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  • Bousquet, J, et al. (författare)
  • Nrf2-interacting nutrients and COVID-19: time for research to develop adaptation strategies
  • 2020
  • Ingår i: Clinical and translational allergy. - : Wiley. - 2045-7022. ; 10:1, s. 58-
  • Tidskriftsartikel (refereegranskat)abstract
    • There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPARγ:Peroxisome proliferator-activated receptor, NFκB: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2α:Elongation initiation factor 2α). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT1R axis (AT1R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity.
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  • Bousquet, J., et al. (författare)
  • Scaling up strategies of the chronic respiratory disease programme of the European Innovation Partnership on Active and Healthy Ageing (Action Plan B3: Area 5)
  • 2016
  • Ingår i: Clinical and Translational Allergy. - : Wiley. - 2045-7022. ; 6:1, s. 1-18
  • Forskningsöversikt (refereegranskat)abstract
    • Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) focuses on the integrated care of chronic diseases. Area 5 (Care Pathways) was initiated using chronic respiratory diseases as a model. The chronic respiratory disease action plan includes (1) AIRWAYS integrated care pathways (ICPs), (2) the joint initiative between the Reference site MACVIA-LR (Contre les MAladies Chroniques pour un VIeillissement Actif) and ARIA (Allergic Rhinitis and its Impact on Asthma), (3) Commitments for Action to the European Innovation Partnership on Active and Healthy Ageing and the AIRWAYS ICPs network. It is deployed in collaboration with the World Health Organization Global Alliance against Chronic Respiratory Diseases (GARD). The European Innovation Partnership on Active and Healthy Ageing has proposed a 5-step framework for developing an individual scaling up strategy: (1) what to scale up: (1-a) databases of good practices, (1-b) assessment of viability of the scaling up of good practices, (1-c) classification of good practices for local replication and (2) how to scale up: (2-a) facilitating partnerships for scaling up, (2-b) implementation of key success factors and lessons learnt, including emerging technologies for individualised and predictive medicine. This strategy has already been applied to the chronic respiratory disease action plan of the European Innovation Partnership on Active and Healthy Ageing.
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  • Sliz, E., et al. (författare)
  • Evidence of a causal effect of genetic tendency to gain muscle mass on uterine leiomyomata
  • 2023
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Uterine leiomyomata (UL) are the most common tumours of the female genital tract and the primary cause of surgical removal of the uterus. Genetic factors contribute to UL susceptibility. To add understanding to the heritable genetic risk factors, we conduct a genome-wide association study (GWAS) of UL in up to 426,558 European women from FinnGen and a previous UL meta-GWAS. In addition to the 50 known UL loci, we identify 22 loci that have not been associated with UL in prior studies. UL-associated loci harbour genes enriched for development, growth, and cellular senescence. Of particular interest are the smooth muscle cell differentiation and proliferation-regulating genes functioning on the myocardin-cyclin dependent kinase inhibitor 1A pathway. Our results further suggest that genetic predisposition to increased fat-free mass may be causally related to higher UL risk, underscoring the involvement of altered muscle tissue biology in UL pathophysiology. Overall, our findings add to the understanding of the genetic pathways underlying UL, which may aid in developing novel therapeutics.
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  • Bousquet, J., et al. (författare)
  • MACVIA-ARIA Sentinel NetworK for allergic rhinitis (MASK-rhinitis): the new generation guideline implementation
  • 2015
  • Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : WILEY-BLACKWELL. - 0105-4538 .- 1398-9995. ; 70:11, s. 1372-1392
  • Tidskriftsartikel (refereegranskat)abstract
    • Several unmet needs have been identified in allergic rhinitis: identification of the time of onset of the pollen season, optimal control of rhinitis and comorbidities, patient stratification, multidisciplinary team for integrated care pathways, innovation in clinical trials and, above all, patient empowerment. MASK-rhinitis (MACVIA-ARIA Sentinel NetworK for allergic rhinitis) is a simple system centred around the patient which was devised to fill many of these gaps using Information and Communications Technology (ICT) tools and a clinical decision support system (CDSS) based on the most widely used guideline in allergic rhinitis and its asthma comorbidity (ARIA 2015 revision). It is one of the implementation systems of Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA). Three tools are used for the electronic monitoring of allergic diseases: a cell phone-based daily visual analogue scale (VAS) assessment of disease control, CARAT (Control of Allergic Rhinitis and Asthma Test) and e-Allergy screening (premedical system of early diagnosis of allergy and asthma based on online tools). These tools are combined with a clinical decision support system (CDSS) and are available in many languages. An e-CRF and an e-learning tool complete MASK. MASK is flexible and other tools can be added. It appears to be an advanced, global and integrated ICT answer for many unmet needs in allergic diseases which will improve policies and standards.
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  • Tabassum, R, et al. (författare)
  • Genetic architecture of human plasma lipidome and its link to cardiovascular disease
  • 2019
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4329-
  • Tidskriftsartikel (refereegranskat)abstract
    • Understanding genetic architecture of plasma lipidome could provide better insights into lipid metabolism and its link to cardiovascular diseases (CVDs). Here, we perform genome-wide association analyses of 141 lipid species (n = 2,181 individuals), followed by phenome-wide scans with 25 CVD related phenotypes (n = 511,700 individuals). We identify 35 lipid-species-associated loci (P <5 ×10−8), 10 of which associate with CVD risk including five new loci-COL5A1, GLTPD2, SPTLC3, MBOAT7 and GALNT16 (false discovery rate<0.05). We identify loci for lipid species that are shown to predict CVD e.g., SPTLC3 for CER(d18:1/24:1). We show that lipoprotein lipase (LPL) may more efficiently hydrolyze medium length triacylglycerides (TAGs) than others. Polyunsaturated lipids have highest heritability and genetic correlations, suggesting considerable genetic regulation at fatty acids levels. We find low genetic correlations between traditional lipids and lipid species. Our results show that lipidomic profiles capture information beyond traditional lipids and identify genetic variants modifying lipid levels and risk of CVD.
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  • Kattge, Jens, et al. (författare)
  • TRY plant trait database - enhanced coverage and open access
  • 2020
  • Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
  • Tidskriftsartikel (refereegranskat)abstract
    • Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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  • Kurki, MI, et al. (författare)
  • FinnGen provides genetic insights from a well-phenotyped isolated population
  • 2023
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 613:7944, s. 508-
  • Tidskriftsartikel (refereegranskat)abstract
    • Population isolates such as those in Finland benefit genetic research because deleterious alleles are often concentrated on a small number of low-frequency variants (0.1% ≤ minor allele frequency < 5%). These variants survived the founding bottleneck rather than being distributed over a large number of ultrarare variants. Although this effect is well established in Mendelian genetics, its value in common disease genetics is less explored1,2. FinnGen aims to study the genome and national health register data of 500,000 Finnish individuals. Given the relatively high median age of participants (63 years) and the substantial fraction of hospital-based recruitment, FinnGen is enriched for disease end points. Here we analyse data from 224,737 participants from FinnGen and study 15 diseases that have previously been investigated in large genome-wide association studies (GWASs). We also include meta-analyses of biobank data from Estonia and the United Kingdom. We identified 30 new associations, primarily low-frequency variants, enriched in the Finnish population. A GWAS of 1,932 diseases also identified 2,733 genome-wide significant associations (893 phenome-wide significant (PWS), P < 2.6 × 10–11) at 2,496 (771 PWS) independent loci with 807 (247 PWS) end points. Among these, fine-mapping implicated 148 (73 PWS) coding variants associated with 83 (42 PWS) end points. Moreover, 91 (47 PWS) had an allele frequency of <5% in non-Finnish European individuals, of which 62 (32 PWS) were enriched by more than twofold in Finland. These findings demonstrate the power of bottlenecked populations to find entry points into the biology of common diseases through low-frequency, high impact variants.
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  • Bousquet, J, et al. (författare)
  • Severe chronic allergic (and related) diseases: a uniform approach--a MeDALL--GA2LEN--ARIA position paper
  • 2012
  • Ingår i: International archives of allergy and immunology. - : S. Karger AG. - 1423-0097 .- 1018-2438. ; 158:3, s. 216-231
  • Tidskriftsartikel (refereegranskat)abstract
    • Concepts of disease severity, activity, control and responsiveness to treatment are linked but different. Severity refers to the loss of function of the organs induced by the disease process or to the occurrence of severe acute exacerbations. Severity may vary over time and needs regular follow-up. Control is the degree to which therapy goals are currently met. These concepts have evolved over time for asthma in guidelines, task forces or consensus meetings. The aim of this paper is to generalize the approach of the uniform definition of severe asthma presented to WHO for chronic allergic and associated diseases (rhinitis, chronic rhinosinusitis, chronic urticaria and atopic dermatitis) in order to have a uniform definition of severity, control and risk, usable in most situations. It is based on the appropriate diagnosis, availability and accessibility of treatments, treatment responsiveness and associated factors such as comorbidities and risk factors. This uniform definition will allow a better definition of the phenotypes of severe allergic (and related) diseases for clinical practice, research (including epidemiology), public health purposes, education and the discovery of novel therapies.
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  • Dramburg, S, et al. (författare)
  • EAACI Molecular Allergology User's Guide 2.0
  • 2023
  • Ingår i: Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology. - 1399-3038. ; 3434 Suppl 28, s. e13854-
  • Tidskriftsartikel (refereegranskat)
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20.
  • Matricardi, PM, et al. (författare)
  • EAACI Molecular Allergology User's Guide
  • 2016
  • Ingår i: Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology. - : Wiley. - 1399-3038. ; 2727 Suppl 23, s. 1-250
  • Tidskriftsartikel (refereegranskat)
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  • Zuberbier, T., et al. (författare)
  • Proposal of 0.5 mg of protein/100 g of processed food as threshold for voluntary declaration of food allergen traces in processed food-A first step in an initiative to better inform patients and avoid fatal allergic reactions: A GA(2)LEN position paper
  • 2022
  • Ingår i: Allergy. - : Wiley. - 0105-4538 .- 1398-9995. ; 77:6, s. 1736-1750
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Food anaphylaxis is commonly elicited by unintentional ingestion of foods containing the allergen above the tolerance threshold level of the individual. While labeling the 14 main allergens used as ingredients in food products is mandatory in the EU, there is no legal definition of declaring potential contaminants. Precautionary allergen labeling such as "may contain traces of" is often used. However, this is unsatisfactory for consumers as they get no information if the contamination is below their personal threshold. In discussions with the food industry and technologists, it was suggested to use a voluntary declaration indicating that all declared contaminants are below a threshold of 0.5 mg protein per 100 g of food. This concentration is known to be below the threshold of most patients, and it can be technically guaranteed in most food production. However, it was also important to assess that in case of accidental ingestion of contaminants below this threshold by highly allergic patients, no fatal anaphylactic reaction could occur. Therefore, we performed a systematic review to assess whether a fatal reaction to 5mg of protein or less has been reported, assuming that a maximum portion size of 1kg of a processed food exceeds any meal and thus gives a sufficient safety margin. Methods MEDLINE and EMBASE were searched until 24 January 2021 for provocation studies and case reports in which one of the 14 major food allergens was reported to elicit fatal or life-threatening anaphylactic reactions and assessed if these occurred below the ingestion of 5mg of protein. A Delphi process was performed to obtain an expert consensus on the results. Results In the 210 studies included, in our search, no reports of fatal anaphylactic reactions reported below 5 mg protein ingested were identified. However, in provocation studies and case reports, severe reactions below 5 mg were reported for the following allergens: eggs, fish, lupin, milk, nuts, peanuts, soy, and sesame seeds. Conclusion Based on the literature studied for this review, it can be stated that cross-contamination of the 14 major food allergens below 0.5 mg/100 g is likely not to endanger most food allergic patients when a standard portion of food is consumed. We propose to use the statement "this product contains the named allergens in the list of ingredients, it may contain traces of other contaminations (to be named, e.g. nut) at concentrations less than 0.5 mg per 100 g of this product" for a voluntary declaration on processed food packages. This level of avoidance of cross-contaminations can be achieved technically for most processed foods, and the statement would be a clear and helpful message to the consumers. However, it is clearly acknowledged that a voluntary declaration is only a first step to a legally binding solution. For this, further research on threshold levels is encouraged.
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  • Bousquet, Jean, et al. (författare)
  • ARIA digital anamorphosis : Digital transformation of health and care in airway diseases from research to practice
  • 2021
  • Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : John Wiley & Sons. - 0105-4538 .- 1398-9995. ; 76:1, s. 168-190
  • Forskningsöversikt (refereegranskat)abstract
    • Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.
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  • Kownacki, J, et al. (författare)
  • The isospin dependent p-n multiplets in the region of doubly magic Sn-100
  • 1996
  • Konferensbidrag (refereegranskat)abstract
    • Experimental data on p-n multiplets appearing in the nuclei near double-magic Sn-100 accesible in heavy-ion fusion-evaporation experiments have been analyzed. Proton-rich nuclei in this region have been investigated using the NORDBALL array. A Ni-58 beams at energies of 270 Mev on Fe-54 and 261 MeV on Cr-50 targets were used. Reaction channel separation was achieved with a 4 pi charged particle multi-detector set-up together with a 1 pi neutron detector wall placed in the forward direction. On the basis of gamma gamma-coincidence and angular correlation relations a level schemes of several light Sn, In, Sb, Te and I nuclei were observed for the first time in the present experiment. The observed structure of nuclei are discussed in the framework of the nuclear shell-model. The p-n multiplets in the A similar to 100 region corresponding to the nucleon pairs with mixed configurations has been considered as a playground for the tests of the T = 0 and T = 1 parts of the effective interaction.
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  • Körber, R., et al. (författare)
  • SQUIDs in biomagnetism: A roadmap towards improved healthcare
  • 2016
  • Ingår i: Superconductors Science and Technology. - : IOP Publishing. - 0953-2048 .- 1361-6668. ; 29:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Globally, the demand for improved health care delivery while managing escalating costs is a major challenge. Measuring the biomagnetic fields that emanate from the human brain already impacts the treatment of epilepsy, brain tumours and other brain disorders. This roadmap explores how superconducting technologies are poised to impact health care. Biomagnetism is the study of magnetic fields of biological origin. Biomagnetic fields are typically very weak, often in the femtotesla range, making their measurement challenging. The earliest in vivo human measurements were made with room-temperature coils. In 1963, Baule and McFee (1963 Am. Heart J. 55 95-6) reported the magnetic field produced by electric currents in the heart ('magnetocardiography'), and in 1968, Cohen (1968 Science 161 784-6) described the magnetic field generated by alpha-rhythm currents in the brain ('magnetoencephalography'). Subsequently, in 1970, Cohen et al (1970 Appl. Phys. Lett. 16 278-80) reported the recording of a magnetocardiogram using a Superconducting QUantum Interference Device (SQUID). Just two years later, in 1972, Cohen (1972 Science 175 664-6) described the use of a SQUID in magnetoencephalography. These last two papers set the scene for applications of SQUIDs in biomagnetism, the subject of this roadmap. The SQUID is a combination of two fundamental properties of superconductors. The first is flux quantization - the fact that the magnetic flux Φ in a closed superconducting loop is quantized in units of the magnetic flux quantum, Φ0 ≡ h/2e, ≈ 2.07 × 10-15 Tm2 (Deaver and Fairbank 1961 Phys. Rev. Lett. 7 43-6, Doll R and Nabauer M 1961 Phys. Rev. Lett. 7 51-2). Here, h is the Planck constant and e the elementary charge. The second property is the Josephson effect, predicted in 1962 by Josephson (1962 Phys. Lett. 1 251-3) and observed by Anderson and Rowell (1963 Phys. Rev. Lett. 10 230-2) in 1963. The Josephson junction consists of two weakly coupled superconductors separated by a tunnel barrier or other weak link. A tiny electric current is able to flow between the superconductors as a supercurrent, without developing a voltage across them. At currents above the 'critical current' (maximum supercurrent), however, a voltage is developed. In 1964, Jaklevic et al (1964 Phys. Rev. Lett. 12 159-60) observed quantum interference between two Josephson junctions connected in series on a superconducting loop, giving birth to the dc SQUID. The essential property of the SQUID is that a steady increase in the magnetic flux threading the loop causes the critical current to oscillate with a period of one flux quantum. In today's SQUIDs, using conventional semiconductor readout electronics, one can typically detect a change in Φ corresponding to 10-6 Φ0 in one second. Although early practical SQUIDs were usually made from bulk superconductors, for example, niobium or Pb-Sn solder blobs, today's devices are invariably made from thin superconducting films patterned with photolithography or even electron lithography. An extensive description of SQUIDs and their applications can be found in the SQUID Handbooks (Clarke and Braginski 2004 Fundamentals and Technology of SQUIDs and SQUID Systems vol I (Weinheim, Germany: Wiley-VCH), Clarke and Braginski 2006 Applications of SQUIDs and SQUID Systems vol II (Weinheim, Germany: Wiley-VCH)). The roadmap begins (chapter 1) with a brief review of the state-of-the-art of SQUID-based magnetometers and gradiometers for biomagnetic measurements. The magnetic field noise referred to the pick-up loop is typically a few fT Hz-1/2, often limited by noise in the metallized thermal insulation of the dewar rather than by intrinsic SQUID noise. The authors describe a pathway to achieve an intrinsic magnetic field noise as low as 0.1 fT Hz-1/2, approximately the Nyquist noise of the human body. They also descibe a technology to defeat dewar noise. Chapter 2 reviews the neuroscientific and clinical use of magnetoencephalography (MEG), by far the most widespread application of biomagnetism with systems containing ty ically 300 sensors cooled to liquid-helium temperature, 4.2 K. Two important clinical applications are presurgical mapping of focal epilepsy and of eloquent cortex in brain-tumor patients. Reducing the sensor-to-brain separation and the system noise level would both improve spatial resolution. The very recent commercial innovation that replaces the need for frequent manual transfer of liquid helium with an automated system that collects and liquefies the gas and transfers the liquid to the dewar will make MEG systems more accessible. A highly promising means of placing the sensors substantially closer to the scalp for MEG is to use high-transition-temperature (high-T c) SQUID sensors and flux transformers (chapter 3). Operation of these devices at liquid-nitrogen temperature, 77 K, enables one to minimize or even omit metallic thermal insulation between the sensors and the dewar. Noise levels of a few fT Hz-1/2 have already been achieved, and lower values are likely. The dewars can be made relatively flexible, and thus able to be placed close to the skull irrespective of the size of the head, potentially providing higher spatial resolution than liquid-helium based systems. The successful realization of a commercial high-T c MEG system would have a major commercial impact. Chapter 4 introduces the concept of SQUID-based ultra-low-field magnetic resonance imaging (ULF MRI) operating at typically several kHz, some four orders of magnitude lower than conventional, clinical MRI machines. Potential advantages of ULF MRI include higher image contrast than for conventional MRI, enabling methodologies not currently available. Examples include screening for cancer without a contrast agent, imaging traumatic brain injury (TBI) and degenerative diseases such as Alzheimer's, and determining the elapsed time since a stroke. The major current problem with ULF MRI is that its signal-to-noise ratio (SNR) is low compared with high-field MRI. Realistic solutions to this problem are proposed, including implementing sensors with a noise level of 0.1 fT Hz-1/2. A logical and exciting prospect (chapter 5) is to combine MEG and ULF MRI into a single system in which both signal sources are detected with the same array of SQUIDs. A prototype system is described. The combination of MEG and ULF MRI allows one to obtain structural images of the head concurrently with the recording of brain activity. Since all MEG images require an MRI to determine source locations underlying the MEG signal, the combined modality would give a precise registration of the two images; the combination of MEG with high-field MRI can produce registration errors as large as 5 mm. The use of multiple sensors for ULF MRI increases both the SNR and the field of view. Chapter 6 describes another potentially far-reaching application of ULF MRI, namely neuronal current imaging (NCI) of the brain. Currently available neuronal imaging techniques include MEG, which is fast but has relatively poor spatial resolution, perhaps 10 mm, and functional MRI (fMRI) which has a millimeter resolution but is slow, on the order of seconds, and furthermore does not directly measure neuronal signals. NCI combines the ability of direct measurement of MEG with the spatial precision of MRI. In essence, the magnetic fields generated by neural currents shift the frequency of the magnetic resonance signal at a location that is imaged by the three-dimensional magnetic field gradients that form the basis of MRI. The currently achieved sensitivity of NCI is not quite sufficient to realize its goal, but it is close. The realization of NCI would represent a revolution in functional brain imaging. Improved techniques for immunoassay are always being sought, and chapter 7 introduces an entirely new topic, magnetic nanoparticles for immunoassay. These particles are bio-funtionalized, for example with a specific antibody which binds to its corresponding antigen, if it is present. Any resulting changes in the properties of the nanoparticles are detected with a SQUID. For liquid-phase detection, there are three ba ic methods: AC susceptibility, magnetic relaxation and remanence measurement. These methods, which have been successfully implemented for both in vivo and ex vivo applications, are highly sensitive and, although further development is required, it appears highly likely that at least some of them will be commercialized. © 2016 IOP Publishing Ltd.
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  • Huhtaniemi, R., et al. (författare)
  • High intratumoral dihydrotestosterone is associated with antiandrogen resistance in VCaP prostate cancer xenografts in castrated mice
  • 2022
  • Ingår i: iScience. - : Elsevier BV. - 2589-0042. ; 25:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Antiandrogen treatment resistance is a major clinical concern in castration-resistant prostate cancer (CRPC) treatment. Using xenografts of VCaP cells we showed that growth of antiandrogen resistant CRPC tumors were characterized by a higher intratumor dihydrotestosterone (DHT) concentration than that of treatment responsive tumors. Furthermore, the slow tumor growth after adrenalectomy was associated with a low intratumor DHT concentration. Reactivation of androgen signaling in enzalutamide-resistant tumors was further shown by the expression of several androgen-dependent genes. The data indicate that intratumor DHT concentration and expression of several androgen-dependent genes in CRPC lesions is an indication of enzalutamide treatment resistance and an indication of the need for further androgen blockade. The presence of an androgen synthesis, independent of CYP17A1 activity, has been shown to exist in prostate cancer cells, and thus, novel androgen synthesis inhibitors are needed for the treatment of enzalutamide-resistant CRPC tumors that do not respond to abiraterone.
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33.
  • Juutinen, S, et al. (författare)
  • Coexistence of collective and quasiparticle structures in Sn-106 and Sn-108
  • 1997
  • Ingår i: Nuclear Physics A. - 0375-9474 .- 1873-1554. ; 617:1, s. 74-90
  • Tidskriftsartikel (refereegranskat)abstract
    • New levels in the neutron deficient nuclei Sn-106 and Sn-108 have been investigated by using the NORDBALL detector array combined with charged particle and neutron detectors. The excited structures are discussed in terms of collectivity and the shell model. The excitations are interpreted to be based on d5/2, g7/2 and h(11/2) both for protons and neutrons and g(9/2) for protons. The systematical behaviour of the specific states in the Sn isotopes is studied in the mass range of A = 106-118.
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34.
  • Juutinen, S, et al. (författare)
  • Coexistence of collective and quasiparticle structures in Sn-106 and Sn-108
  • 1997
  • Ingår i: NUCLEAR PHYSICS A. - : ELSEVIER SCIENCE BV. - 0375-9474. ; 617:1, s. 74-90
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • New levels in the neutron deficient nuclei Sn-106 and Sn-108 have been investigated by using the NORDBALL detector array combined with charged particle and neutron detectors. The excited structures are discussed in terms of collectivity and the shell mode
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  • Laajala, T. D., et al. (författare)
  • Optimized design and analysis of preclinical intervention studies in vivo
  • 2016
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent reports have called into question the reproducibility, validity and translatability of the preclinical animal studies due to limitations in their experimental design and statistical analysis. To this end, we implemented a matching-based modelling approach for optimal intervention group allocation, randomization and power calculations, which takes full account of the complex animal characteristics at baseline prior to interventions. In prostate cancer xenograft studies, the method effectively normalized the confounding baseline variability, and resulted in animal allocations which were supported by RNA-seq profiling of the individual tumours. The matching information increased the statistical power to detect true treatment effects at smaller sample sizes in two castration-resistant prostate cancer models, thereby leading to saving of both animal lives and research costs. The novel modelling approach and its open-source and web-based software implementations enable the researchers to conduct adequately-powered and fully-blinded preclinical intervention studies, with the aim to accelerate the discovery of new therapeutic interventions.
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37.
  • MAKELA, E, et al. (författare)
  • COEXISTENCE OF COLLECTIVE AND QUASI-PARTICLE STRUCTURES IN SN-106,SN-108 NUCLEI
  • 1995
  • Ingår i: Physica scripta. T. - : ROYAL SWEDISH ACAD SCIENCES. - 0281-1847. ; T56, s. 280-283
  • Tidskriftsartikel (refereegranskat)abstract
    • New revels in two neutron deficient nuclei Sn-106.108 have been found by using the Nordball detector array extended with the arrangements of charged particle and neutron detectors. The excited structures are discussed in terms of collectivity and the shell model. The systematical behaviour of the states in Sn isotopes is studied in the mass range of A = 104-118.
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38.
  • Nissila, I, et al. (författare)
  • Auditory hemodynamic studies of newborn infants using near-infrared spectroscopic imaging
  • 2004
  • Ingår i: IEEE Engineering in Medicine and Biology Society. Conference Proceedings. - 1557-170X. ; 2, s. 1244-1274
  • Tidskriftsartikel (refereegranskat)abstract
    • The noninvasive study of tissue blood volume and oxygenation using near-infrared light is a new and actively developing technology. We have used near-infrared spectroscopic imaging (NIRSI) to study hemodynamic responses on the auditory cortices evoked by auditory stimulation. Ten healthy newborn infants were studied. The otoacoustic emission hearing test was performed for each infant. Pulse oximetry was used to monitor the heart rate during the measurement, video recording was used to monitor motion artifacts, and the eye movements were noted in order to determine sleep stage. A 16-channel frequency-domain optical imaging system developed in our laboratory was used for NIRSI measurements. The stimuli were presented in trains of seven 1 kHz beeps with 700-ms inter-stimulus intervals. The stimulus trains were separated by 25-s silent periods in order to allow for the hemodynamic delay. In 3/8 cases, we obtained a clear bilateral increase in [HbO/sub 2/], and in two additional cases, a clear response on one hemisphere. The mean change in [HbO/sub 2/] was +0.9+/-0.9muM and the mean change in [Hb] was -0.3+/-0.4muM for those channels producing the largest response for each subject. No statistically significant response was found in 3/8 cases.
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39.
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40.
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41.
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42.
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43.
  • Santos-Valente, E, et al. (författare)
  • Biologicals in childhood severe asthma: the European PERMEABLE survey on the status quo
  • 2021
  • Ingår i: ERJ open research. - : European Respiratory Society (ERS). - 2312-0541. ; 7:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Severe asthma is a rare disease in children, for which three biologicals, anti-immunoglobulin E, anti-interleukin-5 and anti-IL4RA antibodies, are available in European countries. While global guidelines exist on who should receive biologicals, knowledge is lacking on how those guidelines are implemented in real life and which unmet needs exist in the field. In this survey, we aimed to investigate the status quo and identify open questions in biological therapy of childhood asthma across Europe.MethodsStructured interviews regarding experience with biologicals, regulations on access to the different treatment options, drug selection, therapy success and discontinuation of therapy were performed. Content analysis was used to analyse data.ResultsWe interviewed 37 experts from 25 European countries and Turkey and found a considerable range in the number of children treated with biologicals per centre. All participating countries provide public access to at least one biological. Most countries allow different medical disciplines to prescribe biologicals to children with asthma, and only a few restrict therapy to specialised centres. We observed significant variation in the time point at which treatment success is assessed, in therapy duration and in the success rate of discontinuation. Most participating centres intend to apply a personalised medicine approach in the future to match patients a priori to available biologicals.ConclusionSubstantial differences exist in the management of childhood severe asthma across Europe, and the need for further studies on biomarkers supporting selection of biologicals, on criteria to assess therapy response and on how/when to end therapy in stable patients is evident.
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44.
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45.
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46.
  • Ackerman, I. N., et al. (författare)
  • Lifetime Risk of Primary Total Hip Replacement Surgery for Osteoarthritis From 2003 to 2013: A Multinational Analysis Using National Registry Data
  • 2017
  • Ingår i: Arthritis Care Res (Hoboken). - : Wiley. - 2151-464X. ; 69:11, s. 1659-1667
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To compare the lifetime risk of total hip replacement (THR) surgery for osteoarthritis (OA) between countries, and over time. METHODS: Data on primary THR procedures performed for OA in 2003 and 2013 were extracted from national arthroplasty registries in Australia, Denmark, Finland, Norway, and Sweden. Life tables and population data were also obtained for each country. Lifetime risk of THR was calculated for 2003 and 2013 using registry, life table, and population data. RESULTS: In 2003, lifetime risk of THR ranged from 8.7% (Denmark) to 15.9% (Norway) for females, and from 6.3% (Denmark) to 8.6% (Finland) for males. With the exception of females in Norway (where lifetime risk started and remained high), lifetime risk of THR increased significantly for both sexes in all countries from 2003 to 2013. In 2013, lifetime risk of THR was as high as 1 in 7 women in Norway, and 1 in 10 men in Finland. Females consistently demonstrated the highest lifetime risk of THR at both time points. Notably, lifetime risk for females in Norway was approximately double the risk for males in 2003 (females 15.9% [95% confidence interval (95% CI) 15.6-16.1], males 6.9% [95% CI 6.7-7.1]), and 2013 (females 16.0% [95% CI 15.8-16.3], males 8.3% [95% CI 8.1-8.5]). CONCLUSION: Using representative, population-based data, this study found statistically significant increases in the lifetime risk of THR in 5 countries over a 10-year period, and substantial between-sex differences. These multinational risk estimates can inform resource planning for OA service delivery.
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47.
  • Ackerman, I. N., et al. (författare)
  • Substantial rise in the lifetime risk of primary total knee replacement surgery for osteoarthritis from 2003 to 2013: an international, population-level analysis
  • 2017
  • Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 25:4, s. 455-461
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To estimate and compare the lifetime risk of total knee replacement surgery (TKR) for osteoarthritis (OA) between countries, and over time. Method: Data on primary TKR procedures performed for OA in 2003 and 2013 were extracted from national arthroplasty registries in Australia, Denmark, Finland, Norway and Sweden. Life tables and population data were also obtained for each country. Lifetime risk of TKR was calculated for 2003 and 2013 using registry, life table and population data. Results: Marked international variation in lifetime risk of TKR was evident, with females consistently demonstrating the greatest risk. In 2013, Finland had the highest lifetime risk for females (22.8%, 95% CI 22.5-23.1%) and Australia had the highest risk for males (15.4%, 95% CI 15.1-15.6%). Norway had the lowest lifetime risk for females (9.7%, 95% CI 9.5-9.9%) and males (5.8%, 95% CI 5.6-5.9%) in 2013. All countries showed a significant rise in lifetime risk of TKR for both sexes over the 10-year study period, with the largest increases observed in Australia (females: from 13.6% to 21.1%; males: from 9.8% to 15.4%). Conclusions: Using population-based data, this study identified significant increases in the lifetime risk of TKR in all five countries from 2003 to 2013. Lifetime risk of TKR was as high as 1 in 5 women in Finland, and 1 in 7 males in Australia. These risk estimates quantify the healthcare resource burden of knee OA at the population level, providing an important resource for public health policy development and healthcare planning. (C) 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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48.
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49.
  • Cederkall, J, et al. (författare)
  • First evidence for excited states in In-101
  • 1996
  • Ingår i: PHYSICAL REVIEW C-NUCLEAR PHYSICS. - : AMER INST PHYSICS. - 0556-2813. ; 53:4, s. 1955-1958
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • The first evidence for excited states in In-101 is presented. In-101 is the lightest In isotope observed in an in-beam experiment. Two gamma-ray transitions at 1309 and 341 keV, respectively, are strong candidates for a cascade to the ground state in this
  •  
50.
  • Duursma, R. A., et al. (författare)
  • Contributions of climate, leaf area index and leaf physiology to variation in gross primary production of six coniferous forests across Europe: a model-based analysis
  • 2009
  • Ingår i: Tree Physiology. - : Oxford University Press (OUP). - 1758-4469 .- 0829-318X. ; 29:5, s. 621-639
  • Tidskriftsartikel (refereegranskat)abstract
    • Gross primary production (GPP) is the primary source of all carbon fluxes in the ecosystem. Understanding, variation in this flux is vital to understanding variation in the carbon sink of forest ecosystems, and this would serve as input to forest production models. Using GPP derived from eddy-covariance (EC) Measurements, it is now possible to determine the most important factor to scale GPP across sites. We use long-term EC measurements for six coniferous forest stands in Europe, for a total of 25 site-years, located oil a gradient between Southern France and northern Finland. Eddy-derived GPP varied threefold across the six sites, peak ecosystem leaf area index (LAI) (all-sided) varied from 4 to 22 m(2) m(-2) and mean annual temperature varied from - 1 to 13 degrees C. A process-based model operating at a half-hourly time-step was parameterized with available information for each site, and explained 71-96% in variation between daily totals of GPP within site-years and 62% of annual total GPP across site-years. Using the parameterized model, we performed two simulation experiments: weather datasets were interchanged between sites, so that the model was used to predict GPP at some site using data from either a different year or a different site. The resulting bias in GPP prediction was related to several aggregated weather variables and was found to be closely related to the change in the effective temperature sum or mean annual temperature. High R(2)s resulted even when using weather datasets from unrelated sites, providing a cautionary note on the interpretation of R-2 ill model comparisons. A second experiment interchanged stand-structure information between sites. and the resulting bias was strongly related to the difference in LAI, or the difference in integrated absorbed light. Across the six sites. variation in mean annual temperature had more effect on simulated GPP than the variation in LAI. but both were important determinants of GPP. A sensitivity analysis of leaf physiology parameters showed that the quantum yield was the most influential parameter on annual GPP, followed by a parameter controlling the seasonality of photosynthesis and photosynthetic capacity. Overall, the results are promising for the development of a parsimonious model of GPP.
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