| 1. |
- Halldén, Christer, 1957-, et al.
(författare)
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Investigation of disease-associated factors in haemophilia A patients without detectable mutations
- 2012
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Ingår i: Haemophilia. - : Blackwell. - 1351-8216 .- 1365-2516. ; 18:3, s. e132-e137
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Tidskriftsartikel (refereegranskat)abstract
- To investigate disease causing mechanism in haemophilia A patients without detectable mutation. Screening for F8 mutations in 307 haemophilia A patients using: re-sequencing and inversion PCR, reverse transcription (RT-PCR) of mRNA, MLPA analysis, haplotyping using SNP and microsatellite markers. No F8 mutations were detected in 9 of the 307 patients (2.9%) using re-sequencing and inversion PCR. MLPA analysis detected duplication in exon 6 in one patient and RT-PCR showed no products for different regions of mRNA in four other patients, indicating failed transcription. No obvious associations were observed between the phenotypes of the nine patients, their F8 haplotypes and the putative mutations detected. The mutation-positive patients carrying the same haplotypes as the mutation-negative patients show a multitude of different mutations, emphasizing the lack of associations at the haplotype level. VWF mutation screening and factor V measurements ruled out type 2N VWD and combined factor V and VIII deficiency respectively. To further investigate a possible role for FVIII interacting factors the haplotypes/diplotypes of F2, F9, F10 and VWF were compared. The nine patients had no specific haplotype/diplotype combination in common that can explain disease. Duplications and faulty transcription contribute to the mutational spectrum of haemophilia A patients where conventional mutation screening fail to identify mutations.
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| 2. |
- Ahlström, Christer, 1977-, et al.
(författare)
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Road Vehicle Automation and Its Effects on Fatigue, Sleep, Rest, and Recuperation
- 2023. - 1
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Ingår i: The Handbook of Fatigue Management in Transportation. - Boca Raton : CRC Press. - 9781003213154
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Assisted and automated driving brings new challenges and opportunities when it comes to driver fatigue. With lower levels of vehicle automation, driver monotony and boredom in combination with demanding attentive monitoring leads to higher levels of fatigue, especially during the night when the sleep pressure is high. With higher levels of vehicle automation, when the driver is not required to continuously monitor the roadway and the automation system, task-related fatigue can be counteracted by engaging in non-driving-related activities. Finally, with the highest levels of vehicle automation, it may even become possible for drivers to sleep while on the move. Aside from making it possible for private car drivers to take strategic naps during a drive, this also opens up the possibility for more flexible, risk management-based, hour of service regulations for professional drivers. This chapter summarises the current state of the art on how assisted and piloted driving affects driver fatigue and how automation may facilitate recovery and recuperation from fatigue while on the move. It also covers how automated functions will impact driver monitoring systems and how new ways of counteracting driver fatigue may arise when automation is available.
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| 3. |
- Halldén, Christer, et al.
(författare)
-
Investigation of disease-associated factors in haemophilia A patients without detectable mutations
- 2012
-
Ingår i: Haemophilia. - : Wiley-Blackwell Publishing Ltd. - 1351-8216 .- 1365-2516. ; 18:3, s. e132-e137
-
Tidskriftsartikel (refereegranskat)abstract
- To investigate disease causing mechanism in haemophilia A patients without detectable mutation. Screening for F8 mutations in 307 haemophilia A patients using: re-sequencing and inversion PCR, reverse transcription (RT-PCR) of mRNA, MLPA analysis, haplotyping using SNP and microsatellite markers. No F8 mutations were detected in 9 of the 307 patients (2.9%) using re-sequencing and inversion PCR. MLPA analysis detected duplication in exon 6 in one patient and RT-PCR showed no products for different regions of mRNA in four other patients, indicating failed transcription. No obvious associations were observed between the phenotypes of the nine patients, their F8 haplotypes and the putative mutations detected. The mutation-positive patients carrying the same haplotypes as the mutation-negative patients show a multitude of different mutations, emphasizing the lack of associations at the haplotype level. VWF mutation screening and factor V measurements ruled out type 2N VWD and combined factor V and VIII deficiencyrespectively. To further investigate a possible role for FVIII interacting factors the haplotypes/diplotypes of F2, F9, F10 and VWF were compared. The nine patients had no specific haplotype/diplotype combination in common that can explain disease. Duplications and faulty transcription contribute to the mutational spectrum of haemophilia A patients where conventional mutation screening fail to identify mutations.
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| 4. |
- Halldén, Christer, et al.
(författare)
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Origin of Swedish hemophilia A mutations
- 2012
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 10:12, s. 2503-2511
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Tidskriftsartikel (refereegranskat)abstract
- Background: Hemophilia A (HA) has a high level of variation within the disease class, with more than 1000 mutations being listed in the HAMSTeRS database. At the same time a number of F8 mutations are present in specific populations at high frequencies. Objectives: The simultaneous presence of large numbers of rare mutations and a small number of high-frequency mutations raises questions about the origins of HA mutations. The present study was aimed at describing the origins of HA mutations in the complete Swedish population. The primary issue was to determine what proportion of identical mutations are identical by descent (IBD) and what proportion are attributable to recurrent mutation events. The age of IBD mutations was also determined. Patients/Methods: In Sweden, the care of HA is centralized, and the Swedish HA population consists of 750 patients from > 300 families (35% severe, 15% moderate, and 50% mild). Identical haplotypes were defined by single-nucleotide polymorphism and microsatellite haplotyping, and the ages of the mutations were estimated with estiage. Results: Among 212 presumably unrelated patients with substitution mutations, 97 (46%) had mutations in common with other patients. Haplotyping of the 97 patients showed that 47 had IBD mutations (22%) with estimated ages of between two and 35 generations. The frequency of mild disease increased with an increasing number of patients sharing the mutations. Conclusions: A majority of the IBD mutations are mild and have age estimates of a few hundred years, but some could date back to the Middle Ages.
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| 5. |
- Halldén, Christer, et al.
(författare)
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Origin of Swedish hemophilia B mutations
- 2013
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Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 11:11, s. 2001-2008
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Tidskriftsartikel (refereegranskat)abstract
- Background More than 1100 mutations that cause hemophilia B (HB) have been identified. At the same time, specific F9 mutations are present at high frequencies in certain populations, which raise questions about the origin of HB mutations. ObjectivesTo describe the mutation spectrum of all HB families in Sweden and investigate if mutations appearing in several families are due to independent recurrent mutations (RMs) or to a common mutation event (i.e. are identical by descent (IBD)). Patients/MethodsThe registered Swedish HB population consists of patients from 86 families. Mutations were identified by resequencing and identical haplotypes were defined using 74 markers and a control population of 285 individuals. The ages of IBD mutations were estimated using ESTIAGE. ResultsOut of 77 presumably unrelated patients with substitution mutations, 47 patients (61%) had mutations in common with other patients. Haplotyping of the 47 patients showed that 24 patients had IBD mutations (51%) with estimated ages of between two and 23 generations. A majority of these patients had mild disease. Eight of the 15 mutations observed in more than one family were C>T transitions in CpG sites and all eight were RMs. ConclusionsThe association of IBD mutations with a mild phenotype is similar to what has been previously observed in hemophilia A. Noteworthy features of the mutations that are common to more than one family are the equal proportions of patients with RM and IBD mutations and the correlation between the occurrence of RMs and C>T transitions at CpG sites.
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| 6. |
- Jonsson, Malin, et al.
(författare)
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Biomechanical differences in double poling (DP) for world- and national-class female elite cross-country (XC) skiers during a 10-km classical race
- 2016
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Ingår i: Proceedings ICSS in St. Christoph am Arlberg, Austria.
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Konferensbidrag (refereegranskat)abstract
- Introduction The DP technique of classical XC-skiing involves both the upper and lower body (Holmberg et al.,2005) and has become more important the last years with skiers using exclusively DP during some competitions. Our purpose was to characterize biomechanical differences in DP by world- (WC) and national-class (NC) women skiers. Methods The participants were 40 elite female XC skiers (20 WC and 20 NC) who competed in the 10-km classical race at the Norwegian National Championships, 2016. On a flat measurement section (22 m long) 0.8 km from the start, the skiers employed DP only and were video-filmed (Panasonic GH4, 96 Hz). Three DP cycles were analyzed using the Kinovea software (France, v 8.25) for joint and pole angles at pole plant (PP) and pole off (PO), as well as cycle length (CL) and rate (CR), and poling (PT) and swing times (ST). Results The total racing time for the WC-group was 10.5% faster than for the NC-skiers, with no differences in CL, CR, PT or ST. The WC-group skied faster on the flat section (6.30±0.23 vs 6.04±0.25 m/s) and exhibited a smaller ankle-shoulder angle relative to horizontal at PP (73.0±1.8 vs 75.0±1.5°) and a smaller hip angle at PO (62.7±5.2 vs 69.1±6.4°) with no difference in minimal trunk angle with respect to horizontal (19.2±3.2 vs 21.7±4.8°). 27 of the skiers (15 WC and 12 NC) used active heel raise to create force. There was a difference between the groups for when the heel raise ended, with the NC-group stopping just before PP and the WC-group after. No difference between the groups were found for when the heel raise started . There was a negative correlation between DP velocity and total racing time (r = -0.48, p<0.05) and a positive correlation between total racing time and the ankle-shoulder angle relative to horizontal at PP (r = 0.54, p<0.01), the hip angle at PO (r = 0.51, p<0.01) and minimal trunk angle relative to horizontal during the cycles (r = 0.41, p<0.01). Discussion The WC-group had 4.1% higher DP velocity which correlated with total racing time. Moreover, the finding that faster skiers have a more forward lean of the body at PP and a better timing of the ending of the heel raise, indicates that they can bring more bodyweight on their poles at PP. The WC-group had a smaller hip angle at PO which is in line with the findings of Lindinger et al.(2009). This study shows the importance of a high relative velocity during DP sections of the track and highlights the benefit of a more forward body position at PP to create higher DP velocity in female XC skiers. References Holmberg, H.C., Lindinger, S., Stöggl, T., Eitzlmair, E. & Müller, E. (2005). Biomechanical analysis of double poling in elite cross-country skiers. Med Sci Sports Exerc, 37(5), 807-818 Lindinger, S., Stöggl, T., Müller, E. & Holmberg, H.C. (2009). Control of speed during the double poling technique performed by elite cross-country skiers. Med Sci Sports Exerc, 41(1), 210-220
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| 7. |
- Kircher, Katja, 1973-, et al.
(författare)
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Secondary Task Workload Test Bench – 2TB : final report
- 2014
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The main aim of this study was to investigate a selection of commonly used performance indicators (PIs) that have been reported to be sensitive to distraction and workload. More specifically, the PIs were tested for their ability to differentiate between task modalities (visual, cognitive and haptic) and task difficulty (easy, medium and hard). It was investigated whether possible differences were constant across two traffic situations (with/without lead vehicle) and two driving simulators. The experiment was conducted in the VTI Driving Simulator III, an advanced moving-base simulator, and in the Volvo Car Corporation driving simulator, an advanced fixed-base simulator. Both simulators were equipped with Smart Eye Pro eye tracking systems. A visual, a cognitive and a haptic secondary task were chosen to test the ability of the PIs to distinguish between the tasks’ loading on different modalities. Some of the main results from the study were:There were only minor differences between the two simulators for driving behaviour as described by longitudinal PIs. There was no overall offset, and the main difference was that the visual task led to stronger speed reductions in the moving-base simulator, which influenced both the mean speed and the speeding index.Regarding lateral PIs, major differences between the two simulators were found, both as a general offset and for those factor combinations that include modality and task difficulty level.With the visual or the haptic task active, the drivers positioned themselves further to the left and the variation in lateral position was higher in the fixed-base simulator.The number of lane crossings did not differ considerably between the simulators, but the lane departure area was larger on average in the fixed-base simulator, again influenced by modality, with the largest lane departure areas for the visual task, and in the case of the fixed-base simulator for the haptic task as well.Most of the eye movement related PIs had a general offset between the simulators. The drivers in the fixed-base simulator accumulated more time with their eyes off the road, especially during the visual and the cognitive tasks, while the drivers in the moving-base simulator cast longer single glances at the display.
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| 8. |
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| 9. |
- Ljung, R., et al.
(författare)
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Hemophilia A families with the same mutation are often related : a survey of the Swedish population
- 2012
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Ingår i: Haemophilia (ISSN 1351-8216) 2012: 18 (supplement 3), p. 109. ; , s. 109-109
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Aim: To study if families with hemophilia A in Sweden carrying the same mutation are identical by descent (IBD) or the result of independent mutations (RM).Study group: A total of 284 presumed unrelated and unselected Swedish families with hemophilia A comprising all clinical severities. Control group of 254 healthy individuals.Methods: Haplotyping was performed using 90 SNP markers (18 within the F8 gene) and 5 microsatellite markers. The frequencies of shared haplotypes were determined in the control group and the ages of the shared haplotypes determined using the program ESTIAGE.Results: Analysis of the mutations gave the following results: inversions in introns 1 or 22 were detected in 71 cases, large deletions in 5, small deletions/insertions in 4, and substitutions in 204 patients. For substitutions, a total of 107 mutations occurred in a single individual only, whereas the remaining 35 mutations occurred in 2 or more individuals; 20 mutations occurred in 2 individuals, 9 mutations occurred in 3 individuals, m4 mutations occurred in 4 individuals, and 2 mutations occurred in 7 individuals each, i.e., 97 mutations out of 204 (47%) were either IBD or recurrent mutation. Haplotyping and comparisons with the control group classified 51 of the 97 mutations as IBD. The phenotypes of the 51 individuals were mild (31), moderate (5), and severe (8), and the corresponding mutations had age estimates varying between 150 and 700 years. Inhibitors occurred in both RM and IBD families. One IBD family with mild hemophilia (2105 Tyr>Cys) had 3 members who developed inhibitors.Conclusion: Many families with hemophilia A, in particular those with milder forms, carrying the same mutation are IBD, i.e., revision of ‘‘hot-spots’’ for mutation is needed. Few ‘‘clusters of inhibitors’’ were found.
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| 10. |
- Ljung, R., et al.
(författare)
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Hemophilia B families with the same mutation are often related : a survey of the Swedish population
- 2012
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Ingår i: Haemophilia (ISSN 1351-8216) 2012: 18 (supplement 3), p. 109. ; , s. 109-109
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Aim: To study if families with hemophilia B in Sweden carrying the same mutation are identical by descent (IBD) or the result of independent mutations (RM).Study group: A total of 77 presumed unrelated and unselected Swedish families with hemophilia B comprising all clinical severities (total and large deletions not included). Control group of 256 healthy individuals.Methods: Haplotyping was performed using 90 SNP markers (11 within the F9 gene) and 1 microsatellite marker. The frequencies of shared haplotypes were determined in the control group, and the ages of the shared haplotypes will be determined using the program ESTIAGE.Results: Analysis of the mutations gave the following results: 5 small deletions (<10bp), 2 small insertions (<10bp), 3 splice site mutations, 14 nonsense mutations, and 53 missense mutations. A total of 30 mutations (39%) occurred in a single individual only, whereas the remaining 47 mutations occurred in 2 or more individuals; 7 mutations occurred in 2 individuals, 4 mutations occurred in 3 individuals, 2 mutations occurred in 4 individuals, 1 mutation occurred in 6 individuals, and 1 mutation occurred in 7 individuals each, i.e., 47 mutations out of 77 (61%) were either IBD or recurrent mutation. Haplotyping and comparisons with the control group classified 21/47 mutations as IBD and 25/47 as RM. The phenotypes of the 21 IBD individuals were mild (17), moderate 2), and severe (1); those of the 25 RM individuals were mild (7), moderate (7), and severe (12). Age estimation of the mutations is ongoing.Conclusion: Many families with hemophilia B, in particular those with milder forms, carrying the same mutation are IBD, i.e., revision of ‘‘hot-spots’’ for mutation is needed.
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