiring treatment or acute kidney injury) were encountered over a total of 157 injections. Conclusions. The trans-VW device can achieve superselective injections to the heart, pancreas and kidney for delivery of therapeutic substances without tip detachment. All parts of these organs including the subepicardium, pancreas tail and renal subcapsular space can be efficiently reached.
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  • Hackman, T., et al. (författare)
  • Spot activity of II Peg
  • 2011
  • Ingår i: Astronomical Notes - Astronomische Nachrichten. - : Wiley. - 0004-6337 .- 1521-3994. ; 332:9-10, s. 859-865
  • Tidskriftsartikel (refereegranskat)abstract
    • We have studied the long-term spot activity of the RS CVn star II Peg by means of Doppler imaging based on spectroscopy and time series analysis of photometry. We present 28 Doppler imaging temperature maps spanning the years 1994-2010, of which 14 were calculated for the present study. The longitudinal spot distribution, derived from the surface temperature maps, is compared with epochs of the light curve minima, derived from photometric observations. We detect a longitudinal drift in the major spot structure during 1995-2003. After this there is a clear decrease in the activity level and no clear drift can be seen. We conclude that the variations could be caused by a cyclic behaviour of the underlying magnetic dynamo.
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  • Hunsberger, Monica, 1973, et al. (författare)
  • Bidirectional associations between psychosocial well-being and body mass index in European children: longitudinal findings from the IDEFICS study
  • 2016
  • Ingår i: Bmc Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 16
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The negative impact of childhood overweight on psychosocial well-being has been demonstrated in a number of studies. There is also evidence that psychosocial well-being may influence future overweight. We examined the bidirectional association between childhood overweight and psychosocial well-being in children from a large European cohort. The dual aim was to investigate the chronology of associations between overweight and psychosocial health indicators and the extent to which these associations may be explained by parental education. Methods: Participants from the IDEFICS study were recruited from eight countries between September 2007 and June 2008 when the children were aged 2 to 9.9 years old. Children and families provided data on lifestyle, psychosocial well-being, and measured anthropometry at baseline and at follow-up 2 years later. This study includes children with weight, height, and psychosocial well-being measurements at both time points (n = 7,831). Psychosocial well-being was measured by the KINDL (R) and Strengths and Difficulties Questionnaire respectively. The first instrument measures health-related quality of life including emotional well-being, self-esteem, parent relations and social relations while the second measures well-being based on emotional symptoms, conduct problems and peer-related problems. Logistic regression was used for modeling longitudinal associations. Results: Children who were overweight at baseline had increased risk of poor health-related quality of life (odds ratio (OR) = 1.23; 95 % confidence interval (CI): 1.03-1.48) measured 2 years later; this association was unidirectional. In contrast to health-related quality of life, poor well-being at baseline was associated with increased risk of overweight (OR = 1.39; 95 % CI: 1.03-1.86) at 2 year follow-up; this association was also only observed in one direction. Adjustment for parental education did not change our findings. Conclusion: Our findings indicate that the association between overweight and psychosocial well-being may be bidirectional but varies by assessment measures. Future research should further investigate which aspects of psychosocial well-being are most likely to precede overweight and which are more likely to be consequences of overweight.
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  • Kellokumpu-Lehtinen, P-L, et al. (författare)
  • Toxicity in patients receiving adjuvant docetaxel plus hormonal treatment after radical radiotherapy for intermediate or high-risk prostate cancer : a preplanned safety report of the SPCG-13 trial
  • 2012
  • Ingår i: Prostate Cancer and Prostatic Diseases. - : Springer Science and Business Media LLC. - 1365-7852 .- 1476-5608. ; 15:3, s. 303-307
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Radical radiotherapy (RD combined with androgen deprivation therapy is currently the standard treatment for elderly patients with localized intermediate- or high-risk prostate cancer (PC). To increase the recurrence-free and overall survival, we conducted an adjuvant, randomized trial using docetaxel (T) in PC patients (Scandinavian Prostate Cancer Group trial 13). METHODS: The inclusion criteria are the following: men > 18 and <= 75 years of age, WHO/ECOG performance status 0-1, histologically proven PC within 12 months before randomization and one of the following: T2, Gleason 7 (4 + 3), PSA > 10; T2, Gleason 8-10, any PSA; or any T3 tumors. Neoadjuvant/adjuvant hormone therapy is mandatory for all patients. The patients were randomized to receive six cycles of T (75 mg m(-2) d 1. cycle 21 d) or no docetaxel after radical RI (with a minimum tumor dose of 74 Gy). This study identifier number is NTC 006653848 (http://www.clinicaltrials.org). RESULTS: In this preplanned safety analysis of 100 patients, T treatment induced grade (G) 3 adverse events (AEs) in 15 patients (30%) and G4 AEs in 30 patients (60%), mainly due to bone marrow toxicity. Neutropenia G3-4 was observed in 72% of the patients, febrile neutropenia was found in 24% of patients, neutropenic infection in 10% of patients and G3 infection without neutropenia in 4% of patients. Nonhematological G3 AEs were rare: anorexia, diarrhea, mucositis, nausea, pain (1 patient each) and fatigue (5). Other severe serious AEs related to T were pulmonary embolism and renal failure. However, only three patients discontinued T before completing the planned six cycles. No deaths had occurred. No patients in the control arm experienced G3-4 toxicities at 12 weeks after the randomization. CONCLUSIONS: Adjuvant docetaxel chemotherapy after radiotherapy has a higher frequency of neutropenia than previous studies on patients with metastatic disease. Otherwise, the treatment was quite well tolerated.
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  • Keskitalo, S, et al. (författare)
  • Dominant TOM1 mutation associated with combined immunodeficiency and autoimmune disease
  • 2019
  • Ingår i: NPJ genomic medicine. - : Springer Science and Business Media LLC. - 2056-7944. ; 4, s. 14-
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Mutations in several proteins functioning as endolysosomal components cause monogenic autoimmune diseases, of which pathogenesis is linked to increased endoplasmic reticulum stress, inefficient autophagy, and defective recycling of immune receptors. We report here a heterozygous TOM1 p.G307D missense mutation, detected by whole-exome sequencing, in two related patients presenting with early-onset autoimmunity, antibody deficiency, and features of combined immunodeficiency. The index patient suffered from recurrent respiratory tract infections and oligoarthritis since early teens, and later developed persistent low-copy EBV-viremia, as well as an antibody deficiency. Her infant son developed hypogammaglobulinemia, autoimmune enteropathy, interstitial lung disease, profound growth failure, and treatment-resistant psoriasis vulgaris. Consistent with previous knowledge on TOM1 protein function, we detected impaired autophagy and enhanced susceptibility to apoptosis in patient-derived cells. In addition, we noted diminished STAT and ERK1/2 signaling in patient fibroblasts, as well as poor IFN-γ and IL-17 secretion in T cells. The mutant TOM1 failed to interact with TOLLIP, a protein required for IL-1 recycling, PAMP signaling and autophagosome maturation, further strengthening the link between the candidate mutation and patient pathophysiology. In sum, we report here an identification of a novel gene, TOM1, associating with early-onset autoimmunity, antibody deficiency, and features of combined immunodeficiency. Other patient cases from unrelated families are needed to firmly establish a causal relationship between the genotype and the phenotype.
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  • Kulmala, Markku, et al. (författare)
  • Direct Observations of Atmospheric Aerosol Nucleation
  • 2013
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 339:6122, s. 943-946
  • Tidskriftsartikel (refereegranskat)abstract
    • Atmospheric nucleation is the dominant source of aerosol particles in the global atmosphere and an important player in aerosol climatic effects. The key steps of this process occur in the sub-2-nanometer (nm) size range, in which direct size-segregated observations have not been possible until very recently. Here, we present detailed observations of atmospheric nanoparticles and clusters down to 1-nm mobility diameter. We identified three separate size regimes below 2-nm diameter that build up a physically, chemically, and dynamically consistent framework on atmospheric nucleation-more specifically, aerosol formation via neutral pathways. Our findings emphasize the important role of organic compounds in atmospheric aerosol formation, subsequent aerosol growth, radiative forcing and associated feedbacks between biogenic emissions, clouds, and climate.
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  • Kulmala, Markku, et al. (författare)
  • Measurement of the nucleation of atmospheric aerosol particles
  • 2012
  • Ingår i: Nature Protocols. - : Springer Science and Business Media LLC. - 1754-2189 .- 1750-2799. ; 7:9, s. 1651-1667
  • Tidskriftsartikel (refereegranskat)abstract
    • The formation of new atmospheric aerosol particles and their subsequent growth have been observed frequently at various locations all over the world. The atmospheric nucleation rate (or formation rate) and growth rate (GR) are key parameters to characterize the phenomenon. Recent progress in measurement techniques enables us to measure atmospheric nucleation at the size (mobility diameter) of 1.5 (+/- 0.4) nm. The detection limit has decreased from 3 to 1 nm within the past 10 years. In this protocol, we describe the procedures for identifying new-particle-formation (NPF) events, and for determining the nucleation, formation and growth rates during such events under atmospheric conditions. We describe the present instrumentation, best practices and other tools used to investigate atmospheric nucleation and NPF at a certain mobility diameter (1.5, 2.0 or 3.0 nm). The key instruments comprise devices capable of measuring the number concentration of the formed nanoparticles and their size, such as a suite of modern condensation particle counters (CPCs) and air ion spectrometers, and devices for characterizing the pre-existing particle number concentration distribution, such as a differential mobility particle sizer (DMPS). We also discuss the reliability of the methods used and requirements for proper measurements and data analysis. The time scale for realizing this procedure is 1 year.
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  • Lehtinen, M, et al. (författare)
  • Ten-year follow-up of human papillomavirus vaccine efficacy against the most stringent cervical neoplasia end-point-registry-based follow-up of three cohorts from randomized trials
  • 2017
  • Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 7:8, s. e015867-
  • Tidskriftsartikel (refereegranskat)abstract
    • Due to long lag time between infection/cancer diagnoses human papillomavirus (HPV) vaccination programs will deliver vaccine efficacy (VE) estimates against cancer end-points late. Cancer registry follow-up of population-based, randomised trial cohorts of vaccinated and unvaccinated women was undertaken for the estimation of VE against cervical intraepithelial neoplasia grade three and invasive cancer (CIN3+).MethodsWe report interim results with 98 561 person years of Finnish Cancer Registry -based follow-up of individually and/or cluster randomised cohorts of HPV-16/18 vaccinated and unvaccinated adolescent women enrolled in June 2003/2005, and between May 2004 and April 2005, respectively. The cohorts comprised 15 627 18- to 19-year-old unvaccinated women (NCT01393470), and 2 401 and 64 16- to 17-year-old HPV-16/18 vaccinated women participating the PATRICIA (NCT00122681) and HPV-012 (NCT00169494) trials, respectively. The age-aligned passive follow-up started 6 months after the clinical trials’ end.ResultsDuring the follow-up of 4.5 to 10 years post enrolment we identified 75 cases of cervical intraepithelial neoplasia grade 3 (CIN3) and 4 cases of invasive cervical cancer (ICC) in the unvaccinated cohort, and 4 CIN3 cases in the HPV-16/18 vaccinated women. Diagnostic blocks were available for HPV typing from 87% of the cases. CIN3+ lesions were detectable in 54 cases. HPV16 was found in 26 of 50 unvaccinated CIN3+ cases, and in 3 CIN3+ cases in the HPV-16/18 vaccinated women. The latter were all baseline positive for cervical HPV16 DNA. Baseline data was not available for the unvaccinated women. Intention-to-treat VE against any CIN3+ was 66% (95% CI 8, 88).ConclusionsTen years post vaccination the AS04-adjuvanted HPV-16/18 vaccine shows continued efficacy against CIN3+ irrespectively of HPV type. Vaccine efficacy was not observed in baseline HPV16 DNA positive subjects.Trial registration numberNCT01393470.
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  • Luostarinen, T., et al. (författare)
  • Human papillomavirus, other sexually transmitted infections and risk of cervical cancer : A Nordic Joint Study
  • 2011
  • Ingår i: IEA World Congress of Epidemiology, 7–11 August 2011, Edinburgh International Conference Centre, Edinburgh, Scotland. - : BMJ. ; 65, s. A266-A266
  • Konferensbidrag (refereegranskat)abstract
    • Introduction: Human papillomavirus (HPV) is considered necessary cause of invasive cervical cancer (ICC), but relations between different HPV types and other sexually transmitted infections in cervical carcinogenesis are unresolved. The CCRPB-EU Network conducted a large study, aiming to assess how major high- and low-risk HPV types, 16, 18 and 6, and possible cofactors, Chlamydia trachomatis and herpes simplex virus type 2 (HSV-2), interact in the aetiology of cervical cancer. Methods: A case-control study was nested in four Nordic serum banks containing serum samples from approximately 1 000 000 women. Linkage to cancer registries resulted to 604 ICC cases diagnosed after serum sampling. Five controls were matched to bank, age at sampling and storage time. IgG antibodies specific for HPV types, C trachomatis and HSV-2 were determined, and tobacco smoke exposure measured by serum cotinine, and HPV DNA in cancer tissue PCR-tested. ORs were estimated by conditional logistic regression, and adjusted for cotinine and for HPV16, HPV18 and C trachomatis, when applicable. Results: Seropositivity for HPV16 did not confer any increased risk for HPV18 DNA positive cancer and HPV18 seropositivity had no association with HPV16 DNA positive cancer. HPV6 had no effect on its own but an antagonistic joint effect with HPV16. HSV-2 had little or no association. C trachomatis had a strongly increased risk for cervical cancer, which remained also among HPV18 seropositives. Conclusions: Type-specific HPV DNA persistence is important in cervical carcinogenesis. HSV-2 is possibly not a cofactor, but C trachomatis is probably a strong cofactor for ICC.
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  • Mesher, David, et al. (författare)
  • Population-level effects of human papillomavirus vaccination programs on infections with nonvaccine genotypes
  • 2016
  • Ingår i: Emerging Infectious Diseases. - : Centers for Disease Control and Prevention (CDC). - 1080-6040 .- 1080-6059. ; 22:10, s. 1732-1740
  • Tidskriftsartikel (refereegranskat)abstract
    • We analyzed human papillomavirus (HPV) prevalences during prevaccination and postvaccination periods to consider possible changes in nonvaccine HPV genotypes after introduction of vaccines that confer protection against 2 high-risk types, HPV16 and HPV18. Our meta-analysis included 9 studies with data for 13,886 girls and women ≤19 years of age and 23,340 women 20–24 years of age. We found evidence of cross-protection for HPV31 among the younger age group after vaccine introduction but little evidence for reductions of HPV33 and HPV45. For the group this same age group, we also found slight increases in 2 nonvaccine high-risk HPV types (HPV39 and HPV52) and in 2 possible high-risk types (HPV53 and HPV73). However, results between age groups and vaccines used were inconsistent, and the increases had possible alternative explanations; consequently, these data provided no clear evidence for type replacement. Continued monitoring of these HPV genotypes is important.
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  • Nivala, M., et al. (författare)
  • Histological Knowledge as a Predictor of Medical Students' Performance in Diagnostic Pathology
  • 2013
  • Ingår i: Anatomical Sciences Education. - : Wiley. - 1935-9772. ; 6:6, s. 361-367
  • Tidskriftsartikel (refereegranskat)abstract
    • Over the years, the role and extent of the basic sciences in medical curricula have been challenged by research on clinical expertise, clinical teachers, and medical students, as well as by the development and diversification of the medical curricula themselves. The aim of this study was to examine how prior knowledge of basic histology and histopathology among students predicts early learning of diagnostic pathology. Participants (N=118, representing 91% of the full student cohort) were medical students at the University of Turku, Finland. Data were collected during two preclinical courses that students attended in their first and second years of medical school. The measurements included tests on biomedical and clinical knowledge and a performance test in diagnostic pathology. Second-year performance on the diagnostic pathology examinations was predicted by the students' prior knowledge of histology, but not by the students' prior knowledge of histopathology. Although earlier research has demonstrated similar results in studies with shorter longitudinal designs, the present study demonstrates that the effect remains even if there is a considerably long time delay (a year) between the measurements, thus confirming the long-term value of basic science studies in the preclinical phase.
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  • Nivala, M., et al. (författare)
  • Interactive visual tools as triggers of collaborative reasoning in entry-level pathology
  • 2012
  • Ingår i: International Journal of Computer-Supported Collaborative Learning. - : Springer Science and Business Media LLC. - 1556-1607 .- 1556-1615. ; 7:4, s. 499-518
  • Tidskriftsartikel (refereegranskat)abstract
    • The growing importance of medical imaging in everyday diagnostic practices poses challenges for medical education. While the emergence of novel imaging technologies offers new opportunities, many pedagogical questions remain. In the present study, we explore the use of a new tool, a virtual microscope, for the instruction and the collaborative learning of pathology. Fifteen pairs of medical students were asked to solve diagnostic tasks in a virtual microscopy learning environment. The students' collaborative efforts were analysed on the basis of approximately 20 hours of video recordings. Our analyses show how students use the technology as a mediating tool to organize, manipulate and construct a shared visual field, and later, shared understanding of the problem and solutions. Organization of the visual field is done through multimodal referential practices: gestures, three dimensional manipulation of the image and paced inspection of the specimen. Furthermore, we analyse and describe how the aforementioned practices coincide with students' medical reasoning in this particular learning context. The analysis of medical students' diagnostic work illustrates the collaborative potential of the virtual microscopy environment and how such interactive tools render the traditional distinction between collaborating around or through computers irrelevant, as even face to face collaboration becomes enacted through technology. Finally, we argue that as technologies develop, understanding the technical side of image production, or any representation, becomes an integral part of the interpretative process. How this knowledge is communicated to the students may play a substantive role in how students learn to interpret medical images.
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  • Nivala, Markus, et al. (författare)
  • Using virtual microscopy to scaffold learning of pathology : a naturalistic experiment on the role of visual and conceptual cues.
  • 2012
  • Ingår i: Instructional Science. - : Springer Science and Business Media LLC. - 0020-4277 .- 1573-1952. ; 40:5, s. 799-811
  • Tidskriftsartikel (refereegranskat)abstract
    • New representational technologies, such as virtual microscopy, create new affordances for medical education. In the article, a study on the following two issues is reported: (a) How does collaborative use of virtual microscopy shape students’ engagement with and learning from virtual slides of tissue specimen? (b) How do visual and conceptual cues scaffold students’ reasoning? Fifteen pairs of medical students participated in two sessions in which the students used a virtual microscope as a diagnostic tool in the context of learning pathology. The slides provided the students with varying levels of visual and conceptual cueing. The sessions were videotaped, and the students’ reasoning while using the microscope was analysed. The students’ written answers were analysed in terms of the findings they made and the diagnoses suggested. At a general level, the results show that students engage actively in this kind of virtually-mediated environment. The visual and/or conceptual cues improve students’ performance, and guide the students’ perception and reasoning in a manner that is productive from the point of view of learning to make clinically relevant observations. Scaffolding students’ reasoning process through cues furthermore assists the students in avoiding the most obvious pitfalls such as overlooking critical areas of a specimen. Overall, visual and conceptual cues improve students’ reasoning in perceptual and cognitive terms, while still allowing space for the making of ‘‘relevant mistakes’’ that may further the students’ diagnostic skills.
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