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1.
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2.
  • Enroth, Stefan, et al. (författare)
  • Effects of Long-Term Storage Time and Original Sampling Month on Biobank Plasma Protein Concentrations
  • 2016
  • Ingår i: EBioMedicine. - 2352-3964. ; 12, s. 309-314
  • Tidskriftsartikel (refereegranskat)abstract
    • The quality of clinical biobank samples is crucial to their value for life sciences research. A number of factors related to the collection and storage of samples may affect the biomolecular composition. We have studied the effect of long-time freezer storage, chronological age at sampling, season and month of the year and on the abundance levels of 108 proteins in 380 plasma samples collected from 106 Swedish women. Storage time affected 18 proteins and explained 4.8–34.9% of the observed variance. Chronological age at sample collection after adjustment for storage-time affected 70 proteins and explained 1.1–33.5% of the variance. Seasonal variation had an effect on 15 proteins and month (number of sun hours) affected 36 proteins and explained up to 4.5% of the variance after adjustment for storage-time and age. The results show that freezer storage time and collection date (month and season) exerted similar effect sizes as age on the protein abundance levels. This implies that information on the sample handling history, in particular storage time, should be regarded as equally prominent covariates as age or gender and need to be included in epidemiological studies involving protein levels.
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3.
  • Matar, Amal (författare)
  • Considering a Baby? Responsible Screening for the Future : Ethical and social implications for implementation and use of preconception expanded carrier screening in Sweden
  • 2019
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • Preconception expanded carrier screening is a novel technology that involves the offer of a screening test for many recessive diseases (via an expanded screening panel) to prospective parents, with no priori risk. Test positive couples have a number of reproductive choices; prenatal diagnosis and aborting affected fetus, IVF and preimplantation genetic diagnosis, sperm or ovum donation or simply accept the risk. The test had been piloted in studies and can potentially be implemented in Europe. Therefore, it seemed pertinent to evaluate stakeholders’ perspectives on ethical and social implications of implementing and using preconception ECS in Sweden.Two main stakeholders were examined; healthcare professionals and health policymaking experts, via a mix of qualitative methods for data collection and data analysis. In Study I, we employed in-depth interviews to collect data and content analysis to analyze it. In Studies III and IV, expert interviews were used to gather data while thematic analysis was utilized to interpret it. Furthermore, in Study II, an ethical concept namely; reproductive autonomy, was critically discussed within a setting that expects a couple to make a conjoint reproductive decision about preconception ECS, while each partner still upholds his or her individual autonomy.The main findings of the empirical studies (Studies I, III and IV) echo to a great extent the prevailing ethical and social debates associated with the novel technology. Respondents expressed concerns with reproductive autonomy, medicalization, prioritization of health resources, discrimination and long term societal changes. Furthermore, respondents emphasized the importance to observe Swedish values, such as human dignity, equality and solidarity, when assessing a preconception ECS program. In addition, they described practicalities of implementation and political considerations that are pertinent to the Swedish context. Finally, some respondents recognized the advantages of reduced suffering and decrease in fetal anomalies and abortion as a consequence of preconception ECS.Study II, proposed a notion of couple autonomy, where certain demands if met, a couple’s reproductive decision can be accepted by healthcare staff as autonomous.The findings, in this thesis, steer towards non implementation of preconception ECS in its current status within the publicly-funded healthcare system in Sweden. This is because healthcare providers and experts were of the opinion that it would not solve a medical need, threaten Swedish values and use up resources extensively.
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4.
  • Petzold, Martin, et al. (författare)
  • Towards an Ambient Assisted Living User Interaction Taxonomy
  • 2013
  • Ingår i: CHI '13 Extended Abstracts of the ACM International Conference on Human Factors in Computing Systems. - New York : ACM Press. - 9781450318990 ; , s. 49-54
  • Konferensbidrag (refereegranskat)abstract
    • Extensive research in the field of ambient assisted living (AAL) provides profound knowledge about the design of AAL systems. However, more generic design characteristics for user interaction have not been formalized for this domain yet. Thus, we propose to develop a domain specific taxonomy for the design of user interaction in AAL systems. We adopted a systematic taxonomy development approach that combines an empirical and a pseudo-conceptual strategy. Six co-researchers from different disciplines conduct the iterative research process. Next to AAL systems existing taxonomies in the field of human-computer interaction are analyzed following the Delphi method. In this paper we present our research process and preliminary results from the first iteration. The final taxonomy allows classification and should support the analysis of user interaction utilized in AAL systems. Furthermore, it can deal as a practical design guideline.
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5.
  • Ahonen, Linda, et al. (författare)
  • Targeted Clinical Metabolite Profiling Platform for the Stratification of Diabetic Patients
  • 2019
  • Ingår i: Metabolites. - : MDPI. - 2218-1989 .- 2218-1989. ; 9:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Several small molecule biomarkers have been reported in the literature for prediction and diagnosis of (pre)diabetes, its co-morbidities, and complications. Here, we report the development and validation of a novel, quantitative method for the determination of a selected panel of 34 metabolite biomarkers from human plasma. We selected a panel of metabolites indicative of various clinically-relevant pathogenic stages of diabetes. We combined these candidate biomarkers into a single ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method and optimized it, prioritizing simplicity of sample preparation and time needed for analysis, enabling high-throughput analysis in clinical laboratory settings. We validated the method in terms of limits of detection (LOD) and quantitation (LOQ), linearity (R2), and intra- and inter-day repeatability of each metabolite. The method's performance was demonstrated in the analysis of selected samples from a diabetes cohort study. Metabolite levels were associated with clinical measurements and kidney complications in type 1 diabetes (T1D) patients. Specifically, both amino acids and amino acid-related analytes, as well as specific bile acids, were associated with macro-albuminuria. Additionally, specific bile acids were associated with glycemic control, anti-hypertensive medication, statin medication, and clinical lipid measurements. The developed analytical method is suitable for robust determination of selected plasma metabolites in the diabetes clinic.
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7.
  • Alrifaiy, Ahmed, et al. (författare)
  • A lab-on-a-chip for hypoxic patch clamp measurements combined with optical tweezers and spectroscopy- first investigations of single biological cells
  • 2015
  • Ingår i: Biomedical engineering online. - 1475-925X. ; 14:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The response and the reaction of the brain system to hypoxia is a vital research subject that requires special instrumentation. With this research subject in focus, a new multifunctional lab-on-a-chip (LOC) system with control over the oxygen content for studies on biological cells was developed. The chip was designed to incorporate the patch clamp technique, optical tweezers and absorption spectroscopy. The performance of the LOC was tested by a series of experiments. The oxygen content within the channels of the LOC was monitored by an oxygen sensor and verified by simultaneously studying the oxygenation state of chicken red blood cells (RBCs) with absorption spectra. The chicken RBCs were manipulated optically and steered in three dimensions towards a patch-clamp micropipette in a closed microfluidic channel. The oxygen level within the channels could be changed from a normoxic value of 18% O 2 to an anoxic value of 0.0-0.5% O 2. A time series of 3 experiments were performed, showing that the spectral transfer from the oxygenated to the deoxygenated state occurred after about 227 ± 1 s and a fully developed deoxygenated spectrum was observed after 298 ± 1 s, a mean value of 3 experiments. The tightness of the chamber to oxygen diffusion was verified by stopping the flow into the channel system while continuously recording absorption spectra showing an unchanged deoxygenated state during 5400 ± 2 s. A transfer of the oxygenated absorption spectra was achieved after 426 ± 1 s when exposing the cell to normoxic buffer. This showed the long time viability of the investigated cells. Successful patching and sealing were established on a trapped RBC and the whole-cell access (Ra) and membrane (Rm) resistances were measured to be 5.033 ± 0.412 M Ω and 889.7 ± 1.74 M Ω respectively. © Alrifaiy et al.; licensee BioMed Central Ltd.
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8.
  • Arndt, Anton, 1968-, et al. (författare)
  • The effect of a midfoot cut in the outer sole of a shoe on intrinsic foot kinematics during walking.
  • 2013
  • Ingår i: Footwear Science. - 1942-4280. ; 5:1, s. 63-69
  • Tidskriftsartikel (refereegranskat)abstract
    • Modifications in shoe outer soles are frequently made with the intention of altering biomechanics of the foot inside the shoe. These modifications are however, generally based upon intuition with little or no scientific data for support. The purpose of this study was to quantify changes in intrinsic foot segmental kinematics between walking in a neutral shoe and a shoe modified with a clear cut forming a break underneath the midfoot, approximating the Lisfrancs joint.Five healthy male subjects participated in the study. Intracortical pins were inserted under sterile conditions and local anaesthetic in nine different bones of the foot and shank. The subjects performed 10 walking trials in both a neutral, standard, flatsoled, flexible walking shoe and in the same shoe with an approximately 1 cm deep cut aligned with the subjects’ Lisfrancs joint. Material tests showed that the cut reduced midfoot shoe bending stiffness by 23% to 38% and torsional stiffness by 23% to 28%. A helical axis approach was applied for calculating the 3D rotations about relevant joints.Kinematic trajectories in the sagittal, frontal, and transverse planes were normalised to the stance phase for seven selected joints to compare rotation patterns when wearing the two shoe conditions. Although one out of 21 ranges of motion (ROM) showed a significant difference, there is strong reason to regard this as the result of a type 1 error. Apart from this no differences in ROM occurred between the shoe conditions.The low subject number reduced the statistical power of the results. However, the study indicated that outer sole modifications that may be assumed to have clear effects upon foot kinematics, do not necessarily do so.
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10.
  • Bass, Tarek (författare)
  • Affibody molecules targeting HER3 for cancer therapy
  • 2017
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • The development of targeted therapy has contributed tremendously to the treatment of patients with cancer. The use of highly specific affinity proteins to target cancer cells has become a standard in treatment strategies for several different cancers. In light of this, many cancer cell markers are investigated for their potential use in diagnostics and therapy. One such marker is the human epidermal growth factor receptor 3, HER3. It has been established as an important contributor to many cancer types. The function of HER3 is to relay cell growth signals from outside of the cell to the inside. Interfering with- and inhibit- ing the function of HER3 has emerged as an interesting strategy for cancer therapeutics. The studies presented in this thesis aim to target HER3 with small, engineered affinity domain proteins for therapeutic purposes. Monomeric affibody molecules have previously been engineered to bind and inhibit HER3 in vitro. Due to the relatively low expression of HER3, an increase in valency appears promising to strengthen the therapeutic potential. Affibody molecules targeting the receptor were thus linked to form bivalent and bispecific constructs and evaluated both in vitro and in vivo. In the first study of this thesis affibody molecules specific for HER3 and HER2 were fused to an albumin binding domain to form bivalent and bispecific construct. The constructs inhibited ligand-induced receptor phos- phorylation of both HER2 and HER3 more efficiently than monomeric affibody molecules. A second approach to enhance the potential of affibody molecules in tumor targeting is described in the second study, where monomeric HER3-binding affibody molecules were engineered to increase their affinity for HER3. The resulting variants showed a 20-fold in- creased affinity and higher capacity to inhibit cancer cell growth. Combining the findings of the first two studies, the third study describes the evaluation of a HER3-targeting bivalent affibody construct for potential application as a therapeutic. Here, the bivalent construct inhibited cancer cell growth in vitro and was found to slow down tumor growth in mice, while being well tolerated and showing no visible toxicity. The fourth study built upon these findings and compares a very similar bivalent construct to the clinically-investigated HER3-specific monoclonal antibody seribantumab. The affibody construct showed very comparable efficacy with the antibody in terms of decreasing tumor growth rate and ex- tending mouse survival. Collectively, these works describe for the first time the use of alternative affinity protein constructs with therapeutic potential targeting HER3.
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