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1.
  • Altai, Mohamed, et al. (författare)
  • 188Re-ZHER2:V2, a promising affibody-based targeting agent against HER2-expressing tumors : preclinical assessment
  • 2014
  • Ingår i: Journal of nuclear medicine : official publication, Society of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 55:11, s. 8-1842
  • Tidskriftsartikel (refereegranskat)abstract
    • UNLABELLED: Affibody molecules are small (7 kDa) nonimmunoglobulin scaffold proteins with favorable tumor-targeting properties. Studies concerning the influence of chelators on biodistribution of (99m)Tc-labeled Affibody molecules demonstrated that the variant with a C-terminal glycyl-glycyl-glycyl-cysteine peptide-based chelator (designated ZHER2:V2) has the best biodistribution profile in vivo and the lowest renal retention of radioactivity. The aim of this study was to evaluate (188)Re-ZHER2:V2 as a potential candidate for radionuclide therapy of human epidermal growth factor receptor type 2 (HER2)-expressing tumors.METHODS: ZHER2:V2 was labeled with (188)Re using a gluconate-containing kit. Targeting of HER2-overexpressing SKOV-3 ovarian carcinoma xenografts in nude mice was studied for a dosimetry assessment.RESULTS: Binding of (188)Re-ZHER2:V2 to living SKOV-3 cells was demonstrated to be specific, with an affinity of 6.4 ± 0.4 pM. The biodistribution study showed a rapid blood clearance (1.4 ± 0.1 percentage injected activity per gram [%ID/g] at 1 h after injection). The tumor uptake was 14 ± 2, 12 ± 2, 5 ± 2, and 1.8 ± 0.5 %IA/g at 1, 4, 24, and 48 h after injection, respectively. The in vivo targeting of HER2-expressing xenografts was specific. Already at 4 h after injection, tumor uptake exceeded kidney uptake (2.1 ± 0.2 %IA/g). Scintillation-camera imaging showed that tumor xenografts were the only sites with prominent accumulation of radioactivity at 4 h after injection. Based on the biokinetics, a dosimetry evaluation for humans suggests that (188)Re-ZHER2:V2 would provide an absorbed dose to tumor of 79 Gy without exceeding absorbed doses of 23 Gy to kidneys and 2 Gy to bone marrow. This indicates that future human radiotherapy studies may be feasible.CONCLUSION: (188)Re-ZHER2:V2 can deliver high absorbed doses to tumors without exceeding kidney and bone marrow toxicity limits.
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2.
  • Kristiansson, Amanda, et al. (författare)
  • 177Lu-PSMA-617 Therapy in Mice, with or without the Antioxidant α1-Microglobulin (A1M), Including Kidney Damage Assessment Using 99mTc-MAG3 Imaging
  • 2021
  • Ingår i: Biomolecules. - : MDPI AG. - 2218-273X. ; 11:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Anti-prostate specific membrane antigen (PSMA) radioligand therapy is promising but not curative in castration resistant prostate cancer. One way to broaden the therapeutic index could be to administer higher doses in combination with radioprotectors, since administered radioactivity is kept low today in order to avoid side-effects from a high absorbed dose to healthy tissue. Here, we investigated the human radical scavenger α1-microglobulin (A1M) together with 177-Lutetium (177Lu) labeled PSMA-617 in preclinical models with respect to therapeutic efficacy and kidney toxicity. Nude mice with subcutaneous LNCaP xenografts were injected with 50 or 100 MBq of [177Lu]Lu-PSMA-617, with or without injections of recombinant A1M (rA1M) (at T = 0 and T = 24 h). Kidney absorbed dose was calculated to 7.36 Gy at 4 days post a 100 MBq injection. Activity distribution was imaged with Single-Photon Emission Computed Tomography (SPECT) at 24 h. Tumor volumes were measured continuously, and kidneys and blood were collected at termination (3-4 days and 3-4 weeks after injections). In a parallel set of experiments, mice were given [177Lu]Lu-PSMA-617 and rA1M as above and dynamic technetium-99m mercaptoacetyltriglycine ([99mTc]Tc-MAG3) SPECT imaging was performed prior to injection, and 3- and 6-months post injection. Blood and urine were continuously sampled. At termination (6 months) the kidneys were resected. Biomarkers of kidney function, expression of stress genes and kidney histopathology were analyzed. [177Lu]Lu-PSMA-617 uptake, in tumors and kidneys, as well as treatment efficacy did not differ between rA1M and vehicle groups. In mice given rA1M, [99mTc]Tc-MAG3 imaging revealed a significantly higher slope of initial uptake at three months compared to mice co-injected with [177Lu]Lu-PSMA-617 and vehicle. Little or no change compared to control was seen in urine albumin, serum/plasma urea levels, RT-qPCR analysis of stress response genes and in the kidney histopathological evaluation. In conclusion, [99mTc]Tc-MAG3 imaging presented itself as a sensitive tool to detect changes in kidney function revealing that administration of rA1M has a potentially positive effect on kidney perfusion and tubular function when combined with [177Lu]Lu-PSMA-617 therapy. Furthermore, we could show that rA1M did not affect anti-PSMA radioligand therapy efficacy.
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3.
  • Alattar, Abdul Ghani, et al. (författare)
  • Recombinant alpha(1)-Microglobulin (rA1M) Protects against Hematopoietic and Renal Toxicity, Alone and in Combination with Amino Acids, in a Lu-177-DOTATATE Mouse Radiation Model
  • 2023
  • Ingår i: Biomolecules. - 2218-273X. ; 13:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Lu-177-DOTATATE peptide receptor radionuclide therapy (PRRT) is used clinically to treat metastasized or unresectable neuroendocrine tumors (NETs). Although Lu-177-DOTATATE is mostly well tolerated in patients, bone marrow suppression and long-term renal toxicity are still side effects that should be considered. Amino acids are often used to minimize renal radiotoxicity, however, they are associated with nausea and vomiting in patients. alpha (1)-microglobulin (A1M) is an antioxidant with heme- and radical-scavenging abilities. A recombinant form (rA1M) has previously been shown to be renoprotective in preclinical models, including in PRRT-induced kidney damage. Here, we further investigated rA1M's renal protective effect in a mouse Lu-177-DOTATATE model in terms of administration route and dosing regimen and as a combined therapy with amino acids (Vamin). Moreover, we investigated the protective effect of rA1M on peripheral blood and bone marrow cells, as well as circulatory biomarkers. Intravenous (i.v.) administration of rA1M reduced albuminuria levels and circulatory levels of the oxidative stress-related protein fibroblast growth factor-21 (FGF-21). Dual injections of rA1M (i.e., at 0 and 24 h post-Lu-177-DOTATATE administration) preserved bone marrow cellularity and peripheral blood reticulocytes. Administration of Vamin, alone or in combination with rA1M, did not show any protection of bone marrow cellularity or peripheral reticulocytes. In conclusion, this study suggests that rA1M, administered i.v. for two consecutive days in conjunction with Lu-177-DOTATATE, may reduce hematopoietic and kidney toxicity during PRRT with Lu-177-DOTATATE.
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4.
  • Altai, Mohamed, et al. (författare)
  • Selection of an optimal cysteine-containing peptide-based chelator for labeling of affibody molecules with (188)Re.
  • 2014
  • Ingår i: European Journal of Medicinal Chemistry. - : Elsevier BV. - 0223-5234 .- 1768-3254. ; 87, s. 519-28
  • Tidskriftsartikel (refereegranskat)abstract
    • Affibody molecules constitute a class of small (7 kDa) scaffold proteins that can be engineered to have excellent tumor targeting properties. High reabsorption in kidneys complicates development of affibody molecules for radionuclide therapy. In this study, we evaluated the influence of the composition of cysteine-containing C-terminal peptide-based chelators on the biodistribution and renal retention of (188)Re-labeled anti-HER2 affibody molecules. Biodistribution of affibody molecules containing GGXC or GXGC peptide chelators (where X is G, S, E or K) was compared with biodistribution of a parental affibody molecule ZHER2:2395 having a KVDC peptide chelator. All constructs retained low picomolar affinity to HER2-expressing cells after labeling. The biodistribution of all (188)Re-labeled affibody molecules was in general comparable, with the main observed difference found in the uptake and retention of radioactivity in excretory organs. The (188)Re-ZHER2:V2 affibody molecule with a GGGC chelator provided the lowest uptake in all organs and tissues. The renal retention of (188)Re-ZHER2:V2 (3.1 ± 0.5 %ID/g at 4 h after injection) was 55-fold lower than retention of the parental (188)Re-ZHER2:2395 (172 ± 32 %ID/g). We show that engineering of cysteine-containing peptide-based chelators can be used for significant improvement of biodistribution of (188)Re-labeled scaffold proteins, particularly reduction of their uptake in excretory organs.
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5.
  • Altai, Mohamed, et al. (författare)
  • Selection of an optimal cysteine-containing peptide-based chelator for labeling of Affibody molecules with 188-Re
  • 2013
  • Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 40:Suppl. 2, s. S219-S220
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Affibody molecules constitute a class of small (7 kDa) scaffold proteins that can be engineered to have excellent tumor targeting properties. High reabsorption in kidneys complicates development of affibody molecules for radionuclide therapy. In this study, we evaluated the influence of the composition of cysteine-containing C-terminal peptide-based chelators on the biodistribution and renal retention of 188Re-labeled anti-HER2 affibody molecules. Biodistribution of affibody molecules containing GGXC or GXGC peptide chelators (where X is G, S, E or K) was compared with biodistribution of a parental affibody molecule ZHER2:2395 having a KVDC peptide chelator. All constructs retained low picomolar affinity to HER2-expressing cells after labeling. The biodistribution of all 188Re-labeled affibody molecules was in general comparable, with the main observed difference found in the uptake and retention of radioactivity in excretory organs. The 188Re-ZHER2:V2 affibody molecule with a GGGC chelator provided the lowest uptake in all organs and tissues. The renal retention of 188Re-ZHER2:V2 (3.1±0.5 %ID/g at 4 h after injection) was 55-fold lower than retention of the parental 188Re-ZHER2:2395 (172±32 %ID/g). We show that engineering of cysteine-containing peptide-based chelators can be used for significant improvement of biodistribution of 188Re-labeled scaffold proteins, particularly reduction of their uptake in excretory organs.
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6.
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7.
  • Brodd, Katarina Strand, et al. (författare)
  • Development of Smooth Pursuit Eye Movements in very preterm born infants : 3. Association to perinatal risk factors
  • 2012
  • Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 101:2, s. 164-171
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim:  To investigate the association between perinatal risk factors and neonatal complications and early oculo-motor development in very preterm infants. Methods:  Perinatal risk factors were identified, and the potential association with early oculo-motor development was evaluated by measuring smooth pursuit eye movements (SP) at 2 and 4 months' corrected age (CA) in a population of very preterm infants born in Uppsala County 2004-2007 (n = 113). Results:  Among the 15 tested factors, eight showed significant association in univariate analysis with lower levels of SP at 4 months' CA, namely administration of prenatal corticosteroids, gestational age, birthweight, bronchopulmonary dysplasia, retinopathy of prematurity, periventricular leukomalacia, intraventricular haemorrhage >grade 2, and persistent ductus arteriosus. At 2 months' CA, only retinopathy of prematurity >stage 2 was associated with lower levels of SP. When all factors significant in the univariate tests were included in multiple regressions aimed to assess each factor's independent relation to SP, periventricular leukomalacia was the only significant independent factor. When adding 2-5 of the significant factors using multiple regression analysis, the levels of SP became lower. Conclusion:  Perinatal risk factors were associated with lower levels of SP. This could be interpreted as delayed or disturbed development of normal oculomotor ability.
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8.
  • Brodd, Katarina Strand, et al. (författare)
  • Development of smooth pursuit eye movements in very preterm infants : 1. General aspects
  • 2011
  • Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 100:7, s. 983-991
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim:  To investigate early oculo-motor development in a population-based cohort of very preterm infants.Methods:  Early oculo-motor development was prospectively studied by measuring smooth pursuit eye movements at 2 and 4 months corrected age in a population of very preterm infants born in Uppsala County 2004–2007. Eighty-one preterm infants were studied, and 32 healthy term infants constituted the control group.Results:  The study group consisted of infants with a mean gestational age of28 + 5 weeks. At 2 and 4 months corrected age, infants born very preterm showed lower gain (p < 0.001) and proportion of smooth pursuit eyemovements (p < 0.001) compared to the control group. The boys showed higher gain of smooth pursuit eye movements at both 2 and 4 months corrected age, compared to girls.Conclusions:  Oculo-motor development measured by smooth pursuit eye movements is delayed in very preterm infants at 2 and 4 months corrected age. This might be a risk factor or early indicator of later perceptual and behavioural impairment.
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9.
  • de Morais Lima, Priscila, et al. (författare)
  • Farmers’ perceptions on organic fertilisers towards circularity–a case study in Sweden
  • 2024
  • Ingår i: Acta Agriculturae Scandinavica - Section B. - : Taylor and Francis Ltd.. - 0906-4710 .- 1651-1913. ; 74:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Adequate treatment of organic manures and digestates from livestock production should reduce environmental impacts and provide well-defined and attractive biofertlisers for a crop production market, which can promote the closure of the nutrient cycle in agriculture. In this sense, a survey was conducted during the autumn of 2021 to investigate Swedish farmers’ perspectives on organic fertilisers use. The survey consisted of an online questionnaire, which was distributed broadly in the social media, homepages, different types of networks and at course events in order to reach all types of farms. There were 22 questions focused on current use, reasons for current use and preferences for future use. The analysis of the 99 fully responded surveys, demonstrated that 43% of the respondents think that they will increase their use of organic fertilisers in the coming 5–10 years and 60% think that they will use manure digestate in different forms (both solid and liquid fractions). Soil improvement was the main reason to use organic fertilisers, but there were also preferences for organic fertilisers with fast release of nutrients. The risk of soil compaction was the main reason not to use organic fertilisers and based on the responses, pellets and granulates seem to be more interesting than liquids and solids in general. Animal manures dominate the current use of organic fertilisers in Sweden however, other types of organic waste such as digestate and digestate derived fertilisers seems appealing to Swedish farmers. In conclusion, from this survey with 62% of the respondees in crop production, we found several indications of that there is a potential for increased use of organic fertilisers in Sweden on farms with limited use today. We found an openness, a broad interest and a demand for different types of products of different forms and origin. Since this demand in the end will almost always depend on the price of products in relation to the price of mineral fertilisers, which are fluctuating, we see the need of policy incentives in order to stimulate initiatives for the development towards increased circularity of nutrients. 
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10.
  • Gee, Kira, et al. (författare)
  • BONUS BALTSPACE Deliverable 3.3: Addressing MSP integration challenges: The role of tools and approaches. Geesthacht.
  • 2018
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • This report discusses seven different tools and approaches to address important integration challenges in marine and coastal spatial planning and management, namely in relation to sectors and policies, boundaries, stakeholders and different types of knowledge. BONUS BALTSPACE (2015-2018) was conceived against the background of the EU MSP Directive and the need for Member States to produce marine spatial plans by 2021. MSP is an integrative concept that requires integration of sectors and stakeholders, of different types of knowledge, as well as integration across administrative borders. BALTSPACE was the first transnational, interdisciplinary MSP research project in the BSR to focus on four key integration challenges in MSP, namely policy and sector integration, multi-level and transboundary integration, stakeholder integration and knowledge integration. Work Package 3 was tasked with developing and assessing practitioner-oriented approaches and tools for MSP to help deal with the integration challenges identified (www.baltspace.eu). The capacity of seven problem- and process-specific techniques and approaches (subsequently termed tools) was assessed in different case study settings: •Bowtie •Culturally Significant Areas •Governance Baselines •Integrated Indicator System for monitoring the spatial, economic and environmental effects of MSP solutions •Marxan •Open Standards for the Practice of Conservation •Spatial Economic Benefit Analysis (SEBA) Each tool was applied once in a particular country context in a format determined by the tool user. Some applications were desktop exercises, others were more participative, although most had some form of verification by stakeholders. Tool selection reflected both the variety of available methods and the diverse range of tasks in MSP, leading to the inclusion of product- and process-oriented tools, descriptive and analytical tools, as well as data and forecasting tools. One of the tools (SEBA) was specifically developed for MSP as part of BALTSPACE. An overview of academic literature revealed that “tools” in MSP are mostly understood as technical instruments that provide decision support. To a large part, the tools described in the literature rely on scientific data and information, in line with a view of MSP as an evidence-based exercise requiring data collection and analysis as a basis for planning. There is little mention of the role of process in MSP and the learning that might result from tool-supported processes. Also, most assessments do not focus on the indirect or ‘soft’ impacts of tool use, which are often related to the persons or groups engaging with the tool – and which could have positive integration effects by and for themselves. Examples of such impacts include greater mutual understanding or an improved sense of trust, both of which could arise from improved stakeholder and knowledge integration facilitated by a tool. Integration effects may therefore manifest themselves when the tool is being used - e.g. to generate a particular output such as a map – or when the results are being fed back into the MSP process. After a short overview of the purpose of each tool and where it fits in the MSP cycle, an analytical template is set out. This breaks down the four integration challenges into a series of sub-challenges, so as to enable a comparative evaluation of the seven tools against the same set of challenges. It also sets out some more general contributions the tools could make with respect to MSP, such as contributing to the efficiency of the MSP process or to improved decision-making. The assessment is based on the retrospective evaluation of the BALTSPACE researchers and largely descriptive, focusing also on the direct outputs and indirect outcomes of tool use. Throughout, the assessment focuses on the capacity of each tool, taking account of the fact that tool use is context-dependent and that a range of external factors comes into play when it comes to the actual integration results. The assessment shows that the integration challenges most readily addressed are stakeholder and knowledge integration. Conversely, policy integration is difficult to achieve as a direct result, although some tools are well suited to analysing the existing policy landscape and potential integration gaps. Multi-level (transboundary) integration depends on the scale of tool use and is potentially achievable as all tools can be up-scaled if necessary. Some tools are also well-placed to contribute to land-sea integration. An important difference is noted between the inherent capacity of the tools and their application. Some tools are better at certain tasks than others but ultimately, it is the application that is make or break. For example, some tools (such as OS or CSA) are specifically designed to support stakeholder and knowledge integration, in the sense that they would not deliver a result without them. Other tools that are less specifically designed for this purpose can also contribute to stakeholder integration, but this then happens as a result of how the tool is applied – in this case in a participative setting. To some degree, the capacity to facilitate stakeholder and knowledge integration depends on whether a tool is process- or product-oriented or analytical or experimental. Generally, process-oriented tools, especially complex ones such as OS require active stakeholder involvement and input, but there are also product-oriented tools (such as CSA or SEBA) that rely on the integration of various stakeholders and their knowledge. Analytical tools such as Bowtie or Governance Baselines could in theory be conducted as mere desktop exercises, which would restrict their impact on knowledge integration; if applied as participatory tools they would also make an indirect contribution to stakeholder integration. The mere fact that a tool requires stakeholder involvement does not automatically lead to integration benefits, although involvement is certainly a prerequisite. Especially with respect to process-oriented tools, much depends on the skill of the tool user and the quality of the application process, including for example facilitation skills, timing and resources, also on the part of the participating stakeholders. Much also depends on the quality of the (surrounding) MSP process and whether this is capable of absorbing the benefits that may be generated from tool use. The seven tools are unable to contribute to increasing national/transnational policy coherence and resolving institutional compatibilities, and less well placed to help evaluate the consequences of planned action. Only the most comprehensive process-oriented tool (OS) is able to create a forum for deliberation. A key aspect for applying the seven BALTSPACE tools in practice is to know the precise challenge to be addressed, the capacity of the tool (its potential outcomes) including any soft benefits to be achieved, and the capacity of those using the tool (time, timing, resources). It is also important to consider which role the tool is expected to play in the MSP process: Will it be used as a free-standing, independent entity and process, feeding results into the MSP process? Will it be used as a trigger of the MSP process and “way in” or door-opener, for example to motivate stakeholders? Or is the tool to be intimately linked to the entire MSP process, effectively running large parts of it? Insights and practical tips for using the tools are provided in a separate Tools Handbook which is available for download on the BALTSPACE website (www.baltspace.eu). The website also contains short video tutorials on selected tools, as well as a briefing note and short summary of the opportunities and challenges in using tools to support integration in MSP.
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11.
  • Gee, Kira, et al. (författare)
  • Can tools contribute to integration in MSP? : A comparative review of selected tools and approaches
  • 2019
  • Ingår i: Ocean and Coastal Management. - : Elsevier. - 0964-5691 .- 1873-524X. ; 179, s. 1-11
  • Tidskriftsartikel (refereegranskat)abstract
    • The role of tools and approaches is currently much debated in maritime spatial planning (MSP). Past evaluation has mainly concentrated on decision support tools and the tangible outputs these can provide for MSP, but little attention has so far been been given to the soft or indirect benefits tool use can have in MSP. This paper assesses the potential benefits of tool use in the context of four common integration challenges in MSP. Drawing on case study material from the Baltic Sea region, the paper reviews the potential contribution of five selected tools and approaches to multi-level and transboundary, policy and sector, stakeholder and knowledge integration. Specific end points are defined for each integration challenge, including general desired outcomes of integrated MSP processes as a template for assessment. Our review shows that the selected tools play different roles in moving towards the various end points of MSP integration. There is an important difference between the potential of each tool, or its inherent capacity, and how it is applied, e.g. in a participative or non-participative setting. Another lesson is that some integration benefits can be achieved by the tools alone, while others – often secondary benefits - depend on how the outcomes of tool use are taken up by the subsequent MSP process. Although the nature of a tool does restrict its potential contribution to MSP integration challenges, the secondary “soft” benefits that can be achieved through certain styles of application and good links to the MSP process can add important integration benefits up and beyond the tool itself. The results presented here may also be relevant to other types of spatial planning and conservation management.
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12.
  • Grönqvist, Helena, et al. (författare)
  • Development of smooth pursuit eye movements in very prematurely born infants : 2. The low-risk subgroup.
  • 2011
  • Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 100:7, s. e5-e11
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim:  To investigate the impact of premature birth on visual tracking in a group of 37 infants, born before the 32nd gestational weeks (mean 29 + 6 weeks) and diagnosed as being without major neonatal complications. This paper is a part of the LOVIS study (Strand Brodd, Ewald, Grönqvist, Holmström, Strömberg, Von Hofsten, et al. Acta Pediatrica, 2011). Methods:  At 2 and 4 months corrected age, eye and head movements were measured when the infant tracked a moving object. The eye movements were analysed in terms of smooth pursuit and saccades (Vision Res, 37, 1997, 1799; Exp Brain Res, 146, 2002, 257). Accuracy of gaze, proportion of smooth pursuit, head movements and saccades were calculated. Results:  Between 2 and 4 months of age, all infants improved their ability to smoothly pursue a moving object. However, at both occasions, the preterm infants had less proportion smooth pursuit than the full-term infants. The groups did not differ with respect to gaze and head movements, but the saccade frequency was higher for the very preterms in some of the conditions. Conclusion:  The development of smooth pursuit in the low-risk preterm infant group was strongly delayed compared to typically developed infants. Thus, the 2 months or more extra visual experience did not have a distinguishable positive effect on visuo-motor development as expressed in smooth pursuit.
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13.
  • Grönqvist, Helena, et al. (författare)
  • Reaching strategies of very preterm infants at 8 months corrected age
  • 2011
  • Ingår i: Experimental Brain Research. - : Springer Science and Business Media LLC. - 0014-4819 .- 1432-1106. ; 209:2, s. 225-233
  • Tidskriftsartikel (refereegranskat)abstract
    • Reaching strategies and kinematics for a group of very preterm infants were investigated and compared with a group of full-term infants when reaching for a moving object. Eight-month-old (corrected-age) infants were presented with small toys moving on a semicircular path in the vertical plane. The trajectories of the target and the hands of the infants were measured using a 3D motion analysis system. No differences were found in how often the infants encountered the target. The very preterm group, however, used bimanual strategies more often and had more curved reaching paths than the full-term group. These results suggest that very preterm infants are equally successful as healthy full-term infants in catching a moving object but their reaching strategies are less efficient compared with full-term infants at 8 months (corrected age).
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14.
  • Hassler, Björn, 1964-, et al. (författare)
  • BONUS BALTSPACE: Deliverable 2.7: New generation EU Directives and the role of transnational coordination : Marine Spatial Planning of the Baltic Sea
  • 2018
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • The EU Maritime Spatial Planning Directive (MSP Directive) from 2014 is an example of a so-called new generation directive, which gives Member States room for adaptation to national contexts. Because of this larger room for adaptation, transposition becomes a process of designing domestic policy frameworks that fulfil the broad requirements of the Directive, rather than a simple and linear implementation procedure. However, allowing Member States to design marine spatial planning frameworks that fit domestic contexts, have thus far meant that regional coherence suffers. Although the pivotal role of transnational coordination is emphasised in the Directive, it does not stipulate how to set up such coordination, and the Member States have not yet been able to achieve much of self-organising in this area.A closer look is in this report taken on four policy-dimensions that are emphasised in the MSP Directive: Planning approach, Organisation, Sustainability, and Stakeholder inclusion. Based on in-depth case studies carried out in the BALTSPACE research project on MSP frameworks in Denmark, Germany, Latvia, Lithuania, Poland, and Sweden, examples of coordination and coherency challenges are described and discussed for each dimension.It is shown that planning approaches can differ substantially between neighbouring countries, which can make it challenging to coordinate across country borders. Even though they share the same (EU) regulatory pressures, Latvia and Lithuania, for example, are developing national MSP frameworks based on quite different conceptual foundations. Whereas Latvia has taken the Ecosystem Approach as a point of departure for constructing a new MSP framework, Lithuania has instead chosen to adapt existing functional zoning approaches to management of maritime areas. Such diversity may be possible to explain because of differing domestic contexts, but may nevertheless lead to coordination problems when coordination is needed.Divergence between national MSP frameworks can also emerge from different political, jurisdictional and, administrative systems and traditions, that is, in societal organisation. In an example based on case studies undertaken in Denmark and Sweden, it is shown that degree of societal centralisation and distribution of political power can be related to differences in how environmental protection and blue growth are prioritised. However, it is difficult to tell whether diverging prioritisations have led to differences on organisation, or of it is the other way around, that differences in organisation have led to diverging prioritisations.It is stated in the MSP Directive that the overarching objective is to promote sustainable development. The focus on sustainable development can be said to reflect the Directive’s new generation characteristics. The concept of sustainable development is broad and imprecise, which facilitates political agreement. However, when more precise details must be addressed, disagreements may surface that make implementation challenging. In cases where neighbouring countries diverge substantially on how ecological, economic and social sustainable ought to be balanced, finding agreements on how to coordinate policies and practices, when needed, can be difficult. Based on case studies in Denmark, Latvia, Lithuania, and Sweden, it is, for example, argued that adoption of functional zoning or the Ecosystem Approach may not say much about how ecological, economic, and social dimensions are prioritised in different countries.Stakeholder consultations of some kind have historically been undertaken in all Baltic Sea countries. However, how such consultations have been undertaken, who have been invited, and the role the consultations play in relation to political decision-making differ, as shown in examples from Mecklenburg-Vorpommern and Poland. Because the MSP Directive is silent on how to design stakeholder consultations – it only says that they should be held – there is no political pressure on regional coordination. It is not clear from our data if these differences cause efficiency losses due to coordination deficits, but a reasonable assumption is that when, for example, marine natural resources are shared between two or more countries, jointly designed and undertaken consultations on specific transboundary issues potentially can promote transparency, understanding, and coordination.In conclusion, it is suggested that while regional coherency is often called for as a means to reduce inefficiencies, it might not be a good idea to integrate without discretion. Considering that the MSP Directive allows domestic context to matter when Member States design national MSP frameworks and that adaptation to domestic context is likely to reduce implantation gaps and increase the legitimacy of marine spatial planning, a more reasonable objective can be to embrace domestic diversity, while simultaneously adaptively promoting possibilities to solve coordination problems at lower levels, if they emerge or can be foreseen. From this perspective, increased coherence is a tool to reduce efficiency losses, rather than an intrinsic good.
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15.
  • Hassler, Björn, 1964-, et al. (författare)
  • Collective action and agency in Baltic Sea marine spatial planning: Transnational policy coordination in the promotion of regional coherence
  • 2018
  • Ingår i: Marine Policy. - : Elsevier BV. - 0308-597X .- 1872-9460. ; 92, s. 138-147
  • Tidskriftsartikel (refereegranskat)abstract
    • Despite the increasing attention given to marine spatial planning and the widely acknowledged need for transnational policy coordination, regional coherence has not yet improved a great deal in the Baltic Sea region. Therefore, the main objectives in this article are: (a) to map existing governance structures at all levels that influence how domestic marine spatial planning policy strategies are formed, (b) to identify specific challenges to improved regional cooperation and coordination, and (c) to discuss possible remedies. Based on data from in-depth case studies carried out in the BONUS BALTSPACE research project, it is shown that, despite the shared goal of sustainability and efficient resource use in relevant EU Directives, action plans and other policy instruments, domestic plans are emerging in diverse ways, mainly reflecting varying domestic administrative structures, sectoral interests, political prioritisations, and handling of potentially conflicting policy objectives. A fruitful distinction can be made between, on the one hand, regulatory institutions and structures above the state level where decision-making mechanisms are typically grounded in consensual regimes and, on the other hand, bilateral, issue-specific collaboration, typically between adjacent countries. It is argued that, to improve overall marine spatial planning governance, these two governance components need to be brought together to improve consistency between regional alignment and to enhance opportunities for countries to collaborate at lower levels. Issue-specific transnational working groups or workshops can be one way to identify and act upon such potential synergies. © 2018 The Authors
  •  
16.
  • Hassler, Björn, 1964-, et al. (författare)
  • New generation EU directives, sustainability, and the role of transnationalcoordination in Baltic Sea maritime spatial planning
  • 2019
  • Ingår i: Ocean and Coastal Management. - : Elsevier. - 0964-5691 .- 1873-524X. ; :169, s. 254-263
  • Tidskriftsartikel (refereegranskat)abstract
    • The EU MSP Directive is an example of a so-called new generation directive, which gives Member States room foradaptation to national contexts. The main objective in this article is to identify and analyse potential obstacles toeffective and efficient planning caused by the diversity among national MSP frameworks that the Directive'sbroad regulatory boundaries have led to. It is shown that planning approaches can differ substantially betweenneighbouring countries, which can make it challenging to coordinate across national borders. Divergence betweennational MSP frameworks can also emerge from how political, jurisdictional and, administrative systemsand traditions are organised in different Member States. It is shown that neighbouring countries can divergesubstantially in how the ecological, economic and social dimensions of sustainability are balanced, which canmake transnational coordination challenging. Furthermore, it is shown that stakeholder consultations differamong Member States in terms of, for example, who were invited, how the consultations were undertaken, andthe role they play in relation to political decision-making. Because of these, and other differences in how MSPframeworks are being developed in the Member States, it is suggested that regional integration should bepromoted with discretion. From this perspective, it seems reasonable to embrace diversity, while simultaneouslypromoting the adaptive management of coordination problems at lower levels, when, or if, they emerge or canbe foreseen. Thus, increased integration of national MSP frameworks should be viewed as an instrument toreduce concrete efficiency losses, rather than as an intrinsic good.
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17.
  • Hreinsdottir, Jonina, et al. (författare)
  • Ophthalmological outcome and visuospatial ability in very preterm children measured at 2.5 years corrected age
  • 2013
  • Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 102:12, s. 1144-1149
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim To investigate the ophthalmological outcome of very preterm children at 2.5 years corrected age (CA) and perform a test of visuospatial and cognitive abilities. Methods A population-based, prospective study (LOVIS study) in Uppsala County, Sweden, comprised 111 very preterm children (<32 w gestational age [GA]) born between 1 January 2004 and 31 December 2007. Ophthalmic evaluations were undertaken in 98/109 children (89.9%) alive at 2.5 years. Spatial cognition was investigated with a test of five alternative blocks in 48 preterm and 25 term-born children. Results Visual impairment, strabismus or refractive errors, were found in 12% of the children. None of the children were blind in both eyes. Logistic regression analyses revealed significant associations between strabismus and periventricular leucomalacia/ intraventricular haemorrhage (OR 9.6, p = 0.025) and between refractive errors and severe retinopathy of prematurity (OR 9.8, p = 0.011) and GA (OR 0.763, p = 0.034). Oval and rectangular blocks were significantly more difficult to insert into a box for preterm than full-term children (p = 0.048 and 0.013, respectively). There was a significant correlation between total scores for the five blocks and GA at birth (p = 0.035). Conclusion Eye and visual problems were found in 12% of the preterm children at 30 months CA. Preterm children had difficulties with blocks of complex shapes. ©2013 Foundation Acta Pædiatrica. Published by John Wiley & Sons Ltd.
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18.
  • Kaul, Ylva Fredriksson, et al. (författare)
  • Reaching skills of infants born very preterm predict neurodevelopment at 2.5 years
  • 2019
  • Ingår i: Infant Behavior and Development. - : Elsevier. - 0163-6383 .- 1879-0453. ; 57
  • Tidskriftsartikel (refereegranskat)abstract
    • The purpose was to investigate associations between quality of reaching for moving objects at 8 months corrected age and neurodevelopment at 2.5 years in children born very preterm (gestational age (GA), 24–31 weeks). Thirtysix infants were assessed while reaching for moving objects. The movements were recorded by a 3D motion capture system. Reaching parameters included aiming, relative length of the reach, number of movement units, proportion of bimanual coupled reaches and number of hits. Neurodevelopment was assessed at 2.5 years by the Bayley Scales of Infant Development III. There were strong associations between infant reaching kinematics and neurodevelopment of cognition and language but the patterns differed: in children born extremely preterm (GA < 28 weeks), planning and control of reaching was strongly related to outcome, while in children born very preterm (GA 28–31 weeks) number of hits and bimanual strategies were of greater relevance. In conclusion, for extremely preterm infants, basic problems on how motion information is incorporated with action planning prevail, while in very preterm infants the coordination of bimanual reaches is more at the focus. We conclude that the results reflect GA related differences in neural vulnerability and that early motor coordination deficits have a cascading effect on neurodevelopment.
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19.
  • Kristensson Hallström, Inger, et al. (författare)
  • eHealth as an Aid for Facilitating and Supporting Self-Management in Families with Long-Term Childhood Illness; Development, Evaluation, and Implementation in Clinical Practice
  • 2023
  • Ingår i: Clinical Health Promotion - Research and Best Practice for patients, staff and community. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction eHealth, defined by WHO as: “the transfer of health resources and healthcare by electronic means” are expected to increase communication between healthcare providers and patients and increase accessibility and patient participation in healthcare. The aim of this research programme is to: 1) develop a sustainable multidisciplinary environment for advancing, evaluating, and implementing models of eHealth to promote self-management for children and their families, and 2) increase the present knowledge of clinical and economic cost-effectiveness of eHealth as an aid for supporting self-management in families with long-term childhood illness. Method The research is performed in Sweden, Denmark, and Ethiopia and organized in three research domains: eHealth to enable and promote self-management in advanced paediatric care, eHealth for early diagnosis and treatment in paediatric care, and Co-Creation of multidisciplinary knowledge for the translation of eHealth in practice. The research follows a framework for developing and evaluating complex interventions in healthcare. Through participatory design family members and care providers participate throughout the research process. Quantitative and qualitative data as well as health economics are collected in six clinical areas. Five general areas are run transversal. Results and conclusion Evidence-based best practices in developing and evaluating eHealth in paediatric healthcare will be suggested. As implementation is part of the programme, cost-effective eHealth directly benefiting families and healthcare services will be guaranteed.
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20.
  • Li, Yutang, et al. (författare)
  • Enantiotopic Discrimination by Coordination-Desymmetrized meso-Ligands
  • 2020
  • Ingår i: ChemCatChem. - : Wiley. - 1867-3880 .- 1867-3899. ; 12:6, s. 1575-1579
  • Tidskriftsartikel (refereegranskat)abstract
    • The first examples of enantiopure catalysts that are chiral merely due to coordination of different metal ions at enantiotopic positions of an achiral meso-ligand are reported. These catalysts exhibit a pseudo-Cs symmetry and are able to catalyze reactions demanding simultaneous involvement of two catalytic sites. The latter was demonstrated by application in the asymmetric ring-opening of meso-epoxides.
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21.
  • Lloyd-Spets, Anita, et al. (författare)
  • New materials for chemical and biosensors
  • 2006
  • Ingår i: Materials and Manufacturing Processes. - : Informa UK Limited. - 1042-6914 .- 1532-2475. ; 21:3, s. 253-256
  • Tidskriftsartikel (refereegranskat)abstract
    • Wide band gap materials such as SiC, AlN, GaN, ZnO, and diamond have excellent properties such as high operation temperature when used as field effect devices and a high resonating frequency of the substrate materials used in piezoelectric resonator devices. Integration of FET and resonating sensors on the same chip enables powerful miniaturized devices, which can deliver increased information about a gas mixture or complex liquid. Examples of sensor devices based on different wide band gap materials will be given.
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22.
  • Morf, Andrea, 1968, et al. (författare)
  • Addressing integration challenges in coastal and marine spatial planning using the Open Standards approach – experiences from Sweden.
  • 2018
  • Ingår i: ICES Annual Science Conference (ASC 2018), Session C: Assessing and analysing marine spatial planning - knowledge - indicators – visions. - Hamburg.
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • This presentation reports results from the BONUS financed project BaltSapce and explores how and to what extent the approach of the Open Standards for the Practice of Conservation (OS) (http://cmp-openstandards.org/) could support coastal and marine spatial planning in addressing important integration challenges, i.e. how to include stakeholders and different types of knowledge and link across sectors and policy areas and different boundaries. Our research is part of a broader analysis of integrative tools and approaches within the BONUS project BALTSPACE; it is based on literature and document analysis, 15 interviews with key informants holding various roles in recent OS-supported coastal planning and management processes in Sweden, and on a discussion workshop and direct contacts with the above experts and further OS-facilitators and planners. We find that the OS indeed can help working on complex planning problems with uncertainties and value differences and address the above challenges, especially if used in combination with broad participation. The conceptual model underlying the OS can help planners to more systematically think goal and evaluation oriented, creating a base for learning within and across planning processes. The OS are most easily applicable for marine and coastal planning, which aim to incorporate adaptive management and work with an ecosystem perspective (especially green-blue areas, habitats and living resources) or for integrated planning and management aiming to use the CBD-Ecosystem Approach (https://www.cbd.int/ecosystem/). However, an initial effort is needed in terms of time, resources, method training and capacity building. Moreover, all affected parts with a mandate have to be on board and ready to give an effort. We end discussing the potentials and needs to develop the field of integrative marine and coastal management knowledge and practice further in terms of standards, definitions, training, and community of practice, using the type of practice and community developed around the OS for the practice of conservation as an inspiration.
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23.
  • Morf, Andrea, 1968, et al. (författare)
  • Towards sustainability of marine governance: Challenges and enablers for stakeholder integration in transboundary marine spatial planning in the Baltic Sea
  • 2019
  • Ingår i: Ocean & Coastal Management. - : Elsevier BV. - 0964-5691. ; 177, s. 200-212
  • Tidskriftsartikel (refereegranskat)abstract
    • Integrating stakeholder knowledge, views and needs in marine or maritime spatial planning (MSP) processes is important from a governance and social sustainability perspective both for MSP practitioners and for the evolving field of MSP research. Transboundary MSP appears particularly challenging for participation, which is why it is important to identify opportunities and address obstacles for stakeholder integration in this specific context. This article examines how stakeholder integration is currently practiced in the Baltic Sea Region (BSR), an enclosed sea where policy coherence and addressing conflicting interests across borders are especially relevant. It synthesises a range of challenges and enablers for stakeholder participation and mobilisation that have emerged from two transboundary MSP research and development projects, BaltSpace and Baltic SCOPE. The article finds that with the exception of statutory authorities, stakeholder engagement in the BSR is mostly limited to self-motivated stakeholders and consultation rather than more inclusive forms of participation. This can reduce the quality and legitimacy of MSP processes and risks to concentrate power in the hands of a small group of actors. For transboundary stakeholder integration to become more interactive and effective, five types of challenges need attention, regarding a) timing, b) governance systems, c) capacity and processes, d) stakeholder characteristics and e) knowledge and language. These obstacles can be addressed by (1) a dedicated research and development agenda that critically reflects on integrative tools and processes, and (2) by encouraging transnational institutions in the BSR to devote more resources to transboundary stakeholder integration and adopt flexible and adaptive strategies and tools that can facilitate stakeholder involvement throughout the MSP policy cycle.
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24.
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25.
  • Saunders, Fred P., et al. (författare)
  • BALTSPACE Deliverable: D1.2 : Final Guidance Document on Analysing Possibilities and Challenges for MSP Integration
  • 2016
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • This report makes a case for examining the role of integration and its links to how sustainable development is variably expressed in different marine spatial planning (MSP) contexts. The aim of the report is to refine an analytical approach to examine integration in MSP in the Baltic Sea through consideration of preliminary empirical results from a broad range of case studies. MSP is conceptualised here as a governance platform for improving processes to enable political decision-making with the aim to achieve sustainable development of marine space. Integration is universally espoused as a means to address a variety of challenges closely related to MSP’s sustainable development ambitions, such as supporting inter-sectoral decision-making, stakeholder engagement and cross-border interaction, but its role, value and implementation in MSP has not been examined in any empirical detail. Although increased integration may well have positive effects on MSP processes and outcomes, in some instances, the contrary might also be the case. With these thoughts in mind, this report argues that we need to analyse integration as a multidimensional concept in MSP processes and outcomes. Based on understandings of integration derived from MSP experience and concepts in the broader social science literature, an analytical framework is developed to examine MSP practice in the Baltic Sea. Integration is conceptualised as including transboundary/cross-border, policy/sectoral, stakeholder and knowledge dimensions. Despite common requirements under the European Union MSP Directive and policies, national jurisdictions are likely to adopt MSP differently, which has implications for the role integration is likely to play in national and transnational MSP practice. Drawing on empirical data derived from national MSP studies, stakeholder dialogue forums and preliminary interviews with stakeholders the analytical framework is applied to examine how particular integration challenges play out in both national and transnational marine space across the Baltic Sea Region. The analytical framework is then used to structure an examination of several case studies from different parts of the Baltic Sea Region. Based on consideration of the empirical work and an analyses of previous experiences in science and practice we then propose some revisions to the initial analytical framework presented earlier. The revised analytical framework, while capturing the integration dimensions mentioned earlier, also includes consideration of the following aspects of integration: how ‘balance’ between sustainable development dimensions is exercised; the character of cross-boundary interactions; and temporal dynamics. Instead of a conclusion, short think-pieces are presented to capture the main insights of the report, which could be used to aid the examination of integration in MSP in other MSP contexts, beyond the Baltic Sea.
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26.
  • Selander, Helena, 1975-, et al. (författare)
  • Ready for a Learner's Permit? Clinical Neuropsychological Off-road Tests and Driving Behaviors in a Simulator among Adolescents with ADHD and ASD.
  • 2021
  • Ingår i: Developmental Neurorehabilitation. - : Informa UK Limited. - 1751-8423 .- 1751-8431. ; 24:4, s. 256-265
  • Tidskriftsartikel (refereegranskat)abstract
    • A simulator driving test (SDT) and two neuropsychological tests, the Useful Field of View (UFOV) test and the Test of Variables of Attention (TOVA) were evaluated with regard to validity for fitness to drive on 51 young clients diagnosed with attention deficit hyperactivity disorder (ADHD), 33 of whom also had autism spectrum disorder (ASD), and 38 adolescents without a neurodevelopmental diagnosis. The results show generally much greater variability and significantly poorer performance in the SDT and the TOVA for clients with ADHD/ASD compared with the control group. The SDT results were strongly intratest correlated, but had no interest correlation with either the UFOV test or the TOVA. The greater variability among clients with ADHD/ASD suggests greater effort and susceptibility to motivational issues and decline in sustained attention over several tests. In conclusion, the SDT is sensitive and has good face validity, and the TOVA is sensitive to neuropsychological aspects of safe driving. The SDT and the TOVA thus complement each other, and discrepancy between test scores calls for special consideration.
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27.
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28.
  • Strand, Helena, et al. (författare)
  • Etablera och utveckla vattenbruk i Sverige: Vattenbruksentreprenörers syn på utmaningar och lösningar.
  • 2018
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • Den här rapporten redovisar resultaten från en studie genomförd av SWEMARC, the Swedish mariculture research center, som är ett forskningscentrum för vattenbruk vid Göteborgs universitet. Studiens syfte har varit att synliggöra viktiga frågor eller problem som svenska vattenbruksentreprenörer upplever och ställs inför i sina ambitioner att starta upp, driva eller utveckla sitt vattenbruk, men också vilka behov av stöd som finns för att övervinna dem. Utgångspunkt för studien har varit att följa upp en enkät genomförd av SWEMARC i samband med en utbildning/kurs i januari 2017 på temat ”Hur startar man en vattenbruksverksamhet – fokus på tillstånd och miljöfrågor”, där en grupp vattenbruksentreprenörer fick svara på ett antal frågor gällande sina planer på att etablera eller expandera sitt vattenbruk. Genom semistrukturerade intervjuer har vi nu, ett år senare, följt upp entreprenörernas arbete med sina verksamheter med fokus på tillstånd och tillståndsprocesser; vilka viktiga frågor och problem har man stött på och hur man löst problemen? Om inte, vilka möjliga lösningar finns? Resultaten från studien visar att majoriteten av entreprenörerna arbetat aktivt för att driva vidare och genomföra sina planer på att etablera eller utöka sina vattenbruksanläggningar, dock med olika resultat och framgång. I detta sammanhang kan konstateras att etablering och utveckling av vattenbruk i Sverige tar tid. Kopplat till entreprenörernas arbete under det gångna året, men också utifrån tidigare erfarenheter, utkristalliseras en rad frågor och problem som innefattar: placering, kontakt med myndigheter och tillståndskrav samt att ett flertal tillstånd också är tidsbegränsade, utökning av vattenbruksverksamheten och behovet av tydliga besked, förlegad lagstiftning, möjligheten att söka bidrag, handläggningstider, skillnader i tolkningar och bedömningar men även bristande kunskap om vattenbruk. Utifrån detta beskrivs också vad entreprenörerna ser för behov för att övervinna problemen eller hur vissa frågor skulle kunna lösas, vilket bl.a. inkluderar tydligare platshänvisningar och tillgänglighet till information och data. Vidare skulle arbetet med tillståndsansökningar och kontakten med, men även samordning mellan myndigheter kunna förenklas om ansvar för vattenbruket fanns samlat hos en och samma myndighet. En viktig förutsättning för entreprenörerna är också att öka förutsägbarheten och tydligheten när det gäller exempelvis frågor kring etablering eller utökning av verksamheten. En central fråga kan då vara att höja kunskapsnivå och kompetens kring vattenbruk inom myndigheter. Det kan även vara att vattenbruksnäringens mångfald bättre speglas i regelverken, vilka behöver ses över så att bättre hänsyn tas till dagens teknik och behov. Studien belyser en rad viktiga frågor och behov att hantera för att möjliggöra utveckling av svenskt vattenbruk utifrån entreprenörers perspektiv och erfarenheter. Flertalet av teman som framkommit skiljer sig inte nämnvärt från utmaningar som tidigare diskuterats inom sektorn, vilket understryker behovet av fortsatt förändringsarbete men även ytterligare insatser och åtgärder.
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29.
  • Strand, Tanja, 1978- (författare)
  • European Black Grouse : MHC Genetic Diversity and Population Structure
  • 2011
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Black grouse Tetrao tetrix is a bird species composed of large, continuous as well as severely reduced and fragmented populations, making it an optimal species to investigate how genetic diversity is affected by habitat fragmentation. I have focused on genetic diversity in the Major Histocompatibility Complex (MHC) to measure the ability of the black grouse to respond to environmental changes.I partly characterized MHC class II in black grouse and found striking similarities with chicken MHC class II. I demonstrated that black grouse possess a similar compact MHC as chicken with few MHC class II B (BLB) and Y (YLB) loci. I did not find evidence of balancing selection in YLB so I concentrated further studies on BLB.I developed a PCR-based screening method for amplifying and separating expressed BLB alleles in European black grouse populations. Small fragmented populations had lost neutral genetic diversity (based on microsatellites and SNPs) compared to samples from the historical distribution and contemporary large populations. There was also a trend, albeit less pronounced, for reduced MHC diversity in these populations. Neutral markers in small isolated populations were affected by increased levels of genetic drift and were therefore genetically differentiated compared to other populations. MHC markers on the other hand, were not subjected to genetic drift to the same extent probably due a long historic process of balancing selection.Inferences of heterozygosity and evolutionary patterns as well as detailed correlations to reproductive success and diseases cannot be performed until MHC can be amplified in a locus-specific manner. Therefore, I developed a single locus sequence-based typing method for independently amplifying MHC class II B loci (BLB1 and BLB2). I found that BLB1 and BLB2 were duplicated in a common ancestor to chickens and black grouse and that these loci are subjected to homogenizing concerted evolution due to inter-genetic exchange between loci after species divergence.  I could also verify that both BLB1 and BLB2 were transcribed in black grouse and under balancing selection.This collection of work has significance for future conservation of black grouse as well as research and management of zoonotic diseases.
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30.
  • Strand, Tanja, et al. (författare)
  • The MHC class II of the Black grouse (Tetrao tetrix) consists of low numbers of B and Y genes with variable diversity and expression
  • 2007
  • Ingår i: Immunogenetics. - : Springer Science and Business Media LLC. - 0093-7711 .- 1432-1211. ; 59:9, s. 725-734
  • Tidskriftsartikel (refereegranskat)abstract
    • We found that the Black grouse (Tetrao tetrix) possess low numbers of Mhc class II B (BLB) and Y (YLB) genes with variable diversity and expression. We have therefore shown, for the first time, that another bird species (in this case, a wild lek-breeding galliform) shares several features of the simple Mhc of the domestic chicken (Gallus gallus). The Black grouse BLB genes showed the same level of polymorphism that has been reported in chicken, and we also found indications of balancing selection in the peptide-binding regions. The YLB genes were less variable than the BLB genes, also in accordance with earlier studies in chicken, although their functional significance still remains obscure. We hypothesize that the YLB genes could have been under purifying selection, just as the mammal Mhc-E gene cluster.
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31.
  • Unnerstad, Helle Ericsson, et al. (författare)
  • Suspected transmission and subsequent spread of MRSA from farmer to dairy cows
  • 2018
  • Ingår i: Veterinary Microbiology. - : Elsevier. - 0378-1135 .- 1873-2542. ; 225, s. 114-119
  • Tidskriftsartikel (refereegranskat)abstract
    • In the present study we describe an outbreak where PVL positive MRSA belonging to spa-type t002 and multi-locus sequence type ST2659 persisted in a Swedish dairy herd for at least two years, despite efforts to hinder transmission between animals and between the farmer and his animals. This is the first description of persistence and spread of MRSA in a dairy herd in Sweden. Sampling of animals in the herd was initiated by the finding of MRSA in the farmer and was performed at eight occasions from November 2012 to September 2014. In total, MRSA was detected in 25 animals and in 16 of these MRSA was detected in milk samples. In addition, MRSA was also detected in bulk milk samples. Whole genome sequencing (WGS) of twelve isolates from farmer (n = 1), animals (n = 9) and bulk milk (n = 2) revealed high relatedness, implying a common source. MRSA may initially have been transmitted from humans to cows with further spread within the herd. WGS showed minor differences in one isolate (loss of phage ΦN315) which could indicate adaption of the strain to an animal host.
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