| 1. |
- Ashman Kröönström, Linda, 1982, et al.
(författare)
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Muscle function in adults with congenital heart disease
- 2014
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273. ; 170:3, s. 358-363
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The aim was to assess muscle function in a sample of Swedish adult men and women with congenital heart disease (ACHD) and to compare the results with published reference values in healthy adults. METHODS AND RESULTS: From April 2009 to December 2010, 762 adult outpatients were assessed for their suitability and individual need for tests of physical fitness. The patients performed five muscle function tests, two isotonic tests and three isometric tests. Of the 762 patients, 315 (41.3%) patients performed the tests. Patients with ACHD had lower isotonic muscle function compared to healthy reference values. In the heel lift test, men with ACHD performed at 63% and women at 58% of the healthy reference values and in the shoulder flexion test the corresponding performance level was 60% for men with ACHD and 85% for the women. Multiple regression analyses showed that NYHA class II-IV was a significant predictor for a lower isotonic muscle function i.e. heel lift in women (p<0.001) and men (p=0.05) and in shoulder flexion (p<0.001) in women, as well as in isometric knee extension (p=0.04) and isometric shoulder abduction (p<0.001) in women. CONCLUSION: This is the first report of muscle function in a broad and unselected group of patients with ACHD. Our data shows that patients with ACHD have lower isotonic muscle function. The impacts of low muscle function in activities of daily living and the question of whether muscle function could be improved with exercise training need further investigation.
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| 2. |
- Gad, Helge, et al.
(författare)
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MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool
- 2014
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 508:7495, s. 215-221
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Tidskriftsartikel (refereegranskat)abstract
- Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bindin the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.
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| 3. |
- Johansson, Linda, et al.
(författare)
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Surface acoustic wave induced particle manipulation in a PDMS channel : principle concepts for continuous flow applications
- 2012
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Ingår i: Biomedical microdevices (Print). - : Springer Science and Business Media LLC. - 1387-2176 .- 1572-8781. ; 14:2, s. 279-289
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Tidskriftsartikel (refereegranskat)abstract
- A device for acoustic particle manipulation in the40 MHz range for continuous-flow operation in a 50 μm wide PDMS channel has been evaluated. Unidirectionalinterdigital transducers on a Y-cut Z-propagation lithiumniobate wafer were used to excite a surface acoustic wavethat generated an acoustic standing wave inside the microfluidicchannel. It was shown that particle alignment nodeswith different inter-node spacing could be obtained,depending on device design and driving frequency. Theobserved inter-node spacing differed from the standard halfwavelengthinter-node spacing generally employed in bulkacoustic transducer excited resonant systems. This effectand the related issue of acoustic node positions relative thechannel walls, which is fundamental for most continuousflow particle manipulation operations in channels, wasevaluated in measurements and simulations. Specificapplications of particle separation and alignment wherethese systems can offer benefits relative state-of the artdesigns were identified.
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| 4. |
- Johansson, Linda, et al.
(författare)
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Surface acoustic wave-induced precise particle manipulation in a trapezoidal glass microfluidic channel
- 2012
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Ingår i: Journal of Micromechanics and Microengineering. - : IOP Publishing. - 0960-1317 .- 1361-6439. ; 22:2, s. 025018-
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Tidskriftsartikel (refereegranskat)abstract
- Surface acoustic wave (SAW) excitation of an acoustic field in a trapezoidal glass microfluidic channel for particle manipulation in continuous flow has been demonstrated. A unidirectional interdigital transducer (IDT) on a Y-cut Z-propagation lithium niobate (LiNbO3) substrate was used to excite a surface acoustic wave at approximately 35 MHz. An SU8 layer was used for adhesive bonding of the superstrate glass layer and the substrate piezoelectric layer. This work extends the use of SAWs for acoustic manipulation to also include glass channels in addition to prior work with mainly poly-di-methyl-siloxane channels. Efficient alignment of 1.9 mu m polystyrene particles to narrow nodal regions was successfully demonstrated. In addition, particle alignment with only one IDT active was realized. A finite element method simulation was used to visualize the acoustic field generated in the channel and the possibility of 2D alignment into small nodal regions was demonstrated.
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| 5. |
- Johansson, Linda, et al.
(författare)
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Temperature and trapping characterization of an acoustic trap with miniaturized integrated transducers - towards in-trap temperature regulation
- 2013
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Ingår i: Ultrasonics. - : Elsevier BV. - 0041-624X .- 1874-9968. ; 53:5, s. 1020-1032
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Tidskriftsartikel (refereegranskat)abstract
- An acoustic trap with miniaturized integrated transducers (MITs) for applications in non-contact trapping of cells or particles in a microfluidic channel was characterized by measuring the temperature increase and trapping strength. The fluid temperature was measured by the fluorescent response of Rhodamine B in the microchannel. The trapping strength was measured by the area of a trapped particle cluster counter-balanced by the hydrodynamic force. One of the main objectives was to obtain quantitative values of the temperature in the fluidic channel to ensure safe handling of cells and proteins. Another objective was to evaluate the trapping-to-temperature efficiency for the trap as a function of drive frequency. Thirdly, trapping-to-temperature efficiency data enables identifying frequencies and voltage values to use for in-trap temperature regulation. It is envisioned that operation with only in-trap temperature regulation enables the realization of small, simple and fast temperature-controlled trap systems. The significance of potential gradients at the trap edges due to the finite size of the miniaturized transducers for the operation was emphasized and expressed analytically. The influence of the acoustic near field was evaluated in FEM-simulation and compared with a more ideal 1D standing wave. The working principle of the trap was examined by comparing measurements of impedance, temperature increase and trapping strength with impedance transfer calculations of fluid-reflector resonances and frequencies of high reflectance at the fluid-reflector boundary. The temperature increase was found to be moderate, 7 degrees C for a high trapping strength, at a fluid flow of 0.5 mm s(-1) for the optimal driving frequency. A fast temperature response with a fall time of 8 s and a rise time of 11 s was observed. The results emphasize the importance of selecting the proper drive frequency for long term handling of cells, as opposed to the more pragmatic way of selecting the frequency of the highest acoustic output. Trapping was demonstrated in a large interval between 9 and 11.5 MHz, while the main trapping peak displayed FWHM of 0.5 MHz. A large bandwidth enables a more robust manufacturing and operation while allowing the trapping platform to be used in applications where the fluid wavelength varies due to external variations in fluid temperature, density and pressure.
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| 6. |
- Anderbro, Therese
(författare)
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Behavior change intervention and fear of hypoglycemia in type 1 diabetes
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Individuals with type 1 diabetes require lifelong insulin supply as well as behavioral adjustments for good treatment result. Only a minority reach the goal for glycemic control set in order to reduce the risk of severe long-term complications. Interventions based on cognitive behavior therapy (CBT) have been proposed to improve diabetes-management, but evidence for its efficacy in adults with poorly controlled type 1 diabetes is sparse. One common barrier to optimal diabetes-management is fear of hypoglycemia (FOH), especially in those who have experienced severe hypoglycemic episodes. Thus there is a need for a valid and reliable instrument to assess individuals who are affected by FOH. It is also vital to identify factors associated with FOH in order to find targets for interventions to reduce fear.Aim: The overall aims of this thesis were to evaluate a CBT intervention for poorly controlled individuals with type 1 diabetes and to explore fear of hypoglycemia in an effort to gain deeper knowledge of possible targets for interventions to reduce FOH.Methods: All four studies applied quantitative designs. Study I was a randomized controlled trial in which a cognitive behavioral intervention was evaluated on poorly controlled adult persons with type 1 diabetes. Study II was a psychometric evaluation of a Swedish version of the Hypoglycemia Fear Survey (HFS) in a survey study in adult persons with type 1 diabetes. Studies III and IV were cross-sectional survey studies employed on adults with type 1 diabetes exploring disease-specific, demographic, (studies III and IV) emotional and psychosocial factors (study IV) related to FOH.Results and conclusions: Study I: The intervention group receiving CBT showed significant improvements in HbA1c, diabetes related distress, well-being, FOH, perceived stress, anxiety and depression as well as frequency in self monitoring of blood glucose. Study II: A three- factor solution was found for the Swedish version of the HFS with the dimensions Worry, Behavior and Aloneness. Cronbach’s alpha for the total scale was 0.85 and varied between 0.63 – 0.89 in the subscales. Convergent validity was also supported with moderate correlation between Swe-HFS and Swe-PAID-20. The Swe-HFS seems to be a reliable and valid instrument to measure FOH in adults with type 1 diabetes. Study III: Seven hundred and sixty- four persons (55%) responded to the questionnaire. The HFS-Worry subscale was significantly associated with frequency of severe hypoglycemia, number of symptoms during mild hypoglycemia, gender, hypoglycemic symptoms during hyperglycemia and hypoglycemic unawareness. The HFS-Aloneness subscale was significantly associated with frequency of severe hypoglycemia, number of symptoms during mild hypoglycemia, gender, frequency of mild hypoglycemia, HbA1c, hypoglycaemic unawareness and visits to the emergency room because of severe hypoglycemia. FOH proved to be more prevalent in females. Frequency of severe hypoglycemia was identified as the most important factor associated with FOH. Study IV: A total of 469 (61%) persons responded to the questionnaire. The HFS was significantly associated with The Anxiety Sensitivity Index, the Anxiety subscale of Hospital Anxiety and Depression Scale and Social Phobia Scale. Together with the disease-specific factors the regression model explained 39% of the variance. Support for a positive association between FOH and anxiety was present and previously identified gender differences were confirmed. Differences between the subgroups on factors associated with FOH were found that may have implications in developing interventions
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| 7. |
- Anderbro, Therese, et al.
(författare)
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Fear of hypoglycemia : relationship to hypoglycemic risk and psychological factors
- 2014
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Ingår i: Acta Diabetologica. - : Springer Science and Business Media LLC. - 0940-5429 .- 1432-5233.
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The major aims of this study were to examine (1) the association between fear of hypoglycemia (FOH) in adults with type 1 diabetes with demographic, psychological (anxiety and depression), and disease-specific clinical factors (hypoglycemia history and unawareness, A1c), including severe hypoglycemia (SH), and (2) differences in patient subgroups categorized by level of FOH and risk of SH.RESEARCH DESIGN AND METHODS: Questionnaires were mailed to 764 patients with type 1 diabetes including the Swedish translation of the Hypoglycemia Fear Survey (HFS) and other psychological measures including the Perceived Stress Scale, Hospital Anxiety and Depression Scale, Anxiety Sensitivity Index, Social Phobia Scale, and Fear of Complications Scale. A questionnaire to assess hypoglycemia history was also included and A1c measures were obtained from medical records. Statistical analyses included univariate approaches, multiple stepwise linear regressions, Chi-square t tests, and ANOVAs.RESULTS: Regressions showed that several clinical factors (SH history, frequency of nocturnal hypoglycemia, self-monitoring) were significantly associated with FOH but R (2) increased from 16.25 to 39.2 % when anxiety measures were added to the model. When patients were categorized by level of FOH (low, high) and SH risk (low, high), subgroups showed significant differences in non-diabetes-related anxiety, hypoglycemia history, self-monitoring, and glycemic control.CONCLUSION: There is a strong link between FOH and non-diabetes-related anxiety, as well as hypoglycemia history. Comparison of patient subgroups categorized according to level of FOH and SH risk demonstrated the complexity of FOH and identified important differences in psychological and clinical variables, which have implications for clinical interventions.
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| 8. |
- Andersson, Mikael, et al.
(författare)
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Measuring walking speed in COPD: test-retest reliability of the 30-metre walk test and comparison with the 6-minute walk test
- 2011
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Ingår i: Primary Care Respiratory Journal. - : Springer Science and Business Media LLC. - 1471-4418 .- 1475-1534. ; 20:4, s. 434-440
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To examine test-retest reliability of the 30-metre walk test (30mWT) in patients with chronic obstructive pulmonary disease (COPD) and to compare the 30mWT with the 6-minute walk test (6MWT). Methods: Forty-nine subjects with stable COPD were included. The 30mWT consists of walking at different walking intensities over a distance of 30 metres - self-selected speed (ss-30mWT) and maximal speed (ms-30mWT). The test was conducted twice and the time to walk 30 metres was recorded. The 6MWT was performed in duplicate on the same day. Results: Test-retest reliability was high: intraclass correlation coefficient (ICC2.1) = 0.93 (95% CI 0.87 to 0.97) for maximal walking speed and 0.87 (95% CI 0.78 to 0.93) for self-selected walking speed. Both maximal and self-selected speed had a standard error of measurement (SEM) of 0.07 m/s and SEM% was 4.4 for maximal speed and 5.9 for self-selected speed. The correlation, criterion validity, between ms-30mWT and the 6MWT was r=0.78 (p<0.001). Heart rate, dyspnoea, exertion and oxygen saturation were more affected after the 6MWT than after the 30mWT (p<0.001). Conclusions: The 30mWT is a reliable submaximal test that is easy to perform and can be used to measure physical function (walking ability) in patients with COPD. It may be well suited for primary care settings. (C) 2011 Primary Care Respiratory Society UK. All rights reserved. M Andersson, et al. Prim Care Respir J 2011; 20(4): 434-440 http://dx.doi.org/10.4104/pcrj.2011.00082
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| 9. |
- Aquila, Andrew, et al.
(författare)
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Time-resolved protein nanocrystallography using an X-ray free-electron laser
- 2012
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Ingår i: Optics Express. - 1094-4087. ; 20:3, s. 2706-2716
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Tidskriftsartikel (refereegranskat)abstract
- We demonstrate the use of an X-ray free electron laser synchronized with an optical pump laser to obtain X-ray diffraction snapshots from the photoactivated states of large membrane protein complexes in the form of nanocrystals flowing in a liquid jet. Light-induced changes of Photosystem I-Ferredoxin co-crystals were observed at time delays of 5 to 10 µs after excitation. The result correlates with the microsecond kinetics of electron transfer from Photosystem I to ferredoxin. The undocking process that follows the electron transfer leads to large rearrangements in the crystals that will terminally lead to the disintegration of the crystals. We describe the experimental setup and obtain the first time-resolved femtosecond serial X-ray crystallography results from an irreversible photo-chemical reaction at the Linac Coherent Light Source. This technique opens the door to time-resolved structural studies of reaction dynamics in biological systems.
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| 10. |
- Arnlund, David, et al.
(författare)
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Visualizing a protein quake with time-resolved X-ray scattering at a free-electron laser
- 2014
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Ingår i: Nature Methods. - : Springer Science and Business Media LLC. - 1548-7091 .- 1548-7105. ; 11:9, s. 923-926
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Tidskriftsartikel (refereegranskat)abstract
- We describe a method to measure ultrafast protein structural changes using time-resolved wide-angle X-ray scattering at an X-ray free-electron laser. We demonstrated this approach using multiphoton excitation of the Blastochloris viridis photosynthetic reaction center, observing an ultrafast global conformational change that arises within picoseconds and precedes the propagation of heat through the protein. This provides direct structural evidence for a 'protein quake': the hypothesis that proteins rapidly dissipate energy through quake-like structural motions.
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